PARADIGM pathway analysis of mRNA expression data - Glioblastoma Multiforme (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Glypican 2 network	225
HIF-1-alpha transcription factor network	218
FOXM1 transcription factor network	204
TCGA08_retinoblastoma	191
Endothelins	133
Syndecan-1-mediated signaling events	131
Osteopontin-mediated events	128
EGFR-dependent Endothelin signaling events	118
LPA receptor mediated events	116
amb2 Integrin signaling	110

Pathway.Name	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
Glypican 2 network	225	900	4	-0.23	0	1000	-1000	0	-1000
HIF-1-alpha transcription factor network	218	16588	76	-0.55	0.023	1000	-1000	-0.007	-1000
FOXM1 transcription factor network	204	10405	51	-0.75	0.017	1000	-1000	-0.05	-1000
TCGA08_retinoblastoma	191	1529	8	-0.23	0.072	1000	-1000	-0.004	-1000
Endothelins	133	12853	96	-0.47	0.083	1000	-1000	-0.01	-1000
Syndecan-1-mediated signaling events	131	4461	34	-0.29	0.018	1000	-1000	0	-1000
Osteopontin-mediated events	128	4881	38	-0.32	0.017	1000	-1000	-0.006	-1000
EGFR-dependent Endothelin signaling events	118	2490	21	-0.14	0.017	1000	-1000	-0.006	-1000
LPA receptor mediated events	116	11896	102	-0.18	0.017	1000	-1000	-0.04	-1000
amb2 Integrin signaling	110	9096	82	-0.24	0.022	1000	-1000	0	-1000
PLK1 signaling events	91	7815	85	-0.25	0.022	1000	-1000	-0.005	-1000
BARD1 signaling events	85	4870	57	-0.26	0.049	1000	-1000	-0.011	-1000
Signaling events mediated by VEGFR1 and VEGFR2	81	10239	125	-0.25	0.026	1000	-1000	-0.031	-1000
Syndecan-4-mediated signaling events	81	5440	67	-0.39	0.021	1000	-1000	-0.01	-1000
HIF-2-alpha transcription factor network	76	3309	43	-0.21	0.11	1000	-1000	-0.042	-1000
Fc-epsilon receptor I signaling in mast cells	68	6666	97	-0.19	0.032	1000	-1000	-0.027	-1000
Aurora B signaling	67	4550	67	-0.31	0.023	1000	-1000	-0.013	-1000
VEGFR1 specific signals	64	3600	56	-0.25	0.039	1000	-1000	-0.008	-1000
Regulation of nuclear SMAD2/3 signaling	62	8490	136	-0.28	0.16	1000	-1000	-0.009	-1000
PDGFR-alpha signaling pathway	55	2463	44	-0.25	0.023	1000	-1000	-0.005	-1000
Stabilization and expansion of the E-cadherin adherens junction	53	3960	74	-0.35	0.033	1000	-1000	-0.031	-1000
S1P1 pathway	52	1879	36	-0.21	0.022	1000	-1000	-0.026	-1000
TCGA08_p53	52	366	7	-0.024	0.009	1000	-1000	-0.001	-1000
Paxillin-independent events mediated by a4b1 and a4b7	51	1905	37	-0.27	0.042	1000	-1000	-0.006	-1000
FAS signaling pathway (CD95)	51	2438	47	-0.045	0.031	1000	-1000	-0.011	-1000
IL1-mediated signaling events	50	3100	62	-0.12	0.049	1000	-1000	-0.007	-1000
Class I PI3K signaling events	49	3648	73	-0.094	0.035	1000	-1000	-0.007	-1000
Circadian rhythm pathway	48	1075	22	-0.046	0.026	1000	-1000	-0.011	-1000
Wnt signaling	47	332	7	-0.12	0.017	1000	-1000	0.002	-1000
Noncanonical Wnt signaling pathway	45	1170	26	-0.12	0.017	1000	-1000	-0.029	-1000
Aurora A signaling	45	2729	60	-0.16	0.042	1000	-1000	0	-1000
Plasma membrane estrogen receptor signaling	45	3923	86	-0.42	0.13	1000	-1000	-0.027	-1000
Ras signaling in the CD4+ TCR pathway	44	764	17	-0.095	0.016	1000	-1000	-0.001	-1000
E-cadherin signaling in keratinocytes	42	1848	43	-0.14	0.028	1000	-1000	-0.003	-1000
BCR signaling pathway	41	4100	99	-0.088	0.048	1000	-1000	-0.028	-1000
Angiopoietin receptor Tie2-mediated signaling	41	3610	88	-0.2	0.037	1000	-1000	-0.045	-1000
Integrins in angiogenesis	40	3434	84	-0.22	0.04	1000	-1000	-0.013	-1000
Syndecan-2-mediated signaling events	35	2460	69	-0.19	0.034	1000	-1000	0	-1000
Syndecan-3-mediated signaling events	35	1229	35	-0.14	0.032	1000	-1000	-0.004	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	33	2631	78	-0.047	0.032	1000	-1000	-0.022	-1000
Glypican 1 network	32	1557	48	-0.22	0.028	1000	-1000	-0.011	-1000
S1P3 pathway	32	1356	42	-0.21	0.022	1000	-1000	0	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	30	700	23	-0.086	0.018	1000	-1000	-0.004	-1000
Visual signal transduction: Cones	29	1104	38	-0.13	0.04	1000	-1000	0	-1000
Signaling events mediated by HDAC Class I	29	3075	104	-0.13	0.034	1000	-1000	-0.016	-1000
Nongenotropic Androgen signaling	28	1485	52	-0.059	0.027	1000	-1000	-0.013	-1000
Paxillin-dependent events mediated by a4b1	27	994	36	-0.27	0.042	1000	-1000	-0.006	-1000
Signaling mediated by p38-alpha and p38-beta	27	1205	44	-0.044	0.033	1000	-1000	0	-1000
Arf6 downstream pathway	25	1089	43	-0.016	0.025	1000	-1000	-0.01	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	25	1145	45	-0.13	0.026	1000	-1000	-0.012	-1000
Signaling events mediated by PRL	25	872	34	-0.038	0.025	1000	-1000	-0.005	-1000
ErbB2/ErbB3 signaling events	24	1564	65	-0.094	0.022	1000	-1000	-0.025	-1000
Signaling events mediated by PTP1B	24	1879	76	-0.2	0.033	1000	-1000	-0.006	-1000
TRAIL signaling pathway	24	1196	48	-0.02	0.022	1000	-1000	-0.007	-1000
RXR and RAR heterodimerization with other nuclear receptor	24	1265	52	-0.24	0.051	1000	-1000	0	-1000
Canonical Wnt signaling pathway	24	1271	51	-0.11	0.099	1000	-1000	-0.014	-1000
IL23-mediated signaling events	24	1478	60	-0.025	0.047	1000	-1000	-0.022	-1000
Caspase cascade in apoptosis	23	1731	74	-0.13	0.024	1000	-1000	-0.012	-1000
EPO signaling pathway	23	1318	55	-0.033	0.053	1000	-1000	-0.004	-1000
IL6-mediated signaling events	23	1725	75	-0.2	0.034	1000	-1000	-0.019	-1000
Presenilin action in Notch and Wnt signaling	22	1372	61	-0.092	0.035	1000	-1000	-0.007	-1000
IFN-gamma pathway	22	1532	68	-0.064	0.043	1000	-1000	-0.029	-1000
TCGA08_rtk_signaling	22	585	26	-0.14	0.021	1000	-1000	-0.002	-1000
E-cadherin signaling in the nascent adherens junction	22	1692	76	-0.086	0.039	1000	-1000	-0.03	-1000
Regulation of Telomerase	22	2258	102	-0.14	0.044	1000	-1000	-0.036	-1000
Glucocorticoid receptor regulatory network	21	2491	114	-0.099	0.075	1000	-1000	-0.027	-1000
FoxO family signaling	20	1338	64	-0.2	0.022	1000	-1000	-0.011	-1000
IL2 signaling events mediated by PI3K	20	1183	58	-0.043	0.037	1000	-1000	-0.015	-1000
Coregulation of Androgen receptor activity	19	1480	76	-0.34	0.047	1000	-1000	-0.01	-1000
Ceramide signaling pathway	19	1449	76	-0.13	0.039	1000	-1000	-0.004	-1000
ceramide signaling pathway	19	933	49	-0.13	0.025	1000	-1000	-0.008	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	19	1345	68	-0.19	0.083	1000	-1000	-0.025	-1000
Neurotrophic factor-mediated Trk receptor signaling	19	2372	120	-0.12	0.05	1000	-1000	-0.021	-1000
BMP receptor signaling	18	1471	81	-0.086	0.047	1000	-1000	-0.031	-1000
Retinoic acid receptors-mediated signaling	17	1039	58	-0.18	0.068	1000	-1000	-0.006	-1000
TCR signaling in naïve CD8+ T cells	17	1629	93	-0.094	0.033	1000	-1000	-0.022	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	16	891	54	-0.086	0.026	1000	-1000	-0.011	-1000
Regulation of p38-alpha and p38-beta	16	908	54	-0.053	0.033	1000	-1000	0	-1000
IL2 signaling events mediated by STAT5	16	355	22	-0.096	0.042	1000	-1000	-0.001	-1000
p75(NTR)-mediated signaling	15	1928	125	-0.12	0.082	1000	-1000	-0.034	-1000
IL4-mediated signaling events	15	1451	91	-0.15	0.05	1000	-1000	-0.099	-1000
PDGFR-beta signaling pathway	15	1461	97	-0.066	0.04	1000	-1000	-0.027	-1000
Canonical NF-kappaB pathway	14	548	39	-0.13	0.06	1000	-1000	0	-1000
ErbB4 signaling events	14	1011	69	-0.14	0.05	1000	-1000	-0.011	-1000
JNK signaling in the CD4+ TCR pathway	14	248	17	-0.017	0.027	1000	-1000	-0.007	-1000
Thromboxane A2 receptor signaling	14	1488	105	-0.14	0.035	1000	-1000	-0.032	-1000
Signaling mediated by p38-gamma and p38-delta	13	208	15	-0.013	0.025	1000	-1000	-0.004	-1000
Insulin Pathway	13	1017	74	-0.11	0.048	1000	-1000	-0.026	-1000
IL12-mediated signaling events	12	1116	87	-0.22	0.048	1000	-1000	-0.065	-1000
Cellular roles of Anthrax toxin	12	482	39	-0.084	0.016	1000	-1000	-0.005	-1000
Arf6 signaling events	12	752	62	-0.14	0.044	1000	-1000	0	-1000
IGF1 pathway	12	714	57	-0.032	0.034	1000	-1000	-0.009	-1000
Class I PI3K signaling events mediated by Akt	11	779	68	-0.026	0.036	1000	-1000	-0.008	-1000
Nectin adhesion pathway	11	693	63	-0.086	0.054	1000	-1000	-0.029	-1000
Calcium signaling in the CD4+ TCR pathway	10	312	31	-0.081	0.055	1000	-1000	-0.017	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	10	351	33	-0.039	0.041	1000	-1000	-0.006	-1000
E-cadherin signaling events	10	51	5	0.004	0.023	1000	-1000	0.003	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	9	826	85	-0.084	0.049	1000	-1000	-0.021	-1000
Ephrin B reverse signaling	9	479	48	-0.016	0.026	1000	-1000	-0.011	-1000
Sumoylation by RanBP2 regulates transcriptional repression	9	258	27	-0.036	0.036	1000	-1000	-0.019	-1000
Sphingosine 1-phosphate (S1P) pathway	8	238	28	-0.036	0.024	1000	-1000	-0.002	-1000
Signaling events mediated by the Hedgehog family	8	439	52	-0.03	0.045	1000	-1000	-0.004	-1000
Hedgehog signaling events mediated by Gli proteins	8	550	65	-0.065	0.042	1000	-1000	-0.003	-1000
Aurora C signaling	8	58	7	-0.005	0.02	1000	-1000	0	-1000
Atypical NF-kappaB pathway	8	263	31	-0.012	0.033	1000	-1000	-0.001	-1000
Signaling events mediated by HDAC Class III	7	294	40	-0.034	0.038	1000	-1000	-0.011	-1000
Signaling events regulated by Ret tyrosine kinase	7	585	82	-0.021	0.043	1000	-1000	-0.025	-1000
EPHB forward signaling	7	608	85	-0.094	0.048	1000	-1000	-0.033	-1000
Arf6 trafficking events	7	559	71	-0.026	0.028	1000	-1000	-0.011	-1000
mTOR signaling pathway	6	339	53	-0.1	0.034	1000	-1000	-0.028	-1000
S1P5 pathway	6	104	17	-0.036	0.017	1000	-1000	-0.007	-1000
Nephrin/Neph1 signaling in the kidney podocyte	5	179	34	-0.027	0.047	1000	-1000	-0.009	-1000
FOXA2 and FOXA3 transcription factor networks	5	267	46	-0.017	0.19	1000	-1000	-0.009	-1000
p38 MAPK signaling pathway	5	250	44	-0.02	0.048	1000	-1000	-0.006	-1000
Regulation of Androgen receptor activity	5	389	70	-0.028	0.067	1000	-1000	-0.016	-1000
Insulin-mediated glucose transport	4	132	32	-0.01	0.021	1000	-1000	0	-1000
Reelin signaling pathway	4	279	56	-0.003	0.08	1000	-1000	-0.001	-1000
S1P4 pathway	4	124	25	-0.036	0.022	1000	-1000	0	-1000
Signaling events mediated by HDAC Class II	3	237	75	-0.029	0.043	1000	-1000	-0.017	-1000
a4b1 and a4b7 Integrin signaling	3	17	5	0.013	0.023	1000	-1000	0	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	3	269	83	-0.061	0.047	1000	-1000	-0.005	-1000
IL27-mediated signaling events	3	200	51	-0.025	0.044	1000	-1000	-0.007	-1000
LPA4-mediated signaling events	1	12	12	0	0.014	1000	-1000	-0.005	-1000
Effects of Botulinum toxin	1	41	26	0	0.035	1000	-1000	0	-1000
Arf1 pathway	1	67	54	0	0.027	1000	-1000	-0.003	-1000
Alternative NF-kappaB pathway	1	22	13	0	0.049	1000	-1000	0	-1000
PLK2 and PLK4 events	0	0	3	0.012	0.017	1000	-1000	0.004	-1000
Ephrin A reverse signaling	0	2	7	0	0.023	1000	-1000	-0.001	-1000
Rapid glucocorticoid signaling	0	4	20	0	0.017	1000	-1000	0	-1000
Visual signal transduction: Rods	0	5	52	0	0.042	1000	-1000	-0.007	-1000
Class IB PI3K non-lipid kinase events	0	0	3	-0.017	0.017	1000	-1000	-0.008	-1000
Total	4473	256180	7203	-16	5.1	131000	-131000	-1.7	-131000

Glypican 2 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.23	0.21	-9999	-0.41	300	300
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	-0.16	0.15	-9999	-0.29	300	300
neuron projection morphogenesis	-0.16	0.15	-9999	-0.29	300	300

×

HIF-1-alpha transcription factor network

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
PKM2	-0.45	0.47	-10000	0	-0.79	301	301
HDAC7	-0.006	0.012	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.34	0.37	0.36	28	-0.65	269	297
SMAD4	-0.085	0.18	-10000	0	-0.41	127	127
ID2	-0.45	0.47	-10000	0	-0.79	300	300
AP1	-0.047	0.13	-10000	0	-0.29	125	125
ABCG2	-0.45	0.47	-10000	0	-0.79	302	302
HIF1A	-0.062	0.08	-10000	0	-0.14	157	157
TFF3	-0.45	0.47	-10000	0	-0.79	304	304
GATA2	0.017	0.019	-10000	0	-0.41	1	1
AKT1	-0.055	0.082	0.26	2	-0.14	111	113
response to hypoxia	-0.068	0.068	0.3	1	-0.13	222	223
MCL1	-0.45	0.47	-10000	0	-0.8	301	301
NDRG1	-0.45	0.47	-10000	0	-0.79	301	301
SERPINE1	-0.52	0.53	-10000	0	-0.88	313	313
FECH	-0.45	0.47	-10000	0	-0.79	301	301
FURIN	-0.45	0.47	-10000	0	-0.79	301	301
NCOA2	0.019	0.001	-10000	0	-10000	0	0
EP300	-0.026	0.12	0.45	5	-0.19	6	11
HMOX1	-0.55	0.53	-10000	0	-0.9	329	329
BHLHE40	-0.45	0.47	-10000	0	-0.79	303	303
BHLHE41	-0.45	0.47	-10000	0	-0.79	303	303
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.1	0.13	-10000	0	-0.28	113	113
ENG	-0.07	0.15	0.36	2	-0.29	91	93
JUN	0.017	0.019	-10000	0	-0.41	1	1
RORA	-0.45	0.47	-10000	0	-0.79	301	301
ABCB1	-0.093	0.087	-10000	0	-0.18	233	233
TFRC	-0.45	0.47	-10000	0	-0.79	303	303
CXCR4	-0.54	0.53	-10000	0	-0.88	324	324
TF	-0.42	0.47	-10000	0	-0.79	285	285
CITED2	-0.45	0.48	-10000	0	-0.8	301	301
HIF1A/ARNT	-0.49	0.57	0.48	28	-0.9	300	328
LDHA	-0.052	0.054	-10000	0	-0.13	2	2
ETS1	-0.45	0.47	-10000	0	-0.79	301	301
PGK1	-0.45	0.47	-10000	0	-0.79	301	301
NOS2	-0.45	0.47	-10000	0	-0.79	303	303
ITGB2	-0.52	0.53	-10000	0	-0.89	310	310
ALDOA	-0.45	0.47	-10000	0	-0.79	301	301
Cbp/p300/CITED2	-0.45	0.48	0.31	27	-0.8	302	329
FOS	-0.084	0.18	-10000	0	-0.41	125	125
HK2	-0.45	0.47	-10000	0	-0.79	301	301
SP1	0.023	0.008	-10000	0	-10000	0	0
GCK	-0.037	0.17	0.58	5	-0.27	5	10
HK1	-0.45	0.47	-10000	0	-0.8	299	299
NPM1	-0.45	0.47	-10000	0	-0.79	302	302
EGLN1	-0.45	0.47	-10000	0	-0.79	301	301
CREB1	0.023	0.002	-10000	0	-10000	0	0
PGM1	-0.45	0.47	-10000	0	-0.79	302	302
SMAD3	0.017	0.003	-10000	0	-10000	0	0
EDN1	-0.036	0.15	0.51	1	-0.26	63	64
IGFBP1	-0.45	0.47	-10000	0	-0.8	303	303
VEGFA	-0.41	0.42	-10000	0	-0.71	319	319
HIF1A/JAB1	-0.033	0.054	-10000	0	-0.4	2	2
CP	-0.49	0.51	-10000	0	-0.85	308	308
CXCL12	-0.45	0.48	-10000	0	-0.8	301	301
COPS5	0.018	0.001	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.048	0.13	-10000	0	-0.28	127	127
BNIP3	-0.45	0.47	-10000	0	-0.79	301	301
EGLN3	-0.45	0.47	-10000	0	-0.79	302	302
CA9	-0.46	0.48	-10000	0	-0.81	302	302
TERT	-0.45	0.47	-10000	0	-0.79	301	301
ENO1	-0.45	0.47	-10000	0	-0.79	301	301
PFKL	-0.45	0.47	-10000	0	-0.79	301	301
NCOA1	0.017	0.003	-10000	0	-10000	0	0
ADM	-0.55	0.52	-10000	0	-0.87	334	334
ARNT	-0.063	0.07	-10000	0	-0.14	150	150
HNF4A	0.021	0	-10000	0	-10000	0	0
ADFP	-0.52	0.52	-10000	0	-0.88	316	316
SLC2A1	-0.32	0.36	-10000	0	-0.6	296	296
LEP	-0.45	0.47	-10000	0	-0.79	302	302
HIF1A/ARNT/Cbp/p300	-0.35	0.38	0.36	28	-0.68	273	301
EPO	-0.18	0.28	0.56	2	-0.44	230	232
CREBBP	-0.026	0.12	0.45	5	-0.19	6	11
HIF1A/ARNT/Cbp/p300/HDAC7	-0.39	0.4	0.35	28	-0.7	297	325
PFKFB3	-0.45	0.47	-10000	0	-0.79	301	301
NT5E	-0.47	0.48	-10000	0	-0.81	306	306

×

FOXM1 transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.55	0.55	-9999	-1	273	273
PLK1	-0.03	0.098	-9999	-0.46	22	22
BIRC5	-0.18	0.23	-9999	-0.46	212	212
HSPA1B	-0.56	0.55	-9999	-1	275	275
MAP2K1	-0.013	0.036	-9999	-10000	0	0
BRCA2	-0.55	0.55	-9999	-1	271	271
FOXM1	-0.75	0.8	-9999	-1.3	304	304
XRCC1	-0.55	0.55	-9999	-1	275	275
FOXM1B/p19	-0.63	0.61	-9999	-1.1	275	275
Cyclin D1/CDK4	-0.6	0.55	-9999	-1.1	286	286
CDC2	-0.63	0.63	-9999	-1.2	275	275
TGFA	-0.49	0.48	-9999	-0.92	268	268
SKP2	-0.55	0.55	-9999	-1	273	273
CCNE1	0.005	0.05	-9999	-0.42	7	7
CKS1B	-0.59	0.58	-9999	-1.1	275	275
RB1	-0.26	0.23	-9999	-0.48	215	215
FOXM1C/SP1	-0.68	0.68	-9999	-1.2	277	277
AURKB	-0.034	0.11	-9999	-0.46	27	27
CENPF	-0.6	0.59	-9999	-1.1	275	275
CDK4	-0.27	0.21	-9999	-0.43	343	343
MYC	-0.53	0.5	-9999	-0.93	290	290
CHEK2	-0.025	0.085	-9999	-0.46	16	16
ONECUT1	-0.55	0.54	-9999	-1	271	271
CDKN2A	-0.031	0.13	-9999	-0.41	58	58
LAMA4	-0.55	0.55	-9999	-1	274	274
FOXM1B/HNF6	-0.68	0.68	-9999	-1.3	271	271
FOS	-0.59	0.56	-9999	-1	291	291
SP1	0.016	0.006	-9999	-10000	0	0
CDC25B	-0.56	0.56	-9999	-1	277	277
response to radiation	-0.02	0.026	-9999	-10000	0	0
CENPB	-0.56	0.56	-9999	-1	274	274
CENPA	-0.57	0.58	-9999	-1.1	273	273
NEK2	-0.56	0.56	-9999	-1	275	275
HIST1H2BA	-0.56	0.55	-9999	-1	275	275
CCNA2	-0.1	0.19	-9999	-0.43	139	139
EP300	0.017	0	-9999	-10000	0	0
CCNB1/CDK1	-0.71	0.71	-9999	-1.3	284	284
CCNB2	-0.65	0.6	-9999	-1.1	304	304
CCNB1	-0.64	0.63	-9999	-1.2	282	282
ETV5	-0.55	0.55	-9999	-1	273	273
ESR1	-0.55	0.55	-9999	-1	275	275
CCND1	-0.56	0.53	-9999	-1	272	272
GSK3A	-0.009	0.029	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.075	0.16	-9999	-0.31	146	146
CDK2	-0.011	0.097	-9999	-0.43	27	27
G2/M transition of mitotic cell cycle	-0.024	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.61	0.62	-9999	-1.1	273	273
GAS1	-0.57	0.56	-9999	-1	280	280
MMP2	-0.63	0.57	-9999	-1.1	302	302
RB1/FOXM1C	-0.59	0.55	-9999	-1.1	275	275
CREBBP	0.017	0	-9999	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0	0.018	-10000	0	-10000	0	0
CDKN2C	-0.23	0.21	-10000	0	-0.41	310	310
CDKN2A	-0.013	0.13	-10000	0	-0.38	58	58
CCND2	0.043	0.061	0.089	308	-10000	0	308
RB1	-0.048	0.068	-10000	0	-0.098	308	308
CDK4	0.031	0.071	0.14	115	-10000	0	115
CDK6	0.072	0.073	0.13	318	-10000	0	318
G1/S progression	0.048	0.068	0.14	112	-10000	0	112

×

Endothelins

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
AKT1	-0.26	0.22	-10000	0	-0.35	396	396
PTK2B	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	-0.039	0.099	-10000	0	-0.48	5	5
EDN1	-0.11	0.11	-10000	0	-0.24	143	143
EDN3	0.014	0.037	-10000	0	-0.41	4	4
EDN2	0.016	0.019	-10000	0	-0.41	1	1
HRAS/GDP	-0.023	0.1	-10000	0	-0.22	53	53
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.087	0.1	-10000	0	-0.2	182	182
ADCY4	-0.21	0.18	-10000	0	-0.33	312	312
ADCY5	-0.21	0.18	-10000	0	-0.33	312	312
ADCY6	-0.21	0.18	-10000	0	-0.34	291	291
ADCY7	-0.21	0.18	-10000	0	-0.35	291	291
ADCY1	-0.21	0.18	-10000	0	-0.34	291	291
ADCY2	-0.21	0.18	-10000	0	-0.34	291	291
ADCY3	-0.21	0.18	-10000	0	-0.33	312	312
ADCY8	-0.21	0.18	-10000	0	-0.34	293	293
ADCY9	-0.21	0.18	-10000	0	-0.34	291	291
arachidonic acid secretion	-0.067	0.14	-10000	0	-0.3	103	103
ETB receptor/Endothelin-1/Gq/GTP	-0.032	0.062	-10000	0	-0.18	38	38
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.23	0.21	0.25	1	-0.36	322	323
ETA receptor/Endothelin-1/Gs/GTP	-0.22	0.2	0.24	1	-0.35	311	312
mol:GTP	0	0.003	-10000	0	-10000	0	0
COL3A1	-0.41	0.28	-10000	0	-0.55	400	400
EDNRB	-0.046	0.11	-10000	0	-0.42	40	40
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.26	0.21	-10000	0	-0.41	291	291
CYSLTR1	-0.26	0.21	-10000	0	-0.35	397	397
SLC9A1	-0.13	0.11	-10000	0	-0.21	291	291
mol:GDP	-0.03	0.11	0.18	1	-0.23	55	56
SLC9A3	-0.084	0.12	-10000	0	-0.36	35	35
RAF1	-0.05	0.12	-10000	0	-0.26	96	96
JUN	-0.041	0.098	-10000	0	-0.44	5	5
JAK2	-0.26	0.22	-10000	0	-0.35	396	396
mol:IP3	-0.077	0.09	-10000	0	-0.18	166	166
ETA receptor/Endothelin-1	-0.3	0.25	0.28	1	-0.41	397	398
PLCB1	0.016	0.002	-10000	0	-10000	0	0
PLCB2	0.016	0.003	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.16	0.18	-10000	0	-0.42	157	157
FOS	-0.075	0.18	-10000	0	-0.38	125	125
Gai/GDP	-0.47	0.17	-10000	0	-0.52	482	482
CRK	0.017	0	-10000	0	-10000	0	0
mol:Ca ++	-0.23	0.21	-10000	0	-0.38	297	297
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.015	0.046	-10000	0	-0.19	18	18
GNAQ	0.018	0.004	-10000	0	-10000	0	0
GNAZ	0.015	0.006	-10000	0	-10000	0	0
GNAL	0.017	0	-10000	0	-10000	0	0
Gs family/GDP	-0.023	0.1	-10000	0	-0.22	53	53
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.12	-10000	0	-0.21	264	264
MAPK14	-0.018	0.052	-10000	0	-0.17	25	25
TRPC6	-0.04	0.1	-10000	0	-0.42	8	8
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.02	-10000	0	-0.41	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.021	0.055	-10000	0	-0.16	32	32
ETB receptor/Endothelin-2	-0.022	0.082	-10000	0	-0.29	41	41
ETB receptor/Endothelin-3	-0.023	0.085	-10000	0	-0.29	44	44
ETB receptor/Endothelin-1	-0.11	0.12	-10000	0	-0.24	178	178
MAPK3	-0.068	0.17	-10000	0	-0.35	127	127
MAPK1	-0.072	0.17	-10000	0	-0.35	127	127
Rac1/GDP	-0.022	0.1	0.18	1	-0.22	53	54
cAMP biosynthetic process	-0.17	0.16	-10000	0	-0.3	270	270
MAPK8	-0.053	0.11	-10000	0	-0.36	12	12
SRC	0.017	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.033	0.078	-10000	0	-0.2	87	87
p130Cas/CRK/Src/PYK2	0.005	0.098	-10000	0	-0.28	13	13
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.024	0.1	-10000	0	-0.22	55	55
COL1A2	-0.35	0.29	-10000	0	-0.57	304	304
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.16	0.18	-10000	0	-0.42	157	157
mol:DAG	-0.077	0.09	-10000	0	-0.18	166	166
MAP2K2	-0.06	0.14	-10000	0	-0.3	116	116
MAP2K1	-0.059	0.15	-10000	0	-0.3	115	115
EDNRA	-0.24	0.23	-10000	0	-0.4	288	288
positive regulation of muscle contraction	-0.22	0.19	-10000	0	-0.36	293	293
Gq family/GDP	0.033	0.097	-10000	0	-0.24	18	18
HRAS/GTP	-0.04	0.1	-10000	0	-0.2	92	92
PRKCH	-0.071	0.09	-10000	0	-0.18	157	157
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.07	0.088	-10000	0	-0.18	157	157
PRKCB	-0.075	0.088	-10000	0	-0.18	166	166
PRKCE	-0.071	0.087	-10000	0	-0.18	154	154
PRKCD	-0.071	0.089	-10000	0	-0.18	154	154
PRKCG	-0.071	0.089	-10000	0	-0.18	157	157
regulation of vascular smooth muscle contraction	-0.08	0.19	-10000	0	-0.4	127	127
PRKCQ	-0.072	0.088	-10000	0	-0.18	157	157
PLA2G4A	-0.071	0.15	-10000	0	-0.31	103	103
GNA14	0.016	0.027	-10000	0	-0.41	2	2
GNA15	0.012	0.049	-10000	0	-0.41	7	7
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA11	0.017	0.003	-10000	0	-10000	0	0
Rac1/GTP	-0.23	0.21	0.25	1	-0.36	319	320
MMP1	0.083	0.15	0.19	245	-0.34	43	288

×

Syndecan-1-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.094	-9999	-0.41	27	27
CCL5	-0.006	0.096	-9999	-0.41	28	28
SDCBP	0.017	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.077	0.14	-9999	-0.21	219	219
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.072	0.14	-9999	-0.3	109	109
Syndecan-1/Syntenin	-0.067	0.14	-9999	-0.3	100	100
MAPK3	-0.19	0.16	-9999	-0.25	395	395
HGF/MET	0.018	0.046	-9999	-0.28	12	12
TGFB1/TGF beta receptor Type II	-0.005	0.094	-9999	-0.41	27	27
BSG	0.017	0	-9999	-10000	0	0
keratinocyte migration	-0.071	0.14	-9999	-0.3	109	109
Syndecan-1/RANTES	-0.077	0.16	-9999	-0.33	107	107
Syndecan-1/CD147	-0.2	0.17	-9999	-0.27	395	395
Syndecan-1/Syntenin/PIP2	-0.065	0.13	-9999	-0.29	100	100
LAMA5	0.006	0.069	-9999	-0.41	14	14
positive regulation of cell-cell adhesion	-0.064	0.13	-9999	-0.28	100	100
MMP7	-0.046	0.15	-9999	-0.41	78	78
HGF	0.015	0.026	-9999	-0.41	2	2
Syndecan-1/CASK	-0.074	0.13	-9999	-0.2	219	219
Syndecan-1/HGF/MET	-0.062	0.14	-9999	-0.29	108	108
regulation of cell adhesion	-0.18	0.15	-9999	-0.24	393	393
HPSE	-0.019	0.12	-9999	-0.41	44	44
positive regulation of cell migration	-0.077	0.14	-9999	-0.21	219	219
SDC1	-0.078	0.14	-9999	-0.21	219	219
Syndecan-1/Collagen	-0.077	0.14	-9999	-0.21	219	219
PPIB	-0.29	0.2	-9999	-0.41	374	374
MET	0.009	0.058	-9999	-0.41	10	10
PRKACA	0.017	0	-9999	-10000	0	0
MMP9	-0.13	0.2	-9999	-0.41	179	179
MAPK1	-0.19	0.16	-9999	-0.25	393	393
homophilic cell adhesion	-0.077	0.14	-9999	-0.21	219	219
MMP1	-0.018	0.12	-9999	-0.41	43	43

×

Osteopontin-mediated events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.066	0.13	-9999	-0.23	186	186
NF kappa B1 p50/RelA/I kappa B alpha	-0.056	0.14	-9999	-0.3	83	83
alphaV/beta3 Integrin/Osteopontin/Src	-0.097	0.16	-9999	-0.31	185	185
AP1	-0.2	0.22	-9999	-0.43	203	203
ILK	-0.08	0.13	-9999	-0.24	185	185
bone resorption	-0.21	0.16	-9999	-0.27	426	426
PTK2B	0.017	0	-9999	-10000	0	0
PYK2/p130Cas	-0.065	0.14	-9999	-0.23	200	200
ITGAV	0	0.074	-9999	-0.42	16	16
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.22	0.13	-9999	-0.28	416	416
alphaV/beta3 Integrin/Osteopontin	-0.076	0.15	-9999	-0.27	185	185
MAP3K1	-0.082	0.13	-9999	-0.25	186	186
JUN	0.014	0.019	-9999	-0.41	1	1
MAPK3	-0.079	0.14	-9999	-0.28	129	129
MAPK1	-0.08	0.14	-9999	-0.28	130	130
Rac1/GDP	0.013	0	-9999	-10000	0	0
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAPK8	-0.084	0.12	-9999	-0.24	186	186
ITGB3	0.013	0.011	-9999	-10000	0	0
NFKBIA	-0.075	0.14	-9999	-0.33	80	80
FOS	-0.087	0.18	-9999	-0.42	125	125
CD44	-0.32	0.18	-9999	-0.41	416	416
CHUK	0.016	0.019	-9999	-0.41	1	1
PLAU	-0.13	0.22	-9999	-0.48	131	131
NF kappa B1 p50/RelA	-0.06	0.15	-9999	-0.33	83	83
BCAR1	0	0	-9999	-10000	0	0
RELA	0.017	0	-9999	-10000	0	0
alphaV beta3 Integrin	0.009	0.057	-9999	-0.29	16	16
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.087	0.15	-9999	-0.26	200	200
VAV3	-0.093	0.14	-9999	-0.25	222	222
MAP3K14	-0.079	0.14	-9999	-0.25	185	185
ROCK2	0.017	0	-9999	-10000	0	0
SPP1	-0.14	0.21	-9999	-0.42	181	181
RAC1	0.017	0	-9999	-10000	0	0
Rac1/GTP	-0.079	0.14	-9999	-0.22	222	222
MMP2	-0.24	0.24	-9999	-0.44	298	298

×

EGFR-dependent Endothelin signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0.019	-9999	-0.41	1	1
EGFR	-0.14	0.21	-9999	-0.41	194	194
EGF/EGFR	-0.11	0.14	-9999	-0.22	304	304
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.067	0.12	-9999	-0.2	237	237
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.11	0.2	-9999	-0.41	154	154
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	0.015	0.026	-9999	-0.41	2	2
EGF/EGFR dimer/SHC	-0.088	0.14	-9999	-0.24	238	238
mol:GDP	-0.068	0.12	-9999	-0.2	237	237
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.01	0.055	-9999	-0.41	9	9
GRB2/SOS1	0.013	0.001	-9999	-10000	0	0
HRAS/GTP	-0.066	0.1	-9999	-0.18	238	238
SHC1	-0.021	0.12	-9999	-0.41	47	47
HRAS/GDP	-0.062	0.11	-9999	-0.18	238	238
FRAP1	-0.07	0.11	-9999	-0.19	237	237
EGF/EGFR dimer	-0.09	0.15	-9999	-0.28	196	196
SOS1	0	0	-9999	-10000	0	0
GRB2	0.017	0.002	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.07	0.15	-9999	-0.29	158	158

×

LPA receptor mediated 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
GNB1/GNG2	-0.069	0.091	-10000	0	-0.16	251	251
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.053	-10000	0	-0.21	5	5
AP1	-0.1	0.12	-10000	0	-0.19	303	303
mol:PIP3	-0.12	0.11	-10000	0	-0.2	325	325
AKT1	-0.032	0.073	0.17	3	-0.21	9	12
PTK2B	-0.041	0.059	-10000	0	-0.1	251	251
RHOA	-0.035	0.049	-10000	0	-0.15	6	6
PIK3CB	0.017	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.008	0.029	-10000	0	-10000	0	0
MAGI3	0	0.001	-10000	0	-0.003	13	13
RELA	0.017	0	-10000	0	-10000	0	0
apoptosis	-0.098	0.12	-10000	0	-0.19	285	285
HRAS/GDP	0.012	0.013	-10000	0	-0.29	1	1
positive regulation of microtubule depolymerization	-0.006	0.069	0.13	57	-10000	0	57
NF kappa B1 p50/RelA	-0.055	0.06	-10000	0	-0.17	19	19
endothelial cell migration	-0.18	0.21	-10000	0	-0.4	251	251
ADCY4	-0.015	0.054	-10000	0	-0.18	47	47
ADCY5	-0.015	0.054	-10000	0	-0.18	47	47
ADCY6	-0.015	0.053	-10000	0	-0.18	45	45
ADCY7	-0.016	0.056	-10000	0	-0.19	48	48
ADCY1	-0.015	0.053	-10000	0	-0.18	45	45
ADCY2	-0.015	0.053	-10000	0	-0.18	45	45
ADCY3	-0.015	0.054	-10000	0	-0.18	47	47
ADCY8	-0.015	0.054	-10000	0	-0.18	46	46
ADCY9	-0.015	0.053	-10000	0	-0.18	45	45
GSK3B	-0.035	0.056	-10000	0	-0.094	251	251
arachidonic acid secretion	-0.048	0.069	-10000	0	-0.13	198	198
GNG2	0	0.001	-10000	0	-0.005	21	21
TRIP6	-0.11	0.11	-10000	0	-0.21	285	285
GNAO1	-0.005	0.032	-10000	0	-0.18	16	16
HRAS	0.016	0.019	-10000	0	-0.41	1	1
NFKBIA	-0.02	0.047	-10000	0	-0.14	7	7
GAB1	0.014	0.037	-10000	0	-0.41	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.002	0.14	-10000	0	-0.7	21	21
JUN	0.016	0.019	-10000	0	-0.41	1	1
LPA/LPA2/NHERF2	-0.024	0.04	-10000	0	-10000	0	0
TIAM1	-0.008	0.16	-10000	0	-0.8	21	21
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.009	0.03	-10000	0	-10000	0	0
PLCB3	-0.017	0.035	-10000	0	-10000	0	0
FOS	-0.084	0.18	-10000	0	-0.41	125	125
positive regulation of mitosis	-0.048	0.069	-10000	0	-0.13	198	198
LPA/LPA1-2-3	-0.077	0.088	-10000	0	-0.17	251	251
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	-0.041	0.065	-10000	0	-0.11	251	251
GNAZ	-0.068	0.097	-10000	0	-0.18	216	216
EGFR/PI3K-beta/Gab1	-0.12	0.12	-10000	0	-0.2	325	325
positive regulation of dendritic cell cytokine production	-0.077	0.087	-10000	0	-0.17	251	251
LPA/LPA2/MAGI-3	-0.032	0.036	-10000	0	-0.07	251	251
ARHGEF1	-0.06	0.089	-10000	0	-0.15	252	252
GNAI2	-0.079	0.1	-10000	0	-0.18	251	251
GNAI3	-0.11	0.13	-10000	0	-0.22	282	282
GNAI1	-0.072	0.098	-10000	0	-0.18	223	223
LPA/LPA3	-0.04	0.045	-10000	0	-0.087	251	251
LPA/LPA2	-0.04	0.045	-10000	0	-0.087	251	251
LPA/LPA1	-0.1	0.12	-10000	0	-0.23	251	251
HB-EGF/EGFR	-0.16	0.16	-10000	0	-0.27	320	320
HBEGF	-0.086	0.14	-10000	0	-0.29	179	179
mol:DAG	-0.009	0.03	-10000	0	-10000	0	0
cAMP biosynthetic process	0.001	0.089	0.15	9	-0.16	50	59
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
SRC	0.017	0	-10000	0	-10000	0	0
GNB1	0.017	0.002	-10000	0	-10000	0	0
LYN	-0.039	0.073	-10000	0	-0.19	65	65
GNAQ	-0.023	0.035	-10000	0	-0.06	251	251
LPAR2	0	0.001	-10000	0	-0.003	15	15
LPAR3	0	0	-10000	0	-10000	0	0
LPAR1	-0.063	0.07	-10000	0	-0.14	251	251
IL8	-0.16	0.15	-10000	0	-0.28	296	296
PTK2	-0.065	0.084	-10000	0	-0.15	251	251
Rac1/GDP	0.013	0	-10000	0	-10000	0	0
CASP3	-0.098	0.12	-10000	0	-0.19	285	285
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
PLCG1	-0.016	0.033	-10000	0	-0.05	253	253
PLD2	-0.065	0.084	-10000	0	-0.15	251	251
G12/G13	-0.064	0.1	-10000	0	-0.17	252	252
PI3K-beta	-0.054	0.06	-10000	0	-0.2	5	5
cell migration	-0.046	0.059	-10000	0	-0.21	21	21
SLC9A3R2	0.017	0	-10000	0	-10000	0	0
PXN	-0.041	0.066	-10000	0	-0.11	251	251
HRAS/GTP	-0.049	0.07	-10000	0	-0.14	196	196
RAC1	0.017	0	-10000	0	-10000	0	0
MMP9	-0.13	0.2	-10000	0	-0.41	179	179
PRKCE	0.017	0.001	-10000	0	-10000	0	0
PRKCD	-0.005	0.028	-10000	0	-10000	0	0
Gi(beta/gamma)	-0.017	0.056	-10000	0	-0.19	50	50
mol:LPA	-0.063	0.07	-10000	0	-0.14	251	251
TRIP6/p130 Cas/FAK1/Paxillin	-0.11	0.1	-10000	0	-0.16	381	381
MAPKKK cascade	-0.048	0.069	-10000	0	-0.13	198	198
contractile ring contraction involved in cytokinesis	-0.035	0.049	-10000	0	-0.16	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.024	0.036	-10000	0	-0.18	2	2
GNA15	-0.026	0.043	-10000	0	-0.065	251	251
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA13	0.016	0.026	-10000	0	-0.41	2	2
MAPT	-0.022	0.048	-10000	0	-10000	0	0
GNA11	-0.023	0.035	-10000	0	-0.06	251	251
Rac1/GTP	0.002	0.15	-10000	0	-0.73	21	21
MMP2	-0.18	0.21	-10000	0	-0.41	251	251

×

amb2 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.2	0.18	-9999	-0.31	357	357
alphaM/beta2 Integrin/GPIbA	-0.079	0.14	-9999	-0.24	221	221
alphaM/beta2 Integrin/proMMP-9	-0.16	0.19	-9999	-0.31	299	299
PLAUR	-0.021	0.12	-9999	-0.41	47	47
HMGB1	0.015	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.1	0.16	-9999	-0.26	242	242
AGER	0.012	0.04	-9999	-0.43	4	4
RAP1A	0.017	0	-9999	-10000	0	0
SELPLG	0.017	0	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.065	0.14	-9999	-0.22	223	223
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.2	-9999	-0.41	179	179
CYR61	-0.12	0.2	-9999	-0.41	163	163
TLN1	-0.02	0.12	-9999	-0.41	46	46
Rap1/GTP	-0.037	0.09	-9999	-0.18	110	110
RHOA	0.017	0.001	-9999	-10000	0	0
P-selectin oligomer	0.016	0.019	-9999	-0.41	1	1
MYH2	-0.024	0.096	-9999	-0.18	109	109
MST1R	0.015	0.026	-9999	-0.41	2	2
leukocyte activation during inflammatory response	-0.062	0.12	-9999	-0.2	224	224
APOB	0.015	0.032	-9999	-0.41	3	3
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.19	0.21	-9999	-0.41	251	251
JAM3	0.016	0.019	-9999	-0.41	1	1
GP1BA	0.017	0	-9999	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.096	0.15	-9999	-0.26	236	236
alphaM/beta2 Integrin	-0.046	0.1	-9999	-0.22	111	111
JAM3 homodimer	0.016	0.019	-9999	-0.41	1	1
ICAM2	0.015	0.032	-9999	-0.41	3	3
ICAM1	0.002	0.078	-9999	-0.41	18	18
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.046	0.1	-9999	-0.22	111	111
cell adhesion	-0.079	0.14	-9999	-0.24	221	221
NFKB1	-0.07	0.15	-9999	-0.37	56	56
THY1	0.012	0.008	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
Lipoprotein(a)	0.022	0.02	-9999	-0.24	3	3
alphaM/beta2 Integrin/LRP/tPA	-0.18	0.18	-9999	-0.28	353	353
IL6	-0.08	0.18	-9999	-0.5	56	56
ITGB2	-0.16	0.21	-9999	-0.42	221	221
elevation of cytosolic calcium ion concentration	-0.13	0.21	-9999	-0.32	256	256
alphaM/beta2 Integrin/JAM2/JAM3	-0.097	0.14	-9999	-0.23	267	267
JAM2	-0.044	0.15	-9999	-0.41	75	75
alphaM/beta2 Integrin/ICAM1	-0.061	0.13	-9999	-0.21	231	231
alphaM/beta2 Integrin/uPA/Plg	-0.11	0.18	-9999	-0.28	255	255
RhoA/GTP	-0.029	0.1	-9999	-0.2	110	110
positive regulation of phagocytosis	-0.089	0.16	-9999	-0.25	225	225
Ron/MSP	0.021	0.038	-9999	-0.28	8	8
alphaM/beta2 Integrin/uPAR/uPA	-0.13	0.21	-9999	-0.32	256	256
alphaM/beta2 Integrin/uPAR	-0.099	0.17	-9999	-0.28	227	227
PLAU	-0.083	0.18	-9999	-0.41	123	123
PLAT	-0.18	0.21	-9999	-0.41	244	244
actin filament polymerization	-0.023	0.093	-9999	-0.18	109	109
MST1	0.012	0.045	-9999	-0.41	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.06	0.12	-9999	-0.2	224	224
TNF	-0.062	0.14	-9999	-0.39	42	42
RAP1B	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.13	0.19	-9999	-0.32	255	255
fibrinolysis	-0.11	0.18	-9999	-0.28	255	255
HCK	-0.053	0.16	-9999	-0.41	86	86
dendritic cell antigen processing and presentation	-0.046	0.1	-9999	-0.22	111	111
VTN	0.015	0.026	-9999	-0.41	2	2
alphaM/beta2 Integrin/CYR61	-0.15	0.19	-9999	-0.31	286	286
LPA	0.017	0	-9999	-10000	0	0
LRP1	0.002	0.078	-9999	-0.41	18	18
cell migration	-0.24	0.22	-9999	-0.35	389	389
FN1	-0.065	0.17	-9999	-0.41	101	101
alphaM/beta2 Integrin/Thy1	-0.077	0.12	-9999	-0.24	189	189
MPO	0.017	0	-9999	-10000	0	0
KNG1	0.016	0.019	-9999	-0.41	1	1
RAP1/GDP	0.012	0	-9999	-10000	0	0
ROCK1	-0.024	0.096	-9999	-0.18	109	109
ELA2	0.017	0	-9999	-10000	0	0
PLG	0.017	0	-9999	-10000	0	0
CTGF	-0.014	0.11	-9999	-0.41	38	38
alphaM/beta2 Integrin/Hck	-0.12	0.19	-9999	-0.32	224	224
ITGAM	0.015	0.011	-9999	-10000	0	0
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.063	0.13	-9999	-0.21	221	221
HP	-0.051	0.16	-9999	-0.41	84	84
leukocyte adhesion	-0.074	0.12	-9999	-0.2	196	196
SELP	0.016	0.019	-9999	-0.41	1	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.006	0.012	0.041	37	-10000	0	37
BUB1B	-0.098	0.12	-10000	0	-0.21	242	242
PLK1	-0.012	0.035	-10000	0	-0.12	37	37
PLK1S1	-0.008	0.02	-10000	0	-0.066	37	37
KIF2A	-0.006	0.033	0.14	2	-0.14	19	21
regulation of mitotic centrosome separation	-0.012	0.035	-10000	0	-0.12	37	37
GOLGA2	0.017	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.074	0.12	-10000	0	-0.23	185	185
WEE1	-0.099	0.11	-10000	0	-0.22	218	218
cytokinesis	-0.1	0.14	-10000	0	-0.25	219	219
PP2A-alpha B56	0.004	0.038	-10000	0	-0.22	2	2
AURKA	-0.008	0.036	-10000	0	-0.14	30	30
PICH/PLK1	-0.2	0.2	-10000	0	-0.34	307	307
CENPE	-0.034	0.094	-10000	0	-0.26	70	70
RhoA/GTP	0.013	0.001	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.006	0.033	0.14	2	-0.14	19	21
PPP2CA	0.017	0.001	-10000	0	-10000	0	0
FZR1	0.017	0	-10000	0	-10000	0	0
TPX2	-0.065	0.067	-10000	0	-0.12	297	297
PAK1	0.015	0.001	-10000	0	-10000	0	0
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
CLSPN	-0.001	0.019	-10000	0	-0.099	8	8
GORASP1	0.017	0	-10000	0	-10000	0	0
metaphase	-0.001	0.002	-10000	0	-0.01	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.008	0.02	-10000	0	-0.066	37	37
G2 phase of mitotic cell cycle	-0.002	0.002	-10000	0	-0.01	25	25
STAG2	-0.005	0.094	-10000	0	-0.41	27	27
GRASP65/GM130/RAB1/GTP	-0.011	0.028	-10000	0	-10000	0	0
spindle elongation	-0.012	0.035	-10000	0	-0.12	37	37
ODF2	0.015	0.002	-10000	0	-10000	0	0
BUB1	-0.013	0.036	-10000	0	-0.24	4	4
TPT1	-0.003	0.02	-10000	0	-0.088	16	16
CDC25C	0.001	0.019	-10000	0	-0.099	7	7
CDC25B	-0.007	0.074	-10000	0	-0.42	16	16
SGOL1	-0.006	0.012	-10000	0	-0.041	37	37
RHOA	0.017	0.001	-10000	0	-10000	0	0
CCNB1/CDK1	-0.2	0.2	-10000	0	-0.31	366	366
CDC14B	0.008	0.002	-10000	0	-10000	0	0
CDC20	-0.23	0.21	-10000	0	-0.41	304	304
PLK1/PBIP1	-0.18	0.083	-10000	0	-0.21	450	450
mitosis	-0.003	0.005	0.016	9	-0.021	21	30
FBXO5	-0.084	0.11	-10000	0	-0.21	196	196
CDC2	-0.15	0.21	-10000	0	-0.42	194	194
NDC80	-0.13	0.2	-10000	0	-0.41	184	184
metaphase plate congression	-0.002	0.021	-10000	0	-0.096	13	13
ERCC6L	-0.2	0.2	-10000	0	-0.3	366	366
NLP/gamma Tubulin	-0.008	0.024	-10000	0	-0.086	31	31
microtubule cytoskeleton organization	-0.003	0.02	-10000	0	-0.088	16	16
G2/M transition DNA damage checkpoint	-0.002	0.002	-10000	0	-0.008	21	21
PPP1R12A	0.016	0.019	-10000	0	-0.41	1	1
interphase	-0.002	0.002	-10000	0	-0.008	21	21
PLK1/PRC1-2	-0.15	0.2	-10000	0	-0.35	249	249
GRASP65/GM130/RAB1/GTP/PLK1	0.019	0.032	-10000	0	-0.13	13	13
RAB1A	0.017	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.014	0.055	-10000	0	-0.22	30	30
mitotic prometaphase	-0.001	0.001	-10000	0	-0.007	16	16
proteasomal ubiquitin-dependent protein catabolic process	-0.028	0.048	-10000	0	-0.11	19	19
microtubule-based process	-0.078	0.12	-10000	0	-0.24	187	187
Golgi organization	-0.012	0.035	-10000	0	-0.12	37	37
Cohesin/SA2	-0.014	0.059	-10000	0	-0.2	43	43
PPP1CB/MYPT1	0.022	0.023	-10000	0	-0.29	3	3
KIF20A	-0.13	0.2	-10000	0	-0.41	186	186
APC/C/CDC20	-0.13	0.13	-10000	0	-0.24	304	304
PPP2R1A	0.017	0.003	-10000	0	-10000	0	0
chromosome segregation	-0.17	0.082	-10000	0	-0.2	450	450
PRC1	-0.16	0.21	-10000	0	-0.41	224	224
ECT2	-0.081	0.12	-10000	0	-0.24	183	183
C13orf34	-0.014	0.055	-10000	0	-0.23	27	27
NUDC	-0.002	0.021	-10000	0	-0.096	13	13
regulation of attachment of spindle microtubules to kinetochore	-0.097	0.12	-10000	0	-0.21	242	242
spindle assembly	-0.01	0.031	-10000	0	-0.1	37	37
spindle stabilization	-0.008	0.02	-10000	0	-0.066	37	37
APC/C/HCDH1	0.018	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	-0.079	0.12	-10000	0	-0.24	187	187
CCNB1	-0.23	0.22	-10000	0	-0.42	296	296
PPP1CB	0.015	0.026	-10000	0	-0.41	2	2
BTRC	0.017	0	-10000	0	-10000	0	0
ROCK2	0.003	0.024	-10000	0	-0.12	8	8
TUBG1	-0.003	0.023	-10000	0	-0.1	17	17
G2/M transition of mitotic cell cycle	-0.2	0.19	-10000	0	-0.31	366	366
MLF1IP	-0.25	0.11	-10000	0	-0.3	450	450
INCENP	0.016	0.001	-10000	0	-10000	0	0

×

BARD1 signaling events

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
BARD1/CSTF1	-0.048	0.13	-10000	0	-0.28	126	126
ATM	-0.003	0.091	-10000	0	-0.41	25	25
UBE2D3	0.017	0.001	-10000	0	-10000	0	0
PRKDC	-0.002	0.088	-10000	0	-0.41	23	23
ATR	0.017	0	-10000	0	-10000	0	0
UBE2L3	0.017	0	-10000	0	-10000	0	0
FANCD2	0.005	0.042	-10000	0	-0.18	25	25
protein ubiquitination	-0.035	0.14	-10000	0	-0.24	149	149
XRCC5	0.017	0	-10000	0	-10000	0	0
XRCC6	0.017	0	-10000	0	-10000	0	0
M/R/N Complex	0.035	0	-10000	0	-10000	0	0
MRE11A	0.017	0	-10000	0	-10000	0	0
DNA-PK	0.023	0.055	-10000	0	-0.23	23	23
FA complex/FANCD2/Ubiquitin	0	0.071	-10000	0	-0.17	70	70
FANCF	0.015	0.026	-10000	0	-0.41	2	2
BRCA1	0.013	0.042	-10000	0	-0.41	5	5
CCNE1	0.011	0.049	-10000	0	-0.41	7	7
CDK2/Cyclin E1	0.006	0.082	-10000	0	-0.32	30	30
FANCG	-0.036	0.14	-10000	0	-0.41	66	66
BRCA1/BACH1/BARD1	-0.051	0.14	-10000	0	-0.29	127	127
FANCE	0.016	0.019	-10000	0	-0.41	1	1
FANCC	0.017	0	-10000	0	-10000	0	0
NBN	0.017	0	-10000	0	-10000	0	0
FANCA	0.017	0	-10000	0	-10000	0	0
DNA repair	-0.14	0.16	-10000	0	-0.34	154	154
BRCA1/BARD1/ubiquitin	-0.051	0.14	-10000	0	-0.29	127	127
BARD1/DNA-PK	-0.026	0.12	-10000	0	-0.22	139	139
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.048	0.13	0.28	126	-10000	0	126
BRCA1/BARD1/CTIP/M/R/N Complex	-0.1	0.1	-10000	0	-0.24	141	141
BRCA1/BACH1/BARD1/TopBP1	-0.032	0.12	-10000	0	-0.24	127	127
BRCA1/BARD1/P53	-0.048	0.15	-10000	0	-0.25	167	167
BARD1/CSTF1/BRCA1	-0.031	0.12	-10000	0	-0.24	127	127
BRCA1/BACH1	0.013	0.041	-10000	0	-0.41	5	5
BARD1	-0.085	0.18	-10000	0	-0.41	126	126
PCNA	-0.26	0.2	-10000	0	-0.41	343	343
BRCA1/BARD1/UbcH5C	-0.031	0.12	-10000	0	-0.24	127	127
BRCA1/BARD1/UbcH7	-0.031	0.12	-10000	0	-0.24	127	127
BRCA1/BARD1/RAD51/PCNA	-0.17	0.17	-10000	0	-0.27	360	360
BARD1/DNA-PK/P53	-0.045	0.15	-10000	0	-0.24	172	172
BRCA1/BARD1/Ubiquitin	-0.051	0.14	-10000	0	-0.29	127	127
BRCA1/BARD1/CTIP	-0.22	0.16	-10000	0	-0.28	424	424
FA complex	0.01	0.051	-10000	0	-0.12	68	68
BARD1/EWS	-0.048	0.13	-10000	0	-0.28	126	126
RBBP8	-0.23	0.14	-10000	0	-0.3	412	412
TP53	-0.039	0.14	-10000	0	-0.41	69	69
TOPBP1	0.016	0.019	-10000	0	-0.41	1	1
G1/S transition of mitotic cell cycle	0.049	0.14	0.25	167	-10000	0	167
BRCA1/BARD1	-0.032	0.15	-10000	0	-0.24	149	149
CSTF1	0.017	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.059	0.13	-10000	0	-0.29	126	126
CDK2	-0.005	0.094	-10000	0	-0.41	27	27
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.017	0	-10000	0	-10000	0	0
RAD50	0.017	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.051	0.14	-10000	0	-0.29	127	127
EWSR1	0.017	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.016	0.053	-10000	0	-0.28	16	16
AKT1	-0.048	0.11	-10000	0	-0.28	48	48
PTK2B	-0.088	0.13	-10000	0	-0.36	40	40
VEGFR2 homodimer/Frs2	0.021	0.072	-10000	0	-0.33	20	20
CAV1	-0.25	0.21	-10000	0	-0.41	325	325
CALM1	0.016	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.097	0.14	-10000	0	-0.22	289	289
endothelial cell proliferation	-0.039	0.1	-10000	0	-0.25	49	49
mol:Ca2+	-0.09	0.14	-10000	0	-0.4	39	39
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.13	0.18	-10000	0	-0.25	326	326
RP11-342D11.1	-0.096	0.13	-10000	0	-0.2	292	292
CDH5	-0.006	0.098	-10000	0	-0.41	29	29
VEGFA homodimer	-0.098	0.12	-10000	0	-0.21	288	288
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
SHC2	0.017	0	-10000	0	-10000	0	0
HRAS/GDP	-0.093	0.13	-10000	0	-0.37	55	55
SH2D2A	0.017	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.047	0.11	-10000	0	-0.31	36	36
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.095	0.14	-10000	0	-0.22	289	289
VEGFR1 homodimer	0.017	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.093	0.15	-10000	0	-0.41	55	55
GRB10	-0.095	0.15	-10000	0	-0.48	39	39
PTPN11	0.017	0	-10000	0	-10000	0	0
GRB2	0.017	0.002	-10000	0	-10000	0	0
PAK1	0.017	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.13	0.19	-10000	0	-0.25	327	327
HRAS	0.016	0.019	-10000	0	-0.41	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.034	0.077	-10000	0	-0.2	40	40
HIF1A	0.015	0.026	-10000	0	-0.41	2	2
FRS2	0.015	0.032	-10000	0	-0.41	3	3
oxygen and reactive oxygen species metabolic process	-0.13	0.17	-10000	0	-0.25	326	326
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.017	0	-10000	0	-10000	0	0
Nck/Pak	0.019	0.044	-10000	0	-0.28	11	11
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.097	0.14	-10000	0	-0.22	288	288
mol:GDP	-0.095	0.14	-10000	0	-0.4	55	55
mol:NADP	-0.041	0.098	-10000	0	-0.27	35	35
eNOS/Hsp90	-0.034	0.096	-10000	0	-0.26	35	35
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.091	0.14	-10000	0	-0.4	39	39
HIF1A/ARNT	0.024	0.019	-10000	0	-0.28	2	2
SHB	0.017	0	-10000	0	-10000	0	0
VEGFA	-0.21	0.22	-10000	0	-0.41	286	286
VEGFC	0.007	0.066	-10000	0	-0.41	13	13
FAK1/Vinculin	-0.058	0.12	-10000	0	-0.3	40	40
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.089	0.14	-10000	0	-0.2	295	295
PTPN6	0.008	0.061	-10000	0	-0.41	11	11
EPAS1	0.018	0.051	-10000	0	-0.24	17	17
mol:L-citrulline	-0.041	0.098	-10000	0	-0.27	35	35
ITGAV	0.004	0.073	-10000	0	-0.41	16	16
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.084	0.14	-10000	0	-0.2	289	289
VEGFR2 homodimer/VEGFA homodimer	-0.095	0.16	-10000	0	-0.22	292	292
VEGFR2/3 heterodimer	0.022	0.069	-10000	0	-0.35	17	17
VEGFB	0.017	0	-10000	0	-10000	0	0
MAPK11	-0.089	0.13	-10000	0	-0.39	39	39
VEGFR2 homodimer	0.016	0.08	-10000	0	-0.41	17	17
FLT1	0.017	0	-10000	0	-10000	0	0
NEDD4	0.008	0.066	-10000	0	-0.39	14	14
MAPK3	-0.086	0.12	-10000	0	-0.37	39	39
MAPK1	-0.086	0.12	-10000	0	-0.37	39	39
VEGFA145/NRP2	-0.14	0.16	-10000	0	-0.28	287	287
VEGFR1/2 heterodimer	0.022	0.069	-10000	0	-0.35	17	17
KDR	0.016	0.08	-10000	0	-0.41	17	17
VEGFA165/NRP1/VEGFR2 homodimer	-0.081	0.14	-10000	0	-0.4	39	39
SRC	0.017	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.084	0.13	-10000	0	-0.37	39	39
PI3K	-0.066	0.13	-10000	0	-0.33	51	51
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.1	0.14	-10000	0	-0.22	298	298
FES	-0.092	0.14	-10000	0	-0.41	39	39
GAB1	-0.077	0.13	-10000	0	-0.32	58	58
VEGFR2 homodimer/VEGFA homodimer/Src	-0.095	0.14	-10000	0	-0.22	289	289
CTNNB1	0.017	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0.017	0	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.14	0.14	-10000	0	-0.27	222	222
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.13	0.16	-10000	0	-0.24	325	325
PI3K/GAB1	-0.052	0.12	-10000	0	-0.3	51	51
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.079	0.14	-10000	0	-0.36	37	37
PRKACA	0.017	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.026	0.078	-10000	0	-0.28	28	28
HSP90AA1	0.017	0	-10000	0	-10000	0	0
CDC42	-0.092	0.14	-10000	0	-0.41	39	39
actin cytoskeleton reorganization	-0.095	0.14	-10000	0	-0.22	289	289
PTK2	-0.068	0.12	-10000	0	-0.32	40	40
EDG1	-0.089	0.14	-10000	0	-0.4	39	39
mol:DAG	-0.091	0.14	-10000	0	-0.4	39	39
CaM/Ca2+	-0.079	0.13	-10000	0	-0.37	39	39
MAP2K3	-0.085	0.13	-10000	0	-0.39	39	39
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.089	0.16	-10000	0	-0.49	39	39
PLCG1	-0.092	0.14	-10000	0	-0.41	39	39
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.082	0.14	-10000	0	-0.2	289	289
IQGAP1	-0.086	0.18	-10000	0	-0.41	127	127
YES1	-0.048	0.15	-10000	0	-0.41	80	80
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.095	0.14	-10000	0	-0.22	289	289
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.1	0.15	-10000	0	-0.22	297	297
cell migration	-0.076	0.14	-10000	0	-0.27	126	126
mol:PI-3-4-5-P3	-0.062	0.12	-10000	0	-0.31	51	51
FYN	0.015	0.026	-10000	0	-0.41	2	2
VEGFB/NRP1	-0.085	0.13	-10000	0	-0.38	39	39
mol:NO	-0.041	0.098	-10000	0	-0.27	35	35
PXN	0.017	0	-10000	0	-10000	0	0
HRAS/GTP	-0.11	0.12	-10000	0	-0.37	55	55
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.091	0.16	-10000	0	-0.49	39	39
VHL	0	0	-10000	0	-10000	0	0
ITGB3	0.017	0	-10000	0	-10000	0	0
NOS3	-0.045	0.11	-10000	0	-0.3	35	35
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.095	0.14	-10000	0	-0.22	289	289
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.084	0.13	-10000	0	-0.38	39	39
PRKCB	-0.088	0.13	-10000	0	-0.38	39	39
VCL	0.017	0	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.094	0.14	-10000	0	-0.21	292	292
VEGFR1/2 heterodimer/VEGFA homodimer	-0.095	0.14	-10000	0	-0.22	289	289
VEGFA165/NRP2	-0.14	0.16	-10000	0	-0.28	287	287
MAPKKK cascade	-0.083	0.15	0.25	1	-0.41	55	56
NRP2	0.016	0.019	-10000	0	-0.41	1	1
VEGFC homodimer	0.007	0.066	-10000	0	-0.41	13	13
NCK1	0.008	0.061	-10000	0	-0.41	11	11
ROCK1	0.017	0	-10000	0	-10000	0	0
FAK1/Paxillin	-0.058	0.12	-10000	0	-0.3	40	40
MAP3K13	-0.092	0.14	-10000	0	-0.41	39	39
PDPK1	-0.056	0.11	-10000	0	-0.28	51	51

×

Syndecan-4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.031	0.099	-9999	-0.22	104	104
Syndecan-4/Syndesmos	-0.066	0.12	-9999	-0.3	80	80
positive regulation of JNK cascade	-0.15	0.17	-9999	-0.35	176	176
Syndecan-4/ADAM12	-0.058	0.13	-9999	-0.29	80	80
CCL5	-0.006	0.096	-9999	-0.41	28	28
Rac1/GDP	0.013	0	-9999	-10000	0	0
DNM2	0.017	0	-9999	-10000	0	0
ITGA5	-0.043	0.15	-9999	-0.41	74	74
SDCBP	0.017	0	-9999	-10000	0	0
PLG	0.019	0.005	-9999	-10000	0	0
ADAM12	0.016	0.019	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.025	0.04	-9999	-0.1	69	69
Syndecan-4/Laminin alpha1	-0.066	0.12	-9999	-0.3	80	80
Syndecan-4/CXCL12/CXCR4	-0.15	0.18	-9999	-0.37	176	176
Syndecan-4/Laminin alpha3	-0.063	0.13	-9999	-0.3	89	89
MDK	-0.23	0.21	-9999	-0.41	300	300
Syndecan-4/FZD7	-0.15	0.16	-9999	-0.36	148	148
Syndecan-4/Midkine	-0.17	0.16	-9999	-0.36	173	173
FZD7	-0.18	0.21	-9999	-0.41	245	245
Syndecan-4/FGFR1/FGF	-0.045	0.13	-9999	-0.27	83	83
THBS1	-0.018	0.12	-9999	-0.41	43	43
integrin-mediated signaling pathway	-0.24	0.12	-9999	-0.36	229	229
positive regulation of MAPKKK cascade	-0.15	0.17	-9999	-0.35	176	176
Syndecan-4/TACI	-0.058	0.13	-9999	-0.29	80	80
CXCR4	-0.21	0.21	-9999	-0.41	276	276
cell adhesion	-0.026	0.091	-9999	-0.2	102	102
Syndecan-4/Dynamin	-0.058	0.13	-9999	-0.29	80	80
Syndecan-4/TSP1	-0.073	0.15	-9999	-0.33	96	96
Syndecan-4/GIPC	-0.058	0.13	-9999	-0.29	80	80
Syndecan-4/RANTES	-0.068	0.14	-9999	-0.32	90	90
ITGB1	0.017	0	-9999	-10000	0	0
LAMA1	0	0	-9999	-10000	0	0
LAMA3	0.005	0.071	-9999	-0.41	15	15
RAC1	0.017	0	-9999	-10000	0	0
PRKCA	0.021	0.03	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.073	0.14	-9999	-0.31	95	95
TFPI	-0.077	0.18	-9999	-0.41	116	116
F2	0.01	0.028	-9999	-0.42	2	2
alpha5/beta1 Integrin	-0.018	0.11	-9999	-0.28	74	74
positive regulation of cell adhesion	-0.064	0.13	-9999	-0.29	89	89
ACTN1	-0.017	0.12	-9999	-0.41	42	42
TNC	-0.39	0.089	-9999	-0.41	505	505
Syndecan-4/CXCL12	-0.063	0.14	-9999	-0.31	83	83
FGF6	0.017	0	-9999	-10000	0	0
RHOA	0.017	0.001	-9999	-10000	0	0
CXCL12	0.005	0.071	-9999	-0.41	15	15
TNFRSF13B	0.017	0	-9999	-10000	0	0
FGF2	0.015	0.026	-9999	-0.41	2	2
FGFR1	0.015	0.026	-9999	-0.41	2	2
Syndecan-4/PI-4-5-P2	-0.066	0.12	-9999	-0.3	80	80
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.064	0.17	-9999	-0.41	101	101
cell migration	-0.012	0.012	-9999	-10000	0	0
PRKCD	0.019	0.005	-9999	-10000	0	0
vasculogenesis	-0.071	0.14	-9999	-0.32	96	96
SDC4	-0.063	0.13	-9999	-0.23	181	181
Syndecan-4/Tenascin C	-0.24	0.13	-9999	-0.37	229	229
Syndecan-4/PI-4-5-P2/PKC alpha	-0.024	0.029	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.058	0.13	-9999	-0.29	80	80
MMP9	-0.13	0.2	-9999	-0.41	179	179
Rac1/GTP	-0.026	0.092	-9999	-0.2	101	101
cytoskeleton organization	-0.064	0.12	-9999	-0.29	80	80
GIPC1	0.017	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.1	0.15	-9999	-0.34	115	115

×

HIF-2-alpha transcription factor network

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
MMP14	-0.008	0.032	-10000	0	-0.41	2	2
oxygen homeostasis	-0.008	0.013	-10000	0	-10000	0	0
TCEB2	0.017	0	-10000	0	-10000	0	0
TCEB1	0.017	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.017	0.075	-10000	0	-0.15	31	31
EPO	-0.076	0.18	-10000	0	-0.28	182	182
FIH (dimer)	0.006	0.016	-10000	0	-10000	0	0
APEX1	0.005	0.021	-10000	0	-10000	0	0
SERPINE1	-0.18	0.28	-10000	0	-0.47	228	228
FLT1	-0.006	0.027	-10000	0	-10000	0	0
ADORA2A	-0.11	0.2	-10000	0	-0.34	182	182
germ cell development	-0.11	0.2	-10000	0	-0.34	189	189
SLC11A2	-0.11	0.21	-10000	0	-0.35	182	182
BHLHE40	-0.12	0.2	-10000	0	-0.35	189	189
HIF1AN	0.006	0.016	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.045	0.13	-10000	0	-0.26	43	43
ETS1	0.027	0.012	-10000	0	-10000	0	0
CITED2	-0.016	0.066	-10000	0	-0.4	14	14
KDR	-0.016	0.077	-10000	0	-0.42	17	17
PGK1	-0.11	0.21	-10000	0	-0.35	182	182
SIRT1	0.017	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.11	0.25	-10000	0	-0.39	182	182
EPAS1	-0.029	0.083	0.29	1	-0.18	31	32
SP1	0.023	0.004	-10000	0	-10000	0	0
ABCG2	-0.11	0.21	-10000	0	-0.35	184	184
EFNA1	-0.12	0.22	-10000	0	-0.36	191	191
FXN	-0.11	0.2	-10000	0	-0.33	187	187
POU5F1	-0.12	0.2	-10000	0	-0.35	189	189
neuron apoptosis	0.11	0.24	0.38	182	-10000	0	182
EP300	0.017	0	-10000	0	-10000	0	0
EGLN3	0.003	0.042	-10000	0	-0.44	4	4
EGLN2	0.006	0.016	-10000	0	-10000	0	0
EGLN1	0.006	0.025	-10000	0	-0.42	1	1
VHL/Elongin B/Elongin C	0.023	0	-10000	0	-10000	0	0
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.005	0.021	-10000	0	-10000	0	0
SLC2A1	-0.11	0.2	-10000	0	-0.34	183	183
TWIST1	-0.12	0.22	-10000	0	-0.36	192	192
ELK1	0.021	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.044	0.13	-10000	0	-0.26	43	43
VEGFA	-0.21	0.28	-10000	0	-0.42	298	298
CREBBP	0.017	0	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.016	0.019	-10000	0	-0.41	1	1
LAT2	-0.058	0.1	-10000	0	-0.24	78	78
AP1	-0.063	0.12	-10000	0	-0.27	99	99
mol:PIP3	-0.054	0.11	-10000	0	-0.27	66	66
IKBKB	-0.026	0.07	-10000	0	-0.18	41	41
AKT1	-0.056	0.11	0.23	12	-0.24	35	47
IKBKG	-0.026	0.07	-10000	0	-0.18	41	41
MS4A2	0.021	0.005	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	-0.004	0.091	-10000	0	-0.41	25	25
MAP3K1	-0.041	0.095	-10000	0	-0.21	81	81
mol:Ca2+	-0.041	0.092	-10000	0	-0.21	66	66
LYN	-0.038	0.14	-10000	0	-0.42	64	64
CBLB	-0.057	0.1	-10000	0	-0.24	76	76
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
RasGAP/p62DOK	0.024	0.044	-10000	0	-0.21	18	18
positive regulation of cell migration	0.009	0.001	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.078	0.1	-10000	0	-0.18	260	260
PTPN13	-0.049	0.1	-10000	0	-0.31	37	37
PTPN11	0.013	0.01	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.027	0.089	0.21	9	-0.2	40	49
SYK	-0.015	0.11	-10000	0	-0.42	36	36
GRB2	0.017	0.002	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.078	0.1	-10000	0	-0.28	66	66
LAT	-0.058	0.1	-10000	0	-0.26	67	67
PAK2	-0.048	0.1	-10000	0	-0.24	80	80
NFATC2	-0.039	0.04	-10000	0	-0.079	260	260
HRAS	-0.046	0.099	-10000	0	-0.24	71	71
GAB2	0.016	0.019	-10000	0	-0.41	1	1
PLA2G1B	0.031	0.021	-10000	0	-10000	0	0
Fc epsilon R1	-0.1	0.14	-10000	0	-0.24	260	260
Antigen/IgE/Fc epsilon R1	-0.09	0.13	-10000	0	-0.22	260	260
mol:GDP	-0.045	0.096	-10000	0	-0.23	69	69
JUN	0.016	0.019	-10000	0	-0.41	1	1
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.015	0.004	-10000	0	-10000	0	0
FOS	-0.084	0.18	-10000	0	-0.41	125	125
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.063	0.11	-10000	0	-0.16	260	260
CHUK	-0.026	0.07	-10000	0	-0.18	42	42
KLRG1	-0.06	0.1	-10000	0	-0.24	76	76
VAV1	-0.059	0.1	-10000	0	-0.24	76	76
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.057	0.1	-10000	0	-0.24	76	76
negative regulation of mast cell degranulation	-0.057	0.095	-10000	0	-0.23	76	76
BTK	-0.047	0.094	-10000	0	-0.23	69	69
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.07	0.11	-10000	0	-0.2	156	156
GAB2/PI3K/SHP2	-0.086	0.09	-10000	0	-0.22	73	73
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.077	0.13	-10000	0	-0.18	268	268
RAF1	0.025	0.019	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.13	0.17	-10000	0	-0.27	283	283
FCER1G	-0.19	0.22	-10000	0	-0.41	256	256
FCER1A	0.005	0.059	-10000	0	-0.42	10	10
Antigen/IgE/Fc epsilon R1/Fyn	-0.078	0.12	-10000	0	-0.2	260	260
MAPK3	0.032	0.02	-10000	0	-10000	0	0
MAPK1	0.028	0.027	-10000	0	-10000	0	0
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.004	0.076	-10000	0	-0.34	21	21
DUSP1	0.002	0.078	-10000	0	-0.41	18	18
NF-kappa-B/RelA	-0.014	0.047	-10000	0	-0.13	37	37
actin cytoskeleton reorganization	-0.043	0.099	-10000	0	-0.32	28	28
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.044	0.1	-10000	0	-0.24	76	76
FER	-0.057	0.1	-10000	0	-0.26	66	66
RELA	0.017	0	-10000	0	-10000	0	0
ITK	-0.011	0.032	-10000	0	-0.091	32	32
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.044	0.099	-10000	0	-0.24	65	65
cytokine secretion	-0.02	0.026	-10000	0	-0.093	35	35
SPHK1	-0.065	0.11	-10000	0	-0.27	80	80
PTK2	-0.045	0.1	-10000	0	-0.33	28	28
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.081	0.1	-10000	0	-0.29	66	66
EDG1	0.009	0.001	-10000	0	-10000	0	0
mol:DAG	-0.05	0.11	-10000	0	-0.26	67	67
MAP2K2	0.026	0.016	-10000	0	-10000	0	0
MAP2K1	0.029	0.025	-10000	0	-10000	0	0
MAP2K7	0.017	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.055	0.1	-10000	0	-0.25	66	66
MAP2K4	-0.008	0.14	-10000	0	-0.72	21	21
Fc epsilon R1/FcgammaRIIB	-0.14	0.18	-10000	0	-0.29	283	283
mol:Choline	-0.077	0.1	-10000	0	-0.18	260	260
SHC/Grb2/SOS1	-0.063	0.12	-10000	0	-0.27	95	95
FYN	0.015	0.026	-10000	0	-0.41	2	2
DOK1	0.017	0	-10000	0	-10000	0	0
PXN	-0.039	0.096	-10000	0	-0.31	28	28
HCLS1	-0.094	0.16	-10000	0	-0.34	122	122
PRKCB	-0.04	0.09	-10000	0	-0.21	67	67
FCGR2B	-0.088	0.18	-10000	0	-0.41	129	129
IGHE	-0.004	0.006	-10000	0	-10000	0	0
KLRG1/SHIP	-0.057	0.096	-10000	0	-0.23	76	76
LCP2	-0.008	0.1	-10000	0	-0.41	30	30
PLA2G4A	-0.11	0.14	-10000	0	-0.27	181	181
RASA1	0.017	0.002	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.077	0.1	-10000	0	-0.18	260	260
IKK complex	-0.014	0.056	-10000	0	-0.14	39	39
WIPF1	0.008	0.061	-10000	0	-0.41	11	11

×

Aurora B signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.16	0.18	-9999	-0.22	406	406
STMN1	0.001	0.067	-9999	-0.29	27	27
Aurora B/RasGAP/Survivin	-0.083	0.15	-9999	-0.26	208	208
Chromosomal passenger complex/Cul3 protein complex	-0.038	0.085	-9999	-0.13	212	212
BIRC5	-0.16	0.21	-9999	-0.42	212	212
DES	-0.004	0.058	-9999	-0.24	11	11
Aurora C/Aurora B/INCENP	0.017	0.057	-9999	-0.22	29	29
Aurora B/TACC1	0.009	0.057	-9999	-0.23	27	27
Aurora B/PP2A	0.009	0.069	-9999	-0.29	27	27
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.007	0.021	-9999	-0.082	27	27
mitotic metaphase/anaphase transition	0	0.003	-9999	-10000	0	0
NDC80	-0.1	0.17	-9999	-0.33	185	185
Cul3 protein complex	0.023	0.003	-9999	-10000	0	0
KIF2C	-0.046	0.1	-9999	-0.17	161	161
PEBP1	0.014	0.005	-9999	-10000	0	0
KIF20A	-0.14	0.21	-9999	-0.42	186	186
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.008	0.069	-9999	-0.29	27	27
SEPT1	0	0	-9999	-10000	0	0
SMC2	-0.032	0.14	-9999	-0.41	61	61
SMC4	-0.31	0.18	-9999	-0.41	402	402
NSUN2/NPM1/Nucleolin	-0.023	0.078	-9999	-0.28	30	30
PSMA3	0.017	0.001	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.003	-9999	-10000	0	0
H3F3B	0.004	0.044	-9999	-0.19	27	27
AURKB	-0.006	0.097	-9999	-0.42	27	27
AURKC	0.015	0.026	-9999	-0.41	2	2
CDCA8	0	0.079	-9999	-0.43	17	17
cytokinesis	-0.11	0.2	-9999	-0.34	187	187
Aurora B/Septin1	-0.1	0.19	-9999	-0.33	187	187
AURKA	0.001	0.08	-9999	-0.42	19	19
INCENP	0.013	0.007	-9999	-10000	0	0
KLHL13	0	0	-9999	-10000	0	0
BUB1	0.014	0.038	-9999	-0.42	4	4
hSgo1/Aurora B/Survivin	-0.084	0.14	-9999	-0.24	212	212
EVI5	0.016	0.002	-9999	-10000	0	0
RhoA/GTP	-0.12	0.22	-9999	-0.35	204	204
SGOL1	0	0	-9999	-10000	0	0
CENPA	-0.039	0.11	-9999	-0.25	87	87
NCAPG	-0.077	0.18	-9999	-0.41	116	116
Aurora B/HC8 Proteasome	0.009	0.069	-9999	-0.29	27	27
NCAPD2	-0.068	0.17	-9999	-0.41	105	105
Aurora B/PP1-gamma	0.009	0.069	-9999	-0.29	27	27
RHOA	0.017	0.001	-9999	-10000	0	0
NCAPH	0.004	0.073	-9999	-0.41	16	16
NPM1	-0.009	0.064	-9999	-0.24	32	32
RASA1	0.017	0.002	-9999	-10000	0	0
KLHL9	0.017	0.003	-9999	-10000	0	0
mitotic prometaphase	-0.003	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.068	-9999	-0.29	27	27
PPP1CC	0.017	0.001	-9999	-10000	0	0
Centraspindlin	-0.13	0.23	-9999	-0.38	205	205
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
NSUN2	-0.013	0.055	-9999	-0.24	27	27
MYLK	-0.003	0.059	-9999	-0.2	42	42
KIF23	-0.049	0.16	-9999	-0.42	79	79
VIM	-0.01	0.085	-9999	-0.29	45	45
RACGAP1	-0.12	0.2	-9999	-0.42	166	166
mitosis	0	0	-9999	-10000	0	0
NCL	-0.006	0.055	-9999	-0.23	27	27
Chromosomal passenger complex	-0.066	0.13	-9999	-0.21	186	186
Chromosomal passenger complex/EVI5	-0.069	0.16	-9999	-0.24	212	212
TACC1	0.017	0.001	-9999	-10000	0	0
PPP2R5D	0.017	0	-9999	-10000	0	0
CUL3	0.017	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.031	0.016	-9999	-0.22	2	2
VEGFR1 homodimer/NRP1	0.019	0.015	-9999	-0.23	2	2
mol:DAG	0.019	0.047	-9999	-0.2	23	23
VEGFR1 homodimer/NRP1/VEGFR 121	-0.099	0.12	-9999	-0.21	288	288
CaM/Ca2+	0.026	0.045	-9999	-0.18	22	22
HIF1A	0.024	0.026	-9999	-0.4	2	2
GAB1	0.014	0.037	-9999	-0.41	4	4
AKT1	0.016	0.059	-9999	-0.31	3	3
PLCG1	0.019	0.047	-9999	-0.2	23	23
NOS3	0.03	0.042	-9999	-0.19	3	3
CBL	0.017	0	-9999	-10000	0	0
mol:NO	0.03	0.042	-9999	-0.19	3	3
FLT1	0.025	0.018	-9999	-0.27	2	2
PGF	0	0.084	-9999	-0.41	21	21
VEGFR1 homodimer/NRP2/VEGFR121	-0.092	0.12	-9999	-0.2	289	289
CALM1	0.016	0.004	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
eNOS/Hsp90	0.039	0.042	-9999	-0.2	2	2
endothelial cell proliferation	0.021	0.04	-9999	-0.17	23	23
mol:Ca2+	0.018	0.046	-9999	-0.2	23	23
MAPK3	0.019	0.04	-9999	-0.17	23	23
MAPK1	0.018	0.04	-9999	-0.17	23	23
PIK3R1	0.016	0.004	-9999	-10000	0	0
PLGF homodimer	0	0.084	-9999	-0.41	21	21
PRKACA	0.017	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.25	0.21	-9999	-0.41	325	325
VEGFA homodimer	-0.22	0.21	-9999	-0.41	286	286
VEGFR1 homodimer/VEGFA homodimer	-0.11	0.13	-9999	-0.23	288	288
platelet activating factor biosynthetic process	0.02	0.039	-9999	-10000	0	0
PI3K	0.026	0.069	-9999	-0.2	43	43
PRKCA	0.018	0.043	-9999	-0.18	23	23
PRKCB	0.013	0.042	-9999	-0.18	23	23
VEGFR1 homodimer/PLGF homodimer	0.021	0.053	-9999	-0.23	23	23
VEGFA	-0.22	0.21	-9999	-0.41	286	286
VEGFB	0.017	0	-9999	-10000	0	0
mol:IP3	0.019	0.047	-9999	-0.2	23	23
RASA1	0.027	0.014	-9999	-0.2	2	2
NRP2	0.016	0.019	-9999	-0.41	1	1
VEGFR1 homodimer	0.025	0.018	-9999	-0.27	2	2
VEGFB homodimer	0.017	0	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
eNOS/Caveolin-1	-0.079	0.1	-9999	-0.25	34	34
PTPN11	0.017	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.025	0.068	-9999	-0.19	43	43
mol:L-citrulline	0.03	0.042	-9999	-0.19	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.099	0.13	-9999	-0.2	314	314
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.096	0.12	-9999	-0.2	297	297
CD2AP	-0.023	0.12	-9999	-0.41	49	49
PI3K/GAB1	0.031	0.07	-9999	-0.19	46	46
PDPK1	0.014	0.06	-9999	-0.18	43	43
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.092	0.12	-9999	-0.2	288	288
mol:NADP	0.03	0.042	-9999	-0.19	3	3
HSP90AA1	0.017	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.098	0.13	-9999	-0.2	314	314
VEGFR1 homodimer/NRP2	0.031	0.019	-9999	-0.23	3	3

×

Regulation of nuclear SMAD2/3 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
EP300	0.008	0.012	-10000	0	-10000	0	0
HSPA8	0.019	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.018	0.16	0.18	26	-0.26	121	147
AKT1	0.016	0.037	-10000	0	-0.41	4	4
GSC	0.017	0.037	0.12	5	-10000	0	5
NKX2-5	0.016	0.007	-10000	0	-10000	0	0
muscle cell differentiation	0.025	0.098	0.23	66	-10000	0	66
SMAD2-3/SMAD4/SP1	-0.083	0.15	-10000	0	-0.28	133	133
SMAD4	-0.11	0.2	-10000	0	-0.42	137	137
CBFB	0.014	0.037	-10000	0	-0.41	4	4
SAP18	0.018	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.007	0.059	-10000	0	-0.24	25	25
SMAD3/SMAD4/VDR	-0.034	0.11	-10000	0	-0.25	77	77
MYC	-0.097	0.19	-10000	0	-0.42	137	137
CDKN2B	0.043	0.053	-10000	0	-10000	0	0
AP1	-0.074	0.14	-10000	0	-0.29	122	122
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.013	0.095	-10000	0	-0.19	88	88
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.065	-10000	0	-0.21	12	12
SP3	-0.045	0.15	-10000	0	-0.41	77	77
CREB1	0.017	0	-10000	0	-10000	0	0
FOXH1	0.016	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.037	0.14	-10000	0	-0.26	123	123
GATA3	0.018	0.041	-10000	0	-0.41	5	5
SKI/SIN3/HDAC complex/NCoR1	0.005	0.058	-10000	0	-0.17	21	21
MEF2C/TIF2	-0.016	0.083	-10000	0	-0.2	54	54
endothelial cell migration	0.16	0.2	0.4	215	-10000	0	215
MAX	0.025	0.012	-10000	0	-10000	0	0
RBBP7	0.018	0.001	-10000	0	-10000	0	0
RBBP4	-0.064	0.17	-10000	0	-0.41	101	101
RUNX2	0.017	0	-10000	0	-10000	0	0
RUNX3	0.015	0.032	-10000	0	-0.41	3	3
RUNX1	0.017	0	-10000	0	-10000	0	0
CTBP1	0.017	0.002	-10000	0	-10000	0	0
NR3C1	0.025	0.012	-10000	0	-10000	0	0
VDR	0.017	0	-10000	0	-10000	0	0
CDKN1A	-0.098	0.17	-10000	0	-0.37	112	112
KAT2B	-0.003	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.034	0.11	-10000	0	-0.23	113	113
DCP1A	0.017	0	-10000	0	-10000	0	0
SKI	0.018	0.001	-10000	0	-10000	0	0
SERPINE1	-0.16	0.2	-10000	0	-0.4	215	215
SMAD3/SMAD4/ATF2	-0.058	0.14	-10000	0	-0.26	133	133
SMAD3/SMAD4/ATF3	-0.11	0.18	-10000	0	-0.31	208	208
SAP30	0.018	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.016	0.029	-10000	0	-0.24	2	2
JUN	-0.077	0.14	-10000	0	-0.28	120	120
SMAD3/SMAD4/IRF7	-0.058	0.15	-10000	0	-0.28	126	126
TFE3	-0.032	0.06	-10000	0	-0.14	52	52
COL1A2	-0.2	0.21	-10000	0	-0.41	261	261
mesenchymal cell differentiation	0.058	0.14	0.26	136	-10000	0	136
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.017	0	-10000	0	-10000	0	0
FOS	-0.094	0.18	-10000	0	-0.42	125	125
SMAD3/SMAD4/Max	-0.037	0.14	-10000	0	-0.26	127	127
Cbp/p300/SNIP1	0.029	0.008	-10000	0	-10000	0	0
ZBTB17	0.015	0	-10000	0	-10000	0	0
LAMC1	-0.18	0.24	-10000	0	-0.45	217	217
TGIF2/HDAC complex/SMAD3/SMAD4	-0.061	0.15	-10000	0	-0.27	139	139
IRF7	0.01	0.064	-10000	0	-0.41	12	12
ESR1	0.03	0.017	-10000	0	-10000	0	0
HNF4A	0.017	0	-10000	0	-10000	0	0
MEF2C	-0.024	0.085	-10000	0	-0.22	57	57
SMAD2-3/SMAD4	-0.058	0.14	-10000	0	-0.26	130	130
Cbp/p300/Src-1	0.022	0.017	-10000	0	-10000	0	0
IGHV3OR16-13	-0.012	0.026	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.011	0.052	-10000	0	-0.41	8	8
CREBBP	0.011	0.008	-10000	0	-10000	0	0
SKIL	0.017	0	-10000	0	-10000	0	0
HDAC1	-0.036	0.14	-10000	0	-0.41	66	66
HDAC2	0.014	0.042	-10000	0	-0.41	5	5
SNIP1	0.018	0.002	-10000	0	-10000	0	0
GCN5L2	0.01	0.009	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.11	0.18	-10000	0	-0.29	247	247
MSG1/HSC70	0.013	0.066	-10000	0	-0.28	25	25
SMAD2	0.018	0.008	-10000	0	-10000	0	0
SMAD3	-0.023	0.062	-10000	0	-0.16	4	4
SMAD3/E2F4-5/DP1/p107/SMAD4	-0.026	0.085	-10000	0	-0.18	89	89
SMAD2/SMAD2/SMAD4	-0.028	0.076	0.15	1	-0.15	116	117
NCOR1	0.018	0.001	-10000	0	-10000	0	0
NCOA2	0.017	0	-10000	0	-10000	0	0
NCOA1	0.017	0.003	-10000	0	-10000	0	0
MYOD/E2A	0.025	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	-0.069	0.14	-10000	0	-0.28	105	105
IFNB1	-0.054	0.12	-10000	0	-0.28	85	85
SMAD3/SMAD4/MEF2C	-0.024	0.11	-10000	0	-0.26	57	57
CITED1	-0.003	0.091	-10000	0	-0.41	25	25
SMAD2-3/SMAD4/ARC105	-0.041	0.12	-10000	0	-0.23	117	117
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.005	0.07	-10000	0	-0.23	9	9
RUNX1-3/PEBPB2	0.031	0.031	-10000	0	-0.23	7	7
SMAD7	-0.083	0.15	-10000	0	-0.3	136	136
MYC/MIZ-1	-0.06	0.14	-10000	0	-0.29	137	137
SMAD3/SMAD4	-0.17	0.14	-10000	0	-0.27	289	289
IL10	-0.048	0.12	-10000	0	-0.28	78	78
PIASy/HDAC complex	0.022	0.006	-10000	0	-10000	0	0
PIAS3	0.013	0.027	-10000	0	-0.42	2	2
CDK2	-0.01	0.094	-10000	0	-0.41	27	27
IL5	-0.048	0.12	-10000	0	-0.29	73	73
CDK4	-0.27	0.2	-10000	0	-0.42	343	343
PIAS4	0.022	0.006	-10000	0	-10000	0	0
ATF3	-0.071	0.17	-10000	0	-0.41	108	108
SMAD3/SMAD4/SP1	-0.11	0.16	-10000	0	-0.28	193	193
FOXG1	0.016	0.006	-10000	0	-10000	0	0
FOXO3	0.018	0.026	-10000	0	-0.28	4	4
FOXO1	0.012	0.053	-10000	0	-0.3	14	14
FOXO4	0.018	0.026	-10000	0	-0.28	4	4
heart looping	-0.024	0.085	-10000	0	-0.21	57	57
CEBPB	0.009	0.061	-10000	0	-0.41	11	11
SMAD3/SMAD4/DLX1	-0.066	0.14	-10000	0	-0.26	143	143
MYOD1	0.017	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.058	0.14	-10000	0	-0.27	128	128
SMAD3/SMAD4/GATA3	-0.05	0.15	-10000	0	-0.28	121	121
SnoN/SIN3/HDAC complex/NCoR1	0.017	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.03	0.13	-10000	0	-0.25	91	91
SMAD3/SMAD4/SP1-3	-0.12	0.2	-10000	0	-0.37	147	147
MED15	0.017	0	-10000	0	-10000	0	0
SP1	-0.029	0.053	-10000	0	-0.15	4	4
SIN3B	0.018	0.001	-10000	0	-10000	0	0
SIN3A	0.001	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.014	0.1	-10000	0	-0.2	113	113
ITGB5	-0.12	0.18	-10000	0	-0.37	130	130
TGIF/SIN3/HDAC complex/CtBP	-0.073	0.086	-10000	0	-0.19	139	139
SMAD3/SMAD4/AR	-0.062	0.14	-10000	0	-0.27	141	141
AR	0.011	0.052	-10000	0	-0.41	8	8
negative regulation of cell growth	-0.043	0.1	-10000	0	-0.2	128	128
SMAD3/SMAD4/MYOD	-0.058	0.14	-10000	0	-0.26	133	133
E2F5	0.017	0	-10000	0	-10000	0	0
E2F4	0.017	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.017	0.097	-10000	0	-0.19	111	111
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.074	-10000	0	-0.22	20	20
TFDP1	0.005	0.071	-10000	0	-0.41	15	15
SMAD3/SMAD4/AP1	-0.066	0.15	-10000	0	-0.29	121	121
SMAD3/SMAD4/RUNX2	-0.058	0.14	-10000	0	-0.26	134	134
TGIF2	0.011	0.052	-10000	0	-0.41	8	8
TGIF1	-0.28	0.2	-10000	0	-0.41	372	372
ATF2	0.017	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.032	0.13	-9999	-0.42	51	51
PDGF/PDGFRA/CRKL	-0.007	0.089	-9999	-0.28	51	51
positive regulation of JUN kinase activity	-0.014	0.092	-9999	-0.21	93	93
CRKL	0.017	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.007	0.089	-9999	-0.28	51	51
AP1	-0.089	0.19	-9999	-0.41	125	125
mol:IP3	-0.021	0.091	-9999	-0.29	51	51
PLCG1	-0.021	0.091	-9999	-0.29	51	51
PDGF/PDGFRA/alphaV Integrin	-0.016	0.1	-9999	-0.28	67	67
RAPGEF1	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
mol:Ca2+	-0.021	0.091	-9999	-0.29	51	51
CAV3	0.017	0	-9999	-10000	0	0
CAV1	-0.25	0.21	-9999	-0.41	325	325
SHC/Grb2/SOS1	-0.013	0.093	-9999	-0.21	93	93
PDGF/PDGFRA/Shf	-0.021	0.086	-9999	-0.28	51	51
FOS	-0.091	0.18	-9999	-0.41	125	125
JUN	-0.011	0.027	-9999	-0.34	1	1
oligodendrocyte development	-0.016	0.1	-9999	-0.28	67	67
GRB2	0.017	0.002	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
mol:DAG	-0.021	0.091	-9999	-0.29	51	51
PDGF/PDGFRA	-0.032	0.13	-9999	-0.42	51	51
actin cytoskeleton reorganization	-0.007	0.089	-9999	-0.28	51	51
SRF	0.02	0.007	-9999	-10000	0	0
SHC1	-0.021	0.12	-9999	-0.41	47	47
PI3K	-0.006	0.093	-9999	-0.24	69	69
PDGF/PDGFRA/Crk/C3G	0.007	0.077	-9999	-0.23	51	51
JAK1	-0.016	0.086	-9999	-0.28	51	51
ELK1/SRF	-0.004	0.062	-9999	-0.18	51	51
SHB	0.017	0	-9999	-10000	0	0
SHF	0	0	-9999	-10000	0	0
CSNK2A1	0.023	0.014	-9999	-10000	0	0
GO:0007205	-0.022	0.086	-9999	-0.28	51	51
SOS1	0	0	-9999	-10000	0	0
Ras protein signal transduction	-0.014	0.092	-9999	-0.21	93	93
PDGF/PDGFRA/SHB	-0.007	0.089	-9999	-0.28	51	51
PDGF/PDGFRA/Caveolin-1	-0.2	0.17	-9999	-0.31	348	348
ITGAV	0.004	0.073	-9999	-0.41	16	16
ELK1	-0.02	0.077	-9999	-0.24	51	51
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PDGF/PDGFRA/Crk	-0.007	0.089	-9999	-0.28	51	51
JAK-STAT cascade	-0.016	0.086	-9999	-0.28	51	51
cell proliferation	-0.021	0.086	-9999	-0.28	51	51

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.11	0.059	-10000	0	-0.13	456	456
epithelial cell differentiation	0.029	0.042	-10000	0	-0.19	18	18
CYFIP2	0.01	0.008	-10000	0	-10000	0	0
ENAH	0.008	0.072	-10000	0	-0.26	21	21
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
EPHA2	0.006	0.069	-10000	0	-0.41	14	14
MYO6	0.018	0.037	-10000	0	-0.18	18	18
CTNNB1	0.017	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.02	0.017	-10000	0	-10000	0	0
AQP5	0.027	0.033	-10000	0	-10000	0	0
CTNND1	0.009	0.058	-10000	0	-0.41	10	10
mol:PI-4-5-P2	0.017	0.036	-10000	0	-0.18	17	17
regulation of calcium-dependent cell-cell adhesion	0.018	0.037	-10000	0	-0.18	18	18
EGF	0.015	0.026	-10000	0	-0.41	2	2
NCKAP1	0.017	0	-10000	0	-10000	0	0
AQP3	0.024	0.045	-10000	0	-0.32	3	3
cortical microtubule organization	0.029	0.042	-10000	0	-0.19	18	18
GO:0000145	0.012	0.033	-10000	0	-0.17	17	17
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.033	0.043	-10000	0	-0.19	18	18
MLLT4	0.017	0	-10000	0	-10000	0	0
ARF6/GDP	-0.019	0.068	-10000	0	-0.35	15	15
ARF6	0.017	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.022	0.084	-10000	0	-0.26	38	38
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.015	0.078	-10000	0	-0.22	39	39
PVRL2	0.017	0	-10000	0	-10000	0	0
ZYX	-0.032	0.098	-10000	0	-0.19	140	140
ARF6/GTP	0.028	0.08	-10000	0	-0.24	38	38
CDH1	0.011	0.052	-10000	0	-0.41	8	8
EGFR/EGFR/EGF/EGF	-0.05	0.11	-10000	0	-0.18	207	207
RhoA/GDP	0.03	0.039	-10000	0	-0.18	18	18
actin cytoskeleton organization	0.019	0.035	-10000	0	-0.17	18	18
IGF-1R heterotetramer	0.017	0	-10000	0	-10000	0	0
GIT1	0.017	0	-10000	0	-10000	0	0
IGF1R	0.017	0	-10000	0	-10000	0	0
IGF1	0.014	0.037	-10000	0	-0.41	4	4
DIAPH1	-0.13	0.2	-10000	0	-0.36	226	226
Wnt receptor signaling pathway	-0.029	0.042	0.19	18	-10000	0	18
RHOA	0.017	0.001	-10000	0	-10000	0	0
RhoA/GTP	-0.019	0.068	-10000	0	-0.35	15	15
CTNNA1	0.017	0	-10000	0	-10000	0	0
VCL	0.019	0.036	-10000	0	-0.17	18	18
EFNA1	-0.002	0.088	-10000	0	-0.41	23	23
LPP	0.003	0.068	-10000	0	-0.19	55	55
Ephrin A1/EPHA2	0.012	0.071	-10000	0	-0.2	47	47
SEC6/SEC8	-0.005	0.029	-10000	0	-0.16	18	18
MGAT3	0.018	0.037	-10000	0	-0.18	18	18
HGF/MET	0.022	0.052	-10000	0	-0.19	27	27
HGF	0.015	0.026	-10000	0	-0.41	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.11	0.059	-10000	0	-0.13	456	456
actin cable formation	-0.006	0.07	-10000	0	-0.23	27	27
KIAA1543	0.007	0.034	-10000	0	-0.18	18	18
KIFC3	0.018	0.037	-10000	0	-0.18	18	18
NCK1	0.008	0.061	-10000	0	-0.41	11	11
EXOC3	0.017	0	-10000	0	-10000	0	0
ACTN1	0.002	0.072	-10000	0	-0.2	54	54
NCK1/GIT1	0.019	0.044	-10000	0	-0.28	11	11
mol:GDP	0.029	0.042	-10000	0	-0.19	18	18
EXOC4	0	0	-10000	0	-10000	0	0
STX4	0.018	0.037	-10000	0	-0.18	18	18
PIP5K1C	0.018	0.036	-10000	0	-0.18	17	17
LIMA1	-0.35	0.15	-10000	0	-0.41	454	454
ABI1	0.017	0	-10000	0	-10000	0	0
ROCK1	0.015	0.069	-10000	0	-0.31	15	15
adherens junction assembly	0.015	0.037	-10000	0	-0.17	11	11
IGF-1R heterotetramer/IGF1	0.025	0.044	-10000	0	-0.19	20	20
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.025	0	-10000	0	-10000	0	0
MET	0.009	0.058	-10000	0	-0.41	10	10
PLEKHA7	0.007	0.036	-10000	0	-0.18	18	18
mol:GTP	0.021	0.084	-10000	0	-0.26	38	38
establishment of epithelial cell apical/basal polarity	0.026	0.033	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.11	0.059	-10000	0	-0.13	456	456
regulation of cell-cell adhesion	0.019	0.035	-10000	0	-0.17	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.11	0.059	-10000	0	-0.13	456	456

×

S1P1 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.14	0.16	-9999	-0.29	289	289
PDGFRB	0.014	0.032	-9999	-0.41	3	3
SPHK1	-0.006	0.041	-9999	-0.2	19	19
mol:S1P	-0.005	0.051	-9999	-0.2	26	26
S1P1/S1P/Gi	-0.08	0.1	-9999	-0.27	83	83
GNAO1	0.002	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB/PLCgamma1	-0.064	0.088	-9999	-0.23	78	78
PLCG1	-0.068	0.093	-9999	-0.25	77	77
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.014	0.032	-9999	-0.41	3	3
GNAI2	0.022	0.004	-9999	-10000	0	0
GNAI3	-0.036	0.14	-9999	-0.41	65	65
GNAI1	0.013	0.019	-9999	-0.41	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.11	0.14	-9999	-0.23	289	289
S1P1/S1P	-0.074	0.11	-9999	-0.28	42	42
negative regulation of cAMP metabolic process	-0.079	0.099	-9999	-0.26	83	83
MAPK3	-0.076	0.11	-9999	-0.29	75	75
calcium-dependent phospholipase C activity	0	0.002	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
KDR	0.007	0.076	-9999	-0.41	17	17
PLCB2	-0.067	0.1	-9999	-0.26	41	41
RAC1	0.017	0	-9999	-10000	0	0
RhoA/GTP	-0.068	0.092	-9999	-0.25	41	41
receptor internalization	-0.071	0.1	-9999	-0.27	42	42
PTGS2	-0.084	0.12	-9999	-0.32	70	70
Rac1/GTP	-0.068	0.092	-9999	-0.25	41	41
RHOA	0.017	0.001	-9999	-10000	0	0
VEGFA	-0.21	0.21	-9999	-0.4	286	286
negative regulation of T cell proliferation	-0.079	0.099	-9999	-0.26	83	83
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
MAPK1	-0.074	0.11	-9999	-0.29	73	73
S1P1/S1P/PDGFB-D/PDGFRB	-0.07	0.12	-9999	-0.3	43	43
ABCC1	0.01	0.056	-9999	-0.41	9	9

×

TCGA08_p53

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
CDKN2A	-0.024	0.093	-10000	0	-0.29	58	58
TP53	-0.02	0.066	0.15	18	-0.17	57	75
Senescence	-0.02	0.066	0.15	18	-0.17	57	75
Apoptosis	-0.02	0.066	0.15	18	-0.17	57	75
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.009	0.07	0.16	52	-0.26	18	70
MDM4	0.007	0.066	-10000	0	-0.41	13	13

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.031	-9999	-0.28	5	5
CRKL	0.017	0	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
DOCK1	0.017	0	-9999	-10000	0	0
ITGA4	0.013	0.042	-9999	-0.41	5	5
alpha4/beta7 Integrin/MAdCAM1	0.041	0.034	-9999	-0.29	5	5
EPO	0.017	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.022	0.041	-9999	-0.38	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.023	0.03	-9999	-0.28	5	5
EPO/EPOR (dimer)	0.025	0	-9999	-10000	0	0
lamellipodium assembly	0.01	0.037	-9999	-0.15	25	25
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PI3K	0.009	0.065	-9999	-0.28	25	25
ARF6	0.017	0	-9999	-10000	0	0
JAK2	0.028	0.016	-9999	-0.14	5	5
PXN	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
MADCAM1	0.017	0	-9999	-10000	0	0
cell adhesion	0.039	0.034	-9999	-0.29	5	5
CRKL/CBL	0.025	0	-9999	-10000	0	0
ITGB1	0.017	0	-9999	-10000	0	0
SRC	-0.13	0.11	-9999	-0.21	353	353
ITGB7	0.015	0.026	-9999	-0.41	2	2
RAC1	0.017	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.15	0.13	-9999	-0.24	353	353
p130Cas/Crk/Dock1	-0.1	0.099	-9999	-0.17	353	353
VCAM1	-0.27	0.2	-9999	-0.41	351	351
RHOA	0.017	0.001	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.042	0.024	-9999	-0.21	5	5
BCAR1	-0.12	0.1	-9999	-0.19	353	353
EPOR	0.017	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.017	0	-9999	-10000	0	0
GIT1	0.017	0	-9999	-10000	0	0
Rac1/GTP	0.01	0.038	-9999	-0.16	25	25

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.024	0.057	-10000	0	-0.14	101	101
RFC1	-0.024	0.057	-10000	0	-0.14	103	103
PRKDC	-0.034	0.077	-10000	0	-0.17	117	117
RIPK1	0.01	0.055	-10000	0	-0.41	9	9
CASP7	-0.009	0.071	-10000	0	-0.23	31	31
FASLG/FAS/FADD/FAF1	-0.002	0.062	0.14	26	-0.15	65	91
MAP2K4	0.002	0.078	-10000	0	-0.23	30	30
mol:ceramide	0.01	0.069	-10000	0	-0.22	23	23
GSN	-0.031	0.068	-10000	0	-0.15	116	116
FASLG/FAS/FADD/FAF1/Caspase 8	0.007	0.063	0.13	24	-0.19	25	49
FAS	-0.039	0.14	-10000	0	-0.42	68	68
BID	-0.004	0.043	0.14	1	-0.25	16	17
MAP3K1	-0.013	0.077	-10000	0	-0.22	39	39
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
RB1	-0.024	0.057	-10000	0	-0.14	103	103
CFLAR	0.013	0.041	-10000	0	-0.41	5	5
HGF/MET	0.014	0.074	-10000	0	-0.24	41	41
ARHGDIB	-0.045	0.088	-10000	0	-0.18	139	139
FADD	0.015	0.027	-10000	0	-0.41	2	2
actin filament polymerization	0.031	0.068	0.15	116	-10000	0	116
NFKB1	0.007	0.045	-10000	0	-0.24	2	2
MAPK8	0.001	0.093	-10000	0	-0.24	53	53
DFFA	-0.024	0.057	-10000	0	-0.14	103	103
DNA fragmentation during apoptosis	-0.024	0.057	-10000	0	-0.14	103	103
FAS/FADD/MET	-0.006	0.099	-10000	0	-0.24	79	79
CFLAR/RIP1	0.018	0.049	-10000	0	-0.28	14	14
FAIM3	0.016	0.019	-10000	0	-0.41	1	1
FAF1	0.016	0.007	-10000	0	-10000	0	0
PARP1	-0.024	0.057	-10000	0	-0.14	103	103
DFFB	-0.024	0.057	-10000	0	-0.14	103	103
CHUK	0.009	0.042	-10000	0	-0.21	3	3
FASLG	0.016	0.007	-10000	0	-10000	0	0
FAS/FADD	-0.017	0.11	-10000	0	-0.29	70	70
HGF	0.015	0.026	-10000	0	-0.41	2	2
LMNA	-0.032	0.081	-10000	0	-0.16	122	122
CASP6	-0.035	0.079	-10000	0	-0.17	118	118
CASP10	0.017	0.004	-10000	0	-10000	0	0
CASP3	-0.032	0.066	-10000	0	-0.16	103	103
PTPN13	-0.007	0.099	-10000	0	-0.41	30	30
CASP8	-0.009	0.039	0.22	1	-0.3	9	10
IL6	-0.011	0.13	-10000	0	-0.39	52	52
MET	0.009	0.058	-10000	0	-0.41	10	10
ICAD/CAD	-0.019	0.053	-10000	0	-0.26	1	1
FASLG/FAS/FADD/FAF1/Caspase 10	0.01	0.069	-10000	0	-0.22	23	23
activation of caspase activity by cytochrome c	-0.004	0.043	0.14	1	-0.24	16	17
PAK2	-0.034	0.079	-10000	0	-0.17	115	115
BCL2	0.017	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.013	0.001	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
MAP3K7IP2	0.017	0	-9999	-10000	0	0
ERC1	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.047	0.1	-9999	-0.15	221	221
IRAK/TOLLIP	0.025	0.002	-9999	-10000	0	0
IKBKB	0.017	0	-9999	-10000	0	0
IKBKG	0.017	0	-9999	-10000	0	0
IL1 alpha/IL1R2	0	0.085	-9999	-0.28	43	43
IL1A	0.015	0.032	-9999	-0.41	3	3
IL1B	-0.088	0.15	-9999	-0.3	178	178
IRAK/TRAF6/p62/Atypical PKCs	0.038	0.013	-9999	-0.18	2	2
IL1R2	-0.015	0.11	-9999	-0.41	40	40
IL1R1	0.015	0.032	-9999	-0.41	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.035	0.09	-9999	-0.22	71	71
TOLLIP	0.017	0	-9999	-10000	0	0
TICAM2	0	0	-9999	-10000	0	0
MAP3K3	0.017	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.034	0.012	-9999	-0.23	1	1
IKK complex/ELKS	0.049	0.015	-9999	-0.25	1	1
JUN	0.027	0.012	-9999	-0.16	1	1
MAP3K7	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.056	0.14	-9999	-0.22	196	196
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.013	0.12	-9999	-0.23	112	112
PIK3R1	0.016	0.004	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.005	0.11	-9999	-0.21	113	113
IL1 beta fragment/IL1R1/IL1RAP	-0.069	0.15	-9999	-0.24	198	198
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAPK8	0.027	0.009	-9999	-0.16	1	1
IRAK1	0.016	0.001	-9999	-10000	0	0
IL1RN/IL1R1	0.024	0.023	-9999	-0.28	3	3
IRAK4	0.016	0.019	-9999	-0.41	1	1
PRKCI	0.016	0.019	-9999	-0.41	1	1
TRAF6	0.017	0	-9999	-10000	0	0
PI3K	0.009	0.065	-9999	-0.28	25	25
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.043	0.1	-9999	-0.26	72	72
CHUK	0.016	0.019	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.069	0.15	-9999	-0.24	198	198
IL1 beta/IL1R2	-0.082	0.15	-9999	-0.26	201	201
IRAK/TRAF6/TAK1/TAB1/TAB2	0.048	0.01	-9999	-0.17	1	1
NF kappa B1 p50/RelA	-0.056	0.13	-9999	-0.2	196	196
IRAK3	0.015	0.026	-9999	-0.41	2	2
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.056	0.14	-9999	-0.22	198	198
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.071	-9999	-0.13	113	113
IL1 alpha/IL1R1/IL1RAP	0.009	0.081	-9999	-0.24	50	50
RELA	0.017	0	-9999	-10000	0	0
MAP3K7IP1	0.017	0	-9999	-10000	0	0
SQSTM1	0.016	0.019	-9999	-0.41	1	1
MYD88	-0.041	0.15	-9999	-0.41	72	72
IRAK/TRAF6/MEKK3	0.035	0.002	-9999	-10000	0	0
IL1RAP	-0.019	0.12	-9999	-0.41	45	45
UBE2N	0.017	0.001	-9999	-10000	0	0
IRAK/TRAF6	-0.053	0.11	-9999	-0.18	197	197
CASP1	-0.12	0.2	-9999	-0.41	172	172
IL1RN/IL1R2	0.002	0.082	-9999	-0.28	40	40
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.085	0.17	-9999	-0.27	221	221
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.004	0.063	-9999	-0.13	73	73
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
IL1RN	0.017	0	-9999	-10000	0	0
TRAF6/TAK1/TAB1/TAB2	0.042	0.01	-9999	-0.18	1	1
MAP2K6	0.027	0.01	-9999	-0.17	1	1

×

Class I PI3K 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.028	0.078	-9999	-0.16	132	132
DAPP1	-0.015	0.088	-9999	-0.2	75	75
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.036	0.14	-9999	-0.3	87	87
mol:DAG	-0.019	0.078	-9999	-0.16	93	93
HRAS	0.01	0.021	-9999	-0.41	1	1
RAP1A	0.015	0.004	-9999	-10000	0	0
ARF5/GDP	0.003	0.053	-9999	-0.19	25	25
PLCG2	0.009	0.058	-9999	-0.41	10	10
PLCG1	0.017	0	-9999	-10000	0	0
ARF5	0.017	0	-9999	-10000	0	0
mol:GTP	-0.039	0.078	-9999	-0.17	132	132
ARF1/GTP	-0.033	0.073	-9999	-0.16	132	132
RHOA	0.017	0.001	-9999	-10000	0	0
YES1	-0.048	0.15	-9999	-0.41	80	80
RAP1A/GTP	-0.032	0.082	-9999	-0.17	132	132
ADAP1	-0.037	0.075	-9999	-0.17	132	132
ARAP3	-0.038	0.077	-9999	-0.17	132	132
INPPL1	0.017	0	-9999	-10000	0	0
PREX1	0	0	-9999	-10000	0	0
ARHGEF6	0.01	0.052	-9999	-0.41	8	8
ARHGEF7	0.016	0.019	-9999	-0.41	1	1
ARF1	0.017	0.001	-9999	-10000	0	0
NRAS	-0.094	0.19	-9999	-0.41	137	137
FYN	0.015	0.026	-9999	-0.41	2	2
ARF6	0.017	0	-9999	-10000	0	0
FGR	0.003	0.076	-9999	-0.41	17	17
mol:Ca2+	-0.006	0.042	-9999	-0.12	17	17
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.016	0.003	-9999	-10000	0	0
ZAP70	0.017	0	-9999	-10000	0	0
mol:IP3	-0.01	0.057	-9999	-0.13	46	46
LYN	-0.035	0.14	-9999	-0.41	64	64
ARF1/GDP	0.003	0.053	-9999	-0.19	25	25
RhoA/GDP	-0.018	0.08	-9999	-0.15	133	133
PDK1/Src/Hsp90	0.035	0	-9999	-10000	0	0
BLNK	-0.038	0.14	-9999	-0.41	68	68
actin cytoskeleton reorganization	-0.012	0.069	-9999	-0.13	133	133
SRC	0.017	0	-9999	-10000	0	0
PLEKHA2	0.011	0.011	-9999	-0.24	1	1
RAC1	0.017	0	-9999	-10000	0	0
PTEN	0.019	0.027	-9999	-0.4	2	2
HSP90AA1	0.017	0	-9999	-10000	0	0
ARF6/GTP	-0.028	0.078	-9999	-0.16	132	132
RhoA/GTP	-0.028	0.079	-9999	-0.16	132	132
Src family/SYK family/BLNK-LAT	-0.032	0.13	-9999	-0.28	91	91
BLK	0.017	0	-9999	-10000	0	0
PDPK1	0.017	0	-9999	-10000	0	0
CYTH1	-0.037	0.075	-9999	-0.17	132	132
HCK	-0.053	0.16	-9999	-0.41	86	86
CYTH3	-0.037	0.075	-9999	-0.17	132	132
CYTH2	-0.037	0.075	-9999	-0.17	132	132
KRAS	0.011	0.011	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.005	0.044	-9999	-10000	0	0
SGK1	-0.008	0.047	-9999	-10000	0	0
INPP5D	0	0	-9999	-10000	0	0
mol:GDP	-0.006	0.053	-9999	-0.21	25	25
SOS1	0	0	-9999	-10000	0	0
SYK	-0.012	0.11	-9999	-0.41	36	36
ARF6/GDP	-0.021	0.076	-9999	-0.15	133	133
mol:PI-3-4-5-P3	-0.038	0.079	-9999	-0.17	132	132
ARAP3/RAP1A/GTP	-0.032	0.083	-9999	-0.17	132	132
VAV1	0.016	0.019	-9999	-0.41	1	1
mol:PI-3-4-P2	0.009	0	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	-0.024	0.089	-9999	-0.18	134	134
PLEKHA1	0.01	0.004	-9999	-10000	0	0
Rac1/GDP	0.003	0.053	-9999	-0.19	25	25
LAT	0.016	0.019	-9999	-0.41	1	1
Rac1/GTP	0.011	0.041	-9999	-0.21	11	11
ITK	-0.034	0.08	-9999	-0.17	134	134
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.03	0.1	-9999	-0.21	93	93
LCK	0.014	0.037	-9999	-0.41	4	4
BTK	-0.032	0.077	-9999	-0.16	133	133

×

Circadian rhythm pathway

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
chromatin modification	-0.046	0.19	-10000	0	-0.42	100	100
CLOCK	0.009	0.038	-10000	0	-0.44	3	3
TIMELESS/CRY2	-0.035	0.15	-10000	0	-0.35	100	100
DEC1/BMAL1	0.024	0.007	-10000	0	-10000	0	0
ATR	0.017	0	-10000	0	-10000	0	0
NR1D1	-0.007	0.08	-10000	0	-0.17	100	100
ARNTL	0.012	0.016	-10000	0	-10000	0	0
TIMELESS	-0.046	0.16	-10000	0	-0.38	100	100
NPAS2	0.011	0.024	-10000	0	-0.41	1	1
CRY2	0.017	0	-10000	0	-10000	0	0
mol:CO	0.006	0.034	0.077	100	-10000	0	100
CHEK1	-0.032	0.14	-10000	0	-0.41	60	60
mol:HEME	-0.006	0.034	-10000	0	-0.077	100	100
PER1	0.015	0.032	-10000	0	-0.41	3	3
BMAL/CLOCK/NPAS2	0.026	0.05	-10000	0	-0.29	4	4
BMAL1/CLOCK	-0.003	0.1	-10000	0	-0.34	4	4
S phase of mitotic cell cycle	-0.046	0.19	-10000	0	-0.42	100	100
TIMELESS/CHEK1/ATR	-0.046	0.19	-10000	0	-0.43	100	100
mol:NADPH	-0.006	0.034	-10000	0	-0.077	100	100
PER1/TIMELESS	-0.036	0.15	-10000	0	-0.35	100	100
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.017	0	-10000	0	-10000	0	0

×

Wnt signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.047	0.1	-9999	-0.26	56	56
FZD6	-0.065	0.17	-9999	-0.41	101	101
WNT6	0.017	0	-9999	-10000	0	0
WNT4	0.015	0.026	-9999	-0.41	2	2
FZD3	0.014	0.032	-9999	-0.41	3	3
WNT5A	-0.12	0.2	-9999	-0.41	168	168
WNT11	0.015	0.026	-9999	-0.41	2	2

×

Noncanonical Wnt signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0	0	-9999	-10000	0	0
GNB1/GNG2	-0.035	0.096	-9999	-0.25	51	51
mol:DAG	-0.032	0.088	-9999	-0.23	51	51
PLCG1	-0.032	0.09	-9999	-0.23	51	51
YES1	-0.072	0.13	-9999	-0.28	111	111
FZD3	0.014	0.032	-9999	-0.41	3	3
FZD6	-0.065	0.17	-9999	-0.41	101	101
G protein	-0.031	0.091	-9999	-0.24	51	51
MAP3K7	-0.02	0.074	-9999	-0.19	47	47
mol:Ca2+	-0.031	0.086	-9999	-0.22	51	51
mol:IP3	-0.032	0.088	-9999	-0.23	51	51
NLK	0.016	0.056	-9999	-0.71	3	3
GNB1	0.017	0.002	-9999	-10000	0	0
CAMK2A	-0.024	0.078	-9999	-0.21	47	47
MAP3K7IP1	0.017	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.047	0.1	-9999	-0.26	56	56
CSNK1A1	0.017	0	-9999	-10000	0	0
GNAS	-0.041	0.096	-9999	-0.26	51	51
GO:0007205	-0.032	0.084	-9999	-0.22	51	51
WNT6	0.017	0	-9999	-10000	0	0
WNT4	0.015	0.026	-9999	-0.41	2	2
NFAT1/CK1 alpha	-0.055	0.12	-9999	-0.25	111	111
GNG2	0	0	-9999	-10000	0	0
WNT5A	-0.12	0.2	-9999	-0.41	168	168
WNT11	0.015	0.026	-9999	-0.41	2	2
CDC42	-0.066	0.13	-9999	-0.27	111	111

×

Aurora A signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.002	0.077	-9999	-0.2	62	62
BIRC5	-0.16	0.21	-9999	-0.41	212	212
NFKBIA	0.017	0.031	-9999	-0.19	2	2
CPEB1	0.013	0.007	-9999	-10000	0	0
AKT1	0.016	0.036	-9999	-0.14	20	20
NDEL1	0.016	0.004	-9999	-10000	0	0
Aurora A/BRCA1	0.02	0.036	-9999	-0.22	6	6
NDEL1/TACC3	-0.009	0.093	-9999	-0.2	92	92
GADD45A	-0.02	0.12	-9999	-0.41	46	46
GSK3B	0.019	0.007	-9999	-10000	0	0
PAK1/Aurora A	0.024	0.03	-9999	-0.12	16	16
MDM2	0.002	0.078	-9999	-0.41	18	18
JUB	0	0	-9999	-10000	0	0
TPX2	-0.15	0.15	-9999	-0.28	296	296
TP53	-0.001	0.065	-9999	-0.14	81	81
DLG7	-0.091	0.13	-9999	-0.24	230	230
AURKAIP1	0.017	0	-9999	-10000	0	0
ARHGEF7	0.016	0.019	-9999	-0.41	1	1
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.01	0.099	-9999	-0.22	92	92
G2/M transition of mitotic cell cycle	0.02	0.036	-9999	-0.22	6	6
AURKA	0.018	0.036	-9999	-0.15	19	19
AURKB	-0.002	0.047	-9999	-0.18	30	30
CDC25B	0.015	0.04	-9999	-0.13	33	33
G2/M transition checkpoint	0.01	0.025	-9999	-0.11	19	19
mRNA polyadenylation	0.017	0.022	-9999	-0.1	10	10
Aurora A/CPEB	0.017	0.022	-9999	-0.1	10	10
Aurora A/TACC1/TRAP/chTOG	0.042	0.027	-9999	-10000	0	0
BRCA1	0.013	0.042	-9999	-0.41	5	5
centrosome duplication	0.024	0.03	-9999	-0.12	16	16
regulation of centrosome cycle	-0.009	0.091	-9999	-0.2	92	92
spindle assembly	0.041	0.027	-9999	-10000	0	0
TDRD7	0.017	0.001	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.05	0.12	-9999	-0.19	208	208
CENPA	-0.004	0.054	-9999	-0.12	84	84
Aurora A/PP2A	0.024	0.03	-9999	-0.12	19	19
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	-0.051	0.091	-9999	-0.16	194	194
negative regulation of DNA binding	-0.001	0.064	-9999	-0.14	80	80
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.025	0.013	-9999	-0.28	1	1
RASA1	0.017	0.002	-9999	-10000	0	0
Ajuba/Aurora A	0.011	0.025	-9999	-0.11	19	19
mitotic prometaphase	0	0.009	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.036	-9999	-0.15	19	19
TACC1	0.017	0.001	-9999	-10000	0	0
TACC3	-0.061	0.16	-9999	-0.41	96	96
Aurora A/Antizyme1	0.033	0.028	-9999	-0.12	1	1
Aurora A/RasGAP	0.024	0.03	-9999	-0.14	1	1
OAZ1	0.017	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.019	0.007	-9999	-10000	0	0
GIT1	0.017	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.034	0.012	-9999	-0.23	1	1
Importin alpha/Importin beta/TPX2	-0.15	0.15	-9999	-0.28	296	296
PPP2R5D	0.017	0	-9999	-10000	0	0
Aurora A/TPX2	-0.1	0.12	-9999	-0.21	296	296
PAK1	0.017	0	-9999	-10000	0	0
CKAP5	0.017	0	-9999	-10000	0	0

×

Plasma membrane estrogen 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
GNB1/GNG2	0.03	0.003	-10000	0	-10000	0	0
ER alpha/Gai/GDP/Gbeta gamma	-0.063	0.064	-10000	0	-0.2	63	63
AKT1	0.007	0.03	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.005	0.03	-10000	0	-10000	0	0
mol:Ca2+	0.029	0.018	-10000	0	-0.14	2	2
IGF1R	0.017	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	0.023	0	-10000	0	-10000	0	0
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
apoptosis	-0.007	0.03	-10000	0	-10000	0	0
RhoA/GTP	-0.044	0.074	-10000	0	-0.17	135	135
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.047	0.046	-10000	0	-0.15	49	49
regulation of stress fiber formation	0.13	0.11	0.19	363	-0.21	1	364
E2/ERA-ERB (dimer)	0.023	0	-10000	0	-10000	0	0
KRAS	0.017	0.002	-10000	0	-10000	0	0
G13/GTP	0.021	0.015	-10000	0	-0.22	2	2
pseudopodium formation	-0.13	0.11	0.21	1	-0.19	363	364
E2/ER alpha (dimer)/PELP1	0.023	0	-10000	0	-10000	0	0
GRB2	0.017	0.002	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.03	0.037	-10000	0	-0.16	8	8
E2/ER beta (dimer)	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.006	0.052	-10000	0	-0.2	2	2
mol:NADP	-0.03	0.037	-10000	0	-0.16	8	8
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	0.03	0.018	-10000	0	-0.14	2	2
IGF-1R heterotetramer	0.017	0	-10000	0	-10000	0	0
PLCB1	0.028	0.019	-10000	0	-0.15	2	2
PLCB2	0.028	0.019	-10000	0	-0.15	2	2
IGF1	0.014	0.037	-10000	0	-0.41	4	4
mol:L-citrulline	-0.03	0.037	-10000	0	-0.16	8	8
RHOA	0.017	0.001	-10000	0	-10000	0	0
Gai/GDP	-0.42	0.15	-10000	0	-0.46	481	481
JNK cascade	0.013	0	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.017	0	-10000	0	-10000	0	0
GNAQ	0.017	0	-10000	0	-10000	0	0
ESR1	0.017	0	-10000	0	-10000	0	0
Gq family/GDP/Gbeta gamma	0.026	0.026	-10000	0	-0.16	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.008	0.067	-10000	0	-0.48	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.059	0.074	-10000	0	-0.24	56	56
GNAZ	0.015	0.006	-10000	0	-10000	0	0
E2/ER alpha (dimer)	0.013	0	-10000	0	-10000	0	0
STRN	0.017	0	-10000	0	-10000	0	0
GNAL	0.017	0	-10000	0	-10000	0	0
PELP1	0.017	0	-10000	0	-10000	0	0
MAPK11	0.016	0	-10000	0	-10000	0	0
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.02	-10000	0	-0.41	1	1
HBEGF	-0.16	0.1	-10000	0	-0.22	327	327
cAMP biosynthetic process	0.02	0	-10000	0	-10000	0	0
SRC	-0.059	0.062	-10000	0	-0.19	66	66
PI3K	0.009	0.065	-10000	0	-0.28	25	25
GNB1	0.017	0.002	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.002	0.05	-10000	0	-0.21	2	2
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.05	0.061	-10000	0	-0.2	55	55
Gs family/GTP	0.025	0	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.03	0.11	-10000	0	-0.21	134	134
vasodilation	-0.03	0.036	-10000	0	-0.15	8	8
mol:DAG	0.03	0.018	-10000	0	-0.14	2	2
Gs family/GDP/Gbeta gamma	-0.02	0.034	-10000	0	-0.22	1	1
MSN	-0.14	0.11	0.21	1	-0.2	363	364
Gq family/GTP	0.028	0.02	-10000	0	-0.16	2	2
mol:PI-3-4-5-P3	0.005	0.03	-10000	0	-10000	0	0
NRAS	-0.094	0.19	-10000	0	-0.41	137	137
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.03	0.036	0.15	8	-10000	0	8
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.002	0.053	-10000	0	-0.18	2	2
NOS3	-0.031	0.038	-10000	0	-0.16	8	8
GNA11	0.017	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.015	0.047	-10000	0	-0.2	9	9
E2/ER alpha (dimer)/PELP1/Src	-0.048	0.048	-10000	0	-0.16	49	49
ruffle organization	-0.13	0.11	0.21	1	-0.19	363	364
ROCK2	-0.018	0.083	0.22	1	-0.16	135	136
GNA14	0.015	0.026	-10000	0	-0.41	2	2
GNA15	0.011	0.049	-10000	0	-0.41	7	7
GNA13	0.015	0.026	-10000	0	-0.41	2	2
MMP9	-0.13	0.11	-10000	0	-0.24	229	229
MMP2	-0.15	0.12	-10000	0	-0.25	286	286

×

Ras signaling in the CD4+ TCR 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
ERK1-2/ELK1	-0.021	0.11	-10000	0	-0.2	127	127
MAP3K8	-0.018	0.12	-10000	0	-0.42	42	42
FOS	-0.012	0.069	-10000	0	-0.18	20	20
PRKCA	0.013	0.009	-10000	0	-10000	0	0
PTPN7	0.011	0.022	-10000	0	-0.41	1	1
HRAS	0.016	0.019	-10000	0	-0.41	1	1
PRKCB	-0.002	0.006	0.01	2	-0.012	125	127
NRAS	-0.095	0.19	-10000	0	-0.41	137	137
RAS family/GTP	-0.034	0.1	-10000	0	-0.21	134	134
MAPK3	0.004	0.038	-10000	0	-0.19	1	1
MAP2K1	-0.009	0.048	-10000	0	-0.14	29	29
ELK1	0.011	0.013	-10000	0	-10000	0	0
BRAF	-0.003	0.028	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	0.002	1	-0.004	125	126
MAPK1	-0.005	0.062	-10000	0	-0.27	18	18
RAF1	-0.003	0.029	-10000	0	-0.17	1	1
KRAS	0.016	0.002	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.02	0.048	-10000	0	-0.16	31	31
adherens junction organization	0.02	0.038	-10000	0	-0.18	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.041	0.1	-10000	0	-0.16	196	196
FMN1	0.019	0.038	-10000	0	-0.18	10	10
mol:IP3	0.017	0.047	-10000	0	-0.17	26	26
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.02	0.04	-10000	0	-0.19	10	10
CTNNB1	0.017	0.002	-10000	0	-10000	0	0
AKT1	0.02	0.051	-10000	0	-0.16	30	30
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.028	0.041	-10000	0	-0.22	8	8
CTNND1	0.009	0.059	-10000	0	-0.41	10	10
mol:PI-4-5-P2	0.022	0.04	-10000	0	-0.19	11	11
VASP	0.022	0.04	-10000	0	-0.19	11	11
ZYX	-0.026	0.094	-10000	0	-0.18	137	137
JUB	0.019	0.038	-10000	0	-0.18	10	10
EGFR(dimer)	-0.046	0.11	-10000	0	-0.18	202	202
E-cadherin/beta catenin-gamma catenin	0.022	0.063	-10000	0	-0.29	19	19
mol:PI-3-4-5-P3	0.024	0.052	-10000	0	-0.17	27	27
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PI3K	0.024	0.053	-10000	0	-0.18	27	27
FYN	0.023	0.044	-10000	0	-0.22	5	5
mol:Ca2+	0.017	0.047	-10000	0	-0.16	26	26
JUP	0.004	0.073	-10000	0	-0.41	16	16
PIK3R1	0.016	0.005	-10000	0	-10000	0	0
mol:DAG	0.017	0.047	-10000	0	-0.17	26	26
CDH1	0.011	0.052	-10000	0	-0.41	8	8
RhoA/GDP	-0.041	0.1	-10000	0	-0.16	196	196
establishment of polarity of embryonic epithelium	0.022	0.039	-10000	0	-0.19	11	11
SRC	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
CASR	0.018	0.044	-10000	0	-0.15	26	26
RhoA/GTP	0.023	0.045	-10000	0	-0.15	26	26
AKT2	0.022	0.048	-10000	0	-0.16	26	26
actin cable formation	0.021	0.039	-10000	0	-0.18	11	11
apoptosis	-0.019	0.048	0.15	31	-10000	0	31
CTNNA1	0.018	0.002	-10000	0	-10000	0	0
mol:GDP	-0.051	0.1	-10000	0	-0.17	207	207
PIP5K1A	0.022	0.04	-10000	0	-0.19	11	11
PLCG1	0.017	0.048	-10000	0	-0.17	26	26
Rac1/GTP	-0.037	0.1	-10000	0	-0.16	201	201
homophilic cell adhesion	0	0.002	-10000	0	-10000	0	0

×

BCR signaling pathway

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
JUN	0	0.077	-10000	0	-0.19	50	50
IKBKB	0.007	0.051	-10000	0	-0.16	18	18
AKT1	-0.013	0.069	0.18	1	-0.17	58	59
IKBKG	0.007	0.053	-10000	0	-0.16	22	22
CALM1	-0.011	0.079	-10000	0	-0.25	38	38
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
MAP3K1	-0.01	0.095	-10000	0	-0.23	58	58
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
mol:Ca2+	-0.015	0.086	-10000	0	-0.27	40	40
DOK1	0.017	0	-10000	0	-10000	0	0
AP-1	-0.011	0.071	-10000	0	-0.17	43	43
LYN	-0.035	0.14	-10000	0	-0.41	64	64
BLNK	-0.038	0.14	-10000	0	-0.41	68	68
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
BCR complex	0.024	0.028	-10000	0	-0.41	2	2
CD22	-0.038	0.11	-10000	0	-0.24	94	94
CAMK2G	-0.006	0.058	0.14	1	-0.23	26	27
CSNK2A1	0.017	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.07	0.14	-10000	0	-0.27	135	135
GO:0007205	-0.016	0.087	-10000	0	-0.28	40	40
SYK	-0.012	0.11	-10000	0	-0.41	36	36
ELK1	-0.012	0.083	-10000	0	-0.26	40	40
NFATC1	-0.019	0.093	0.14	1	-0.23	66	67
B-cell antigen/BCR complex	0.024	0.028	-10000	0	-0.41	2	2
PAG1/CSK	0.013	0	-10000	0	-10000	0	0
NFKBIB	0.013	0.021	-10000	0	-0.085	2	2
HRAS	-0.016	0.093	-10000	0	-0.25	53	53
NFKBIA	0.013	0.021	-10000	0	-0.086	2	2
NF-kappa-B/RelA/I kappa B beta	0.017	0.02	-10000	0	-0.091	4	4
RasGAP/Csk	-0.009	0.11	-10000	0	-0.19	126	126
mol:GDP	-0.013	0.084	-10000	0	-0.26	40	40
PTEN	0.015	0.026	-10000	0	-0.41	2	2
CD79B	0.016	0.019	-10000	0	-0.41	1	1
NF-kappa-B/RelA/I kappa B alpha	0.017	0.02	-10000	0	-0.092	4	4
GRB2	0.017	0.002	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.024	0.11	-10000	0	-0.29	60	60
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.016	0.088	-10000	0	-0.28	40	40
CSK	0.017	0	-10000	0	-10000	0	0
FOS	-0.051	0.12	-10000	0	-0.22	145	145
CHUK	0.007	0.053	-10000	0	-0.16	26	26
IBTK	0.017	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.006	0.093	-10000	0	-0.23	60	60
PTPN6	-0.037	0.11	-10000	0	-0.25	94	94
RELA	0.017	0	-10000	0	-10000	0	0
BCL2A1	-0.001	0.037	-10000	0	-0.064	129	129
VAV2	-0.034	0.12	-10000	0	-0.29	67	67
ubiquitin-dependent protein catabolic process	0.016	0.02	-10000	0	-0.091	1	1
BTK	0.011	0.009	-10000	0	-10000	0	0
CD19	-0.038	0.11	-10000	0	-0.24	94	94
MAP4K1	0.016	0.019	-10000	0	-0.41	1	1
CD72	0.017	0	-10000	0	-10000	0	0
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	-0.005	0.086	-10000	0	-0.21	59	59
SH3BP5	0.016	0.005	-10000	0	-10000	0	0
PIK3AP1	-0.018	0.09	-10000	0	-0.23	62	62
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.009	0.11	-10000	0	-0.34	40	40
RAF1	-0.012	0.089	-10000	0	-0.26	46	46
RasGAP/p62DOK/SHIP	-0.013	0.099	-10000	0	-0.19	126	126
CD79A	0.015	0.026	-10000	0	-0.41	2	2
re-entry into mitotic cell cycle	-0.011	0.071	-10000	0	-0.17	43	43
RASA1	0.017	0.002	-10000	0	-10000	0	0
MAPK3	-0.001	0.079	0.16	2	-0.23	40	42
MAPK1	-0.002	0.079	0.26	1	-0.23	40	41
CD72/SHP1	-0.027	0.11	-10000	0	-0.24	94	94
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.004	0.085	-10000	0	-0.21	57	57
actin cytoskeleton organization	-0.027	0.1	-10000	0	-0.26	65	65
NF-kappa-B/RelA	0.037	0.035	-10000	0	-0.15	2	2
Calcineurin	0.006	0.069	-10000	0	-0.21	35	35
PI3K	-0.061	0.11	-10000	0	-0.3	80	80
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.019	0.095	-10000	0	-0.24	62	62
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.011	0.094	-10000	0	-0.25	38	38
DAPP1	-0.022	0.095	-10000	0	-0.27	38	38
cytokine secretion	-0.017	0.088	0.14	1	-0.22	66	67
mol:DAG	-0.016	0.088	-10000	0	-0.28	40	40
PLCG2	0.009	0.058	-10000	0	-0.41	10	10
MAP2K1	-0.007	0.083	0.17	1	-0.25	41	42
B-cell antigen/BCR complex/FcgammaRIIB	-0.032	0.12	-10000	0	-0.24	129	129
mol:PI-3-4-5-P3	-0.046	0.084	0.27	1	-0.22	80	81
ETS1	0.048	0.091	0.22	18	-0.2	30	48
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.022	0.16	-10000	0	-0.3	111	111
B-cell antigen/BCR complex/LYN	-0.043	0.11	-10000	0	-0.22	135	135
MALT1	-0.003	0.091	-10000	0	-0.41	25	25
TRAF6	0.017	0	-10000	0	-10000	0	0
RAC1	-0.029	0.11	-10000	0	-0.27	65	65
B-cell antigen/BCR complex/LYN/SYK	-0.042	0.16	-10000	0	-0.3	108	108
CARD11	-0.015	0.083	-10000	0	-0.26	40	40
FCGR2B	-0.088	0.18	-10000	0	-0.41	129	129
PPP3CA	0.014	0.007	-10000	0	-10000	0	0
BCL10	0.015	0.032	-10000	0	-0.41	3	3
IKK complex	0.011	0.025	-10000	0	-0.071	9	9
PTPRC	-0.086	0.18	-10000	0	-0.41	127	127
PDPK1	-0.016	0.069	0.17	1	-0.16	66	67
PPP3CB	0.017	0.002	-10000	0	-10000	0	0
PPP3CC	0.017	0	-10000	0	-10000	0	0
POU2F2	0.016	0.013	-10000	0	-0.054	1	1

×

Angiopoietin receptor Tie2-mediated 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
AKT1	-0.13	0.17	-10000	0	-0.44	52	52
NCK1/PAK1/Dok-R	-0.083	0.075	-10000	0	-0.24	47	47
NCK1/Dok-R	-0.011	0.11	-10000	0	-0.27	48	48
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
mol:beta2-estradiol	0.012	0.044	0.12	78	-10000	0	78
RELA	0.017	0	-10000	0	-10000	0	0
SHC1	-0.022	0.12	-10000	0	-0.41	47	47
Rac/GDP	0.013	0	-10000	0	-10000	0	0
F2	0.037	0.054	-10000	0	-0.42	2	2
TNIP2	0.008	0.061	-10000	0	-0.41	11	11
NF kappa B/RelA	0.005	0.11	-10000	0	-0.31	10	10
FN1	-0.065	0.17	-10000	0	-0.41	101	101
PLD2	-0.013	0.1	-10000	0	-0.25	79	79
PTPN11	0.017	0	-10000	0	-10000	0	0
GRB14	0.002	0.078	-10000	0	-0.41	18	18
ELK1	-0.003	0.098	-10000	0	-0.25	46	46
GRB7	0.016	0.019	-10000	0	-0.41	1	1
PAK1	0.017	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.055	0.17	-10000	0	-0.39	65	65
CDKN1A	-0.16	0.2	-10000	0	-0.47	93	93
ITGA5	-0.043	0.15	-10000	0	-0.41	74	74
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.007	0.1	-10000	0	-0.26	46	46
CRK	0.017	0	-10000	0	-10000	0	0
mol:NO	-0.1	0.14	-10000	0	-0.36	52	52
PLG	-0.013	0.1	-10000	0	-0.26	52	52
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.1	0.15	-10000	0	-0.4	52	52
GRB2	0.017	0.002	-10000	0	-10000	0	0
PIK3R1	0.015	0.004	-10000	0	-10000	0	0
ANGPT2	-0.2	0.21	-10000	0	-0.39	280	280
BMX	-0.013	0.1	-10000	0	-0.27	49	49
ANGPT1	-0.038	0.13	-10000	0	-0.34	78	78
tube development	-0.16	0.19	0.28	1	-0.41	102	103
ANGPT4	0.012	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.006	0.012	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.014	0.11	-10000	0	-0.28	47	47
alpha5/beta1 Integrin	-0.018	0.11	-10000	0	-0.28	74	74
FGF2	0.02	0.027	-10000	0	-0.41	2	2
STAT5A (dimer)	-0.17	0.22	-10000	0	-0.51	87	87
mol:L-citrulline	-0.1	0.14	-10000	0	-0.36	52	52
AGTR1	0.002	0.029	-10000	0	-0.41	2	2
MAPK14	-0.047	0.12	-10000	0	-0.32	45	45
Tie2/SHP2	0.016	0.045	-10000	0	-0.21	1	1
TEK	0.009	0.05	-10000	0	-0.19	3	3
RPS6KB1	-0.1	0.15	-10000	0	-0.4	43	43
Angiotensin II/AT1	-0.006	0.026	-10000	0	-0.29	2	2
Tie2/Ang1/GRB2	-0.006	0.11	-10000	0	-0.27	46	46
MAPK3	-0.009	0.098	-10000	0	-0.25	48	48
MAPK1	-0.01	0.096	-10000	0	-0.25	48	48
Tie2/Ang1/GRB7	-0.007	0.11	-10000	0	-0.27	46	46
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MAPK8	-0.013	0.1	-10000	0	-0.25	79	79
PI3K	-0.12	0.16	-10000	0	-0.41	58	58
FES	-0.049	0.12	-10000	0	-0.33	45	45
Crk/Dok-R	-0.007	0.1	-10000	0	-0.26	46	46
Tie2/Ang1/ABIN2	-0.011	0.11	-10000	0	-0.28	46	46
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.12	0.16	-10000	0	-0.41	52	52
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.1	0.15	-10000	0	-0.4	43	43
Tie2/Ang2	-0.19	0.23	-10000	0	-0.5	104	104
Tie2/Ang1	-0.016	0.11	-10000	0	-0.27	79	79
FOXO1	-0.14	0.18	-10000	0	-0.43	81	81
ELF1	0.016	0.049	-10000	0	-0.41	7	7
ELF2	-0.015	0.11	-10000	0	-0.26	79	79
mol:Choline	-0.012	0.1	-10000	0	-0.26	49	49
cell migration	-0.064	0.057	-10000	0	-0.16	101	101
FYN	-0.17	0.2	-10000	0	-0.45	103	103
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.14	0.19	-10000	0	-0.43	93	93
ETS1	0.008	0.047	-10000	0	-10000	0	0
PXN	-0.089	0.14	-10000	0	-0.36	42	42
ITGB1	0.017	0	-10000	0	-10000	0	0
NOS3	-0.11	0.16	-10000	0	-0.4	52	52
RAC1	0.017	0	-10000	0	-10000	0	0
TNF	0.002	0.053	-10000	0	-0.41	2	2
MAPKKK cascade	-0.012	0.1	-10000	0	-0.26	49	49
RASA1	0.017	0.002	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.031	0.12	-10000	0	-0.31	49	49
NCK1	0.008	0.061	-10000	0	-0.41	11	11
vasculogenesis	-0.097	0.14	-10000	0	-0.33	52	52
mol:Phosphatidic acid	-0.012	0.1	-10000	0	-0.26	49	49
mol:Angiotensin II	-0.009	0.01	-10000	0	-10000	0	0
mol:NADP	-0.1	0.14	-10000	0	-0.36	52	52
Rac1/GTP	-0.099	0.14	-10000	0	-0.38	43	43
MMP2	-0.11	0.14	-10000	0	-0.33	84	84

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.15	0.16	-9999	-0.3	291	291
alphaV beta3 Integrin	0.026	0.049	-9999	-0.23	18	18
PTK2	-0.058	0.095	-9999	-0.28	28	28
IGF1R	0.017	0	-9999	-10000	0	0
PI4KB	0.016	0.019	-9999	-0.41	1	1
MFGE8	0.015	0.032	-9999	-0.41	3	3
SRC	0.017	0	-9999	-10000	0	0
CDKN1B	0.022	0.023	-9999	-0.19	2	2
VEGFA	-0.22	0.21	-9999	-0.41	286	286
ILK	0.022	0.023	-9999	-0.19	2	2
ROCK1	0.017	0	-9999	-10000	0	0
AKT1	0.021	0.028	-9999	-0.18	6	6
PTK2B	-0.1	0.12	-9999	-0.2	297	297
alphaV/beta3 Integrin/JAM-A	0.021	0.071	-9999	-0.19	53	53
CBL	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.027	0.046	-9999	-0.23	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.04	0.033	-9999	-0.21	9	9
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.04	0.07	-9999	-0.21	21	21
alphaV/beta3 Integrin/Syndecan-1	0.003	0.092	-9999	-0.25	60	60
PI4KA	0.006	0.008	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.011	0.1	-9999	-0.19	114	114
PI4 Kinase	0.009	0.014	-9999	-0.14	1	1
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
alphaV/beta3 Integrin/Osteopontin	-0.065	0.14	-9999	-0.25	185	185
RPS6KB1	-0.013	0.095	-9999	-0.36	13	13
TLN1	-0.02	0.12	-9999	-0.41	46	46
MAPK3	0.003	0.069	-9999	-0.18	49	49
GPR124	0.014	0.037	-9999	-0.41	4	4
MAPK1	0.003	0.068	-9999	-0.19	45	45
PXN	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.027	0.046	-9999	-0.23	16	16
cell adhesion	0.029	0.045	-9999	-0.2	20	20
ANGPTL3	0.017	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.12	0.14	-9999	-0.24	291	291
IGF-1R heterotetramer	0.017	0	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
TGFBR2	0.011	0.049	-9999	-0.41	7	7
ITGB3	0.017	0	-9999	-10000	0	0
IGF1	0.014	0.037	-9999	-0.41	4	4
RAC1	0.017	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.024	0.051	-9999	-0.23	20	20
apoptosis	0.004	0.073	-9999	-0.41	16	16
CD47	0.015	0.026	-9999	-0.41	2	2
alphaV/beta3 Integrin/CD47	0.026	0.049	-9999	-0.23	18	18
VCL	0.017	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	0.027	0.046	-9999	-0.23	16	16
CSF1	0.017	0	-9999	-10000	0	0
PIK3C2A	0.012	0.023	-9999	-0.19	2	2
PI4 Kinase/Pyk2	-0.054	0.079	-9999	-0.28	23	23
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.14	-9999	-0.22	297	297
FAK1/Vinculin	-0.044	0.084	-9999	-0.23	28	28
alphaV beta3/Integrin/ppsTEM5	0.025	0.051	-9999	-0.23	20	20
RHOA	0.017	0.001	-9999	-10000	0	0
VTN	0.015	0.026	-9999	-0.41	2	2
BCAR1	0	0	-9999	-10000	0	0
FGF2	0.015	0.026	-9999	-0.41	2	2
F11R	-0.002	0.075	-9999	-0.28	35	35
alphaV/beta3 Integrin/Lactadherin	0.025	0.05	-9999	-0.23	19	19
alphaV/beta3 Integrin/TGFBR2	0.023	0.055	-9999	-0.23	23	23
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.026	0.042	-9999	-0.21	16	16
HSP90AA1	0.017	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.005	0.084	-9999	-0.23	57	57
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.065	0.17	-9999	-0.41	101	101
alphaV/beta3 Integrin/Pyk2	-0.097	0.13	-9999	-0.2	297	297
SDC1	-0.022	0.12	-9999	-0.41	48	48
VAV3	0.001	0.069	-9999	-0.21	48	48
PTPN11	0.017	0	-9999	-10000	0	0
IRS1	0.013	0.042	-9999	-0.41	5	5
FAK1/Paxillin	-0.044	0.084	-9999	-0.23	28	28
cell migration	-0.038	0.079	-9999	-0.21	28	28
ITGAV	0.004	0.073	-9999	-0.41	16	16
PI3K	0.022	0.072	-9999	-0.18	51	51
SPP1	-0.13	0.2	-9999	-0.41	181	181
KDR	0.003	0.076	-9999	-0.41	17	17
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.004	0.073	-9999	-0.41	16	16
COL4A3	0.017	0	-9999	-10000	0	0
angiogenesis	0.008	0.064	-9999	-0.22	18	18
Rac1/GTP	0.011	0.065	-9999	-0.19	48	48
EDIL3	0.017	0	-9999	-10000	0	0
cell proliferation	0.023	0.055	-9999	-0.23	23	23

×

Syndecan-2-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.03	0.11	-9999	-0.24	105	105
EPHB2	0.015	0.026	-9999	-0.41	2	2
Syndecan-2/TACI	0.019	0.036	-9999	-0.19	13	13
LAMA1	0	0	-9999	-10000	0	0
Syndecan-2/alpha2 ITGB1	-0.009	0.1	-9999	-0.21	106	106
HRAS	0.016	0.019	-9999	-0.41	1	1
Syndecan-2/CASK	0.007	0.034	-9999	-0.2	13	13
ITGA5	-0.043	0.15	-9999	-0.41	74	74
BAX	0.018	0.056	-9999	-0.3	14	14
EPB41	0.017	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.017	0.032	-9999	-0.22	8	8
LAMA3	0.005	0.071	-9999	-0.41	15	15
EZR	0	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.041	0.15	-9999	-0.41	72	72
Syndecan-2/MMP2	-0.1	0.13	-9999	-0.24	257	257
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.029	0.12	-9999	-0.28	93	93
dendrite morphogenesis	0.018	0.039	-9999	-0.24	10	10
Syndecan-2/GM-CSF	0.019	0.036	-9999	-0.25	8	8
determination of left/right symmetry	0.01	0.041	-9999	-0.23	13	13
Syndecan-2/PKC delta	0.019	0.036	-9999	-0.25	8	8
GNB2L1	0.017	0	-9999	-10000	0	0
MAPK3	0.019	0.032	-9999	-0.22	8	8
MAPK1	0.018	0.032	-9999	-0.22	8	8
Syndecan-2/RACK1	0.027	0.033	-9999	-0.2	9	9
NF1	0.017	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.01	0.041	-9999	-0.23	13	13
ITGA2	-0.058	0.16	-9999	-0.41	93	93
MAPK8	0.017	0.042	-9999	-0.24	13	13
Syndecan-2/alpha2/beta1 Integrin	-0.012	0.091	-9999	-0.2	99	99
Syndecan-2/Kininogen	0.018	0.037	-9999	-0.19	14	14
ITGB1	0.017	0	-9999	-10000	0	0
SRC	0.021	0.03	-9999	-0.19	9	9
Syndecan-2/CASK/Protein 4.1	0.017	0.032	-9999	-0.22	8	8
extracellular matrix organization	0.006	0.067	-9999	-0.24	34	34
actin cytoskeleton reorganization	-0.03	0.11	-9999	-0.24	105	105
Syndecan-2/Caveolin-2/Ras	-0.004	0.091	-9999	-0.22	76	76
Syndecan-2/Laminin alpha3	0.012	0.056	-9999	-0.24	23	23
Syndecan-2/RasGAP	0.034	0.033	-9999	-0.19	9	9
alpha5/beta1 Integrin	-0.018	0.11	-9999	-0.28	74	74
PRKCD	0.017	0	-9999	-10000	0	0
Syndecan-2 dimer	0.018	0.039	-9999	-0.24	10	10
GO:0007205	0.002	0.01	-9999	-0.11	1	1
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.033	0.031	-9999	-0.18	9	9
RHOA	0.017	0.001	-9999	-10000	0	0
SDCBP	0.017	0	-9999	-10000	0	0
TNFRSF13B	0.017	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.029	0.12	-9999	-0.28	93	93
Syndecan-2/Synbindin	0.019	0.036	-9999	-0.25	8	8
TGFB1	-0.005	0.094	-9999	-0.41	27	27
CASP3	-0.023	0.093	-9999	-0.21	103	103
FN1	-0.065	0.17	-9999	-0.41	101	101
Syndecan-2/IL8	-0.037	0.11	-9999	-0.24	121	121
SDC2	0.01	0.041	-9999	-0.24	13	13
KNG1	0.016	0.019	-9999	-0.41	1	1
Syndecan-2/Neurofibromin	0.019	0.036	-9999	-0.25	8	8
TRAPPC4	0.017	0.001	-9999	-10000	0	0
CSF2	0.017	0	-9999	-10000	0	0
Syndecan-2/TGFB1	0.006	0.067	-9999	-0.24	34	34
Syndecan-2/Syntenin/PI-4-5-P2	0.017	0.032	-9999	-0.22	8	8
Syndecan-2/Ezrin	0.017	0.032	-9999	-0.22	8	8
PRKACA	0.019	0.032	-9999	-0.22	8	8
angiogenesis	-0.037	0.11	-9999	-0.24	121	121
MMP2	-0.19	0.21	-9999	-0.41	251	251
IL8	-0.076	0.18	-9999	-0.41	115	115
calcineurin-NFAT signaling pathway	0.019	0.036	-9999	-0.19	13	13

×

Syndecan-3-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.017	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.023	0.063	-9999	-0.21	25	25
Syndecan-3/Neurocan	0.003	0.062	-9999	-0.2	37	37
POMC	0.017	0	-9999	-10000	0	0
EGFR	-0.14	0.21	-9999	-0.41	194	194
Syndecan-3/EGFR	-0.073	0.12	-9999	-0.21	219	219
AGRP	0.017	0	-9999	-10000	0	0
NCSTN	-0.007	0.099	-9999	-0.41	30	30
PSENEN	0.017	0.001	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.017	0	-9999	-10000	0	0
APH1A	0.008	0.061	-9999	-0.41	11	11
NCAN	0.013	0.027	-9999	-0.41	2	2
long-term memory	0.014	0.065	-9999	-0.21	37	37
Syndecan-3/IL8	-0.042	0.11	-9999	-0.21	145	145
PSEN1	0.016	0.019	-9999	-0.41	1	1
Src/Cortactin	0.025	0	-9999	-10000	0	0
FYN	0.015	0.026	-9999	-0.41	2	2
limb bud formation	0.001	0.058	-9999	-0.26	21	21
MC4R	0.016	0.019	-9999	-0.41	1	1
SRC	0.017	0	-9999	-10000	0	0
PTN	0.016	0.004	-9999	-10000	0	0
FGFR/FGF/Syndecan-3	0.001	0.059	-9999	-0.26	21	21
neuron projection morphogenesis	0.016	0.05	-9999	-0.22	13	13
Syndecan-3/AgRP	0.003	0.073	-9999	-0.25	36	36
Syndecan-3/AgRP/MC4R	0.013	0.073	-9999	-0.24	37	37
Fyn/Cortactin	0.023	0.02	-9999	-0.28	2	2
SDC3	0.001	0.059	-9999	-0.26	21	21
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.041	0.11	-9999	-0.21	145	145
IL8	-0.076	0.18	-9999	-0.41	115	115
Syndecan-3/Fyn/Cortactin	0.014	0.066	-9999	-0.21	37	37
Syndecan-3/CASK	-0.007	0.071	-9999	-0.25	36	36
alpha-MSH/MC4R	0.025	0.013	-9999	-0.28	1	1
Gamma Secretase	0.032	0.068	-9999	-0.2	40	40

×

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

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
MAP4K1	0.004	0.085	-10000	0	-0.23	53	53
CRKL	0.001	0.089	-10000	0	-0.24	53	53
HRAS	0.007	0.097	-10000	0	-0.23	53	53
mol:PIP3	-0.008	0.086	0.18	3	-0.24	52	55
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.017	0	-10000	0	-10000	0	0
GAB1	-0.002	0.093	-10000	0	-0.26	53	53
FOXO3	0.004	0.089	-10000	0	-0.33	9	9
AKT1	0	0.095	-10000	0	-0.26	52	52
BAD	0.004	0.089	-10000	0	-0.33	9	9
megakaryocyte differentiation	0.001	0.088	-10000	0	-0.25	49	49
GSK3B	0.005	0.09	-10000	0	-0.33	9	9
RAF1	0.01	0.083	-10000	0	-0.27	14	14
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
STAT3	-0.004	0.095	-10000	0	-0.26	55	55
STAT1	-0.004	0.16	-10000	0	-0.44	53	53
HRAS/SPRED1	0.006	0.082	-10000	0	-0.2	53	53
cell proliferation	0	0.091	-10000	0	-0.25	53	53
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
TEC	0.017	0	-10000	0	-10000	0	0
RPS6KB1	0.002	0.095	-10000	0	-0.26	53	53
HRAS/SPRED2	0.015	0.085	-10000	0	-0.27	14	14
LYN/TEC/p62DOK	-0.004	0.11	-10000	0	-0.24	57	57
MAPK3	0.017	0.064	-10000	0	-0.2	12	12
STAP1	-0.001	0.093	-10000	0	-0.26	53	53
GRAP2	0.017	0	-10000	0	-10000	0	0
JAK2	-0.001	0.14	-10000	0	-0.4	53	53
STAT1 (dimer)	-0.003	0.15	-10000	0	-0.43	53	53
mol:Gleevec	-0.001	0.004	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	0.02	0.093	-10000	0	-0.24	53	53
actin filament polymerization	-0.004	0.09	-10000	0	-0.25	62	62
LYN	-0.035	0.14	-10000	0	-0.41	64	64
STAP1/STAT5A (dimer)	0.004	0.12	-10000	0	-0.33	53	53
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.018	0.087	-10000	0	-0.22	53	53
PI3K	0.007	0.097	-10000	0	-0.25	46	46
PTEN	0.015	0.026	-10000	0	-0.41	2	2
SCF/KIT/EPO/EPOR	0.008	0.17	-10000	0	-0.47	53	53
MAPK8	-0.001	0.092	-10000	0	-0.26	53	53
STAT3 (dimer)	-0.004	0.093	-10000	0	-0.25	55	55
positive regulation of transcription	0.017	0.055	-10000	0	-0.17	12	12
mol:GDP	0.006	0.1	-10000	0	-0.24	54	54
PIK3C2B	-0.004	0.095	-10000	0	-0.26	56	56
CBL/CRKL	0.01	0.087	-10000	0	-0.23	53	53
FER	-0.001	0.092	-10000	0	-0.26	53	53
SH2B3	-0.004	0.097	-10000	0	-0.27	53	53
PDPK1	-0.004	0.081	0.18	3	-0.22	52	55
SNAI2	-0.047	0.12	-10000	0	-0.3	59	59
positive regulation of cell proliferation	-0.002	0.14	-10000	0	-0.38	53	53
KITLG	0.018	0.011	-10000	0	-10000	0	0
cell motility	-0.002	0.14	-10000	0	-0.38	53	53
PTPN6	0.008	0.062	-10000	0	-0.41	11	11
EPOR	0.024	0.065	-10000	0	-10000	0	0
STAT5A (dimer)	0.003	0.12	-10000	0	-0.33	53	53
SOCS1	0.017	0	-10000	0	-10000	0	0
cell migration	0	0.091	0.25	53	-10000	0	53
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.018	0.005	-10000	0	-10000	0	0
VAV1	0.016	0.019	-10000	0	-0.41	1	1
GRB10	-0.007	0.1	-10000	0	-0.28	53	53
PTPN11	0.017	0.004	-10000	0	-10000	0	0
SCF/KIT	-0.004	0.097	-10000	0	-0.26	62	62
GO:0007205	0	0.006	-10000	0	-10000	0	0
MAP2K1	0.013	0.068	-10000	0	-0.23	12	12
CBL	0.017	0	-10000	0	-10000	0	0
KIT	0.032	0.071	-10000	0	-0.41	12	12
MAP2K2	0.013	0.069	-10000	0	-0.23	12	12
SHC/Grb2/SOS1	-0.006	0.11	-10000	0	-0.28	54	54
STAT5A	0.003	0.12	-10000	0	-0.34	53	53
GRB2	0.017	0.002	-10000	0	-10000	0	0
response to radiation	-0.046	0.12	-10000	0	-0.3	59	59
SHC/GRAP2	-0.002	0.088	-10000	0	-0.28	47	47
PTPRO	0	0.089	-10000	0	-0.26	49	49
SH2B2	-0.004	0.092	-10000	0	-0.25	62	62
DOK1	0.017	0	-10000	0	-10000	0	0
MATK	-0.001	0.092	-10000	0	-0.26	53	53
CREBBP	0.026	0.03	-10000	0	-10000	0	0
BCL2	0.024	0.064	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.029	0.04	-10000	0	-0.23	12	12
fibroblast growth factor receptor signaling pathway	0.028	0.04	-10000	0	-0.23	12	12
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.016	0.004	-10000	0	-10000	0	0
GPC1/SLIT2	0.012	0.037	-10000	0	-0.22	11	11
SMAD2	0.018	0.038	-10000	0	-0.21	15	15
GPC1/PrPc/Cu2+	0.018	0.032	-10000	0	-0.24	8	8
GPC1/Laminin alpha1	0.008	0.037	-10000	0	-0.29	8	8
TDGF1	0.015	0.026	-10000	0	-0.41	2	2
CRIPTO/GPC1	0.02	0.042	-10000	0	-0.28	10	10
APP/GPC1	0.021	0.038	-10000	0	-0.28	8	8
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.022	0.1	-10000	0	-0.24	86	86
FLT1	0.017	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.027	0.045	-10000	0	-0.23	15	15
SERPINC1	0.016	0.019	-10000	0	-0.41	1	1
FYN	0.015	0.038	-10000	0	-0.23	12	12
FGR	0.009	0.056	-10000	0	-0.23	27	27
positive regulation of MAPKKK cascade	-0.022	0.095	-10000	0	-0.22	77	77
SLIT2	0.009	0.033	-10000	0	-0.41	3	3
GPC1/NRG	0.021	0.038	-10000	0	-0.28	8	8
NRG1	0.017	0	-10000	0	-10000	0	0
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.11	0.14	-10000	0	-0.24	289	289
LYN	-0.014	0.09	-10000	0	-0.24	73	73
mol:Spermine	0.004	0.036	-10000	0	-0.29	8	8
cell growth	0.028	0.04	-10000	0	-0.23	12	12
BMP signaling pathway	-0.011	0.052	0.41	8	-10000	0	8
SRC	0.017	0.035	-10000	0	-0.23	10	10
TGFBR1	0.017	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.14	0.21	-10000	0	-0.41	191	191
GPC1	0.011	0.052	-10000	0	-0.41	8	8
TGFBR1 (dimer)	0.017	0	-10000	0	-10000	0	0
VEGFA	-0.22	0.21	-10000	0	-0.41	286	286
BLK	0.017	0.035	-10000	0	-0.23	10	10
HCK	-0.025	0.1	-10000	0	-0.24	95	95
FGF2	0.015	0.026	-10000	0	-0.41	2	2
FGFR1	0.015	0.026	-10000	0	-0.41	2	2
VEGFR1 homodimer	0.017	0	-10000	0	-10000	0	0
TGFBR2	0.011	0.049	-10000	0	-0.41	7	7
cell death	0.021	0.038	-10000	0	-0.28	8	8
ATIII/GPC1	0.02	0.04	-10000	0	-0.28	9	9
PLA2G2A/GPC1	-0.091	0.15	-10000	0	-0.29	196	196
LCK	0.015	0.043	-10000	0	-0.25	13	13
neuron differentiation	0.021	0.038	-10000	0	-0.28	8	8
PrPc/Cu2+	0.012	0.003	-10000	0	-10000	0	0
APP	0.017	0.001	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.011	0.049	-10000	0	-0.41	7	7

×

S1P3 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.032	-9999	-0.41	3	3
mol:S1P	0.001	0.001	-9999	-0.015	1	1
S1P1/S1P/Gi	-0.015	0.052	-9999	-0.15	62	62
GNAO1	0.002	0.005	-9999	-10000	0	0
S1P/S1P3/G12/G13	0.021	0.025	-9999	-0.21	6	6
AKT1	0	0.02	-9999	-0.16	7	7
AKT3	-0.058	0.065	-9999	-0.18	36	36
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.032	-9999	-0.41	3	3
GNAI2	0.018	0.002	-9999	-10000	0	0
GNAI3	-0.035	0.14	-9999	-0.41	65	65
GNAI1	0.015	0.02	-9999	-0.41	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.001	-9999	-0.022	1	1
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.017	0.001	-9999	-10000	0	0
mol:Ca2+	0.002	0.016	-9999	-0.25	1	1
MAPK3	0.002	0.015	-9999	-0.23	1	1
MAPK1	0.002	0.015	-9999	-0.23	1	1
JAK2	-0.074	0.081	-9999	-0.15	262	262
CXCR4	-0.11	0.11	-9999	-0.21	273	273
FLT1	0.019	0.002	-9999	-10000	0	0
RhoA/GDP	0.013	0.001	-9999	-10000	0	0
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.002	0.015	-9999	-0.23	1	1
S1P/S1P3/Gi	0.002	0.016	-9999	-0.25	1	1
RAC1	0.017	0	-9999	-10000	0	0
RhoA/GTP	-0.011	0.039	-9999	-0.16	13	13
VEGFA	-0.21	0.21	-9999	-0.41	286	286
S1P/S1P2/Gi	0.001	0.014	-9999	-0.13	3	3
VEGFR1 homodimer/VEGFA homodimer	-0.14	0.16	-9999	-0.28	286	286
RHOA	0.017	0.001	-9999	-10000	0	0
S1P/S1P3/Gq	0.02	0.019	-9999	-0.13	9	9
GNAQ	0.017	0	-9999	-10000	0	0
GNAZ	0.016	0.006	-9999	-10000	0	0
G12/G13	0.022	0.033	-9999	-0.28	6	6
GNA14	0.015	0.026	-9999	-0.41	2	2
GNA15	0.011	0.049	-9999	-0.41	7	7
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
GNA11	0.017	0	-9999	-10000	0	0
Rac1/GTP	-0.011	0.039	-9999	-0.16	13	13

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	-0.086	0.18	-9999	-0.41	127	127
SMAD2	0.013	0.02	-9999	-0.12	2	2
SMAD3	0.018	0.04	-9999	-0.21	2	2
SMAD3/SMAD4	0.001	0.068	-9999	-0.23	10	10
SMAD4/Ubc9/PIASy	-0.03	0.12	-9999	-0.23	127	127
SMAD2/SMAD2/SMAD4	-0.01	0.1	-9999	-0.19	123	123
PPM1A	0.017	0	-9999	-10000	0	0
CALM1	0.016	0.004	-9999	-10000	0	0
SMAD2/SMAD4	-0.032	0.097	-9999	-0.2	127	127
MAP3K1	0.016	0.019	-9999	-0.41	1	1
TRAP-1/SMAD4	-0.049	0.13	-9999	-0.28	127	127
MAPK3	0.017	0	-9999	-10000	0	0
MAPK1	0.017	0.003	-9999	-10000	0	0
NUP214	0.017	0	-9999	-10000	0	0
CTDSP1	0.015	0.032	-9999	-0.41	3	3
CTDSP2	-0.013	0.11	-9999	-0.41	37	37
CTDSPL	0.017	0	-9999	-10000	0	0
KPNB1	0.017	0	-9999	-10000	0	0
TGFBRAP1	0.017	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
NUP153	0.015	0.026	-9999	-0.41	2	2
KPNA2	0.007	0.064	-9999	-0.41	12	12
PIAS4	0.017	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.02	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	-0.068	0.12	-9999	-0.24	184	184
mol:ADP	0	0	-9999	-10000	0	0
GNAT2	0.017	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.023	0	-9999	-10000	0	0
GRK7	0	0	-9999	-10000	0	0
CNGB3	0.017	0	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.06	0.11	-9999	-0.21	184	184
Cone PDE6	0.04	0.005	-9999	-10000	0	0
Cone Metarhodopsin II	0	0	-9999	-10000	0	0
Na + (4 Units)	-0.052	0.12	-9999	-0.21	184	184
GNAT2/GDP	0.03	0.003	-9999	-10000	0	0
GNB5	0.017	0.002	-9999	-10000	0	0
mol:GMP (4 units)	0.02	0	-9999	-10000	0	0
Cone Transducin	0.022	0	-9999	-10000	0	0
SLC24A2	0.017	0	-9999	-10000	0	0
GNB3/GNGT2	0.013	0	-9999	-10000	0	0
GNB3	0.017	0	-9999	-10000	0	0
GNAT2/GTP	0.013	0	-9999	-10000	0	0
CNGA3	-0.13	0.2	-9999	-0.41	184	184
ARR3	0.017	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.068	0.12	-9999	-0.24	184	184
mol:Pi	0.023	0.003	-9999	-10000	0	0
Cone CNG Channel	-0.036	0.11	-9999	-0.18	184	184
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0.017	0	-9999	-10000	0	0
RGS9	0.017	0	-9999	-10000	0	0
PDE6C	0.017	0	-9999	-10000	0	0
GNGT2	0	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.017	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.032	0.11	-9999	-0.18	187	187
Ran/GTP/Exportin 1/HDAC1	-0.022	0.058	-9999	-0.17	66	66
NF kappa B1 p50/RelA/I kappa B alpha	-0.02	0.086	-9999	-0.25	4	4
SUMO1	0.017	0	-9999	-10000	0	0
ZFPM1	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0.005	-9999	-0.11	1	1
FKBP3	0.017	0.001	-9999	-10000	0	0
Histones	-0.032	0.092	-9999	-0.21	69	69
YY1/LSF	0.026	0	-9999	-10000	0	0
SMG5	0.017	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.03	0.081	-9999	-0.14	186	186
I kappa B alpha/HDAC1	-0.043	0.096	-9999	-0.24	67	67
SAP18	0.017	0	-9999	-10000	0	0
RELA	-0.02	0.07	-9999	-0.12	185	185
HDAC1/Smad7	0.001	0.091	-9999	-0.24	66	66
RANGAP1	0.017	0	-9999	-10000	0	0
HDAC3/TR2	-0.014	0.063	-9999	-10000	0	0
NuRD/MBD3 Complex	-0.009	0.068	-9999	-0.19	40	40
NF kappa B1 p50/RelA	-0.013	0.069	-9999	-0.25	4	4
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.016	0.019	-9999	-0.41	1	1
GATA1	0.017	0	-9999	-10000	0	0
Mad/Max	0.025	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.007	0.073	-9999	-0.19	40	40
RBBP7	0.017	0	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
RBBP4	-0.065	0.17	-9999	-0.41	101	101
MAX	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.017	0	-9999	-10000	0	0
NFKBIA	-0.025	0.068	-9999	-0.18	1	1
KAT2B	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.01	0.07	-9999	-0.23	21	21
SIN3 complex	0.033	0	-9999	-10000	0	0
SMURF1	0.017	0	-9999	-10000	0	0
CHD3	0.017	0	-9999	-10000	0	0
SAP30	0.017	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.017	0	-9999	-10000	0	0
YY1/HDAC3	-0.008	0.056	-9999	-10000	0	0
YY1/HDAC2	0.024	0.024	-9999	-0.22	5	5
YY1/HDAC1	-0.005	0.082	-9999	-0.22	66	66
NuRD/MBD2 Complex (MeCP1)	-0.009	0.068	-9999	-0.19	40	40
PPARG	-0.033	0.088	-9999	-0.15	185	185
HDAC8/hEST1B	0.023	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
HDAC3/SMRT (N-CoR2)	-0.014	0.063	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.001	0.09	-9999	-0.24	66	66
CREBBP	0.017	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.011	0.076	-9999	-0.2	40	40
HDAC1	-0.036	0.14	-9999	-0.41	66	66
HDAC3	-0.025	0.068	-9999	-0.12	185	185
HDAC2	0.013	0.042	-9999	-0.41	5	5
YY1	0.018	0	-9999	-10000	0	0
HDAC8	0	0	-9999	-10000	0	0
SMAD7	0.016	0.019	-9999	-0.41	1	1
NCOR2	0.017	0	-9999	-10000	0	0
MXD1	0.017	0	-9999	-10000	0	0
STAT3	0.019	0.027	-9999	-0.18	10	10
NFKB1	0.014	0.037	-9999	-0.41	4	4
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
YY1/LSF/HDAC1	0.006	0.077	-9999	-0.2	66	66
YY1/SAP30/HDAC1	0.006	0.077	-9999	-0.2	66	66
EP300	0.017	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.018	0.027	-9999	-0.18	10	10
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.068	-9999	-0.18	1	1
histone deacetylation	-0.009	0.068	-9999	-0.19	40	40
STAT3 (dimer non-phopshorylated)/HDAC3	-0.009	0.063	-9999	-0.22	10	10
nuclear export	-0.023	0	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GATAD2B	0	0	-9999	-10000	0	0
GATAD2A	-0.023	0.12	-9999	-0.41	49	49
GATA2/HDAC3	-0.014	0.064	-9999	-0.2	1	1
GATA1/HDAC1	-0.013	0.1	-9999	-0.28	66	66
GATA1/HDAC3	-0.014	0.063	-9999	-10000	0	0
CHD4	0.017	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.083	0.15	-9999	-0.28	185	185
SIN3/HDAC complex/Mad/Max	0.001	0.059	-9999	-0.18	21	21
NuRD Complex	-0.007	0.076	-9999	-0.2	40	40
positive regulation of chromatin silencing	-0.033	0.09	-9999	-0.21	69	69
SIN3B	0.017	0	-9999	-10000	0	0
MTA2	0.017	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
XPO1	0.017	0	-9999	-10000	0	0
SUMO1/HDAC1	0.006	0.071	-9999	-0.18	66	66
HDAC complex	-0.036	0.13	-9999	-0.24	150	150
GATA1/Fog1	0.013	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	-0.001	0.094	-9999	-0.24	69	69
TNF	0.015	0.026	-9999	-0.41	2	2
negative regulation of cell growth	0.001	0.058	-9999	-0.18	21	21
NuRD/MBD2/PRMT5 Complex	-0.009	0.068	-9999	-0.19	40	40
Ran/GTP/Exportin 1	0.034	0.006	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.027	0.084	-9999	-0.14	185	185
SIN3/HDAC complex/NCoR1	-0.005	0.064	-9999	-0.2	21	21
TFCP2	0.017	0	-9999	-10000	0	0
NR2C1	0.017	0	-9999	-10000	0	0
MBD3	0.017	0	-9999	-10000	0	0
MBD2	0.017	0	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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
PTK2	0.009	0.001	-10000	0	-10000	0	0
GNB1/GNG2	0.018	0.029	-10000	0	-0.22	8	8
regulation of S phase of mitotic cell cycle	0.014	0.038	-10000	0	-0.13	32	32
GNAO1	0.002	0.005	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
SHBG/T-DHT	0.012	0	-10000	0	-10000	0	0
PELP1	0.017	0.001	-10000	0	-10000	0	0
AKT1	0.007	0.026	-10000	0	-0.29	4	4
MAP2K1	0.005	0.044	-10000	0	-0.18	10	10
T-DHT/AR	0.008	0.037	-10000	0	-0.29	8	8
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.005	127	127
GNAI2	0.017	0.001	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNAI1	0.014	0.019	-10000	0	-0.41	1	1
mol:GDP	-0.007	0.036	-10000	0	-0.14	31	31
cell proliferation	-0.011	0.096	-10000	0	-0.21	22	22
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
FOS	-0.046	0.15	-10000	0	-0.32	125	125
mol:Ca2+	0	0.006	-10000	0	-0.047	8	8
MAPK3	-0.003	0.073	-10000	0	-0.24	5	5
MAPK1	-0.011	0.07	-10000	0	-0.23	21	21
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
mol:IP3	-0.001	0.001	-10000	0	-0.003	127	127
cAMP biosynthetic process	0.001	0.005	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	-0.001	0.001	-10000	0	-0.003	127	127
HRAS/GTP	0.018	0.037	-10000	0	-0.2	9	9
actin cytoskeleton reorganization	0.015	0.044	-10000	0	-0.18	24	24
SRC	0.017	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.001	-10000	0	-0.003	127	127
PI3K	0.01	0.055	-10000	0	-0.23	25	25
apoptosis	0.018	0.098	0.19	127	-10000	0	127
T-DHT/AR/PELP1	0.018	0.032	-10000	0	-0.24	8	8
HRAS/GDP	0.012	0.039	-10000	0	-0.17	14	14
CREB1	-0.019	0.1	-10000	0	-0.2	125	125
RAC1-CDC42/GTP	0.021	0.046	-10000	0	-0.18	24	24
AR	0.01	0.053	-10000	0	-0.41	8	8
GNB1	0.017	0.002	-10000	0	-10000	0	0
RAF1	0.009	0.04	-10000	0	-0.19	10	10
RAC1-CDC42/GDP	0.023	0.039	-10000	0	-0.19	8	8
T-DHT/AR/PELP1/Src	0.027	0.031	-10000	0	-0.22	8	8
MAP2K2	0.006	0.045	-10000	0	-0.18	10	10
T-DHT/AR/PELP1/Src/PI3K	0.014	0.038	-10000	0	-0.13	32	32
GNAZ	0.015	0.006	-10000	0	-10000	0	0
SHBG	0.017	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.059	0.063	-10000	0	-0.19	65	65
mol:T-DHT	0	0.001	-10000	0	-0.002	106	106
RAC1	0.017	0	-10000	0	-10000	0	0
GNRH1	0.009	0	-10000	0	-10000	0	0
Gi family/GTP	-0.001	0.021	-10000	0	-0.15	8	8
CDC42	0.017	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.017	0	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.003	-10000	0	-10000	0	0
DOCK1	0.017	0	-10000	0	-10000	0	0
ITGA4	0.013	0.042	-10000	0	-0.41	5	5
RAC1	0.017	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.022	0.041	-10000	0	-0.38	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.032	0.026	-10000	0	-0.23	5	5
alpha4/beta7 Integrin/Paxillin	0.032	0.033	-10000	0	-0.29	5	5
lamellipodium assembly	0.018	0.05	-10000	0	-0.26	1	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PI3K	0.009	0.065	-10000	0	-0.28	25	25
ARF6	0.017	0	-10000	0	-10000	0	0
TLN1	-0.02	0.12	-10000	0	-0.41	46	46
PXN	0.018	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
ARF6/GTP	0.04	0.021	-10000	0	-0.17	5	5
cell adhesion	0.021	0.07	-10000	0	-0.19	50	50
CRKL/CBL	0.025	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.033	0.023	-10000	0	-0.21	5	5
ITGB1	0.017	0	-10000	0	-10000	0	0
ITGB7	0.015	0.026	-10000	0	-0.41	2	2
ARF6/GDP	0.013	0.003	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.11	0.11	-10000	0	-0.19	353	353
p130Cas/Crk/Dock1	0.023	0	-10000	0	-10000	0	0
VCAM1	-0.27	0.2	-10000	0	-0.41	351	351
alpha4/beta1 Integrin/Paxillin/Talin	0.022	0.071	-10000	0	-0.2	50	50
alpha4/beta1 Integrin/Paxillin/GIT1	0.042	0.023	-10000	0	-0.19	5	5
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.041	0.022	0.19	5	-10000	0	5
CBL	0.017	0	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
GIT1	0.017	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.022	0.071	-10000	0	-0.2	50	50
Rac1/GTP	0.018	0.053	-10000	0	-0.28	1	1

×

Signaling mediated by p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.011	0.096	-9999	-0.38	29	29
MKNK1	0.017	0	-9999	-10000	0	0
MAPK14	0.015	0.049	-9999	-0.17	31	31
ATF2/c-Jun	0.027	0.034	-9999	-0.39	1	1
MAPK11	0.017	0.042	-9999	-0.16	29	29
MITF	0.021	0.046	-9999	-0.16	33	33
MAPKAPK5	0.022	0.044	-9999	-0.15	31	31
KRT8	0.011	0.069	-9999	-0.19	53	53
MAPKAPK3	0.015	0.026	-9999	-0.41	2	2
MAPKAPK2	0.017	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.022	0.059	-9999	-0.21	31	31
CEBPB	0.018	0.06	-9999	-0.19	36	36
SLC9A1	0.022	0.044	-9999	-0.15	31	31
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.025	0.045	-9999	-0.15	31	31
p38alpha-beta/MNK1	0.033	0.048	-9999	-0.16	31	31
JUN	0.025	0.034	-9999	-0.39	1	1
PPARGC1A	0.021	0.048	-9999	-0.16	33	33
USF1	0.015	0.044	-9999	-0.16	31	31
RAB5/GDP/GDI1	0.021	0.033	-9999	-0.13	9	9
NOS2	0.014	0.044	-9999	-0.16	31	31
DDIT3	0.006	0.074	-9999	-0.18	67	67
RAB5A	0.017	0	-9999	-10000	0	0
HSPB1	0.016	0.05	-9999	-0.24	10	10
p38alpha-beta/HBP1	0.033	0.048	-9999	-0.16	31	31
CREB1	0.026	0.043	-9999	-0.14	31	31
RAB5/GDP	0.013	0	-9999	-10000	0	0
EIF4E	0.02	0.043	-9999	-0.2	6	6
RPS6KA4	0.022	0.044	-9999	-0.15	31	31
PLA2G4A	-0.044	0.12	-9999	-0.23	144	144
GDI1	0.023	0.039	-9999	-0.16	23	23
TP53	-0.005	0.078	-9999	-0.22	31	31
RPS6KA5	0.022	0.044	-9999	-0.15	31	31
ESR1	0.022	0.044	-9999	-0.15	31	31
HBP1	0.017	0	-9999	-10000	0	0
MEF2C	0.02	0.039	-9999	-0.16	22	22
MEF2A	0.022	0.044	-9999	-0.15	31	31
EIF4EBP1	-0.009	0.057	-9999	-0.19	31	31
KRT19	0.011	0.068	-9999	-0.18	54	54
ELK4	0.022	0.044	-9999	-0.15	31	31
ATF6	0.022	0.044	-9999	-0.15	31	31
ATF1	0.022	0.047	-9999	-0.16	31	31
p38alpha-beta/MAPKAPK2	0.033	0.048	-9999	-0.16	31	31
p38alpha-beta/MAPKAPK3	0.032	0.051	-9999	-0.16	33	33

×

Arf6 downstream pathway

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
PLAUR	-0.006	0.12	-10000	0	-0.38	47	47
regulation of axonogenesis	-0.013	0.029	0.14	2	-10000	0	2
myoblast fusion	-0.002	0.062	0.2	47	-10000	0	47
mol:GTP	0.001	0.041	-10000	0	-0.13	47	47
regulation of calcium-dependent cell-cell adhesion	-0.016	0.041	0.12	45	-10000	0	45
ARF1/GTP	0.014	0.033	-10000	0	-10000	0	0
mol:GM1	0	0.03	-10000	0	-0.095	47	47
mol:Choline	0.011	0.03	-10000	0	-0.22	2	2
lamellipodium assembly	0.001	0.063	-10000	0	-0.2	47	47
MAPK3	0.007	0.059	-10000	0	-0.18	47	47
ARF6/GTP/NME1/Tiam1	0.016	0.041	-10000	0	-0.12	45	45
ARF1	0.017	0.001	-10000	0	-10000	0	0
ARF6/GDP	0.002	0.062	-10000	0	-0.2	47	47
ARF1/GDP	0.01	0.058	-10000	0	-0.18	47	47
ARF6	0.011	0.027	-10000	0	-10000	0	0
RAB11A	0.017	0.001	-10000	0	-10000	0	0
TIAM1	0.015	0.008	-10000	0	-10000	0	0
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.007	0.059	-10000	0	-0.18	47	47
actin filament bundle formation	-0.012	0.059	0.18	47	-10000	0	47
KALRN	0.003	0.049	-10000	0	-0.15	47	47
RAB11FIP3/RAB11A	0.025	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.013	0.059	-10000	0	-0.18	47	47
NME1	-0.001	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.013	0.059	-10000	0	-0.18	47	47
substrate adhesion-dependent cell spreading	0.001	0.041	-10000	0	-0.13	47	47
cortical actin cytoskeleton organization	0.001	0.063	-10000	0	-0.2	47	47
RAC1	0.017	0	-10000	0	-10000	0	0
liver development	0.001	0.041	-10000	0	-0.13	47	47
ARF6/GTP	0.001	0.041	-10000	0	-0.13	47	47
RhoA/GTP	0.014	0.033	-10000	0	-10000	0	0
mol:GDP	-0.001	0.062	-10000	0	-0.2	47	47
ARF6/GTP/RAB11FIP3/RAB11A	0.025	0.03	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
PLD1	0.009	0.035	-10000	0	-0.26	2	2
RAB11FIP3	0.017	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.063	-10000	0	-0.2	47	47
ruffle organization	0.013	0.029	-10000	0	-0.14	2	2
regulation of epithelial cell migration	0.001	0.041	-10000	0	-0.13	47	47
PLD2	0.01	0.031	-10000	0	-10000	0	0
PIP5K1A	0.013	0.029	-10000	0	-0.14	2	2
mol:Phosphatidic acid	0.011	0.03	-10000	0	-0.22	2	2
Rac1/GTP	0.001	0.063	-10000	0	-0.2	47	47

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.017	0	-9999	-10000	0	0
Caspase 8 (4 units)	0.019	0.066	-9999	-0.26	12	12
NEF	0.004	0	-9999	-10000	0	0
NFKBIA	0.012	0.032	-9999	-0.5	1	1
BIRC3	0.002	0.11	-9999	-0.39	36	36
CYCS	0.013	0.054	-9999	-0.2	12	12
RIPK1	0.01	0.055	-9999	-0.41	9	9
CD247	0.019	0.026	-9999	-0.41	2	2
MAP2K7	0.02	0.044	-9999	-10000	0	0
protein ubiquitination	0.009	0.056	-9999	-0.18	8	8
CRADD	0.017	0	-9999	-10000	0	0
DAXX	0.016	0.019	-9999	-0.41	1	1
FAS	-0.038	0.14	-9999	-0.41	68	68
BID	0.01	0.056	-9999	-0.21	12	12
NF-kappa-B/RelA/I kappa B alpha	0.026	0.07	-9999	-0.23	36	36
TRADD	0.017	0	-9999	-10000	0	0
MAP3K5	0.017	0.001	-9999	-10000	0	0
CFLAR	0.013	0.042	-9999	-0.41	5	5
FADD	0.015	0.026	-9999	-0.41	2	2
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.026	0.071	-9999	-0.23	36	36
MAPK8	0.023	0.042	-9999	-10000	0	0
APAF1	0.017	0	-9999	-10000	0	0
TRAF1	0.016	0.019	-9999	-0.41	1	1
TRAF2	0.017	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.054	-9999	-0.12	69	69
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.004	0.064	-9999	-0.17	24	24
CHUK	0.009	0.058	-9999	-0.19	8	8
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.014	0.091	-9999	-0.2	75	75
TCRz/NEF	0.021	0.019	-9999	-0.28	2	2
TNF	0.015	0.026	-9999	-0.41	2	2
FASLG	0.022	0.015	-9999	-0.23	2	2
NFKB1	0.01	0.045	-9999	-0.43	4	4
TNFR1A/BAG4/TNF-alpha	-0.059	0.13	-9999	-0.23	185	185
CASP6	0.023	0.068	-9999	-0.3	9	9
CASP7	0.007	0.11	-9999	-0.28	51	51
RELA	0.013	0.023	-9999	-10000	0	0
CASP2	0.016	0.019	-9999	-0.41	1	1
CASP3	-0.002	0.11	-9999	-0.28	48	48
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
TNFR1A/BAG4	-0.082	0.15	-9999	-0.28	183	183
CASP8	0.01	0.055	-9999	-0.41	9	9
CASP9	0.014	0.037	-9999	-0.41	4	4
MAP3K14	0.006	0.062	-9999	-0.21	8	8
APAF-1/Caspase 9	0.012	0.089	-9999	-0.28	37	37
BCL2	0.025	0.04	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	0.011	0.049	-10000	0	-0.41	7	7
mol:Halofuginone	0.004	0.015	-10000	0	-0.17	4	4
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	0.009	0.052	-10000	0	-0.14	54	54
PRL-3/alpha Tubulin	0.007	0.073	-10000	0	-0.28	31	31
mol:Ca2+	0.009	0.052	0.22	31	-10000	0	31
AGT	0.016	0.005	-10000	0	-10000	0	0
CCNA2	-0.038	0.1	-10000	0	-0.2	148	148
TUBA1B	0.017	0	-10000	0	-10000	0	0
EGR1	0.011	0.051	-10000	0	-0.28	16	16
CDK2/Cyclin E1	0.012	0.076	-10000	0	-0.28	13	13
MAPK3	0	0.071	-10000	0	-0.28	31	31
PRL-2 /Rab GGTase beta	0.025	0.001	-10000	0	-10000	0	0
MAPK1	-0.001	0.071	-10000	0	-0.28	31	31
PTP4A1	0.015	0.044	-10000	0	-0.21	19	19
PTP4A3	-0.008	0.1	-10000	0	-0.41	31	31
PTP4A2	0.017	0.001	-10000	0	-10000	0	0
ITGB1	0	0.071	-10000	0	-0.28	31	31
SRC	0.017	0	-10000	0	-10000	0	0
RAC1	0.015	0.042	-10000	0	-0.14	32	32
Rab GGTase beta/Rab GGTase alpha	0.025	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.024	0.043	-10000	0	-0.19	20	20
RABGGTA	0.017	0	-10000	0	-10000	0	0
BCAR1	0.002	0.051	0.21	31	-10000	0	31
RHOC	-0.032	0.081	-10000	0	-0.14	185	185
RHOA	0.015	0.042	-10000	0	-0.14	32	32
cell motility	-0.004	0.055	-10000	0	-0.2	14	14
PRL-1/alpha Tubulin	0.024	0.042	-10000	0	-0.19	19	19
PRL-3/alpha1 Integrin	-0.005	0.071	-10000	0	-0.29	31	31
ROCK1	-0.004	0.055	-10000	0	-0.2	14	14
RABGGTB	0.017	0	-10000	0	-10000	0	0
CDK2	-0.005	0.094	-10000	0	-0.41	27	27
mitosis	0.015	0.044	-10000	0	-0.21	19	19
ATF5	0.016	0.019	-10000	0	-0.41	1	1

×

ErbB2/ErbB3 signaling events

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
USP8	0.01	0.022	-10000	0	-0.24	4	4
RAS family/GTP	-0.034	0.11	-10000	0	-0.19	134	134
NFATC4	0.015	0.04	-10000	0	-10000	0	0
ERBB2IP	-0.008	0.1	-10000	0	-0.41	31	31
HSP90 (dimer)	0.017	0	-10000	0	-10000	0	0
mammary gland morphogenesis	0.019	0.054	0.15	18	-0.15	34	52
JUN	0.015	0.047	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
DOCK7	0.009	0.046	-10000	0	-0.14	34	34
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.005	0.085	0.16	26	-0.2	65	91
AKT1	0.007	0.026	-10000	0	-0.29	4	4
BAD	0.01	0.022	-10000	0	-0.24	4	4
MAPK10	0.01	0.025	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.021	0.057	0.16	18	-0.16	34	52
RAF1	-0.032	0.1	-10000	0	-0.22	62	62
ErbB2/ErbB3/neuregulin 2	0.015	0.066	0.16	30	-0.21	32	62
STAT3	0.019	0.027	-10000	0	-10000	0	0
cell migration	0.011	0.029	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-0.003	34	34
cell proliferation	-0.026	0.12	-10000	0	-0.36	13	13
FOS	-0.039	0.13	-10000	0	-0.24	121	121
NRAS	-0.094	0.19	-10000	0	-0.41	137	137
mol:Ca2+	0.019	0.054	0.15	18	-0.15	34	52
MAPK3	-0.017	0.098	-10000	0	-0.33	8	8
MAPK1	-0.028	0.11	-10000	0	-0.38	15	15
JAK2	0.016	0.047	-10000	0	-0.16	4	4
NF2	0.012	0.007	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.004	0.061	-10000	0	-0.15	74	74
NRG1	0.017	0.001	-10000	0	-10000	0	0
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
MAPK8	0.022	0.042	-10000	0	-0.13	4	4
MAPK9	0.019	0.029	-10000	0	-10000	0	0
ERBB2	0.009	0.052	0.22	31	-10000	0	31
ERBB3	-0.01	0.1	-10000	0	-0.41	32	32
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
RAC1	0.017	0	-10000	0	-10000	0	0
apoptosis	-0.007	0.022	0.23	4	-10000	0	4
STAT3 (dimer)	0.019	0.027	-10000	0	-10000	0	0
RNF41	0.012	0.02	-10000	0	-0.21	4	4
FRAP1	0.01	0.024	-10000	0	-0.24	5	5
RAC1-CDC42/GTP	-0.006	0.027	-10000	0	-0.12	3	3
ErbB2/ErbB2/HSP90 (dimer)	0.022	0.035	0.16	31	-10000	0	31
CHRNA1	-0.011	0.085	-10000	0	-0.25	12	12
myelination	0.021	0.042	-10000	0	-10000	0	0
PPP3CB	0.015	0.045	-10000	0	-0.15	4	4
KRAS	0.017	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.014	0.058	-10000	0	-0.18	9	9
NRG2	0.017	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.061	-10000	0	-0.15	74	74
SOS1	0	0	-10000	0	-10000	0	0
MAP2K2	-0.027	0.096	-10000	0	-0.23	47	47
SRC	0.017	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.016	0.047	-10000	0	-0.16	4	4
MAP2K1	-0.028	0.12	-10000	0	-0.4	22	22
heart morphogenesis	0.019	0.054	0.15	18	-0.15	34	52
RAS family/GDP	-0.033	0.11	-10000	0	-0.2	134	134
GRB2	0.017	0.002	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
CHRNE	0.01	0.013	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
activation of caspase activity	-0.007	0.026	0.29	4	-10000	0	4
nervous system development	0.019	0.054	0.15	18	-0.15	34	52
CDC42	0.017	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.015	0.032	-10000	0	-0.41	3	3
Jak2/Leptin Receptor	0.017	0.034	-10000	0	-0.16	3	3
PTP1B/AKT1	-0.002	0.048	-10000	0	-0.2	7	7
FYN	0.015	0.026	-10000	0	-0.41	2	2
p210 bcr-abl/PTP1B	-0.01	0.045	-10000	0	-0.13	41	41
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
EGF/EGFR	-0.055	0.1	-10000	0	-0.18	197	197
CSF1	0.017	0	-10000	0	-10000	0	0
AKT1	0.014	0.037	-10000	0	-0.41	4	4
INSR	0.017	0	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.004	0.049	-10000	0	-0.18	9	9
Insulin Receptor/Insulin	0.018	0.041	-10000	0	-0.21	4	4
HCK	-0.053	0.16	-10000	0	-0.41	86	86
CRK	0.017	0	-10000	0	-10000	0	0
TYK2	-0.006	0.044	-10000	0	-0.18	5	5
EGF	0.013	0.027	-10000	0	-0.41	2	2
YES1	-0.048	0.15	-10000	0	-0.41	80	80
CAV1	-0.069	0.068	-10000	0	-0.16	150	150
TXN	0.015	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.003	0.05	-10000	0	-0.18	7	7
cell migration	0.01	0.045	0.13	41	-10000	0	41
STAT3	0.009	0.059	-10000	0	-0.41	10	10
PRLR	0.02	0	-10000	0	-10000	0	0
ITGA2B	0.016	0	-10000	0	-10000	0	0
CSF1R	-0.016	0.12	-10000	0	-0.41	41	41
Prolactin Receptor/Prolactin	0.029	0.033	-10000	0	-0.28	6	6
FGR	0.003	0.076	-10000	0	-0.41	17	17
PTP1B/p130 Cas	-0.01	0.042	-10000	0	-0.12	42	42
Crk/p130 Cas	-0.003	0.044	-10000	0	-0.13	11	11
DOK1	0.003	0.04	-10000	0	-0.16	4	4
JAK2	0.011	0.03	-10000	0	-10000	0	0
Jak2/Leptin Receptor/Leptin	0.022	0.051	-10000	0	-0.21	8	8
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
PTPN1	-0.01	0.046	-10000	0	-0.13	42	42
LYN	-0.035	0.14	-10000	0	-0.41	64	64
CDH2	0.014	0.032	-10000	0	-0.41	3	3
SRC	0.014	0.019	-10000	0	-10000	0	0
ITGB3	0.016	0	-10000	0	-10000	0	0
CAT1/PTP1B	-0.027	0.093	-10000	0	-0.22	76	76
CAPN1	0.016	0.001	-10000	0	-10000	0	0
CSK	0.017	0	-10000	0	-10000	0	0
PI3K	0.015	0.057	-10000	0	-0.18	28	28
mol:H2O2	-0.002	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	0.023	0.048	-10000	0	-0.21	8	8
negative regulation of transcription	0.011	0.03	-10000	0	-10000	0	0
FCGR2A	-0.2	0.22	-10000	0	-0.41	266	266
FER	0.015	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.023	0.001	-10000	0	-10000	0	0
BLK	0.017	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.011	0.077	-10000	0	-0.24	47	47
RHOA	0.016	0.001	-10000	0	-10000	0	0
LEPR	0.014	0.032	-10000	0	-0.41	3	3
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.017	0.002	-10000	0	-10000	0	0
mol:NADPH	-0.002	0.002	-10000	0	-10000	0	0
TRPV6	-0.021	0.1	-10000	0	-0.23	75	75
PRL	0.015	0.045	-10000	0	-0.41	6	6
SOCS3	0.009	0.009	-10000	0	-10000	0	0
SPRY2	0.009	0.053	-10000	0	-0.42	8	8
Insulin Receptor/Insulin/IRS1	0.033	0.026	-10000	0	-0.24	5	5
CSF1/CSF1R	-0.011	0.068	-10000	0	-0.18	43	43
Ras protein signal transduction	0.013	0.031	0.29	5	-10000	0	5
IRS1	0.013	0.042	-10000	0	-0.41	5	5
INS	0.017	0	-10000	0	-10000	0	0
LEP	0.017	0	-10000	0	-10000	0	0
STAT5B	0.003	0.039	-10000	0	-0.16	2	2
STAT5A	0.003	0.039	-10000	0	-0.16	2	2
GRB2	0.017	0.002	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.004	0.048	-10000	0	-0.16	10	10
CSN2	0.023	0.015	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
LAT	-0.065	0.081	-10000	0	-0.18	49	49
YBX1	0.015	0.064	-10000	0	-0.4	12	12
LCK	0.014	0.037	-10000	0	-0.41	4	4
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
NOX4	-0.042	0.15	-10000	0	-0.42	70	70

×

TRAIL signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.02	0.12	-9999	-0.41	46	46
positive regulation of NF-kappaB transcription factor activity	-0.002	0.087	-9999	-0.28	46	46
MAP2K4	0.018	0.042	-9999	-0.19	4	4
IKBKB	0.017	0	-9999	-10000	0	0
TNFRSF10B	0.011	0.049	-9999	-0.41	7	7
TNFRSF10A	0	0	-9999	-10000	0	0
SMPD1	0.002	0.043	-9999	-0.13	52	52
IKBKG	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.017	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.006	0.094	-9999	-0.29	52	52
TRAIL/TRAILR3	-0.002	0.087	-9999	-0.28	46	46
TRAIL/TRAILR1	-0.014	0.085	-9999	-0.29	46	46
TRAIL/TRAILR4	-0.002	0.087	-9999	-0.28	46	46
TRAIL/TRAILR1/DAP3/GTP	0.001	0.067	-9999	-0.22	46	46
IKK complex	0.021	0.037	-9999	-0.15	5	5
RIPK1	0.01	0.055	-9999	-0.41	9	9
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.013	0	-9999	-10000	0	0
MAPK3	-0.009	0.085	-9999	-0.28	46	46
MAP3K1	0.016	0.047	-9999	-0.12	54	54
TRAILR4 (trimer)	0.017	0	-9999	-10000	0	0
TRADD	0.017	0	-9999	-10000	0	0
TRAILR1 (trimer)	0	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.011	0.049	-9999	-0.13	54	54
CFLAR	0.013	0.042	-9999	-0.41	5	5
MAPK1	-0.006	0.081	-9999	-0.28	41	41
TRAIL/TRAILR1/FADD/TRADD/RIP	0.016	0.076	-9999	-0.2	54	54
mol:ceramide	0.002	0.043	-9999	-0.13	52	52
FADD	0.015	0.026	-9999	-0.41	2	2
MAPK8	0.02	0.04	-9999	-0.18	4	4
TRAF2	0.017	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
TRAIL/TRAILR1/FADD	0	0.076	-9999	-0.24	47	47
DAP3	0.017	0	-9999	-10000	0	0
CASP10	-0.006	0.063	-9999	-0.19	53	53
JNK cascade	-0.002	0.087	-9999	-0.28	46	46
TRAIL (trimer)	-0.02	0.12	-9999	-0.41	46	46
TNFRSF10C	0.017	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.01	0.067	-9999	-0.2	47	47
TRAIL/TRAILR2/FADD	0.007	0.084	-9999	-0.24	53	53
cell death	0.002	0.043	-9999	-0.13	52	52
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.014	0.053	-9999	-0.13	60	60
TRAILR2 (trimer)	0.011	0.049	-9999	-0.41	7	7
CASP8	0.01	0.035	-9999	-0.22	7	7
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.022	0.083	-9999	-0.2	60	60

×

RXR and RAR heterodimerization with other nuclear receptor

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.005	0.093	-9999	-0.39	28	28
VDR	0.017	0	-9999	-10000	0	0
FAM120B	0	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.074	0.079	-9999	-0.26	5	5
RXRs/LXRs/DNA/Oxysterols	-0.12	0.11	-9999	-0.18	382	382
MED1	0.017	0	-9999	-10000	0	0
mol:9cRA	-0.021	0.016	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.031	0.005	-9999	-10000	0	0
RXRs/NUR77	-0.008	0.044	-9999	-0.26	3	3
RXRs/PPAR	0.001	0.028	-9999	-0.14	8	8
NCOR2	0.017	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.013	0	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	0.041	0	-9999	-10000	0	0
RARA	0.017	0	-9999	-10000	0	0
NCOA1	0.017	0.003	-9999	-10000	0	0
VDR/VDR/DNA	0.017	0	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	0.02	0.009	-9999	-10000	0	0
RARG	0.017	0	-9999	-10000	0	0
RPS6KB1	0.017	0.057	-9999	-0.22	28	28
RARs/THRs/DNA/SMRT	0.032	0	-9999	-10000	0	0
THRA	0.017	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.013	0	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.035	0.056	-9999	-0.29	3	3
NR1H4	0.017	0	-9999	-10000	0	0
RXRs/LXRs/DNA	-0.041	0.075	-9999	-0.26	7	7
NR1H2	-0.006	0.017	-9999	-10000	0	0
NR1H3	-0.012	0.041	-9999	-0.42	4	4
RXRs/VDR/DNA/Vit D3	-0.008	0.041	-9999	-0.24	3	3
NR4A1	0.017	0	-9999	-10000	0	0
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.015	0.032	-9999	-0.15	3	3
RXRG	-0.009	0.037	-9999	-0.44	3	3
RXR alpha/CCPG	-0.003	0.012	-9999	-10000	0	0
RXRA	-0.006	0.017	-9999	-10000	0	0
RXRB	-0.009	0.02	-9999	-10000	0	0
THRB	0.017	0	-9999	-10000	0	0
PPARG	0.013	0.042	-9999	-0.41	5	5
PPARD	0.017	0	-9999	-10000	0	0
TNF	-0.1	0.1	-9999	-0.3	7	7
mol:Oxysterols	-0.017	0.014	-9999	-10000	0	0
cholesterol transport	-0.11	0.11	-9999	-0.18	382	382
PPARA	0.017	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.017	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	0.013	0.016	-9999	-0.15	3	3
SREBF1	-0.1	0.099	-9999	-0.28	5	5
RXRs/RXRs/DNA/9cRA	-0.035	0.056	-9999	-0.29	3	3
ABCA1	-0.24	0.18	-9999	-0.35	380	380
RARs/THRs	0.051	0	-9999	-10000	0	0
RXRs/FXR	-0.008	0.044	-9999	-0.26	3	3
BCL2	0.017	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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
HDAC1	-0.023	0.14	-10000	0	-0.39	66	66
AES	0.028	0.02	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.044	-10000	0	-0.28	11	11
SMAD4	-0.086	0.18	-10000	0	-0.41	127	127
DKK2	0.009	0.058	-10000	0	-0.41	10	10
TLE1	0.028	0.02	-10000	0	-10000	0	0
MACF1	0.018	0.001	-10000	0	-10000	0	0
CTNNB1	0.065	0.034	0.22	1	-0.14	1	2
WIF1	0.002	0.006	-10000	0	-10000	0	0
beta catenin/RanBP3	0.092	0.13	0.26	187	-10000	0	187
KREMEN2	0.017	0	-10000	0	-10000	0	0
DKK1	-0.078	0.18	-10000	0	-0.41	117	117
beta catenin/beta TrCP1	0.072	0.033	0.22	1	-10000	0	1
FZD1	0.009	0.058	-10000	0	-0.41	10	10
AXIN2	-0.043	0.066	-10000	0	-0.13	169	169
AXIN1	0.018	0	-10000	0	-10000	0	0
RAN	0.017	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.046	0.035	-10000	0	-0.31	4	4
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.042	0.065	-10000	0	-0.2	1	1
Axin1/APC/GSK3	0.059	0.02	0.19	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.056	0.036	-10000	0	-10000	0	0
HNF1A	0.028	0.021	-10000	0	-10000	0	0
CTBP1	0.028	0.022	-10000	0	-10000	0	0
MYC	-0.11	0.19	-10000	0	-0.43	137	137
RANBP3	0.018	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.03	0.038	-10000	0	-0.23	11	11
NKD1	0	0	-10000	0	-10000	0	0
TCF4	0.028	0.022	-10000	0	-10000	0	0
TCF3	0.028	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.038	0.036	-10000	0	-0.21	11	11
Ran/GTP	0.014	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.099	0.14	0.28	169	-0.18	1	170
LEF1	0.027	0.038	-10000	0	-0.39	3	3
DVL1	0.004	0.012	-10000	0	-10000	0	0
CSNK2A1	0.017	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.04	0.052	-10000	0	-0.18	2	2
DKK1/LRP6/Kremen 2	-0.025	0.11	-10000	0	-0.23	118	118
LRP6	0.016	0.019	-10000	0	-0.41	1	1
CSNK1A1	0.031	0.024	-10000	0	-10000	0	0
NLK	0.015	0.005	-10000	0	-10000	0	0
CCND1	-0.087	0.17	-10000	0	-0.44	98	98
WNT1	0.017	0.001	-10000	0	-10000	0	0
GSK3A	0.017	0.001	-10000	0	-10000	0	0
GSK3B	0.017	0.002	-10000	0	-10000	0	0
FRAT1	0.016	0.019	-10000	0	-0.41	1	1
PPP2R5D	0.007	0.016	-10000	0	-10000	0	0
APC	0.021	0.031	-10000	0	-0.19	11	11
WNT1/LRP6/FZD1	0.003	0.011	-10000	0	-0.12	2	2
CREBBP	0.028	0.021	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.025	0.29	-9999	-0.55	86	86
IL23A	0.027	0.23	-9999	-0.69	20	20
NF kappa B1 p50/RelA/I kappa B alpha	0.034	0.23	-9999	-0.56	40	40
positive regulation of T cell mediated cytotoxicity	0.028	0.24	-9999	-0.6	40	40
ITGA3	0.025	0.24	-9999	-0.58	40	40
IL17F	0.025	0.18	-9999	-0.44	33	33
IL12B	0.025	0.029	-9999	-10000	0	0
STAT1 (dimer)	0.017	0.23	-9999	-0.58	40	40
CD4	0.026	0.24	-9999	-0.57	45	45
IL23	0.026	0.22	-9999	-0.67	20	20
IL23R	0.018	0.064	-9999	-0.13	18	18
IL1B	0.027	0.24	-9999	-0.58	43	43
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	0.032	0.22	-9999	-0.55	39	39
TYK2	0.02	0.027	-9999	-0.39	1	1
STAT4	0.01	0.008	-9999	-10000	0	0
STAT3	0.009	0.058	-9999	-0.41	10	10
IL18RAP	0.018	0.002	-9999	-10000	0	0
IL12RB1	0.021	0.021	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
IL12Rbeta1/TYK2	0.028	0.029	-9999	-0.26	1	1
IL23R/JAK2	0.034	0.085	-9999	-0.17	10	10
positive regulation of chronic inflammatory response	0.028	0.24	-9999	-0.6	40	40
natural killer cell activation	-0.001	0.006	-9999	-10000	0	0
JAK2	0.025	0.029	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
NFKB1	0.015	0.038	-9999	-0.42	4	4
RELA	0.018	0.003	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.027	0.22	-9999	-0.65	20	20
ALOX12B	0.032	0.22	-9999	-0.55	39	39
CXCL1	0.022	0.25	-9999	-0.61	46	46
T cell proliferation	0.028	0.24	-9999	-0.6	40	40
NFKBIA	0.017	0.019	-9999	-0.42	1	1
IL17A	0.047	0.16	-9999	-0.38	22	22
PI3K	0.024	0.22	-9999	-0.56	35	35
IFNG	0.012	0.017	-9999	-0.045	16	16
STAT3 (dimer)	0.028	0.22	-9999	-0.57	33	33
IL18R1	0.018	0.002	-9999	-10000	0	0
IL23/IL23R/JAK2/TYK2/SOCS3	0.039	0.16	-9999	-0.4	18	18
IL18/IL18R	0.016	0.075	-9999	-0.23	45	45
macrophage activation	0.001	0.014	-9999	-0.037	19	19
TNF	0.029	0.23	-9999	-0.57	40	40
STAT3/STAT4	-0.017	0.2	-9999	-0.57	37	37
STAT4 (dimer)	-0.018	0.2	-9999	-0.58	37	37
IL18	-0.019	0.12	-9999	-0.41	45	45
IL19	0.033	0.22	-9999	-0.55	39	39
STAT5A (dimer)	0.024	0.23	-9999	-0.58	39	39
STAT1	0.002	0.078	-9999	-0.41	18	18
SOCS3	0.017	0	-9999	-10000	0	0
CXCL9	0.01	0.25	-9999	-0.56	57	57
MPO	0.033	0.22	-9999	-0.55	39	39
positive regulation of humoral immune response	0.028	0.24	-9999	-0.6	40	40
IL23/IL23R/JAK2/TYK2	0.027	0.24	-9999	-0.61	40	40
IL6	0.014	0.26	-9999	-0.68	39	39
STAT5A	0.016	0.019	-9999	-0.41	1	1
IL2	0.018	0.004	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	-0.001	0.006	-9999	-10000	0	0
CD3E	0.032	0.22	-9999	-0.55	39	39
keratinocyte proliferation	0.028	0.24	-9999	-0.6	40	40
NOS2	0.026	0.22	-9999	-0.55	39	39

×

Caspase cascade in apoptosis

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
TOP1	0.01	0.055	-10000	0	-0.21	9	9
ACTA1	0.004	0.062	0.15	16	-0.19	19	35
NUMA1	0.01	0.055	0.14	2	-0.2	10	12
SPTAN1	0.012	0.063	0.16	30	-0.19	12	42
LIMK1	0.006	0.06	0.15	15	-0.18	18	33
BIRC3	-0.01	0.1	-10000	0	-0.41	33	33
BIRC2	0.017	0	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
CASP10	0.006	0.056	-10000	0	-0.25	22	22
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.009	0.056	-10000	0	-0.2	11	11
DIABLO	0.017	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.014	0.065	0.16	30	-0.19	12	42
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.017	0	-10000	0	-10000	0	0
GSN	0	0.068	0.15	15	-0.2	28	43
MADD	0.017	0.001	-10000	0	-10000	0	0
TFAP2A	0.019	0.026	-10000	0	-0.28	1	1
BID	0.006	0.041	-10000	0	-0.14	35	35
MAP3K1	0.011	0.029	-10000	0	-0.15	2	2
TRADD	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0.027	-10000	0	-0.28	4	4
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.011	0.087	0.16	13	-0.22	52	65
CASP9	0.014	0.037	-10000	0	-0.41	4	4
DNA repair	-0.006	0.039	0.1	16	-0.13	23	39
neuron apoptosis	0.015	0.036	-10000	0	-0.56	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.012	0.059	0.15	7	-0.22	9	16
APAF1	0.017	0	-10000	0	-10000	0	0
CASP6	0.004	0.055	-10000	0	-0.27	1	1
TRAF2	0.017	0	-10000	0	-10000	0	0
ICAD/CAD	0.01	0.058	0.15	8	-0.21	9	17
CASP7	-0.008	0.07	0.19	26	-0.18	55	81
KRT18	0.001	0.049	-10000	0	-0.2	20	20
apoptosis	0.005	0.071	0.18	6	-0.21	21	27
DFFA	0.006	0.06	0.15	15	-0.18	17	32
DFFB	0.006	0.06	0.15	15	-0.18	17	32
PARP1	0.006	0.039	0.13	23	-0.1	16	39
actin filament polymerization	-0.006	0.056	0.17	17	-0.14	15	32
TNF	0.015	0.026	-10000	0	-0.41	2	2
CYCS	0.011	0.029	-10000	0	-0.13	10	10
SATB1	0.024	0.059	-10000	0	-10000	0	0
SLK	0.006	0.06	0.15	15	-0.18	18	33
p15 BID/BAX	0.013	0.047	-10000	0	-0.14	41	41
CASP2	-0.005	0.058	-10000	0	-0.16	25	25
JNK cascade	-0.011	0.029	0.15	2	-10000	0	2
CASP3	0.003	0.064	0.15	22	-0.19	19	41
LMNB2	0.002	0.051	-10000	0	-0.23	5	5
RIPK1	0.01	0.055	-10000	0	-0.41	9	9
CASP4	-0.07	0.17	-10000	0	-0.41	107	107
Mammalian IAPs/DIABLO	0.018	0.059	-10000	0	-0.21	33	33
negative regulation of DNA binding	0.019	0.026	-10000	0	-0.28	1	1
stress fiber formation	0.007	0.059	0.15	15	-0.18	18	33
GZMB	0.004	0.066	-10000	0	-0.31	22	22
CASP1	-0.087	0.14	-10000	0	-0.26	194	194
LMNB1	-0.014	0.059	-10000	0	-0.21	12	12
APP	0.015	0.037	-10000	0	-0.56	1	1
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.004	0.039	-10000	0	-0.29	9	9
VIM	0.002	0.072	0.17	12	-0.21	24	36
LMNA	0.005	0.048	-10000	0	-0.2	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.008	0.061	-10000	0	-0.18	24	24
LRDD	0.017	0	-10000	0	-10000	0	0
SREBF1	0.006	0.06	0.15	15	-0.18	17	32
APAF-1/Caspase 9	0.01	0.026	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.01	0.054	0.14	2	-0.2	10	12
CFL2	0.006	0.057	0.14	15	-0.18	17	32
GAS2	-0.009	0.083	0.15	14	-0.2	56	70
positive regulation of apoptosis	-0.003	0.054	-10000	0	-0.21	9	9
PRF1	0.007	0.064	-10000	0	-0.41	12	12

×

EPO signaling pathway

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
BCL2L1	0.033	0.072	-10000	0	-0.24	18	18
CRKL	0.027	0.04	-10000	0	-0.17	19	19
mol:DAG	0.017	0.076	-10000	0	-0.17	64	64
HRAS	0.015	0.068	-10000	0	-0.3	8	8
MAPK8	-0.001	0.079	-10000	0	-0.22	64	64
RAP1A	0.027	0.04	-10000	0	-0.17	19	19
GAB1	0.026	0.043	-10000	0	-0.17	23	23
MAPK14	-0.002	0.08	-10000	0	-0.22	66	66
EPO	0.019	0.007	-10000	0	-10000	0	0
PLCG1	0.017	0.077	-10000	0	-0.18	64	64
EPOR/TRPC2/IP3 Receptors	0.019	0.007	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.038	0.006	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.017	0.073	-10000	0	-0.18	52	52
EPO/EPOR (dimer)	0.028	0.011	-10000	0	-10000	0	0
IRS2	0.027	0.039	-10000	0	-0.17	18	18
STAT1	0.019	0.088	-10000	0	-0.31	18	18
STAT5B	0.021	0.077	-10000	0	-0.17	64	64
cell proliferation	-0.001	0.074	-10000	0	-0.2	66	66
GAB1/SHIP/PIK3R1/SHP2/SHC	0.012	0.065	-10000	0	-0.17	46	46
TEC	0.027	0.04	-10000	0	-0.17	19	19
SOCS3	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)	0.019	0.087	-10000	0	-0.3	18	18
JAK2	0.018	0.007	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.053	0.047	-10000	0	-0.18	19	19
EPO/EPOR	0.028	0.011	-10000	0	-10000	0	0
LYN	-0.033	0.14	-10000	0	-0.41	64	64
TEC/VAV2	0.038	0.04	-10000	0	-0.32	2	2
elevation of cytosolic calcium ion concentration	0.018	0.007	-10000	0	-10000	0	0
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
EPO/EPOR (dimer)/LYN	0.009	0.096	-10000	0	-0.25	64	64
mol:IP3	0.017	0.076	-10000	0	-0.17	64	64
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.032	0.036	-10000	0	-0.16	15	15
SH2B3	0.01	0.059	-10000	0	-0.41	10	10
NFKB1	-0.003	0.084	-10000	0	-0.22	66	66
EPO/EPOR (dimer)/JAK2/SOCS3	0.017	0.02	0.16	10	-10000	0	10
PTPN6	0.024	0.041	-10000	0	-0.18	19	19
TEC/VAV2/GRB2	0.045	0.04	-10000	0	-0.3	2	2
EPOR	0.019	0.007	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.073	-10000	0	-0.18	52	52
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.009	0.058	-10000	0	-0.41	10	10
CRKL/CBL/C3G	0.046	0.04	-10000	0	-0.3	2	2
VAV2	0.027	0.04	-10000	0	-0.17	19	19
CBL	0.027	0.04	-10000	0	-0.17	19	19
SHC/Grb2/SOS1	0.008	0.071	-10000	0	-0.18	55	55
STAT5A	0.021	0.078	-10000	0	-0.25	18	18
GRB2	0.017	0.002	-10000	0	-10000	0	0
STAT5 (dimer)	0.038	0.083	-10000	0	-0.3	13	13
LYN/PLCgamma2	-0.016	0.12	-10000	0	-0.32	65	65
PTPN11	0.017	0	-10000	0	-10000	0	0
BTK	0.027	0.042	-10000	0	-0.18	19	19
BCL2	0.033	0.072	-10000	0	-0.24	18	18

×

IL6-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.038	0.16	-9999	-0.43	36	36
CRP	-0.038	0.16	-9999	-0.43	36	36
cell cycle arrest	-0.059	0.17	-9999	-0.44	56	56
TIMP1	-0.2	0.22	-9999	-0.46	143	143
IL6ST	0.016	0.008	-9999	-10000	0	0
Rac1/GDP	0.007	0.075	-9999	-0.23	15	15
AP1	-0.035	0.1	-9999	-0.28	20	20
GAB2	0.017	0.019	-9999	-0.41	1	1
TNFSF11	-0.038	0.16	-9999	-0.43	36	36
HSP90B1	0.014	0.055	-9999	-0.39	2	2
GAB1	0.014	0.037	-9999	-0.41	4	4
MAPK14	0.019	0.048	-9999	-10000	0	0
AKT1	0.028	0.039	-9999	-0.32	1	1
FOXO1	0.025	0.05	-9999	-0.29	4	4
MAP2K6	0.012	0.056	-9999	-0.18	7	7
mol:GTP	-0.001	0.002	-9999	-10000	0	0
MAP2K4	-0.001	0.096	-9999	-0.3	14	14
MITF	0.004	0.067	-9999	-0.2	28	28
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0.019	-9999	-0.41	1	1
A2M	-0.009	0.11	-9999	-0.44	30	30
CEBPB	0.015	0.062	-9999	-0.41	11	11
GRB2/SOS1/GAB family/SHP2	0.009	0.052	-9999	-0.32	3	3
STAT3	-0.061	0.18	-9999	-0.45	56	56
STAT1	0.003	0.046	-9999	-0.25	4	4
CEBPD	-0.038	0.16	-9999	-0.43	36	36
PIK3CA	-0.002	0.091	-9999	-0.41	25	25
PI3K	0.011	0.065	-9999	-0.28	25	25
JUN	0.016	0.019	-9999	-0.41	1	1
PIAS3/MITF	0.011	0.068	-9999	-0.21	18	18
MAPK11	0.02	0.047	-9999	-10000	0	0
STAT3 (dimer)/FOXO1	-0.036	0.16	-9999	-0.48	22	22
GRB2/SOS1/GAB family	0.007	0.077	-9999	-0.22	22	22
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.008	0.085	-9999	-0.19	66	66
GRB2	0.017	0.003	-9999	-10000	0	0
JAK2	0.017	0	-9999	-10000	0	0
LBP	-0.026	0.15	-9999	-0.43	24	24
PIK3R1	0.016	0.005	-9999	-10000	0	0
JAK1	0.017	0.003	-9999	-10000	0	0
MYC	-0.084	0.22	-9999	-0.46	95	95
FGG	-0.041	0.17	-9999	-0.46	39	39
macrophage differentiation	-0.059	0.17	-9999	-0.44	56	56
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.025	0.078	-9999	-0.21	52	52
JUNB	-0.04	0.16	-9999	-0.45	37	37
FOS	-0.085	0.18	-9999	-0.41	125	125
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.002	0.069	-9999	-0.2	28	28
STAT1/PIAS1	-0.004	0.086	-9999	-0.23	29	29
GRB2/SOS1/GAB family/SHP2/PI3K	0.024	0.033	-9999	-0.23	2	2
STAT3 (dimer)	-0.061	0.18	-9999	-0.45	56	56
PRKCD	-0.008	0.12	-9999	-0.36	14	14
IL6R	0.018	0.003	-9999	-10000	0	0
SOCS3	0.027	0.04	-9999	-10000	0	0
gp130 (dimer)/JAK1/JAK1/LMO4	0.033	0.018	-9999	-10000	0	0
Rac1/GTP	0.003	0.084	-9999	-0.26	15	15
HCK	-0.053	0.16	-9999	-0.41	86	86
MAPKKK cascade	0.014	0.051	-9999	-0.4	3	3
bone resorption	-0.036	0.16	-9999	-0.42	36	36
IRF1	-0.061	0.2	-9999	-0.48	71	71
mol:GDP	0.003	0.07	-9999	-0.2	26	26
SOS1	0.001	0.003	-9999	-10000	0	0
VAV1	0.003	0.07	-9999	-0.21	26	26
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.025	0.047	-9999	-0.25	2	2
PTPN11	0.011	0.017	-9999	-10000	0	0
IL6/IL6RA	-0.006	0.095	-9999	-0.29	52	52
gp130 (dimer)/TYK2/TYK2/LMO4	0.033	0.016	-9999	-0.23	1	1
gp130 (dimer)/JAK2/JAK2/LMO4	0.034	0.012	-9999	-10000	0	0
IL6	-0.026	0.13	-9999	-0.42	52	52
PIAS3	0.015	0.026	-9999	-0.41	2	2
PTPRE	0.017	0.01	-9999	-10000	0	0
PIAS1	0.017	0	-9999	-10000	0	0
RAC1	0.017	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.004	0.055	-9999	-0.16	33	33
LMO4	0.016	0.008	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.044	0.17	-9999	-0.48	36	36
MCL1	0.03	0.049	-9999	-0.38	4	4

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	0.006	0.057	-10000	0	-0.2	34	34
HDAC1	-0.03	0.14	-10000	0	-0.4	66	66
AES	0.019	0.004	-10000	0	-10000	0	0
FBXW11	0.017	0	-10000	0	-10000	0	0
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.044	-10000	0	-0.29	11	11
TLE1	0.019	0.004	-10000	0	-10000	0	0
AP1	-0.02	0.068	-10000	0	-0.14	125	125
NCSTN	-0.007	0.099	-10000	0	-0.41	30	30
ADAM10	0.003	0.078	-10000	0	-0.41	18	18
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.016	0.08	-10000	0	-10000	0	0
NICD/RBPSUH	0.018	0.059	-10000	0	-0.2	30	30
WIF1	0.002	0.006	-10000	0	-10000	0	0
NOTCH1	0.009	0.06	-10000	0	-0.21	34	34
PSENEN	0.017	0.001	-10000	0	-10000	0	0
KREMEN2	0.017	0	-10000	0	-10000	0	0
DKK1	-0.078	0.18	-10000	0	-0.41	117	117
beta catenin/beta TrCP1	0.023	0.03	-10000	0	-10000	0	0
APH1B	0.017	0	-10000	0	-10000	0	0
APH1A	0.008	0.061	-10000	0	-0.41	11	11
AXIN1	0.003	0.028	0.18	5	-10000	0	5
CtBP/CBP/TCF1/TLE1/AES	0.035	0.065	0.17	31	-0.13	32	63
PSEN1	0.016	0.019	-10000	0	-0.41	1	1
FOS	-0.084	0.18	-10000	0	-0.41	125	125
JUN	0.016	0.019	-10000	0	-0.41	1	1
MAP3K7	0.019	0.02	-10000	0	-0.41	1	1
CTNNB1	0.016	0.028	-10000	0	-10000	0	0
MAPK3	0.017	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.029	0.038	-10000	0	-0.24	11	11
HNF1A	0.019	0.004	-10000	0	-10000	0	0
CTBP1	0.019	0.005	-10000	0	-10000	0	0
MYC	-0.092	0.18	-10000	0	-0.4	137	137
NKD1	0.001	0.002	-10000	0	-10000	0	0
FZD1	0.009	0.059	-10000	0	-0.41	10	10
NOTCH1 precursor/Deltex homolog 1	0.007	0.057	-10000	0	-0.2	34	34
apoptosis	-0.02	0.068	-10000	0	-0.14	125	125
Delta 1/NOTCHprecursor	0.007	0.057	-10000	0	-0.2	34	34
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.003	0.031	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.068	-10000	0	-0.2	40	40
APC	-0.01	0.063	0.18	2	-0.29	21	23
DVL1	0.003	0.009	-10000	0	-10000	0	0
CSNK2A1	0.016	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0.02	0.006	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.025	0.11	-10000	0	-0.23	118	118
LRP6	0.016	0.019	-10000	0	-0.41	1	1
CSNK1A1	0.016	0.002	-10000	0	-10000	0	0
NLK	0.028	0.017	-10000	0	-0.18	1	1
CCND1	-0.065	0.17	-10000	0	-0.41	98	98
WNT1	0.017	0	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.024	0.052	0.19	2	-0.2	6	8
DKK2	0.009	0.058	-10000	0	-0.41	10	10
NOTCH1 precursor/DVL1	0.01	0.051	-10000	0	-0.2	13	13
GSK3B	0.017	0.002	-10000	0	-10000	0	0
FRAT1	0.017	0.019	-10000	0	-0.4	1	1
NOTCH/Deltex homolog 1	0.006	0.057	-10000	0	-0.2	34	34
PPP2R5D	0.002	0.007	-10000	0	-10000	0	0
MAPK1	0.017	0.003	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.003	0.023	-10000	0	-0.21	2	2
RBPJ	0.017	0	-10000	0	-10000	0	0
CREBBP	0.013	0.01	-10000	0	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.028	0.046	-10000	0	-0.18	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.01	0.11	-10000	0	-0.24	74	74
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.027	0.042	-10000	0	-0.24	13	13
antigen processing and presentation of peptide antigen via MHC class I	-0.051	0.077	-10000	0	-0.16	158	158
CaM/Ca2+	0.028	0.042	-10000	0	-0.16	13	13
RAP1A	0.017	0	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	0.009	0.068	-10000	0	-0.22	32	32
AKT1	0.008	0.053	-10000	0	-0.17	33	33
MAP2K1	0.017	0.036	-10000	0	-0.18	7	7
MAP3K11	0.016	0.038	-10000	0	-0.17	14	14
IFNGR1	0.007	0.067	-10000	0	-0.41	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.003	0.033	-10000	0	-0.19	10	10
Rap1/GTP	-0.006	0.022	-10000	0	-0.17	3	3
CRKL/C3G	0.025	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.042	0.041	-10000	0	-0.19	15	15
CEBPB	0.037	0.056	-10000	0	-0.24	6	6
STAT3	0.009	0.058	-10000	0	-0.41	10	10
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.043	0.036	-10000	0	-10000	0	0
STAT1	0.003	0.066	-10000	0	-0.22	32	32
CALM1	0.016	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.016	0.019	-10000	0	-0.41	1	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
STAT1 (dimer)/PIAS1	0.012	0.065	-10000	0	-0.2	32	32
CEBPB/PTGES2/Cbp/p300	-0.002	0.041	-10000	0	-0.23	4	4
mol:Ca2+	0.026	0.045	-10000	0	-0.18	14	14
MAPK3	0.03	0.035	-10000	0	-10000	0	0
STAT1 (dimer)	-0.064	0.11	-10000	0	-0.21	155	155
MAPK1	0.013	0.11	-10000	0	-0.58	15	15
JAK2	0.017	0.006	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.038	0.042	-10000	0	-0.19	3	3
SMAD7	-0.001	0.06	-10000	0	-0.11	67	67
CBL/CRKL/C3G	0.031	0.039	-10000	0	-0.2	3	3
PI3K	0.016	0.059	-10000	0	-0.18	35	35
IFNG	0.016	0.019	-10000	0	-0.41	1	1
apoptosis	0.026	0.043	0.22	4	-0.21	1	5
CAMK2G	0.008	0.008	-10000	0	-10000	0	0
STAT3 (dimer)	0.009	0.058	-10000	0	-0.41	10	10
CAMK2A	0.016	0.004	-10000	0	-10000	0	0
CAMK2B	0.002	0.006	-10000	0	-10000	0	0
FRAP1	0.016	0.058	0.19	2	-0.23	6	8
PRKCD	0.015	0.059	0.2	2	-0.17	32	34
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.051	0.077	-10000	0	-0.16	158	158
PTPN2	0.016	0.019	-10000	0	-0.41	1	1
EP300	0.017	0.002	-10000	0	-10000	0	0
IRF1	-0.015	0.14	-10000	0	-0.36	70	70
STAT1 (dimer)/PIASy	0.009	0.065	-10000	0	-0.22	28	28
SOCS1	0.017	0.003	-10000	0	-10000	0	0
mol:GDP	0.028	0.037	-10000	0	-0.18	4	4
CASP1	-0.044	0.12	-10000	0	-0.21	172	172
PTGES2	0.017	0	-10000	0	-10000	0	0
IRF9	0.029	0.028	-10000	0	-0.12	1	1
mol:PI-3-4-5-P3	0.008	0.054	-10000	0	-0.17	35	35
RAP1/GDP	0.02	0.031	-10000	0	-0.17	3	3
CBL	0.015	0.038	-10000	0	-0.17	14	14
MAP3K1	0.016	0.039	-10000	0	-0.17	15	15
PIAS1	0.017	0	-10000	0	-10000	0	0
PIAS4	0.017	0	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.051	0.077	-10000	0	-0.16	158	158
PTPN11	0.011	0.039	-10000	0	-0.18	14	14
CREBBP	0.017	0.002	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.025	0.13	-9999	-0.41	51	51
HRAS	0.016	0.019	-9999	-0.41	1	1
EGFR	-0.14	0.21	-9999	-0.41	194	194
AKT	0.015	0.035	-9999	-0.27	5	5
FOXO3	0.017	0	-9999	-10000	0	0
AKT1	0.014	0.037	-9999	-0.41	4	4
FOXO1	0.008	0.061	-9999	-0.41	11	11
AKT3	0.016	0.019	-9999	-0.41	1	1
FOXO4	0.017	0	-9999	-10000	0	0
MET	0.009	0.058	-9999	-0.41	10	10
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PIK3CB	0.017	0	-9999	-10000	0	0
NRAS	-0.094	0.19	-9999	-0.41	137	137
PIK3CG	0.017	0	-9999	-10000	0	0
PIK3R3	0.016	0.019	-9999	-0.41	1	1
PIK3R2	0.017	0	-9999	-10000	0	0
NF1	0.017	0	-9999	-10000	0	0
RAS	-0.047	0.063	-9999	-0.17	61	61
ERBB2	0.017	0	-9999	-10000	0	0
proliferation/survival/translation	-0.041	0.026	-9999	-10000	0	0
PI3K	-0.028	0.056	-9999	-0.12	71	71
PIK3R1	0.016	0.004	-9999	-10000	0	0
KRAS	0.017	0.002	-9999	-10000	0	0
FOXO	0.021	0.034	-9999	-0.13	11	11
AKT2	0.017	0	-9999	-10000	0	0
PTEN	0.015	0.026	-9999	-0.41	2	2

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.025	0.029	-9999	-0.15	8	8
KLHL20	0.004	0.065	-9999	-0.13	94	94
CYFIP2	0.01	0.008	-9999	-10000	0	0
Rac1/GDP	0.033	0.027	-9999	-0.14	2	2
ENAH	0.016	0.054	-9999	-0.18	34	34
AP1M1	0	0	-9999	-10000	0	0
RAP1B	0	0	-9999	0	4	4
RAP1A	0.017	0	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
CDC42/GTP	0	0.02	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.015	0.032	-9999	-0.088	79	79
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.037	-9999	-0.23	9	9
RAPGEF1	0.027	0.026	-9999	-10000	0	0
CTNND1	0.009	0.058	-9999	-0.41	10	10
regulation of calcium-dependent cell-cell adhesion	0.024	0.03	-9999	-0.16	8	8
CRK	0.026	0.028	-9999	-0.14	8	8
E-cadherin/gamma catenin/alpha catenin	0.023	0.064	-9999	-0.29	19	19
alphaE/beta7 Integrin	0.024	0.019	-9999	-0.28	2	2
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
NCKAP1	0.017	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.022	0.001	-9999	-10000	0	0
DLG1	0.025	0.03	-9999	-0.16	9	9
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.025	-9999	-0.12	12	12
MLLT4	0.017	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.021	0.004	-9999	-10000	0	0
PI3K	-0.008	0.031	-9999	-0.16	12	12
ARF6	0.017	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-0.001	92	92
E-cadherin/gamma catenin	0.012	0.073	-9999	-0.35	19	19
TIAM1	0.016	0.003	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	0.032	0.043	-9999	-0.2	18	18
AKT1	0.016	0.028	-9999	-0.12	8	8
PIK3R1	0.016	0.004	-9999	-10000	0	0
CDH1	0.01	0.052	-9999	-0.41	8	8
RhoA/GDP	0.034	0.025	-9999	-10000	0	0
actin cytoskeleton organization	0.004	0.049	-9999	-0.098	94	94
CDC42/GDP	0.035	0.025	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.012	0.043	-9999	-0.16	28	28
ITGB7	0.015	0.026	-9999	-0.41	2	2
RAC1	0.017	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.035	0.046	-9999	-0.21	18	18
E-cadherin/Ca2+/beta catenin/alpha catenin	0.027	0.028	-9999	-0.2	8	8
mol:GDP	0.027	0.027	-9999	-0.16	2	2
CDC42/GTP/IQGAP1	-0.04	0.11	-9999	-0.24	127	127
JUP	0.004	0.073	-9999	-0.41	16	16
p120 catenin/RhoA/GDP	0.036	0.032	-9999	-0.15	4	4
RAC1/GTP/IQGAP1	-0.04	0.11	-9999	-0.24	127	127
PIP5K1C/AP1M1	0.012	0.002	-9999	-10000	0	0
RHOA	0.017	0.001	-9999	-10000	0	0
CDC42	0.017	0	-9999	-10000	0	0
CTNNA1	0.017	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.013	0.074	-9999	-0.17	98	98
NME1	0	0	-9999	-0.001	98	98
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.025	0.029	-9999	-0.15	8	8
regulation of cell-cell adhesion	-0.003	0.016	-9999	-10000	0	0
WASF2	-0.008	0.018	-9999	-0.049	79	79
Rap1/GTP	0.025	0.026	-9999	-0.14	4	4
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.039	0.061	-9999	-0.25	20	20
CCND1	-0.017	0.09	-9999	-0.2	98	98
VAV2	0.031	0.03	-9999	-10000	0	0
RAP1/GDP	0.028	0.026	-9999	-0.15	2	2
adherens junction assembly	0.025	0.028	-9999	-0.15	8	8
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.017	0	-9999	-10000	0	0
PIP5K1C	0.016	0.003	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.037	0.058	-9999	-0.24	20	20
E-cadherin/beta catenin	0.019	0.032	-9999	-0.16	8	8
mol:GTP	0	0	-9999	-0.001	98	98
SRC	0.025	0.029	-9999	-0.16	8	8
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
Rac1/GTP	-0.037	0.077	-9999	-0.2	94	94
E-cadherin/beta catenin/alpha catenin	0.03	0.033	-9999	-0.24	8	8
ITGAE	0.017	0.001	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.024	0.03	-9999	-0.16	8	8

×

Regulation of Telomerase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.028	0.11	-9999	-0.31	17	17
RAD9A	0.016	0.019	-9999	-0.41	1	1
AP1	-0.049	0.13	-9999	-0.29	125	125
IFNAR2	0.017	0.005	-9999	-10000	0	0
AKT1	0.018	0.021	-9999	-0.2	4	4
ER alpha/Oestrogen	0.012	0.003	-9999	-10000	0	0
NFX1/SIN3/HDAC complex	-0.006	0.061	-9999	-0.19	23	23
EGF	0.015	0.026	-9999	-0.41	2	2
SMG5	0.017	0	-9999	-10000	0	0
SMG6	0.017	0	-9999	-10000	0	0
SP3/HDAC2	-0.023	0.12	-9999	-0.3	78	78
TERT/c-Abl	-0.024	0.1	-9999	-0.32	13	13
SAP18	0.017	0.001	-9999	-10000	0	0
MRN complex	0.035	0	-9999	-10000	0	0
WT1	0.013	0.042	-9999	-0.42	5	5
WRN	0.013	0.042	-9999	-0.41	5	5
SP1	0.016	0.008	-9999	-10000	0	0
SP3	-0.046	0.15	-9999	-0.41	77	77
TERF2IP	0.016	0.005	-9999	-10000	0	0
Telomerase/Nucleolin	-0.009	0.1	-9999	-0.31	10	10
Mad/Max	0.025	0.006	-9999	-10000	0	0
TERT	-0.029	0.11	-9999	-0.3	27	27
CCND1	-0.053	0.17	-9999	-0.39	98	98
MAX	0.017	0.002	-9999	-10000	0	0
RBBP7	0.017	0.001	-9999	-10000	0	0
RBBP4	-0.065	0.17	-9999	-0.41	101	101
TERF2	0.016	0.01	-9999	-10000	0	0
PTGES3	0.017	0.001	-9999	-10000	0	0
SIN3A	0	0.001	-9999	-10000	0	0
Telomerase/911	0.026	0.034	-9999	-0.22	5	5
CDKN1B	-0.005	0.086	-9999	-0.22	71	71
RAD1	0.015	0.026	-9999	-0.41	2	2
XRCC5	0.017	0	-9999	-10000	0	0
XRCC6	0.017	0	-9999	-10000	0	0
SAP30	0.017	0.001	-9999	-10000	0	0
TRF2/PARP2	0.024	0.01	-9999	-10000	0	0
UBE3A	0.017	0.002	-9999	-10000	0	0
JUN	0.016	0.019	-9999	-0.41	1	1
E6	0	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.012	0.006	-9999	-10000	0	0
FOS	-0.085	0.18	-9999	-0.41	125	125
IFN-gamma/IRF1	-0.007	0.11	-9999	-0.28	71	71
PARP2	0.017	0.001	-9999	-10000	0	0
BLM	-0.083	0.18	-9999	-0.41	124	124
Telomerase	0.013	0.034	-9999	-0.17	7	7
IRF1	-0.036	0.14	-9999	-0.41	70	70
ESR1	0.017	0.001	-9999	-10000	0	0
KU/TER	0.025	0	-9999	-10000	0	0
ATM/TRF2	0.011	0.055	-9999	-0.24	25	25
ubiquitin-dependent protein catabolic process	-0.003	0.064	-9999	-0.19	23	23
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.003	0.065	-9999	-0.19	23	23
HDAC1	-0.037	0.14	-9999	-0.41	66	66
HDAC2	0.012	0.043	-9999	-0.42	5	5
ATM	-0.007	0.056	-9999	-0.26	25	25
SMAD3	0.002	0.066	-9999	-0.28	27	27
ABL1	0.016	0.019	-9999	-0.41	1	1
MXD1	0.017	0.002	-9999	-10000	0	0
MRE11A	0.017	0	-9999	-10000	0	0
HUS1	0.017	0	-9999	-10000	0	0
RPS6KB1	0.016	0.019	-9999	-0.41	1	1
TERT/NF kappa B1/14-3-3	-0.003	0.1	-9999	-0.33	5	5
NR2F2	0.014	0.037	-9999	-0.41	4	4
MAPK3	0.017	0.004	-9999	-10000	0	0
MAPK1	0.017	0.005	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	-0.005	0.094	-9999	-0.41	27	27
NFKB1	0.014	0.037	-9999	-0.41	4	4
HNRNPC	0.017	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.007	0.056	-9999	-0.26	25	25
NBN	0.017	0	-9999	-10000	0	0
EGFR	-0.14	0.21	-9999	-0.41	194	194
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.09	0.15	-9999	-0.28	196	196
MYC	-0.094	0.19	-9999	-0.41	137	137
IL2	0.016	0.009	-9999	-10000	0	0
KU	0.025	0	-9999	-10000	0	0
RAD50	0.017	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
TGFB1	-0.005	0.094	-9999	-0.41	27	27
TRF2/BLM	-0.044	0.12	-9999	-0.26	124	124
FRAP1	0.016	0.019	-9999	-0.41	1	1
KU/TERT	-0.013	0.11	-9999	-0.31	12	12
SP1/HDAC2	0.021	0.034	-9999	-0.3	5	5
PINX1	0	0	-9999	-10000	0	0
Telomerase/EST1A	-0.009	0.1	-9999	-0.31	11	11
Smad3/Myc	-0.054	0.13	-9999	-0.25	153	153
911 complex	0.033	0.02	-9999	-0.23	3	3
IFNG	0.02	0.019	-9999	-0.41	1	1
Telomerase/PinX1	-0.033	0.09	-9999	-0.31	11	11
Telomerase/AKT1/mTOR/p70S6K	0.024	0.04	-9999	-0.21	3	3
SIN3B	0.017	0.001	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
Telomerase/EST1B	-0.009	0.1	-9999	-0.31	10	10
response to DNA damage stimulus	0	0.014	-9999	-0.062	25	25
MRN complex/TRF2/Rap1	0.044	0.017	-9999	-10000	0	0
TRF2/WRN	0.021	0.03	-9999	-0.26	5	5
Telomerase/hnRNP C1/C2	-0.009	0.1	-9999	-0.31	10	10
E2F1	0.017	0.005	-9999	-10000	0	0
ZNFX1	0	0.001	-9999	-10000	0	0
PIF1	0	0	-9999	-10000	0	0
NCL	0.017	0	-9999	-10000	0	0
DKC1	0.011	0.049	-9999	-0.41	7	7
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.01	0.052	0.2	5	-0.32	10	15
SMARCC2	0.016	0.019	-10000	0	-0.41	1	1
SMARCC1	0.002	0.078	-10000	0	-0.41	18	18
TBX21	0.016	0.033	-10000	0	-0.19	1	1
SUMO2	0.018	0.004	-10000	0	-10000	0	0
STAT1 (dimer)	-0.012	0.11	-10000	0	-0.26	62	62
FKBP4	0.017	0	-10000	0	-10000	0	0
FKBP5	-0.004	0.093	-10000	0	-0.41	26	26
GR alpha/HSP90/FKBP51/HSP90	-0.009	0.048	0.2	1	-0.26	11	12
PRL	0.014	0.056	-10000	0	-0.42	6	6
cortisol/GR alpha (dimer)/TIF2	-0.015	0.059	0.32	6	-0.32	2	8
RELA	-0.01	0.073	-10000	0	-0.2	40	40
FGG	-0.021	0.061	0.29	2	-0.41	5	7
GR beta/TIF2	-0.005	0.026	0.2	1	-10000	0	1
IFNG	-0.038	0.13	-10000	0	-0.28	92	92
apoptosis	0.022	0.078	0.32	26	-0.27	2	28
CREB1	0.023	0.024	-10000	0	-0.18	7	7
histone acetylation	0.013	0.025	0.15	1	-10000	0	1
BGLAP	0.017	0.034	-10000	0	-0.18	1	1
GR/PKAc	0.006	0.015	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.014	0.14	-10000	0	-0.24	106	106
SMARCD1	0.017	0	-10000	0	-10000	0	0
MDM2	-0.009	0.029	0.16	1	-0.14	11	12
GATA3	0.026	0.042	-10000	0	-0.4	5	5
AKT1	0.01	0.041	-10000	0	-0.42	4	4
CSF2	0.004	0.04	-10000	0	-10000	0	0
GSK3B	0.018	0.004	-10000	0	-10000	0	0
NR1I3	0.075	0.1	0.35	20	-0.25	2	22
CSN2	0	0.086	0.32	28	-0.29	2	30
BRG1/BAF155/BAF170/BAF60A	0.035	0.047	-10000	0	-0.21	19	19
NFATC1	0.026	0	-10000	0	-10000	0	0
POU2F1	0.022	0.015	-10000	0	-10000	0	0
CDKN1A	-0.058	0.15	-10000	0	-0.32	108	108
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.005	-10000	0	-10000	0	0
SFN	-0.01	0.1	-10000	0	-0.41	33	33
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.012	0.063	-10000	0	-0.24	27	27
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.069	0.11	0.34	16	-0.33	6	22
JUN	0.018	0.058	-10000	0	-0.3	9	9
IL4	0.018	0.033	-10000	0	-10000	0	0
CDK5R1	0.014	0.007	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.021	0.081	0.13	1	-0.25	43	44
GR alpha/HSP90/FKBP51/HSP90/PP5C	0	0.045	0.2	1	-0.24	11	12
cortisol/GR alpha (monomer)	-0.022	0.07	0.35	6	-0.39	2	8
NCOA2	0.017	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.071	0.18	-10000	0	-0.4	125	125
AP-1/NFAT1-c-4	-0.027	0.13	-10000	0	-0.42	22	22
AFP	0.016	0.062	-10000	0	-0.51	2	2
SUV420H1	0.016	0.019	-10000	0	-0.41	1	1
IRF1	-0.043	0.11	0.22	2	-0.31	65	67
TP53	-0.046	0.17	-10000	0	-0.43	71	71
PPP5C	0.017	0	-10000	0	-10000	0	0
KRT17	-0.043	0.14	-10000	0	-0.31	94	94
KRT14	0.003	0.063	-10000	0	-0.48	8	8
TBP	0.025	0.019	-10000	0	-0.4	1	1
CREBBP	0.01	0.018	0.16	7	-10000	0	7
HDAC1	-0.042	0.14	-10000	0	-0.42	66	66
HDAC2	0.011	0.042	-10000	0	-0.41	5	5
AP-1	-0.027	0.13	-10000	0	-0.42	22	22
MAPK14	0.017	0.027	-10000	0	-0.41	2	2
MAPK10	0.01	0.01	-10000	0	-10000	0	0
MAPK11	0.018	0.004	-10000	0	-10000	0	0
KRT5	-0.043	0.14	-10000	0	-0.31	92	92
interleukin-1 receptor activity	-0.002	0	-10000	0	-10000	0	0
NCOA1	0.017	0.01	-10000	0	-10000	0	0
STAT1	-0.012	0.11	-10000	0	-0.26	62	62
CGA	0.012	0.059	-10000	0	-0.4	7	7
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.007	0.034	0.18	5	-0.21	3	8
MAPK3	0.018	0.005	-10000	0	-10000	0	0
MAPK1	0.018	0.005	-10000	0	-10000	0	0
ICAM1	-0.053	0.16	-10000	0	-0.33	111	111
NFKB1	-0.013	0.084	-10000	0	-0.23	43	43
MAPK8	0.019	0.048	0.19	1	-0.23	7	8
MAPK9	0.018	0.004	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.022	0.077	0.32	26	-0.28	2	28
BAX	-0.035	0.099	-10000	0	-0.21	101	101
POMC	-0.045	0.083	0.21	1	-10000	0	1
EP300	0.01	0.018	0.16	8	-10000	0	8
cortisol/GR alpha (dimer)/p53	-0.029	0.088	0.34	5	-0.33	21	26
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.018	-10000	0	-0.19	1	1
SGK1	0.025	0.029	0.18	8	-10000	0	8
IL13	-0.015	0.092	-10000	0	-0.25	24	24
IL6	-0.069	0.2	-10000	0	-0.39	115	115
PRKACG	0.017	0	-10000	0	-10000	0	0
IL5	-0.004	0.087	0.24	6	-0.23	8	14
IL2	-0.037	0.13	-10000	0	-0.28	87	87
CDK5	0.017	0.005	-10000	0	-10000	0	0
PRKACB	0.016	0.005	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
IL8	-0.099	0.23	-10000	0	-0.47	135	135
CDK5R1/CDK5	0.021	0.012	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.021	0.1	-10000	0	-0.26	36	36
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.011	0.055	0.31	6	-0.29	2	8
SMARCA4	0.017	0.001	-10000	0	-10000	0	0
chromatin remodeling	-0.007	0.034	0.2	4	-0.17	6	10
NF kappa B1 p50/RelA/Cbp	0.004	0.11	0.22	2	-0.28	41	43
JUN (dimer)	0.018	0.058	-10000	0	-0.3	9	9
YWHAH	0.008	0.009	-10000	0	-10000	0	0
VIPR1	0.016	0.033	0.17	1	-0.19	1	2
NR3C1	-0.013	0.039	0.21	3	-0.21	2	5
NR4A1	0.023	0.001	-10000	0	-10000	0	0
TIF2/SUV420H1	0.025	0.014	-10000	0	-0.28	1	1
MAPKKK cascade	0.022	0.078	0.32	26	-0.27	2	28
cortisol/GR alpha (dimer)/Src-1	-0.014	0.054	0.36	3	-0.28	2	5
PBX1	0.022	0.015	-10000	0	-10000	0	0
POU1F1	0.022	0.015	-10000	0	-10000	0	0
SELE	-0.045	0.14	-10000	0	-0.29	110	110
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.007	0.034	0.2	4	-0.17	6	10
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.011	0.055	0.31	6	-0.29	2	8
mol:cortisol	-0.017	0.041	0.17	5	-0.16	9	14
MMP1	-0.025	0.13	-10000	0	-0.44	43	43

×

FoxO family signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.016	0.041	-9999	-0.27	1	1
PLK1	-0.078	0.15	-9999	-0.53	23	23
CDKN1B	-0.071	0.1	-9999	-0.24	38	38
FOXO3	-0.083	0.14	-9999	-0.3	56	56
KAT2B	-0.012	0.016	-9999	-0.041	25	25
FOXO1/SIRT1	0.014	0.045	-9999	-0.25	2	2
CAT	-0.071	0.13	-9999	-0.36	26	26
CTNNB1	0.017	0	-9999	-10000	0	0
AKT1	-0.001	0.042	-9999	-0.43	4	4
FOXO1	0.011	0.046	-9999	-0.15	28	28
MAPK10	-0.002	0.044	-9999	-0.21	21	21
mol:GTP	-0.001	0.003	-9999	-10000	0	0
FOXO4	-0.013	0.08	-9999	-0.28	10	10
response to oxidative stress	-0.01	0.016	-9999	-0.039	28	28
FOXO3A/SIRT1	-0.094	0.12	-9999	-0.34	37	37
XPO1	0.017	0.001	-9999	-10000	0	0
EP300	0.018	0.001	-9999	-10000	0	0
BCL2L11	0.006	0.022	-9999	-10000	0	0
FOXO1/SKP2	0.018	0.048	-9999	-0.29	4	4
mol:GDP	-0.01	0.016	-9999	-0.039	28	28
RAN	0.017	0.002	-9999	-10000	0	0
GADD45A	-0.063	0.14	-9999	-0.42	47	47
YWHAQ	0.017	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.012	0.044	-9999	-0.16	6	6
MST1	-0.004	0.05	-9999	-0.43	6	6
CSNK1D	0.015	0.026	-9999	-0.41	2	2
CSNK1E	0.017	0.001	-9999	-10000	0	0
FOXO4/14-3-3 family	-0.035	0.079	-9999	-0.25	28	28
YWHAB	0.017	0.001	-9999	-10000	0	0
MAPK8	-0.008	0.063	-9999	-0.21	45	45
MAPK9	-0.007	0.063	-9999	-0.21	45	45
YWHAG	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
YWHAZ	0.017	0.002	-9999	-10000	0	0
SIRT1	0.013	0.006	-9999	-10000	0	0
SOD2	-0.2	0.2	-9999	-0.42	186	186
RBL2	-0.051	0.1	-9999	-0.31	3	3
RAL/GDP	-0.009	0.074	-9999	-0.25	45	45
CHUK	0	0.026	-9999	-0.4	1	1
Ran/GTP	0.012	0.005	-9999	-10000	0	0
CSNK1G2	0.017	0	-9999	-10000	0	0
RAL/GTP	-0.008	0.069	-9999	-0.22	45	45
CSNK1G1	0.017	0	-9999	-10000	0	0
FASLG	0.006	0.022	-9999	-10000	0	0
SKP2	0.015	0.026	-9999	-0.41	2	2
USP7	0.017	0.002	-9999	-10000	0	0
IKBKB	0.001	0.02	-9999	-10000	0	0
CCNB1	-0.18	0.21	-9999	-0.36	296	296
FOXO1-3a-4/beta catenin	-0.08	0.13	-9999	-0.32	16	16
proteasomal ubiquitin-dependent protein catabolic process	0.018	0.047	-9999	-0.29	4	4
CSNK1A1	0.017	0	-9999	-10000	0	0
SGK1	-0.012	0.016	-9999	-0.041	25	25
CSNK1G3	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.022	0.007	-9999	-10000	0	0
ZFAND5	-0.005	0.071	-9999	-0.24	8	8
SFN	-0.01	0.1	-9999	-0.41	33	33
CDK2	-0.003	0.094	-9999	-0.41	27	27
FOXO3A/14-3-3	-0.041	0.072	-9999	-0.21	40	40
CREBBP	0.019	0.002	-9999	-10000	0	0
FBXO32	-0.076	0.12	-9999	-0.33	34	34
BCL6	-0.059	0.12	-9999	-0.44	18	18
RALB	0.016	0.019	-9999	-0.41	1	1
RALA	-0.019	0.12	-9999	-0.41	44	44
YWHAH	0.008	0.009	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.034	0.044	-10000	0	-0.26	5	5
UGCG	0.012	0.026	-10000	0	-0.22	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	0.017	0.092	-10000	0	-0.24	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.012	0.026	-10000	0	-0.22	1	1
mol:DAG	0.006	0.01	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.01	0.1	-10000	0	-0.26	24	24
FRAP1	0.002	0.12	-10000	0	-0.27	46	46
FOXO3	-0.003	0.12	-10000	0	-0.26	50	50
AKT1	-0.008	0.13	-10000	0	-0.2	137	137
GAB2	0.015	0.019	-10000	0	-0.41	1	1
SMPD1	0.013	0.024	-10000	0	-10000	0	0
SGMS1	0.012	0.027	-10000	0	-0.26	1	1
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	-0.001	0.053	-10000	0	-0.23	25	25
CALM1	0.016	0.004	-10000	0	-10000	0	0
cell proliferation	-0.001	0.077	-10000	0	-0.19	13	13
EIF3A	0.017	0	-10000	0	-10000	0	0
PI3K	0.011	0.066	-10000	0	-0.28	25	25
RPS6KB1	0.017	0.027	-10000	0	-0.34	1	1
mol:sphingomyelin	0.006	0.01	-10000	0	-10000	0	0
natural killer cell activation	-0.001	0.003	-10000	0	-0.006	133	133
JAK3	0.018	0.003	-10000	0	-10000	0	0
PIK3R1	0.017	0.006	-10000	0	-10000	0	0
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
MYC	-0.043	0.18	-10000	0	-0.35	137	137
MYB	0.023	0.05	-10000	0	-0.38	8	8
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.092	-10000	0	-0.22	39	39
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.037	0.026	-10000	0	-0.3	1	1
mol:PI-3-4-5-P3	0.008	0.09	-10000	0	-0.22	39	39
Rac1/GDP	0.01	0.049	-10000	0	-0.21	24	24
T cell proliferation	0.008	0.086	-10000	0	-0.2	40	40
SHC1	-0.022	0.12	-10000	0	-0.41	47	47
RAC1	0.017	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.005	-10000	0	-0.039	8	8
PRKCZ	0.007	0.088	-10000	0	-0.21	40	40
NF kappa B1 p50/RelA	0.014	0.12	-10000	0	-0.29	23	23
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.03	0.047	-10000	0	-0.21	10	10
HSP90AA1	0.017	0	-10000	0	-10000	0	0
RELA	0.017	0	-10000	0	-10000	0	0
IL2RA	0.011	0.046	-10000	0	-0.41	6	6
IL2RB	0.015	0.038	-10000	0	-0.42	4	4
TERT	0.017	0	-10000	0	-10000	0	0
E2F1	0.023	0.032	-10000	0	-0.23	8	8
SOS1	-0.001	0.003	-10000	0	-0.006	132	132
RPS6	0.017	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.002	0.018	8	-10000	0	8
PTPN11	0.016	0.003	-10000	0	-10000	0	0
IL2RG	0.01	0.056	-10000	0	-0.42	9	9
actin cytoskeleton organization	0.008	0.086	-10000	0	-0.2	40	40
GRB2	0.016	0.003	-10000	0	-10000	0	0
IL2	0.018	0.004	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
Rac1/GTP	0.019	0.051	-10000	0	-0.2	25	25
LCK	0.014	0.038	-10000	0	-0.42	4	4
BCL2	0.012	0.1	-10000	0	-0.25	23	23

×

Coregulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.015	0.037	-9999	-0.41	4	4
SVIL	0.003	0.08	-9999	-0.41	19	19
ZNF318	0.014	0	-9999	-10000	0	0
JMJD2C	0.023	0	-9999	-10000	0	0
T-DHT/AR/Ubc9	0.03	0.034	-9999	-0.23	8	8
CARM1	0.017	0	-9999	-10000	0	0
PRDX1	0.017	0.001	-9999	-10000	0	0
PELP1	0.017	0	-9999	-10000	0	0
CTNNB1	0.018	0	-9999	-10000	0	0
AKT1	0.013	0.037	-9999	-0.41	4	4
PTK2B	0.018	0	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
MAK	0.008	0.052	-9999	-0.41	8	8
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	-0.026	0.13	-9999	-0.41	54	54
GSN	0.006	0.071	-9999	-0.41	15	15
NCOA2	0.017	0	-9999	-10000	0	0
NCOA6	0.018	0.001	-9999	-10000	0	0
DNA-PK	0.02	0.055	-9999	-0.24	23	23
NCOA4	0.017	0.001	-9999	-10000	0	0
PIAS3	0.016	0.026	-9999	-0.41	2	2
cell proliferation	0.012	0.033	-9999	-0.24	8	8
XRCC5	0.017	0	-9999	-10000	0	0
UBE3A	0.019	0	-9999	-10000	0	0
T-DHT/AR/SNURF	0.019	0.032	-9999	-0.23	8	8
FHL2	0.028	0.038	-9999	-0.37	4	4
RANBP9	0.018	0.001	-9999	-10000	0	0
JMJD1A	0.021	0.065	-9999	-0.4	12	12
CDK6	0.017	0	-9999	-10000	0	0
TGFB1I1	-0.34	0.16	-9999	-0.41	441	441
T-DHT/AR/CyclinD1	-0.017	0.11	-9999	-0.24	103	103
XRCC6	0.017	0	-9999	-10000	0	0
T-DHT/AR	0.047	0.04	-9999	-0.22	8	8
CTDSP1	0.015	0.032	-9999	-0.41	3	3
CTDSP2	-0.015	0.11	-9999	-0.41	37	37
BRCA1	0.014	0.042	-9999	-0.41	5	5
TCF4	0.016	0.002	-9999	-10000	0	0
CDKN2A	-0.031	0.13	-9999	-0.41	58	58
SRF	0.021	0.011	-9999	-10000	0	0
NKX3-1	0.032	0.038	-9999	-0.18	11	11
KLK3	0.017	0.029	-9999	-10000	0	0
TMF1	0.014	0.037	-9999	-0.41	4	4
HNRNPA1	0.016	0	-9999	-10000	0	0
AOF2	0.013	0.049	-9999	-0.41	7	7
APPL1	0.014	0.026	-9999	-0.29	4	4
T-DHT/AR/Caspase 8	0.024	0.049	-9999	-0.24	17	17
AR	0.015	0.052	-9999	-0.4	8	8
UBA3	0	0	-9999	-10000	0	0
PATZ1	0.016	0	-9999	-10000	0	0
PAWR	0.017	0	-9999	-10000	0	0
PRKDC	-0.002	0.088	-9999	-0.41	23	23
PA2G4	0.015	0.019	-9999	-0.41	1	1
UBE2I	0.017	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.028	0.032	-9999	-0.2	9	9
RPS6KA3	0.018	0.019	-9999	-0.41	1	1
T-DHT/AR/ARA70	0.03	0.034	-9999	-0.23	8	8
LATS2	-0.001	0	-9999	-10000	0	0
T-DHT/AR/PRX1	0.027	0.031	-9999	-0.2	8	8
Cyclin D3/CDK11 p58	0.012	0.013	-9999	-0.29	1	1
VAV3	-0.011	0.11	-9999	-0.41	36	36
KLK2	0.033	0.017	-9999	-10000	0	0
CASP8	0.009	0.056	-9999	-0.41	9	9
T-DHT/AR/TIF2/CARM1	0.04	0.033	-9999	-0.2	8	8
TMPRSS2	0.031	0.047	-9999	-0.22	15	15
CCND1	-0.062	0.17	-9999	-0.41	98	98
PIAS1	0.019	0	-9999	-10000	0	0
mol:T-DHT	0.005	0.006	-9999	-0.045	7	7
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.02	0	-9999	-10000	0	0
T-DHT/AR/CDK6	0.029	0.034	-9999	-0.23	8	8
CMTM2	0	0	-9999	-10000	0	0
SNURF	0	0	-9999	-10000	0	0
ZMIZ1	0.021	0.009	-9999	-10000	0	0
CCND3	0.016	0.019	-9999	-0.41	1	1
TGIF1	-0.29	0.2	-9999	-0.41	372	372
FKBP4	0.018	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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
SPHK2	0.012	0.041	-10000	0	-0.28	10	10
MAP4K4	-0.014	0.067	-10000	0	-0.2	24	24
BAG4	0.017	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.005	0.019	0.1	10	-0.1	8	18
NFKBIA	0.016	0.019	-10000	0	-0.41	1	1
BIRC3	-0.01	0.1	-10000	0	-0.41	33	33
BAX	0.004	0.021	-10000	0	-0.15	7	7
RIPK1	0.01	0.055	-10000	0	-0.41	9	9
AKT1	0.007	0.034	-10000	0	-0.38	4	4
BAD	-0.001	0.02	0.11	10	-0.1	3	13
SMPD1	-0.021	0.056	-10000	0	-0.097	185	185
RB1	-0.001	0.02	0.11	10	-0.1	3	13
FADD/Caspase 8	-0.007	0.068	-10000	0	-0.18	32	32
MAP2K4	0.002	0.02	0.11	6	-0.19	1	7
NSMAF	0.015	0.026	-10000	0	-0.41	2	2
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.002	0.021	-10000	0	-0.19	1	1
EGF	0.015	0.026	-10000	0	-0.41	2	2
mol:ceramide	-0.005	0.021	0.12	10	-0.11	8	18
MADD	0.017	0.001	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.012	0.041	-10000	0	-0.28	10	10
ASAH1	0.017	0.001	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.001	0.02	0.11	10	-0.1	2	12
cell proliferation	0.026	0.026	-10000	0	-0.16	5	5
BID	-0.002	0.053	-10000	0	-0.21	4	4
MAP3K1	-0.001	0.022	0.11	10	-0.11	9	19
EIF2A	0.003	0.019	-10000	0	-10000	0	0
TRADD	0.017	0	-10000	0	-10000	0	0
CRADD	0.017	0	-10000	0	-10000	0	0
MAPK3	0.011	0.022	-10000	0	-0.18	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.008	0.027	-10000	0	-0.18	2	2
Cathepsin D/ceramide	0.001	0.042	0.11	10	-0.17	24	34
FADD	-0.015	0.068	-10000	0	-0.19	26	26
KSR1	-0.001	0.02	0.11	10	-0.097	7	17
MAPK8	0.008	0.023	0.11	10	-0.12	1	11
PRKRA	-0.001	0.02	0.11	10	-0.1	1	11
PDGFA	0.009	0.058	-10000	0	-0.41	10	10
TRAF2	0.017	0	-10000	0	-10000	0	0
IGF1	0.014	0.037	-10000	0	-0.41	4	4
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.005	0.021	0.12	10	-0.11	8	18
CTSD	0.004	0.073	-10000	0	-0.41	16	16
regulation of nitric oxide biosynthetic process	0.023	0.027	-10000	0	-0.28	4	4
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.028	0.027	-10000	0	-0.16	5	5
PRKCD	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.012	0.041	-10000	0	-0.28	10	10
RelA/NF kappa B1	0.023	0.027	-10000	0	-0.28	4	4
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.017	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.018	0.072	-10000	0	-0.21	24	24
TNFR1A/BAG4/TNF-alpha	-0.059	0.13	-10000	0	-0.23	185	185
mol:Sphingosine-1-phosphate	0.012	0.041	-10000	0	-0.28	10	10
MAP2K1	0.005	0.02	-10000	0	-0.18	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.017	0	-10000	0	-10000	0	0
CYCS	0.002	0.018	-10000	0	-0.1	5	5
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
TNFR1A/BAG4	-0.082	0.15	-10000	0	-0.28	183	183
EIF2AK2	0.003	0.02	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.06	0.13	-10000	0	-0.23	187	187
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.004	0.051	-10000	0	-0.2	11	11
MAP2K2	0.005	0.02	-10000	0	-0.18	1	1
SMPD3	-0.018	0.058	-10000	0	-0.14	24	24
TNF	0.015	0.026	-10000	0	-0.41	2	2
PKC zeta/PAR4	0.013	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.013	0.022	0.1	8	-0.082	2	10
NF kappa B1/RelA/I kappa B alpha	0.039	0.023	-10000	0	-0.19	5	5
AIFM1	-0.001	0.028	-10000	0	-0.14	12	12
BCL2	0.017	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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
MAP4K4	-0.013	0.074	-10000	0	-0.21	24	24
BAG4	0.017	0	-10000	0	-10000	0	0
BAD	0.003	0.027	-10000	0	-10000	0	0
NFKBIA	0.016	0.019	-10000	0	-0.41	1	1
BIRC3	-0.009	0.1	-10000	0	-0.41	33	33
BAX	0.001	0.036	-10000	0	-0.21	7	7
EnzymeConsortium:3.1.4.12	-0.002	0.021	-10000	0	-0.055	24	24
IKBKB	-0.009	0.071	-10000	0	-0.2	24	24
MAP2K2	0.01	0.026	-10000	0	-0.15	1	1
MAP2K1	0.009	0.025	-10000	0	-0.15	1	1
SMPD1	0.002	0.021	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.008	0.073	-10000	0	-0.19	30	30
MAP2K4	0.006	0.026	-10000	0	-0.16	1	1
protein ubiquitination	-0.009	0.071	-10000	0	-0.2	24	24
EnzymeConsortium:2.7.1.37	0.015	0.03	0.13	5	-0.15	1	6
response to UV	0	0	0.001	5	-0.001	1	6
RAF1	0.008	0.027	-10000	0	-0.16	1	1
CRADD	0.017	0	-10000	0	-10000	0	0
mol:ceramide	0	0.028	-10000	0	-0.073	24	24
I-kappa-B-alpha/RELA/p50/ubiquitin	0.023	0.011	-10000	0	-0.24	1	1
MADD	0.017	0.002	-10000	0	-10000	0	0
MAP3K1	0.003	0.028	-10000	0	-0.17	1	1
TRADD	0.017	0	-10000	0	-10000	0	0
RELA/p50	0.017	0	-10000	0	-10000	0	0
MAPK3	0.014	0.028	-10000	0	-0.14	1	1
MAPK1	0.012	0.028	-10000	0	-0.14	1	1
p50/RELA/I-kappa-B-alpha	0.025	0.013	-10000	0	-0.28	1	1
FADD	-0.014	0.074	-10000	0	-0.21	26	26
KSR1	0.004	0.027	-10000	0	-10000	0	0
MAPK8	0.013	0.032	0.13	15	-0.14	1	16
TRAF2	0.017	0.001	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	-0.01	0.071	-10000	0	-0.2	24	24
TNF R/SODD	-0.082	0.15	-10000	0	-0.28	183	183
TNF	0.016	0.026	-10000	0	-0.41	2	2
CYCS	0.002	0.03	-10000	0	-0.14	5	5
IKBKG	-0.009	0.071	-10000	0	-0.2	24	24
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.017	0.077	-10000	0	-0.22	24	24
RELA	0.017	0	-10000	0	-10000	0	0
RIPK1	0.01	0.055	-10000	0	-0.41	9	9
AIFM1	0	0.033	-10000	0	-0.15	7	7
TNF/TNF R/SODD	-0.059	0.13	-10000	0	-0.23	185	185
TNFRSF1A	-0.13	0.2	-10000	0	-0.41	183	183
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.013	0.032	-10000	0	-0.21	1	1
NSMAF	-0.013	0.073	-10000	0	-0.2	26	26
response to hydrogen peroxide	0	0	0.001	5	-0.001	1	6
BCL2	0.017	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.022	0.005	-10000	0	-10000	0	0
NFATC2	0.041	0.11	-10000	0	-0.29	14	14
NFATC3	0.03	0.086	0.2	2	-0.22	1	3
CD40LG	-0.038	0.18	-10000	0	-0.45	36	36
ITCH	0.026	0.037	-10000	0	-0.17	17	17
CBLB	0.026	0.034	-10000	0	-0.16	16	16
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	0.004	0.12	-10000	0	-0.36	14	14
JUNB	0.011	0.052	-10000	0	-0.41	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.043	-10000	0	-0.21	16	16
T cell anergy	0.012	0.053	0.14	3	-0.22	18	21
TLE4	0.031	0.072	-10000	0	-0.22	5	5
Jun/NFAT1-c-4/p21SNFT	0.028	0.16	-10000	0	-0.34	16	16
AP-1/NFAT1-c-4	-0.022	0.22	-10000	0	-0.49	36	36
IKZF1	0.031	0.072	-10000	0	-0.22	5	5
T-helper 2 cell differentiation	0.019	0.092	-10000	0	-0.32	1	1
AP-1/NFAT1	-0.029	0.14	-10000	0	-0.25	99	99
CALM1	0.022	0.026	-10000	0	-0.12	16	16
EGR2	0.075	0.14	-10000	0	-0.39	12	12
EGR3	0.083	0.12	-10000	0	-0.67	1	1
NFAT1/FOXP3	0.042	0.082	-10000	0	-0.22	5	5
EGR1	0.006	0.071	-10000	0	-0.41	15	15
JUN	0.013	0.028	-10000	0	-0.4	1	1
EGR4	0.018	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.005	0.029	-10000	0	-0.14	20	20
GBP3	0.024	0.069	-10000	0	-0.19	14	14
FOSL1	0.007	0.066	-10000	0	-0.41	13	13
NFAT1-c-4/MAF/IRF4	0.033	0.15	-10000	0	-0.35	6	6
DGKA	0.031	0.072	-10000	0	-0.22	5	5
CREM	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	0.022	0.16	-10000	0	-0.34	15	15
CTLA4	0.037	0.055	-10000	0	-0.19	2	2
NFAT1-c-4 (dimer)/EGR1	0.022	0.16	-10000	0	-0.33	18	18
NFAT1-c-4 (dimer)/EGR4	0.028	0.16	-10000	0	-0.32	14	14
FOS	-0.087	0.18	-10000	0	-0.42	125	125
IFNG	0.019	0.08	-10000	0	-0.23	6	6
T cell activation	-0.003	0.11	-10000	0	-0.38	2	2
MAF	0.017	0.019	-10000	0	-0.41	1	1
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.083	0.13	0.32	6	-0.3	74	80
TNF	0.016	0.14	-10000	0	-0.36	6	6
FASLG	-0.013	0.21	-10000	0	-0.46	21	21
TBX21	0.022	0.004	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.02	0.001	-10000	0	-10000	0	0
PTPN1	0.031	0.072	-10000	0	-0.22	5	5
NFAT1-c-4/ICER1	0.022	0.16	-10000	0	-0.3	20	20
GATA3	0.016	0.042	-10000	0	-0.41	5	5
T-helper 1 cell differentiation	0.019	0.08	-10000	0	-0.27	3	3
IL2RA	0.003	0.13	-10000	0	-0.37	15	15
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.024	0.16	-10000	0	-0.34	98	98
E2F1	-0.059	0.062	-10000	0	-10000	0	0
PPARG	0.013	0.041	-10000	0	-0.41	5	5
SLC3A2	0.025	0.093	-10000	0	-0.41	11	11
IRF4	0.017	0.019	-10000	0	-0.41	1	1
PTGS2	-0.049	0.2	-10000	0	-0.53	42	42
CSF2	-0.038	0.18	-10000	0	-0.45	36	36
JunB/Fra1/NFAT1-c-4	0.023	0.16	-10000	0	-0.37	9	9
IL4	0.019	0.093	-10000	0	-0.33	1	1
IL5	-0.038	0.18	-10000	0	-0.45	35	35
IL2	-0.003	0.11	-10000	0	-0.38	2	2
IL3	-0.001	0.03	-10000	0	-10000	0	0
RNF128	0.016	0.076	-10000	0	-0.37	19	19
NFATC1	0.083	0.13	0.3	74	-0.32	6	80
CDK4	-0.19	0.18	0.29	4	-0.44	154	158
PTPRK	0.031	0.072	-10000	0	-0.22	5	5
IL8	-0.08	0.23	-10000	0	-0.5	90	90
POU2F1	0.023	0	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.017	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.01	0.065	-10000	0	-0.12	132	132
NT3 (dimer)/TRKC	0.025	0.004	-10000	0	-10000	0	0
NT3 (dimer)/TRKB	0.021	0.052	-10000	0	-0.23	20	20
SHC/Grb2/SOS1/GAB1/PI3K	0.004	0.057	-10000	0	-0.14	71	71
RAPGEF1	0.017	0	-10000	0	-10000	0	0
BDNF	0.005	0.008	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DYNLT1	-0.044	0.15	-10000	0	-0.41	75	75
NTRK1	0.015	0.026	-10000	0	-0.41	2	2
NTRK2	0.015	0.005	-10000	0	-10000	0	0
NTRK3	0.017	0.003	-10000	0	-10000	0	0
NT-4/5 (dimer)/TRKB	0.011	0.05	-10000	0	-0.23	22	22
neuron apoptosis	0.01	0.048	0.17	25	-10000	0	25
SHC 2-3/Grb2	-0.011	0.051	-10000	0	-0.18	25	25
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
SHC2	-0.012	0.05	-10000	0	-0.15	51	51
SHC3	-0.014	0.06	-10000	0	-0.17	52	52
STAT3 (dimer)	-0.027	0.11	-10000	0	-0.24	104	104
NT3 (dimer)/TRKA	0.023	0.058	-10000	0	-0.24	23	23
RIN/GDP	0.014	0.029	-10000	0	-0.12	5	5
GIPC1	0.017	0	-10000	0	-10000	0	0
KRAS	0.017	0.002	-10000	0	-10000	0	0
DNAJA3	0.002	0.043	-10000	0	-0.17	23	23
RIN/GTP	0.005	0.023	-10000	0	-0.29	3	3
CCND1	-0.058	0.17	-10000	0	-0.4	104	104
MAGED1	0.017	0.001	-10000	0	-10000	0	0
PTPN11	0.017	0	-10000	0	-10000	0	0
RICS	0.012	0.008	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0	0.074	-10000	0	-0.24	47	47
GRB2	0.017	0.002	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.022	0.016	-10000	0	-0.24	2	2
TRKA/NEDD4-2	0.024	0.019	-10000	0	-0.28	2	2
ELMO1	0.011	0.008	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0.015	0.011	-10000	0	-10000	0	0
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.016	0.019	-10000	0	-0.41	1	1
DOCK1	0.017	0	-10000	0	-10000	0	0
GAB2	0.016	0.019	-10000	0	-0.41	1	1
RIT2	0.007	0.033	-10000	0	-0.41	3	3
RIT1	-0.12	0.2	-10000	0	-0.41	163	163
FRS2	0.015	0.032	-10000	0	-0.41	3	3
DNM1	0.003	0.007	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.017	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.004	0.04	-10000	0	-0.17	19	19
mol:GDP	0.016	0.048	-10000	0	-0.13	15	15
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.008	0.006	-10000	0	-10000	0	0
RIT1/GDP	-0.023	0.08	-10000	0	-0.13	167	167
TIAM1	0.016	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.001	0.044	-10000	0	-0.23	12	12
KIDINS220/CRKL/C3G	0.025	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.003	0.088	-10000	0	-0.28	47	47
FRS2 family/SHP2	0.033	0.02	-10000	0	-0.23	3	3
SHC/GRB2/SOS1/GAB1	0.009	0.072	-10000	0	-0.21	51	51
RIT1/GTP	-0.08	0.14	-10000	0	-0.29	163	163
NT3 (dimer)	0.017	0	-10000	0	-10000	0	0
RAP1/GDP	-0.005	0.021	-10000	0	-10000	0	0
KIDINS220/CRKL	0.017	0	-10000	0	-10000	0	0
BDNF (dimer)	0.005	0.008	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.022	0.016	-10000	0	-0.24	2	2
Schwann cell development	-0.002	0.007	-10000	0	-10000	0	0
EHD4	-0.01	0.1	-10000	0	-0.41	34	34
FRS2 family/GRB2/SOS1	0.031	0.019	-10000	0	-0.21	3	3
FRS2 family/SHP2/CRK family/C3G/GAB2	0.033	0.011	-10000	0	-10000	0	0
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.017	0	-10000	0	-10000	0	0
CDC42/GTP	0.002	0.03	-10000	0	-0.16	9	9
ABL1	0.016	0.019	-10000	0	-0.41	1	1
SH2B family/GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
Rap1/GTP	0.005	0.021	-10000	0	-10000	0	0
STAT3	-0.027	0.11	-10000	0	-0.24	104	104
axon guidance	0	0.027	-10000	0	-0.16	9	9
MAPK3	0.019	0.014	-10000	0	-0.21	2	2
MAPK1	0.018	0.014	-10000	0	-0.21	2	2
CDC42/GDP	0.02	0.037	-10000	0	-0.1	6	6
NTF3	0.017	0	-10000	0	-10000	0	0
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.013	0.05	-10000	0	-0.24	20	20
PI3K	0.009	0.065	-10000	0	-0.28	25	25
FRS3	0.017	0	-10000	0	-10000	0	0
FAIM	0.002	0.078	-10000	0	-0.41	18	18
GAB1	0.014	0.037	-10000	0	-0.41	4	4
RASGRF1	0.001	0.045	-10000	0	-0.17	25	25
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	0.018	0.008	-10000	0	-10000	0	0
RGS19	0.017	0	-10000	0	-10000	0	0
CDC42	0.017	0	-10000	0	-10000	0	0
RAS family/GTP	0.001	0.061	-10000	0	-0.18	29	29
Rac1/GDP	0.02	0.037	-10000	0	-0.1	7	7
NGF (dimer)/TRKA/GRIT	0.016	0.019	-10000	0	-0.24	2	2
neuron projection morphogenesis	0	0.064	-10000	0	-0.32	3	3
NGF (dimer)/TRKA/NEDD4-2	0.022	0.016	-10000	0	-0.24	2	2
MAP2K1	0.001	0.064	-10000	0	-0.19	51	51
NGFR	-0.001	0.086	-10000	0	-0.41	22	22
NGF (dimer)/TRKA/GIPC/GAIP	-0.015	0.052	-10000	0	-0.14	76	76
RAS family/GTP/PI3K	-0.023	0.076	-10000	0	-0.14	157	157
FRS2 family/SHP2/GRB2/SOS1	0.039	0.018	-10000	0	-0.19	3	3
NRAS	-0.094	0.19	-10000	0	-0.41	137	137
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
PRKCI	0.016	0.019	-10000	0	-0.41	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.003	0.031	-10000	0	-10000	0	0
RASA1	0.017	0.002	-10000	0	-10000	0	0
TRKA/c-Abl	0.024	0.023	-10000	0	-0.28	3	3
SQSTM1	0.016	0.019	-10000	0	-0.41	1	1
BDNF (dimer)/TRKB/GIPC	-0.005	0.049	-10000	0	-0.21	15	15
NGF (dimer)/TRKA/p62/Atypical PKCs	0.029	0.02	-10000	0	-0.2	4	4
MATK	0.017	0	-10000	0	-10000	0	0
NEDD4L	0.017	0	-10000	0	-10000	0	0
RAS family/GDP	-0.025	0.041	-10000	0	-0.15	25	25
NGF (dimer)/TRKA	-0.001	0.046	-10000	0	-0.14	44	44
Rac1/GTP	-0.015	0.033	-10000	0	-0.14	15	15
FRS2 family/SHP2/CRK family	0.05	0.018	-10000	0	-0.19	3	3

×

BMP 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.04	0.051	-9999	-0.19	25	25
SMAD6-7/SMURF1	0.034	0.012	-9999	-0.23	1	1
NOG	0	0	-9999	-10000	0	0
SMAD9	0.02	0.019	-9999	-10000	0	0
SMAD4	-0.086	0.18	-9999	-0.41	127	127
SMAD5	0.02	0.034	-9999	-0.19	6	6
BMP7/USAG1	0.02	0.04	-9999	-0.28	9	9
SMAD5/SKI	0.029	0.035	-9999	-0.19	5	5
SMAD1	-0.004	0.074	-9999	-0.27	8	8
BMP2	-0.027	0.13	-9999	-0.41	54	54
SMAD1/SMAD1/SMAD4	-0.058	0.084	-9999	-0.26	49	49
BMPR1A	0.012	0.045	-9999	-0.41	6	6
BMPR1B	0.016	0.019	-9999	-0.41	1	1
BMPR1A-1B/BAMBI	0.014	0.074	-9999	-0.25	39	39
AHSG	0.015	0.026	-9999	-0.41	2	2
CER1	0.017	0	-9999	-10000	0	0
BMP2-4/CER1	0.003	0.087	-9999	-0.23	62	62
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	0.016	0.046	-9999	-0.2	9	9
BMP2-4 (homodimer)	-0.011	0.1	-9999	-0.28	62	62
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.04	0.033	-9999	-0.21	9	9
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	0.007	0.039	-9999	-0.15	11	11
BMP2-4/USAG1	0	0.094	-9999	-0.24	66	66
SMAD6/SMURF1/SMAD5	0.029	0.035	-9999	-0.19	5	5
SOSTDC1	0.011	0.049	-9999	-0.41	7	7
BMP7/BMPR2/BMPR1A-1B	0.04	0.033	-9999	-0.21	9	9
SKI	0.017	0	-9999	-10000	0	0
BMP6 (homodimer)	0.015	0.026	-9999	-0.41	2	2
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.013	0.042	-9999	-0.41	5	5
MAP3K7	0.016	0.019	-9999	-0.41	1	1
BMP2-4/CHRD	0.003	0.087	-9999	-0.23	62	62
SMAD5/SMAD5/SMAD4	-0.019	0.098	-9999	-0.18	128	128
MAPK1	0.017	0.003	-9999	-10000	0	0
TAK1/TAB family	0.035	0.041	-9999	-0.16	6	6
BMP7 (homodimer)	0.015	0.026	-9999	-0.41	2	2
NUP214	0.017	0	-9999	-10000	0	0
BMP6/FETUA	0.023	0.027	-9999	-0.28	4	4
SMAD1/SKI	0.003	0.075	-9999	-0.25	8	8
SMAD6	0.017	0	-9999	-10000	0	0
CTDSP2	-0.013	0.11	-9999	-0.41	37	37
BMP2-4/FETUA	0.002	0.089	-9999	-0.24	63	63
MAP3K7IP1	0.017	0	-9999	-10000	0	0
GREM1	-0.002	0.088	-9999	-0.41	23	23
BMPR2 (homodimer)	0.017	0	-9999	-10000	0	0
GADD34/PP1CA	0.032	0.029	-9999	-0.23	6	6
BMPR1A-1B (homodimer)	0.021	0.035	-9999	-0.28	7	7
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	0.001	0.077	-9999	-0.23	13	13
SMAD6-7/SMURF1/SMAD1	0.016	0.075	-9999	-0.26	6	6
SMAD6/SMURF1	0.017	0	-9999	-10000	0	0
BAMBI	-0.011	0.1	-9999	-0.41	34	34
SMURF2	0.015	0.026	-9999	-0.41	2	2
BMP2-4/CHRDL1	-0.007	0.084	-9999	-0.24	62	62
BMP2-4/GREM1	-0.008	0.1	-9999	-0.24	82	82
SMAD7	0.016	0.019	-9999	-0.41	1	1
SMAD8A/SMAD8A/SMAD4	-0.023	0.096	-9999	-0.19	127	127
SMAD1/SMAD6	0.003	0.075	-9999	-0.25	8	8
TAK1/SMAD6	0.025	0.013	-9999	-0.28	1	1
BMP7	0.015	0.026	-9999	-0.41	2	2
BMP6	0.015	0.026	-9999	-0.41	2	2
MAP3K7IP2	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	0.013	0.038	-9999	-0.19	5	5
PPM1A	0.017	0	-9999	-10000	0	0
SMAD1/SMURF2	0.002	0.075	-9999	-0.23	10	10
SMAD7/SMURF1	0.025	0.013	-9999	-0.28	1	1
CTDSPL	0.017	0	-9999	-10000	0	0
PPP1CA	0.017	0	-9999	-10000	0	0
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.015	0.032	-9999	-0.41	3	3
PPP1R15A	0.016	0.019	-9999	-0.41	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	0.007	0.046	-9999	-0.14	26	26
CHRD	0.017	0	-9999	-10000	0	0
BMPR2	0.017	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	0.006	0.045	-9999	-0.11	64	64
BMP4	0.011	0.052	-9999	-0.41	8	8
FST	0.004	0.073	-9999	-0.41	16	16
BMP2-4/NOG	-0.007	0.084	-9999	-0.24	62	62
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.047	0.031	-9999	-0.19	9	9

×

Retinoic acid receptors-mediated signaling

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
HDAC1	-0.036	0.14	-10000	0	-0.41	66	66
HDAC3	0.017	0	-10000	0	-10000	0	0
VDR	0.017	0	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.023	0	-10000	0	-10000	0	0
EP300	0.017	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.034	0.011	-10000	0	-10000	0	0
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.015	0.026	-10000	0	-0.41	2	2
AKT1	0.068	0.053	0.12	233	-0.12	3	236
RAR alpha/9cRA/Cyclin H	0.012	0.053	-10000	0	-0.2	7	7
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.031	0.006	-10000	0	-10000	0	0
CDC2	-0.14	0.21	-10000	0	-0.41	194	194
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.025	0.005	-10000	0	-10000	0	0
NCOR2	0.017	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.013	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	0.043	0.036	-10000	0	-0.23	4	4
NCOA2	0.017	0	-10000	0	-10000	0	0
NCOA3	0.015	0.032	-10000	0	-0.41	3	3
NCOA1	0.017	0.003	-10000	0	-10000	0	0
VDR/VDR/DNA	0.017	0	-10000	0	-10000	0	0
RARG	0.018	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.024	0.001	-10000	0	-10000	0	0
MAPK3	0.018	0.001	-10000	0	-10000	0	0
MAPK1	0.017	0.003	-10000	0	-10000	0	0
MAPK8	0.018	0.002	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.011	0.052	-10000	0	-0.23	4	4
RARA	0.025	0.005	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.032	0.004	-10000	0	-10000	0	0
PRKCA	0.019	0.004	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.022	0.045	-10000	0	-0.32	4	4
RXRG	0.025	0.016	-10000	0	-0.17	3	3
RXRA	-0.014	0.061	-10000	0	-0.2	4	4
RXRB	0.026	0.005	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.013	0	-10000	0	-10000	0	0
RBP1	-0.18	0.21	-10000	0	-0.41	237	237
CRBP1/9-cic-RA	-0.12	0.15	-10000	0	-0.29	237	237
RARB	0.019	0.002	-10000	0	-10000	0	0
PRKCG	0.019	0.004	-10000	0	-10000	0	0
MNAT1	0.016	0.019	-10000	0	-0.41	1	1
RAR alpha/RXRs	0.056	0.059	-10000	0	-0.23	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.049	0.028	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.036	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.028	0.038	-10000	0	-0.3	4	4
positive regulation of DNA binding	0.007	0.048	-10000	0	-0.19	7	7
NRIP1	0.032	0.043	-10000	0	-0.4	4	4
RXRs/RARs	0.028	0.032	-10000	0	-0.23	4	4
RXRs/RXRs/DNA/9cRA	0.004	0.051	-10000	0	-0.24	4	4
PRKACA	0.017	0	-10000	0	-10000	0	0
CDK7	0.015	0.026	-10000	0	-0.41	2	2
TFIIH	0.033	0.02	-10000	0	-0.23	3	3
RAR alpha/9cRA	0.045	0.016	-10000	0	-0.16	3	3
CCNH	0.017	0.001	-10000	0	-10000	0	0
CREBBP	0.017	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.032	0.02	-10000	0	-0.17	5	5

×

TCR signaling in naïve CD8+ T cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.016	0.071	-9999	-0.2	34	34
FYN	0.011	0.079	-9999	-0.25	26	26
LAT/GRAP2/SLP76	0.026	0.074	-9999	-0.22	35	35
IKBKB	0.017	0	-9999	-10000	0	0
AKT1	0.029	0.054	-9999	-0.2	15	15
B2M	0.018	0.004	-9999	-10000	0	0
IKBKG	0.016	0.026	-9999	-0.086	12	12
MAP3K8	-0.017	0.12	-9999	-0.41	42	42
mol:Ca2+	-0.001	0.006	-9999	-10000	0	0
integrin-mediated signaling pathway	0.011	0	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.029	0.068	-9999	-0.24	18	18
TRPV6	0.002	0.003	-9999	-10000	0	0
CD28	0.017	0.001	-9999	-10000	0	0
SHC1	0.011	0.081	-9999	-0.19	59	59
receptor internalization	0.029	0.046	-9999	-0.24	8	8
PRF1	0.027	0.073	-9999	-0.41	13	13
KRAS	0.017	0.002	-9999	-10000	0	0
GRB2	0.017	0.002	-9999	-10000	0	0
COT/AKT1	0.022	0.076	-9999	-0.2	47	47
LAT	0.027	0.055	-9999	-0.22	15	15
EntrezGene:6955	0.001	0.002	-9999	-10000	0	0
CD3D	0.002	0.083	-9999	-0.42	20	20
CD3E	0.017	0.019	-9999	-0.42	1	1
CD3G	0.017	0.019	-9999	-0.42	1	1
RASGRP2	0.01	0.008	-9999	-10000	0	0
RASGRP1	-0.006	0.076	-9999	-0.23	30	30
HLA-A	0.017	0.019	-9999	-0.41	1	1
RASSF5	0	0	-9999	-10000	0	0
RAP1A/GTP/RAPL	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:GDP	0.004	0.032	-9999	-0.079	29	29
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.01	0.03	-9999	-0.12	21	21
PRKCA	0.021	0.042	-9999	-0.14	24	24
GRAP2	0.017	0	-9999	-10000	0	0
mol:IP3	-0.014	0.047	-9999	-0.2	24	24
EntrezGene:6957	0.001	0.003	-9999	-10000	0	0
TCR/CD3/MHC I/CD8	0.025	0.039	-9999	-0.26	6	6
ORAI1	0	0	-9999	-10000	0	0
CSK	0.026	0.055	-9999	-0.22	14	14
B7 family/CD28	0.033	0.082	-9999	-0.23	35	35
CHUK	0.016	0.019	-9999	-0.41	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.025	0.059	-9999	-0.21	19	19
PTPN6	0.02	0.07	-9999	-0.26	21	21
VAV1	0.027	0.056	-9999	-0.22	15	15
Monovalent TCR/CD3	0.017	0.041	-9999	-0.17	20	20
CBL	0.017	0	-9999	-10000	0	0
LCK	0.01	0.079	-9999	-0.25	26	26
PAG1	0.024	0.055	-9999	-0.23	14	14
RAP1A	0.017	0	-9999	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.023	0.062	-9999	-0.23	19	19
CD80	0.017	0.019	-9999	-0.41	1	1
CD86	-0.003	0.091	-9999	-0.41	25	25
PDK1/CARD11/BCL10/MALT1	-0.011	0.036	-9999	-0.14	23	23
HRAS	0.016	0.019	-9999	-0.41	1	1
GO:0035030	0.019	0.07	-9999	-0.2	37	37
CD8A	0.001	0.003	-9999	-10000	0	0
CD8B	0.016	0.027	-9999	-0.42	2	2
PTPRC	-0.086	0.18	-9999	-0.41	127	127
PDK1/PKC theta	0.033	0.063	-9999	-0.24	14	14
CSK/PAG1	0.026	0.053	-9999	-0.22	14	14
SOS1	0	0	-9999	-10000	0	0
peptide-MHC class I	0.026	0.015	-9999	-0.28	1	1
GRAP2/SLP76	0.027	0.08	-9999	-0.24	35	35
STIM1	0.002	0.003	-9999	-10000	0	0
RAS family/GTP	-0.006	0.053	-9999	-0.11	46	46
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.029	0.047	-9999	-0.25	8	8
mol:DAG	-0.013	0.044	-9999	-0.18	25	25
RAP1A/GDP	0.004	0.015	-9999	-0.04	17	17
PLCG1	0.017	0	-9999	-10000	0	0
CD247	0.016	0.027	-9999	-0.42	2	2
cytotoxic T cell degranulation	0.027	0.071	-9999	-0.4	13	13
RAP1A/GTP	0	0.002	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.029	0.061	-9999	-0.23	16	16
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.015	0.058	-9999	-0.24	24	24
NRAS	-0.094	0.19	-9999	-0.41	137	137
ZAP70	0.017	0	-9999	-10000	0	0
GRB2/SOS1	0.013	0.001	-9999	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.023	0.071	-9999	-0.21	35	35
MALT1	-0.003	0.091	-9999	-0.41	25	25
TRAF6	0.017	0	-9999	-10000	0	0
CD8 heterodimer	0.013	0.019	-9999	-0.29	2	2
CARD11	0	0	-9999	-10000	0	0
PRKCB	-0.01	0.032	-9999	-0.12	35	35
PRKCE	0.021	0.042	-9999	-0.14	24	24
PRKCQ	0.031	0.067	-9999	-0.26	15	15
LCP2	-0.007	0.099	-9999	-0.41	30	30
BCL10	0.015	0.032	-9999	-0.41	3	3
regulation of survival gene product expression	0.028	0.049	-9999	-0.18	15	15
IKK complex	0.025	0.022	-9999	-0.068	7	7
RAS family/GDP	-0.013	0.02	-9999	-0.046	136	136
MAP3K14	0.021	0.061	-9999	-0.16	44	44
PDPK1	0.03	0.053	-9999	-0.2	13	13
TCR/CD3/MHC I/CD8/Fyn	0.028	0.051	-9999	-0.23	12	12

×

Lissencephaly gene (LIS1) in neuronal migration and development

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.017	0.002	-9999	-10000	0	0
VLDLR	0.015	0.032	-9999	-0.41	3	3
LRPAP1	0.017	0	-9999	-10000	0	0
NUDC	0.017	0	-9999	-10000	0	0
RELN/LRP8	0.015	0.026	-9999	-0.23	3	3
CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
KATNA1	0.012	0.045	-9999	-0.41	6	6
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.01	0.019	-9999	-0.21	2	2
IQGAP1/CaM	-0.047	0.13	-9999	-0.27	127	127
DAB1	0.017	0	-9999	-10000	0	0
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
PLA2G7	0.011	0.052	-9999	-0.41	8	8
CALM1	0.016	0.004	-9999	-10000	0	0
DYNLT1	-0.044	0.15	-9999	-0.41	75	75
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.025	0	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.017	0	-9999	-10000	0	0
CDK5R1	0.014	0.007	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0.013	0.001	-9999	-10000	0	0
CDK5R2	0.007	0.008	-9999	-10000	0	0
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	0.014	0.029	-9999	-0.23	4	4
YWHAE	0.017	0.001	-9999	-10000	0	0
NDEL1/14-3-3 E	0.025	0.045	-9999	-10000	0	0
MAP1B	0.006	0.002	-9999	-10000	0	0
RAC1	-0.01	0.048	-9999	-0.096	127	127
p35/CDK5	0.013	0.019	-9999	-0.18	1	1
RELN	0.006	0.033	-9999	-0.41	3	3
PAFAH/LIS1	0.022	0.032	-9999	-0.23	8	8
LIS1/CLIP170	0.026	0.003	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.004	0.039	-9999	-0.27	1	1
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0.015	0.02	-9999	-0.11	3	3
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.023	0.043	-9999	-10000	0	0
LIS1/IQGAP1	-0.037	0.11	-9999	-0.23	127	127
RHOA	-0.01	0.048	-9999	-0.096	127	127
PAFAH1B1	0.017	0.002	-9999	-10000	0	0
PAFAH1B3	0.016	0.019	-9999	-0.41	1	1
PAFAH1B2	0.017	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.023	0.008	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.025	0.047	-9999	-10000	0	0
LRP8	0.017	0	-9999	-10000	0	0
NDEL1/Katanin 60	0.024	0.047	-9999	-10000	0	0
P39/CDK5	0.006	0.016	-9999	-0.18	1	1
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.026	0.003	-9999	-10000	0	0
CDK5	0.009	0.017	-9999	-0.19	2	2
PPP2R5D	0.017	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.022	0.002	-9999	-10000	0	0
CSNK2A1	0.017	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	0.019	0.029	-9999	-0.19	4	4
RELN/VLDLR	0.019	0.03	-9999	-0.21	4	4
CDC42	-0.01	0.048	-9999	-0.096	127	127

×

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.019	0.034	-9999	-0.24	9	9
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.01	0.055	-9999	-0.41	9	9
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.002	0.027	-9999	-0.13	19	19
response to UV	0	0	-9999	-10000	0	0
YES1	-0.048	0.15	-9999	-0.41	80	80
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.017	0	-9999	-10000	0	0
FYN	0.015	0.026	-9999	-0.41	2	2
MAP3K12	0.017	0	-9999	-10000	0	0
FGR	0.003	0.076	-9999	-0.41	17	17
p38 alpha/TAB1	-0.003	0.067	-9999	-0.16	46	46
PRKG1	0.017	0	-9999	-10000	0	0
DUSP8	0.013	0.007	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.005	0.064	-9999	-0.16	45	45
apoptosis	-0.003	0.065	-9999	-0.16	46	46
RAL/GTP	0.001	0.073	-9999	-0.24	45	45
LYN	-0.035	0.14	-9999	-0.41	64	64
DUSP1	0.002	0.078	-9999	-0.41	18	18
PAK1	0.017	0	-9999	-10000	0	0
SRC	0.017	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.033	0	-9999	-10000	0	0
TRAF6	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.023	0	-9999	-10000	0	0
MAPK11	-0.014	0.076	-9999	-0.18	53	53
BLK	0.017	0	-9999	-10000	0	0
HCK	-0.053	0.16	-9999	-0.41	86	86
MAP2K3	0.017	0	-9999	-10000	0	0
DUSP16	0	0	-9999	-10000	0	0
DUSP10	0.011	0.049	-9999	-0.41	7	7
TRAF6/MEKK3	0.022	0	-9999	-10000	0	0
MAP3K7IP1	0.017	0	-9999	-10000	0	0
MAPK14	-0.01	0.07	-9999	-0.15	71	71
positive regulation of innate immune response	-0.015	0.086	-9999	-0.2	57	57
LCK	0.014	0.037	-9999	-0.41	4	4
p38alpha-beta/MKP7	-0.016	0.083	-9999	-0.2	57	57
p38alpha-beta/MKP5	-0.01	0.09	-9999	-0.21	51	51
PGK/cGMP	0.013	0	-9999	-10000	0	0
PAK2	-0.002	0.088	-9999	-0.41	23	23
p38alpha-beta/MKP1	-0.013	0.096	-9999	-0.23	54	54
CDC42	0.017	0	-9999	-10000	0	0
RALB	0.016	0.019	-9999	-0.41	1	1
RALA	-0.019	0.12	-9999	-0.41	44	44
PAK3	0.003	0.006	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0.019	-9999	-0.41	1	1
ELF1	0.018	0.055	-9999	-0.32	13	13
CCNA2	-0.096	0.19	-9999	-0.41	139	139
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
JAK3	0.018	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
JAK1	0.018	0.002	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.039	0.054	-9999	-0.2	11	11
SHC1	-0.02	0.12	-9999	-0.41	47	47
SP1	0.019	0.039	-9999	-0.22	14	14
IL2RA	0.018	0.056	-9999	-0.33	13	13
IL2RB	0.014	0.037	-9999	-0.41	4	4
SOS1	0.001	0	-9999	-10000	0	0
IL2RG	0.01	0.056	-9999	-0.41	9	9
G1/S transition of mitotic cell cycle	-0.027	0.1	-9999	-0.24	56	56
PTPN11	0.018	0	-9999	-10000	0	0
CCND2	0.014	0.068	-9999	-0.4	14	14
LCK	0.014	0.037	-9999	-0.41	4	4
GRB2	0.017	0.002	-9999	-10000	0	0
IL2	0.018	0	-9999	-10000	0	0
CDK6	0.017	0	-9999	-10000	0	0
CCND3	0.042	0.052	-9999	-0.26	5	5

×

p75(NTR)-mediated signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.025	0	-9999	-10000	0	0
Necdin/E2F1	0.016	0.012	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.03	0.047	-9999	-0.19	22	22
NGF (dimer)/p75(NTR)/BEX1	0.007	0.048	-9999	-0.21	22	22
NT-4/5 (dimer)/p75(NTR)	0	0.06	-9999	-0.29	22	22
IKBKB	0.017	0	-9999	-10000	0	0
AKT1	0.001	0.066	-9999	-0.2	47	47
IKBKG	0.017	0	-9999	-10000	0	0
BDNF	0.005	0.008	-9999	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.001	0.051	-9999	-0.24	22	22
FURIN	0.017	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.002	0.04	-9999	-0.23	10	10
LINGO1	0	0	-9999	-10000	0	0
Sortilin/TRAF6/NRIF	-0.014	0.048	-9999	-0.34	2	2
proBDNF (dimer)	0.005	0.008	-9999	-10000	0	0
NTRK1	0.015	0.026	-9999	-0.41	2	2
RTN4R	0	0	-9999	-10000	0	0
neuron apoptosis	0.052	0.071	-9999	-0.21	12	12
IRAK1	0.017	0.001	-9999	-10000	0	0
SHC1	-0.017	0.088	-9999	-0.24	67	67
ARHGDIA	0.017	0	-9999	-10000	0	0
RhoA/GTP	0.013	0.001	-9999	-10000	0	0
Gamma Secretase	0.032	0.068	-9999	-0.2	40	40
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.021	0.047	-9999	-0.21	20	20
MAGEH1	0.016	0.005	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.012	0.043	-9999	-0.21	15	15
Mammalian IAPs/DIABLO	0.018	0.059	-9999	-0.21	33	33
proNGF (dimer)	0	0	-9999	-10000	0	0
MAGED1	0.017	0.001	-9999	-10000	0	0
APP	0.017	0.001	-9999	-10000	0	0
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.013	0.042	-9999	-0.41	5	5
RhoA/GDP/RHOGDI	0.018	0.045	-9999	-0.2	22	22
NGF	0	0	-9999	-10000	0	0
cell cycle arrest	0	0.042	-9999	-0.2	22	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0	0.059	-9999	-0.13	93	93
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.012	0.052	-9999	-0.24	22	22
NCSTN	-0.007	0.099	-9999	-0.41	30	30
mol:GTP	0.01	0.051	-9999	-0.23	22	22
PSENEN	0.017	0.001	-9999	-10000	0	0
mol:ceramide	0.01	0.046	-9999	-0.21	22	22
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.026	-9999	-0.098	25	25
p75(NTR)/beta APP	0.012	0.062	-9999	-0.28	22	22
BEX1	0.012	0.008	-9999	-10000	0	0
mol:GDP	-0.004	0.049	-9999	-0.24	22	22
NGF (dimer)	-0.003	0.087	-9999	-0.21	78	78
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.012	0.047	-9999	-0.22	22	22
PIK3R1	0.016	0.004	-9999	-10000	0	0
RAC1/GTP	0.011	0.044	-9999	-0.2	22	22
MYD88	-0.041	0.15	-9999	-0.41	72	72
CHUK	0.016	0.019	-9999	-0.41	1	1
NGF (dimer)/p75(NTR)/PKA	0.011	0.051	-9999	-0.23	22	22
RHOB	0.013	0.037	-9999	-0.41	4	4
RHOA	0.017	0.001	-9999	-10000	0	0
MAGE-G1/E2F1	0.013	0	-9999	-10000	0	0
NT3 (dimer)	0.017	0	-9999	-10000	0	0
TP53	-0.015	0.061	-9999	-0.21	38	38
PRDM4	0.01	0.046	-9999	-0.21	22	22
BDNF (dimer)	-0.012	0.068	-9999	-0.23	32	32
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
SORT1	0.017	0	-9999	-10000	0	0
activation of caspase activity	0.027	0.046	-9999	-0.19	22	22
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.023	0.049	-9999	-0.21	22	22
RHOC	-0.12	0.2	-9999	-0.41	164	164
XIAP	0	0	-9999	-10000	0	0
MAPK10	0.044	0.06	-9999	-10000	0	0
DIABLO	0.017	0	-9999	-10000	0	0
SMPD2	0.01	0.046	-9999	-0.21	22	22
APH1B	0.017	0	-9999	-10000	0	0
APH1A	0.008	0.061	-9999	-0.41	11	11
proNGF (dimer)/p75(NTR)/Sortilin	0.012	0.052	-9999	-0.24	22	22
PSEN1	0.016	0.019	-9999	-0.41	1	1
APAF-1/Pro-Caspase 9	0.023	0.027	-9999	-0.28	4	4
NT3 (dimer)/p75(NTR)	0.013	0.062	-9999	-0.28	22	22
MAPK8	0.081	0.053	-9999	-10000	0	0
MAPK9	0.08	0.053	-9999	-10000	0	0
APAF1	0.017	0	-9999	-10000	0	0
NTF3	0.017	0	-9999	-10000	0	0
NTF4	0	0	-9999	-10000	0	0
NDN	0.011	0.008	-9999	-10000	0	0
RAC1/GDP	0.013	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.04	0.11	-9999	-0.19	171	171
p75 CTF/Sortilin/TRAF6/NRIF	0.039	0.034	-9999	-0.21	10	10
RhoA-B-C/GTP	0.01	0.051	-9999	-0.23	22	22
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.007	0.041	-9999	-0.19	12	12
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.006	0.039	-9999	-0.21	10	10
PRKACB	0.016	0.005	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	0.005	0.026	-9999	-0.23	5	5
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.01	0.1	-9999	-0.41	33	33
BIRC2	0.017	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.007	0.035	-9999	-0.18	20	20
BAD	0.082	0.052	-9999	-10000	0	0
RIPK2	0.016	0.019	-9999	-0.41	1	1
NGFR	-0.001	0.086	-9999	-0.41	22	22
CYCS	0.014	0.043	-9999	-0.19	22	22
ADAM17	0.013	0.042	-9999	-0.41	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.022	0.05	-9999	-0.21	23	23
BCL2L11	0.082	0.052	-9999	-10000	0	0
BDNF (dimer)/p75(NTR)	-0.002	0.046	-9999	-0.2	22	22
PI3K	0.01	0.072	-9999	-0.22	43	43
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.012	0.047	-9999	-0.22	22	22
NDNL2	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
PRKCI	0.016	0.019	-9999	-0.41	1	1
NGF (dimer)/p75(NTR)	0	0.06	-9999	-0.29	22	22
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.023	0.049	-9999	-0.21	22	22
TRAF6	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
PRKCZ	0	0	-9999	-10000	0	0
PLG	0.017	0	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.007	0.049	-9999	-0.15	46	46
SQSTM1	0.016	0.019	-9999	-0.41	1	1
NGFRAP1	0.017	0.002	-9999	-10000	0	0
CASP3	0.078	0.051	-9999	-10000	0	0
E2F1	0.017	0	-9999	-10000	0	0
CASP9	0.014	0.037	-9999	-0.41	4	4
IKK complex	0.037	0.029	-9999	-0.19	3	3
NGF (dimer)/TRKA	0.012	0.019	-9999	-0.29	2	2
MMP7	-0.046	0.15	-9999	-0.41	78	78
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.029	0.052	-9999	-0.19	27	27
MMP3	0.011	0.049	-9999	-0.41	7	7
APAF-1/Caspase 9	-0.016	0.046	-9999	-0.31	1	1

×

IL4-mediated signaling events

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
BCL2L1	-0.053	0.22	-10000	0	-0.69	12	12
STAT6 (cleaved dimer)	-0.11	0.16	-10000	0	-0.66	15	15
IGHG1	-0.015	0.12	-10000	0	-0.39	13	13
IGHG3	-0.058	0.21	-10000	0	-0.69	11	11
AKT1	-0.004	0.15	-10000	0	-0.5	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.015	0.11	-10000	0	-0.38	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.008	0.14	-10000	0	-0.46	8	8
THY1	-0.076	0.28	-10000	0	-0.64	73	73
MYB	0.011	0.052	-10000	0	-0.41	8	8
HMGA1	0.016	0.019	-10000	0	-0.41	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.013	0.16	-10000	0	-0.47	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.011	0.14	-10000	0	-0.46	8	8
SP1	-0.021	0.045	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.015	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.041	0.21	-10000	0	-0.71	11	11
SOCS1	-0.012	0.18	-10000	0	-0.54	9	9
SOCS3	-0.006	0.14	-10000	0	-0.5	6	6
FCER2	-0.034	0.19	-10000	0	-0.69	6	6
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.053	0.22	-10000	0	-0.69	12	12
GRB2	0.017	0.002	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.015	0.14	-10000	0	-0.38	22	22
T cell proliferation	-0.042	0.22	-10000	0	-0.71	12	12
IL4R/JAK1	-0.056	0.22	-10000	0	-0.69	14	14
EGR2	-0.057	0.24	-10000	0	-0.71	17	17
JAK2	0.012	0.03	-10000	0	-10000	0	0
JAK3	0.021	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.013	-10000	0	-10000	0	0
COL1A2	-0.15	0.23	-10000	0	-0.42	183	183
CCL26	-0.059	0.22	-10000	0	-0.65	16	16
IL4R	-0.06	0.24	-10000	0	-0.72	15	15
PTPN6	0.01	0.06	-10000	0	-0.4	11	11
IL13RA2	-0.13	0.28	-10000	0	-0.64	52	52
IL13RA1	-0.054	0.16	-10000	0	-0.43	80	80
IRF4	0.017	0.075	-10000	0	-0.62	1	1
ARG1	0.002	0.11	-10000	0	-0.44	7	7
CBL	-0.016	0.15	-10000	0	-0.49	9	9
GTF3A	0.014	0.027	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
IL13RA1/JAK2	-0.029	0.12	-10000	0	-0.3	80	80
IRF4/BCL6	0.013	0.078	-10000	0	-0.56	1	1
CD40LG	0.024	0.003	-10000	0	-10000	0	0
MAPK14	-0.012	0.15	-10000	0	-0.48	10	10
mitosis	-0.002	0.15	-10000	0	-0.48	8	8
STAT6	-0.052	0.24	-10000	0	-0.57	40	40
SPI1	0.016	0.053	-10000	0	-0.41	8	8
RPS6KB1	0	0.14	-10000	0	-0.46	9	9
STAT6 (dimer)	-0.038	0.24	-10000	0	-0.57	40	40
STAT6 (dimer)/PARP14	-0.067	0.22	-10000	0	-0.74	11	11
mast cell activation	0	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.001	0.13	-10000	0	-0.42	10	10
FRAP1	-0.004	0.15	-10000	0	-0.5	8	8
LTA	-0.054	0.22	-10000	0	-0.72	11	11
FES	0.017	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.05	0.24	0.66	20	-10000	0	20
CCL11	-0.054	0.22	-10000	0	-0.67	14	14
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.002	0.13	-10000	0	-0.43	9	9
IL2RG	0.013	0.056	-10000	0	-0.41	9	9
IL10	-0.053	0.22	-10000	0	-0.71	11	11
IRS1	0.013	0.042	-10000	0	-0.41	5	5
IRS2	0.017	0.002	-10000	0	-10000	0	0
IL4	0.004	0.087	-10000	0	-10000	0	0
IL5	-0.053	0.22	-10000	0	-0.71	11	11
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.053	0.22	-10000	0	-0.58	19	19
COL1A1	-0.043	0.19	-10000	0	-0.47	66	66
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.055	0.22	-10000	0	-0.76	10	10
IL2R gamma/JAK3	0.026	0.041	-10000	0	-0.29	9	9
TFF3	-0.058	0.23	-10000	0	-0.69	19	19
ALOX15	-0.053	0.22	-10000	0	-0.69	12	12
MYBL1	-0.048	0.15	-10000	0	-0.41	80	80
T-helper 2 cell differentiation	-0.041	0.2	-10000	0	-0.67	9	9
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
CEBPB	0.013	0.061	-10000	0	-0.41	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.006	0.14	-10000	0	-0.46	7	7
mol:PI-3-4-5-P3	-0.003	0.15	-10000	0	-0.5	8	8
PI3K	-0.005	0.15	-10000	0	-0.52	8	8
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.016	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.012	0.14	-10000	0	-0.4	15	15
ITGB3	-0.053	0.22	-10000	0	-0.71	11	11
PIGR	-0.054	0.23	-10000	0	-0.71	12	12
IGHE	0.021	0.05	0.15	22	-0.13	1	23
MAPKKK cascade	-0.012	0.13	-10000	0	-0.4	15	15
BCL6	0.003	0.074	-10000	0	-0.41	16	16
OPRM1	-0.053	0.22	-10000	0	-0.71	11	11
RETNLB	-0.059	0.22	-10000	0	-0.65	16	16
SELP	-0.054	0.22	-10000	0	-0.72	11	11
AICDA	-0.053	0.21	-10000	0	-0.7	11	11

×

PDGFR-beta signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.011	0.061	-9999	-0.23	15	15
PDGFB-D/PDGFRB/SLAP	0.002	0.082	-9999	-0.3	37	37
PDGFB-D/PDGFRB/APS/CBL	0.021	0.02	-9999	-0.24	3	3
AKT1	0.025	0.051	-9999	-0.24	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.007	0.058	-9999	-0.23	16	16
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
FGR	0.004	0.044	-9999	-0.19	19	19
mol:Ca2+	0.008	0.038	-9999	-0.22	4	4
MYC	-0.066	0.17	-9999	-0.34	138	138
SHC1	-0.021	0.12	-9999	-0.41	47	47
HRAS/GDP	0.027	0.022	-9999	-0.18	5	5
LRP1/PDGFRB/PDGFB	0.023	0.053	-9999	-0.24	21	21
GRB10	0.004	0.073	-9999	-0.41	16	16
PTPN11	0.017	0	-9999	-10000	0	0
GO:0007205	0.008	0.039	-9999	-0.22	4	4
PTEN	0.015	0.026	-9999	-0.41	2	2
GRB2	0.017	0.002	-9999	-10000	0	0
GRB7	0.016	0.019	-9999	-0.41	1	1
PDGFB-D/PDGFRB/SHP2	0.023	0.023	-9999	-0.28	3	3
PDGFB-D/PDGFRB/GRB10	0.013	0.058	-9999	-0.29	19	19
cell cycle arrest	0.002	0.082	-9999	-0.3	37	37
HRAS	0.016	0.019	-9999	-0.41	1	1
HIF1A	0.025	0.049	-9999	-0.21	1	1
GAB1	-0.008	0.065	-9999	-0.21	19	19
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.008	0.065	-9999	-0.21	18	18
PDGFB-D/PDGFRB	0.027	0.029	-9999	-0.24	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.023	0.023	-9999	-0.28	3	3
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.003	0.079	-9999	-0.23	25	25
positive regulation of MAPKKK cascade	0.023	0.023	-9999	-0.28	3	3
PIK3R1	0.016	0.004	-9999	-10000	0	0
mol:IP3	0.008	0.039	-9999	-0.22	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0.017	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.022	0.027	-9999	-0.28	4	4
SHB	0.017	0	-9999	-10000	0	0
BLK	-0.002	0.022	-9999	-0.21	4	4
PTPN2	0.015	0.019	-9999	-0.42	1	1
PDGFB-D/PDGFRB/SNX15	0.023	0.023	-9999	-0.28	3	3
BCAR1	0	0	-9999	-10000	0	0
VAV2	-0.024	0.093	-9999	-0.23	50	50
CBL	0.017	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.023	0.023	-9999	-0.28	3	3
LCK	-0.005	0.028	-9999	-0.2	8	8
PDGFRB	0.014	0.033	-9999	-0.42	3	3
ACP1	0.017	0.001	-9999	-10000	0	0
HCK	-0.031	0.064	-9999	-0.19	44	44
ABL1	-0.003	0.055	-9999	-0.18	18	18
PDGFB-D/PDGFRB/CBL	-0.006	0.065	-9999	-0.22	16	16
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.017	0	-9999	-10000	0	0
STAT3	0.009	0.058	-9999	-0.41	10	10
STAT1	0.002	0.078	-9999	-0.41	18	18
cell proliferation	-0.06	0.16	-9999	-0.32	138	138
SLA	-0.011	0.11	-9999	-0.41	35	35
actin cytoskeleton reorganization	0.026	0.036	-9999	-0.18	15	15
SRC	-0.003	0.022	-9999	-0.21	4	4
PI3K	-0.01	0.038	-9999	-0.17	29	29
PDGFB-D/PDGFRB/GRB7/SHC	0.008	0.081	-9999	-0.24	50	50
SH2B2	0	0	-9999	-10000	0	0
PLCgamma1/SPHK1	0.007	0.06	-9999	-0.24	16	16
LYN	-0.025	0.06	-9999	-0.2	35	35
LRP1	0.002	0.078	-9999	-0.41	18	18
SOS1	0	0	-9999	-10000	0	0
STAT5B	0.017	0	-9999	-10000	0	0
STAT5A	0.016	0.019	-9999	-0.41	1	1
NCK1-2/p130 Cas	0.032	0.04	-9999	-0.19	15	15
SPHK1	0.001	0.082	-9999	-0.41	20	20
EDG1	0.017	0.002	-9999	-10000	0	0
mol:DAG	0.008	0.039	-9999	-0.22	4	4
PLCG1	0.008	0.039	-9999	-0.23	4	4
NHERF/PDGFRB	0.032	0.026	-9999	-0.24	5	5
YES1	-0.029	0.063	-9999	-0.19	41	41
cell migration	0.031	0.026	-9999	-0.24	5	5
SHC/Grb2/SOS1	0.016	0.07	-9999	-0.2	49	49
SLC9A3R2	0.017	0	-9999	-10000	0	0
SLC9A3R1	0.015	0.026	-9999	-0.41	2	2
NHERF1-2/PDGFRB/PTEN	0.04	0.029	-9999	-0.21	7	7
FYN	-0.014	0.064	-9999	-0.31	22	22
DOK1	0.021	0.021	-9999	-0.21	4	4
HRAS/GTP	0.012	0.013	-9999	-0.29	1	1
PDGFB	0.017	0	-9999	-10000	0	0
RAC1	-0.041	0.12	-9999	-0.23	139	139
PRKCD	0.02	0.021	-9999	-0.21	4	4
FER	0.02	0.021	-9999	-0.21	4	4
MAPKKK cascade	-0.018	0.057	-9999	-0.19	49	49
RASA1	0.02	0.022	-9999	-0.21	4	4
NCK1	0.008	0.061	-9999	-0.41	11	11
NCK2	0.017	0.001	-9999	-10000	0	0
p62DOK/Csk	0.033	0.019	-9999	-0.19	4	4
PDGFB-D/PDGFRB/SHB	0.023	0.023	-9999	-0.28	3	3
chemotaxis	-0.003	0.054	-9999	-0.18	18	18
STAT1-3-5/STAT1-3-5	0.025	0.055	-9999	-0.19	29	29
Bovine Papilomavirus E5/PDGFRB	0.009	0.023	-9999	-0.29	3	3
PTPRJ	0.017	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.019	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.06	0.024	-9999	-0.16	2	2
ERC1	0.016	0.019	-9999	-0.41	1	1
RIP2/NOD2	0.02	0.04	-9999	-0.28	9	9
NFKBIA	0.025	0.027	-9999	-0.24	5	5
BIRC2	0.017	0	-9999	-10000	0	0
IKBKB	0.017	0	-9999	-10000	0	0
RIPK2	0.016	0.019	-9999	-0.41	1	1
IKBKG	0.031	0.024	-9999	-0.17	1	1
IKK complex/A20	-0.017	0.1	-9999	-0.23	25	25
NEMO/A20/RIP2	0.016	0.019	-9999	-0.41	1	1
XPO1	0.017	0	-9999	-10000	0	0
NEMO/ATM	0.03	0.051	-9999	-0.17	26	26
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
Exportin 1/RanGTP	0.023	0.002	-9999	-10000	0	0
IKK complex/ELKS	0.043	0.028	-9999	-0.32	1	1
BCL10/MALT1/TRAF6	0.021	0.06	-9999	-0.23	28	28
NOD2	0.011	0.052	-9999	-0.41	8	8
NFKB1	0.016	0.037	-9999	-0.41	4	4
RELA	0.019	0.004	-9999	-10000	0	0
MALT1	-0.003	0.091	-9999	-0.41	25	25
cIAP1/UbcH5C	0.025	0.001	-9999	-10000	0	0
ATM	-0.003	0.091	-9999	-0.41	25	25
TNF/TNFR1A	-0.083	0.15	-9999	-0.28	185	185
TRAF6	0.017	0	-9999	-10000	0	0
PRKCA	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
UBE2D3	0.017	0.001	-9999	-10000	0	0
TNF	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p50/RelA	0.042	0.026	-9999	-0.22	5	5
BCL10	0.015	0.032	-9999	-0.41	3	3
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.027	-9999	-0.24	5	5
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-9999	-10000	0	0
TNFRSF1A	-0.13	0.2	-9999	-0.41	183	183
IKK complex	0.048	0.027	-9999	-0.15	2	2
CYLD	0.017	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.053	0.028	-9999	-10000	0	0

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.029	0.028	-10000	0	-0.22	3	3
epithelial cell differentiation	0.032	0.031	-10000	0	-0.21	1	1
ITCH	0.018	0.02	-10000	0	-0.41	1	1
WWP1	0.025	0.025	-10000	0	-0.39	1	1
FYN	0.015	0.026	-10000	0	-0.41	2	2
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
PRL	0.012	0.045	-10000	0	-0.41	6	6
neuron projection morphogenesis	0.021	0.059	-10000	0	-0.19	7	7
PTPRZ1	-0.003	0.087	-10000	0	-0.41	23	23
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.032	0.068	-10000	0	-0.2	11	11
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.026	0.028	-10000	0	-0.21	6	6
ADAM17	0.014	0.041	-10000	0	-0.4	5	5
ErbB4/ErbB4	0.026	0.025	-10000	0	-0.24	2	2
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.017	0.023	-10000	0	-0.26	1	1
NCOR1	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.034	0.026	-10000	0	-0.2	5	5
GRIN2B	0.033	0.024	-10000	0	-0.19	4	4
ErbB4/ErbB2/betacellulin	0.035	0.027	-10000	0	-0.19	6	6
STAT1	0.002	0.078	-10000	0	-0.41	18	18
HBEGF	0.015	0.026	-10000	0	-0.41	2	2
PRLR	0.017	0	-10000	0	-10000	0	0
E4ICDs/ETO2	0.029	0.025	-10000	0	-0.26	1	1
axon guidance	0.023	0.031	-10000	0	-0.27	1	1
NEDD4	0.007	0.069	-10000	0	-0.41	14	14
Prolactin receptor/Prolactin receptor/Prolactin	0.022	0.033	-10000	0	-0.28	6	6
CBFA2T3	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.034	0.03	-10000	0	-0.19	8	8
MAPK3	0.022	0.061	-10000	0	-0.2	8	8
STAT1 (dimer)	0.021	0.051	-10000	0	-0.22	19	19
MAPK1	0.021	0.061	-10000	0	-0.2	8	8
JAK2	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	0.03	0.026	-10000	0	-0.19	6	6
NRG1	0.016	0.028	-10000	0	-0.27	5	5
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.017	0	-10000	0	-10000	0	0
NRG4	0	0	-10000	0	-10000	0	0
heart development	0.023	0.031	-10000	0	-0.27	1	1
neural crest cell migration	0.029	0.026	-10000	0	-0.19	6	6
ERBB2	0.016	0.028	-10000	0	-0.27	5	5
WWOX/E4ICDs	0.029	0.025	-10000	0	-0.26	1	1
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
ErbB4/EGFR/neuregulin 4	-0.054	0.11	-10000	0	-0.19	194	194
apoptosis	-0.022	0.026	0.2	2	-10000	0	2
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.029	0.025	-10000	0	-0.26	1	1
ErbB4/ErbB2/epiregulin	0.031	0.043	-10000	0	-0.21	14	14
ErbB4/ErbB4/betacellulin/betacellulin	0.029	0.025	-10000	0	-0.26	1	1
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.05	0.035	-10000	0	-0.21	1	1
MDM2	0.018	0.047	-10000	0	-0.21	20	20
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.03	0.027	-10000	0	-0.19	7	7
STAT5A	0.027	0.031	-10000	0	-0.25	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.046	0.11	-10000	0	-0.19	196	196
DLG4	0.017	0	-10000	0	-10000	0	0
GRB2/SHC	-0.002	0.088	-10000	0	-0.28	47	47
E4ICDs/TAB2/NCoR1	0.038	0.023	-10000	0	-0.24	1	1
STAT5A (dimer)	0.047	0.036	-10000	0	-0.22	1	1
MAP3K7IP2	0.017	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.034	0.031	-10000	0	-0.25	1	1
LRIG1	-0.002	0.087	-10000	0	-0.41	23	23
EREG	0.009	0.058	-10000	0	-0.41	10	10
BTC	0.017	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.023	0.031	-10000	0	-0.27	1	1
ERBB4	0.026	0.025	-10000	0	-0.24	2	2
STAT5B	0.017	0	-10000	0	-10000	0	0
YAP1	-0.001	0.061	-10000	0	-0.2	46	46
GRB2	0.017	0.002	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.023	0.026	-10000	0	-0.2	6	6
glial cell differentiation	-0.038	0.023	0.24	1	-10000	0	1
WWOX	0.017	0	-10000	0	-10000	0	0
cell proliferation	0.033	0.025	-10000	0	-0.2	1	1

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.029	0.06	-9999	-0.21	32	32
MAP4K1	0.016	0.019	-9999	-0.41	1	1
MAP3K8	-0.017	0.12	-9999	-0.41	42	42
PRKCB	0	0	-9999	-10000	0	0
DBNL	0	0	-9999	-10000	0	0
CRKL	0.017	0	-9999	-10000	0	0
MAP3K1	0.021	0.034	-9999	-0.11	31	31
JUN	0.019	0.015	-9999	-0.18	1	1
MAP3K7	0.021	0.034	-9999	-0.11	31	31
GRAP2	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
MAP2K4	0.018	0.045	-9999	-0.18	15	15
LAT	0.016	0.019	-9999	-0.41	1	1
LCP2	-0.007	0.099	-9999	-0.41	30	30
MAPK8	0.016	0.014	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.02	0.035	-9999	-0.12	32	32
LAT/GRAP2/SLP76/HPK1/HIP-55	0.027	0.056	-9999	-0.19	32	32

×

Thromboxane A2 receptor signaling

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
TGM2	0.013	0.037	-10000	0	-0.41	4	4
GNB1/GNG2	-0.045	0.035	-10000	0	-0.14	15	15
AKT1	-0.016	0.081	-10000	0	-0.17	6	6
EGF	0.015	0.026	-10000	0	-0.41	2	2
mol:TXA2	0	0	-10000	0	-10000	0	0
FGR	0.023	0.033	-10000	0	-0.16	17	17
mol:Ca2+	-0.029	0.11	-10000	0	-0.23	15	15
LYN	0.007	0.059	-10000	0	-0.15	64	64
RhoA/GTP	-0.031	0.026	-10000	0	-0.099	15	15
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.047	0.12	-10000	0	-0.26	37	37
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.017	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.027	0.019	-10000	0	-0.13	7	7
G beta5/gamma2	-0.058	0.045	-10000	0	-0.19	15	15
PRKCH	-0.041	0.12	-10000	0	-0.28	16	16
DNM1	0.003	0.007	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.002	0.005	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.002	15	15
PTGDR	0.017	0	-10000	0	-10000	0	0
G12 family/GTP	-0.071	0.055	-10000	0	-0.22	19	19
ADRBK1	0.017	0	-10000	0	-10000	0	0
ADRBK2	0.017	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.023	0.002	-10000	0	-10000	0	0
mol:GDP	0.003	0.065	0.15	2	-10000	0	2
mol:NADP	0.017	0	-10000	0	-10000	0	0
RAB11A	0.017	0.001	-10000	0	-10000	0	0
PRKG1	0.017	0	-10000	0	-10000	0	0
mol:IP3	-0.039	0.12	-10000	0	-0.28	15	15
cell morphogenesis	0.023	0.002	-10000	0	-10000	0	0
PLCB2	-0.054	0.14	-10000	0	-0.36	15	15
mol:cGMP	0	0	-10000	0	-10000	0	0
BLK	0.029	0.006	-10000	0	-10000	0	0
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0	0.067	-10000	0	-0.15	86	86
RHOA	0.017	0.001	-10000	0	-10000	0	0
PTGIR	0.017	0	-10000	0	-10000	0	0
PRKCB1	-0.009	0.049	-10000	0	-0.24	15	15
GNAQ	0.017	0	-10000	0	-10000	0	0
mol:L-citrulline	0.017	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.062	0.15	-10000	0	-0.38	15	15
LCK	0.027	0.016	-10000	0	-0.15	4	4
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.033	0.002	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.022	0.039	-10000	0	-0.31	6	6
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.033	0.002	-10000	0	-10000	0	0
MAPK14	-0.028	0.093	-10000	0	-0.18	39	39
TGM2/GTP	-0.035	0.13	-10000	0	-0.3	15	15
MAPK11	-0.028	0.093	-10000	0	-0.18	37	37
ARHGEF1	-0.018	0.07	-10000	0	-0.13	19	19
GNAI2	0.017	0.001	-10000	0	-10000	0	0
JNK cascade	-0.045	0.13	-10000	0	-0.29	15	15
RAB11/GDP	0.017	0.001	-10000	0	-10000	0	0
ICAM1	-0.035	0.11	-10000	0	-0.28	18	18
cAMP biosynthetic process	-0.032	0.11	-10000	0	-0.25	15	15
Gq family/GTP/EBP50	0.02	0.021	-10000	0	-0.13	8	8
actin cytoskeleton reorganization	0.023	0.002	-10000	0	-10000	0	0
SRC	0.029	0.006	-10000	0	-10000	0	0
GNB5	0.017	0.002	-10000	0	-10000	0	0
GNB1	0.017	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.013	0.061	-10000	0	-0.16	34	34
VCAM1	-0.078	0.13	-10000	0	-0.17	351	351
TP beta/Gq family/GDP/G beta5/gamma2	0.027	0.019	-10000	0	-0.13	7	7
platelet activation	-0.03	0.12	-10000	0	-0.24	17	17
PGI2/IP	0.013	0.001	-10000	0	-10000	0	0
PRKACA	0.019	0.001	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.026	0.019	-10000	0	-0.12	7	7
TXA2/TP beta/beta Arrestin2	0.002	0.006	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.019	0.002	-10000	0	-10000	0	0
mol:DAG	-0.049	0.13	-10000	0	-0.32	15	15
EGFR	-0.14	0.21	-10000	0	-0.41	194	194
TXA2/TP alpha	-0.041	0.14	-10000	0	-0.33	15	15
Gq family/GTP	0.016	0.017	-10000	0	-0.11	9	9
YES1	0.002	0.065	-10000	0	-0.15	80	80
GNAI2/GTP	0.023	0.005	-10000	0	-10000	0	0
PGD2/DP	0.013	0.001	-10000	0	-10000	0	0
SLC9A3R1	0.015	0.026	-10000	0	-0.41	2	2
FYN	0.027	0.013	-10000	0	-0.15	2	2
mol:NO	0.017	0	-10000	0	-10000	0	0
GNA15	0.011	0.049	-10000	0	-0.41	7	7
PGK/cGMP	0.023	0.001	-10000	0	-10000	0	0
RhoA/GDP	0.017	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.034	0.018	-10000	0	-0.16	4	4
NOS3	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
PRKCA	-0.041	0.12	-10000	0	-0.27	15	15
PRKCB	-0.046	0.12	-10000	0	-0.27	15	15
PRKCE	-0.044	0.12	-10000	0	-0.28	15	15
PRKCD	-0.051	0.12	-10000	0	-0.29	15	15
PRKCG	-0.047	0.12	-10000	0	-0.29	15	15
muscle contraction	-0.056	0.14	-10000	0	-0.36	15	15
PRKCZ	-0.041	0.12	-10000	0	-0.26	15	15
ARR3	0.017	0	-10000	0	-10000	0	0
TXA2/TP beta	0.034	0.005	-10000	0	-10000	0	0
PRKCQ	-0.044	0.12	-10000	0	-0.27	15	15
MAPKKK cascade	-0.051	0.13	-10000	0	-0.33	15	15
SELE	-0.038	0.11	-10000	0	-0.24	15	15
TP beta/GNAI2/GDP/G beta/gamma	0.035	0.004	-10000	0	-10000	0	0
ROCK1	0.017	0	-10000	0	-10000	0	0
GNA14	0.015	0.026	-10000	0	-0.41	2	2
chemotaxis	-0.077	0.16	-10000	0	-0.44	15	15
GNA12	0.014	0.037	-10000	0	-0.41	4	4
GNA13	0.015	0.026	-10000	0	-0.41	2	2
GNA11	0.017	0	-10000	0	-10000	0	0
Rac1/GTP	0.013	0.001	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.005	0.041	-9999	-0.24	15	15
SNTA1	0.017	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.01	0.042	-9999	-0.23	15	15
MAPK12	0.015	0.02	-9999	-0.13	10	10
CCND1	-0.013	0.062	-9999	-0.14	98	98
p38 gamma/SNTA1	0.025	0.02	-9999	-10000	0	0
MAP2K3	0.017	0	-9999	-10000	0	0
PKN1	0.009	0.058	-9999	-0.41	10	10
G2/M transition checkpoint	0.015	0.02	-9999	-0.13	10	10
MAP2K6	0.013	0.023	-9999	-0.15	10	10
MAPT	0.009	0.035	-9999	-0.18	15	15
MAPK13	0.009	0.05	-9999	-0.28	15	15
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.011	0.027	-9999	-0.18	10	10

×

Insulin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.029	0.02	-9999	-0.18	5	5
TC10/GTP	0.027	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.044	0.025	-9999	-0.21	5	5
HRAS	0.016	0.019	-9999	-0.41	1	1
APS homodimer	0	0	-9999	-10000	0	0
GRB14	0.002	0.078	-9999	-0.41	18	18
FOXO3	0.012	0.013	-9999	-10000	0	0
AKT1	0.021	0.061	-9999	-0.33	1	1
INSR	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.048	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.004	0.073	-9999	-0.41	16	16
SORBS1	0.017	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
PTPN1	0.024	0.009	-9999	-10000	0	0
CAV1	-0.11	0.11	-9999	-0.2	325	325
CBL/APS/CAP/Crk-II/C3G	0.041	0	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	0.044	0.025	-9999	-0.21	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.023	0.049	-9999	-0.18	27	27
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.023	0.044	-9999	-0.23	3	3
RPS6KB1	0.022	0.058	-9999	-0.3	1	1
PARD6A	0.017	0	-9999	-10000	0	0
CBL	0.017	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.016	0.011	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	0.022	0.053	-9999	-0.29	1	1
HRAS/GTP	-0.016	0.051	-9999	-0.17	50	50
Insulin Receptor	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.029	0.077	-9999	-0.21	49	49
PRKCI	0.025	0.027	-9999	-0.15	6	6
Insulin Receptor/Insulin/GRB14/PDK1	-0.014	0.047	-9999	-0.17	43	43
SHC1	-0.021	0.12	-9999	-0.41	47	47
negative regulation of MAPKKK cascade	0.029	0.033	-9999	-0.19	10	10
PI3K	0.03	0.052	-9999	-0.18	27	27
NCK2	0.017	0.001	-9999	-10000	0	0
RHOQ	0.017	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.012	0.013	-9999	-0.29	1	1
AKT2	0.023	0.059	-9999	-0.33	1	1
PRKCZ	0.015	0.026	-9999	-0.16	6	6
SH2B2	0	0	-9999	-10000	0	0
SHC/SHIP	0.003	0.066	-9999	-0.2	49	49
F2RL2	0.017	0	-9999	-10000	0	0
TRIP10	0.012	0.045	-9999	-0.41	6	6
Insulin Receptor/Insulin/Shc	0.013	0.071	-9999	-0.22	47	47
TC10/GTP/CIP4/Exocyst	0.02	0.028	-9999	-0.24	6	6
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.021	0.068	-9999	-0.2	47	47
RAPGEF1	0.017	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
CBL/APS/CAP/Crk-II	0.033	0	-9999	-10000	0	0
TC10/GDP	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.016	0.087	-9999	-0.22	60	60
INPP5D	0.011	0.021	-9999	-0.2	5	5
SOS1	0	0	-9999	-10000	0	0
SGK1	-0.002	0.005	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.017	0	-9999	-10000	0	0
IRS1	0.013	0.042	-9999	-0.41	5	5
p62DOK/RasGAP	0.03	0.034	-9999	-0.2	10	10
INS	0.019	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.011	0.02	-9999	-0.2	5	5
GRB2	0.017	0.002	-9999	-10000	0	0
EIF4EBP1	-0.071	0.11	-9999	-0.31	27	27
PTPRA	0.019	0.002	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
TC10/GTP/CIP4	0.02	0.028	-9999	-0.24	6	6
PDPK1	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.013	0.048	-9999	-0.13	49	49
Insulin Receptor/Insulin/IRS1	0.033	0.024	-9999	-0.22	5	5
Insulin Receptor/Insulin/IRS3	0.028	0	-9999	-10000	0	0
Par3/Par6	0.038	0.025	-9999	-0.19	6	6

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	0.037	0.043	-10000	0	-0.17	1	1
TBX21	0.045	0.12	-10000	0	-0.43	12	12
B2M	0.017	0	-10000	0	-10000	0	0
TYK2	0.017	0.026	-10000	0	-0.44	1	1
IL12RB1	0.017	0.016	-10000	0	-10000	0	0
GADD45B	0.046	0.12	-10000	0	-0.44	14	14
IL12RB2	0.018	0.017	-10000	0	-10000	0	0
GADD45G	0.044	0.12	-10000	0	-0.4	12	12
natural killer cell activation	0.002	0.014	-10000	0	-10000	0	0
RELB	0.016	0.019	-10000	0	-0.41	1	1
RELA	0.017	0	-10000	0	-10000	0	0
IL18	-0.017	0.12	-10000	0	-0.41	45	45
IL2RA	0.012	0.045	-10000	0	-0.41	6	6
IFNG	0.016	0.019	-10000	0	-0.41	1	1
STAT3 (dimer)	0.042	0.14	-10000	0	-0.44	9	9
HLA-DRB5	-0.002	0.005	-10000	0	-10000	0	0
FASLG	0.045	0.12	-10000	0	-0.43	12	12
NF kappa B2 p52/RelB	0.028	0.14	-10000	0	-0.45	11	11
CD4	-0.001	0.081	-10000	0	-0.42	19	19
SOCS1	0.017	0	-10000	0	-10000	0	0
EntrezGene:6955	-0.003	0.006	-10000	0	-10000	0	0
CD3D	-0.003	0.082	-10000	0	-0.42	20	20
CD3E	0.014	0.02	-10000	0	-0.41	1	1
CD3G	0.012	0.021	-10000	0	-0.41	1	1
IL12Rbeta2/JAK2	0.028	0.027	-10000	0	-10000	0	0
CCL3	0.038	0.12	-10000	0	-0.38	22	22
CCL4	0.045	0.14	-10000	0	-0.49	19	19
HLA-A	0.016	0.019	-10000	0	-0.41	1	1
IL18/IL18R	0.033	0.083	-10000	0	-0.23	45	45
NOS2	0.039	0.12	-10000	0	-0.35	22	22
IL12/IL12R/TYK2/JAK2/SPHK2	0.037	0.043	-10000	0	-0.17	1	1
IL1R1	0.044	0.13	-10000	0	-0.44	14	14
IL4	0.015	0.014	-10000	0	-10000	0	0
JAK2	0.017	0.016	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.016	0.032	-10000	0	-0.16	9	9
RAB7A	0.048	0.12	-10000	0	-0.41	5	5
lysosomal transport	0.048	0.12	-10000	0	-0.43	3	3
FOS	-0.08	0.2	-10000	0	-0.4	130	130
STAT4 (dimer)	0.038	0.13	-10000	0	-0.44	8	8
STAT5A (dimer)	0.027	0.14	-10000	0	-0.42	12	12
GZMA	0.034	0.15	-10000	0	-0.53	19	19
GZMB	0.038	0.14	-10000	0	-0.52	17	17
HLX	0.013	0.042	-10000	0	-0.41	5	5
LCK	0.041	0.13	-10000	0	-0.4	24	24
TCR/CD3/MHC II/CD4	-0.075	0.1	-10000	0	-0.23	110	110
IL2/IL2R	0.035	0.053	-10000	0	-0.26	15	15
MAPK14	0.043	0.13	-10000	0	-0.43	9	9
CCR5	0.043	0.13	-10000	0	-0.51	11	11
IL1B	0.006	0.07	-10000	0	-0.41	14	14
STAT6	0.033	0.048	-10000	0	-0.18	3	3
STAT4	0.01	0.008	-10000	0	-10000	0	0
STAT3	0.009	0.058	-10000	0	-0.41	10	10
STAT1	0.002	0.078	-10000	0	-0.41	18	18
NFKB1	0.014	0.037	-10000	0	-0.41	4	4
NFKB2	0.017	0	-10000	0	-10000	0	0
IL12B	0.018	0.017	-10000	0	-10000	0	0
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0.015	0.026	-10000	0	-0.41	2	2
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.037	0.043	0.17	1	-10000	0	1
IL2RB	0.014	0.037	-10000	0	-0.41	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.13	-10000	0	-0.41	8	8
IL2RG	0.01	0.055	-10000	0	-0.41	9	9
IL12	0.028	0.027	-10000	0	-10000	0	0
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
CD247	0.013	0.027	-10000	0	-0.42	2	2
IL2	0.017	0	-10000	0	-10000	0	0
SPHK2	0.017	0	-10000	0	-10000	0	0
FRAP1	0.016	0.019	-10000	0	-0.41	1	1
IL12A	0.017	0.016	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	0.046	0.13	-10000	0	-0.41	22	22
MAP2K3	0.039	0.13	-10000	0	-0.42	11	11
RIPK2	0.016	0.019	-10000	0	-0.41	1	1
MAP2K6	0.039	0.13	-10000	0	-0.42	11	11
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.22	0.21	-10000	0	-0.42	291	291
IL18RAP	0.02	0.006	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.025	0.028	-10000	0	-0.32	1	1
EOMES	-0.002	0.019	-10000	0	-10000	0	0
STAT1 (dimer)	0.039	0.13	-10000	0	-0.43	10	10
T cell proliferation	0.024	0.11	-10000	0	-0.36	8	8
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.006	-10000	0	-10000	0	0
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.028	0.088	-10000	0	-0.38	12	12
ATF2	0.045	0.13	-10000	0	-0.45	5	5

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.014	0.037	-10000	0	-0.41	4	4
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.051	4	4
monocyte activation	-0.084	0.071	-10000	0	-0.16	4	4
MAP2K2	0.012	0.002	-10000	0	-10000	0	0
MAP2K1	0.004	0.004	-10000	0	-10000	0	0
MAP2K7	0.005	0.004	-10000	0	-10000	0	0
MAP2K6	0.005	0.004	-10000	0	-10000	0	0
CYAA	0.002	0.018	-10000	0	-0.2	4	4
MAP2K4	0.004	0.004	-10000	0	-10000	0	0
IL1B	-0.006	0.036	-10000	0	-0.21	14	14
Channel	0.009	0.02	-10000	0	-0.22	4	4
NLRP1	0.005	0.004	-10000	0	-10000	0	0
CALM1	0.016	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.01	0.006	-10000	0	-0.055	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.051	4	-10000	0	4
MAPK3	0.005	0.004	-10000	0	-10000	0	0
MAPK1	0.004	0.004	-10000	0	-10000	0	0
PGR	0.005	0.004	-10000	0	-10000	0	0
PA/Cellular Receptors	0.01	0.022	-10000	0	-0.24	4	4
apoptosis	0	0.004	-10000	0	-0.051	4	4
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.009	0.018	-10000	0	-0.19	4	4
macrophage activation	0.007	0.004	-10000	0	-10000	0	0
TNF	0.015	0.026	-10000	0	-0.41	2	2
VCAM1	-0.084	0.071	-10000	0	-0.13	353	353
platelet activation	0.01	0.006	-10000	0	-0.055	4	4
MAPKKK cascade	-0.009	0.009	-10000	0	-10000	0	0
IL18	-0.018	0.061	-10000	0	-0.22	45	45
negative regulation of macrophage activation	0	0.004	-10000	0	-0.051	4	4
LEF	0	0.004	-10000	0	-0.051	4	4
CASP1	-0.005	0.015	-10000	0	-0.063	4	4
mol:cAMP	0.01	0.006	-10000	0	-0.055	4	4
necrosis	0	0.004	-10000	0	-0.051	4	4
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.009	0.019	-10000	0	-0.2	4	4
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Arf6 signaling events

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
CENTA1/KIF3B	0.011	0.016	-9999	0	-0.24	2	2
ARNO/beta Arrestin1-2	0.025	0.009	-9999	0	-0.17	1	1
EGFR	-0.14	0.21	-9999	0	-0.41	194	194
EPHA2	0.006	0.069	-9999	0	-0.41	14	14
USP6	0.017	0	-9999	0	-10000	0	0
IQSEC1	0.017	0.002	-9999	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.089	0.15	-9999	0	-0.28	196	196
ARRB2	0.015	0	-9999	0	-10000	0	0
mol:GTP	0.002	0.005	-9999	0	-10000	0	0
ARRB1	0.017	0	-9999	0	-10000	0	0
FBXO8	0	0	-9999	0	-10000	0	0
TSHR	0.014	0.037	-9999	0	-0.41	4	4
EGF	0.015	0.026	-9999	0	-0.41	2	2
somatostatin receptor activity	0	0	-9999	0	0	1	1
ARAP2	0	0	-9999	0	0	1	1
mol:GDP	0.019	0.019	-9999	0	-0.089	1	1
mol:PI-3-4-5-P3	0	0	-9999	0	0	1	1
ITGA2B	0.017	0	-9999	0	-10000	0	0
ARF6	0.017	0	-9999	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.022	0.084	-9999	0	-0.26	38	38
ADAP1	0	0	-9999	0	-10000	0	0
KIF13B	0.015	0.026	-9999	0	-0.41	2	2
HGF/MET	0.018	0.046	-9999	0	-0.28	12	12
PXN	0.017	0	-9999	0	-10000	0	0
ARF6/GTP	0.028	0.033	-9999	0	-0.094	1	1
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.065	0.13	-9999	0	-0.23	194	194
ADRB2	0.016	0.019	-9999	0	-0.41	1	1
receptor agonist activity	0	0	0	4	0	1	5
actin filament binding	0	0	-9999	0	0	1	1
SRC	0.017	0	-9999	0	-10000	0	0
ITGB3	0.017	0	-9999	0	-10000	0	0
GNAQ	0.017	0	-9999	0	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	0	-10000	0	0
ARF6/GDP	0.021	0.024	-9999	0	-0.11	6	6
ARF6/GDP/GULP/ACAP1	0.033	0.023	-9999	0	-0.16	3	3
alphaIIb/beta3 Integrin/paxillin/GIT1	0.044	0	-9999	0	-10000	0	0
ACAP1	0	0	-9999	0	-10000	0	0
ACAP2	0	0	-9999	0	0	1	1
LHCGR/beta Arrestin2	0.018	0	-9999	0	-10000	0	0
EFNA1	-0.002	0.088	-9999	0	-0.41	23	23
HGF	0.015	0.026	-9999	0	-0.41	2	2
CYTH3	0	0	-9999	0	0	1	1
CYTH2	0	0	-9999	0	-0.002	1	1
NCK1	0.008	0.061	-9999	0	-0.41	11	11
fibronectin binding	0	0	-9999	0	-10000	0	0
endosomal lumen acidification	0	0	-9999	0	0	1	1
microtubule-based process	0	0	-9999	0	-10000	0	0
GULP1	0.015	0.032	-9999	0	-0.41	3	3
GNAQ/ARNO	0.013	0.001	-9999	0	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	0	0	1	1
PIP3-E	0.001	0.004	-9999	0	-10000	0	0
MET	0.009	0.058	-9999	0	-0.41	10	10
GNA14	0.016	0.026	-9999	0	-0.41	2	2
GNA15	0.011	0.049	-9999	0	-0.41	7	7
GIT1	0.017	0	-9999	0	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	0	0	1	1
GNA11	0.017	0	-9999	0	-10000	0	0
LHCGR	0.017	0	-9999	0	-10000	0	0
AGTR1	0.016	0.026	-9999	0	-0.41	2	2
desensitization of G-protein coupled receptor protein signaling pathway	0.018	0	-9999	0	-10000	0	0
IPCEF1/ARNO	-0.029	0.042	-9999	0	-0.18	6	6
alphaIIb/beta3 Integrin	0.025	0	-9999	0	-10000	0	0

×

IGF1 pathway

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
NCK2	0.017	0.001	-10000	0	-10000	0	0
PTK2	0.017	0.001	-10000	0	-10000	0	0
CRKL	0.018	0.023	-10000	0	-0.16	9	9
GRB2/SOS1/SHC	0	0.074	-10000	0	-0.24	47	47
HRAS	0.016	0.019	-10000	0	-0.41	1	1
IRS1/Crk	0.022	0.024	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1/PTP1B	0.031	0.022	-10000	0	-0.21	4	4
AKT1	0.012	0.046	-10000	0	-0.17	28	28
BAD	0.021	0.05	-10000	0	-0.16	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.018	0.023	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.024	0.024	-10000	0	-0.16	9	9
RAF1	0.027	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.029	0.024	-10000	0	-0.15	9	9
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.021	0.026	-10000	0	-0.18	9	9
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
RPS6KB1	0.013	0.044	-10000	0	-0.17	25	25
GNB2L1	0.017	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.02	0.047	0.28	2	-10000	0	2
PXN	0.017	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.013	0.001	-10000	0	-10000	0	0
HRAS/GTP	-0.001	0.06	-10000	0	-0.18	53	53
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.016	0.072	-10000	0	-0.21	50	50
IGF-1R heterotetramer	0.017	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.031	0.025	-10000	0	-0.16	9	9
Crk/p130 Cas/Paxillin	0.031	0.022	-10000	0	-0.14	9	9
IGF1R	0.017	0.008	-10000	0	-10000	0	0
IGF1	0.014	0.037	-10000	0	-0.41	4	4
IRS2/Crk	0.025	0.023	-10000	0	-0.14	9	9
PI3K	0.027	0.052	-10000	0	-0.18	30	30
apoptosis	-0.028	0.047	-10000	0	-10000	0	0
HRAS/GDP	0.012	0.013	-10000	0	-0.29	1	1
PRKCD	0.015	0.035	-10000	0	-0.16	7	7
RAF1/14-3-3 E	0.034	0.045	-10000	0	-10000	0	0
BAD/14-3-3	0.029	0.049	-10000	0	-10000	0	0
PRKCZ	0.009	0.042	-10000	0	-0.17	24	24
Crk/p130 Cas/Paxillin/FAK1	0.021	0.04	-10000	0	-10000	0	0
PTPN1	0.017	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.013	0.038	-10000	0	-0.17	7	7
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.009	0.092	-10000	0	-0.24	63	63
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.024	0.024	-10000	0	-0.16	9	9
GRB10	0.004	0.073	-10000	0	-0.41	16	16
PTPN11	0.018	0.023	-10000	0	-0.16	9	9
IRS1	0.014	0.025	-10000	0	-0.18	9	9
IRS2	0.017	0.023	-10000	0	-0.16	9	9
IGF-1R heterotetramer/IGF1	0.021	0.028	-10000	0	-0.28	4	4
GRB2	0.017	0.002	-10000	0	-10000	0	0
PDPK1	0.014	0.046	-10000	0	-0.18	24	24
YWHAE	0.017	0.001	-10000	0	-10000	0	0
PRKD1	-0.032	0.09	-10000	0	-0.18	131	131
SHC1	-0.021	0.12	-10000	0	-0.41	47	47

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.018	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.035	0.004	-10000	0	-10000	0	0
CDKN1B	0.02	0.037	-10000	0	-0.14	27	27
CDKN1A	0	0.069	-10000	0	-0.16	80	80
FRAP1	0.016	0.019	-10000	0	-0.41	1	1
PRKDC	-0.002	0.088	-10000	0	-0.41	23	23
FOXO3	0.02	0.037	-10000	0	-0.14	27	27
AKT1	0.017	0.038	-10000	0	-0.15	27	27
BAD	0.017	0	-10000	0	-10000	0	0
AKT3	0.015	0.009	-10000	0	-0.18	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.02	0.037	-10000	0	-0.14	27	27
AKT1/ASK1	0.025	0.037	-10000	0	-0.13	27	27
BAD/YWHAZ	0.034	0.004	-10000	0	-10000	0	0
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.016	0.019	-10000	0	-0.41	1	1
JNK cascade	-0.024	0.036	0.13	27	-10000	0	27
TSC1	0.019	0.037	-10000	0	-0.14	27	27
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
AKT1/RAF1	0.026	0.039	-10000	0	-0.14	28	28
EP300	0.017	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.038	-10000	0	-0.15	27	27
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.02	0.037	-10000	0	-0.14	27	27
YWHAQ	0.017	0	-10000	0	-10000	0	0
TBC1D4	0.016	0	-10000	0	-10000	0	0
MAP3K5	0.017	0.001	-10000	0	-10000	0	0
MAPKAP1	0.017	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.002	0.036	0.15	10	-10000	0	10
YWHAH	0.008	0.009	-10000	0	-10000	0	0
AKT1S1	0.016	0.037	-10000	0	-0.14	27	27
CASP9	0.018	0.045	-10000	0	-0.16	28	28
YWHAB	0.017	0.001	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.029	0.037	-10000	0	-0.18	1	1
GBL	0.017	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.035	0	-10000	0	-10000	0	0
YWHAE	0.017	0.001	-10000	0	-10000	0	0
SRC	0.017	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0.004	0.066	-10000	0	-0.16	55	55
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.026	0.015	-10000	0	-10000	0	0
CHUK	0.019	0.038	-10000	0	-0.14	28	28
BAD/BCL-XL	0.036	0.037	-10000	0	-0.17	1	1
mTORC2	0.033	0.011	-10000	0	-0.21	1	1
AKT2	0.015	0	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.005	0.048	-10000	0	-0.2	10	10
PDPK1	0.017	0	-10000	0	-10000	0	0
MDM2	0.013	0.051	-10000	0	-0.16	44	44
MAPKKK cascade	-0.026	0.039	0.14	28	-10000	0	28
MDM2/Cbp/p300	0.031	0.052	-10000	0	-0.16	19	19
TSC1/TSC2	0.022	0.036	-10000	0	-0.17	2	2
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.05	-10000	0	-0.16	19	19
glucose import	0.018	0	-10000	0	-10000	0	0
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.027	0.027	-10000	0	-0.22	1	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0.018	0	-10000	0	-10000	0	0
GSK3A	0.02	0.037	-10000	0	-0.14	27	27
FOXO1	0.016	0.047	-10000	0	-0.15	37	37
GSK3B	0.02	0.036	-10000	0	-0.14	26	26
SFN	-0.01	0.1	-10000	0	-0.41	33	33
G1/S transition of mitotic cell cycle	0.022	0.035	-10000	0	-0.18	1	1
p27Kip1/14-3-3 family	0.012	0.026	-10000	0	-0.15	4	4
PRKACA	0.017	0	-10000	0	-10000	0	0
KPNA1	0.017	0	-10000	0	-10000	0	0
HSP90AA1	0.017	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.017	0	-10000	0	-10000	0	0
CREBBP	0.017	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.032	-9999	-0.41	3	3
alphaV beta3 Integrin	0.016	0.053	-9999	-0.28	16	16
PTK2	0.026	0.04	-9999	-0.18	7	7
positive regulation of JNK cascade	0	0.007	-9999	-10000	0	0
CDC42/GDP	0.053	0.02	-9999	-10000	0	0
Rac1/GDP	0.054	0.02	-9999	-10000	0	0
RAP1B	0	0	-9999	-10000	0	0
RAP1A	0.017	0	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
CDC42/GTP	0.04	0.018	-9999	-10000	0	0
nectin-3/I-afadin	0.024	0.019	-9999	-0.28	2	2
RAPGEF1	0.04	0.022	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.04	0.023	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.032	-9999	-0.41	3	3
TLN1	0	0.059	-9999	-0.19	46	46
Rap1/GTP	0	0.008	-9999	-10000	0	0
IQGAP1	-0.086	0.18	-9999	-0.41	127	127
Rap1/GTP/I-afadin	0.022	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.024	0.019	-9999	-0.28	2	2
PVR	0.017	0	-9999	-10000	0	0
Necl-5(dimer)	0.017	0	-9999	-10000	0	0
mol:GDP	0.049	0.022	-9999	-10000	0	0
MLLT4	0.017	0	-9999	-10000	0	0
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
PI3K	0.034	0.056	-9999	-0.19	29	29
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	0	0.008	-9999	-10000	0	0
PVRL1	0.017	0	-9999	-10000	0	0
PVRL3	0.015	0.026	-9999	-0.41	2	2
PVRL2	0.017	0	-9999	-10000	0	0
PIK3R1	0.016	0.004	-9999	-10000	0	0
CDH1	0.011	0.052	-9999	-0.41	8	8
CLDN1	0.01	0.055	-9999	-0.41	9	9
JAM-A/CLDN1	0.024	0.079	-9999	-0.26	35	35
SRC	0.035	0.025	-9999	-0.18	2	2
ITGB3	0.017	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
FARP2	0.046	0.021	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
CTNNA1	0.017	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.034	0.017	-9999	-0.23	2	2
nectin-1/I-afadin	0.025	0	-9999	-10000	0	0
nectin-2/I-afadin	0.025	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	-0.04	0.11	-9999	-0.24	127	127
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.034	0.017	-9999	-0.23	2	2
CDC42/GTP/IQGAP1/filamentous actin	-0.04	0.11	-9999	-0.24	127	127
F11R	-0.01	0.1	-9999	-0.41	33	33
positive regulation of filopodium formation	0	0.007	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	0.013	0.072	-9999	-0.19	56	56
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.025	0	-9999	-10000	0	0
PIP5K1C	0.017	0.009	-9999	-10000	0	0
VAV2	0.047	0.022	-9999	-10000	0	0
RAP1/GDP	0.041	0.019	-9999	-10000	0	0
ITGAV	0.004	0.073	-9999	-0.41	16	16
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.034	0.017	-9999	-0.23	2	2
nectin-3(dimer)/I-afadin/I-afadin	0.024	0.019	-9999	-0.28	2	2
Rac1/GTP	0.045	0.018	-9999	-10000	0	0
PTPRM	0.016	0.009	-9999	-0.12	2	2
E-cadherin/beta catenin/alpha catenin	0.047	0.028	-9999	-0.18	8	8
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.017	0	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.021	0.012	-9999	-10000	0	0
NFATC2	0.012	0.01	-9999	-10000	0	0
NFATC3	0.021	0.012	-9999	-10000	0	0
CD40LG	0.019	0.1	-9999	-0.33	15	15
PTGS2	0.009	0.13	-9999	-0.39	31	31
JUNB	0.011	0.052	-9999	-0.41	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	0.015	0.008	-9999	-10000	0	0
CaM/Ca2+	0.015	0.008	-9999	-10000	0	0
CALM1	0.018	0.005	-9999	-10000	0	0
JUN	0.019	0.019	-9999	-0.41	1	1
mol:Ca2+	0.002	0.004	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.012	0.011	-9999	-0.24	1	1
FOSL1	0.007	0.066	-9999	-0.41	13	13
CREM	0.017	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.055	0.041	-9999	-0.19	3	3
FOS	-0.081	0.18	-9999	-0.41	125	125
IFNG	0.019	0.1	-9999	-0.33	16	16
AP-1/NFAT1-c-4	0.05	0.13	-9999	-0.37	15	15
FASLG	0.019	0.1	-9999	-0.33	15	15
NFAT1-c-4/ICER1	0.039	0.026	-9999	-10000	0	0
IL2RA	0.017	0.11	-9999	-0.37	17	17
FKBP12/FK506	0.012	0.013	-9999	-0.29	1	1
CSF2	0.019	0.1	-9999	-0.33	15	15
JunB/Fra1/NFAT1-c-4	0.042	0.051	-9999	-0.18	20	20
IL4	0.019	0.1	-9999	-0.33	15	15
IL2	0.001	0.004	-9999	-10000	0	0
IL3	0.003	0.008	-9999	-10000	0	0
FKBP1A	0.016	0.019	-9999	-0.41	1	1
BATF3	0	0	-9999	-10000	0	0
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.023	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.017	0	-9999	-10000	0	0
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.017	0	-9999	-10000	0	0
TCEB1	0.017	0	-9999	-10000	0	0
HIF1A/p53	-0.001	0.072	-9999	-0.18	69	69
HIF1A	0.015	0.021	-9999	-10000	0	0
COPS5	0.017	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.041	0	-9999	-10000	0	0
FIH (dimer)	0.017	0	-9999	-10000	0	0
CDKN2A	-0.03	0.13	-9999	-0.41	58	58
ARNT/IPAS	0.025	0	-9999	-10000	0	0
HIF1AN	0.017	0	-9999	-10000	0	0
GNB2L1	0.017	0	-9999	-10000	0	0
HIF1A/ARNT	0.024	0.023	-9999	-10000	0	0
CUL2	0.017	0	-9999	-10000	0	0
OS9	-0.018	0.12	-9999	-0.41	43	43
RACK1/Elongin B/Elongin C	0.035	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.024	0.023	-9999	-10000	0	0
PHD1-3/OS9	0.021	0.072	-9999	-0.21	48	48
HIF1A/RACK1/Elongin B/Elongin C	0.038	0.024	-9999	-10000	0	0
VHL	0	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
HIF1A/JAB1	0.024	0.023	-9999	-10000	0	0
EGLN3	0.014	0.037	-9999	-0.41	4	4
EGLN2	0.017	0	-9999	-10000	0	0
EGLN1	0.016	0.019	-9999	-0.41	1	1
TP53	-0.039	0.14	-9999	-0.41	69	69
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.028	0.005	-9999	-10000	0	0
ARNT	0.017	0	-9999	-10000	0	0
ARD1A	0.016	0.019	-9999	-0.41	1	1
RBX1	0.017	0	-9999	-10000	0	0
HIF1A/p19ARF	0.003	0.071	-9999	-0.19	58	58

×

E-cadherin signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.023	0.064	-9999	-0.29	19	19
E-cadherin/beta catenin	0.021	0.038	-9999	-0.28	8	8
CTNNB1	0.017	0	-9999	-10000	0	0
JUP	0.004	0.073	-9999	-0.41	16	16
CDH1	0.011	0.052	-9999	-0.41	8	8

×

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

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
MET/RANBP9	0.02	0.042	-10000	0	-0.28	10	10
CRKL	0.027	0.022	-10000	0	-10000	0	0
mol:PIP3	-0.011	0.023	0.35	2	-10000	0	2
AKT1	-0.003	0.025	0.26	2	-0.21	4	6
PTK2B	0.017	0	-10000	0	-10000	0	0
RAPGEF1	0.03	0.021	-10000	0	-10000	0	0
RANBP10	0.017	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
HGF/MET/SHIP2	0.029	0.04	-10000	0	-0.23	12	12
MAP3K5	0.038	0.022	-10000	0	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	0.028	0.036	-10000	0	-0.21	12	12
AP1	-0.042	0.12	-10000	0	-0.25	125	125
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
apoptosis	-0.015	0.082	-10000	0	-0.66	2	2
STAT3 (dimer)	0.029	0.021	-10000	0	-10000	0	0
GAB1/CRKL/SHP2/PI3K	0.038	0.047	-10000	0	-0.26	1	1
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.037	0.022	-10000	0	-10000	0	0
PTPN11	0.017	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.017	0	-10000	0	-10000	0	0
PTEN	0.015	0.026	-10000	0	-0.41	2	2
ELK1	-0.001	0.044	0.21	17	-0.16	10	27
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.021	0.015	-10000	0	-10000	0	0
PAK1	0	0.023	0.24	2	-0.2	4	6
HGF/MET/RANBP10	0.029	0.04	-10000	0	-0.23	12	12
HRAS	0.028	0.029	-10000	0	-0.16	10	10
DOCK1	0.03	0.021	-10000	0	-10000	0	0
GAB1	0.025	0.023	-10000	0	-10000	0	0
CRK	0.027	0.022	-10000	0	-10000	0	0
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.028	-10000	0	-0.16	12	12
JUN	0.016	0.019	-10000	0	-0.41	1	1
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.01	0.022	-10000	0	-0.14	12	12
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
cell morphogenesis	0.041	0.047	-10000	0	-0.19	1	1
GRB2/SHC	0.011	0.067	-10000	0	-0.18	55	55
FOS	-0.084	0.18	-10000	0	-0.41	125	125
GLMN	0.003	0	-10000	0	-10000	0	0
cell motility	-0.001	0.044	0.21	17	-0.16	10	27
HGF/MET/MUC20	0.017	0.039	-10000	0	-0.24	12	12
cell migration	0.011	0.066	-10000	0	-0.18	55	55
GRB2	0.017	0.002	-10000	0	-10000	0	0
CBL	0.017	0	-10000	0	-10000	0	0
MET/RANBP10	0.02	0.042	-10000	0	-0.28	10	10
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.028	0.023	-10000	0	-0.12	12	12
MET/MUC20	0.007	0.041	-10000	0	-0.29	10	10
RAP1B	0.029	0.02	-10000	0	-10000	0	0
RAP1A	0.032	0.02	-10000	0	-10000	0	0
HGF/MET/RANBP9	0.029	0.04	-10000	0	-0.23	12	12
RAF1	0.03	0.029	-10000	0	-0.16	1	1
STAT3	0.029	0.021	-10000	0	-10000	0	0
cell proliferation	0.018	0.06	-10000	0	-0.16	47	47
RPS6KB1	0.012	0.01	-10000	0	-10000	0	0
MAPK3	-0.013	0.02	-10000	0	-10000	0	0
MAPK1	0.006	0.11	0.59	17	-10000	0	17
RANBP9	0.017	0.001	-10000	0	-10000	0	0
MAPK8	0.049	0.027	-10000	0	-10000	0	0
SRC	0.028	0.021	-10000	0	-10000	0	0
PI3K	0.019	0.049	-10000	0	-0.17	31	31
MET/Glomulin	0.01	0.036	-10000	0	-0.25	10	10
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.032	0.028	-10000	0	-10000	0	0
MET	0.009	0.058	-10000	0	-0.41	10	10
MAP4K1	0.035	0.022	-10000	0	-10000	0	0
PTK2	0.017	0.001	-10000	0	-10000	0	0
MAP2K2	0.032	0.028	-10000	0	-0.16	1	1
BAD	0	0.023	0.24	2	-0.2	4	6
MAP2K4	0.038	0.022	-10000	0	-10000	0	0
SHP2/GRB2/SOS1/GAB1	0.028	0.027	-10000	0	-10000	0	0
INPPL1	0.017	0	-10000	0	-10000	0	0
PXN	0.017	0	-10000	0	-10000	0	0
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.013	0.021	-10000	0	-0.12	12	12
PLCgamma1/PKC	0.013	0	-10000	0	-10000	0	0
HGF	0.015	0.026	-10000	0	-0.41	2	2
RASA1	0.017	0.002	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
PTPRJ	0.017	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.027	0.037	-10000	0	-0.15	21	21
PDPK1	-0.006	0.018	0.29	2	-10000	0	2
HGF/MET/SHIP	0.017	0.039	-10000	0	-0.24	12	12

×

Ephrin B reverse 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
EFNB2	0.016	0.003	-10000	0	-10000	0	0
EPHB2	0.016	0.026	-10000	0	-0.41	2	2
EFNB1	0.003	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.024	-10000	0	-0.18	1	1
Ephrin B2/EPHB1-2	0.026	0.039	-10000	0	-0.21	13	13
neuron projection morphogenesis	0.004	0.019	-10000	0	-0.17	1	1
Ephrin B1/EPHB1-2/Tiam1	0.005	0.024	-10000	0	-0.2	1	1
DNM1	0.003	0.006	-10000	0	-10000	0	0
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.007	0.038	-10000	0	-0.16	9	9
YES1	-0.015	0.053	-10000	0	-0.23	20	20
Ephrin B1/EPHB1-2/NCK2	0.005	0.024	-10000	0	-0.2	1	1
PI3K	0.01	0.062	-10000	0	-0.19	40	40
mol:GDP	0.005	0.023	-10000	0	-0.19	1	1
ITGA2B	0.017	0	-10000	0	-10000	0	0
endothelial cell proliferation	0.022	0.005	-10000	0	-10000	0	0
FYN	-0.006	0.047	-10000	0	-0.2	20	20
MAP3K7	-0.007	0.038	-10000	0	-0.16	31	31
FGR	-0.01	0.046	-10000	0	-0.2	17	17
TIAM1	0.016	0.003	-10000	0	-10000	0	0
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
RGS3	0.016	0.019	-10000	0	-0.41	1	1
cell adhesion	0.015	0.057	-10000	0	-0.19	24	24
LYN	-0.013	0.049	-10000	0	-0.21	13	13
Ephrin B1/EPHB1-2/Src Family Kinases	-0.008	0.041	-10000	0	-0.18	20	20
Ephrin B1/EPHB1-2	-0.009	0.042	-10000	0	-0.18	30	30
SRC	-0.008	0.044	-10000	0	-0.19	20	20
ITGB3	0.017	0	-10000	0	-10000	0	0
EPHB1	0.008	0.064	-10000	0	-0.41	12	12
EPHB4	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.005	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	0.025	0	-10000	0	-10000	0	0
BLK	-0.006	0.045	-10000	0	-0.19	20	20
HCK	-0.016	0.051	-10000	0	-0.2	30	30
regulation of stress fiber formation	-0.005	0.023	0.19	1	-10000	0	1
MAPK8	0.015	0.043	-10000	0	-0.16	3	3
Ephrin B1/EPHB1-2/RGS3	0.005	0.024	-10000	0	-0.2	1	1
endothelial cell migration	-0.001	0.04	0.13	12	-0.15	17	29
NCK2	0.017	0.001	-10000	0	-10000	0	0
PTPN13	-0.009	0.098	-10000	0	-0.41	30	30
regulation of focal adhesion formation	-0.005	0.023	0.19	1	-10000	0	1
chemotaxis	-0.005	0.023	0.19	1	-10000	0	1
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
Rac1/GTP	0.005	0.022	-10000	0	-0.18	1	1
angiogenesis	-0.009	0.041	-10000	0	-0.18	30	30
LCK	-0.008	0.045	-10000	0	-0.19	30	30

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.036	0.14	-9999	-0.41	66	66
Ran/GTP/Exportin 1/HDAC4	0	0.007	-9999	-0.16	1	1
MDM2/SUMO1	0.025	0.039	-9999	-0.18	18	18
HDAC4	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.02	0.053	-9999	-0.16	66	66
SUMO1	0.017	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.014	0.005	-9999	-0.11	1	1
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.02	0.005	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
SUMO1/HDAC4	0.033	0.005	-9999	-10000	0	0
SUMO1/HDAC1	0.006	0.071	-9999	-0.18	66	66
RANGAP1	0.017	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.036	0.046	-9999	-0.21	18	18
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.017	0.005	-9999	-0.11	1	1
Ran/GTP	0.026	0.006	-9999	-0.093	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.002	0.078	-9999	-0.41	18	18
UBE2I	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.005	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
PIAS2	0.017	0	-9999	-10000	0	0
PIAS1	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.017	0	-9999	-10000	0	0
SPHK1	0.001	0.082	-9999	-0.41	20	20
GNAI2	0.017	0.001	-9999	-10000	0	0
mol:S1P	0.009	0.04	-9999	-0.16	27	27
GNAO1	0.002	0.005	-9999	-10000	0	0
mol:Sphinganine-1-P	0.006	0.058	-9999	-0.28	20	20
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.024	0.04	-9999	-0.21	8	8
GNAI3	-0.036	0.14	-9999	-0.41	65	65
G12/G13	0.022	0.033	-9999	-0.28	6	6
S1PR3	0	0	-9999	-10000	0	0
S1PR2	0	0	-9999	-10000	0	0
EDG1	0.017	0.001	-9999	-10000	0	0
S1P1/S1P	0.018	0.035	-9999	-0.13	26	26
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
GNAI1	0.014	0.02	-9999	-0.41	1	1
S1P/S1P5/G12	0.014	0.037	-9999	-0.13	31	31
S1P/S1P3/Gq	0.023	0.029	-9999	-0.17	7	7
S1P/S1P4/Gi	0	0.027	-9999	-0.32	3	3
GNAQ	0.017	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
GNA14	0.015	0.026	-9999	-0.41	2	2
GNA15	0.011	0.049	-9999	-0.41	7	7
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
GNA11	0.017	0	-9999	-10000	0	0
ABCC1	0.01	0.055	-9999	-0.41	9	9

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.033	0.074	-10000	0	-0.32	22	22
IHH	0.024	0.023	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	-0.002	0.073	-10000	0	-0.21	58	58
LRPAP1	0.017	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.002	0.073	0.21	58	-10000	0	58
SMO/beta Arrestin2	0.045	0.047	-10000	0	-0.27	7	7
SMO	0.038	0.048	-10000	0	-0.28	7	7
AKT1	0.029	0.055	-10000	0	-0.27	11	11
ARRB2	0.017	0	-10000	0	-10000	0	0
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.017	0	-10000	0	-10000	0	0
heart looping	0.038	0.048	-10000	0	-0.28	7	7
STIL	0.005	0.084	-10000	0	-0.33	9	9
DHH N/PTCH2	0.013	0	-10000	0	-10000	0	0
DHH N/PTCH1	0.025	0.053	-10000	0	-0.26	14	14
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.033	0.076	-10000	0	-0.33	22	22
determination of left/right symmetry	0.038	0.048	-10000	0	-0.28	7	7
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
skeletal system development	0.033	0.075	-10000	0	-0.33	22	22
IHH N/Hhip	0.016	0.012	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.038	0.048	-10000	0	-0.28	7	7
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.017	0	-10000	0	-10000	0	0
PI3K	0.009	0.065	-10000	0	-0.28	25	25
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.03	0.13	-10000	0	-0.41	58	58
somite specification	0.038	0.048	-10000	0	-0.28	7	7
SHH Np/Cholesterol/PTCH1	0.035	0.048	-10000	0	-0.3	7	7
SHH Np/Cholesterol/PTCH2	0.024	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.023	0.01	-10000	0	-0.21	1	1
SHH	0.018	0	-10000	0	-10000	0	0
catabolic process	0.03	0.061	-10000	0	-0.29	14	14
SMO/Vitamin D3	0.042	0.047	-10000	0	-0.27	7	7
SHH Np/Cholesterol/Hhip	0.012	0	-10000	0	-10000	0	0
LRP2	0.016	0.019	-10000	0	-0.41	1	1
receptor-mediated endocytosis	0.042	0.044	-10000	0	-0.25	7	7
SHH Np/Cholesterol/BOC	0.012	0	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.024	0	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.012	0	-10000	0	-10000	0	0
mol:Vitamin D3	0.037	0.049	-10000	0	-0.3	7	7
IHH N/PTCH2	0.029	0.014	-10000	0	-10000	0	0
CDON	0.017	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.037	0.063	-10000	0	-0.3	14	14
Megalin/LRPAP1	0.025	0.013	-10000	0	-0.28	1	1
PTCH2	0.017	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0.015	0	-10000	0	-10000	0	0
PTCH1	0.03	0.061	-10000	0	-0.29	14	14
HHIP	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.037	0.14	-9999	-0.41	66	66
HDAC2	0.013	0.042	-9999	-0.41	5	5
GNB1/GNG2	0.023	0.012	-9999	-0.24	1	1
forebrain development	0.02	0.049	-9999	-0.31	8	8
GNAO1	0.002	0.005	-9999	-10000	0	0
SMO/beta Arrestin2	0.027	0.014	-9999	-0.28	1	1
SMO	0.017	0.019	-9999	-0.41	1	1
ARRB2	0.018	0.001	-9999	-10000	0	0
GLI3/SPOP	0.02	0.04	-9999	-0.21	3	3
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.017	0.001	-9999	-10000	0	0
GNAI2	0.018	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.032	0.001	-9999	-10000	0	0
GNAI1	0.014	0.02	-9999	-0.41	1	1
XPO1	0.019	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.001	0.038	-9999	-0.28	7	7
SAP30	0.017	0	-9999	-10000	0	0
mol:GDP	0.017	0.019	-9999	-0.41	1	1
MIM/GLI2A	0.023	0.007	-9999	-10000	0	0
IFT88	0.017	0	-9999	-10000	0	0
GNAI3	-0.035	0.14	-9999	-0.41	65	65
GLI2	0.035	0.008	-9999	-10000	0	0
GLI3	0.011	0.04	-9999	-0.14	13	13
CSNK1D	0.015	0.026	-9999	-0.41	2	2
CSNK1E	0.017	0.001	-9999	-10000	0	0
SAP18	0.017	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.017	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
Gi family/GTP	0.001	0.017	-9999	-0.2	2	2
SIN3B	0.017	0	-9999	-10000	0	0
SIN3A	0	0	-9999	-10000	0	0
GLI3/Su(fu)	0.017	0.031	-9999	-0.17	3	3
GLI2/Su(fu)	0.037	0.01	-9999	-10000	0	0
FOXA2	0.03	0.037	-9999	-0.38	4	4
neural tube patterning	0.02	0.049	-9999	-0.31	8	8
SPOP	0.017	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.02	0.006	-9999	-0.11	1	1
GNB1	0.017	0.002	-9999	-10000	0	0
CSNK1G2	0.017	0	-9999	-10000	0	0
CSNK1G3	0.017	0	-9999	-10000	0	0
MTSS1	0.023	0.007	-9999	-10000	0	0
embryonic limb morphogenesis	0.02	0.049	-9999	-0.31	8	8
SUFU	0.009	0.007	-9999	-0.13	1	1
LGALS3	-0.033	0.14	-9999	-0.41	61	61
catabolic process	0.041	0.039	-9999	-0.16	6	6
GLI3A/CBP	0.023	0.03	-9999	-0.22	8	8
KIF3A	0.016	0.005	-9999	-10000	0	0
GLI1	0.02	0.05	-9999	-0.31	8	8
RAB23	0.013	0.042	-9999	-0.41	5	5
CSNK1A1	0.017	0	-9999	-10000	0	0
IFT172	0	0	-9999	-10000	0	0
RBBP7	0.017	0	-9999	-10000	0	0
Su(fu)/Galectin3	-0.007	0.074	-9999	-0.21	61	61
GNAZ	0.015	0.006	-9999	-10000	0	0
RBBP4	-0.065	0.17	-9999	-0.41	101	101
CSNK1G1	0.017	0	-9999	-10000	0	0
PIAS1	0.017	0	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GLI2/SPOP	0.042	0.008	-9999	-10000	0	0
STK36	0.002	0.002	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.01	0.039	-9999	-0.12	53	53
PTCH1	0.023	0.063	-9999	-0.47	7	7
MIM/GLI1	0.038	0.054	-9999	-0.3	10	10
CREBBP	0.023	0.03	-9999	-0.22	8	8
Su(fu)/SIN3/HDAC complex	-0.005	0.062	-9999	-0.2	21	21

×

Aurora C signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.017	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	0.02	0.056	-9999	-0.21	29	29
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.01	0.017	-9999	-10000	0	0
AURKB	-0.005	0.094	-9999	-0.41	27	27
AURKC	0.015	0.026	-9999	-0.41	2	2

×

Atypical NF-kappaB pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.025	0	-9999	-10000	0	0
FBXW11	0.017	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.024	0.023	-9999	-0.23	4	4
NF kappa B1 p50/RelA/I kappa B alpha	0.03	0.043	-9999	-0.25	6	6
NFKBIA	0.012	0.037	-9999	-0.11	40	40
MAPK14	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p105/p50	0.024	0.023	-9999	-0.23	4	4
ARRB2	0.014	0.012	-9999	-0.18	2	2
REL	0.017	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0.023	-9999	-0.23	4	4
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.024	0.023	-9999	-0.23	4	4
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
NF kappa B1 p50 dimer	0.016	0.026	-9999	-0.28	4	4
PIK3R1	0.016	0.004	-9999	-10000	0	0
NFKB1	0.015	0.026	-9999	-0.28	4	4
RELA	0.017	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.017	0.038	-9999	-0.11	40	40
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.033	0.043	-9999	-0.24	6	6
SRC	0.017	0	-9999	-10000	0	0
PI3K	0.009	0.065	-9999	-0.28	25	25
NF kappa B1 p50/RelA	0.017	0.038	-9999	-0.11	40	40
IKBKB	0.017	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
SYK	-0.012	0.11	-9999	-0.41	36	36
I kappa B alpha/PIK3R1	0.021	0.033	-9999	-0.18	3	3
cell death	0.032	0.041	-9999	-0.23	6	6
NF kappa B1 p105/c-Rel	0.024	0.023	-9999	-0.23	4	4
LCK	0.014	0.037	-9999	-0.41	4	4
BCL3	0.017	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
EP300	0.017	0	-10000	0	-10000	0	0
HDAC4	0.017	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.014	-10000	0	-10000	0	0
CDKN1A	-0.019	0.098	-10000	0	-0.3	54	54
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
FOXO3	-0.006	0.003	-10000	0	-10000	0	0
FOXO1	0.008	0.061	-10000	0	-0.41	11	11
FOXO4	0.018	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.017	0	-10000	0	-10000	0	0
TAT	0.017	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.009	0	-10000	0	-10000	0	0
PPARGC1A	0.015	0.032	-10000	0	-0.41	3	3
FHL2	0.013	0.037	-10000	0	-0.41	4	4
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.019	-10000	0	-10000	0	0
HIST2H4A	0.011	0.014	-10000	0	-10000	0	0
SIRT1/FOXO3a	0.012	0.02	-10000	0	-10000	0	0
SIRT1	0.022	0.027	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.038	0.018	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.029	0.021	-10000	0	-0.12	1	1
apoptosis	-0.034	0.035	0.23	7	-10000	0	7
SIRT1/PGC1A	0.025	0.027	-10000	0	-0.24	3	3
p53/SIRT1	-0.004	0.12	0.25	43	-0.28	69	112
SIRT1/FOXO4	0.03	0.02	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.028	0.044	-10000	0	-0.21	15	15
HIST1H1E	0.018	0.007	-10000	0	-0.15	1	1
SIRT1/p300	0.029	0.019	-10000	0	-10000	0	0
muscle cell differentiation	-0.019	0.018	-10000	0	-10000	0	0
TP53	-0.034	0.15	-10000	0	-0.41	69	69
KU70/SIRT1/BAX	0.034	0.035	-10000	0	-0.23	7	7
CREBBP	0.017	0	-10000	0	-10000	0	0
MEF2D	0.017	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.029	0.019	-10000	0	-10000	0	0
ACSS2	0.011	0.014	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.019	0.018	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.026	0.006	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.007	0.024	-9999	-0.18	5	5
JUN	0.028	0.023	-9999	-0.17	1	1
HRAS	0.016	0.019	-9999	-0.41	1	1
RET51/GFRalpha1/GDNF/GRB10	0.035	0.047	-9999	-0.21	19	19
RAP1A	0.017	0	-9999	-10000	0	0
FRS2	0.015	0.032	-9999	-0.41	3	3
RAP1A/GDP	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	0.043	0.019	-9999	-0.21	3	3
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	0.032	0.015	-9999	-0.21	2	2
RHOA	0.017	0.001	-9999	-10000	0	0
RAP1A/GTP	0.04	0.017	-9999	-0.18	3	3
GRB7	0.016	0.019	-9999	-0.41	1	1
RET51/GFRalpha1/GDNF	0.043	0.019	-9999	-0.21	3	3
MAPKKK cascade	0.029	0.022	-9999	-0.15	3	3
BCAR1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.03	0.028	-9999	-0.21	7	7
lamellipodium assembly	0.02	0.036	-9999	-0.18	5	5
RET51/GFRalpha1/GDNF/SHC	0.021	0.076	-9999	-0.22	48	48
PIK3CA	-0.003	0.091	-9999	-0.41	25	25
RET9/GFRalpha1/GDNF/SHC	0.011	0.073	-9999	-0.22	47	47
RET9/GFRalpha1/GDNF/Shank3	0.021	0.015	-9999	-0.22	2	2
MAPK3	0.026	0.015	-9999	-0.17	3	3
DOK1	0.017	0	-9999	-10000	0	0
DOK6	0	0	-9999	-10000	0	0
PXN	0.017	0	-9999	-10000	0	0
neurite development	0.03	0.015	-9999	-10000	0	0
DOK5	0.015	0.019	-9999	-0.41	1	1
GFRA1	0.015	0.026	-9999	-0.41	2	2
MAPK8	0.028	0.023	-9999	-10000	0	0
HRAS/GTP	0.037	0.027	-9999	-0.17	4	4
tube development	0.023	0.014	-9999	-0.2	2	2
MAPK1	0.026	0.016	-9999	-0.17	3	3
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.025	0.015	-9999	-0.12	5	5
Rac1/GDP	0.013	0	-9999	-10000	0	0
SRC	0.017	0	-9999	-10000	0	0
PDLIM7	0.017	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	0.039	0.018	-9999	-0.19	3	3
SHC1	-0.021	0.12	-9999	-0.41	47	47
RET51/GFRalpha1/GDNF/Dok4	0.043	0.019	-9999	-0.21	3	3
RET51/GFRalpha1/GDNF/Dok5	0.039	0.024	-9999	-0.21	4	4
PRKCA	0.017	0	-9999	-10000	0	0
HRAS/GDP	0.012	0.013	-9999	-0.29	1	1
CREB1	0.014	0.045	-9999	-0.13	47	47
PIK3R1	0.016	0.004	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.012	0.047	-9999	-0.13	51	51
RET51/GFRalpha1/GDNF/Grb7	0.042	0.022	-9999	-0.21	4	4
mol:GDP	0	0	-9999	-10000	0	0
RET	0.016	0.019	-9999	-0.41	1	1
DOK4	0.017	0	-9999	-10000	0	0
JNK cascade	0.028	0.023	-9999	-0.16	1	1
RET9/GFRalpha1/GDNF/FRS2	0.031	0.024	-9999	-0.21	5	5
SHANK3	0	0	-9999	-10000	0	0
RASA1	0.017	0.002	-9999	-10000	0	0
NCK1	0.008	0.061	-9999	-0.41	11	11
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.007	0.045	-9999	-0.14	47	47
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	0.03	0.016	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	0.028	0.025	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.012	0.046	-9999	-0.13	48	48
PI3K	0.027	0.047	-9999	-0.2	9	9
SOS1	0	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.029	0.014	-9999	-0.2	2	2
GRB10	0.004	0.073	-9999	-0.41	16	16
activation of MAPKK activity	0.029	0.015	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2	0.041	0.027	-9999	-0.21	6	6
GAB1	0.014	0.037	-9999	-0.41	4	4
IRS1	0.013	0.042	-9999	-0.41	5	5
IRS2	0.017	0.002	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.017	0.048	-9999	-0.12	52	52
RET51/GFRalpha1/GDNF/PKC alpha	0.043	0.019	-9999	-0.21	3	3
GRB2	0.017	0.002	-9999	-10000	0	0
PRKACA	0.017	0	-9999	-10000	0	0
GDNF	0.017	0	-9999	-10000	0	0
RAC1	0.017	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	0.04	0.031	-9999	-0.21	8	8
Rac1/GTP	0.025	0.042	-9999	-0.2	5	5
RET9/GFRalpha1/GDNF	0.022	0.016	-9999	-0.24	2	2
GFRalpha1/GDNF	0.024	0.019	-9999	-0.28	2	2

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.022	0.016	-10000	0	-0.24	2	2
cell-cell adhesion	0.004	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.047	0.019	-10000	0	-0.19	2	2
ITSN1	0.017	0	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
SHC1	-0.021	0.12	-10000	0	-0.41	47	47
Ephrin B1/EPHB3	0.017	0.04	-10000	0	-0.24	13	13
Ephrin B1/EPHB1	0.017	0.039	-10000	0	-0.24	12	12
HRAS/GDP	0.024	0.029	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	0.043	0.038	-10000	0	-0.19	12	12
Endophilin/SYNJ1	0.022	0.014	-10000	0	-0.18	2	2
KRAS	0.017	0.002	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.043	0.036	-10000	0	-0.19	11	11
endothelial cell migration	0.023	0.048	-10000	0	-0.19	23	23
GRB2	0.017	0.002	-10000	0	-10000	0	0
GRB7	0.016	0.019	-10000	0	-0.41	1	1
PAK1	0.027	0.014	-10000	0	-0.18	2	2
HRAS	0.016	0.019	-10000	0	-0.41	1	1
RRAS	0.016	0.039	-10000	0	-0.18	19	19
DNM1	0.003	0.007	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.02	0.03	-10000	0	-0.18	11	11
lamellipodium assembly	-0.004	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.015	0.05	-10000	0	-0.19	7	7
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
EPHB2	0.015	0.026	-10000	0	-0.41	2	2
EPHB3	0.007	0.066	-10000	0	-0.41	13	13
EPHB1	0.007	0.064	-10000	0	-0.41	12	12
EPHB4	0.017	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.029	-10000	0	-0.16	1	1
Ephrin B/EPHB2	0.038	0.017	-10000	0	-0.19	2	2
Ephrin B/EPHB3	0.033	0.037	-10000	0	-0.19	13	13
JNK cascade	0.016	0.046	-10000	0	-0.19	26	26
Ephrin B/EPHB1	0.034	0.035	-10000	0	-0.19	11	11
RAP1/GDP	0.03	0.028	-10000	0	-10000	0	0
EFNB2	0.016	0.003	-10000	0	-10000	0	0
EFNB3	0.017	0.001	-10000	0	-10000	0	0
EFNB1	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.026	0.038	-10000	0	-0.21	13	13
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.017	0	-10000	0	-10000	0	0
CDC42/GTP	0.037	0.032	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.024	-10000	0	-10000	0	0
axon guidance	0.022	0.016	-10000	0	-0.24	2	2
MAPK3	0.018	0.044	-10000	0	-0.18	5	5
MAPK1	0.017	0.044	-10000	0	-0.18	5	5
Rac1/GDP	0.033	0.029	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.031	0.053	-10000	0	-0.26	4	4
CDC42/GDP	0.033	0.029	-10000	0	-10000	0	0
PI3K	0.026	0.049	-10000	0	-0.19	23	23
EFNA5	0.017	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.022	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.03	0.012	-10000	0	-0.12	2	2
CDC42	0.017	0	-10000	0	-10000	0	0
RAS family/GTP	-0.041	0.069	-10000	0	-0.32	4	4
PTK2	0.008	0.007	-10000	0	-10000	0	0
MAP4K4	0.016	0.047	-10000	0	-0.19	26	26
SRC	0.017	0	-10000	0	-10000	0	0
KALRN	0.017	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.025	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.04	0.028	-10000	0	-10000	0	0
MAP2K1	0.016	0.047	-10000	0	-0.17	7	7
WASL	0.017	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.032	0.053	-10000	0	-0.21	25	25
cell migration	0.024	0.048	0.17	3	-0.18	7	10
NRAS	-0.094	0.19	-10000	0	-0.41	137	137
SYNJ1	0.022	0.015	-10000	0	-0.18	2	2
PXN	0.017	0	-10000	0	-10000	0	0
TF	0.016	0.02	-10000	0	-10000	0	0
HRAS/GTP	0.034	0.034	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	0.027	0.039	-10000	0	-0.21	14	14
cell adhesion mediated by integrin	-0.015	0.031	-10000	0	-0.16	4	4
RAC1	0.017	0	-10000	0	-10000	0	0
mol:GTP	0.038	0.036	-10000	0	-0.17	13	13
RAC1-CDC42/GTP	-0.007	0.032	-10000	0	-10000	0	0
RASA1	0.017	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.041	0.028	-10000	0	-10000	0	0
ruffle organization	0.03	0.032	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
receptor internalization	0.005	0.012	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	0.048	0.018	-10000	0	-0.19	2	2
ROCK1	0.014	0.036	-10000	0	-0.21	13	13
RAS family/GDP	-0.032	0.055	-10000	0	-0.25	4	4
Rac1/GTP	-0.004	0.025	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.027	0.024	-10000	0	-0.12	12	12

×

Arf6 trafficking events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.017	0	-9999	-10000	0	0
CLTC	0.018	0.013	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.01	0.033	-9999	-0.097	44	44
Dynamin 2/GTP	0.018	0	-9999	-10000	0	0
EXOC4	0	0	-9999	-10000	0	0
CD59	0.014	0.017	-9999	-10000	0	0
CPE	0.014	0.004	-9999	-10000	0	0
CTNNB1	0.017	0	-9999	-10000	0	0
membrane fusion	0.009	0.035	-9999	-0.11	44	44
CTNND1	0.014	0.029	-9999	-0.2	10	10
DNM2	0.017	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.015	0.022	-9999	-0.11	1	1
TSHR	0.014	0.022	-9999	-0.24	4	4
INS	0.015	0.008	-9999	-10000	0	0
BIN1	0.016	0.005	-9999	-10000	0	0
mol:Choline	0.009	0.035	-9999	-0.11	44	44
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.006	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.017	0	-9999	-10000	0	0
mol:Ca2+	0.017	0	-9999	-10000	0	0
JUP	0.011	0.029	-9999	-0.18	4	4
ASAP2/amphiphysin II	0.02	0.006	-9999	-10000	0	0
ARF6/GTP	0.013	0	-9999	-10000	0	0
CDH1	0.012	0.022	-9999	-0.11	8	8
clathrin-independent pinocytosis	0.013	0	-9999	-10000	0	0
MAPK8IP3	0.017	0	-9999	-10000	0	0
positive regulation of endocytosis	0.013	0	-9999	-10000	0	0
EXOC2	0.017	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0.019	0.024	-9999	-0.092	24	24
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0.019	-9999	-0.41	1	1
regulation of calcium-dependent cell-cell adhesion	-0.026	0.02	-9999	-10000	0	0
positive regulation of phagocytosis	0.015	0.011	-9999	-0.24	1	1
ARF6/GTP/JIP3	0.023	0	-9999	-10000	0	0
ACAP1	0.009	0.031	-9999	-0.092	44	44
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.014	0.017	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.016	0.027	-9999	-0.14	1	1
JIP4/KLC1	0.024	0.018	-9999	-0.21	1	1
EXOC1	0.011	0.049	-9999	-0.41	7	7
exocyst	0.019	0.025	-9999	-0.093	24	24
RALA/GTP	-0.012	0.083	-9999	-0.29	44	44
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.023	0.011	-9999	-0.24	1	1
receptor recycling	0.013	0	-9999	-10000	0	0
CTNNA1	0.018	0	-9999	-10000	0	0
NME1	0.006	0	-9999	-10000	0	0
clathrin coat assembly	0.018	0.013	-9999	-10000	0	0
IL2RA	0.013	0.021	-9999	-0.11	6	6
VAMP3	0.015	0.011	-9999	-0.24	1	1
GLUT4/clathrin heavy chain/ACAP1	0.023	0.027	-9999	-0.13	1	1
EXOC6	0	0	-9999	-10000	0	0
PLD1	0.009	0.032	-9999	-0.094	45	45
PLD2	0.009	0.03	-9999	-0.09	44	44
EXOC5	0.003	0.076	-9999	-0.41	17	17
PIP5K1C	0.015	0.021	-9999	-0.11	1	1
SDC1	0.003	0.042	-9999	-0.12	48	48
ARF6/GDP	0.013	0	-9999	-10000	0	0
EXOC7	0.017	0	-9999	-10000	0	0
E-cadherin/beta catenin	0.028	0.021	-9999	-10000	0	0
mol:Phosphatidic acid	0.009	0.035	-9999	-0.11	44	44
endocytosis	-0.02	0.006	-9999	-10000	0	0
SCAMP2	0.017	0	-9999	-10000	0	0
ADRB2	0.02	0.015	-9999	-0.17	1	1
EXOC3	0.017	0	-9999	-10000	0	0
ASAP2	0	0	-9999	-10000	0	0
Dynamin 2/GDP	0.017	0	-9999	-10000	0	0
KLC1	0.013	0.008	-9999	-10000	0	0
AVPR2	0.02	0.013	-9999	-10000	0	0
RALA	-0.019	0.12	-9999	-0.41	44	44
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.028	0.032	-9999	-10000	0	0

×

mTOR signaling pathway

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
GBL	0.017	0	-10000	0	-10000	0	0
MKNK1	0.017	0	-10000	0	-10000	0	0
mol:PIP3	0.002	0.044	0.22	2	-0.18	27	29
FRAP1	0.018	0.026	-10000	0	-0.37	1	1
AKT1	0.007	0.04	0.16	2	-0.16	24	26
INSR	0.017	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.023	0	-10000	0	-10000	0	0
mol:GTP	0.027	0.042	0.19	1	-0.14	25	26
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.006	0.025	-10000	0	-0.17	7	7
TSC2	0.017	0	-10000	0	-10000	0	0
RHEB/GDP	0.016	0.034	-10000	0	-0.13	25	25
TSC1	0.016	0.019	-10000	0	-0.41	1	1
Insulin Receptor/IRS1	0.017	0.015	-10000	0	-0.14	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.018	0.036	-10000	0	-0.19	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.017	0	-10000	0	-10000	0	0
RPS6KB1	0.022	0.034	0.17	1	-0.26	1	2
MAP3K5	0.007	0.008	-10000	0	-0.086	4	4
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
apoptosis	0.007	0.008	-10000	0	-0.086	4	4
mol:LY294002	0	0	0.001	1	-0.001	5	6
EIF4B	0.024	0.031	0.16	1	-0.22	1	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.031	0.16	1	-0.21	1	2
eIF4E/eIF4G1/eIF4A1	-0.005	0.025	-10000	0	-0.19	5	5
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.017	0.046	-10000	0	-0.18	27	27
mTOR/RHEB/GTP/Raptor/GBL	0.027	0.028	0.16	1	-0.2	1	2
FKBP1A	0.016	0.019	-10000	0	-0.41	1	1
RHEB/GTP	0.024	0.037	-10000	0	-0.16	2	2
mol:Amino Acids	0	0	0.001	1	-0.001	5	6
FKBP12/Rapamycin	0.012	0.013	-10000	0	-0.29	1	1
PDPK1	0.005	0.041	0.17	2	-0.17	24	26
EIF4E	0.014	0.037	-10000	0	-0.41	4	4
ASK1/PP5C	0.028	0.05	-10000	0	-0.45	5	5
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.021	0.016	-10000	0	-0.16	4	4
TSC1/TSC2	0.03	0.045	0.2	1	-0.15	25	26
tumor necrosis factor receptor activity	0	0	0.001	5	-0.001	1	6
RPS6	0.017	0	-10000	0	-10000	0	0
PPP5C	0.017	0	-10000	0	-10000	0	0
EIF4G1	0.014	0.037	-10000	0	-0.41	4	4
IRS1	0.007	0.015	-10000	0	-0.15	5	5
INS	0.017	0	-10000	0	-10000	0	0
PTEN	0.015	0.026	-10000	0	-0.41	2	2
PDK2	0.005	0.041	0.17	2	-0.17	24	26
EIF4EBP1	-0.1	0.12	-10000	0	-10000	0	0
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
PPP2R5D	0.02	0.024	-10000	0	-0.33	1	1
peptide biosynthetic process	0.02	0	-10000	0	-10000	0	0
RHEB	0.017	0	-10000	0	-10000	0	0
EIF4A1	0.009	0.058	-10000	0	-0.41	10	10
mol:Rapamycin	0	0.001	0.003	1	-0.003	1	2
EEF2	0.02	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	-0.087	0.11	-10000	0	-0.41	2	2

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.015	0.038	0.16	12	-10000	0	12
GNAI2	0.017	0.001	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.022	-10000	0	-0.24	4	4
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.002	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.039	-10000	0	-0.16	12	12
negative regulation of cAMP metabolic process	0.001	0.01	-10000	0	-0.1	3	3
GNAZ	0.015	0.006	-10000	0	-10000	0	0
GNAI3	-0.036	0.14	-10000	0	-0.41	65	65
GNA12	0.014	0.037	-10000	0	-0.41	4	4
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.001	0.01	-10000	0	-0.1	3	3
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
RHOA	0.017	0.001	-10000	0	-10000	0	0
GNAI1	0.014	0.02	-10000	0	-0.41	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.027	0.022	0.28	2	-10000	0	2
KIRREL	0.018	0.02	-10000	0	-0.41	1	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.027	0.022	-10000	0	-0.28	2	2
PLCG1	0.017	0	-10000	0	-10000	0	0
ARRB2	0.017	0	-10000	0	-10000	0	0
WASL	0.017	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.019	0.078	-10000	0	-0.22	51	51
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.029	0.021	-10000	0	-0.12	4	4
FYN	0.019	0.017	-10000	0	-0.17	4	4
mol:Ca2+	0.043	0.023	-10000	0	-0.19	2	2
mol:DAG	0.044	0.024	-10000	0	-0.19	2	2
NPHS2	0.019	0.006	-10000	0	-10000	0	0
mol:IP3	0.044	0.024	-10000	0	-0.19	2	2
regulation of endocytosis	0.037	0.019	-10000	0	-0.16	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.034	0.023	-10000	0	-0.2	2	2
establishment of cell polarity	0.027	0.022	-10000	0	-0.28	2	2
Nephrin/NEPH1/podocin/NCK1-2	0.047	0.037	-10000	0	-0.17	13	13
Nephrin/NEPH1/beta Arrestin2	0.039	0.019	-10000	0	-0.16	4	4
NPHS1	0.018	0.02	-10000	0	-0.41	1	1
Nephrin/NEPH1/podocin	0.032	0.019	-10000	0	-0.17	4	4
TJP1	0.017	0	-10000	0	-10000	0	0
NCK1	0.008	0.061	-10000	0	-0.41	11	11
NCK2	0.017	0.001	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.045	0.024	-10000	0	-0.19	2	2
CD2AP	-0.023	0.12	-10000	0	-0.41	49	49
Nephrin/NEPH1/podocin/GRB2	0.044	0.023	-10000	0	-0.19	2	2
GRB2	0.017	0.002	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.022	0.023	-10000	0	-0.19	5	5
cytoskeleton organization	0.031	0.023	0.17	4	-0.15	2	6
Nephrin/NEPH1	0.023	0.016	-10000	0	-0.19	2	2
Nephrin/NEPH1/ZO-1	0.036	0.018	-10000	0	-0.22	2	2

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.12	0.1	-10000	0	-0.44	6	6
PCK1	0.11	0.073	-10000	0	-0.34	7	7
HNF4A	0.14	0.11	-10000	0	-0.58	5	5
KCNJ11	0.14	0.11	-10000	0	-0.46	5	5
AKT1	0.096	0.069	-10000	0	-0.27	6	6
response to starvation	0.005	0.004	-10000	0	-10000	0	0
DLK1	0.12	0.16	-10000	0	-0.46	13	13
NKX2-1	0.1	0.076	0.27	17	-0.31	4	21
ACADM	0.12	0.1	-10000	0	-0.43	7	7
TAT	0.11	0.065	-10000	0	-0.4	2	2
CEBPB	0.013	0.061	-10000	0	-0.41	11	11
CEBPA	0.01	0.074	-10000	0	-0.41	16	16
TTR	0.095	0.083	-10000	0	-0.66	3	3
PKLR	0.12	0.1	-10000	0	-0.46	5	5
APOA1	0.15	0.12	-10000	0	-0.77	3	3
CPT1C	0.12	0.099	-10000	0	-0.47	5	5
ALAS1	0.11	0.068	-10000	0	-0.33	2	2
TFRC	0.13	0.093	-10000	0	-0.31	10	10
FOXF1	-0.017	0.11	-10000	0	-0.41	36	36
NF1	0.023	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	0.033	0.004	-10000	0	-10000	0	0
CPT1A	0.12	0.1	-10000	0	-0.51	4	4
HMGCS1	0.12	0.1	-10000	0	-0.46	5	5
NR3C1	0.026	0.019	-10000	0	-10000	0	0
CPT1B	0.12	0.1	-10000	0	-0.46	5	5
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.023	0	-10000	0	-10000	0	0
GCK	0.12	0.1	-10000	0	-0.46	5	5
CREB1	0.025	0.011	-10000	0	-10000	0	0
IGFBP1	0.09	0.085	-10000	0	-0.31	13	13
PDX1	0.12	0.066	-10000	0	-0.29	2	2
UCP2	0.095	0.16	-10000	0	-0.42	20	20
ALDOB	0.14	0.11	-10000	0	-0.45	5	5
AFP	0.026	0.031	-10000	0	-0.33	3	3
BDH1	0.12	0.1	-10000	0	-0.46	5	5
HADH	0.14	0.11	-10000	0	-0.44	6	6
F2	0.15	0.12	-10000	0	-0.97	2	2
HNF1A	0.033	0.004	-10000	0	-10000	0	0
G6PC	0.048	0.037	-10000	0	-0.23	1	1
SLC2A2	0.13	0.082	-10000	0	-0.5	2	2
INS	0.008	0.019	-10000	0	-10000	0	0
FOXA1	0.012	0.019	0.13	3	-0.19	3	6
FOXA3	0.036	0.025	-10000	0	-0.12	8	8
FOXA2	0.19	0.13	-10000	0	-0.53	5	5
ABCC8	0.14	0.11	-10000	0	-0.45	5	5
ALB	0.026	0.031	-10000	0	-0.43	2	2

×

p38 MAPK signaling pathway

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
TRAF6/ASK1	0.02	0.002	-10000	0	-10000	0	0
TRAF2/ASK1	0.023	0.002	-10000	0	-10000	0	0
ATM	-0.003	0.091	-10000	0	-0.41	25	25
MAP2K3	0.048	0.035	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.046	0.035	-10000	0	-0.12	3	3
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.007	0.066	-10000	0	-0.41	13	13
TXN	0.007	0	-10000	0	-10000	0	0
CALM1	0.016	0.004	-10000	0	-10000	0	0
GADD45A	-0.02	0.12	-10000	0	-0.41	46	46
GADD45B	0.01	0.055	-10000	0	-0.41	9	9
MAP3K1	0.016	0.019	-10000	0	-0.41	1	1
MAP3K6	0.015	0.032	-10000	0	-0.41	3	3
MAP3K7	0.016	0.019	-10000	0	-0.41	1	1
MAP3K4	0.017	0.001	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.023	0.023	-10000	0	-0.28	3	3
TAK1/TAB family	0.012	0.009	0.12	2	-0.12	1	3
RAC1/OSM/MEKK3	0.022	0	-10000	0	-10000	0	0
TRAF2	0.017	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.022	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.002	0.006	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.003	0.008	-10000	0	-10000	0	0
MAPK11	0.017	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.005	0.012	-10000	0	-10000	0	0
OSM/MEKK3	0.013	0	-10000	0	-10000	0	0
TAOK1	-0.002	0.042	-10000	0	-0.19	25	25
TAOK2	0.005	0.042	-10000	0	-0.18	25	25
TAOK3	0.005	0.042	-10000	0	-0.18	25	25
MAP3K7IP1	0.017	0	-10000	0	-10000	0	0
MAPK14	0.015	0.026	-10000	0	-0.41	2	2
MAP3K7IP2	0.017	0	-10000	0	-10000	0	0
MAP3K5	0.017	0.001	-10000	0	-10000	0	0
MAP3K10	0.017	0	-10000	0	-10000	0	0
MAP3K3	0.017	0	-10000	0	-10000	0	0
TRX/ASK1	0.018	0.002	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	0.011	0.081	-10000	0	-0.2	66	66

×

Regulation of Androgen receptor activity

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.028	0.099	-9999	-0.29	66	66
SMARCC1	0.012	0.075	-9999	-0.39	18	18
REL	0.016	0	-9999	-10000	0	0
HDAC7	0.038	0.03	-9999	-10000	0	0
JUN	0.017	0.019	-9999	-0.41	1	1
EP300	0.017	0	-9999	-10000	0	0
KAT2B	0	0	-9999	-10000	0	0
KAT5	0	0	-9999	-10000	0	0
MAPK14	0.02	0.019	-9999	-0.28	2	2
FOXO1	0.008	0.061	-9999	-0.41	11	11
T-DHT/AR	0.058	0.035	-9999	-10000	0	0
MAP2K6	0.019	0.002	-9999	-10000	0	0
BRM/BAF57	0.027	0	-9999	-10000	0	0
MAP2K4	0.018	0.004	-9999	-10000	0	0
SMARCA2	0.018	0	-9999	-10000	0	0
PDE9A	0.034	0.044	-9999	-0.39	5	5
NCOA2	0.018	0	-9999	-10000	0	0
CEBPA	0.004	0.074	-9999	-0.41	16	16
EHMT2	0.018	0	-9999	-10000	0	0
cell proliferation	0.067	0.031	-9999	-0.18	1	1
NR0B1	-0.023	0.12	-9999	-0.41	49	49
EGR1	0.005	0.071	-9999	-0.41	15	15
RXRs/9cRA	0.033	0.018	-9999	-0.21	3	3
AR/RACK1/Src	0.043	0.02	-9999	-0.15	2	2
AR/GR	0.034	0.02	-9999	-0.12	1	1
GNB2L1	0.017	0	-9999	-10000	0	0
PKN1	0.009	0.058	-9999	-0.41	10	10
RCHY1	0.017	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
MAPK8	0.02	0.006	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.052	0.023	-9999	-0.16	2	2
SRC	0.024	0.016	-9999	-0.18	2	2
NR3C1	0.017	0	-9999	-10000	0	0
KLK3	0.025	0.024	-9999	-10000	0	0
APPBP2	0.018	0.002	-9999	-10000	0	0
TRIM24	0.011	0.055	-9999	-0.41	9	9
T-DHT/AR/TIP60	0.023	0.018	-9999	-0.17	2	2
TMPRSS2	0.035	0.035	-9999	-0.33	4	4
RXRG	0.015	0.032	-9999	-0.41	3	3
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.017	0	-9999	-10000	0	0
RXRB	0.017	0	-9999	-10000	0	0
CARM1	0.018	0	-9999	-10000	0	0
NR2C2	0.017	0	-9999	-10000	0	0
KLK2	0.055	0.02	-9999	-10000	0	0
AR	0.026	0.022	-9999	-0.12	10	10
SENP1	0	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
MDM2	0.001	0.078	-9999	-0.41	18	18
SRY	0.015	0.019	-9999	-0.41	1	1
GATA2	0.016	0.019	-9999	-0.41	1	1
MYST2	0.017	0	-9999	-10000	0	0
HOXB13	0.018	0	-9999	-10000	0	0
T-DHT/AR/RACK1/Src	0.039	0.02	-9999	-0.16	2	2
positive regulation of transcription	0.016	0.019	-9999	-0.41	1	1
DNAJA1	0.018	0.002	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.062	-9999	-0.15	81	81
NCOA1	0.017	0.02	-9999	-10000	0	0
SPDEF	0.019	0	-9999	-10000	0	0
T-DHT/AR/TIF2	0.035	0.021	-9999	-0.12	1	1
T-DHT/AR/Hsp90	0.034	0.021	-9999	-0.17	2	2
GSK3B	0.018	0.002	-9999	-10000	0	0
NR2C1	0.017	0	-9999	-10000	0	0
mol:T-DHT	0.023	0.017	-9999	-0.2	2	2
SIRT1	0.017	0	-9999	-10000	0	0
ZMIZ2	0.016	0	-9999	-10000	0	0
POU2F1	0.028	0.009	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.015	0.064	-9999	-0.18	48	48
CREBBP	0.017	0	-9999	-10000	0	0
SMARCE1	0.018	0	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.01	0.028	-9999	-0.2	1	1
CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
AKT1	0.014	0.037	-9999	-0.41	4	4
AKT2	0.017	0	-9999	-10000	0	0
STXBP4	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	-0.002	0.03	-9999	-0.13	4	4
YWHAZ	0.017	0.002	-9999	-10000	0	0
CALM1	0.016	0.004	-9999	-10000	0	0
YWHAQ	0.017	0	-9999	-10000	0	0
TBC1D4	0.015	0.026	-9999	-0.28	4	4
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.008	0.009	-9999	-10000	0	0
YWHAB	0.017	0.001	-9999	-10000	0	0
SNARE/Synip	0.021	0.007	-9999	-10000	0	0
YWHAG	0	0	-9999	-10000	0	0
ASIP	0.017	0	-9999	-10000	0	0
PRKCI	0.016	0.019	-9999	-0.41	1	1
AS160/CaM/Ca2+	0.012	0.003	-9999	-10000	0	0
RHOQ	0.017	0	-9999	-10000	0	0
GYS1	0.004	0.063	-9999	-0.22	40	40
PRKCZ	0	0	-9999	-10000	0	0
TRIP10	0.012	0.045	-9999	-0.41	6	6
TC10/GTP/CIP4/Exocyst	0.02	0.028	-9999	-0.24	6	6
AS160/14-3-3	0.006	0.037	-9999	-0.13	24	24
VAMP2	0.015	0.005	-9999	-10000	0	0
SLC2A4	-0.003	0.031	-9999	-0.14	4	4
STX4	0.017	0	-9999	-10000	0	0
GSK3B	0.021	0.017	-9999	-0.18	4	4
SFN	-0.01	0.1	-9999	-0.41	33	33
LNPEP	0.016	0.019	-9999	-0.41	1	1
YWHAE	0.017	0.001	-9999	-10000	0	0

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.02	0.011	-10000	0	-10000	0	0
VLDLR	0.015	0.032	-10000	0	-0.41	3	3
CRKL	0.017	0	-10000	0	-10000	0	0
LRPAP1	0.017	0	-10000	0	-10000	0	0
FYN	0.015	0.026	-10000	0	-0.41	2	2
ITGA3	0.002	0.08	-10000	0	-0.41	19	19
RELN/VLDLR/Fyn	0.013	0.03	-10000	0	-0.23	4	4
MAPK8IP1/MKK7/MAP3K11/JNK1	0.051	0	-10000	0	-10000	0	0
AKT1	0.002	0.043	-10000	0	-0.15	33	33
MAP2K7	0.017	0	-10000	0	-10000	0	0
RAPGEF1	0.017	0	-10000	0	-10000	0	0
DAB1	0.017	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1	0.014	0.024	-10000	0	-0.21	3	3
LRPAP1/LRP8	0.025	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1/Fyn	0.017	0.026	-10000	0	-0.19	3	3
DAB1/alpha3/beta1 Integrin	0.014	0.035	-10000	0	-0.2	6	6
long-term memory	0.016	0.027	-10000	0	-0.18	2	2
DAB1/LIS1	0.021	0.031	-10000	0	-0.18	4	4
DAB1/CRLK/C3G	0.017	0.026	-10000	0	-0.17	4	4
PIK3CA	-0.003	0.091	-10000	0	-0.41	25	25
DAB1/NCK2	0.022	0.031	-10000	0	-0.18	4	4
ARHGEF2	0.017	0	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.011	0.008	-10000	0	-10000	0	0
CDK5R1	0.014	0.007	-10000	0	-10000	0	0
RELN	0.006	0.033	-10000	0	-0.41	3	3
PIK3R1	0.016	0.004	-10000	0	-10000	0	0
RELN/LRP8/Fyn	0.014	0.027	-10000	0	-0.23	3	3
GRIN2A/RELN/LRP8/DAB1/Fyn	0.016	0.028	-10000	0	-0.19	2	2
MAPK8	0.017	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.013	0.026	-10000	0	-0.21	4	4
ITGB1	0.017	0	-10000	0	-10000	0	0
MAP1B	0.011	0.018	-10000	0	-0.18	2	2
RELN/LRP8	0.015	0.026	-10000	0	-0.23	3	3
GRIN2B/RELN/LRP8/DAB1/Fyn	0.021	0.031	-10000	0	-0.19	3	3
PI3K	0.009	0.065	-10000	0	-0.28	25	25
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.014	0.058	-10000	0	-0.28	19	19
RAP1A	0.08	0.052	-10000	0	-10000	0	0
PAFAH1B1	0.017	0.002	-10000	0	-10000	0	0
MAPK8IP1	0.017	0	-10000	0	-10000	0	0
CRLK/C3G	0.025	0	-10000	0	-10000	0	0
GRIN2B	0.017	0	-10000	0	-10000	0	0
NCK2	0.017	0.001	-10000	0	-10000	0	0
neuron differentiation	0.016	0.021	-10000	0	-0.12	2	2
neuron adhesion	0.077	0.058	-10000	0	-0.32	1	1
LRP8	0.017	0	-10000	0	-10000	0	0
GSK3B	0.003	0.041	-10000	0	-0.18	17	17
RELN/VLDLR/DAB1/Fyn	0.016	0.029	-10000	0	-0.19	4	4
MAP3K11	0.017	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	0.002	0.043	-10000	0	-0.16	30	30
CDK5	0.016	0.004	-10000	0	-10000	0	0
MAPT	0.024	0.08	0.33	33	-10000	0	33
neuron migration	0.01	0.035	-10000	0	-0.16	10	10
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.016	0.021	-10000	0	-0.12	2	2
RELN/VLDLR	0.019	0.03	-10000	0	-0.21	4	4

×

S1P4 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.002	0.005	-9999	-10000	0	0
CDC42/GTP	-0.015	0.039	-9999	-0.16	12	12
PLCG1	0.002	0.01	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.017	0.001	-9999	-10000	0	0
GNAI3	-0.036	0.14	-9999	-0.41	65	65
G12/G13	0.022	0.033	-9999	-0.28	6	6
cell migration	-0.015	0.038	-9999	-0.16	12	12
S1PR5	0	0	-9999	-10000	0	0
S1PR4	0	0	-9999	-10000	0	0
MAPK3	0.002	0.01	-9999	-10000	0	0
MAPK1	0.002	0.01	-9999	-10000	0	0
S1P/S1P5/Gi	0.001	0.01	-9999	-0.1	3	3
GNAI1	0.014	0.02	-9999	-0.41	1	1
CDC42/GDP	0.013	0	-9999	-10000	0	0
S1P/S1P5/G12	0.01	0.022	-9999	-0.24	4	4
RHOA	0.016	0.023	-9999	-0.2	6	6
S1P/S1P4/Gi	0.001	0.01	-9999	-0.1	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.015	0.006	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.019	0.025	-9999	-0.22	6	6
GNA12	0.014	0.037	-9999	-0.41	4	4
GNA13	0.015	0.026	-9999	-0.41	2	2
CDC42	0.017	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.033	0.004	-9999	-10000	0	0
HDAC3	0.017	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.007	-9999	-0.17	1	1
GATA1/HDAC4	0.025	0	-9999	-10000	0	0
GATA1/HDAC5	0.025	0	-9999	-10000	0	0
GATA2/HDAC5	0.025	0.013	-9999	-0.28	1	1
HDAC5/BCL6/BCoR	0.024	0.053	-9999	-0.23	21	21
HDAC9	0.015	0.026	-9999	-0.41	2	2
Glucocorticoid receptor/Hsp90/HDAC6	0.035	0	-9999	-10000	0	0
HDAC4/ANKRA2	0.025	0.013	-9999	-0.28	1	1
HDAC5/YWHAB	0.025	0.002	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.017	0.005	-9999	-0.11	1	1
GATA2	0.016	0.019	-9999	-0.41	1	1
HDAC4/RFXANK	-0.006	0.093	-9999	-0.28	53	53
BCOR	0.013	0.042	-9999	-0.41	5	5
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0	0	-9999	-10000	0	0
HDAC5	0.017	0	-9999	-10000	0	0
GNB1/GNG2	0.013	0.001	-9999	-10000	0	0
Histones	0.024	0.008	-9999	-0.1	2	2
ADRBK1	0.017	0	-9999	-10000	0	0
HDAC4	0.017	0	-9999	-10000	0	0
XPO1	0.017	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.025	0.013	-9999	-0.28	1	1
HDAC4/Ubc9	0.025	0	-9999	-10000	0	0
HDAC7	0	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.025	0.002	-9999	-10000	0	0
TUBA1B	0.017	0	-9999	-10000	0	0
HDAC6	0.017	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.006	0.093	-9999	-0.28	53	53
CAMK4	0.017	0	-9999	-10000	0	0
Tubulin/HDAC6	0.033	0.009	-9999	-10000	0	0
SUMO1	0.017	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.017	0.001	-9999	-10000	0	0
GATA1	0.017	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.017	0.001	-9999	-10000	0	0
NR3C1	0.017	0	-9999	-10000	0	0
SUMO1/HDAC4	0.033	0.005	-9999	-10000	0	0
SRF	0.017	0	-9999	-10000	0	0
HDAC4/YWHAB	0.025	0.002	-9999	-10000	0	0
Tubulin	0.024	0.006	-9999	-10000	0	0
HDAC4/14-3-3 E	0.025	0.002	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
RANGAP1	0.017	0	-9999	-10000	0	0
BCL6/BCoR	0.013	0.061	-9999	-0.28	21	21
HDAC4/HDAC3/SMRT (N-CoR2)	0.035	0	-9999	-10000	0	0
HDAC4/SRF	0.035	0	-9999	-10000	0	0
HDAC4/ER alpha	0.025	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.023	0.008	-9999	-0.1	2	2
cell motility	0.032	0.008	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.017	0	-9999	-10000	0	0
HDAC7/HDAC3	0.013	0	-9999	-10000	0	0
BCL6	0.004	0.073	-9999	-0.41	16	16
HDAC4/CaMK II delta B	0.017	0	-9999	-10000	0	0
Hsp90/HDAC6	0.025	0	-9999	-10000	0	0
ESR1	0.017	0	-9999	-10000	0	0
HDAC6/HDAC11	0.025	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.034	0.006	-9999	-10000	0	0
NPC	0.01	0.009	-9999	-0.2	1	1
MEF2C	0.014	0.006	-9999	-10000	0	0
RAN	0.017	0.001	-9999	-10000	0	0
HDAC4/MEF2C	0.043	0.019	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
NCOR2	0.017	0	-9999	-10000	0	0
TUBB2A	0.016	0.004	-9999	-10000	0	0
HDAC11	0.017	0	-9999	-10000	0	0
HSP90AA1	0.017	0	-9999	-10000	0	0
RANBP2	0.016	0.019	-9999	-0.41	1	1
ANKRA2	0.016	0.019	-9999	-0.41	1	1
RFXANK	-0.026	0.13	-9999	-0.41	53	53
nuclear import	-0.029	0.002	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.017	0	-9999	-10000	0	0
ITGB7	0.015	0.026	-9999	-0.41	2	2
ITGA4	0.013	0.042	-9999	-0.41	5	5
alpha4/beta7 Integrin	0.022	0.041	-9999	-0.38	5	5
alpha4/beta1 Integrin	0.023	0.03	-9999	-0.28	5	5

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.017	0	-10000	0	-10000	0	0
NFATC1	0.038	0.016	-10000	0	-10000	0	0
NFATC2	0.01	0.031	-10000	0	-0.11	7	7
NFATC3	0.012	0.003	-10000	0	-10000	0	0
YWHAE	0.017	0.001	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.001	0.011	-10000	0	-0.14	2	2
Exportin 1/Ran/NUP214	0.035	0.003	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.029	0.012	-10000	0	-10000	0	0
BCL2/BAX	0.021	0.035	-10000	0	-0.28	7	7
CaM/Ca2+/Calcineurin A alpha-beta B1	0.013	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.013	0.003	-10000	0	-10000	0	0
BAX	0.011	0.049	-10000	0	-0.41	7	7
MAPK14	0.016	0.026	-10000	0	-0.41	2	2
BAD	0.017	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.015	0.011	-10000	0	-0.13	2	2
Calcineurin A alpha-beta B1/BCL2	0.017	0	-10000	0	-10000	0	0
FKBP8	0.017	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.015	0.011	0.13	2	-10000	0	2
KPNB1	0.017	0	-10000	0	-10000	0	0
KPNA2	0.007	0.064	-10000	0	-0.41	12	12
XPO1	0.017	0	-10000	0	-10000	0	0
SFN	-0.01	0.1	-10000	0	-0.41	33	33
MAP3K8	-0.017	0.12	-10000	0	-0.41	42	42
NFAT4/CK1 alpha	0.027	0.011	-10000	0	-0.19	1	1
MEF2D/NFAT1/Cbp/p300	0.047	0.031	-10000	0	-10000	0	0
CABIN1	0.001	0.011	-10000	0	-0.14	2	2
CALM1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.017	0.001	-10000	0	-10000	0	0
MAP3K1	0.016	0.019	-10000	0	-0.41	1	1
CAMK4	0.017	0	-10000	0	-10000	0	0
mol:Ca2+	0.001	0	-10000	0	-10000	0	0
MAPK3	0.017	0	-10000	0	-10000	0	0
YWHAH	0.008	0.009	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.026	0	-10000	0	-10000	0	0
YWHAB	0.017	0.001	-10000	0	-10000	0	0
MAPK8	0.017	0	-10000	0	-10000	0	0
MAPK9	0.017	0.001	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.016	0.019	-10000	0	-0.41	1	1
NFAT1-c-4/YWHAQ	0.043	0.024	-10000	0	-10000	0	0
PRKCH	0.015	0.026	-10000	0	-0.41	2	2
CABIN1/Cbp/p300	0.026	0	-10000	0	-10000	0	0
CASP3	-0.061	0.16	-10000	0	-0.41	96	96
PIM1	0.015	0.026	-10000	0	-0.41	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.011	-10000	0	-0.24	1	1
apoptosis	0.015	0.019	-10000	0	-0.15	7	7
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.038	-10000	0	-0.14	25	25
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.017	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.005	-10000	0	-10000	0	0
BAD/BCL-XL	0.025	0	-10000	0	-10000	0	0
PRKCD	0.017	0	-10000	0	-10000	0	0
NUP214	0.017	0	-10000	0	-10000	0	0
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.017	0	-10000	0	-10000	0	0
PRKCG	0.017	0	-10000	0	-10000	0	0
PRKCQ	0.017	0	-10000	0	-10000	0	0
FKBP38/BCL2	0.025	0	-10000	0	-10000	0	0
EP300	0.018	0	-10000	0	-10000	0	0
PRKCB1	0.001	0.004	-10000	0	-10000	0	0
CSNK2A1	0.017	0	-10000	0	-10000	0	0
NFATc/JNK1	0.047	0.017	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.023	0.005	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0.013	-10000	0	-0.29	1	1
CSNK1A1	0.016	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.023	0.005	-10000	0	-10000	0	0
NFATc/ERK1	0.046	0.017	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.029	0.012	-10000	0	-10000	0	0
NR4A1	0.032	0.028	-10000	0	-10000	0	0
GSK3B	0.017	0.002	-10000	0	-10000	0	0
positive T cell selection	0.012	0.003	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.013	0.023	-10000	0	-10000	0	0
RCH1/ KPNB1	0.018	0.046	-10000	0	-0.28	12	12
YWHAQ	0.017	0	-10000	0	-10000	0	0
PRKACA	0.017	0	-10000	0	-10000	0	0
AKAP5	0.017	0	-10000	0	-10000	0	0
MEF2D	0.018	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.017	0.002	-10000	0	-10000	0	0
NFATc/p38 alpha	0.046	0.022	-10000	0	-0.21	2	2
CREBBP	0.018	0	-10000	0	-10000	0	0
BCL2	0.017	0	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.002	0.094	-10000	0	-0.4	27	27
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.025	0.011	-10000	0	-10000	0	0
IL27/IL27R/JAK1	0.037	0.019	-10000	0	-10000	0	0
TBX21	0.024	0.033	-10000	0	-10000	0	0
IL12B	0.018	0.001	-10000	0	-10000	0	0
IL12A	0.009	0	-10000	0	-10000	0	0
IL6ST	0.018	0.001	-10000	0	-10000	0	0
IL27RA/JAK1	0.022	0.003	-10000	0	-10000	0	0
IL27	0.001	0.001	-10000	0	-10000	0	0
TYK2	0.017	0.019	-10000	0	-0.41	1	1
T-helper cell lineage commitment	0.002	0.07	-10000	0	-0.34	5	5
T-helper 2 cell differentiation	-0.025	0.011	-10000	0	-10000	0	0
T cell proliferation during immune response	-0.025	0.011	-10000	0	-10000	0	0
MAPKKK cascade	0.025	0.011	-10000	0	-10000	0	0
STAT3	0.009	0.058	-10000	0	-0.41	10	10
STAT2	0.017	0	-10000	0	-10000	0	0
STAT1	0.003	0.078	-10000	0	-0.41	18	18
IL12RB1	0.017	0	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.025	0.033	-10000	0	-10000	0	0
IL27/IL27R/JAK2/TYK2	0.025	0.011	-10000	0	-10000	0	0
positive regulation of T cell mediated cytotoxicity	0.025	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.037	0.046	0.28	4	-0.34	1	5
JAK2	0.017	0.001	-10000	0	-10000	0	0
JAK1	0.017	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	0.034	0.012	-10000	0	-10000	0	0
T cell proliferation	0.009	0.062	-10000	0	-0.27	2	2
IL12/IL12R/TYK2/JAK2	0.044	0.011	-10000	0	-10000	0	0
IL17A	0.002	0.071	-10000	0	-0.34	5	5
mast cell activation	-0.025	0.011	-10000	0	-10000	0	0
IFNG	0.011	0.004	-10000	0	-0.072	1	1
T cell differentiation	0.001	0.001	-10000	0	-0.013	1	1
STAT3 (dimer)	0.03	0.031	-10000	0	-10000	0	0
STAT5A (dimer)	0.033	0.015	-10000	0	-10000	0	0
STAT4 (dimer)	0.019	0.02	-10000	0	-10000	0	0
STAT4	0.01	0.008	-10000	0	-10000	0	0
T cell activation	-0.006	0	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	0.04	0.011	-10000	0	-10000	0	0
GATA3	0.003	0.034	-10000	0	-0.35	5	5
IL18	-0.016	0.083	-10000	0	-0.29	45	45
positive regulation of mast cell cytokine production	0.03	0.03	-10000	0	-10000	0	0
IL27/EBI3	0.011	0.023	-10000	0	-0.29	3	3
IL27RA	0.012	0.002	-10000	0	-10000	0	0
IL6	-0.018	0.13	-10000	0	-0.4	52	52
STAT5A	0.016	0.019	-10000	0	-0.41	1	1
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.005	0.002	-10000	0	-10000	0	0
IL1B	0.001	0.048	-10000	0	-0.29	14	14
EBI3	0.014	0.032	-10000	0	-0.41	3	3
TNF	0.008	0.018	-10000	0	-0.29	2	2

×

LPA4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.006	0	-9999	-10000	0	0
ADCY5	0.006	0	-9999	-10000	0	0
ADCY6	0.012	0	-9999	-10000	0	0
ADCY7	0.009	0.024	-9999	-0.24	5	5
ADCY1	0.012	0	-9999	-10000	0	0
ADCY2	0.012	0	-9999	-10000	0	0
ADCY3	0.006	0	-9999	-10000	0	0
ADCY8	0.008	0.029	-9999	-0.24	7	7
PRKCE	0.009	0	-9999	-10000	0	0
ADCY9	0.012	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.014	0.013	-9999	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.025	0.001	-10000	0	-10000	0	0
STXBP1	0.002	0.005	-10000	0	-10000	0	0
ACh/CHRNA1	0.029	0.021	-10000	0	-0.24	3	3
RAB3GAP2/RIMS1/UNC13B	0.035	0.002	-10000	0	-10000	0	0
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	0.017	0	-10000	0	-10000	0	0
mol:ACh	0.029	0.012	0.05	32	-10000	0	32
RAB3GAP2	0.017	0	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.001	0.006	-10000	0	-10000	0	0
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.029	0.021	-10000	0	-0.24	3	3
UNC13B	0.017	0.001	-10000	0	-10000	0	0
CHRNA1	0.015	0.032	-10000	0	-0.41	3	3
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.002	0.008	-10000	0	-10000	0	0
SNAP25	0.001	0.002	-10000	0	-10000	0	0
VAMP2	0.005	0.002	-10000	0	-10000	0	0
SYT1	0.001	0.004	-10000	0	-10000	0	0
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.001	0.003	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.001	0.006	-10000	0	-10000	0	0

×

Arf1 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
coatomer protein complex	0.015	0.006	0.11	2	-10000	0	2
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.015	0.007	-10000	0	-10000	0	0
AP2	0.012	0.002	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.024	0.001	-10000	0	-10000	0	0
CLTB	0.017	0.001	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0.002	-10000	0	-10000	0	0
CD4	0.002	0.08	-10000	0	-0.41	19	19
CLTA	0.017	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
ARFGAP1	0.009	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.008	0.007	-10000	0	-0.15	1	1
ARF1/GTP	0.01	0.006	-10000	0	-0.12	1	1
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.019	0.002	-10000	0	-10000	0	0
mol:Choline	0.007	0.007	-10000	0	-0.14	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.017	0.001	-10000	0	-10000	0	0
DDEF1	0.007	0.007	-10000	0	-0.14	1	1
ARF1/GDP	0.007	0.002	-10000	0	-10000	0	0
AP2M1	0.017	0.002	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.013	0.001	-10000	0	-10000	0	0
Rac/GTP	0.013	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.027	0.002	-10000	0	-10000	0	0
ARFIP2	0.016	0.001	-10000	0	-10000	0	0
COPA	0.017	0	-10000	0	-10000	0	0
RAC1	0.017	0	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.019	0.003	-10000	0	-10000	0	0
ARF1/GTP/ARHGAP10	0.011	0.001	-10000	0	-10000	0	0
GGA3	0.017	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.016	0.004	-10000	0	-10000	0	0
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.021	0.002	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.018	0.003	-10000	0	-10000	0	0
Arfaptin 2/Rac/GDP	0.023	0.001	-10000	0	-10000	0	0
CYTH2	0	0.001	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.022	0.001	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.013	0	-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	0.02	0.023	-10000	0	-0.1	19	19
PLD2	0.007	0.007	-10000	0	-0.15	1	1
ARF-GAP1/v-SNARE	0.009	0	-10000	0	-10000	0	0
PIP5K1A	0.008	0.007	-10000	0	-0.15	1	1
ARF1/GTP/Membrin/GBF1/p115	0.016	0.005	-10000	0	-0.099	1	1
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.007	-10000	0	-0.14	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.009	0	-10000	0	-10000	0	0
GOSR2	0.012	0.003	-10000	0	-10000	0	0
USO1	0.012	0.003	-10000	0	-10000	0	0
GBF1	0.012	0.003	-10000	0	-10000	0	0
ARF1/GTP/Arfaptin 2	0.023	0.002	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.013	0.049	-10000	0	-0.24	19	19

×

Alternative NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.024	0.023	-9999	-0.28	3	3
FBXW11	0.017	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
CHUK	0.016	0.019	-9999	-0.41	1	1
NF kappa B2 p100/RelB	0.049	0.021	-9999	-0.19	4	4
NFKB1	0.014	0.037	-9999	-0.41	4	4
MAP3K14	0.015	0.026	-9999	-0.41	2	2
NF kappa B1 p50/RelB	0.023	0.03	-9999	-0.28	5	5
RELB	0.016	0.019	-9999	-0.41	1	1
NFKB2	0.017	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.023	0.011	-9999	-0.24	1	1
regulation of B cell activation	0.022	0.011	-9999	-0.24	1	1

×

PLK2 and PLK4 events

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	Mean.of.Down.Perturbations
PLK2	0.012	0.008	-9999	-9999
PLK4	0.017	0	-9999	-9999
regulation of centriole replication	0.012	0.008	-9999	-9999

×

Ephrin A reverse signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.023	0	-9999	-10000	0	0
EFNA5	0.017	0	-9999	-10000	0	0
FYN	0.018	0.015	-9999	-0.21	2	2
neuron projection morphogenesis	0.023	0	-9999	-10000	0	0
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	0.023	0	-9999	-10000	0	0
EPHA5	0.017	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.02	0.002	-9999	-10000	0	0
MAPK9	0.007	0.001	-9999	-10000	0	0
adrenocorticotropin secretion	0.008	0.013	-9999	-0.29	1	1
GNB1/GNG2	0.011	0.001	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.007	0.012	-9999	-0.19	2	2
Gs family/GTP	0.011	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.017	0	-9999	-10000	0	0
GNG2	0	0	-9999	-10000	0	0
CRH	0.016	0.019	-9999	-0.41	1	1
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.007	0	-9999	-10000	0	0
MAPK11	0.007	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.017	0	-9999	-10000	0	0
GNAT1/GTP	0.013	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0.023	0.011	-9999	-0.24	1	1
PDE6G/GNAT1/GTP	0.023	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.017	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	0.034	0	-9999	-10000	0	0
mol:Na +	0.027	0	-9999	-10000	0	0
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.023	0.003	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.034	0	-9999	-10000	0	0
CNGB1	0.017	0	-9999	-10000	0	0
RDH5	0.016	0.019	-9999	-0.41	1	1
SAG	0.016	0.019	-9999	-0.41	1	1
mol:Ca2+	0.027	0	-9999	-10000	0	0
Na + (4 Units)	0.024	0	-9999	-10000	0	0
RGS9	0.017	0	-9999	-10000	0	0
GNB1/GNGT1	0.025	0.003	-9999	-10000	0	0
GNAT1/GDP	0.03	0.003	-9999	-10000	0	0
GUCY2D	0.017	0	-9999	-10000	0	0
GNGT1	0.017	0	-9999	-10000	0	0
GUCY2F	0.017	0	-9999	-10000	0	0
GNB5	0.017	0.002	-9999	-10000	0	0
mol:GMP (4 units)	0.028	0	-9999	-10000	0	0
mol:11-cis-retinal	0.016	0.019	-9999	-0.41	1	1
mol:cGMP	0.022	0	-9999	-10000	0	0
GNB1	0.017	0.002	-9999	-10000	0	0
Rhodopsin	0.025	0.013	-9999	-0.28	1	1
SLC24A1	0.017	0	-9999	-10000	0	0
CNGA1	0.017	0	-9999	-10000	0	0
Metarhodopsin II	0.011	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.022	0	-9999	-10000	0	0
RGS9BP	0	0	-9999	-10000	0	0
Metarhodopsin II/Transducin	0.021	0.002	-9999	-10000	0	0
GCAP Family/Ca ++	0.011	0	-9999	-10000	0	0
PDE6A/B	0.025	0	-9999	-10000	0	0
mol:Pi	0.023	0.003	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.033	0.004	-9999	-10000	0	0
PDE6B	0.017	0	-9999	-10000	0	0
PDE6A	0.017	0	-9999	-10000	0	0
PDE6G	0.017	0	-9999	-10000	0	0
RHO	0.017	0	-9999	-10000	0	0
PDE6	0.042	0.005	-9999	-10000	0	0
GUCA1A	0	0	-9999	-10000	0	0
GC2/GCAP Family	0.022	0	-9999	-10000	0	0
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.017	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
cAMP biosynthetic process	-0.017	-9999	-9999
PI3K Class IB/PDE3B	0.017	-9999	-9999
PDE3B	0.017	-9999	-9999

pid_entity	TCGA.87.5896	TCGA.81.5910	TCGA.76.6285	TCGA.76.6282
109_MAP3K5	-0.073	0.041	0.041	0.041
47_PPARGC1A	0.017	0.017	0.017	0.017
105_BMP4	0.017	0.017	0.017	0.017
105_BMP6	0.017	0.017	0.017	0.017
105_BMP7	0.017	0.017	0.017	0.017
105_BMP2	0.017	0.017	-0.41	0.017
131_RELN/VLDLR	0.044	-0.092	0.044	0
30_TGFB1/TGF beta receptor Type II	-0.41	0.017	0.019	-0.41
84_STAT5B	-0.16	-0.098	0.033	-0.098
84_STAT5A	-0.16	-0.098	0.033	-0.098