PARADIGM pathway analysis of mRNASeq expression and copy number data - Breast Invasive Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	334
Class IB PI3K non-lipid kinase events	287
Signaling events mediated by Stem cell factor receptor (c-Kit)	285
Signaling mediated by p38-alpha and p38-beta	275
Reelin signaling pathway	236
EGFR-dependent Endothelin signaling events	200
Aurora B signaling	193
FOXA2 and FOXA3 transcription factor networks	166
PLK1 signaling events	166
Angiopoietin receptor Tie2-mediated signaling	164

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
FOXM1 transcription factor network	0.3056	334	17073	51	-0.053	0.69	1000	-1000	-0.048	-1000
Class IB PI3K non-lipid kinase events	0.2626	287	861	3	-0.13	-1000	1000	-1000	-0.019	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.2608	285	22300	78	-0.57	0.18	1000	-1000	-0.057	-1000
Signaling mediated by p38-alpha and p38-beta	0.2516	275	12131	44	-0.32	0.024	1000	-1000	-0.019	-1000
Reelin signaling pathway	0.2159	236	13266	56	-0.32	0.054	1000	-1000	-0.03	-1000
EGFR-dependent Endothelin signaling events	0.1830	200	4205	21	-0.21	0.034	1000	-1000	-0.033	-1000
Aurora B signaling	0.1766	193	12988	67	-0.21	0.27	1000	-1000	-0.04	-1000
FOXA2 and FOXA3 transcription factor networks	0.1519	166	7649	46	-1.1	0.034	1000	-1000	-0.057	-1000
PLK1 signaling events	0.1519	166	14140	85	-0.063	0.23	1000	-1000	-0.032	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1500	164	14439	88	-0.32	0.11	1000	-1000	-0.058	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1482	162	11024	68	-0.34	0.15	1000	-1000	-0.046	-1000
HIF-1-alpha transcription factor network	0.1455	159	12102	76	-0.48	0.035	1000	-1000	-0.057	-1000
Glucocorticoid receptor regulatory network	0.1400	153	17489	114	-0.72	0.28	1000	-1000	-0.043	-1000
EPHB forward signaling	0.1391	152	12921	85	-0.2	0.14	1000	-1000	-0.058	-1000
Endothelins	0.1354	148	14252	96	-0.34	0.17	1000	-1000	-0.03	-1000
p75(NTR)-mediated signaling	0.1308	143	17891	125	-0.22	0.096	1000	-1000	-0.06	-1000
IL4-mediated signaling events	0.1199	131	11973	91	-0.66	0.25	1000	-1000	-0.051	-1000
Ephrin B reverse signaling	0.1125	123	5923	48	-0.2	0.089	1000	-1000	-0.024	-1000
Wnt signaling	0.1089	119	836	7	-0.097	0.017	1000	-1000	-0.009	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1052	115	6256	54	-0.32	0.054	1000	-1000	-0.04	-1000
IGF1 pathway	0.1043	114	6547	57	-0.11	0.044	1000	-1000	-0.033	-1000
Noncanonical Wnt signaling pathway	0.1006	110	2882	26	-0.097	0.024	1000	-1000	-0.03	-1000
Arf6 signaling events	0.1006	110	6827	62	-0.21	0.05	1000	-1000	-0.019	-1000
Plasma membrane estrogen receptor signaling	0.0961	105	9047	86	-0.12	0.11	1000	-1000	-0.045	-1000
IL23-mediated signaling events	0.0942	103	6207	60	-0.3	0.084	1000	-1000	-0.046	-1000
Nongenotropic Androgen signaling	0.0933	102	5320	52	-0.25	0.13	1000	-1000	-0.026	-1000
ErbB2/ErbB3 signaling events	0.0897	98	6381	65	-0.26	0.034	1000	-1000	-0.059	-1000
BMP receptor signaling	0.0897	98	7966	81	-0.38	0.1	1000	-1000	-0.038	-1000
Signaling events regulated by Ret tyrosine kinase	0.0878	96	7935	82	-0.07	0.097	1000	-1000	-0.053	-1000
Calcium signaling in the CD4+ TCR pathway	0.0860	94	2933	31	-0.19	0.027	1000	-1000	-0.042	-1000
Signaling events mediated by PTP1B	0.0851	93	7141	76	-0.44	0.082	1000	-1000	-0.036	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0851	93	11277	120	-0.35	0.17	1000	-1000	-0.044	-1000
S1P1 pathway	0.0796	87	3150	36	-0.33	0.024	1000	-1000	-0.026	-1000
Visual signal transduction: Rods	0.0796	87	4562	52	-0.33	0.055	1000	-1000	-0.029	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0787	86	7388	85	-0.24	0.024	1000	-1000	-0.033	-1000
Aurora C signaling	0.0769	84	588	7	0	0.14	1000	-1000	-0.015	-1000
TCR signaling in naïve CD8+ T cells	0.0741	81	7620	93	-0.089	0.084	1000	-1000	-0.035	-1000
Effects of Botulinum toxin	0.0732	80	2093	26	-0.003	0.1	1000	-1000	-0.003	-1000
ErbB4 signaling events	0.0723	79	5468	69	-0.27	0.06	1000	-1000	-0.028	-1000
Glypican 1 network	0.0723	79	3801	48	-0.2	0.045	1000	-1000	-0.02	-1000
IL6-mediated signaling events	0.0704	77	5834	75	-0.18	0.053	1000	-1000	-0.032	-1000
amb2 Integrin signaling	0.0695	76	6263	82	-0.33	0.12	1000	-1000	-0.025	-1000
LPA receptor mediated events	0.0659	72	7394	102	-0.19	0.12	1000	-1000	-0.054	-1000
Signaling events mediated by the Hedgehog family	0.0650	71	3700	52	-0.12	0.028	1000	-1000	-0.027	-1000
Integrins in angiogenesis	0.0650	71	6022	84	-0.2	0.11	1000	-1000	-0.049	-1000
Syndecan-1-mediated signaling events	0.0640	70	2395	34	-0.073	0.18	1000	-1000	-0.037	-1000
Ephrin A reverse signaling	0.0622	68	481	7	-0.028	0.023	1000	-1000	-0.004	-1000
IL12-mediated signaling events	0.0613	67	5914	87	-0.32	0.072	1000	-1000	-0.06	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0576	63	2156	34	-0.024	0.058	1000	-1000	-0.024	-1000
PDGFR-alpha signaling pathway	0.0567	62	2758	44	-0.3	0.036	1000	-1000	-0.032	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0558	61	3212	52	-0.12	0.071	1000	-1000	-0.029	-1000
Canonical Wnt signaling pathway	0.0540	59	3017	51	-0.28	0.12	1000	-1000	-0.041	-1000
Visual signal transduction: Cones	0.0531	58	2226	38	-0.024	0.16	1000	-1000	-0.013	-1000
Fc-epsilon receptor I signaling in mast cells	0.0531	58	5659	97	-0.14	0.033	1000	-1000	-0.051	-1000
Syndecan-2-mediated signaling events	0.0522	57	3997	69	-0.12	0.11	1000	-1000	-0.031	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0512	56	1877	33	-0.38	0.059	1000	-1000	-0.036	-1000
Presenilin action in Notch and Wnt signaling	0.0494	54	3342	61	-0.27	0.12	1000	-1000	-0.039	-1000
Nectin adhesion pathway	0.0494	54	3450	63	-0.056	0.047	1000	-1000	-0.04	-1000
TCGA08_rtk_signaling	0.0494	54	1410	26	-0.19	0.037	1000	-1000	-0.009	-1000
Glypican 2 network	0.0467	51	207	4	0.033	0.058	1000	-1000	0.016	-1000
Rapid glucocorticoid signaling	0.0467	51	1030	20	-0.11	0.026	1000	-1000	-0.004	-1000
E-cadherin signaling in keratinocytes	0.0467	51	2235	43	-0.19	0.033	1000	-1000	-0.028	-1000
Ras signaling in the CD4+ TCR pathway	0.0467	51	875	17	-0.056	0.025	1000	-1000	-0.012	-1000
FAS signaling pathway (CD95)	0.0457	50	2359	47	-0.43	0.039	1000	-1000	-0.024	-1000
Syndecan-3-mediated signaling events	0.0448	49	1744	35	-0.23	0.054	1000	-1000	-0.019	-1000
Signaling events mediated by HDAC Class III	0.0430	47	1892	40	-0.32	0.045	1000	-1000	-0.022	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0421	46	3438	74	-0.19	0.049	1000	-1000	-0.062	-1000
LPA4-mediated signaling events	0.0412	45	540	12	-0.11	0.006	1000	-1000	-0.023	-1000
Aurora A signaling	0.0393	43	2627	60	-0.079	0.18	1000	-1000	-0.013	-1000
Signaling events mediated by PRL	0.0393	43	1474	34	-0.12	0.035	1000	-1000	-0.034	-1000
Coregulation of Androgen receptor activity	0.0384	42	3204	76	-0.14	0.063	1000	-1000	-0.016	-1000
Regulation of Androgen receptor activity	0.0384	42	2958	70	-0.16	0.11	1000	-1000	-0.043	-1000
Syndecan-4-mediated signaling events	0.0375	41	2777	67	-0.2	0.12	1000	-1000	-0.04	-1000
Thromboxane A2 receptor signaling	0.0348	38	4041	105	-0.19	0.036	1000	-1000	-0.035	-1000
Regulation of p38-alpha and p38-beta	0.0348	38	2091	54	-0.24	0.052	1000	-1000	-0.042	-1000
TCGA08_retinoblastoma	0.0348	38	310	8	-0.018	0.06	1000	-1000	-0.002	-1000
Regulation of Telomerase	0.0348	38	3932	102	-0.2	0.14	1000	-1000	-0.034	-1000
Insulin Pathway	0.0348	38	2848	74	-0.12	0.06	1000	-1000	-0.047	-1000
IL27-mediated signaling events	0.0339	37	1919	51	-0.18	0.075	1000	-1000	-0.038	-1000
BCR signaling pathway	0.0339	37	3679	99	-0.077	0.056	1000	-1000	-0.045	-1000
Regulation of nuclear SMAD2/3 signaling	0.0311	34	4637	136	-0.19	0.077	1000	-1000	-0.027	-1000
Osteopontin-mediated events	0.0302	33	1275	38	-0.14	0.086	1000	-1000	-0.031	-1000
IL2 signaling events mediated by STAT5	0.0293	32	719	22	0.006	0.11	1000	-1000	-0.028	-1000
TCGA08_p53	0.0265	29	207	7	-0.011	0.02	1000	-1000	-0.004	-1000
HIF-2-alpha transcription factor network	0.0247	27	1179	43	-0.15	0.16	1000	-1000	-0.038	-1000
Class I PI3K signaling events mediated by Akt	0.0229	25	1702	68	-0.16	0.043	1000	-1000	-0.024	-1000
Caspase cascade in apoptosis	0.0220	24	1786	74	-0.025	0.057	1000	-1000	-0.028	-1000
Ceramide signaling pathway	0.0220	24	1851	76	-0.1	0.063	1000	-1000	-0.03	-1000
S1P5 pathway	0.0220	24	414	17	-0.007	0.033	1000	-1000	-0.004	-1000
S1P4 pathway	0.0220	24	622	25	-0.012	0.044	1000	-1000	-0.014	-1000
IL2 signaling events mediated by PI3K	0.0201	22	1311	58	-0.001	0.065	1000	-1000	-0.047	-1000
Hedgehog signaling events mediated by Gli proteins	0.0192	21	1375	65	-0.087	0.056	1000	-1000	-0.045	-1000
BARD1 signaling events	0.0183	20	1165	57	-0.046	0.1	1000	-1000	-0.031	-1000
Cellular roles of Anthrax toxin	0.0183	20	818	39	-0.079	0.027	1000	-1000	-0.018	-1000
mTOR signaling pathway	0.0183	20	1073	53	-0.022	0.028	1000	-1000	-0.034	-1000
JNK signaling in the CD4+ TCR pathway	0.0174	19	325	17	0.002	0.064	1000	-1000	-0.025	-1000
S1P3 pathway	0.0165	18	788	42	-0.014	0.042	1000	-1000	-0.027	-1000
FoxO family signaling	0.0156	17	1093	64	-0.016	0.23	1000	-1000	-0.032	-1000
Retinoic acid receptors-mediated signaling	0.0156	17	1039	58	-0.051	0.051	1000	-1000	-0.025	-1000
ceramide signaling pathway	0.0146	16	801	49	-0.001	0.036	1000	-1000	-0.03	-1000
Signaling mediated by p38-gamma and p38-delta	0.0146	16	251	15	-0.026	0.024	1000	-1000	-0.025	-1000
Arf6 trafficking events	0.0146	16	1162	71	-0.27	0.042	1000	-1000	-0.019	-1000
IL1-mediated signaling events	0.0137	15	948	62	-0.015	0.061	1000	-1000	-0.025	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0128	14	393	28	-0.007	0.051	1000	-1000	-0.015	-1000
PLK2 and PLK4 events	0.0128	14	44	3	0.016	0.033	1000	-1000	-0.005	-1000
E-cadherin signaling in the nascent adherens junction	0.0128	14	1068	76	-0.023	0.054	1000	-1000	-0.049	-1000
PDGFR-beta signaling pathway	0.0128	14	1403	97	-0.024	0.056	1000	-1000	-0.05	-1000
p38 MAPK signaling pathway	0.0119	13	610	44	-0.018	0.067	1000	-1000	-0.018	-1000
TRAIL signaling pathway	0.0110	12	582	48	-0.015	0.043	1000	-1000	-0.026	-1000
Class I PI3K signaling events	0.0110	12	927	73	-0.018	0.051	1000	-1000	-0.029	-1000
IFN-gamma pathway	0.0101	11	783	68	-0.006	0.076	1000	-1000	-0.042	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0101	11	419	37	-0.009	0.067	1000	-1000	-0.023	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0101	11	517	45	0.003	0.054	1000	-1000	-0.036	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0091	10	877	83	-0.019	0.047	1000	-1000	-0.028	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0091	10	1260	125	-0.1	0.053	1000	-1000	-0.031	-1000
E-cadherin signaling events	0.0091	10	54	5	0.012	0.033	1000	-1000	0.007	-1000
Signaling events mediated by HDAC Class II	0.0082	9	702	75	-0.035	0.062	1000	-1000	-0.03	-1000
a4b1 and a4b7 Integrin signaling	0.0082	9	48	5	0.024	0.041	1000	-1000	0.013	-1000
EPO signaling pathway	0.0082	9	528	55	0.014	0.08	1000	-1000	-0.024	-1000
Insulin-mediated glucose transport	0.0082	9	297	32	-0.12	0.039	1000	-1000	-0.021	-1000
Canonical NF-kappaB pathway	0.0073	8	349	39	0	0.051	1000	-1000	-0.031	-1000
VEGFR1 specific signals	0.0073	8	473	56	-0.1	0.052	1000	-1000	-0.038	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0046	5	119	23	-0.004	0.043	1000	-1000	-0.019	-1000
Signaling events mediated by HDAC Class I	0.0046	5	612	104	-0.06	0.057	1000	-1000	-0.028	-1000
Atypical NF-kappaB pathway	0.0046	5	179	31	0	0.028	1000	-1000	-0.013	-1000
Circadian rhythm pathway	0.0037	4	97	22	-0.007	0.049	1000	-1000	-0.013	-1000
Paxillin-dependent events mediated by a4b1	0.0037	4	177	36	-0.047	0.051	1000	-1000	-0.034	-1000
Arf6 downstream pathway	0.0027	3	153	43	-0.055	0.056	1000	-1000	-0.023	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0009	1	27	27	-0.008	0.056	1000	-1000	-0.035	-1000
Arf1 pathway	0.0009	1	97	54	-0.001	0.045	1000	-1000	-0.011	-1000
Alternative NF-kappaB pathway	0.0000	0	11	13	0	0.067	1000	-1000	0	-1000
Total	NA	8463	501486	7203	-20	-990	131000	-131000	-3.9	-131000

FOXM1 transcription factor network

Figure S1. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S1. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.57	0.39	0.97	399	-1	3	402
PLK1	0.35	0.24	0.62	336	-0.9	1	337
BIRC5	0.37	0.24	0.66	263	-0.89	3	266
HSPA1B	0.57	0.38	0.97	398	-1	3	401
MAP2K1	0.16	0.11	0.3	320	-10000	0	320
BRCA2	0.58	0.4	0.98	409	-0.99	4	413
FOXM1	0.66	0.48	1.1	457	-1.3	3	460
XRCC1	0.57	0.39	0.97	399	-1	3	402
FOXM1B/p19	0.12	0.26	0.78	66	-0.99	5	71
Cyclin D1/CDK4	0.5	0.37	0.88	402	-0.99	3	405
CDC2	0.62	0.43	1	456	-1.1	3	459
TGFA	0.5	0.39	0.87	430	-0.92	8	438
SKP2	0.58	0.39	0.98	401	-1	3	404
CCNE1	0.09	0.095	0.29	179	-10000	0	179
CKS1B	0.57	0.39	0.93	457	-1	3	460
RB1	0.29	0.3	0.66	341	-0.62	6	347
FOXM1C/SP1	0.52	0.36	0.89	375	-1.1	5	380
AURKB	0.29	0.3	0.63	258	-0.83	18	276
CENPF	0.66	0.45	1.1	484	-0.99	3	487
CDK4	0.08	0.053	0.23	25	-10000	0	25
MYC	0.34	0.36	0.82	270	-0.96	6	276
CHEK2	0.16	0.11	0.3	305	-10000	0	305
ONECUT1	0.53	0.39	0.9	431	-1.1	3	434
CDKN2A	-0.053	0.11	0.22	27	-0.22	217	244
LAMA4	0.57	0.4	0.97	406	-1.1	6	412
FOXM1B/HNF6	0.53	0.4	0.94	395	-1.3	3	398
FOS	0.27	0.64	0.99	313	-0.99	76	389
SP1	0.024	0.021	-10000	0	-0.2	5	5
CDC25B	0.58	0.39	0.97	405	-1	3	408
response to radiation	0.11	0.084	0.23	260	-10000	0	260
CENPB	0.57	0.39	0.97	402	-1	3	405
CENPA	0.63	0.43	1	469	-1	3	472
NEK2	0.69	0.44	1.1	512	-0.97	3	515
HIST1H2BA	0.57	0.39	0.97	391	-1	3	394
CCNA2	0.14	0.13	0.3	401	-10000	0	401
EP300	0.023	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.6	0.42	1	399	-1.2	3	402
CCNB2	0.63	0.43	1	475	-1	3	478
CCNB1	0.63	0.45	1.1	435	-1.1	3	438
ETV5	0.58	0.4	0.99	396	-1	3	399
ESR1	0.44	0.55	1	367	-0.99	19	386
CCND1	0.52	0.41	0.93	426	-1	3	429
GSK3A	0.13	0.089	0.27	190	-10000	0	190
Cyclin A-E1/CDK1-2	0.23	0.16	0.41	406	-10000	0	406
CDK2	0.056	0.028	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.14	0.11	0.26	366	-10000	0	366
FOXM1B/Cbp/p300	0.26	0.29	0.72	84	-1.1	3	87
GAS1	0.52	0.49	0.96	394	-1.1	38	432
MMP2	0.57	0.41	0.97	398	-1.2	10	408
RB1/FOXM1C	0.46	0.38	0.86	399	-1	3	402
CREBBP	0.023	0.007	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

Figure S2. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S2. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.13	0.26	0.56	287	-10000	0	287
PI3K Class IB/PDE3B	-0.13	0.26	-10000	0	-0.56	287	287
PDE3B	-0.13	0.26	-10000	0	-0.57	287	287

×

Signaling events mediated by Stem cell factor receptor (c-Kit)

Figure S3. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S3. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.16	0.2	0.34	3	-0.38	469	472
CRKL	-0.17	0.21	0.26	1	-0.4	482	483
HRAS	-0.12	0.18	-10000	0	-0.35	321	321
mol:PIP3	-0.14	0.2	0.29	1	-0.38	355	356
SPRED1	0.024	0.005	-10000	0	-10000	0	0
SPRED2	0.024	0.003	-10000	0	-10000	0	0
GAB1	-0.18	0.22	-10000	0	-0.42	489	489
FOXO3	-0.14	0.2	0.53	1	-0.36	402	403
AKT1	-0.16	0.21	0.37	1	-0.38	450	451
BAD	-0.15	0.2	0.34	2	-0.36	440	442
megakaryocyte differentiation	-0.18	0.22	-10000	0	-0.41	489	489
GSK3B	-0.14	0.2	0.53	1	-0.36	420	421
RAF1	-0.097	0.16	0.25	4	-0.3	244	248
SHC1	0.02	0.009	-10000	0	-10000	0	0
STAT3	-0.18	0.22	-10000	0	-0.42	486	486
STAT1	-0.44	0.52	-10000	0	-1	495	495
HRAS/SPRED1	-0.094	0.16	-10000	0	-0.34	76	76
cell proliferation	-0.18	0.22	-10000	0	-0.42	489	489
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
TEC	0.022	0.031	-10000	0	-0.57	3	3
RPS6KB1	-0.17	0.22	-10000	0	-0.4	493	493
HRAS/SPRED2	-0.094	0.16	-10000	0	-0.3	306	306
LYN/TEC/p62DOK	-0.15	0.22	-10000	0	-0.4	411	411
MAPK3	-0.066	0.12	0.3	7	-0.27	35	42
STAP1	-0.18	0.22	-10000	0	-0.42	490	490
GRAP2	0.017	0.063	0.26	3	-0.57	12	15
JAK2	-0.37	0.44	-10000	0	-0.84	495	495
STAT1 (dimer)	-0.43	0.51	-10000	0	-0.97	495	495
mol:Gleevec	0.007	0.009	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.14	0.22	-10000	0	-0.4	418	418
actin filament polymerization	-0.18	0.22	0.33	1	-0.41	489	490
LYN	0.021	0.008	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.26	0.32	-10000	0	-0.59	497	497
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
CBL/CRKL/GRB2	-0.14	0.2	-10000	0	-0.37	434	434
PI3K	-0.15	0.22	-10000	0	-0.4	463	463
PTEN	0.023	0.019	-10000	0	-0.57	1	1
SCF/KIT/EPO/EPOR	-0.51	0.63	-10000	0	-1.2	492	492
MAPK8	-0.19	0.22	-10000	0	-0.42	489	489
STAT3 (dimer)	-0.18	0.22	0.27	1	-0.41	486	487
positive regulation of transcription	-0.052	0.1	0.24	13	-0.23	24	37
mol:GDP	-0.13	0.19	-10000	0	-0.37	337	337
PIK3C2B	-0.17	0.21	-10000	0	-0.42	380	380
CBL/CRKL	-0.16	0.2	-10000	0	-0.38	471	471
FER	-0.18	0.22	-10000	0	-0.42	490	490
SH2B3	-0.18	0.22	-10000	0	-0.42	491	491
PDPK1	-0.12	0.19	0.34	9	-0.35	329	338
SNAI2	-0.18	0.21	0.28	4	-0.42	437	441
positive regulation of cell proliferation	-0.32	0.38	-10000	0	-0.73	495	495
KITLG	-0.004	0.058	0.25	10	-0.59	5	15
cell motility	-0.32	0.38	-10000	0	-0.73	495	495
PTPN6	0.032	0.017	0.27	2	-10000	0	2
EPOR	-0.12	0.19	-10000	0	-1	15	15
STAT5A (dimer)	-0.26	0.32	-10000	0	-0.6	497	497
SOCS1	0.025	0.033	0.26	14	-0.57	1	15
cell migration	0.18	0.22	0.42	493	-10000	0	493
SOS1	0.024	0.003	-10000	0	-10000	0	0
EPO	0.041	0.091	0.24	169	-10000	0	169
VAV1	0.023	0.033	0.26	2	-0.57	3	5
GRB10	-0.18	0.22	-10000	0	-0.42	488	488
PTPN11	0.031	0.009	-10000	0	-10000	0	0
SCF/KIT	-0.19	0.23	-10000	0	-0.44	495	495
GO:0007205	0.009	0.012	-10000	0	-10000	0	0
MAP2K1	-0.075	0.13	0.3	7	-0.28	45	52
CBL	0.022	0.007	-10000	0	-10000	0	0
KIT	-0.57	0.66	-10000	0	-1.3	493	493
MAP2K2	-0.075	0.13	0.28	12	-0.28	49	61
SHC/Grb2/SOS1	-0.14	0.21	-10000	0	-0.4	359	359
STAT5A	-0.27	0.33	-10000	0	-0.62	497	497
GRB2	0.023	0.009	0.26	1	-10000	0	1
response to radiation	-0.17	0.21	0.28	4	-0.41	436	440
SHC/GRAP2	0.024	0.046	-10000	0	-0.29	17	17
PTPRO	-0.18	0.22	-10000	0	-0.42	489	489
SH2B2	-0.18	0.22	-10000	0	-0.42	489	489
DOK1	0.025	0.014	0.26	4	-10000	0	4
MATK	-0.19	0.22	-10000	0	-0.42	495	495
CREBBP	-0.027	0.072	-10000	0	-0.18	19	19
BCL2	-0.16	0.32	-10000	0	-1.3	60	60

×

Signaling mediated by p38-alpha and p38-beta

Figure S4. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S4. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.32	0.5	0.42	4	-1	357	361
MKNK1	0.024	0.004	-10000	0	-10000	0	0
MAPK14	-0.088	0.18	-10000	0	-0.34	351	351
ATF2/c-Jun	-0.081	0.16	-10000	0	-0.41	99	99
MAPK11	-0.082	0.18	-10000	0	-0.35	322	322
MITF	-0.12	0.22	0.28	1	-0.41	353	354
MAPKAPK5	-0.11	0.21	-10000	0	-0.4	359	359
KRT8	-0.11	0.21	-10000	0	-0.4	335	335
MAPKAPK3	0.024	0.005	-10000	0	-10000	0	0
MAPKAPK2	0.02	0.009	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.14	0.29	-10000	0	-0.52	356	356
CEBPB	-0.1	0.2	0.28	1	-0.4	332	333
SLC9A1	-0.11	0.21	-10000	0	-0.41	352	352
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.11	0.2	-10000	0	-0.39	348	348
p38alpha-beta/MNK1	-0.1	0.25	-10000	0	-0.45	325	325
JUN	-0.081	0.16	-10000	0	-0.41	99	99
PPARGC1A	-0.2	0.33	0.26	1	-0.56	420	421
USF1	-0.1	0.19	0.31	3	-0.38	335	338
RAB5/GDP/GDI1	-0.081	0.16	-10000	0	-0.3	351	351
NOS2	-0.11	0.22	-10000	0	-0.55	93	93
DDIT3	-0.11	0.2	-10000	0	-0.4	353	353
RAB5A	0.024	0.003	-10000	0	-10000	0	0
HSPB1	-0.094	0.17	0.28	4	-0.32	356	360
p38alpha-beta/HBP1	-0.11	0.25	-10000	0	-0.45	323	323
CREB1	-0.12	0.22	-10000	0	-0.43	356	356
RAB5/GDP	0.018	0.002	-10000	0	-10000	0	0
EIF4E	-0.11	0.21	-10000	0	-0.4	320	320
RPS6KA4	-0.11	0.21	-10000	0	-0.4	351	351
PLA2G4A	-0.13	0.22	-10000	0	-0.42	353	353
GDI1	-0.11	0.21	-10000	0	-0.4	358	358
TP53	-0.15	0.27	0.28	1	-0.52	337	338
RPS6KA5	-0.12	0.22	-10000	0	-0.41	360	360
ESR1	-0.15	0.24	0.28	1	-0.42	409	410
HBP1	0.024	0.004	-10000	0	-10000	0	0
MEF2C	-0.11	0.21	-10000	0	-0.4	354	354
MEF2A	-0.11	0.21	0.28	1	-0.4	353	354
EIF4EBP1	-0.12	0.22	0.28	1	-0.43	341	342
KRT19	-0.11	0.21	0.31	1	-0.41	327	328
ELK4	-0.1	0.19	0.3	3	-0.38	336	339
ATF6	-0.1	0.19	0.31	3	-0.38	339	342
ATF1	-0.12	0.22	-10000	0	-0.43	360	360
p38alpha-beta/MAPKAPK2	-0.095	0.22	-10000	0	-0.41	308	308
p38alpha-beta/MAPKAPK3	-0.1	0.25	-10000	0	-0.45	325	325

×

Reelin signaling pathway

Figure S5. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S5. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.037	0.027	-10000	0	-10000	0	0
VLDLR	0.007	0.096	-10000	0	-0.57	29	29
CRKL	0.023	0.006	-10000	0	-10000	0	0
LRPAP1	0.023	0.005	-10000	0	-10000	0	0
FYN	0.021	0.026	-10000	0	-0.57	2	2
ITGA3	0.022	0.021	0.26	1	-0.57	1	2
RELN/VLDLR/Fyn	-0.19	0.21	-10000	0	-0.37	604	604
MAPK8IP1/MKK7/MAP3K11/JNK1	0.054	0.044	-10000	0	-0.32	7	7
AKT1	-0.15	0.14	-10000	0	-0.27	550	550
MAP2K7	0.024	0.004	-10000	0	-10000	0	0
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0
DAB1	0.035	0.054	0.26	61	-10000	0	61
RELN/LRP8/DAB1	-0.16	0.19	0.32	4	-0.32	608	612
LRPAP1/LRP8	0.048	0.047	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.14	0.18	0.31	4	-0.3	592	596
DAB1/alpha3/beta1 Integrin	-0.14	0.17	-10000	0	-0.3	528	528
long-term memory	-0.18	0.22	0.32	6	-0.35	584	590
DAB1/LIS1	-0.14	0.19	0.3	4	-0.3	603	607
DAB1/CRLK/C3G	-0.14	0.18	-10000	0	-0.3	595	595
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
DAB1/NCK2	-0.14	0.19	0.3	4	-0.3	604	608
ARHGEF2	0.02	0.009	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.033	0.18	0.26	13	-0.57	107	120
CDK5R1	0.028	0.034	0.26	23	-10000	0	23
RELN	-0.32	0.29	0.26	2	-0.57	619	621
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
RELN/LRP8/Fyn	-0.18	0.2	-10000	0	-0.35	596	596
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.16	0.22	0.33	4	-0.35	559	563
MAPK8	0.02	0.051	-10000	0	-0.57	8	8
RELN/VLDLR/DAB1	-0.17	0.19	0.32	2	-0.34	608	610
ITGB1	0.024	0.004	-10000	0	-10000	0	0
MAP1B	-0.18	0.18	0.22	2	-0.32	609	611
RELN/LRP8	-0.18	0.2	-10000	0	-0.35	612	612
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.16	0.2	0.36	3	-0.32	614	617
PI3K	0.028	0.049	-10000	0	-0.38	14	14
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.031	0.021	-10000	0	-0.25	3	3
RAP1A	-0.16	0.15	0.31	5	-0.3	468	473
PAFAH1B1	0.022	0.007	-10000	0	-10000	0	0
MAPK8IP1	0.024	0.029	0.26	4	-0.57	2	6
CRLK/C3G	0.033	0.01	-10000	0	-10000	0	0
GRIN2B	-0.018	0.14	0.26	1	-0.57	70	71
NCK2	0.024	0.003	-10000	0	-10000	0	0
neuron differentiation	-0.086	0.12	-10000	0	-0.35	78	78
neuron adhesion	-0.14	0.15	0.34	6	-0.47	24	30
LRP8	0.046	0.068	0.26	103	-10000	0	103
GSK3B	-0.14	0.14	-10000	0	-0.3	188	188
RELN/VLDLR/DAB1/Fyn	-0.16	0.19	0.31	2	-0.32	594	596
MAP3K11	0.023	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.15	0.16	-10000	0	-0.28	591	591
CDK5	0.025	0.015	0.26	4	-10000	0	4
MAPT	-0.021	0.2	0.88	21	-0.51	106	127
neuron migration	-0.18	0.18	0.27	2	-0.34	505	507
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.087	0.12	-10000	0	-0.35	78	78
RELN/VLDLR	-0.17	0.2	-10000	0	-0.33	612	612

×

EGFR-dependent Endothelin signaling events

Figure S6. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S6. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.026	0.022	0.26	9	-10000	0	9
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
EGF/EGFR	-0.16	0.22	-10000	0	-0.36	518	518
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.12	0.2	-10000	0	-0.35	395	395
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.023	0.027	0.26	1	-0.57	2	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	-0.082	0.23	0.26	2	-0.57	194	196
EGF/EGFR dimer/SHC	-0.15	0.22	-10000	0	-0.4	422	422
mol:GDP	-0.12	0.19	-10000	0	-0.35	395	395
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	-0.017	0.15	0.26	1	-0.57	74	75
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.18	-10000	0	-0.32	394	394
SHC1	0.02	0.009	-10000	0	-10000	0	0
HRAS/GDP	-0.11	0.18	-10000	0	-0.33	394	394
FRAP1	-0.14	0.16	0.16	3	-0.33	395	398
EGF/EGFR dimer	-0.21	0.25	-10000	0	-0.45	537	537
SOS1	0.024	0.003	-10000	0	-10000	0	0
GRB2	0.023	0.009	0.26	1	-10000	0	1
ETA receptor/Endothelin-1	0.002	0.12	-10000	0	-0.41	78	78

×

Aurora B signaling

Figure S7. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S7. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.1	0.099	0.23	313	-0.26	2	315
STMN1	0.078	0.078	0.26	68	-10000	0	68
Aurora B/RasGAP/Survivin	0.19	0.14	0.33	504	-10000	0	504
Chromosomal passenger complex/Cul3 protein complex	0.006	0.14	0.19	189	-0.24	133	322
BIRC5	0.18	0.11	0.26	711	-10000	0	711
DES	-0.16	0.32	-10000	0	-0.59	250	250
Aurora C/Aurora B/INCENP	0.11	0.078	0.32	9	-0.3	1	10
Aurora B/TACC1	0.072	0.098	-10000	0	-0.33	25	25
Aurora B/PP2A	0.11	0.082	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.032	0.026	0.14	8	-10000	0	8
mitotic metaphase/anaphase transition	-0.006	0.005	-10000	0	-10000	0	0
NDC80	0.14	0.12	0.26	484	-10000	0	484
Cul3 protein complex	-0.11	0.2	-10000	0	-0.36	415	415
KIF2C	0.15	0.1	0.23	597	-10000	0	597
PEBP1	0.027	0.004	-10000	0	-10000	0	0
KIF20A	0.19	0.1	0.25	790	-10000	0	790
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.11	0.082	-10000	0	-10000	0	0
SEPT1	0.03	0.042	0.26	35	-10000	0	35
SMC2	0.024	0.003	-10000	0	-10000	0	0
SMC4	0.026	0.021	0.26	9	-10000	0	9
NSUN2/NPM1/Nucleolin	0.074	0.19	0.32	26	-0.45	90	116
PSMA3	0.024	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.004	0.006	-10000	0	-10000	0	0
H3F3B	0.07	0.06	0.23	33	-10000	0	33
AURKB	0.14	0.12	0.25	560	-10000	0	560
AURKC	0.026	0.032	0.26	14	-0.57	1	15
CDCA8	0.11	0.11	0.26	355	-10000	0	355
cytokinesis	0.14	0.14	0.32	310	-0.33	6	316
Aurora B/Septin1	0.18	0.17	0.36	382	-0.33	3	385
AURKA	0.11	0.11	0.25	428	-10000	0	428
INCENP	0.03	0.008	-10000	0	-10000	0	0
KLHL13	-0.21	0.29	-10000	0	-0.57	424	424
BUB1	0.17	0.11	0.25	709	-10000	0	709
hSgo1/Aurora B/Survivin	0.27	0.18	0.41	630	-10000	0	630
EVI5	0.028	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.18	0.14	0.36	331	-10000	0	331
SGOL1	0.16	0.11	0.26	656	-10000	0	656
CENPA	0.17	0.14	0.3	497	-0.23	2	499
NCAPG	0.13	0.12	0.26	505	-10000	0	505
Aurora B/HC8 Proteasome	0.11	0.082	-10000	0	-10000	0	0
NCAPD2	0.024	0.009	0.26	1	-10000	0	1
Aurora B/PP1-gamma	0.11	0.081	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
NCAPH	0.11	0.11	0.26	408	-10000	0	408
NPM1	0.067	0.12	0.25	5	-0.36	35	40
RASA1	0.024	0.004	-10000	0	-10000	0	0
KLHL9	0.023	0.006	-10000	0	-10000	0	0
mitotic prometaphase	0.002	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.11	0.081	-10000	0	-10000	0	0
PPP1CC	0.024	0.002	-10000	0	-10000	0	0
Centraspindlin	0.2	0.15	0.37	391	-10000	0	391
RhoA/GDP	0.018	0.003	-10000	0	-10000	0	0
NSUN2	0.073	0.12	0.27	15	-0.77	2	17
MYLK	0.02	0.14	0.23	8	-0.31	128	136
KIF23	0.098	0.11	0.26	319	-10000	0	319
VIM	0.078	0.084	0.37	32	-0.41	2	34
RACGAP1	0.04	0.046	0.27	41	-10000	0	41
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.062	0.14	-10000	0	-0.47	34	34
Chromosomal passenger complex	0.17	0.12	0.28	547	-10000	0	547
Chromosomal passenger complex/EVI5	0.24	0.17	0.4	490	-10000	0	490
TACC1	0.006	0.089	-10000	0	-0.57	25	25
PPP2R5D	0.024	0.004	-10000	0	-10000	0	0
CUL3	0.024	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

Figure S8. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S8. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.24	0.27	0.52	1	-0.72	125	126
PCK1	-0.92	0.63	-10000	0	-1.4	655	655
HNF4A	-0.23	0.28	0.66	2	-0.8	73	75
KCNJ11	-0.28	0.29	-10000	0	-0.76	163	163
AKT1	-0.16	0.16	0.37	1	-0.4	109	110
response to starvation	0.005	0.011	-10000	0	-10000	0	0
DLK1	-0.44	0.47	-10000	0	-1.1	348	348
NKX2-1	-0.044	0.16	0.39	21	-0.38	35	56
ACADM	-0.25	0.27	0.52	1	-0.76	106	107
TAT	-1.1	0.63	-10000	0	-1.4	765	765
CEBPB	0.024	0.01	-10000	0	-10000	0	0
CEBPA	0.02	0.058	-10000	0	-0.57	10	10
TTR	-0.4	0.29	0.57	1	-0.79	253	254
PKLR	-0.22	0.27	0.62	3	-0.76	85	88
APOA1	-0.28	0.31	0.79	1	-0.87	92	93
CPT1C	-0.24	0.27	0.55	2	-0.74	111	113
ALAS1	-0.15	0.16	-10000	0	-0.69	8	8
TFRC	-0.42	0.26	-10000	0	-0.73	282	282
FOXF1	0.02	0.041	0.26	6	-0.57	4	10
NF1	0.026	0.007	-10000	0	-10000	0	0
HNF1A (dimer)	0.034	0.032	0.27	8	-10000	0	8
CPT1A	-0.23	0.27	0.53	2	-0.73	116	118
HMGCS1	-0.24	0.27	0.62	2	-0.74	116	118
NR3C1	-0.12	0.12	-10000	0	-0.26	269	269
CPT1B	-0.24	0.27	0.52	1	-0.76	106	107
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.031	0.023	-10000	0	-10000	0	0
GCK	-0.27	0.32	0.52	1	-0.89	134	135
CREB1	-0.076	0.093	-10000	0	-0.26	46	46
IGFBP1	-0.41	0.54	-10000	0	-1.4	238	238
PDX1	-0.12	0.15	-10000	0	-0.57	4	4
UCP2	-0.24	0.27	0.52	2	-0.74	106	108
ALDOB	-0.28	0.28	0.68	1	-0.77	137	138
AFP	-0.56	0.5	-10000	0	-1.1	472	472
BDH1	-0.24	0.26	-10000	0	-0.77	92	92
HADH	-0.27	0.28	-10000	0	-0.8	107	107
F2	-0.28	0.3	0.79	1	-0.88	79	80
HNF1A	0.034	0.032	0.27	8	-10000	0	8
G6PC	-0.18	0.12	-10000	0	-0.55	10	10
SLC2A2	-0.16	0.17	0.62	1	-0.78	2	3
INS	0.018	0.077	0.24	5	-10000	0	5
FOXA1	-0.22	0.23	0.34	4	-0.43	429	433
FOXA3	-0.36	0.21	0.3	6	-0.46	795	801
FOXA2	-0.32	0.32	0.77	1	-0.81	191	192
ABCC8	-0.32	0.38	-10000	0	-1	178	178
ALB	-0.76	0.54	0.35	1	-1.1	715	716

×

PLK1 signaling events

Figure S9. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S9. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.063	0.048	0.1	8	-0.1	577	585
BUB1B	0.082	0.066	0.15	419	-10000	0	419
PLK1	0.049	0.038	0.11	151	-10000	0	151
PLK1S1	0.025	0.034	0.13	10	-0.17	19	29
KIF2A	0.041	0.039	0.25	8	-10000	0	8
regulation of mitotic centrosome separation	0.048	0.038	0.11	151	-10000	0	151
GOLGA2	0.024	0.003	-10000	0	-10000	0	0
Hec1/SPC24	0.23	0.14	0.32	692	-10000	0	692
WEE1	0.043	0.06	0.23	2	-0.27	25	27
cytokinesis	0.12	0.086	0.21	269	-0.37	2	271
PP2A-alpha B56	0.11	0.12	-10000	0	-0.46	22	22
AURKA	0.063	0.052	0.12	444	-0.14	4	448
PICH/PLK1	0.096	0.087	0.21	312	-10000	0	312
CENPE	0.061	0.054	0.16	87	-10000	0	87
RhoA/GTP	0.018	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.041	0.038	0.25	8	-10000	0	8
PPP2CA	0.024	0.004	-10000	0	-10000	0	0
FZR1	0.024	0.004	-10000	0	-10000	0	0
TPX2	0.078	0.054	0.12	569	-0.14	2	571
PAK1	0.022	0.019	0.25	6	-10000	0	6
SPC24	0.17	0.11	0.26	664	-10000	0	664
FBXW11	0.024	0.004	-10000	0	-10000	0	0
CLSPN	0.071	0.069	0.14	435	-0.19	22	457
GORASP1	0.024	0.004	-10000	0	-10000	0	0
metaphase	0.001	0.004	0.015	55	-10000	0	55
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.022	0.019	0.054	137	-10000	0	137
G2 phase of mitotic cell cycle	0.001	0.003	0.015	12	-10000	0	12
STAG2	0.024	0.018	-10000	0	-0.57	1	1
GRASP65/GM130/RAB1/GTP	0.011	0.08	-10000	0	-0.5	25	25
spindle elongation	0.048	0.038	0.11	151	-10000	0	151
ODF2	0.026	0.004	-10000	0	-10000	0	0
BUB1	0.1	0.13	-10000	0	-0.48	33	33
TPT1	0.013	0.056	0.12	2	-0.17	77	79
CDC25C	0.11	0.067	0.16	482	-0.2	14	496
CDC25B	0.029	0.031	0.26	18	-10000	0	18
SGOL1	0.063	0.048	0.1	577	-0.1	8	585
RHOA	0.024	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.068	0.064	0.31	11	-10000	0	11
CDC14B	-0.01	0.075	-10000	0	-0.42	34	34
CDC20	0.14	0.12	0.26	565	-10000	0	565
PLK1/PBIP1	0.036	0.046	0.14	139	-10000	0	139
mitosis	-0.004	0.005	0.027	4	-10000	0	4
FBXO5	0.03	0.035	0.16	15	-0.12	1	16
CDC2	0.003	0.004	0.011	192	-10000	0	192
NDC80	0.16	0.12	0.26	619	-10000	0	619
metaphase plate congression	0.028	0.054	0.14	2	-0.19	49	51
ERCC6L	0.087	0.083	0.24	169	-10000	0	169
NLP/gamma Tubulin	0.023	0.024	0.078	24	-0.085	10	34
microtubule cytoskeleton organization	0.013	0.056	0.12	2	-0.17	78	80
G2/M transition DNA damage checkpoint	-0.001	0.002	0.012	13	-10000	0	13
PPP1R12A	0.025	0.004	-10000	0	-10000	0	0
interphase	-0.001	0.002	0.012	13	-10000	0	13
PLK1/PRC1-2	0.2	0.12	0.27	759	-10000	0	759
GRASP65/GM130/RAB1/GTP/PLK1	0.069	0.03	-10000	0	-10000	0	0
RAB1A	0.024	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.041	0.035	0.098	157	-10000	0	157
mitotic prometaphase	0.002	0.005	0.022	51	-10000	0	51
proteasomal ubiquitin-dependent protein catabolic process	0.051	0.051	-10000	0	-0.31	3	3
microtubule-based process	0.17	0.089	0.22	784	-10000	0	784
Golgi organization	0.048	0.038	0.11	151	-10000	0	151
Cohesin/SA2	0.053	0.031	0.16	3	-0.3	1	4
PPP1CB/MYPT1	0.037	0.007	-10000	0	-10000	0	0
KIF20A	0.19	0.1	0.26	790	-10000	0	790
APC/C/CDC20	0.14	0.099	0.23	560	-10000	0	560
PPP2R1A	0.024	0.004	-10000	0	-10000	0	0
chromosome segregation	0.03	0.046	0.14	139	-10000	0	139
PRC1	0.079	0.099	0.26	257	-10000	0	257
ECT2	0.049	0.057	0.23	59	-10000	0	59
C13orf34	0.04	0.033	0.094	143	-10000	0	143
NUDC	0.028	0.054	0.14	2	-0.19	49	51
regulation of attachment of spindle microtubules to kinetochore	0.082	0.066	0.15	422	-10000	0	422
spindle assembly	0.035	0.029	0.092	81	-10000	0	81
spindle stabilization	0.025	0.034	0.13	10	-0.17	19	29
APC/C/HCDH1	0.009	0.067	-10000	0	-0.35	36	36
MKLP2/PLK1	0.17	0.089	0.22	784	-10000	0	784
CCNB1	0.069	0.091	0.26	205	-10000	0	205
PPP1CB	0.025	0.003	-10000	0	-10000	0	0
BTRC	0.024	0.003	-10000	0	-10000	0	0
ROCK2	0.026	0.086	0.23	1	-0.38	39	40
TUBG1	0.023	0.038	0.13	3	-0.16	33	36
G2/M transition of mitotic cell cycle	0.041	0.043	0.19	12	-10000	0	12
MLF1IP	0.023	0.045	0.14	147	-10000	0	147
INCENP	0.024	0.005	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

Figure S10. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S10. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.16	0.39	-10000	0	-0.86	241	241
NCK1/PAK1/Dok-R	-0.096	0.17	-10000	0	-0.41	241	241
NCK1/Dok-R	-0.19	0.46	-10000	0	-1	241	241
PIK3CA	0.024	0.005	-10000	0	-10000	0	0
mol:beta2-estradiol	0.044	0.099	0.24	212	-10000	0	212
RELA	0.023	0.005	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
Rac/GDP	0.018	0.003	-10000	0	-10000	0	0
F2	0.048	0.11	0.27	210	-10000	0	210
TNIP2	0.023	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	-0.17	0.44	-10000	0	-0.97	240	240
FN1	0.11	0.11	0.26	421	-10000	0	421
PLD2	-0.22	0.47	-10000	0	-1.1	240	240
PTPN11	0.024	0.002	-10000	0	-10000	0	0
GRB14	0.011	0.18	0.26	142	-0.57	80	222
ELK1	-0.19	0.42	-10000	0	-0.96	241	241
GRB7	0.019	0.032	-10000	0	-0.57	3	3
PAK1	0.023	0.019	0.26	6	-10000	0	6
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.49	-10000	0	-1	241	241
CDKN1A	-0.11	0.26	-10000	0	-0.62	175	175
ITGA5	0.024	0.007	0.26	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.19	0.46	-10000	0	-1	240	240
CRK	0.022	0.007	-10000	0	-10000	0	0
mol:NO	-0.11	0.29	0.38	2	-0.64	241	243
PLG	-0.22	0.47	-10000	0	-1.1	241	241
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.16	0.36	-10000	0	-0.82	241	241
GRB2	0.023	0.009	0.26	1	-10000	0	1
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
ANGPT2	-0.15	0.28	-10000	0	-0.72	151	151
BMX	-0.32	0.51	-10000	0	-1.2	242	242
ANGPT1	-0.23	0.5	-10000	0	-1.2	212	212
tube development	-0.13	0.29	-10000	0	-0.66	219	219
ANGPT4	-0.15	0.26	-10000	0	-0.57	305	305
response to hypoxia	-0.014	0.028	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.22	0.51	-10000	0	-1.1	240	240
alpha5/beta1 Integrin	0.035	0.008	-10000	0	-10000	0	0
FGF2	-0.2	0.29	-10000	0	-0.57	413	413
STAT5A (dimer)	-0.15	0.34	-10000	0	-0.78	203	203
mol:L-citrulline	-0.11	0.29	0.38	2	-0.64	241	243
AGTR1	-0.097	0.26	0.26	59	-0.57	244	303
MAPK14	-0.21	0.47	-10000	0	-1.1	243	243
Tie2/SHP2	-0.1	0.32	-10000	0	-1.1	90	90
TEK	-0.11	0.35	-10000	0	-1.2	90	90
RPS6KB1	-0.14	0.38	-10000	0	-0.82	241	241
Angiotensin II/AT1	-0.071	0.19	0.18	59	-0.41	247	306
Tie2/Ang1/GRB2	-0.21	0.49	-10000	0	-1.1	241	241
MAPK3	-0.19	0.43	-10000	0	-0.98	240	240
MAPK1	-0.2	0.43	-10000	0	-0.99	240	240
Tie2/Ang1/GRB7	-0.22	0.49	-10000	0	-1.1	241	241
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MAPK8	-0.22	0.48	-10000	0	-1.1	241	241
PI3K	-0.19	0.44	-10000	0	-0.99	241	241
FES	-0.21	0.47	-10000	0	-1.1	243	243
Crk/Dok-R	-0.19	0.46	-10000	0	-1	241	241
Tie2/Ang1/ABIN2	-0.21	0.5	-10000	0	-1.1	241	241
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.14	0.34	-10000	0	-0.77	241	241
STAT5A	0.02	0.044	-10000	0	-0.57	6	6
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.13	0.38	0.47	1	-0.8	240	241
Tie2/Ang2	-0.18	0.4	-10000	0	-0.93	207	207
Tie2/Ang1	-0.23	0.52	-10000	0	-1.2	241	241
FOXO1	-0.14	0.35	0.47	1	-0.78	241	242
ELF1	0.011	0.037	-10000	0	-10000	0	0
ELF2	-0.21	0.47	-10000	0	-1.1	240	240
mol:Choline	-0.2	0.45	-10000	0	-1	240	240
cell migration	-0.039	0.1	-10000	0	-0.23	241	241
FYN	-0.15	0.33	-10000	0	-0.77	208	208
DOK2	0.02	0.031	0.26	4	-0.57	2	6
negative regulation of cell cycle	-0.1	0.24	-10000	0	-0.56	175	175
ETS1	-0.023	0.11	-10000	0	-0.27	173	173
PXN	-0.1	0.32	0.42	2	-0.67	240	242
ITGB1	0.024	0.004	-10000	0	-10000	0	0
NOS3	-0.13	0.33	-10000	0	-0.73	241	241
RAC1	0.024	0.003	-10000	0	-10000	0	0
TNF	-0.026	0.13	0.26	21	-0.27	201	222
MAPKKK cascade	-0.2	0.45	-10000	0	-1	240	240
RASA1	0.024	0.004	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.21	0.48	-10000	0	-1.1	241	241
NCK1	0.024	0.003	-10000	0	-10000	0	0
vasculogenesis	-0.099	0.26	0.37	2	-0.57	241	243
mol:Phosphatidic acid	-0.2	0.45	-10000	0	-1	240	240
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	-0.11	0.29	0.38	2	-0.64	241	243
Rac1/GTP	-0.14	0.35	-10000	0	-0.77	241	241
MMP2	-0.22	0.48	-10000	0	-1.1	241	241

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

Figure S11. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S11. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.099	0.13	0.3	282	-0.22	2	284
NFATC2	-0.025	0.23	0.47	9	-0.58	106	115
NFATC3	-0.04	0.12	-10000	0	-0.28	172	172
CD40LG	-0.29	0.5	0.65	6	-0.97	321	327
ITCH	-0.002	0.082	-10000	0	-0.26	98	98
CBLB	-0.002	0.083	-10000	0	-0.26	99	99
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.093	0.39	0.59	53	-0.98	94	147
JUNB	0.024	0.011	0.26	2	-10000	0	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.1	-10000	0	-0.3	105	105
T cell anergy	-0.026	0.14	0.33	1	-0.41	104	105
TLE4	-0.026	0.19	0.36	1	-0.55	87	88
Jun/NFAT1-c-4/p21SNFT	-0.17	0.43	0.67	6	-0.84	258	264
AP-1/NFAT1-c-4	-0.31	0.61	0.74	15	-1.1	316	331
IKZF1	-0.017	0.16	0.47	7	-0.46	80	87
T-helper 2 cell differentiation	-0.084	0.28	0.48	1	-0.81	90	91
AP-1/NFAT1	-0.098	0.26	0.44	13	-0.46	288	301
CALM1	0.011	0.063	-10000	0	-10000	0	0
EGR2	-0.25	0.55	0.69	2	-1.4	165	167
EGR3	-0.33	0.62	0.67	2	-1.3	298	300
NFAT1/FOXP3	0.05	0.22	0.46	107	-0.44	89	196
EGR1	-0.16	0.27	-10000	0	-0.56	336	336
JUN	0.015	0.054	-10000	0	-0.57	6	6
EGR4	0.04	0.06	0.26	75	-10000	0	75
mol:Ca2+	-0.01	0.054	-10000	0	-0.18	96	96
GBP3	-0.021	0.17	0.39	2	-0.55	58	60
FOSL1	0.027	0.048	0.26	26	-0.57	3	29
NFAT1-c-4/MAF/IRF4	-0.19	0.45	0.59	7	-0.86	286	293
DGKA	-0.017	0.16	0.56	1	-0.45	81	82
CREM	0.023	0.007	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.26	0.48	0.6	3	-0.93	306	309
CTLA4	0.038	0.21	0.43	124	-0.48	53	177
NFAT1-c-4 (dimer)/EGR1	-0.28	0.51	0.61	4	-1	319	323
NFAT1-c-4 (dimer)/EGR4	-0.18	0.45	0.59	6	-0.84	289	295
FOS	-0.15	0.27	-10000	0	-0.57	310	310
IFNG	-0.054	0.27	0.47	18	-0.7	101	119
T cell activation	-0.15	0.29	0.62	4	-0.66	190	194
MAF	0.021	0.008	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.15	0.33	0.64	300	-0.61	2	302
TNF	-0.25	0.44	0.54	4	-0.89	311	315
FASLG	-0.32	0.63	0.79	2	-1.2	309	311
TBX21	0.021	0.12	0.35	15	-0.57	36	51
BATF3	0.021	0.015	0.26	3	-10000	0	3
PRKCQ	0.006	0.11	0.28	8	-0.57	39	47
PTPN1	-0.017	0.16	0.39	3	-0.48	63	66
NFAT1-c-4/ICER1	-0.19	0.44	0.54	4	-0.84	289	293
GATA3	0.01	0.11	0.26	28	-0.57	35	63
T-helper 1 cell differentiation	-0.052	0.27	0.46	20	-0.68	102	122
IL2RA	-0.094	0.37	0.59	47	-0.82	127	174
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.017	0.16	0.36	1	-0.48	64	65
E2F1	0.096	0.11	0.26	320	-10000	0	320
PPARG	-0.11	0.25	-10000	0	-0.57	252	252
SLC3A2	-0.018	0.16	0.36	1	-0.48	65	66
IRF4	-0.019	0.16	0.26	13	-0.57	83	96
PTGS2	-0.34	0.54	0.63	4	-1	348	352
CSF2	-0.28	0.48	0.64	9	-0.95	315	324
JunB/Fra1/NFAT1-c-4	-0.17	0.43	0.6	4	-0.81	284	288
IL4	-0.089	0.29	0.48	1	-0.86	90	91
IL5	-0.28	0.48	0.58	7	-0.94	320	327
IL2	-0.15	0.3	0.62	4	-0.67	186	190
IL3	-0.05	0.13	-10000	0	-0.82	18	18
RNF128	-0.041	0.2	0.27	5	-0.65	105	110
NFATC1	-0.15	0.34	0.61	2	-0.65	300	302
CDK4	0.12	0.24	0.61	97	-0.57	2	99
PTPRK	-0.02	0.17	0.42	3	-0.52	68	71
IL8	-0.28	0.49	0.58	9	-0.96	313	322
POU2F1	0.021	0.012	0.26	1	-10000	0	1

×

HIF-1-alpha transcription factor network

Figure S12. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S12. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.26	0.36	-10000	0	-0.78	224	224
HDAC7	0.025	0.004	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.19	0.34	0.66	3	-0.78	133	136
SMAD4	0.024	0.005	-10000	0	-10000	0	0
ID2	-0.24	0.37	-10000	0	-0.79	219	219
AP1	-0.1	0.21	-10000	0	-0.42	310	310
ABCG2	-0.26	0.39	-10000	0	-0.81	239	239
HIF1A	-0.048	0.084	-10000	0	-0.29	5	5
TFF3	-0.25	0.41	0.66	5	-0.8	254	259
GATA2	0.009	0.095	0.25	13	-0.57	26	39
AKT1	-0.055	0.094	0.24	1	-0.24	55	56
response to hypoxia	-0.062	0.084	0.21	1	-0.22	92	93
MCL1	-0.24	0.35	-10000	0	-0.79	208	208
NDRG1	-0.22	0.36	-10000	0	-0.8	186	186
SERPINE1	-0.24	0.38	0.65	4	-0.79	220	224
FECH	-0.24	0.37	-10000	0	-0.79	219	219
FURIN	-0.24	0.37	-10000	0	-0.8	210	210
NCOA2	-0.002	0.12	-10000	0	-0.56	48	48
EP300	-0.06	0.13	0.34	2	-0.33	115	117
HMOX1	-0.24	0.37	0.65	1	-0.79	219	220
BHLHE40	-0.24	0.37	-10000	0	-0.79	219	219
BHLHE41	-0.25	0.38	-10000	0	-0.81	220	220
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.019	0.11	-10000	0	-0.3	1	1
ENG	-0.016	0.11	0.38	3	-10000	0	3
JUN	0.018	0.046	-10000	0	-0.57	6	6
RORA	-0.25	0.37	-10000	0	-0.79	221	221
ABCB1	-0.26	0.45	-10000	0	-1.1	220	220
TFRC	-0.24	0.37	-10000	0	-0.79	217	217
CXCR4	-0.24	0.37	0.65	1	-0.79	219	220
TF	-0.4	0.45	-10000	0	-0.87	408	408
CITED2	-0.24	0.37	-10000	0	-0.79	217	217
HIF1A/ARNT	-0.27	0.42	0.75	2	-0.95	172	174
LDHA	-0.037	0.12	-10000	0	-0.76	20	20
ETS1	-0.25	0.37	-10000	0	-0.79	220	220
PGK1	-0.24	0.37	-10000	0	-0.79	220	220
NOS2	-0.24	0.37	-10000	0	-0.79	214	214
ITGB2	-0.24	0.37	0.65	1	-0.79	218	219
ALDOA	-0.24	0.37	-10000	0	-0.79	211	211
Cbp/p300/CITED2	-0.25	0.39	-10000	0	-0.9	170	170
FOS	-0.15	0.27	-10000	0	-0.57	306	306
HK2	-0.24	0.37	-10000	0	-0.79	220	220
SP1	0.001	0.057	-10000	0	-0.2	3	3
GCK	-0.12	0.33	0.57	1	-1.4	59	60
HK1	-0.24	0.37	-10000	0	-0.79	218	218
NPM1	-0.24	0.37	-10000	0	-0.79	221	221
EGLN1	-0.24	0.36	-10000	0	-0.78	208	208
CREB1	0.028	0.004	-10000	0	-10000	0	0
PGM1	-0.25	0.37	-10000	0	-0.79	219	219
SMAD3	0.024	0.004	-10000	0	-10000	0	0
EDN1	-0.18	0.36	-10000	0	-1	132	132
IGFBP1	-0.31	0.42	-10000	0	-0.87	279	279
VEGFA	-0.16	0.29	0.56	1	-0.69	114	115
HIF1A/JAB1	-0.009	0.067	-10000	0	-0.27	1	1
CP	-0.3	0.45	0.64	2	-0.89	301	303
CXCL12	-0.26	0.4	-10000	0	-0.83	238	238
COPS5	0.024	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4	0.035	0.011	-10000	0	-0.17	1	1
BNIP3	-0.24	0.37	0.72	1	-0.82	195	196
EGLN3	-0.24	0.38	0.68	2	-0.79	219	221
CA9	-0.21	0.39	0.66	6	-0.78	211	217
TERT	-0.23	0.37	0.66	4	-0.78	214	218
ENO1	-0.25	0.37	-10000	0	-0.79	221	221
PFKL	-0.24	0.37	-10000	0	-0.8	203	203
NCOA1	0.024	0.019	-10000	0	-0.57	1	1
ADM	-0.26	0.4	-10000	0	-0.84	236	236
ARNT	-0.035	0.07	-10000	0	-10000	0	0
HNF4A	0.019	0.041	0.26	19	-10000	0	19
ADFP	-0.26	0.36	-10000	0	-0.78	224	224
SLC2A1	-0.16	0.29	0.62	3	-0.68	118	121
LEP	-0.48	0.41	-10000	0	-0.86	444	444
HIF1A/ARNT/Cbp/p300	-0.2	0.34	0.66	1	-0.79	145	146
EPO	-0.11	0.26	0.64	4	-0.75	49	53
CREBBP	-0.05	0.12	0.34	2	-0.33	82	84
HIF1A/ARNT/Cbp/p300/HDAC7	-0.19	0.33	0.72	1	-0.79	125	126
PFKFB3	-0.24	0.37	-10000	0	-0.8	213	213
NT5E	-0.25	0.37	-10000	0	-0.8	223	223

×

Glucocorticoid receptor regulatory network

Figure S13. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S13. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.09	0.1	0.42	5	-10000	0	5
SMARCC2	0.024	0.013	-10000	0	-0.19	1	1
SMARCC1	0.024	0.012	-10000	0	-0.15	2	2
TBX21	-0.12	0.21	0.39	6	-0.6	94	100
SUMO2	0.001	0.023	-10000	0	-10000	0	0
STAT1 (dimer)	0.033	0.032	0.26	19	-10000	0	19
FKBP4	0.025	0.017	0.26	5	-10000	0	5
FKBP5	0.015	0.078	0.26	5	-0.57	18	23
GR alpha/HSP90/FKBP51/HSP90	0.11	0.13	0.31	126	-0.35	7	133
PRL	-0.062	0.12	0.52	3	-0.49	1	4
cortisol/GR alpha (dimer)/TIF2	0.18	0.28	0.52	335	-0.48	17	352
RELA	-0.037	0.1	0.28	1	-0.26	34	35
FGG	0.21	0.24	0.48	360	-0.49	3	363
GR beta/TIF2	0.078	0.16	0.31	158	-0.4	42	200
IFNG	-0.3	0.36	0.41	9	-0.67	441	450
apoptosis	-0.26	0.3	0.85	1	-0.66	283	284
CREB1	0.06	0.053	-10000	0	-10000	0	0
histone acetylation	0.025	0.13	0.36	54	-0.37	23	77
BGLAP	-0.08	0.14	0.41	1	-0.5	19	20
GR/PKAc	0.13	0.13	0.36	78	-0.33	3	81
NF kappa B1 p50/RelA	-0.062	0.18	0.42	4	-0.35	159	163
SMARCD1	0.024	0.012	-10000	0	-10000	0	0
MDM2	0.098	0.11	0.23	319	-10000	0	319
GATA3	0.014	0.11	0.26	28	-0.56	35	63
AKT1	0.02	0.009	-10000	0	-10000	0	0
CSF2	-0.024	0.1	0.47	1	-0.5	7	8
GSK3B	0.001	0.023	-10000	0	-10000	0	0
NR1I3	-0.2	0.26	0.79	1	-0.62	148	149
CSN2	0.16	0.19	0.38	335	-0.43	4	339
BRG1/BAF155/BAF170/BAF60A	0.06	0.041	-10000	0	-0.44	6	6
NFATC1	0.023	0.026	-10000	0	-0.57	2	2
POU2F1	0.023	0.015	0.26	1	-10000	0	1
CDKN1A	0.016	0.086	-10000	0	-1.3	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.007	0.007	-10000	0	-10000	0	0
SFN	0.021	0.07	0.26	21	-0.57	12	33
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.12	0.13	0.32	90	-0.32	6	96
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.36	0.39	0.62	2	-0.84	374	376
JUN	-0.25	0.29	0.44	6	-0.55	413	419
IL4	-0.11	0.15	-10000	0	-0.47	42	42
CDK5R1	0.022	0.036	0.25	23	-10000	0	23
PRKACA	0.024	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.24	-10000	0	-0.48	494	494
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.12	0.13	0.33	75	-0.34	5	80
cortisol/GR alpha (monomer)	0.28	0.32	0.6	442	-0.53	4	446
NCOA2	-0.006	0.12	-10000	0	-0.57	48	48
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.18	0.28	-10000	0	-0.59	315	315
AP-1/NFAT1-c-4	-0.42	0.45	0.47	7	-0.8	562	569
AFP	-0.53	0.64	-10000	0	-1.4	352	352
SUV420H1	0.023	0.007	-10000	0	-10000	0	0
IRF1	0.16	0.16	0.43	114	-10000	0	114
TP53	0.031	0.027	-10000	0	-0.52	2	2
PPP5C	0.024	0.003	-10000	0	-10000	0	0
KRT17	-0.64	0.68	0.42	4	-1.3	500	504
KRT14	-0.69	0.66	-10000	0	-1.3	556	556
TBP	0.028	0.013	-10000	0	-10000	0	0
CREBBP	0.14	0.14	0.29	477	-10000	0	477
HDAC1	0.022	0.011	-10000	0	-10000	0	0
HDAC2	0.021	0.011	-10000	0	-10000	0	0
AP-1	-0.43	0.45	0.47	7	-0.8	562	569
MAPK14	0.004	0.022	-10000	0	-10000	0	0
MAPK10	-0.083	0.2	-10000	0	-0.57	158	158
MAPK11	-0.001	0.038	-10000	0	-0.58	3	3
KRT5	-0.72	0.7	0.42	4	-1.4	567	571
interleukin-1 receptor activity	-0.001	0.004	-10000	0	-10000	0	0
NCOA1	0.025	0.019	-10000	0	-0.56	1	1
STAT1	0.033	0.032	0.26	19	-10000	0	19
CGA	-0.053	0.17	0.42	2	-0.47	25	27
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.15	0.18	0.36	399	-10000	0	399
MAPK3	0.001	0.022	-10000	0	-10000	0	0
MAPK1	0.003	0.022	-10000	0	-10000	0	0
ICAM1	-0.18	0.24	0.6	3	-0.56	220	223
NFKB1	-0.038	0.1	0.28	1	-0.25	45	46
MAPK8	-0.19	0.22	0.41	4	-0.43	375	379
MAPK9	0.003	0.022	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.27	0.32	0.86	1	-0.7	283	284
BAX	0.017	0.064	-10000	0	-10000	0	0
POMC	-0.16	0.3	-10000	0	-0.96	73	73
EP300	0.14	0.14	0.29	464	-10000	0	464
cortisol/GR alpha (dimer)/p53	0.21	0.26	0.53	350	-0.5	3	353
proteasomal ubiquitin-dependent protein catabolic process	0.077	0.11	0.27	157	-10000	0	157
SGK1	0.19	0.2	0.45	38	-1.1	6	44
IL13	-0.25	0.28	0.51	5	-0.59	292	297
IL6	-0.43	0.52	0.49	2	-1.1	404	406
PRKACG	0.018	0.004	-10000	0	-10000	0	0
IL5	-0.21	0.23	0.49	4	-0.53	202	206
IL2	-0.33	0.35	0.45	3	-0.69	441	444
CDK5	0.018	0.019	0.25	4	-10000	0	4
PRKACB	0.032	0.06	0.26	47	-0.57	4	51
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
IL8	-0.19	0.29	0.52	4	-0.63	203	207
CDK5R1/CDK5	0.019	0.036	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.018	0.15	0.38	3	-0.38	40	43
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.26	0.5	417	-0.46	3	420
SMARCA4	0.024	0.011	-10000	0	-10000	0	0
chromatin remodeling	0.15	0.16	0.35	267	-0.63	1	268
NF kappa B1 p50/RelA/Cbp	0.061	0.19	0.4	71	-0.4	19	90
JUN (dimer)	-0.25	0.29	0.44	6	-0.55	412	418
YWHAH	0.023	0.006	-10000	0	-10000	0	0
VIPR1	-0.13	0.2	-10000	0	-0.65	85	85
NR3C1	0.17	0.2	0.39	365	-0.43	4	369
NR4A1	-0.03	0.18	-10000	0	-0.55	112	112
TIF2/SUV420H1	0.008	0.094	-10000	0	-0.42	48	48
MAPKKK cascade	-0.26	0.3	0.85	1	-0.66	283	284
cortisol/GR alpha (dimer)/Src-1	0.25	0.27	0.52	428	-0.5	3	431
PBX1	0.023	0.015	0.26	1	-10000	0	1
POU1F1	0.021	0.015	0.26	2	-10000	0	2
SELE	-0.19	0.31	0.55	3	-0.75	163	166
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.15	0.16	0.36	263	-0.64	1	264
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.26	0.5	417	-0.46	3	420
mol:cortisol	0.16	0.19	0.35	442	-0.28	3	445
MMP1	0.031	0.31	0.42	2	-0.92	84	86

×

EPHB forward signaling

Figure S14. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S14. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.002	0.11	-10000	0	-0.36	95	95
cell-cell adhesion	0.13	0.15	0.31	391	-10000	0	391
Ephrin B/EPHB2/RasGAP	0.031	0.11	-10000	0	-0.31	82	82
ITSN1	0.023	0.026	-10000	0	-0.57	2	2
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.033	0.013	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.12	0.19	-10000	0	-0.36	412	412
HRAS/GDP	-0.11	0.18	-10000	0	-0.41	181	181
Ephrin B/EPHB1/GRB7	-0.1	0.2	-10000	0	-0.35	398	398
Endophilin/SYNJ1	-0.027	0.083	0.22	2	-0.29	80	82
KRAS	0.023	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.1	0.21	-10000	0	-0.36	411	411
endothelial cell migration	0.04	0.042	-10000	0	-0.32	11	11
GRB2	0.023	0.009	0.26	1	-10000	0	1
GRB7	0.019	0.032	-10000	0	-0.57	3	3
PAK1	-0.031	0.099	0.35	2	-0.33	83	85
HRAS	0.026	0.022	0.26	9	-10000	0	9
RRAS	-0.027	0.084	0.23	2	-0.3	80	82
DNM1	0.02	0.048	0.26	1	-0.57	7	8
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.14	0.18	0.35	2	-0.34	429	431
lamellipodium assembly	-0.13	0.15	-10000	0	-0.31	391	391
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.089	0.16	-10000	0	-0.32	319	319
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
EPHB2	0.027	0.031	0.26	19	-10000	0	19
EPHB3	0.025	0.02	0.26	8	-10000	0	8
EPHB1	-0.2	0.29	0.26	1	-0.57	412	413
EPHB4	0.024	0.004	-10000	0	-10000	0	0
mol:GDP	-0.11	0.17	-10000	0	-0.42	173	173
Ephrin B/EPHB2	0.021	0.1	-10000	0	-0.31	82	82
Ephrin B/EPHB3	0.02	0.097	-10000	0	-0.31	77	77
JNK cascade	-0.12	0.15	0.36	9	-0.31	408	417
Ephrin B/EPHB1	-0.11	0.21	-10000	0	-0.35	430	430
RAP1/GDP	-0.093	0.16	-10000	0	-0.38	153	153
EFNB2	0.023	0.007	-10000	0	-10000	0	0
EFNB3	-0.023	0.16	-10000	0	-0.57	82	82
EFNB1	0.024	0.001	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.098	0.18	-10000	0	-0.32	411	411
RAP1B	0.024	0.005	-10000	0	-10000	0	0
RAP1A	0.024	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.1	0.19	-10000	0	-0.41	162	162
Rap1/GTP	-0.11	0.17	-10000	0	-0.32	325	325
axon guidance	-0.002	0.11	-10000	0	-0.36	95	95
MAPK3	-0.084	0.14	-10000	0	-0.39	107	107
MAPK1	-0.089	0.14	-10000	0	-0.39	110	110
Rac1/GDP	-0.1	0.16	-10000	0	-0.39	165	165
actin cytoskeleton reorganization	-0.11	0.12	-10000	0	-0.34	135	135
CDC42/GDP	-0.1	0.16	-10000	0	-0.39	167	167
PI3K	0.045	0.044	-10000	0	-0.32	11	11
EFNA5	-0.028	0.17	0.26	1	-0.57	95	96
Ephrin B2/EPHB4	0.03	0.011	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.005	0.089	-10000	0	-0.27	85	85
CDC42	0.023	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.11	0.16	-10000	0	-0.31	332	332
PTK2	0.14	0.26	0.67	204	-10000	0	204
MAP4K4	-0.12	0.15	0.36	9	-0.31	408	417
SRC	0.023	0.005	-10000	0	-10000	0	0
KALRN	0.014	0.078	-10000	0	-0.57	19	19
Intersectin/N-WASP	0.034	0.021	-10000	0	-0.42	2	2
neuron projection morphogenesis	-0.1	0.14	0.29	9	-0.42	81	90
MAP2K1	-0.086	0.15	-10000	0	-0.3	299	299
WASL	0.024	0.004	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.088	0.19	-10000	0	-0.33	409	409
cell migration	-0.1	0.18	0.29	6	-0.35	289	295
NRAS	0.024	0.004	-10000	0	-10000	0	0
SYNJ1	-0.027	0.084	0.23	2	-0.3	80	82
PXN	0.024	0.002	-10000	0	-10000	0	0
TF	-0.18	0.17	0.22	2	-0.32	577	579
HRAS/GTP	-0.099	0.19	-10000	0	-0.32	414	414
Ephrin B1/EPHB1-2	-0.096	0.18	-10000	0	-0.33	410	410
cell adhesion mediated by integrin	0.011	0.086	0.28	79	-0.21	20	99
RAC1	0.024	0.003	-10000	0	-10000	0	0
mol:GTP	-0.1	0.2	-10000	0	-0.33	425	425
RAC1-CDC42/GTP	-0.13	0.15	-10000	0	-0.32	337	337
RASA1	0.024	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.095	0.16	-10000	0	-0.38	157	157
ruffle organization	-0.12	0.16	0.36	5	-0.49	71	76
NCK1	0.024	0.003	-10000	0	-10000	0	0
receptor internalization	-0.03	0.086	0.22	2	-0.3	82	84
Ephrin B/EPHB2/KALRN	0.026	0.12	-10000	0	-0.34	92	92
ROCK1	0.017	0.031	0.19	30	-0.33	1	31
RAS family/GDP	-0.1	0.12	-10000	0	-0.34	131	131
Rac1/GTP	-0.12	0.17	-10000	0	-0.32	391	391
Ephrin B/EPHB1/Src/Paxillin	-0.12	0.18	-10000	0	-0.32	416	416

×

Endothelins

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S15. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.073	0.14	-10000	0	-0.42	104	104
PTK2B	0.02	0.009	-10000	0	-10000	0	0
mol:Ca2+	-0.053	0.2	-10000	0	-0.81	47	47
EDN1	-0.073	0.16	-10000	0	-0.53	98	98
EDN3	-0.22	0.29	0.26	3	-0.57	442	445
EDN2	0.074	0.11	0.26	245	-0.57	5	250
HRAS/GDP	-0.094	0.2	-10000	0	-0.48	154	154
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.062	0.14	-10000	0	-0.4	112	112
ADCY4	-0.13	0.2	0.28	2	-0.42	279	281
ADCY5	-0.21	0.24	-10000	0	-0.44	470	470
ADCY6	-0.12	0.19	0.28	2	-0.4	270	272
ADCY7	-0.12	0.18	0.28	2	-0.4	269	271
ADCY1	-0.12	0.2	0.25	2	-0.4	284	286
ADCY2	-0.14	0.22	0.29	6	-0.44	292	298
ADCY3	-0.12	0.18	0.26	1	-0.4	270	271
ADCY8	-0.1	0.17	0.27	2	-0.4	207	209
ADCY9	-0.11	0.18	0.26	1	-0.4	256	257
arachidonic acid secretion	-0.16	0.28	0.32	1	-0.51	345	346
ETB receptor/Endothelin-1/Gq/GTP	-0.05	0.15	-10000	0	-0.36	157	157
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
HRAS	0.025	0.022	0.26	9	-10000	0	9
ETA receptor/Endothelin-1/G12/GTP	-0.059	0.14	-10000	0	-0.39	104	104
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.2	-10000	0	-0.42	275	275
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
COL3A1	-0.064	0.16	0.37	10	-0.44	98	108
EDNRB	-0.029	0.17	-10000	0	-0.56	100	100
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.078	0.16	-10000	0	-0.5	106	106
CYSLTR1	-0.081	0.16	-10000	0	-0.49	102	102
SLC9A1	-0.045	0.093	-10000	0	-0.28	109	109
mol:GDP	-0.1	0.21	0.33	2	-0.49	168	170
SLC9A3	-0.11	0.28	-10000	0	-0.63	199	199
RAF1	-0.14	0.24	0.33	1	-0.47	282	283
JUN	-0.05	0.18	-10000	0	-0.77	44	44
JAK2	-0.072	0.14	-10000	0	-0.42	104	104
mol:IP3	-0.075	0.17	-10000	0	-0.45	126	126
ETA receptor/Endothelin-1	-0.083	0.16	0.32	7	-0.49	106	113
PLCB1	-0.019	0.15	-10000	0	-0.57	74	74
PLCB2	0.014	0.026	0.26	1	-0.57	1	2
ETA receptor/Endothelin-3	-0.19	0.21	0.24	1	-0.43	449	450
FOS	-0.29	0.44	-10000	0	-0.94	334	334
Gai/GDP	-0.1	0.29	-10000	0	-0.74	166	166
CRK	0.022	0.007	-10000	0	-10000	0	0
mol:Ca ++	-0.11	0.21	0.27	2	-0.54	146	148
BCAR1	0.022	0.008	-10000	0	-10000	0	0
PRKCB1	-0.078	0.16	-10000	0	-0.42	138	138
GNAQ	0.013	0.036	-10000	0	-0.57	3	3
GNAZ	0.018	0.057	-10000	0	-0.57	10	10
GNAL	-0.11	0.24	-10000	0	-0.57	235	235
Gs family/GDP	-0.15	0.24	-10000	0	-0.5	265	265
ETA receptor/Endothelin-1/Gq/GTP	-0.047	0.12	-10000	0	-0.39	77	77
MAPK14	-0.066	0.16	-10000	0	-0.41	142	142
TRPC6	-0.057	0.21	-10000	0	-0.91	44	44
GNAI2	0.024	0.005	-10000	0	-10000	0	0
GNAI3	0.024	0.004	-10000	0	-10000	0	0
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.067	0.17	-10000	0	-0.42	149	149
ETB receptor/Endothelin-2	0.022	0.15	0.24	17	-0.4	102	119
ETB receptor/Endothelin-3	-0.19	0.24	0.24	1	-0.44	502	503
ETB receptor/Endothelin-1	-0.078	0.18	-10000	0	-0.47	168	168
MAPK3	-0.25	0.38	-10000	0	-0.79	340	340
MAPK1	-0.26	0.4	-10000	0	-0.81	341	341
Rac1/GDP	-0.094	0.19	-10000	0	-0.48	152	152
cAMP biosynthetic process	-0.16	0.22	0.4	2	-0.48	248	250
MAPK8	-0.059	0.21	-10000	0	-0.75	64	64
SRC	0.023	0.005	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.068	0.17	-10000	0	-0.36	208	208
p130Cas/CRK/Src/PYK2	-0.097	0.22	0.49	1	-0.57	126	127
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.093	0.19	-10000	0	-0.48	151	151
COL1A2	-0.089	0.2	0.37	9	-0.48	156	165
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.021	0.097	0.25	14	-0.38	11	25
mol:DAG	-0.075	0.17	-10000	0	-0.45	126	126
MAP2K2	-0.19	0.3	0.34	2	-0.6	341	343
MAP2K1	-0.19	0.3	0.32	2	-0.59	344	346
EDNRA	-0.035	0.07	0.28	1	-0.3	25	26
positive regulation of muscle contraction	-0.063	0.12	-10000	0	-0.38	97	97
Gq family/GDP	-0.059	0.19	-10000	0	-0.49	105	105
HRAS/GTP	-0.1	0.2	0.34	1	-0.47	170	171
PRKCH	-0.077	0.16	-10000	0	-0.44	122	122
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCA	-0.073	0.18	0.28	3	-0.46	133	136
PRKCB	-0.074	0.18	0.24	1	-0.46	126	127
PRKCE	-0.08	0.16	-10000	0	-0.44	131	131
PRKCD	-0.076	0.16	-10000	0	-0.44	120	120
PRKCG	-0.078	0.17	0.27	1	-0.44	130	131
regulation of vascular smooth muscle contraction	-0.34	0.51	-10000	0	-1.1	331	331
PRKCQ	-0.084	0.18	-10000	0	-0.48	136	136
PLA2G4A	-0.18	0.31	0.33	1	-0.56	345	346
GNA14	0.014	0.067	0.25	19	-0.57	10	29
GNA15	0.022	0.027	0.25	6	-0.57	1	7
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA11	0.019	0.037	-10000	0	-0.57	4	4
Rac1/GTP	-0.059	0.14	0.29	1	-0.39	104	105
MMP1	0.17	0.13	0.4	74	-10000	0	74

×

p75(NTR)-mediated signaling

Figure S16. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S16. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.034	0.016	-10000	0	-0.42	1	1
Necdin/E2F1	0.061	0.11	-10000	0	-0.39	34	34
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.045	0.17	-10000	0	-0.32	290	290
NGF (dimer)/p75(NTR)/BEX1	-0.1	0.24	0.34	1	-0.4	372	373
NT-4/5 (dimer)/p75(NTR)	-0.22	0.29	-10000	0	-0.49	513	513
IKBKB	0.02	0.009	-10000	0	-10000	0	0
AKT1	-0.082	0.16	0.36	1	-0.32	275	276
IKBKG	0.024	0.002	-10000	0	-10000	0	0
BDNF	-0.012	0.16	0.26	24	-0.57	75	99
MGDIs/NGR/p75(NTR)/LINGO1	-0.037	0.2	0.34	7	-0.34	281	288
FURIN	0.024	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.087	0.2	-10000	0	-0.39	318	318
LINGO1	0.077	0.097	0.26	247	-10000	0	247
Sortilin/TRAF6/NRIF	0.024	0.024	-10000	0	-0.55	1	1
proBDNF (dimer)	-0.012	0.16	0.26	24	-0.56	75	99
NTRK1	0.024	0.051	0.26	25	-0.57	4	29
RTN4R	0.032	0.044	0.26	40	-10000	0	40
neuron apoptosis	-0.078	0.19	0.34	6	-0.51	72	78
IRAK1	0.025	0.014	0.26	4	-10000	0	4
SHC1	-0.079	0.15	-10000	0	-0.36	224	224
ARHGDIA	0.023	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.018	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.054	0.034	-10000	0	-0.32	1	1
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.053	0.18	-10000	0	-0.34	286	286
MAGEH1	0.024	0.018	-10000	0	-0.57	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.063	0.19	-10000	0	-0.36	294	294
Mammalian IAPs/DIABLO	0.057	0.032	-10000	0	-0.33	2	2
proNGF (dimer)	0.017	0.074	0.26	8	-0.56	16	24
MAGED1	0.025	0.01	0.26	2	-10000	0	2
APP	0.024	0.005	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.18	0.28	-10000	0	-0.56	363	363
ZNF274	0.024	0.004	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.064	0.15	-10000	0	-0.32	277	277
NGF	0.017	0.074	0.26	8	-0.57	16	24
cell cycle arrest	-0.072	0.15	0.23	47	-0.29	286	333
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.052	0.12	-10000	0	-0.27	209	209
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.18	0.26	-10000	0	-0.45	465	465
NCSTN	0.02	0.009	-10000	0	-10000	0	0
mol:GTP	-0.067	0.19	-10000	0	-0.36	290	290
PSENEN	0.024	0.011	0.26	2	-10000	0	2
mol:ceramide	-0.076	0.16	-10000	0	-0.33	285	285
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.043	0.11	-10000	0	-0.36	30	30
p75(NTR)/beta APP	-0.089	0.2	-10000	0	-0.41	287	287
BEX1	-0.016	0.23	0.26	172	-0.57	139	311
mol:GDP	-0.1	0.16	-10000	0	-0.36	292	292
NGF (dimer)	0.002	0.14	0.34	1	-0.34	133	134
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.021	0.18	0.34	6	-0.32	267	273
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
RAC1/GTP	-0.059	0.16	-10000	0	-0.31	288	288
MYD88	0.024	0.004	-10000	0	-10000	0	0
CHUK	0.024	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.067	0.19	-10000	0	-0.36	290	290
RHOB	0.024	0.003	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.077	0.073	-10000	0	-10000	0	0
NT3 (dimer)	-0.06	0.21	0.26	12	-0.56	157	169
TP53	-0.089	0.16	0.35	3	-0.33	304	307
PRDM4	-0.076	0.16	-10000	0	-0.34	286	286
BDNF (dimer)	0.023	0.2	0.33	21	-0.35	192	213
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
SORT1	0.023	0.018	-10000	0	-0.57	1	1
activation of caspase activity	-0.048	0.17	-10000	0	-0.32	290	290
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.053	0.18	-10000	0	-0.34	283	283
RHOC	0.024	0.004	-10000	0	-10000	0	0
XIAP	0.024	0.002	-10000	0	-10000	0	0
MAPK10	-0.13	0.2	0.29	5	-0.41	290	295
DIABLO	0.024	0.002	-10000	0	-10000	0	0
SMPD2	-0.076	0.16	-10000	0	-0.33	285	285
APH1B	0.023	0.018	-10000	0	-0.57	1	1
APH1A	0.02	0.009	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.069	0.18	-10000	0	-0.36	290	290
PSEN1	0.024	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.034	0.009	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.15	0.25	-10000	0	-0.45	398	398
MAPK8	-0.094	0.18	0.3	8	-0.36	262	270
MAPK9	-0.093	0.17	0.28	8	-0.36	262	270
APAF1	0.024	0.003	-10000	0	-10000	0	0
NTF3	-0.061	0.21	0.26	12	-0.57	157	169
NTF4	-0.18	0.28	-10000	0	-0.57	363	363
NDN	0.005	0.1	-10000	0	-0.57	34	34
RAC1/GDP	0.018	0.003	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.041	0.16	-10000	0	-0.3	287	287
p75 CTF/Sortilin/TRAF6/NRIF	0.057	0.022	-10000	0	-0.33	1	1
RhoA-B-C/GTP	-0.067	0.19	-10000	0	-0.36	290	290
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.059	0.19	-10000	0	-0.34	311	311
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.07	0.2	-10000	0	-0.36	313	313
PRKACB	0.032	0.06	0.26	47	-0.57	4	51
proBDNF (dimer)/p75 ECD	0.007	0.12	-10000	0	-0.42	75	75
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.023	0.04	0.26	12	-0.57	3	15
BIRC2	0.022	0.007	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.086	0.17	0.28	14	-0.34	281	295
BAD	-0.11	0.18	0.34	8	-0.38	272	280
RIPK2	0.02	0.016	0.26	3	-10000	0	3
NGFR	-0.14	0.26	-10000	0	-0.57	287	287
CYCS	-0.084	0.15	0.36	2	-0.32	276	278
ADAM17	0.024	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.044	0.16	-10000	0	-0.34	209	209
BCL2L11	-0.11	0.18	0.34	8	-0.38	272	280
BDNF (dimer)/p75(NTR)	-0.11	0.23	-10000	0	-0.44	326	326
PI3K	-0.057	0.18	-10000	0	-0.34	278	278
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.053	0.18	-10000	0	-0.34	285	285
NDNL2	0.023	0.005	-10000	0	-10000	0	0
YWHAE	0.022	0.007	-10000	0	-10000	0	0
PRKCI	0.024	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.094	0.2	-10000	0	-0.41	307	307
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.053	0.18	-10000	0	-0.34	286	286
TRAF6	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCZ	0.023	0.019	-10000	0	-0.57	1	1
PLG	0.018	0.021	0.26	8	-10000	0	8
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.1	0.18	-10000	0	-0.37	324	324
SQSTM1	0.024	0.008	0.26	1	-10000	0	1
NGFRAP1	0.023	0.031	-10000	0	-0.57	3	3
CASP3	-0.1	0.17	0.33	7	-0.36	280	287
E2F1	0.093	0.11	0.26	320	-10000	0	320
CASP9	0.023	0.005	-10000	0	-10000	0	0
IKK complex	-0.002	0.11	-10000	0	-0.4	19	19
NGF (dimer)/TRKA	0.026	0.066	-10000	0	-0.4	20	20
MMP7	-0.037	0.19	0.26	33	-0.57	121	154
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.043	0.17	-10000	0	-0.32	279	279
MMP3	0.096	0.14	0.26	380	-0.57	14	394
APAF-1/Caspase 9	-0.085	0.11	-10000	0	-0.44	10	10

×

IL4-mediated signaling events

Figure S17. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S17. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.23	0.61	0.77	17	-1.2	207	224
STAT6 (cleaved dimer)	-0.3	0.58	-10000	0	-1.2	251	251
IGHG1	-0.025	0.26	0.51	62	-0.52	11	73
IGHG3	-0.23	0.57	0.66	21	-1.1	241	262
AKT1	-0.082	0.34	0.55	30	-0.74	90	120
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.044	0.29	0.51	33	-0.69	62	95
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.083	0.36	0.57	32	-0.8	76	108
THY1	-0.23	0.61	0.78	17	-1.2	198	215
MYB	0.011	0.086	0.26	1	-0.57	23	24
HMGA1	0.034	0.048	0.26	48	-10000	0	48
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.11	0.41	0.62	63	-0.71	191	254
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.075	0.35	0.57	32	-0.8	64	96
SP1	0.034	0.025	-10000	0	-10000	0	0
INPP5D	0.024	0.004	-10000	0	-10000	0	0
SOCS5	0.014	0.046	-10000	0	-0.54	1	1
STAT6 (dimer)/ETS1	-0.26	0.6	0.67	14	-1.2	242	256
SOCS1	-0.13	0.4	0.6	28	-0.74	197	225
SOCS3	-0.089	0.35	0.61	12	-0.81	70	82
FCER2	-0.37	0.73	0.79	27	-1.3	344	371
PARP14	0.017	0.031	0.24	3	-10000	0	3
CCL17	-0.22	0.62	0.85	41	-1.2	193	234
GRB2	0.023	0.009	0.26	1	-10000	0	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.039	0.29	0.52	36	-0.69	42	78
T cell proliferation	-0.25	0.61	0.72	12	-1.2	229	241
IL4R/JAK1	-0.24	0.6	0.7	6	-1.2	227	233
EGR2	-0.34	0.74	0.85	14	-1.4	258	272
JAK2	0.012	0.076	0.26	1	-10000	0	1
JAK3	0.022	0.035	0.27	14	-10000	0	14
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
JAK1	0.017	0.041	-10000	0	-10000	0	0
COL1A2	-0.022	0.27	0.56	11	-1.1	18	29
CCL26	-0.23	0.61	0.89	7	-1.2	192	199
IL4R	-0.24	0.66	0.86	33	-1.3	221	254
PTPN6	0.014	0.035	0.21	2	-10000	0	2
IL13RA2	-0.23	0.61	0.79	16	-1.2	194	210
IL13RA1	0.012	0.077	0.26	1	-10000	0	1
IRF4	-0.13	0.49	0.57	12	-1.4	119	131
ARG1	-0.004	0.22	0.57	6	-0.64	6	12
CBL	-0.11	0.38	0.56	47	-0.68	178	225
GTF3A	0.055	0.048	0.26	1	-10000	0	1
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
IL13RA1/JAK2	0.025	0.11	0.3	22	-10000	0	22
IRF4/BCL6	-0.11	0.44	0.51	2	-1.3	118	120
CD40LG	-0.011	0.13	0.31	12	-0.57	51	63
MAPK14	-0.1	0.38	0.58	39	-0.7	166	205
mitosis	-0.075	0.33	0.54	34	-0.69	90	124
STAT6	-0.27	0.76	0.93	52	-1.4	236	288
SPI1	0.027	0.019	0.26	6	-10000	0	6
RPS6KB1	-0.058	0.32	0.53	43	-0.68	78	121
STAT6 (dimer)	-0.26	0.76	0.93	51	-1.4	236	287
STAT6 (dimer)/PARP14	-0.29	0.66	0.73	14	-1.3	254	268
mast cell activation	0	0.023	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.088	0.35	0.56	38	-0.72	111	149
FRAP1	-0.082	0.34	0.55	30	-0.74	90	120
LTA	-0.22	0.62	0.85	39	-1.2	194	233
FES	0.022	0.031	-10000	0	-0.57	3	3
T-helper 1 cell differentiation	0.25	0.72	1.3	236	-0.93	51	287
CCL11	-0.17	0.59	0.76	23	-1.2	191	214
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.069	0.34	0.55	39	-0.73	80	119
IL2RG	0.025	0.071	0.26	46	-0.56	7	53
IL10	-0.2	0.6	0.8	25	-1.2	197	222
IRS1	0.001	0.11	-10000	0	-0.57	42	42
IRS2	0.003	0.1	-10000	0	-0.57	35	35
IL4	-0.008	0.26	0.62	20	-1.1	20	40
IL5	-0.23	0.61	0.77	21	-1.2	222	243
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.15	0.52	0.79	53	-0.91	197	250
COL1A1	0.002	0.36	0.69	32	-1	46	78
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.25	0.61	-10000	0	-1.3	193	193
IL2R gamma/JAK3	0.037	0.068	0.31	26	-0.38	7	33
TFF3	-0.28	0.7	0.84	27	-1.3	260	287
ALOX15	-0.3	0.7	0.8	23	-1.3	266	289
MYBL1	0.038	0.063	0.26	81	-10000	0	81
T-helper 2 cell differentiation	-0.19	0.52	0.7	30	-0.96	230	260
SHC1	0.02	0.009	-10000	0	-10000	0	0
CEBPB	0.025	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.079	0.34	0.55	34	-0.74	83	117
mol:PI-3-4-5-P3	-0.082	0.34	0.55	30	-0.74	90	120
PI3K	-0.09	0.36	0.57	24	-0.8	90	114
DOK2	0.02	0.031	0.26	4	-0.57	2	6
ETS1	0.003	0.054	-10000	0	-0.53	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.029	0.27	0.48	50	-0.63	38	88
ITGB3	-0.25	0.63	0.82	6	-1.3	204	210
PIGR	-0.66	0.8	0.84	14	-1.3	586	600
IGHE	-0.015	0.086	0.18	26	-0.22	29	55
MAPKKK cascade	-0.028	0.27	0.48	51	-0.61	38	89
BCL6	0.022	0.046	-10000	0	-0.56	6	6
OPRM1	-0.23	0.61	0.87	8	-1.2	195	203
RETNLB	-0.24	0.61	0.77	17	-1.2	217	234
SELP	-0.35	0.77	0.79	28	-1.4	300	328
AICDA	-0.23	0.58	0.77	12	-1.2	193	205

×

Ephrin B reverse signaling

Figure S18. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S18. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.023	0.007	-10000	0	-10000	0	0
EPHB2	0.027	0.031	0.26	19	-10000	0	19
EFNB1	0.002	0.036	-10000	0	-0.42	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.077	0.17	-10000	0	-0.3	400	400
Ephrin B2/EPHB1-2	-0.097	0.18	-10000	0	-0.32	411	411
neuron projection morphogenesis	-0.083	0.16	-10000	0	-0.28	400	400
Ephrin B1/EPHB1-2/Tiam1	-0.088	0.18	-10000	0	-0.31	407	407
DNM1	0.02	0.048	0.27	1	-0.57	7	8
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.021	0.12	-10000	0	-0.56	45	45
YES1	-0.023	0.17	-10000	0	-0.77	50	50
Ephrin B1/EPHB1-2/NCK2	-0.089	0.18	-10000	0	-0.31	410	410
PI3K	0.006	0.13	-10000	0	-0.5	59	59
mol:GDP	-0.088	0.18	-10000	0	-0.31	407	407
ITGA2B	0.033	0.06	0.26	54	-0.57	3	57
endothelial cell proliferation	0.029	0.011	-10000	0	-10000	0	0
FYN	-0.024	0.16	-10000	0	-0.76	49	49
MAP3K7	-0.023	0.12	-10000	0	-0.57	48	48
FGR	-0.02	0.16	-10000	0	-0.76	49	49
TIAM1	0.025	0.015	0.26	4	-10000	0	4
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
RGS3	0.024	0.003	-10000	0	-10000	0	0
cell adhesion	-0.008	0.13	-10000	0	-0.52	54	54
LYN	-0.021	0.16	-10000	0	-0.75	49	49
Ephrin B1/EPHB1-2/Src Family Kinases	-0.026	0.15	-10000	0	-0.71	50	50
Ephrin B1/EPHB1-2	-0.022	0.13	-10000	0	-0.63	45	45
SRC	-0.019	0.16	-10000	0	-0.75	50	50
ITGB3	0.006	0.1	0.26	4	-0.57	33	37
EPHB1	-0.2	0.29	0.26	1	-0.57	412	413
EPHB4	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.029	0.011	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.027	0.089	-10000	0	-0.41	36	36
BLK	-0.019	0.17	-10000	0	-0.78	47	47
HCK	-0.019	0.16	-10000	0	-0.75	50	50
regulation of stress fiber formation	0.089	0.18	0.31	410	-10000	0	410
MAPK8	-0.024	0.12	-10000	0	-0.54	47	47
Ephrin B1/EPHB1-2/RGS3	-0.088	0.18	-10000	0	-0.31	409	409
endothelial cell migration	-0.017	0.11	-10000	0	-0.51	42	42
NCK2	0.024	0.003	-10000	0	-10000	0	0
PTPN13	0.009	0.11	-10000	0	-0.68	26	26
regulation of focal adhesion formation	0.089	0.18	0.31	410	-10000	0	410
chemotaxis	0.088	0.18	0.31	409	-10000	0	409
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
Rac1/GTP	-0.08	0.17	-10000	0	-0.29	400	400
angiogenesis	-0.023	0.13	-10000	0	-0.62	47	47
LCK	-0.02	0.17	-10000	0	-0.77	49	49

×

Wnt signaling

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.097	0.21	0.22	1	-0.39	297	298
FZD6	0.014	0.054	-10000	0	-0.57	9	9
WNT6	-0.076	0.24	0.26	47	-0.57	200	247
WNT4	0.017	0.086	0.26	20	-0.57	20	40
FZD3	0.015	0.054	-10000	0	-0.57	9	9
WNT5A	0.017	0.073	0.26	9	-0.57	15	24
WNT11	-0.085	0.23	0.26	10	-0.57	199	209

×

Lissencephaly gene (LIS1) in neuronal migration and development

Figure S20. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S20. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.024	0.004	-10000	0	-10000	0	0
VLDLR	0.007	0.096	-10000	0	-0.57	29	29
LRPAP1	0.023	0.005	-10000	0	-10000	0	0
NUDC	0.023	0.005	-10000	0	-10000	0	0
RELN/LRP8	-0.18	0.2	-10000	0	-0.35	612	612
CaM/Ca2+	0.018	0.003	-10000	0	-10000	0	0
KATNA1	0.023	0.006	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.18	0.17	-10000	0	-0.32	609	609
IQGAP1/CaM	0.034	0.009	-10000	0	-10000	0	0
DAB1	0.035	0.054	0.26	61	-10000	0	61
IQGAP1	0.024	0.005	-10000	0	-10000	0	0
PLA2G7	0.023	0.066	0.26	23	-0.57	10	33
CALM1	0.024	0.004	-10000	0	-10000	0	0
DYNLT1	0.023	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.048	0.047	-10000	0	-10000	0	0
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.024	0.002	-10000	0	-10000	0	0
CDK5R1	0.028	0.034	0.26	23	-10000	0	23
LIS1/Poliovirus Protein 3A	0.007	0.003	-10000	0	-10000	0	0
CDK5R2	0.054	0.083	0.26	155	-10000	0	155
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.19	0.21	0.34	2	-0.37	608	610
YWHAE	0.022	0.007	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.13	0.15	0.33	4	-0.32	59	63
MAP1B	-0.001	0.045	-10000	0	-0.31	21	21
RAC1	0.011	0.004	-10000	0	-10000	0	0
p35/CDK5	-0.15	0.15	-10000	0	-0.3	498	498
RELN	-0.32	0.29	0.26	2	-0.57	619	621
PAFAH/LIS1	0.023	0.045	0.32	2	-0.36	9	11
LIS1/CLIP170	0.023	0.009	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.11	0.13	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.15	0.17	-10000	0	-0.36	224	224
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.14	0.15	0.31	4	-0.34	66	70
LIS1/IQGAP1	0.023	0.009	-10000	0	-10000	0	0
RHOA	0.01	0.004	-10000	0	-10000	0	0
PAFAH1B1	0.01	0.004	-10000	0	-10000	0	0
PAFAH1B3	0.051	0.074	0.26	123	-10000	0	123
PAFAH1B2	0.019	0.044	-10000	0	-0.57	6	6
MAP1B/LIS1/Dynein heavy chain	0.014	0.043	-10000	0	-0.35	2	2
NDEL1/Katanin 60/Dynein heavy chain	-0.12	0.15	0.34	3	-0.33	39	42
LRP8	0.046	0.068	0.26	103	-10000	0	103
NDEL1/Katanin 60	-0.13	0.15	0.35	3	-0.33	62	65
P39/CDK5	-0.15	0.16	0.34	6	-0.3	452	458
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.023	0.009	-10000	0	-10000	0	0
CDK5	-0.18	0.15	0.2	1	-0.3	601	602
PPP2R5D	0.024	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.02	0.007	-10000	0	-10000	0	0
CSNK2A1	0.023	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.16	0.19	0.33	1	-0.32	602	603
RELN/VLDLR	-0.17	0.2	-10000	0	-0.33	612	612
CDC42	0.01	0.005	-10000	0	-10000	0	0

×

IGF1 pathway

Figure S21. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S21. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.024	0.003	-10000	0	-10000	0	0
PTK2	0.019	0.01	-10000	0	-10000	0	0
CRKL	-0.067	0.15	-10000	0	-0.34	240	240
GRB2/SOS1/SHC	0.038	0.022	-10000	0	-10000	0	0
HRAS	0.026	0.022	0.26	9	-10000	0	9
IRS1/Crk	-0.061	0.16	-10000	0	-0.34	246	246
IGF-1R heterotetramer/IGF1/PTP1B	-0.044	0.17	-10000	0	-0.36	213	213
AKT1	-0.067	0.14	0.25	2	-0.32	199	201
BAD	-0.065	0.13	0.24	2	-0.31	182	184
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.068	0.16	-10000	0	-0.34	244	244
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.058	0.16	-10000	0	-0.34	246	246
RAF1	-0.047	0.13	0.28	2	-0.47	48	50
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.032	0.16	-10000	0	-0.33	214	214
YWHAZ	0.019	0.01	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.062	0.17	-10000	0	-0.36	246	246
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
RPS6KB1	-0.063	0.13	0.25	2	-0.32	165	167
GNB2L1	0.024	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.029	0.12	0.3	10	-0.4	43	53
PXN	0.024	0.002	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
HRAS/GTP	-0.039	0.13	-10000	0	-0.31	161	161
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.01	0.14	-10000	0	-0.3	160	160
IGF-1R heterotetramer	-0.011	0.098	0.25	1	-0.62	20	21
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.045	0.17	-10000	0	-0.34	243	243
Crk/p130 Cas/Paxillin	-0.037	0.16	-10000	0	-0.32	227	227
IGF1R	-0.011	0.098	0.25	1	-0.62	20	21
IGF1	-0.11	0.25	-10000	0	-0.59	233	233
IRS2/Crk	-0.067	0.17	-10000	0	-0.35	245	245
PI3K	-0.036	0.17	-10000	0	-0.34	224	224
apoptosis	0.044	0.11	0.37	40	-0.27	5	45
HRAS/GDP	0.019	0.015	-10000	0	-10000	0	0
PRKCD	-0.078	0.17	-10000	0	-0.39	230	230
RAF1/14-3-3 E	-0.024	0.13	0.3	1	-0.41	47	48
BAD/14-3-3	-0.046	0.11	0.28	5	-0.4	40	45
PRKCZ	-0.067	0.14	0.25	2	-0.32	199	201
Crk/p130 Cas/Paxillin/FAK1	-0.028	0.12	-10000	0	-0.41	38	38
PTPN1	0.024	0.018	0.26	6	-10000	0	6
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.082	0.18	-10000	0	-0.41	240	240
BCAR1	0.021	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.022	0.14	-10000	0	-0.32	176	176
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.024	0.003	-10000	0	-10000	0	0
IRS1/NCK2	-0.054	0.16	-10000	0	-0.34	243	243
GRB10	0.024	0.003	-10000	0	-10000	0	0
PTPN11	-0.068	0.16	-10000	0	-0.34	246	246
IRS1	-0.071	0.17	-10000	0	-0.36	246	246
IRS2	-0.076	0.17	-10000	0	-0.36	245	245
IGF-1R heterotetramer/IGF1	-0.078	0.21	-10000	0	-0.46	232	232
GRB2	0.023	0.009	0.26	1	-10000	0	1
PDPK1	-0.069	0.14	0.28	1	-0.33	205	206
YWHAE	0.022	0.007	-10000	0	-10000	0	0
PRKD1	-0.089	0.19	-10000	0	-0.42	238	238
SHC1	0.02	0.009	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

Figure S22. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S22. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.026	0.16	-10000	0	-0.57	88	88
GNB1/GNG2	-0.076	0.21	-10000	0	-0.48	159	159
mol:DAG	-0.077	0.18	0.24	1	-0.44	151	152
PLCG1	-0.08	0.19	0.24	1	-0.46	151	152
YES1	-0.095	0.19	0.2	1	-0.49	147	148
FZD3	0.015	0.054	-10000	0	-0.57	9	9
FZD6	0.014	0.054	-10000	0	-0.57	9	9
G protein	-0.063	0.2	0.3	2	-0.47	144	146
MAP3K7	-0.071	0.15	0.23	2	-0.4	128	130
mol:Ca2+	-0.074	0.18	0.23	1	-0.43	151	152
mol:IP3	-0.077	0.18	0.24	1	-0.44	151	152
NLK	-0.009	0.13	-10000	0	-0.84	24	24
GNB1	0.023	0.005	-10000	0	-10000	0	0
CAMK2A	-0.072	0.17	0.23	4	-0.41	145	149
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.097	0.21	0.22	1	-0.39	297	298
CSNK1A1	0.024	0.003	-10000	0	-10000	0	0
GNAS	-0.09	0.19	-10000	0	-0.49	142	142
GO:0007205	-0.081	0.18	0.22	2	-0.43	152	154
WNT6	-0.076	0.24	0.26	47	-0.57	200	247
WNT4	0.017	0.086	0.26	20	-0.57	20	40
NFAT1/CK1 alpha	-0.09	0.2	0.32	2	-0.49	144	146
GNG2	0.017	0.065	-10000	0	-0.57	13	13
WNT5A	0.017	0.073	0.26	9	-0.57	15	24
WNT11	-0.085	0.23	0.26	10	-0.57	199	209
CDC42	-0.083	0.19	-10000	0	-0.47	139	139

×

Arf6 signaling events

Figure S23. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S23. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.027	0.029	-10000	0	-0.39	3	3
ARNO/beta Arrestin1-2	-0.063	0.16	-10000	0	-0.55	45	45
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
EPHA2	0.02	0.04	-10000	0	-0.57	5	5
USP6	0.022	0.007	-10000	0	-10000	0	0
IQSEC1	0.024	0.004	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.21	0.25	-10000	0	-0.45	537	537
ARRB2	-0.042	0.13	-10000	0	-0.36	146	146
mol:GTP	0.012	0.049	0.16	18	-0.21	17	35
ARRB1	0.021	0.026	-10000	0	-0.57	2	2
FBXO8	0.023	0.005	-10000	0	-10000	0	0
TSHR	0.001	0.12	0.26	4	-0.57	42	46
EGF	-0.083	0.23	0.26	2	-0.57	194	196
somatostatin receptor activity	0	0	0.001	1	-0.001	277	278
ARAP2	0.021	0.04	-10000	0	-0.57	5	5
mol:GDP	-0.12	0.16	-10000	0	-0.33	296	296
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	183	183
ITGA2B	0.033	0.06	0.26	54	-0.57	3	57
ARF6	0.024	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.038	-10000	0	-0.33	5	5
ADAP1	0.025	0.029	0.26	10	-0.57	1	11
KIF13B	0.019	0.027	-10000	0	-0.57	2	2
HGF/MET	-0.066	0.2	-10000	0	-0.44	225	225
PXN	0.024	0.002	-10000	0	-10000	0	0
ARF6/GTP	-0.12	0.13	0.19	1	-0.28	306	307
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.17	0.23	-10000	0	-0.4	514	514
ADRB2	-0.1	0.24	-10000	0	-0.57	229	229
receptor agonist activity	0	0	0	1	0	271	272
actin filament binding	0	0	0	1	-0.001	280	281
SRC	0.023	0.005	-10000	0	-10000	0	0
ITGB3	0.006	0.1	0.26	4	-0.57	33	37
GNAQ	0.022	0.031	-10000	0	-0.57	3	3
EFA6/PI-4-5-P2	0	0	0.001	1	-0.001	172	173
ARF6/GDP	-0.037	0.15	0.25	2	-0.43	92	94
ARF6/GDP/GULP/ACAP1	-0.11	0.19	-10000	0	-0.4	226	226
alphaIIb/beta3 Integrin/paxillin/GIT1	0.05	0.079	-10000	0	-0.32	36	36
ACAP1	0.029	0.066	0.26	47	-0.57	6	53
ACAP2	0.024	0.004	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	-0.055	0.17	-10000	0	-0.48	146	146
EFNA1	0.02	0.009	-10000	0	-10000	0	0
HGF	-0.011	0.14	0.26	2	-0.57	65	67
CYTH3	0.004	0.018	-10000	0	-0.42	2	2
CYTH2	0.006	0.099	-10000	0	-1	10	10
NCK1	0.024	0.003	-10000	0	-10000	0	0
fibronectin binding	0	0	0	1	0	220	221
endosomal lumen acidification	0	0	0.001	6	0	263	269
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.014	0.14	-10000	0	-0.57	69	69
GNAQ/ARNO	0.018	0.095	-10000	0	-0.95	10	10
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	-10000	0	0	188	188
MET	-0.073	0.22	-10000	0	-0.57	177	177
GNA14	0.022	0.065	0.26	19	-0.57	10	29
GNA15	0.024	0.025	0.26	6	-0.57	1	7
GIT1	0.023	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	1	-0.001	233	234
GNA11	0.021	0.036	-10000	0	-0.57	4	4
LHCGR	-0.069	0.2	-10000	0	-0.57	146	146
AGTR1	-0.098	0.26	0.26	59	-0.57	244	303
desensitization of G-protein coupled receptor protein signaling pathway	-0.055	0.17	-10000	0	-0.48	146	146
IPCEF1/ARNO	-0.13	0.19	-10000	0	-0.58	71	71
alphaIIb/beta3 Integrin	0.027	0.089	-10000	0	-0.41	36	36

×

Plasma membrane estrogen receptor signaling

Figure S24. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S24. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0	0.15	-10000	0	-0.32	176	176
ER alpha/Gai/GDP/Gbeta gamma	-0.085	0.22	-10000	0	-0.46	221	221
AKT1	-0.12	0.33	-10000	0	-0.77	205	205
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.11	0.33	-10000	0	-0.78	204	204
mol:Ca2+	-0.026	0.1	0.26	2	-0.45	29	31
IGF1R	0.013	0.079	0.26	3	-0.57	19	22
E2/ER alpha (dimer)/Striatin	-0.016	0.16	-10000	0	-0.36	168	168
SHC1	0.02	0.009	-10000	0	-10000	0	0
apoptosis	0.11	0.31	0.73	205	-10000	0	205
RhoA/GTP	-0.015	0.1	-10000	0	-0.28	123	123
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.067	0.21	0.31	4	-0.46	200	204
regulation of stress fiber formation	0.024	0.1	0.24	137	-0.24	21	158
E2/ERA-ERB (dimer)	-0.019	0.16	-10000	0	-0.36	169	169
KRAS	0.023	0.005	-10000	0	-10000	0	0
G13/GTP	-0.009	0.13	-10000	0	-0.32	139	139
pseudopodium formation	-0.024	0.1	0.24	21	-0.24	137	158
E2/ER alpha (dimer)/PELP1	-0.013	0.15	-10000	0	-0.35	153	153
GRB2	0.023	0.009	0.26	1	-10000	0	1
GNG2	0.017	0.065	-10000	0	-0.57	13	13
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
HRAS	0.026	0.022	0.26	9	-10000	0	9
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.088	0.23	-10000	0	-0.5	222	222
E2/ER beta (dimer)	0.008	0.063	-10000	0	-0.4	24	24
mol:GDP	-0.039	0.16	0.25	13	-0.39	169	182
mol:NADP	-0.088	0.23	-10000	0	-0.5	222	222
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:IP3	-0.027	0.11	0.27	2	-0.47	28	30
IGF-1R heterotetramer	0.013	0.079	0.26	3	-0.56	19	22
PLCB1	-0.025	0.11	0.28	2	-0.45	33	35
PLCB2	-0.005	0.082	-10000	0	-0.49	17	17
IGF1	-0.1	0.24	-10000	0	-0.57	233	233
mol:L-citrulline	-0.088	0.23	-10000	0	-0.5	222	222
RHOA	0.024	0.005	-10000	0	-10000	0	0
Gai/GDP	-0.078	0.25	-10000	0	-0.64	159	159
JNK cascade	0.008	0.063	-10000	0	-0.4	24	24
BCAR1	0.021	0.008	-10000	0	-10000	0	0
ESR2	0.011	0.085	-10000	0	-0.57	23	23
GNAQ	0.022	0.031	-10000	0	-0.57	3	3
ESR1	-0.035	0.23	0.26	116	-0.57	151	267
Gq family/GDP/Gbeta gamma	-0.01	0.16	-10000	0	-0.74	39	39
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.017	0.13	-10000	0	-0.57	19	19
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.059	0.2	0.31	5	-0.46	169	174
GNAZ	0.018	0.057	-10000	0	-0.57	10	10
E2/ER alpha (dimer)	-0.028	0.16	0.18	116	-0.41	157	273
STRN	0.013	0.08	-10000	0	-0.57	20	20
GNAL	-0.11	0.24	-10000	0	-0.57	235	235
PELP1	0.022	0.007	-10000	0	-10000	0	0
MAPK11	0.002	0.057	-10000	0	-0.36	26	26
GNAI2	0.024	0.005	-10000	0	-10000	0	0
GNAI3	0.024	0.004	-10000	0	-10000	0	0
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
HBEGF	-0.056	0.21	0.33	22	-0.49	123	145
cAMP biosynthetic process	-0.086	0.18	-10000	0	-0.32	348	348
SRC	-0.079	0.21	0.29	7	-0.44	213	220
PI3K	0.028	0.049	-10000	0	-0.38	14	14
GNB1	0.023	0.005	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.02	0.16	-10000	0	-0.38	142	142
SOS1	0.024	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.11	0.19	-10000	0	-0.43	223	223
Gs family/GTP	-0.083	0.18	-10000	0	-0.33	348	348
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.044	0.019	-10000	0	-10000	0	0
vasodilation	-0.083	0.22	0.24	1	-0.48	222	223
mol:DAG	-0.027	0.11	0.27	2	-0.47	28	30
Gs family/GDP/Gbeta gamma	-0.09	0.18	-10000	0	-0.36	263	263
MSN	-0.026	0.11	0.24	21	-0.26	137	158
Gq family/GTP	-0.001	0.087	-10000	0	-0.51	16	16
mol:PI-3-4-5-P3	-0.11	0.32	-10000	0	-0.75	204	204
NRAS	0.024	0.004	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.083	0.22	0.48	222	-0.24	1	223
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
RhoA/GDP	-0.023	0.16	0.26	10	-0.38	166	176
NOS3	-0.094	0.25	-10000	0	-0.53	222	222
GNA11	0.022	0.036	-10000	0	-0.57	4	4
MAPKKK cascade	-0.084	0.25	0.31	2	-0.56	208	210
E2/ER alpha (dimer)/PELP1/Src	-0.071	0.22	0.31	8	-0.47	206	214
ruffle organization	-0.024	0.1	0.24	21	-0.24	137	158
ROCK2	-0.025	0.12	0.34	8	-0.28	137	145
GNA14	0.023	0.065	0.26	19	-0.57	10	29
GNA15	0.025	0.025	0.26	6	-0.57	1	7
GNA13	0.022	0.007	-10000	0	-10000	0	0
MMP9	-0.048	0.2	0.35	24	-0.48	117	141
MMP2	-0.069	0.2	0.27	12	-0.42	210	222

×

IL23-mediated signaling events

Figure S25. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S25. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.02	0.48	0.8	45	-1.1	74	119
IL23A	-0.031	0.48	0.85	31	-1.1	71	102
NF kappa B1 p50/RelA/I kappa B alpha	-0.059	0.44	0.76	8	-0.91	129	137
positive regulation of T cell mediated cytotoxicity	-0.023	0.54	0.87	61	-1	131	192
ITGA3	-0.016	0.47	0.81	35	-1.1	70	105
IL17F	-0.007	0.36	0.59	72	-0.68	75	147
IL12B	0.084	0.15	0.36	207	-10000	0	207
STAT1 (dimer)	-0.037	0.5	0.75	45	-0.96	134	179
CD4	-0.015	0.48	0.84	37	-1	70	107
IL23	-0.016	0.48	0.82	48	-1.1	69	117
IL23R	0.047	0.2	0.54	28	-0.89	18	46
IL1B	-0.033	0.5	0.84	35	-1.1	75	110
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.018	0.48	0.84	57	-1	69	126
TYK2	0.026	0.058	0.21	6	-10000	0	6
STAT4	0.001	0.12	0.26	1	-0.57	43	44
STAT3	0.024	0.005	-10000	0	-10000	0	0
IL18RAP	0.008	0.11	0.27	5	-0.56	35	40
IL12RB1	0.034	0.091	0.37	42	-0.58	2	44
PIK3CA	0.024	0.005	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.039	0.088	0.3	45	-0.43	2	47
IL23R/JAK2	0.06	0.22	0.53	36	-0.84	16	52
positive regulation of chronic inflammatory response	-0.023	0.54	0.87	61	-1	131	192
natural killer cell activation	-0.004	0.015	-10000	0	-0.051	35	35
JAK2	0.038	0.081	0.26	28	-10000	0	28
PIK3R1	0.017	0.064	-10000	0	-0.56	13	13
NFKB1	0.026	0.009	-10000	0	-10000	0	0
RELA	0.026	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.01	0.47	0.81	51	-1	70	121
ALOX12B	-0.017	0.47	0.83	39	-1	68	107
CXCL1	-0.18	0.69	0.83	45	-1.2	276	321
T cell proliferation	-0.023	0.54	0.87	61	-1	131	192
NFKBIA	0.026	0.009	-10000	0	-10000	0	0
IL17A	0.02	0.31	0.56	81	-0.55	59	140
PI3K	-0.055	0.46	0.68	25	-0.93	130	155
IFNG	0.025	0.067	0.17	139	-0.11	17	156
STAT3 (dimer)	-0.056	0.44	0.71	14	-1	81	95
IL18R1	0.016	0.078	-10000	0	-0.56	19	19
IL23/IL23R/JAK2/TYK2/SOCS3	0.036	0.34	0.64	85	-0.64	50	135
IL18/IL18R	0.041	0.1	0.28	11	-0.36	52	63
macrophage activation	0	0.029	0.056	102	-0.044	53	155
TNF	-0.03	0.49	0.85	35	-1.1	74	109
STAT3/STAT4	-0.054	0.48	0.68	24	-0.96	133	157
STAT4 (dimer)	-0.049	0.51	0.74	39	-0.98	148	187
IL18	0.03	0.038	0.26	26	-10000	0	26
IL19	0.022	0.48	0.84	53	-1	66	119
STAT5A (dimer)	-0.04	0.49	0.74	39	-0.97	132	171
STAT1	0.028	0.031	0.26	19	-10000	0	19
SOCS3	0.02	0.041	-10000	0	-0.57	5	5
CXCL9	0.008	0.5	0.87	61	-1.1	71	132
MPO	-0.045	0.54	0.82	41	-1.2	109	150
positive regulation of humoral immune response	-0.023	0.54	0.87	61	-1	131	192
IL23/IL23R/JAK2/TYK2	-0.03	0.55	0.88	60	-1.1	114	174
IL6	-0.3	0.74	0.8	34	-1.2	395	429
STAT5A	0.02	0.044	-10000	0	-0.57	6	6
IL2	0.021	0.037	0.3	8	-10000	0	8
positive regulation of tyrosine phosphorylation of STAT protein	-0.004	0.015	-10000	0	-0.051	35	35
CD3E	-0.027	0.5	0.85	46	-1.1	79	125
keratinocyte proliferation	-0.023	0.54	0.87	61	-1	131	192
NOS2	-0.016	0.48	0.8	44	-1.1	73	117

×

Nongenotropic Androgen signaling

Figure S26. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S26. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.003	0.004	-10000	0	-10000	0	0
GNB1/GNG2	-0.01	0.13	-10000	0	-0.33	152	152
regulation of S phase of mitotic cell cycle	-0.024	0.11	-10000	0	-0.29	135	135
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
HRAS	0.025	0.022	0.25	9	-10000	0	9
SHBG/T-DHT	0.015	0.005	-10000	0	-10000	0	0
PELP1	0.021	0.007	-10000	0	-10000	0	0
AKT1	0.005	0.003	-10000	0	-10000	0	0
MAP2K1	-0.069	0.11	-10000	0	-0.32	125	125
T-DHT/AR	-0.042	0.15	0.17	1	-0.42	142	143
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.007	321	321
GNAI2	0.023	0.005	-10000	0	-10000	0	0
GNAI3	0.024	0.004	-10000	0	-10000	0	0
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
mol:GDP	-0.063	0.16	-10000	0	-0.47	144	144
cell proliferation	-0.14	0.21	0.27	3	-0.44	290	293
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
FOS	-0.25	0.38	-10000	0	-0.81	325	325
mol:Ca2+	-0.013	0.028	-10000	0	-0.073	148	148
MAPK3	-0.1	0.16	0.26	4	-0.42	118	122
MAPK1	-0.08	0.14	-10000	0	-0.39	108	108
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:IP3	-0.001	0.002	-10000	0	-0.004	317	317
cAMP biosynthetic process	0.004	0.021	-10000	0	-10000	0	0
GNG2	0.017	0.065	-10000	0	-0.57	13	13
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	317	317
HRAS/GTP	-0.028	0.12	-10000	0	-0.32	139	139
actin cytoskeleton reorganization	0.029	0.037	-10000	0	-0.3	12	12
SRC	0.023	0.005	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	317	317
PI3K	0.026	0.042	-10000	0	-0.34	13	13
apoptosis	0.13	0.21	0.44	315	-10000	0	315
T-DHT/AR/PELP1	-0.025	0.13	-10000	0	-0.36	141	141
HRAS/GDP	-0.052	0.16	-10000	0	-0.45	141	141
CREB1	-0.14	0.23	-10000	0	-0.47	313	313
RAC1-CDC42/GTP	0.037	0.04	-10000	0	-0.3	12	12
AR	-0.054	0.2	0.25	1	-0.57	141	142
GNB1	0.023	0.005	-10000	0	-10000	0	0
RAF1	-0.061	0.11	-10000	0	-0.32	134	134
RAC1-CDC42/GDP	-0.028	0.16	-10000	0	-0.44	141	141
T-DHT/AR/PELP1/Src	-0.022	0.13	-10000	0	-0.34	140	140
MAP2K2	-0.07	0.11	-10000	0	-0.32	127	127
T-DHT/AR/PELP1/Src/PI3K	-0.025	0.11	-10000	0	-0.3	135	135
GNAZ	0.017	0.057	-10000	0	-0.57	10	10
SHBG	0.022	0.007	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.052	0.16	-10000	0	-0.47	99	99
mol:T-DHT	-0.001	0.001	0.002	1	-0.004	86	87
RAC1	0.024	0.003	-10000	0	-10000	0	0
GNRH1	0.001	0.029	-10000	0	-0.42	5	5
Gi family/GTP	-0.036	0.1	-10000	0	-0.28	103	103
CDC42	0.023	0.005	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

Figure S27. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S27. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.008	0.009	-10000	0	-10000	0	0
RAS family/GTP	-0.022	0.14	0.31	2	-0.3	62	64
NFATC4	-0.063	0.12	0.27	9	-0.26	84	93
ERBB2IP	0.024	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.024	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.069	0.15	-10000	0	-0.3	252	252
JUN	-0.009	0.096	0.23	25	-0.45	3	28
HRAS	0.026	0.022	0.26	9	-10000	0	9
DOCK7	-0.079	0.14	0.28	2	-0.3	251	253
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.052	0.15	-10000	0	-0.33	207	207
AKT1	-0.001	0.009	-10000	0	-10000	0	0
BAD	-0.007	0.006	-10000	0	-10000	0	0
MAPK10	-0.07	0.11	0.2	10	-0.27	138	148
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.073	0.16	-10000	0	-0.33	252	252
RAF1	-0.019	0.14	0.32	15	-0.3	59	74
ErbB2/ErbB3/neuregulin 2	-0.14	0.18	-10000	0	-0.34	437	437
STAT3	-0.001	0.16	-10000	0	-0.86	34	34
cell migration	-0.055	0.1	0.24	15	-0.25	86	101
mol:PI-3-4-5-P3	-0.002	0.002	-10000	0	-10000	0	0
cell proliferation	-0.044	0.24	0.44	9	-0.53	80	89
FOS	-0.1	0.28	0.37	12	-0.49	326	338
NRAS	0.024	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.069	0.15	-10000	0	-0.3	252	252
MAPK3	-0.015	0.2	0.39	13	-0.53	22	35
MAPK1	-0.027	0.21	0.4	11	-0.6	39	50
JAK2	-0.077	0.14	0.26	1	-0.3	247	248
NF2	-0.002	0.057	-10000	0	-0.68	7	7
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.053	0.13	0.22	4	-0.28	234	238
NRG1	-0.14	0.26	0.25	4	-0.57	292	296
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
MAPK8	-0.08	0.15	0.25	2	-0.3	255	257
MAPK9	-0.042	0.083	0.2	11	-0.26	3	14
ERBB2	0.001	0.071	0.24	85	-0.44	1	86
ERBB3	0.021	0.041	-10000	0	-0.57	5	5
SHC1	0.021	0.01	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
apoptosis	0.019	0.025	-10000	0	-0.16	7	7
STAT3 (dimer)	0	0.15	-10000	0	-0.84	34	34
RNF41	-0.012	0.011	-10000	0	-10000	0	0
FRAP1	-0.004	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.07	0.093	-10000	0	-0.23	227	227
ErbB2/ErbB2/HSP90 (dimer)	-0.011	0.02	-10000	0	-0.38	1	1
CHRNA1	0.017	0.18	0.36	42	-0.45	12	54
myelination	-0.058	0.12	0.3	17	-0.26	32	49
PPP3CB	-0.074	0.13	0.27	2	-0.28	248	250
KRAS	0.024	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.036	0.14	-10000	0	-0.26	197	197
NRG2	-0.26	0.29	-10000	0	-0.57	509	509
mol:GDP	-0.053	0.13	0.22	4	-0.28	234	238
SOS1	0.025	0.003	-10000	0	-10000	0	0
MAP2K2	-0.017	0.14	0.32	16	-0.31	50	66
SRC	0.023	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.002	-10000	0	-10000	0	0
PTPN11	-0.079	0.14	0.28	2	-0.3	251	253
MAP2K1	-0.053	0.22	0.44	3	-0.61	41	44
heart morphogenesis	-0.069	0.15	-10000	0	-0.3	252	252
RAS family/GDP	-0.021	0.14	0.33	2	-0.29	61	63
GRB2	0.023	0.009	0.25	1	-10000	0	1
PRKACA	-0.002	0.067	-10000	0	-0.68	10	10
CHRNE	0.004	0.027	0.12	4	-0.21	3	7
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.001	0.009	-10000	0	-10000	0	0
nervous system development	-0.069	0.15	-10000	0	-0.3	252	252
CDC42	0.023	0.005	-10000	0	-10000	0	0

×

BMP receptor signaling

Figure S28. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S28. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.058	0.16	0.31	7	-0.35	114	121
SMAD6-7/SMURF1	0.046	0.015	-10000	0	-10000	0	0
NOG	0.012	0.095	0.26	19	-0.57	25	44
SMAD9	-0.088	0.25	-10000	0	-0.59	189	189
SMAD4	0.023	0.005	-10000	0	-10000	0	0
SMAD5	-0.021	0.14	-10000	0	-0.44	68	68
BMP7/USAG1	-0.19	0.25	-10000	0	-0.42	532	532
SMAD5/SKI	-0.015	0.15	0.27	1	-0.44	67	68
SMAD1	0.013	0.062	-10000	0	-0.43	7	7
BMP2	-0.074	0.22	0.26	2	-0.57	179	181
SMAD1/SMAD1/SMAD4	0.018	0.069	-10000	0	-0.42	7	7
BMPR1A	0.023	0.026	-10000	0	-0.57	2	2
BMPR1B	0.1	0.15	0.26	425	-0.57	23	448
BMPR1A-1B/BAMBI	0.083	0.12	0.34	9	-0.33	53	62
AHSG	0.021	0.029	0.26	16	-10000	0	16
CER1	0.018	0.013	0.26	3	-10000	0	3
BMP2-4/CER1	-0.046	0.18	-10000	0	-0.39	214	214
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.038	0.16	-10000	0	-0.4	117	117
BMP2-4 (homodimer)	-0.066	0.2	-10000	0	-0.45	219	219
RGMB	0.023	0.019	-10000	0	-0.57	1	1
BMP6/BMPR2/BMPR1A-1B	0.07	0.14	-10000	0	-0.31	96	96
RGMA	-0.053	0.2	-10000	0	-0.57	139	139
SMURF1	0.024	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.036	0.16	-10000	0	-0.41	123	123
BMP2-4/USAG1	-0.22	0.26	-10000	0	-0.44	577	577
SMAD6/SMURF1/SMAD5	-0.016	0.15	0.27	1	-0.44	68	69
SOSTDC1	-0.25	0.3	0.26	3	-0.57	507	510
BMP7/BMPR2/BMPR1A-1B	0.068	0.14	0.3	4	-0.32	90	94
SKI	0.023	0.005	-10000	0	-10000	0	0
BMP6 (homodimer)	-0.016	0.15	0.26	2	-0.56	72	74
HFE2	0.018	0.023	0.26	9	-10000	0	9
ZFYVE16	0.024	0.005	-10000	0	-10000	0	0
MAP3K7	0.023	0.006	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.043	0.2	-10000	0	-0.4	220	220
SMAD5/SMAD5/SMAD4	-0.016	0.15	0.27	1	-0.44	71	72
MAPK1	0.023	0.006	-10000	0	-10000	0	0
TAK1/TAB family	-0.022	0.15	-10000	0	-0.37	112	112
BMP7 (homodimer)	-0.011	0.16	0.26	30	-0.56	73	103
NUP214	0.024	0.004	-10000	0	-10000	0	0
BMP6/FETUA	0.001	0.12	-10000	0	-0.41	75	75
SMAD1/SKI	0.02	0.076	-10000	0	-0.43	11	11
SMAD6	0.024	0.004	-10000	0	-10000	0	0
CTDSP2	0.024	0.003	-10000	0	-10000	0	0
BMP2-4/FETUA	-0.045	0.18	0.34	1	-0.39	216	217
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.036	0.095	0.26	94	-0.57	14	108
BMPR2 (homodimer)	0.024	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.044	0.016	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.085	0.11	-10000	0	-0.41	25	25
CHRDL1	-0.38	0.28	-10000	0	-0.57	729	729
ENDOFIN/SMAD1	0.019	0.078	-10000	0	-0.45	11	11
SMAD6-7/SMURF1/SMAD1	0.036	0.081	-10000	0	-0.44	9	9
SMAD6/SMURF1	0.024	0.004	-10000	0	-10000	0	0
BAMBI	0.016	0.11	0.26	39	-0.57	30	69
SMURF2	0.022	0.007	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.3	0.26	-10000	0	-0.45	729	729
BMP2-4/GREM1	-0.037	0.2	-10000	0	-0.4	224	224
SMAD7	0.023	0.005	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.081	0.25	-10000	0	-0.57	193	193
SMAD1/SMAD6	0.019	0.078	-10000	0	-0.45	11	11
TAK1/SMAD6	0.033	0.01	-10000	0	-10000	0	0
BMP7	-0.011	0.16	0.26	30	-0.57	73	103
BMP6	-0.016	0.15	0.26	2	-0.57	72	74
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.034	0.17	-10000	0	-0.42	122	122
PPM1A	0.024	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.017	0.075	-10000	0	-0.45	10	10
SMAD7/SMURF1	0.034	0.009	-10000	0	-10000	0	0
CTDSPL	0.024	0.004	-10000	0	-10000	0	0
PPP1CA	0.023	0.007	-10000	0	-10000	0	0
XIAP	0.024	0.002	-10000	0	-10000	0	0
CTDSP1	0.024	0.003	-10000	0	-10000	0	0
PPP1R15A	0.024	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.047	0.2	0.23	1	-0.48	133	134
CHRD	0.026	0.095	0.26	58	-0.57	19	77
BMPR2	0.024	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.05	0.18	-10000	0	-0.48	123	123
BMP4	-0.01	0.14	0.26	1	-0.57	62	63
FST	-0.001	0.12	0.26	3	-0.57	45	48
BMP2-4/NOG	-0.047	0.19	0.34	1	-0.4	209	210
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.072	0.14	0.3	4	-0.3	90	94

×

Signaling events regulated by Ret tyrosine kinase

Figure S29. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S29. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.002	0.082	-10000	0	-0.55	14	14
Crk/p130 Cas/Paxillin	-0.056	0.12	-10000	0	-0.34	135	135
JUN	-0.015	0.12	0.25	1	-0.41	26	27
HRAS	0.026	0.022	0.26	9	-10000	0	9
RET51/GFRalpha1/GDNF/GRB10	0.041	0.19	0.34	53	-0.34	177	230
RAP1A	0.024	0.004	-10000	0	-10000	0	0
FRS2	0.024	0.011	0.26	2	-10000	0	2
RAP1A/GDP	0.018	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.042	0.19	0.34	52	-0.34	176	228
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.024	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.022	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.011	0.15	0.32	5	-0.33	180	185
RHOA	0.024	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.02	0.16	0.28	37	-0.3	179	216
GRB7	0.019	0.032	-10000	0	-0.57	3	3
RET51/GFRalpha1/GDNF	0.04	0.19	0.34	52	-0.34	176	228
MAPKKK cascade	0	0.15	0.28	11	-0.32	130	141
BCAR1	0.021	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.024	0.18	0.32	4	-0.38	192	196
lamellipodium assembly	-0.033	0.13	-10000	0	-0.31	143	143
RET51/GFRalpha1/GDNF/SHC	0.035	0.18	0.34	42	-0.34	139	181
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.008	0.14	0.32	5	-0.33	135	140
RET9/GFRalpha1/GDNF/Shank3	-0.013	0.15	0.32	5	-0.33	180	185
MAPK3	-0.031	0.13	0.25	6	-0.3	155	161
DOK1	0.025	0.014	0.26	4	-10000	0	4
DOK6	0.017	0.07	0.26	7	-0.57	14	21
PXN	0.024	0.002	-10000	0	-10000	0	0
neurite development	-0.031	0.12	-10000	0	-0.32	82	82
DOK5	0.011	0.087	0.26	5	-0.57	23	28
GFRA1	-0.07	0.24	0.26	53	-0.57	192	245
MAPK8	-0.009	0.13	0.21	4	-0.45	25	29
HRAS/GTP	0.028	0.18	0.29	53	-0.34	169	222
tube development	-0.006	0.14	0.34	11	-0.31	171	182
MAPK1	-0.031	0.13	0.28	4	-0.3	141	145
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.023	0.11	0.25	1	-0.26	171	172
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
SRC	0.023	0.005	-10000	0	-10000	0	0
PDLIM7	0.024	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.037	0.19	0.33	49	-0.33	182	231
SHC1	0.02	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	0.027	0.18	0.34	38	-0.34	179	217
RET51/GFRalpha1/GDNF/Dok5	0.025	0.2	0.34	48	-0.35	187	235
PRKCA	0.01	0.084	0.26	1	-0.57	22	23
HRAS/GDP	0.019	0.015	0.18	9	-10000	0	9
CREB1	-0.014	0.13	0.22	14	-0.31	104	118
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.02	0.1	0.25	1	-0.26	127	128
RET51/GFRalpha1/GDNF/Grb7	0.04	0.18	0.33	66	-0.34	146	212
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.097	0.13	0.26	374	-0.57	13	387
DOK4	0.022	0.008	-10000	0	-10000	0	0
JNK cascade	-0.014	0.12	0.24	1	-0.4	26	27
RET9/GFRalpha1/GDNF/FRS2	-0.012	0.15	0.32	5	-0.33	181	186
SHANK3	0.023	0.006	-10000	0	-10000	0	0
RASA1	0.024	0.004	-10000	0	-10000	0	0
NCK1	0.024	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.02	0.1	0.25	1	-0.26	127	128
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.005	0.14	0.24	16	-0.28	140	156
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.002	0.14	0.25	4	-0.29	142	146
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.01	0.13	0.25	16	-0.3	105	121
PI3K	-0.029	0.2	0.28	11	-0.47	144	155
SOS1	0.024	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.004	0.14	0.31	4	-0.31	171	175
GRB10	0.024	0.003	-10000	0	-10000	0	0
activation of MAPKK activity	-0.005	0.12	0.23	9	-0.26	134	143
RET51/GFRalpha1/GDNF/FRS2	0.038	0.19	0.34	56	-0.34	178	234
GAB1	0.024	0.004	-10000	0	-10000	0	0
IRS1	0.001	0.11	-10000	0	-0.57	42	42
IRS2	0.003	0.1	-10000	0	-0.57	35	35
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.01	0.13	0.25	16	-0.3	105	121
RET51/GFRalpha1/GDNF/PKC alpha	0.024	0.19	0.35	42	-0.34	185	227
GRB2	0.023	0.009	0.26	1	-10000	0	1
PRKACA	0.024	0.004	-10000	0	-10000	0	0
GDNF	0.032	0.052	0.26	54	-10000	0	54
RAC1	0.024	0.003	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.027	0.22	0.34	50	-0.38	191	241
Rac1/GTP	-0.022	0.16	0.23	4	-0.37	143	147
RET9/GFRalpha1/GDNF	-0.026	0.16	0.18	70	-0.34	197	267
GFRalpha1/GDNF	-0.033	0.18	0.36	5	-0.4	197	202

×

Calcium signaling in the CD4+ TCR pathway

Figure S30. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S30. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.003	0.039	0.22	2	-0.37	2	4
NFATC2	-0.026	0.11	0.19	4	-0.37	88	92
NFATC3	0.006	0.034	0.22	2	-10000	0	2
CD40LG	-0.14	0.29	0.47	17	-0.55	260	277
PTGS2	-0.19	0.33	0.48	13	-0.64	328	341
JUNB	0.024	0.01	0.26	2	-10000	0	2
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.027	0.15	2	-10000	0	2
CaM/Ca2+	0.008	0.027	0.15	2	-10000	0	2
CALM1	0.016	0.022	-10000	0	-10000	0	0
JUN	0.013	0.049	-10000	0	-0.57	6	6
mol:Ca2+	-0.003	0.011	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.013	0.012	-10000	0	-10000	0	0
FOSL1	0.027	0.048	0.26	26	-0.57	3	29
CREM	0.023	0.006	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.005	0.15	0.46	12	-0.4	55	67
FOS	-0.15	0.27	-10000	0	-0.57	306	306
IFNG	-0.11	0.28	0.46	42	-0.53	228	270
AP-1/NFAT1-c-4	-0.13	0.34	0.52	40	-0.6	261	301
FASLG	-0.12	0.26	0.5	24	-0.54	198	222
NFAT1-c-4/ICER1	-0.018	0.12	0.29	9	-0.34	78	87
IL2RA	-0.12	0.28	0.47	32	-0.54	236	268
FKBP12/FK506	0.018	0.003	-10000	0	-10000	0	0
CSF2	-0.13	0.27	0.47	20	-0.53	239	259
JunB/Fra1/NFAT1-c-4	-0.007	0.13	0.34	12	-0.34	77	89
IL4	-0.13	0.26	0.46	14	-0.53	239	253
IL2	-0.014	0.15	-10000	0	-0.94	27	27
IL3	-0.017	0.11	-10000	0	-0.72	23	23
FKBP1A	0.024	0.004	-10000	0	-10000	0	0
BATF3	0.021	0.015	0.26	3	-10000	0	3
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.021	0.012	0.26	1	-10000	0	1

×

Signaling events mediated by PTP1B

Figure S31. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S31. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.036	-10000	0	-0.57	4	4
Jak2/Leptin Receptor	-0.11	0.19	0.27	1	-0.4	244	245
PTP1B/AKT1	-0.067	0.13	0.22	1	-0.33	147	148
FYN	0.021	0.026	-10000	0	-0.57	2	2
p210 bcr-abl/PTP1B	-0.082	0.14	0.22	2	-0.35	162	164
EGFR	-0.2	0.28	-10000	0	-0.58	390	390
EGF/EGFR	-0.2	0.24	-10000	0	-0.41	531	531
CSF1	0.021	0.044	-10000	0	-0.57	6	6
AKT1	0.023	0.005	-10000	0	-10000	0	0
INSR	0.023	0.005	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.048	0.16	0.24	14	-0.36	142	156
Insulin Receptor/Insulin	-0.043	0.12	-10000	0	-0.37	54	54
HCK	0.027	0.026	0.26	13	-10000	0	13
CRK	0.022	0.007	-10000	0	-10000	0	0
TYK2	-0.078	0.13	0.28	3	-0.35	146	149
EGF	-0.099	0.22	0.25	2	-0.58	194	196
YES1	0.023	0.019	-10000	0	-0.57	1	1
CAV1	-0.16	0.21	0.27	2	-0.42	332	334
TXN	0.017	0.017	0.25	3	-10000	0	3
PTP1B/IRS1/GRB2	-0.073	0.15	-10000	0	-0.37	151	151
cell migration	0.082	0.14	0.35	162	-0.22	2	164
STAT3	0.022	0.004	-10000	0	-10000	0	0
PRLR	0.022	0.052	0.25	7	-0.57	7	14
ITGA2B	0.031	0.06	0.25	54	-0.57	3	57
CSF1R	0.024	0.008	0.26	1	-10000	0	1
Prolactin Receptor/Prolactin	0.031	0.043	0.31	1	-0.39	7	8
FGR	0.024	0.009	0.26	1	-10000	0	1
PTP1B/p130 Cas	-0.069	0.14	0.22	1	-0.35	141	142
Crk/p130 Cas	-0.062	0.14	-10000	0	-0.36	118	118
DOK1	-0.067	0.13	0.23	2	-0.34	131	133
JAK2	-0.048	0.12	-10000	0	-0.45	56	56
Jak2/Leptin Receptor/Leptin	-0.26	0.16	-10000	0	-0.39	441	441
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
PTPN1	-0.083	0.14	0.22	2	-0.35	162	164
LYN	0.021	0.008	-10000	0	-10000	0	0
CDH2	0.063	0.092	0.26	187	-0.57	2	189
SRC	-0.018	0.098	-10000	0	-0.62	21	21
ITGB3	0.005	0.1	0.25	4	-0.57	33	37
CAT1/PTP1B	-0.092	0.19	0.32	4	-0.45	165	169
CAPN1	0.021	0.006	-10000	0	-10000	0	0
CSK	0.024	0.004	-10000	0	-10000	0	0
PI3K	-0.038	0.12	-10000	0	-0.42	46	46
mol:H2O2	-0.004	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.24	0.14	-10000	0	-0.36	406	406
negative regulation of transcription	-0.047	0.12	-10000	0	-0.44	56	56
FCGR2A	0.02	0.012	0.26	1	-10000	0	1
FER	0.011	0.058	-10000	0	-0.58	10	10
alphaIIb/beta3 Integrin	0.023	0.09	-10000	0	-0.42	36	36
BLK	0.051	0.087	0.26	151	-0.57	2	153
Insulin Receptor/Insulin/Shc	0.035	0.019	-10000	0	-10000	0	0
RHOA	0.021	0.006	-10000	0	-10000	0	0
LEPR	-0.12	0.26	-10000	0	-0.57	266	266
BCAR1	0.021	0.008	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.023	0.009	0.26	1	-10000	0	1
mol:NADPH	-0.005	0.004	-10000	0	-10000	0	0
TRPV6	-0.041	0.17	0.32	5	-0.44	109	114
PRL	0.007	0.032	0.26	10	-10000	0	10
SOCS3	0.01	0.16	-10000	0	-1.2	16	16
SPRY2	-0.041	0.18	-10000	0	-0.57	106	106
Insulin Receptor/Insulin/IRS1	0.026	0.08	-10000	0	-0.37	41	41
CSF1/CSF1R	-0.065	0.14	-10000	0	-0.36	137	137
Ras protein signal transduction	0.051	0.15	0.64	60	-10000	0	60
IRS1	0.001	0.11	-10000	0	-0.57	42	42
INS	0.009	0.015	-10000	0	-10000	0	0
LEP	-0.44	0.24	-10000	0	-0.57	841	841
STAT5B	-0.069	0.14	0.2	3	-0.35	145	148
STAT5A	-0.07	0.14	0.2	3	-0.35	147	150
GRB2	0.023	0.009	0.26	1	-10000	0	1
PDGFB-D/PDGFRB	-0.073	0.14	0.22	1	-0.35	150	151
CSN2	0.025	0.057	0.4	1	-10000	0	1
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
LAT	-0.01	0.072	-10000	0	-0.55	9	9
YBX1	0.027	0.015	0.22	1	-10000	0	1
LCK	0.026	0.075	0.26	40	-0.57	11	51
SHC1	0.02	0.009	-10000	0	-10000	0	0
NOX4	0.019	0.036	0.25	10	-0.57	2	12

×

Neurotrophic factor-mediated Trk receptor signaling

Figure S32. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S32. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.023	0.006	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.069	0.11	-10000	0	-0.28	94	94
NT3 (dimer)/TRKC	-0.17	0.26	-10000	0	-0.46	448	448
NT3 (dimer)/TRKB	-0.29	0.3	-10000	0	-0.52	615	615
SHC/Grb2/SOS1/GAB1/PI3K	0.015	0.033	-10000	0	-0.26	8	8
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0
BDNF	-0.012	0.16	0.26	24	-0.57	75	99
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
DYNLT1	0.023	0.006	-10000	0	-10000	0	0
NTRK1	0.024	0.051	0.26	25	-0.57	4	29
NTRK2	-0.28	0.3	-10000	0	-0.57	552	552
NTRK3	-0.17	0.28	0.26	5	-0.57	347	352
NT-4/5 (dimer)/TRKB	-0.35	0.33	-10000	0	-0.56	691	691
neuron apoptosis	0.17	0.22	0.47	288	-10000	0	288
SHC 2-3/Grb2	-0.18	0.24	-10000	0	-0.52	288	288
SHC1	0.02	0.009	-10000	0	-10000	0	0
SHC2	-0.18	0.25	-10000	0	-0.54	288	288
SHC3	-0.17	0.23	-10000	0	-0.52	281	281
STAT3 (dimer)	0.033	0.043	-10000	0	-0.36	4	4
NT3 (dimer)/TRKA	-0.1	0.21	-10000	0	-0.41	303	303
RIN/GDP	-0.045	0.12	0.3	4	-0.26	84	88
GIPC1	0.024	0.008	0.26	1	-10000	0	1
KRAS	0.023	0.005	-10000	0	-10000	0	0
DNAJA3	-0.078	0.15	-10000	0	-0.33	265	265
RIN/GTP	0.014	0.008	0.18	2	-10000	0	2
CCND1	0.025	0.094	0.43	39	-0.82	4	43
MAGED1	0.025	0.01	0.26	2	-10000	0	2
PTPN11	0.024	0.002	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.18	0.28	-10000	0	-0.56	363	363
SHC/GRB2/SOS1	0.038	0.022	-10000	0	-10000	0	0
GRB2	0.023	0.009	0.26	1	-10000	0	1
NGF (dimer)/TRKA/MATK	0.035	0.082	0.34	3	-0.35	34	37
TRKA/NEDD4-2	0.031	0.04	-10000	0	-0.37	5	5
ELMO1	0.024	0.004	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.031	0.008	-10000	0	-10000	0	0
NGF	0.017	0.074	0.26	8	-0.57	16	24
HRAS	0.026	0.022	0.26	9	-10000	0	9
DOCK1	0.024	0.005	-10000	0	-10000	0	0
GAB2	0.021	0.019	-10000	0	-0.57	1	1
RIT2	0.018	0.011	0.26	2	-10000	0	2
RIT1	0.021	0.009	-10000	0	-10000	0	0
FRS2	0.024	0.011	0.26	2	-10000	0	2
DNM1	0.02	0.048	0.26	1	-0.57	7	8
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.022	0.007	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.071	0.16	-10000	0	-0.32	281	281
mol:GDP	-0.074	0.16	0.35	5	-0.36	121	126
NGF (dimer)	0.017	0.074	0.26	8	-0.56	16	24
RhoG/GDP	0.018	0.003	-10000	0	-10000	0	0
RIT1/GDP	-0.044	0.1	0.38	2	-0.25	80	82
TIAM1	0.025	0.015	0.26	4	-10000	0	4
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
BDNF (dimer)/TRKB	-0.18	0.23	-10000	0	-0.39	572	572
KIDINS220/CRKL/C3G	0.033	0.01	-10000	0	-10000	0	0
SHC/RasGAP	0.029	0.014	-10000	0	-10000	0	0
FRS2 family/SHP2	0.046	0.015	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.048	0.028	-10000	0	-10000	0	0
RIT1/GTP	0.015	0.007	-10000	0	-10000	0	0
NT3 (dimer)	-0.06	0.21	0.26	12	-0.56	157	169
RAP1/GDP	-0.041	0.093	-10000	0	-0.22	76	76
KIDINS220/CRKL	0.023	0.006	-10000	0	-10000	0	0
BDNF (dimer)	-0.012	0.16	0.26	24	-0.56	75	99
ubiquitin-dependent protein catabolic process	0.036	0.061	-10000	0	-0.36	18	18
Schwann cell development	-0.048	0.038	-10000	0	-10000	0	0
EHD4	0.024	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.055	0.023	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.02	0.048	-10000	0	-0.27	8	8
RAP1B	0.024	0.005	-10000	0	-10000	0	0
RAP1A	0.024	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.27	0.28	-10000	0	-0.46	647	647
ABL1	0.024	0.004	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
Rap1/GTP	-0.077	0.13	-10000	0	-0.43	64	64
STAT3	0.033	0.043	-10000	0	-0.36	4	4
axon guidance	-0.26	0.26	-10000	0	-0.44	647	647
MAPK3	0.024	0.085	0.24	3	-0.35	27	30
MAPK1	0.027	0.088	0.24	4	-0.35	28	32
CDC42/GDP	-0.043	0.12	0.29	5	-0.25	85	90
NTF3	-0.061	0.21	0.26	12	-0.57	157	169
NTF4	-0.18	0.28	-10000	0	-0.57	363	363
NGF (dimer)/TRKA/FAIM	0.037	0.061	-10000	0	-0.36	18	18
PI3K	0.028	0.049	-10000	0	-0.38	14	14
FRS3	0.024	0.005	-10000	0	-10000	0	0
FAIM	0.024	0.004	-10000	0	-10000	0	0
GAB1	0.024	0.004	-10000	0	-10000	0	0
RASGRF1	-0.077	0.16	0.25	3	-0.33	272	275
SOS1	0.024	0.003	-10000	0	-10000	0	0
MCF2L	-0.16	0.22	0.21	1	-0.41	425	426
RGS19	0.023	0.01	0.26	1	-10000	0	1
CDC42	0.023	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.017	0.094	0.33	3	-0.43	10	13
Rac1/GDP	-0.044	0.12	0.31	4	-0.25	91	95
NGF (dimer)/TRKA/GRIT	0.024	0.057	-10000	0	-0.34	20	20
neuron projection morphogenesis	-0.068	0.21	-10000	0	-0.74	50	50
NGF (dimer)/TRKA/NEDD4-2	0.036	0.061	-10000	0	-0.36	18	18
MAP2K1	0.029	0.085	0.36	17	-10000	0	17
NGFR	-0.14	0.26	-10000	0	-0.57	287	287
NGF (dimer)/TRKA/GIPC/GAIP	0.015	0.05	-10000	0	-0.29	21	21
RAS family/GTP/PI3K	0.017	0.03	-10000	0	-0.26	9	9
FRS2 family/SHP2/GRB2/SOS1	0.063	0.026	-10000	0	-10000	0	0
NRAS	0.024	0.004	-10000	0	-10000	0	0
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
PRKCI	0.024	0.005	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCZ	0.023	0.019	-10000	0	-0.57	1	1
MAPKKK cascade	-0.039	0.14	-10000	0	-0.65	41	41
RASA1	0.024	0.004	-10000	0	-10000	0	0
TRKA/c-Abl	0.032	0.039	-10000	0	-0.42	4	4
SQSTM1	0.024	0.008	0.26	1	-10000	0	1
BDNF (dimer)/TRKB/GIPC	-0.16	0.22	-10000	0	-0.36	566	566
NGF (dimer)/TRKA/p62/Atypical PKCs	0.052	0.062	-10000	0	-0.31	18	18
MATK	0.02	0.086	0.26	30	-0.57	18	48
NEDD4L	0.023	0.019	-10000	0	-0.57	1	1
RAS family/GDP	-0.055	0.07	-10000	0	-0.2	70	70
NGF (dimer)/TRKA	-0.085	0.16	-10000	0	-0.34	298	298
Rac1/GTP	-0.083	0.12	-10000	0	-0.27	254	254
FRS2 family/SHP2/CRK family	0.06	0.029	-10000	0	-10000	0	0

×

S1P1 pathway

Figure S33. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S33. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.017	0.044	-10000	0	-0.39	6	6
PDGFRB	0.018	0.037	-10000	0	-0.57	4	4
SPHK1	-0.018	0.097	-10000	0	-0.75	14	14
mol:S1P	-0.021	0.095	0.39	1	-0.66	14	15
S1P1/S1P/Gi	-0.13	0.23	0.31	2	-0.43	362	364
GNAO1	0.006	0.092	0.24	32	-0.57	20	52
PDGFB-D/PDGFRB/PLCgamma1	-0.11	0.21	0.34	3	-0.4	316	319
PLCG1	-0.13	0.22	0.35	2	-0.42	325	327
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.018	0.037	-10000	0	-0.57	4	4
GNAI2	0.009	0.023	-10000	0	-10000	0	0
GNAI3	0.009	0.023	-10000	0	-10000	0	0
GNAI1	-0.021	0.13	-10000	0	-0.58	57	57
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.014	0.031	0.2	1	-0.37	5	6
S1P1/S1P	-0.034	0.097	0.34	1	-0.46	18	19
negative regulation of cAMP metabolic process	-0.13	0.23	0.31	2	-0.42	362	364
MAPK3	-0.18	0.3	0.3	12	-0.58	357	369
calcium-dependent phospholipase C activity	-0.003	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.003	-10000	0	-10000	0	0
KDR	0.011	0.044	-10000	0	-0.57	5	5
PLCB2	-0.025	0.097	0.29	7	-0.41	19	26
RAC1	0.024	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.032	0.081	-10000	0	-0.39	18	18
receptor internalization	-0.035	0.088	-10000	0	-0.43	18	18
PTGS2	-0.33	0.5	0.38	2	-1	367	369
Rac1/GTP	-0.032	0.081	-10000	0	-0.39	18	18
RHOA	0.024	0.005	-10000	0	-10000	0	0
VEGFA	0.015	0.027	0.25	7	-10000	0	7
negative regulation of T cell proliferation	-0.13	0.23	0.31	2	-0.42	362	364
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.004	0.06	-10000	0	-0.57	10	10
MAPK1	-0.2	0.33	0.34	2	-0.62	372	374
S1P1/S1P/PDGFB-D/PDGFRB	-0.034	0.12	0.31	4	-0.48	17	21
ABCC1	0.012	0.019	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

Figure S34. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S34. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.024	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.017	0.019	0.18	14	-10000	0	14
Metarhodopsin II/Arrestin	0.036	0.037	0.32	2	-10000	0	2
PDE6G/GNAT1/GTP	0.035	0.033	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.023	0.027	0.26	14	-10000	0	14
GRK1	0.019	0.016	0.26	4	-10000	0	4
CNG Channel	-0.048	0.16	-10000	0	-0.3	284	284
mol:Na +	-0.047	0.16	-10000	0	-0.3	274	274
mol:ADP	0.019	0.016	0.26	4	-10000	0	4
RGS9-1/Gbeta5/R9AP	0.016	0.12	0.34	1	-0.36	86	87
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	-0.041	0.16	0.28	5	-0.3	272	277
CNGB1	0.03	0.051	0.26	52	-10000	0	52
RDH5	-0.33	0.29	-10000	0	-0.57	641	641
SAG	0.032	0.052	0.26	54	-10000	0	54
mol:Ca2+	-0.08	0.14	0.36	18	-0.49	5	23
Na + (4 Units)	-0.051	0.14	-10000	0	-0.29	250	250
RGS9	-0.024	0.16	0.26	11	-0.57	88	99
GNB1/GNGT1	0.054	0.059	0.2	159	-10000	0	159
GNAT1/GDP	0.025	0.11	0.3	5	-0.31	86	91
GUCY2D	0.024	0.044	0.26	19	-0.57	3	22
GNGT1	0.055	0.086	0.26	169	-10000	0	169
GUCY2F	0.018	0.011	0.26	2	-10000	0	2
GNB5	0.024	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	0.02	0.049	0.2	3	-0.31	16	19
mol:11-cis-retinal	-0.33	0.29	-10000	0	-0.56	641	641
mol:cGMP	0.042	0.044	-10000	0	-0.32	7	7
GNB1	0.023	0.005	-10000	0	-10000	0	0
Rhodopsin	-0.24	0.22	-10000	0	-0.42	634	634
SLC24A1	0.024	0.004	-10000	0	-10000	0	0
CNGA1	-0.14	0.26	0.26	4	-0.57	294	298
Metarhodopsin II	0.026	0.019	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.054	0.05	-10000	0	-0.34	7	7
RGS9BP	0.036	0.052	0.26	57	-10000	0	57
Metarhodopsin II/Transducin	0.024	0.031	0.17	8	-0.17	1	9
GCAP Family/Ca ++	0.044	0.037	-10000	0	-0.33	4	4
PDE6A/B	0.029	0.064	-10000	0	-0.38	21	21
mol:Pi	0.016	0.12	0.33	1	-0.36	86	87
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.058	0.053	0.32	2	-10000	0	2
PDE6B	0.014	0.077	0.26	3	-0.57	18	21
PDE6A	0.028	0.032	0.26	20	-10000	0	20
PDE6G	0.032	0.045	0.26	42	-10000	0	42
RHO	0.024	0.028	0.26	15	-10000	0	15
PDE6	0.035	0.12	0.3	8	-0.31	97	105
GUCA1A	0.031	0.045	0.26	42	-10000	0	42
GC2/GCAP Family	0.054	0.039	-10000	0	-0.34	4	4
GUCA1C	0.017	0.008	0.26	1	-10000	0	1
GUCA1B	0.022	0.036	-10000	0	-0.57	4	4

×

Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)

Figure S35. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S35. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.041	0.17	-10000	0	-0.42	172	172
CRKL	-0.047	0.15	0.31	2	-0.4	87	89
mol:PIP3	0.002	0.059	0.56	1	-0.89	4	5
AKT1	0.01	0.074	0.37	3	-0.79	4	7
PTK2B	0.02	0.009	-10000	0	-10000	0	0
RAPGEF1	-0.046	0.14	0.33	2	-0.4	73	75
RANBP10	0.022	0.008	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
HGF/MET/SHIP2	-0.042	0.18	-10000	0	-0.38	214	214
MAP3K5	-0.04	0.15	0.36	1	-0.44	61	62
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.03	0.17	-10000	0	-0.35	222	222
AP1	-0.11	0.19	-10000	0	-0.39	307	307
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
apoptosis	-0.24	0.38	-10000	0	-0.77	356	356
STAT3 (dimer)	-0.047	0.15	-10000	0	-0.45	82	82
GAB1/CRKL/SHP2/PI3K	-0.02	0.15	-10000	0	-0.44	58	58
INPP5D	0.024	0.004	-10000	0	-10000	0	0
CBL/CRK	-0.036	0.14	0.34	1	-0.42	64	65
PTPN11	0.024	0.002	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.023	0.005	-10000	0	-10000	0	0
PTEN	0.022	0.019	-10000	0	-0.57	1	1
ELK1	-0.03	0.096	0.29	25	-0.22	36	61
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.026	0.092	-10000	0	-0.32	41	41
PAK1	0.024	0.087	0.36	7	-0.75	4	11
HGF/MET/RANBP10	-0.045	0.18	-10000	0	-0.38	223	223
HRAS	-0.11	0.26	-10000	0	-0.64	193	193
DOCK1	-0.046	0.14	0.52	1	-0.41	71	72
GAB1	-0.05	0.15	-10000	0	-0.42	95	95
CRK	-0.049	0.15	0.36	1	-0.41	85	86
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.1	0.25	-10000	0	-0.57	231	231
JUN	0.02	0.044	-10000	0	-0.57	6	6
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.052	0.12	-10000	0	-0.28	226	226
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
cell morphogenesis	-0.049	0.16	0.37	6	-0.45	88	94
GRB2/SHC	-0.016	0.11	-10000	0	-0.28	123	123
FOS	-0.14	0.27	-10000	0	-0.57	306	306
GLMN	0.003	0.001	-10000	0	-10000	0	0
cell motility	-0.03	0.095	0.29	25	-0.22	39	64
HGF/MET/MUC20	-0.055	0.17	-10000	0	-0.38	225	225
cell migration	-0.016	0.11	-10000	0	-0.28	123	123
GRB2	0.023	0.009	0.26	1	-10000	0	1
CBL	0.022	0.007	-10000	0	-10000	0	0
MET/RANBP10	-0.042	0.17	-10000	0	-0.41	180	180
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.048	0.14	-10000	0	-0.33	186	186
MET/MUC20	-0.055	0.16	-10000	0	-0.4	186	186
RAP1B	-0.039	0.14	0.33	4	-0.43	48	52
RAP1A	-0.045	0.13	0.32	3	-0.38	70	73
HGF/MET/RANBP9	-0.043	0.18	-10000	0	-0.38	218	218
RAF1	-0.099	0.24	-10000	0	-0.6	192	192
STAT3	-0.048	0.15	-10000	0	-0.45	82	82
cell proliferation	-0.042	0.19	0.32	12	-0.42	159	171
RPS6KB1	-0.015	0.063	-10000	0	-0.26	22	22
MAPK3	-0.042	0.093	0.62	8	-10000	0	8
MAPK1	-0.011	0.17	0.68	54	-10000	0	54
RANBP9	0.023	0.005	-10000	0	-10000	0	0
MAPK8	-0.029	0.14	0.43	1	-0.47	41	42
SRC	-0.052	0.13	0.2	1	-0.4	75	76
PI3K	-0.028	0.13	-10000	0	-0.29	180	180
MET/Glomulin	-0.047	0.14	-10000	0	-0.37	179	179
SOS1	0.024	0.003	-10000	0	-10000	0	0
MAP2K1	-0.091	0.23	0.47	1	-0.55	192	193
MET	-0.073	0.22	-10000	0	-0.57	177	177
MAP4K1	-0.042	0.15	0.38	1	-0.46	67	68
PTK2	0.019	0.01	-10000	0	-10000	0	0
MAP2K2	-0.09	0.23	0.47	1	-0.55	192	193
BAD	0.008	0.071	0.34	4	-0.75	4	8
MAP2K4	-0.037	0.13	0.34	1	-0.42	52	53
SHP2/GRB2/SOS1/GAB1	-0.041	0.17	-10000	0	-0.4	174	174
INPPL1	0.023	0.006	-10000	0	-10000	0	0
PXN	0.024	0.002	-10000	0	-10000	0	0
SH3KBP1	0.024	0.003	-10000	0	-10000	0	0
HGS	-0.048	0.11	-10000	0	-0.27	206	206
PLCgamma1/PKC	0.017	0.004	-10000	0	-10000	0	0
HGF	-0.011	0.14	0.26	2	-0.57	65	67
RASA1	0.024	0.004	-10000	0	-10000	0	0
NCK1	0.024	0.003	-10000	0	-10000	0	0
PTPRJ	0.024	0.004	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.022	0.13	-10000	0	-0.26	210	210
PDPK1	0.012	0.077	0.42	1	-0.83	4	5
HGF/MET/SHIP	-0.043	0.18	-10000	0	-0.38	224	224

×

Aurora C signaling

Figure S36. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S36. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.024	0.005	-10000	0	-10000	0	0
Aurora C/Aurora B/INCENP	0.11	0.078	0.31	10	-0.3	1	11
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	0.019	0.019	-10000	0	-0.3	2	2
AURKB	0.14	0.12	0.26	560	-10000	0	560
AURKC	0.026	0.032	0.26	14	-0.57	1	15

×

TCR signaling in naïve CD8+ T cells

Figure S37. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S37. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.043	0.17	0.3	134	-0.45	57	191
FYN	0.02	0.19	0.32	63	-0.52	71	134
LAT/GRAP2/SLP76	0.026	0.17	0.34	47	-0.5	57	104
IKBKB	0.02	0.009	-10000	0	-10000	0	0
AKT1	0.022	0.15	0.3	83	-0.36	85	168
B2M	0.024	0.008	-10000	0	-10000	0	0
IKBKG	0.016	0.058	0.16	74	-0.14	28	102
MAP3K8	0.02	0.048	-10000	0	-0.57	7	7
mol:Ca2+	-0.022	0.032	-10000	0	-0.089	170	170
integrin-mediated signaling pathway	0.026	0.022	-10000	0	-0.29	3	3
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.01	0.2	0.35	50	-0.52	82	132
TRPV6	-0.089	0.26	1.2	15	-0.57	195	210
CD28	0.024	0.05	0.26	10	-0.57	6	16
SHC1	0.029	0.21	0.31	158	-0.45	103	261
receptor internalization	-0.012	0.22	0.35	36	-0.47	144	180
PRF1	-0.011	0.24	0.55	7	-0.97	43	50
KRAS	0.023	0.005	-10000	0	-10000	0	0
GRB2	0.023	0.009	0.26	1	-10000	0	1
COT/AKT1	0.031	0.13	0.29	76	-0.3	79	155
LAT	0.012	0.2	0.32	72	-0.46	102	174
EntrezGene:6955	0.001	0.003	-10000	0	-10000	0	0
CD3D	0.023	0.095	0.26	49	-0.57	19	68
CD3E	0.023	0.086	0.27	37	-0.58	16	53
CD3G	0.012	0.11	0.26	38	-0.57	33	71
RASGRP2	0	0.05	0.14	15	-0.17	70	85
RASGRP1	0.024	0.15	0.32	54	-0.4	61	115
HLA-A	0.001	0.005	-10000	0	-10000	0	0
RASSF5	0.019	0.033	0.26	1	-0.57	3	4
RAP1A/GTP/RAPL	0.026	0.022	-10000	0	-0.29	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.039	0.079	0.17	169	-0.13	28	197
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.014	0.055	-10000	0	-0.21	42	42
PRKCA	0.014	0.098	0.22	55	-0.26	57	112
GRAP2	0.017	0.063	0.25	3	-0.57	12	15
mol:IP3	0.014	0.14	0.26	129	-0.38	52	181
EntrezGene:6957	0.001	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.005	0.17	0.3	36	-0.66	48	84
ORAI1	0.037	0.17	0.64	4	-0.96	15	19
CSK	0.007	0.2	0.35	40	-0.46	107	147
B7 family/CD28	0.062	0.21	0.39	60	-0.59	53	113
CHUK	0.024	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0	0.22	0.37	38	-0.5	116	154
PTPN6	0.003	0.19	0.33	45	-0.46	101	146
VAV1	0.003	0.2	0.35	42	-0.47	104	146
Monovalent TCR/CD3	-0.001	0.14	0.26	39	-0.5	56	95
CBL	0.022	0.007	-10000	0	-10000	0	0
LCK	0.017	0.2	0.32	64	-0.57	65	129
PAG1	0.02	0.2	0.31	75	-0.45	104	179
RAP1A	0.024	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0	0.22	0.36	37	-0.49	114	151
CD80	0.084	0.1	0.26	279	-10000	0	279
CD86	0.026	0.018	0.26	6	-10000	0	6
PDK1/CARD11/BCL10/MALT1	-0.005	0.071	0.19	4	-0.25	44	48
HRAS	0.026	0.022	0.26	9	-10000	0	9
GO:0035030	0.021	0.16	0.32	44	-0.48	54	98
CD8A	0.029	0.058	0.27	29	-0.58	5	34
CD8B	0.014	0.11	0.27	30	-0.57	32	62
PTPRC	0.021	0.041	0.26	12	-0.57	3	15
PDK1/PKC theta	0.024	0.18	0.37	80	-0.45	75	155
CSK/PAG1	0.021	0.19	0.31	70	-0.53	67	137
SOS1	0.024	0.003	-10000	0	-10000	0	0
peptide-MHC class I	0.019	0.01	-10000	0	-10000	0	0
GRAP2/SLP76	0.019	0.2	0.38	35	-0.48	90	125
STIM1	0.025	0.095	1.3	4	-10000	0	4
RAS family/GTP	0.044	0.091	0.22	90	-0.18	39	129
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.016	0.23	0.35	36	-0.5	144	180
mol:DAG	-0.016	0.096	0.12	32	-0.32	64	96
RAP1A/GDP	0.021	0.038	0.098	94	-0.065	9	103
PLCG1	0.023	0.005	-10000	0	-10000	0	0
CD247	0.016	0.077	0.26	16	-0.57	15	31
cytotoxic T cell degranulation	-0.008	0.22	0.54	7	-0.9	43	50
RAP1A/GTP	-0.001	0.017	-10000	0	-0.063	68	68
mol:PI-3-4-5-P3	0.017	0.17	0.33	55	-0.43	82	137
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.022	0.17	0.29	119	-0.48	54	173
NRAS	0.024	0.004	-10000	0	-10000	0	0
ZAP70	0.027	0.098	0.26	61	-0.57	20	81
GRB2/SOS1	0.034	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.006	0.16	0.36	16	-0.5	55	71
MALT1	0.023	0.005	-10000	0	-10000	0	0
TRAF6	0.024	0.004	-10000	0	-10000	0	0
CD8 heterodimer	0.032	0.11	0.38	21	-0.48	32	53
CARD11	0.027	0.041	0.26	21	-0.57	2	23
PRKCB	0.014	0.1	0.25	52	-0.27	45	97
PRKCE	0.019	0.095	0.22	62	-0.26	45	107
PRKCQ	0.012	0.2	0.35	55	-0.5	82	137
LCP2	0.024	0.008	0.25	1	-10000	0	1
BCL10	0.024	0.004	-10000	0	-10000	0	0
regulation of survival gene product expression	0.025	0.14	0.29	86	-0.31	83	169
IKK complex	0.035	0.08	0.21	121	-0.12	27	148
RAS family/GDP	-0.001	0.01	-10000	0	-10000	0	0
MAP3K14	0.025	0.11	0.25	77	-0.26	49	126
PDPK1	0.027	0.15	0.33	81	-0.35	75	156
TCR/CD3/MHC I/CD8/Fyn	-0.028	0.24	0.39	29	-0.57	116	145

×

Effects of Botulinum toxin

Figure S38. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S38. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.01	0.024	0.13	40	-10000	0	40
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.031	0.11	-10000	0	-0.41	46	46
STXBP1	0.02	0.048	-10000	0	-0.57	7	7
ACh/CHRNA1	0.072	0.09	0.19	351	-0.16	8	359
RAB3GAP2/RIMS1/UNC13B	0.035	0.087	-10000	0	-0.36	33	33
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.023	0.14	0.26	117	-0.57	45	162
mol:ACh	-0.003	0.036	0.089	12	-0.14	43	55
RAB3GAP2	0.02	0.009	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.021	0.082	0.23	1	-0.27	43	44
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.072	0.09	0.19	351	-0.15	8	359
UNC13B	0.024	0.004	-10000	0	-10000	0	0
CHRNA1	0.1	0.11	0.26	362	-10000	0	362
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.032	0.11	0.2	196	-0.36	43	239
SNAP25	0	0.058	0.094	59	-0.3	34	93
VAMP2	0.004	0.001	-10000	0	-10000	0	0
SYT1	0.046	0.15	0.26	204	-0.57	39	243
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.023	0.036	-10000	0	-0.36	7	7
STX1A/SNAP25 fragment 1/VAMP2	0.021	0.082	0.23	1	-0.27	43	44

×

ErbB4 signaling events

Figure S39. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S39. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.015	0.081	0.28	1	-0.33	2	3
epithelial cell differentiation	0.032	0.08	0.39	1	-0.43	3	4
ITCH	0.032	0.018	-10000	0	-10000	0	0
WWP1	0.022	0.097	0.46	8	-10000	0	8
FYN	0.021	0.026	-10000	0	-0.57	2	2
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
PRL	0.022	0.023	0.26	10	-10000	0	10
neuron projection morphogenesis	-0.041	0.14	0.37	13	-0.36	34	47
PTPRZ1	-0.27	0.3	0.26	6	-0.57	541	547
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.053	0.14	-10000	0	-0.38	42	42
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.087	0.15	-10000	0	-0.34	243	243
ADAM17	0.031	0.019	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.007	0.074	0.38	8	-0.3	6	14
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.002	0.11	-10000	0	-0.36	41	41
NCOR1	0.022	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.079	0.15	-10000	0	-0.32	232	232
GRIN2B	-0.097	0.16	-10000	0	-0.32	261	261
ErbB4/ErbB2/betacellulin	0.013	0.097	-10000	0	-0.32	32	32
STAT1	0.028	0.031	0.26	19	-10000	0	19
HBEGF	0.023	0.026	-10000	0	-0.57	2	2
PRLR	0.021	0.051	0.26	7	-0.57	7	14
E4ICDs/ETO2	0.006	0.087	0.35	1	-0.4	11	12
axon guidance	0.054	0.11	0.4	8	-0.37	2	10
NEDD4	0.03	0.018	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	0.031	0.04	-10000	0	-0.39	7	7
CBFA2T3	0.014	0.071	0.26	4	-0.57	15	19
ErbB4/ErbB2/HBEGF	0.03	0.072	-10000	0	-0.34	3	3
MAPK3	-0.047	0.14	0.34	4	-0.36	41	45
STAT1 (dimer)	0.019	0.081	-10000	0	-10000	0	0
MAPK1	-0.047	0.14	0.36	5	-0.36	41	46
JAK2	0.023	0.006	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.071	0.15	0.27	1	-0.32	220	221
NRG1	-0.1	0.19	-10000	0	-0.42	288	288
NRG3	0.001	0.13	0.26	24	-0.57	50	74
NRG2	-0.26	0.29	-10000	0	-0.57	509	509
NRG4	0.026	0.028	0.26	15	-10000	0	15
heart development	0.054	0.11	0.4	8	-0.37	2	10
neural crest cell migration	-0.07	0.15	0.27	1	-0.32	222	223
ERBB2	0.035	0.071	0.27	87	-0.41	1	88
WWOX/E4ICDs	0.011	0.076	0.28	1	-10000	0	1
SHC1	0.02	0.009	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.097	0.16	-10000	0	-0.32	278	278
apoptosis	0.012	0.12	0.46	47	-0.26	2	49
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.15	0.17	-10000	0	-0.34	389	389
ErbB4/ErbB2/epiregulin	0.007	0.13	0.35	12	-0.31	76	88
ErbB4/ErbB4/betacellulin/betacellulin	-0.004	0.11	0.28	1	-0.35	45	46
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.04	0.087	0.39	1	-0.4	6	7
MDM2	0.008	0.079	0.29	8	-10000	0	8
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.083	0.14	-10000	0	-0.32	244	244
STAT5A	0.049	0.11	0.36	12	-0.37	3	15
ErbB4/EGFR/neuregulin 1 beta	-0.18	0.23	-10000	0	-0.43	426	426
DLG4	0.022	0.007	-10000	0	-10000	0	0
GRB2/SHC	0.028	0.016	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.01	0.07	-10000	0	-10000	0	0
STAT5A (dimer)	0.059	0.1	0.45	1	-0.46	3	4
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.06	0.11	0.35	6	-0.35	3	9
LRIG1	0.022	0.031	-10000	0	-0.57	3	3
EREG	-0.024	0.2	0.26	77	-0.57	116	193
BTC	-0.007	0.13	0.26	2	-0.57	57	59
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.044	0.11	0.4	7	-0.37	2	9
ERBB4	-0.007	0.074	0.38	8	-0.3	6	14
STAT5B	0.022	0.026	-10000	0	-0.57	2	2
YAP1	-0.013	0.11	0.22	3	-0.39	74	77
GRB2	0.023	0.009	0.26	1	-10000	0	1
ErbB4/ErbB2/neuregulin 4	0.033	0.071	0.32	1	-0.41	1	2
glial cell differentiation	-0.01	0.07	-10000	0	-10000	0	0
WWOX	0.021	0.013	0.26	2	-10000	0	2
cell proliferation	-0.038	0.17	0.34	14	-0.45	47	61

×

Glypican 1 network

Figure S40. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S40. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.1	0.19	-10000	0	-0.36	330	330
fibroblast growth factor receptor signaling pathway	-0.1	0.18	-10000	0	-0.36	330	330
LAMA1	-0.034	0.18	0.26	3	-0.57	105	108
PRNP	0.015	0.072	-10000	0	-0.57	16	16
GPC1/SLIT2	-0.015	0.14	-10000	0	-0.42	117	117
SMAD2	-0.001	0.068	0.24	1	-0.33	42	43
GPC1/PrPc/Cu2+	0.026	0.05	-10000	0	-0.36	17	17
GPC1/Laminin alpha1	-0.011	0.14	-10000	0	-0.42	106	106
TDGF1	0.019	0.048	0.26	1	-0.57	7	8
CRIPTO/GPC1	0.031	0.042	-10000	0	-0.42	8	8
APP/GPC1	0.035	0.02	-10000	0	-0.42	1	1
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.006	0.034	-10000	0	-0.36	8	8
FLT1	0.023	0.006	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.031	0.082	-10000	0	-0.36	43	43
SERPINC1	0.031	0.05	0.26	50	-10000	0	50
FYN	0.005	0.037	-10000	0	-0.36	10	10
FGR	0.006	0.034	-10000	0	-0.36	8	8
positive regulation of MAPKKK cascade	0.011	0.079	0.28	3	-0.36	23	26
SLIT2	-0.04	0.18	-10000	0	-0.57	116	116
GPC1/NRG	-0.11	0.2	-10000	0	-0.42	293	293
NRG1	-0.14	0.26	0.26	4	-0.57	292	296
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.045	0.025	-10000	0	-0.36	1	1
LYN	0.006	0.031	-10000	0	-0.36	6	6
mol:Spermine	0.006	0.016	-10000	0	-0.42	1	1
cell growth	-0.1	0.18	-10000	0	-0.36	330	330
BMP signaling pathway	-0.025	0.025	0.56	1	-0.26	6	7
SRC	0.006	0.034	-10000	0	-0.36	8	8
TGFBR1	0.024	0.008	0.26	1	-10000	0	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.14	0.27	0.26	26	-0.57	310	336
GPC1	0.025	0.025	0.26	6	-0.57	1	7
TGFBR1 (dimer)	0.024	0.008	0.26	1	-10000	0	1
VEGFA	0.025	0.019	0.26	7	-10000	0	7
BLK	0.021	0.062	-10000	0	-0.37	10	10
HCK	0.008	0.037	-10000	0	-0.36	8	8
FGF2	-0.2	0.29	-10000	0	-0.57	413	413
FGFR1	0.016	0.048	-10000	0	-0.57	7	7
VEGFR1 homodimer	0.023	0.006	-10000	0	-10000	0	0
TGFBR2	0.001	0.11	-10000	0	-0.57	42	42
cell death	0.035	0.02	-10000	0	-0.42	1	1
ATIII/GPC1	0.037	0.04	-10000	0	-0.42	1	1
PLA2G2A/GPC1	-0.098	0.21	-10000	0	-0.42	310	310
LCK	0.007	0.056	-10000	0	-0.36	19	19
neuron differentiation	-0.11	0.2	-10000	0	-0.42	293	293
PrPc/Cu2+	0.011	0.053	-10000	0	-0.42	16	16
APP	0.024	0.005	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.001	0.11	-10000	0	-0.56	42	42

×

IL6-mediated signaling events

Figure S41. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S41. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.028	0.22	0.63	2	-0.64	29	31
CRP	-0.006	0.24	0.59	15	-0.68	23	38
cell cycle arrest	-0.039	0.25	0.55	12	-0.67	48	60
TIMP1	-0.021	0.21	0.61	2	-0.63	21	23
IL6ST	-0.037	0.19	-10000	0	-0.56	120	120
Rac1/GDP	-0.069	0.2	0.38	2	-0.46	108	110
AP1	-0.073	0.21	0.37	1	-0.55	63	64
GAB2	0.022	0.02	-10000	0	-0.57	1	1
TNFSF11	-0.018	0.24	0.6	12	-0.65	28	40
HSP90B1	0.022	0.11	-10000	0	-0.74	13	13
GAB1	0.024	0.004	-10000	0	-10000	0	0
MAPK14	-0.095	0.18	-10000	0	-0.52	92	92
AKT1	0.022	0.066	-10000	0	-0.66	4	4
FOXO1	0.023	0.068	0.43	1	-0.54	5	6
MAP2K6	-0.096	0.18	0.27	2	-0.46	130	132
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	-0.053	0.2	0.38	13	-0.48	85	98
MITF	-0.09	0.19	0.26	11	-0.41	177	188
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.024	0.004	-10000	0	-10000	0	0
A2M	-0.003	0.18	-10000	0	-1.2	25	25
CEBPB	0.021	0.018	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.018	0.13	-10000	0	-0.52	33	33
STAT3	-0.045	0.26	0.56	11	-0.73	48	59
STAT1	0.012	0.093	-10000	0	-0.83	10	10
CEBPD	-0.014	0.23	0.57	9	-0.66	32	41
PIK3CA	0.024	0.005	-10000	0	-10000	0	0
PI3K	0.029	0.05	-10000	0	-0.38	14	14
JUN	0.02	0.044	-10000	0	-0.57	6	6
PIAS3/MITF	-0.072	0.18	0.32	2	-0.46	97	99
MAPK11	-0.094	0.18	-10000	0	-0.53	91	91
STAT3 (dimer)/FOXO1	-0.026	0.22	0.51	13	-0.56	46	59
GRB2/SOS1/GAB family	-0.061	0.18	-10000	0	-0.48	77	77
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.1	0.19	0.24	1	-0.34	313	314
GRB2	0.023	0.009	0.26	1	-10000	0	1
JAK2	0.023	0.006	-10000	0	-10000	0	0
LBP	-0.17	0.46	0.61	13	-0.92	259	272
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
JAK1	0.026	0.008	-10000	0	-10000	0	0
MYC	-0.004	0.27	0.54	26	-0.91	37	63
FGG	-0.026	0.23	0.6	12	-0.64	31	43
macrophage differentiation	-0.039	0.25	0.55	12	-0.67	48	60
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.092	0.21	-10000	0	-0.35	355	355
JUNB	-0.03	0.22	0.6	2	-0.62	30	32
FOS	-0.14	0.27	-10000	0	-0.57	306	306
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.092	0.2	0.29	11	-0.42	181	192
STAT1/PIAS1	-0.061	0.2	0.35	11	-0.39	169	180
GRB2/SOS1/GAB family/SHP2/PI3K	0.023	0.07	-10000	0	-0.52	8	8
STAT3 (dimer)	-0.044	0.26	0.56	11	-0.72	47	58
PRKCD	-0.037	0.2	0.44	17	-0.51	61	78
IL6R	0.001	0.11	-10000	0	-0.56	38	38
SOCS3	-0.092	0.19	-10000	0	-0.65	50	50
gp130 (dimer)/JAK1/JAK1/LMO4	0.012	0.13	-10000	0	-0.35	120	120
Rac1/GTP	-0.064	0.2	0.34	10	-0.47	102	112
HCK	0.026	0.026	0.26	13	-10000	0	13
MAPKKK cascade	-0.002	0.14	-10000	0	-0.62	30	30
bone resorption	-0.015	0.23	0.59	12	-0.61	28	40
IRF1	-0.031	0.22	0.52	11	-0.63	33	44
mol:GDP	-0.084	0.19	0.28	12	-0.4	176	188
SOS1	0.024	0.004	-10000	0	-10000	0	0
VAV1	-0.085	0.2	0.28	12	-0.41	176	188
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.1	0.2	-10000	0	-0.58	97	97
PTPN11	0.011	0.081	-10000	0	-0.84	8	8
IL6/IL6RA	-0.12	0.22	-10000	0	-0.39	377	377
gp130 (dimer)/TYK2/TYK2/LMO4	0.007	0.13	-10000	0	-0.35	120	120
gp130 (dimer)/JAK2/JAK2/LMO4	0.007	0.13	-10000	0	-0.35	114	114
IL6	-0.18	0.28	0.27	1	-0.56	380	381
PIAS3	0.02	0.009	-10000	0	-10000	0	0
PTPRE	0.008	0.035	-10000	0	-0.57	2	2
PIAS1	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.004	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.19	0.22	2	-0.33	332	334
LMO4	0.028	0.036	0.28	2	-0.56	3	5
STAT3 (dimer)/PIAS3	-0.049	0.24	0.53	10	-0.68	48	58
MCL1	0.053	0.098	0.49	1	-0.55	5	6

×

amb2 Integrin signaling

Figure S42. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S42. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.006	0.07	0.34	1	-0.33	10	11
alphaM/beta2 Integrin/GPIbA	0.01	0.075	0.33	4	-0.4	6	10
alphaM/beta2 Integrin/proMMP-9	0.074	0.11	0.34	17	-0.41	1	18
PLAUR	0.042	0.062	0.26	83	-10000	0	83
HMGB1	-0.003	0.04	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.009	0.063	0.34	1	-10000	0	1
AGER	-0.006	0.05	0.26	1	-0.47	3	4
RAP1A	0.024	0.004	-10000	0	-10000	0	0
SELPLG	0.024	0.003	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.025	0.14	0.32	4	-0.36	14	18
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.12	0.12	0.26	453	-0.57	1	454
CYR61	-0.004	0.12	-10000	0	-0.57	51	51
TLN1	0.024	0.004	-10000	0	-10000	0	0
Rap1/GTP	-0.001	0.11	-10000	0	-0.37	33	33
RHOA	0.024	0.005	-10000	0	-10000	0	0
P-selectin oligomer	-0.092	0.23	-10000	0	-0.56	205	205
MYH2	-0.013	0.14	0.29	8	-0.47	36	44
MST1R	0.022	0.053	0.26	10	-0.57	7	17
leukocyte activation during inflammatory response	-0.18	0.17	0.29	1	-0.33	587	588
APOB	-0.33	0.29	-10000	0	-0.57	647	647
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.018	0.048	0.26	1	-0.57	7	8
JAM3	0.019	0.041	-10000	0	-0.57	5	5
GP1BA	0.024	0.057	0.26	26	-0.57	6	32
alphaM/beta2 Integrin/CTGF	0.004	0.077	0.34	1	-0.4	13	14
alphaM/beta2 Integrin	-0.012	0.12	0.2	7	-0.4	41	48
JAM3 homodimer	0.019	0.041	-10000	0	-0.56	5	5
ICAM2	0.019	0.041	-10000	0	-0.57	5	5
ICAM1	0.027	0.027	0.26	15	-10000	0	15
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.011	0.12	0.22	6	-0.39	43	49
cell adhesion	0.01	0.075	0.33	4	-0.4	6	10
NFKB1	-0.098	0.2	0.41	5	-0.37	335	340
THY1	0.024	0.021	0.26	8	-10000	0	8
RhoA/GDP	0.018	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	-0.21	0.19	-10000	0	-0.36	646	646
alphaM/beta2 Integrin/LRP/tPA	0.008	0.09	0.34	1	-0.38	27	28
IL6	-0.26	0.39	0.36	4	-0.76	391	395
ITGB2	-0.002	0.052	0.26	16	-10000	0	16
elevation of cytosolic calcium ion concentration	0.031	0.085	0.33	20	-10000	0	20
alphaM/beta2 Integrin/JAM2/JAM3	0	0.1	0.34	1	-0.38	47	48
JAM2	-0.007	0.13	-10000	0	-0.57	55	55
alphaM/beta2 Integrin/ICAM1	0.024	0.086	0.33	4	-0.33	17	21
alphaM/beta2 Integrin/uPA/Plg	0.019	0.07	0.33	1	-10000	0	1
RhoA/GTP	-0.018	0.15	0.24	15	-0.47	44	59
positive regulation of phagocytosis	-0.001	0.1	0.3	5	-0.36	19	24
Ron/MSP	0.03	0.061	0.36	1	-0.4	18	19
alphaM/beta2 Integrin/uPAR/uPA	0.032	0.087	0.34	20	-10000	0	20
alphaM/beta2 Integrin/uPAR	0.02	0.079	0.38	4	-10000	0	4
PLAU	0.03	0.036	0.26	26	-10000	0	26
PLAT	0.006	0.091	0.26	1	-0.57	26	27
actin filament polymerization	-0.011	0.14	0.29	8	-0.45	35	43
MST1	0.021	0.055	0.26	8	-0.57	8	16
alphaM/beta2 Integrin/lipoprotein(a)	-0.18	0.17	0.32	1	-0.33	587	588
TNF	-0.098	0.2	0.39	3	-0.76	17	20
RAP1B	0.024	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.013	0.068	0.34	1	-10000	0	1
fibrinolysis	0.017	0.069	0.32	1	-10000	0	1
HCK	0.027	0.026	0.26	13	-10000	0	13
dendritic cell antigen processing and presentation	-0.011	0.12	0.22	6	-0.39	43	49
VTN	0.033	0.077	0.26	68	-0.57	8	76
alphaM/beta2 Integrin/CYR61	-0.008	0.1	0.34	1	-0.4	48	49
LPA	0.018	0.017	0.26	5	-10000	0	5
LRP1	0.018	0.062	-10000	0	-0.57	12	12
cell migration	0.043	0.083	0.28	15	-0.36	8	23
FN1	0.11	0.11	0.26	421	-10000	0	421
alphaM/beta2 Integrin/Thy1	0.01	0.063	0.34	1	-10000	0	1
MPO	-0.01	0.13	0.26	2	-0.57	58	60
KNG1	0.023	0.032	0.26	20	-10000	0	20
RAP1/GDP	0.031	0.008	-10000	0	-10000	0	0
ROCK1	-0.012	0.15	0.28	14	-0.47	38	52
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.018	0.021	0.26	8	-10000	0	8
CTGF	0.016	0.068	0.26	3	-0.57	14	17
alphaM/beta2 Integrin/Hck	0.011	0.067	0.35	5	-10000	0	5
ITGAM	-0.003	0.043	0.25	5	-10000	0	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.043	0.16	0.34	1	-0.36	185	186
HP	-0.07	0.22	0.26	34	-0.57	178	212
leukocyte adhesion	-0.039	0.14	0.28	4	-0.43	39	43
SELP	-0.092	0.23	-10000	0	-0.57	205	205

×

LPA receptor mediated events

Figure S43. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S43. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.033	0.077	-10000	0	-0.34	40	40
NF kappa B1 p50/RelA/I kappa B alpha	0.002	0.12	-10000	0	-0.41	17	17
AP1	-0.093	0.19	-10000	0	-0.33	388	388
mol:PIP3	-0.13	0.18	-10000	0	-0.34	416	416
AKT1	0.006	0.08	0.3	4	-0.42	13	17
PTK2B	-0.027	0.1	-10000	0	-0.34	55	55
RHOA	0.003	0.061	0.26	2	-0.3	27	29
PIK3CB	0.024	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.013	0.11	0.28	3	-0.28	95	98
MAGI3	0.023	0.018	-10000	0	-0.56	1	1
RELA	0.023	0.005	-10000	0	-10000	0	0
apoptosis	-0.025	0.12	-10000	0	-0.32	143	143
HRAS/GDP	0.019	0.015	0.18	9	-10000	0	9
positive regulation of microtubule depolymerization	-0.05	0.12	0.26	3	-0.32	121	124
NF kappa B1 p50/RelA	-0.011	0.12	-10000	0	-0.33	96	96
endothelial cell migration	0.002	0.081	0.26	1	-0.42	33	34
ADCY4	-0.023	0.12	-10000	0	-0.49	45	45
ADCY5	-0.076	0.15	-10000	0	-0.48	84	84
ADCY6	-0.015	0.099	-10000	0	-0.46	35	35
ADCY7	-0.014	0.098	-10000	0	-0.47	34	34
ADCY1	-0.017	0.11	-10000	0	-0.48	39	39
ADCY2	-0.029	0.13	-10000	0	-0.5	51	51
ADCY3	-0.015	0.099	-10000	0	-0.46	35	35
ADCY8	-0.012	0.091	-10000	0	-0.45	30	30
ADCY9	-0.015	0.098	-10000	0	-0.46	35	35
GSK3B	-0.026	0.099	0.24	6	-0.34	49	55
arachidonic acid secretion	-0.019	0.11	-10000	0	-0.37	68	68
GNG2	0.017	0.065	-10000	0	-0.57	13	13
TRIP6	0.018	0.015	-10000	0	-0.4	1	1
GNAO1	0.002	0.083	-10000	0	-0.36	47	47
HRAS	0.026	0.022	0.26	9	-10000	0	9
NFKBIA	-0.02	0.13	0.28	3	-0.34	101	104
GAB1	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.027	0.12	-10000	0	-0.81	22	22
JUN	0.02	0.044	-10000	0	-0.57	6	6
LPA/LPA2/NHERF2	0.031	0.017	-10000	0	-10000	0	0
TIAM1	0.012	0.14	-10000	0	-0.95	22	22
PIK3R1	0.016	0.065	-10000	0	-0.56	13	13
mol:IP3	-0.013	0.11	0.28	3	-0.29	95	98
PLCB3	0.025	0.045	0.2	3	-10000	0	3
FOS	-0.14	0.27	-10000	0	-0.57	306	306
positive regulation of mitosis	-0.019	0.11	-10000	0	-0.37	68	68
LPA/LPA1-2-3	0.002	0.14	-10000	0	-0.33	142	142
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.021	0.008	-10000	0	-10000	0	0
stress fiber formation	-0.016	0.1	-10000	0	-0.38	42	42
GNAZ	0.003	0.07	-10000	0	-0.34	40	40
EGFR/PI3K-beta/Gab1	-0.13	0.2	-10000	0	-0.35	416	416
positive regulation of dendritic cell cytokine production	0	0.13	-10000	0	-0.33	142	142
LPA/LPA2/MAGI-3	0.033	0.02	-10000	0	-0.35	1	1
ARHGEF1	0.018	0.07	-10000	0	-0.3	25	25
GNAI2	0.006	0.06	-10000	0	-0.33	32	32
GNAI3	0.006	0.06	-10000	0	-0.33	32	32
GNAI1	-0.013	0.11	-10000	0	-0.37	83	83
LPA/LPA3	-0.025	0.14	0.18	39	-0.41	123	162
LPA/LPA2	0.019	0.015	0.18	2	-10000	0	2
LPA/LPA1	0.011	0.071	-10000	0	-0.38	33	33
HB-EGF/EGFR	-0.079	0.2	0.27	2	-0.34	362	364
HBEGF	0.066	0.073	0.27	24	-0.42	3	27
mol:DAG	-0.013	0.11	0.28	3	-0.29	95	98
cAMP biosynthetic process	-0.033	0.11	0.32	2	-0.42	57	59
NFKB1	0.024	0.004	-10000	0	-10000	0	0
SRC	0.023	0.005	-10000	0	-10000	0	0
GNB1	0.023	0.005	-10000	0	-10000	0	0
LYN	-0.008	0.13	0.27	24	-0.34	83	107
GNAQ	-0.02	0.11	0.21	1	-0.31	122	123
LPAR2	0.025	0.011	0.26	2	-10000	0	2
LPAR3	-0.034	0.19	0.26	39	-0.57	119	158
LPAR1	0.012	0.088	-10000	0	-0.49	29	29
IL8	-0.13	0.23	0.35	30	-0.43	291	321
PTK2	-0.022	0.1	0.24	1	-0.32	99	100
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
CASP3	-0.026	0.12	-10000	0	-0.32	143	143
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
PLCG1	-0.022	0.11	0.2	4	-0.32	120	124
PLD2	-0.027	0.12	0.24	1	-0.31	136	137
G12/G13	0.036	0.061	-10000	0	-0.31	26	26
PI3K-beta	0	0.079	-10000	0	-0.45	15	15
cell migration	0.002	0.063	-10000	0	-0.25	22	22
SLC9A3R2	0.023	0.01	0.26	1	-10000	0	1
PXN	-0.017	0.1	-10000	0	-0.38	42	42
HRAS/GTP	-0.02	0.11	-10000	0	-0.38	68	68
RAC1	0.024	0.003	-10000	0	-10000	0	0
MMP9	0.12	0.12	0.26	453	-0.57	1	454
PRKCE	0.024	0.003	-10000	0	-10000	0	0
PRKCD	-0.014	0.1	0.3	2	-0.41	10	12
Gi(beta/gamma)	-0.014	0.11	-10000	0	-0.44	47	47
mol:LPA	0.001	0.016	-10000	0	-0.18	6	6
TRIP6/p130 Cas/FAK1/Paxillin	-0.013	0.12	-10000	0	-0.44	25	25
MAPKKK cascade	-0.019	0.11	-10000	0	-0.37	68	68
contractile ring contraction involved in cytokinesis	0.002	0.063	0.26	2	-0.3	27	29
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.02	0.11	0.21	1	-0.31	127	128
GNA15	-0.018	0.1	0.2	2	-0.31	120	122
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.007	-10000	0	-10000	0	0
MAPT	-0.051	0.12	0.26	3	-0.33	122	125
GNA11	-0.02	0.1	0.21	1	-0.31	123	124
Rac1/GTP	0.028	0.13	-10000	0	-0.86	22	22
MMP2	0.002	0.081	0.26	1	-0.43	33	34

×

Signaling events mediated by the Hedgehog family

Figure S44. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S44. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.04	0.22	0.41	5	-0.63	113	118
IHH	0.016	0.082	0.26	31	-0.22	37	68
SHH Np/Cholesterol/GAS1	0	0.075	-10000	0	-0.33	49	49
LRPAP1	0.023	0.005	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0	0.075	0.33	49	-10000	0	49
SMO/beta Arrestin2	-0.019	0.21	-10000	0	-0.62	97	97
SMO	-0.042	0.21	0.32	1	-0.65	97	98
AKT1	-0.004	0.13	-10000	0	-0.59	25	25
ARRB2	0.022	0.007	-10000	0	-10000	0	0
BOC	-0.018	0.15	-10000	0	-0.57	76	76
ADRBK1	0.023	0.006	-10000	0	-10000	0	0
heart looping	-0.041	0.21	0.32	1	-0.64	97	98
STIL	0.006	0.17	0.3	31	-0.48	87	118
DHH N/PTCH2	-0.008	0.14	-10000	0	-0.44	97	97
DHH N/PTCH1	-0.027	0.2	-10000	0	-0.51	144	144
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
DHH	0.008	0.096	0.26	2	-0.57	29	31
PTHLH	-0.061	0.3	0.43	10	-0.83	120	130
determination of left/right symmetry	-0.041	0.21	0.32	1	-0.64	97	98
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
skeletal system development	-0.059	0.29	0.42	14	-0.82	120	134
IHH N/Hhip	0.027	0.056	0.24	2	-0.46	2	4
DHH N/Hhip	0.022	0.077	-10000	0	-0.41	31	31
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.041	0.21	0.32	1	-0.64	97	98
pancreas development	0.023	0.03	0.26	5	-0.56	2	7
HHAT	0.02	0.02	-10000	0	-0.57	1	1
PI3K	0.028	0.049	-10000	0	-0.38	14	14
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.009	0.14	-10000	0	-0.57	61	61
somite specification	-0.041	0.21	0.32	1	-0.64	97	98
SHH Np/Cholesterol/PTCH1	-0.024	0.16	0.26	4	-0.48	97	101
SHH Np/Cholesterol/PTCH2	-0.004	0.082	-10000	0	-0.33	59	59
SHH Np/Cholesterol/Megalin	-0.06	0.15	0.28	3	-0.33	228	231
SHH	0	0.037	0.34	7	-0.42	1	8
catabolic process	-0.033	0.21	0.31	2	-0.57	123	125
SMO/Vitamin D3	-0.009	0.2	0.36	15	-0.57	88	103
SHH Np/Cholesterol/Hhip	0.015	0.028	0.25	3	-0.33	3	6
LRP2	-0.12	0.26	0.26	26	-0.57	277	303
receptor-mediated endocytosis	-0.079	0.22	0.3	11	-0.62	101	112
SHH Np/Cholesterol/BOC	-0.004	0.083	-10000	0	-0.33	61	61
SHH Np/Cholesterol/CDO	0.013	0.04	-10000	0	-0.33	12	12
mesenchymal cell differentiation	-0.015	0.028	0.33	3	-0.24	3	6
mol:Vitamin D3	0.002	0.18	0.34	21	-0.49	93	114
IHH N/PTCH2	-0.006	0.14	-10000	0	-0.47	76	76
CDON	0.015	0.065	-10000	0	-0.57	13	13
IHH N/PTCH1	-0.024	0.21	0.35	4	-0.57	123	127
Megalin/LRPAP1	-0.079	0.2	-10000	0	-0.42	277	277
PTCH2	-0.018	0.15	-10000	0	-0.57	76	76
SHH Np/Cholesterol	0.01	0.013	-10000	0	-0.33	1	1
PTCH1	-0.033	0.21	0.31	2	-0.57	123	125
HHIP	0.023	0.03	0.26	5	-0.57	2	7

×

Integrins in angiogenesis

Figure S45. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S45. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.033	0.035	-10000	0	-0.42	5	5
alphaV beta3 Integrin	-0.12	0.21	-10000	0	-0.38	407	407
PTK2	-0.056	0.15	0.32	2	-0.51	44	46
IGF1R	0.013	0.079	0.26	3	-0.57	19	22
PI4KB	0.02	0.009	-10000	0	-10000	0	0
MFGE8	0.018	0.067	0.26	6	-0.57	13	19
SRC	0.023	0.005	-10000	0	-10000	0	0
CDKN1B	-0.044	0.12	-10000	0	-0.53	35	35
VEGFA	0.025	0.019	0.26	7	-10000	0	7
ILK	-0.042	0.12	-10000	0	-0.49	32	32
ROCK1	0.023	0.018	-10000	0	-0.57	1	1
AKT1	-0.043	0.1	-10000	0	-0.49	28	28
PTK2B	-0.013	0.069	0.36	2	-0.33	32	34
alphaV/beta3 Integrin/JAM-A	-0.076	0.17	0.3	1	-0.34	270	271
CBL	0.022	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.032	0.072	-10000	0	-0.36	33	33
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.044	0.19	-10000	0	-0.38	246	246
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.013	0.068	-10000	0	-0.44	10	10
alphaV/beta3 Integrin/Syndecan-1	0.043	0.081	-10000	0	-0.36	33	33
PI4KA	0.023	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.14	0.27	-10000	0	-0.58	197	197
PI4 Kinase	0.028	0.015	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	0.068	0.099	0.34	3	-0.35	33	36
RPS6KB1	-0.16	0.22	0.42	3	-0.55	177	180
TLN1	0.024	0.004	-10000	0	-10000	0	0
MAPK3	-0.2	0.29	-10000	0	-0.58	334	334
GPR124	0.016	0.048	-10000	0	-0.57	7	7
MAPK1	-0.2	0.29	-10000	0	-0.58	356	356
PXN	0.024	0.002	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
alphaV/beta3 Integrin/Tumstatin	-0.031	0.16	-10000	0	-0.37	197	197
cell adhesion	0.023	0.082	0.25	1	-0.36	42	43
ANGPTL3	0.021	0.015	0.26	4	-10000	0	4
VEGFR2 homodimer/VEGFA homodimer/Src	0.044	0.032	-10000	0	-0.36	4	4
IGF-1R heterotetramer	0.013	0.079	0.26	3	-0.56	19	22
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
TGFBR2	0.001	0.11	-10000	0	-0.57	42	42
ITGB3	0.006	0.1	0.26	4	-0.57	33	37
IGF1	-0.1	0.24	-10000	0	-0.57	233	233
RAC1	0.024	0.003	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.025	0.077	-10000	0	-0.39	29	29
apoptosis	0.024	0.003	-10000	0	-10000	0	0
CD47	0.024	0.018	-10000	0	-0.57	1	1
alphaV/beta3 Integrin/CD47	0.034	0.072	-10000	0	-0.36	33	33
VCL	0.024	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.014	0.13	-10000	0	-0.45	72	72
CSF1	0.021	0.044	-10000	0	-0.57	6	6
PIK3C2A	-0.04	0.11	-10000	0	-0.49	28	28
PI4 Kinase/Pyk2	-0.076	0.15	-10000	0	-0.51	24	24
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.045	0.078	-10000	0	-0.36	33	33
FAK1/Vinculin	-0.037	0.13	0.34	4	-0.41	40	44
alphaV beta3/Integrin/ppsTEM5	0.026	0.077	-10000	0	-0.4	29	29
RHOA	0.024	0.005	-10000	0	-10000	0	0
VTN	0.033	0.077	0.26	68	-0.57	8	76
BCAR1	0.021	0.008	-10000	0	-10000	0	0
FGF2	-0.2	0.29	-10000	0	-0.57	413	413
F11R	-0.12	0.19	-10000	0	-0.42	312	312
alphaV/beta3 Integrin/Lactadherin	0.03	0.087	0.34	1	-0.38	42	43
alphaV/beta3 Integrin/TGFBR2	0.02	0.12	-10000	0	-0.45	55	55
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.049	0.038	-10000	0	-0.33	6	6
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.033	0.065	-10000	0	-0.33	32	32
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.11	0.11	0.26	421	-10000	0	421
alphaV/beta3 Integrin/Pyk2	0.027	0.072	-10000	0	-0.33	33	33
SDC1	0.038	0.059	0.26	68	-0.57	1	69
VAV3	-0.011	0.041	-10000	0	-0.31	13	13
PTPN11	0.024	0.002	-10000	0	-10000	0	0
IRS1	0.001	0.11	-10000	0	-0.57	42	42
FAK1/Paxillin	-0.037	0.13	0.34	4	-0.41	40	44
cell migration	-0.036	0.12	0.3	6	-0.38	36	42
ITGAV	0.024	0.003	-10000	0	-10000	0	0
PI3K	-0.066	0.17	-10000	0	-0.32	245	245
SPP1	0.084	0.1	0.26	279	-10000	0	279
KDR	0.021	0.04	-10000	0	-0.57	5	5
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.024	0.003	-10000	0	-10000	0	0
COL4A3	-0.074	0.22	0.26	4	-0.57	179	183
angiogenesis	-0.19	0.3	-10000	0	-0.58	333	333
Rac1/GTP	0.021	0.038	-10000	0	-0.29	11	11
EDIL3	-0.007	0.14	0.26	15	-0.57	62	77
cell proliferation	0.02	0.12	-10000	0	-0.45	55	55

×

Syndecan-1-mediated signaling events

Figure S46. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S46. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.025	0.013	0.26	3	-10000	0	3
CCL5	0.029	0.056	0.26	38	-0.57	4	42
SDCBP	0.021	0.008	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.063	0.12	0.27	24	-0.41	9	33
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.049	0.12	0.27	2	-0.37	17	19
Syndecan-1/Syntenin	0.051	0.12	0.29	7	-0.38	14	21
MAPK3	0.047	0.11	0.27	8	-0.42	7	15
HGF/MET	-0.066	0.2	-10000	0	-0.44	225	225
TGFB1/TGF beta receptor Type II	0.025	0.013	0.26	3	-10000	0	3
BSG	0.024	0.009	0.26	1	-10000	0	1
keratinocyte migration	0.049	0.12	0.27	2	-0.36	17	19
Syndecan-1/RANTES	0.058	0.13	0.31	35	-0.4	18	53
Syndecan-1/CD147	0.063	0.12	0.33	5	-0.4	10	15
Syndecan-1/Syntenin/PIP2	0.047	0.11	0.27	7	-0.37	14	21
LAMA5	0.023	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.046	0.11	0.26	6	-0.36	14	20
MMP7	-0.037	0.19	0.26	33	-0.57	121	154
HGF	-0.011	0.14	0.26	2	-0.57	65	67
Syndecan-1/CASK	0.042	0.12	0.26	7	-0.37	17	24
Syndecan-1/HGF/MET	-0.004	0.2	0.32	4	-0.46	105	109
regulation of cell adhesion	0.041	0.11	0.29	4	-0.4	7	11
HPSE	0.027	0.035	0.26	18	-0.57	1	19
positive regulation of cell migration	0.063	0.12	0.27	24	-0.41	9	33
SDC1	0.065	0.12	0.28	20	-0.41	9	29
Syndecan-1/Collagen	0.063	0.12	0.27	24	-0.41	9	33
PPIB	0.024	0.013	0.26	3	-10000	0	3
MET	-0.073	0.22	-10000	0	-0.57	177	177
PRKACA	0.024	0.004	-10000	0	-10000	0	0
MMP9	0.12	0.12	0.26	453	-0.57	1	454
MAPK1	0.048	0.11	0.27	8	-0.41	7	15
homophilic cell adhesion	0.061	0.12	0.27	24	-0.38	14	38
MMP1	0.18	0.11	0.26	739	-10000	0	739

×

Ephrin A reverse signaling

Figure S47. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S47. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.005	0.11	-10000	0	-0.36	95	95
EFNA5	-0.028	0.17	0.26	1	-0.57	95	96
FYN	-0.022	0.098	-10000	0	-0.33	95	95
neuron projection morphogenesis	-0.005	0.11	-10000	0	-0.36	95	95
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	-0.004	0.11	-10000	0	-0.36	95	95
EPHA5	0.023	0.017	0.26	5	-10000	0	5

×

IL12-mediated signaling events

Figure S48. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S48. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.042	0.14	0.36	56	-0.36	42	98
TBX21	0.014	0.34	0.76	21	-1.2	49	70
B2M	0.025	0.012	-10000	0	-10000	0	0
TYK2	0.024	0.036	0.19	1	-10000	0	1
IL12RB1	0.031	0.072	0.32	41	-0.6	2	43
GADD45B	0.037	0.26	0.64	22	-0.89	32	54
IL12RB2	0.028	0.15	0.27	118	-0.57	42	160
GADD45G	0.055	0.26	0.67	25	-0.9	29	54
natural killer cell activation	0.007	0.025	0.081	53	-0.043	21	74
RELB	0.026	0.022	0.26	10	-10000	0	10
RELA	0.023	0.005	-10000	0	-10000	0	0
IL18	0.034	0.04	0.27	26	-10000	0	26
IL2RA	0.027	0.088	0.26	58	-0.57	15	73
IFNG	0.054	0.08	0.26	146	-10000	0	146
STAT3 (dimer)	0.035	0.24	0.56	39	-0.71	45	84
HLA-DRB5	-0.006	0.011	-10000	0	-0.025	249	249
FASLG	0.049	0.31	0.75	29	-1.1	37	66
NF kappa B2 p52/RelB	0.022	0.25	0.67	5	-0.8	48	53
CD4	0.009	0.024	-10000	0	-10000	0	0
SOCS1	0.025	0.033	0.26	14	-0.57	1	15
EntrezGene:6955	-0.006	0.016	0.023	57	-0.028	273	330
CD3D	0.009	0.098	0.26	49	-0.58	19	68
CD3E	0.009	0.089	0.26	37	-0.57	16	53
CD3G	-0.001	0.12	0.26	38	-0.57	33	71
IL12Rbeta2/JAK2	0.037	0.12	0.3	28	-0.43	42	70
CCL3	0.033	0.28	0.69	21	-0.96	34	55
CCL4	0.035	0.27	0.69	21	-0.94	32	53
HLA-A	0.002	0.008	0.023	73	-0.048	12	85
IL18/IL18R	0.065	0.12	0.38	15	-0.37	52	67
NOS2	0.032	0.28	0.68	23	-0.95	37	60
IL12/IL12R/TYK2/JAK2/SPHK2	0.039	0.14	0.36	56	-0.36	47	103
IL1R1	0.017	0.31	0.68	22	-1.1	47	69
IL4	-0.011	0.037	-10000	0	-10000	0	0
JAK2	0.023	0.036	-10000	0	-10000	0	0
EntrezGene:6957	-0.005	0.014	0.023	58	-0.026	248	306
TCR/CD3/MHC I/CD8	-0.024	0.22	0.37	33	-0.77	57	90
RAB7A	0.052	0.24	0.64	18	-0.81	23	41
lysosomal transport	0.053	0.23	0.64	19	-0.76	23	42
FOS	-0.32	0.62	0.6	12	-1.2	349	361
STAT4 (dimer)	0.063	0.28	0.6	35	-0.85	47	82
STAT5A (dimer)	0.047	0.28	0.61	48	-0.77	53	101
GZMA	0.025	0.29	0.7	27	-1.1	34	61
GZMB	0.023	0.32	0.73	23	-1.1	43	66
HLX	0.021	0.015	0.26	3	-10000	0	3
LCK	0.028	0.29	0.66	36	-0.88	52	88
TCR/CD3/MHC II/CD4	-0.054	0.17	0.24	27	-0.32	215	242
IL2/IL2R	0.065	0.098	0.41	39	-0.36	21	60
MAPK14	0.048	0.27	0.64	28	-0.89	35	63
CCR5	0.037	0.27	0.7	25	-0.92	31	56
IL1B	0.017	0.078	0.29	3	-0.58	14	17
STAT6	0.039	0.12	0.41	31	-0.6	7	38
STAT4	0.001	0.12	0.26	1	-0.57	43	44
STAT3	0.024	0.005	-10000	0	-10000	0	0
STAT1	0.028	0.031	0.26	19	-10000	0	19
NFKB1	0.024	0.004	-10000	0	-10000	0	0
NFKB2	0.024	0.008	0.26	1	-10000	0	1
IL12B	0.072	0.11	0.28	227	-10000	0	227
CD8A	0.029	0.059	0.28	29	-0.57	5	34
CD8B	0.014	0.11	0.27	30	-0.57	32	62
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.042	0.14	0.36	42	-0.36	56	98
IL2RB	0.03	0.05	0.26	38	-0.57	2	40
proteasomal ubiquitin-dependent protein catabolic process	0.066	0.26	0.58	41	-0.76	47	88
IL2RG	0.03	0.067	0.26	46	-0.57	7	53
IL12	0.049	0.15	0.29	94	-0.42	57	151
STAT5A	0.02	0.044	-10000	0	-0.57	6	6
CD247	0.006	0.079	0.26	16	-0.57	15	31
IL2	0.022	0.021	0.26	8	-10000	0	8
SPHK2	0.024	0.003	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.004	0.14	0.29	18	-0.58	57	75
IL12/IL12R/TYK2/JAK2	0.033	0.3	0.71	35	-0.88	53	88
MAP2K3	0.042	0.28	0.63	28	-0.86	43	71
RIPK2	0.02	0.016	0.26	3	-10000	0	3
MAP2K6	0.046	0.27	0.63	28	-0.84	41	69
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.007	0.013	-10000	0	-0.028	275	275
IL18RAP	0.012	0.11	0.28	5	-0.57	35	40
IL12Rbeta1/TYK2	0.04	0.068	0.29	34	-0.46	2	36
EOMES	-0.021	0.18	-10000	0	-1	30	30
STAT1 (dimer)	0.067	0.26	0.62	60	-0.74	37	97
T cell proliferation	0.05	0.22	0.51	26	-0.64	43	69
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.08	-10000	0	-0.57	19	19
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.012	0.19	0.42	2	-0.72	39	41
ATF2	0.045	0.25	0.6	27	-0.82	35	62

×

Nephrin/Neph1 signaling in the kidney podocyte

Figure S49. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S49. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.014	0.14	0.42	85	-0.24	2	87
KIRREL	-0.024	0.16	-10000	0	-0.57	87	87
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.014	0.14	0.24	2	-0.42	85	87
PLCG1	0.023	0.005	-10000	0	-10000	0	0
ARRB2	0.022	0.007	-10000	0	-10000	0	0
WASL	0.024	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.034	0.12	0.29	3	-0.32	84	87
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.008	0.088	0.24	1	-0.28	70	71
FYN	0.013	0.13	0.27	110	-0.3	83	193
mol:Ca2+	0.031	0.11	0.28	3	-0.32	79	82
mol:DAG	0.032	0.11	0.28	3	-0.32	79	82
NPHS2	0.014	0.032	0.26	5	-10000	0	5
mol:IP3	0.032	0.11	0.28	3	-0.32	79	82
regulation of endocytosis	0.023	0.1	0.24	4	-0.29	83	87
Nephrin/NEPH1/podocin/Cholesterol	0.023	0.11	0.25	9	-0.32	84	93
establishment of cell polarity	0.014	0.14	0.24	2	-0.42	85	87
Nephrin/NEPH1/podocin/NCK1-2	0.043	0.11	0.32	1	-0.3	82	83
Nephrin/NEPH1/beta Arrestin2	0.026	0.11	0.25	4	-0.29	83	87
NPHS1	0.058	0.09	0.26	166	-10000	0	166
Nephrin/NEPH1/podocin	0.024	0.11	0.3	4	-0.31	83	87
TJP1	0.023	0.019	-10000	0	-0.57	1	1
NCK1	0.024	0.003	-10000	0	-10000	0	0
NCK2	0.024	0.003	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.033	0.12	0.29	3	-0.32	79	82
CD2AP	0.024	0.004	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.031	0.12	0.32	2	-0.32	81	83
GRB2	0.023	0.009	0.26	1	-10000	0	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.012	0.13	0.29	97	-0.31	89	186
cytoskeleton organization	0.003	0.11	0.29	12	-0.33	66	78
Nephrin/NEPH1	0.016	0.1	0.2	2	-0.3	85	87
Nephrin/NEPH1/ZO-1	0.025	0.12	-10000	0	-0.34	85	85

×

PDGFR-alpha signaling pathway

Figure S50. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S50. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.033	0.15	-10000	0	-0.59	66	66
PDGF/PDGFRA/CRKL	-0.011	0.11	-10000	0	-0.41	69	69
positive regulation of JUN kinase activity	0.024	0.083	-10000	0	-0.33	47	47
CRKL	0.023	0.006	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.014	0.11	-10000	0	-0.42	67	67
AP1	-0.3	0.44	-10000	0	-0.96	323	323
mol:IP3	-0.036	0.11	-10000	0	-0.45	63	63
PLCG1	-0.036	0.11	-10000	0	-0.45	63	63
PDGF/PDGFRA/alphaV Integrin	-0.011	0.11	-10000	0	-0.43	66	66
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0
CRK	0.022	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.036	0.11	-10000	0	-0.45	63	63
CAV3	0.02	0.011	0.26	2	-10000	0	2
CAV1	-0.1	0.24	-10000	0	-0.57	225	225
SHC/Grb2/SOS1	0.026	0.084	-10000	0	-0.33	47	47
PDGF/PDGFRA/Shf	-0.011	0.11	-10000	0	-0.42	68	68
FOS	-0.3	0.43	0.32	1	-0.94	323	324
JUN	-0.038	0.044	-10000	0	-0.44	6	6
oligodendrocyte development	-0.011	0.11	-10000	0	-0.42	66	66
GRB2	0.023	0.009	0.26	1	-10000	0	1
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:DAG	-0.036	0.11	-10000	0	-0.45	63	63
PDGF/PDGFRA	-0.033	0.15	-10000	0	-0.59	66	66
actin cytoskeleton reorganization	-0.011	0.11	-10000	0	-0.42	67	67
SRF	0.016	0.013	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
PI3K	0.012	0.11	-10000	0	-0.38	72	72
PDGF/PDGFRA/Crk/C3G	0.015	0.098	-10000	0	-0.36	66	66
JAK1	-0.027	0.1	0.23	1	-0.42	67	68
ELK1/SRF	-0.035	0.091	0.32	1	-0.35	64	65
SHB	0.024	0.008	0.26	1	-10000	0	1
SHF	0.024	0.021	0.26	2	-0.57	1	3
CSNK2A1	0.036	0.023	-10000	0	-10000	0	0
GO:0007205	-0.047	0.11	0.22	1	-0.46	66	67
SOS1	0.024	0.003	-10000	0	-10000	0	0
Ras protein signal transduction	0.024	0.083	-10000	0	-0.33	47	47
PDGF/PDGFRA/SHB	-0.011	0.11	-10000	0	-0.42	67	67
PDGF/PDGFRA/Caveolin-1	-0.099	0.22	-10000	0	-0.48	256	256
ITGAV	0.024	0.003	-10000	0	-10000	0	0
ELK1	-0.053	0.11	0.24	1	-0.43	65	66
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Crk	-0.012	0.11	-10000	0	-0.41	69	69
JAK-STAT cascade	-0.027	0.1	0.23	1	-0.42	67	68
cell proliferation	-0.011	0.11	-10000	0	-0.42	68	68

×

RXR and RAR heterodimerization with other nuclear receptor

Figure S51. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S51. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.034	0.1	0.99	2	-10000	0	2
VDR	0.024	0.002	-10000	0	-10000	0	0
FAM120B	0.023	0.006	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.025	0.12	-10000	0	-0.35	14	14
RXRs/LXRs/DNA/Oxysterols	-0.006	0.12	-10000	0	-0.42	16	16
MED1	0.021	0.008	-10000	0	-10000	0	0
mol:9cRA	0.004	0.01	-10000	0	-0.15	1	1
RARs/THRs/DNA/Src-1	0.001	0.083	-10000	0	-0.3	62	62
RXRs/NUR77	-0.05	0.18	-10000	0	-0.35	266	266
RXRs/PPAR	-0.1	0.17	-10000	0	-0.32	350	350
NCOR2	0.024	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.002	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.048	0.043	-10000	0	-0.31	12	12
RARA	0.023	0.012	0.26	2	-10000	0	2
NCOA1	0.023	0.018	-10000	0	-0.57	1	1
VDR/VDR/DNA	0.024	0.002	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.037	0.041	-10000	0	-0.3	12	12
RARG	0.024	0.002	-10000	0	-10000	0	0
RPS6KB1	0.071	0.18	0.61	99	-10000	0	99
RARs/THRs/DNA/SMRT	0.002	0.079	-10000	0	-0.29	60	60
THRA	0.022	0.008	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.018	0.002	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.028	0.15	-10000	0	-0.32	216	216
NR1H4	0.021	0.026	0.26	13	-10000	0	13
RXRs/LXRs/DNA	-0.007	0.15	-10000	0	-0.3	197	197
NR1H2	0.027	0.012	-10000	0	-10000	0	0
NR1H3	0.028	0.012	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.022	0.15	-10000	0	-0.3	215	215
NR4A1	-0.028	0.17	-10000	0	-0.57	95	95
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.031	0.1	-10000	0	-0.23	190	190
RXRG	-0.098	0.24	0.26	2	-0.56	219	221
RXR alpha/CCPG	0.035	0.014	-10000	0	-10000	0	0
RXRA	0.027	0.012	-10000	0	-10000	0	0
RXRB	0.027	0.012	-10000	0	-10000	0	0
THRB	-0.006	0.13	-10000	0	-0.57	55	55
PPARG	-0.12	0.25	-10000	0	-0.57	252	252
PPARD	0.024	0.004	-10000	0	-10000	0	0
TNF	-0.01	0.14	-10000	0	-1	10	10
mol:Oxysterols	0.004	0.009	-10000	0	-0.12	1	1
cholesterol transport	-0.005	0.12	-10000	0	-0.42	16	16
PPARA	0.02	0.044	-10000	0	-0.57	6	6
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.016	0.067	-10000	0	-0.57	14	14
RXRs/NUR77/BCL2	-0.069	0.15	-10000	0	-0.3	282	282
SREBF1	-0.006	0.11	0.44	1	-0.5	3	4
RXRs/RXRs/DNA/9cRA	-0.028	0.15	-10000	0	-0.32	216	216
ABCA1	-0.01	0.13	-10000	0	-0.84	8	8
RARs/THRs	0.04	0.096	-10000	0	-0.33	60	60
RXRs/FXR	-0.024	0.16	-10000	0	-0.33	216	216
BCL2	0.008	0.094	-10000	0	-0.57	28	28

×

Canonical Wnt signaling pathway

Figure S52. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S52. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.021	0.22	3	-10000	0	3
AES	0.022	0.019	0.21	2	-10000	0	2
FBXW11	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.009	-10000	0	-10000	0	0
SMAD4	0.023	0.005	-10000	0	-10000	0	0
DKK2	0.009	0.095	0.26	2	-0.57	28	30
TLE1	0.019	0.048	0.22	1	-0.57	6	7
MACF1	0.024	0.004	-10000	0	-10000	0	0
CTNNB1	0.1	0.1	0.3	47	-0.37	4	51
WIF1	-0.28	0.3	0.26	13	-0.56	544	557
beta catenin/RanBP3	0.02	0.089	0.41	40	-0.4	1	41
KREMEN2	0.12	0.12	0.26	473	-10000	0	473
DKK1	0.026	0.16	0.26	146	-0.57	54	200
beta catenin/beta TrCP1	0.11	0.094	0.3	36	-0.38	2	38
FZD1	0.024	0.004	-10000	0	-10000	0	0
AXIN2	0.016	0.26	0.6	83	-1.3	22	105
AXIN1	0.023	0.007	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.046	0.076	-10000	0	-0.56	12	12
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.064	0.13	0.29	10	-0.57	24	34
Axin1/APC/GSK3	0.046	0.053	0.24	2	-0.31	1	3
Axin1/APC/GSK3/beta catenin/Macf1	0.043	0.063	0.31	2	-0.4	4	6
HNF1A	0.025	0.028	0.25	11	-10000	0	11
CTBP1	0.021	0.02	0.25	2	-10000	0	2
MYC	0.11	0.33	0.57	261	-1.3	24	285
RANBP3	0.024	0.004	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.091	0.099	0.34	1	-0.33	22	23
NKD1	0.022	0.053	0.26	16	-0.57	6	22
TCF4	0.016	0.062	0.23	2	-0.56	11	13
TCF3	0.022	0.022	0.27	3	-10000	0	3
WNT1/LRP6/FZD1/Axin1	0.057	0.023	-10000	0	-10000	0	0
Ran/GTP	0.018	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.005	0.12	0.45	36	-0.5	15	51
LEF1	0.052	0.082	0.25	140	-0.53	1	141
DVL1	0.055	0.053	0.22	1	-0.36	2	3
CSNK2A1	0.024	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.14	0.29	13	-0.59	30	43
DKK1/LRP6/Kremen 2	0.099	0.14	0.34	80	-0.34	47	127
LRP6	0.024	0.005	-10000	0	-10000	0	0
CSNK1A1	0.023	0.021	0.24	2	-10000	0	2
NLK	0.023	0.014	0.25	2	-10000	0	2
CCND1	0.091	0.26	0.61	179	-1.2	6	185
WNT1	0.024	0.011	0.26	2	-10000	0	2
GSK3A	0.025	0.003	-10000	0	-10000	0	0
GSK3B	0.024	0.004	-10000	0	-10000	0	0
FRAT1	0.024	0.003	-10000	0	-10000	0	0
PPP2R5D	0.038	0.055	0.29	5	-0.3	9	14
APC	0.016	0.056	0.36	6	-10000	0	6
WNT1/LRP6/FZD1	0.12	0.11	0.22	518	-0.24	1	519
CREBBP	0.021	0.018	0.27	1	-10000	0	1

×

Visual signal transduction: Cones

Figure S53. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S53. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.033	0.043	-10000	0	-0.31	13	13
RGS9BP	0.036	0.052	0.26	57	-10000	0	57
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.019	0.016	0.26	4	-10000	0	4
mol:Na +	0.037	0.045	-10000	0	-10000	0	0
mol:ADP	-0.006	0.025	0.25	5	-10000	0	5
GNAT2	0.024	0.015	0.26	4	-10000	0	4
RGS9-1/Gbeta5/R9AP	0.016	0.12	0.34	1	-0.36	86	87
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.028	0.015	-10000	0	-10000	0	0
GRK7	0.023	0.019	0.26	7	-10000	0	7
CNGB3	0.022	0.037	0.26	25	-10000	0	25
Cone Metarhodopsin II/X-Arrestin	0.015	0.014	0.18	8	-10000	0	8
mol:Ca2+	0.12	0.1	0.29	177	-10000	0	177
Cone PDE6	0.031	0.11	0.31	3	-0.31	82	85
Cone Metarhodopsin II	0.025	0.017	-10000	0	-10000	0	0
Na + (4 Units)	0.11	0.092	0.31	69	-10000	0	69
GNAT2/GDP	0.025	0.1	0.28	3	-0.31	85	88
GNB5	0.024	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.007	0.032	0.22	2	-10000	0	2
Cone Transducin	0.036	0.046	-10000	0	-0.33	13	13
SLC24A2	0.16	0.12	0.26	621	-10000	0	621
GNB3/GNGT2	0.026	0.053	-10000	0	-0.4	14	14
GNB3	0.018	0.064	0.26	5	-0.57	12	17
GNAT2/GTP	0.018	0.01	0.18	4	-10000	0	4
CNGA3	0.045	0.068	0.26	101	-10000	0	101
ARR3	0.021	0.021	0.26	8	-10000	0	8
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.038	0.045	-10000	0	-10000	0	0
mol:Pi	0.016	0.12	0.33	1	-0.36	86	87
Cone CNG Channel	0.049	0.043	0.28	2	-10000	0	2
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.16	0.12	0.26	621	-10000	0	621
RGS9	-0.024	0.16	0.26	11	-0.57	88	99
PDE6C	0.019	0.008	0.26	1	-10000	0	1
GNGT2	0.021	0.026	-10000	0	-0.57	2	2
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.019	0.017	0.26	5	-10000	0	5

×

Fc-epsilon receptor I signaling in mast cells

Figure S54. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S54. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.022	0.026	-10000	0	-0.57	2	2
LAT2	-0.02	0.1	-10000	0	-0.36	56	56
AP1	-0.059	0.18	-10000	0	-0.44	120	120
mol:PIP3	0.009	0.17	0.35	46	-0.42	55	101
IKBKB	0.033	0.13	0.28	119	-0.26	29	148
AKT1	0.012	0.17	0.32	146	-0.44	21	167
IKBKG	0.016	0.11	0.25	74	-0.28	31	105
MS4A2	-0.022	0.15	0.25	5	-0.55	82	87
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
MAP3K1	0.011	0.12	0.3	25	-0.39	32	57
mol:Ca2+	0.014	0.14	0.3	57	-0.32	53	110
LYN	0.022	0.012	-10000	0	-10000	0	0
CBLB	-0.019	0.1	-10000	0	-0.36	55	55
SHC1	0.02	0.009	-10000	0	-10000	0	0
RasGAP/p62DOK	0.001	0.12	-10000	0	-0.33	124	124
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.024	0.004	-10000	0	-10000	0	0
PLD2	-0.004	0.17	0.33	126	-0.33	137	263
PTPN13	-0.015	0.15	-10000	0	-0.55	44	44
PTPN11	0.023	0.018	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.012	0.13	0.32	39	-0.34	31	70
SYK	0.025	0.01	-10000	0	-10000	0	0
GRB2	0.023	0.009	0.26	1	-10000	0	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.027	0.13	-10000	0	-0.42	58	58
LAT	-0.019	0.1	-10000	0	-0.36	57	57
PAK2	0.012	0.13	0.29	31	-0.43	31	62
NFATC2	-0.049	0.16	-10000	0	-0.55	86	86
HRAS	0.008	0.13	0.27	21	-0.45	35	56
GAB2	0.021	0.019	-10000	0	-0.57	1	1
PLA2G1B	0.002	0.098	-10000	0	-0.84	12	12
Fc epsilon R1	-0.022	0.16	-10000	0	-0.4	144	144
Antigen/IgE/Fc epsilon R1	-0.018	0.14	-10000	0	-0.36	144	144
mol:GDP	-0.014	0.12	0.25	1	-0.47	33	34
JUN	0.02	0.044	-10000	0	-0.57	6	6
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
FOS	-0.14	0.27	-10000	0	-0.57	306	306
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.017	0.11	-10000	0	-0.37	60	60
CHUK	0.015	0.11	0.25	74	-0.27	33	107
KLRG1	-0.018	0.097	-10000	0	-0.32	57	57
VAV1	-0.02	0.1	-10000	0	-0.37	57	57
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.017	0.1	-10000	0	-0.36	55	55
negative regulation of mast cell degranulation	-0.006	0.098	-10000	0	-0.37	32	32
BTK	-0.013	0.11	-10000	0	-0.48	32	32
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.03	0.13	-10000	0	-0.33	144	144
GAB2/PI3K/SHP2	-0.048	0.1	-10000	0	-0.34	84	84
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.024	0.11	-10000	0	-0.45	34	34
RAF1	0.002	0.1	-10000	0	-0.92	12	12
Fc epsilon R1/FcgammaRIIB/SHIP	0	0.15	-10000	0	-0.35	146	146
FCER1G	0.019	0.017	0.25	1	-10000	0	1
FCER1A	-0.044	0.18	-10000	0	-0.57	115	115
Antigen/IgE/Fc epsilon R1/Fyn	-0.009	0.14	-10000	0	-0.34	140	140
MAPK3	0.003	0.099	-10000	0	-0.86	12	12
MAPK1	-0.002	0.1	-10000	0	-0.86	12	12
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MAPK8	-0.023	0.18	-10000	0	-0.59	68	68
DUSP1	-0.045	0.19	-10000	0	-0.57	126	126
NF-kappa-B/RelA	0.007	0.058	0.14	5	-0.18	17	22
actin cytoskeleton reorganization	-0.007	0.15	-10000	0	-0.57	37	37
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.003	0.12	-10000	0	-0.45	32	32
FER	-0.021	0.11	-10000	0	-0.37	61	61
RELA	0.023	0.005	-10000	0	-10000	0	0
ITK	-0.012	0.091	-10000	0	-0.4	48	48
SOS1	0.024	0.003	-10000	0	-10000	0	0
PLCG1	0.004	0.13	0.28	9	-0.48	32	41
cytokine secretion	-0.003	0.035	-10000	0	-10000	0	0
SPHK1	-0.018	0.1	0.21	2	-0.36	57	59
PTK2	-0.009	0.15	-10000	0	-0.6	37	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.024	0.14	-10000	0	-0.44	58	58
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.006	0.16	0.33	42	-0.42	58	100
MAP2K2	-0.001	0.098	-10000	0	-0.85	12	12
MAP2K1	0	0.099	-10000	0	-0.86	12	12
MAP2K7	0.024	0.004	-10000	0	-10000	0	0
KLRG1/SHP2	-0.008	0.095	-10000	0	-0.36	32	32
MAP2K4	-0.072	0.29	-10000	0	-0.83	134	134
Fc epsilon R1/FcgammaRIIB	-0.008	0.15	-10000	0	-0.37	146	146
mol:Choline	-0.004	0.17	0.33	126	-0.32	137	263
SHC/Grb2/SOS1	0.011	0.11	-10000	0	-0.42	29	29
FYN	0.021	0.026	-10000	0	-0.57	2	2
DOK1	0.025	0.014	0.26	4	-10000	0	4
PXN	-0.009	0.14	-10000	0	-0.55	36	36
HCLS1	-0.019	0.1	-10000	0	-0.36	56	56
PRKCB	0.013	0.14	0.28	72	-0.37	37	109
FCGR2B	0.018	0.038	0.26	1	-0.57	4	5
IGHE	0.001	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.007	0.1	-10000	0	-0.38	32	32
LCP2	0.024	0.008	0.26	1	-10000	0	1
PLA2G4A	-0.045	0.14	-10000	0	-0.37	129	129
RASA1	0.024	0.004	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.004	0.17	0.33	126	-0.32	137	263
IKK complex	0.032	0.11	0.27	98	-0.21	18	116
WIPF1	0.024	0.003	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

Figure S55. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S55. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.094	0.1	0.21	421	-0.34	2	423
EPHB2	0.027	0.031	0.26	19	-10000	0	19
Syndecan-2/TACI	0.024	0.06	0.2	63	-0.36	12	75
LAMA1	-0.034	0.18	0.26	3	-0.57	105	108
Syndecan-2/alpha2 ITGB1	-0.038	0.15	-10000	0	-0.32	201	201
HRAS	0.026	0.022	0.26	9	-10000	0	9
Syndecan-2/CASK	0.005	0.016	-10000	0	-0.35	2	2
ITGA5	0.024	0.007	0.26	1	-10000	0	1
BAX	0.002	0.031	0.45	1	-10000	0	1
EPB41	0.024	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.017	0.018	-10000	0	-0.32	2	2
LAMA3	-0.12	0.25	-10000	0	-0.57	252	252
EZR	0.023	0.012	0.26	2	-10000	0	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.052	0.2	-10000	0	-0.57	138	138
Syndecan-2/MMP2	0.015	0.038	0.18	1	-0.36	9	10
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.023	0.071	-10000	0	-0.39	29	29
dendrite morphogenesis	0.022	0.033	0.21	19	-0.35	2	21
Syndecan-2/GM-CSF	0.022	0.036	0.21	26	-0.36	2	28
determination of left/right symmetry	0.007	0.019	-10000	0	-0.41	2	2
Syndecan-2/PKC delta	0.019	0.021	0.31	1	-0.35	2	3
GNB2L1	0.024	0.004	-10000	0	-10000	0	0
MAPK3	0.032	0.073	0.19	172	-0.32	2	174
MAPK1	0.037	0.076	0.19	196	-0.32	2	198
Syndecan-2/RACK1	0.03	0.026	0.26	2	-0.31	2	4
NF1	0.023	0.006	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.007	0.019	-10000	0	-0.41	2	2
ITGA2	0.008	0.094	-10000	0	-0.57	28	28
MAPK8	0.005	0.033	0.27	5	-0.35	6	11
Syndecan-2/alpha2/beta1 Integrin	0.004	0.12	-10000	0	-0.35	84	84
Syndecan-2/Kininogen	0.02	0.033	0.21	19	-0.36	2	21
ITGB1	0.024	0.004	-10000	0	-10000	0	0
SRC	0.042	0.069	0.27	12	-0.29	2	14
Syndecan-2/CASK/Protein 4.1	0.017	0.018	-10000	0	-0.32	2	2
extracellular matrix organization	0.02	0.023	0.24	3	-0.35	2	5
actin cytoskeleton reorganization	0.093	0.1	0.21	421	-0.34	2	423
Syndecan-2/Caveolin-2/Ras	-0.009	0.11	0.27	2	-0.33	104	106
Syndecan-2/Laminin alpha3	-0.057	0.14	-10000	0	-0.3	254	254
Syndecan-2/RasGAP	0.038	0.03	0.26	2	-0.3	2	4
alpha5/beta1 Integrin	0.035	0.008	-10000	0	-10000	0	0
PRKCD	0.024	0.009	0.26	1	-10000	0	1
Syndecan-2 dimer	0.022	0.033	0.21	19	-0.35	2	21
GO:0007205	0.002	0.003	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.025	0.024	-10000	0	-0.29	2	2
RHOA	0.024	0.005	-10000	0	-10000	0	0
SDCBP	0.021	0.008	-10000	0	-10000	0	0
TNFRSF13B	0.028	0.084	0.26	63	-0.57	12	75
RASA1	0.024	0.004	-10000	0	-10000	0	0
alpha2/beta1 Integrin	0.023	0.071	-10000	0	-0.39	29	29
Syndecan-2/Synbindin	0.018	0.02	-10000	0	-0.34	2	2
TGFB1	0.025	0.013	0.26	3	-10000	0	3
CASP3	0.042	0.071	0.19	190	-0.32	2	192
FN1	0.11	0.11	0.26	421	-10000	0	421
Syndecan-2/IL8	0.023	0.07	0.21	60	-0.32	23	83
SDC2	0.007	0.019	-10000	0	-0.41	2	2
KNG1	0.023	0.032	0.26	20	-10000	0	20
Syndecan-2/Neurofibromin	0.018	0.02	-10000	0	-0.35	2	2
TRAPPC4	0.022	0.007	-10000	0	-10000	0	0
CSF2	0.026	0.037	0.26	26	-10000	0	26
Syndecan-2/TGFB1	0.02	0.023	0.24	3	-0.35	2	5
Syndecan-2/Syntenin/PI-4-5-P2	0.018	0.018	-10000	0	-0.32	2	2
Syndecan-2/Ezrin	0.029	0.025	0.29	1	-0.32	2	3
PRKACA	0.044	0.072	0.19	203	-0.32	2	205
angiogenesis	0.023	0.07	0.21	60	-0.32	23	83
MMP2	0.018	0.048	0.26	1	-0.57	7	8
IL8	0.025	0.099	0.26	60	-0.57	21	81
calcineurin-NFAT signaling pathway	0.024	0.06	0.2	63	-0.35	12	75

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

Figure S56. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S56. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.38	0.28	-10000	0	-0.57	728	728
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.027	0.033	0.26	21	-10000	0	21
TCEB1	0.021	0.009	-10000	0	-10000	0	0
HIF1A/p53	0.029	0.049	-10000	0	-0.27	16	16
HIF1A	0.004	0.029	-10000	0	-0.26	12	12
COPS5	0.021	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.056	0.037	0.28	1	-10000	0	1
FIH (dimer)	0.024	0.003	-10000	0	-10000	0	0
CDKN2A	0.059	0.085	0.26	170	-10000	0	170
ARNT/IPAS	-0.25	0.2	-10000	0	-0.38	728	728
HIF1AN	0.024	0.003	-10000	0	-10000	0	0
GNB2L1	0.024	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.02	0.046	-10000	0	-0.28	15	15
CUL2	0.024	0.004	-10000	0	-10000	0	0
OS9	0.024	0.004	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.041	0.027	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.032	0.05	-10000	0	-0.28	15	15
PHD1-3/OS9	0.056	0.048	-10000	0	-0.33	2	2
HIF1A/RACK1/Elongin B/Elongin C	0.042	0.054	0.31	1	-0.3	5	6
VHL	0.024	0.004	-10000	0	-10000	0	0
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	0.026	0.049	-10000	0	-0.28	14	14
EGLN3	0.04	0.063	0.26	77	-0.57	1	78
EGLN2	0.025	0.016	0.26	5	-10000	0	5
EGLN1	0.02	0.02	-10000	0	-0.57	1	1
TP53	0.022	0.008	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.03	0.065	-10000	0	-0.51	13	13
ARNT	0.02	0.009	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.023	0.006	-10000	0	-10000	0	0
HIF1A/p19ARF	0.052	0.073	0.24	38	-0.27	14	52

×

Presenilin action in Notch and Wnt signaling

Figure S57. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S57. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.021	0.084	-10000	0	-0.46	14	14
HDAC1	0.021	0.012	-10000	0	-10000	0	0
AES	0.023	0.005	-10000	0	-10000	0	0
FBXW11	0.024	0.004	-10000	0	-10000	0	0
DTX1	-0.028	0.17	-10000	0	-0.57	95	95
LRP6/FZD1	0.034	0.009	-10000	0	-10000	0	0
TLE1	0.02	0.044	-10000	0	-0.57	6	6
AP1	-0.074	0.15	-10000	0	-0.31	293	293
NCSTN	0.02	0.009	-10000	0	-10000	0	0
ADAM10	0.021	0.036	-10000	0	-0.57	4	4
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.013	0.1	-10000	0	-0.63	19	19
NICD/RBPSUH	0.02	0.081	-10000	0	-0.41	28	28
WIF1	-0.27	0.3	0.26	13	-0.57	544	557
NOTCH1	0.008	0.075	-10000	0	-0.43	29	29
PSENEN	0.024	0.011	0.26	2	-10000	0	2
KREMEN2	0.12	0.12	0.26	473	-10000	0	473
DKK1	0.026	0.16	0.26	146	-0.57	54	200
beta catenin/beta TrCP1	0.009	0.067	-10000	0	-0.36	5	5
APH1B	0.023	0.018	-10000	0	-0.57	1	1
APH1A	0.02	0.009	-10000	0	-10000	0	0
AXIN1	0.011	0.061	-10000	0	-0.45	9	9
CtBP/CBP/TCF1/TLE1/AES	0.012	0.038	-10000	0	-0.28	7	7
PSEN1	0.024	0.005	-10000	0	-10000	0	0
FOS	-0.14	0.27	-10000	0	-0.57	306	306
JUN	0.02	0.044	-10000	0	-0.57	6	6
MAP3K7	0.021	0.009	-10000	0	-10000	0	0
CTNNB1	0	0.066	0.25	1	-0.37	6	7
MAPK3	0.023	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.091	0.099	0.34	1	-0.33	22	23
HNF1A	0.025	0.02	0.25	8	-10000	0	8
CTBP1	0.023	0.006	-10000	0	-10000	0	0
MYC	-0.013	0.21	-10000	0	-1.3	27	27
NKD1	0.022	0.053	0.26	16	-0.57	6	22
FZD1	0.024	0.004	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.006	0.12	-10000	0	-0.45	28	28
apoptosis	-0.074	0.15	-10000	0	-0.31	293	293
Delta 1/NOTCHprecursor	0.018	0.083	-10000	0	-0.42	23	23
DLL1	0.02	0.041	-10000	0	-0.57	5	5
PPARD	0.015	0.092	-10000	0	-0.82	12	12
Gamma Secretase	0.055	0.034	-10000	0	-0.31	1	1
APC	0.004	0.082	-10000	0	-0.49	20	20
DVL1	-0.029	0.077	-10000	0	-0.36	35	35
CSNK2A1	0.024	0.005	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.099	0.14	0.34	80	-0.34	47	127
LRP6	0.023	0.005	-10000	0	-10000	0	0
CSNK1A1	0.024	0.004	-10000	0	-10000	0	0
NLK	0.009	0.009	-10000	0	-10000	0	0
CCND1	0.02	0.1	-10000	0	-1.1	7	7
WNT1	0.023	0.011	0.26	2	-10000	0	2
Axin1/APC/beta catenin	0.013	0.098	0.32	5	-0.46	14	19
DKK2	0.009	0.095	0.26	2	-0.57	28	30
NOTCH1 precursor/DVL1	-0.02	0.11	-10000	0	-0.59	24	24
GSK3B	0.024	0.004	-10000	0	-10000	0	0
FRAT1	0.024	0.004	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.003	0.12	-10000	0	-0.46	28	28
PPP2R5D	-0.004	0.057	0.29	5	-0.36	16	21
MAPK1	0.023	0.006	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.14	0.19	-10000	0	-0.33	526	526
RBPJ	0.023	0.005	-10000	0	-10000	0	0
CREBBP	0.024	0.009	-10000	0	-10000	0	0

×

Nectin adhesion pathway

Figure S58. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S58. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.036	-10000	0	-0.57	4	4
alphaV beta3 Integrin	0.021	0.079	-10000	0	-0.42	33	33
PTK2	-0.04	0.16	-10000	0	-0.48	92	92
positive regulation of JNK cascade	-0.021	0.12	-10000	0	-0.32	120	120
CDC42/GDP	-0.018	0.17	0.42	1	-0.43	127	128
Rac1/GDP	-0.018	0.17	-10000	0	-0.43	126	126
RAP1B	0.024	0.005	-10000	0	-10000	0	0
RAP1A	0.024	0.004	-10000	0	-10000	0	0
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.022	0.15	-10000	0	-0.4	118	118
nectin-3/I-afadin	-0.015	0.14	-10000	0	-0.42	115	115
RAPGEF1	-0.036	0.17	0.46	1	-0.47	113	114
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.05	0.18	-10000	0	-0.54	113	113
PDGFB-D/PDGFRB	0.022	0.036	-10000	0	-0.56	4	4
TLN1	-0.024	0.071	-10000	0	-0.4	14	14
Rap1/GTP	-0.024	0.12	-10000	0	-0.34	109	109
IQGAP1	0.024	0.005	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.027	-10000	0	-0.33	3	3
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.015	0.14	-10000	0	-0.42	115	115
PVR	0.024	0.004	-10000	0	-10000	0	0
Necl-5(dimer)	0.024	0.004	-10000	0	-10000	0	0
mol:GDP	-0.038	0.2	0.44	1	-0.52	128	129
MLLT4	0.021	0.032	0.26	1	-0.57	3	4
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
PI3K	0.018	0.13	-10000	0	-0.34	116	116
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.029	0.029	-10000	0	-0.3	6	6
positive regulation of lamellipodium assembly	-0.02	0.13	-10000	0	-0.34	128	128
PVRL1	0.022	0.007	-10000	0	-10000	0	0
PVRL3	-0.039	0.18	-10000	0	-0.57	114	114
PVRL2	0.024	0.004	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
CDH1	0.012	0.076	-10000	0	-0.57	18	18
CLDN1	0.007	0.12	0.26	23	-0.57	40	63
JAM-A/CLDN1	0.003	0.13	-10000	0	-0.35	112	112
SRC	-0.056	0.21	-10000	0	-0.58	119	119
ITGB3	0.006	0.1	0.26	4	-0.57	33	37
nectin-1(dimer)/I-afadin/I-afadin	0.029	0.029	-10000	0	-0.3	6	6
FARP2	-0.038	0.2	0.43	1	-0.54	110	111
RAC1	0.024	0.003	-10000	0	-10000	0	0
CTNNA1	0.024	0.004	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.001	0.13	-10000	0	-0.37	114	114
nectin-1/I-afadin	0.029	0.029	-10000	0	-0.3	6	6
nectin-2/I-afadin	0.032	0.029	-10000	0	-0.3	6	6
RAC1/GTP/IQGAP1/filamentous actin	0.031	0.007	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.001	0.13	-10000	0	-0.36	115	115
CDC42/GTP/IQGAP1/filamentous actin	0.031	0.009	-10000	0	-10000	0	0
F11R	0.02	0.009	-10000	0	-10000	0	0
positive regulation of filopodium formation	-0.021	0.12	-10000	0	-0.32	120	120
alphaV/beta3 Integrin/Talin	-0.006	0.1	0.26	2	-0.41	40	42
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.029	-10000	0	-0.3	6	6
nectin-2(dimer)/I-afadin/I-afadin	0.032	0.029	-10000	0	-0.3	6	6
PIP5K1C	-0.019	0.079	-10000	0	-0.23	112	112
VAV2	-0.038	0.21	0.43	1	-0.54	128	129
RAP1/GDP	-0.014	0.16	0.39	1	-0.4	116	117
ITGAV	0.024	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.001	0.13	-10000	0	-0.37	114	114
nectin-3(dimer)/I-afadin/I-afadin	-0.015	0.14	-10000	0	-0.42	115	115
Rac1/GTP	-0.021	0.16	-10000	0	-0.41	128	128
PTPRM	-0.017	0.088	-10000	0	-0.25	116	116
E-cadherin/beta catenin/alpha catenin	0.047	0.062	-10000	0	-0.32	20	20
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.023	0.005	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

Figure S59. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S59. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.012	0.14	-10000	0	-0.57	66	66
HRAS	0.026	0.022	0.26	9	-10000	0	9
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
AKT	-0.014	0.12	0.28	7	-0.28	101	108
FOXO3	0.022	0.019	-10000	0	-0.57	1	1
AKT1	0.024	0.004	-10000	0	-10000	0	0
FOXO1	0.019	0.041	-10000	0	-0.57	5	5
AKT3	0.014	0.06	-10000	0	-0.57	11	11
FOXO4	0.024	0.001	-10000	0	-10000	0	0
MET	-0.073	0.22	-10000	0	-0.57	177	177
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
PIK3CB	0.024	0.004	-10000	0	-10000	0	0
NRAS	0.024	0.004	-10000	0	-10000	0	0
PIK3CG	0.016	0.073	0.26	4	-0.57	16	20
PIK3R3	0.024	0.008	0.26	1	-10000	0	1
PIK3R2	0.024	0.004	-10000	0	-10000	0	0
NF1	0.023	0.006	-10000	0	-10000	0	0
RAS	-0.061	0.14	0.21	4	-0.24	354	358
ERBB2	0.02	0.02	-10000	0	-0.57	1	1
proliferation/survival/translation	-0.006	0.089	0.32	50	-0.26	1	51
PI3K	-0.05	0.14	0.24	14	-0.32	171	185
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
KRAS	0.023	0.005	-10000	0	-10000	0	0
FOXO	0.037	0.057	0.24	11	-0.16	2	13
AKT2	0.024	0.004	-10000	0	-10000	0	0
PTEN	0.022	0.019	-10000	0	-0.57	1	1

×

Glypican 2 network

Figure S60. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S60. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.033	0.044	0.26	40	-10000	0	40
GPC2	0.049	0.081	0.26	126	-0.57	3	129
GPC2/Midkine	0.058	0.069	0.36	16	-0.42	3	19
neuron projection morphogenesis	0.057	0.069	0.36	16	-0.42	3	19

×

Rapid glucocorticoid signaling

Figure S61. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S61. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.042	0.15	-10000	0	-0.32	238	238
MAPK9	0.006	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.005	0.014	0.13	9	-10000	0	9
GNB1/GNG2	0.026	0.043	-10000	0	-0.36	13	13
GNB1	0.023	0.005	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.006	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.061	0.14	-10000	0	-0.31	251	251
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.02	0.034	0.081	251	-10000	0	251
GNAL	-0.11	0.24	-10000	0	-0.57	235	235
GNG2	0.017	0.065	-10000	0	-0.57	13	13
CRH	0.017	0.023	0.26	9	-10000	0	9
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.004	0.031	-10000	0	-0.35	8	8
MAPK11	0.005	0.019	-10000	0	-0.35	3	3

×

E-cadherin signaling in keratinocytes

Figure S62. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S62. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.001	0.064	0.22	2	-0.32	12	14
adherens junction organization	-0.013	0.091	0.22	1	-0.34	50	51
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.085	0.15	0.3	5	-0.33	117	122
FMN1	-0.011	0.085	-10000	0	-0.3	54	54
mol:IP3	-0.001	0.053	-10000	0	-0.28	13	13
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.007	0.087	-10000	0	-0.32	48	48
CTNNB1	0.025	0.005	-10000	0	-10000	0	0
AKT1	0.002	0.063	-10000	0	-0.28	13	13
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.012	0.13	-10000	0	-0.54	35	35
CTNND1	0.024	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.008	0.075	-10000	0	-0.3	42	42
VASP	-0.009	0.08	-10000	0	-0.3	46	46
ZYX	-0.009	0.081	-10000	0	-0.31	44	44
JUB	-0.008	0.082	-10000	0	-0.3	48	48
EGFR(dimer)	-0.1	0.18	-10000	0	-0.32	375	375
E-cadherin/beta catenin-gamma catenin	0.033	0.055	-10000	0	-0.35	18	18
mol:PI-3-4-5-P3	0.016	0.073	-10000	0	-0.28	19	19
PIK3CA	0.023	0.007	-10000	0	-10000	0	0
PI3K	0.016	0.075	-10000	0	-0.28	19	19
FYN	-0.003	0.067	0.22	2	-0.32	11	13
mol:Ca2+	-0.001	0.053	-10000	0	-0.27	13	13
JUP	0.024	0.006	-10000	0	-10000	0	0
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
mol:DAG	-0.001	0.053	-10000	0	-0.28	13	13
CDH1	0.012	0.076	-10000	0	-0.57	18	18
RhoA/GDP	-0.084	0.15	0.32	3	-0.34	110	113
establishment of polarity of embryonic epithelium	-0.009	0.079	-10000	0	-0.3	46	46
SRC	0.023	0.005	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
CASR	-0.003	0.055	0.23	2	-0.27	11	13
RhoA/GTP	0.013	0.057	-10000	0	-0.26	10	10
AKT2	0.001	0.063	-10000	0	-0.29	11	11
actin cable formation	-0.016	0.086	0.25	2	-0.32	43	45
apoptosis	-0.005	0.073	0.28	25	-0.23	10	35
CTNNA1	0.024	0.006	-10000	0	-10000	0	0
mol:GDP	-0.097	0.15	-10000	0	-0.3	345	345
PIP5K1A	-0.008	0.077	-10000	0	-0.31	42	42
PLCG1	-0.001	0.054	-10000	0	-0.28	13	13
Rac1/GTP	-0.092	0.17	-10000	0	-0.38	141	141
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

Figure S63. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S63. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.056	0.2	0.29	1	-0.39	192	193
MAP3K8	0.009	0.051	-10000	0	-0.57	7	7
FOS	-0.02	0.14	0.29	2	-0.44	52	54
PRKCA	-0.002	0.086	0.24	1	-0.57	22	23
PTPN7	0.021	0.06	0.24	61	-10000	0	61
HRAS	0.024	0.022	0.25	9	-10000	0	9
PRKCB	0.006	0.079	0.25	19	-0.57	15	34
NRAS	0.023	0.004	-10000	0	-10000	0	0
RAS family/GTP	0.025	0.036	-10000	0	-10000	0	0
MAPK3	0.008	0.09	-10000	0	-0.66	7	7
MAP2K1	-0.012	0.12	-10000	0	-0.5	45	45
ELK1	0.006	0.029	-10000	0	-10000	0	0
BRAF	-0.012	0.099	-10000	0	-0.48	39	39
mol:GTP	-0.002	0.003	-10000	0	-0.006	323	323
MAPK1	-0.009	0.12	-10000	0	-0.47	41	41
RAF1	-0.011	0.097	-10000	0	-0.48	39	39
KRAS	0.022	0.005	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

Figure S64. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S64. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	-0.003	0.04	0.22	27	-10000	0	27
RFC1	-0.003	0.036	0.22	23	-0.19	4	27
PRKDC	0.016	0.078	0.23	106	-10000	0	106
RIPK1	0.027	0.007	-10000	0	-10000	0	0
CASP7	-0.018	0.1	-10000	0	-0.63	22	22
FASLG/FAS/FADD/FAF1	-0.005	0.059	0.22	11	-0.29	14	25
MAP2K4	-0.084	0.18	0.39	2	-0.42	113	115
mol:ceramide	-0.024	0.1	-10000	0	-0.39	27	27
GSN	-0.006	0.053	0.22	26	-0.35	11	37
FASLG/FAS/FADD/FAF1/Caspase 8	-0.008	0.078	0.28	1	-0.37	17	18
FAS	0.003	0.044	-10000	0	-0.58	4	4
BID	-0.018	0.021	-10000	0	-10000	0	0
MAP3K1	-0.047	0.12	0.39	1	-0.43	35	36
MAP3K7	0.011	0.019	-10000	0	-10000	0	0
RB1	-0.003	0.036	0.22	22	-10000	0	22
CFLAR	0.027	0.018	-10000	0	-0.54	1	1
HGF/MET	-0.052	0.19	-10000	0	-0.4	233	233
ARHGDIB	-0.001	0.043	0.22	34	-10000	0	34
FADD	0.006	0.023	-10000	0	-10000	0	0
actin filament polymerization	0.009	0.059	0.35	11	-0.21	30	41
NFKB1	-0.044	0.12	-10000	0	-0.58	18	18
MAPK8	-0.15	0.26	0.56	2	-0.47	389	391
DFFA	-0.004	0.036	0.22	22	-10000	0	22
DNA fragmentation during apoptosis	-0.006	0.045	0.21	26	-10000	0	26
FAS/FADD/MET	-0.038	0.14	-10000	0	-0.38	143	143
CFLAR/RIP1	0.039	0.018	-10000	0	-0.38	1	1
FAIM3	0.026	0.035	0.26	22	-10000	0	22
FAF1	0.003	0.029	-10000	0	-10000	0	0
PARP1	-0.001	0.046	0.22	36	-10000	0	36
DFFB	-0.004	0.037	0.22	22	-10000	0	22
CHUK	-0.039	0.11	-10000	0	-0.56	15	15
FASLG	0.006	0.089	0.25	42	-0.58	15	57
FAS/FADD	0.009	0.039	-10000	0	-0.32	4	4
HGF	-0.011	0.14	0.26	2	-0.57	65	67
LMNA	-0.003	0.053	-10000	0	-10000	0	0
CASP6	-0.003	0.036	0.22	22	-10000	0	22
CASP10	0.004	0.04	-10000	0	-0.58	3	3
CASP3	0	0.042	0.26	24	-10000	0	24
PTPN13	0.01	0.091	-10000	0	-0.57	26	26
CASP8	-0.021	0.024	-10000	0	-10000	0	0
IL6	-0.43	0.62	-10000	0	-1.2	399	399
MET	-0.073	0.22	-10000	0	-0.57	177	177
ICAD/CAD	-0.006	0.032	0.2	13	-10000	0	13
FASLG/FAS/FADD/FAF1/Caspase 10	-0.024	0.1	-10000	0	-0.39	27	27
activation of caspase activity by cytochrome c	-0.018	0.02	-10000	0	-10000	0	0
PAK2	-0.003	0.047	0.22	35	-0.19	6	41
BCL2	0.008	0.094	-10000	0	-0.56	28	28

×

Syndecan-3-mediated signaling events

Figure S65. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S65. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.021	0.009	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	-0.071	0.16	-10000	0	-0.48	25	25
Syndecan-3/Neurocan	0.027	0.073	0.27	18	-0.37	20	38
POMC	0.019	0.093	0.26	30	-0.57	22	52
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
Syndecan-3/EGFR	-0.088	0.16	-10000	0	-0.31	305	305
AGRP	0.021	0.024	0.26	10	-10000	0	10
NCSTN	0.02	0.009	-10000	0	-10000	0	0
PSENEN	0.024	0.011	0.26	2	-10000	0	2
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.023	0.018	-10000	0	-0.57	1	1
APH1A	0.02	0.009	-10000	0	-10000	0	0
NCAN	0.036	0.055	0.26	64	-10000	0	64
long-term memory	0.035	0.062	-10000	0	-0.35	16	16
Syndecan-3/IL8	0.02	0.081	0.28	9	-0.34	36	45
PSEN1	0.024	0.005	-10000	0	-10000	0	0
Src/Cortactin	0.03	0.014	-10000	0	-10000	0	0
FYN	0.021	0.026	-10000	0	-0.57	2	2
limb bud formation	0.002	0.055	-10000	0	-0.39	21	21
MC4R	0.023	0.026	0.26	13	-10000	0	13
SRC	0.023	0.005	-10000	0	-10000	0	0
PTN	-0.23	0.29	0.26	2	-0.57	455	457
FGFR/FGF/Syndecan-3	0.002	0.056	-10000	0	-0.39	21	21
neuron projection morphogenesis	-0.071	0.15	0.33	5	-0.47	23	28
Syndecan-3/AgRP	0.015	0.06	0.26	1	-0.37	21	22
Syndecan-3/AgRP/MC4R	0.038	0.068	0.33	1	-0.36	20	21
Fyn/Cortactin	0.028	0.021	-10000	0	-0.3	2	2
SDC3	0.002	0.056	-10000	0	-0.39	21	21
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.02	0.08	0.28	9	-0.33	36	45
IL8	0.025	0.099	0.26	60	-0.57	21	81
Syndecan-3/Fyn/Cortactin	0.036	0.064	-10000	0	-0.36	16	16
Syndecan-3/CASK	0	0.054	-10000	0	-0.37	21	21
alpha-MSH/MC4R	0.029	0.072	0.36	2	-0.41	22	24
Gamma Secretase	0.054	0.034	-10000	0	-0.32	1	1

×

Signaling events mediated by HDAC Class III

Figure S66. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S66. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.023	0.006	-10000	0	-10000	0	0
HDAC4	0.023	0.018	-10000	0	-0.57	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.02	0.07	0.42	1	-0.26	52	53
CDKN1A	-0.009	0.033	-10000	0	-0.77	2	2
KAT2B	0.024	0.018	-10000	0	-0.57	1	1
BAX	0.025	0.014	0.26	4	-10000	0	4
FOXO3	-0.005	0.008	-10000	0	-0.25	1	1
FOXO1	0.019	0.041	-10000	0	-0.57	5	5
FOXO4	0.012	0.004	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.023	0.006	-10000	0	-10000	0	0
TAT	-0.32	0.3	0.26	26	-0.57	635	661
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.008	0.023	-10000	0	-0.42	1	1
PPARGC1A	-0.09	0.24	0.26	10	-0.57	211	221
FHL2	0.022	0.041	0.26	1	-0.57	5	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.032	0.011	-10000	0	-10000	0	0
HIST2H4A	0.02	0.07	0.26	52	-0.42	1	53
SIRT1/FOXO3a	0.015	0.026	-10000	0	-0.19	4	4
SIRT1	0.022	0.009	0.21	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.039	0.023	-10000	0	-0.36	1	1
SIRT1/Histone H1b	0.028	0.043	-10000	0	-0.21	6	6
apoptosis	-0.044	0.016	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.047	0.16	-10000	0	-0.36	209	209
p53/SIRT1	0.027	0.019	0.41	2	-10000	0	2
SIRT1/FOXO4	0.022	0.037	-10000	0	-0.21	4	4
FOXO1/FHL2/SIRT1	0.037	0.041	-10000	0	-0.33	10	10
HIST1H1E	0.021	0.03	0.2	6	-10000	0	6
SIRT1/p300	0.032	0.011	-10000	0	-10000	0	0
muscle cell differentiation	-0.029	0.023	0.36	1	-10000	0	1
TP53	0.02	0.011	0.21	2	-10000	0	2
KU70/SIRT1/BAX	0.045	0.016	-10000	0	-10000	0	0
CREBBP	0.023	0.007	-10000	0	-10000	0	0
MEF2D	0.021	0.009	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.25	0.21	-10000	0	-0.42	635	635
ACSS2	-0.007	0.008	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.029	0.023	-10000	0	-0.36	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

Figure S67. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S67. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.012	0.041	-10000	0	-0.26	19	19
epithelial cell differentiation	0.037	0.052	-10000	0	-0.31	18	18
CYFIP2	0.028	0.048	0.26	26	-0.57	3	29
ENAH	-0.003	0.059	0.3	11	-10000	0	11
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
EPHA2	0.02	0.04	-10000	0	-0.57	5	5
MYO6	-0.011	0.05	0.36	1	-0.3	19	20
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.049	0.034	-10000	0	-0.36	3	3
AQP5	-0.18	0.26	0.31	2	-0.5	419	421
CTNND1	0.024	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.011	0.049	0.36	1	-0.3	18	19
regulation of calcium-dependent cell-cell adhesion	-0.022	0.074	0.36	1	-0.29	62	63
EGF	-0.082	0.23	0.26	2	-0.57	194	196
NCKAP1	0.024	0.003	-10000	0	-10000	0	0
AQP3	-0.015	0.12	0.29	1	-0.47	55	56
cortical microtubule organization	0.037	0.052	-10000	0	-0.31	18	18
GO:0000145	-0.011	0.046	0.35	1	-0.28	18	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.041	0.053	-10000	0	-0.31	18	18
MLLT4	0.021	0.032	0.26	1	-0.57	3	4
ARF6/GDP	-0.02	0.037	-10000	0	-0.27	18	18
ARF6	0.024	0.004	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.038	-10000	0	-0.33	5	5
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0	0.048	-10000	0	-0.28	18	18
PVRL2	0.024	0.004	-10000	0	-10000	0	0
ZYX	-0.011	0.049	0.36	1	-0.3	18	19
ARF6/GTP	0.049	0.04	-10000	0	-0.31	5	5
CDH1	0.012	0.076	-10000	0	-0.57	18	18
EGFR/EGFR/EGF/EGF	-0.14	0.2	-10000	0	-0.33	519	519
RhoA/GDP	0.038	0.051	-10000	0	-0.3	18	18
actin cytoskeleton organization	-0.012	0.047	0.34	1	-0.29	19	20
IGF-1R heterotetramer	0.013	0.079	0.26	3	-0.56	19	22
GIT1	0.023	0.006	-10000	0	-10000	0	0
IGF1R	0.013	0.079	0.26	3	-0.57	19	22
IGF1	-0.1	0.24	-10000	0	-0.57	233	233
DIAPH1	0.026	0.1	-10000	0	-0.55	15	15
Wnt receptor signaling pathway	-0.037	0.052	0.31	18	-10000	0	18
RHOA	0.024	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.02	0.037	-10000	0	-0.28	15	15
CTNNA1	0.024	0.004	-10000	0	-10000	0	0
VCL	-0.013	0.048	0.35	1	-0.3	19	20
EFNA1	0.02	0.009	-10000	0	-10000	0	0
LPP	-0.014	0.052	-10000	0	-0.29	25	25
Ephrin A1/EPHA2	0.026	0.051	-10000	0	-0.29	20	20
SEC6/SEC8	-0.021	0.04	-10000	0	-0.3	19	19
MGAT3	-0.022	0.075	0.36	1	-0.3	62	63
HGF/MET	-0.039	0.15	-10000	0	-0.32	232	232
HGF	-0.011	0.14	0.26	2	-0.57	65	67
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.012	0.042	-10000	0	-0.26	19	19
actin cable formation	0.042	0.094	0.32	34	-0.29	1	35
KIAA1543	-0.012	0.053	0.35	1	-0.33	18	19
KIFC3	-0.012	0.047	0.36	1	-0.3	18	19
NCK1	0.024	0.003	-10000	0	-10000	0	0
EXOC3	0.024	0.005	-10000	0	-10000	0	0
ACTN1	-0.011	0.048	-10000	0	-0.3	18	18
NCK1/GIT1	0.033	0.01	-10000	0	-10000	0	0
mol:GDP	0.037	0.052	-10000	0	-0.31	18	18
EXOC4	0.024	0.004	-10000	0	-10000	0	0
STX4	-0.011	0.047	0.36	1	-0.3	17	18
PIP5K1C	-0.011	0.05	0.36	1	-0.3	18	19
LIMA1	0.024	0.018	-10000	0	-0.57	1	1
ABI1	0.024	0.004	-10000	0	-10000	0	0
ROCK1	0.017	0.088	0.31	26	-10000	0	26
adherens junction assembly	-0.021	0.1	0.3	3	-0.63	16	19
IGF-1R heterotetramer/IGF1	-0.041	0.15	-10000	0	-0.31	234	234
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.032	0.029	-10000	0	-0.3	6	6
MET	-0.073	0.22	-10000	0	-0.57	177	177
PLEKHA7	-0.012	0.056	0.36	1	-0.35	18	19
mol:GTP	0.043	0.037	-10000	0	-0.33	5	5
establishment of epithelial cell apical/basal polarity	-0.007	0.066	0.37	7	-0.51	1	8
cortical actin cytoskeleton stabilization	0.012	0.041	-10000	0	-0.26	19	19
regulation of cell-cell adhesion	-0.012	0.047	0.34	1	-0.29	19	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.012	0.042	-10000	0	-0.26	19	19

×

LPA4-mediated signaling events

Figure S68. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S68. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.018	0.063	-10000	0	-0.36	36	36
ADCY5	-0.11	0.16	-10000	0	-0.36	328	328
ADCY6	-0.007	0.001	-10000	0	-10000	0	0
ADCY7	-0.006	0.002	-10000	0	-10000	0	0
ADCY1	-0.009	0.062	-10000	0	-0.36	28	28
ADCY2	-0.03	0.1	0.24	8	-0.36	85	93
ADCY3	-0.007	0.003	-10000	0	-10000	0	0
ADCY8	-0.004	0.023	0.23	6	-10000	0	6
PRKCE	0.006	0.001	-10000	0	-10000	0	0
ADCY9	-0.006	0.002	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.011	0.085	0.23	16	-0.25	33	49

×

Aurora A signaling

Figure S69. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S69. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.044	0.041	-10000	0	-10000	0	0
BIRC5	0.18	0.11	0.26	711	-10000	0	711
NFKBIA	0.024	0.04	0.28	8	-10000	0	8
CPEB1	-0.079	0.22	0.26	1	-0.57	187	188
AKT1	0.023	0.04	0.29	7	-10000	0	7
NDEL1	0.022	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0.033	0.036	0.21	1	-10000	0	1
NDEL1/TACC3	0.066	0.067	0.26	17	-10000	0	17
GADD45A	0.024	0.004	-10000	0	-10000	0	0
GSK3B	-0.001	0.026	-10000	0	-10000	0	0
PAK1/Aurora A	0.04	0.043	0.27	2	-10000	0	2
MDM2	0.024	0.005	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.09	0.067	0.27	26	-10000	0	26
TP53	0.022	0.051	0.19	1	-0.22	13	14
DLG7	0.022	0.03	0.18	1	-10000	0	1
AURKAIP1	0.026	0.024	0.26	11	-10000	0	11
ARHGEF7	0.022	0.007	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.069	0.071	0.28	17	-10000	0	17
G2/M transition of mitotic cell cycle	0.031	0.034	0.2	1	-10000	0	1
AURKA	0.037	0.045	0.24	1	-10000	0	1
AURKB	0.086	0.074	0.17	434	-10000	0	434
CDC25B	0.031	0.039	0.22	3	-10000	0	3
G2/M transition checkpoint	0.019	0.028	-10000	0	-10000	0	0
mRNA polyadenylation	-0.026	0.13	-10000	0	-0.29	185	185
Aurora A/CPEB	-0.025	0.13	-10000	0	-0.3	185	185
Aurora A/TACC1/TRAP/chTOG	0.044	0.07	-10000	0	-0.3	22	22
BRCA1	0.023	0.02	0.26	1	-0.57	1	2
centrosome duplication	0.04	0.043	0.27	2	-10000	0	2
regulation of centrosome cycle	0.064	0.066	0.26	17	-10000	0	17
spindle assembly	0.042	0.069	-10000	0	-0.3	22	22
TDRD7	0.024	0.003	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.14	0.087	0.28	29	-10000	0	29
CENPA	0.095	0.081	0.18	445	-0.21	3	448
Aurora A/PP2A	0.043	0.042	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.03	0.039	0.24	1	-10000	0	1
negative regulation of DNA binding	0.018	0.063	-10000	0	-0.22	13	13
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.031	0.013	-10000	0	-10000	0	0
RASA1	0.024	0.004	-10000	0	-10000	0	0
Ajuba/Aurora A	0.019	0.028	-10000	0	-10000	0	0
mitotic prometaphase	-0.009	0.028	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.045	0.24	1	-10000	0	1
TACC1	0.006	0.089	-10000	0	-0.57	25	25
TACC3	0.058	0.083	0.26	162	-10000	0	162
Aurora A/Antizyme1	0.054	0.043	-10000	0	-10000	0	0
Aurora A/RasGAP	0.043	0.042	-10000	0	-10000	0	0
OAZ1	0.024	0.005	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.001	0.027	-10000	0	-10000	0	0
GIT1	0.023	0.006	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.039	0.024	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.089	0.067	0.27	26	-10000	0	26
PPP2R5D	0.024	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.094	0.072	0.24	39	-10000	0	39
PAK1	0.023	0.019	0.26	6	-10000	0	6
CKAP5	0.024	0.003	-10000	0	-10000	0	0

×

Signaling events mediated by PRL

Figure S70. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S70. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.062	0.087	0.26	179	-10000	0	179
mol:Halofuginone	0.002	0.004	-10000	0	-10000	0	0
ITGA1	0.018	0.057	-10000	0	-0.57	10	10
CDKN1A	-0.031	0.093	-10000	0	-0.44	29	29
PRL-3/alpha Tubulin	0.03	0.019	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.075	0.24	44	-0.42	13	57
AGT	0.029	0.089	0.26	73	-0.57	13	86
CCNA2	-0.065	0.14	-10000	0	-10000	0	0
TUBA1B	0.024	0.002	-10000	0	-10000	0	0
EGR1	-0.12	0.2	-10000	0	-0.41	336	336
CDK2/Cyclin E1	0.016	0.11	-10000	0	-0.49	16	16
MAPK3	0.01	0.018	0.26	4	-10000	0	4
PRL-2 /Rab GGTase beta	0.035	0.007	-10000	0	-10000	0	0
MAPK1	0.01	0.018	0.26	4	-10000	0	4
PTP4A1	-0.093	0.14	-10000	0	-0.32	299	299
PTP4A3	0.021	0.02	0.26	6	-10000	0	6
PTP4A2	0.024	0.004	-10000	0	-10000	0	0
ITGB1	0.01	0.017	0.26	3	-10000	0	3
SRC	0.023	0.005	-10000	0	-10000	0	0
RAC1	-0.016	0.071	-10000	0	-0.43	12	12
Rab GGTase beta/Rab GGTase alpha	0.035	0.008	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.072	0.15	-10000	0	-10000	0	0
RABGGTA	0.024	0.004	-10000	0	-10000	0	0
BCAR1	-0.014	0.015	-10000	0	-10000	0	0
RHOC	-0.019	0.079	-10000	0	-0.42	19	19
RHOA	-0.021	0.089	-10000	0	-0.47	24	24
cell motility	-0.026	0.1	0.25	1	-0.37	40	41
PRL-1/alpha Tubulin	-0.073	0.15	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.026	0.041	-10000	0	-0.33	10	10
ROCK1	-0.024	0.098	0.25	1	-0.36	36	37
RABGGTB	0.024	0.004	-10000	0	-10000	0	0
CDK2	0.024	0.002	-10000	0	-10000	0	0
mitosis	-0.093	0.14	-10000	0	-0.32	299	299
ATF5	0.025	0.013	0.26	3	-10000	0	3

×

Coregulation of Androgen receptor activity

Figure S71. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S71. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.012	0.04	-10000	0	-0.57	1	1
SVIL	0.01	0.052	-10000	0	-0.57	5	5
ZNF318	0.039	0.054	0.19	90	-10000	0	90
JMJD2C	-0.001	0.042	0.11	32	-0.13	78	110
T-DHT/AR/Ubc9	-0.034	0.14	-10000	0	-0.37	139	139
CARM1	0.019	0.015	-10000	0	-10000	0	0
PRDX1	0.025	0.006	-10000	0	-10000	0	0
PELP1	0.025	0.011	-10000	0	-10000	0	0
CTNNB1	0.014	0.029	-10000	0	-10000	0	0
AKT1	0.027	0.018	-10000	0	-10000	0	0
PTK2B	0.012	0.026	-10000	0	-10000	0	0
MED1	0.025	0.02	-10000	0	-10000	0	0
MAK	0.034	0.083	0.25	14	-0.54	11	25
response to oxidative stress	0.001	0.004	-10000	0	-10000	0	0
HIP1	0.01	0.052	-10000	0	-0.57	5	5
GSN	0.006	0.071	-10000	0	-0.57	12	12
NCOA2	-0.01	0.12	-10000	0	-0.57	48	48
NCOA6	0.013	0.033	-10000	0	-10000	0	0
DNA-PK	0.05	0.053	0.23	2	-10000	0	2
NCOA4	0.02	0.013	-10000	0	-10000	0	0
PIAS3	0.013	0.027	-10000	0	-10000	0	0
cell proliferation	0.004	0.11	0.35	1	-0.57	24	25
XRCC5	0.026	0.015	-10000	0	-10000	0	0
UBE3A	0.009	0.044	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.042	0.15	-10000	0	-0.39	151	151
FHL2	0.002	0.1	-10000	0	-0.86	7	7
RANBP9	0.013	0.033	-10000	0	-10000	0	0
JMJD1A	-0.015	0.047	0.12	1	-0.14	131	132
CDK6	0.02	0.058	0.26	2	-0.57	10	12
TGFB1I1	0.01	0.046	-10000	0	-0.57	3	3
T-DHT/AR/CyclinD1	-0.042	0.14	-10000	0	-0.38	140	140
XRCC6	0.025	0.016	-10000	0	-10000	0	0
T-DHT/AR	-0.041	0.16	-10000	0	-0.38	150	150
CTDSP1	0.018	0.019	-10000	0	-10000	0	0
CTDSP2	0.034	0.037	-10000	0	-10000	0	0
BRCA1	0.012	0.039	-10000	0	-0.57	1	1
TCF4	0.024	0.066	-10000	0	-0.56	11	11
CDKN2A	0.063	0.088	0.26	170	-10000	0	170
SRF	0.032	0.023	-10000	0	-10000	0	0
NKX3-1	-0.047	0.096	-10000	0	-0.21	248	248
KLK3	-0.14	0.46	-10000	0	-1.4	126	126
TMF1	0.018	0.016	-10000	0	-10000	0	0
HNRNPA1	0.028	0.02	-10000	0	-10000	0	0
AOF2	-0.007	0.023	-10000	0	-0.069	126	126
APPL1	0.019	0.032	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.028	0.14	-10000	0	-0.36	150	150
AR	-0.067	0.2	-10000	0	-0.58	141	141
UBA3	0.017	0.019	-10000	0	-10000	0	0
PATZ1	0.027	0.021	-10000	0	-10000	0	0
PAWR	0.018	0.024	-10000	0	-0.57	1	1
PRKDC	0.023	0.016	-10000	0	-10000	0	0
PA2G4	0.031	0.027	-10000	0	-10000	0	0
UBE2I	0.023	0.006	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.024	0.13	-10000	0	-0.34	130	130
RPS6KA3	0.008	0.062	-10000	0	-0.57	8	8
T-DHT/AR/ARA70	-0.037	0.14	-10000	0	-0.37	139	139
LATS2	0.027	0.022	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.022	0.14	-10000	0	-0.34	140	140
Cyclin D3/CDK11 p58	0.019	0.005	-10000	0	-10000	0	0
VAV3	0.014	0.063	0.25	19	-0.57	7	26
KLK2	-0.076	0.27	0.32	2	-0.99	81	83
CASP8	0.026	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.042	0.15	-10000	0	-0.37	149	149
TMPRSS2	-0.13	0.33	-10000	0	-0.98	136	136
CCND1	0.012	0.042	0.26	1	-0.57	4	5
PIAS1	0.01	0.044	-10000	0	-10000	0	0
mol:T-DHT	-0.009	0.028	-10000	0	-0.07	168	168
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	0.003	0.063	-10000	0	-0.21	4	4
T-DHT/AR/CDK6	-0.035	0.14	-10000	0	-0.36	159	159
CMTM2	0.023	0.012	0.25	1	-10000	0	1
SNURF	0.012	0.082	-10000	0	-0.57	21	21
ZMIZ1	0.01	0.039	-10000	0	-10000	0	0
CCND3	0.024	0.005	-10000	0	-10000	0	0
TGIF1	0.027	0.021	-10000	0	-10000	0	0
FKBP4	0.014	0.036	0.26	4	-10000	0	4

×

Regulation of Androgen receptor activity

Figure S72. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S72. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.008	0.01	-10000	0	-10000	0	0
SMARCC1	0.006	0.027	-10000	0	-0.5	2	2
REL	0.017	0.068	-10000	0	-0.57	14	14
HDAC7	-0.036	0.11	0.37	3	-0.41	36	39
JUN	0.019	0.044	-10000	0	-0.57	6	6
EP300	0.023	0.006	-10000	0	-10000	0	0
KAT2B	0.023	0.018	-10000	0	-0.57	1	1
KAT5	0.024	0.005	-10000	0	-10000	0	0
MAPK14	-0.008	0.065	-10000	0	-0.43	23	23
FOXO1	0.019	0.041	-10000	0	-0.57	5	5
T-DHT/AR	-0.023	0.12	0.33	1	-0.39	59	60
MAP2K6	0.002	0.088	0.24	1	-0.57	23	24
BRM/BAF57	0.026	0.027	-10000	0	-10000	0	0
MAP2K4	0.014	0.02	-10000	0	-10000	0	0
SMARCA2	0.018	0.018	-10000	0	-10000	0	0
PDE9A	-0.061	0.26	-10000	0	-1	63	63
NCOA2	-0.008	0.12	-10000	0	-0.57	48	48
CEBPA	0.019	0.057	-10000	0	-0.57	10	10
EHMT2	0.021	0.012	-10000	0	-10000	0	0
cell proliferation	0.001	0.15	0.38	24	-0.45	25	49
NR0B1	0.027	0.042	0.26	35	-10000	0	35
EGR1	-0.16	0.27	-10000	0	-0.57	336	336
RXRs/9cRA	-0.042	0.15	-10000	0	-0.33	216	216
AR/RACK1/Src	-0.016	0.11	0.32	6	-0.36	36	42
AR/GR	-0.028	0.12	0.29	1	-0.3	128	129
GNB2L1	0.023	0.007	-10000	0	-10000	0	0
PKN1	0.024	0.004	-10000	0	-10000	0	0
RCHY1	0.024	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.003	-10000	0	-0.013	14	14
MAPK8	-0.002	0.042	-10000	0	-0.43	8	8
T-DHT/AR/TIF2/CARM1	-0.017	0.12	0.32	1	-0.42	35	36
SRC	-0.019	0.068	0.19	29	-0.34	27	56
NR3C1	0.018	0.06	-10000	0	-0.57	11	11
KLK3	-0.14	0.39	0.38	1	-1.1	134	135
APPBP2	0.016	0.019	-10000	0	-10000	0	0
TRIM24	0.019	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.015	0.097	0.42	1	-0.39	29	30
TMPRSS2	-0.12	0.36	-10000	0	-1.1	135	135
RXRG	-0.1	0.24	0.26	2	-0.57	219	221
mol:9cRA	-0.001	0.002	-10000	0	-0.011	5	5
RXRA	0.023	0.005	-10000	0	-10000	0	0
RXRB	0.024	0.005	-10000	0	-10000	0	0
CARM1	0.022	0.011	-10000	0	-10000	0	0
NR2C2	0.018	0.057	-10000	0	-0.57	10	10
KLK2	-0.051	0.2	0.32	5	-0.66	85	90
AR	-0.04	0.11	-10000	0	-0.3	138	138
SENP1	0.024	0.003	-10000	0	-10000	0	0
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
MDM2	0.025	0.016	-10000	0	-10000	0	0
SRY	0.003	0.012	0.032	126	-0.023	42	168
GATA2	0.013	0.095	0.26	13	-0.57	26	39
MYST2	0	0.002	-10000	0	-10000	0	0
HOXB13	0.11	0.12	0.25	446	-10000	0	446
T-DHT/AR/RACK1/Src	-0.013	0.1	0.34	9	-0.38	30	39
positive regulation of transcription	0.013	0.094	0.26	13	-0.56	26	39
DNAJA1	0.017	0.02	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.016	0.01	-10000	0	-10000	0	0
NCOA1	0.022	0.029	-10000	0	-0.6	1	1
SPDEF	-0.01	0.15	0.26	33	-0.57	68	101
T-DHT/AR/TIF2	-0.005	0.1	0.32	6	-0.37	31	37
T-DHT/AR/Hsp90	-0.016	0.097	0.37	2	-0.38	30	32
GSK3B	0.021	0.01	-10000	0	-10000	0	0
NR2C1	0.025	0.004	-10000	0	-10000	0	0
mol:T-DHT	-0.024	0.062	0.23	1	-0.35	28	29
SIRT1	0.024	0.003	-10000	0	-10000	0	0
ZMIZ2	0.025	0.016	-10000	0	-10000	0	0
POU2F1	0.009	0.05	-10000	0	-0.2	2	2
T-DHT/AR/DAX-1	-0.015	0.1	0.33	3	-0.39	31	34
CREBBP	0.022	0.007	-10000	0	-10000	0	0
SMARCE1	0.018	0.018	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

Figure S73. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S73. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.083	0.1	0.3	6	-0.57	6	12
Syndecan-4/Syndesmos	0.094	0.1	0.39	4	-0.7	6	10
positive regulation of JNK cascade	0.083	0.13	0.36	6	-0.64	8	14
Syndecan-4/ADAM12	0.1	0.12	0.41	8	-0.72	6	14
CCL5	0.029	0.056	0.26	38	-0.57	4	42
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
DNM2	0.024	0.004	-10000	0	-10000	0	0
ITGA5	0.024	0.007	0.26	1	-10000	0	1
SDCBP	0.021	0.008	-10000	0	-10000	0	0
PLG	-0.008	0.034	0.25	8	-10000	0	8
ADAM12	0.036	0.061	0.26	64	-0.57	2	66
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.023	0.012	0.26	2	-10000	0	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.028	0.018	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.066	0.15	0.41	2	-0.74	8	10
Syndecan-4/CXCL12/CXCR4	0.087	0.14	0.38	6	-0.69	8	14
Syndecan-4/Laminin alpha3	0.033	0.15	0.39	3	-0.74	7	10
MDK	0.033	0.044	0.26	40	-10000	0	40
Syndecan-4/FZD7	0.094	0.12	0.38	6	-0.69	7	13
Syndecan-4/Midkine	0.1	0.11	0.38	8	-0.69	6	14
FZD7	0.013	0.082	-10000	0	-0.57	21	21
Syndecan-4/FGFR1/FGF	-0.01	0.16	-10000	0	-0.56	16	16
THBS1	0.021	0.04	-10000	0	-0.57	5	5
integrin-mediated signaling pathway	0.092	0.12	0.37	6	-0.69	7	13
positive regulation of MAPKKK cascade	0.083	0.13	0.36	6	-0.64	8	14
Syndecan-4/TACI	0.098	0.12	0.38	8	-0.72	6	14
CXCR4	0.029	0.034	0.26	24	-10000	0	24
cell adhesion	0.06	0.083	0.25	84	-0.25	21	105
Syndecan-4/Dynamin	0.098	0.1	0.41	2	-0.73	6	8
Syndecan-4/TSP1	0.097	0.11	0.39	4	-0.72	6	10
Syndecan-4/GIPC	0.098	0.1	0.4	2	-0.73	6	8
Syndecan-4/RANTES	0.099	0.11	0.37	5	-0.72	6	11
ITGB1	0.024	0.004	-10000	0	-10000	0	0
LAMA1	-0.034	0.18	0.26	3	-0.57	105	108
LAMA3	-0.12	0.25	-10000	0	-0.57	252	252
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCA	0.024	0.22	0.7	96	-0.53	22	118
Syndecan-4/alpha-Actinin	0.098	0.1	0.4	3	-0.72	6	9
TFPI	-0.005	0.13	0.26	1	-0.57	54	55
F2	0.025	0.034	0.26	13	-10000	0	13
alpha5/beta1 Integrin	0.035	0.008	-10000	0	-10000	0	0
positive regulation of cell adhesion	0	0.17	0.37	3	-0.55	31	34
ACTN1	0.024	0.005	-10000	0	-10000	0	0
TNC	0.013	0.092	0.26	11	-0.57	25	36
Syndecan-4/CXCL12	0.076	0.14	0.38	5	-0.72	8	13
FGF6	0.015	0.025	-10000	0	-0.57	2	2
RHOA	0.024	0.005	-10000	0	-10000	0	0
CXCL12	-0.019	0.15	-10000	0	-0.57	78	78
TNFRSF13B	0.028	0.084	0.26	63	-0.57	12	75
FGF2	-0.2	0.29	-10000	0	-0.57	413	413
FGFR1	0.016	0.048	-10000	0	-0.57	7	7
Syndecan-4/PI-4-5-P2	0.075	0.1	0.34	2	-0.72	6	8
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.11	0.12	0.25	416	-10000	0	416
cell migration	-0.02	0.012	-10000	0	-10000	0	0
PRKCD	0.012	0.025	-10000	0	-10000	0	0
vasculogenesis	0.095	0.1	0.37	6	-0.68	6	12
SDC4	0.087	0.1	0.4	3	-0.78	5	8
Syndecan-4/Tenascin C	0.093	0.12	0.39	4	-0.72	7	11
Syndecan-4/PI-4-5-P2/PKC alpha	-0.023	0.013	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.085	0.1	0.37	3	-0.7	6	9
MMP9	0.12	0.12	0.26	453	-0.56	1	454
Rac1/GTP	0.061	0.084	0.25	83	-0.25	21	104
cytoskeleton organization	0.092	0.1	0.37	6	-0.67	6	12
GIPC1	0.024	0.008	0.26	1	-10000	0	1
Syndecan-4/TFPI	0.085	0.13	0.4	3	-0.72	7	10

×

Thromboxane A2 receptor signaling

Figure S74. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S74. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.027	0.027	0.26	14	-10000	0	14
GNB1/GNG2	-0.016	0.048	-10000	0	-0.19	66	66
AKT1	0.023	0.092	0.36	10	-0.28	26	36
EGF	-0.082	0.23	0.26	2	-0.57	194	196
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.014	0.06	0.25	2	-0.31	6	8
mol:Ca2+	0.021	0.11	0.42	10	-0.3	73	83
LYN	0.013	0.056	0.25	2	-0.35	3	5
RhoA/GTP	0.009	0.045	0.13	3	-0.14	25	28
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.019	0.12	0.44	10	-0.35	63	73
GNG2	0.017	0.065	-10000	0	-0.57	13	13
ARRB2	0.022	0.007	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.007	0.12	-10000	0	-0.57	40	40
G beta5/gamma2	-0.012	0.067	-10000	0	-0.26	65	65
PRKCH	0.017	0.12	0.45	8	-0.36	63	71
DNM1	0.02	0.048	0.26	1	-0.57	7	8
TXA2/TP beta/beta Arrestin3	0.008	0.031	-10000	0	-0.4	2	2
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.008	0.1	0.26	7	-0.57	32	39
G12 family/GTP	0	0.09	-10000	0	-0.3	64	64
ADRBK1	0.023	0.006	-10000	0	-10000	0	0
ADRBK2	0.02	0.041	-10000	0	-0.57	5	5
RhoA/GTP/ROCK1	0.031	0.014	-10000	0	-0.36	1	1
mol:GDP	-0.011	0.099	0.37	33	-0.33	8	41
mol:NADP	0.024	0.004	-10000	0	-10000	0	0
RAB11A	0.024	0.004	-10000	0	-10000	0	0
PRKG1	-0.014	0.14	-10000	0	-0.57	69	69
mol:IP3	0.019	0.14	0.46	9	-0.38	74	83
cell morphogenesis	0.031	0.014	-10000	0	-0.36	1	1
PLCB2	0.01	0.17	0.52	7	-0.52	74	81
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	0.026	0.072	0.26	6	-0.31	6	12
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.015	0.061	0.25	3	-0.32	5	8
RHOA	0.024	0.005	-10000	0	-10000	0	0
PTGIR	0.026	0.021	0.26	9	-10000	0	9
PRKCB1	0.018	0.13	0.46	8	-0.38	66	74
GNAQ	0.022	0.031	-10000	0	-0.57	3	3
mol:L-citrulline	0.024	0.004	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.014	0.17	0.54	7	-0.53	65	72
LCK	0.016	0.074	0.25	2	-0.36	14	16
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.023	0.054	-10000	0	-0.25	27	27
TXA2-R family/G12 family/GDP/G beta/gamma	0.006	0.1	-10000	0	-0.43	49	49
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.023	0.051	-10000	0	-0.24	21	21
MAPK14	0.018	0.089	0.32	17	-0.23	60	77
TGM2/GTP	0.014	0.15	0.51	8	-0.43	69	77
MAPK11	0.017	0.089	0.35	13	-0.24	52	65
ARHGEF1	0.011	0.066	0.27	10	-0.18	54	64
GNAI2	0.024	0.005	-10000	0	-10000	0	0
JNK cascade	0.02	0.13	0.47	9	-0.39	65	74
RAB11/GDP	0.023	0.006	-10000	0	-10000	0	0
ICAM1	0.022	0.1	0.4	11	-0.28	62	73
cAMP biosynthetic process	0.016	0.13	0.45	8	-0.36	71	79
Gq family/GTP/EBP50	0.015	0.043	0.22	5	-0.27	6	11
actin cytoskeleton reorganization	0.031	0.014	-10000	0	-0.36	1	1
SRC	0.013	0.058	0.25	2	-0.32	5	7
GNB5	0.024	0.005	-10000	0	-10000	0	0
GNB1	0.023	0.005	-10000	0	-10000	0	0
EGF/EGFR	-0.047	0.1	0.26	2	-0.29	76	78
VCAM1	0.02	0.11	0.39	11	-0.31	63	74
TP beta/Gq family/GDP/G beta5/gamma2	-0.007	0.12	-10000	0	-0.57	40	40
platelet activation	0.023	0.12	0.43	12	-0.31	62	74
PGI2/IP	0.019	0.015	0.18	9	-10000	0	9
PRKACA	0.008	0.053	-10000	0	-0.28	33	33
Gq family/GDP/G beta5/gamma2	-0.001	0.1	-10000	0	-0.48	36	36
TXA2/TP beta/beta Arrestin2	-0.006	0.066	-10000	0	-0.44	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.002	0.047	-10000	0	-0.26	30	30
mol:DAG	0.017	0.14	0.51	7	-0.42	70	77
EGFR	-0.19	0.28	-10000	0	-0.57	390	390
TXA2/TP alpha	0.014	0.16	0.52	7	-0.49	73	80
Gq family/GTP	0.001	0.049	0.25	1	-0.22	45	46
YES1	0.014	0.061	0.25	2	-0.3	6	8
GNAI2/GTP	0.013	0.052	-10000	0	-0.26	22	22
PGD2/DP	0.005	0.076	0.18	7	-0.4	35	42
SLC9A3R1	0.036	0.054	0.26	60	-10000	0	60
FYN	0.012	0.059	0.26	1	-0.34	7	8
mol:NO	0.024	0.004	-10000	0	-10000	0	0
GNA15	0.025	0.025	0.26	6	-0.57	1	7
PGK/cGMP	0.007	0.096	-10000	0	-0.36	69	69
RhoA/GDP	0.023	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.034	0.072	-10000	0	-0.32	29	29
NOS3	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCA	0.021	0.13	0.43	10	-0.38	60	70
PRKCB	0.02	0.13	0.44	9	-0.37	63	72
PRKCE	0.018	0.12	0.47	8	-0.36	61	69
PRKCD	0.017	0.13	0.46	8	-0.39	63	71
PRKCG	0.019	0.13	0.47	8	-0.39	63	71
muscle contraction	0.014	0.16	0.51	8	-0.49	68	76
PRKCZ	0.017	0.12	0.44	9	-0.35	63	72
ARR3	0.021	0.021	0.26	8	-10000	0	8
TXA2/TP beta	0.024	0.06	-10000	0	-0.27	32	32
PRKCQ	0.015	0.14	0.42	12	-0.39	65	77
MAPKKK cascade	0.014	0.15	0.5	7	-0.46	72	79
SELE	0.016	0.12	0.41	10	-0.39	62	72
TP beta/GNAI2/GDP/G beta/gamma	0.034	0.071	-10000	0	-0.32	29	29
ROCK1	0.023	0.018	-10000	0	-0.57	1	1
GNA14	0.023	0.065	0.26	19	-0.57	10	29
chemotaxis	0.012	0.18	0.57	7	-0.61	63	70
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.007	-10000	0	-10000	0	0
GNA11	0.022	0.036	-10000	0	-0.57	4	4
Rac1/GTP	0.018	0.003	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

Figure S75. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S75. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.029	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.024	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.01	0.086	0.26	1	-0.57	23	24
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.022	0.008	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.091	0.12	-10000	0	-0.24	418	418
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.023	0.019	-10000	0	-0.57	1	1
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.022	0.007	-10000	0	-10000	0	0
FYN	0.021	0.026	-10000	0	-0.57	2	2
MAP3K12	0.024	0.003	-10000	0	-10000	0	0
FGR	0.024	0.009	0.26	1	-10000	0	1
p38 alpha/TAB1	-0.039	0.098	-10000	0	-0.34	73	73
PRKG1	-0.014	0.14	-10000	0	-0.57	69	69
DUSP8	0.022	0.031	-10000	0	-0.57	3	3
PGK/cGMP/p38 alpha	-0.018	0.13	-10000	0	-0.35	97	97
apoptosis	-0.038	0.093	-10000	0	-0.33	71	71
RAL/GTP	0.032	0.006	-10000	0	-10000	0	0
LYN	0.021	0.008	-10000	0	-10000	0	0
DUSP1	-0.045	0.19	-10000	0	-0.57	126	126
PAK1	0.023	0.019	0.26	6	-10000	0	6
SRC	0.023	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.052	0.024	-10000	0	-10000	0	0
TRAF6	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.024	0.008	0.26	1	-10000	0	1
RAC1-CDC42/GTP	0.031	0.008	-10000	0	-10000	0	0
MAPK11	-0.009	0.13	0.29	5	-0.38	65	70
BLK	0.051	0.087	0.26	151	-0.57	2	153
HCK	0.027	0.026	0.26	13	-10000	0	13
MAP2K3	0.023	0.007	-10000	0	-10000	0	0
DUSP16	0.023	0.005	-10000	0	-10000	0	0
DUSP10	0.021	0.014	0.26	2	-10000	0	2
TRAF6/MEKK3	0.028	0.01	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.004	0.13	0.3	4	-0.38	70	74
positive regulation of innate immune response	-0.01	0.15	0.33	5	-0.45	64	69
LCK	0.026	0.075	0.26	40	-0.57	11	51
p38alpha-beta/MKP7	-0.002	0.14	0.34	4	-0.43	60	64
p38alpha-beta/MKP5	-0.003	0.14	0.37	3	-0.44	54	57
PGK/cGMP	-0.01	0.11	-10000	0	-0.42	69	69
PAK2	0.024	0.005	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.032	0.17	0.34	4	-0.44	94	98
CDC42	0.023	0.005	-10000	0	-10000	0	0
RALB	0.024	0.003	-10000	0	-10000	0	0
RALA	0.024	0.004	-10000	0	-10000	0	0
PAK3	-0.24	0.29	-10000	0	-0.57	479	479

×

TCGA08_retinoblastoma

Figure S76. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S76. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.023	0.025	0.26	2	-0.54	1	3
CDKN2C	0.014	0.028	-10000	0	-0.55	1	1
CDKN2A	0.06	0.085	0.26	170	-10000	0	170
CCND2	-0.016	0.036	0.2	2	-0.21	14	16
RB1	0.015	0.047	0.26	15	-0.23	8	23
CDK4	-0.017	0.037	0.21	2	-0.22	12	14
CDK6	-0.018	0.04	0.22	2	-0.2	24	26
G1/S progression	-0.01	0.059	0.19	42	-0.27	15	57

×

Regulation of Telomerase

Figure S77. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S77. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.058	0.13	0.47	9	-0.52	2	11
RAD9A	0.023	0.007	-10000	0	-10000	0	0
AP1	-0.094	0.21	-10000	0	-0.42	305	305
IFNAR2	0.028	0.02	-10000	0	-0.57	1	1
AKT1	-0.003	0.088	-10000	0	-0.23	101	101
ER alpha/Oestrogen	-0.025	0.16	0.18	116	-0.4	157	273
NFX1/SIN3/HDAC complex	0.023	0.059	0.24	1	-0.33	16	17
EGF	-0.081	0.23	0.26	2	-0.56	194	196
SMG5	0.021	0.009	-10000	0	-10000	0	0
SMG6	0.022	0.007	-10000	0	-10000	0	0
SP3/HDAC2	0.041	0.018	-10000	0	-10000	0	0
TERT/c-Abl	0.055	0.12	0.42	4	-0.49	2	6
SAP18	0.023	0.007	-10000	0	-10000	0	0
MRN complex	0.036	0.022	-10000	0	-10000	0	0
WT1	0.14	0.12	0.26	534	-10000	0	534
WRN	0.02	0.009	-10000	0	-10000	0	0
SP1	0.031	0.013	-10000	0	-10000	0	0
SP3	0.026	0.005	-10000	0	-10000	0	0
TERF2IP	0.021	0.008	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.051	0.1	-10000	0	-0.5	1	1
Mad/Max	0.041	0.014	-10000	0	-10000	0	0
TERT	0.058	0.13	0.49	7	-0.59	1	8
CCND1	0.081	0.16	0.54	20	-1	4	24
MAX	0.026	0.006	-10000	0	-10000	0	0
RBBP7	0.027	0.019	0.26	7	-10000	0	7
RBBP4	0.024	0.019	-10000	0	-0.56	1	1
TERF2	0.021	0.013	-10000	0	-10000	0	0
PTGES3	0.024	0.002	-10000	0	-10000	0	0
SIN3A	0.025	0.004	-10000	0	-10000	0	0
Telomerase/911	0.039	0.05	-10000	0	-0.38	5	5
CDKN1B	0.029	0.049	-10000	0	-0.67	3	3
RAD1	0.024	0.004	-10000	0	-10000	0	0
XRCC5	0.024	0.003	-10000	0	-10000	0	0
XRCC6	0.023	0.006	-10000	0	-10000	0	0
SAP30	0.025	0.015	0.26	4	-10000	0	4
TRF2/PARP2	0.032	0.015	-10000	0	-10000	0	0
UBE3A	0.025	0.007	-10000	0	-10000	0	0
JUN	0.022	0.044	-10000	0	-0.56	6	6
E6	0.002	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.022	0.01	-10000	0	-10000	0	0
FOS	-0.14	0.27	-10000	0	-0.56	306	306
IFN-gamma/IRF1	0.064	0.063	0.26	11	-0.32	3	14
PARP2	0.024	0.004	-10000	0	-10000	0	0
BLM	0.044	0.067	0.26	97	-10000	0	97
Telomerase	0.03	0.08	0.27	2	-0.6	6	8
IRF1	0.029	0.018	0.26	3	-0.18	3	6
ESR1	-0.034	0.23	0.26	116	-0.56	151	267
KU/TER	0.034	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.03	0.014	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.027	0.056	0.23	1	-0.33	10	11
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.027	0.057	0.23	1	-0.34	10	11
HDAC1	0.025	0.005	-10000	0	-10000	0	0
HDAC2	0.028	0.012	-10000	0	-10000	0	0
ATM	0.012	0.016	-10000	0	-10000	0	0
SMAD3	0.005	0.014	-10000	0	-10000	0	0
ABL1	0.024	0.004	-10000	0	-10000	0	0
MXD1	0.027	0.008	0.26	1	-10000	0	1
MRE11A	0.022	0.007	-10000	0	-10000	0	0
HUS1	0.024	0.003	-10000	0	-10000	0	0
RPS6KB1	0.022	0.008	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.06	0.13	0.46	2	-0.59	5	7
NR2F2	0.012	0.037	-10000	0	-0.57	3	3
MAPK3	0.006	0.019	-10000	0	-10000	0	0
MAPK1	0.006	0.019	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.022	0.014	0.25	3	-10000	0	3
NFKB1	0.024	0.004	-10000	0	-10000	0	0
HNRNPC	0.024	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.012	0.016	-10000	0	-10000	0	0
NBN	0.02	0.01	-10000	0	-10000	0	0
EGFR	-0.19	0.28	-10000	0	-0.56	390	390
mol:Oestrogen	0.001	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.2	0.25	-10000	0	-0.44	534	534
MYC	0.008	0.084	-10000	0	-0.57	22	22
IL2	0.029	0.024	0.26	8	-10000	0	8
KU	0.034	0.009	-10000	0	-10000	0	0
RAD50	0.024	0.004	-10000	0	-10000	0	0
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
TGFB1	0.023	0.014	0.25	3	-10000	0	3
TRF2/BLM	0.043	0.045	0.23	7	-10000	0	7
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.068	0.12	0.45	5	-0.55	1	6
SP1/HDAC2	0.046	0.026	-10000	0	-10000	0	0
PINX1	0.02	0.009	-10000	0	-10000	0	0
Telomerase/EST1A	0.049	0.1	-10000	0	-0.49	1	1
Smad3/Myc	0.007	0.054	-10000	0	-0.36	20	20
911 complex	0.044	0.016	-10000	0	-10000	0	0
IFNG	0.058	0.081	0.26	146	-0.19	3	149
Telomerase/PinX1	0.041	0.097	-10000	0	-0.49	1	1
Telomerase/AKT1/mTOR/p70S6K	0.027	0.1	0.29	6	-0.57	14	20
SIN3B	0.025	0.004	-10000	0	-10000	0	0
YWHAE	0.022	0.007	-10000	0	-10000	0	0
Telomerase/EST1B	0.045	0.095	-10000	0	-10000	0	0
response to DNA damage stimulus	-0.002	0.027	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.047	0.033	-10000	0	-10000	0	0
TRF2/WRN	0.028	0.016	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.051	0.1	-10000	0	-0.5	1	1
E2F1	0.097	0.11	0.26	320	-10000	0	320
ZNFX1	0.024	0.006	-10000	0	-10000	0	0
PIF1	0.069	0.092	0.26	211	-10000	0	211
NCL	0.024	0.004	-10000	0	-10000	0	0
DKC1	0.025	0.01	0.26	2	-10000	0	2
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Insulin Pathway

Figure S78. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S78. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.049	0.16	-10000	0	-0.32	252	252
TC10/GTP	-0.039	0.14	-10000	0	-0.29	259	259
Insulin Receptor/Insulin/IRS1/Shp2	0.043	0.078	-10000	0	-0.34	41	41
HRAS	0.026	0.022	0.26	9	-10000	0	9
APS homodimer	0.034	0.046	0.26	45	-10000	0	45
GRB14	0.011	0.18	0.26	142	-0.57	80	222
FOXO3	-0.022	0.16	-10000	0	-0.6	74	74
AKT1	-0.02	0.11	0.3	10	-0.45	2	12
INSR	0.027	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.055	0.046	0.42	5	-10000	0	5
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.024	0.003	-10000	0	-10000	0	0
SORBS1	-0.12	0.26	-10000	0	-0.57	267	267
CRK	0.022	0.007	-10000	0	-10000	0	0
PTPN1	-0.001	0.024	-10000	0	-10000	0	0
CAV1	-0.083	0.15	-10000	0	-0.35	238	238
CBL/APS/CAP/Crk-II/C3G	-0.028	0.16	-10000	0	-0.31	262	262
Insulin Receptor/Insulin/IRS1/NCK2	0.043	0.078	-10000	0	-0.34	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.028	0.075	-10000	0	-0.3	49	49
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.014	0.064	-10000	0	-0.43	6	6
RPS6KB1	-0.019	0.096	0.29	9	-0.48	1	10
PARD6A	0.023	0.019	0.26	6	-10000	0	6
CBL	0.022	0.007	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.015	0.038	-10000	0	-0.55	4	4
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.007	0.094	-10000	0	-0.36	1	1
HRAS/GTP	-0.02	0.044	-10000	0	-0.28	21	21
Insulin Receptor	0.026	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.042	0.069	-10000	0	-0.32	26	26
PRKCI	0.013	0.059	-10000	0	-0.45	6	6
Insulin Receptor/Insulin/GRB14/PDK1	-0.005	0.1	-10000	0	-0.29	108	108
SHC1	0.02	0.009	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.041	0.035	-10000	0	-0.46	4	4
PI3K	0.037	0.079	-10000	0	-0.3	49	49
NCK2	0.024	0.003	-10000	0	-10000	0	0
RHOQ	0.024	0.003	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.015	0.18	9	-10000	0	9
AKT2	-0.019	0.11	0.31	7	-0.45	2	9
PRKCZ	0.004	0.086	-10000	0	-0.48	17	17
SH2B2	0.034	0.046	0.26	45	-10000	0	45
SHC/SHIP	0.012	0.057	-10000	0	-0.3	28	28
F2RL2	0.046	0.12	0.26	155	-0.57	20	175
TRIP10	0.024	0.003	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.036	0.021	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.032	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.053	0.033	-10000	0	-10000	0	0
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0
RASA1	0.024	0.004	-10000	0	-10000	0	0
NCK1	0.024	0.003	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	-0.038	0.17	-10000	0	-0.32	266	266
TC10/GDP	0.018	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.049	0.028	-10000	0	-10000	0	0
INPP5D	-0.019	0.062	-10000	0	-0.31	41	41
SOS1	0.024	0.003	-10000	0	-10000	0	0
SGK1	-0.02	0.14	-10000	0	-0.69	47	47
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.024	0.002	-10000	0	-10000	0	0
IRS1	0.001	0.11	-10000	0	-0.57	42	42
p62DOK/RasGAP	0.042	0.035	-10000	0	-0.47	4	4
INS	0.019	0.009	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.019	0.062	-10000	0	-0.31	41	41
GRB2	0.023	0.009	0.26	1	-10000	0	1
EIF4EBP1	-0.021	0.089	0.26	6	-0.48	1	7
PTPRA	0.026	0.007	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
TC10/GTP/CIP4	0.032	0.006	-10000	0	-10000	0	0
PDPK1	0.023	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.009	0.052	-10000	0	-0.27	26	26
Insulin Receptor/Insulin/IRS1	0.029	0.074	-10000	0	-0.34	41	41
Insulin Receptor/Insulin/IRS3	0.034	0.014	-10000	0	-10000	0	0
Par3/Par6	0.06	0.073	-10000	0	-0.31	20	20

×

IL27-mediated signaling events

Figure S79. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S79. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.014	0.26	3	-10000	0	3
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.012	0.12	0.48	8	-0.5	4	12
IL27/IL27R/JAK1	0.037	0.16	0.73	6	-0.62	11	17
TBX21	-0.001	0.17	0.49	16	-0.5	46	62
IL12B	0.075	0.098	0.26	227	-10000	0	227
IL12A	-0.013	0.097	0.14	18	-0.42	57	75
IL6ST	-0.041	0.19	0.2	1	-0.56	120	121
IL27RA/JAK1	0.022	0.079	0.51	2	-1.2	3	5
IL27	0.048	0.076	0.27	112	-10000	0	112
TYK2	0.03	0.015	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.097	0.16	1.1	1	-0.79	2	3
T-helper 2 cell differentiation	-0.012	0.12	0.48	8	-0.5	4	12
T cell proliferation during immune response	-0.012	0.12	0.48	8	-0.5	4	12
MAPKKK cascade	0.012	0.12	0.5	4	-0.48	8	12
STAT3	0.024	0.005	-10000	0	-10000	0	0
STAT2	0.024	0.002	-10000	0	-10000	0	0
STAT1	0.028	0.033	0.26	19	-10000	0	19
IL12RB1	0.033	0.053	0.26	41	-0.57	2	43
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.009	0.18	0.47	33	-0.52	51	84
IL27/IL27R/JAK2/TYK2	0.012	0.12	0.51	4	-0.48	8	12
positive regulation of T cell mediated cytotoxicity	0.012	0.12	0.5	4	-0.48	8	12
STAT1 (dimer)	0.035	0.21	0.67	23	-0.67	18	41
JAK2	0.027	0.012	-10000	0	-10000	0	0
JAK1	0.024	0.01	-10000	0	-10000	0	0
STAT2 (dimer)	0.024	0.12	0.44	4	-0.46	8	12
T cell proliferation	-0.091	0.18	0.37	4	-0.47	75	79
IL12/IL12R/TYK2/JAK2	0.059	0.18	0.44	5	-0.72	28	33
IL17A	-0.097	0.16	1.1	1	-0.79	2	3
mast cell activation	-0.012	0.12	0.48	8	-0.5	4	12
IFNG	0.021	0.045	0.12	120	-0.097	9	129
T cell differentiation	0	0.006	0.017	9	-0.02	7	16
STAT3 (dimer)	0.023	0.12	0.44	4	-0.46	8	12
STAT5A (dimer)	0.021	0.12	0.44	4	-0.46	13	17
STAT4 (dimer)	0.011	0.14	0.44	4	-0.44	25	29
STAT4	0.001	0.12	0.26	1	-0.57	43	44
T cell activation	-0.005	0.011	0.12	3	-0.1	6	9
IL27R/JAK2/TYK2	0.016	0.14	-10000	0	-1.1	3	3
GATA3	-0.023	0.27	0.61	39	-1.3	35	74
IL18	0.009	0.02	0.13	26	-10000	0	26
positive regulation of mast cell cytokine production	0.022	0.11	0.43	4	-0.45	8	12
IL27/EBI3	0.053	0.072	0.25	53	-0.38	6	59
IL27RA	0.01	0.081	0.74	1	-1.3	3	4
IL6	-0.18	0.28	0.26	1	-0.57	380	381
STAT5A	0.02	0.044	-10000	0	-0.57	6	6
monocyte differentiation	0.001	0.002	-10000	0	-10000	0	0
IL2	-0.014	0.041	0.45	3	-0.52	1	4
IL1B	0.001	0.048	0.13	3	-0.42	14	17
EBI3	0.025	0.054	0.26	14	-0.57	6	20
TNF	0.006	0.043	0.14	25	-0.42	9	34

×

BCR signaling pathway

Figure S80. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S80. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.024	0.13	0.3	15	-0.39	38	53
IKBKB	0.024	0.089	0.32	7	-0.31	15	22
AKT1	0.04	0.11	0.26	96	-0.24	21	117
IKBKG	0.028	0.073	0.35	4	-0.31	5	9
CALM1	0.002	0.096	0.25	1	-0.42	21	22
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
MAP3K1	0.025	0.16	0.35	14	-0.52	46	60
MAP3K7	0.023	0.006	-10000	0	-10000	0	0
mol:Ca2+	0.003	0.1	-10000	0	-0.35	47	47
DOK1	0.025	0.014	0.26	4	-10000	0	4
AP-1	-0.021	0.098	0.25	8	-0.25	48	56
LYN	0.021	0.008	-10000	0	-10000	0	0
BLNK	0.024	0.003	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
BCR complex	0.005	0.16	0.36	21	-0.44	95	116
CD22	-0.01	0.13	0.27	23	-0.44	64	87
CAMK2G	0.003	0.094	0.26	7	-0.41	18	25
CSNK2A1	0.023	0.005	-10000	0	-10000	0	0
INPP5D	0.024	0.004	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.002	0.086	-10000	0	-0.33	55	55
GO:0007205	0.002	0.1	-10000	0	-0.36	47	47
SYK	0.024	0.003	-10000	0	-10000	0	0
ELK1	0.002	0.1	0.26	1	-0.42	21	22
NFATC1	0.031	0.13	0.28	44	-0.43	37	81
B-cell antigen/BCR complex	0.005	0.16	0.36	21	-0.44	95	116
PAG1/CSK	0.03	0.016	-10000	0	-10000	0	0
NFKBIB	0.023	0.048	0.17	10	-0.13	28	38
HRAS	0.012	0.11	0.27	15	-0.35	39	54
NFKBIA	0.024	0.047	0.17	10	-0.12	23	33
NF-kappa-B/RelA/I kappa B beta	0.027	0.042	0.17	10	-10000	0	10
RasGAP/Csk	0.033	0.12	0.33	21	-0.36	69	90
mol:GDP	0.004	0.098	-10000	0	-0.33	47	47
PTEN	0.022	0.019	-10000	0	-0.57	1	1
CD79B	0.012	0.098	0.26	21	-0.57	27	48
NF-kappa-B/RelA/I kappa B alpha	0.028	0.042	0.17	10	-10000	0	10
GRB2	0.023	0.009	0.26	1	-10000	0	1
PI3K/BCAP/CD19	0.024	0.16	0.35	11	-0.49	53	64
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:IP3	0.003	0.1	-10000	0	-0.36	46	46
CSK	0.024	0.004	-10000	0	-10000	0	0
FOS	-0.077	0.16	-10000	0	-0.43	82	82
CHUK	0.024	0.082	0.29	7	-0.3	19	26
IBTK	0.023	0.005	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.018	0.095	-10000	0	-0.4	18	18
PTPN6	-0.012	0.12	0.25	22	-0.56	32	54
RELA	0.024	0.005	-10000	0	-10000	0	0
BCL2A1	0.025	0.035	0.19	6	-10000	0	6
VAV2	0.014	0.14	0.28	11	-0.58	31	42
ubiquitin-dependent protein catabolic process	0.025	0.047	0.17	10	-0.12	36	46
BTK	0.015	0.061	-10000	0	-0.97	4	4
CD19	0.006	0.14	0.27	35	-0.43	63	98
MAP4K1	0.033	0.054	0.26	48	-0.57	2	50
CD72	0.03	0.042	0.26	30	-0.57	1	31
PAG1	0.02	0.014	0.26	2	-10000	0	2
MAPK14	0.027	0.14	0.35	16	-0.44	44	60
SH3BP5	0.023	0.018	-10000	0	-0.57	1	1
PIK3AP1	0.004	0.11	0.23	1	-0.38	47	48
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.003	0.13	0.26	3	-0.42	75	78
RAF1	0.011	0.1	0.26	16	-0.41	19	35
RasGAP/p62DOK/SHIP	0.032	0.12	0.3	21	-0.35	69	90
CD79A	-0.002	0.17	0.26	85	-0.57	81	166
re-entry into mitotic cell cycle	-0.021	0.097	0.26	6	-0.25	47	53
RASA1	0.024	0.004	-10000	0	-10000	0	0
MAPK3	0.018	0.097	0.27	27	-0.36	14	41
MAPK1	0.011	0.09	0.26	11	-0.36	17	28
CD72/SHP1	0.03	0.14	0.35	29	-0.54	31	60
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MAPK8	0.025	0.14	0.33	19	-0.44	46	65
actin cytoskeleton organization	0.032	0.14	0.31	29	-0.5	30	59
NF-kappa-B/RelA	0.056	0.081	0.3	10	-0.21	1	11
Calcineurin	0.019	0.091	-10000	0	-0.39	16	16
PI3K	-0.013	0.095	-10000	0	-0.44	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.006	0.11	-10000	0	-0.39	51	51
SOS1	0.024	0.003	-10000	0	-10000	0	0
Bam32/HPK1	0.014	0.2	0.43	6	-0.7	51	57
DAPP1	-0.015	0.2	-10000	0	-0.79	51	51
cytokine secretion	0.032	0.13	0.26	53	-0.4	37	90
mol:DAG	0.003	0.1	-10000	0	-0.36	46	46
PLCG2	0.02	0.028	0.26	1	-0.57	2	3
MAP2K1	0.011	0.097	0.27	11	-0.4	17	28
B-cell antigen/BCR complex/FcgammaRIIB	0.016	0.13	0.34	21	-0.41	70	91
mol:PI-3-4-5-P3	0.005	0.089	0.22	17	-0.32	25	42
ETS1	0.001	0.089	0.27	3	-0.39	19	22
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.034	0.13	0.33	22	-0.36	75	97
B-cell antigen/BCR complex/LYN	-0.01	0.14	0.25	20	-0.45	67	87
MALT1	0.023	0.005	-10000	0	-10000	0	0
TRAF6	0.024	0.004	-10000	0	-10000	0	0
RAC1	0.025	0.14	0.31	25	-0.54	30	55
B-cell antigen/BCR complex/LYN/SYK	0.015	0.14	0.35	24	-0.44	58	82
CARD11	0.004	0.1	0.28	6	-0.44	21	27
FCGR2B	0.018	0.038	0.26	1	-0.57	4	5
PPP3CA	0.024	0.011	0.26	2	-10000	0	2
BCL10	0.024	0.004	-10000	0	-10000	0	0
IKK complex	0.027	0.051	0.16	49	-0.14	4	53
PTPRC	0.021	0.041	0.26	12	-0.57	3	15
PDPK1	0.02	0.082	0.21	56	-0.23	20	76
PPP3CB	0.024	0.004	-10000	0	-10000	0	0
PPP3CC	0.02	0.009	-10000	0	-10000	0	0
POU2F2	0.021	0.033	0.21	6	-10000	0	6

×

Regulation of nuclear SMAD2/3 signaling

Figure S81. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S81. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.025	0.011	-10000	0	-10000	0	0
HSPA8	0.021	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.016	0.16	0.3	3	-0.39	149	152
AKT1	0.025	0.01	-10000	0	-10000	0	0
GSC	-0.03	0.27	-10000	0	-1.3	41	41
NKX2-5	0.001	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.026	0.065	0.32	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.068	0.065	-10000	0	-0.44	1	1
SMAD4	0.012	0.045	-10000	0	-10000	0	0
CBFB	0.022	0.008	-10000	0	-10000	0	0
SAP18	0.023	0.006	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.099	0.19	0.26	1	-0.36	379	380
SMAD3/SMAD4/VDR	0.055	0.058	-10000	0	-0.34	1	1
MYC	0.005	0.084	-10000	0	-0.57	22	22
CDKN2B	-0.042	0.17	-10000	0	-0.79	28	28
AP1	-0.05	0.16	-10000	0	-0.3	267	267
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.01	0.086	-10000	0	-0.36	32	32
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.013	0.057	-10000	0	-0.34	12	12
SP3	0.025	0.004	-10000	0	-10000	0	0
CREB1	0.024	0.003	-10000	0	-10000	0	0
FOXH1	0.046	0.081	0.26	127	-10000	0	127
SMAD3/SMAD4/GR	0.024	0.072	-10000	0	-0.37	12	12
GATA3	0.013	0.11	0.26	28	-0.55	36	64
SKI/SIN3/HDAC complex/NCoR1	0.005	0.077	-10000	0	-0.35	34	34
MEF2C/TIF2	0.023	0.087	0.32	3	-0.31	21	24
endothelial cell migration	-0.029	0.094	0.57	13	-10000	0	13
MAX	0.02	0.015	-10000	0	-10000	0	0
RBBP7	0.026	0.019	0.26	7	-10000	0	7
RBBP4	0.023	0.018	-10000	0	-0.57	1	1
RUNX2	0.027	0.028	0.26	15	-10000	0	15
RUNX3	0.022	0.043	0.26	5	-0.57	5	10
RUNX1	0.023	0.019	-10000	0	-0.57	1	1
CTBP1	0.023	0.005	-10000	0	-10000	0	0
NR3C1	0.014	0.061	-10000	0	-0.57	11	11
VDR	0.024	0.002	-10000	0	-10000	0	0
CDKN1A	0.016	0.078	-10000	0	-1.1	3	3
KAT2B	0.024	0.019	-10000	0	-0.57	1	1
SMAD2/SMAD2/SMAD4/FOXH1	0.056	0.078	0.3	1	-0.26	22	23
DCP1A	0.024	0.005	-10000	0	-10000	0	0
SKI	0.023	0.005	-10000	0	-10000	0	0
SERPINE1	0.029	0.094	-10000	0	-0.58	13	13
SMAD3/SMAD4/ATF2	0.033	0.061	-10000	0	-0.41	3	3
SMAD3/SMAD4/ATF3	-0.011	0.14	-10000	0	-0.39	113	113
SAP30	0.024	0.015	0.26	4	-10000	0	4
Cbp/p300/PIAS3	0.04	0.031	-10000	0	-10000	0	0
JUN	-0.059	0.15	0.29	1	-0.3	265	266
SMAD3/SMAD4/IRF7	0.052	0.081	0.32	25	-10000	0	25
TFE3	0.028	0.009	-10000	0	-10000	0	0
COL1A2	0.045	0.094	0.39	4	-0.6	8	12
mesenchymal cell differentiation	-0.035	0.058	-10000	0	-10000	0	0
DLX1	0.055	0.1	0.26	168	-0.57	9	177
TCF3	0.024	0.009	0.26	1	-10000	0	1
FOS	-0.14	0.27	-10000	0	-0.57	307	307
SMAD3/SMAD4/Max	0.028	0.058	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.044	0.019	-10000	0	-10000	0	0
ZBTB17	0.022	0.007	-10000	0	-10000	0	0
LAMC1	0.013	0.038	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.034	0.055	-10000	0	-0.2	1	1
IRF7	0.048	0.072	0.27	102	-10000	0	102
ESR1	-0.04	0.23	0.25	116	-0.57	151	267
HNF4A	0.023	0.032	0.26	20	-10000	0	20
MEF2C	0.047	0.087	0.4	8	-0.44	3	11
SMAD2-3/SMAD4	0.034	0.065	-10000	0	-0.22	1	1
Cbp/p300/Src-1	0.045	0.025	-10000	0	-0.36	1	1
IGHV3OR16-13	0.006	0.039	-10000	0	-0.34	12	12
TGIF2/HDAC complex	0.023	0.005	-10000	0	-10000	0	0
CREBBP	0.023	0.009	-10000	0	-10000	0	0
SKIL	0.026	0.023	0.26	10	-10000	0	10
HDAC1	0.024	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.006	-10000	0	-10000	0	0
SNIP1	0.023	0.006	-10000	0	-10000	0	0
GCN5L2	0.001	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.043	0.061	-10000	0	-0.45	1	1
MSG1/HSC70	-0.13	0.22	-10000	0	-0.42	400	400
SMAD2	0.022	0.03	-10000	0	-10000	0	0
SMAD3	0.015	0.04	-10000	0	-0.18	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.016	0.042	-10000	0	-0.32	3	3
SMAD2/SMAD2/SMAD4	0.026	0.058	0.25	9	-0.51	3	12
NCOR1	0.022	0.007	-10000	0	-10000	0	0
NCOA2	-0.006	0.12	-10000	0	-0.57	48	48
NCOA1	0.023	0.018	-10000	0	-0.57	1	1
MYOD/E2A	0.032	0.02	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.064	-10000	0	-0.41	1	1
IFNB1	0.022	0.071	0.31	38	-10000	0	38
SMAD3/SMAD4/MEF2C	0.065	0.084	-10000	0	-0.42	3	3
CITED1	-0.19	0.29	0.26	15	-0.57	400	415
SMAD2-3/SMAD4/ARC105	0.042	0.066	-10000	0	-10000	0	0
RBL1	0.023	0.027	0.26	1	-0.57	2	3
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.017	0.065	-10000	0	-0.43	12	12
RUNX1-3/PEBPB2	0.04	0.039	-10000	0	-0.42	5	5
SMAD7	-0.032	0.14	-10000	0	-0.48	10	10
MYC/MIZ-1	0.015	0.065	-10000	0	-0.42	22	22
SMAD3/SMAD4	0.033	0.073	0.3	24	-0.37	3	27
IL10	0.007	0.08	0.3	5	-0.36	30	35
PIASy/HDAC complex	0.02	0.015	-10000	0	-10000	0	0
PIAS3	0.021	0.01	-10000	0	-10000	0	0
CDK2	0.025	0.008	-10000	0	-10000	0	0
IL5	0.004	0.083	0.29	5	-0.35	35	40
CDK4	0.025	0.009	-10000	0	-10000	0	0
PIAS4	0.02	0.015	-10000	0	-10000	0	0
ATF3	-0.041	0.18	0.26	1	-0.57	112	113
SMAD3/SMAD4/SP1	0.047	0.064	-10000	0	-0.37	2	2
FOXG1	0.017	0.068	0.26	74	-10000	0	74
FOXO3	0.011	0.017	-10000	0	-0.42	1	1
FOXO1	0.009	0.031	-10000	0	-0.42	5	5
FOXO4	0.012	0.01	-10000	0	-10000	0	0
heart looping	0.047	0.086	0.4	8	-0.43	3	11
CEBPB	0.023	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.054	0.089	0.29	5	-0.39	9	14
MYOD1	0.021	0.027	0.26	14	-10000	0	14
SMAD3/SMAD4/HNF4	0.033	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/GATA3	0.029	0.099	0.35	1	-0.38	37	38
SnoN/SIN3/HDAC complex/NCoR1	0.026	0.023	0.26	10	-10000	0	10
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.044	0.069	-10000	0	-0.4	4	4
SMAD3/SMAD4/SP1-3	0.062	0.063	-10000	0	-0.44	1	1
MED15	0.023	0.006	-10000	0	-10000	0	0
SP1	0.03	0.015	-10000	0	-0.2	1	1
SIN3B	0.024	0.004	-10000	0	-10000	0	0
SIN3A	0.024	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.056	0.074	0.28	1	-0.25	13	14
ITGB5	0.016	0.042	-10000	0	-0.4	1	1
TGIF/SIN3/HDAC complex/CtBP	0.013	0.062	-10000	0	-0.3	24	24
SMAD3/SMAD4/AR	-0.019	0.15	-10000	0	-0.38	137	137
AR	-0.053	0.2	0.26	1	-0.57	141	142
negative regulation of cell growth	0	0.083	-10000	0	-0.31	30	30
SMAD3/SMAD4/MYOD	0.032	0.057	-10000	0	-0.21	1	1
E2F5	0.022	0.021	0.26	7	-10000	0	7
E2F4	0.022	0.008	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.069	0.073	-10000	0	-0.33	1	1
SMAD2-3/SMAD4/FOXO1-3a-4	0.016	0.054	-10000	0	-0.37	11	11
TFDP1	0.022	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.035	0.17	-10000	0	-0.3	266	266
SMAD3/SMAD4/RUNX2	0.035	0.058	-10000	0	-10000	0	0
TGIF2	0.023	0.005	-10000	0	-10000	0	0
TGIF1	0.023	0.006	-10000	0	-10000	0	0
ATF2	0.022	0.031	-10000	0	-0.57	3	3

×

Osteopontin-mediated events

Figure S82. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S82. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.043	0.072	0.32	1	-0.3	27	28
NF kappa B1 p50/RelA/I kappa B alpha	0.046	0.082	0.36	9	-0.34	1	10
alphaV/beta3 Integrin/Osteopontin/Src	0.081	0.071	0.23	3	-10000	0	3
AP1	-0.036	0.18	-10000	0	-0.54	32	32
ILK	0.03	0.074	0.29	1	-0.32	27	28
bone resorption	0.019	0.088	-10000	0	-0.5	12	12
PTK2B	0.02	0.009	-10000	0	-10000	0	0
PYK2/p130Cas	0.068	0.092	0.3	8	-0.3	21	29
ITGAV	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.022	0.075	-10000	0	-0.41	31	31
alphaV/beta3 Integrin/Osteopontin	0.077	0.1	0.36	3	-0.34	33	36
MAP3K1	0.029	0.077	0.26	14	-0.32	33	47
JUN	0.021	0.044	-10000	0	-0.57	6	6
MAPK3	0.02	0.069	0.27	10	-0.3	24	34
MAPK1	0.021	0.07	0.27	11	-0.3	22	33
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MAPK8	0.016	0.082	0.26	15	-0.37	28	43
ITGB3	0.009	0.1	0.26	4	-0.56	33	37
NFKBIA	0.018	0.068	0.32	4	-0.34	4	8
FOS	-0.14	0.27	-10000	0	-0.57	306	306
CD44	0.024	0.004	-10000	0	-10000	0	0
CHUK	0.024	0.003	-10000	0	-10000	0	0
PLAU	0.022	0.098	0.45	6	-0.55	2	8
NF kappa B1 p50/RelA	0.063	0.076	0.37	5	-10000	0	5
BCAR1	0.021	0.008	-10000	0	-10000	0	0
RELA	0.023	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.026	0.08	-10000	0	-0.41	33	33
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.03	0.075	0.25	14	-0.32	33	47
VAV3	0.017	0.075	0.26	16	-0.3	31	47
MAP3K14	0.031	0.075	0.26	9	-0.32	28	37
ROCK2	0.007	0.099	-10000	0	-0.57	31	31
SPP1	0.086	0.1	0.26	279	-10000	0	279
RAC1	0.024	0.003	-10000	0	-10000	0	0
Rac1/GTP	0.028	0.069	0.3	3	-0.28	29	32
MMP2	-0.054	0.14	0.34	2	-0.51	31	33

×

IL2 signaling events mediated by STAT5

Figure S83. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S83. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.022	0.02	-10000	0	-0.57	1	1
ELF1	0.03	0.054	-10000	0	-0.36	12	12
CCNA2	0.11	0.11	0.26	401	-10000	0	401
PIK3CA	0.024	0.005	-10000	0	-10000	0	0
JAK3	0.027	0.027	0.26	14	-10000	0	14
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
JAK1	0.024	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.046	0.1	0.3	18	-0.49	13	31
SHC1	0.021	0.009	-10000	0	-10000	0	0
SP1	0.024	0.045	-10000	0	-0.38	12	12
IL2RA	0.02	0.12	0.43	11	-0.76	15	26
IL2RB	0.031	0.05	0.26	38	-0.57	2	40
SOS1	0.025	0.003	-10000	0	-10000	0	0
IL2RG	0.031	0.067	0.26	46	-0.57	7	53
G1/S transition of mitotic cell cycle	0.042	0.14	0.35	3	-0.8	17	20
PTPN11	0.025	0.003	-10000	0	-10000	0	0
CCND2	0.006	0.087	0.43	1	-0.8	12	13
LCK	0.027	0.075	0.26	40	-0.57	11	51
GRB2	0.023	0.009	0.26	1	-10000	0	1
IL2	0.022	0.021	0.26	8	-10000	0	8
CDK6	0.019	0.058	0.26	2	-0.57	10	12
CCND3	0.047	0.1	0.42	6	-0.57	5	11

×

TCGA08_p53

Figure S84. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S84. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.025	0.046	0.13	170	-10000	0	170
TP53	0.009	0.018	-10000	0	-0.19	2	2
Senescence	0.008	0.022	-10000	0	-0.19	2	2
Apoptosis	0.008	0.022	-10000	0	-0.19	2	2
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.011	0.06	0.29	31	-10000	0	31
MDM4	0.02	0.009	-10000	0	-10000	0	0

×

HIF-2-alpha transcription factor network

Figure S85. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S85. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.024	0.088	-10000	0	-0.63	9	9
oxygen homeostasis	0.011	0.013	-10000	0	-10000	0	0
TCEB2	0.027	0.033	0.26	21	-10000	0	21
TCEB1	0.021	0.009	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.087	0.088	0.36	9	-0.43	1	10
EPO	0.15	0.17	0.51	76	-0.49	4	80
FIH (dimer)	0.032	0.02	-10000	0	-10000	0	0
APEX1	0.033	0.025	-10000	0	-10000	0	0
SERPINE1	0.14	0.16	0.48	47	-0.52	6	53
FLT1	-0.018	0.17	-10000	0	-0.71	34	34
ADORA2A	0.16	0.17	0.47	88	-0.5	5	93
germ cell development	0.14	0.16	0.48	46	-0.5	5	51
SLC11A2	0.14	0.16	0.47	38	-0.54	4	42
BHLHE40	0.13	0.16	0.47	36	-0.55	5	41
HIF1AN	0.032	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.12	0.13	0.41	48	-0.38	3	51
ETS1	0.026	0.039	-10000	0	-0.58	4	4
CITED2	0.015	0.09	-10000	0	-0.66	7	7
KDR	-0.018	0.18	-10000	0	-0.7	40	40
PGK1	0.14	0.16	0.47	43	-0.52	5	48
SIRT1	0.025	0.004	-10000	0	-10000	0	0
response to hypoxia	0.001	0.003	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.18	0.58	20	-0.55	8	28
EPAS1	0.068	0.088	0.29	48	-0.37	6	54
SP1	0.029	0.012	-10000	0	-10000	0	0
ABCG2	0.12	0.2	0.48	35	-0.55	42	77
EFNA1	0.11	0.14	0.49	10	-0.53	3	13
FXN	0.15	0.16	0.46	52	-0.52	4	56
POU5F1	0.14	0.16	0.49	44	-0.52	5	49
neuron apoptosis	-0.15	0.18	0.53	8	-0.58	20	28
EP300	0.023	0.006	-10000	0	-10000	0	0
EGLN3	0.047	0.067	0.27	77	-0.58	1	78
EGLN2	0.033	0.026	0.27	5	-10000	0	5
EGLN1	0.027	0.028	-10000	0	-0.58	1	1
VHL/Elongin B/Elongin C	0.041	0.027	-10000	0	-10000	0	0
VHL	0.024	0.004	-10000	0	-10000	0	0
ARNT	0.028	0.024	-10000	0	-10000	0	0
SLC2A1	0.14	0.16	0.46	58	-0.49	6	64
TWIST1	0.13	0.19	0.46	50	-0.55	39	89
ELK1	0.028	0.003	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.1	0.11	0.41	10	-0.38	3	13
VEGFA	0.13	0.16	0.48	36	-0.54	4	40
CREBBP	0.023	0.007	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

Figure S86. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S86. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0.002	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.03	0.02	0.3	1	-10000	0	1
CDKN1B	0.011	0.056	-10000	0	-0.34	15	15
CDKN1A	0.01	0.061	-10000	0	-0.34	19	19
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.021	0.008	-10000	0	-10000	0	0
FOXO3	0.013	0.055	-10000	0	-0.34	13	13
AKT1	0.006	0.056	-10000	0	-0.33	25	25
BAD	0.024	0.009	0.26	1	-10000	0	1
AKT3	0.006	0.035	-10000	0	-0.35	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.009	0.059	0.21	1	-0.34	19	20
AKT1/ASK1	0.031	0.067	-10000	0	-0.32	21	21
BAD/YWHAZ	0.037	0.023	-10000	0	-10000	0	0
RICTOR	0.024	0.004	-10000	0	-10000	0	0
RAF1	0.024	0.004	-10000	0	-10000	0	0
JNK cascade	-0.03	0.065	0.31	21	-10000	0	21
TSC1	0.011	0.051	-10000	0	-0.34	13	13
YWHAZ	0.019	0.01	-10000	0	-10000	0	0
AKT1/RAF1	0.036	0.07	0.27	1	-0.34	18	19
EP300	0.023	0.006	-10000	0	-10000	0	0
mol:GDP	0.01	0.059	-10000	0	-0.32	27	27
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.007	0.054	0.32	1	-0.33	17	18
YWHAQ	0.024	0.003	-10000	0	-10000	0	0
TBC1D4	0.004	0.015	-10000	0	-0.34	2	2
MAP3K5	0.022	0.032	-10000	0	-0.57	3	3
MAPKAP1	0.024	0.003	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.026	0.075	0.29	23	-0.21	12	35
YWHAH	0.023	0.006	-10000	0	-10000	0	0
AKT1S1	0.011	0.06	-10000	0	-0.35	17	17
CASP9	0.011	0.045	-10000	0	-0.32	11	11
YWHAB	0.023	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.036	0.072	0.32	5	-0.34	14	19
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.043	0.017	-10000	0	-10000	0	0
YWHAE	0.022	0.007	-10000	0	-10000	0	0
SRC	0.023	0.005	-10000	0	-10000	0	0
AKT2/p21CIP1	0.011	0.058	0.25	2	-0.37	10	12
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.006	0.051	-10000	0	-0.32	21	21
CHUK	0.01	0.055	-10000	0	-0.33	17	17
BAD/BCL-XL	0.038	0.066	0.28	3	-0.34	13	16
mTORC2	0.03	0.007	-10000	0	-10000	0	0
AKT2	0.011	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.032	0.097	0.29	10	-0.39	24	34
PDPK1	0.023	0.006	-10000	0	-10000	0	0
MDM2	0.012	0.064	0.27	2	-0.34	19	21
MAPKKK cascade	-0.036	0.069	0.34	18	-0.25	3	21
MDM2/Cbp/p300	0.042	0.072	0.31	7	-0.34	14	21
TSC1/TSC2	0.014	0.068	0.26	37	-0.36	13	50
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.069	0.29	8	-0.32	14	22
glucose import	-0.16	0.15	0.21	2	-0.31	521	523
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.011	0.048	0.18	3	-0.41	4	7
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.15	0.16	-10000	0	-0.31	521	521
GSK3A	0.01	0.059	-10000	0	-0.35	17	17
FOXO1	0.012	0.04	-10000	0	-0.28	9	9
GSK3B	0.01	0.059	-10000	0	-0.35	18	18
SFN	0.021	0.07	0.26	21	-0.57	12	33
G1/S transition of mitotic cell cycle	0.014	0.065	0.27	7	-0.35	16	23
p27Kip1/14-3-3 family	0.021	0.049	0.31	2	-0.39	4	6
PRKACA	0.024	0.004	-10000	0	-10000	0	0
KPNA1	0.024	0.003	-10000	0	-10000	0	0
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
YWHAG	0.024	0.003	-10000	0	-10000	0	0
RHEB	0.024	0.004	-10000	0	-10000	0	0
CREBBP	0.023	0.007	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

Figure S87. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S87. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.008	0.11	0.26	2	-0.41	44	46
ACTA1	0.012	0.11	0.26	6	-0.48	31	37
NUMA1	0.004	0.11	0.26	2	-0.39	48	50
SPTAN1	-0.002	0.11	0.27	7	-0.48	32	39
LIMK1	-0.001	0.11	0.26	6	-0.48	32	38
BIRC3	0.023	0.04	0.26	12	-0.57	3	15
BIRC2	0.022	0.007	-10000	0	-10000	0	0
BAX	0.025	0.014	0.26	4	-10000	0	4
CASP10	-0.011	0.09	0.2	11	-0.44	33	44
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.024	0.002	-10000	0	-10000	0	0
PTK2	0.003	0.12	0.26	2	-0.44	45	47
DIABLO	0.024	0.002	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.002	0.1	0.27	7	-0.47	32	39
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.024	0.003	-10000	0	-10000	0	0
GSN	-0.006	0.12	0.28	4	-0.47	40	44
MADD	0.024	0.003	-10000	0	-10000	0	0
TFAP2A	0.013	0.13	-10000	0	-0.64	33	33
BID	0.003	0.053	0.18	3	-0.26	32	35
MAP3K1	-0.003	0.093	-10000	0	-0.4	47	47
TRADD	0.022	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.034	0.009	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.001	0.11	0.26	7	-0.48	31	38
CASP9	0.023	0.005	-10000	0	-10000	0	0
DNA repair	-0.016	0.043	0.25	4	-0.21	4	8
neuron apoptosis	0.004	0.12	-10000	0	-0.69	25	25
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0	0.11	0.26	2	-0.44	41	43
APAF1	0.024	0.003	-10000	0	-10000	0	0
CASP6	0	0.15	-10000	0	-0.91	25	25
TRAF2	0.025	0.015	0.26	4	-10000	0	4
ICAD/CAD	-0.004	0.1	0.24	2	-0.48	30	32
CASP7	0.002	0.06	0.28	2	-0.39	4	6
KRT18	0.015	0.079	-10000	0	-0.72	9	9
apoptosis	0.002	0.12	0.3	5	-0.45	45	50
DFFA	-0.003	0.1	0.25	3	-0.48	32	35
DFFB	-0.003	0.1	0.25	3	-0.48	32	35
PARP1	0.016	0.043	0.21	4	-0.25	4	8
actin filament polymerization	0.001	0.1	0.45	33	-0.29	9	42
TNF	0.024	0.065	0.26	25	-0.57	9	34
CYCS	0.005	0.048	0.2	8	-0.22	23	31
SATB1	-0.008	0.15	-10000	0	-0.78	31	31
SLK	-0.002	0.1	0.28	4	-0.49	31	35
p15 BID/BAX	0.013	0.062	0.24	2	-0.24	36	38
CASP2	0.003	0.063	0.29	2	-0.38	6	8
JNK cascade	0.003	0.093	0.39	47	-10000	0	47
CASP3	0	0.11	0.26	4	-0.5	33	37
LMNB2	0.001	0.13	0.33	2	-0.52	41	43
RIPK1	0.024	0.005	-10000	0	-10000	0	0
CASP4	0.022	0.008	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.057	0.032	-10000	0	-0.33	2	2
negative regulation of DNA binding	0.014	0.13	-10000	0	-0.63	33	33
stress fiber formation	-0.002	0.1	0.28	4	-0.48	31	35
GZMB	0.011	0.1	0.27	11	-0.49	32	43
CASP1	0.011	0.012	-10000	0	-0.35	1	1
LMNB1	0.02	0.12	0.3	7	-0.51	28	35
APP	0.004	0.12	-10000	0	-0.7	25	25
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.006	0.001	-10000	0	-10000	0	0
VIM	0.004	0.12	0.29	5	-0.44	49	54
LMNA	0.008	0.08	0.32	2	-0.37	23	25
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.005	0.066	-10000	0	-0.3	20	20
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.001	0.1	0.27	4	-0.48	32	36
APAF-1/Caspase 9	-0.004	0.12	-10000	0	-0.61	38	38
nuclear fragmentation during apoptosis	0.004	0.1	0.26	2	-0.38	48	50
CFL2	-0.001	0.11	0.3	8	-0.46	34	42
GAS2	-0.025	0.14	0.27	6	-0.38	95	101
positive regulation of apoptosis	0.014	0.11	0.27	8	-0.49	31	39
PRF1	0.016	0.077	0.26	8	-0.57	17	25

×

Ceramide signaling pathway

Figure S88. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S88. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.011	0.004	-10000	0	-10000	0	0
MAP4K4	0.004	0.059	-10000	0	-0.38	5	5
BAG4	0.018	0.032	-10000	0	-0.57	3	3
PKC zeta/ceramide	-0.001	0.052	-10000	0	-0.25	16	16
NFKBIA	0.024	0.004	-10000	0	-10000	0	0
BIRC3	0.023	0.04	0.26	12	-0.57	3	15
BAX	0.001	0.041	-10000	0	-0.35	11	11
RIPK1	0.024	0.005	-10000	0	-10000	0	0
AKT1	0.001	0.068	0.7	10	-10000	0	10
BAD	-0.015	0.046	0.19	4	-0.24	15	19
SMPD1	0.014	0.056	0.23	7	-0.24	17	24
RB1	-0.015	0.044	-10000	0	-0.26	11	11
FADD/Caspase 8	0.026	0.085	0.28	5	-0.36	9	14
MAP2K4	-0.016	0.044	0.2	1	-0.3	8	9
NSMAF	0.021	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.009	0.056	0.19	33	-0.3	7	40
EGF	-0.082	0.23	0.26	2	-0.57	194	196
mol:ceramide	-0.014	0.048	0.14	1	-0.25	15	16
MADD	0.024	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.01	0.009	-10000	0	-10000	0	0
ASAH1	0.021	0.015	0.26	3	-10000	0	3
negative regulation of cell cycle	-0.016	0.044	-10000	0	-0.26	11	11
cell proliferation	-0.044	0.12	0.27	1	-0.27	204	205
BID	-0.02	0.17	-10000	0	-0.66	60	60
MAP3K1	-0.015	0.047	0.2	3	-0.24	16	19
EIF2A	-0.014	0.049	0.29	3	-0.25	6	9
TRADD	0.022	0.008	-10000	0	-10000	0	0
CRADD	0.024	0.003	-10000	0	-10000	0	0
MAPK3	-0.006	0.054	0.25	4	-0.3	6	10
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.011	0.059	0.26	4	-0.31	6	10
Cathepsin D/ceramide	0.004	0.057	0.17	31	-0.24	14	45
FADD	0.006	0.059	0.26	3	-0.39	4	7
KSR1	-0.009	0.055	0.2	24	-0.25	13	37
MAPK8	-0.014	0.058	-10000	0	-0.28	19	19
PRKRA	-0.015	0.047	0.2	4	-0.27	11	15
PDGFA	0.024	0.008	0.26	1	-10000	0	1
TRAF2	0.025	0.015	0.26	4	-10000	0	4
IGF1	-0.1	0.24	-10000	0	-0.57	233	233
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.014	0.047	0.14	1	-0.25	15	16
CTSD	0.031	0.041	0.26	34	-10000	0	34
regulation of nitric oxide biosynthetic process	0.034	0.009	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.047	0.13	0.29	1	-0.29	203	204
PRKCD	0.024	0.009	0.26	1	-10000	0	1
PRKCZ	0.023	0.019	-10000	0	-0.57	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.01	0.009	-10000	0	-10000	0	0
RelA/NF kappa B1	0.034	0.009	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.023	0.018	-10000	0	-0.57	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.016	0.044	-10000	0	-0.35	5	5
TNFR1A/BAG4/TNF-alpha	0.036	0.051	-10000	0	-0.36	11	11
mol:Sphingosine-1-phosphate	0.011	0.004	-10000	0	-10000	0	0
MAP2K1	-0.009	0.055	0.24	5	-0.3	6	11
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.023	0.005	-10000	0	-10000	0	0
CYCS	0	0.049	0.18	19	-0.22	13	32
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
NFKB1	0.024	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.029	-10000	0	-0.42	3	3
EIF2AK2	-0.016	0.043	0.19	3	-0.28	7	10
TNF-alpha/TNFR1A/FAN	0.04	0.044	-10000	0	-0.36	7	7
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.078	-10000	0	-0.37	31	31
MAP2K2	-0.01	0.055	0.23	6	-0.29	7	13
SMPD3	-0.002	0.098	0.26	4	-0.29	95	99
TNF	0.024	0.065	0.26	25	-0.57	9	34
PKC zeta/PAR4	0.033	0.021	-10000	0	-0.42	2	2
mol:PHOSPHOCHOLINE	0.042	0.097	0.24	195	-0.24	2	197
NF kappa B1/RelA/I kappa B alpha	0.063	0.03	-10000	0	-0.31	2	2
AIFM1	-0.001	0.049	0.18	20	-0.22	12	32
BCL2	0.008	0.094	-10000	0	-0.57	28	28

×

S1P5 pathway

Figure S89. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S89. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.004	0.09	0.29	47	-10000	0	47
GNAI2	0.024	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.033	0.026	-10000	0	-0.28	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
RhoA/GTP	-0.003	0.091	-10000	0	-0.29	47	47
negative regulation of cAMP metabolic process	-0.004	0.088	-10000	0	-0.27	88	88
GNAZ	0.018	0.057	-10000	0	-0.57	10	10
GNAI3	0.024	0.004	-10000	0	-10000	0	0
GNA12	0.024	0.004	-10000	0	-10000	0	0
S1PR5	0.027	0.041	0.26	20	-0.57	2	22
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.004	0.088	-10000	0	-0.27	88	88
RhoA/GDP	0.018	0.003	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57

×

S1P4 pathway

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
CDC42/GTP	-0.005	0.096	-10000	0	-0.3	52	52
PLCG1	-0.012	0.087	-10000	0	-0.31	50	50
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.024	0.005	-10000	0	-10000	0	0
GNAI3	0.024	0.004	-10000	0	-10000	0	0
G12/G13	0.033	0.011	-10000	0	-10000	0	0
cell migration	-0.005	0.094	-10000	0	-0.3	52	52
S1PR5	0.027	0.041	0.26	20	-0.57	2	22
S1PR4	0.029	0.062	0.26	38	-0.57	6	44
MAPK3	-0.008	0.082	0.26	1	-0.31	41	42
MAPK1	-0.008	0.084	-10000	0	-0.32	45	45
S1P/S1P5/Gi	-0.004	0.088	-10000	0	-0.27	88	88
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
CDC42/GDP	0.017	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.033	0.026	-10000	0	-0.28	3	3
RHOA	0.006	0.058	0.24	1	-0.31	6	7
S1P/S1P4/Gi	-0.004	0.094	-10000	0	-0.28	92	92
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.018	0.057	-10000	0	-0.57	10	10
S1P/S1P4/G12/G13	0.044	0.041	-10000	0	-0.33	6	6
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.007	-10000	0	-10000	0	0
CDC42	0.023	0.005	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

Figure S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S91. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.022	0.077	-10000	0	-0.51	7	7
UGCG	0.009	0.12	-10000	0	-0.67	30	30
AKT1/mTOR/p70S6K/Hsp90/TERT	0.048	0.12	0.3	10	-0.42	26	36
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.011	0.12	-10000	0	-0.66	30	30
mol:DAG	0.004	0.085	-10000	0	-0.76	12	12
CaM/Ca2+/Calcineurin A alpha-beta B1	0.037	0.13	0.3	6	-0.41	54	60
FRAP1	0.031	0.15	0.33	6	-0.46	58	64
FOXO3	0.036	0.14	0.33	12	-0.49	34	46
AKT1	0.037	0.14	0.31	12	-0.51	38	50
GAB2	0.021	0.02	-10000	0	-0.57	1	1
SMPD1	0.01	0.11	-10000	0	-0.64	25	25
SGMS1	0.018	0.065	-10000	0	-0.54	12	12
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0	0.039	-10000	0	-0.33	14	14
CALM1	0.024	0.004	-10000	0	-10000	0	0
cell proliferation	0.046	0.11	0.32	4	-0.48	22	26
EIF3A	0.024	0.004	-10000	0	-10000	0	0
PI3K	0.029	0.05	-10000	0	-0.39	14	14
RPS6KB1	0.012	0.091	-10000	0	-0.84	10	10
mol:sphingomyelin	0.004	0.085	-10000	0	-0.76	12	12
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	0.027	0.027	0.26	14	-10000	0	14
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
JAK1	0.024	0.007	-10000	0	-10000	0	0
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MYC	0.065	0.2	0.39	14	-0.86	31	45
MYB	0.028	0.19	0.48	2	-1.1	24	26
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.036	0.11	0.29	18	-0.43	23	41
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.037	0.088	-10000	0	-0.75	10	10
mol:PI-3-4-5-P3	0.04	0.11	0.29	17	-0.42	23	40
Rac1/GDP	0.014	0.039	-10000	0	-0.33	12	12
T cell proliferation	0.04	0.1	0.29	12	-0.49	12	24
SHC1	0.02	0.011	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.013	0.1	3	-0.076	23	26
PRKCZ	0.04	0.1	0.3	10	-0.51	12	22
NF kappa B1 p50/RelA	0.047	0.14	0.32	6	-0.42	51	57
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.025	0.075	0.29	11	-0.52	8	19
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
RELA	0.023	0.005	-10000	0	-10000	0	0
IL2RA	0.027	0.088	0.26	58	-0.57	15	73
IL2RB	0.031	0.051	0.26	38	-0.57	2	40
TERT	0.054	0.08	0.26	147	-10000	0	147
E2F1	0.051	0.094	0.34	2	-0.36	30	32
SOS1	0.024	0.007	-10000	0	-10000	0	0
RPS6	0.024	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.006	0.033	23	-0.05	3	26
PTPN11	0.023	0.008	-10000	0	-10000	0	0
IL2RG	0.031	0.068	0.26	46	-0.57	7	53
actin cytoskeleton organization	0.04	0.1	0.29	12	-0.49	12	24
GRB2	0.023	0.011	0.26	1	-10000	0	1
IL2	0.021	0.023	0.26	8	-10000	0	8
PIK3CA	0.024	0.008	-10000	0	-10000	0	0
Rac1/GTP	0.038	0.043	-10000	0	-0.31	12	12
LCK	0.027	0.075	0.26	40	-0.57	11	51
BCL2	0.018	0.19	0.42	2	-0.79	44	46

×

Hedgehog signaling events mediated by Gli proteins

Figure S92. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S92. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.006	-10000	0	-10000	0	0
GNB1/GNG2	0.037	0.062	-10000	0	-0.39	20	20
forebrain development	-0.042	0.2	0.35	1	-0.52	128	129
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
SMO/beta Arrestin2	0.027	0.045	-10000	0	-0.42	9	9
SMO	0.017	0.055	-10000	0	-0.57	9	9
ARRB2	0.021	0.011	-10000	0	-10000	0	0
GLI3/SPOP	0.024	0.081	0.32	2	-0.49	11	13
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.024	0.004	-10000	0	-10000	0	0
GNAI2	0.022	0.01	-10000	0	-10000	0	0
SIN3/HDAC complex	0.056	0.022	-10000	0	-10000	0	0
GNAI1	-0.008	0.13	-10000	0	-0.57	57	57
XPO1	0.022	0.015	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.034	0.19	-10000	0	-0.61	68	68
SAP30	0.024	0.015	0.26	4	-10000	0	4
mol:GDP	0.017	0.055	-10000	0	-0.57	9	9
MIM/GLI2A	0.021	0.02	0.26	2	-10000	0	2
IFT88	0.023	0.006	-10000	0	-10000	0	0
GNAI3	0.022	0.009	-10000	0	-10000	0	0
GLI2	0.01	0.066	-10000	0	-0.3	23	23
GLI3	0.013	0.084	0.34	2	-0.44	16	18
CSNK1D	0.023	0.006	-10000	0	-10000	0	0
CSNK1E	0.023	0.006	-10000	0	-10000	0	0
SAP18	0.023	0.006	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.023	0.006	-10000	0	-10000	0	0
GNG2	0.017	0.065	-10000	0	-0.57	13	13
Gi family/GTP	-0.009	0.098	-10000	0	-0.33	62	62
SIN3B	0.024	0.004	-10000	0	-10000	0	0
SIN3A	0.024	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	0.017	0.086	-10000	0	-0.46	19	19
GLI2/Su(fu)	0.013	0.081	-10000	0	-0.39	20	20
FOXA2	0.008	0.1	-10000	0	-0.73	12	12
neural tube patterning	-0.042	0.2	0.35	1	-0.52	128	129
SPOP	0.022	0.007	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.02	0.043	-10000	0	-0.37	1	1
GNB1	0.023	0.005	-10000	0	-10000	0	0
CSNK1G2	0.024	0.005	-10000	0	-10000	0	0
CSNK1G3	0.024	0.004	-10000	0	-10000	0	0
MTSS1	0.021	0.02	0.26	2	-10000	0	2
embryonic limb morphogenesis	-0.042	0.2	0.35	1	-0.52	128	129
SUFU	0.015	0.027	-10000	0	-0.4	1	1
LGALS3	0.016	0.067	-10000	0	-0.57	14	14
catabolic process	0.026	0.1	0.32	2	-0.5	20	22
GLI3A/CBP	0.003	0.089	-10000	0	-0.36	59	59
KIF3A	0.024	0.004	-10000	0	-10000	0	0
GLI1	-0.044	0.21	0.35	1	-0.54	126	127
RAB23	0.024	0.004	-10000	0	-10000	0	0
CSNK1A1	0.024	0.003	-10000	0	-10000	0	0
IFT172	0.024	0.018	-10000	0	-0.57	1	1
RBBP7	0.026	0.019	0.26	7	-10000	0	7
Su(fu)/Galectin3	0.017	0.061	-10000	0	-0.38	15	15
GNAZ	0.016	0.057	-10000	0	-0.57	10	10
RBBP4	0.023	0.019	-10000	0	-0.57	1	1
CSNK1G1	0.024	0.004	-10000	0	-10000	0	0
PIAS1	0.024	0.004	-10000	0	-10000	0	0
PRKACA	0.024	0.004	-10000	0	-10000	0	0
GLI2/SPOP	0.018	0.07	-10000	0	-0.33	20	20
STK36	0.021	0.023	-10000	0	-0.57	1	1
Gi family/GNB1/GNG2/GDP	-0.015	0.11	-10000	0	-0.4	51	51
PTCH1	-0.087	0.32	-10000	0	-1.1	89	89
MIM/GLI1	-0.03	0.19	-10000	0	-0.63	63	63
CREBBP	0.003	0.089	-10000	0	-0.36	59	59
Su(fu)/SIN3/HDAC complex	0.007	0.09	-10000	0	-0.41	35	35

×

BARD1 signaling events

Figure S93. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S93. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.026	0.057	-10000	0	-0.39	18	18
ATM	0.022	0.008	-10000	0	-10000	0	0
UBE2D3	0.024	0.004	-10000	0	-10000	0	0
PRKDC	0.021	0.008	-10000	0	-10000	0	0
ATR	0.024	0.004	-10000	0	-10000	0	0
UBE2L3	0.023	0.006	-10000	0	-10000	0	0
FANCD2	0.018	0.015	-10000	0	-10000	0	0
protein ubiquitination	0.065	0.071	0.3	2	-0.3	18	20
XRCC5	0.024	0.003	-10000	0	-10000	0	0
XRCC6	0.023	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.036	0.022	-10000	0	-10000	0	0
MRE11A	0.022	0.007	-10000	0	-10000	0	0
DNA-PK	0.04	0.02	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.015	0.086	-10000	0	-0.47	14	14
FANCF	0.024	0.004	-10000	0	-10000	0	0
BRCA1	0.023	0.02	0.26	1	-0.57	1	2
CCNE1	0.062	0.087	0.26	179	-10000	0	179
CDK2/Cyclin E1	0.06	0.06	-10000	0	-10000	0	0
FANCG	0.024	0.004	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.027	0.06	-10000	0	-0.41	19	19
FANCE	0.024	0.004	-10000	0	-10000	0	0
FANCC	0.024	0.003	-10000	0	-10000	0	0
NBN	0.02	0.01	-10000	0	-10000	0	0
FANCA	0.059	0.088	0.26	178	-10000	0	178
DNA repair	0.027	0.085	0.3	4	-0.37	7	11
BRCA1/BARD1/ubiquitin	0.027	0.06	-10000	0	-0.41	19	19
BARD1/DNA-PK	0.045	0.052	-10000	0	-0.33	15	15
FANCL	0.024	0.002	-10000	0	-10000	0	0
mRNA polyadenylation	-0.026	0.056	0.39	18	-10000	0	18
BRCA1/BARD1/CTIP/M/R/N Complex	0.011	0.07	-10000	0	-0.27	22	22
BRCA1/BACH1/BARD1/TopBP1	0.039	0.055	-10000	0	-0.36	18	18
BRCA1/BARD1/P53	0.048	0.054	-10000	0	-0.33	18	18
BARD1/CSTF1/BRCA1	0.037	0.053	-10000	0	-0.36	16	16
BRCA1/BACH1	0.023	0.02	0.26	1	-0.56	1	2
BARD1	0.014	0.076	0.26	1	-0.57	18	19
PCNA	0.024	0.011	0.26	2	-10000	0	2
BRCA1/BARD1/UbcH5C	0.04	0.053	-10000	0	-0.36	17	17
BRCA1/BARD1/UbcH7	0.038	0.054	-10000	0	-0.36	17	17
BRCA1/BARD1/RAD51/PCNA	0.091	0.088	0.31	2	-0.31	17	19
BARD1/DNA-PK/P53	0.05	0.054	-10000	0	-0.31	15	15
BRCA1/BARD1/Ubiquitin	0.027	0.06	-10000	0	-0.41	19	19
BRCA1/BARD1/CTIP	0.028	0.05	-10000	0	-0.33	18	18
FA complex	0.035	0.037	0.25	2	-0.26	1	3
BARD1/EWS	0.026	0.059	-10000	0	-0.42	18	18
RBBP8	0.01	0.005	-10000	0	-10000	0	0
TP53	0.022	0.008	-10000	0	-10000	0	0
TOPBP1	0.024	0.003	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.046	0.053	0.33	18	-10000	0	18
BRCA1/BARD1	0.071	0.075	0.33	2	-0.3	18	20
CSTF1	0.023	0.006	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.011	0.056	0.18	1	-0.42	18	19
CDK2	0.024	0.002	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.1	0.11	0.26	373	-10000	0	373
RAD50	0.024	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.06	-10000	0	-0.41	19	19
EWSR1	0.023	0.006	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

Figure S94. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S94. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.022	0.037	0.26	1	-0.57	4	5
ANTXR2	0.018	0.06	-10000	0	-0.57	11	11
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.009	-10000	0	-0.078	14	14
monocyte activation	0.003	0.085	0.25	2	-0.35	55	57
MAP2K2	0.003	0.082	-10000	0	-0.58	21	21
MAP2K1	-0.004	0.008	-10000	0	-0.11	2	2
MAP2K7	-0.004	0.009	0.12	1	-0.11	2	3
MAP2K6	-0.01	0.044	0.085	1	-0.3	24	25
CYAA	-0.009	0.039	-10000	0	-0.35	13	13
MAP2K4	-0.004	0.008	-10000	0	-10000	0	0
IL1B	-0.008	0.045	0.22	2	-0.28	25	27
Channel	0.025	0.046	-10000	0	-0.37	13	13
NLRP1	-0.007	0.033	-10000	0	-0.32	11	11
CALM1	0.024	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.001	0.066	-10000	0	-0.39	29	29
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.009	0.078	14	-10000	0	14
MAPK3	-0.004	0.008	0.085	1	-0.11	1	2
MAPK1	-0.004	0.009	0.12	2	-0.11	2	4
PGR	-0.079	0.14	0.2	2	-0.31	280	282
PA/Cellular Receptors	0.027	0.05	-10000	0	-0.4	13	13
apoptosis	-0.002	0.009	-10000	0	-0.078	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.025	0.044	-10000	0	-0.35	13	13
macrophage activation	-0.005	0.01	0.12	3	-10000	0	3
TNF	0.024	0.065	0.26	25	-0.57	9	34
VCAM1	0.003	0.085	0.25	2	-0.35	55	57
platelet activation	-0.001	0.066	-10000	0	-0.39	29	29
MAPKKK cascade	-0.002	0.026	0.12	3	-0.14	5	8
IL18	-0.003	0.026	-10000	0	-0.22	10	10
negative regulation of macrophage activation	-0.002	0.009	-10000	0	-0.078	14	14
LEF	-0.002	0.009	-10000	0	-0.079	14	14
CASP1	-0.003	0.027	-10000	0	-0.17	20	20
mol:cAMP	-0.001	0.067	-10000	0	-0.39	29	29
necrosis	-0.002	0.009	-10000	0	-0.078	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.025	0.044	-10000	0	-0.35	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

mTOR signaling pathway

Figure S95. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S95. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.024	0.004	-10000	0	-10000	0	0
mol:PIP3	-0.019	0.065	0.16	1	-0.29	51	52
FRAP1	-0.001	0.082	0.4	1	-0.45	25	26
AKT1	-0.011	0.065	0.18	2	-0.28	38	40
INSR	0.024	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.027	0.006	-10000	0	-10000	0	0
mol:GTP	0.023	0.07	0.23	5	-0.26	15	20
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.002	0.035	-10000	0	-0.21	4	4
TSC2	0.023	0.006	-10000	0	-10000	0	0
RHEB/GDP	0.005	0.048	-10000	0	-0.25	14	14
TSC1	0.024	0.004	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.005	0.077	-10000	0	-0.31	58	58
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.015	0.046	-10000	0	-0.23	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.024	0.004	-10000	0	-10000	0	0
RPS6KB1	0.012	0.075	0.26	7	-0.31	21	28
MAP3K5	-0.001	0.046	0.2	10	-0.19	46	56
PIK3R1	0.017	0.065	-10000	0	-0.57	13	13
apoptosis	-0.001	0.046	0.2	10	-0.19	47	57
mol:LY294002	0	0	-10000	0	-0.001	52	52
EIF4B	0.011	0.069	0.3	4	-0.3	13	17
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.028	0.066	0.23	1	-0.28	12	13
eIF4E/eIF4G1/eIF4A1	0.004	0.049	-10000	0	-0.28	22	22
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.015	0.081	-10000	0	-0.3	60	60
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.055	0.22	17	-0.19	3	20
FKBP1A	0.024	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.027	0.061	-10000	0	-0.24	14	14
mol:Amino Acids	0	0	-10000	0	-0.001	52	52
FKBP12/Rapamycin	0.018	0.004	-10000	0	-10000	0	0
PDPK1	-0.02	0.06	0.17	5	-0.28	44	49
EIF4E	0.024	0.004	-10000	0	-10000	0	0
ASK1/PP5C	-0.005	0.14	-10000	0	-0.52	65	65
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.003	0.048	-10000	0	-0.24	7	7
TSC1/TSC2	0.026	0.075	0.25	6	-0.28	15	21
tumor necrosis factor receptor activity	0	0	0.001	52	-10000	0	52
RPS6	0.024	0.005	-10000	0	-10000	0	0
PPP5C	0.024	0.003	-10000	0	-10000	0	0
EIF4G1	0.024	0.004	-10000	0	-10000	0	0
IRS1	-0.011	0.079	-10000	0	-0.33	60	60
INS	0.016	0.003	-10000	0	-10000	0	0
PTEN	0.022	0.019	-10000	0	-0.56	1	1
PDK2	-0.018	0.059	0.18	8	-0.28	38	46
EIF4EBP1	-0.022	0.22	-10000	0	-1	46	46
PIK3CA	0.024	0.005	-10000	0	-10000	0	0
PPP2R5D	0.001	0.078	0.36	3	-0.42	23	26
peptide biosynthetic process	-0.01	0.018	-10000	0	-10000	0	0
RHEB	0.024	0.004	-10000	0	-10000	0	0
EIF4A1	0.022	0.007	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.004	26	-0.003	3	29
EEF2	-0.01	0.018	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.011	0.21	-10000	0	-0.97	46	46

×

JNK signaling in the CD4+ TCR pathway

Figure S96. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S96. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.056	0.07	0.38	14	-0.38	11	25
MAP4K1	0.033	0.054	0.26	48	-0.57	2	50
MAP3K8	0.02	0.048	-10000	0	-0.57	7	7
PRKCB	0.019	0.076	0.26	19	-0.57	15	34
DBNL	0.024	0.003	-10000	0	-10000	0	0
CRKL	0.023	0.006	-10000	0	-10000	0	0
MAP3K1	0.015	0.054	0.25	1	-0.31	16	17
JUN	0.002	0.13	-10000	0	-0.6	42	42
MAP3K7	0.015	0.052	0.23	2	-0.29	14	16
GRAP2	0.017	0.063	0.26	3	-0.57	12	15
CRK	0.022	0.007	-10000	0	-10000	0	0
MAP2K4	0.013	0.066	0.24	1	-0.38	13	14
LAT	0.025	0.038	0.26	15	-0.57	2	17
LCP2	0.024	0.008	0.26	1	-10000	0	1
MAPK8	0.006	0.14	-10000	0	-0.63	42	42
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.022	0.058	0.25	3	-0.31	17	20
LAT/GRAP2/SLP76/HPK1/HIP-55	0.064	0.07	0.37	14	-0.37	11	25

×

S1P3 pathway

Figure S97. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S97. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.022	0.036	-10000	0	-0.57	4	4
mol:S1P	0	0.004	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.014	0.096	-10000	0	-0.29	96	96
GNAO1	0.018	0.09	0.26	32	-0.57	20	52
S1P/S1P3/G12/G13	0.042	0.02	-10000	0	-10000	0	0
AKT1	0.006	0.091	-10000	0	-0.47	29	29
AKT3	-0.014	0.17	-10000	0	-1.1	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.022	0.036	-10000	0	-0.56	4	4
GNAI2	0.023	0.009	-10000	0	-10000	0	0
GNAI3	0.024	0.009	-10000	0	-10000	0	0
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.026	0.021	0.26	7	-10000	0	7
S1PR2	0.024	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.1	-10000	0	-0.35	56	56
MAPK3	-0.009	0.091	0.27	2	-0.38	33	35
MAPK1	-0.008	0.092	0.27	1	-0.4	31	32
JAK2	-0.01	0.1	-10000	0	-0.39	41	41
CXCR4	-0.011	0.096	-10000	0	-0.4	32	32
FLT1	0.023	0.012	-10000	0	-10000	0	0
RhoA/GDP	0.018	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
SRC	-0.011	0.094	-10000	0	-0.4	30	30
S1P/S1P3/Gi	-0.004	0.1	-10000	0	-0.35	56	56
RAC1	0.024	0.003	-10000	0	-10000	0	0
RhoA/GTP	-0.003	0.1	-10000	0	-0.38	33	33
VEGFA	0.025	0.021	0.26	6	-10000	0	6
S1P/S1P2/Gi	-0.005	0.093	-10000	0	-0.28	92	92
VEGFR1 homodimer/VEGFA homodimer	0.035	0.022	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
S1P/S1P3/Gq	0.019	0.042	-10000	0	-0.28	18	18
GNAQ	0.022	0.031	-10000	0	-0.57	3	3
GNAZ	0.017	0.057	-10000	0	-0.57	10	10
G12/G13	0.033	0.011	-10000	0	-10000	0	0
GNA14	0.023	0.065	0.26	19	-0.57	10	29
GNA15	0.025	0.025	0.26	6	-0.57	1	7
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.007	-10000	0	-10000	0	0
GNA11	0.022	0.036	-10000	0	-0.57	4	4
Rac1/GTP	-0.004	0.1	-10000	0	-0.39	33	33

×

FoxO family signaling

Figure S98. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S98. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.012	0.06	-10000	0	-10000	0	0
PLK1	0.24	0.18	0.57	59	-0.57	1	60
CDKN1B	0.15	0.13	0.4	41	-0.45	5	46
FOXO3	0.2	0.16	0.45	173	-0.55	2	175
KAT2B	0.055	0.033	-10000	0	-0.57	1	1
FOXO1/SIRT1	0.012	0.055	-10000	0	-0.28	7	7
CAT	0.18	0.17	0.61	14	-1	5	19
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
AKT1	0.056	0.028	-10000	0	-10000	0	0
FOXO1	0.017	0.062	-10000	0	-0.3	9	9
MAPK10	-0.016	0.12	0.2	12	-0.29	156	168
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
FOXO4	0.034	0.084	0.38	3	-0.42	2	5
response to oxidative stress	0.034	0.026	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.17	0.13	0.44	39	-0.5	3	42
XPO1	0.024	0.003	-10000	0	-10000	0	0
EP300	0.025	0.007	-10000	0	-10000	0	0
BCL2L11	0.062	0.084	-10000	0	-0.69	10	10
FOXO1/SKP2	0.026	0.058	-10000	0	-0.3	5	5
mol:GDP	0.034	0.026	-10000	0	-10000	0	0
RAN	0.025	0.003	-10000	0	-10000	0	0
GADD45A	0.13	0.13	0.45	3	-0.54	10	13
YWHAQ	0.024	0.003	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.022	0.12	-10000	0	-0.5	36	36
MST1	0.052	0.059	0.27	8	-0.51	8	16
CSNK1D	0.023	0.006	-10000	0	-10000	0	0
CSNK1E	0.023	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.01	0.12	-10000	0	-0.45	47	47
YWHAB	0.023	0.005	-10000	0	-10000	0	0
MAPK8	0.029	0.037	0.2	14	-0.3	8	22
MAPK9	0.031	0.024	0.2	15	-10000	0	15
YWHAG	0.024	0.003	-10000	0	-10000	0	0
YWHAE	0.022	0.007	-10000	0	-10000	0	0
YWHAZ	0.019	0.01	-10000	0	-10000	0	0
SIRT1	0.012	0.02	-10000	0	-10000	0	0
SOD2	0.15	0.13	0.46	16	-0.42	3	19
RBL2	0.1	0.25	0.54	2	-0.62	73	75
RAL/GDP	0.056	0.021	-10000	0	-10000	0	0
CHUK	0.055	0.028	-10000	0	-10000	0	0
Ran/GTP	0.02	0.003	-10000	0	-10000	0	0
CSNK1G2	0.024	0.005	-10000	0	-10000	0	0
RAL/GTP	0.057	0.021	-10000	0	-10000	0	0
CSNK1G1	0.024	0.004	-10000	0	-10000	0	0
FASLG	0.055	0.18	-10000	0	-1.3	16	16
SKP2	0.024	0.004	-10000	0	-10000	0	0
USP7	0.023	0.006	-10000	0	-10000	0	0
IKBKB	0.047	0.032	-10000	0	-10000	0	0
CCNB1	0.2	0.17	0.55	53	-0.57	1	54
FOXO1-3a-4/beta catenin	0.15	0.12	0.41	45	-0.39	6	51
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.058	-10000	0	-0.29	5	5
CSNK1A1	0.024	0.003	-10000	0	-10000	0	0
SGK1	0.051	0.05	-10000	0	-0.55	5	5
CSNK1G3	0.024	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.035	0.007	-10000	0	-10000	0	0
ZFAND5	0.032	0.075	0.44	1	-10000	0	1
SFN	0.021	0.07	0.26	21	-0.57	12	33
CDK2	0.023	0.005	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.062	0.11	0.28	4	-0.39	21	25
CREBBP	0.022	0.008	-10000	0	-10000	0	0
FBXO32	0.23	0.2	0.62	97	-1.2	3	100
BCL6	0.16	0.16	0.52	3	-0.87	10	13
RALB	0.025	0.003	-10000	0	-10000	0	0
RALA	0.025	0.004	-10000	0	-10000	0	0
YWHAH	0.023	0.006	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

Figure S99. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S99. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.004	-10000	0	-10000	0	0
HDAC3	0.024	0.004	-10000	0	-10000	0	0
VDR	0.024	0.002	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.043	0.021	-10000	0	-0.36	1	1
EP300	0.023	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.015	0.062	-10000	0	-0.35	16	16
KAT2B	0.024	0.018	-10000	0	-0.57	1	1
MAPK14	0.024	0.003	-10000	0	-10000	0	0
AKT1	0.006	0.067	0.2	6	-0.37	17	23
RAR alpha/9cRA/Cyclin H	0.046	0.074	-10000	0	-0.34	19	19
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.021	0.066	-10000	0	-0.4	14	14
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.023	0.064	-10000	0	-0.42	12	12
NCOR2	0.024	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.018	0.002	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.009	0.11	-10000	0	-0.52	26	26
NCOA2	-0.006	0.12	-10000	0	-0.57	48	48
NCOA3	0.023	0.006	-10000	0	-10000	0	0
NCOA1	0.023	0.018	-10000	0	-0.57	1	1
VDR/VDR/DNA	0.024	0.002	-10000	0	-10000	0	0
RARG	0.025	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.033	0.006	-10000	0	-10000	0	0
MAPK3	0.023	0.006	-10000	0	-10000	0	0
MAPK1	0.023	0.006	-10000	0	-10000	0	0
MAPK8	0.02	0.051	-10000	0	-0.57	8	8
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.009	0.1	-10000	0	-0.47	25	25
RARA	0.013	0.055	0.18	25	-0.27	28	53
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.007	0.079	-10000	0	-0.38	22	22
PRKCA	0.012	0.084	0.26	1	-0.57	22	23
RXRs/RARs/NRIP1/9cRA/HDAC1	0.011	0.12	0.45	1	-0.52	27	28
RXRG	-0.051	0.15	0.24	13	-0.35	204	217
RXRA	0.022	0.064	0.2	11	-0.26	28	39
RXRB	0.016	0.061	0.22	17	-0.34	22	39
VDR/Vit D3/DNA	0.018	0.002	-10000	0	-10000	0	0
RBP1	0.036	0.076	0.26	73	-0.57	7	80
CRBP1/9-cic-RA	0.026	0.053	0.18	73	-0.42	7	80
RARB	0.017	0.067	-10000	0	-0.57	14	14
PRKCG	0.032	0.045	0.26	41	-10000	0	41
MNAT1	0.024	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.009	0.1	-10000	0	-0.5	30	30
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.008	0.1	0.25	2	-0.43	30	32
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.079	0.24	12	-0.36	18	30
RXRs/RARs/NRIP1/9cRA/HDAC3	0.011	0.12	0.45	1	-0.52	27	28
positive regulation of DNA binding	0.032	0.064	-10000	0	-0.32	19	19
NRIP1	0.012	0.12	0.54	1	-0.74	10	11
RXRs/RARs	0.01	0.12	0.28	1	-0.5	31	32
RXRs/RXRs/DNA/9cRA	-0.013	0.091	-10000	0	-0.48	25	25
PRKACA	0.024	0.004	-10000	0	-10000	0	0
CDK7	0.023	0.005	-10000	0	-10000	0	0
TFIIH	0.047	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.051	0.056	-10000	0	-0.35	2	2
CCNH	0.024	0.004	-10000	0	-10000	0	0
CREBBP	0.023	0.007	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.044	0.015	-10000	0	-10000	0	0

×

ceramide signaling pathway

Figure S100. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S100. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.001	0.098	0.26	2	-0.43	26	28
BAG4	0.018	0.032	-10000	0	-0.57	3	3
BAD	0.005	0.038	0.2	4	-0.17	8	12
NFKBIA	0.024	0.004	-10000	0	-10000	0	0
BIRC3	0.023	0.04	0.26	12	-0.57	3	15
BAX	0.005	0.042	0.22	6	-0.18	6	12
EnzymeConsortium:3.1.4.12	0.002	0.026	0.085	4	-0.094	24	28
IKBKB	0.017	0.1	0.34	3	-0.42	19	22
MAP2K2	0.008	0.051	0.21	17	-0.24	2	19
MAP2K1	0.009	0.053	0.23	15	-0.24	2	17
SMPD1	0.002	0.032	0.2	1	-0.16	13	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.026	0.11	0.3	12	-0.44	22	34
MAP2K4	0.006	0.034	0.19	4	-0.22	3	7
protein ubiquitination	0.004	0.1	0.34	4	-0.41	24	28
EnzymeConsortium:2.7.1.37	0.008	0.054	0.23	14	-0.25	2	16
response to UV	0	0.001	0.002	21	-0.002	2	23
RAF1	0.009	0.052	0.19	41	-0.22	4	45
CRADD	0.024	0.004	-10000	0	-10000	0	0
mol:ceramide	0.006	0.04	0.14	5	-0.15	20	25
I-kappa-B-alpha/RELA/p50/ubiquitin	0.031	0.009	-10000	0	-10000	0	0
MADD	0.024	0.004	-10000	0	-10000	0	0
MAP3K1	0.004	0.039	0.18	4	-0.19	7	11
TRADD	0.022	0.008	-10000	0	-10000	0	0
RELA/p50	0.023	0.005	-10000	0	-10000	0	0
MAPK3	0.01	0.052	0.22	14	-0.22	3	17
MAPK1	0.007	0.059	0.22	14	-0.23	8	22
p50/RELA/I-kappa-B-alpha	0.034	0.01	-10000	0	-10000	0	0
FADD	0.024	0.11	0.28	12	-0.44	20	32
KSR1	0.009	0.05	0.18	36	-0.2	7	43
MAPK8	0.002	0.048	0.24	8	-0.28	8	16
TRAF2	0.025	0.015	0.26	4	-10000	0	4
response to radiation	0	0	0.002	10	-10000	0	10
CHUK	-0.001	0.093	-10000	0	-0.41	24	24
TNF R/SODD	0.027	0.029	-10000	0	-0.42	3	3
TNF	0.025	0.065	0.26	25	-0.57	9	34
CYCS	0.008	0.045	0.18	14	-0.18	5	19
IKBKG	-0.001	0.095	0.43	1	-0.42	23	24
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.002	0.1	-10000	0	-0.44	27	27
RELA	0.023	0.005	-10000	0	-10000	0	0
RIPK1	0.024	0.005	-10000	0	-10000	0	0
AIFM1	0.007	0.044	0.17	13	-0.2	4	17
TNF/TNF R/SODD	0.036	0.051	-10000	0	-0.36	11	11
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
response to heat	0	0	0.002	10	-10000	0	10
CASP8	0.003	0.13	-10000	0	-0.62	42	42
NSMAF	0.017	0.11	0.26	11	-0.41	25	36
response to hydrogen peroxide	0	0.001	0.002	21	-0.002	2	23
BCL2	0.008	0.094	-10000	0	-0.57	28	28

×

Signaling mediated by p38-gamma and p38-delta

Figure S101. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S101. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.008	0.011	0.23	2	-10000	0	2
SNTA1	0.024	0.004	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.001	0.034	0.3	8	-10000	0	8
MAPK12	-0.009	0.048	0.21	1	-0.33	22	23
CCND1	0.01	0.047	-10000	0	-0.38	7	7
p38 gamma/SNTA1	0.021	0.07	0.32	2	-0.32	22	24
MAP2K3	0.023	0.007	-10000	0	-10000	0	0
PKN1	0.024	0.004	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.009	0.048	0.21	1	-0.33	22	23
MAP2K6	-0.006	0.051	-10000	0	-0.35	23	23
MAPT	-0.026	0.12	0.25	15	-0.32	124	139
MAPK13	0.011	0.011	0.26	2	-10000	0	2
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.006	0.001	-10000	0	-10000	0	0

×

Arf6 trafficking events

Figure S102. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S102. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.27	0.29	-10000	0	-0.57	524	524
CLTC	0.025	0.067	0.28	1	-0.42	13	14
calcium ion-dependent exocytosis	0.009	0.025	-10000	0	-0.26	2	2
Dynamin 2/GTP	0.022	0.013	-10000	0	-10000	0	0
EXOC4	0.024	0.004	-10000	0	-10000	0	0
CD59	0.016	0.046	-10000	0	-0.34	10	10
CPE	0.005	0.049	-10000	0	-0.36	19	19
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
membrane fusion	0.011	0.019	-10000	0	-10000	0	0
CTNND1	0.008	0.056	0.19	91	-10000	0	91
DNM2	0.024	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.014	0.043	0.21	3	-0.33	7	10
TSHR	-0.003	0.072	-10000	0	-0.36	42	42
INS	-0.001	0.088	-10000	0	-0.48	34	34
BIN1	0.02	0.051	-10000	0	-0.57	8	8
mol:Choline	0.011	0.019	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.013	0.017	0.14	17	-10000	0	17
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.024	0.004	-10000	0	-10000	0	0
mol:Ca2+	0.022	0.013	-10000	0	-10000	0	0
JUP	0.017	0.039	0.23	1	-0.33	7	8
ASAP2/amphiphysin II	0.042	0.033	-10000	0	-0.33	7	7
ARF6/GTP	0.018	0.003	-10000	0	-10000	0	0
CDH1	0.01	0.053	-10000	0	-0.37	9	9
clathrin-independent pinocytosis	0.018	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.023	0.006	-10000	0	-10000	0	0
positive regulation of endocytosis	0.018	0.003	-10000	0	-10000	0	0
EXOC2	0.027	0.028	0.26	16	-10000	0	16
substrate adhesion-dependent cell spreading	0.016	0.039	-10000	0	-0.33	4	4
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.022	0.007	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.064	0.34	7	-10000	0	7
positive regulation of phagocytosis	0.011	0.003	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.03	0.01	-10000	0	-10000	0	0
ACAP1	0.015	0.028	-10000	0	-0.25	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.014	0.043	-10000	0	-0.34	10	10
clathrin heavy chain/ACAP1	0.024	0.063	0.29	5	-0.35	12	17
JIP4/KLC1	0.041	0.016	-10000	0	-10000	0	0
EXOC1	0.024	0.004	-10000	0	-10000	0	0
exocyst	0.02	0.033	-10000	0	-0.34	4	4
RALA/GTP	0.018	0.003	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.029	0.011	-10000	0	-10000	0	0
receptor recycling	0.018	0.003	-10000	0	-10000	0	0
CTNNA1	0.008	0.057	0.19	94	-10000	0	94
NME1	0.013	0.017	0.14	17	-10000	0	17
clathrin coat assembly	0.028	0.069	0.28	3	-0.41	13	16
IL2RA	0.019	0.054	-10000	0	-0.32	13	13
VAMP3	0.011	0.003	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.12	0.14	-10000	0	-0.37	35	35
EXOC6	0.024	0.003	-10000	0	-10000	0	0
PLD1	0.009	0.029	-10000	0	-0.29	9	9
PLD2	0.011	0.006	-10000	0	-10000	0	0
EXOC5	0.024	0.004	-10000	0	-10000	0	0
PIP5K1C	0.013	0.039	0.19	1	-0.36	6	7
SDC1	0.019	0.043	-10000	0	-0.33	8	8
ARF6/GDP	0.021	0.014	-10000	0	-10000	0	0
EXOC7	0.023	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.04	0.067	-10000	0	-0.35	7	7
mol:Phosphatidic acid	0.011	0.019	-10000	0	-10000	0	0
endocytosis	-0.04	0.033	0.33	7	-10000	0	7
SCAMP2	0.024	0.004	-10000	0	-10000	0	0
ADRB2	-0.037	0.14	0.26	1	-0.39	47	48
EXOC3	0.024	0.005	-10000	0	-10000	0	0
ASAP2	0.023	0.018	-10000	0	-0.57	1	1
Dynamin 2/GDP	0.026	0.017	-10000	0	-10000	0	0
KLC1	0.024	0.004	-10000	0	-10000	0	0
AVPR2	-0.079	0.15	0.27	2	-0.43	36	38
RALA	0.024	0.004	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.036	0.065	0.32	2	-0.36	5	7

×

IL1-mediated signaling events

Figure S103. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S103. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.018	0.002	-10000	0	-10000	0	0
PRKCZ	0.023	0.019	-10000	0	-0.57	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.023	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.012	0.05	-10000	0	-0.35	8	8
IRAK/TOLLIP	0.026	0.009	-10000	0	-10000	0	0
IKBKB	0.02	0.009	-10000	0	-10000	0	0
IKBKG	0.024	0.002	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.025	0.094	0.36	3	-0.42	40	43
IL1A	0.028	0.03	0.26	18	-10000	0	18
IL1B	0.004	0.053	0.26	1	-0.43	15	16
IRAK/TRAF6/p62/Atypical PKCs	0.056	0.027	-10000	0	-0.3	1	1
IL1R2	0.008	0.12	0.26	29	-0.57	40	69
IL1R1	0.012	0.084	-10000	0	-0.57	22	22
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.062	0.26	4	-0.3	20	24
TOLLIP	0.024	0.004	-10000	0	-10000	0	0
TICAM2	0.024	0.004	-10000	0	-10000	0	0
MAP3K3	0.022	0.007	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.016	0.004	-10000	0	-10000	0	0
IKK complex/ELKS	0.026	0.056	-10000	0	-0.37	1	1
JUN	-0.015	0.056	0.26	2	-0.27	35	37
MAP3K7	0.023	0.006	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.037	0.085	-10000	0	-0.34	45	45
IL1 alpha/IL1R1/IL1RAP/MYD88	0.053	0.061	-10000	0	-0.33	23	23
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.061	0.061	-10000	0	-0.31	23	23
IL1 beta fragment/IL1R1/IL1RAP	0.022	0.073	-10000	0	-0.35	36	36
NFKB1	0.024	0.004	-10000	0	-10000	0	0
MAPK8	-0.011	0.054	0.34	1	-0.28	28	29
IRAK1	0.012	0.008	-10000	0	-10000	0	0
IL1RN/IL1R1	0.031	0.074	-10000	0	-0.42	24	24
IRAK4	0.024	0.003	-10000	0	-10000	0	0
PRKCI	0.024	0.005	-10000	0	-10000	0	0
TRAF6	0.024	0.004	-10000	0	-10000	0	0
PI3K	0.028	0.049	-10000	0	-0.38	14	14
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.011	0.059	-10000	0	-0.29	25	25
CHUK	0.024	0.003	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.022	0.073	-10000	0	-0.35	36	36
IL1 beta/IL1R2	0.013	0.093	-10000	0	-0.37	53	53
IRAK/TRAF6/TAK1/TAB1/TAB2	0.032	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.026	0.077	-10000	0	-0.32	44	44
IRAK3	0.003	0.11	0.26	1	-0.57	39	40
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.042	0.074	-10000	0	-0.32	36	36
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.019	0.047	-10000	0	-0.27	23	23
IL1 alpha/IL1R1/IL1RAP	0.041	0.063	-10000	0	-0.36	23	23
RELA	0.023	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.024	0.008	0.26	1	-10000	0	1
MYD88	0.024	0.004	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.038	0.021	-10000	0	-10000	0	0
IL1RAP	0.023	0.018	-10000	0	-0.57	1	1
UBE2N	0.024	0.003	-10000	0	-10000	0	0
IRAK/TRAF6	0.018	0.06	-10000	0	-0.29	35	35
CASP1	0.021	0.019	-10000	0	-0.57	1	1
IL1RN/IL1R2	0.028	0.099	0.36	5	-0.42	42	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.034	0.073	-10000	0	-0.33	36	36
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.071	-10000	0	-0.34	34	34
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
IL1RN	0.031	0.049	0.26	37	-0.57	2	39
TRAF6/TAK1/TAB1/TAB2	0.033	0.011	-10000	0	-10000	0	0
MAP2K6	-0.008	0.053	0.25	5	-0.29	22	27

×

Sphingosine 1-phosphate (S1P) pathway

Figure S104. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S104. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0.003	-10000	0	-10000	0	0
SPHK1	0.026	0.041	0.26	20	-0.57	2	22
GNAI2	0.024	0.005	-10000	0	-10000	0	0
mol:S1P	0.013	0.019	0.22	1	-0.29	2	3
GNAO1	0.017	0.09	0.26	32	-0.57	20	52
mol:Sphinganine-1-P	0.012	0.026	0.26	1	-0.42	2	3
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.051	0.035	-10000	0	-0.23	3	3
GNAI3	0.024	0.004	-10000	0	-10000	0	0
G12/G13	0.033	0.011	-10000	0	-10000	0	0
S1PR3	0.026	0.02	0.26	8	-10000	0	8
S1PR2	0.024	0.004	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.006	0.023	-10000	0	-0.24	5	5
S1PR5	0.027	0.041	0.26	20	-0.57	2	22
S1PR4	0.029	0.062	0.26	38	-0.57	6	44
GNAI1	-0.007	0.13	-10000	0	-0.57	57	57
S1P/S1P5/G12	0.046	0.041	0.24	4	-0.24	5	9
S1P/S1P3/Gq	0.026	0.063	-10000	0	-0.29	31	31
S1P/S1P4/Gi	0	0.097	-10000	0	-0.28	81	81
GNAQ	0.022	0.031	-10000	0	-0.57	3	3
GNAZ	0.018	0.057	-10000	0	-0.57	10	10
GNA14	0.023	0.065	0.26	19	-0.57	10	29
GNA15	0.025	0.025	0.26	6	-0.57	1	7
GNA12	0.024	0.004	-10000	0	-10000	0	0
GNA13	0.022	0.007	-10000	0	-10000	0	0
GNA11	0.022	0.036	-10000	0	-0.57	4	4
ABCC1	0.023	0.006	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

Figure S105. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S105. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.024	0.009	0.26	1	-9999	1
PLK4	0.033	0.044	0.26	41	-9999	41
regulation of centriole replication	0.016	0.026	0.26	2	-9999	2

×

E-cadherin signaling in the nascent adherens junction

Figure S106. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S106. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.019	0.11	-10000	0	-0.43	34	34
KLHL20	0.016	0.064	0.24	8	-0.22	13	21
CYFIP2	0.028	0.048	0.26	26	-0.57	3	29
Rac1/GDP	0.001	0.084	0.26	8	-0.31	17	25
ENAH	-0.015	0.1	-10000	0	-0.45	24	24
AP1M1	0.024	0.004	-10000	0	-10000	0	0
RAP1B	0.024	0.005	-10000	0	-10000	0	0
RAP1A	0.024	0.004	-10000	0	-10000	0	0
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
CDC42/GTP	0.01	0.046	-10000	0	-0.32	2	2
ABI1/Sra1/Nap1	-0.012	0.031	-10000	0	-0.16	11	11
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.047	0.064	-10000	0	-0.33	20	20
RAPGEF1	-0.018	0.1	0.26	2	-0.39	28	30
CTNND1	0.024	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.021	0.12	-10000	0	-0.41	50	50
CRK	-0.015	0.099	-10000	0	-0.42	30	30
E-cadherin/gamma catenin/alpha catenin	0.033	0.057	-10000	0	-0.36	18	18
alphaE/beta7 Integrin	0.036	0.034	-10000	0	-0.42	2	2
IQGAP1	0.024	0.005	-10000	0	-10000	0	0
NCKAP1	0.024	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.04	0.027	-10000	0	-0.33	3	3
DLG1	-0.023	0.12	-10000	0	-0.44	32	32
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.017	0.031	-10000	0	-0.21	4	4
MLLT4	0.021	0.032	0.26	1	-0.57	3	4
ARF6/GTP/NME1/Tiam1	0.044	0.025	-10000	0	-10000	0	0
PI3K	-0.003	0.045	-10000	0	-0.29	3	3
ARF6	0.024	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.021	0.062	-10000	0	-0.42	18	18
TIAM1	0.025	0.015	0.26	4	-10000	0	4
E-cadherin(dimer)/Ca2+	0.041	0.054	-10000	0	-0.31	18	18
AKT1	-0.007	0.035	0.14	1	-0.21	1	2
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
CDH1	0.012	0.076	-10000	0	-0.57	18	18
RhoA/GDP	0.002	0.083	0.26	8	-0.31	16	24
actin cytoskeleton organization	0.015	0.052	0.18	18	-0.16	11	29
CDC42/GDP	0.002	0.082	0.26	9	-0.31	16	25
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.008	0.04	-10000	0	-0.26	18	18
ITGB7	0.03	0.046	0.26	30	-0.57	2	32
RAC1	0.024	0.003	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.045	0.057	-10000	0	-0.33	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin	0.03	0.049	-10000	0	-0.31	18	18
mol:GDP	-0.012	0.09	0.26	9	-0.36	17	26
CDC42/GTP/IQGAP1	0.031	0.009	-10000	0	-10000	0	0
JUP	0.023	0.005	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.006	0.085	0.26	7	-0.32	16	23
RAC1/GTP/IQGAP1	0.032	0.007	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.035	0.007	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
CDC42	0.023	0.005	-10000	0	-10000	0	0
CTNNA1	0.024	0.004	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.014	0.047	0.18	39	-0.24	4	43
NME1	0.026	0.031	0.26	18	-10000	0	18
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.021	0.11	-10000	0	-0.45	31	31
regulation of cell-cell adhesion	0.004	0.039	-10000	0	-0.28	2	2
WASF2	0.008	0.026	-10000	0	-10000	0	0
Rap1/GTP	0.014	0.056	0.24	3	-0.37	2	5
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.054	0.064	-10000	0	-0.32	19	19
CCND1	0.015	0.054	0.2	38	-0.3	4	42
VAV2	-0.018	0.15	-10000	0	-0.55	36	36
RAP1/GDP	0.008	0.069	0.26	4	-0.35	3	7
adherens junction assembly	-0.02	0.11	-10000	0	-0.43	31	31
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.024	0.004	-10000	0	-10000	0	0
PIP5K1C	0.024	0.004	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.042	0.061	-10000	0	-0.3	19	19
E-cadherin/beta catenin	0.001	0.057	-10000	0	-0.34	28	28
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.022	0.12	-10000	0	-0.44	32	32
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.089	0.26	34	-0.34	25	59
E-cadherin/beta catenin/alpha catenin	0.034	0.057	-10000	0	-0.36	18	18
ITGAE	0.022	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.022	0.12	-10000	0	-0.42	50	50

×

PDGFR-beta signaling pathway

Figure S107. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S107. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.025	0.073	0.3	4	-0.36	15	19
PDGFB-D/PDGFRB/SLAP	0.028	0.033	0.2	9	-0.36	4	13
PDGFB-D/PDGFRB/APS/CBL	0.048	0.042	-10000	0	-0.35	4	4
AKT1	0.025	0.095	0.34	38	-10000	0	38
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.032	0.084	0.32	6	-0.38	18	24
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
FGR	0	0.1	-10000	0	-0.44	40	40
mol:Ca2+	0.024	0.087	0.29	7	-0.42	18	25
MYC	0.053	0.17	0.36	35	-0.73	29	64
SHC1	0.02	0.009	-10000	0	-10000	0	0
HRAS/GDP	0.035	0.044	-10000	0	-0.3	3	3
LRP1/PDGFRB/PDGFB	0.041	0.054	-10000	0	-0.4	14	14
GRB10	0.024	0.003	-10000	0	-10000	0	0
PTPN11	0.024	0.002	-10000	0	-10000	0	0
GO:0007205	0.023	0.088	0.29	7	-0.43	18	25
PTEN	0.022	0.019	-10000	0	-0.57	1	1
GRB2	0.023	0.009	0.26	1	-10000	0	1
GRB7	0.019	0.032	-10000	0	-0.57	3	3
PDGFB-D/PDGFRB/SHP2	0.034	0.028	-10000	0	-0.42	4	4
PDGFB-D/PDGFRB/GRB10	0.034	0.028	-10000	0	-0.42	4	4
cell cycle arrest	0.028	0.033	0.2	9	-0.36	4	13
HRAS	0.026	0.022	0.26	9	-10000	0	9
HIF1A	0.019	0.089	0.33	37	-10000	0	37
GAB1	0.026	0.093	0.29	8	-0.4	20	28
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.026	0.086	0.32	10	-0.37	14	24
PDGFB-D/PDGFRB	0.042	0.031	-10000	0	-0.37	3	3
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.034	0.026	-10000	0	-0.42	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.023	0.065	0.28	3	-0.37	10	13
positive regulation of MAPKKK cascade	0.034	0.028	-10000	0	-0.42	4	4
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:IP3	0.024	0.089	0.29	7	-0.43	18	25
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.023	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.028	0.039	-10000	0	-0.42	7	7
SHB	0.024	0.008	0.26	1	-10000	0	1
BLK	-0.024	0.16	0.29	5	-0.4	144	149
PTPN2	0.024	0.008	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.033	0.029	-10000	0	-0.41	4	4
BCAR1	0.021	0.008	-10000	0	-10000	0	0
VAV2	0.028	0.1	0.3	9	-0.43	23	32
CBL	0.022	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.034	0.029	-10000	0	-0.42	4	4
LCK	0.006	0.11	-10000	0	-0.5	36	36
PDGFRB	0.022	0.037	-10000	0	-0.57	4	4
ACP1	0.024	0.003	-10000	0	-10000	0	0
HCK	0.016	0.06	-10000	0	-0.5	7	7
ABL1	0.021	0.093	0.3	7	-0.37	28	35
PDGFB-D/PDGFRB/CBL	0.021	0.1	0.3	3	-0.44	29	32
PTPN1	0.024	0.019	0.25	6	-10000	0	6
SNX15	0.023	0.005	-10000	0	-10000	0	0
STAT3	0.024	0.005	-10000	0	-10000	0	0
STAT1	0.028	0.031	0.26	19	-10000	0	19
cell proliferation	0.054	0.15	0.33	49	-0.64	29	78
SLA	0.021	0.024	0.26	9	-10000	0	9
actin cytoskeleton reorganization	0.034	0.05	0.33	2	-0.3	2	4
SRC	0.012	0.059	-10000	0	-0.49	8	8
PI3K	-0.013	0.032	-10000	0	-0.28	10	10
PDGFB-D/PDGFRB/GRB7/SHC	0.033	0.038	-10000	0	-0.36	6	6
SH2B2	0.034	0.046	0.26	45	-10000	0	45
PLCgamma1/SPHK1	0.032	0.086	0.32	6	-0.4	18	24
LYN	0.009	0.064	-10000	0	-0.46	12	12
LRP1	0.018	0.062	-10000	0	-0.57	12	12
SOS1	0.024	0.003	-10000	0	-10000	0	0
STAT5B	0.022	0.026	-10000	0	-0.57	2	2
STAT5A	0.02	0.044	-10000	0	-0.57	6	6
NCK1-2/p130 Cas	0.055	0.04	-10000	0	-0.3	3	3
SPHK1	0.027	0.041	0.26	20	-0.57	2	22
EDG1	0.001	0.002	-10000	0	-10000	0	0
mol:DAG	0.024	0.089	0.29	7	-0.43	18	25
PLCG1	0.024	0.09	0.3	6	-0.44	18	24
NHERF/PDGFRB	0.049	0.045	-10000	0	-0.36	4	4
YES1	0.001	0.11	-10000	0	-0.51	37	37
cell migration	0.048	0.045	-10000	0	-0.36	4	4
SHC/Grb2/SOS1	0.049	0.041	-10000	0	-0.3	3	3
SLC9A3R2	0.023	0.01	0.26	1	-10000	0	1
SLC9A3R1	0.036	0.054	0.26	60	-10000	0	60
NHERF1-2/PDGFRB/PTEN	0.056	0.048	0.29	2	-0.33	4	6
FYN	-0.003	0.1	-10000	0	-0.42	45	45
DOK1	0.021	0.049	0.33	1	-0.33	3	4
HRAS/GTP	0.019	0.015	0.18	9	-10000	0	9
PDGFB	0.023	0.006	-10000	0	-10000	0	0
RAC1	0.023	0.12	0.33	4	-0.49	33	37
PRKCD	0.022	0.051	0.33	1	-0.33	3	4
FER	0.018	0.059	-10000	0	-0.34	12	12
MAPKKK cascade	0.037	0.096	0.36	34	-0.3	3	37
RASA1	0.021	0.049	-10000	0	-0.33	3	3
NCK1	0.024	0.003	-10000	0	-10000	0	0
NCK2	0.024	0.003	-10000	0	-10000	0	0
p62DOK/Csk	0.035	0.043	0.3	1	-0.31	3	4
PDGFB-D/PDGFRB/SHB	0.034	0.03	-10000	0	-0.42	4	4
chemotaxis	0.021	0.091	0.28	9	-0.36	28	37
STAT1-3-5/STAT1-3-5	0.049	0.047	-10000	0	-0.36	8	8
Bovine Papilomavirus E5/PDGFRB	0.016	0.027	-10000	0	-0.42	4	4
PTPRJ	0.024	0.004	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

Figure S108. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S108. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.017	0.019	-10000	0	-0.3	3	3
TRAF2/ASK1	0.03	0.024	-10000	0	-0.36	3	3
ATM	0.022	0.008	-10000	0	-10000	0	0
MAP2K3	-0.018	0.11	0.27	1	-0.35	57	58
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	-0.014	0.098	0.26	1	-0.34	43	44
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.054	0.077	0.26	138	-10000	0	138
TXN	0.007	0.006	-10000	0	-10000	0	0
CALM1	0.024	0.004	-10000	0	-10000	0	0
GADD45A	0.024	0.004	-10000	0	-10000	0	0
GADD45B	0.024	0.004	-10000	0	-10000	0	0
MAP3K1	0.023	0.019	-10000	0	-0.57	1	1
MAP3K6	0.023	0.005	-10000	0	-10000	0	0
MAP3K7	0.023	0.006	-10000	0	-10000	0	0
MAP3K4	0.023	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.027	-10000	0	-0.41	3	3
TAK1/TAB family	0	0.019	0.18	2	-0.14	6	8
RAC1/OSM/MEKK3	0.042	0.016	-10000	0	-10000	0	0
TRAF2	0.025	0.015	0.26	4	-10000	0	4
RAC1/OSM/MEKK3/MKK3	0	0.091	-10000	0	-0.31	31	31
TRAF6	0.006	0.001	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.005	0.15	0.26	44	-0.57	69	113
CCM2	0.024	0.008	0.26	1	-10000	0	1
CaM/Ca2+/CAMKIIB	0.012	0.1	-10000	0	-0.36	69	69
MAPK11	0.021	0.032	-10000	0	-0.57	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.023	0.1	-10000	0	-0.33	71	71
OSM/MEKK3	0.032	0.013	-10000	0	-10000	0	0
TAOK1	-0.008	0.081	-10000	0	-0.36	54	54
TAOK2	0.011	0.005	-10000	0	-10000	0	0
TAOK3	0.011	0.004	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.024	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.022	0.032	-10000	0	-0.57	3	3
MAP3K10	0.024	0.004	-10000	0	-10000	0	0
MAP3K3	0.022	0.007	-10000	0	-10000	0	0
TRX/ASK1	0.019	0.025	-10000	0	-0.34	3	3
GADD45/MTK1/MTK1	0.067	0.047	-10000	0	-10000	0	0

×

TRAIL signaling pathway

Figure S109. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S109. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.02	0.048	-10000	0	-0.57	7	7
positive regulation of NF-kappaB transcription factor activity	-0.005	0.11	-10000	0	-0.4	71	71
MAP2K4	0.016	0.046	-10000	0	-0.38	4	4
IKBKB	0.02	0.009	-10000	0	-10000	0	0
TNFRSF10B	0.02	0.009	-10000	0	-10000	0	0
TNFRSF10A	0.018	0.032	-10000	0	-0.57	3	3
SMPD1	0.008	0.029	-10000	0	-0.34	6	6
IKBKG	0.024	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.015	0.14	0.26	1	-0.57	64	65
TRAIL/TRAILR2	0.026	0.038	-10000	0	-0.37	8	8
TRAIL/TRAILR3	0.027	0.042	-10000	0	-0.42	7	7
TRAIL/TRAILR1	0.024	0.046	-10000	0	-0.41	10	10
TRAIL/TRAILR4	-0.005	0.11	-10000	0	-0.4	71	71
TRAIL/TRAILR1/DAP3/GTP	0.029	0.038	-10000	0	-0.32	7	7
IKK complex	0.011	0.04	-10000	0	-0.41	1	1
RIPK1	0.024	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.015	0.007	-10000	0	-10000	0	0
MAPK3	0.007	0.035	0.25	1	-0.42	7	8
MAP3K1	0.019	0.059	-10000	0	-0.44	7	7
TRAILR4 (trimer)	-0.015	0.14	0.26	1	-0.56	64	65
TRADD	0.022	0.008	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.018	0.032	-10000	0	-0.56	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.013	0.044	-10000	0	-0.36	9	9
CFLAR	0.024	0.018	-10000	0	-0.57	1	1
MAPK1	0.008	0.035	0.25	1	-0.42	7	8
TRAIL/TRAILR1/FADD/TRADD/RIP	0.042	0.046	-10000	0	-0.3	7	7
mol:ceramide	0.008	0.029	-10000	0	-0.34	6	6
FADD	0.021	0.009	-10000	0	-10000	0	0
MAPK8	0.013	0.062	0.26	1	-0.44	7	8
TRAF2	0.025	0.015	0.26	4	-10000	0	4
TRAILR3 (trimer)	0.022	0.021	0.26	7	-10000	0	7
CHUK	0.024	0.003	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.031	0.041	-10000	0	-0.35	7	7
DAP3	0.021	0.009	-10000	0	-10000	0	0
CASP10	0.036	0.084	0.28	61	-0.34	3	64
JNK cascade	-0.005	0.11	-10000	0	-0.4	71	71
TRAIL (trimer)	0.02	0.048	-10000	0	-0.56	7	7
TNFRSF10C	0.022	0.021	0.26	7	-10000	0	7
TRAIL/TRAILR1/DAP3/GTP/FADD	0.032	0.039	-10000	0	-0.31	5	5
TRAIL/TRAILR2/FADD	0.032	0.036	-10000	0	-0.35	5	5
cell death	0.008	0.029	-10000	0	-0.34	6	6
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.014	0.041	-10000	0	-0.41	6	6
TRAILR2 (trimer)	0.02	0.009	-10000	0	-10000	0	0
CASP8	0.012	0.05	-10000	0	-0.56	6	6
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.043	0.043	-10000	0	-0.29	5	5

×

Class I PI3K signaling events

Figure S110. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S110. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.013	0.04	0.3	4	-0.28	1	5
DAPP1	0.017	0.1	0.27	7	-0.35	36	43
Src family/SYK family/BLNK-LAT/BTK-ITK	0.019	0.14	0.28	19	-0.48	39	58
mol:DAG	0.022	0.078	0.23	36	-0.24	13	49
HRAS	0.027	0.022	0.25	9	-10000	0	9
RAP1A	0.025	0.006	-10000	0	-10000	0	0
ARF5/GDP	0.029	0.059	0.27	1	-0.32	9	10
PLCG2	0.02	0.028	0.26	1	-0.57	2	3
PLCG1	0.023	0.005	-10000	0	-10000	0	0
ARF5	0.024	0.008	0.26	1	-10000	0	1
mol:GTP	-0.01	0.037	0.31	5	-0.28	1	6
ARF1/GTP	-0.004	0.033	0.26	8	-0.28	1	9
RHOA	0.024	0.005	-10000	0	-10000	0	0
YES1	0.023	0.019	-10000	0	-0.57	1	1
RAP1A/GTP	-0.011	0.033	0.2	1	-0.27	1	2
ADAP1	-0.011	0.04	0.3	5	-0.28	2	7
ARAP3	-0.01	0.037	0.31	5	-0.28	1	6
INPPL1	0.023	0.006	-10000	0	-10000	0	0
PREX1	0.027	0.033	0.26	21	-10000	0	21
ARHGEF6	0.017	0.067	-10000	0	-0.57	14	14
ARHGEF7	0.022	0.007	-10000	0	-10000	0	0
ARF1	0.02	0.009	-10000	0	-10000	0	0
NRAS	0.025	0.006	-10000	0	-10000	0	0
FYN	0.021	0.026	-10000	0	-0.57	2	2
ARF6	0.024	0.004	-10000	0	-10000	0	0
FGR	0.024	0.009	0.26	1	-10000	0	1
mol:Ca2+	0.016	0.053	0.23	19	-10000	0	19
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.025	0.015	0.26	4	-10000	0	4
ZAP70	0.026	0.098	0.26	61	-0.57	20	81
mol:IP3	0.017	0.066	0.21	44	-0.2	4	48
LYN	0.021	0.008	-10000	0	-10000	0	0
ARF1/GDP	0.024	0.057	0.28	2	-0.32	9	11
RhoA/GDP	0.03	0.041	0.25	1	-10000	0	1
PDK1/Src/Hsp90	0.043	0.017	-10000	0	-10000	0	0
BLNK	0.024	0.003	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.02	0.068	0.3	13	-0.35	2	15
SRC	0.023	0.005	-10000	0	-10000	0	0
PLEKHA2	-0.007	0.011	0.23	2	-10000	0	2
RAC1	0.024	0.003	-10000	0	-10000	0	0
PTEN	0.022	0.02	-10000	0	-0.54	1	1
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.013	0.038	0.3	5	-0.27	1	6
RhoA/GTP	-0.012	0.037	0.33	4	-0.27	1	5
Src family/SYK family/BLNK-LAT	0.026	0.096	0.25	18	-0.37	24	42
BLK	0.051	0.087	0.26	151	-0.57	2	153
PDPK1	0.023	0.006	-10000	0	-10000	0	0
CYTH1	-0.011	0.037	0.32	4	-0.26	1	5
HCK	0.027	0.026	0.26	13	-10000	0	13
CYTH3	-0.012	0.039	0.33	3	-0.27	3	6
CYTH2	-0.011	0.039	0.32	4	-0.26	1	5
KRAS	0.024	0.007	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.009	0.053	0.31	1	-0.41	11	12
SGK1	0.005	0.076	-10000	0	-0.35	39	39
INPP5D	0.024	0.004	-10000	0	-10000	0	0
mol:GDP	0.017	0.06	0.24	4	-0.31	12	16
SOS1	0.024	0.003	-10000	0	-10000	0	0
SYK	0.024	0.003	-10000	0	-10000	0	0
ARF6/GDP	0.018	0.044	0.31	6	-10000	0	6
mol:PI-3-4-5-P3	-0.011	0.035	0.28	4	-0.27	1	5
ARAP3/RAP1A/GTP	-0.011	0.033	0.2	1	-0.28	1	2
VAV1	0.023	0.033	0.26	2	-0.57	3	5
mol:PI-3-4-P2	0.01	0.003	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.04	0.039	-10000	0	-0.28	1	1
PLEKHA1	-0.009	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.03	0.059	0.27	1	-0.33	8	9
LAT	0.025	0.038	0.26	15	-0.57	2	17
Rac1/GTP	0.016	0.051	-10000	0	-0.32	14	14
ITK	-0.018	0.062	0.32	4	-0.31	30	34
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.021	0.095	0.26	32	-0.33	15	47
LCK	0.026	0.075	0.26	40	-0.57	11	51
BTK	-0.011	0.039	0.32	4	-0.26	1	5

×

IFN-gamma pathway

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.069	0.051	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.023	0.006	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.055	0.046	0.33	5	-10000	0	5
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.048	0.02	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	0.014	0.042	-10000	0	-0.22	2	2
CaM/Ca2+	0.067	0.046	-10000	0	-10000	0	0
RAP1A	0.024	0.004	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.042	0.042	0.28	2	-10000	0	2
AKT1	0.01	0.064	0.29	11	-0.28	10	21
MAP2K1	0.007	0.045	0.29	4	-0.29	1	5
MAP3K11	0.023	0.042	0.29	4	-10000	0	4
IFNGR1	0.026	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.019	0.095	-10000	0	-0.39	11	11
Rap1/GTP	0.017	0.013	-10000	0	-10000	0	0
CRKL/C3G	0.033	0.01	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.076	0.054	-10000	0	-10000	0	0
CEBPB	0.028	0.094	0.32	2	-0.49	7	9
STAT3	0.024	0.005	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.075	0.094	-10000	0	-0.67	10	10
STAT1	0.026	0.047	0.29	6	-10000	0	6
CALM1	0.024	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.054	0.08	0.26	146	-10000	0	146
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/PIAS1	0.041	0.045	0.28	6	-10000	0	6
CEBPB/PTGES2/Cbp/p300	0.028	0.061	0.34	2	-0.33	4	6
mol:Ca2+	0.065	0.048	-10000	0	-10000	0	0
MAPK3	0.022	0.078	-10000	0	-0.56	12	12
STAT1 (dimer)	0.026	0.059	-10000	0	-0.29	1	1
MAPK1	-0.006	0.16	-10000	0	-0.67	58	58
JAK2	0.025	0.007	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
JAK1	0.026	0.006	-10000	0	-10000	0	0
CAMK2D	0.022	0.031	-10000	0	-0.57	3	3
DAPK1	0.027	0.069	0.29	3	-0.34	2	5
SMAD7	0.017	0.036	0.17	8	-10000	0	8
CBL/CRKL/C3G	0.045	0.038	0.29	4	-10000	0	4
PI3K	0.056	0.056	-10000	0	-0.29	12	12
IFNG	0.054	0.08	0.26	146	-10000	0	146
apoptosis	0.024	0.071	0.28	1	-0.4	10	11
CAMK2G	0.024	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	0.023	0.005	-10000	0	-10000	0	0
CAMK2A	0.032	0.042	0.26	36	-10000	0	36
CAMK2B	-0.004	0.15	0.26	44	-0.57	69	113
FRAP1	0.008	0.06	0.28	11	-0.26	10	21
PRKCD	0.011	0.067	0.3	13	-0.28	10	23
RAP1B	0.024	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	0.014	0.042	-10000	0	-0.22	2	2
PTPN2	0.024	0.005	-10000	0	-10000	0	0
EP300	0.023	0.006	-10000	0	-10000	0	0
IRF1	0.022	0.057	0.28	13	-0.32	1	14
STAT1 (dimer)/PIASy	0.038	0.046	0.27	6	-10000	0	6
SOCS1	0.016	0.11	-10000	0	-1	10	10
mol:GDP	0.041	0.036	0.27	4	-10000	0	4
CASP1	0.016	0.039	0.19	9	-0.24	3	12
PTGES2	0.024	0.008	0.26	1	-10000	0	1
IRF9	0.028	0.041	0.24	8	-10000	0	8
mol:PI-3-4-5-P3	0.041	0.047	-10000	0	-0.28	12	12
RAP1/GDP	0.035	0.022	-10000	0	-10000	0	0
CBL	0.021	0.04	0.29	4	-10000	0	4
MAP3K1	0.022	0.042	0.29	4	-0.3	1	5
PIAS1	0.024	0.004	-10000	0	-10000	0	0
PIAS4	0.024	0.004	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	0.014	0.042	-10000	0	-0.22	2	2
PTPN11	0.025	0.044	0.29	4	-10000	0	4
CREBBP	0.023	0.007	-10000	0	-10000	0	0
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

Figure S112. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S112. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.019	0.023	0.21	5	-0.3	1	6
CRKL	0.023	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.003	-10000	0	-10000	0	0
DOCK1	0.024	0.005	-10000	0	-10000	0	0
ITGA4	0.026	0.022	0.26	10	-10000	0	10
alpha4/beta7 Integrin/MAdCAM1	0.067	0.048	0.35	10	-0.33	2	12
EPO	0.059	0.085	0.26	169	-10000	0	169
alpha4/beta7 Integrin	0.041	0.039	0.36	4	-0.42	2	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.022	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.036	0.016	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.059	0.059	-10000	0	-10000	0	0
lamellipodium assembly	0.011	0.077	-10000	0	-0.42	23	23
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
PI3K	0.028	0.049	-10000	0	-0.38	14	14
ARF6	0.024	0.004	-10000	0	-10000	0	0
JAK2	0.033	0.03	-10000	0	-10000	0	0
PXN	0.024	0.002	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
MADCAM1	0.031	0.044	0.26	39	-10000	0	39
cell adhesion	0.064	0.047	0.34	10	-0.33	2	12
CRKL/CBL	0.032	0.012	-10000	0	-10000	0	0
ITGB1	0.024	0.004	-10000	0	-10000	0	0
SRC	0.013	0.043	-10000	0	-0.33	10	10
ITGB7	0.03	0.046	0.26	30	-0.57	2	32
RAC1	0.024	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.044	0.046	-10000	0	-0.36	11	11
p130Cas/Crk/Dock1	0.026	0.041	0.35	1	-0.28	9	10
VCAM1	0.019	0.062	0.26	6	-0.57	11	17
RHOA	0.024	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.057	0.023	-10000	0	-10000	0	0
BCAR1	-0.009	0.042	0.38	1	-0.3	10	11
EPOR	0.024	0.008	0.26	1	-10000	0	1
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.022	0.007	-10000	0	-10000	0	0
GIT1	0.023	0.006	-10000	0	-10000	0	0
Rac1/GTP	0.01	0.079	-10000	0	-0.43	23	23

×

HIV-1 Nef: Negative effector of Fas and TNF-alpha

Figure S113. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S113. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.018	0.032	-10000	0	-0.57	3	3
Caspase 8 (4 units)	0.038	0.062	-10000	0	-0.46	3	3
NEF	0.003	0.024	-10000	0	-0.18	11	11
NFKBIA	0.025	0.012	-10000	0	-10000	0	0
BIRC3	0.02	0.054	-10000	0	-0.5	5	5
CYCS	0.036	0.077	0.26	26	-0.29	12	38
RIPK1	0.024	0.005	-10000	0	-10000	0	0
CD247	0.017	0.086	0.29	16	-0.43	26	42
MAP2K7	0.041	0.13	0.37	2	-0.7	17	19
protein ubiquitination	0.015	0.082	0.31	5	-0.37	11	16
CRADD	0.024	0.003	-10000	0	-10000	0	0
DAXX	0.024	0.003	-10000	0	-10000	0	0
FAS	0.022	0.036	-10000	0	-0.57	4	4
BID	0.035	0.073	0.23	2	-0.29	16	18
NF-kappa-B/RelA/I kappa B alpha	0.05	0.033	-10000	0	-0.31	3	3
TRADD	0.022	0.008	-10000	0	-10000	0	0
MAP3K5	0.022	0.032	-10000	0	-0.57	3	3
CFLAR	0.024	0.018	-10000	0	-0.57	1	1
FADD	0.021	0.009	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.051	0.033	-10000	0	-0.31	3	3
MAPK8	0.038	0.12	0.4	5	-0.63	18	23
APAF1	0.024	0.003	-10000	0	-10000	0	0
TRAF1	0.025	0.013	0.26	3	-10000	0	3
TRAF2	0.025	0.015	0.26	4	-10000	0	4
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.024	0.059	0.23	4	-0.3	16	20
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.014	0.091	-10000	0	-0.42	18	18
CHUK	0.014	0.085	0.33	3	-0.4	11	14
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.054	0.041	-10000	0	-0.33	5	5
TCRz/NEF	0.016	0.08	0.31	9	-0.42	26	35
TNF	0.024	0.065	0.26	25	-0.57	9	34
FASLG	0.011	0.11	0.28	42	-0.57	26	68
NFKB1	0.025	0.011	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.036	0.051	-10000	0	-0.36	11	11
CASP6	0.052	0.1	0.38	1	-0.49	23	24
CASP7	0.04	0.1	0.38	6	-0.46	11	17
RELA	0.025	0.011	-10000	0	-10000	0	0
CASP2	0.024	0.004	-10000	0	-10000	0	0
CASP3	0.036	0.1	0.38	5	-0.47	10	15
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.029	-10000	0	-0.42	3	3
CASP8	0.024	0.003	-10000	0	-10000	0	0
CASP9	0.023	0.005	-10000	0	-10000	0	0
MAP3K14	0.016	0.087	0.29	1	-0.42	13	14
APAF-1/Caspase 9	0.032	0.061	0.25	5	-0.37	5	10
BCL2	0.031	0.12	0.42	6	-0.53	24	30

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

Figure S114. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S114. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.024	0.004	-10000	0	-10000	0	0
NFATC1	0.02	0.084	0.31	5	-0.43	11	16
NFATC2	-0.006	0.071	0.19	2	-0.26	35	37
NFATC3	0.014	0.016	-10000	0	-0.4	1	1
YWHAE	0.022	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.012	0.094	0.29	2	-0.38	28	30
Exportin 1/Ran/NUP214	0.047	0.011	-10000	0	-10000	0	0
mol:DAG	0	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.032	0.087	0.27	2	-0.44	11	13
BCL2/BAX	0.021	0.074	-10000	0	-0.41	28	28
CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.013	-10000	0	-10000	0	0
CaM/Ca2+	0.014	0.013	-10000	0	-10000	0	0
BAX	0.025	0.014	0.26	4	-10000	0	4
MAPK14	0.023	0.007	-10000	0	-10000	0	0
BAD	0.024	0.009	0.26	1	-10000	0	1
CABIN1/MEF2D	0.019	0.083	-10000	0	-0.4	16	16
Calcineurin A alpha-beta B1/BCL2	0.008	0.094	-10000	0	-0.56	28	28
FKBP8	0.024	0.004	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.019	0.082	0.4	16	-10000	0	16
KPNB1	0.023	0.006	-10000	0	-10000	0	0
KPNA2	0.036	0.056	0.26	64	-10000	0	64
XPO1	0.024	0.003	-10000	0	-10000	0	0
SFN	0.021	0.07	0.26	21	-0.57	12	33
MAP3K8	0.019	0.048	-10000	0	-0.57	7	7
NFAT4/CK1 alpha	0.018	0.028	-10000	0	-0.28	2	2
MEF2D/NFAT1/Cbp/p300	0.008	0.11	-10000	0	-0.3	66	66
CABIN1	0.012	0.093	0.29	2	-0.38	27	29
CALM1	0.02	0.013	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
MAP3K1	0.023	0.019	-10000	0	-0.57	1	1
CAMK4	0.031	0.046	0.26	37	-0.57	1	38
mol:Ca2+	-0.001	0.005	-10000	0	-10000	0	0
MAPK3	0.023	0.006	-10000	0	-10000	0	0
YWHAH	0.023	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.041	0.038	-10000	0	-0.42	1	1
YWHAB	0.023	0.005	-10000	0	-10000	0	0
MAPK8	0.018	0.051	-10000	0	-0.57	8	8
MAPK9	0.024	0.004	-10000	0	-10000	0	0
YWHAG	0.024	0.003	-10000	0	-10000	0	0
FKBP1A	0.024	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.021	0.096	0.28	2	-0.45	12	14
PRKCH	0.023	0.018	-10000	0	-0.57	1	1
CABIN1/Cbp/p300	0.027	0.023	-10000	0	-10000	0	0
CASP3	0.022	0.008	-10000	0	-10000	0	0
PIM1	0.024	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.009	-10000	0	-10000	0	0
apoptosis	0.011	0.034	-10000	0	-0.35	2	2
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.009	0.039	-10000	0	-0.28	4	4
PRKCB	0.019	0.076	0.26	19	-0.57	15	34
PRKCE	0.024	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	0.008	0.059	-10000	0	-0.37	1	1
BAD/BCL-XL	0.034	0.009	-10000	0	-10000	0	0
PRKCD	0.024	0.009	0.26	1	-10000	0	1
NUP214	0.024	0.004	-10000	0	-10000	0	0
PRKCZ	0.021	0.02	-10000	0	-0.57	1	1
PRKCA	0.01	0.084	0.26	1	-0.57	22	23
PRKCG	0.03	0.045	0.26	41	-10000	0	41
PRKCQ	0.004	0.11	0.26	8	-0.57	39	47
FKBP38/BCL2	0.021	0.074	-10000	0	-0.42	28	28
EP300	0.019	0.016	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.023	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.029	0.086	0.32	1	-0.42	10	11
CaM/Ca2+/FKBP38	0.027	0.017	-10000	0	-10000	0	0
FKBP12/FK506	0.018	0.003	-10000	0	-10000	0	0
CSNK1A1	0.009	0.013	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.032	0.034	-10000	0	-0.36	1	1
NFATc/ERK1	0.03	0.082	0.32	1	-0.41	10	11
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.039	0.093	0.28	1	-0.42	18	19
NR4A1	-0.013	0.17	-10000	0	-0.51	94	94
GSK3B	0.022	0.008	-10000	0	-10000	0	0
positive T cell selection	0.014	0.016	-10000	0	-0.4	1	1
NFAT1/CK1 alpha	-0.002	0.056	-10000	0	-0.26	12	12
RCH1/ KPNB1	0.041	0.04	-10000	0	-10000	0	0
YWHAQ	0.024	0.003	-10000	0	-10000	0	0
PRKACA	0.023	0.007	-10000	0	-10000	0	0
AKAP5	0.034	0.053	0.26	52	-0.57	1	53
MEF2D	0.017	0.015	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.019	0.01	-10000	0	-10000	0	0
NFATc/p38 alpha	0.031	0.082	0.32	1	-0.41	10	11
CREBBP	0.019	0.015	-10000	0	-10000	0	0
BCL2	0.008	0.094	-10000	0	-0.57	28	28

×

Signaling events mediated by VEGFR1 and VEGFR2

Figure S115. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S115. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.021	0.079	-10000	0	-0.42	33	33
AKT1	0.031	0.088	0.37	3	-0.56	8	11
PTK2B	0.003	0.084	0.35	1	-0.69	7	8
VEGFR2 homodimer/Frs2	0.024	0.063	-10000	0	-0.61	9	9
CAV1	-0.1	0.24	-10000	0	-0.57	225	225
CALM1	0.024	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.038	0.062	-10000	0	-0.57	9	9
endothelial cell proliferation	0.043	0.11	0.35	24	-0.56	9	33
mol:Ca2+	0.014	0.056	-10000	0	-0.5	9	9
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.05	0.062	-10000	0	-0.52	10	10
RP11-342D11.1	0.004	0.055	-10000	0	-0.5	10	10
CDH5	0.018	0.048	-10000	0	-0.57	7	7
VEGFA homodimer	0.05	0.028	-10000	0	-10000	0	0
SHC1	0.02	0.009	-10000	0	-10000	0	0
SHC2	0.011	0.086	0.26	1	-0.57	23	24
HRAS/GDP	0.03	0.049	-10000	0	-0.57	4	4
SH2D2A	0.04	0.072	0.26	95	-0.57	2	97
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.043	0.086	-10000	0	-0.54	10	10
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.045	0.074	-10000	0	-0.48	11	11
VEGFR1 homodimer	0.023	0.006	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.049	0.059	-10000	0	-0.64	4	4
GRB10	0.014	0.057	-10000	0	-0.63	6	6
PTPN11	0.024	0.002	-10000	0	-10000	0	0
GRB2	0.023	0.009	0.26	1	-10000	0	1
PAK1	0.023	0.019	0.26	6	-10000	0	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.05	0.075	-10000	0	-0.71	7	7
HRAS	0.026	0.022	0.26	9	-10000	0	9
VEGF/Rho/ROCK1/Integrin Complex	0.01	0.073	-10000	0	-0.48	11	11
HIF1A	0.024	0.004	-10000	0	-10000	0	0
FRS2	0.024	0.011	0.26	2	-10000	0	2
oxygen and reactive oxygen species metabolic process	0.048	0.061	-10000	0	-0.51	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.022	0.031	-10000	0	-0.57	3	3
Nck/Pak	0.033	0.017	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.036	0.066	-10000	0	-0.54	11	11
mol:GDP	0.039	0.054	-10000	0	-0.62	4	4
mol:NADP	0.025	0.083	0.56	1	-0.47	11	12
eNOS/Hsp90	0.036	0.08	0.54	1	-0.45	10	11
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
mol:IP3	0.014	0.056	-10000	0	-0.51	9	9
HIF1A/ARNT	0.029	0.015	-10000	0	-10000	0	0
SHB	0.024	0.008	0.26	1	-10000	0	1
VEGFA	0.026	0.019	0.26	7	-10000	0	7
VEGFC	0.023	0.005	-10000	0	-10000	0	0
FAK1/Vinculin	0.022	0.1	0.35	1	-0.68	9	10
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.039	0.095	-10000	0	-0.4	37	37
PTPN6	0.024	0.011	0.26	2	-10000	0	2
EPAS1	0.024	0.057	-10000	0	-0.53	10	10
mol:L-citrulline	0.025	0.083	0.56	1	-0.47	11	12
ITGAV	0.024	0.003	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.048	0.061	-10000	0	-0.52	9	9
VEGFR2 homodimer/VEGFA homodimer	0.041	0.062	-10000	0	-0.54	10	10
VEGFR2/3 heterodimer	0.023	0.07	-10000	0	-0.62	11	11
VEGFB	0.024	0.005	-10000	0	-10000	0	0
MAPK11	0.004	0.069	-10000	0	-0.66	7	7
VEGFR2 homodimer	0.011	0.069	-10000	0	-0.66	10	10
FLT1	0.023	0.006	-10000	0	-10000	0	0
NEDD4	0.025	0.005	-10000	0	-10000	0	0
MAPK3	0.006	0.073	0.26	5	-0.56	7	12
MAPK1	0.009	0.075	0.26	3	-0.57	7	10
VEGFA145/NRP2	0.035	0.025	-10000	0	-0.39	2	2
VEGFR1/2 heterodimer	0.023	0.065	-10000	0	-0.6	10	10
KDR	0.011	0.069	-10000	0	-0.66	10	10
VEGFA165/NRP1/VEGFR2 homodimer	0.041	0.064	-10000	0	-0.56	9	9
SRC	0.023	0.005	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.014	0.082	0.33	3	-0.52	9	12
PI3K	0.025	0.072	-10000	0	-0.73	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.039	0.062	-10000	0	-0.54	10	10
FES	0.013	0.061	-10000	0	-0.48	12	12
GAB1	0.014	0.062	-10000	0	-0.67	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.038	0.061	-10000	0	-0.53	10	10
CTNNB1	0.024	0.004	-10000	0	-10000	0	0
SOS1	0.024	0.003	-10000	0	-10000	0	0
ARNT	0.02	0.009	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.018	0.13	-10000	0	-0.53	18	18
VEGFR2 homodimer/VEGFA homodimer/Yes	0.037	0.063	-10000	0	-0.52	11	11
PI3K/GAB1	0.039	0.082	-10000	0	-0.55	8	8
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.053	0.063	-10000	0	-0.57	7	7
PRKACA	0.024	0.004	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.036	0.068	-10000	0	-0.57	11	11
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
CDC42	0.014	0.059	-10000	0	-0.54	9	9
actin cytoskeleton reorganization	0.045	0.074	-10000	0	-0.47	11	11
PTK2	0.005	0.088	-10000	0	-0.74	9	9
EDG1	0.004	0.055	-10000	0	-0.5	10	10
mol:DAG	0.014	0.056	-10000	0	-0.51	9	9
CaM/Ca2+	0.025	0.054	-10000	0	-0.57	6	6
MAP2K3	-0.006	0.061	-10000	0	-0.62	6	6
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.039	0.061	-10000	0	-0.66	6	6
PLCG1	0.014	0.057	-10000	0	-0.52	9	9
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.049	0.061	-10000	0	-0.5	10	10
IQGAP1	0.024	0.005	-10000	0	-10000	0	0
YES1	0.023	0.019	-10000	0	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.039	0.062	-10000	0	-0.54	10	10
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.039	0.062	-10000	0	-0.57	9	9
cell migration	0.024	0.093	0.33	1	-0.64	8	9
mol:PI-3-4-5-P3	0.025	0.067	-10000	0	-0.61	7	7
FYN	0.021	0.026	-10000	0	-0.57	2	2
VEGFB/NRP1	0.019	0.055	-10000	0	-0.52	8	8
mol:NO	0.025	0.083	0.56	1	-0.47	11	12
PXN	0.024	0.002	-10000	0	-10000	0	0
HRAS/GTP	0.017	0.044	-10000	0	-0.57	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.032	0.059	-10000	0	-0.66	6	6
VHL	0.024	0.004	-10000	0	-10000	0	0
ITGB3	0.006	0.1	0.26	4	-0.57	33	37
NOS3	0.025	0.09	0.57	1	-0.54	11	12
VEGFR2 homodimer/VEGFA homodimer/Sck	0.03	0.081	-10000	0	-0.4	31	31
RAC1	0.024	0.003	-10000	0	-10000	0	0
PRKCA	-0.009	0.073	0.35	1	-0.4	21	22
PRKCB	-0.006	0.067	-10000	0	-0.44	14	14
VCL	0.024	0.004	-10000	0	-10000	0	0
VEGFA165/NRP1	0.022	0.057	-10000	0	-0.5	10	10
VEGFR1/2 heterodimer/VEGFA homodimer	0.037	0.064	-10000	0	-0.55	10	10
VEGFA165/NRP2	0.035	0.025	-10000	0	-0.39	2	2
MAPKKK cascade	0.05	0.079	0.33	11	-0.58	4	15
NRP2	0.023	0.027	0.26	1	-0.57	2	3
VEGFC homodimer	0.023	0.005	-10000	0	-10000	0	0
NCK1	0.024	0.003	-10000	0	-10000	0	0
ROCK1	0.023	0.018	-10000	0	-0.57	1	1
FAK1/Paxillin	0.022	0.1	0.42	2	-0.65	10	12
MAP3K13	0.012	0.061	-10000	0	-0.45	14	14
PDPK1	0.014	0.06	0.27	1	-0.58	5	6

×

E-cadherin signaling events

Figure S116. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S116. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.033	0.057	-9999	-0.36	18	18
E-cadherin/beta catenin	0.022	0.062	-9999	-0.42	18	18
CTNNB1	0.024	0.004	-9999	-10000	0	0
JUP	0.023	0.005	-9999	-10000	0	0
CDH1	0.012	0.076	-9999	-0.57	18	18

×

Signaling events mediated by HDAC Class II

Figure S117. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S117. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.049	0.045	-10000	0	-0.33	11	11
HDAC3	0.024	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.009	0.008	-10000	0	-0.28	1	1
GATA1/HDAC4	0.036	0.025	-10000	0	-0.42	1	1
GATA1/HDAC5	0.036	0.022	-10000	0	-10000	0	0
GATA2/HDAC5	0.025	0.072	-10000	0	-0.42	26	26
HDAC5/BCL6/BCoR	0.043	0.037	-10000	0	-0.36	8	8
HDAC9	0.021	0.061	0.26	10	-0.57	10	20
Glucocorticoid receptor/Hsp90/HDAC6	0.043	0.043	-10000	0	-0.36	11	11
HDAC4/ANKRA2	0.034	0.016	-10000	0	-0.42	1	1
HDAC5/YWHAB	0.033	0.01	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.011	0.004	-10000	0	-10000	0	0
GATA2	0.013	0.095	0.26	13	-0.57	26	39
HDAC4/RFXANK	0.035	0.018	-10000	0	-0.42	1	1
BCOR	0.023	0.026	-10000	0	-0.57	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.023	0.012	0.26	2	-10000	0	2
HDAC5	0.024	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.028	0.05	-10000	0	-0.4	14	14
Histones	0.016	0.049	-10000	0	-0.32	9	9
ADRBK1	0.023	0.006	-10000	0	-10000	0	0
HDAC4	0.023	0.018	-10000	0	-0.57	1	1
XPO1	0.024	0.003	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.034	0.009	-10000	0	-10000	0	0
HDAC4/Ubc9	0.032	0.018	-10000	0	-0.42	1	1
HDAC7	0.024	0.002	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.033	0.011	-10000	0	-10000	0	0
TUBA1B	0.024	0.002	-10000	0	-10000	0	0
HDAC6	0.024	0.002	-10000	0	-10000	0	0
HDAC5/RFXANK	0.035	0.012	-10000	0	-10000	0	0
CAMK4	0.031	0.046	0.26	37	-0.57	1	38
Tubulin/HDAC6	0.047	0.018	-10000	0	-0.36	1	1
SUMO1	0.024	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.023	0.005	-10000	0	-10000	0	0
GATA1	0.026	0.029	0.26	17	-10000	0	17
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.022	0.007	-10000	0	-10000	0	0
NR3C1	0.018	0.06	-10000	0	-0.57	11	11
SUMO1/HDAC4	0.035	0.039	-10000	0	-0.24	4	4
SRF	0.024	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.033	0.017	-10000	0	-0.42	1	1
Tubulin	0.034	0.017	-10000	0	-0.42	1	1
HDAC4/14-3-3 E	0.032	0.018	-10000	0	-0.42	1	1
GNB1	0.023	0.005	-10000	0	-10000	0	0
RANGAP1	0.023	0.006	-10000	0	-10000	0	0
BCL6/BCoR	0.031	0.04	-10000	0	-0.42	8	8
HDAC4/HDAC3/SMRT (N-CoR2)	0.046	0.017	-10000	0	-0.36	1	1
HDAC4/SRF	0.05	0.034	-10000	0	-0.36	2	2
HDAC4/ER alpha	-0.015	0.17	-10000	0	-0.41	155	155
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.016	0.049	-10000	0	-0.32	9	9
cell motility	0.046	0.018	-10000	0	-0.36	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.023	0.006	-10000	0	-10000	0	0
HDAC7/HDAC3	0.035	0.006	-10000	0	-10000	0	0
BCL6	0.02	0.044	-10000	0	-0.57	6	6
HDAC4/CaMK II delta B	0.023	0.018	-10000	0	-0.56	1	1
Hsp90/HDAC6	0.035	0.007	-10000	0	-10000	0	0
ESR1	-0.035	0.23	0.26	116	-0.57	151	267
HDAC6/HDAC11	0.036	0.009	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.035	0.038	-10000	0	-0.24	4	4
NPC	0.014	0.002	-10000	0	-10000	0	0
MEF2C	0.023	0.026	-10000	0	-0.57	2	2
RAN	0.024	0.003	-10000	0	-10000	0	0
HDAC4/MEF2C	0.062	0.03	-10000	0	-0.31	2	2
GNG2	0.017	0.065	-10000	0	-0.57	13	13
NCOR2	0.024	0.003	-10000	0	-10000	0	0
TUBB2A	0.023	0.021	0.26	2	-0.57	1	3
HDAC11	0.024	0.011	0.26	2	-10000	0	2
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
RANBP2	0.024	0.003	-10000	0	-10000	0	0
ANKRA2	0.024	0.005	-10000	0	-10000	0	0
RFXANK	0.025	0.013	0.26	3	-10000	0	3
nuclear import	-0.027	0.016	0.33	1	-10000	0	1

×

a4b1 and a4b7 Integrin signaling

Figure S118. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S118. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.024	0.004	-10000	0	-10000	0	0
ITGB7	0.03	0.046	0.26	30	-0.57	2	32
ITGA4	0.026	0.022	0.26	10	-10000	0	10
alpha4/beta7 Integrin	0.041	0.039	0.36	4	-0.42	2	6
alpha4/beta1 Integrin	0.036	0.016	-10000	0	-10000	0	0

×

EPO signaling pathway

Figure S119. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S119. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.051	0.081	-10000	0	-0.48	1	1
CRKL	0.025	0.047	0.31	6	-10000	0	6
mol:DAG	0.038	0.051	-10000	0	-10000	0	0
HRAS	0.034	0.078	0.31	18	-10000	0	18
MAPK8	0.04	0.07	0.25	28	-0.34	5	33
RAP1A	0.027	0.048	0.3	8	-10000	0	8
GAB1	0.026	0.046	0.32	5	-10000	0	5
MAPK14	0.042	0.065	0.25	28	-10000	0	28
EPO	0.061	0.085	0.26	169	-10000	0	169
PLCG1	0.038	0.051	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.026	0.013	0.26	1	-10000	0	1
RAPGEF1	0.024	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.063	0.061	-10000	0	-0.35	5	5
GAB1/SHC/GRB2/SOS1	0.042	0.041	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.06	0.059	-10000	0	-10000	0	0
IRS2	0.014	0.071	0.31	5	-0.3	26	31
STAT1	0.044	0.064	0.32	3	-10000	0	3
STAT5B	0.04	0.058	-10000	0	-0.34	1	1
cell proliferation	0.022	0.075	0.24	30	-0.32	5	35
GAB1/SHIP/PIK3R1/SHP2/SHC	0.032	0.044	-10000	0	-0.33	1	1
TEC	0.025	0.047	0.29	5	-0.3	1	6
SOCS3	0.02	0.041	-10000	0	-0.57	5	5
STAT1 (dimer)	0.044	0.063	0.32	3	-10000	0	3
JAK2	0.025	0.01	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
EPO/EPOR (dimer)/JAK2	0.08	0.062	0.33	3	-10000	0	3
EPO/EPOR	0.06	0.059	-10000	0	-10000	0	0
LYN	0.021	0.012	-10000	0	-10000	0	0
TEC/VAV2	0.039	0.046	0.28	3	-0.29	1	4
elevation of cytosolic calcium ion concentration	0.026	0.013	0.26	1	-10000	0	1
SHC1	0.02	0.009	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.061	0.054	-10000	0	-10000	0	0
mol:IP3	0.038	0.051	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.03	0.079	0.29	2	-0.3	32	34
SH2B3	0.026	0.009	-10000	0	-10000	0	0
NFKB1	0.042	0.066	0.25	28	-10000	0	28
EPO/EPOR (dimer)/JAK2/SOCS3	0.025	0.042	-10000	0	-0.27	2	2
PTPN6	0.023	0.039	0.28	3	-10000	0	3
TEC/VAV2/GRB2	0.047	0.048	0.28	3	-0.28	1	4
EPOR	0.026	0.013	0.26	1	-10000	0	1
INPP5D	0.024	0.004	-10000	0	-10000	0	0
mol:GDP	0.041	0.041	-10000	0	-10000	0	0
SOS1	0.024	0.003	-10000	0	-10000	0	0
PLCG2	0.02	0.028	0.26	1	-0.57	2	3
CRKL/CBL/C3G	0.046	0.047	0.28	4	-10000	0	4
VAV2	0.027	0.048	0.3	8	-10000	0	8
CBL	0.025	0.047	0.31	6	-10000	0	6
SHC/Grb2/SOS1	0.036	0.037	-10000	0	-10000	0	0
STAT5A	0.038	0.063	-10000	0	-0.33	6	6
GRB2	0.023	0.009	0.26	1	-10000	0	1
STAT5 (dimer)	0.051	0.079	0.34	1	-0.43	2	3
LYN/PLCgamma2	0.027	0.026	-10000	0	-0.42	2	2
PTPN11	0.024	0.002	-10000	0	-10000	0	0
BTK	0.027	0.048	0.3	8	-10000	0	8
BCL2	0.031	0.17	-10000	0	-0.83	35	35

×

Insulin-mediated glucose transport

Figure S120. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S120. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.1	0.15	-10000	0	-0.41	67	67
CaM/Ca2+	0.018	0.003	-10000	0	-10000	0	0
AKT1	0.024	0.004	-10000	0	-10000	0	0
AKT2	0.024	0.004	-10000	0	-10000	0	0
STXBP4	0.022	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.11	0.15	0.4	1	-0.42	74	75
YWHAZ	0.019	0.01	-10000	0	-10000	0	0
CALM1	0.024	0.004	-10000	0	-10000	0	0
YWHAQ	0.024	0.003	-10000	0	-10000	0	0
TBC1D4	0.008	0.026	-10000	0	-0.42	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.023	0.006	-10000	0	-10000	0	0
YWHAB	0.023	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.039	0.02	-10000	0	-10000	0	0
YWHAG	0.024	0.003	-10000	0	-10000	0	0
ASIP	0.024	0.024	0.26	11	-10000	0	11
PRKCI	0.024	0.005	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.018	0.003	-10000	0	-10000	0	0
RHOQ	0.024	0.003	-10000	0	-10000	0	0
GYS1	0.01	0.016	0.24	5	-10000	0	5
PRKCZ	0.023	0.019	-10000	0	-0.57	1	1
TRIP10	0.024	0.003	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.032	0.006	-10000	0	-10000	0	0
AS160/14-3-3	0.019	0.063	0.26	1	-0.3	17	18
VAMP2	0.022	0.007	-10000	0	-10000	0	0
SLC2A4	-0.12	0.16	0.41	1	-0.47	74	75
STX4	0.023	0.006	-10000	0	-10000	0	0
GSK3B	0.018	0.005	-10000	0	-10000	0	0
SFN	0.021	0.07	0.26	21	-0.57	12	33
LNPEP	0.019	0.051	-10000	0	-0.57	8	8
YWHAE	0.022	0.007	-10000	0	-10000	0	0

×

Canonical NF-kappaB pathway

Figure S121. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S121. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.025	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.033	0.11	0.29	13	-0.32	27	40
ERC1	0.023	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.03	0.034	0.36	1	-0.42	1	2
NFKBIA	0.012	0.025	-10000	0	-10000	0	0
BIRC2	0.022	0.007	-10000	0	-10000	0	0
IKBKB	0.02	0.009	-10000	0	-10000	0	0
RIPK2	0.02	0.016	0.26	3	-10000	0	3
IKBKG	0.019	0.03	-10000	0	-10000	0	0
IKK complex/A20	0.021	0.12	-10000	0	-0.42	30	30
NEMO/A20/RIP2	0.02	0.016	0.26	3	-10000	0	3
XPO1	0.024	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.014	0.12	-10000	0	-0.4	49	49
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.032	0.005	-10000	0	-10000	0	0
IKK complex/ELKS	0.012	0.11	-10000	0	-0.41	31	31
BCL10/MALT1/TRAF6	0.045	0.014	-10000	0	-10000	0	0
NOD2	0.028	0.043	0.26	30	-0.57	1	31
NFKB1	0.025	0.004	-10000	0	-10000	0	0
RELA	0.025	0.005	-10000	0	-10000	0	0
MALT1	0.023	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.032	0.012	-10000	0	-10000	0	0
ATM	0.022	0.008	-10000	0	-10000	0	0
TNF/TNFR1A	0.034	0.049	-10000	0	-0.42	9	9
TRAF6	0.024	0.004	-10000	0	-10000	0	0
PRKCA	0.01	0.084	0.26	1	-0.57	22	23
CHUK	0.024	0.003	-10000	0	-10000	0	0
UBE2D3	0.024	0.004	-10000	0	-10000	0	0
TNF	0.024	0.065	0.26	25	-0.57	9	34
NF kappa B1 p50/RelA	0.051	0.016	-10000	0	-10000	0	0
BCL10	0.024	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.012	0.025	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.025	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
IKK complex	0.015	0.12	-10000	0	-0.4	45	45
CYLD	0.022	0.008	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.013	0.13	-10000	0	-0.42	49	49

×

VEGFR1 specific signals

Figure S122. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S122. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.026	0.018	-10000	0	-0.46	1	1
VEGFR1 homodimer/NRP1	0.01	0.015	-10000	0	-0.48	1	1
mol:DAG	0.013	0.03	-10000	0	-0.38	2	2
VEGFR1 homodimer/NRP1/VEGFR 121	0.024	0.02	-10000	0	-0.44	1	1
CaM/Ca2+	0.026	0.029	-10000	0	-0.36	2	2
HIF1A	0.028	0.011	-10000	0	-0.31	1	1
GAB1	0.024	0.004	-10000	0	-10000	0	0
AKT1	0.009	0.051	-10000	0	-0.42	1	1
PLCG1	0.013	0.03	-10000	0	-0.38	2	2
NOS3	0.016	0.052	-10000	0	-0.52	2	2
CBL	0.022	0.007	-10000	0	-10000	0	0
mol:NO	0.02	0.061	0.29	2	-0.45	5	7
FLT1	0.013	0.018	-10000	0	-0.55	1	1
PGF	0.024	0.024	0.26	5	-0.57	1	6
VEGFR1 homodimer/NRP2/VEGFR121	0.038	0.03	-10000	0	-0.44	2	2
CALM1	0.024	0.004	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
eNOS/Hsp90	0.032	0.063	-10000	0	-0.43	6	6
endothelial cell proliferation	0.011	0.081	0.33	6	-0.6	4	10
mol:Ca2+	0.013	0.03	-10000	0	-0.38	2	2
MAPK3	-0.012	0.049	-10000	0	-0.32	19	19
MAPK1	-0.012	0.048	-10000	0	-0.32	17	17
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
PLGF homodimer	0.024	0.024	0.26	5	-0.56	1	6
PRKACA	0.024	0.004	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.1	0.24	-10000	0	-0.57	225	225
VEGFA homodimer	0.025	0.019	0.26	7	-10000	0	7
VEGFR1 homodimer/VEGFA homodimer	0.027	0.022	-10000	0	-0.48	1	1
platelet activating factor biosynthetic process	-0.013	0.046	-10000	0	-0.63	1	1
PI3K	0.044	0.048	-10000	0	-0.32	14	14
PRKCA	-0.011	0.052	0.24	1	-0.33	20	21
PRKCB	-0.009	0.048	-10000	0	-0.35	11	11
VEGFR1 homodimer/PLGF homodimer	0.027	0.024	-10000	0	-0.42	2	2
VEGFA	0.025	0.019	0.26	7	-10000	0	7
VEGFB	0.024	0.005	-10000	0	-10000	0	0
mol:IP3	0.013	0.03	-10000	0	-0.38	2	2
RASA1	0.013	0.028	-10000	0	-0.43	1	1
NRP2	0.023	0.027	0.26	1	-0.57	2	3
VEGFR1 homodimer	0.013	0.018	-10000	0	-0.55	1	1
VEGFB homodimer	0.023	0.005	-10000	0	-10000	0	0
NCK1	0.024	0.003	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.029	0.14	-10000	0	-0.44	25	25
PTPN11	0.024	0.002	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.042	0.047	-10000	0	-0.32	14	14
mol:L-citrulline	0.02	0.061	0.29	2	-0.45	5	7
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.047	0.028	-10000	0	-0.41	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.038	0.023	-10000	0	-0.45	1	1
CD2AP	0.024	0.004	-10000	0	-10000	0	0
PI3K/GAB1	0.052	0.05	-10000	0	-0.31	14	14
PDPK1	-0.004	0.053	-10000	0	-0.4	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.039	0.023	-10000	0	-0.45	1	1
mol:NADP	0.02	0.061	0.29	2	-0.45	5	7
HSP90AA1	0.024	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.046	0.027	-10000	0	-0.4	1	1
VEGFR1 homodimer/NRP2	0.025	0.027	-10000	0	-0.44	3	3

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

Figure S123. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S123. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.023	0.005	-10000	0	-10000	0	0
SMAD2	-0.004	0.039	0.21	1	-0.31	3	4
SMAD3	0.022	0.025	-10000	0	-10000	0	0
SMAD3/SMAD4	0.036	0.063	-10000	0	-0.44	11	11
SMAD4/Ubc9/PIASy	0.043	0.018	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.041	0.058	-10000	0	-10000	0	0
PPM1A	0.024	0.004	-10000	0	-10000	0	0
CALM1	0.024	0.004	-10000	0	-10000	0	0
SMAD2/SMAD4	0.008	0.045	-10000	0	-0.28	7	7
MAP3K1	0.023	0.019	-10000	0	-0.57	1	1
TRAP-1/SMAD4	0.027	0.056	-10000	0	-0.42	16	16
MAPK3	0.023	0.006	-10000	0	-10000	0	0
MAPK1	0.023	0.006	-10000	0	-10000	0	0
NUP214	0.024	0.004	-10000	0	-10000	0	0
CTDSP1	0.024	0.003	-10000	0	-10000	0	0
CTDSP2	0.024	0.003	-10000	0	-10000	0	0
CTDSPL	0.024	0.004	-10000	0	-10000	0	0
KPNB1	0.023	0.006	-10000	0	-10000	0	0
TGFBRAP1	0.015	0.072	-10000	0	-0.57	16	16
UBE2I	0.023	0.006	-10000	0	-10000	0	0
NUP153	0.024	0.005	-10000	0	-10000	0	0
KPNA2	0.036	0.056	0.26	64	-10000	0	64
PIAS4	0.024	0.004	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

Figure S124. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S124. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	0.05	0.061	-10000	0	-0.37	8	8
Ran/GTP/Exportin 1/HDAC1	-0.009	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.031	0.061	-10000	0	-0.35	7	7
SUMO1	0.024	0.003	-10000	0	-10000	0	0
ZFPM1	0.023	0.021	0.26	7	-10000	0	7
NPC/RanGAP1/SUMO1/Ubc9	0.011	0.004	-10000	0	-10000	0	0
FKBP3	0.024	0.004	-10000	0	-10000	0	0
Histones	0.053	0.041	-10000	0	-0.4	1	1
YY1/LSF	0.024	0.049	-10000	0	-0.3	7	7
SMG5	0.021	0.009	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.021	0.03	-10000	0	-0.3	7	7
I kappa B alpha/HDAC1	0.03	0.036	-10000	0	-0.42	1	1
SAP18	0.023	0.006	-10000	0	-10000	0	0
RELA	0.019	0.036	-10000	0	-0.3	7	7
HDAC1/Smad7	0.046	0.014	-10000	0	-10000	0	0
RANGAP1	0.023	0.006	-10000	0	-10000	0	0
HDAC3/TR2	0.031	0.036	-10000	0	-0.43	1	1
NuRD/MBD3 Complex	0.025	0.052	-10000	0	-0.39	3	3
NF kappa B1 p50/RelA	0.026	0.064	0.38	1	-0.38	4	5
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.013	0.095	0.26	13	-0.57	26	39
GATA1	0.026	0.029	0.26	17	-10000	0	17
Mad/Max	0.035	0.009	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.017	0.079	-10000	0	-0.36	20	20
RBBP7	0.026	0.019	0.26	7	-10000	0	7
NPC	0.014	0.002	-10000	0	-10000	0	0
RBBP4	0.023	0.018	-10000	0	-0.57	1	1
MAX	0.024	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.024	0.004	-10000	0	-10000	0	0
NFKBIA	0.018	0.026	-10000	0	-0.47	1	1
KAT2B	0.024	0.018	-10000	0	-0.57	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.018	0.029	-10000	0	-0.36	1	1
SIN3 complex	0.056	0.022	-10000	0	-10000	0	0
SMURF1	0.024	0.004	-10000	0	-10000	0	0
CHD3	0.022	0.007	-10000	0	-10000	0	0
SAP30	0.024	0.015	0.26	4	-10000	0	4
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.022	0.007	-10000	0	-10000	0	0
YY1/HDAC3	0.022	0.046	-10000	0	-0.38	3	3
YY1/HDAC2	0.024	0.045	-10000	0	-0.29	5	5
YY1/HDAC1	0.025	0.047	-10000	0	-0.24	13	13
NuRD/MBD2 Complex (MeCP1)	0.024	0.054	-10000	0	-0.27	13	13
PPARG	-0.06	0.16	-10000	0	-0.34	225	225
HDAC8/hEST1B	0.041	0.019	-10000	0	-10000	0	0
UBE2I	0.023	0.006	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.024	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.023	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.031	0.036	-10000	0	-0.43	1	1
MBD3L2	0.017	0.011	0.26	2	-10000	0	2
ubiquitin-dependent protein catabolic process	0.045	0.014	-10000	0	-10000	0	0
CREBBP	0.023	0.007	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.023	0.066	-10000	0	-0.35	14	14
HDAC1	0.024	0.004	-10000	0	-10000	0	0
HDAC3	0.019	0.027	-10000	0	-0.48	1	1
HDAC2	0.023	0.006	-10000	0	-10000	0	0
YY1	0.015	0.011	-10000	0	-0.29	1	1
HDAC8	0.024	0.001	-10000	0	-10000	0	0
SMAD7	0.023	0.005	-10000	0	-10000	0	0
NCOR2	0.024	0.003	-10000	0	-10000	0	0
MXD1	0.024	0.007	0.26	1	-10000	0	1
STAT3	0.016	0.007	-10000	0	-10000	0	0
NFKB1	0.024	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.024	0.003	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.036	0.048	-10000	0	-0.27	6	6
YY1/SAP30/HDAC1	0.036	0.047	-10000	0	-0.25	6	6
EP300	0.023	0.006	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.016	0.007	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.026	-10000	0	-0.47	1	1
histone deacetylation	0.024	0.053	-10000	0	-0.4	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.019	0.035	-10000	0	-0.41	1	1
nuclear export	-0.041	0.019	-10000	0	-10000	0	0
PRKACA	0.024	0.004	-10000	0	-10000	0	0
GATAD2B	0.02	0.009	-10000	0	-10000	0	0
GATAD2A	0.024	0.003	-10000	0	-10000	0	0
GATA2/HDAC3	0.025	0.065	-10000	0	-0.33	23	23
GATA1/HDAC1	0.036	0.02	-10000	0	-10000	0	0
GATA1/HDAC3	0.032	0.041	-10000	0	-0.45	1	1
CHD4	0.023	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.034	0.049	-10000	0	-0.42	9	9
SIN3/HDAC complex/Mad/Max	0.016	0.053	-10000	0	-0.29	18	18
NuRD Complex	0.025	0.065	-10000	0	-0.38	9	9
positive regulation of chromatin silencing	0.05	0.039	-10000	0	-0.39	1	1
SIN3B	0.024	0.004	-10000	0	-10000	0	0
MTA2	0.024	0.005	-10000	0	-10000	0	0
SIN3A	0.024	0.004	-10000	0	-10000	0	0
XPO1	0.024	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.035	0.038	-10000	0	-0.23	4	4
HDAC complex	0.057	0.022	-10000	0	-10000	0	0
GATA1/Fog1	0.033	0.025	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.044	0.015	-10000	0	-10000	0	0
TNF	0.024	0.065	0.26	25	-0.57	9	34
negative regulation of cell growth	0.016	0.053	-10000	0	-0.29	18	18
NuRD/MBD2/PRMT5 Complex	0.024	0.054	-10000	0	-0.27	13	13
Ran/GTP/Exportin 1	0.035	0.038	-10000	0	-0.24	4	4
NF kappa B/RelA/I kappa B alpha	0.018	0.052	-10000	0	-0.35	8	8
SIN3/HDAC complex/NCoR1	0.007	0.066	-10000	0	-0.32	28	28
TFCP2	0.024	0.018	-10000	0	-0.57	1	1
NR2C1	0.024	0.003	-10000	0	-10000	0	0
MBD3	0.024	0.009	0.26	1	-10000	0	1
MBD2	0.023	0.005	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

Figure S125. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S125. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.034	0.011	-10000	0	-10000	0	0
FBXW11	0.024	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.018	0.037	-10000	0	-0.36	8	8
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.043	-10000	0	-0.33	2	2
NFKBIA	0.014	0.037	-10000	0	-0.25	11	11
MAPK14	0.024	0.003	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.021	0.01	-10000	0	-10000	0	0
ARRB2	0.011	0.004	-10000	0	-10000	0	0
REL	0.017	0.067	-10000	0	-0.57	14	14
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.022	0.013	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.021	0.011	-10000	0	-10000	0	0
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
NF kappa B1 p50 dimer	0.016	0.012	0.25	2	-10000	0	2
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
NFKB1	0.01	0.011	0.26	2	-10000	0	2
RELA	0.023	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.024	0.046	-10000	0	-0.26	10	10
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.025	0.046	-10000	0	-0.33	3	3
SRC	0.023	0.005	-10000	0	-10000	0	0
PI3K	0.028	0.049	-10000	0	-0.38	14	14
NF kappa B1 p50/RelA	0.024	0.046	-10000	0	-0.26	10	10
IKBKB	0.02	0.009	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.024	0.004	-10000	0	-10000	0	0
SYK	0.024	0.003	-10000	0	-10000	0	0
I kappa B alpha/PIK3R1	0.023	0.057	-10000	0	-0.26	26	26
cell death	0.024	0.044	-10000	0	-0.32	3	3
NF kappa B1 p105/c-Rel	0.018	0.037	-10000	0	-0.36	8	8
LCK	0.026	0.075	0.26	40	-0.57	11	51
BCL3	0.024	0.011	0.26	2	-10000	0	2

×

Circadian rhythm pathway

Figure S126. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S126. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.041	0.035	-10000	0	-10000	0	0
CLOCK	0.02	0.06	-10000	0	-0.56	11	11
TIMELESS/CRY2	0.031	0.026	-10000	0	-10000	0	0
DEC1/BMAL1	0.033	0.014	-10000	0	-10000	0	0
ATR	0.024	0.004	-10000	0	-10000	0	0
NR1D1	0.015	0.017	-10000	0	-10000	0	0
ARNTL	0.026	0.004	-10000	0	-10000	0	0
TIMELESS	0.018	0.024	-10000	0	-10000	0	0
NPAS2	0.023	0.041	0.26	1	-0.56	5	6
CRY2	0.024	0.003	-10000	0	-10000	0	0
mol:CO	-0.007	0.006	-10000	0	-0.09	6	6
CHEK1	0.027	0.035	0.26	23	-10000	0	23
mol:HEME	0.007	0.006	0.09	6	-10000	0	6
PER1	0.013	0.072	-10000	0	-0.57	16	16
BMAL/CLOCK/NPAS2	0.049	0.052	-10000	0	-0.36	16	16
BMAL1/CLOCK	0.019	0.062	-10000	0	-0.48	1	1
S phase of mitotic cell cycle	0.041	0.035	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.042	0.036	-10000	0	-10000	0	0
mol:NADPH	0.007	0.006	0.09	6	-10000	0	6
PER1/TIMELESS	0.024	0.046	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.019	0.018	0.26	6	-10000	0	6

×

Paxillin-dependent events mediated by a4b1

Figure S127. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S127. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.023	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.022	0.009	-10000	0	-10000	0	0
DOCK1	0.024	0.005	-10000	0	-10000	0	0
ITGA4	0.026	0.022	0.26	10	-10000	0	10
RAC1	0.024	0.003	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.041	0.039	0.36	4	-0.42	2	6
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.022	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.048	0.017	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.043	0.035	0.33	4	-0.33	2	6
lamellipodium assembly	-0.003	0.088	-10000	0	-0.41	34	34
PIK3CA	0.023	0.005	-10000	0	-10000	0	0
PI3K	0.028	0.049	-10000	0	-0.38	14	14
ARF6	0.024	0.004	-10000	0	-10000	0	0
TLN1	0.024	0.004	-10000	0	-10000	0	0
PXN	0.011	0.002	-10000	0	-10000	0	0
PIK3R1	0.016	0.065	-10000	0	-0.57	13	13
ARF6/GTP	0.047	0.02	-10000	0	-10000	0	0
cell adhesion	0.05	0.019	-10000	0	-10000	0	0
CRKL/CBL	0.032	0.012	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.04	0.016	-10000	0	-10000	0	0
ITGB1	0.024	0.004	-10000	0	-10000	0	0
ITGB7	0.03	0.046	0.26	30	-0.57	2	32
ARF6/GDP	0.022	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.048	0.043	-10000	0	-0.31	11	11
p130Cas/Crk/Dock1	0.041	0.019	-10000	0	-10000	0	0
VCAM1	0.019	0.062	0.26	6	-0.57	11	17
alpha4/beta1 Integrin/Paxillin/Talin	0.051	0.019	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.049	0.021	-10000	0	-10000	0	0
BCAR1	0.021	0.008	-10000	0	-10000	0	0
mol:GDP	-0.047	0.021	-10000	0	-10000	0	0
CBL	0.022	0.007	-10000	0	-10000	0	0
PRKACA	0.024	0.004	-10000	0	-10000	0	0
GIT1	0.023	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.051	0.019	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.097	-10000	0	-0.46	34	34

×

Arf6 downstream pathway

Figure S128. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S128. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.04	0.069	0.35	3	-10000	0	3
regulation of axonogenesis	-0.011	0.026	0.24	4	-10000	0	4
myoblast fusion	-0.026	0.047	-10000	0	-0.22	1	1
mol:GTP	0.023	0.031	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.055	0.044	-10000	0	-0.3	2	2
ARF1/GTP	0.03	0.028	-10000	0	-10000	0	0
mol:GM1	0.012	0.024	-10000	0	-10000	0	0
mol:Choline	0.008	0.038	-10000	0	-0.34	9	9
lamellipodium assembly	0.018	0.058	-10000	0	-0.36	7	7
MAPK3	0.032	0.045	0.2	5	-10000	0	5
ARF6/GTP/NME1/Tiam1	0.056	0.045	0.31	2	-10000	0	2
ARF1	0.02	0.009	-10000	0	-10000	0	0
ARF6/GDP	0.026	0.047	0.22	1	-10000	0	1
ARF1/GDP	0.025	0.047	-10000	0	-0.26	2	2
ARF6	0.032	0.017	-10000	0	-10000	0	0
RAB11A	0.024	0.004	-10000	0	-10000	0	0
TIAM1	0.027	0.015	0.25	4	-10000	0	4
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.032	0.044	0.2	9	-10000	0	9
actin filament bundle formation	-0.032	0.05	0.25	4	-10000	0	4
KALRN	0.01	0.054	-10000	0	-0.31	20	20
RAB11FIP3/RAB11A	0.033	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.033	0.05	-10000	0	-0.25	4	4
NME1	0.028	0.031	0.26	18	-10000	0	18
Rac1/GDP	0.033	0.051	-10000	0	-0.25	4	4
substrate adhesion-dependent cell spreading	0.023	0.031	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.018	0.058	-10000	0	-0.37	7	7
RAC1	0.024	0.003	-10000	0	-10000	0	0
liver development	0.023	0.031	-10000	0	-10000	0	0
ARF6/GTP	0.023	0.031	-10000	0	-10000	0	0
RhoA/GTP	0.034	0.028	-10000	0	-10000	0	0
mol:GDP	0.02	0.047	0.21	2	-0.21	5	7
ARF6/GTP/RAB11FIP3/RAB11A	0.046	0.029	-10000	0	-10000	0	0
RHOA	0.024	0.005	-10000	0	-10000	0	0
PLD1	0.017	0.045	-10000	0	-0.39	9	9
RAB11FIP3	0.023	0.006	-10000	0	-10000	0	0
tube morphogenesis	0.018	0.058	-10000	0	-0.36	7	7
ruffle organization	0.011	0.026	-10000	0	-0.24	4	4
regulation of epithelial cell migration	0.023	0.031	-10000	0	-10000	0	0
PLD2	0.02	0.024	-10000	0	-10000	0	0
PIP5K1A	0.011	0.026	-10000	0	-0.24	4	4
mol:Phosphatidic acid	0.008	0.038	-10000	0	-0.34	9	9
Rac1/GTP	0.018	0.058	-10000	0	-0.37	7	7

×

Sumoylation by RanBP2 regulates transcriptional repression

Figure S129. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S129. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.008	0.011	-10000	0	-0.26	1	1
MDM2/SUMO1	0.033	0.039	-10000	0	-0.23	4	4
HDAC4	0.023	0.018	-10000	0	-0.57	1	1
Ran/GTP/Exportin 1/HDAC1	-0.008	0.007	-10000	0	-10000	0	0
SUMO1	0.024	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.008	0.017	-10000	0	-0.22	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.007	0.01	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.024	0.003	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.024	0.003	-10000	0	-10000	0	0
SUMO1/HDAC4	0.035	0.039	-10000	0	-0.24	4	4
SUMO1/HDAC1	0.035	0.038	-10000	0	-0.23	4	4
RANGAP1	0.023	0.006	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.056	0.02	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.011	0.004	-10000	0	-10000	0	0
Ran/GTP	0.023	0.036	-10000	0	-0.24	4	4
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.024	0.005	-10000	0	-10000	0	0
UBE2I	0.023	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.022	0.038	0.25	1	-0.24	4	5
NPC	0.014	0.002	-10000	0	-10000	0	0
PIAS2	0.024	0.005	-10000	0	-10000	0	0
PIAS1	0.024	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Arf1 pathway

Figure S130. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S130. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.011	0.032	0.17	7	-10000	0	7
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.027	0.047	-10000	0	-0.19	4	4
AP2	0.034	0.009	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.031	0.01	-10000	0	-10000	0	0
CLTB	0.025	0.015	0.26	4	-10000	0	4
coatomer protein complex/ARF1/GTP/ER cargo protein	0.014	0.01	-10000	0	-10000	0	0
CD4	0.023	0.005	-10000	0	-10000	0	0
CLTA	0.024	0.004	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.006	0.006	0.13	2	-10000	0	2
mol:PI-4-5-P2	0.007	0.015	-10000	0	-10000	0	0
ARF1/GTP	0.024	0.015	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.008	0.012	0.2	3	-10000	0	3
mol:Choline	0.007	0.016	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.021	0.011	-10000	0	-10000	0	0
DDEF1	0.006	0.016	-10000	0	-10000	0	0
ARF1/GDP	0.001	0.02	-10000	0	-0.13	2	2
AP2M1	0.024	0.005	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.01	0.006	-10000	0	-10000	0	0
Rac/GTP	0.021	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.026	0.017	-10000	0	-10000	0	0
ARFIP2	0.014	0.018	-10000	0	-10000	0	0
COPA	0.02	0.009	-10000	0	-10000	0	0
RAC1	0.024	0.003	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.01	0.023	-10000	0	-0.2	3	3
ARF1/GTP/ARHGAP10	0.014	0.008	-10000	0	-10000	0	0
GGA3	0.023	0.006	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.012	0.041	-10000	0	-0.24	20	20
AP2A1	0.024	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.01	0.023	-10000	0	-0.22	5	5
ARF1/GDP/Membrin	0.013	0.048	-10000	0	-0.26	28	28
Arfaptin 2/Rac/GDP	0.028	0.011	-10000	0	-10000	0	0
CYTH2	0.029	0.009	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.027	0.015	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.018	0.003	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.019	0.023	-10000	0	-10000	0	0
PLD2	0.007	0.016	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	0.006	0.006	0.13	2	-10000	0	2
PIP5K1A	0.007	0.016	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.013	0.02	-10000	0	-10000	0	0
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.016	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.006	0.006	0.13	2	-10000	0	2
GOSR2	0.008	0.028	-10000	0	-0.31	7	7
USO1	0.009	0.02	-10000	0	-0.32	3	3
GBF1	0.009	0.024	-10000	0	-0.31	5	5
ARF1/GTP/Arfaptin 2	0.028	0.015	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.045	0.015	-10000	0	-10000	0	0

×

Alternative NF-kappaB pathway

Figure S131. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S131. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.034	0.009	-10000	0	-9999	0
FBXW11	0.024	0.004	-10000	0	-9999	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-9999	0
beta TrCP1/SCF ubiquitin ligase complex	0.024	0.004	-10000	0	-9999	0
CHUK	0.024	0.003	-10000	0	-9999	0
NF kappa B2 p100/RelB	0.067	0.025	-10000	0	-9999	0
NFKB1	0.024	0.004	-10000	0	-9999	0
MAP3K14	0.023	0.005	-10000	0	-9999	0
NF kappa B1 p50/RelB	0.036	0.016	-10000	0	-9999	0
RELB	0.026	0.022	0.26	10	-9999	10
NFKB2	0.024	0.008	0.26	1	-9999	1
NF kappa B2 p52/RelB	0.033	0.016	-10000	0	-9999	0
regulation of B cell activation	0.033	0.016	-10000	0	-9999	0

pid_entity	TCGA.Z7.A8R6	TCGA.Z7.A8R5	TCGA.XX.A89A	TCGA.XX.A899
109_MAP3K5	-0.33	0.025	0.025	0.025
47_PPARGC1A	-0.57	0.024	0.024	0.024
105_BMP4	0.024	0.024	0.024	0.024
105_BMP6	0.024	0.024	0.024	0.024
105_BMP7	0.024	0.024	0.024	0.024
105_BMP2	-0.57	0.024	0.024	0.024
131_RELN/VLDLR	-0.33	-0.33	0.063	0.063
30_TGFB1/TGF beta receptor Type II	-0.033	0.024	0.018	0.019
84_STAT5B	-0.16	-0.06	0.12	0.029
84_STAT5A	-0.16	-0.06	0.12	0.029