PARADIGM pathway analysis of mRNA expression data - Ovarian Serous Cystadenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	390
PLK2 and PLK4 events	246
PLK1 signaling events	212
TCGA08_retinoblastoma	209
Aurora B signaling	164
Signaling events regulated by Ret tyrosine kinase	119
Osteopontin-mediated events	116
Circadian rhythm pathway	115
S1P3 pathway	108
IL2 signaling events mediated by STAT5	99

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
FOXM1 transcription factor network	0.6842	390	19898	51	-0.022	2.1	1000	-1000	-0.14	-1000
PLK2 and PLK4 events	0.4316	246	739	3	0.057	0.14	1000	-1000	-0.007	-1000
PLK1 signaling events	0.3719	212	18043	85	-0.13	0.29	1000	-1000	-0.026	-1000
TCGA08_retinoblastoma	0.3667	209	1673	8	-0.13	0.14	1000	-1000	-0.001	-1000
Aurora B signaling	0.2877	164	11023	67	-0.3	0.36	1000	-1000	-0.027	-1000
Signaling events regulated by Ret tyrosine kinase	0.2088	119	9810	82	-0.22	0.085	1000	-1000	-0.047	-1000
Osteopontin-mediated events	0.2035	116	4410	38	-0.14	0.18	1000	-1000	-0.029	-1000
Circadian rhythm pathway	0.2018	115	2550	22	-0.082	0.24	1000	-1000	-0.042	-1000
S1P3 pathway	0.1895	108	4575	42	-0.63	0.009	1000	-1000	-0.019	-1000
IL2 signaling events mediated by STAT5	0.1737	99	2191	22	-0.5	0.19	1000	-1000	-0.034	-1000
HIF-1-alpha transcription factor network	0.1684	96	7317	76	-0.064	0.41	1000	-1000	-0.042	-1000
Nongenotropic Androgen signaling	0.1649	94	4904	52	-0.2	0.16	1000	-1000	-0.019	-1000
TCGA08_p53	0.1544	88	620	7	-0.073	0.015	1000	-1000	-0.004	-1000
IGF1 pathway	0.1544	88	5038	57	-0.12	0.083	1000	-1000	-0.046	-1000
PDGFR-alpha signaling pathway	0.1421	81	3583	44	-0.18	0.056	1000	-1000	-0.015	-1000
Endothelins	0.1333	76	7299	96	-0.23	0.11	1000	-1000	-0.028	-1000
LPA receptor mediated events	0.1316	75	7653	102	-0.094	0.036	1000	-1000	-0.039	-1000
TCGA08_rtk_signaling	0.1298	74	1931	26	-0.22	0.099	1000	-1000	-0.004	-1000
Thromboxane A2 receptor signaling	0.1281	73	7697	105	-0.2	0.035	1000	-1000	-0.042	-1000
mTOR signaling pathway	0.1281	73	3880	53	-0.17	0.055	1000	-1000	-0.032	-1000
Insulin Pathway	0.1281	73	5433	74	-0.21	0.056	1000	-1000	-0.046	-1000
Aurora A signaling	0.1263	72	4371	60	-0.3	0.29	1000	-1000	-0.014	-1000
IL4-mediated signaling events	0.1263	72	6593	91	-0.89	0.29	1000	-1000	-0.14	-1000
Syndecan-1-mediated signaling events	0.1175	67	2297	34	-0.081	0.049	1000	-1000	-0.024	-1000
Coregulation of Androgen receptor activity	0.1140	65	4948	76	-0.52	0.13	1000	-1000	-0.024	-1000
Ephrin B reverse signaling	0.1123	64	3075	48	-0.17	0.056	1000	-1000	-0.017	-1000
Integrins in angiogenesis	0.1035	59	5005	84	-0.21	0.15	1000	-1000	-0.039	-1000
IL23-mediated signaling events	0.1035	59	3595	60	-0.18	0.12	1000	-1000	-0.11	-1000
Ras signaling in the CD4+ TCR pathway	0.1018	58	996	17	-0.051	0.098	1000	-1000	-0.011	-1000
Cellular roles of Anthrax toxin	0.0965	55	2181	39	-0.25	0.023	1000	-1000	-0.013	-1000
Reelin signaling pathway	0.0947	54	3068	56	-0.056	0.056	1000	-1000	-0.022	-1000
Signaling events mediated by PRL	0.0930	53	1820	34	-0.11	0.13	1000	-1000	-0.017	-1000
BARD1 signaling events	0.0912	52	2981	57	-0.045	0.2	1000	-1000	-0.032	-1000
FAS signaling pathway (CD95)	0.0895	51	2434	47	-0.091	0.061	1000	-1000	-0.016	-1000
Signaling mediated by p38-alpha and p38-beta	0.0842	48	2135	44	-0.09	0.014	1000	-1000	-0.019	-1000
IL1-mediated signaling events	0.0807	46	2855	62	-0.081	0.12	1000	-1000	-0.036	-1000
Effects of Botulinum toxin	0.0807	46	1203	26	-0.16	0.016	1000	-1000	-0.018	-1000
amb2 Integrin signaling	0.0789	45	3756	82	-0.13	0.074	1000	-1000	-0.025	-1000
Plasma membrane estrogen receptor signaling	0.0789	45	3933	86	-0.13	0.099	1000	-1000	-0.043	-1000
Syndecan-2-mediated signaling events	0.0772	44	3047	69	-0.081	0.074	1000	-1000	-0.01	-1000
TRAIL signaling pathway	0.0772	44	2120	48	-0.16	0.012	1000	-1000	-0.024	-1000
HIF-2-alpha transcription factor network	0.0754	43	1890	43	-0.14	0.19	1000	-1000	-0.049	-1000
Nectin adhesion pathway	0.0702	40	2562	63	-0.13	0.056	1000	-1000	-0.041	-1000
Insulin-mediated glucose transport	0.0667	38	1245	32	-0.27	0.12	1000	-1000	-0.018	-1000
Retinoic acid receptors-mediated signaling	0.0667	38	2209	58	-0.29	0.2	1000	-1000	-0.034	-1000
Signaling events mediated by the Hedgehog family	0.0632	36	1911	52	-0.038	0.13	1000	-1000	-0.029	-1000
Signaling events mediated by PTP1B	0.0632	36	2752	76	-0.21	0.084	1000	-1000	-0.036	-1000
p75(NTR)-mediated signaling	0.0632	36	4556	125	-0.23	0.12	1000	-1000	-0.04	-1000
Fc-epsilon receptor I signaling in mast cells	0.0632	36	3567	97	-0.12	0.054	1000	-1000	-0.038	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0632	36	1895	52	-0.23	0.074	1000	-1000	-0.025	-1000
IL6-mediated signaling events	0.0632	36	2758	75	-0.29	0.096	1000	-1000	-0.025	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0614	35	2993	85	-0.13	0.056	1000	-1000	-0.027	-1000
Regulation of Androgen receptor activity	0.0614	35	2476	70	-0.63	0.019	1000	-1000	-0.035	-1000
Aurora C signaling	0.0579	33	235	7	-0.004	0.049	1000	-1000	-0.01	-1000
FoxO family signaling	0.0579	33	2134	64	-0.011	0.32	1000	-1000	-0.023	-1000
TCR signaling in naïve CD8+ T cells	0.0544	31	2924	93	-0.065	0.099	1000	-1000	-0.036	-1000
PDGFR-beta signaling pathway	0.0544	31	3093	97	-0.097	0.12	1000	-1000	-0.037	-1000
IL2 signaling events mediated by PI3K	0.0526	30	1759	58	-0.13	0.052	1000	-1000	-0.043	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0509	29	674	23	-0.029	0.19	1000	-1000	-0.02	-1000
Arf6 signaling events	0.0509	29	1818	62	-0.13	0.032	1000	-1000	-0.014	-1000
Signaling mediated by p38-gamma and p38-delta	0.0509	29	443	15	-0.094	0.021	1000	-1000	-0.012	-1000
Wnt signaling	0.0509	29	205	7	0.006	0.034	1000	-1000	-0.009	-1000
Glucocorticoid receptor regulatory network	0.0491	28	3263	114	-0.31	0.14	1000	-1000	-0.046	-1000
ErbB4 signaling events	0.0474	27	1918	69	-0.27	0.22	1000	-1000	-0.035	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0474	27	2006	74	-0.14	0.032	1000	-1000	-0.049	-1000
Regulation of Telomerase	0.0474	27	2818	102	-0.27	0.068	1000	-1000	-0.064	-1000
LPA4-mediated signaling events	0.0456	26	313	12	-0.088	0	1000	-1000	-0.013	-1000
Caspase cascade in apoptosis	0.0456	26	1931	74	-0.076	0.1	1000	-1000	-0.022	-1000
EPHB forward signaling	0.0456	26	2273	85	-0.038	0.099	1000	-1000	-0.042	-1000
Glypican 1 network	0.0439	25	1246	48	-0.24	0.045	1000	-1000	-0.014	-1000
IL12-mediated signaling events	0.0421	24	2169	87	-0.25	0.12	1000	-1000	-0.091	-1000
IFN-gamma pathway	0.0421	24	1680	68	-0.07	0.065	1000	-1000	-0.043	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0421	24	918	37	-0.038	0.056	1000	-1000	-0.02	-1000
ceramide signaling pathway	0.0421	24	1196	49	-0.078	0.007	1000	-1000	-0.029	-1000
Syndecan-3-mediated signaling events	0.0421	24	845	35	-0.039	0.027	1000	-1000	-0.018	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0421	24	1116	45	-0.1	0.018	1000	-1000	-0.052	-1000
Syndecan-4-mediated signaling events	0.0421	24	1631	67	-0.083	0.087	1000	-1000	-0.026	-1000
E-cadherin signaling in keratinocytes	0.0404	23	1013	43	-0.037	0.052	1000	-1000	-0.021	-1000
Paxillin-dependent events mediated by a4b1	0.0386	22	796	36	-0.038	0.056	1000	-1000	-0.026	-1000
Canonical Wnt signaling pathway	0.0386	22	1130	51	-0.34	0.13	1000	-1000	-0.029	-1000
EGFR-dependent Endothelin signaling events	0.0386	22	471	21	-0.03	0.014	1000	-1000	-0.016	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0386	22	2712	120	-0.16	0.12	1000	-1000	-0.033	-1000
Regulation of nuclear SMAD2/3 signaling	0.0368	21	2865	136	-0.17	0.13	1000	-1000	-0.019	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0368	21	1136	54	-0.046	0.019	1000	-1000	-0.048	-1000
Ceramide signaling pathway	0.0368	21	1632	76	-0.076	0.044	1000	-1000	-0.028	-1000
Presenilin action in Notch and Wnt signaling	0.0351	20	1249	61	-0.32	0.029	1000	-1000	-0.037	-1000
BMP receptor signaling	0.0351	20	1700	81	-0.18	0.047	1000	-1000	-0.047	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0351	20	1693	83	-0.15	0.19	1000	-1000	-0.03	-1000
S1P1 pathway	0.0351	20	725	36	-0.086	0.015	1000	-1000	-0.034	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0351	20	1371	68	-0.15	0.017	1000	-1000	-0.06	-1000
Class I PI3K signaling events	0.0351	20	1484	73	-0.039	0.094	1000	-1000	-0.023	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0351	20	1594	78	-0.12	0.056	1000	-1000	-0.041	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0333	19	538	28	-0.13	0.017	1000	-1000	-0.014	-1000
IL27-mediated signaling events	0.0333	19	1013	51	-0.08	0.12	1000	-1000	-0.035	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0333	19	627	33	-0.045	0.13	1000	-1000	-0.023	-1000
ErbB2/ErbB3 signaling events	0.0316	18	1219	65	-0.063	0.099	1000	-1000	-0.035	-1000
E-cadherin signaling in the nascent adherens junction	0.0316	18	1397	76	-0.068	0.056	1000	-1000	-0.042	-1000
Canonical NF-kappaB pathway	0.0298	17	693	39	-0.023	0.065	1000	-1000	-0.038	-1000
Noncanonical Wnt signaling pathway	0.0298	17	466	26	-0.003	0.035	1000	-1000	-0.017	-1000
Atypical NF-kappaB pathway	0.0298	17	544	31	-0.038	0.056	1000	-1000	-0.012	-1000
Calcium signaling in the CD4+ TCR pathway	0.0298	17	532	31	-0.097	0.007	1000	-1000	-0.033	-1000
BCR signaling pathway	0.0298	17	1698	99	-0.057	0.056	1000	-1000	-0.042	-1000
Arf6 downstream pathway	0.0281	16	712	43	-0.021	0.021	1000	-1000	-0.015	-1000
Regulation of p38-alpha and p38-beta	0.0281	16	902	54	-0.12	0.028	1000	-1000	-0.03	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0281	16	2004	125	-0.098	0.056	1000	-1000	-0.054	-1000
E-cadherin signaling events	0.0263	15	79	5	-0.005	0.007	1000	-1000	-0.007	-1000
Arf1 pathway	0.0228	13	727	54	-0.021	0.009	1000	-1000	-0.014	-1000
Ephrin A reverse signaling	0.0211	12	90	7	-0.027	0.007	1000	-1000	-0.009	-1000
Signaling events mediated by HDAC Class III	0.0211	12	505	40	-0.034	0.019	1000	-1000	-0.008	-1000
EPO signaling pathway	0.0175	10	566	55	-0.06	0.037	1000	-1000	-0.035	-1000
FOXA2 and FOXA3 transcription factor networks	0.0158	9	445	46	-0.008	0.19	1000	-1000	-0.045	-1000
S1P5 pathway	0.0158	9	154	17	-0.005	0.017	1000	-1000	-0.01	-1000
VEGFR1 specific signals	0.0158	9	507	56	-0.062	0.056	1000	-1000	-0.034	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0158	9	828	88	-0.042	0.074	1000	-1000	-0.068	-1000
a4b1 and a4b7 Integrin signaling	0.0140	8	42	5	0.003	0.017	1000	-1000	-0.007	-1000
Class I PI3K signaling events mediated by Akt	0.0140	8	573	68	-0.16	0.048	1000	-1000	-0.026	-1000
Signaling events mediated by HDAC Class I	0.0140	8	886	104	-0.016	0.027	1000	-1000	-0.025	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0123	7	269	34	-0.016	0.026	1000	-1000	-0.012	-1000
Hedgehog signaling events mediated by Gli proteins	0.0123	7	468	65	-0.05	0.024	1000	-1000	-0.04	-1000
S1P4 pathway	0.0123	7	193	25	-0.014	0.017	1000	-1000	-0.014	-1000
p38 MAPK signaling pathway	0.0123	7	348	44	-0.014	0.024	1000	-1000	-0.035	-1000
Signaling events mediated by HDAC Class II	0.0105	6	455	75	-0.036	0.026	1000	-1000	-0.023	-1000
JNK signaling in the CD4+ TCR pathway	0.0105	6	112	17	-0.013	0.009	1000	-1000	-0.014	-1000
Class IB PI3K non-lipid kinase events	0.0105	6	18	3	-0.009	0.009	1000	-1000	-0.004	-1000
Arf6 trafficking events	0.0070	4	301	71	-0.009	0.014	1000	-1000	-0.02	-1000
Alternative NF-kappaB pathway	0.0053	3	49	13	-0.001	0.02	1000	-1000	-0.005	-1000
Visual signal transduction: Rods	0.0035	2	152	52	-0.013	0.017	1000	-1000	-0.025	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0018	1	51	27	-0.004	0.02	1000	-1000	-0.03	-1000
Rapid glucocorticoid signaling	0.0018	1	27	20	-0.002	0.007	1000	-1000	-0.007	-1000
Visual signal transduction: Cones	0.0000	0	36	38	-0.004	0.016	1000	-1000	-0.009	-1000
Glypican 2 network	0.0000	0	2	4	0.006	0.009	1000	-1000	-0.005	-1000
Total	NA	5586	303901	7203	-16	13	131000	-131000	-3.9	-131000

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	1.2	0.34	1.3	504	-10000	0	504
PLK1	0.43	0.27	0.7	200	-10000	0	200
BIRC5	0.43	0.27	0.67	238	-10000	0	238
HSPA1B	1.2	0.34	1.3	517	-0.91	1	518
MAP2K1	0.44	0.15	0.47	523	-10000	0	523
BRCA2	1.4	0.46	1.5	506	-0.91	1	507
FOXM1	2.1	0.88	2.3	514	-1.1	1	515
XRCC1	1.2	0.34	1.3	503	-10000	0	503
FOXM1B/p19	0.75	0.57	1.2	345	-0.91	1	346
Cyclin D1/CDK4	0.7	0.48	1	357	-1.2	1	358
CDC2	1.8	0.6	2	518	-0.96	1	519
TGFA	0.74	0.51	1.1	361	-0.96	1	362
SKP2	1.3	0.44	1.5	505	-10000	0	505
CCNE1	0.25	0.065	0.27	512	-10000	0	512
CKS1B	1.4	0.5	1.6	504	-0.91	1	505
RB1	-0.001	0.023	-10000	0	-10000	0	0
FOXM1C/SP1	0.9	0.41	1.1	440	-1	1	441
AURKB	0.46	0.3	0.72	253	-10000	0	253
CENPF	1.6	0.49	1.7	514	-0.91	1	515
CDK4	0.11	0.069	0.31	10	-10000	0	10
MYC	0.88	0.4	1.1	445	-0.82	1	446
CHEK2	0.47	0.16	0.5	527	-10000	0	527
ONECUT1	0.78	0.53	1.2	362	-1.1	1	363
CDKN2A	0.054	0.14	0.22	199	-0.27	44	243
LAMA4	1.1	0.58	1.3	448	-1.1	2	450
FOXM1B/HNF6	0.79	0.54	1.2	356	-1.3	1	357
FOS	1	0.61	1.3	410	-1.4	1	411
SP1	-0.022	0.091	-10000	0	-0.29	59	59
CDC25B	1.2	0.35	1.3	504	-0.91	1	505
response to radiation	0.22	0.068	0.24	512	-10000	0	512
CENPB	1.2	0.35	1.3	504	-0.91	1	505
CENPA	1.2	0.36	1.3	504	-0.91	1	505
NEK2	1.5	0.51	1.7	507	-10000	0	507
HIST1H2BA	1.2	0.34	1.3	505	-0.91	1	506
CCNA2	0.24	0.083	0.27	473	-10000	0	473
EP300	0.003	0.037	-10000	0	-0.38	5	5
CCNB1/CDK1	1.7	0.55	1.8	505	-1	1	506
CCNB2	1.6	0.48	1.8	515	-10000	0	515
CCNB1	1.8	0.61	1.9	513	-0.96	1	514
ETV5	1.3	0.39	1.4	509	-0.91	1	510
ESR1	1.1	0.52	1.3	449	-1.1	3	452
CCND1	0.79	0.54	1.2	362	-1.2	1	363
GSK3A	0.23	0.078	0.25	473	-0.35	2	475
Cyclin A-E1/CDK1-2	0.24	0.23	0.44	301	-10000	0	301
CDK2	0.18	0.097	0.28	255	-10000	0	255
G2/M transition of mitotic cell cycle	0.42	0.15	0.46	525	-10000	0	525
FOXM1B/Cbp/p300	-0.004	0.057	-10000	0	-0.97	1	1
GAS1	1.1	0.49	1.3	459	-1.2	1	460
MMP2	1	0.61	1.4	426	-1.1	5	431
RB1/FOXM1C	0.76	0.53	1.1	373	-1.1	1	374
CREBBP	0.001	0.046	-10000	0	-0.38	8	8

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.057	0.098	0.22	139	-0.38	3	142
PLK4	0.1	0.11	0.22	259	-10000	0	259
regulation of centriole replication	0.14	0.14	0.24	337	-0.27	1	338

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.13	0.048	-10000	0	-0.15	493	493
BUB1B	0.22	0.07	0.24	505	-10000	0	505
PLK1	0.1	0.036	0.11	514	-10000	0	514
PLK1S1	0.051	0.021	0.06	429	-10000	0	429
KIF2A	0.087	0.035	0.12	195	-0.15	2	197
regulation of mitotic centrosome separation	0.1	0.036	0.11	514	-10000	0	514
GOLGA2	0.006	0	-10000	0	-10000	0	0
Hec1/SPC24	0.24	0.098	0.26	506	-10000	0	506
WEE1	0.14	0.045	0.17	403	-10000	0	403
cytokinesis	0.24	0.094	0.28	468	-10000	0	468
PP2A-alpha B56	0.035	0.063	-10000	0	-10000	0	0
AURKA	0.13	0.036	0.14	539	-10000	0	539
PICH/PLK1	0.27	0.098	0.28	527	-10000	0	527
CENPE	0.099	0.056	0.15	206	-10000	0	206
RhoA/GTP	0.004	0.016	-10000	0	-0.27	2	2
positive regulation of microtubule depolymerization	0.087	0.034	0.12	195	-0.15	2	197
PPP2CA	0.006	0.016	-10000	0	-0.38	1	1
FZR1	0.006	0	-10000	0	-10000	0	0
TPX2	0.15	0.031	0.16	554	-10000	0	554
PAK1	0.014	0.04	0.22	18	-0.39	1	19
SPC24	0.066	0.097	0.22	158	-10000	0	158
FBXW11	0.006	0	-10000	0	-10000	0	0
CLSPN	0.07	0.04	0.16	74	-10000	0	74
GORASP1	0.006	0	-10000	0	-10000	0	0
metaphase	0.001	0.002	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.051	0.021	0.06	429	-10000	0	429
G2 phase of mitotic cell cycle	0.007	0.002	0.009	106	-10000	0	106
STAG2	0.016	0.049	0.22	27	-0.38	1	28
GRASP65/GM130/RAB1/GTP	0	0.001	-10000	0	-10000	0	0
spindle elongation	0.1	0.036	0.11	514	-10000	0	514
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	0.005	0.026	-10000	0	-10000	0	0
TPT1	0.052	0.024	0.098	31	-0.18	1	32
CDC25C	0.11	0.07	0.19	214	-10000	0	214
CDC25B	0.027	0.02	0.23	5	-10000	0	5
SGOL1	0.13	0.048	0.15	493	-10000	0	493
RHOA	0.005	0.023	-10000	0	-0.38	2	2
CCNB1/CDK1	0.12	0.14	0.28	236	-10000	0	236
CDC14B	0.005	0.002	-10000	0	-10000	0	0
CDC20	0.17	0.092	0.22	434	-10000	0	434
PLK1/PBIP1	0.009	0.037	0.18	21	-10000	0	21
mitosis	0	0	-10000	0	-10000	0	0
FBXO5	0.15	0.078	0.19	430	-10000	0	430
CDC2	0.21	0.055	0.22	530	-10000	0	530
NDC80	0.2	0.07	0.22	503	-10000	0	503
metaphase plate congression	0.064	0.024	0.11	30	-0.17	1	31
ERCC6L	0.26	0.096	0.3	430	-10000	0	430
NLP/gamma Tubulin	0.052	0.024	0.08	198	-10000	0	198
microtubule cytoskeleton organization	0.052	0.023	0.098	31	-0.18	1	32
G2/M transition DNA damage checkpoint	0.001	0.001	0.021	1	-10000	0	1
PPP1R12A	0.009	0.001	-10000	0	-10000	0	0
interphase	0.001	0.001	0.021	1	-10000	0	1
PLK1/PRC1-2	0.29	0.12	0.32	490	-10000	0	490
GRASP65/GM130/RAB1/GTP/PLK1	0.049	0.032	-10000	0	-10000	0	0
RAB1A	0.006	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.12	0.069	0.14	428	-10000	0	428
mitotic prometaphase	0.003	0.002	0.034	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.033	-10000	0	-10000	0	0
microtubule-based process	0.2	0.078	0.24	464	-10000	0	464
Golgi organization	0.1	0.036	0.11	514	-10000	0	514
Cohesin/SA2	0.057	0.05	0.16	62	-0.11	1	63
PPP1CB/MYPT1	0.015	0.012	-10000	0	-0.27	1	1
KIF20A	0.18	0.087	0.22	455	-10000	0	455
APC/C/CDC20	0.2	0.081	0.24	442	-10000	0	442
PPP2R1A	0.006	0	-10000	0	-10000	0	0
chromosome segregation	0.007	0.032	0.17	18	-10000	0	18
PRC1	0.16	0.099	0.22	399	-10000	0	399
ECT2	0.23	0.064	0.24	525	-10000	0	525
C13orf34	0.11	0.069	0.14	419	-10000	0	419
NUDC	0.065	0.024	0.11	30	-0.17	1	31
regulation of attachment of spindle microtubules to kinetochore	0.22	0.07	0.24	505	-10000	0	505
spindle assembly	0.077	0.031	0.09	420	-10000	0	420
spindle stabilization	0.051	0.021	0.06	429	-10000	0	429
APC/C/HCDH1	0.009	0.001	-10000	0	-10000	0	0
MKLP2/PLK1	0.2	0.078	0.24	464	-10000	0	464
CCNB1	0.17	0.093	0.22	420	-10000	0	420
PPP1CB	0.008	0.017	-10000	0	-0.39	1	1
BTRC	0.006	0	-10000	0	-10000	0	0
ROCK2	0.072	0.027	0.2	3	-10000	0	3
TUBG1	0.054	0.024	0.11	35	-10000	0	35
G2/M transition of mitotic cell cycle	0.25	0.08	0.27	514	-10000	0	514
MLF1IP	0.01	0.041	0.2	24	-10000	0	24
INCENP	0.012	0.013	0.22	2	-10000	0	2

×

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	-0.032	0.019	-10000	0	-10000	0	0
CDKN2C	0.001	0.052	0.21	26	-10000	0	26
CDKN2A	0.14	0.11	0.24	317	-10000	0	317
CCND2	-0.13	0.082	-10000	0	-0.2	261	261
RB1	0.12	0.083	0.2	271	-10000	0	271
CDK4	-0.094	0.094	-10000	0	-0.18	259	259
CDK6	-0.1	0.1	-10000	0	-0.2	268	268
G1/S progression	-0.12	0.082	-10000	0	-0.19	271	271

×

Aurora B signaling

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
Condensin I complex	0.36	0.16	0.4	503	-10000	0	503
STMN1	0.08	0.13	0.26	161	-10000	0	161
Aurora B/RasGAP/Survivin	0.046	0.052	0.16	88	-0.22	2	90
Chromosomal passenger complex/Cul3 protein complex	0.006	0.11	0.21	55	-0.17	38	93
BIRC5	0.047	0.068	0.23	69	-10000	0	69
DES	-0.079	0.17	-10000	0	-0.44	103	103
Aurora C/Aurora B/INCENP	0.053	0.05	0.15	110	-10000	0	110
Aurora B/TACC1	-0.15	0.1	-10000	0	-0.22	345	345
Aurora B/PP2A	0.027	0.042	0.16	51	-10000	0	51
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.019	0.039	0.16	12	-0.14	6	18
mitotic metaphase/anaphase transition	-0.008	0.005	-10000	0	-10000	0	0
NDC80	0.23	0.12	0.26	504	-10000	0	504
Cul3 protein complex	-0.056	0.11	-10000	0	-0.23	164	164
KIF2C	0.21	0.085	0.24	485	-10000	0	485
PEBP1	0.018	0.004	-10000	0	-10000	0	0
KIF20A	0.17	0.086	0.22	455	-10000	0	455
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.026	0.047	0.16	51	-0.27	3	54
SEPT1	0.006	0	-10000	0	-10000	0	0
SMC2	0.063	0.095	0.22	149	-10000	0	149
SMC4	0.2	0.058	0.22	525	-10000	0	525
NSUN2/NPM1/Nucleolin	0.045	0.096	0.26	91	-10000	0	91
PSMA3	0.006	0.019	0.22	1	-0.38	1	2
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	0.033	0.065	0.15	112	-0.27	6	118
AURKB	0.057	0.083	0.22	113	-10000	0	113
AURKC	0.006	0	-10000	0	-10000	0	0
CDCA8	0.043	0.063	0.23	58	-10000	0	58
cytokinesis	0.01	0.059	0.33	16	-10000	0	16
Aurora B/Septin1	0.092	0.15	0.34	128	-10000	0	128
AURKA	0.21	0.049	0.22	539	-10000	0	539
INCENP	0.024	0.014	0.23	2	-10000	0	2
KLHL13	-0.1	0.18	0.22	9	-0.38	161	170
BUB1	0.2	0.059	0.22	520	-10000	0	520
hSgo1/Aurora B/Survivin	0.095	0.079	0.17	312	-10000	0	312
EVI5	0.012	0.025	0.22	1	-0.37	2	3
RhoA/GTP	0.011	0.045	0.2	27	-10000	0	27
SGOL1	0.19	0.074	0.22	493	-10000	0	493
CENPA	0.2	0.086	0.22	509	-10000	0	509
NCAPG	0.2	0.071	0.22	500	-10000	0	500
Aurora B/HC8 Proteasome	0.027	0.044	0.16	51	-0.27	1	52
NCAPD2	0.12	0.11	0.22	289	-10000	0	289
Aurora B/PP1-gamma	0.027	0.044	0.16	50	-0.27	1	51
RHOA	0.005	0.023	-10000	0	-0.38	2	2
NCAPH	0.13	0.11	0.22	335	-10000	0	335
NPM1	0	0	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
KLHL9	0.004	0.028	-10000	0	-0.38	3	3
mitotic prometaphase	0.011	0.004	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.044	0.16	51	-0.27	1	52
PPP1CC	0.007	0.023	0.22	3	-0.38	1	4
Centraspindlin	0.35	0.14	0.39	508	-10000	0	508
RhoA/GDP	0.004	0.016	-10000	0	-0.27	2	2
NSUN2	0.001	0.021	0.35	2	-10000	0	2
MYLK	0.005	0.1	0.15	95	-0.27	56	151
KIF23	0.22	0.053	0.23	535	-10000	0	535
VIM	-0.008	0.13	0.19	77	-0.27	85	162
RACGAP1	0.19	0.082	0.23	470	-10000	0	470
mitosis	0	0	-10000	0	-10000	0	0
NCL	0	0	-10000	0	-10000	0	0
Chromosomal passenger complex	0.22	0.096	0.24	481	-10000	0	481
Chromosomal passenger complex/EVI5	0.01	0.024	-10000	0	-0.19	1	1
TACC1	-0.3	0.16	-10000	0	-0.38	440	440
PPP2R5D	0.006	0	-10000	0	-10000	0	0
CUL3	0.006	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.008	0.064	-10000	0	-0.46	2	2
Crk/p130 Cas/Paxillin	-0.17	0.12	-10000	0	-0.3	234	234
JUN	-0.06	0.1	0.22	2	-0.32	2	4
HRAS	0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.063	0.11	-10000	0	-0.2	210	210
RAP1A	0.007	0.009	0.22	1	-10000	0	1
FRS2	0.013	0.038	0.22	18	-10000	0	18
RAP1A/GDP	0.005	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.064	0.11	-10000	0	-0.2	212	212
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.068	0.11	0.14	9	-0.2	217	226
RHOA	0.005	0.023	-10000	0	-0.38	2	2
RAP1A/GTP	-0.059	0.095	-10000	0	-0.18	210	210
GRB7	0.006	0.035	0.22	5	-0.38	3	8
RET51/GFRalpha1/GDNF	-0.063	0.11	-10000	0	-0.2	211	211
MAPKKK cascade	-0.071	0.1	-10000	0	-0.2	196	196
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
RET9/GFRalpha1/GDNF/IRS1	-0.18	0.15	0.14	8	-0.26	400	408
lamellipodium assembly	-0.16	0.12	-10000	0	-0.28	229	229
RET51/GFRalpha1/GDNF/SHC	-0.063	0.11	-10000	0	-0.2	211	211
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
RET9/GFRalpha1/GDNF/SHC	-0.067	0.11	0.14	9	-0.2	215	224
RET9/GFRalpha1/GDNF/Shank3	-0.067	0.11	0.14	9	-0.2	215	224
MAPK3	-0.082	0.1	0.23	1	-0.2	232	233
DOK1	0.006	0.016	-10000	0	-0.38	1	1
DOK6	0.006	0	-10000	0	-10000	0	0
PXN	-0.002	0.056	-10000	0	-0.38	12	12
neurite development	-0.088	0.12	0.23	1	-0.35	50	51
DOK5	0.085	0.14	0.22	241	-0.38	18	259
GFRA1	-0.14	0.19	0.22	9	-0.38	215	224
MAPK8	-0.061	0.1	0.22	2	-0.2	197	199
HRAS/GTP	-0.073	0.11	-10000	0	-0.22	196	196
tube development	-0.064	0.1	0.14	9	-0.19	215	224
MAPK1	-0.067	0.087	0.23	1	-0.18	209	210
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.07	0.11	0.21	1	-0.21	207	208
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
SRC	0.006	0	-10000	0	-10000	0	0
PDLIM7	0.004	0.028	-10000	0	-0.38	3	3
RET51/GFRalpha1/GDNF/Dok6	-0.058	0.11	-10000	0	-0.19	211	211
SHC1	0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.063	0.11	-10000	0	-0.2	211	211
RET51/GFRalpha1/GDNF/Dok5	-0.015	0.13	-10000	0	-0.22	133	133
PRKCA	0.005	0.044	0.22	7	-0.38	5	12
HRAS/GDP	0.005	0	-10000	0	-10000	0	0
CREB1	-0.083	0.12	0.22	1	-0.25	199	200
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.076	0.11	-10000	0	-0.21	215	215
RET51/GFRalpha1/GDNF/Grb7	-0.063	0.11	-10000	0	-0.2	210	210
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.01	0.028	0.22	10	-10000	0	10
DOK4	0.006	0	-10000	0	-10000	0	0
JNK cascade	-0.059	0.099	0.22	2	-0.31	2	4
RET9/GFRalpha1/GDNF/FRS2	-0.064	0.11	0.14	17	-0.2	207	224
SHANK3	0.006	0	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
NCK1	0.024	0.059	0.22	47	-10000	0	47
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.07	0.11	0.22	1	-0.21	203	204
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.068	0.11	0.22	2	-0.21	203	205
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.064	0.11	0.22	1	-0.21	199	200
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.067	0.11	0.21	2	-0.21	199	201
PI3K	-0.22	0.18	0.23	1	-0.4	229	230
SOS1	0.014	0.04	0.22	20	-10000	0	20
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.062	0.1	-10000	0	-0.19	215	215
GRB10	0.007	0.009	0.22	1	-10000	0	1
activation of MAPKK activity	-0.065	0.1	0.19	2	-0.2	203	205
RET51/GFRalpha1/GDNF/FRS2	-0.06	0.11	-10000	0	-0.2	203	203
GAB1	0.004	0.033	-10000	0	-0.38	4	4
IRS1	-0.21	0.2	-10000	0	-0.38	311	311
IRS2	0.006	0	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.073	0.11	0.21	1	-0.21	211	212
RET51/GFRalpha1/GDNF/PKC alpha	-0.064	0.11	-10000	0	-0.21	213	213
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PRKACA	0.006	0	-10000	0	-10000	0	0
GDNF	0.006	0	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
RET51/GFRalpha1/GDNF/IRS1	-0.18	0.15	-10000	0	-0.26	396	396
Rac1/GTP	-0.18	0.14	-10000	0	-0.33	229	229
RET9/GFRalpha1/GDNF	-0.08	0.11	-10000	0	-0.22	215	215
GFRalpha1/GDNF	-0.096	0.14	-10000	0	-0.27	215	215

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.12	0.17	0.32	177	-0.24	22	199
NF kappa B1 p50/RelA/I kappa B alpha	0.089	0.19	0.36	136	-0.36	23	159
alphaV/beta3 Integrin/Osteopontin/Src	0	0.034	0.21	2	-0.34	4	6
AP1	0.066	0.27	0.43	141	-0.41	59	200
ILK	0.099	0.16	0.28	157	-0.47	3	160
bone resorption	0.009	0.17	0.22	131	-0.32	55	186
PTK2B	0.005	0.023	-10000	0	-0.38	2	2
PYK2/p130Cas	0.097	0.14	0.25	166	-0.25	23	189
ITGAV	0.028	0.065	0.23	35	-0.39	3	38
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.097	0.14	-10000	0	-0.27	216	216
alphaV/beta3 Integrin/Osteopontin	0.03	0.12	0.25	8	-0.25	48	56
MAP3K1	0.098	0.16	0.28	164	-0.27	22	186
JUN	0.008	0.041	0.22	9	-0.39	3	12
MAPK3	0.13	0.22	0.43	163	-0.37	12	175
MAPK1	0.15	0.22	0.43	177	-0.44	3	180
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MAPK8	0.097	0.16	0.29	164	-0.27	20	184
ITGB3	-0.034	0.15	0.24	13	-0.39	82	95
NFKBIA	0.14	0.23	0.43	173	-0.36	17	190
FOS	-0.066	0.16	0.23	8	-0.39	110	118
CD44	-0.14	0.19	-10000	0	-0.38	218	218
CHUK	0.011	0.031	0.22	12	-10000	0	12
PLAU	0.18	0.31	0.64	157	-0.44	4	161
NF kappa B1 p50/RelA	0.093	0.2	0.41	130	-0.36	17	147
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
RELA	0.005	0.023	-10000	0	-0.38	2	2
alphaV beta3 Integrin	-0.015	0.12	0.22	3	-0.28	83	86
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	0.095	0.15	0.26	166	-0.26	22	188
VAV3	0.1	0.16	0.27	192	-0.39	4	196
MAP3K14	0.13	0.19	0.37	173	-0.26	22	195
ROCK2	0.007	0.016	0.22	3	-10000	0	3
SPP1	0.15	0.11	0.23	381	-0.39	3	384
RAC1	0.006	0.016	-10000	0	-0.38	1	1
Rac1/GTP	0.023	0.098	0.22	32	-0.26	10	42
MMP2	0.024	0.28	0.37	137	-0.47	72	209

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.089	0.1	0.38	7	-10000	0	7
CLOCK	0.031	0.039	0.23	13	-10000	0	13
TIMELESS/CRY2	0.17	0.18	0.38	253	-10000	0	253
DEC1/BMAL1	0.024	0.019	0.18	1	-10000	0	1
ATR	0.071	0.099	0.22	170	-10000	0	170
NR1D1	0.12	0.23	-10000	0	-0.95	14	14
ARNTL	0.027	0.029	0.23	3	-10000	0	3
TIMELESS	0.24	0.27	0.53	254	-10000	0	254
NPAS2	0.03	0.046	0.23	14	-0.35	2	16
CRY2	0.006	0	-10000	0	-10000	0	0
mol:CO	-0.082	0.093	0.14	3	-0.18	254	257
CHEK1	0.2	0.063	0.22	516	-10000	0	516
mol:HEME	0.082	0.093	0.18	254	-0.14	3	257
PER1	0.006	0.016	-10000	0	-0.38	1	1
BMAL/CLOCK/NPAS2	0.1	0.1	0.22	253	-0.23	1	254
BMAL1/CLOCK	0.13	0.18	0.4	6	-0.8	4	10
S phase of mitotic cell cycle	0.089	0.1	0.38	7	-10000	0	7
TIMELESS/CHEK1/ATR	0.091	0.11	0.39	7	-10000	0	7
mol:NADPH	0.082	0.093	0.18	254	-0.14	3	257
PER1/TIMELESS	0.17	0.18	0.38	253	-10000	0	253
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.006	0	-10000	0	-10000	0	0

×

S1P3 pathway

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
PDGFRB	-0.01	0.079	-10000	0	-0.38	24	24
mol:S1P	-0.017	0.016	0.055	4	-0.03	335	339
S1P1/S1P/Gi	-0.067	0.086	0.2	5	-0.3	26	31
GNAO1	-0.019	0.043	0.22	6	-0.4	3	9
S1P/S1P3/G12/G13	-0.017	0.025	0.11	1	-0.2	1	2
AKT1	-0.073	0.12	-10000	0	-0.53	24	24
AKT3	-0.63	0.54	0.55	4	-1.1	337	341
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.01	0.079	-10000	0	-0.38	24	24
GNAI2	-0.019	0.023	-10000	0	-10000	0	0
GNAI3	-0.006	0.055	0.21	29	-10000	0	29
GNAI1	-0.023	0.066	0.2	7	-0.4	13	20
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.02	0.019	0.066	4	-0.034	337	341
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.003	0.058	-10000	0	-0.38	13	13
mol:Ca2+	-0.14	0.14	0.34	4	-0.26	322	326
MAPK3	-0.15	0.15	0.3	4	-0.27	325	329
MAPK1	-0.14	0.14	0.3	4	-0.25	321	325
JAK2	-0.14	0.14	0.3	4	-0.25	307	311
CXCR4	-0.13	0.14	0.3	4	-0.25	308	312
FLT1	-0.024	0.028	-10000	0	-10000	0	0
RhoA/GDP	0.004	0.016	-10000	0	-0.27	2	2
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
SRC	-0.14	0.13	0.3	4	-0.25	321	325
S1P/S1P3/Gi	-0.14	0.14	0.34	4	-0.26	322	326
RAC1	0.006	0.016	-10000	0	-0.38	1	1
RhoA/GTP	-0.13	0.13	0.27	4	-0.24	321	325
VEGFA	-0.018	0.044	0.22	11	-10000	0	11
S1P/S1P2/Gi	-0.083	0.094	0.22	5	-0.29	22	27
VEGFR1 homodimer/VEGFA homodimer	-0.033	0.046	0.25	4	-10000	0	4
RHOA	0.005	0.023	-10000	0	-0.38	2	2
S1P/S1P3/Gq	-0.094	0.12	-10000	0	-0.24	200	200
GNAQ	-0.005	0.065	-10000	0	-0.38	16	16
GNAZ	-0.021	0.045	-10000	0	-0.4	6	6
G12/G13	0.009	0.012	-10000	0	-0.27	1	1
GNA14	0.006	0.026	0.22	2	-0.38	2	4
GNA15	0.003	0.037	-10000	0	-0.38	5	5
GNA12	0.006	0	-10000	0	-10000	0	0
GNA13	0.006	0.016	-10000	0	-0.38	1	1
GNA11	-0.13	0.18	-10000	0	-0.38	193	193
Rac1/GTP	-0.13	0.13	0.27	4	-0.24	321	325

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.003	0.069	0.22	16	-0.38	13	29
ELF1	0.005	0.046	0.18	4	-0.39	7	11
CCNA2	0.19	0.081	0.22	473	-10000	0	473
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
JAK3	0.006	0	-10000	0	-10000	0	0
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
JAK1	0.004	0.028	-10000	0	-0.38	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0	0.087	-10000	0	-0.46	1	1
SHC1	0.006	0	-10000	0	-10000	0	0
SP1	-0.24	0.14	-10000	0	-0.32	446	446
IL2RA	0.004	0.045	0.41	4	-0.27	7	11
IL2RB	0.001	0.046	-10000	0	-0.38	8	8
SOS1	0.014	0.04	0.22	20	-10000	0	20
IL2RG	-0.007	0.11	0.22	31	-0.38	37	68
G1/S transition of mitotic cell cycle	-0.37	0.27	0.34	9	-0.51	446	455
PTPN11	0.006	0	-10000	0	-10000	0	0
CCND2	-0.5	0.27	0.41	5	-0.64	446	451
LCK	0.006	0	-10000	0	-10000	0	0
GRB2	0.006	0.016	-10000	0	-0.38	1	1
IL2	0.006	0	-10000	0	-10000	0	0
CDK6	0.004	0.057	0.22	10	-0.38	9	19
CCND3	0.001	0.08	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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
PKM2	0.25	0.44	0.82	100	-0.89	21	121
HDAC7	0.011	0.036	0.16	14	-10000	0	14
HIF1A/ARNT/Cbp/p300/Src-1	0.009	0.26	0.78	25	-0.72	14	39
SMAD4	0.004	0.012	-10000	0	-10000	0	0
ID2	0.25	0.44	0.81	100	-0.89	21	121
AP1	-0.042	0.12	0.17	10	-0.27	111	121
ABCG2	0.22	0.44	0.8	100	-0.89	25	125
HIF1A	0.083	0.14	0.3	99	-0.46	2	101
TFF3	-0.011	0.37	0.86	26	-0.89	38	64
GATA2	0.008	0.037	0.19	6	-0.38	3	9
AKT1	0.11	0.15	0.35	91	-10000	0	91
response to hypoxia	0.071	0.14	0.32	120	-10000	0	120
MCL1	0.25	0.44	0.8	110	-0.89	21	131
NDRG1	0.26	0.45	0.83	113	-0.92	22	135
SERPINE1	0.28	0.46	0.87	117	-0.89	21	138
FECH	0.25	0.44	0.81	101	-0.89	21	122
FURIN	0.25	0.44	0.81	100	-0.9	22	122
NCOA2	0.007	0.013	0.22	2	-10000	0	2
EP300	0.21	0.24	0.56	139	-0.31	1	140
HMOX1	0.25	0.44	0.81	110	-0.9	23	133
BHLHE40	0.22	0.44	0.78	131	-0.89	21	152
BHLHE41	0.22	0.44	0.78	131	-0.89	21	152
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.012	0.1	0.41	16	-0.3	4	20
ENG	0.11	0.16	0.37	26	-0.39	8	34
JUN	0.01	0.037	0.22	9	-0.38	2	11
RORA	0.25	0.44	0.81	100	-0.89	21	121
ABCB1	-0.015	0.076	0.68	4	-10000	0	4
TFRC	0.3	0.47	0.88	130	-0.89	21	151
CXCR4	0.26	0.44	0.82	112	-0.89	21	133
TF	0.25	0.44	0.82	102	-0.89	21	123
CITED2	0.24	0.44	0.82	97	-0.93	21	118
HIF1A/ARNT	-0.064	0.24	0.76	4	-0.98	22	26
LDHA	0.044	0.19	0.64	50	-10000	0	50
ETS1	0.25	0.44	0.81	110	-0.89	21	131
PGK1	0.32	0.49	0.91	152	-0.9	20	172
NOS2	0.22	0.44	0.78	131	-0.89	21	152
ITGB2	0.25	0.44	0.81	110	-0.92	23	133
ALDOA	0.25	0.44	0.81	100	-0.89	21	121
Cbp/p300/CITED2	0.2	0.43	0.83	91	-0.93	20	111
FOS	-0.064	0.16	0.22	8	-0.38	110	118
HK2	0.25	0.44	0.82	100	-0.89	21	121
SP1	0.007	0.022	0.21	4	-10000	0	4
GCK	0.26	0.3	0.76	89	-10000	0	89
HK1	0.25	0.44	0.81	100	-0.89	21	121
NPM1	0.25	0.44	0.82	95	-0.89	21	116
EGLN1	0.25	0.44	0.81	101	-0.89	21	122
CREB1	0.05	0.086	0.22	112	-10000	0	112
PGM1	0.26	0.45	0.83	119	-0.89	21	140
SMAD3	0	0.038	-10000	0	-0.39	5	5
EDN1	0.15	0.23	0.72	26	-1.2	1	27
IGFBP1	0.25	0.44	0.81	101	-0.89	21	122
VEGFA	0.29	0.4	0.83	115	-0.64	14	129
HIF1A/JAB1	-0.001	0.046	0.22	11	-0.33	2	13
CP	0.41	0.48	0.92	175	-0.93	23	198
CXCL12	0.21	0.45	0.81	101	-0.9	27	128
COPS5	0.021	0.053	0.22	37	-10000	0	37
SMAD3/SMAD4	0.003	0.032	-10000	0	-0.23	7	7
BNIP3	0.27	0.46	0.88	105	-0.88	22	127
EGLN3	0.26	0.46	0.84	107	-0.9	25	132
CA9	0.28	0.46	0.87	117	-0.89	21	138
TERT	0.25	0.44	0.81	100	-0.89	21	121
ENO1	0.25	0.44	0.81	100	-0.89	21	121
PFKL	0.25	0.44	0.82	100	-0.89	21	121
NCOA1	0.004	0.028	-10000	0	-0.38	3	3
ADM	0.26	0.46	0.89	103	-0.89	21	124
ARNT	0.085	0.13	0.3	99	-10000	0	99
HNF4A	0.007	0.009	0.22	1	-10000	0	1
ADFP	0.3	0.48	0.91	123	-0.89	21	144
SLC2A1	0.3	0.41	0.87	106	-0.64	14	120
LEP	0.25	0.44	0.81	100	-0.89	21	121
HIF1A/ARNT/Cbp/p300	0.015	0.28	0.84	28	-0.75	14	42
EPO	0.26	0.34	0.74	85	-0.82	1	86
CREBBP	0.21	0.25	0.58	131	-10000	0	131
HIF1A/ARNT/Cbp/p300/HDAC7	0.003	0.25	0.72	23	-0.72	14	37
PFKFB3	0.23	0.45	0.8	108	-0.91	25	133
NT5E	0.25	0.47	0.85	116	-0.93	27	143

×

Nongenotropic Androgen signaling

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
PTK2	0.018	0.06	0.2	57	-10000	0	57
GNB1/GNG2	-0.086	0.11	-10000	0	-0.21	252	252
regulation of S phase of mitotic cell cycle	-0.086	0.13	-10000	0	-0.23	223	223
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
HRAS	0.004	0.006	-10000	0	-10000	0	0
SHBG/T-DHT	0.004	0	-10000	0	-10000	0	0
PELP1	0.004	0.006	-10000	0	-10000	0	0
AKT1	-0.001	0.008	0.2	1	-10000	0	1
MAP2K1	-0.094	0.095	0.2	5	-0.27	49	54
T-DHT/AR	-0.12	0.14	-10000	0	-0.27	251	251
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	0.007	8	-0.006	82	90
GNAI2	0.006	0	-10000	0	-10000	0	0
GNAI3	0.017	0.047	0.22	29	-10000	0	29
GNAI1	0	0.064	0.22	7	-0.39	13	20
mol:GDP	-0.16	0.18	-10000	0	-0.34	262	262
cell proliferation	-0.2	0.19	0.28	7	-0.43	185	192
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
FOS	-0.2	0.29	0.43	8	-0.78	111	119
mol:Ca2+	-0.018	0.021	0.042	5	-0.056	62	67
MAPK3	-0.18	0.16	0.33	2	-0.36	198	200
MAPK1	-0.087	0.095	0.22	7	-0.26	76	83
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.001	0.002	0.012	8	-0.004	62	70
cAMP biosynthetic process	0.012	0.016	-10000	0	-10000	0	0
GNG2	0.004	0.034	0.22	1	-0.38	4	5
potassium channel inhibitor activity	-0.001	0.002	0.012	8	-0.004	62	70
HRAS/GTP	-0.083	0.099	0.13	5	-0.19	248	253
actin cytoskeleton reorganization	-0.013	0.057	-10000	0	-0.18	57	57
SRC	0.004	0.006	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	0.012	8	-0.004	62	70
PI3K	-0.017	0.069	-10000	0	-0.22	56	56
apoptosis	0.16	0.18	0.48	111	-0.33	7	118
T-DHT/AR/PELP1	-0.097	0.12	-10000	0	-0.23	251	251
HRAS/GDP	-0.15	0.17	-10000	0	-0.33	251	251
CREB1	-0.17	0.19	0.42	2	-0.5	120	122
RAC1-CDC42/GTP	-0.012	0.058	-10000	0	-0.18	57	57
AR	-0.17	0.19	-10000	0	-0.39	251	251
GNB1	0.006	0.016	-10000	0	-0.38	1	1
RAF1	-0.092	0.092	0.16	5	-0.19	248	253
RAC1-CDC42/GDP	-0.15	0.17	-10000	0	-0.32	251	251
T-DHT/AR/PELP1/Src	-0.088	0.11	-10000	0	-0.21	251	251
MAP2K2	-0.16	0.12	0.23	2	-0.32	148	150
T-DHT/AR/PELP1/Src/PI3K	-0.087	0.13	-10000	0	-0.23	223	223
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
SHBG	0.006	0	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.032	0.067	-10000	0	-0.29	14	14
mol:T-DHT	0	0.001	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
GNRH1	-0.002	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.052	0.074	-10000	0	-0.25	19	19
CDC42	0.006	0	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	0.11	0.099	0.2	317	-10000	0	317
TP53	0	0.1	0.22	1	-0.22	91	92
Senescence	0.001	0.1	0.22	1	-0.22	91	92
Apoptosis	0.001	0.1	0.22	1	-0.22	91	92
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.073	0.067	0.22	3	-0.27	1	4
MDM4	0.015	0.043	0.22	23	-10000	0	23

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.006	0	-10000	0	-10000	0	0
PTK2	0.028	0.065	0.22	57	-10000	0	57
CRKL	-0.12	0.13	-10000	0	-0.32	135	135
GRB2/SOS1/SHC	0.012	0.01	-10000	0	-0.23	1	1
HRAS	0.006	0	-10000	0	-10000	0	0
IRS1/Crk	-0.12	0.13	-10000	0	-0.32	135	135
IGF-1R heterotetramer/IGF1/PTP1B	-0.07	0.11	-10000	0	-0.26	135	135
AKT1	-0.097	0.13	-10000	0	-0.29	131	131
BAD	-0.093	0.12	-10000	0	-0.3	110	110
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.13	-10000	0	-0.32	135	135
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.13	-10000	0	-0.32	135	135
RAF1	-0.085	0.12	-10000	0	-0.29	89	89
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.1	0.13	-10000	0	-0.3	135	135
YWHAZ	0.006	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.12	0.14	-10000	0	-0.22	339	339
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
RPS6KB1	-0.095	0.13	0.24	1	-0.29	129	130
GNB2L1	0.006	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.076	0.1	-10000	0	-0.26	89	89
PXN	-0.002	0.056	-10000	0	-0.38	12	12
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
HRAS/GTP	-0.099	0.12	-10000	0	-0.28	135	135
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.047	0.094	-10000	0	-0.21	131	131
IGF-1R heterotetramer	-0.11	0.17	-10000	0	-0.44	121	121
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.11	0.13	-10000	0	-0.32	135	135
Crk/p130 Cas/Paxillin	-0.11	0.13	-10000	0	-0.3	146	146
IGF1R	-0.11	0.17	-10000	0	-0.44	121	121
IGF1	-0.042	0.077	0.18	4	-0.42	16	20
IRS2/Crk	-0.11	0.12	-10000	0	-0.3	135	135
PI3K	-0.1	0.15	-10000	0	-0.28	178	178
apoptosis	0.083	0.11	0.26	110	-10000	0	110
HRAS/GDP	0.005	0	-10000	0	-10000	0	0
PRKCD	-0.099	0.13	-10000	0	-0.32	134	134
RAF1/14-3-3 E	-0.074	0.11	-10000	0	-0.26	89	89
BAD/14-3-3	-0.088	0.12	-10000	0	-0.28	110	110
PRKCZ	-0.097	0.13	-10000	0	-0.29	131	131
Crk/p130 Cas/Paxillin/FAK1	-0.094	0.11	-10000	0	-0.28	105	105
PTPN1	0.006	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.1	0.14	-10000	0	-0.33	134	134
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.058	0.097	0.15	1	-0.22	135	136
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.014	0.04	0.22	20	-10000	0	20
IRS1/NCK2	-0.12	0.13	-10000	0	-0.32	135	135
GRB10	0.007	0.009	0.22	1	-10000	0	1
PTPN11	-0.12	0.13	-10000	0	-0.32	135	135
IRS1	-0.08	0.15	-10000	0	-0.34	135	135
IRS2	-0.12	0.13	-10000	0	-0.32	135	135
IGF-1R heterotetramer/IGF1	-0.096	0.14	-10000	0	-0.34	135	135
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PDPK1	-0.1	0.14	-10000	0	-0.28	174	174
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
PRKD1	-0.097	0.13	-10000	0	-0.32	128	128
SHC1	0.006	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.075	0.16	0.21	6	-0.4	108	114
PDGF/PDGFRA/CRKL	-0.049	0.11	-10000	0	-0.27	110	110
positive regulation of JUN kinase activity	-0.026	0.087	-10000	0	-0.2	103	103
CRKL	0.006	0	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.05	0.11	-10000	0	-0.27	111	111
AP1	-0.18	0.34	0.52	8	-0.83	112	120
mol:IP3	-0.061	0.11	0.18	9	-0.29	106	115
PLCG1	-0.061	0.11	0.19	9	-0.29	106	115
PDGF/PDGFRA/alphaV Integrin	-0.05	0.11	-10000	0	-0.27	109	109
RAPGEF1	0.006	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
mol:Ca2+	-0.061	0.11	0.18	9	-0.28	106	115
CAV3	0.006	0.016	-10000	0	-0.38	1	1
CAV1	-0.062	0.15	0.22	3	-0.38	101	104
SHC/Grb2/SOS1	-0.025	0.088	-10000	0	-0.2	103	103
PDGF/PDGFRA/Shf	-0.049	0.11	-10000	0	-0.27	110	110
FOS	-0.18	0.33	0.56	6	-0.82	112	118
JUN	-0.018	0.046	0.22	9	-0.31	3	12
oligodendrocyte development	-0.05	0.11	-10000	0	-0.27	109	109
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:DAG	-0.061	0.11	0.18	9	-0.29	106	115
PDGF/PDGFRA	-0.075	0.16	0.21	6	-0.4	108	114
actin cytoskeleton reorganization	-0.049	0.11	-10000	0	-0.27	110	110
SRF	0	0.03	-10000	0	-0.27	6	6
SHC1	0.006	0	-10000	0	-10000	0	0
PI3K	-0.057	0.12	-10000	0	-0.27	125	125
PDGF/PDGFRA/Crk/C3G	-0.038	0.092	-10000	0	-0.22	108	108
JAK1	-0.057	0.11	0.18	6	-0.27	110	116
ELK1/SRF	-0.053	0.089	-10000	0	-0.23	110	110
SHB	0.006	0	-10000	0	-10000	0	0
SHF	0.006	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0.019	-10000	0	-10000	0	0
GO:0007205	-0.066	0.13	0.2	9	-0.31	108	117
SOS1	0.014	0.04	0.22	20	-10000	0	20
Ras protein signal transduction	-0.026	0.087	-10000	0	-0.2	103	103
PDGF/PDGFRA/SHB	-0.049	0.11	-10000	0	-0.27	110	110
PDGF/PDGFRA/Caveolin-1	-0.095	0.16	-10000	0	-0.32	176	176
ITGAV	0.017	0.06	0.22	35	-0.38	3	38
ELK1	-0.065	0.11	0.2	6	-0.28	108	114
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PDGF/PDGFRA/Crk	-0.049	0.11	-10000	0	-0.27	110	110
JAK-STAT cascade	-0.057	0.11	0.18	6	-0.27	110	116
cell proliferation	-0.049	0.11	-10000	0	-0.27	110	110

×

Endothelins

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
AKT1	0.022	0.2	0.39	88	-0.36	18	106
PTK2B	0.005	0.023	-10000	0	-0.39	2	2
mol:Ca2+	-0.017	0.16	0.43	8	-0.46	8	16
EDN1	0.02	0.15	0.3	90	-0.29	11	101
EDN3	0.008	0.018	0.22	4	-10000	0	4
EDN2	0.011	0.031	0.22	12	-10000	0	12
HRAS/GDP	-0.024	0.18	0.31	19	-0.38	38	57
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.15	0.3	12	-0.32	55	67
ADCY4	0.039	0.17	0.27	148	-0.3	18	166
ADCY5	0.039	0.17	0.27	148	-0.3	18	166
ADCY6	0.038	0.17	0.27	148	-0.3	18	166
ADCY7	0.038	0.17	0.27	148	-0.3	18	166
ADCY1	0.038	0.17	0.27	148	-0.3	18	166
ADCY2	0.038	0.17	0.27	148	-0.3	18	166
ADCY3	0.039	0.17	0.27	148	-0.3	18	166
ADCY8	-0.037	0.18	0.27	75	-0.34	62	137
ADCY9	0.022	0.18	0.27	144	-0.32	40	184
arachidonic acid secretion	-0.15	0.26	0.43	9	-0.52	131	140
ETB receptor/Endothelin-1/Gq/GTP	-0.023	0.15	0.23	16	-0.28	72	88
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
HRAS	0.004	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.016	0.18	0.37	92	-0.33	19	111
ETA receptor/Endothelin-1/Gs/GTP	0.015	0.17	0.36	86	-0.32	18	104
mol:GTP	0	0.009	-10000	0	-10000	0	0
COL3A1	0.11	0.31	0.54	169	-0.59	14	183
EDNRB	0.053	0.078	0.17	163	-10000	0	163
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.031	0.28	0.39	89	-0.49	114	203
CYSLTR1	0.036	0.23	0.43	110	-0.42	10	120
SLC9A1	0.009	0.13	0.27	87	-0.23	13	100
mol:GDP	-0.026	0.19	0.33	17	-0.4	38	55
SLC9A3	0.049	0.16	0.36	9	-0.41	5	14
RAF1	-0.048	0.21	0.38	12	-0.4	87	99
JUN	-0.02	0.18	0.52	8	-0.68	8	16
JAK2	0.02	0.2	0.39	88	-0.37	20	108
mol:IP3	-0.034	0.16	0.26	62	-0.34	48	110
ETA receptor/Endothelin-1	0.013	0.23	0.45	92	-0.3	108	200
PLCB1	0.023	0.061	0.22	49	-10000	0	49
PLCB2	0.003	0.008	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	0.007	0.092	0.19	86	-0.17	13	99
FOS	-0.18	0.38	0.56	8	-0.91	110	118
Gai/GDP	0.007	0.073	-10000	0	-0.66	3	3
CRK	0.006	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.004	0.23	0.36	115	-0.39	51	166
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
PRKCB1	-0.03	0.16	0.29	17	-0.36	35	52
GNAQ	-0.007	0.066	-10000	0	-0.39	16	16
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
GNAL	0.006	0	-10000	0	-10000	0	0
Gs family/GDP	-0.07	0.12	-10000	0	-0.35	47	47
ETA receptor/Endothelin-1/Gq/GTP	-0.049	0.17	0.26	62	-0.36	62	124
MAPK14	-0.016	0.13	0.23	9	-0.3	32	41
TRPC6	-0.019	0.17	0.46	5	-0.49	7	12
GNAI2	0.006	0	-10000	0	-10000	0	0
GNAI3	0.017	0.047	0.22	29	-10000	0	29
GNAI1	0	0.063	0.22	7	-0.38	13	20
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.017	0.14	0.24	12	-0.28	47	59
ETB receptor/Endothelin-2	0.037	0.053	0.14	22	-10000	0	22
ETB receptor/Endothelin-3	0.038	0.052	0.14	22	-10000	0	22
ETB receptor/Endothelin-1	0.036	0.15	0.35	92	-0.26	10	102
MAPK3	-0.17	0.36	0.52	8	-0.8	121	129
MAPK1	-0.15	0.33	0.52	8	-0.75	113	121
Rac1/GDP	-0.024	0.18	0.31	16	-0.39	36	52
cAMP biosynthetic process	-0.013	0.17	0.26	51	-0.31	61	112
MAPK8	-0.027	0.18	0.44	7	-0.46	24	31
SRC	0.006	0.001	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.044	0.099	0.19	100	-0.26	3	103
p130Cas/CRK/Src/PYK2	-0.022	0.18	0.39	11	-0.43	27	38
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.023	0.18	0.31	16	-0.39	35	51
COL1A2	0.08	0.3	0.63	109	-0.72	11	120
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.006	0.091	0.19	83	-0.17	13	96
mol:DAG	-0.034	0.16	0.26	62	-0.34	48	110
MAP2K2	-0.15	0.28	0.44	8	-0.59	128	136
MAP2K1	-0.075	0.25	0.48	9	-0.51	109	118
EDNRA	0.01	0.14	0.27	87	-0.23	21	108
positive regulation of muscle contraction	0.014	0.17	0.32	88	-0.32	18	106
Gq family/GDP	-0.11	0.15	0.28	5	-0.4	78	83
HRAS/GTP	-0.026	0.18	0.3	19	-0.36	53	72
PRKCH	-0.031	0.16	0.29	15	-0.36	36	51
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCA	-0.031	0.16	0.3	16	-0.37	36	52
PRKCB	-0.031	0.15	0.24	68	-0.33	50	118
PRKCE	-0.03	0.16	0.29	16	-0.38	30	46
PRKCD	-0.032	0.16	0.29	17	-0.37	35	52
PRKCG	-0.031	0.16	0.29	17	-0.33	49	66
regulation of vascular smooth muscle contraction	-0.23	0.44	0.54	8	-1.1	110	118
PRKCQ	-0.033	0.16	0.28	18	-0.37	39	57
PLA2G4A	-0.17	0.28	0.43	9	-0.58	131	140
GNA14	0.003	0.028	0.22	2	-0.39	2	4
GNA15	0.001	0.038	-10000	0	-0.39	5	5
GNA12	0.006	0	-10000	0	-10000	0	0
GNA11	-0.13	0.18	-10000	0	-0.39	193	193
Rac1/GTP	0.016	0.18	0.37	92	-0.33	19	111
MMP1	0.05	0.11	0.42	38	-10000	0	38

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.029	0.081	-10000	0	-0.2	105	105
NF kappa B1 p50/RelA/I kappa B alpha	-0.051	0.097	-10000	0	-0.26	62	62
AP1	-0.05	0.12	0.16	37	-0.2	175	212
mol:PIP3	-0.065	0.1	-10000	0	-0.21	171	171
AKT1	-0.034	0.091	-10000	0	-0.28	26	26
PTK2B	-0.037	0.079	0.16	16	-0.19	103	119
RHOA	-0.014	0.055	-10000	0	-0.4	2	2
PIK3CB	0.021	0.059	0.22	41	-0.38	1	42
mol:Ca2+	-0.051	0.072	-10000	0	-0.2	72	72
MAGI3	0.011	0.03	0.22	11	-10000	0	11
RELA	0.005	0.023	-10000	0	-0.38	2	2
apoptosis	-0.025	0.087	0.18	24	-0.2	99	123
HRAS/GDP	0.005	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.035	0.07	0.15	11	-0.17	97	108
NF kappa B1 p50/RelA	-0.054	0.11	0.18	39	-0.21	133	172
endothelial cell migration	-0.072	0.2	0.42	16	-0.49	101	117
ADCY4	-0.032	0.1	0.21	17	-0.23	96	113
ADCY5	-0.032	0.1	0.21	17	-0.23	96	113
ADCY6	-0.033	0.1	0.21	17	-0.23	96	113
ADCY7	-0.033	0.1	0.21	17	-0.23	96	113
ADCY1	-0.033	0.1	0.21	17	-0.23	96	113
ADCY2	-0.033	0.1	0.21	17	-0.23	96	113
ADCY3	-0.032	0.1	0.21	17	-0.23	96	113
ADCY8	-0.094	0.12	0.21	7	-0.21	248	255
ADCY9	-0.048	0.12	0.21	17	-0.27	102	119
GSK3B	-0.037	0.075	0.15	16	-0.18	103	119
arachidonic acid secretion	-0.032	0.097	0.2	16	-0.22	98	114
GNG2	0.004	0.034	0.22	1	-0.38	4	5
TRIP6	-0.007	0.031	-10000	0	-0.34	3	3
GNAO1	-0.032	0.098	0.22	21	-0.22	102	123
HRAS	0.006	0	-10000	0	-10000	0	0
NFKBIA	-0.058	0.097	-10000	0	-0.27	61	61
GAB1	0.004	0.033	-10000	0	-0.38	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.01	0.038	-10000	0	-0.86	1	1
JUN	0.008	0.039	0.22	9	-0.38	3	12
LPA/LPA2/NHERF2	-0.021	0.06	-10000	0	-0.12	119	119
TIAM1	0.007	0.044	-10000	0	-1	1	1
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.052	0.073	-10000	0	-0.2	72	72
PLCB3	-0.021	0.055	-10000	0	-0.22	28	28
FOS	-0.066	0.16	0.22	8	-0.38	110	118
positive regulation of mitosis	-0.032	0.097	0.2	16	-0.22	98	114
LPA/LPA1-2-3	-0.031	0.076	-10000	0	-0.19	101	101
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
stress fiber formation	-0.03	0.092	0.19	16	-0.22	53	69
GNAZ	-0.035	0.097	0.24	16	-0.22	106	122
EGFR/PI3K-beta/Gab1	-0.066	0.11	-10000	0	-0.21	171	171
positive regulation of dendritic cell cytokine production	-0.031	0.076	-10000	0	-0.19	101	101
LPA/LPA2/MAGI-3	-0.01	0.032	-10000	0	-10000	0	0
ARHGEF1	-0.03	0.08	0.2	16	-0.18	102	118
GNAI2	-0.033	0.095	0.24	16	-0.22	101	117
GNAI3	-0.025	0.1	0.19	42	-0.22	98	140
GNAI1	-0.036	0.1	0.22	21	-0.23	106	127
LPA/LPA3	-0.017	0.038	-10000	0	-0.099	101	101
LPA/LPA2	-0.017	0.038	-10000	0	-0.098	101	101
LPA/LPA1	-0.044	0.1	-10000	0	-0.26	101	101
HB-EGF/EGFR	0.007	0.086	0.19	16	-0.23	47	63
HBEGF	0.025	0.072	0.2	79	-10000	0	79
mol:DAG	-0.052	0.073	-10000	0	-0.2	72	72
cAMP biosynthetic process	-0.043	0.1	0.19	17	-0.24	100	117
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
SRC	0.006	0	-10000	0	-10000	0	0
GNB1	0.005	0.017	-10000	0	-0.38	1	1
LYN	-0.06	0.097	-10000	0	-0.26	67	67
GNAQ	-0.015	0.051	0.1	16	-0.23	16	32
LPAR2	0	0.001	-10000	0	-10000	0	0
LPAR3	0	0.001	-10000	0	-10000	0	0
LPAR1	-0.024	0.064	0.13	16	-0.15	101	117
IL8	-0.018	0.2	0.48	46	-0.37	52	98
PTK2	-0.009	0.092	0.16	63	-0.18	93	156
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
CASP3	-0.025	0.088	0.18	24	-0.2	99	123
EGFR	-0.03	0.12	0.23	1	-0.38	54	55
PLCG1	-0.049	0.07	0.1	11	-0.13	189	200
PLD2	-0.023	0.08	0.2	16	-0.18	101	117
G12/G13	-0.027	0.08	-10000	0	-0.2	102	102
PI3K-beta	-0.044	0.089	-10000	0	-0.31	28	28
cell migration	-0.006	0.05	0.19	2	-0.27	1	3
SLC9A3R2	-0.013	0.085	-10000	0	-0.38	28	28
PXN	-0.03	0.093	0.19	16	-0.23	52	68
HRAS/GTP	-0.033	0.098	0.2	16	-0.22	98	114
RAC1	0.006	0.016	-10000	0	-0.38	1	1
MMP9	0.036	0.074	0.22	77	-10000	0	77
PRKCE	0.007	0.009	0.22	1	-10000	0	1
PRKCD	-0.05	0.071	-10000	0	-0.2	71	71
Gi(beta/gamma)	-0.031	0.1	0.21	17	-0.22	96	113
mol:LPA	-0.024	0.064	0.13	16	-0.15	101	117
TRIP6/p130 Cas/FAK1/Paxillin	-0.02	0.098	0.2	16	-0.2	89	105
MAPKKK cascade	-0.032	0.097	0.2	16	-0.22	98	114
contractile ring contraction involved in cytokinesis	-0.014	0.055	-10000	0	-0.4	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.009	0.039	0.1	17	-0.082	97	114
GNA15	-0.011	0.043	0.1	16	-0.25	5	21
GNA12	0.006	0	-10000	0	-10000	0	0
GNA13	0.006	0.016	-10000	0	-0.39	1	1
MAPT	-0.036	0.071	0.15	11	-0.17	97	108
GNA11	-0.082	0.11	0.1	11	-0.23	188	199
Rac1/GTP	0.01	0.04	-10000	0	-0.92	1	1
MMP2	-0.072	0.2	0.42	16	-0.49	101	117

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.067	0.16	0.22	6	-0.38	110	116
HRAS	0.006	0	-10000	0	-10000	0	0
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
AKT	-0.11	0.16	0.21	12	-0.27	219	231
FOXO3	0.001	0.046	-10000	0	-0.38	8	8
AKT1	0.007	0.009	0.22	1	-10000	0	1
FOXO1	0	0.049	-10000	0	-0.38	9	9
AKT3	-0.22	0.2	0.22	4	-0.38	337	341
FOXO4	0.006	0	-10000	0	-10000	0	0
MET	-0.013	0.12	0.22	32	-0.38	45	77
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PIK3CB	0.021	0.058	0.22	41	-0.38	1	42
NRAS	0.099	0.11	0.22	245	-10000	0	245
PIK3CG	0.013	0.037	0.22	17	-10000	0	17
PIK3R3	0.061	0.094	0.22	144	-10000	0	144
PIK3R2	0.007	0.013	0.22	2	-10000	0	2
NF1	-0.01	0.079	0.22	1	-0.38	24	25
RAS	0.015	0.11	0.18	54	-0.28	30	84
ERBB2	0.005	0.039	0.22	5	-0.38	4	9
proliferation/survival/translation	0.065	0.11	0.21	126	-0.18	7	133
PI3K	0.009	0.12	0.19	60	-0.28	42	102
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
KRAS	0.03	0.067	0.22	62	-10000	0	62
FOXO	0.019	0.043	0.18	15	-10000	0	15
AKT2	0.009	0.024	0.22	7	-10000	0	7
PTEN	-0.001	0.054	-10000	0	-0.38	11	11

×

Thromboxane A2 receptor 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
TGM2	-0.2	0.2	0.22	2	-0.39	295	297
GNB1/GNG2	-0.06	0.071	-10000	0	-0.19	94	94
AKT1	-0.022	0.19	0.36	86	-10000	0	86
EGF	0.009	0.024	0.22	7	-10000	0	7
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.008	0.034	-10000	0	-10000	0	0
mol:Ca2+	-0.062	0.25	0.44	86	-0.36	67	153
LYN	-0.013	0.047	-10000	0	-0.31	2	2
RhoA/GTP	-0.053	0.058	-10000	0	-0.13	106	106
mol:PGI2	0	0.001	-10000	0	-10000	0	0
SYK	-0.061	0.26	0.45	86	-0.37	88	174
GNG2	0.004	0.034	0.22	1	-0.38	4	5
ARRB2	0.006	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.11	0.16	-10000	0	-0.33	198	198
G beta5/gamma2	-0.062	0.11	0.17	40	-0.26	88	128
PRKCH	-0.073	0.27	0.45	87	-0.4	88	175
DNM1	0.006	0	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3	0.03	0.03	-10000	0	-10000	0	0
mol:GTP	0.001	0.005	-10000	0	-10000	0	0
PTGDR	0.006	0.016	-10000	0	-0.38	1	1
G12 family/GTP	-0.12	0.13	-10000	0	-0.25	270	270
ADRBK1	0.006	0	-10000	0	-10000	0	0
ADRBK2	-0.006	0.071	0.22	1	-0.38	19	20
RhoA/GTP/ROCK1	0.007	0.014	-10000	0	-0.23	2	2
mol:GDP	0.035	0.18	0.46	15	-0.31	85	100
mol:NADP	0.006	0.001	-10000	0	-10000	0	0
RAB11A	0.006	0	-10000	0	-10000	0	0
PRKG1	0.007	0.009	0.22	1	-10000	0	1
mol:IP3	-0.089	0.29	0.46	86	-0.43	87	173
cell morphogenesis	0.007	0.014	-10000	0	-0.23	2	2
PLCB2	-0.14	0.35	0.49	84	-0.61	88	172
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.007	0.035	-10000	0	-10000	0	0
mol:PDG2	0	0.001	-10000	0	-10000	0	0
HCK	-0.007	0.035	-10000	0	-10000	0	0
RHOA	0.005	0.023	-10000	0	-0.38	2	2
PTGIR	0.005	0.023	-10000	0	-0.38	2	2
PRKCB1	-0.082	0.28	0.46	86	-0.43	87	173
GNAQ	-0.005	0.065	-10000	0	-0.38	16	16
mol:L-citrulline	0.006	0.001	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.11	0.34	0.51	86	-0.58	87	173
LCK	-0.008	0.034	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.006	0.017	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.004	0.024	-10000	0	-0.46	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.006	0.017	-10000	0	-10000	0	0
MAPK14	-0.03	0.2	0.38	86	-0.25	63	149
TGM2/GTP	-0.13	0.33	0.49	84	-0.43	269	353
MAPK11	-0.03	0.2	0.38	86	-0.25	58	144
ARHGEF1	-0.029	0.16	0.3	84	-0.2	8	92
GNAI2	0.006	0	-10000	0	-10000	0	0
JNK cascade	-0.071	0.28	0.48	86	-0.42	87	173
RAB11/GDP	0.004	0.01	-10000	0	-10000	0	0
ICAM1	-0.033	0.24	0.44	86	-0.32	64	150
cAMP biosynthetic process	-0.1	0.27	0.43	84	-0.39	97	181
Gq family/GTP/EBP50	-0.14	0.17	-10000	0	-0.29	276	276
actin cytoskeleton reorganization	0.007	0.014	-10000	0	-0.23	2	2
SRC	-0.008	0.034	-10000	0	-10000	0	0
GNB5	0.002	0.043	-10000	0	-0.38	7	7
GNB1	0.006	0.016	-10000	0	-0.38	1	1
EGF/EGFR	-0.023	0.058	-10000	0	-0.22	17	17
VCAM1	-0.04	0.26	0.47	87	-0.39	88	175
TP beta/Gq family/GDP/G beta5/gamma2	-0.11	0.16	-10000	0	-0.33	198	198
platelet activation	-0.056	0.24	0.44	86	-0.34	64	150
PGI2/IP	0.004	0.016	-10000	0	-0.27	2	2
PRKACA	0.001	0.016	-10000	0	-0.2	3	3
Gq family/GDP/G beta5/gamma2	-0.1	0.15	-10000	0	-0.3	198	198
TXA2/TP beta/beta Arrestin2	0.028	0.03	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.002	0.016	-10000	0	-0.19	3	3
mol:DAG	-0.096	0.3	0.48	84	-0.49	87	171
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
TXA2/TP alpha	-0.15	0.34	0.49	84	-0.54	107	191
Gq family/GTP	-0.064	0.097	-10000	0	-0.19	200	200
YES1	-0.005	0.039	-10000	0	-10000	0	0
GNAI2/GTP	-0.006	0.035	-10000	0	-0.17	7	7
PGD2/DP	0.004	0.012	-10000	0	-0.27	1	1
SLC9A3R1	-0.097	0.17	-10000	0	-0.38	151	151
FYN	-0.025	0.066	-10000	0	-0.3	10	10
mol:NO	0.006	0.001	-10000	0	-10000	0	0
GNA15	0.003	0.037	-10000	0	-0.38	5	5
PGK/cGMP	0.007	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.002	0.024	-10000	0	-0.38	2	2
TP alpha/TGM2/GDP/G beta/gamma	-0.087	0.09	-10000	0	-0.34	3	3
NOS3	0.006	0.001	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCA	-0.072	0.27	0.45	86	-0.4	90	176
PRKCB	-0.07	0.27	0.45	87	-0.4	87	174
PRKCE	-0.069	0.27	0.46	86	-0.4	87	173
PRKCD	-0.074	0.28	0.46	86	-0.42	88	174
PRKCG	-0.083	0.28	0.46	86	-0.44	87	173
muscle contraction	-0.11	0.32	0.49	86	-0.54	87	173
PRKCZ	-0.06	0.26	0.45	86	-0.37	87	173
ARR3	0.006	0	-10000	0	-10000	0	0
TXA2/TP beta	-0.001	0.04	-10000	0	-10000	0	0
PRKCQ	-0.071	0.27	0.45	87	-0.4	93	180
MAPKKK cascade	-0.11	0.32	0.48	86	-0.52	88	174
SELE	-0.038	0.23	0.43	86	-0.31	64	150
TP beta/GNAI2/GDP/G beta/gamma	0.007	0.022	-10000	0	-10000	0	0
ROCK1	0.007	0.009	0.22	1	-10000	0	1
GNA14	0.006	0.026	0.22	2	-0.38	2	4
chemotaxis	-0.11	0.36	0.53	86	-0.62	87	173
GNA12	0.006	0	-10000	0	-10000	0	0
GNA13	0.006	0.016	-10000	0	-0.38	1	1
GNA11	-0.13	0.18	-10000	0	-0.38	193	193
Rac1/GTP	0.001	0.013	-10000	0	-0.27	1	1

×

mTOR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.006	0	-10000	0	-10000	0	0
MKNK1	0.006	0	-10000	0	-10000	0	0
mol:PIP3	-0.13	0.14	0.2	1	-0.26	254	255
FRAP1	-0.012	0.036	-10000	0	-10000	0	0
AKT1	-0.11	0.12	0.17	1	-0.23	251	252
INSR	-0.02	0.098	-10000	0	-0.38	38	38
Insulin Receptor/Insulin	-0.007	0.058	-10000	0	-0.22	38	38
mol:GTP	-0.086	0.1	-10000	0	-0.19	207	207
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.036	0.039	-10000	0	-10000	0	0
TSC2	0.006	0	-10000	0	-10000	0	0
RHEB/GDP	-0.079	0.082	-10000	0	-0.27	30	30
TSC1	0.006	0.016	-10000	0	-0.38	1	1
Insulin Receptor/IRS1	-0.17	0.16	-10000	0	-0.31	320	320
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.039	0.044	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.006	0	-10000	0	-10000	0	0
RPS6KB1	-0.048	0.073	0.18	1	-0.21	23	24
MAP3K5	-0.002	0.036	0.23	1	-0.32	7	8
PIK3R1	-0.038	0.12	-10000	0	-0.39	64	64
apoptosis	-0.002	0.036	0.23	1	-0.32	7	8
mol:LY294002	-0.001	0.001	-10000	0	-0.001	311	311
EIF4B	-0.044	0.067	0.17	1	-10000	0	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.04	0.065	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.013	0.022	-10000	0	-10000	0	0
KIAA1303	0.006	0	-10000	0	-10000	0	0
PI3K	-0.14	0.16	0.14	1	-0.25	341	342
mTOR/RHEB/GTP/Raptor/GBL	-0.024	0.055	0.18	1	-10000	0	1
FKBP1A	0.005	0.003	-10000	0	-10000	0	0
RHEB/GTP	-0.076	0.085	-10000	0	-0.27	30	30
mol:Amino Acids	-0.001	0.001	-10000	0	-0.001	311	311
FKBP12/Rapamycin	0.004	0.004	-10000	0	-10000	0	0
PDPK1	-0.12	0.13	0.18	1	-0.24	254	255
EIF4E	0.006	0	-10000	0	-10000	0	0
ASK1/PP5C	-0.007	0.069	-10000	0	-0.58	7	7
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.014	0.028	-10000	0	-10000	0	0
TSC1/TSC2	-0.091	0.11	-10000	0	-0.21	207	207
tumor necrosis factor receptor activity	0.001	0.001	0.001	311	-10000	0	311
RPS6	0.006	0	-10000	0	-10000	0	0
PPP5C	0.007	0.009	0.22	1	-10000	0	1
EIF4G1	0.006	0	-10000	0	-10000	0	0
IRS1	-0.17	0.16	-10000	0	-0.32	311	311
INS	0.006	0	-10000	0	-10000	0	0
PTEN	-0.001	0.054	-10000	0	-0.38	11	11
PDK2	-0.12	0.13	0.18	1	-0.24	255	256
EIF4EBP1	0.008	0.009	-10000	0	-10000	0	0
PIK3CA	0.055	0.091	0.22	131	-10000	0	131
PPP2R5D	-0.012	0.034	-10000	0	-10000	0	0
peptide biosynthetic process	-0.024	0.06	-10000	0	-0.21	55	55
RHEB	0.017	0.047	0.22	28	-10000	0	28
EIF4A1	0.006	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.002	11	-10000	0	11
EEF2	-0.024	0.06	-10000	0	-0.21	55	55
eIF4E/4E-BP1	0.011	0.006	-10000	0	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.12	0.12	-10000	0	-0.21	342	342
TC10/GTP	-0.006	0.052	-10000	0	-0.18	49	49
Insulin Receptor/Insulin/IRS1/Shp2	-0.12	0.13	-10000	0	-0.23	320	320
HRAS	0.006	0	-10000	0	-10000	0	0
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.015	0.042	0.22	22	-10000	0	22
FOXO3	-0.03	0.089	-10000	0	-0.74	8	8
AKT1	-0.093	0.11	0.22	1	-0.32	50	51
INSR	-0.02	0.098	-10000	0	-0.39	38	38
Insulin Receptor/Insulin	0.002	0.05	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.007	0.009	0.22	1	-10000	0	1
SORBS1	-0.027	0.11	-10000	0	-0.38	49	49
CRK	0.006	0	-10000	0	-10000	0	0
PTPN1	-0.017	0.044	-10000	0	-10000	0	0
CAV1	-0.15	0.13	0.14	3	-0.23	367	370
CBL/APS/CAP/Crk-II/C3G	-0.003	0.058	-10000	0	-0.19	49	49
Insulin Receptor/Insulin/IRS1/NCK2	-0.12	0.13	-10000	0	-0.23	320	320
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.11	0.12	-10000	0	-0.22	273	273
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.12	0.15	-10000	0	-0.55	39	39
RPS6KB1	-0.085	0.11	0.22	2	-0.3	45	47
PARD6A	0.006	0.016	-10000	0	-0.38	1	1
CBL	0.006	0	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.005	0.031	-10000	0	-0.73	1	1
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.1	0.095	-10000	0	-0.3	55	55
HRAS/GTP	-0.1	0.09	-10000	0	-0.18	301	301
Insulin Receptor	-0.02	0.098	-10000	0	-0.39	38	38
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.11	0.12	-10000	0	-0.21	321	321
PRKCI	0.042	0.074	0.22	1	-10000	0	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.1	0.11	-10000	0	-0.21	258	258
SHC1	0.006	0	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.022	0.049	-10000	0	-0.63	1	1
PI3K	-0.11	0.12	-10000	0	-0.22	273	273
NCK2	0.006	0	-10000	0	-10000	0	0
RHOQ	0.007	0.016	0.22	3	-10000	0	3
mol:H2O2	-0.003	0.006	-10000	0	-10000	0	0
HRAS/GDP	0.005	0	-10000	0	-10000	0	0
AKT2	-0.091	0.12	0.23	2	-0.31	55	57
PRKCZ	-0.028	0.034	-10000	0	-10000	0	0
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.11	0.1	-10000	0	-0.2	320	320
F2RL2	0.006	0	-10000	0	-10000	0	0
TRIP10	0.006	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.051	-10000	0	-0.19	38	38
TC10/GTP/CIP4/Exocyst	0.009	0.001	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.01	0.055	-10000	0	-0.18	37	37
RAPGEF1	0.006	0	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
NCK1	0.024	0.059	0.22	47	-10000	0	47
CBL/APS/CAP/Crk-II	-0.006	0.061	-10000	0	-0.2	49	49
TC10/GDP	0.005	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.003	0.053	-10000	0	-0.19	38	38
INPP5D	-0.12	0.11	-10000	0	-0.21	320	320
SOS1	0.014	0.04	0.22	20	-10000	0	20
SGK1	-0.012	0.011	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.006	0	-10000	0	-10000	0	0
IRS1	-0.21	0.2	-10000	0	-0.38	311	311
p62DOK/RasGAP	0.023	0.049	-10000	0	-0.64	1	1
INS	0.004	0.009	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.12	0.11	-10000	0	-0.21	320	320
GRB2	0.006	0.016	-10000	0	-0.38	1	1
EIF4EBP1	-0.087	0.11	0.21	1	-0.3	46	47
PTPRA	0.004	0.012	0.2	1	-10000	0	1
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
TC10/GTP/CIP4	0.009	0.001	-10000	0	-10000	0	0
PDPK1	0.006	0	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.12	0.12	-10000	0	-0.35	38	38
Insulin Receptor/Insulin/IRS1	-0.12	0.12	-10000	0	-0.23	320	320
Insulin Receptor/Insulin/IRS3	-0.009	0.071	-10000	0	-0.27	38	38
Par3/Par6	0.015	0.012	-10000	0	-0.19	1	1

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.11	0.052	0.26	44	-10000	0	44
BIRC5	0.032	0.07	0.22	69	-10000	0	69
NFKBIA	0.11	0.037	-10000	0	-10000	0	0
CPEB1	0.006	0	-10000	0	-10000	0	0
AKT1	0.11	0.033	0.32	1	-10000	0	1
NDEL1	0.006	0	-10000	0	-10000	0	0
Aurora A/BRCA1	0	0.001	-10000	0	-10000	0	0
NDEL1/TACC3	0.051	0.046	-10000	0	-10000	0	0
GADD45A	0.024	0.059	0.22	46	-10000	0	46
GSK3B	0.007	0.004	-10000	0	-10000	0	0
PAK1/Aurora A	0.1	0.039	0.27	17	-10000	0	17
MDM2	0.007	0.024	0.22	4	-0.38	1	5
JUB	0.021	0.054	0.22	38	-10000	0	38
TPX2	0.19	0.033	0.2	554	-10000	0	554
TP53	0.053	0.098	0.23	7	-0.24	6	13
DLG7	0.29	0.07	0.31	527	-10000	0	527
AURKAIP1	-0.005	0.067	-10000	0	-0.38	17	17
ARHGEF7	0.007	0.009	0.22	1	-10000	0	1
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.14	0.076	0.24	219	-10000	0	219
G2/M transition of mitotic cell cycle	0	0.001	-10000	0	-10000	0	0
AURKA	0.14	0.04	-10000	0	-10000	0	0
AURKB	0.06	0.043	0.14	112	-10000	0	112
CDC25B	0.11	0.036	0.19	40	-10000	0	40
G2/M transition checkpoint	0.001	0.006	0.14	1	-10000	0	1
mRNA polyadenylation	0	0.001	-10000	0	-10000	0	0
Aurora A/CPEB	0	0.001	-10000	0	-10000	0	0
Aurora A/TACC1/TRAP/chTOG	-0.038	0.097	0.23	26	-0.2	20	46
BRCA1	0.018	0.048	0.22	30	-10000	0	30
centrosome duplication	0.1	0.039	0.26	17	-10000	0	17
regulation of centrosome cycle	0.002	0.013	-10000	0	-10000	0	0
spindle assembly	-0.049	0.078	-10000	0	-0.19	21	21
TDRD7	0.007	0.038	0.22	8	-0.38	3	11
Aurora A/RasGAP/Survivin	0.07	0.037	-10000	0	-10000	0	0
CENPA	0.076	0.032	0.13	115	-10000	0	115
Aurora A/PP2A	0.097	0.026	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.15	0.085	0.22	274	-10000	0	274
negative regulation of DNA binding	0.053	0.098	0.23	7	-0.24	6	13
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.009	0.001	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
Ajuba/Aurora A	0.001	0.006	0.14	1	-10000	0	1
mitotic prometaphase	0	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.14	0.04	-10000	0	-10000	0	0
TACC1	-0.3	0.16	-10000	0	-0.38	440	440
TACC3	0.095	0.11	0.22	233	-10000	0	233
Aurora A/Antizyme1	0.007	0.11	-10000	0	-0.26	21	21
Aurora A/RasGAP	0.096	0.027	-10000	0	-10000	0	0
OAZ1	-0.14	0.19	-10000	0	-0.38	219	219
RAN	0.006	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.007	0.004	-10000	0	-10000	0	0
GIT1	0.007	0.009	0.22	1	-10000	0	1
GIT1/beta-PIX/PAK1	0.012	0.01	-10000	0	-0.23	1	1
Importin alpha/Importin beta/TPX2	0.19	0.033	0.2	554	-10000	0	554
PPP2R5D	0.006	0	-10000	0	-10000	0	0
Aurora A/TPX2	0.24	0.04	0.25	533	-10000	0	533
PAK1	0.012	0.041	0.22	18	-0.38	1	19
CKAP5	0.05	0.087	0.22	115	-10000	0	115

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.26	0.62	0.92	3	-1.3	100	103
STAT6 (cleaved dimer)	-0.41	0.53	-10000	0	-1.2	160	160
IGHG1	-0.052	0.28	0.6	24	-1.2	4	28
IGHG3	-0.26	0.58	0.77	3	-1.2	105	108
AKT1	-0.16	0.37	0.57	2	-0.94	46	48
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.12	0.35	0.52	5	-1.1	39	44
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.25	0.41	0.62	2	-0.93	88	90
THY1	-0.22	0.66	1.1	23	-1.3	90	113
MYB	-0.025	0.11	0.22	1	-0.38	46	47
HMGA1	0.007	0.032	0.22	6	-0.38	2	8
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.14	0.42	0.67	24	-0.91	48	72
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.15	0.41	0.61	5	-1.2	38	43
SP1	0.073	0.11	0.24	169	-10000	0	169
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.003	0.033	0.22	3	-10000	0	3
STAT6 (dimer)/ETS1	-0.31	0.62	-10000	0	-1.3	124	124
SOCS1	-0.19	0.41	-10000	0	-0.8	108	108
SOCS3	-0.13	0.37	-10000	0	-1	29	29
FCER2	-0.15	0.45	0.89	4	-0.88	56	60
PARP14	0.053	0.096	0.22	128	-0.38	3	131
CCL17	-0.27	0.62	0.92	3	-1.3	100	103
GRB2	0.006	0.016	-10000	0	-0.38	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.098	0.31	0.54	8	-0.76	35	43
T cell proliferation	-0.34	0.68	-10000	0	-1.4	128	128
IL4R/JAK1	-0.36	0.7	-10000	0	-1.5	132	132
EGR2	-0.26	0.62	1	3	-1.3	100	103
JAK2	0.002	0.079	0.2	23	-0.4	4	27
JAK3	0.006	0.011	-10000	0	-10000	0	0
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
JAK1	0.005	0.041	-10000	0	-0.38	3	3
COL1A2	0.024	0.36	0.63	60	-1.3	9	69
CCL26	-0.27	0.62	0.92	3	-1.3	100	103
IL4R	-0.36	0.79	0.99	13	-1.6	128	141
PTPN6	0.004	0.026	-10000	0	-10000	0	0
IL13RA2	-0.26	0.62	0.95	4	-1.3	95	99
IL13RA1	-0.006	0.097	0.23	3	-0.42	15	18
IRF4	-0.019	0.17	-10000	0	-10000	0	0
ARG1	-0.035	0.24	0.6	3	-0.86	7	10
CBL	-0.14	0.39	0.63	8	-0.86	48	56
GTF3A	0.11	0.12	0.24	246	-10000	0	246
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
IL13RA1/JAK2	0.009	0.12	0.29	26	-0.31	18	44
IRF4/BCL6	-0.028	0.15	-10000	0	-10000	0	0
CD40LG	0.008	0.014	0.25	2	-10000	0	2
MAPK14	-0.14	0.39	0.65	5	-0.98	38	43
mitosis	-0.15	0.35	0.56	3	-0.86	46	49
STAT6	-0.31	0.75	1.1	24	-1.5	101	125
SPI1	0.003	0.041	0.2	1	-0.38	6	7
RPS6KB1	-0.15	0.34	0.58	3	-0.85	42	45
STAT6 (dimer)	-0.31	0.75	1.1	24	-1.5	101	125
STAT6 (dimer)/PARP14	-0.28	0.65	0.87	2	-1.4	106	108
mast cell activation	0.001	0.023	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.14	0.4	0.62	5	-1.1	43	48
FRAP1	-0.16	0.37	0.57	2	-0.94	46	48
LTA	-0.27	0.62	0.92	3	-1.3	100	103
FES	0.006	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.29	0.72	1.5	101	-1.1	24	125
CCL11	-0.25	0.6	0.88	15	-1.2	100	115
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.14	0.4	0.6	5	-1.1	43	48
IL2RG	-0.007	0.11	0.23	31	-0.37	37	68
IL10	-0.27	0.62	0.92	3	-1.3	100	103
IRS1	-0.21	0.2	-10000	0	-0.38	311	311
IRS2	0.006	0	-10000	0	-10000	0	0
IL4	-0.007	0.23	0.7	13	-10000	0	13
IL5	-0.27	0.62	0.92	3	-1.3	100	103
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.2	0.57	0.93	24	-1	99	123
COL1A1	0.11	0.42	0.81	75	-1.5	5	80
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.38	0.71	-10000	0	-1.5	128	128
IL2R gamma/JAK3	-0.008	0.067	0.26	1	-0.26	37	38
TFF3	-0.89	0.6	0.92	2	-1.3	290	292
ALOX15	-0.27	0.62	0.92	3	-1.3	100	103
MYBL1	0.034	0.072	0.22	72	-10000	0	72
T-helper 2 cell differentiation	-0.22	0.54	0.79	8	-1	113	121
SHC1	0.006	0	-10000	0	-10000	0	0
CEBPB	0.005	0.035	0.21	2	-0.38	4	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.14	0.4	0.6	5	-1.2	37	42
mol:PI-3-4-5-P3	-0.16	0.37	0.57	2	-0.94	46	48
PI3K	-0.18	0.4	0.58	2	-1	50	52
DOK2	0.007	0.009	0.22	1	-10000	0	1
ETS1	0	0.043	0.23	4	-0.35	1	5
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.092	0.3	0.53	8	-0.74	36	44
ITGB3	-0.34	0.72	1.1	5	-1.4	128	133
PIGR	-0.48	0.75	0.99	6	-1.4	174	180
IGHE	-0.027	0.093	-10000	0	-0.26	41	41
MAPKKK cascade	-0.09	0.3	0.53	8	-0.73	35	43
BCL6	-0.004	0.063	-10000	0	-0.38	15	15
OPRM1	-0.27	0.62	0.92	3	-1.3	100	103
RETNLB	-0.27	0.62	0.92	3	-1.3	100	103
SELP	-0.31	0.66	0.95	4	-1.3	118	122
AICDA	-0.26	0.58	-10000	0	-1.2	100	100

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.081	0.16	-10000	0	-0.38	127	127
CCL5	-0.037	0.13	0.22	6	-0.38	66	72
SDCBP	0.006	0.026	0.22	2	-0.38	2	4
FGFR/FGF2/Syndecan-1	-0.042	0.17	0.22	44	-0.42	52	96
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.041	0.16	0.2	42	-0.4	52	94
Syndecan-1/Syntenin	-0.041	0.16	0.2	41	-0.4	52	93
MAPK3	-0.053	0.16	0.26	5	-0.38	66	71
HGF/MET	-0.013	0.075	-10000	0	-0.27	45	45
TGFB1/TGF beta receptor Type II	-0.081	0.16	-10000	0	-0.38	127	127
BSG	0.006	0	-10000	0	-10000	0	0
keratinocyte migration	-0.04	0.16	0.2	42	-0.4	52	94
Syndecan-1/RANTES	-0.06	0.19	0.2	43	-0.44	76	119
Syndecan-1/CD147	-0.041	0.15	-10000	0	-0.39	52	52
Syndecan-1/Syntenin/PIP2	-0.055	0.14	-10000	0	-0.39	52	52
LAMA5	0.007	0.013	0.22	2	-10000	0	2
positive regulation of cell-cell adhesion	-0.054	0.14	-10000	0	-0.38	52	52
MMP7	-0.069	0.2	0.22	69	-0.38	148	217
HGF	0.008	0.018	0.22	4	-10000	0	4
Syndecan-1/CASK	-0.044	0.16	0.19	44	-0.4	52	96
Syndecan-1/HGF/MET	-0.047	0.17	0.25	15	-0.39	69	84
regulation of cell adhesion	-0.054	0.15	0.26	5	-0.37	66	71
HPSE	0.012	0.036	0.22	16	-10000	0	16
positive regulation of cell migration	-0.042	0.17	0.22	44	-0.42	52	96
SDC1	-0.038	0.17	0.22	44	-0.42	52	96
Syndecan-1/Collagen	-0.042	0.17	0.22	44	-0.42	52	96
PPIB	0.006	0	-10000	0	-10000	0	0
MET	-0.013	0.12	0.22	32	-0.38	45	77
PRKACA	0.006	0	-10000	0	-10000	0	0
MMP9	0.035	0.074	0.22	77	-10000	0	77
MAPK1	-0.039	0.15	0.26	5	-0.37	52	57
homophilic cell adhesion	-0.042	0.17	0.22	44	-0.42	52	96
MMP1	0.049	0.086	0.22	114	-10000	0	114

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.11	0.18	-10000	0	-0.38	165	165
SVIL	-0.005	0.067	0.22	1	-0.38	17	18
ZNF318	0.006	0.009	0.22	1	-10000	0	1
JMJD2C	0.007	0.021	0.22	2	-0.39	1	3
T-DHT/AR/Ubc9	-0.15	0.12	-10000	0	-0.27	251	251
CARM1	0.007	0.009	0.22	1	-10000	0	1
PRDX1	0.006	0	-10000	0	-10000	0	0
PELP1	0.006	0	-10000	0	-10000	0	0
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
AKT1	0.007	0.009	0.22	1	-10000	0	1
PTK2B	0.005	0.023	-10000	0	-0.38	2	2
MED1	0.007	0.013	0.22	2	-10000	0	2
MAK	-0.083	0.16	0.22	2	-0.39	130	132
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	0.007	0.009	0.22	1	-10000	0	1
GSN	-0.032	0.12	-10000	0	-0.38	56	56
NCOA2	0.007	0.013	0.22	2	-10000	0	2
NCOA6	0.007	0.009	0.22	1	-10000	0	1
DNA-PK	0.009	0.005	-10000	0	-10000	0	0
NCOA4	0.006	0	-10000	0	-10000	0	0
PIAS3	0.007	0.009	0.22	1	-10000	0	1
cell proliferation	-0.2	0.29	0.22	1	-0.72	130	131
XRCC5	0.029	0.066	0.22	60	-10000	0	60
UBE3A	0.006	0	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.12	-10000	0	-0.28	251	251
FHL2	-0.093	0.073	0.44	1	-0.52	6	7
RANBP9	0.007	0.013	0.22	2	-10000	0	2
JMJD1A	-0.028	0.11	0.22	66	-10000	0	66
CDK6	0.004	0.057	0.22	10	-0.38	9	19
TGFB1I1	-0.03	0.11	-10000	0	-0.38	53	53
T-DHT/AR/CyclinD1	-0.21	0.15	-10000	0	-0.32	324	324
XRCC6	0.006	0	-10000	0	-10000	0	0
T-DHT/AR	-0.21	0.13	-10000	0	-0.3	325	325
CTDSP1	0.004	0.028	-10000	0	-0.38	3	3
CTDSP2	0.005	0.023	-10000	0	-0.39	2	2
BRCA1	0.018	0.048	0.22	30	-10000	0	30
TCF4	0.004	0.028	-10000	0	-0.38	3	3
CDKN2A	0.13	0.11	0.22	317	-10000	0	317
SRF	0.003	0.041	0.24	1	-0.39	6	7
NKX3-1	-0.12	0.13	-10000	0	-10000	0	0
KLK3	-0.011	0.063	-10000	0	-10000	0	0
TMF1	0.007	0.013	0.22	2	-10000	0	2
HNRNPA1	0.006	0	-10000	0	-10000	0	0
AOF2	0.007	0.009	0.22	1	-10000	0	1
APPL1	-0.004	0.008	0.2	1	-10000	0	1
T-DHT/AR/Caspase 8	-0.15	0.12	-10000	0	-0.27	251	251
AR	-0.21	0.19	-10000	0	-0.42	251	251
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.007	0.009	0.22	1	-10000	0	1
PAWR	0.006	0	-10000	0	-10000	0	0
PRKDC	0.048	0.085	0.22	110	-10000	0	110
PA2G4	0.007	0.009	0.22	1	-10000	0	1
UBE2I	0.006	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.14	0.11	-10000	0	-0.25	251	251
RPS6KA3	0.004	0.039	0.22	2	-0.38	5	7
T-DHT/AR/ARA70	-0.15	0.12	-10000	0	-0.27	251	251
LATS2	0.006	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	-0.14	0.11	-10000	0	-0.25	251	251
Cyclin D3/CDK11 p58	0.005	0	-10000	0	-10000	0	0
VAV3	0.03	0.068	0.22	63	-10000	0	63
KLK2	-0.089	0.058	-10000	0	-0.57	1	1
CASP8	0.006	0	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.14	0.11	-10000	0	-0.25	251	251
TMPRSS2	-0.52	0.41	-10000	0	-0.83	356	356
CCND1	-0.093	0.17	0.22	1	-0.38	145	146
PIAS1	0.007	0.009	0.22	1	-10000	0	1
mol:T-DHT	-0.037	0.031	-10000	0	-0.07	212	212
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.007	0	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.15	0.12	-10000	0	-0.28	252	252
CMTM2	0.006	0	-10000	0	-10000	0	0
SNURF	0.006	0.016	-10000	0	-0.38	1	1
ZMIZ1	-0.039	0.049	0.21	1	-0.39	5	6
CCND3	0.006	0	-10000	0	-10000	0	0
TGIF1	0.006	0	-10000	0	-10000	0	0
FKBP4	0.023	0.057	0.22	43	-10000	0	43

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	-0.013	0.1	0.22	15	-0.38	36	51
EPHB2	0.01	0.027	0.22	9	-10000	0	9
EFNB1	-0.003	0.026	-10000	0	-0.27	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.034	0.24	3	-0.18	5	8
Ephrin B2/EPHB1-2	0.007	0.062	0.15	14	-0.2	36	50
neuron projection morphogenesis	0.01	0.021	-10000	0	-0.17	7	7
Ephrin B1/EPHB1-2/Tiam1	0.02	0.037	0.27	3	-0.19	6	9
DNM1	0.007	0.002	-10000	0	-10000	0	0
cell-cell signaling	0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.11	0.23	0.24	1	-0.52	131	132
YES1	-0.16	0.32	0.23	1	-0.75	127	128
Ephrin B1/EPHB1-2/NCK2	0.02	0.035	0.27	3	-0.18	5	8
PI3K	-0.098	0.26	0.23	10	-0.47	160	170
mol:GDP	0.02	0.036	0.26	3	-0.18	6	9
ITGA2B	0.006	0	-10000	0	-10000	0	0
endothelial cell proliferation	-0.006	0.057	-10000	0	-0.22	36	36
FYN	-0.17	0.33	-10000	0	-0.78	127	127
MAP3K7	-0.12	0.24	0.21	2	-0.56	127	129
FGR	-0.16	0.32	-10000	0	-0.75	127	127
TIAM1	0.006	0.021	0.22	2	-0.38	1	3
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
RGS3	0.006	0	-10000	0	-10000	0	0
cell adhesion	-0.12	0.25	0.24	12	-0.53	136	148
LYN	-0.16	0.32	-10000	0	-0.76	127	127
Ephrin B1/EPHB1-2/Src Family Kinases	-0.15	0.3	-10000	0	-0.7	127	127
Ephrin B1/EPHB1-2	-0.13	0.26	-10000	0	-0.61	127	127
SRC	-0.16	0.32	-10000	0	-0.75	127	127
ITGB3	-0.045	0.14	0.22	13	-0.38	82	95
EPHB1	0.012	0.033	0.22	14	-10000	0	14
EPHB4	0.006	0	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
Ephrin B2/EPHB4	-0.006	0.057	-10000	0	-0.22	36	36
alphaIIb/beta3 Integrin	-0.031	0.098	-10000	0	-0.27	82	82
BLK	-0.16	0.32	-10000	0	-0.75	127	127
HCK	-0.16	0.32	-10000	0	-0.75	127	127
regulation of stress fiber formation	-0.019	0.034	0.18	5	-0.26	3	8
MAPK8	-0.11	0.22	0.22	1	-0.5	131	132
Ephrin B1/EPHB1-2/RGS3	0.02	0.035	0.27	3	-0.19	4	7
endothelial cell migration	-0.11	0.21	0.22	1	-0.44	149	150
NCK2	0.006	0	-10000	0	-10000	0	0
PTPN13	-0.094	0.22	0.21	34	-0.5	127	161
regulation of focal adhesion formation	-0.019	0.034	0.18	5	-0.26	3	8
chemotaxis	-0.019	0.034	0.19	4	-0.26	3	7
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
Rac1/GTP	0.013	0.022	-10000	0	-0.17	7	7
angiogenesis	-0.13	0.26	-10000	0	-0.6	127	127
LCK	-0.16	0.32	-10000	0	-0.75	127	127

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.009	0.002	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.024	0.087	-10000	0	-0.23	83	83
PTK2	-0.012	0.13	0.25	14	-0.31	72	86
IGF1R	-0.077	0.16	-10000	0	-0.38	121	121
PI4KB	0.008	0.018	0.22	4	-10000	0	4
MFGE8	-0.004	0.086	0.22	15	-0.38	23	38
SRC	0.006	0	-10000	0	-10000	0	0
CDKN1B	-0.012	0.052	-10000	0	-0.45	3	3
VEGFA	0.018	0.048	0.22	30	-10000	0	30
ILK	-0.012	0.039	-10000	0	-10000	0	0
ROCK1	0.007	0.009	0.22	1	-10000	0	1
AKT1	-0.013	0.035	-10000	0	-10000	0	0
PTK2B	-0.016	0.09	0.28	6	-0.2	82	88
alphaV/beta3 Integrin/JAM-A	-0.006	0.088	0.27	3	-0.2	82	85
CBL	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.023	0.086	-10000	0	-0.23	82	82
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.15	0.16	-10000	0	-0.26	339	339
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.011	0.084	0.21	6	-0.4	4	10
alphaV/beta3 Integrin/Syndecan-1	-0.024	0.086	-10000	0	-0.23	82	82
PI4KA	0.007	0.016	0.22	3	-10000	0	3
IGF-1R heterotetramer/IGF1/IRS1	-0.14	0.14	-10000	0	-0.26	280	280
PI4 Kinase	0.009	0.001	-10000	0	-10000	0	0
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
alphaV/beta3 Integrin/Osteopontin	-0.022	0.073	-10000	0	-0.24	48	48
RPS6KB1	-0.11	0.16	0.23	10	-0.32	135	145
TLN1	0.005	0.023	-10000	0	-0.38	2	2
MAPK3	-0.11	0.17	-10000	0	-0.46	86	86
GPR124	-0.012	0.082	-10000	0	-0.38	26	26
MAPK1	-0.093	0.16	-10000	0	-0.45	82	82
PXN	-0.002	0.056	-10000	0	-0.38	12	12
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
alphaV/beta3 Integrin/Tumstatin	-0.024	0.087	-10000	0	-0.23	83	83
cell adhesion	-0.023	0.1	0.29	2	-0.24	92	94
ANGPTL3	0.007	0.009	0.22	1	-10000	0	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.012	0.003	-10000	0	-10000	0	0
IGF-1R heterotetramer	-0.077	0.16	-10000	0	-0.38	121	121
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
TGFBR2	-0.003	0.058	-10000	0	-0.38	13	13
ITGB3	-0.045	0.14	0.22	13	-0.38	82	95
IGF1	-0.003	0.067	0.22	4	-0.38	16	20
RAC1	0.006	0.016	-10000	0	-0.38	1	1
regulation of cell-matrix adhesion	-0.034	0.1	-10000	0	-0.24	101	101
apoptosis	0.017	0.059	0.22	35	-0.38	3	38
CD47	0.02	0.056	0.22	37	-0.38	1	38
alphaV/beta3 Integrin/CD47	-0.024	0.085	-10000	0	-0.23	80	80
VCL	0.007	0.016	0.22	3	-10000	0	3
alphaV/beta3 Integrin/Del1	-0.025	0.086	-10000	0	-0.23	80	80
CSF1	-0.01	0.079	0.22	1	-0.38	24	25
PIK3C2A	-0.01	0.041	-10000	0	-10000	0	0
PI4 Kinase/Pyk2	-0.033	0.06	-10000	0	-0.33	2	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.002	0.094	-10000	0	-0.21	80	80
FAK1/Vinculin	-0.005	0.11	0.23	14	-0.26	72	86
alphaV beta3/Integrin/ppsTEM5	-0.034	0.1	-10000	0	-0.24	101	101
RHOA	0.005	0.023	-10000	0	-0.38	2	2
VTN	0.006	0	-10000	0	-10000	0	0
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
FGF2	0.006	0	-10000	0	-10000	0	0
F11R	-0.004	0.008	0.2	1	-10000	0	1
alphaV/beta3 Integrin/Lactadherin	-0.032	0.098	-10000	0	-0.24	96	96
alphaV/beta3 Integrin/TGFBR2	-0.028	0.095	-10000	0	-0.24	88	88
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.013	0.06	-10000	0	-0.21	28	28
HSP90AA1	0.006	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.011	0.09	0.14	42	-0.21	84	126
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.074	0.12	0.22	201	-0.38	13	214
alphaV/beta3 Integrin/Pyk2	-0.003	0.094	0.29	6	-0.2	82	88
SDC1	0.007	0.016	0.22	3	-10000	0	3
VAV3	0.008	0.073	0.27	8	-0.2	25	33
PTPN11	0.006	0	-10000	0	-10000	0	0
IRS1	-0.21	0.2	-10000	0	-0.38	311	311
FAK1/Paxillin	-0.008	0.11	0.23	14	-0.26	73	87
cell migration	-0.009	0.11	0.23	14	-0.24	72	86
ITGAV	0.017	0.06	0.22	35	-0.38	3	38
PI3K	-0.009	0.11	-10000	0	-0.2	108	108
SPP1	0.15	0.11	0.22	381	-0.38	3	384
KDR	0.007	0.013	0.22	2	-10000	0	2
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.017	0.059	0.22	35	-0.38	3	38
COL4A3	0.006	0	-10000	0	-10000	0	0
angiogenesis	-0.095	0.18	-10000	0	-0.49	83	83
Rac1/GTP	0.006	0.067	0.24	8	-0.18	26	34
EDIL3	0.032	0.073	0.22	69	-0.38	1	70
cell proliferation	-0.028	0.095	-10000	0	-0.24	88	88

×

IL23-mediated signaling events

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
CCL2	-0.013	0.54	1.1	40	-1.3	35	75
IL23A	-0.003	0.47	0.99	32	-1.1	21	53
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.32	-10000	0	-0.92	60	60
positive regulation of T cell mediated cytotoxicity	0.004	0.53	1.1	47	-0.98	58	105
ITGA3	-0.062	0.53	0.9	33	-1.2	48	81
IL17F	-0.003	0.35	0.68	44	-0.72	23	67
IL12B	0.036	0.095	0.29	47	-10000	0	47
STAT1 (dimer)	0.045	0.48	0.86	56	-0.97	44	100
CD4	-0.001	0.47	0.99	35	-1.1	22	57
IL23	-0.015	0.44	0.92	18	-1.1	20	38
IL23R	0.056	0.2	0.61	44	-10000	0	44
IL1B	0	0.48	1	32	-1.1	21	53
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.004	0.46	0.93	32	-1.1	21	53
TYK2	0.022	0.064	0.25	18	-10000	0	18
STAT4	0.007	0.013	0.22	2	-10000	0	2
STAT3	-0.002	0.056	-10000	0	-0.39	12	12
IL18RAP	0.005	0.014	-10000	0	-10000	0	0
IL12RB1	0.022	0.064	0.25	18	-10000	0	18
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
IL12Rbeta1/TYK2	0.026	0.072	0.22	36	-10000	0	36
IL23R/JAK2	0.061	0.22	0.59	48	-10000	0	48
positive regulation of chronic inflammatory response	0.004	0.53	1.1	47	-0.98	58	105
natural killer cell activation	-0.005	0.019	-10000	0	-0.068	22	22
JAK2	0.034	0.1	0.29	49	-0.41	4	53
PIK3R1	-0.038	0.12	-10000	0	-0.39	64	64
NFKB1	-0.003	0.056	-10000	0	-0.39	11	11
RELA	0.003	0.026	-10000	0	-0.39	2	2
positive regulation of dendritic cell antigen processing and presentation	-0.011	0.43	0.84	32	-1	20	52
ALOX12B	-0.004	0.46	0.93	32	-1.1	21	53
CXCL1	-0.18	0.68	0.97	34	-1.2	134	168
T cell proliferation	0.004	0.53	1.1	47	-0.98	58	105
NFKBIA	-0.006	0.067	-10000	0	-0.39	16	16
IL17A	0.015	0.31	0.63	45	-0.56	22	67
PI3K	-0.13	0.34	0.5	24	-0.9	59	83
IFNG	0.027	0.072	0.26	37	-10000	0	37
STAT3 (dimer)	-0.15	0.31	-10000	0	-0.91	50	50
IL18R1	0.006	0.016	0.22	1	-10000	0	1
IL23/IL23R/JAK2/TYK2/SOCS3	0.03	0.35	0.77	48	-0.77	8	56
IL18/IL18R	0.02	0.059	0.26	29	-10000	0	29
macrophage activation	-0.008	0.017	0.048	13	-10000	0	13
TNF	-0.004	0.48	0.98	32	-1.1	21	53
STAT3/STAT4	-0.16	0.31	-10000	0	-0.91	59	59
STAT4 (dimer)	-0.027	0.46	0.81	32	-0.95	57	89
IL18	0.045	0.085	0.22	103	-10000	0	103
IL19	-0.003	0.46	0.95	32	-1.1	21	53
STAT5A (dimer)	-0.03	0.46	0.81	32	-0.95	58	90
STAT1	0.12	0.11	0.22	297	-10000	0	297
SOCS3	0.001	0.051	0.22	2	-0.38	9	11
CXCL9	0.032	0.51	0.99	58	-1.1	21	79
MPO	-0.004	0.46	0.93	32	-1.1	21	53
positive regulation of humoral immune response	0.004	0.53	1.1	47	-0.98	58	105
IL23/IL23R/JAK2/TYK2	-0.004	0.54	1.1	47	-1	58	105
IL6	-0.054	0.54	0.91	34	-1.3	53	87
STAT5A	0	0.049	-10000	0	-0.38	9	9
IL2	0.009	0.035	0.15	25	-10000	0	25
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.019	-10000	0	-0.068	22	22
CD3E	-0.013	0.49	0.97	32	-1.2	28	60
keratinocyte proliferation	0.004	0.53	1.1	47	-0.98	58	105
NOS2	-0.005	0.46	0.87	47	-0.87	58	105

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.051	0.16	0.42	8	-0.33	108	116
MAP3K8	0.003	0.008	-10000	0	-10000	0	0
FOS	-0.03	0.11	0.34	8	-0.3	34	42
PRKCA	0.001	0.045	0.22	7	-0.39	5	12
PTPN7	0.001	0.016	-10000	0	-10000	0	0
HRAS	0.003	0.006	-10000	0	-10000	0	0
PRKCB	-0.002	0.009	0.049	8	-0.016	109	117
NRAS	0.098	0.11	0.22	245	-10000	0	245
RAS family/GTP	0.051	0.065	0.14	187	-10000	0	187
MAPK3	-0.038	0.14	0.22	8	-0.44	51	59
MAP2K1	0.01	0.056	0.2	11	-0.33	5	16
ELK1	0	0.015	-10000	0	-10000	0	0
BRAF	-0.002	0.039	0.29	2	-0.31	5	7
mol:GTP	-0.001	0.003	0.008	8	-0.006	110	118
MAPK1	0.002	0.05	0.22	8	-0.38	1	9
RAF1	-0.002	0.038	0.29	1	-0.31	5	6
KRAS	0.027	0.068	0.22	62	-10000	0	62

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	-0.001	0.064	0.22	5	-0.38	14	19
ANTXR2	-0.021	0.1	0.22	2	-0.38	41	43
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.005	0.016	-10000	0	-0.057	49	49
monocyte activation	-0.034	0.15	0.26	1	-0.39	82	83
MAP2K2	-0.25	0.33	-10000	0	-0.69	207	207
MAP2K1	-0.006	0.016	0.13	1	-0.081	6	7
MAP2K7	-0.006	0.015	-10000	0	-0.081	6	6
MAP2K6	0.007	0.045	0.13	57	-0.081	6	63
CYAA	-0.019	0.063	0.12	7	-0.21	49	56
MAP2K4	-0.009	0.026	-10000	0	-0.14	13	13
IL1B	-0.003	0.044	0.13	36	-0.12	8	44
Channel	-0.012	0.068	-10000	0	-0.23	49	49
NLRP1	-0.006	0.015	0.085	1	-10000	0	1
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
negative regulation of phagocytosis	-0.019	0.087	-10000	0	-0.49	18	18
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.005	0.016	0.057	49	-10000	0	49
MAPK3	-0.023	0.055	-10000	0	-0.18	57	57
MAPK1	-0.006	0.018	0.13	1	-0.19	1	2
PGR	-0.18	0.059	-10000	0	-0.19	512	512
PA/Cellular Receptors	-0.014	0.075	-10000	0	-0.25	49	49
apoptosis	-0.005	0.016	-10000	0	-0.057	49	49
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.01	0.067	0.13	7	-0.22	49	56
macrophage activation	-0.023	0.054	0.12	1	-0.19	52	53
TNF	0.007	0.009	0.22	1	-10000	0	1
VCAM1	-0.034	0.15	0.26	1	-0.39	82	83
platelet activation	-0.019	0.087	-10000	0	-0.49	18	18
MAPKKK cascade	0.023	0.036	0.067	189	-10000	0	189
IL18	0.012	0.06	0.13	96	-0.12	8	104
negative regulation of macrophage activation	-0.005	0.016	-10000	0	-0.057	49	49
LEF	-0.005	0.016	-10000	0	-0.057	49	49
CASP1	-0.012	0.027	-10000	0	-0.082	62	62
mol:cAMP	-0.019	0.087	-10000	0	-0.49	18	18
necrosis	-0.005	0.016	-10000	0	-0.057	49	49
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.009	0.066	0.13	7	-0.21	49	56
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.008	0.003	-10000	0	-10000	0	0
VLDLR	-0.002	0.072	0.22	8	-0.38	17	25
CRKL	0.006	0	-10000	0	-10000	0	0
LRPAP1	0.006	0.028	0.22	3	-0.38	2	5
FYN	-0.039	0.13	0.22	1	-0.38	67	68
ITGA3	-0.025	0.11	0.22	4	-0.38	48	52
RELN/VLDLR/Fyn	-0.056	0.12	-10000	0	-0.24	151	151
MAPK8IP1/MKK7/MAP3K11/JNK1	0.02	0.017	-10000	0	-0.19	1	1
AKT1	-0.025	0.11	0.2	7	-0.22	117	124
MAP2K7	0.006	0	-10000	0	-10000	0	0
RAPGEF1	0.006	0	-10000	0	-10000	0	0
DAB1	0.006	0	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.012	0.085	0.14	32	-0.2	84	116
LRPAP1/LRP8	0.008	0.017	-10000	0	-0.27	2	2
RELN/LRP8/DAB1/Fyn	-0.033	0.1	-10000	0	-0.2	140	140
DAB1/alpha3/beta1 Integrin	-0.036	0.087	-10000	0	-0.19	135	135
long-term memory	-0.024	0.1	0.26	2	-0.2	133	135
DAB1/LIS1	-0.019	0.077	-10000	0	-0.19	97	97
DAB1/CRLK/C3G	-0.021	0.074	-10000	0	-0.18	98	98
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
DAB1/NCK2	-0.012	0.084	-10000	0	-0.19	98	98
ARHGEF2	0.007	0.013	0.22	2	-10000	0	2
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.018	0.048	0.22	30	-10000	0	30
CDK5R1	0.006	0	-10000	0	-10000	0	0
RELN	-0.041	0.15	0.22	27	-0.38	84	111
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
RELN/LRP8/Fyn	-0.05	0.11	-10000	0	-0.24	140	140
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.024	0.11	-10000	0	-0.2	133	133
MAPK8	0.008	0.02	0.22	5	-10000	0	5
RELN/VLDLR/DAB1	-0.02	0.089	0.14	27	-0.2	99	126
ITGB1	0.007	0.016	0.22	3	-10000	0	3
MAP1B	-0.052	0.11	0.28	3	-0.22	145	148
RELN/LRP8	-0.024	0.086	-10000	0	-0.23	85	85
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.029	0.11	-10000	0	-0.2	140	140
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	-0.014	0.078	-10000	0	-0.27	48	48
RAP1A	-0.029	0.076	0.25	4	-0.33	1	5
PAFAH1B1	0.007	0.009	0.22	1	-10000	0	1
MAPK8IP1	0.007	0.013	0.22	2	-10000	0	2
CRLK/C3G	0.009	0	-10000	0	-10000	0	0
GRIN2B	0.007	0.016	0.22	3	-10000	0	3
NCK2	0.006	0	-10000	0	-10000	0	0
neuron differentiation	-0.033	0.089	0.18	2	-0.37	10	12
neuron adhesion	-0.042	0.085	0.25	4	-0.32	6	10
LRP8	0.01	0.027	0.22	9	-10000	0	9
GSK3B	-0.027	0.11	0.19	7	-0.35	14	21
RELN/VLDLR/DAB1/Fyn	-0.039	0.11	-10000	0	-0.21	151	151
MAP3K11	0.006	0.016	-10000	0	-0.38	1	1
RELN/VLDLR/DAB1/P13K	-0.025	0.12	0.22	7	-0.23	117	124
CDK5	0.031	0.069	0.22	65	-10000	0	65
MAPT	0.005	0.013	-10000	0	-10000	0	0
neuron migration	-0.038	0.13	0.24	8	-0.28	77	85
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.033	0.089	0.18	2	-0.37	10	12
RELN/VLDLR	-0.015	0.093	-10000	0	-0.21	98	98

×

Signaling events mediated by PRL

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
CCNE1	0.2	0.065	0.22	512	-10000	0	512
mol:Halofuginone	-0.001	0.022	-10000	0	-0.2	7	7
ITGA1	0.036	0.074	0.22	78	-10000	0	78
CDKN1A	-0.063	0.12	-10000	0	-0.46	42	42
PRL-3/alpha Tubulin	0.006	0.031	-10000	0	-0.27	7	7
mol:Ca2+	-0.019	0.074	0.31	7	-0.27	33	40
AGT	-0.016	0.091	-10000	0	-0.38	33	33
CCNA2	0.047	0.12	0.27	2	-0.74	7	9
TUBA1B	0.006	0	-10000	0	-10000	0	0
EGR1	-0.11	0.14	0.2	4	-0.27	233	237
CDK2/Cyclin E1	0.13	0.13	0.28	107	-0.34	24	131
MAPK3	-0.028	0.087	0.2	8	-0.28	56	64
PRL-2 /Rab GGTase beta	0.006	0.005	-10000	0	-10000	0	0
MAPK1	-0.005	0.04	0.2	9	-0.27	8	17
PTP4A1	-0.09	0.13	-10000	0	-0.79	7	7
PTP4A3	0.004	0.05	0.22	8	-0.38	7	15
PTP4A2	0.006	0	-10000	0	-10000	0	0
ITGB1	-0.003	0.038	0.2	10	-0.27	6	16
SRC	0.006	0	-10000	0	-10000	0	0
RAC1	-0.041	0.082	-10000	0	-0.41	15	15
Rab GGTase beta/Rab GGTase alpha	0.006	0.005	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.081	0.12	-10000	0	-0.75	7	7
RABGGTA	0.006	0	-10000	0	-10000	0	0
BCAR1	-0.005	0.044	0.31	7	-0.27	3	10
RHOC	-0.041	0.08	-10000	0	-0.4	15	15
RHOA	-0.042	0.081	-10000	0	-0.4	16	16
cell motility	-0.043	0.082	-10000	0	-0.41	14	14
PRL-1/alpha Tubulin	-0.081	0.12	-10000	0	-0.75	7	7
PRL-3/alpha1 Integrin	0.005	0.031	-10000	0	-0.27	7	7
ROCK1	-0.043	0.082	-10000	0	-0.41	14	14
RABGGTB	0.095	0.11	0.22	235	-10000	0	235
CDK2	0.1	0.11	0.22	255	-10000	0	255
mitosis	-0.089	0.12	-10000	0	-0.78	7	7
ATF5	0.006	0.021	0.22	2	-0.38	1	3

×

BARD1 signaling events

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
BARD1/CSTF1	0.008	0.004	-10000	0	-10000	0	0
ATM	0.014	0.04	0.22	20	-10000	0	20
UBE2D3	0.006	0	-10000	0	-10000	0	0
PRKDC	0.048	0.085	0.22	110	-10000	0	110
ATR	0.071	0.099	0.22	170	-10000	0	170
UBE2L3	0.006	0	-10000	0	-10000	0	0
FANCD2	0.12	0.12	0.34	109	-10000	0	109
protein ubiquitination	0.059	0.062	-10000	0	-10000	0	0
XRCC5	0.029	0.066	0.22	60	-10000	0	60
XRCC6	0.006	0	-10000	0	-10000	0	0
M/R/N Complex	0.008	0.015	-10000	0	-0.23	2	2
MRE11A	0.058	0.092	0.22	136	-10000	0	136
DNA-PK	0.009	0.006	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.001	0.011	-10000	0	-10000	0	0
FANCF	0.006	0	-10000	0	-10000	0	0
BRCA1	0.018	0.048	0.22	30	-10000	0	30
CCNE1	0.2	0.065	0.22	512	-10000	0	512
CDK2/Cyclin E1	0.001	0.002	-10000	0	-10000	0	0
FANCG	0.007	0.009	0.22	1	-10000	0	1
BRCA1/BACH1/BARD1	0.007	0.004	-10000	0	-10000	0	0
FANCE	0.006	0	-10000	0	-10000	0	0
FANCC	0.008	0.02	0.22	5	-10000	0	5
NBN	0.019	0.055	0.22	35	-0.38	1	36
FANCA	0.012	0.035	0.22	15	-10000	0	15
DNA repair	0.18	0.18	0.34	267	-10000	0	267
BRCA1/BARD1/ubiquitin	0.007	0.004	-10000	0	-10000	0	0
BARD1/DNA-PK	0.046	0.056	-10000	0	-10000	0	0
FANCL	0.02	0.053	0.22	36	-10000	0	36
mRNA polyadenylation	-0.008	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.075	0.097	0.25	105	-0.2	1	106
BRCA1/BACH1/BARD1/TopBP1	0.006	0.006	-10000	0	-10000	0	0
BRCA1/BARD1/P53	0.028	0.092	-10000	0	-0.2	44	44
BARD1/CSTF1/BRCA1	0.01	0.005	-10000	0	-10000	0	0
BRCA1/BACH1	0.018	0.048	0.22	30	-10000	0	30
BARD1	0.045	0.083	0.22	103	-10000	0	103
PCNA	0.042	0.081	0.22	95	-10000	0	95
BRCA1/BARD1/UbcH5C	0.01	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	0.01	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.051	0.061	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	0.02	0.082	-10000	0	-0.19	45	45
BRCA1/BARD1/Ubiquitin	0.007	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/CTIP	0.046	0.064	0.28	9	-10000	0	9
FA complex	0.042	0.055	0.21	21	-10000	0	21
BARD1/EWS	0.008	0.004	-10000	0	-10000	0	0
RBBP8	0.038	0.084	0.2	116	-10000	0	116
TP53	-0.045	0.13	0.22	3	-0.38	76	79
TOPBP1	0.11	0.11	0.22	284	-10000	0	284
G1/S transition of mitotic cell cycle	-0.027	0.09	0.2	44	-10000	0	44
BRCA1/BARD1	0.065	0.068	-10000	0	-10000	0	0
CSTF1	0.009	0.025	0.22	8	-10000	0	8
BARD1/EWS-Fli1	0.004	0.002	-10000	0	-10000	0	0
CDK2	0.1	0.11	0.22	255	-10000	0	255
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.093	0.11	0.22	230	-10000	0	230
RAD50	0.006	0.021	0.22	2	-0.38	1	3
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.007	0.004	-10000	0	-10000	0	0
EWSR1	0.006	0	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.022	0.067	0.18	78	-0.21	3	81
RFC1	0.03	0.076	0.19	94	-10000	0	94
PRKDC	0.054	0.094	0.22	82	-10000	0	82
RIPK1	0.007	0.005	-10000	0	-10000	0	0
CASP7	0	0.034	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	0.024	0.091	0.17	112	-0.22	18	130
MAP2K4	-0.017	0.094	0.29	4	-0.29	41	45
mol:ceramide	-0.012	0.07	0.25	4	-0.36	6	10
GSN	0.004	0.085	0.18	66	-0.21	41	107
FASLG/FAS/FADD/FAF1/Caspase 8	0.015	0.082	0.26	3	-0.28	6	9
FAS	-0.01	0.075	0.22	1	-0.39	21	22
BID	-0.003	0.027	0.24	7	-10000	0	7
MAP3K1	-0.002	0.062	0.21	4	-0.26	4	8
MAP3K7	0.009	0.029	0.22	10	-10000	0	10
RB1	0.026	0.076	0.19	79	-0.21	6	85
CFLAR	0.006	0.017	-10000	0	-0.38	1	1
HGF/MET	-0.059	0.12	-10000	0	-0.25	151	151
ARHGDIB	0.009	0.087	0.18	74	-0.22	37	111
FADD	0.004	0.009	-10000	0	-10000	0	0
actin filament polymerization	-0.004	0.084	0.21	41	-0.18	66	107
NFKB1	-0.023	0.12	0.29	4	-0.79	11	15
MAPK8	-0.029	0.13	0.36	4	-0.44	46	50
DFFA	0.023	0.065	0.18	79	-10000	0	79
DNA fragmentation during apoptosis	0.023	0.065	0.18	79	-10000	0	79
FAS/FADD/MET	-0.017	0.083	0.2	1	-0.25	60	61
CFLAR/RIP1	0.01	0.014	-10000	0	-0.27	1	1
FAIM3	0.002	0.04	-10000	0	-0.38	6	6
FAF1	0.006	0.023	0.22	5	-10000	0	5
PARP1	0.037	0.081	0.2	79	-10000	0	79
DFFB	0.023	0.065	0.18	79	-10000	0	79
CHUK	-0.02	0.12	0.25	4	-0.74	11	15
FASLG	0.004	0.01	-10000	0	-10000	0	0
FAS/FADD	-0.004	0.054	-10000	0	-0.27	21	21
HGF	0.008	0.018	0.22	4	-10000	0	4
LMNA	0.051	0.093	0.22	75	-0.19	4	79
CASP6	0.061	0.1	0.2	180	-10000	0	180
CASP10	0.004	0.031	0.22	4	-0.38	2	6
CASP3	0.03	0.079	0.22	79	-0.18	2	81
PTPN13	-0.068	0.18	0.22	34	-0.38	127	161
CASP8	-0.003	0.033	0.31	6	-10000	0	6
IL6	-0.091	0.33	0.54	4	-1.1	48	52
MET	-0.013	0.12	0.22	32	-0.38	45	77
ICAD/CAD	0.02	0.058	0.16	67	-10000	0	67
FASLG/FAS/FADD/FAF1/Caspase 10	-0.012	0.071	0.25	4	-0.37	6	10
activation of caspase activity by cytochrome c	-0.003	0.027	0.24	7	-10000	0	7
PAK2	0.024	0.066	0.18	79	-10000	0	79
BCL2	-0.043	0.13	0.22	2	-0.38	73	75

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.072	0.28	0.47	6	-0.95	50	56
MKNK1	0.006	0	-10000	0	-10000	0	0
MAPK14	-0.014	0.089	0.19	7	-0.29	50	57
ATF2/c-Jun	-0.009	0.096	0.43	9	-0.52	3	12
MAPK11	-0.015	0.088	-10000	0	-0.29	50	50
MITF	-0.022	0.1	-10000	0	-0.34	50	50
MAPKAPK5	-0.022	0.1	-10000	0	-0.34	50	50
KRT8	-0.022	0.1	-10000	0	-0.34	51	51
MAPKAPK3	0.006	0	-10000	0	-10000	0	0
MAPKAPK2	0.006	0.016	-10000	0	-0.38	1	1
p38alpha-beta/CK2	-0.022	0.13	0.26	6	-0.42	50	56
CEBPB	-0.023	0.11	0.22	6	-0.34	53	59
SLC9A1	-0.022	0.1	-10000	0	-0.34	50	50
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.018	0.11	0.3	9	-0.33	49	58
p38alpha-beta/MNK1	-0.013	0.1	0.22	6	-0.33	50	56
JUN	-0.01	0.095	0.44	9	-0.52	3	12
PPARGC1A	-0.02	0.1	0.22	6	-0.34	50	56
USF1	-0.021	0.1	-10000	0	-0.34	50	50
RAB5/GDP/GDI1	-0.016	0.075	-10000	0	-0.25	50	50
NOS2	-0.022	0.1	0.22	6	-0.34	50	56
DDIT3	0	0.12	0.38	3	-0.34	43	46
RAB5A	0.006	0	-10000	0	-10000	0	0
HSPB1	-0.024	0.089	-10000	0	-0.28	56	56
p38alpha-beta/HBP1	-0.013	0.1	0.22	6	-0.33	49	55
CREB1	-0.024	0.11	-10000	0	-0.37	50	50
RAB5/GDP	0.005	0	-10000	0	-10000	0	0
EIF4E	-0.028	0.086	-10000	0	-0.3	50	50
RPS6KA4	-0.022	0.1	-10000	0	-0.34	50	50
PLA2G4A	-0.09	0.14	0.31	2	-0.27	196	198
GDI1	-0.022	0.1	0.22	6	-0.34	52	58
TP53	-0.054	0.14	0.24	6	-0.45	50	56
RPS6KA5	-0.022	0.1	-10000	0	-0.34	51	51
ESR1	-0.051	0.14	-10000	0	-0.32	105	105
HBP1	0.014	0.041	0.22	21	-10000	0	21
MEF2C	-0.03	0.12	-10000	0	-0.35	62	62
MEF2A	-0.022	0.1	-10000	0	-0.34	50	50
EIF4EBP1	-0.024	0.11	-10000	0	-0.37	50	50
KRT19	-0.042	0.14	0.22	6	-0.37	78	84
ELK4	-0.022	0.1	-10000	0	-0.34	50	50
ATF6	-0.022	0.1	-10000	0	-0.34	50	50
ATF1	-0.024	0.11	-10000	0	-0.37	50	50
p38alpha-beta/MAPKAPK2	-0.013	0.1	0.22	6	-0.33	51	57
p38alpha-beta/MAPKAPK3	-0.013	0.1	0.22	6	-0.33	50	56

×

IL1-mediated signaling events

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
UBC13/UEV1A	0.004	0.011	-10000	0	-0.27	1	1
PRKCZ	0.006	0	-10000	0	-10000	0	0
MAP3K7IP2	0.005	0.025	0.22	1	-0.38	2	3
ERC1	0.008	0.029	0.22	7	-0.38	1	8
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.011	0.066	0.22	15	-0.23	17	32
IRAK/TOLLIP	0.006	0.01	0.14	1	-0.2	1	2
IKBKB	0.007	0.016	0.22	3	-10000	0	3
IKBKG	0.006	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.006	0.031	-10000	0	-0.27	7	7
IL1A	0.011	0.031	0.22	12	-10000	0	12
IL1B	-0.011	0.11	0.21	52	-0.27	57	109
IRAK/TRAF6/p62/Atypical PKCs	0.075	0.056	-10000	0	-10000	0	0
IL1R2	0.007	0.055	0.22	14	-0.38	7	21
IL1R1	-0.081	0.16	0.22	1	-0.38	127	128
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.017	0.13	0.19	8	-0.26	85	93
TOLLIP	0.006	0	-10000	0	-10000	0	0
TICAM2	0.006	0.019	0.22	1	-0.38	1	2
MAP3K3	0.006	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.012	0.014	-10000	0	-0.23	2	2
IKK complex/ELKS	0.008	0.032	-10000	0	-0.3	1	1
JUN	0.007	0.048	0.22	5	-10000	0	5
MAP3K7	0.01	0.028	0.22	10	-10000	0	10
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.013	0.16	0.26	64	-0.24	116	180
IL1 alpha/IL1R1/IL1RAP/MYD88	0.02	0.12	-10000	0	-0.2	84	84
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.021	0.11	-10000	0	-0.19	82	82
IL1 beta fragment/IL1R1/IL1RAP	-0.001	0.14	-10000	0	-0.24	107	107
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MAPK8	0.008	0.046	0.24	3	-0.17	3	6
IRAK1	-0.003	0.012	0.16	1	-0.22	1	2
IL1RN/IL1R1	-0.053	0.12	-10000	0	-0.27	126	126
IRAK4	0.017	0.047	0.22	28	-10000	0	28
PRKCI	0.12	0.11	0.22	306	-10000	0	306
TRAF6	0.007	0.013	0.22	2	-10000	0	2
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.002	0.12	0.2	35	-0.31	23	58
CHUK	0.011	0.031	0.22	12	-10000	0	12
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.001	0.14	-10000	0	-0.24	107	107
IL1 beta/IL1R2	-0.012	0.083	0.17	24	-0.23	64	88
IRAK/TRAF6/TAK1/TAB1/TAB2	0.017	0.022	-10000	0	-0.18	3	3
NF kappa B1 p50/RelA	-0.054	0.11	-10000	0	-0.34	49	49
IRAK3	0.015	0.042	0.22	22	-10000	0	22
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.016	0.14	0.25	31	-0.22	106	137
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.008	0.11	0.22	19	-0.21	82	101
IL1 alpha/IL1R1/IL1RAP	-0.034	0.083	-10000	0	-0.23	83	83
RELA	0.005	0.023	-10000	0	-0.38	2	2
MAP3K7IP1	0.006	0	-10000	0	-10000	0	0
SQSTM1	0.006	0	-10000	0	-10000	0	0
MYD88	0.006	0.016	-10000	0	-0.38	1	1
IRAK/TRAF6/MEKK3	0.011	0.013	-10000	0	-0.19	1	1
IL1RAP	0.095	0.11	0.22	235	-0.38	1	236
UBE2N	0.006	0.016	-10000	0	-0.38	1	1
IRAK/TRAF6	-0.045	0.077	-10000	0	-0.3	22	22
CASP1	-0.026	0.12	0.22	17	-0.38	57	74
IL1RN/IL1R2	0.005	0.031	-10000	0	-0.27	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.01	0.14	0.26	17	-0.22	107	124
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.021	0.14	-10000	0	-0.3	81	81
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
IL1RN	0.012	0.035	0.22	15	-10000	0	15
TRAF6/TAK1/TAB1/TAB2	0.014	0.015	-10000	0	-0.18	3	3
MAP2K6	0.009	0.047	0.25	1	-0.18	3	4

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.002	0	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.009	0	-10000	0	-10000	0	0
STXBP1	-0.038	0.12	-10000	0	-0.38	65	65
ACh/CHRNA1	-0.04	0.05	0.13	26	-10000	0	26
RAB3GAP2/RIMS1/UNC13B	0.013	0.001	-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	0.006	0	-10000	0	-10000	0	0
mol:ACh	-0.065	0.042	0.069	1	-0.092	400	401
RAB3GAP2	0.009	0.024	0.22	7	-10000	0	7
STX1A/SNAP25/VAMP2	-0.12	0.091	-10000	0	-0.28	65	65
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	-0.04	0.05	0.13	26	-10000	0	26
UNC13B	0.006	0	-10000	0	-10000	0	0
CHRNA1	0.016	0.045	0.22	26	-10000	0	26
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.041	0.047	0.12	21	-10000	0	21
SNAP25	0.003	0.016	0.14	8	-10000	0	8
VAMP2	-0.16	0.099	-10000	0	-0.22	407	407
SYT1	0.014	0.041	0.22	21	-10000	0	21
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	-0.021	0.073	-10000	0	-0.22	65	65
STX1A/SNAP25 fragment 1/VAMP2	-0.12	0.091	-10000	0	-0.28	65	65

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.039	0.098	-10000	0	-0.24	108	108
alphaM/beta2 Integrin/GPIbA	0.003	0.035	-10000	0	-0.23	9	9
alphaM/beta2 Integrin/proMMP-9	0.002	0.035	-10000	0	-0.23	9	9
PLAUR	0.011	0.032	0.22	13	-10000	0	13
HMGB1	0.002	0.016	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.002	0.038	-10000	0	-0.23	11	11
AGER	0.002	0.016	-10000	0	-10000	0	0
RAP1A	0.007	0.009	0.22	1	-10000	0	1
SELPLG	-0.009	0.075	-10000	0	-0.38	22	22
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.001	0.062	-10000	0	-0.19	51	51
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.035	0.074	0.22	77	-10000	0	77
CYR61	-0.028	0.12	0.22	7	-0.38	54	61
TLN1	0.005	0.023	-10000	0	-0.38	2	2
Rap1/GTP	-0.063	0.091	-10000	0	-0.33	31	31
RHOA	0.005	0.023	-10000	0	-0.38	2	2
P-selectin oligomer	-0.02	0.099	0.22	1	-0.38	39	40
MYH2	-0.049	0.16	0.2	41	-0.39	31	72
MST1R	0.008	0.018	0.22	4	-10000	0	4
leukocyte activation during inflammatory response	0.005	0.03	-10000	0	-0.19	9	9
APOB	0.006	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	-0.057	0.16	0.22	16	-0.38	101	117
JAM3	0.007	0.013	0.22	2	-10000	0	2
GP1BA	0.006	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CTGF	-0.043	0.1	-10000	0	-0.24	117	117
alphaM/beta2 Integrin	-0.034	0.14	0.19	50	-0.38	31	81
JAM3 homodimer	0.007	0.013	0.22	2	-10000	0	2
ICAM2	0.001	0.043	-10000	0	-0.38	7	7
ICAM1	0.015	0.089	0.22	49	-0.38	15	64
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.034	0.14	0.19	50	-0.37	31	81
cell adhesion	0.003	0.035	-10000	0	-0.23	9	9
NFKB1	-0.034	0.1	0.38	5	-0.34	46	51
THY1	0.073	0.1	0.22	177	-0.38	1	178
RhoA/GDP	0.004	0.016	-10000	0	-0.27	2	2
Lipoprotein(a)	0.009	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.038	0.1	-10000	0	-0.22	128	128
IL6	-0.057	0.18	0.48	5	-0.63	46	51
ITGB2	-0.003	0.053	0.22	2	-0.39	9	11
elevation of cytosolic calcium ion concentration	0.039	0.068	-10000	0	-0.2	9	9
alphaM/beta2 Integrin/JAM2/JAM3	-0.068	0.11	-10000	0	-0.21	206	206
JAM2	-0.13	0.19	0.22	1	-0.38	204	205
alphaM/beta2 Integrin/ICAM1	0.015	0.062	-10000	0	-0.23	20	20
alphaM/beta2 Integrin/uPA/Plg	0.037	0.077	-10000	0	-0.21	18	18
RhoA/GTP	-0.05	0.17	0.21	49	-0.25	180	229
positive regulation of phagocytosis	-0.052	0.082	0.17	1	-0.3	30	31
Ron/MSP	0.009	0.001	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.041	0.07	-10000	0	-0.2	9	9
alphaM/beta2 Integrin/uPAR	0.003	0.035	-10000	0	-0.23	9	9
PLAU	0.066	0.097	0.22	158	-10000	0	158
PLAT	-0.071	0.16	0.22	7	-0.38	116	123
actin filament polymerization	-0.046	0.16	0.2	41	-0.38	31	72
MST1	0.007	0.009	0.22	1	-10000	0	1
alphaM/beta2 Integrin/lipoprotein(a)	0.008	0.033	-10000	0	-0.19	9	9
TNF	-0.032	0.097	0.39	5	-0.4	4	9
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
alphaM/beta2 Integrin/uPA	0	0.035	-10000	0	-0.23	9	9
fibrinolysis	0.036	0.075	-10000	0	-0.21	18	18
HCK	0.007	0.009	0.22	1	-10000	0	1
dendritic cell antigen processing and presentation	-0.034	0.14	0.19	50	-0.37	31	81
VTN	0.006	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/CYR61	-0.019	0.079	-10000	0	-0.24	60	60
LPA	0.006	0	-10000	0	-10000	0	0
LRP1	-0.001	0.054	-10000	0	-0.38	11	11
cell migration	-0.018	0.1	-10000	0	-0.22	99	99
FN1	0.074	0.12	0.22	201	-0.38	13	214
alphaM/beta2 Integrin/Thy1	0.003	0.033	0.12	1	-0.23	6	7
MPO	0.006	0	-10000	0	-10000	0	0
KNG1	0.007	0.009	0.22	1	-10000	0	1
RAP1/GDP	0.008	0.01	-10000	0	-0.22	1	1
ROCK1	-0.048	0.16	0.2	41	-0.32	55	96
ELA2	0.006	0	-10000	0	-10000	0	0
PLG	-0.001	0.054	-10000	0	-0.38	11	11
CTGF	-0.071	0.16	-10000	0	-0.38	112	112
alphaM/beta2 Integrin/Hck	0.003	0.035	-10000	0	-0.23	9	9
ITGAM	0.004	0.022	0.22	3	-10000	0	3
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.014	0.084	-10000	0	-0.24	62	62
HP	-0.13	0.24	0.22	93	-0.38	254	347
leukocyte adhesion	-0.038	0.13	0.26	1	-0.3	36	37
SELP	-0.02	0.099	0.22	1	-0.38	39	40

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.009	0.067	-10000	0	-0.2	64	64
ER alpha/Gai/GDP/Gbeta gamma	-0.025	0.11	-10000	0	-0.31	56	56
AKT1	-0.064	0.23	-10000	0	-0.7	61	61
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.063	0.24	-10000	0	-0.7	61	61
mol:Ca2+	-0.069	0.11	-10000	0	-0.36	36	36
IGF1R	-0.077	0.16	-10000	0	-0.38	121	121
E2/ER alpha (dimer)/Striatin	-0.016	0.072	-10000	0	-0.22	61	61
SHC1	0.006	0	-10000	0	-10000	0	0
apoptosis	0.06	0.22	0.66	61	-10000	0	61
RhoA/GTP	-0.014	0.035	-10000	0	-0.17	22	22
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.031	0.11	-10000	0	-0.33	60	60
regulation of stress fiber formation	-0.032	0.079	0.24	6	-0.21	28	34
E2/ERA-ERB (dimer)	-0.016	0.072	-10000	0	-0.22	61	61
KRAS	0.03	0.067	0.22	62	-10000	0	62
G13/GTP	-0.015	0.065	-10000	0	-0.2	62	62
pseudopodium formation	0.032	0.079	0.21	28	-0.24	6	34
E2/ER alpha (dimer)/PELP1	-0.016	0.072	-10000	0	-0.22	61	61
GRB2	0.006	0.016	-10000	0	-0.38	1	1
GNG2	0.004	0.034	0.22	1	-0.38	4	5
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
HRAS	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.035	0.14	-10000	0	-0.41	60	60
E2/ER beta (dimer)	0.005	0	-10000	0	-10000	0	0
mol:GDP	-0.023	0.078	-10000	0	-0.25	56	56
mol:NADP	-0.035	0.14	-10000	0	-0.41	60	60
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.071	0.12	-10000	0	-0.38	36	36
IGF-1R heterotetramer	-0.077	0.16	-10000	0	-0.38	121	121
PLCB1	-0.071	0.12	-10000	0	-0.38	36	36
PLCB2	-0.082	0.12	-10000	0	-0.38	38	38
IGF1	-0.003	0.067	0.22	4	-0.38	16	20
mol:L-citrulline	-0.035	0.14	-10000	0	-0.41	60	60
RHOA	0.005	0.023	-10000	0	-0.38	2	2
Gai/GDP	0.005	0.065	-10000	0	-0.65	3	3
JNK cascade	0.005	0	-10000	0	-10000	0	0
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
ESR2	0.006	0	-10000	0	-10000	0	0
GNAQ	-0.005	0.065	-10000	0	-0.38	16	16
ESR1	-0.036	0.12	-10000	0	-0.38	61	61
Gq family/GDP/Gbeta gamma	-0.12	0.19	-10000	0	-0.37	194	194
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.013	0.077	-10000	0	-0.5	1	1
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.03	0.11	-10000	0	-0.33	60	60
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
E2/ER alpha (dimer)	-0.025	0.084	-10000	0	-0.27	61	61
STRN	0.007	0.013	0.22	2	-10000	0	2
GNAL	0.006	0	-10000	0	-10000	0	0
PELP1	0.006	0	-10000	0	-10000	0	0
MAPK11	-0.003	0	-10000	0	-10000	0	0
GNAI2	0.006	0	-10000	0	-10000	0	0
GNAI3	0.017	0.047	0.22	29	-10000	0	29
GNAI1	0	0.063	0.22	7	-0.38	13	20
HBEGF	-0.029	0.1	-10000	0	-0.29	46	46
cAMP biosynthetic process	-0.013	0.058	-10000	0	-0.18	61	61
SRC	-0.026	0.1	-10000	0	-0.3	55	55
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
GNB1	0.006	0.016	-10000	0	-0.38	1	1
G13/GDP/Gbeta gamma	-0.018	0.073	-10000	0	-0.23	56	56
SOS1	0.014	0.04	0.22	20	-10000	0	20
IGF-1R heterotetramer/IGF1	-0.063	0.11	-10000	0	-0.31	64	64
Gs family/GTP	-0.011	0.059	-10000	0	-0.18	61	61
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.067	0.064	0.14	245	-10000	0	245
vasodilation	-0.033	0.13	-10000	0	-0.4	60	60
mol:DAG	-0.071	0.12	-10000	0	-0.38	36	36
Gs family/GDP/Gbeta gamma	-0.02	0.071	-10000	0	-0.22	56	56
MSN	0.032	0.083	0.21	28	-0.26	6	34
Gq family/GTP	-0.084	0.13	-10000	0	-0.4	38	38
mol:PI-3-4-5-P3	-0.06	0.23	-10000	0	-0.68	61	61
NRAS	0.099	0.11	0.22	245	-10000	0	245
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.033	0.13	0.4	60	-10000	0	60
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
RhoA/GDP	-0.021	0.076	-10000	0	-0.24	56	56
NOS3	-0.037	0.14	-10000	0	-0.43	60	60
GNA11	-0.13	0.18	-10000	0	-0.38	193	193
MAPKKK cascade	-0.044	0.16	-10000	0	-0.5	61	61
E2/ER alpha (dimer)/PELP1/Src	-0.028	0.12	-10000	0	-0.34	60	60
ruffle organization	0.032	0.079	0.21	28	-0.24	6	34
ROCK2	0.036	0.081	0.22	28	-10000	0	28
GNA14	0.006	0.026	0.22	2	-0.38	2	4
GNA15	0.003	0.037	-10000	0	-0.38	5	5
GNA13	0.006	0.016	-10000	0	-0.38	1	1
MMP9	-0.009	0.1	0.21	4	-0.29	42	46
MMP2	-0.051	0.12	-10000	0	-0.31	57	57

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	0.049	0.097	0.16	205	-0.23	28	233
EPHB2	0.01	0.027	0.22	9	-10000	0	9
Syndecan-2/TACI	0.001	0.042	0.14	7	-0.22	17	24
LAMA1	0.045	0.083	0.22	102	-10000	0	102
Syndecan-2/alpha2 ITGB1	-0.03	0.099	-10000	0	-0.22	115	115
HRAS	0.006	0	-10000	0	-10000	0	0
Syndecan-2/CASK	-0.004	0.041	0.14	7	-0.22	17	24
ITGA5	0.008	0.018	0.22	4	-10000	0	4
BAX	-0.004	0.04	-10000	0	-10000	0	0
EPB41	0.016	0.045	0.22	26	-10000	0	26
positive regulation of cell-cell adhesion	-0.001	0.04	0.14	2	-0.21	18	20
LAMA3	-0.02	0.1	0.22	6	-0.38	42	48
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.013	0.089	0.22	3	-0.38	30	33
Syndecan-2/MMP2	-0.035	0.11	0.15	23	-0.24	107	130
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	-0.026	0.093	-10000	0	-0.27	72	72
dendrite morphogenesis	0.003	0.046	0.15	16	-0.22	17	33
Syndecan-2/GM-CSF	0.001	0.042	0.14	7	-0.22	17	24
determination of left/right symmetry	-0.004	0.051	0.2	7	-0.27	17	24
Syndecan-2/PKC delta	0	0.044	0.14	7	-0.22	19	26
GNB2L1	0.006	0	-10000	0	-10000	0	0
MAPK3	-0.026	0.071	-10000	0	-0.22	62	62
MAPK1	-0.008	0.039	-10000	0	-0.2	18	18
Syndecan-2/RACK1	0.005	0.037	0.13	7	-0.19	17	24
NF1	-0.01	0.079	0.22	1	-0.38	24	25
FGFR/FGF/Syndecan-2	-0.004	0.051	0.2	7	-0.27	17	24
ITGA2	-0.044	0.13	0.22	2	-0.38	74	76
MAPK8	-0.005	0.045	-10000	0	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	0.006	0.092	0.27	1	-0.2	66	67
Syndecan-2/Kininogen	0.001	0.043	0.14	8	-0.22	17	25
ITGB1	0.007	0.016	0.22	3	-10000	0	3
SRC	-0.008	0.033	-10000	0	-0.18	17	17
Syndecan-2/CASK/Protein 4.1	0.005	0.044	0.14	24	-0.2	15	39
extracellular matrix organization	-0.05	0.11	0.14	6	-0.23	136	142
actin cytoskeleton reorganization	0.049	0.096	0.16	205	-0.23	28	233
Syndecan-2/Caveolin-2/Ras	-0.005	0.065	0.14	3	-0.22	42	45
Syndecan-2/Laminin alpha3	-0.014	0.076	0.15	13	-0.23	58	71
Syndecan-2/RasGAP	0.007	0.038	-10000	0	-0.18	20	20
alpha5/beta1 Integrin	0.009	0.001	-10000	0	-10000	0	0
PRKCD	0.005	0.023	-10000	0	-0.38	2	2
Syndecan-2 dimer	0.003	0.047	0.15	16	-0.22	17	33
GO:0007205	0	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.002	0.037	-10000	0	-0.18	20	20
RHOA	0.005	0.023	-10000	0	-0.38	2	2
SDCBP	0.006	0.026	0.22	2	-0.38	2	4
TNFRSF13B	0.006	0	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
alpha2/beta1 Integrin	-0.026	0.093	-10000	0	-0.27	72	72
Syndecan-2/Synbindin	0.011	0.058	0.16	44	-0.22	16	60
TGFB1	-0.081	0.16	-10000	0	-0.38	127	127
CASP3	-0.006	0.043	-10000	0	-0.2	18	18
FN1	0.074	0.12	0.22	201	-0.38	13	214
Syndecan-2/IL8	0.013	0.06	0.16	52	-0.22	16	68
SDC2	-0.004	0.051	0.2	7	-0.27	17	24
KNG1	0.007	0.009	0.22	1	-10000	0	1
Syndecan-2/Neurofibromin	-0.008	0.06	0.15	6	-0.22	39	45
TRAPPC4	0.021	0.055	0.22	40	-10000	0	40
CSF2	0.006	0	-10000	0	-10000	0	0
Syndecan-2/TGFB1	-0.05	0.11	0.14	6	-0.24	136	142
Syndecan-2/Syntenin/PI-4-5-P2	-0.001	0.04	0.14	2	-0.21	18	20
Syndecan-2/Ezrin	-0.001	0.037	-10000	0	-0.2	19	19
PRKACA	-0.016	0.053	-10000	0	-0.2	39	39
angiogenesis	0.013	0.06	0.16	52	-0.22	16	68
MMP2	-0.057	0.16	0.22	16	-0.38	101	117
IL8	0.024	0.059	0.22	47	-10000	0	47
calcineurin-NFAT signaling pathway	0.001	0.042	0.14	7	-0.22	17	24

×

TRAIL signaling pathway

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
TNFSF10	-0.004	0.13	0.22	60	-0.38	48	108
positive regulation of NF-kappaB transcription factor activity	-0.016	0.079	-10000	0	-0.27	48	48
MAP2K4	-0.009	0.077	-10000	0	-0.28	7	7
IKBKB	0.007	0.016	0.22	3	-10000	0	3
TNFRSF10B	0.007	0.009	0.22	1	-10000	0	1
TNFRSF10A	0.007	0.016	0.22	3	-10000	0	3
SMPD1	-0.012	0.048	-10000	0	-0.17	49	49
IKBKG	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.006	0.019	0.22	1	-0.38	1	2
TRAIL/TRAILR2	-0.015	0.077	-10000	0	-0.27	48	48
TRAIL/TRAILR3	-0.13	0.15	-10000	0	-0.29	257	257
TRAIL/TRAILR1	-0.015	0.077	-10000	0	-0.27	48	48
TRAIL/TRAILR4	-0.016	0.079	-10000	0	-0.28	48	48
TRAIL/TRAILR1/DAP3/GTP	0.009	0.076	-10000	0	-0.2	47	47
IKK complex	-0.003	0.037	-10000	0	-10000	0	0
RIPK1	0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.005	0	-10000	0	-10000	0	0
MAPK3	-0.028	0.12	0.2	53	-0.28	90	143
MAP3K1	-0.006	0.078	-10000	0	-0.28	6	6
TRAILR4 (trimer)	0.006	0.019	0.22	1	-0.38	1	2
TRADD	0.002	0.04	-10000	0	-0.38	6	6
TRAILR1 (trimer)	0.007	0.016	0.22	3	-10000	0	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.003	0.075	-10000	0	-0.21	53	53
CFLAR	0.006	0.016	-10000	0	-0.38	1	1
MAPK1	-0.005	0.1	0.2	61	-0.27	49	110
TRAIL/TRAILR1/FADD/TRADD/RIP	0.012	0.077	-10000	0	-0.2	53	53
mol:ceramide	-0.012	0.047	-10000	0	-0.17	49	49
FADD	0.006	0	-10000	0	-10000	0	0
MAPK8	-0.009	0.073	-10000	0	-0.26	7	7
TRAF2	0.006	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.16	0.2	0.22	1	-0.38	249	250
CHUK	0.011	0.031	0.22	12	-10000	0	12
TRAIL/TRAILR1/FADD	-0.009	0.066	-10000	0	-0.23	48	48
DAP3	0.007	0.016	0.22	3	-10000	0	3
CASP10	-0.009	0.086	-10000	0	-0.25	48	48
JNK cascade	-0.016	0.079	-10000	0	-0.27	48	48
TRAIL (trimer)	-0.004	0.13	0.22	60	-0.38	48	108
TNFRSF10C	-0.16	0.2	0.22	1	-0.38	249	250
TRAIL/TRAILR1/DAP3/GTP/FADD	0.011	0.072	-10000	0	-0.19	47	47
TRAIL/TRAILR2/FADD	-0.009	0.066	-10000	0	-0.23	48	48
cell death	-0.012	0.047	-10000	0	-0.16	49	49
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.003	0.074	-10000	0	-0.21	53	53
TRAILR2 (trimer)	0.007	0.009	0.22	1	-10000	0	1
CASP8	0.001	0.036	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.012	0.076	-10000	0	-0.2	53	53

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.005	0.1	0.53	16	-1	1	17
oxygen homeostasis	0.029	0.048	0.19	18	-10000	0	18
TCEB2	0.006	0	-10000	0	-10000	0	0
TCEB1	0.006	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.015	0.12	-10000	0	-0.33	20	20
EPO	0.14	0.31	0.71	82	-10000	0	82
FIH (dimer)	0.033	0.047	0.2	16	-10000	0	16
APEX1	0.052	0.077	0.23	75	-10000	0	75
SERPINE1	0.16	0.36	0.81	88	-0.56	3	91
FLT1	-0.009	0.036	-10000	0	-0.74	1	1
ADORA2A	0.15	0.32	0.71	86	-0.55	3	89
germ cell development	0.14	0.34	0.75	82	-0.62	4	86
SLC11A2	0.14	0.34	0.76	84	-0.56	3	87
BHLHE40	0.14	0.33	0.74	81	-0.56	3	84
HIF1AN	0.033	0.047	0.2	16	-10000	0	16
HIF2A/ARNT/SIRT1	0.007	0.17	0.48	7	-0.41	10	17
ETS1	0.01	0.028	0.23	6	-0.38	1	7
CITED2	-0.039	0.17	-10000	0	-0.93	20	20
KDR	-0.008	0.045	0.62	1	-0.74	1	2
PGK1	0.19	0.38	0.81	106	-0.56	3	109
SIRT1	0.006	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.15	0.34	0.78	71	-0.64	3	74
EPAS1	0.078	0.26	0.57	78	-0.36	20	98
SP1	0.018	0.052	0.24	28	-10000	0	28
ABCG2	0.11	0.35	0.74	78	-0.64	15	93
EFNA1	0.15	0.34	0.76	86	-0.56	3	89
FXN	0.15	0.32	0.72	83	-0.55	3	86
POU5F1	0.14	0.34	0.75	82	-0.64	4	86
neuron apoptosis	-0.14	0.33	0.63	3	-0.77	71	74
EP300	0.003	0.037	-10000	0	-0.38	5	5
EGLN3	0.027	0.11	0.24	45	-0.38	25	70
EGLN2	0.035	0.049	0.2	17	-10000	0	17
EGLN1	0.033	0.047	0.2	16	-10000	0	16
VHL/Elongin B/Elongin C	0.013	0.001	-10000	0	-10000	0	0
VHL	0.007	0.016	0.22	3	-10000	0	3
ARNT	0.03	0.046	0.2	17	-10000	0	17
SLC2A1	0.16	0.34	0.76	88	-0.55	3	91
TWIST1	0.15	0.32	0.71	86	-0.55	3	89
ELK1	0.003	0.021	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.009	0.17	0.48	7	-0.42	11	18
VEGFA	0.15	0.34	0.76	88	-0.56	3	91
CREBBP	0.001	0.046	-10000	0	-0.38	8	8

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.01	0.079	-10000	0	-0.38	24	24
alphaV beta3 Integrin	-0.033	0.1	-10000	0	-0.28	83	83
PTK2	-0.044	0.12	0.28	2	-0.46	27	29
positive regulation of JNK cascade	-0.022	0.068	-10000	0	-0.31	27	27
CDC42/GDP	-0.012	0.1	-10000	0	-0.42	27	27
Rac1/GDP	-0.012	0.1	-10000	0	-0.42	27	27
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
RAP1A	0.007	0.009	0.22	1	-10000	0	1
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
CDC42/GTP	-0.025	0.085	-10000	0	-0.38	27	27
nectin-3/I-afadin	-0.005	0.062	-10000	0	-0.28	27	27
RAPGEF1	-0.02	0.11	0.23	1	-0.47	27	28
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.022	0.13	-10000	0	-0.53	27	27
PDGFB-D/PDGFRB	-0.01	0.079	-10000	0	-0.38	24	24
TLN1	-0.11	0.15	-10000	0	-0.29	212	212
Rap1/GTP	-0.027	0.074	-10000	0	-0.34	27	27
IQGAP1	0.005	0.025	0.22	1	-0.38	2	3
Rap1/GTP/I-afadin	0.006	0.041	0.14	6	-0.2	19	25
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.005	0.062	-10000	0	-0.28	27	27
PVR	0.006	0	-10000	0	-10000	0	0
Necl-5(dimer)	0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.018	0.12	-10000	0	-0.52	27	27
MLLT4	-0.006	0.068	-10000	0	-0.38	18	18
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PI3K	0.011	0.11	-10000	0	-0.21	87	87
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.001	0.049	-10000	0	-0.27	18	18
positive regulation of lamellipodium assembly	-0.024	0.074	-10000	0	-0.33	29	29
PVRL1	0.007	0.009	0.22	1	-10000	0	1
PVRL3	0.022	0.088	0.22	61	-0.38	11	72
PVRL2	0.006	0.019	0.22	1	-0.38	1	2
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
CDH1	-0.005	0.067	-10000	0	-0.38	17	17
CLDN1	-0.078	0.16	0.22	5	-0.38	125	130
JAM-A/CLDN1	-0.028	0.11	-10000	0	-0.22	127	127
SRC	-0.026	0.14	-10000	0	-0.59	27	27
ITGB3	-0.045	0.14	0.22	13	-0.38	82	95
nectin-1(dimer)/I-afadin/I-afadin	0.001	0.049	-10000	0	-0.27	18	18
FARP2	-0.016	0.12	-10000	0	-0.5	27	27
RAC1	0.006	0.016	-10000	0	-0.38	1	1
CTNNA1	0.005	0.023	-10000	0	-0.38	2	2
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0	0.053	-10000	0	-0.23	27	27
nectin-1/I-afadin	0.001	0.049	-10000	0	-0.27	18	18
nectin-2/I-afadin	0	0.05	-10000	0	-0.27	19	19
RAC1/GTP/IQGAP1/filamentous actin	0.007	0.017	-10000	0	-0.22	3	3
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0	0.053	-10000	0	-0.23	27	27
CDC42/GTP/IQGAP1/filamentous actin	0.008	0.014	-10000	0	-0.22	2	2
F11R	0.007	0.009	0.22	1	-10000	0	1
positive regulation of filopodium formation	-0.022	0.068	-10000	0	-0.31	27	27
alphaV/beta3 Integrin/Talin	-0.12	0.16	0.22	7	-0.3	207	214
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0.05	-10000	0	-0.27	19	19
nectin-2(dimer)/I-afadin/I-afadin	0	0.05	-10000	0	-0.27	19	19
PIP5K1C	-0.11	0.16	-10000	0	-0.31	210	210
VAV2	-0.018	0.13	-10000	0	-0.52	29	29
RAP1/GDP	-0.019	0.092	-10000	0	-0.4	27	27
ITGAV	0.017	0.06	0.22	35	-0.38	3	38
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.001	0.054	-10000	0	-0.23	28	28
nectin-3(dimer)/I-afadin/I-afadin	-0.005	0.062	-10000	0	-0.28	27	27
Rac1/GTP	-0.026	0.091	-10000	0	-0.4	29	29
PTPRM	-0.13	0.17	-10000	0	-0.33	219	219
E-cadherin/beta catenin/alpha catenin	0.006	0.054	-10000	0	-0.2	34	34
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.006	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.1	0.1	0.2	1	-0.28	9	10
CaM/Ca2+	-0.004	0.048	-10000	0	-0.27	18	18
AKT1	0.007	0.009	0.22	1	-10000	0	1
AKT2	0.009	0.024	0.22	7	-10000	0	7
STXBP4	0.007	0.013	0.22	2	-10000	0	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.031	0.068	-10000	0	-0.26	1	1
YWHAZ	0.006	0	-10000	0	-10000	0	0
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
YWHAQ	0.006	0	-10000	0	-10000	0	0
TBC1D4	-0.003	0.015	0.2	3	-10000	0	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.005	0.03	0.22	1	-0.38	3	4
YWHAB	0.007	0.009	0.22	1	-10000	0	1
SNARE/Synip	-0.16	0.11	-10000	0	-0.23	405	405
YWHAG	0.004	0.033	-10000	0	-0.38	4	4
ASIP	0.005	0.03	0.22	1	-0.38	3	4
PRKCI	0.12	0.11	0.22	306	-10000	0	306
AS160/CaM/Ca2+	-0.004	0.048	-10000	0	-0.27	18	18
RHOQ	0.007	0.016	0.22	3	-10000	0	3
GYS1	0.001	0.015	-10000	0	-10000	0	0
PRKCZ	0.006	0	-10000	0	-10000	0	0
TRIP10	0.006	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.009	0.001	-10000	0	-10000	0	0
AS160/14-3-3	0.005	0.029	-10000	0	-10000	0	0
VAMP2	-0.27	0.18	-10000	0	-0.38	407	407
SLC2A4	-0.034	0.072	-10000	0	-0.28	1	1
STX4	0.006	0	-10000	0	-10000	0	0
GSK3B	0.006	0.018	-10000	0	-10000	0	0
SFN	0.013	0.039	0.22	19	-10000	0	19
LNPEP	0.009	0.037	0.22	10	-0.38	2	12
YWHAE	0.006	0.016	-10000	0	-0.38	1	1

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.047	0.22	28	-10000	0	28
HDAC3	0.006	0	-10000	0	-10000	0	0
VDR	0.007	0.013	0.22	2	-10000	0	2
Cbp/p300/PCAF	0.003	0.039	-10000	0	-0.26	11	11
EP300	0.003	0.037	-10000	0	-0.38	5	5
RARs/AIB1/Cbp/p300/PCAF/9cRA	-0.011	0.05	0.18	2	-0.28	7	9
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.007	0.009	0.22	1	-10000	0	1
AKT1	0.036	0.085	0.22	14	-10000	0	14
RAR alpha/9cRA/Cyclin H	-0.052	0.084	-10000	0	-0.31	29	29
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.015	0.053	0.19	1	-0.24	13	14
CDC2	0.2	0.055	0.22	530	-10000	0	530
response to UV	-0.007	0.012	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.019	0.046	0.18	4	-0.17	5	9
NCOR2	0	0.049	-10000	0	-0.38	9	9
VDR/VDR/Vit D3	0.005	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.12	0.26	-10000	0	-0.51	159	159
NCOA2	0.007	0.013	0.22	2	-10000	0	2
NCOA3	0.01	0.028	0.22	10	-10000	0	10
NCOA1	0.004	0.028	-10000	0	-0.38	3	3
VDR/VDR/DNA	0.007	0.013	0.22	2	-10000	0	2
RARG	0.008	0.042	0.21	22	-10000	0	22
RAR gamma1/9cRA	0.003	0.008	-10000	0	-10000	0	0
MAPK3	-0.037	0.11	-10000	0	-0.39	51	51
MAPK1	0.006	0.019	0.22	1	-0.38	1	2
MAPK8	-0.002	0.026	0.22	5	-10000	0	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.046	0.16	-10000	0	-0.39	35	35
RARA	-0.024	0.05	-10000	0	-0.22	5	5
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.013	0.052	0.19	1	-0.26	10	11
PRKCA	-0.015	0.049	0.22	3	-0.38	5	8
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.13	0.27	-10000	0	-0.55	165	165
RXRG	-0.023	0.061	-10000	0	-0.27	7	7
RXRA	0.013	0.12	0.2	3	-0.32	30	33
RXRB	-0.025	0.051	-10000	0	-0.27	5	5
VDR/Vit D3/DNA	0.005	0	-10000	0	-10000	0	0
RBP1	-0.11	0.18	-10000	0	-0.38	174	174
CRBP1/9-cic-RA	-0.079	0.13	-10000	0	-0.27	174	174
RARB	0.002	0.038	0.22	14	-10000	0	14
PRKCG	-0.012	0.03	-10000	0	-10000	0	0
MNAT1	0.006	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.02	0.19	0.3	2	-0.42	24	26
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.045	0.15	-10000	0	-0.4	34	34
proteasomal ubiquitin-dependent protein catabolic process	-0.021	0.058	-10000	0	-0.26	6	6
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.13	0.27	-10000	0	-0.55	165	165
positive regulation of DNA binding	-0.05	0.079	-10000	0	-0.28	35	35
NRIP1	-0.29	0.51	-10000	0	-1.1	165	165
RXRs/RARs	-0.091	0.2	-10000	0	-0.4	166	166
RXRs/RXRs/DNA/9cRA	-0.048	0.16	-10000	0	-0.4	35	35
PRKACA	0.006	0	-10000	0	-10000	0	0
CDK7	0.014	0.04	0.22	20	-10000	0	20
TFIIH	0.012	0.002	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.044	-10000	0	-10000	0	0
CCNH	0.007	0.009	0.22	1	-10000	0	1
CREBBP	0.001	0.046	-10000	0	-0.38	8	8
RAR gamma2/9cRA	0.005	0.01	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.085	0.21	0.46	117	-0.47	15	132
IHH	0.023	0.074	-10000	0	-0.42	7	7
SHH Np/Cholesterol/GAS1	-0.016	0.066	-10000	0	-0.21	57	57
LRPAP1	0.006	0.028	0.22	3	-0.38	2	5
dorsoventral neural tube patterning	0.016	0.065	0.21	57	-10000	0	57
SMO/beta Arrestin2	0.039	0.13	-10000	0	-0.5	10	10
SMO	0.04	0.14	-10000	0	-0.52	10	10
AKT1	0.023	0.12	-10000	0	-10000	0	0
ARRB2	0.006	0	-10000	0	-10000	0	0
BOC	-0.033	0.12	0.22	1	-0.38	58	59
ADRBK1	0.006	0	-10000	0	-10000	0	0
heart looping	0.04	0.14	-10000	0	-0.51	10	10
STIL	0.13	0.13	0.32	116	-10000	0	116
DHH N/PTCH2	0.009	0	-10000	0	-10000	0	0
DHH N/PTCH1	-0.005	0.066	-10000	0	-0.37	15	15
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
DHH	0.006	0	-10000	0	-10000	0	0
PTHLH	0.074	0.2	-10000	0	-0.51	15	15
determination of left/right symmetry	0.04	0.14	-10000	0	-0.51	10	10
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
skeletal system development	0.074	0.2	-10000	0	-0.5	15	15
IHH N/Hhip	0.02	0.045	0.24	1	-0.24	6	7
DHH N/Hhip	0.009	0.001	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.04	0.14	-10000	0	-0.51	10	10
pancreas development	0.008	0.02	0.22	5	-10000	0	5
HHAT	0.001	0.046	-10000	0	-0.38	8	8
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.029	0.11	-10000	0	-0.38	51	51
somite specification	0.04	0.14	-10000	0	-0.51	10	10
SHH Np/Cholesterol/PTCH1	-0.008	0.062	-10000	0	-0.38	10	10
SHH Np/Cholesterol/PTCH2	0.003	0.025	-10000	0	-0.2	8	8
SHH Np/Cholesterol/Megalin	0.038	0.065	0.14	148	-0.2	6	154
SHH	-0.007	0.032	0.2	1	-0.27	8	9
catabolic process	0.055	0.15	0.31	117	-0.41	15	132
SMO/Vitamin D3	0.038	0.12	-10000	0	-0.46	10	10
SHH Np/Cholesterol/Hhip	0.004	0.028	0.14	5	-0.2	8	13
LRP2	0.063	0.095	0.22	151	-10000	0	151
receptor-mediated endocytosis	0.038	0.13	0.32	28	-0.47	10	38
SHH Np/Cholesterol/BOC	-0.018	0.068	0.14	1	-0.21	65	66
SHH Np/Cholesterol/CDO	0.005	0.034	0.14	12	-0.2	10	22
mesenchymal cell differentiation	-0.004	0.028	0.2	8	-0.14	5	13
mol:Vitamin D3	0.041	0.12	0.24	115	-0.38	10	125
IHH N/PTCH2	0.02	0.046	-10000	0	-0.24	7	7
CDON	0.009	0.039	0.22	12	-0.38	2	14
IHH N/PTCH1	0.054	0.14	0.29	117	-0.41	15	132
Megalin/LRPAP1	0.006	0.017	-10000	0	-0.27	2	2
PTCH2	0.006	0	-10000	0	-10000	0	0
SHH Np/Cholesterol	0	0.024	-10000	0	-0.2	8	8
PTCH1	0.055	0.15	0.31	117	-0.41	15	132
HHIP	0.008	0.02	0.22	5	-10000	0	5

×

Signaling events mediated by PTP1B

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
PDGFRB	-0.01	0.079	-10000	0	-0.38	24	24
Jak2/Leptin Receptor	-0.001	0.076	0.21	3	-0.38	7	10
PTP1B/AKT1	-0.017	0.091	-10000	0	-0.3	11	11
FYN	-0.039	0.13	0.22	1	-0.38	67	68
p210 bcr-abl/PTP1B	-0.018	0.099	-10000	0	-0.28	26	26
EGFR	-0.032	0.12	0.22	1	-0.39	54	55
EGF/EGFR	-0.045	0.094	0.19	3	-0.32	34	37
CSF1	-0.01	0.079	0.22	1	-0.38	24	25
AKT1	0.004	0.011	0.22	1	-10000	0	1
INSR	-0.021	0.098	-10000	0	-0.39	38	38
PTP1B/N-cadherin	-0.009	0.13	0.22	33	-0.31	45	78
Insulin Receptor/Insulin	-0.027	0.09	-10000	0	-0.32	21	21
HCK	0.007	0.009	0.22	1	-10000	0	1
CRK	0.006	0	-10000	0	-10000	0	0
TYK2	-0.018	0.094	-10000	0	-0.26	26	26
EGF	0.005	0.025	0.22	7	-10000	0	7
YES1	0.011	0.031	0.22	12	-10000	0	12
CAV1	-0.047	0.12	-10000	0	-0.32	46	46
TXN	-0.017	0.09	-10000	0	-0.39	31	31
PTP1B/IRS1/GRB2	-0.11	0.13	-10000	0	-0.31	100	100
cell migration	0.018	0.099	0.28	26	-10000	0	26
STAT3	-0.003	0.056	-10000	0	-0.39	12	12
PRLR	0.014	0.039	0.22	19	-10000	0	19
ITGA2B	0.004	0.005	-10000	0	-10000	0	0
CSF1R	-0.014	0.09	0.22	3	-0.38	31	34
Prolactin Receptor/Prolactin	0.011	0.015	0.21	3	-10000	0	3
FGR	0.006	0	-10000	0	-10000	0	0
PTP1B/p130 Cas	-0.017	0.095	-10000	0	-0.26	27	27
Crk/p130 Cas	-0.015	0.093	-10000	0	-0.26	27	27
DOK1	-0.028	0.098	-10000	0	-0.31	20	20
JAK2	-0.004	0.073	-10000	0	-0.42	5	5
Jak2/Leptin Receptor/Leptin	-0.026	0.093	-10000	0	-0.33	20	20
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
PTPN1	-0.018	0.1	-10000	0	-0.28	26	26
LYN	-0.007	0.07	-10000	0	-0.38	19	19
CDH2	-0.001	0.17	0.22	118	-0.38	76	194
SRC	0	0.041	-10000	0	-10000	0	0
ITGB3	-0.046	0.14	0.22	13	-0.39	82	95
CAT1/PTP1B	-0.03	0.11	-10000	0	-0.31	22	22
CAPN1	0.001	0.033	-10000	0	-0.39	4	4
CSK	0.006	0	-10000	0	-10000	0	0
PI3K	-0.036	0.1	-10000	0	-0.31	34	34
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.025	0.09	0.22	1	-0.37	15	16
negative regulation of transcription	-0.004	0.072	-10000	0	-0.42	5	5
FCGR2A	-0.002	0.066	0.22	5	-0.38	15	20
FER	0.004	0.011	0.22	1	-10000	0	1
alphaIIb/beta3 Integrin	-0.032	0.099	-10000	0	-0.27	82	82
BLK	0.007	0.009	0.22	1	-10000	0	1
Insulin Receptor/Insulin/Shc	-0.004	0.06	-10000	0	-0.23	38	38
RHOA	0.003	0.024	-10000	0	-0.39	2	2
LEPR	0.007	0.031	0.22	5	-0.38	2	7
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
p210 bcr-abl/Grb2	0.006	0.016	-10000	0	-0.38	1	1
mol:NADPH	-0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.023	0.079	-10000	0	-0.23	31	31
PRL	0.007	0.01	0.22	1	-10000	0	1
SOCS3	-0.014	0.15	0.55	2	-1.2	9	11
SPRY2	-0.048	0.16	0.22	37	-0.39	91	128
Insulin Receptor/Insulin/IRS1	-0.13	0.14	-10000	0	-0.25	320	320
CSF1/CSF1R	-0.029	0.12	0.24	1	-0.32	51	52
Ras protein signal transduction	0	0.034	-10000	0	-0.32	1	1
IRS1	-0.21	0.2	-10000	0	-0.38	311	311
INS	0.004	0.006	-10000	0	-10000	0	0
LEP	0.005	0.017	-10000	0	-0.38	1	1
STAT5B	-0.014	0.089	-10000	0	-0.24	30	30
STAT5A	-0.013	0.087	-10000	0	-0.23	29	29
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PDGFB-D/PDGFRB	-0.023	0.1	-10000	0	-0.28	33	33
CSN2	0.008	0.035	0.52	1	-10000	0	1
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
LAT	-0.012	0.1	-10000	0	-0.56	15	15
YBX1	0.007	0.006	-10000	0	-10000	0	0
LCK	0.006	0	-10000	0	-10000	0	0
SHC1	0.006	0	-10000	0	-10000	0	0
NOX4	0.084	0.1	0.22	212	-10000	0	212

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.009	0.001	-10000	0	-10000	0	0
Necdin/E2F1	-0.16	0.14	-10000	0	-0.27	342	342
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.015	0.021	-10000	0	-0.19	4	4
NGF (dimer)/p75(NTR)/BEX1	-0.045	0.098	-10000	0	-0.22	130	130
NT-4/5 (dimer)/p75(NTR)	0.005	0	-10000	0	-10000	0	0
IKBKB	0.007	0.016	0.22	3	-10000	0	3
AKT1	0.005	0.084	-10000	0	-0.19	55	55
IKBKG	0.006	0	-10000	0	-10000	0	0
BDNF	0.006	0	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1	0.013	0.001	-10000	0	-10000	0	0
FURIN	0.002	0.04	-10000	0	-0.38	6	6
proBDNF (dimer)/p75(NTR)/Sortilin	0.013	0.001	-10000	0	-10000	0	0
LINGO1	0.009	0.022	0.22	6	-10000	0	6
Sortilin/TRAF6/NRIF	-0.028	0.054	-10000	0	-0.18	65	65
proBDNF (dimer)	0.006	0	-10000	0	-10000	0	0
NTRK1	0.006	0	-10000	0	-10000	0	0
RTN4R	0.007	0.009	0.22	1	-10000	0	1
neuron apoptosis	-0.003	0.076	-10000	0	-10000	0	0
IRAK1	0.007	0.009	0.22	1	-10000	0	1
SHC1	-0.003	0.007	0.15	1	-10000	0	1
ARHGDIA	-0.079	0.16	-10000	0	-0.38	124	124
RhoA/GTP	0.004	0.016	-10000	0	-0.27	2	2
Gamma Secretase	-0.005	0.07	-10000	0	-0.2	66	66
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.009	0.031	0.14	5	-0.2	10	15
MAGEH1	-0.001	0.054	-10000	0	-0.38	11	11
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.12	0.11	-10000	0	-0.2	337	337
Mammalian IAPs/DIABLO	0.021	0.11	-10000	0	-0.2	68	68
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.006	0.028	0.22	3	-0.38	2	5
APP	0	0.049	-10000	0	-0.38	9	9
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.006	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.035	0.084	-10000	0	-0.19	125	125
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.021	0.048	0.17	6	-10000	0	6
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.034	0.048	0.21	1	-0.21	1	2
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.009	0.001	-10000	0	-10000	0	0
NCSTN	0.007	0.009	0.22	1	-10000	0	1
mol:GTP	0.008	0.001	-10000	0	-10000	0	0
PSENEN	-0.006	0.068	-10000	0	-0.38	18	18
mol:ceramide	-0.004	0.02	0.14	6	-0.2	3	9
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.079	0.064	0.19	98	-10000	0	98
p75(NTR)/beta APP	0.005	0.035	-10000	0	-0.27	9	9
BEX1	-0.067	0.18	0.22	43	-0.38	130	173
mol:GDP	-0.001	0.006	0.15	1	-10000	0	1
NGF (dimer)	-0.035	0.12	-10000	0	-0.21	158	158
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.031	0.093	-10000	0	-0.2	124	124
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
RAC1/GTP	0.007	0.008	-10000	0	-0.19	1	1
MYD88	0.006	0.016	-10000	0	-0.38	1	1
CHUK	0.011	0.031	0.22	12	-10000	0	12
NGF (dimer)/p75(NTR)/PKA	0.008	0.001	-10000	0	-10000	0	0
RHOB	-0.012	0.082	-10000	0	-0.38	26	26
RHOA	0.005	0.023	-10000	0	-0.38	2	2
MAGE-G1/E2F1	0.008	0.017	-10000	0	-0.27	2	2
NT3 (dimer)	0.037	0.075	0.22	81	-10000	0	81
TP53	-0.028	0.064	-10000	0	-10000	0	0
PRDM4	-0.003	0.014	0.14	6	-10000	0	6
BDNF (dimer)	-0.029	0.12	-10000	0	-0.21	154	154
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
SORT1	0.008	0.02	0.22	5	-10000	0	5
activation of caspase activity	0.012	0.017	-10000	0	-0.19	4	4
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.014	0.015	0.14	8	-10000	0	8
RHOC	0.006	0.016	-10000	0	-0.38	1	1
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	-0.011	0.04	-10000	0	-10000	0	0
DIABLO	0.1	0.11	0.22	248	-10000	0	248
SMPD2	-0.004	0.02	0.14	6	-0.2	3	9
APH1B	-0.027	0.11	-10000	0	-0.38	49	49
APH1A	0.007	0.009	0.22	1	-10000	0	1
proNGF (dimer)/p75(NTR)/Sortilin	0.008	0.001	-10000	0	-10000	0	0
PSEN1	0.007	0.009	0.22	1	-10000	0	1
APAF-1/Pro-Caspase 9	0.009	0.001	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	0.008	0.003	-10000	0	-10000	0	0
MAPK8	-0.004	0.028	-10000	0	-10000	0	0
MAPK9	-0.005	0.028	-10000	0	-10000	0	0
APAF1	0.01	0.03	0.22	11	-10000	0	11
NTF3	0.037	0.075	0.22	81	-10000	0	81
NTF4	0	0	-10000	0	-10000	0	0
NDN	-0.23	0.19	-10000	0	-0.38	342	342
RAC1/GDP	0.004	0.011	-10000	0	-0.27	1	1
RhoA-B-C/GDP	0.004	0.042	-10000	0	-0.18	29	29
p75 CTF/Sortilin/TRAF6/NRIF	0.043	0.053	-10000	0	-10000	0	0
RhoA-B-C/GTP	0.008	0.001	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.02	0.014	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.018	0.015	-10000	0	-10000	0	0
PRKACB	0.01	0.027	0.22	9	-10000	0	9
proBDNF (dimer)/p75 ECD	0.007	0.004	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.076	0.17	0.22	13	-0.38	127	140
BIRC2	0.037	0.075	0.22	81	-10000	0	81
neuron projection morphogenesis	-0.048	0.085	0.16	3	-0.25	19	22
BAD	-0.007	0.031	-10000	0	-10000	0	0
RIPK2	0.065	0.096	0.22	156	-10000	0	156
NGFR	0.007	0.009	0.22	1	-10000	0	1
CYCS	-0.003	0.021	0.14	1	-0.19	2	3
ADAM17	0.051	0.088	0.22	118	-10000	0	118
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.048	0.058	0.14	159	-10000	0	159
BCL2L11	-0.007	0.031	-10000	0	-10000	0	0
BDNF (dimer)/p75(NTR)	0.009	0	-10000	0	-10000	0	0
PI3K	0.018	0.091	-10000	0	-0.2	56	56
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.013	0.018	-10000	0	-0.2	2	2
NDNL2	0.005	0.023	-10000	0	-0.38	2	2
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
PRKCI	0.12	0.11	0.22	306	-10000	0	306
NGF (dimer)/p75(NTR)	0.005	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.013	0.021	0.14	9	-0.2	2	11
TRAF6	0.007	0.013	0.22	2	-10000	0	2
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCZ	0.006	0	-10000	0	-10000	0	0
PLG	-0.001	0.054	-10000	0	-0.38	11	11
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.034	0.054	0.26	1	-10000	0	1
SQSTM1	0.006	0	-10000	0	-10000	0	0
NGFRAP1	0.004	0.028	-10000	0	-0.38	3	3
CASP3	-0.006	0.03	-10000	0	-10000	0	0
E2F1	0.006	0	-10000	0	-10000	0	0
CASP9	0.007	0.009	0.22	1	-10000	0	1
IKK complex	0.004	0.006	-10000	0	-10000	0	0
NGF (dimer)/TRKA	0.005	0	-10000	0	-10000	0	0
MMP7	-0.069	0.2	0.22	69	-0.38	148	217
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.017	0.014	-10000	0	-10000	0	0
MMP3	0.009	0.025	0.22	8	-10000	0	8
APAF-1/Caspase 9	-0.029	0.052	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.006	0.019	0.22	1	-0.38	1	2
LAT2	-0.016	0.088	-10000	0	-0.28	47	47
AP1	-0.037	0.12	0.25	4	-0.36	36	40
mol:PIP3	-0.02	0.11	0.19	1	-0.33	48	49
IKBKB	-0.009	0.064	0.14	7	-0.21	30	37
AKT1	-0.025	0.11	0.21	11	-0.31	32	43
IKBKG	-0.01	0.063	0.14	7	-0.2	42	49
MS4A2	0.006	0.007	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.054	0.091	0.22	131	-10000	0	131
MAP3K1	-0.011	0.089	0.19	6	-0.3	28	34
mol:Ca2+	-0.014	0.084	0.16	7	-0.26	48	55
LYN	-0.008	0.073	-10000	0	-0.4	19	19
CBLB	-0.014	0.088	0.2	1	-0.27	47	48
SHC1	0.006	0	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.057	0.1	-10000	0	-0.2	183	183
positive regulation of cell migration	-0.008	0.04	-10000	0	-0.27	13	13
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.033	0.083	-10000	0	-0.2	79	79
PTPN13	-0.032	0.13	-10000	0	-0.42	25	25
PTPN11	0.004	0.008	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.009	0.1	0.19	28	-0.26	25	53
SYK	0.001	0.044	0.22	3	-0.39	6	9
GRB2	0.005	0.017	-10000	0	-0.39	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.03	0.098	-10000	0	-0.33	48	48
LAT	-0.015	0.087	-10000	0	-0.27	47	47
PAK2	-0.01	0.096	0.19	7	-0.3	41	48
NFATC2	-0.015	0.078	-10000	0	-0.5	13	13
HRAS	-0.011	0.1	0.2	7	-0.32	41	48
GAB2	0.003	0.069	0.22	16	-0.38	13	29
PLA2G1B	-0.048	0.068	-10000	0	-10000	0	0
Fc epsilon R1	-0.008	0.062	-10000	0	-0.21	47	47
Antigen/IgE/Fc epsilon R1	-0.001	0.061	0.14	21	-0.19	47	68
mol:GDP	-0.011	0.11	0.21	16	-0.33	41	57
JUN	0.008	0.039	0.22	9	-0.38	3	12
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	-0.038	0.12	-10000	0	-0.39	64	64
FOS	-0.066	0.16	0.22	8	-0.38	110	118
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.014	0.091	-10000	0	-0.28	48	48
CHUK	-0.008	0.065	0.14	8	-0.2	41	49
KLRG1	-0.011	0.078	-10000	0	-0.24	44	44
VAV1	-0.015	0.089	0.23	1	-0.28	47	48
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.015	0.087	-10000	0	-0.27	47	47
negative regulation of mast cell degranulation	-0.012	0.072	-10000	0	-0.22	44	44
BTK	-0.016	0.1	0.22	15	-0.36	28	43
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	0	0.071	0.2	21	-0.19	20	41
GAB2/PI3K/SHP2	-0.054	0.092	-10000	0	-0.22	103	103
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.016	0.095	-10000	0	-0.26	57	57
RAF1	0.005	0.012	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	0.003	0.061	-10000	0	-0.18	47	47
FCER1G	-0.015	0.12	0.21	33	-0.39	47	80
FCER1A	0.006	0.016	0.22	3	-10000	0	3
Antigen/IgE/Fc epsilon R1/Fyn	-0.018	0.094	-10000	0	-0.2	103	103
MAPK3	-0.053	0.08	-10000	0	-0.31	27	27
MAPK1	-0.038	0.057	-10000	0	-0.31	1	1
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MAPK8	0.004	0.057	-10000	0	-0.4	7	7
DUSP1	-0.12	0.18	0.22	1	-0.38	179	180
NF-kappa-B/RelA	-0.01	0.044	-10000	0	-0.18	23	23
actin cytoskeleton reorganization	-0.001	0.11	-10000	0	-0.4	16	16
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.007	0.13	0.22	7	-0.37	31	38
FER	-0.015	0.087	-10000	0	-0.27	47	47
RELA	0.005	0.023	-10000	0	-0.38	2	2
ITK	-0.002	0.032	0.15	12	-10000	0	12
SOS1	0.014	0.04	0.22	20	-10000	0	20
PLCG1	-0.012	0.1	0.21	7	-0.32	41	48
cytokine secretion	-0.01	0.031	-10000	0	-0.16	11	11
SPHK1	-0.015	0.087	-10000	0	-0.27	47	47
PTK2	-0.002	0.11	-10000	0	-0.42	16	16
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.029	0.1	-10000	0	-0.34	49	49
EDG1	-0.008	0.04	-10000	0	-0.27	13	13
mol:DAG	-0.018	0.11	0.19	1	-0.34	42	43
MAP2K2	-0.07	0.097	-10000	0	-10000	0	0
MAP2K1	0.003	0.012	-10000	0	-10000	0	0
MAP2K7	0.006	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.012	0.064	-10000	0	-0.28	18	18
MAP2K4	-0.002	0.095	-10000	0	-0.85	7	7
Fc epsilon R1/FcgammaRIIB	0.003	0.066	-10000	0	-0.19	47	47
mol:Choline	-0.032	0.082	-10000	0	-0.2	79	79
SHC/Grb2/SOS1	-0.003	0.088	-10000	0	-0.27	42	42
FYN	-0.039	0.13	0.22	1	-0.38	67	68
DOK1	0.006	0.016	-10000	0	-0.38	1	1
PXN	-0.006	0.1	-10000	0	-0.4	15	15
HCLS1	-0.014	0.099	0.23	5	-0.29	48	53
PRKCB	-0.014	0.083	0.16	7	-0.25	48	55
FCGR2B	0.019	0.055	0.22	36	-0.38	1	37
IGHE	-0.001	0.003	-10000	0	-10000	0	0
KLRG1/SHIP	-0.012	0.073	-10000	0	-0.23	44	44
LCP2	-0.013	0.085	-10000	0	-0.39	28	28
PLA2G4A	-0.069	0.13	-10000	0	-0.29	76	76
RASA1	0.004	0.028	-10000	0	-0.38	3	3
mol:Phosphatidic acid	-0.032	0.082	-10000	0	-0.2	79	79
IKK complex	-0.005	0.052	0.13	8	-0.17	22	30
WIPF1	0.006	0.016	-10000	0	-0.38	1	1

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.23	0.44	-10000	0	-1.1	127	127
VDR	0.007	0.013	0.22	2	-10000	0	2
FAM120B	0.004	0.028	-10000	0	-0.38	3	3
RXRs/LXRs/DNA/9cRA	0.023	0.11	0.33	38	-0.4	3	41
RXRs/LXRs/DNA/Oxysterols	0.026	0.13	0.41	38	-0.41	7	45
MED1	0.007	0.013	0.22	2	-10000	0	2
mol:9cRA	0.01	0.023	0.1	2	-10000	0	2
RARs/THRs/DNA/Src-1	-0.022	0.095	0.21	2	-0.21	96	98
RXRs/NUR77	-0.041	0.13	0.26	4	-0.22	135	139
RXRs/PPAR	0.015	0.056	0.24	2	-10000	0	2
NCOR2	0	0.049	-10000	0	-0.38	9	9
VDR/VDR/Vit D3	0.005	0	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.023	0.031	-10000	0	-10000	0	0
RARA	0.006	0	-10000	0	-10000	0	0
NCOA1	0.004	0.028	-10000	0	-0.38	3	3
VDR/VDR/DNA	0.007	0.013	0.22	2	-10000	0	2
RARs/RARs/DNA/9cRA	0.025	0.033	0.14	37	-10000	0	37
RARG	0.015	0.042	0.22	22	-10000	0	22
RPS6KB1	-0.085	0.18	0.36	9	-0.41	125	134
RARs/THRs/DNA/SMRT	-0.024	0.099	0.21	2	-0.22	100	102
THRA	-0.065	0.15	-10000	0	-0.38	104	104
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.005	0	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.074	0.12	0.31	45	-10000	0	45
NR1H4	0.008	0.02	0.22	5	-10000	0	5
RXRs/LXRs/DNA	0.043	0.1	0.32	38	-0.36	3	41
NR1H2	-0.002	0.073	-10000	0	-0.38	19	19
NR1H3	0.01	0.037	-10000	0	-0.38	3	3
RXRs/VDR/DNA/Vit D3	0.04	0.073	0.25	5	-0.19	15	20
NR4A1	-0.13	0.19	0.22	5	-0.38	201	206
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.019	0.059	0.22	2	-10000	0	2
RXRG	0.02	0.047	0.22	17	-0.35	2	19
RXR alpha/CCPG	0.003	0.06	-10000	0	-0.26	26	26
RXRA	0	0.08	-10000	0	-0.38	23	23
RXRB	0.016	0.023	-10000	0	-10000	0	0
THRB	0.018	0.049	0.22	31	-10000	0	31
PPARG	0.009	0.022	0.22	6	-10000	0	6
PPARD	0.006	0	-10000	0	-10000	0	0
TNF	0.025	0.12	0.49	2	-0.49	1	3
mol:Oxysterols	0.005	0.021	-10000	0	-10000	0	0
cholesterol transport	0.026	0.12	0.41	38	-0.41	7	45
PPARA	0.006	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.013	0.038	0.22	18	-10000	0	18
RXRs/NUR77/BCL2	-0.095	0.14	0.22	1	-0.24	222	223
SREBF1	0.015	0.16	0.45	1	-0.89	9	10
RXRs/RXRs/DNA/9cRA	0.072	0.12	0.31	45	-10000	0	45
ABCA1	0.035	0.15	0.53	37	-0.49	1	38
RARs/THRs	-0.006	0.092	-10000	0	-0.19	95	95
RXRs/FXR	0.044	0.079	0.25	8	-0.2	15	23
BCL2	-0.043	0.13	0.22	2	-0.38	73	75

×

IL6-mediated signaling events

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
BCL2L1	-0.18	0.29	-10000	0	-0.82	64	64
CRP	-0.18	0.29	-10000	0	-0.82	64	64
cell cycle arrest	-0.22	0.35	-10000	0	-0.92	82	82
TIMP1	-0.19	0.31	-10000	0	-0.82	79	79
IL6ST	-0.021	0.085	-10000	0	-0.39	28	28
Rac1/GDP	-0.062	0.13	0.38	1	-0.41	39	40
AP1	-0.032	0.13	0.53	2	-0.56	14	16
GAB2	0.005	0.07	0.22	16	-0.38	13	29
TNFSF11	-0.18	0.29	-10000	0	-0.82	64	64
HSP90B1	-0.029	0.094	-10000	0	-1	4	4
GAB1	0.005	0.033	-10000	0	-0.39	4	4
MAPK14	-0.031	0.13	0.49	1	-0.59	17	18
AKT1	0.004	0.083	0.6	1	-10000	0	1
FOXO1	-0.001	0.082	0.56	1	-10000	0	1
MAP2K6	-0.037	0.12	0.46	1	-0.47	23	24
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
MAP2K4	-0.093	0.16	0.47	1	-0.49	40	41
MITF	-0.057	0.12	0.37	1	-0.39	39	40
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.006	0	-10000	0	-10000	0	0
A2M	-0.086	0.32	0.53	2	-1.2	41	43
CEBPB	0.005	0.034	0.22	1	-0.38	4	5
GRB2/SOS1/GAB family/SHP2	-0.012	0.092	-10000	0	-0.44	11	11
STAT3	-0.23	0.39	-10000	0	-0.97	88	88
STAT1	0.096	0.1	-10000	0	-10000	0	0
CEBPD	-0.2	0.33	-10000	0	-0.95	67	67
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PI3K	-0.021	0.084	0.26	1	-0.27	56	57
JUN	0.007	0.039	0.22	9	-0.38	3	12
PIAS3/MITF	-0.052	0.11	0.33	1	-0.37	38	39
MAPK11	-0.031	0.13	0.49	1	-0.59	17	18
STAT3 (dimer)/FOXO1	-0.18	0.29	-10000	0	-0.75	75	75
GRB2/SOS1/GAB family	-0.021	0.1	0.25	2	-0.36	17	19
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.038	0.1	0.27	1	-0.32	40	41
GRB2	0.007	0.017	-10000	0	-0.38	1	1
JAK2	0.004	0.035	0.22	2	-0.38	4	6
LBP	-0.14	0.23	0.56	1	-0.67	38	39
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
JAK1	-0.004	0.031	-10000	0	-0.39	3	3
MYC	-0.23	0.37	-10000	0	-0.98	89	89
FGG	-0.18	0.29	-10000	0	-0.82	60	60
macrophage differentiation	-0.22	0.35	-10000	0	-0.92	82	82
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.027	0.092	0.2	1	-0.24	71	72
JUNB	-0.29	0.44	-10000	0	-0.98	156	156
FOS	-0.067	0.16	0.22	8	-0.38	110	118
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.058	0.13	0.41	1	-0.4	41	42
STAT1/PIAS1	-0.06	0.12	-10000	0	-0.42	27	27
GRB2/SOS1/GAB family/SHP2/PI3K	0.006	0.086	0.5	1	-0.27	3	4
STAT3 (dimer)	-0.23	0.38	-10000	0	-0.98	85	85
PRKCD	-0.13	0.21	0.53	1	-0.57	54	55
IL6R	-0.002	0.023	0.22	1	-0.4	1	2
SOCS3	-0.027	0.16	0.54	1	-1.1	9	10
gp130 (dimer)/JAK1/JAK1/LMO4	-0.014	0.065	0.22	1	-0.26	27	28
Rac1/GTP	-0.073	0.14	0.41	1	-0.44	41	42
HCK	0.007	0.009	0.22	1	-10000	0	1
MAPKKK cascade	-0.008	0.11	0.42	1	-0.54	13	14
bone resorption	-0.17	0.28	-10000	0	-0.76	64	64
IRF1	-0.2	0.33	-10000	0	-0.92	65	65
mol:GDP	-0.06	0.12	0.4	1	-0.39	41	42
SOS1	0.015	0.041	0.23	20	-10000	0	20
VAV1	-0.061	0.12	0.4	1	-0.4	41	42
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.021	0.11	0.44	1	-0.52	17	18
PTPN11	-0.004	0.021	-10000	0	-10000	0	0
IL6/IL6RA	-0.024	0.081	0.15	1	-0.29	46	47
gp130 (dimer)/TYK2/TYK2/LMO4	-0.01	0.055	-10000	0	-0.23	28	28
gp130 (dimer)/JAK2/JAK2/LMO4	-0.011	0.06	0.16	1	-0.24	30	31
IL6	-0.032	0.11	0.22	4	-0.39	46	50
PIAS3	0.007	0.009	0.22	1	-10000	0	1
PTPRE	0.012	0.015	-10000	0	-10000	0	0
PIAS1	0.007	0.009	0.22	1	-10000	0	1
RAC1	0.001	0.018	-10000	0	-0.39	1	1
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.038	0.095	-10000	0	-0.3	40	40
LMO4	0.001	0.037	0.22	10	-0.39	1	11
STAT3 (dimer)/PIAS3	-0.21	0.34	-10000	0	-0.86	91	91
MCL1	0.004	0.079	0.7	1	-10000	0	1

×

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

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
MET/RANBP9	-0.013	0.075	-10000	0	-0.27	45	45
CRKL	-0.009	0.08	-10000	0	-0.25	44	44
mol:PIP3	0.01	0.051	0.36	11	-10000	0	11
AKT1	0.005	0.036	0.25	11	-10000	0	11
PTK2B	0.005	0.023	-10000	0	-0.38	2	2
RAPGEF1	-0.01	0.076	-10000	0	-0.24	44	44
RANBP10	0.006	0.016	-10000	0	-0.38	1	1
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
HGF/MET/SHIP2	-0.007	0.064	-10000	0	-0.23	45	45
MAP3K5	-0.009	0.076	-10000	0	-0.32	10	10
HGF/MET/CIN85/CBL/ENDOPHILINS	0.007	0.07	-10000	0	-0.2	45	45
AP1	-0.038	0.1	0.15	7	-0.23	112	119
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.006	0	-10000	0	-10000	0	0
apoptosis	-0.13	0.29	0.33	1	-0.71	112	113
STAT3 (dimer)	-0.005	0.084	0.21	7	-0.23	52	59
GAB1/CRKL/SHP2/PI3K	0.004	0.11	0.21	9	-0.34	16	25
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	-0.006	0.077	-10000	0	-0.24	44	44
PTPN11	0.006	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.009	0.022	0.22	6	-10000	0	6
PTEN	-0.001	0.054	-10000	0	-0.38	11	11
ELK1	0.016	0.086	0.21	74	-10000	0	74
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.006	0.043	-10000	0	-0.16	5	5
PAK1	0.007	0.041	0.23	11	-0.2	1	12
HGF/MET/RANBP10	-0.007	0.064	-10000	0	-0.23	45	45
HRAS	-0.028	0.15	-10000	0	-0.54	45	45
DOCK1	-0.01	0.078	0.21	1	-0.24	44	45
GAB1	-0.008	0.084	0.18	1	-0.26	44	45
CRK	-0.009	0.08	-10000	0	-0.25	44	44
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.022	0.14	-10000	0	-0.48	45	45
JUN	0.008	0.039	0.22	9	-0.38	3	12
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.008	0.067	0.12	33	-0.22	45	78
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
cell morphogenesis	-0.003	0.11	0.21	23	-0.38	13	36
GRB2/SHC	-0.001	0.061	-10000	0	-0.19	46	46
FOS	-0.066	0.16	0.22	8	-0.38	110	118
GLMN	0.022	0.048	0.13	94	-10000	0	94
cell motility	0.015	0.086	0.21	74	-10000	0	74
HGF/MET/MUC20	-0.01	0.063	-10000	0	-0.22	45	45
cell migration	-0.001	0.06	-10000	0	-0.19	46	46
GRB2	0.006	0.016	-10000	0	-0.38	1	1
CBL	0.006	0	-10000	0	-10000	0	0
MET/RANBP10	-0.014	0.076	-10000	0	-0.27	46	46
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0	0.084	0.22	7	-0.22	52	59
MET/MUC20	-0.017	0.074	-10000	0	-0.27	45	45
RAP1B	-0.01	0.073	-10000	0	-0.32	8	8
RAP1A	-0.01	0.073	-10000	0	-0.32	8	8
HGF/MET/RANBP9	-0.007	0.064	-10000	0	-0.23	45	45
RAF1	-0.027	0.15	-10000	0	-0.51	45	45
STAT3	-0.005	0.085	0.21	7	-0.23	52	59
cell proliferation	-0.015	0.1	0.2	8	-0.33	45	53
RPS6KB1	0.011	0.041	0.13	12	-10000	0	12
MAPK3	0.054	0.2	0.67	51	-10000	0	51
MAPK1	-0.005	0.057	0.68	1	-10000	0	1
RANBP9	0.007	0.013	0.22	2	-10000	0	2
MAPK8	-0.005	0.074	-10000	0	-0.26	16	16
SRC	-0.003	0.079	0.2	7	-0.38	4	11
PI3K	0.008	0.11	0.22	9	-0.2	85	94
MET/Glomulin	0.009	0.08	0.19	32	-0.23	38	70
SOS1	0.014	0.04	0.22	20	-10000	0	20
MAP2K1	-0.026	0.14	0.25	1	-0.48	45	46
MET	-0.013	0.12	0.22	32	-0.38	45	77
MAP4K1	-0.007	0.076	-10000	0	-0.24	43	43
PTK2	0.028	0.065	0.22	57	-10000	0	57
MAP2K2	-0.085	0.15	-10000	0	-0.52	45	45
BAD	0.003	0.034	0.23	11	-10000	0	11
MAP2K4	-0.011	0.073	-10000	0	-0.3	11	11
SHP2/GRB2/SOS1/GAB1	-0.018	0.085	-10000	0	-0.3	46	46
INPPL1	0.007	0.013	0.22	2	-10000	0	2
PXN	-0.002	0.056	-10000	0	-0.38	12	12
SH3KBP1	0.007	0.009	0.22	1	-10000	0	1
HGS	-0.01	0.062	0.21	1	-0.2	45	46
PLCgamma1/PKC	0.005	0	-10000	0	-10000	0	0
HGF	0.008	0.018	0.22	4	-10000	0	4
RASA1	0.004	0.028	-10000	0	-0.38	3	3
NCK1	0.024	0.059	0.22	47	-10000	0	47
PTPRJ	0.007	0.016	0.22	3	-10000	0	3
NCK/PLCgamma1	0.012	0.074	0.15	53	-0.19	45	98
PDPK1	0.007	0.041	0.29	11	-10000	0	11
HGF/MET/SHIP	-0.01	0.063	-10000	0	-0.22	45	45

×

Regulation of Androgen receptor activity

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
HDAC1	0.017	0.071	0.23	53	-10000	0	53
SMARCC1	-0.012	0.022	-10000	0	-10000	0	0
REL	0.006	0	-10000	0	-10000	0	0
HDAC7	-0.14	0.11	0.23	4	-0.27	174	178
JUN	0.008	0.039	0.22	9	-0.38	3	12
EP300	0.003	0.037	-10000	0	-0.38	5	5
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.002	0.064	0.18	58	-10000	0	58
FOXO1	0	0.049	-10000	0	-0.38	9	9
T-DHT/AR	-0.15	0.12	-10000	0	-0.28	173	173
MAP2K6	0.01	0.07	0.22	57	-10000	0	57
BRM/BAF57	-0.054	0.12	-10000	0	-0.27	130	130
MAP2K4	-0.017	0.045	-10000	0	-0.4	7	7
SMARCA2	-0.083	0.16	-10000	0	-0.38	130	130
PDE9A	-0.21	0.32	-10000	0	-1.1	64	64
NCOA2	0.007	0.013	0.22	2	-10000	0	2
CEBPA	0.006	0	-10000	0	-10000	0	0
EHMT2	0.007	0.009	0.22	1	-10000	0	1
cell proliferation	-0.17	0.12	-10000	0	-0.33	120	120
NR0B1	0.014	0.041	0.22	21	-10000	0	21
EGR1	-0.15	0.19	0.22	4	-0.38	227	231
RXRs/9cRA	0.007	0.048	-10000	0	-0.2	23	23
AR/RACK1/Src	-0.074	0.07	-10000	0	-0.31	6	6
AR/GR	-0.12	0.12	-10000	0	-0.24	238	238
GNB2L1	0.006	0	-10000	0	-10000	0	0
PKN1	0.009	0.032	0.22	9	-0.38	1	10
RCHY1	0.011	0.032	0.22	13	-10000	0	13
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.024	0.038	0.17	5	-0.29	7	12
T-DHT/AR/TIF2/CARM1	-0.074	0.073	0.25	1	-0.3	6	7
SRC	-0.033	0.058	0.22	2	-0.24	6	8
NR3C1	-0.003	0.058	-10000	0	-0.38	13	13
KLK3	-0.06	0.077	-10000	0	-10000	0	0
APPBP2	-0.011	0.03	0.22	5	-0.39	1	6
TRIM24	0.008	0.02	0.22	5	-10000	0	5
T-DHT/AR/TIP60	-0.077	0.073	0.18	1	-0.23	22	23
TMPRSS2	-0.63	0.48	-10000	0	-1	356	356
RXRG	0.011	0.044	0.22	17	-0.38	2	19
mol:9cRA	0	0	-10000	0	-10000	0	0
RXRA	-0.01	0.077	-10000	0	-0.38	23	23
RXRB	0.006	0	-10000	0	-10000	0	0
CARM1	0.007	0.009	0.22	1	-10000	0	1
NR2C2	0.006	0	-10000	0	-10000	0	0
KLK2	-0.06	0.06	-10000	0	-10000	0	0
AR	-0.12	0.13	-10000	0	-0.26	237	237
SENP1	0.018	0.049	0.22	31	-10000	0	31
HSP90AA1	0.006	0	-10000	0	-10000	0	0
MDM2	0.007	0.024	0.22	4	-0.38	1	5
SRY	0.006	0	-10000	0	-10000	0	0
GATA2	0.004	0.034	0.22	1	-0.38	4	5
MYST2	0.006	0.019	0.22	1	-0.38	1	2
HOXB13	0.007	0.009	0.22	1	-10000	0	1
T-DHT/AR/RACK1/Src	-0.076	0.072	-10000	0	-0.32	6	6
positive regulation of transcription	0.004	0.034	0.22	1	-0.38	4	5
DNAJA1	-0.01	0.028	0.21	7	-10000	0	7
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.052	0.27	10	-0.29	1	11
NCOA1	0.009	0.032	-10000	0	-0.42	3	3
SPDEF	-0.041	0.13	0.22	1	-0.38	69	70
T-DHT/AR/TIF2	-0.053	0.062	0.17	2	-0.26	13	15
T-DHT/AR/Hsp90	-0.077	0.075	0.18	1	-0.23	22	23
GSK3B	-0.005	0.009	-10000	0	-10000	0	0
NR2C1	0.012	0.033	0.22	14	-10000	0	14
mol:T-DHT	-0.034	0.064	0.24	2	-0.26	6	8
SIRT1	0.006	0	-10000	0	-10000	0	0
ZMIZ2	0.006	0	-10000	0	-10000	0	0
POU2F1	-0.064	0.056	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.072	0.08	0.22	5	-0.33	6	11
CREBBP	0.001	0.046	-10000	0	-0.38	8	8
SMARCE1	0.006	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.007	0.013	0.22	2	-10000	0	2
Aurora C/Aurora B/INCENP	0.038	0.051	0.14	113	-10000	0	113
metaphase	0	0	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
H3F3B	-0.004	0.05	-10000	0	-0.45	7	7
AURKB	0.049	0.086	0.22	113	-10000	0	113
AURKC	0.006	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.055	0.072	-10000	0	-10000	0	0
PLK1	0.24	0.31	0.89	43	-0.77	1	44
CDKN1B	0.16	0.25	0.58	61	-0.48	2	63
FOXO3	0.23	0.31	0.72	66	-0.57	8	74
KAT2B	0.048	0.054	0.14	66	-10000	0	66
FOXO1/SIRT1	0.007	0.056	-10000	0	-0.31	3	3
CAT	0.21	0.31	0.71	41	-1	9	50
CTNNB1	0.006	0.009	0.22	1	-10000	0	1
AKT1	0.053	0.059	0.23	5	-10000	0	5
FOXO1	0.062	0.082	-10000	0	-0.35	2	2
MAPK10	0.014	0.053	0.17	4	-0.18	19	23
mol:GTP	0	0.006	-10000	0	-10000	0	0
FOXO4	0.025	0.13	0.38	26	-0.47	2	28
response to oxidative stress	0.048	0.056	0.15	66	-10000	0	66
FOXO3A/SIRT1	0.096	0.25	0.61	44	-0.51	17	61
XPO1	0.025	0.063	0.22	52	-10000	0	52
EP300	0.002	0.037	-10000	0	-0.39	5	5
BCL2L11	0.07	0.081	0.58	2	-10000	0	2
FOXO1/SKP2	0.085	0.1	0.26	82	-0.32	2	84
mol:GDP	0.048	0.056	0.15	66	-10000	0	66
RAN	0.004	0.007	-10000	0	-10000	0	0
GADD45A	0.16	0.23	0.64	55	-10000	0	55
YWHAQ	0.006	0	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.029	0.035	-10000	0	-10000	0	0
MST1	0.052	0.058	0.18	41	-10000	0	41
CSNK1D	0.006	0	-10000	0	-10000	0	0
CSNK1E	0.006	0	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.01	0.041	-10000	0	-0.27	5	5
YWHAB	0.007	0.009	0.22	1	-10000	0	1
MAPK8	0.021	0.043	0.18	5	-0.2	1	6
MAPK9	0.019	0.042	0.16	6	-0.18	2	8
YWHAG	0.004	0.033	-10000	0	-0.38	4	4
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
YWHAZ	0.006	0	-10000	0	-10000	0	0
SIRT1	-0.002	0.026	-10000	0	-10000	0	0
SOD2	0.031	0.45	0.56	57	-0.79	113	170
RBL2	0.18	0.24	0.59	38	-0.92	1	39
RAL/GDP	0.039	0.045	0.18	6	-0.21	1	7
CHUK	0.056	0.062	0.19	52	-10000	0	52
Ran/GTP	0.004	0.012	-10000	0	-10000	0	0
CSNK1G2	0.006	0	-10000	0	-10000	0	0
RAL/GTP	0.039	0.053	0.18	27	-0.2	1	28
CSNK1G1	0.006	0	-10000	0	-10000	0	0
FASLG	0.069	0.075	-10000	0	-10000	0	0
SKP2	0.056	0.091	0.22	131	-10000	0	131
USP7	0.004	0.02	0.23	1	-0.38	1	2
IKBKB	0.053	0.059	0.19	41	-10000	0	41
CCNB1	0.32	0.34	0.78	74	-0.68	2	76
FOXO1-3a-4/beta catenin	0.12	0.26	0.54	59	-0.44	2	61
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.099	0.26	82	-0.32	2	84
CSNK1A1	0.007	0.009	0.22	1	-10000	0	1
SGK1	0.048	0.054	0.14	66	-10000	0	66
CSNK1G3	0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.009	0.023	0.2	4	-10000	0	4
ZFAND5	0.026	0.12	0.42	5	-0.87	1	6
SFN	0.013	0.039	0.22	19	-10000	0	19
CDK2	0.096	0.11	0.22	255	-10000	0	255
FOXO3A/14-3-3	0.08	0.091	0.26	37	-0.34	2	39
CREBBP	-0.011	0.046	-10000	0	-0.39	8	8
FBXO32	0.016	0.56	0.72	42	-0.92	130	172
BCL6	0.16	0.3	0.59	36	-1	15	51
RALB	0.003	0.018	-10000	0	-0.39	1	1
RALA	0.004	0.012	0.22	1	-10000	0	1
YWHAH	0.005	0.03	0.22	1	-0.38	3	4

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.027	0.11	-10000	0	-0.39	31	31
FYN	-0.056	0.16	0.29	9	-0.45	51	60
LAT/GRAP2/SLP76	-0.037	0.12	-10000	0	-0.4	42	42
IKBKB	0.007	0.016	0.22	3	-10000	0	3
AKT1	-0.03	0.11	0.24	8	-0.34	42	50
B2M	0	0.041	-10000	0	-0.39	6	6
IKBKG	-0.013	0.031	-10000	0	-0.11	24	24
MAP3K8	0.006	0	-10000	0	-10000	0	0
mol:Ca2+	-0.011	0.014	-10000	0	-0.05	46	46
integrin-mediated signaling pathway	0.006	0.022	-10000	0	-0.22	5	5
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.042	0.15	0.27	8	-0.46	42	50
TRPV6	0.006	0.032	0.51	1	-10000	0	1
CD28	0.004	0.005	-10000	0	-10000	0	0
SHC1	-0.036	0.13	0.29	6	-0.46	33	39
receptor internalization	-0.03	0.12	0.27	6	-0.42	29	35
PRF1	-0.065	0.25	0.69	1	-1.1	28	29
KRAS	0.03	0.067	0.22	62	-10000	0	62
GRB2	0.006	0.016	-10000	0	-0.38	1	1
COT/AKT1	-0.021	0.09	0.21	8	-0.28	39	47
LAT	-0.036	0.13	0.28	6	-0.44	36	42
EntrezGene:6955	-0.001	0.004	0.053	1	-10000	0	1
CD3D	-0.056	0.15	0.23	2	-0.39	90	92
CD3E	-0.004	0.066	0.23	5	-0.4	14	19
CD3G	0.015	0.055	0.22	33	-0.4	1	34
RASGRP2	-0.002	0.012	0.068	1	-10000	0	1
RASGRP1	-0.05	0.14	0.26	5	-0.35	76	81
HLA-A	-0.008	0.066	-10000	0	-0.4	16	16
RASSF5	0.003	0.037	-10000	0	-0.38	5	5
RAP1A/GTP/RAPL	0.006	0.022	-10000	0	-0.22	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.042	0.14	6	-0.11	37	43
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.021	0.05	-10000	0	-0.17	41	41
PRKCA	-0.025	0.062	0.12	4	-0.2	42	46
GRAP2	0.006	0	-10000	0	-10000	0	0
mol:IP3	-0.031	0.091	-10000	0	-0.3	41	41
EntrezGene:6957	-0.001	0.005	0.06	1	-10000	0	1
TCR/CD3/MHC I/CD8	-0.034	0.12	0.36	2	-0.42	29	31
ORAI1	-0.02	0.067	-10000	0	-0.27	38	38
CSK	-0.037	0.13	0.28	6	-0.45	36	42
B7 family/CD28	-0.028	0.14	0.36	7	-0.44	37	44
CHUK	0.011	0.031	0.22	12	-10000	0	12
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.042	0.14	0.3	5	-0.49	36	41
PTPN6	-0.038	0.14	0.26	9	-0.46	36	45
VAV1	-0.036	0.13	0.28	6	-0.46	33	39
Monovalent TCR/CD3	-0.031	0.11	0.26	6	-0.25	91	97
CBL	0.006	0	-10000	0	-10000	0	0
LCK	-0.041	0.15	0.28	9	-0.44	48	57
PAG1	-0.037	0.13	0.28	6	-0.45	36	42
RAP1A	0.007	0.009	0.22	1	-10000	0	1
TCR/CD3/MHC I/CD8/LCK	-0.042	0.15	0.3	5	-0.49	36	41
CD80	0.008	0.028	0.22	9	-10000	0	9
CD86	0.012	0.041	0.22	21	-10000	0	21
PDK1/CARD11/BCL10/MALT1	-0.023	0.06	-10000	0	-0.2	42	42
HRAS	0.006	0	-10000	0	-10000	0	0
GO:0035030	-0.03	0.12	0.3	11	-0.38	37	48
CD8A	0.004	0.007	-10000	0	-10000	0	0
CD8B	0.004	0.017	0.21	3	-10000	0	3
PTPRC	-0.008	0.13	0.22	49	-0.39	45	94
PDK1/PKC theta	-0.038	0.13	0.29	5	-0.4	42	47
CSK/PAG1	-0.037	0.13	0.28	5	-0.45	33	38
SOS1	0.014	0.04	0.22	20	-10000	0	20
peptide-MHC class I	-0.005	0.061	-10000	0	-0.32	19	19
GRAP2/SLP76	-0.041	0.14	-10000	0	-0.44	45	45
STIM1	-0.026	0.094	-10000	0	-0.38	37	37
RAS family/GTP	0.023	0.066	0.16	35	-0.15	14	49
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.031	0.12	0.27	6	-0.43	29	35
mol:DAG	-0.032	0.081	-10000	0	-0.27	44	44
RAP1A/GDP	-0.003	0.019	0.064	5	-0.055	20	25
PLCG1	0.009	0.022	0.22	6	-10000	0	6
CD247	0.004	0.007	-10000	0	-10000	0	0
cytotoxic T cell degranulation	-0.061	0.23	0.68	1	-1	28	29
RAP1A/GTP	-0.001	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.13	0.26	8	-0.39	42	50
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.037	0.11	-10000	0	-0.38	41	41
NRAS	0.099	0.11	0.22	245	-10000	0	245
ZAP70	0.006	0.002	-10000	0	-10000	0	0
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
LAT/GRAP2/SLP76/VAV1	-0.041	0.11	-10000	0	-0.37	45	45
MALT1	0.017	0.047	0.22	29	-10000	0	29
TRAF6	0.007	0.013	0.22	2	-10000	0	2
CD8 heterodimer	0.005	0.012	-10000	0	-10000	0	0
CARD11	0.007	0.013	0.22	2	-10000	0	2
PRKCB	-0.027	0.057	-10000	0	-0.19	44	44
PRKCE	-0.025	0.059	-10000	0	-0.2	40	40
PRKCQ	-0.041	0.14	0.3	5	-0.44	42	47
LCP2	-0.013	0.085	-10000	0	-0.38	28	28
BCL10	0.006	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.025	0.095	0.22	9	-0.29	41	50
IKK complex	-0.004	0.033	0.11	12	-0.096	15	27
RAS family/GDP	-0.002	0.007	-10000	0	-0.037	2	2
MAP3K14	-0.018	0.071	0.21	5	-0.21	39	44
PDPK1	-0.029	0.1	0.24	8	-0.32	41	49
TCR/CD3/MHC I/CD8/Fyn	-0.044	0.15	0.29	5	-0.52	33	38

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.026	0.093	-10000	0	-0.4	25	25
PDGFB-D/PDGFRB/SLAP	-0.005	0.056	-10000	0	-0.27	24	24
PDGFB-D/PDGFRB/APS/CBL	-0.003	0.047	-10000	0	-0.22	24	24
AKT1	-0.06	0.1	-10000	0	-0.29	35	35
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	-0.025	0.091	-10000	0	-0.43	24	24
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
FGR	-0.015	0.055	-10000	0	-0.26	23	23
mol:Ca2+	-0.027	0.094	-10000	0	-0.45	24	24
MYC	-0.095	0.24	-10000	0	-0.76	60	60
SHC1	0.006	0	-10000	0	-10000	0	0
HRAS/GDP	-0.008	0.041	-10000	0	-0.19	27	27
LRP1/PDGFRB/PDGFB	-0.004	0.058	-10000	0	-0.23	34	34
GRB10	0.007	0.009	0.22	1	-10000	0	1
PTPN11	0.006	0	-10000	0	-10000	0	0
GO:0007205	-0.027	0.095	-10000	0	-0.46	24	24
PTEN	-0.001	0.054	-10000	0	-0.38	11	11
GRB2	0.006	0.016	-10000	0	-0.38	1	1
GRB7	0.006	0.035	0.22	5	-0.38	3	8
PDGFB-D/PDGFRB/SHP2	-0.005	0.056	-10000	0	-0.27	24	24
PDGFB-D/PDGFRB/GRB10	-0.005	0.056	-10000	0	-0.27	24	24
cell cycle arrest	-0.005	0.056	-10000	0	-0.27	24	24
HRAS	0.006	0	-10000	0	-10000	0	0
HIF1A	-0.057	0.094	-10000	0	-0.28	28	28
GAB1	-0.037	0.097	-10000	0	-0.43	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	-0.037	0.092	-10000	0	-0.39	24	24
PDGFB-D/PDGFRB	-0.001	0.05	-10000	0	-0.24	24	24
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.005	0.056	-10000	0	-0.27	24	24
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.034	0.097	-10000	0	-0.38	25	25
positive regulation of MAPKKK cascade	-0.005	0.056	-10000	0	-0.27	24	24
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.027	0.096	-10000	0	-0.46	24	24
E5	-0.001	0.001	-10000	0	-10000	0	0
CSK	0.007	0.001	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.006	0.059	-10000	0	-0.27	27	27
SHB	0.006	0	-10000	0	-10000	0	0
BLK	-0.015	0.055	-10000	0	-0.26	23	23
PTPN2	0.004	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.005	0.056	-10000	0	-0.27	24	24
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
VAV2	-0.047	0.11	-10000	0	-0.4	30	30
CBL	0.006	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.005	0.056	-10000	0	-0.27	24	24
LCK	-0.015	0.055	-10000	0	-0.26	24	24
PDGFRB	-0.012	0.08	-10000	0	-0.39	24	24
ACP1	0.024	0.059	0.22	46	-10000	0	46
HCK	-0.016	0.055	-10000	0	-0.26	24	24
ABL1	-0.03	0.08	-10000	0	-0.36	24	24
PDGFB-D/PDGFRB/CBL	-0.039	0.11	-10000	0	-0.5	24	24
PTPN1	0.004	0.007	-10000	0	-10000	0	0
SNX15	0.006	0	-10000	0	-10000	0	0
STAT3	-0.002	0.056	-10000	0	-0.38	12	12
STAT1	0.12	0.11	0.22	297	-10000	0	297
cell proliferation	-0.085	0.21	-10000	0	-0.67	60	60
SLA	0.007	0.013	0.22	2	-10000	0	2
actin cytoskeleton reorganization	-0.008	0.052	-10000	0	-0.36	1	1
SRC	-0.014	0.055	-10000	0	-0.26	23	23
PI3K	-0.077	0.095	-10000	0	-0.22	112	112
PDGFB-D/PDGFRB/GRB7/SHC	-0.001	0.051	-10000	0	-0.23	27	27
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	-0.026	0.094	-10000	0	-0.44	24	24
LYN	-0.033	0.11	-10000	0	-0.38	42	42
LRP1	-0.001	0.054	-10000	0	-0.38	11	11
SOS1	0.014	0.04	0.22	20	-10000	0	20
STAT5B	-0.001	0.054	-10000	0	-0.38	11	11
STAT5A	0	0.049	-10000	0	-0.38	9	9
NCK1-2/p130 Cas	0.014	0.055	-10000	0	-0.2	24	24
SPHK1	0.004	0.011	0.22	1	-10000	0	1
EDG1	-0.005	0.059	-10000	0	-0.39	13	13
mol:DAG	-0.027	0.096	-10000	0	-0.46	24	24
PLCG1	-0.028	0.098	-10000	0	-0.47	24	24
NHERF/PDGFRB	-0.073	0.13	-10000	0	-0.25	185	185
YES1	-0.013	0.057	-10000	0	-0.26	23	23
cell migration	-0.073	0.12	-10000	0	-0.25	185	185
SHC/Grb2/SOS1	0.01	0.047	-10000	0	-0.19	23	23
SLC9A3R2	-0.013	0.085	-10000	0	-0.38	28	28
SLC9A3R1	-0.097	0.17	-10000	0	-0.38	151	151
NHERF1-2/PDGFRB/PTEN	-0.068	0.12	-10000	0	-0.22	194	194
FYN	-0.072	0.17	-10000	0	-0.45	87	87
DOK1	-0.015	0.042	-10000	0	-0.21	25	25
HRAS/GTP	0.005	0	-10000	0	-10000	0	0
PDGFB	0.006	0	-10000	0	-10000	0	0
RAC1	-0.067	0.15	-10000	0	-0.42	83	83
PRKCD	-0.016	0.043	-10000	0	-0.21	26	26
FER	-0.015	0.042	0.15	1	-0.21	24	25
MAPKKK cascade	-0.012	0.042	-10000	0	-0.19	9	9
RASA1	-0.017	0.043	-10000	0	-0.21	27	27
NCK1	0.024	0.059	0.22	47	-10000	0	47
NCK2	0.006	0	-10000	0	-10000	0	0
p62DOK/Csk	-0.013	0.039	-10000	0	-0.19	25	25
PDGFB-D/PDGFRB/SHB	-0.005	0.056	-10000	0	-0.27	24	24
chemotaxis	-0.03	0.078	-10000	0	-0.35	24	24
STAT1-3-5/STAT1-3-5	-0.008	0.049	-10000	0	-0.19	32	32
Bovine Papilomavirus E5/PDGFRB	-0.009	0.055	-10000	0	-0.27	24	24
PTPRJ	0.007	0.016	0.22	3	-10000	0	3

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.01	0.093	0.62	1	-10000	0	1
UGCG	-0.009	0.039	-10000	0	-0.6	1	1
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.065	0.15	-10000	0	-0.42	47	47
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.008	0.04	-10000	0	-0.59	1	1
mol:DAG	-0.012	0.1	-10000	0	-0.88	8	8
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.098	0.19	-10000	0	-0.43	116	116
FRAP1	-0.1	0.23	-10000	0	-0.53	94	94
FOXO3	-0.076	0.18	-10000	0	-0.5	60	60
AKT1	-0.078	0.19	-10000	0	-0.51	69	69
GAB2	-0.001	0.07	0.22	16	-0.39	13	29
SMPD1	-0.009	0.042	-10000	0	-0.71	1	1
SGMS1	-0.018	0.088	-10000	0	-0.71	8	8
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	0.004	0.099	0.15	120	-0.23	56	176
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
cell proliferation	-0.037	0.11	-10000	0	-0.29	57	57
EIF3A	0.006	0	-10000	0	-10000	0	0
PI3K	-0.025	0.084	0.28	1	-0.27	56	57
RPS6KB1	-0.016	0.067	0.38	1	-10000	0	1
mol:sphingomyelin	-0.012	0.1	-10000	0	-0.88	8	8
natural killer cell activation	-0.002	0.004	-10000	0	-10000	0	0
JAK3	0.002	0.008	-10000	0	-10000	0	0
PIK3R1	-0.042	0.12	-10000	0	-0.39	64	64
JAK1	0	0.029	-10000	0	-0.39	3	3
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MYC	-0.12	0.3	-10000	0	-0.93	61	61
MYB	-0.086	0.31	0.54	1	-1.1	46	47
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.044	0.13	0.29	1	-0.38	34	35
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.012	0.062	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.043	0.13	0.29	1	-0.37	34	35
Rac1/GDP	-0.001	0.085	0.19	1	-0.2	57	58
T cell proliferation	-0.041	0.12	0.27	1	-0.35	33	34
SHC1	0.002	0.007	-10000	0	-10000	0	0
RAC1	0.005	0.017	-10000	0	-0.38	1	1
positive regulation of cyclin-dependent protein kinase activity	-0.004	0.019	0.18	1	-0.064	46	47
PRKCZ	-0.043	0.12	0.27	1	-0.36	33	34
NF kappa B1 p50/RelA	-0.09	0.2	-10000	0	-0.46	100	100
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.011	0.099	0.5	1	-0.37	8	9
HSP90AA1	0.006	0	-10000	0	-10000	0	0
RELA	0.005	0.023	-10000	0	-0.38	2	2
IL2RA	0.004	0.02	0.22	4	-10000	0	4
IL2RB	-0.003	0.046	-10000	0	-0.38	8	8
TERT	0.006	0	-10000	0	-10000	0	0
E2F1	-0.03	0.12	0.48	1	-0.43	46	47
SOS1	0.01	0.041	0.22	20	-10000	0	20
RPS6	0.006	0	-10000	0	-10000	0	0
mol:cAMP	0.002	0.01	0.033	4	-0.13	1	5
PTPN11	0.002	0.008	-10000	0	-10000	0	0
IL2RG	-0.011	0.11	0.22	31	-0.39	37	68
actin cytoskeleton organization	-0.041	0.12	0.27	1	-0.35	33	34
GRB2	0.001	0.018	-10000	0	-0.38	1	1
IL2	0.002	0.009	-10000	0	-10000	0	0
PIK3CA	0.052	0.092	0.22	131	-10000	0	131
Rac1/GTP	0.004	0.083	0.22	1	-0.19	57	58
LCK	0.002	0.009	-10000	0	-10000	0	0
BCL2	-0.13	0.29	-10000	0	-0.76	90	90

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.006	0	-10000	0	-10000	0	0
SMAD2	0.006	0.041	0.19	2	-0.2	3	5
SMAD3	-0.018	0.062	-10000	0	-0.3	5	5
SMAD3/SMAD4	0.094	0.044	0.22	13	-10000	0	13
SMAD4/Ubc9/PIASy	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.12	0.054	0.21	61	-10000	0	61
PPM1A	0.006	0	-10000	0	-10000	0	0
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
SMAD2/SMAD4	0.009	0.035	-10000	0	-0.18	3	3
MAP3K1	0.004	0.033	-10000	0	-0.38	4	4
TRAP-1/SMAD4	0.009	0	-10000	0	-10000	0	0
MAPK3	-0.029	0.11	-10000	0	-0.38	51	51
MAPK1	0.006	0.019	0.22	1	-0.38	1	2
NUP214	0.006	0	-10000	0	-10000	0	0
CTDSP1	0.004	0.028	-10000	0	-0.38	3	3
CTDSP2	0.005	0.023	-10000	0	-0.38	2	2
CTDSPL	0.006	0	-10000	0	-10000	0	0
KPNB1	0.006	0	-10000	0	-10000	0	0
TGFBRAP1	0.006	0	-10000	0	-10000	0	0
UBE2I	0.006	0	-10000	0	-10000	0	0
NUP153	0.012	0.036	0.22	16	-10000	0	16
KPNA2	0.19	0.075	0.22	491	-10000	0	491
PIAS4	0.006	0	-10000	0	-10000	0	0

×

Arf6 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.029	0.08	-10000	0	-0.22	82	82
ARNO/beta Arrestin1-2	-0.001	0.025	0.12	1	-0.17	11	12
EGFR	-0.03	0.12	0.22	1	-0.39	54	55
EPHA2	0.007	0.009	0.22	1	-10000	0	1
USP6	0.006	0	-10000	0	-10000	0	0
IQSEC1	0.006	0	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.017	0.082	-10000	0	-0.27	54	54
ARRB2	0.003	0.011	0.15	3	-10000	0	3
mol:GTP	0.009	0.016	0.063	10	-10000	0	10
ARRB1	-0.001	0.055	0.22	1	-0.38	11	12
FBXO8	0.006	0	-10000	0	-10000	0	0
TSHR	0.013	0.038	0.22	18	-10000	0	18
EGF	0.009	0.024	0.22	7	-10000	0	7
somatostatin receptor activity	0	0	-10000	0	-0.001	32	32
ARAP2	0	0	-10000	0	0	19	19
mol:GDP	-0.048	0.079	-10000	0	-0.22	47	47
mol:PI-3-4-5-P3	0	0	-10000	0	-0.001	25	25
ITGA2B	0.006	0	-10000	0	-10000	0	0
ARF6	0.006	0.016	-10000	0	-0.39	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.032	0.042	-10000	0	-10000	0	0
ADAP1	0	0	-10000	0	0	16	16
KIF13B	-0.05	0.14	-10000	0	-0.38	82	82
HGF/MET	-0.013	0.075	-10000	0	-0.27	45	45
PXN	-0.002	0.056	-10000	0	-0.38	12	12
ARF6/GTP	-0.046	0.076	-10000	0	-0.25	31	31
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.01	0.07	-10000	0	-0.23	54	54
ADRB2	0.006	0	-10000	0	-10000	0	0
receptor agonist activity	0	0	-10000	0	0	31	31
actin filament binding	0	0	-10000	0	0	40	40
SRC	0.006	0	-10000	0	-10000	0	0
ITGB3	-0.045	0.14	0.22	13	-0.38	82	95
GNAQ	-0.005	0.065	-10000	0	-0.39	16	16
EFA6/PI-4-5-P2	0	0	-10000	0	-0.001	22	22
ARF6/GDP	-0.004	0.039	-10000	0	-0.26	2	2
ARF6/GDP/GULP/ACAP1	-0.066	0.097	-10000	0	-0.25	74	74
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.017	0.087	-10000	0	-0.21	91	91
ACAP1	0	0	-10000	0	-10000	0	0
ACAP2	0	0	-10000	0	0	21	21
LHCGR/beta Arrestin2	0.007	0.013	0.18	3	-10000	0	3
EFNA1	0.017	0.047	0.22	28	-10000	0	28
HGF	0.008	0.018	0.22	4	-10000	0	4
CYTH3	0	0	-10000	0	-0.001	24	24
CYTH2	-0.001	0.001	-10000	0	-0.004	47	47
NCK1	0.024	0.059	0.22	47	-10000	0	47
fibronectin binding	0	0	-10000	0	0	36	36
endosomal lumen acidification	0	0	-10000	0	0	42	42
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.052	0.14	0.22	3	-0.38	86	89
GNAQ/ARNO	-0.004	0.031	-10000	0	-0.18	16	16
mol:Phosphatidic acid	0	0	-10000	0	0	21	21
PIP3-E	0.005	0.023	-10000	0	-0.38	2	2
MET	-0.013	0.12	0.22	32	-0.38	45	77
GNA14	0.006	0.027	0.22	2	-0.39	2	4
GNA15	0.003	0.037	-10000	0	-0.39	5	5
GIT1	0.007	0.009	0.22	1	-10000	0	1
mol:PI-4-5-P2	0	0	-10000	0	-0.001	22	22
GNA11	-0.13	0.18	-10000	0	-0.39	193	193
LHCGR	0.007	0.016	0.22	3	-10000	0	3
AGTR1	0.006	0	-10000	0	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0.007	0.013	0.18	3	-10000	0	3
IPCEF1/ARNO	-0.01	0.057	0.17	3	-0.17	56	59
alphaIIb/beta3 Integrin	-0.031	0.098	-10000	0	-0.27	82	82

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.006	0.023	0.16	2	-0.23	5	7
SNTA1	0.006	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.021	0.064	0.17	89	-0.23	3	92
MAPK12	0.006	0.062	0.26	1	-0.21	21	22
CCND1	-0.094	0.17	-10000	0	-0.38	145	145
p38 gamma/SNTA1	0.003	0.057	0.22	1	-0.2	21	22
MAP2K3	0.003	0.037	-10000	0	-0.38	5	5
PKN1	0.009	0.032	0.22	9	-0.38	1	10
G2/M transition checkpoint	0.006	0.062	0.26	1	-0.21	21	22
MAP2K6	0.009	0.07	0.17	57	-0.23	21	78
MAPT	0.002	0.031	0.17	1	-0.18	4	5
MAPK13	-0.006	0.028	0.2	2	-0.27	5	7
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	-0.006	0.055	0.15	7	-0.27	21	28

×

Wnt signaling

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
Noncanonical Wnts/FZD	0.034	0.061	0.22	19	-0.21	7	26
FZD6	0.022	0.06	0.22	43	-0.38	1	44
WNT6	0.006	0.016	-10000	0	-0.38	1	1
WNT4	0.006	0	-10000	0	-10000	0	0
FZD3	0.031	0.08	0.22	72	-0.38	4	76
WNT5A	0.006	0.029	0.22	4	-0.38	2	6
WNT11	0.026	0.062	0.22	52	-10000	0	52

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.048	0.05	-10000	0	-10000	0	0
SMARCC2	0.007	0.009	0.22	1	-10000	0	1
SMARCC1	0.006	0	-10000	0	-10000	0	0
TBX21	0.058	0.06	-10000	0	-10000	0	0
SUMO2	0	0.01	-10000	0	-10000	0	0
STAT1 (dimer)	0.11	0.12	0.22	294	-0.2	5	299
FKBP4	0.023	0.057	0.22	43	-10000	0	43
FKBP5	-0.051	0.14	0.22	2	-0.38	84	86
GR alpha/HSP90/FKBP51/HSP90	-0.075	0.1	-10000	0	-0.28	82	82
PRL	0.035	0.055	0.59	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.1	0.14	-10000	0	-0.47	14	14
RELA	0.008	0.08	0.23	14	-0.27	8	22
FGG	-0.1	0.13	-10000	0	-0.5	10	10
GR beta/TIF2	-0.053	0.07	-10000	0	-0.32	11	11
IFNG	0.097	0.17	0.58	26	-10000	0	26
apoptosis	-0.16	0.22	0.56	2	-0.58	39	41
CREB1	0.008	0	-10000	0	-10000	0	0
histone acetylation	0.035	0.081	-10000	0	-0.37	7	7
BGLAP	0.051	0.065	0.53	2	-10000	0	2
GR/PKAc	-0.038	0.055	-10000	0	-0.27	8	8
NF kappa B1 p50/RelA	0.014	0.15	0.41	14	-0.32	63	77
SMARCD1	0.006	0	-10000	0	-10000	0	0
MDM2	-0.031	0.045	-10000	0	-0.28	1	1
GATA3	0.009	0.013	0.22	2	-10000	0	2
AKT1	0.006	0.009	0.22	1	-10000	0	1
CSF2	0.027	0.054	-10000	0	-0.48	1	1
GSK3B	0	0.01	-10000	0	-10000	0	0
NR1I3	-0.14	0.2	0.65	1	-0.52	23	24
CSN2	-0.093	0.12	-10000	0	-0.46	10	10
BRG1/BAF155/BAF170/BAF60A	0.017	0.019	-10000	0	-0.2	2	2
NFATC1	0.007	0.016	-10000	0	-0.39	1	1
POU2F1	0.007	0.006	0.16	1	-10000	0	1
CDKN1A	-0.1	0.32	-10000	0	-1.3	35	35
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.008	-10000	0	-10000	0	0
SFN	0.013	0.039	0.22	19	-10000	0	19
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.064	0.095	-10000	0	-0.26	82	82
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.31	0.39	0.56	4	-0.78	227	231
JUN	0.11	0.14	0.47	37	-10000	0	37
IL4	0.05	0.06	-10000	0	-10000	0	0
CDK5R1	0.001	0.009	-10000	0	-10000	0	0
PRKACA	0.006	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.053	0.079	-10000	0	-0.26	51	51
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.068	0.092	-10000	0	-0.26	78	78
cortisol/GR alpha (monomer)	-0.12	0.16	-10000	0	-0.54	15	15
NCOA2	0.007	0.013	0.22	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.011	0.17	0.26	38	-0.37	95	133
AP-1/NFAT1-c-4	0.097	0.2	0.57	35	-0.45	1	36
AFP	0.069	0.1	0.47	2	-10000	0	2
SUV420H1	0.008	0.02	0.22	5	-10000	0	5
IRF1	-0.011	0.22	0.5	4	-0.84	26	30
TP53	-0.072	0.17	-10000	0	-0.43	106	106
PPP5C	0.007	0.009	0.22	1	-10000	0	1
KRT17	0.092	0.18	0.69	23	-10000	0	23
KRT14	0.057	0.11	0.6	16	-10000	0	16
TBP	0.008	0.011	0.2	2	-10000	0	2
CREBBP	-0.005	0.054	-10000	0	-0.25	22	22
HDAC1	0.016	0.047	0.22	28	-10000	0	28
HDAC2	0.01	0.036	0.22	13	-0.39	1	14
AP-1	0.097	0.2	0.57	35	-0.45	1	36
MAPK14	0	0.014	0.22	1	-10000	0	1
MAPK10	-0.012	0.069	0.21	1	-0.39	18	19
MAPK11	0	0.01	-10000	0	-10000	0	0
KRT5	0.14	0.24	0.58	108	-10000	0	108
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
NCOA1	0.004	0.028	-10000	0	-0.39	3	3
STAT1	0.11	0.12	0.23	294	-0.2	5	299
CGA	0.05	0.059	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.058	0.088	-10000	0	-0.41	10	10
MAPK3	-0.035	0.11	-10000	0	-0.39	51	51
MAPK1	-0.001	0.021	0.21	1	-0.37	1	2
ICAM1	0.055	0.25	0.58	48	-0.98	15	63
NFKB1	0.001	0.1	0.23	14	-0.34	21	35
MAPK8	0.095	0.12	0.39	37	-10000	0	37
MAPK9	-0.001	0.021	0.24	1	-0.37	1	2
cortisol/GR alpha (dimer)	-0.17	0.23	0.56	2	-0.6	42	44
BAX	-0.045	0.13	-10000	0	-10000	0	0
POMC	-0.014	0.13	-10000	0	-10000	0	0
EP300	-0.003	0.046	-10000	0	-0.35	6	6
cortisol/GR alpha (dimer)/p53	-0.15	0.16	-10000	0	-0.5	32	32
proteasomal ubiquitin-dependent protein catabolic process	-0.027	0.041	0.21	3	-0.24	1	4
SGK1	-0.018	0.065	-10000	0	-0.28	25	25
IL13	0.068	0.12	0.49	8	-10000	0	8
IL6	-0.009	0.29	0.57	5	-0.94	46	51
PRKACG	0.006	0	-10000	0	-10000	0	0
IL5	0.054	0.12	-10000	0	-10000	0	0
IL2	0.08	0.15	0.51	17	-10000	0	17
CDK5	0.026	0.07	0.22	65	-10000	0	65
PRKACB	0.01	0.027	0.22	9	-10000	0	9
HSP90AA1	0.006	0	-10000	0	-10000	0	0
IL8	0.074	0.18	0.57	47	-10000	0	47
CDK5R1/CDK5	0.003	0.017	0.18	2	-10000	0	2
NF kappa B1 p50/RelA/PKAc	0.025	0.12	0.33	16	-0.37	10	26
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.083	0.13	0.41	1	-0.47	10	11
SMARCA4	0.007	0.032	0.22	6	-0.38	2	8
chromatin remodeling	-0.062	0.086	-10000	0	-0.32	10	10
NF kappa B1 p50/RelA/Cbp	0.009	0.13	0.34	13	-0.43	10	23
JUN (dimer)	0.1	0.14	0.47	37	-10000	0	37
YWHAH	0.005	0.03	0.22	1	-0.38	3	4
VIPR1	0.058	0.06	-10000	0	-10000	0	0
NR3C1	-0.081	0.099	-10000	0	-0.42	13	13
NR4A1	-0.13	0.19	0.22	5	-0.38	200	205
TIF2/SUV420H1	0.009	0.001	-10000	0	-10000	0	0
MAPKKK cascade	-0.16	0.22	0.56	2	-0.58	39	41
cortisol/GR alpha (dimer)/Src-1	-0.1	0.13	-10000	0	-0.51	10	10
PBX1	0	0.054	-10000	0	-0.38	11	11
POU1F1	0.007	0.006	-10000	0	-10000	0	0
SELE	0.049	0.12	0.48	3	-10000	0	3
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.063	0.086	-10000	0	-0.32	10	10
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.083	0.13	0.41	1	-0.47	10	11
mol:cortisol	-0.069	0.082	-10000	0	-0.28	11	11
MMP1	0.12	0.22	0.55	112	-10000	0	112

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.008	0.076	0.36	1	-0.63	3	4
epithelial cell differentiation	-0.003	0.053	-10000	0	-0.59	3	3
ITCH	0.003	0.022	0.19	2	-10000	0	2
WWP1	0.007	0.11	0.53	2	-1.2	3	5
FYN	-0.039	0.13	0.22	1	-0.38	67	68
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
PRL	0.007	0.009	0.22	1	-10000	0	1
neuron projection morphogenesis	-0.001	0.08	0.28	2	-0.34	7	9
PTPRZ1	0.007	0.013	0.22	2	-10000	0	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.027	0.07	0.24	1	-0.51	3	4
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.024	0.085	0.34	3	-0.57	3	6
ADAM17	0.051	0.085	0.21	119	-10000	0	119
ErbB4/ErbB4	0.011	0.09	0.49	2	-0.7	3	5
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.13	-10000	0	-0.34	52	52
NCOR1	0.002	0.04	-10000	0	-0.38	6	6
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.001	0.1	0.27	2	-0.37	9	11
GRIN2B	-0.001	0.097	0.3	4	-0.35	9	13
ErbB4/ErbB2/betacellulin	0.024	0.081	0.27	3	-0.48	4	7
STAT1	0.12	0.11	0.22	297	-10000	0	297
HBEGF	0.007	0.016	0.22	3	-10000	0	3
PRLR	0.013	0.039	0.22	19	-10000	0	19
E4ICDs/ETO2	0.007	0.074	0.36	1	-0.63	3	4
axon guidance	0.015	0.072	0.36	2	-0.68	3	5
NEDD4	0.004	0.026	0.21	4	-10000	0	4
Prolactin receptor/Prolactin receptor/Prolactin	0.009	0.002	-10000	0	-10000	0	0
CBFA2T3	0.006	0	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	0.024	0.079	0.26	3	-0.55	3	6
MAPK3	0	0.082	0.29	2	-0.35	7	9
STAT1 (dimer)	0.088	0.11	0.31	11	-0.59	3	14
MAPK1	0.013	0.071	0.26	3	-0.49	3	6
JAK2	0.004	0.035	0.22	2	-0.38	4	6
ErbB4/ErbB2/neuregulin 1 beta	0.02	0.082	0.3	3	-0.55	3	6
NRG1	0.038	0.08	0.19	118	-10000	0	118
NRG3	-0.27	0.18	0.22	1	-0.38	407	408
NRG2	0.006	0	-10000	0	-10000	0	0
NRG4	0.009	0.056	0.22	19	-0.38	6	25
heart development	0.015	0.072	0.36	2	-0.68	3	5
neural crest cell migration	0.02	0.081	0.3	3	-0.54	3	6
ERBB2	0.038	0.083	0.19	122	-0.28	3	125
WWOX/E4ICDs	0.007	0.074	0.36	1	-0.63	3	4
SHC1	0.006	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.007	0.094	-10000	0	-0.38	10	10
apoptosis	0.22	0.16	0.33	332	-10000	0	332
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.007	0.074	0.36	1	-0.63	3	4
ErbB4/ErbB2/epiregulin	0.023	0.078	0.23	1	-0.55	3	4
ErbB4/ErbB4/betacellulin/betacellulin	0.009	0.079	0.32	2	-0.56	4	6
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.018	0.071	-10000	0	-0.56	3	3
MDM2	0.007	0.08	0.35	4	-0.63	3	7
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.019	0.067	0.25	3	-0.5	3	6
STAT5A	0.01	0.071	0.32	2	-0.66	3	5
ErbB4/EGFR/neuregulin 1 beta	0.006	0.094	0.24	2	-0.44	5	7
DLG4	0.006	0	-10000	0	-10000	0	0
GRB2/SHC	0.009	0.012	-10000	0	-0.27	1	1
E4ICDs/TAB2/NCoR1	0.006	0.075	-10000	0	-0.66	3	3
STAT5A (dimer)	0.01	0.064	-10000	0	-0.65	3	3
MAP3K7IP2	0.005	0.025	0.22	1	-0.38	2	3
STAT5B (dimer)	0.013	0.071	0.3	2	-0.66	3	5
LRIG1	0.012	0.05	0.22	21	-0.38	3	24
EREG	0.007	0.009	0.22	1	-10000	0	1
BTC	0.007	0.043	0.22	9	-0.38	4	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.015	0.072	0.36	2	-0.69	3	5
ERBB4	0.011	0.089	0.65	1	-0.7	3	4
STAT5B	-0.001	0.054	-10000	0	-0.38	11	11
YAP1	0.006	0.024	0.23	1	-10000	0	1
GRB2	0.006	0.016	-10000	0	-0.38	1	1
ErbB4/ErbB2/neuregulin 4	0.026	0.083	0.25	2	-0.44	5	7
glial cell differentiation	-0.006	0.074	0.65	3	-10000	0	3
WWOX	0.006	0	-10000	0	-10000	0	0
cell proliferation	0.023	0.079	0.3	3	-0.48	4	7

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.016	0.065	-10000	0	-0.21	56	56
epithelial cell differentiation	0.007	0.037	-10000	0	-0.19	19	19
CYFIP2	-0.001	0.051	-10000	0	-0.38	10	10
ENAH	-0.001	0.044	0.19	4	-10000	0	4
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
EPHA2	0.007	0.009	0.22	1	-10000	0	1
MYO6	-0.011	0.042	-10000	0	-0.19	23	23
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
ABI1/Sra1/Nap1	0.008	0.031	-10000	0	-0.23	10	10
AQP5	0.029	0.067	-10000	0	-10000	0	0
CTNND1	0.006	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.012	0.032	-10000	0	-0.18	19	19
regulation of calcium-dependent cell-cell adhesion	-0.014	0.038	-10000	0	-0.18	27	27
EGF	0.009	0.024	0.22	7	-10000	0	7
NCKAP1	0.01	0.028	0.22	10	-10000	0	10
AQP3	-0.14	0.19	-10000	0	-0.42	176	176
cortical microtubule organization	0.007	0.037	-10000	0	-0.19	19	19
GO:0000145	-0.011	0.03	-10000	0	-0.17	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.008	0.038	-10000	0	-0.19	19	19
MLLT4	-0.006	0.068	-10000	0	-0.38	18	18
ARF6/GDP	-0.013	0.028	-10000	0	-10000	0	0
ARF6	0.006	0.016	-10000	0	-0.38	1	1
Ephrin A1/EPHA2/NCK1/GIT1	0.032	0.042	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.048	0.096	-10000	0	-0.25	84	84
PVRL2	0.006	0.019	0.22	1	-0.38	1	2
ZYX	-0.038	0.071	-10000	0	-0.19	99	99
ARF6/GTP	0.031	0.038	-10000	0	-0.19	1	1
CDH1	-0.005	0.067	-10000	0	-0.38	17	17
EGFR/EGFR/EGF/EGF	-0.013	0.066	-10000	0	-0.19	70	70
RhoA/GDP	0.006	0.037	-10000	0	-0.18	21	21
actin cytoskeleton organization	-0.01	0.042	-10000	0	-0.19	19	19
IGF-1R heterotetramer	-0.077	0.16	-10000	0	-0.38	121	121
GIT1	0.007	0.009	0.22	1	-10000	0	1
IGF1R	-0.077	0.16	-10000	0	-0.38	121	121
IGF1	-0.003	0.067	0.22	4	-0.38	16	20
DIAPH1	0.002	0.08	-10000	0	-0.55	11	11
Wnt receptor signaling pathway	-0.007	0.037	0.19	19	-10000	0	19
RHOA	0.005	0.023	-10000	0	-0.38	2	2
RhoA/GTP	-0.014	0.029	-10000	0	-10000	0	0
CTNNA1	0.005	0.023	-10000	0	-0.38	2	2
VCL	-0.011	0.042	-10000	0	-0.2	19	19
EFNA1	0.017	0.047	0.22	28	-10000	0	28
LPP	-0.022	0.053	-10000	0	-0.19	48	48
Ephrin A1/EPHA2	0.005	0.033	-10000	0	-0.18	17	17
SEC6/SEC8	-0.019	0.043	-10000	0	-0.33	3	3
MGAT3	-0.014	0.038	-10000	0	-0.18	27	27
HGF/MET	-0.01	0.064	-10000	0	-0.19	58	58
HGF	0.008	0.018	0.22	4	-10000	0	4
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.016	0.066	-10000	0	-0.21	56	56
actin cable formation	-0.02	0.066	0.16	4	-0.23	16	20
KIAA1543	-0.013	0.037	-10000	0	-0.19	19	19
KIFC3	-0.012	0.032	-10000	0	-0.18	19	19
NCK1	0.024	0.059	0.22	47	-10000	0	47
EXOC3	0.007	0.009	0.22	1	-10000	0	1
ACTN1	-0.015	0.043	-10000	0	-0.2	29	29
NCK1/GIT1	0.009	0.003	-10000	0	-10000	0	0
mol:GDP	0.007	0.037	-10000	0	-0.19	19	19
EXOC4	0.009	0.024	0.22	7	-10000	0	7
STX4	-0.012	0.032	-10000	0	-0.18	19	19
PIP5K1C	-0.012	0.032	-10000	0	-0.18	19	19
LIMA1	-0.02	0.098	-10000	0	-0.38	38	38
ABI1	0.007	0.009	0.22	1	-10000	0	1
ROCK1	-0.001	0.047	0.2	4	-10000	0	4
adherens junction assembly	-0.008	0.039	-10000	0	-0.62	1	1
IGF-1R heterotetramer/IGF1	-0.04	0.088	-10000	0	-0.18	150	150
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0.05	-10000	0	-0.27	19	19
MET	-0.013	0.12	0.22	32	-0.38	45	77
PLEKHA7	-0.012	0.035	-10000	0	-0.19	19	19
mol:GTP	0.031	0.041	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	-0.018	0.044	-10000	0	-0.32	3	3
cortical actin cytoskeleton stabilization	-0.016	0.065	-10000	0	-0.21	56	56
regulation of cell-cell adhesion	-0.01	0.042	-10000	0	-0.19	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.016	0.066	-10000	0	-0.21	56	56

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.12	0.2	0.46	1	-0.56	26	27
RAD9A	0.006	0	-10000	0	-10000	0	0
AP1	-0.052	0.11	-10000	0	-0.28	112	112
IFNAR2	0.001	0.014	0.21	1	-10000	0	1
AKT1	-0.022	0.054	-10000	0	-0.2	14	14
ER alpha/Oestrogen	-0.028	0.084	-10000	0	-0.27	61	61
NFX1/SIN3/HDAC complex	0.007	0.038	0.21	2	-0.21	1	3
EGF	0.005	0.025	0.22	7	-10000	0	7
SMG5	0.007	0.016	0.22	3	-10000	0	3
SMG6	0.006	0	-10000	0	-10000	0	0
SP3/HDAC2	0	0.02	-10000	0	-0.29	1	1
TERT/c-Abl	-0.12	0.19	-10000	0	-0.5	48	48
SAP18	0.002	0.017	-10000	0	-0.38	1	1
MRN complex	0.008	0.015	-10000	0	-0.23	2	2
WT1	-0.023	0.092	-10000	0	-0.39	34	34
WRN	0.034	0.073	0.22	74	-10000	0	74
SP1	-0.002	0.014	-10000	0	-10000	0	0
SP3	0.001	0.009	-10000	0	-10000	0	0
TERF2IP	0.006	0	-10000	0	-10000	0	0
Telomerase/Nucleolin	-0.11	0.17	-10000	0	-0.48	43	43
Mad/Max	0.002	0.013	-10000	0	-10000	0	0
TERT	-0.12	0.2	0.46	1	-0.58	22	23
CCND1	-0.27	0.45	0.57	1	-1	145	146
MAX	0.001	0.009	-10000	0	-10000	0	0
RBBP7	0.003	0.02	0.22	1	-0.38	1	2
RBBP4	0.012	0.042	0.22	22	-10000	0	22
TERF2	0.005	0.001	-10000	0	-10000	0	0
PTGES3	-0.03	0.11	0.22	1	-0.38	53	54
SIN3A	0.003	0.006	-10000	0	-10000	0	0
Telomerase/911	0.007	0.084	0.24	3	-0.26	5	8
CDKN1B	-0.008	0.079	0.39	7	-0.44	3	10
RAD1	0.015	0.043	0.22	23	-10000	0	23
XRCC5	0.029	0.066	0.22	60	-10000	0	60
XRCC6	0.006	0	-10000	0	-10000	0	0
SAP30	0.003	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.007	0.004	-10000	0	-10000	0	0
UBE3A	0.002	0.008	-10000	0	-10000	0	0
JUN	0.003	0.04	0.22	9	-0.38	3	12
E6	-0.002	0.004	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0	0.009	-10000	0	-10000	0	0
FOS	-0.07	0.16	0.22	8	-0.39	110	118
IFN-gamma/IRF1	-0.01	0.06	-10000	0	-0.27	27	27
PARP2	0.032	0.07	0.22	68	-10000	0	68
BLM	0.068	0.098	0.22	163	-10000	0	163
Telomerase	0.009	0.073	0.23	1	-10000	0	1
IRF1	-0.015	0.085	0.22	3	-0.37	28	31
ESR1	-0.039	0.12	-10000	0	-0.39	61	61
KU/TER	0.008	0.003	-10000	0	-10000	0	0
ATM/TRF2	0.014	0.026	0.15	20	-10000	0	20
ubiquitin-dependent protein catabolic process	0.008	0.039	0.25	1	-0.21	1	2
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.008	0.039	0.25	1	-0.21	1	2
HDAC1	0.014	0.048	0.22	28	-10000	0	28
HDAC2	0.003	0.039	0.22	13	-0.4	1	14
ATM	0.009	0.036	0.2	20	-10000	0	20
SMAD3	-0.062	0.11	-10000	0	-0.27	131	131
ABL1	0	0.049	-10000	0	-0.38	9	9
MXD1	0.001	0.009	-10000	0	-10000	0	0
MRE11A	0.058	0.092	0.22	136	-10000	0	136
HUS1	0.006	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0.03	0.22	11	-10000	0	11
TERT/NF kappa B1/14-3-3	-0.12	0.18	-10000	0	-0.52	25	25
NR2F2	0.004	0.049	-10000	0	-0.38	9	9
MAPK3	-0.031	0.076	-10000	0	-0.27	51	51
MAPK1	-0.007	0.015	0.18	1	-0.27	1	2
TGFB1/TGF beta receptor Type II	-0.08	0.16	-10000	0	-0.38	127	127
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
HNRNPC	0.006	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.009	0.036	0.2	20	-10000	0	20
NBN	0.019	0.055	0.22	35	-0.38	1	36
EGFR	-0.035	0.12	0.22	1	-0.39	54	55
mol:Oestrogen	-0.001	0.003	-10000	0	-10000	0	0
EGF/EGFR	-0.023	0.082	-10000	0	-0.28	54	54
MYC	-0.039	0.12	-10000	0	-0.39	60	60
IL2	-0.002	0.015	-10000	0	-10000	0	0
KU	0.008	0.003	-10000	0	-10000	0	0
RAD50	0.006	0.021	0.22	2	-0.38	1	3
HSP90AA1	0.006	0	-10000	0	-10000	0	0
TGFB1	-0.08	0.16	-10000	0	-0.38	127	127
TRF2/BLM	0.006	0.004	-10000	0	-10000	0	0
FRAP1	0.006	0	-10000	0	-10000	0	0
KU/TERT	-0.1	0.2	-10000	0	-0.49	44	44
SP1/HDAC2	-0.002	0.024	-10000	0	-0.29	1	1
PINX1	0.009	0.025	0.22	8	-10000	0	8
Telomerase/EST1A	-0.11	0.17	-10000	0	-0.48	43	43
Smad3/Myc	-0.069	0.13	-10000	0	-0.25	167	167
911 complex	0.012	0.003	-10000	0	-10000	0	0
IFNG	0.013	0.052	0.22	28	-0.22	1	29
Telomerase/PinX1	-0.11	0.17	-10000	0	-0.48	42	42
Telomerase/AKT1/mTOR/p70S6K	-0.028	0.11	-10000	0	-0.38	17	17
SIN3B	0.003	0.011	0.22	1	-10000	0	1
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
Telomerase/EST1B	-0.11	0.17	-10000	0	-0.48	46	46
response to DNA damage stimulus	0.004	0.018	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.041	0.05	-10000	0	-0.19	2	2
TRF2/WRN	0.007	0.004	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	-0.11	0.17	-10000	0	-0.48	42	42
E2F1	0	0.011	-10000	0	-10000	0	0
ZNFX1	0.005	0.023	0.22	6	-10000	0	6
PIF1	0.006	0	-10000	0	-10000	0	0
NCL	0.008	0.018	0.22	4	-10000	0	4
DKC1	0.064	0.096	0.22	152	-10000	0	152
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.003	0.01	0.17	2	-10000	0	2
ADCY5	-0.002	0.014	0.17	4	-10000	0	4
ADCY6	-0.003	0.007	0.17	1	-10000	0	1
ADCY7	-0.003	0.007	0.17	1	-10000	0	1
ADCY1	-0.003	0.007	0.17	1	-10000	0	1
ADCY2	-0.003	0.007	0.17	1	-10000	0	1
ADCY3	-0.003	0.01	0.17	2	-10000	0	2
ADCY8	-0.088	0.12	0.17	14	-0.23	228	242
PRKCE	-0.002	0.008	0.2	1	-10000	0	1
ADCY9	-0.025	0.067	0.17	1	-0.23	56	57
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.046	0.053	0.14	1	-10000	0	1

×

Caspase cascade in apoptosis

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
TOP1	0.042	0.071	0.18	32	-0.21	9	41
ACTA1	0.019	0.084	0.19	13	-0.27	12	25
NUMA1	0.042	0.071	0.2	14	-0.23	1	15
SPTAN1	0.026	0.081	0.2	10	-0.25	12	22
LIMK1	0.027	0.079	0.2	10	-0.25	12	22
BIRC3	-0.076	0.17	0.22	13	-0.39	127	140
BIRC2	0.037	0.075	0.22	81	-10000	0	81
BAX	0.006	0	-10000	0	-10000	0	0
CASP10	-0.008	0.061	0.17	24	-0.23	27	51
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	0.049	0.074	0.19	41	-0.21	7	48
DIABLO	0.1	0.11	0.22	248	-10000	0	248
apoptotic nuclear changes	0.026	0.08	0.2	10	-0.25	12	22
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.006	0	-10000	0	-10000	0	0
GSN	0.009	0.096	0.2	8	-0.29	17	25
MADD	0.006	0	-10000	0	-10000	0	0
TFAP2A	0.037	0.049	-10000	0	-10000	0	0
BID	-0.003	0.039	0.23	1	-0.16	25	26
MAP3K1	0.015	0.056	-10000	0	-0.45	4	4
TRADD	0.002	0.04	-10000	0	-0.38	6	6
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.009	0.002	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.014	0.083	0.21	6	-0.26	15	21
CASP9	0.007	0.009	0.22	1	-10000	0	1
DNA repair	-0.043	0.07	-10000	0	-0.16	120	120
neuron apoptosis	0.008	0.084	-10000	0	-0.63	9	9
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.041	0.077	0.21	11	-0.24	9	20
APAF1	0.01	0.03	0.22	11	-10000	0	11
CASP6	0.043	0.07	-10000	0	-10000	0	0
TRAF2	0.006	0	-10000	0	-10000	0	0
ICAD/CAD	0.025	0.076	0.19	9	-0.24	12	21
CASP7	0.052	0.1	0.23	127	-0.22	13	140
KRT18	0.017	0.041	-10000	0	-0.54	2	2
apoptosis	0.023	0.097	0.22	24	-0.26	9	33
DFFA	0.027	0.079	0.2	10	-0.25	12	22
DFFB	0.027	0.079	0.2	10	-0.25	12	22
PARP1	0.043	0.07	0.16	120	-10000	0	120
actin filament polymerization	-0.023	0.077	0.24	12	-0.19	10	22
TNF	0.007	0.009	0.22	1	-10000	0	1
CYCS	-0.005	0.034	0.18	1	-10000	0	1
SATB1	-0.024	0.1	-10000	0	-0.31	3	3
SLK	0.026	0.081	0.21	8	-0.25	12	20
p15 BID/BAX	0.001	0.034	0.17	1	-10000	0	1
CASP2	-0.036	0.086	-10000	0	-0.37	13	13
JNK cascade	-0.015	0.055	0.45	4	-10000	0	4
CASP3	0.031	0.085	0.19	40	-0.26	12	52
LMNB2	0.006	0.062	0.18	3	-0.27	4	7
RIPK1	0.006	0	-10000	0	-10000	0	0
CASP4	0.003	0.066	0.22	14	-0.39	12	26
Mammalian IAPs/DIABLO	0.021	0.11	-10000	0	-0.2	68	68
negative regulation of DNA binding	0.037	0.049	-10000	0	-10000	0	0
stress fiber formation	0.026	0.08	0.2	9	-0.25	12	21
GZMB	-0.008	0.069	0.21	20	-0.27	25	45
CASP1	-0.023	0.12	0.19	25	-0.33	59	84
LMNB1	0.048	0.07	0.19	17	-0.26	1	18
APP	0.008	0.085	-10000	0	-0.64	9	9
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.002	0	-10000	0	-10000	0	0
VIM	0.026	0.1	0.22	27	-0.26	9	36
LMNA	0.004	0.073	0.18	3	-0.37	8	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.04	0.09	-10000	0	-0.39	13	13
LRDD	0.006	0	-10000	0	-10000	0	0
SREBF1	0.024	0.084	0.2	9	-0.27	14	23
APAF-1/Caspase 9	-0.001	0.11	-10000	0	-0.29	7	7
nuclear fragmentation during apoptosis	0.042	0.07	0.2	14	-0.22	1	15
CFL2	0.023	0.078	0.19	10	-0.24	12	22
GAS2	0.029	0.083	0.22	16	-0.25	12	28
positive regulation of apoptosis	0.027	0.069	0.19	6	-0.28	6	12
PRF1	-0.011	0.081	0.22	1	-0.38	25	26

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.007	0.017	-10000	0	-0.22	3	3
cell-cell adhesion	0.021	0.044	0.32	1	-10000	0	1
Ephrin B/EPHB2/RasGAP	0.007	0.065	-10000	0	-0.2	45	45
ITSN1	0.007	0.009	0.22	1	-10000	0	1
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
SHC1	0.006	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.006	0.022	-10000	0	-0.22	5	5
Ephrin B1/EPHB1	0.006	0.022	-10000	0	-0.22	5	5
HRAS/GDP	-0.01	0.064	-10000	0	-0.24	39	39
Ephrin B/EPHB1/GRB7	0.008	0.066	-10000	0	-0.2	44	44
Endophilin/SYNJ1	-0.014	0.055	-10000	0	-0.18	42	42
KRAS	0.03	0.067	0.22	62	-10000	0	62
Ephrin B/EPHB1/Src	0.008	0.064	-10000	0	-0.2	42	42
endothelial cell migration	-0.022	0.078	-10000	0	-0.21	78	78
GRB2	0.006	0.016	-10000	0	-0.38	1	1
GRB7	0.006	0.035	0.22	5	-0.38	3	8
PAK1	-0.01	0.063	0.25	4	-0.19	40	44
HRAS	0.006	0	-10000	0	-10000	0	0
RRAS	-0.033	0.08	-10000	0	-0.2	93	93
DNM1	0.006	0	-10000	0	-10000	0	0
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.013	0.057	0.24	1	-0.19	42	43
lamellipodium assembly	-0.021	0.044	-10000	0	-0.32	1	1
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.006	0.062	0.21	1	-0.21	36	37
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
EPHB2	0.01	0.027	0.22	9	-10000	0	9
EPHB3	0.012	0.033	0.22	14	-10000	0	14
EPHB1	0.012	0.033	0.22	14	-10000	0	14
EPHB4	0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.017	0.074	0.22	1	-0.26	39	40
Ephrin B/EPHB2	0.004	0.062	-10000	0	-0.2	42	42
Ephrin B/EPHB3	0.004	0.062	-10000	0	-0.2	42	42
JNK cascade	0.01	0.051	0.28	5	-0.19	3	8
Ephrin B/EPHB1	0.005	0.063	-10000	0	-0.2	42	42
RAP1/GDP	-0.007	0.07	0.23	3	-0.24	35	38
EFNB2	-0.013	0.1	0.22	15	-0.38	36	51
EFNB3	0.005	0.03	0.22	1	-0.38	3	4
EFNB1	0.003	0.037	-10000	0	-0.38	5	5
Ephrin B2/EPHB1-2	0.005	0.061	0.14	30	-0.2	36	66
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
RAP1A	0.007	0.009	0.22	1	-10000	0	1
CDC42/GTP	-0.005	0.062	-10000	0	-0.22	42	42
Rap1/GTP	-0.022	0.044	-10000	0	-0.32	1	1
axon guidance	0.007	0.017	-10000	0	-0.22	3	3
MAPK3	-0.025	0.077	0.19	1	-0.35	8	9
MAPK1	-0.01	0.056	0.19	1	-0.35	1	2
Rac1/GDP	-0.017	0.07	0.21	1	-0.25	39	40
actin cytoskeleton reorganization	-0.014	0.038	-10000	0	-0.18	22	22
CDC42/GDP	-0.017	0.07	0.21	1	-0.25	39	40
PI3K	0.008	0.1	-10000	0	-0.21	78	78
EFNA5	0.006	0.035	0.22	5	-0.38	3	8
Ephrin B2/EPHB4	-0.006	0.057	-10000	0	-0.22	36	36
Ephrin B/EPHB2/Intersectin/N-WASP	-0.006	0.063	-10000	0	-0.21	42	42
CDC42	0.006	0	-10000	0	-10000	0	0
RAS family/GTP	-0.014	0.036	-10000	0	-0.32	1	1
PTK2	0.035	0.11	0.38	57	-10000	0	57
MAP4K4	0.01	0.052	0.29	5	-0.19	3	8
SRC	0.006	0	-10000	0	-10000	0	0
KALRN	0.009	0.022	0.22	6	-10000	0	6
Intersectin/N-WASP	0.009	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.011	0.064	0.2	9	-0.33	1	10
MAP2K1	-0.007	0.058	0.2	1	-0.36	1	2
WASL	0.006	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.028	0.043	-10000	0	-0.2	3	3
cell migration	-0.02	0.072	0.2	1	-0.32	9	10
NRAS	0.099	0.11	0.22	245	-10000	0	245
SYNJ1	-0.014	0.056	-10000	0	-0.19	42	42
PXN	-0.002	0.056	-10000	0	-0.38	12	12
TF	-0.012	0.055	-10000	0	-0.34	1	1
HRAS/GTP	-0.003	0.051	-10000	0	-0.18	45	45
Ephrin B1/EPHB1-2	0.014	0.03	-10000	0	-0.2	5	5
cell adhesion mediated by integrin	0.016	0.059	0.21	42	-0.14	12	54
RAC1	0.006	0.016	-10000	0	-0.38	1	1
mol:GTP	0.004	0.061	0.24	1	-0.18	45	46
RAC1-CDC42/GTP	-0.022	0.045	-10000	0	-0.32	1	1
RASA1	0.004	0.028	-10000	0	-0.38	3	3
RAC1-CDC42/GDP	-0.008	0.07	0.2	1	-0.24	36	37
ruffle organization	-0.015	0.057	0.22	4	-0.32	1	5
NCK1	0.024	0.059	0.22	47	-10000	0	47
receptor internalization	-0.014	0.053	-10000	0	-0.34	1	1
Ephrin B/EPHB2/KALRN	0.009	0.063	-10000	0	-0.2	40	40
ROCK1	-0.002	0.029	0.14	15	-0.2	5	20
RAS family/GDP	-0.015	0.041	-10000	0	-0.19	22	22
Rac1/GTP	-0.022	0.046	-10000	0	-0.33	1	1
Ephrin B/EPHB1/Src/Paxillin	-0.01	0.071	0.21	1	-0.22	53	54

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.007	0.036	-10000	0	-0.23	13	13
fibroblast growth factor receptor signaling pathway	0.007	0.036	-10000	0	-0.23	13	13
LAMA1	0.045	0.083	0.22	102	-10000	0	102
PRNP	0	0.052	0.22	1	-0.38	10	11
GPC1/SLIT2	-0.01	0.07	-10000	0	-0.27	39	39
SMAD2	-0.011	0.032	-10000	0	-0.2	15	15
GPC1/PrPc/Cu2+	0.004	0.031	-10000	0	-0.22	10	10
GPC1/Laminin alpha1	0.008	0.004	-10000	0	-10000	0	0
TDGF1	0.006	0	-10000	0	-10000	0	0
CRIPTO/GPC1	0.009	0	-10000	0	-10000	0	0
APP/GPC1	0.005	0.035	-10000	0	-0.27	9	9
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.001	0.024	0.16	12	-10000	0	12
FLT1	0.006	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.007	0.036	-10000	0	-0.23	13	13
SERPINC1	0.006	0	-10000	0	-10000	0	0
FYN	-0.031	0.072	0.16	1	-0.23	67	68
FGR	-0.005	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.018	0.05	-10000	0	-0.26	1	1
SLIT2	-0.01	0.11	0.22	28	-0.38	39	67
GPC1/NRG	0.009	0	-10000	0	-10000	0	0
NRG1	0.007	0.009	0.22	1	-10000	0	1
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.012	0.003	-10000	0	-10000	0	0
LYN	-0.012	0.04	-10000	0	-0.23	19	19
mol:Spermine	-0.002	0	-10000	0	-10000	0	0
cell growth	0.007	0.036	-10000	0	-0.23	13	13
BMP signaling pathway	-0.006	0	-10000	0	-10000	0	0
SRC	-0.005	0	-10000	0	-10000	0	0
TGFBR1	0.006	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.24	0.19	0.22	4	-0.38	365	369
GPC1	0.006	0	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.006	0	-10000	0	-10000	0	0
VEGFA	0.018	0.048	0.22	30	-10000	0	30
BLK	-0.004	0.007	0.16	1	-10000	0	1
HCK	-0.004	0.007	0.16	1	-10000	0	1
FGF2	0.006	0	-10000	0	-10000	0	0
FGFR1	0	0.063	0.22	7	-0.38	13	20
VEGFR1 homodimer	0.006	0	-10000	0	-10000	0	0
TGFBR2	-0.003	0.058	-10000	0	-0.38	13	13
cell death	0.005	0.035	-10000	0	-0.27	9	9
ATIII/GPC1	0.009	0	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.17	0.13	-10000	0	-0.27	365	365
LCK	-0.005	0	-10000	0	-10000	0	0
neuron differentiation	0.009	0	-10000	0	-10000	0	0
PrPc/Cu2+	0	0.036	-10000	0	-0.27	10	10
APP	0	0.049	-10000	0	-0.38	9	9
TGFBR2 (dimer)	-0.003	0.058	-10000	0	-0.38	13	13

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.017	0.092	0.33	7	-0.31	9	16
TBX21	-0.067	0.23	0.76	5	-0.83	2	7
B2M	0.002	0.04	-10000	0	-0.38	6	6
TYK2	-0.001	0.028	0.18	1	-10000	0	1
IL12RB1	-0.001	0.028	0.18	1	-10000	0	1
GADD45B	-0.032	0.19	0.82	6	-0.58	1	7
IL12RB2	0.002	0.037	0.22	7	-10000	0	7
GADD45G	-0.034	0.19	0.78	5	-0.74	2	7
natural killer cell activation	-0.004	0.026	0.15	5	-10000	0	5
RELB	0.004	0.028	-10000	0	-0.38	3	3
RELA	0.005	0.023	-10000	0	-0.38	2	2
IL18	0.042	0.085	0.22	103	-10000	0	103
IL2RA	0.008	0.018	0.22	4	-10000	0	4
IFNG	0.017	0.047	0.22	28	-10000	0	28
STAT3 (dimer)	-0.058	0.21	0.66	6	-0.63	13	19
HLA-DRB5	0.032	0.11	0.22	110	-0.39	17	127
FASLG	-0.067	0.23	0.76	5	-0.83	2	7
NF kappa B2 p52/RelB	-0.093	0.18	-10000	0	-0.57	33	33
CD4	0.005	0.041	0.22	12	-0.39	2	14
SOCS1	-0.013	0.085	-10000	0	-0.38	28	28
EntrezGene:6955	-0.003	0.011	-10000	0	-10000	0	0
CD3D	-0.059	0.14	0.2	2	-0.39	90	92
CD3E	-0.006	0.065	0.21	5	-0.39	14	19
CD3G	0.013	0.054	0.22	33	-0.38	1	34
IL12Rbeta2/JAK2	0	0.05	0.24	6	-0.28	4	10
CCL3	-0.063	0.24	0.78	10	-0.83	2	12
CCL4	-0.068	0.23	0.7	7	-0.57	33	40
HLA-A	-0.005	0.065	-10000	0	-0.38	16	16
IL18/IL18R	0.014	0.055	0.35	10	-10000	0	10
NOS2	-0.05	0.21	0.73	7	-0.5	28	35
IL12/IL12R/TYK2/JAK2/SPHK2	-0.006	0.077	0.33	7	-0.28	1	8
IL1R1	-0.22	0.49	0.76	5	-1.1	125	130
IL4	0.008	0.028	-10000	0	-0.19	1	1
JAK2	-0.003	0.045	0.18	5	-0.4	4	9
EntrezGene:6957	-0.003	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.034	0.097	-10000	0	-0.39	21	21
RAB7A	-0.023	0.18	0.76	5	-10000	0	5
lysosomal transport	-0.021	0.18	0.75	5	-10000	0	5
FOS	-0.25	0.5	0.61	9	-1.2	112	121
STAT4 (dimer)	-0.022	0.21	0.75	6	-0.66	2	8
STAT5A (dimer)	-0.09	0.19	-10000	0	-0.56	33	33
GZMA	-0.071	0.25	0.76	5	-1.3	4	9
GZMB	-0.064	0.24	0.76	6	-0.83	2	8
HLX	0.006	0	-10000	0	-10000	0	0
LCK	-0.073	0.24	0.7	7	-0.6	33	40
TCR/CD3/MHC II/CD4	-0.093	0.21	0.3	11	-0.5	89	100
IL2/IL2R	0.005	0.072	-10000	0	-0.23	40	40
MAPK14	-0.029	0.2	0.78	6	-10000	0	6
CCR5	-0.035	0.19	0.74	5	-0.58	1	6
IL1B	0.013	0.065	0.24	38	-10000	0	38
STAT6	-0.02	0.12	0.45	7	-0.53	6	13
STAT4	0.007	0.013	0.22	2	-10000	0	2
STAT3	-0.002	0.056	-10000	0	-0.38	12	12
STAT1	0.12	0.11	0.22	297	-10000	0	297
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
NFKB2	0.006	0	-10000	0	-10000	0	0
IL12B	-0.001	0.029	0.2	1	-10000	0	1
CD8A	0.006	0	-10000	0	-10000	0	0
CD8B	0.008	0.016	0.22	3	-10000	0	3
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.016	0.092	0.3	9	-0.33	7	16
IL2RB	0.001	0.046	-10000	0	-0.38	8	8
proteasomal ubiquitin-dependent protein catabolic process	-0.019	0.2	0.71	7	-0.61	2	9
IL2RG	-0.007	0.11	0.22	31	-0.38	37	68
IL12	0.002	0.047	0.23	8	-0.27	1	9
STAT5A	0	0.049	-10000	0	-0.38	9	9
CD247	0.002	0.012	-10000	0	-10000	0	0
IL2	0.006	0	-10000	0	-10000	0	0
SPHK2	0.006	0	-10000	0	-10000	0	0
FRAP1	0.006	0	-10000	0	-10000	0	0
IL12A	0.012	0.063	0.22	38	-0.39	1	39
IL12/IL12R/TYK2/JAK2	-0.075	0.25	0.82	7	-0.63	32	39
MAP2K3	-0.034	0.2	0.78	6	-0.62	2	8
RIPK2	0.065	0.096	0.22	156	-10000	0	156
MAP2K6	-0.026	0.19	0.78	6	-10000	0	6
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.09	0.17	-10000	0	-0.39	134	134
IL18RAP	0.003	0.013	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0	0.036	0.2	3	-10000	0	3
EOMES	-0.004	0.044	-10000	0	-10000	0	0
STAT1 (dimer)	0.02	0.22	0.61	20	-0.58	4	24
T cell proliferation	-0.005	0.18	0.66	7	-0.5	1	8
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.004	0.016	0.22	1	-10000	0	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.066	0.12	0.25	1	-0.5	5	6
ATF2	-0.028	0.18	0.73	6	-10000	0	6

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.009	0.066	0.23	4	-0.24	25	29
positive regulation of NF-kappaB transcription factor activity	0	0.002	-10000	0	-10000	0	0
CRKL	0.006	0	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.044	0.13	0.27	27	-0.32	26	53
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.001	0.063	-10000	0	-0.28	25	25
antigen processing and presentation of peptide antigen via MHC class I	-0.036	0.082	0.18	2	-0.26	55	57
CaM/Ca2+	0.001	0.067	0.17	1	-0.21	39	40
RAP1A	0.007	0.009	0.22	1	-10000	0	1
STAT1 (dimer)/SHP2	0.063	0.11	0.24	42	-0.35	8	50
AKT1	-0.001	0.1	0.26	8	-0.32	24	32
MAP2K1	-0.01	0.061	0.23	4	-0.3	9	13
MAP3K11	-0.009	0.062	0.24	4	-0.27	13	17
IFNGR1	-0.01	0.079	-10000	0	-0.4	23	23
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.022	0.089	-10000	0	-0.38	23	23
Rap1/GTP	-0.018	0.04	-10000	0	-0.26	9	9
CRKL/C3G	0.009	0	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.013	0.062	0.22	2	-0.23	25	27
CEBPB	-0.025	0.1	0.4	3	-0.39	13	16
STAT3	-0.002	0.056	-10000	0	-0.38	12	12
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.058	0.23	-10000	0	-0.98	31	31
STAT1	0.064	0.11	0.24	43	-0.35	8	51
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
IFN-gamma (dimer)	0.014	0.044	0.2	28	-10000	0	28
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
STAT1 (dimer)/PIAS1	0.062	0.1	0.23	43	-0.33	8	51
CEBPB/PTGES2/Cbp/p300	-0.028	0.083	0.42	2	-0.3	15	17
mol:Ca2+	0.008	0.065	0.21	5	-0.23	25	30
MAPK3	-0.07	0.21	0.34	1	-0.69	54	55
STAT1 (dimer)	-0.044	0.12	0.39	7	-0.42	35	42
MAPK1	-0.006	0.071	0.34	1	-0.54	2	3
JAK2	0.003	0.038	0.21	2	-0.42	4	6
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
JAK1	0.003	0.031	-10000	0	-0.4	3	3
CAMK2D	-0.01	0.077	-10000	0	-0.39	23	23
DAPK1	-0.016	0.089	0.44	3	-0.57	5	8
SMAD7	0.02	0.086	0.32	17	-0.21	2	19
CBL/CRKL/C3G	-0.01	0.055	0.19	1	-0.29	9	10
PI3K	-0.017	0.087	0.16	4	-0.25	57	61
IFNG	0.014	0.044	0.2	28	-10000	0	28
apoptosis	-0.002	0.079	0.39	4	-0.36	6	10
CAMK2G	0.006	0	-10000	0	-10000	0	0
STAT3 (dimer)	-0.002	0.056	-10000	0	-0.38	12	12
CAMK2A	0.006	0	-10000	0	-10000	0	0
CAMK2B	0.006	0	-10000	0	-10000	0	0
FRAP1	-0.002	0.098	0.25	8	-0.3	24	32
PRKCD	-0.002	0.1	0.25	9	-0.32	24	33
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
negative regulation of cell growth	-0.036	0.082	0.18	2	-0.26	55	57
PTPN2	0.006	0	-10000	0	-10000	0	0
EP300	0.001	0.037	-10000	0	-0.38	5	5
IRF1	0.012	0.14	0.55	5	-0.38	40	45
STAT1 (dimer)/PIASy	0.065	0.11	0.26	43	-0.33	8	51
SOCS1	-0.06	0.27	-10000	0	-1.2	28	28
mol:GDP	-0.011	0.051	-10000	0	-0.28	9	9
CASP1	0.012	0.13	0.45	19	-0.26	55	74
PTGES2	0.006	0	-10000	0	-10000	0	0
IRF9	-0.011	0.052	0.3	6	-0.27	3	9
mol:PI-3-4-5-P3	-0.022	0.082	-10000	0	-0.24	60	60
RAP1/GDP	-0.017	0.041	-10000	0	-0.25	10	10
CBL	-0.008	0.061	0.24	4	-0.26	15	19
MAP3K1	-0.01	0.063	0.24	4	-0.27	14	18
PIAS1	0.007	0.009	0.22	1	-10000	0	1
PIAS4	0.007	0.002	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.036	0.082	0.18	2	-0.26	55	57
PTPN11	-0.008	0.063	0.23	5	-0.24	25	30
CREBBP	-0.001	0.046	-10000	0	-0.38	8	8
RAPGEF1	0.006	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.023	0.055	0.29	4	-0.22	3	7
CRKL	0.006	0	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
DOCK1	0.006	0.026	0.22	2	-0.38	2	4
ITGA4	0.017	0.047	0.22	29	-10000	0	29
alpha4/beta7 Integrin/MAdCAM1	0.02	0.036	-10000	0	-0.2	6	6
EPO	0.006	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.007	0.024	-10000	0	-0.27	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.009	0.002	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.009	0.001	-10000	0	-10000	0	0
lamellipodium assembly	0.002	0.095	-10000	0	-0.24	56	56
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
ARF6	0.006	0.016	-10000	0	-0.38	1	1
JAK2	0.01	0.038	0.26	1	-0.29	4	5
PXN	-0.002	0.056	-10000	0	-0.38	12	12
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
MADCAM1	0.006	0	-10000	0	-10000	0	0
cell adhesion	0.019	0.035	-10000	0	-0.2	6	6
CRKL/CBL	0.009	0	-10000	0	-10000	0	0
ITGB1	0.007	0.016	0.22	3	-10000	0	3
SRC	-0.005	0.1	0.27	12	-0.2	82	94
ITGB7	0.003	0.038	0.22	1	-0.38	5	6
RAC1	0.006	0.016	-10000	0	-0.38	1	1
alpha4/beta1 Integrin/VCAM1	-0.024	0.083	-10000	0	-0.23	82	82
p130Cas/Crk/Dock1	-0.007	0.092	0.24	12	-0.34	1	13
VCAM1	-0.017	0.17	0.22	87	-0.38	82	169
RHOA	0.005	0.023	-10000	0	-0.38	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	0.019	0.042	-10000	0	-0.2	10	10
BCAR1	-0.006	0.099	0.26	12	-0.19	84	96
EPOR	0.007	0.016	0.22	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.006	0	-10000	0	-10000	0	0
GIT1	0.007	0.009	0.22	1	-10000	0	1
Rac1/GTP	0.001	0.097	-10000	0	-0.24	56	56

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.067	0.13	-10000	0	-0.36	43	43
BAG4	0.006	0	-10000	0	-10000	0	0
BAD	-0.026	0.041	-10000	0	-0.16	14	14
NFKBIA	-0.005	0.065	-10000	0	-0.38	16	16
BIRC3	-0.076	0.17	0.22	13	-0.38	127	140
BAX	-0.026	0.041	-10000	0	-0.16	14	14
EnzymeConsortium:3.1.4.12	-0.018	0.03	-10000	0	-0.083	44	44
IKBKB	-0.064	0.12	-10000	0	-0.53	14	14
MAP2K2	-0.078	0.084	-10000	0	-0.18	202	202
MAP2K1	-0.028	0.036	-10000	0	-0.17	6	6
SMPD1	-0.018	0.031	-10000	0	-0.13	14	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.066	0.13	-10000	0	-0.56	14	14
MAP2K4	-0.028	0.044	-10000	0	-0.17	25	25
protein ubiquitination	-0.064	0.13	-10000	0	-0.54	14	14
EnzymeConsortium:2.7.1.37	-0.053	0.055	-10000	0	-0.2	16	16
response to UV	0	0	-10000	0	-0.002	11	11
RAF1	-0.029	0.038	-10000	0	-0.16	14	14
CRADD	0.006	0.001	-10000	0	-10000	0	0
mol:ceramide	-0.026	0.042	-10000	0	-0.16	15	15
I-kappa-B-alpha/RELA/p50/ubiquitin	0.001	0.041	-10000	0	-0.22	18	18
MADD	0.006	0.001	-10000	0	-10000	0	0
MAP3K1	-0.026	0.043	-10000	0	-0.17	18	18
TRADD	0.002	0.04	-10000	0	-0.39	6	6
RELA/p50	0.005	0.023	-10000	0	-0.38	2	2
MAPK3	-0.067	0.073	-10000	0	-0.21	69	69
MAPK1	-0.056	0.06	-10000	0	-0.18	42	42
p50/RELA/I-kappa-B-alpha	0.001	0.049	-10000	0	-0.27	18	18
FADD	-0.068	0.13	-10000	0	-0.36	45	45
KSR1	-0.027	0.04	-10000	0	-0.16	14	14
MAPK8	-0.026	0.041	-10000	0	-0.17	15	15
TRAF2	0.007	0.001	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.062	0.13	-10000	0	-0.52	14	14
TNF R/SODD	-0.003	0.057	-10000	0	-0.27	25	25
TNF	0.006	0.009	0.22	1	-10000	0	1
CYCS	-0.014	0.049	0.13	2	-0.16	12	14
IKBKG	-0.065	0.13	-10000	0	-0.53	14	14
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.07	0.14	-10000	0	-0.37	48	48
RELA	0.005	0.023	-10000	0	-0.38	2	2
RIPK1	0.007	0.001	-10000	0	-10000	0	0
AIFM1	-0.004	0.056	0.13	19	-0.16	12	31
TNF/TNF R/SODD	0.002	0.049	-10000	0	-0.23	25	25
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	-0.013	0.06	-10000	0	-0.84	2	2
NSMAF	-0.066	0.13	-10000	0	-0.35	44	44
response to hydrogen peroxide	0	0	-10000	0	-0.002	11	11
BCL2	-0.043	0.13	0.22	2	-0.38	73	75

×

Syndecan-3-mediated signaling events

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
CTTN	0.007	0.013	0.22	2	-10000	0	2
Syndecan-3/Src/Cortactin	0.003	0.12	-10000	0	-0.48	24	24
Syndecan-3/Neurocan	-0.019	0.1	-10000	0	-0.54	20	20
POMC	0.007	0.009	0.22	1	-10000	0	1
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
Syndecan-3/EGFR	-0.036	0.11	-10000	0	-0.29	72	72
AGRP	0.006	0	-10000	0	-10000	0	0
NCSTN	0.007	0.009	0.22	1	-10000	0	1
PSENEN	-0.006	0.068	-10000	0	-0.38	18	18
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	-0.027	0.11	-10000	0	-0.38	49	49
APH1A	0.007	0.009	0.22	1	-10000	0	1
NCAN	0.006	0	-10000	0	-10000	0	0
long-term memory	-0.035	0.11	-10000	0	-0.44	28	28
Syndecan-3/IL8	-0.007	0.11	-10000	0	-0.53	20	20
PSEN1	0.007	0.009	0.22	1	-10000	0	1
Src/Cortactin	0.009	0.001	-10000	0	-10000	0	0
FYN	-0.039	0.13	0.22	1	-0.38	67	68
limb bud formation	-0.023	0.1	-10000	0	-0.56	20	20
MC4R	0	0	-10000	0	-10000	0	0
SRC	0.006	0	-10000	0	-10000	0	0
PTN	0.027	0.12	0.22	95	-0.38	22	117
FGFR/FGF/Syndecan-3	-0.023	0.1	-10000	0	-0.56	20	20
neuron projection morphogenesis	-0.011	0.11	-10000	0	-0.51	20	20
Syndecan-3/AgRP	-0.019	0.1	-10000	0	-0.54	20	20
Syndecan-3/AgRP/MC4R	-0.018	0.098	-10000	0	-0.52	20	20
Fyn/Cortactin	-0.024	0.09	-10000	0	-0.27	67	67
SDC3	-0.023	0.1	-10000	0	-0.57	20	20
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.007	0.11	-10000	0	-0.52	20	20
IL8	0.024	0.059	0.22	47	-10000	0	47
Syndecan-3/Fyn/Cortactin	-0.036	0.12	-10000	0	-0.46	28	28
Syndecan-3/CASK	-0.022	0.1	-10000	0	-0.54	20	20
alpha-MSH/MC4R	0.005	0	-10000	0	-10000	0	0
Gamma Secretase	-0.005	0.07	-10000	0	-0.2	66	66

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.006	0	-10000	0	-10000	0	0
Caspase 8 (4 units)	0	0.056	-10000	0	-0.49	4	4
NEF	-0.001	0	-10000	0	-10000	0	0
NFKBIA	-0.024	0.083	-10000	0	-0.44	16	16
BIRC3	-0.1	0.21	0.45	13	-0.47	127	140
CYCS	-0.01	0.05	-10000	0	-0.43	4	4
RIPK1	0.006	0	-10000	0	-10000	0	0
CD247	0.007	0	-10000	0	-10000	0	0
MAP2K7	-0.009	0.06	-10000	0	-0.47	5	5
protein ubiquitination	-0.022	0.07	-10000	0	-0.28	11	11
CRADD	0.006	0	-10000	0	-10000	0	0
DAXX	0.007	0.013	0.22	2	-10000	0	2
FAS	-0.008	0.074	0.22	1	-0.38	21	22
BID	-0.008	0.052	-10000	0	-0.45	4	4
NF-kappa-B/RelA/I kappa B alpha	-0.054	0.13	-10000	0	-0.28	132	132
TRADD	0.002	0.04	-10000	0	-0.38	6	6
MAP3K5	0.002	0.044	0.22	1	-0.38	7	8
CFLAR	0.006	0.016	-10000	0	-0.38	1	1
FADD	0.006	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.054	0.13	-10000	0	-0.28	132	132
MAPK8	-0.009	0.054	-10000	0	-0.4	5	5
APAF1	0.01	0.03	0.22	11	-10000	0	11
TRAF1	0.006	0	-10000	0	-10000	0	0
TRAF2	0.006	0	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.006	0.055	-10000	0	-0.24	24	24
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.028	0.083	-10000	0	-0.33	18	18
CHUK	-0.024	0.074	-10000	0	-0.31	11	11
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.009	0.052	-10000	0	-0.22	24	24
TCRz/NEF	0.007	0	-10000	0	-10000	0	0
TNF	0.007	0.009	0.22	1	-10000	0	1
FASLG	-0.004	0	-10000	0	-10000	0	0
NFKB1	-0.02	0.075	-10000	0	-0.46	11	11
TNFR1A/BAG4/TNF-alpha	0.002	0.049	-10000	0	-0.23	25	25
CASP6	0.018	0.086	-10000	0	-0.55	4	4
CASP7	-0.1	0.21	0.34	12	-0.48	127	139
RELA	-0.014	0.051	-10000	0	-0.47	2	2
CASP2	0.012	0.033	0.22	14	-10000	0	14
CASP3	-0.099	0.21	0.34	12	-0.48	127	139
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
TNFR1A/BAG4	-0.003	0.057	-10000	0	-0.27	25	25
CASP8	0.006	0	-10000	0	-10000	0	0
CASP9	0.007	0.009	0.22	1	-10000	0	1
MAP3K14	-0.028	0.078	-10000	0	-0.3	18	18
APAF-1/Caspase 9	-0.08	0.14	-10000	0	-0.32	126	126
BCL2	-0.03	0.073	-10000	0	-0.38	6	6

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.071	0.12	0.25	60	-0.43	14	74
Syndecan-4/Syndesmos	0.056	0.089	0.33	2	-0.34	1	3
positive regulation of JNK cascade	0.017	0.11	0.35	5	-0.36	8	13
Syndecan-4/ADAM12	0.087	0.12	0.38	28	-10000	0	28
CCL5	-0.037	0.13	0.22	6	-0.38	66	72
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
DNM2	0.007	0.009	0.22	1	-10000	0	1
ITGA5	0.008	0.018	0.22	4	-10000	0	4
SDCBP	0.006	0.026	0.22	2	-0.38	2	4
PLG	-0.011	0.053	-10000	0	-0.38	11	11
ADAM12	0.057	0.092	0.22	135	-10000	0	135
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.007	0.009	0.22	1	-10000	0	1
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.006	0.006	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.079	0.097	0.35	7	-10000	0	7
Syndecan-4/CXCL12/CXCR4	0.033	0.13	0.35	6	-0.37	8	14
Syndecan-4/Laminin alpha3	0.045	0.1	0.33	2	-0.4	4	6
MDK	0.007	0.013	0.22	2	-10000	0	2
Syndecan-4/FZD7	0.06	0.091	0.35	3	-10000	0	3
Syndecan-4/Midkine	0.056	0.089	0.33	2	-0.34	1	3
FZD7	0.014	0.041	0.22	21	-10000	0	21
Syndecan-4/FGFR1/FGF	0.033	0.071	-10000	0	-0.33	2	2
THBS1	-0.04	0.13	0.22	8	-0.38	72	80
integrin-mediated signaling pathway	0.086	0.12	0.35	32	-10000	0	32
positive regulation of MAPKKK cascade	0.017	0.11	0.35	5	-0.36	8	13
Syndecan-4/TACI	0.055	0.089	0.33	2	-0.34	1	3
CXCR4	0.014	0.049	0.22	23	-0.38	2	25
cell adhesion	0.041	0.077	0.19	12	-0.22	19	31
Syndecan-4/Dynamin	0.056	0.089	0.33	2	-0.34	1	3
Syndecan-4/TSP1	0.036	0.12	0.36	4	-0.36	9	13
Syndecan-4/GIPC	0.057	0.09	0.33	2	-0.34	1	3
Syndecan-4/RANTES	0.037	0.12	0.34	7	-0.38	9	16
ITGB1	0.007	0.016	0.22	3	-10000	0	3
LAMA1	0.045	0.083	0.22	102	-10000	0	102
LAMA3	-0.02	0.1	0.22	6	-0.38	42	48
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCA	-0.022	0.063	0.37	7	-0.36	5	12
Syndecan-4/alpha-Actinin	0.052	0.095	0.33	2	-0.36	5	7
TFPI	-0.083	0.17	0.22	3	-0.38	131	134
F2	0.005	0.015	0.25	1	-10000	0	1
alpha5/beta1 Integrin	0.009	0.001	-10000	0	-10000	0	0
positive regulation of cell adhesion	0.064	0.11	0.36	6	-0.37	2	8
ACTN1	-0.002	0.056	-10000	0	-0.38	12	12
TNC	0.058	0.092	0.22	137	-10000	0	137
Syndecan-4/CXCL12	0.029	0.13	0.35	3	-0.36	9	12
FGF6	0.006	0	-10000	0	-10000	0	0
RHOA	0.005	0.023	-10000	0	-0.38	2	2
CXCL12	-0.055	0.15	0.22	9	-0.38	94	103
TNFRSF13B	0.006	0	-10000	0	-10000	0	0
FGF2	0.006	0	-10000	0	-10000	0	0
FGFR1	0	0.063	0.22	7	-0.38	13	20
Syndecan-4/PI-4-5-P2	0.051	0.088	0.31	3	-0.34	1	4
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.077	0.13	0.23	201	-0.37	13	214
cell migration	-0.003	0.004	-10000	0	-10000	0	0
PRKCD	-0.005	0.026	-10000	0	-0.37	2	2
vasculogenesis	0.035	0.12	0.35	4	-0.35	9	13
SDC4	0.056	0.095	0.33	3	-0.36	1	4
Syndecan-4/Tenascin C	0.088	0.12	0.36	31	-10000	0	31
Syndecan-4/PI-4-5-P2/PKC alpha	-0.005	0.004	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.055	0.09	0.33	2	-0.35	2	4
MMP9	0.032	0.079	0.23	77	-10000	0	77
Rac1/GTP	0.041	0.078	0.19	12	-0.22	19	31
cytoskeleton organization	0.055	0.087	0.33	2	-0.33	1	3
GIPC1	0.009	0.025	0.22	8	-10000	0	8
Syndecan-4/TFPI	0.017	0.13	0.3	4	-0.36	10	14

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.003	0.097	0.2	3	-0.24	55	58
adherens junction organization	-0.006	0.073	0.2	1	-0.27	25	26
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.1	0.22	2	-0.32	18	20
FMN1	-0.012	0.074	-10000	0	-0.26	27	27
mol:IP3	0.002	0.087	0.21	2	-0.31	5	7
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.006	0.072	-10000	0	-0.27	25	25
CTNNB1	0.006	0.01	0.22	1	-10000	0	1
AKT1	0.001	0.088	0.19	2	-0.34	5	7
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.072	-10000	0	-0.37	17	17
CTNND1	0.005	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.003	0.074	0.18	13	-0.25	24	37
VASP	-0.007	0.068	-10000	0	-0.26	25	25
ZYX	-0.028	0.093	-10000	0	-0.29	35	35
JUB	0.001	0.077	0.19	6	-0.26	25	31
EGFR(dimer)	-0.02	0.09	0.19	1	-0.27	37	38
E-cadherin/beta catenin-gamma catenin	0	0.055	-10000	0	-0.23	29	29
mol:PI-3-4-5-P3	0.007	0.095	0.2	2	-0.35	5	7
PIK3CA	0.052	0.089	0.22	131	-10000	0	131
PI3K	0.007	0.097	0.2	2	-0.36	5	7
FYN	-0.032	0.12	0.21	1	-0.32	62	63
mol:Ca2+	0.002	0.086	0.21	2	-0.3	5	7
JUP	-0.005	0.063	-10000	0	-0.38	15	15
PIK3R1	-0.037	0.12	-10000	0	-0.39	64	64
mol:DAG	0.002	0.087	0.21	2	-0.31	5	7
CDH1	-0.006	0.066	-10000	0	-0.38	17	17
RhoA/GDP	-0.013	0.1	0.22	2	-0.32	18	20
establishment of polarity of embryonic epithelium	-0.007	0.067	-10000	0	-0.26	25	25
SRC	0.006	0	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
RHOA	0.005	0.023	-10000	0	-0.38	2	2
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
CASR	-0.002	0.081	0.2	2	-0.29	5	7
RhoA/GTP	0.002	0.079	0.21	1	-0.28	5	6
AKT2	0.002	0.089	0.21	4	-0.34	5	9
actin cable formation	-0.014	0.072	-10000	0	-0.25	27	27
apoptosis	0.002	0.092	0.21	55	-0.19	2	57
CTNNA1	0.004	0.024	-10000	0	-0.39	2	2
mol:GDP	-0.017	0.1	0.22	3	-0.33	18	21
PIP5K1A	0.003	0.075	0.18	13	-0.25	24	37
PLCG1	0.001	0.088	0.21	2	-0.31	5	7
Rac1/GTP	-0.018	0.085	-10000	0	-0.25	36	36
homophilic cell adhesion	0	0.004	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.006	0	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.017	-10000	0	-0.38	1	1
DOCK1	0.006	0.026	0.22	2	-0.38	2	4
ITGA4	0.017	0.047	0.22	29	-10000	0	29
RAC1	0.006	0.016	-10000	0	-0.38	1	1
alpha4/beta7 Integrin	0.007	0.024	-10000	0	-0.27	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.012	0.003	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.011	0.047	0.28	1	-0.22	13	14
lamellipodium assembly	-0.01	0.12	0.23	1	-0.33	56	57
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
ARF6	0.006	0.016	-10000	0	-0.38	1	1
TLN1	0.005	0.023	-10000	0	-0.38	2	2
PXN	-0.01	0.038	-10000	0	-0.27	12	12
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
ARF6/GTP	0.008	0.027	-10000	0	-0.18	11	11
cell adhesion	0.015	0.043	-10000	0	-0.21	11	11
CRKL/CBL	0.009	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.013	0.042	-10000	0	-0.2	10	10
ITGB1	0.007	0.016	0.22	3	-10000	0	3
ITGB7	0.003	0.038	0.22	1	-0.38	5	6
ARF6/GDP	0.006	0.017	-10000	0	-0.38	1	1
alpha4/beta1 Integrin/Paxillin/VCAM1	0.006	0.1	0.27	12	-0.19	90	102
p130Cas/Crk/Dock1	0.011	0.022	-10000	0	-0.23	5	5
VCAM1	-0.017	0.17	0.22	87	-0.38	82	169
alpha4/beta1 Integrin/Paxillin/Talin	0.016	0.044	-10000	0	-0.21	11	11
alpha4/beta1 Integrin/Paxillin/GIT1	0.017	0.041	-10000	0	-0.19	10	10
BCAR1	0.004	0.028	-10000	0	-0.38	3	3
mol:GDP	-0.016	0.04	0.19	10	-10000	0	10
CBL	0.006	0	-10000	0	-10000	0	0
PRKACA	0.006	0	-10000	0	-10000	0	0
GIT1	0.007	0.009	0.22	1	-10000	0	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.016	0.044	-10000	0	-0.21	11	11
Rac1/GTP	-0.013	0.13	-10000	0	-0.36	56	56

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.044	0.065	0.23	45	-10000	0	45
AES	-0.031	0.14	0.15	14	-0.37	84	98
FBXW11	0.006	0	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
LRP6/FZD1	0.007	0.004	-10000	0	-10000	0	0
SMAD4	0.006	0	-10000	0	-10000	0	0
DKK2	0.006	0	-10000	0	-10000	0	0
TLE1	0.031	0.049	0.19	25	-0.34	1	26
MACF1	0.009	0.03	0.22	8	-0.39	1	9
CTNNB1	0.016	0.047	0.24	3	-10000	0	3
WIF1	0.011	0.03	0.22	11	-10000	0	11
beta catenin/RanBP3	0.12	0.18	0.37	186	-10000	0	186
KREMEN2	0.006	0	-10000	0	-10000	0	0
DKK1	0.012	0.036	0.22	16	-10000	0	16
beta catenin/beta TrCP1	0.032	0.047	0.23	3	-10000	0	3
FZD1	0.005	0.003	-10000	0	-10000	0	0
AXIN2	-0.071	0.14	0.54	2	-0.56	17	19
AXIN1	0.007	0.001	-10000	0	-10000	0	0
RAN	0.007	0.002	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.018	0.038	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.001	0.12	0.26	5	-0.29	38	43
Axin1/APC/GSK3	0.017	0.034	0.2	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.022	0.044	0.24	1	-10000	0	1
HNF1A	0.028	0.044	0.16	13	-0.34	2	15
CTBP1	0.03	0.04	0.17	13	-10000	0	13
MYC	-0.18	0.41	-10000	0	-1.3	60	60
RANBP3	0.007	0.002	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.012	0.007	0.16	1	-10000	0	1
NKD1	0.006	0.009	0.22	1	-10000	0	1
TCF4	0.029	0.05	0.17	17	-0.37	3	20
TCF3	0.03	0.039	0.16	14	-10000	0	14
WNT1/LRP6/FZD1/Axin1	0.029	0.039	-10000	0	-10000	0	0
Ran/GTP	0.007	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.13	0.24	0.48	148	-0.45	1	149
LEF1	0.056	0.082	0.23	87	-0.34	1	88
DVL1	0.021	0.029	-10000	0	-10000	0	0
CSNK2A1	0.006	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.088	0.15	-10000	0	-0.45	45	45
DKK1/LRP6/Kremen 2	0.011	0.004	-10000	0	-10000	0	0
LRP6	0.028	0.066	0.22	60	-10000	0	60
CSNK1A1	0.034	0.045	0.19	21	-10000	0	21
NLK	0.001	0.019	0.22	3	-10000	0	3
CCND1	-0.34	0.56	0.53	1	-1.3	145	146
WNT1	0.005	0.003	-10000	0	-10000	0	0
GSK3A	0.001	0.04	-10000	0	-0.39	6	6
GSK3B	0.004	0.005	-10000	0	-10000	0	0
FRAT1	0.004	0.023	-10000	0	-0.38	2	2
PPP2R5D	0.015	0.02	-10000	0	-0.22	1	1
APC	0.008	0.04	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.015	0.04	-10000	0	-10000	0	0
CREBBP	0.024	0.061	0.16	16	-0.37	8	24

×

EGFR-dependent Endothelin 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
HRAS	0.006	0	-10000	0	-10000	0	0
EGFR	-0.03	0.12	0.22	1	-0.38	54	55
EGF/EGFR	-0.007	0.058	-10000	0	-0.18	55	55
EGF/EGFR dimer/SHC/GRB2/SOS1	0.003	0.065	-10000	0	-0.19	50	50
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.008	0.018	0.22	4	-10000	0	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.009	0.024	0.22	7	-10000	0	7
EGF/EGFR dimer/SHC	-0.01	0.07	-10000	0	-0.23	54	54
mol:GDP	0.002	0.064	-10000	0	-0.19	50	50
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.012	0.039	0.22	16	-0.38	1	17
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
HRAS/GTP	-0.006	0.054	-10000	0	-0.18	50	50
SHC1	0.006	0	-10000	0	-10000	0	0
HRAS/GDP	-0.002	0.057	-10000	0	-0.18	50	50
FRAP1	-0.018	0.058	0.24	2	-10000	0	2
EGF/EGFR dimer	-0.017	0.082	-10000	0	-0.27	54	54
SOS1	0.014	0.04	0.22	20	-10000	0	20
GRB2	0.006	0.016	-10000	0	-0.38	1	1
ETA receptor/Endothelin-1	0.009	0.012	-10000	0	-0.27	1	1

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.006	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	0.071	0.07	0.21	74	-10000	0	74
NT3 (dimer)/TRKC	0.008	0.003	-10000	0	-10000	0	0
NT3 (dimer)/TRKB	0.011	0.005	-10000	0	-10000	0	0
SHC/Grb2/SOS1/GAB1/PI3K	0.007	0.089	0.22	8	-0.21	60	68
RAPGEF1	0.006	0	-10000	0	-10000	0	0
BDNF	0.006	0	-10000	0	-10000	0	0
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
DYNLT1	-0.043	0.13	-10000	0	-0.38	72	72
NTRK1	0.006	0	-10000	0	-10000	0	0
NTRK2	0.007	0.016	0.22	3	-10000	0	3
NTRK3	0.007	0.016	0.22	3	-10000	0	3
NT-4/5 (dimer)/TRKB	0.008	0.001	-10000	0	-10000	0	0
neuron apoptosis	0.004	0.069	0.27	13	-10000	0	13
SHC 2-3/Grb2	-0.004	0.073	-10000	0	-0.29	13	13
SHC1	0.006	0	-10000	0	-10000	0	0
SHC2	-0.014	0.1	-10000	0	-0.4	29	29
SHC3	0.008	0.043	-10000	0	-0.23	1	1
STAT3 (dimer)	-0.082	0.15	0.18	1	-0.32	157	158
NT3 (dimer)/TRKA	0.011	0.005	-10000	0	-10000	0	0
RIN/GDP	0.038	0.04	0.18	8	-10000	0	8
GIPC1	0.009	0.025	0.22	8	-10000	0	8
KRAS	0.03	0.067	0.22	62	-10000	0	62
DNAJA3	0.002	0.058	0.19	2	-0.31	1	3
RIN/GTP	0.005	0	-10000	0	-10000	0	0
CCND1	-0.16	0.28	0.41	1	-0.61	157	158
MAGED1	0.006	0.028	0.22	3	-0.38	2	5
PTPN11	0.006	0	-10000	0	-10000	0	0
RICS	-0.079	0.16	-10000	0	-0.38	124	124
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.012	0.01	-10000	0	-0.23	1	1
GRB2	0.006	0.016	-10000	0	-0.38	1	1
NGF (dimer)/TRKA/MATK	0.009	0	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.009	0.012	-10000	0	-0.27	1	1
ELMO1	0.012	0.033	0.22	14	-10000	0	14
RhoG/GTP/ELMO1/DOCK1	0.007	0.014	-10000	0	-0.22	2	2
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.006	0	-10000	0	-10000	0	0
DOCK1	0.006	0.026	0.22	2	-0.38	2	4
GAB2	0.003	0.069	0.22	16	-0.38	13	29
RIT2	0.006	0	-10000	0	-10000	0	0
RIT1	0.02	0.052	0.22	35	-10000	0	35
FRS2	0.013	0.038	0.22	18	-10000	0	18
DNM1	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.004	0.051	0.2	9	-0.3	1	10
mol:GDP	0.046	0.052	0.22	8	-10000	0	8
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.005	0.001	-10000	0	-10000	0	0
RIT1/GDP	0.044	0.047	0.18	20	-10000	0	20
TIAM1	0.006	0.021	0.22	2	-0.38	1	3
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
BDNF (dimer)/TRKB	0.013	0.001	-10000	0	-10000	0	0
KIDINS220/CRKL/C3G	0.009	0	-10000	0	-10000	0	0
SHC/RasGAP	0.008	0.02	-10000	0	-0.27	3	3
FRS2 family/SHP2	0.012	0.002	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.019	0.032	-10000	0	-0.2	5	5
RIT1/GTP	0.004	0.001	-10000	0	-10000	0	0
NT3 (dimer)	0.037	0.075	0.22	81	-10000	0	81
RAP1/GDP	0.007	0.015	-10000	0	-0.22	1	1
KIDINS220/CRKL	0.006	0	-10000	0	-10000	0	0
BDNF (dimer)	0.006	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.008	0.01	-10000	0	-0.22	1	1
Schwann cell development	-0.002	0.005	-10000	0	-10000	0	0
EHD4	0.006	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.024	0.033	-10000	0	-0.2	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.006	0.035	0.19	1	-10000	0	1
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
RAP1A	0.007	0.009	0.22	1	-10000	0	1
CDC42/GTP	0.01	0.004	-10000	0	-10000	0	0
ABL1	0	0.049	-10000	0	-0.38	9	9
SH2B family/GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
Rap1/GTP	0.009	0.023	-10000	0	-0.24	1	1
STAT3	-0.082	0.15	0.18	1	-0.32	157	158
axon guidance	0.007	0.003	-10000	0	-10000	0	0
MAPK3	-0.022	0.057	-10000	0	-0.2	51	51
MAPK1	-0.004	0.011	0.15	1	-0.2	1	2
CDC42/GDP	0.038	0.04	0.18	8	-10000	0	8
NTF3	0.037	0.075	0.22	81	-10000	0	81
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.009	0	-10000	0	-10000	0	0
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
FRS3	0.006	0	-10000	0	-10000	0	0
FAIM	0.006	0	-10000	0	-10000	0	0
GAB1	0.004	0.033	-10000	0	-0.38	4	4
RASGRF1	0.002	0.057	0.18	1	-0.31	1	2
SOS1	0.014	0.04	0.22	20	-10000	0	20
MCF2L	0.018	0.056	0.15	83	-10000	0	83
RGS19	0.006	0	-10000	0	-10000	0	0
CDC42	0.006	0	-10000	0	-10000	0	0
RAS family/GTP	0.054	0.066	0.27	6	-0.37	1	7
Rac1/GDP	0.037	0.04	0.18	8	-10000	0	8
NGF (dimer)/TRKA/GRIT	-0.042	0.096	-10000	0	-0.22	124	124
neuron projection morphogenesis	-0.067	0.16	-10000	0	-0.84	12	12
NGF (dimer)/TRKA/NEDD4-2	0.008	0.01	-10000	0	-0.22	1	1
MAP2K1	-0.003	0.031	-10000	0	-0.19	5	5
NGFR	0.007	0.009	0.22	1	-10000	0	1
NGF (dimer)/TRKA/GIPC/GAIP	-0.021	0.072	-10000	0	-0.21	72	72
RAS family/GTP/PI3K	0.063	0.11	0.23	89	-0.21	26	115
FRS2 family/SHP2/GRB2/SOS1	0.026	0.031	-10000	0	-0.19	1	1
NRAS	0.099	0.11	0.22	245	-10000	0	245
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
PRKCI	0.12	0.11	0.22	306	-10000	0	306
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCZ	0.006	0	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.032	-10000	0	-10000	0	0
RASA1	0.004	0.028	-10000	0	-0.38	3	3
TRKA/c-Abl	0.005	0.035	-10000	0	-0.27	9	9
SQSTM1	0.006	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.009	0.077	-10000	0	-0.2	72	72
NGF (dimer)/TRKA/p62/Atypical PKCs	0.079	0.06	-10000	0	-10000	0	0
MATK	0.006	0	-10000	0	-10000	0	0
NEDD4L	0.008	0.029	0.22	7	-0.38	1	8
RAS family/GDP	-0.001	0.007	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.012	0.045	0.19	1	-0.32	1	2
Rac1/GTP	-0.004	0.02	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family	0.023	0.021	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.008	0.039	-10000	0	-0.38	5	5
HSPA8	0.004	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.041	0.091	-10000	0	-0.28	54	54
AKT1	0.006	0.01	0.22	1	-10000	0	1
GSC	-0.01	0.021	-10000	0	-10000	0	0
NKX2-5	0.004	0.012	-10000	0	-10000	0	0
muscle cell differentiation	-0.007	0.075	0.37	3	-0.23	1	4
SMAD2-3/SMAD4/SP1	0.035	0.1	0.3	11	-0.35	2	13
SMAD4	-0.003	0.051	-10000	0	-10000	0	0
CBFB	0.004	0.028	-10000	0	-0.38	3	3
SAP18	0.004	0.017	-10000	0	-0.38	1	1
Cbp/p300/MSG1	0.016	0.047	0.22	2	-0.26	10	12
SMAD3/SMAD4/VDR	0.014	0.066	0.23	3	-0.27	7	10
MYC	-0.035	0.12	-10000	0	-0.39	60	60
CDKN2B	0.007	0.042	-10000	0	-10000	0	0
AP1	-0.029	0.11	0.51	2	-0.32	15	17
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.053	0.062	0.23	12	-10000	0	12
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.002	0.042	-10000	0	-0.29	1	1
SP3	0.009	0.017	-10000	0	-10000	0	0
CREB1	0.006	0	-10000	0	-10000	0	0
FOXH1	0.004	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/GR	-0.023	0.064	-10000	0	-0.28	12	12
GATA3	0.007	0.013	0.22	2	-10000	0	2
SKI/SIN3/HDAC complex/NCoR1	0.009	0.041	0.18	11	-10000	0	11
MEF2C/TIF2	-0.013	0.071	-10000	0	-0.38	17	17
endothelial cell migration	-0.076	0.17	-10000	0	-0.54	69	69
MAX	-0.006	0.034	-10000	0	-10000	0	0
RBBP7	0.004	0.019	0.22	1	-0.39	1	2
RBBP4	0.013	0.042	0.22	22	-10000	0	22
RUNX2	0.007	0.013	0.22	2	-10000	0	2
RUNX3	0.007	0.009	0.22	1	-10000	0	1
RUNX1	0.006	0.016	-10000	0	-0.38	1	1
CTBP1	0.006	0	-10000	0	-10000	0	0
NR3C1	-0.015	0.066	-10000	0	-0.39	13	13
VDR	0.007	0.013	0.22	2	-10000	0	2
CDKN1A	-0.034	0.29	-10000	0	-1.1	35	35
KAT2B	0.001	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.006	0.04	-10000	0	-0.24	2	2
DCP1A	0.006	0	-10000	0	-10000	0	0
SKI	0.005	0.004	-10000	0	-10000	0	0
SERPINE1	0.076	0.17	0.54	69	-10000	0	69
SMAD3/SMAD4/ATF2	-0.006	0.048	0.2	4	-0.27	3	7
SMAD3/SMAD4/ATF3	-0.006	0.049	0.2	4	-0.29	4	8
SAP30	0.005	0.004	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.02	0.054	-10000	0	-0.26	11	11
JUN	-0.024	0.12	0.52	9	-0.34	12	21
SMAD3/SMAD4/IRF7	-0.004	0.049	0.21	3	-0.31	2	5
TFE3	0.022	0.041	0.18	8	-0.39	1	9
COL1A2	0.13	0.25	0.47	169	-0.8	9	178
mesenchymal cell differentiation	0.006	0.048	0.31	2	-0.2	3	5
DLX1	0.007	0.013	0.22	2	-10000	0	2
TCF3	0.006	0	-10000	0	-10000	0	0
FOS	-0.067	0.16	0.22	8	-0.39	110	118
SMAD3/SMAD4/Max	-0.019	0.055	-10000	0	-0.3	3	3
Cbp/p300/SNIP1	0.012	0.041	-10000	0	-0.26	11	11
ZBTB17	0.006	0	-10000	0	-10000	0	0
LAMC1	0.034	0.13	0.44	45	-0.31	1	46
TGIF2/HDAC complex/SMAD3/SMAD4	-0.006	0.049	0.21	3	-0.27	4	7
IRF7	0.006	0	-10000	0	-10000	0	0
ESR1	-0.055	0.13	-10000	0	-0.41	61	61
HNF4A	0.007	0.009	0.22	1	-10000	0	1
MEF2C	-0.014	0.073	-10000	0	-0.4	17	17
SMAD2-3/SMAD4	-0.007	0.052	0.21	3	-0.28	4	7
Cbp/p300/Src-1	0.014	0.048	-10000	0	-0.25	14	14
IGHV3OR16-13	-0.003	0.01	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.006	0.016	-10000	0	-0.38	1	1
CREBBP	0.004	0.047	-10000	0	-0.38	8	8
SKIL	0.11	0.11	0.22	281	-10000	0	281
HDAC1	0.015	0.047	0.22	28	-10000	0	28
HDAC2	0.009	0.037	0.22	13	-0.38	1	14
SNIP1	0.005	0.014	0.22	2	-10000	0	2
GCN5L2	0.01	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.012	0.071	0.37	5	-0.3	3	8
MSG1/HSC70	0.006	0.008	-10000	0	-10000	0	0
SMAD2	0.002	0.026	-10000	0	-0.39	2	2
SMAD3	-0.004	0.056	0.17	2	-0.47	2	4
SMAD3/E2F4-5/DP1/p107/SMAD4	0.03	0.062	0.22	14	-0.24	1	15
SMAD2/SMAD2/SMAD4	0.002	0.034	0.16	1	-10000	0	1
NCOR1	0.001	0.04	-10000	0	-0.39	6	6
NCOA2	0.007	0.013	0.22	2	-10000	0	2
NCOA1	0.004	0.028	-10000	0	-0.38	3	3
MYOD/E2A	0.009	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.036	0.096	0.3	6	-0.32	2	8
IFNB1	0.001	0.06	-10000	0	-0.31	1	1
SMAD3/SMAD4/MEF2C	-0.008	0.084	-10000	0	-0.38	17	17
CITED1	0.011	0.032	0.22	13	-10000	0	13
SMAD2-3/SMAD4/ARC105	-0.001	0.056	0.22	1	-0.25	6	7
RBL1	0.023	0.058	0.22	45	-10000	0	45
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.002	0.049	-10000	0	-0.29	1	1
RUNX1-3/PEBPB2	0.011	0.02	-10000	0	-0.23	4	4
SMAD7	0.002	0.15	0.48	6	-0.5	4	10
MYC/MIZ-1	-0.021	0.086	-10000	0	-0.27	60	60
SMAD3/SMAD4	0.067	0.11	0.35	37	-0.4	2	39
IL10	0.001	0.06	-10000	0	-0.31	1	1
PIASy/HDAC complex	0.001	0.014	-10000	0	-10000	0	0
PIAS3	0.008	0.01	0.22	1	-10000	0	1
CDK2	0.11	0.11	0.22	255	-10000	0	255
IL5	0.001	0.06	-10000	0	-0.31	1	1
CDK4	0.014	0.029	0.22	9	-10000	0	9
PIAS4	0.001	0.014	-10000	0	-10000	0	0
ATF3	0.009	0.033	0.22	10	-0.38	1	11
SMAD3/SMAD4/SP1	0.026	0.1	0.32	6	-0.27	12	18
FOXG1	0.008	0.01	0.22	1	-10000	0	1
FOXO3	-0.008	0.033	0.2	1	-0.27	8	9
FOXO1	-0.008	0.035	0.2	1	-0.27	9	10
FOXO4	-0.004	0.009	0.2	1	-10000	0	1
heart looping	-0.014	0.073	-10000	0	-0.4	17	17
CEBPB	0.004	0.034	0.22	1	-0.38	4	5
SMAD3/SMAD4/DLX1	-0.006	0.048	0.21	3	-0.27	3	6
MYOD1	0.006	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.006	0.048	0.21	3	-0.27	3	6
SMAD3/SMAD4/GATA3	-0.003	0.05	0.21	3	-0.31	2	5
SnoN/SIN3/HDAC complex/NCoR1	0.11	0.11	0.22	281	-10000	0	281
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.011	0.057	0.21	2	-0.24	6	8
SMAD3/SMAD4/SP1-3	0.036	0.098	0.29	10	-0.35	2	12
MED15	0.005	0.03	0.22	1	-0.38	3	4
SP1	0.026	0.055	0.17	8	-10000	0	8
SIN3B	0.005	0.01	0.22	1	-10000	0	1
SIN3A	0.005	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.009	0.053	-10000	0	-0.24	13	13
ITGB5	0.032	0.12	0.5	20	-0.32	2	22
TGIF/SIN3/HDAC complex/CtBP	0.012	0.035	0.21	2	-10000	0	2
SMAD3/SMAD4/AR	-0.11	0.13	-10000	0	-0.26	229	229
AR	-0.17	0.19	-10000	0	-0.38	251	251
negative regulation of cell growth	0.023	0.065	0.25	3	-0.31	3	6
SMAD3/SMAD4/MYOD	-0.006	0.048	0.19	5	-0.27	3	8
E2F5	0.026	0.063	0.22	53	-10000	0	53
E2F4	0.006	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.016	0.046	-10000	0	-0.2	5	5
SMAD2-3/SMAD4/FOXO1-3a-4	-0.005	0.051	-10000	0	-0.29	2	2
TFDP1	0.012	0.036	0.22	16	-10000	0	16
SMAD3/SMAD4/AP1	-0.022	0.1	-10000	0	-0.33	15	15
SMAD3/SMAD4/RUNX2	-0.005	0.048	0.21	3	-0.31	2	5
TGIF2	0.006	0.016	-10000	0	-0.38	1	1
TGIF1	0.006	0	-10000	0	-10000	0	0
ATF2	0.007	0.016	0.22	3	-10000	0	3

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.007	0.009	0.22	1	-10000	0	1
VLDLR	-0.002	0.072	0.22	8	-0.38	17	25
LRPAP1	0.006	0.028	0.22	3	-0.38	2	5
NUDC	0.006	0.016	-10000	0	-0.38	1	1
RELN/LRP8	-0.024	0.086	-10000	0	-0.23	85	85
CaM/Ca2+	-0.004	0.048	-10000	0	-0.27	18	18
KATNA1	0.007	0.013	0.22	2	-10000	0	2
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.029	0.087	0.27	2	-0.21	94	96
IQGAP1/CaM	0	0.051	-10000	0	-0.27	20	20
DAB1	0.006	0	-10000	0	-10000	0	0
IQGAP1	0.005	0.025	0.22	1	-0.38	2	3
PLA2G7	0.019	0.072	0.22	45	-0.38	6	51
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
DYNLT1	-0.043	0.13	-10000	0	-0.38	72	72
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.008	0.017	-10000	0	-0.27	2	2
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.006	0	-10000	0	-10000	0	0
CDK5R1	0.006	0	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	-0.003	0.006	0.14	1	-10000	0	1
CDK5R2	0.006	0	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.03	0.09	-10000	0	-0.23	99	99
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
NDEL1/14-3-3 E	-0.012	0.083	0.25	5	-0.32	1	6
MAP1B	-0.029	0.081	-10000	0	-0.24	72	72
RAC1	0.001	0.017	-10000	0	-0.22	3	3
p35/CDK5	-0.013	0.089	0.27	5	-0.35	1	6
RELN	-0.041	0.15	0.22	27	-0.38	84	111
PAFAH/LIS1	0.016	0.049	0.16	45	-0.23	6	51
LIS1/CLIP170	0.006	0.006	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.046	0.067	-10000	0	-0.3	6	6
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.022	0.09	0.23	5	-0.24	15	20
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.011	0.086	0.26	5	-0.34	1	6
LIS1/IQGAP1	0.006	0.016	0.16	1	-0.23	2	3
RHOA	0	0.023	-10000	0	-0.36	2	2
PAFAH1B1	-0.004	0.008	0.2	1	-10000	0	1
PAFAH1B3	0.018	0.049	0.22	31	-10000	0	31
PAFAH1B2	0.005	0.023	-10000	0	-0.38	2	2
MAP1B/LIS1/Dynein heavy chain	-0.014	0.055	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.012	0.08	0.22	4	-0.31	1	5
LRP8	0.01	0.027	0.22	9	-10000	0	9
NDEL1/Katanin 60	-0.011	0.083	0.25	5	-0.32	1	6
P39/CDK5	-0.013	0.089	0.27	5	-0.35	1	6
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.006	0.011	-10000	0	-0.23	1	1
CDK5	-0.012	0.094	0.3	5	-0.19	85	90
PPP2R5D	0.006	0	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.005	0	-10000	0	-10000	0	0
CSNK2A1	0.006	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.015	0.088	0.27	3	-0.19	98	101
RELN/VLDLR	-0.015	0.093	-10000	0	-0.21	98	98
CDC42	0.002	0.009	-10000	0	-10000	0	0

×

Ceramide signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.017	0.057	-10000	0	-0.27	28	28
MAP4K4	-0.042	0.09	-10000	0	-0.36	13	13
BAG4	0.006	0	-10000	0	-10000	0	0
PKC zeta/ceramide	0.011	0.022	0.14	2	-10000	0	2
NFKBIA	-0.005	0.065	-10000	0	-0.38	16	16
BIRC3	-0.076	0.17	0.22	13	-0.38	127	140
BAX	0.006	0.013	-10000	0	-10000	0	0
RIPK1	0.006	0	-10000	0	-10000	0	0
AKT1	-0.003	0.016	0.39	1	-10000	0	1
BAD	0.006	0.024	0.11	28	-10000	0	28
SMPD1	-0.017	0.043	-10000	0	-0.18	25	25
RB1	0.008	0.04	0.15	21	-0.18	6	27
FADD/Caspase 8	-0.043	0.093	-10000	0	-0.39	13	13
MAP2K4	0.001	0.033	0.14	2	-0.18	10	12
NSMAF	0.008	0.02	0.22	5	-10000	0	5
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.004	0.022	0.14	2	-10000	0	2
EGF	0.009	0.024	0.22	7	-10000	0	7
mol:ceramide	0.008	0.026	0.12	28	-10000	0	28
MADD	0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.018	0.059	-10000	0	-0.27	30	30
ASAH1	0.005	0.023	-10000	0	-0.38	2	2
negative regulation of cell cycle	0.008	0.04	0.14	24	-0.18	6	30
cell proliferation	-0.041	0.073	-10000	0	-0.23	44	44
BID	-0.026	0.072	-10000	0	-0.34	7	7
MAP3K1	0.005	0.027	0.12	6	-0.18	3	9
EIF2A	0.041	0.064	0.22	19	-10000	0	19
TRADD	0.002	0.04	-10000	0	-0.38	6	6
CRADD	0.006	0	-10000	0	-10000	0	0
MAPK3	-0.045	0.071	-10000	0	-0.27	27	27
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.032	0.051	-10000	0	-0.28	1	1
Cathepsin D/ceramide	0.007	0.035	0.14	2	-0.18	11	13
FADD	-0.044	0.09	-10000	0	-0.36	13	13
KSR1	0.006	0.024	0.11	28	-10000	0	28
MAPK8	0.006	0.028	0.16	3	-10000	0	3
PRKRA	0.007	0.026	0.11	30	-10000	0	30
PDGFA	-0.013	0.085	-10000	0	-0.38	28	28
TRAF2	0.006	0	-10000	0	-10000	0	0
IGF1	-0.003	0.067	0.22	4	-0.38	16	20
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.008	0.026	0.12	28	-10000	0	28
CTSD	-0.001	0.054	-10000	0	-0.38	11	11
regulation of nitric oxide biosynthetic process	0.003	0.042	-10000	0	-0.27	13	13
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.043	0.078	-10000	0	-0.24	44	44
PRKCD	0.005	0.023	-10000	0	-0.38	2	2
PRKCZ	0.006	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.018	0.059	-10000	0	-0.27	30	30
RelA/NF kappa B1	0.003	0.042	-10000	0	-0.27	13	13
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.006	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.045	0.096	-10000	0	-0.38	13	13
TNFR1A/BAG4/TNF-alpha	0.002	0.049	-10000	0	-0.23	25	25
mol:Sphingosine-1-phosphate	-0.017	0.057	-10000	0	-0.27	28	28
MAP2K1	0.003	0.022	0.13	2	-10000	0	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.005	0.023	-10000	0	-0.38	2	2
CYCS	0.022	0.05	0.14	73	-10000	0	73
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
TNFR1A/BAG4	-0.003	0.057	-10000	0	-0.27	25	25
EIF2AK2	0.044	0.066	0.14	176	-10000	0	176
TNF-alpha/TNFR1A/FAN	0.002	0.049	-10000	0	-0.23	25	25
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.029	0.087	-10000	0	-0.48	13	13
MAP2K2	-0.06	0.083	-10000	0	-0.17	192	192
SMPD3	-0.02	0.05	-10000	0	-0.23	14	14
TNF	0.007	0.009	0.22	1	-10000	0	1
PKC zeta/PAR4	0.009	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0	0.029	0.11	21	-0.15	5	26
NF kappa B1/RelA/I kappa B alpha	0.008	0.05	-10000	0	-0.21	26	26
AIFM1	0.037	0.063	0.17	82	-10000	0	82
BCL2	-0.043	0.13	0.22	2	-0.38	73	75

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.01	0.094	-10000	0	-0.54	17	17
HDAC1	0.028	0.051	0.24	28	-10000	0	28
AES	-0.051	0.14	-10000	0	-0.38	89	89
FBXW11	0.006	0	-10000	0	-10000	0	0
DTX1	0.006	0	-10000	0	-10000	0	0
LRP6/FZD1	0.008	0.003	-10000	0	-10000	0	0
TLE1	0.011	0.03	0.23	7	-0.37	1	8
AP1	-0.051	0.11	0.22	4	-0.24	130	134
NCSTN	0.006	0.009	0.22	1	-10000	0	1
ADAM10	0.007	0.013	0.22	2	-10000	0	2
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.12	0.16	-10000	0	-0.46	60	60
NICD/RBPSUH	-0.011	0.094	-10000	0	-0.54	17	17
WIF1	0.01	0.03	0.22	11	-10000	0	11
NOTCH1	-0.016	0.098	-10000	0	-0.56	17	17
PSENEN	-0.006	0.069	-10000	0	-0.39	18	18
KREMEN2	0.006	0	-10000	0	-10000	0	0
DKK1	0.012	0.036	0.22	16	-10000	0	16
beta catenin/beta TrCP1	-0.017	0.041	-10000	0	-10000	0	0
APH1B	-0.028	0.11	-10000	0	-0.39	49	49
APH1A	0.006	0.009	0.22	1	-10000	0	1
AXIN1	-0.004	0.033	0.19	2	-0.19	1	3
CtBP/CBP/TCF1/TLE1/AES	0.019	0.11	0.26	28	-10000	0	28
PSEN1	0.006	0.009	0.22	1	-10000	0	1
FOS	-0.066	0.16	0.22	8	-0.38	110	118
JUN	0.008	0.039	0.22	9	-0.38	3	12
MAP3K7	0.015	0.029	0.22	10	-10000	0	10
CTNNB1	-0.02	0.04	0.21	1	-10000	0	1
MAPK3	-0.029	0.11	-10000	0	-0.38	51	51
DKK2/LRP6/Kremen 2	0.011	0.004	-10000	0	-10000	0	0
HNF1A	0.009	0.024	-10000	0	-0.38	2	2
CTBP1	0.01	0.008	-10000	0	-10000	0	0
MYC	-0.15	0.38	-10000	0	-1.3	60	60
NKD1	0.008	0.009	0.22	1	-10000	0	1
FZD1	0.006	0.001	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.012	0.094	-10000	0	-0.54	17	17
apoptosis	-0.05	0.11	0.21	4	-0.24	130	134
Delta 1/NOTCHprecursor	-0.012	0.094	-10000	0	-0.54	17	17
DLL1	0.006	0	-10000	0	-10000	0	0
PPARD	-0.026	0.042	-10000	0	-10000	0	0
Gamma Secretase	-0.014	0.069	-10000	0	-0.2	66	66
APC	-0.004	0.033	0.19	2	-10000	0	2
DVL1	-0.001	0.009	-10000	0	-10000	0	0
CSNK2A1	0.002	0.006	-10000	0	-10000	0	0
MAP3K7IP1	0.011	0.008	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.011	0.004	-10000	0	-10000	0	0
LRP6	0.029	0.066	0.22	60	-10000	0	60
CSNK1A1	0.002	0.011	0.22	1	-10000	0	1
NLK	0.019	0.029	0.19	3	-10000	0	3
CCND1	-0.32	0.54	0.53	1	-1.2	145	146
WNT1	0.006	0.001	-10000	0	-10000	0	0
Axin1/APC/beta catenin	-0.021	0.046	0.22	1	-10000	0	1
DKK2	0.006	0	-10000	0	-10000	0	0
NOTCH1 precursor/DVL1	-0.012	0.086	-10000	0	-0.49	17	17
GSK3B	0.007	0.002	-10000	0	-10000	0	0
FRAT1	0.007	0.024	-10000	0	-0.38	2	2
NOTCH/Deltex homolog 1	-0.01	0.094	-10000	0	-0.54	17	17
PPP2R5D	-0.001	0.01	-10000	0	-10000	0	0
MAPK1	0.006	0.019	0.22	1	-0.38	1	2
WNT1/LRP6/FZD1	0.028	0.042	-10000	0	-10000	0	0
RBPJ	0.007	0.009	0.22	1	-10000	0	1
CREBBP	-0.001	0.045	-10000	0	-0.38	8	8

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.012	0.098	-10000	0	-0.21	72	72
SMAD6-7/SMURF1	0.013	0.001	-10000	0	-10000	0	0
NOG	0.006	0.021	0.22	2	-0.38	1	3
SMAD9	-0.01	0.077	-10000	0	-0.46	14	14
SMAD4	0.006	0	-10000	0	-10000	0	0
SMAD5	-0.012	0.062	-10000	0	-0.31	5	5
BMP7/USAG1	-0.014	0.072	-10000	0	-0.28	39	39
SMAD5/SKI	-0.008	0.061	-10000	0	-0.29	5	5
SMAD1	-0.002	0.03	-10000	0	-0.31	3	3
BMP2	0.006	0.016	-10000	0	-0.38	1	1
SMAD1/SMAD1/SMAD4	0.004	0.026	-10000	0	-0.26	3	3
BMPR1A	0.005	0.042	0.22	5	-0.38	5	10
BMPR1B	-0.014	0.095	0.22	7	-0.38	33	40
BMPR1A-1B/BAMBI	-0.003	0.058	-10000	0	-0.23	33	33
AHSG	0.006	0	-10000	0	-10000	0	0
CER1	0.007	0.009	0.22	1	-10000	0	1
BMP2-4/CER1	0.012	0.01	-10000	0	-0.23	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.025	0.08	-10000	0	-0.35	10	10
BMP2-4 (homodimer)	0.009	0.012	-10000	0	-0.27	1	1
RGMB	0.006	0	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.004	0.061	-10000	0	-0.21	38	38
RGMA	-0.01	0.077	-10000	0	-0.38	23	23
SMURF1	0.006	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.011	0.062	0.19	1	-0.35	4	5
BMP2-4/USAG1	0.009	0.018	-10000	0	-0.23	3	3
SMAD6/SMURF1/SMAD5	-0.008	0.061	-10000	0	-0.29	5	5
SOSTDC1	0.047	0.089	0.22	111	-0.38	2	113
BMP7/BMPR2/BMPR1A-1B	0.002	0.099	-10000	0	-0.22	72	72
SKI	0.006	0	-10000	0	-10000	0	0
BMP6 (homodimer)	0.007	0.013	0.22	2	-10000	0	2
HFE2	0.006	0	-10000	0	-10000	0	0
ZFYVE16	0.007	0.016	0.22	3	-10000	0	3
MAP3K7	0.01	0.028	0.22	10	-10000	0	10
BMP2-4/CHRD	0.012	0.01	-10000	0	-0.23	1	1
SMAD5/SMAD5/SMAD4	-0.008	0.061	-10000	0	-0.31	4	4
MAPK1	0.006	0.019	0.22	1	-0.38	1	2
TAK1/TAB family	0.002	0.06	-10000	0	-0.31	4	4
BMP7 (homodimer)	0.003	0.13	0.22	69	-0.38	43	112
NUP214	0.006	0	-10000	0	-10000	0	0
BMP6/FETUA	0.009	0.001	-10000	0	-10000	0	0
SMAD1/SKI	0.002	0.029	-10000	0	-0.3	3	3
SMAD6	0.008	0.02	0.22	5	-10000	0	5
CTDSP2	0.005	0.023	-10000	0	-0.38	2	2
BMP2-4/FETUA	0.012	0.01	-10000	0	-0.23	1	1
MAP3K7IP1	0.006	0	-10000	0	-10000	0	0
GREM1	0.013	0.038	0.22	18	-10000	0	18
BMPR2 (homodimer)	0.006	0.016	-10000	0	-0.38	1	1
GADD34/PP1CA	-0.01	0.071	-10000	0	-0.23	55	55
BMPR1A-1B (homodimer)	-0.009	0.071	-10000	0	-0.28	37	37
CHRDL1	-0.18	0.2	0.22	2	-0.38	270	272
ENDOFIN/SMAD1	0.003	0.031	-10000	0	-0.3	3	3
SMAD6-7/SMURF1/SMAD1	0.009	0.031	-10000	0	-0.28	3	3
SMAD6/SMURF1	0.006	0	-10000	0	-10000	0	0
BAMBI	0.022	0.064	0.22	46	-0.38	2	48
SMURF2	0.007	0.009	0.22	1	-10000	0	1
BMP2-4/CHRDL1	-0.1	0.12	-10000	0	-0.23	266	266
BMP2-4/GREM1	0.012	0.01	-10000	0	-0.23	1	1
SMAD7	0.006	0	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.007	0.074	-10000	0	-0.44	14	14
SMAD1/SMAD6	0.002	0.029	-10000	0	-0.3	3	3
TAK1/SMAD6	0.009	0.001	-10000	0	-10000	0	0
BMP7	0.003	0.13	0.22	69	-0.38	43	112
BMP6	0.007	0.013	0.22	2	-10000	0	2
MAP3K7IP2	0.005	0.025	0.22	1	-0.38	2	3
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.009	0.058	-10000	0	-0.33	4	4
PPM1A	0.006	0	-10000	0	-10000	0	0
SMAD1/SMURF2	0.002	0.03	-10000	0	-0.3	3	3
SMAD7/SMURF1	0.009	0	-10000	0	-10000	0	0
CTDSPL	0.006	0	-10000	0	-10000	0	0
PPP1CA	0.006	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0.004	0.028	-10000	0	-0.38	3	3
PPP1R15A	-0.031	0.12	0.22	1	-0.38	55	56
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.004	0.071	0.19	7	-0.38	4	11
CHRD	0.006	0	-10000	0	-10000	0	0
BMPR2	0.006	0.016	-10000	0	-0.38	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.012	0.066	0.19	1	-0.38	4	5
BMP4	0.011	0.031	0.22	12	-10000	0	12
FST	0.023	0.057	0.22	43	-10000	0	43
BMP2-4/NOG	0.012	0.014	-10000	0	-0.23	2	2
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.005	0.094	-10000	0	-0.21	72	72

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.007	0.009	0.22	1	-10000	0	1
NFATC1	0.062	0.037	-10000	0	-10000	0	0
NFATC2	-0.02	0.046	0.16	5	-0.18	12	17
NFATC3	-0.007	0.03	-10000	0	-10000	0	0
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
Calcineurin A alpha-beta B1/CABIN1	0.001	0.037	-10000	0	-0.34	1	1
Exportin 1/Ran/NUP214	0.005	0.01	-10000	0	-10000	0	0
mol:DAG	-0.002	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.007	0.047	-10000	0	-0.2	7	7
BCL2/BAX	-0.026	0.093	-10000	0	-0.27	73	73
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.049	-10000	0	-0.27	18	18
CaM/Ca2+	-0.011	0.049	-10000	0	-0.27	18	18
BAX	0.006	0	-10000	0	-10000	0	0
MAPK14	0.002	0.012	0.22	1	-10000	0	1
BAD	0.006	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.001	0.036	-10000	0	-0.33	1	1
Calcineurin A alpha-beta B1/BCL2	-0.043	0.13	0.22	2	-0.38	73	75
FKBP8	-0.007	0.072	-10000	0	-0.38	20	20
activation-induced cell death of T cells	-0.001	0.035	0.32	1	-10000	0	1
KPNB1	0.006	0	-10000	0	-10000	0	0
KPNA2	0.19	0.075	0.22	491	-10000	0	491
XPO1	0.022	0.063	0.22	52	-10000	0	52
SFN	0.013	0.039	0.22	19	-10000	0	19
MAP3K8	0.001	0.008	-10000	0	-10000	0	0
NFAT4/CK1 alpha	-0.012	0.048	-10000	0	-0.23	22	22
MEF2D/NFAT1/Cbp/p300	-0.08	0.14	0.4	5	-0.25	199	204
CABIN1	0.001	0.037	-10000	0	-0.34	1	1
CALM1	-0.012	0.068	-10000	0	-0.39	18	18
RAN	0.002	0.005	-10000	0	-10000	0	0
MAP3K1	0.004	0.033	-10000	0	-0.38	4	4
CAMK4	0.01	0.027	0.22	9	-10000	0	9
mol:Ca2+	-0.004	0.008	-10000	0	-10000	0	0
MAPK3	-0.029	0.11	-10000	0	-0.38	51	51
YWHAH	0.005	0.03	0.22	1	-0.38	3	4
Calcineurin A alpha-beta B1/AKAP79/PKA	0.004	0.008	-10000	0	-10000	0	0
YWHAB	0.007	0.009	0.22	1	-10000	0	1
MAPK8	0.003	0.022	0.22	5	-10000	0	5
MAPK9	0.006	0.019	0.22	1	-0.38	1	2
YWHAG	0.004	0.033	-10000	0	-0.38	4	4
FKBP1A	0.006	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.042	0.055	-10000	0	-10000	0	0
PRKCH	0.005	0.023	-10000	0	-0.38	2	2
CABIN1/Cbp/p300	-0.01	0.048	-10000	0	-0.32	11	11
CASP3	0.005	0.03	0.22	10	-10000	0	10
PIM1	0.007	0.016	0.22	3	-10000	0	3
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.006	-10000	0	-10000	0	0
apoptosis	-0.002	0.041	0.16	16	-10000	0	16
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.002	0.04	-10000	0	-0.39	1	1
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.007	0.009	0.22	1	-10000	0	1
JNK2/NFAT4	-0.004	0.03	-10000	0	-0.2	1	1
BAD/BCL-XL	0.009	0	-10000	0	-10000	0	0
PRKCD	0.005	0.023	-10000	0	-0.38	2	2
NUP214	0.002	0.005	-10000	0	-10000	0	0
PRKCZ	0.001	0.008	-10000	0	-10000	0	0
PRKCA	0.005	0.044	0.22	7	-0.38	5	12
PRKCG	0.006	0	-10000	0	-10000	0	0
PRKCQ	0.002	0.06	0.22	8	-0.38	11	19
FKBP38/BCL2	-0.036	0.11	-10000	0	-0.28	89	89
EP300	-0.006	0.038	-10000	0	-0.39	5	5
PRKCB1	0.009	0.022	0.22	6	-10000	0	6
CSNK2A1	0.006	0	-10000	0	-10000	0	0
NFATc/JNK1	0.06	0.039	0.22	3	-10000	0	3
CaM/Ca2+/FKBP38	-0.015	0.059	-10000	0	-0.23	38	38
FKBP12/FK506	0.005	0	-10000	0	-10000	0	0
CSNK1A1	-0.016	0.041	0.16	1	-0.23	18	19
CaM/Ca2+/CAMK IV	-0.007	0.041	-10000	0	-0.23	17	17
NFATc/ERK1	0.054	0.047	-10000	0	-0.35	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.004	0.045	-10000	0	-0.3	1	1
NR4A1	-0.15	0.2	0.51	5	-0.41	203	208
GSK3B	0.001	0.008	-10000	0	-10000	0	0
positive T cell selection	-0.007	0.03	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.024	0.054	0.14	6	-0.25	18	24
RCH1/ KPNB1	0.001	0.003	-10000	0	-10000	0	0
YWHAQ	0.006	0	-10000	0	-10000	0	0
PRKACA	0.001	0.007	-10000	0	-10000	0	0
AKAP5	0.006	0	-10000	0	-10000	0	0
MEF2D	-0.003	0.013	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.006	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.06	0.037	-10000	0	-10000	0	0
CREBBP	-0.008	0.047	-10000	0	-0.39	8	8
BCL2	-0.043	0.13	0.22	2	-0.38	73	75

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.002	0.044	0.2	1	-0.27	13	14
PDGFRB	-0.012	0.079	-10000	0	-0.39	24	24
SPHK1	-0.004	0.022	-10000	0	-10000	0	0
mol:S1P	-0.007	0.032	0.3	1	-10000	0	1
S1P1/S1P/Gi	-0.024	0.13	0.41	6	-0.37	45	51
GNAO1	0.004	0.037	0.22	6	-0.39	3	9
PDGFB-D/PDGFRB/PLCgamma1	-0.026	0.12	0.38	6	-0.35	42	48
PLCG1	-0.025	0.12	0.39	6	-0.36	42	48
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.012	0.079	-10000	0	-0.39	24	24
GNAI2	0.004	0.009	-10000	0	-10000	0	0
GNAI3	0.015	0.048	0.22	29	-10000	0	29
GNAI1	-0.002	0.064	0.22	7	-0.39	13	20
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.008	0.084	0.22	1	-0.5	13	14
S1P1/S1P	-0.01	0.086	0.33	2	-0.43	13	15
negative regulation of cAMP metabolic process	-0.023	0.12	0.41	6	-0.36	45	51
MAPK3	-0.056	0.18	0.47	6	-0.55	54	60
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.004	0.011	-10000	0	-0.27	1	1
RhoA/GDP	0.004	0.016	-10000	0	-0.27	2	2
KDR	0.002	0.029	0.22	2	-0.16	13	15
PLCB2	-0.014	0.079	0.31	2	-0.39	13	15
RAC1	0.006	0.016	-10000	0	-0.38	1	1
RhoA/GTP	-0.018	0.066	-10000	0	-0.37	13	13
receptor internalization	-0.01	0.081	0.31	2	-0.4	13	15
PTGS2	-0.086	0.29	0.55	6	-0.97	50	56
Rac1/GTP	-0.018	0.065	-10000	0	-0.37	13	13
RHOA	0.005	0.023	-10000	0	-0.38	2	2
VEGFA	0.013	0.056	0.22	30	-0.16	13	43
negative regulation of T cell proliferation	-0.023	0.12	0.41	6	-0.36	45	51
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0	0.041	-10000	0	-0.39	6	6
MAPK1	-0.04	0.17	0.47	6	-0.51	52	58
S1P1/S1P/PDGFB-D/PDGFRB	-0.015	0.1	0.3	6	-0.47	14	20
ABCC1	0.006	0.023	0.22	6	-10000	0	6

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.009	0.022	0.3	2	-10000	0	2
NFATC2	-0.035	0.2	0.45	2	-0.62	24	26
NFATC3	0.017	0.045	0.36	1	-0.26	2	3
CD40LG	-0.047	0.2	0.56	3	-0.71	8	11
ITCH	-0.007	0.054	0.42	1	-10000	0	1
CBLB	-0.006	0.06	0.42	4	-10000	0	4
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.05	0.16	0.64	6	-0.69	10	16
JUNB	-0.097	0.17	-10000	0	-0.38	151	151
CaM/Ca2+/Calcineurin A alpha-beta B1	0.002	0.049	-10000	0	-0.28	17	17
T cell anergy	-0.01	0.075	0.37	10	-0.35	2	12
TLE4	-0.09	0.26	0.4	1	-0.63	92	93
Jun/NFAT1-c-4/p21SNFT	0.005	0.16	0.51	1	-0.72	4	5
AP-1/NFAT1-c-4	-0.024	0.23	0.7	2	-0.79	8	10
IKZF1	-0.027	0.14	-10000	0	-0.46	20	20
T-helper 2 cell differentiation	-0.027	0.14	-10000	0	-0.63	8	8
AP-1/NFAT1	-0.048	0.18	0.38	3	-0.43	53	56
CALM1	-0.002	0.071	-10000	0	-0.39	17	17
EGR2	-0.007	0.14	0.7	2	-0.87	1	3
EGR3	-0.008	0.13	0.73	1	-0.87	1	2
NFAT1/FOXP3	-0.014	0.15	0.46	5	-0.45	23	28
EGR1	-0.15	0.19	0.22	4	-0.39	226	230
JUN	0.01	0.043	0.22	9	-0.36	3	12
EGR4	0.007	0.009	0.22	1	-10000	0	1
mol:Ca2+	0	0.02	0.13	12	-10000	0	12
GBP3	-0.048	0.23	0.43	21	-0.65	52	73
FOSL1	0.006	0	-10000	0	-10000	0	0
NFAT1-c-4/MAF/IRF4	0.002	0.14	-10000	0	-0.69	4	4
DGKA	-0.024	0.14	0.42	5	-0.46	20	25
CREM	0.007	0.009	0.22	1	-10000	0	1
NFAT1-c-4/PPARG	0	0.14	-10000	0	-0.72	4	4
CTLA4	-0.03	0.12	0.53	5	-0.4	19	24
NFAT1-c-4 (dimer)/EGR1	-0.088	0.18	-10000	0	-0.66	11	11
NFAT1-c-4 (dimer)/EGR4	0.001	0.15	-10000	0	-0.72	4	4
FOS	-0.063	0.16	0.22	8	-0.38	110	118
IFNG	-0.026	0.17	0.48	26	-0.58	11	37
T cell activation	-0.03	0.14	-10000	0	-0.58	5	5
MAF	0.004	0.028	-10000	0	-0.38	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.001	0.12	1.3	1	-0.63	1	2
TNF	-0.087	0.17	-10000	0	-0.64	7	7
FASLG	-0.011	0.14	-10000	0	-0.94	1	1
TBX21	0.017	0.044	0.21	28	-10000	0	28
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.002	0.06	0.22	8	-0.38	11	19
PTPN1	-0.027	0.14	-10000	0	-0.46	20	20
NFAT1-c-4/ICER1	-0.001	0.14	-10000	0	-0.72	4	4
GATA3	0.007	0.013	0.22	2	-10000	0	2
T-helper 1 cell differentiation	-0.024	0.17	0.48	26	-0.57	11	37
IL2RA	-0.05	0.16	0.69	4	-0.59	20	24
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.023	0.15	0.43	9	-0.46	20	29
E2F1	0.009	0.016	-10000	0	-10000	0	0
PPARG	0.009	0.022	0.22	6	-10000	0	6
SLC3A2	-0.026	0.14	0.42	2	-0.46	20	22
IRF4	0.007	0.013	0.22	2	-10000	0	2
PTGS2	-0.06	0.23	0.67	3	-0.76	14	17
CSF2	-0.047	0.2	0.56	3	-0.71	8	11
JunB/Fra1/NFAT1-c-4	-0.053	0.18	-10000	0	-0.67	10	10
IL4	-0.028	0.15	-10000	0	-0.67	6	6
IL5	-0.047	0.2	0.56	3	-0.71	8	11
IL2	-0.031	0.14	-10000	0	-0.58	5	5
IL3	-0.019	0.033	-10000	0	-10000	0	0
RNF128	-0.005	0.065	0.42	7	-10000	0	7
NFATC1	-0.001	0.12	0.63	1	-1.3	1	2
CDK4	0.014	0.13	0.73	5	-10000	0	5
PTPRK	-0.034	0.16	0.4	2	-0.54	28	30
IL8	-0.034	0.23	0.64	7	-0.71	8	15
POU2F1	0.007	0	-10000	0	-10000	0	0

×

Class I PI3K 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
ARF5/GTP	0.056	0.07	0.21	41	-10000	0	41
DAPP1	-0.019	0.064	-10000	0	-0.32	1	1
Src family/SYK family/BLNK-LAT/BTK-ITK	0	0.08	-10000	0	-0.31	9	9
mol:DAG	0.027	0.068	0.17	35	-0.16	3	38
HRAS	0.011	0.005	-10000	0	-10000	0	0
RAP1A	0.011	0.01	0.21	1	-10000	0	1
ARF5/GDP	0.033	0.034	0.17	2	-10000	0	2
PLCG2	0.006	0	-10000	0	-10000	0	0
PLCG1	0.009	0.022	0.22	6	-10000	0	6
ARF5	0.006	0	-10000	0	-10000	0	0
mol:GTP	0.058	0.072	0.22	41	-10000	0	41
ARF1/GTP	0.05	0.07	0.22	37	-10000	0	37
RHOA	0.005	0.023	-10000	0	-0.38	2	2
YES1	0.011	0.031	0.22	12	-10000	0	12
RAP1A/GTP	0.058	0.071	0.22	41	-10000	0	41
ADAP1	0.056	0.069	0.22	41	-10000	0	41
ARAP3	0.057	0.071	0.22	41	-10000	0	41
INPPL1	0.007	0.013	0.22	2	-10000	0	2
PREX1	0.006	0.016	-10000	0	-0.38	1	1
ARHGEF6	0.007	0.031	0.22	5	-0.38	2	7
ARHGEF7	0.007	0.009	0.22	1	-10000	0	1
ARF1	-0.02	0.098	-10000	0	-0.38	38	38
NRAS	0.094	0.1	0.21	245	-10000	0	245
FYN	-0.039	0.13	0.22	1	-0.38	67	68
ARF6	0.006	0.016	-10000	0	-0.38	1	1
FGR	0.006	0	-10000	0	-10000	0	0
mol:Ca2+	0.015	0.039	0.14	7	-10000	0	7
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.006	0.021	0.22	2	-0.38	1	3
ZAP70	0.006	0	-10000	0	-10000	0	0
mol:IP3	0.017	0.049	0.15	9	-0.12	1	10
LYN	-0.007	0.07	-10000	0	-0.38	19	19
ARF1/GDP	0.027	0.044	0.17	2	-0.17	11	13
RhoA/GDP	0.052	0.056	0.22	12	-0.17	1	13
PDK1/Src/Hsp90	0.013	0	-10000	0	-10000	0	0
BLNK	-0.013	0.085	-10000	0	-0.38	28	28
actin cytoskeleton reorganization	0.058	0.067	0.2	47	-10000	0	47
SRC	0.006	0	-10000	0	-10000	0	0
PLEKHA2	-0.003	0.017	0.17	2	-0.23	2	4
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PTEN	-0.009	0.05	-10000	0	-0.36	11	11
HSP90AA1	0.006	0	-10000	0	-10000	0	0
ARF6/GTP	0.055	0.07	0.21	41	-0.18	1	42
RhoA/GTP	0.055	0.07	0.21	41	-0.18	1	42
Src family/SYK family/BLNK-LAT	-0.027	0.079	-10000	0	-0.37	9	9
BLK	0.007	0.009	0.22	1	-10000	0	1
PDPK1	0.006	0	-10000	0	-10000	0	0
CYTH1	0.056	0.069	0.22	41	-10000	0	41
HCK	0.007	0.009	0.22	1	-10000	0	1
CYTH3	0.056	0.069	0.22	41	-10000	0	41
CYTH2	0.056	0.069	0.22	41	-10000	0	41
KRAS	0.032	0.063	0.21	62	-10000	0	62
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.039	0.047	0.22	5	-10000	0	5
SGK1	0.004	0.025	0.17	11	-10000	0	11
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.031	0.036	0.18	2	-0.16	3	5
SOS1	0.014	0.04	0.22	20	-10000	0	20
SYK	0.003	0.043	0.22	3	-0.38	6	9
ARF6/GDP	0.057	0.068	0.21	41	-10000	0	41
mol:PI-3-4-5-P3	0.059	0.074	0.23	41	-10000	0	41
ARAP3/RAP1A/GTP	0.058	0.071	0.22	41	-10000	0	41
VAV1	0.008	0.018	0.22	4	-10000	0	4
mol:PI-3-4-P2	-0.001	0.012	0.2	2	-10000	0	2
RAS family/GTP/PI3K Class I	0.074	0.072	0.24	41	-10000	0	41
PLEKHA1	-0.001	0.017	0.17	6	-10000	0	6
Rac1/GDP	0.033	0.035	0.17	2	-0.17	1	3
LAT	0.006	0	-10000	0	-10000	0	0
Rac1/GTP	0.018	0.033	-10000	0	-0.25	4	4
ITK	0.058	0.073	0.22	46	-10000	0	46
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.029	0.083	0.2	32	-0.22	3	35
LCK	0.006	0	-10000	0	-10000	0	0
BTK	0.061	0.077	0.22	58	-10000	0	58

×

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

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
MAP4K1	0.003	0.1	0.34	19	-0.36	1	20
CRKL	0.004	0.11	0.34	19	-0.38	1	20
HRAS	0.006	0.097	0.32	16	-10000	0	16
mol:PIP3	0.013	0.11	0.34	19	-0.28	3	22
SPRED1	0.003	0.038	0.22	1	-0.38	5	6
SPRED2	0.006	0	-10000	0	-10000	0	0
GAB1	0.005	0.11	0.37	19	-0.31	3	22
FOXO3	0.008	0.1	0.33	18	-0.32	3	21
AKT1	0.011	0.1	0.34	18	-10000	0	18
BAD	0.01	0.099	0.33	18	-10000	0	18
megakaryocyte differentiation	0.008	0.11	0.38	19	-0.28	1	20
GSK3B	0.01	0.099	0.33	18	-10000	0	18
RAF1	0.005	0.085	0.3	16	-10000	0	16
SHC1	0.006	0	-10000	0	-10000	0	0
STAT3	0.002	0.11	0.37	17	-0.3	2	19
STAT1	0.012	0.21	0.57	11	-0.55	27	38
HRAS/SPRED1	0.008	0.086	0.29	16	-0.3	1	17
cell proliferation	0.008	0.11	0.38	19	-0.28	1	20
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
TEC	0.033	0.071	0.22	71	-10000	0	71
RPS6KB1	0.012	0.11	0.36	19	-10000	0	19
HRAS/SPRED2	0.009	0.085	0.29	15	-10000	0	15
LYN/TEC/p62DOK	0.012	0.097	-10000	0	-0.29	4	4
MAPK3	-0.038	0.089	0.24	10	-0.26	28	38
STAP1	0.007	0.11	0.37	19	-0.28	1	20
GRAP2	0.006	0	-10000	0	-10000	0	0
JAK2	-0.001	0.19	0.54	11	-0.46	20	31
STAT1 (dimer)	0.012	0.21	0.57	11	-0.54	27	38
mol:Gleevec	-0.001	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.005	0.093	-10000	0	-0.33	5	5
actin filament polymerization	0.008	0.11	0.36	19	-0.27	2	21
LYN	-0.007	0.07	-10000	0	-0.38	19	19
STAP1/STAT5A (dimer)	0.001	0.15	0.41	18	-0.52	4	22
PIK3R1	-0.038	0.12	-10000	0	-0.39	64	64
CBL/CRKL/GRB2	0.005	0.096	0.29	16	-0.35	1	17
PI3K	0.017	0.13	0.34	10	-0.38	7	17
PTEN	-0.001	0.054	-10000	0	-0.38	11	11
SCF/KIT/EPO/EPOR	0.01	0.2	0.69	2	-10000	0	2
MAPK8	0.007	0.11	0.38	19	-0.28	2	21
STAT3 (dimer)	0.002	0.11	0.37	17	-0.3	2	19
positive regulation of transcription	-0.03	0.076	0.23	10	-0.24	14	24
mol:GDP	0.006	0.1	0.32	16	-0.32	2	18
PIK3C2B	0.007	0.11	0.37	19	-0.28	1	20
CBL/CRKL	0.006	0.1	0.32	19	-0.36	1	20
FER	0.007	0.11	0.37	19	-0.28	2	21
SH2B3	0.006	0.11	0.37	19	-0.28	1	20
PDPK1	0.012	0.1	0.32	19	-0.27	3	22
SNAI2	0	0.12	0.37	18	-0.36	6	24
positive regulation of cell proliferation	0.006	0.18	0.47	17	-0.43	23	40
KITLG	0.01	0.026	0.23	3	-10000	0	3
cell motility	0.006	0.18	0.47	17	-0.43	23	40
PTPN6	0.001	0.014	-10000	0	-10000	0	0
EPOR	0	0.14	0.62	4	-0.64	8	12
STAT5A (dimer)	0.003	0.16	0.43	18	-0.54	4	22
SOCS1	-0.013	0.085	-10000	0	-0.38	28	28
cell migration	-0.007	0.11	0.28	1	-0.36	19	20
SOS1	0.014	0.04	0.22	20	-10000	0	20
EPO	0.007	0.013	-10000	0	-10000	0	0
VAV1	0.008	0.018	0.22	4	-10000	0	4
GRB10	0.007	0.11	0.37	19	-0.28	1	20
PTPN11	0.001	0.011	-10000	0	-10000	0	0
SCF/KIT	0.009	0.12	0.4	19	-0.29	2	21
GO:0007205	-0.001	0.01	-10000	0	-10000	0	0
MAP2K1	0.005	0.074	0.27	16	-10000	0	16
CBL	0.006	0	-10000	0	-10000	0	0
KIT	0.009	0.16	0.57	18	-0.58	7	25
MAP2K2	-0.047	0.096	0.26	10	-0.26	29	39
SHC/Grb2/SOS1	0.006	0.088	-10000	0	-0.27	1	1
STAT5A	0.002	0.16	0.44	18	-0.55	4	22
GRB2	0.006	0.016	-10000	0	-0.38	1	1
response to radiation	0	0.12	0.37	18	-0.35	6	24
SHC/GRAP2	0.009	0	-10000	0	-10000	0	0
PTPRO	0.007	0.11	0.38	19	-0.28	1	20
SH2B2	0.007	0.11	0.37	19	-0.27	2	21
DOK1	0.006	0.016	-10000	0	-0.38	1	1
MATK	0.006	0.11	0.37	19	-0.28	1	20
CREBBP	0.001	0.082	0.28	20	-0.4	8	28
BCL2	-0.12	0.41	0.81	2	-1.1	79	81

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.006	0	-10000	0	-10000	0	0
SPHK1	0.007	0.009	0.22	1	-10000	0	1
GNAI2	0.006	0	-10000	0	-10000	0	0
mol:S1P	0.004	0.015	-10000	0	-10000	0	0
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
mol:Sphinganine-1-P	-0.004	0.008	0.2	1	-10000	0	1
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.01	0.012	-10000	0	-0.19	1	1
GNAI3	0.017	0.047	0.22	29	-10000	0	29
G12/G13	0.009	0.012	-10000	0	-0.27	1	1
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	-0.003	0.058	-10000	0	-0.38	13	13
S1P1/S1P	0.003	0.035	-10000	0	-0.22	13	13
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0	0.063	0.22	7	-0.38	13	20
S1P/S1P5/G12	0.006	0.001	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.072	0.12	-10000	0	-0.22	198	198
S1P/S1P4/Gi	0.004	0.045	0.18	1	-0.19	20	21
GNAQ	-0.005	0.065	-10000	0	-0.38	16	16
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
GNA14	0.006	0.026	0.22	2	-0.38	2	4
GNA15	0.003	0.037	-10000	0	-0.38	5	5
GNA12	0.006	0	-10000	0	-10000	0	0
GNA13	0.006	0.016	-10000	0	-0.38	1	1
GNA11	-0.13	0.18	-10000	0	-0.38	193	193
ABCC1	0.009	0.022	0.22	6	-10000	0	6

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.08	0.16	-10000	0	-0.38	127	127
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	-0.007	0.093	0.51	4	-0.4	2	6
IL27/IL27R/JAK1	0.012	0.099	0.51	1	-0.99	2	3
TBX21	0.047	0.11	0.47	5	-0.59	2	7
IL12B	0.009	0.01	-10000	0	-10000	0	0
IL12A	0.012	0.051	0.2	37	-0.27	1	38
IL6ST	-0.011	0.087	-10000	0	-0.39	28	28
IL27RA/JAK1	0.004	0.073	-10000	0	-1.1	2	2
IL27	0.008	0.012	-10000	0	-10000	0	0
TYK2	0.01	0.02	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.074	0.14	-10000	0	-0.55	18	18
T-helper 2 cell differentiation	-0.007	0.093	0.51	4	-0.4	2	6
T cell proliferation during immune response	-0.007	0.093	0.51	4	-0.4	2	6
MAPKKK cascade	0.007	0.093	0.4	2	-0.51	4	6
STAT3	-0.002	0.056	-10000	0	-0.38	12	12
STAT2	0.031	0.068	0.22	64	-10000	0	64
STAT1	0.12	0.11	0.22	297	-10000	0	297
IL12RB1	0.007	0.005	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.05	0.12	0.5	9	-0.59	2	11
IL27/IL27R/JAK2/TYK2	0.006	0.094	0.4	2	-0.52	4	6
positive regulation of T cell mediated cytotoxicity	0.007	0.093	0.4	2	-0.51	4	6
STAT1 (dimer)	0.053	0.11	0.51	3	-0.84	2	5
JAK2	0.007	0.039	0.25	2	-0.39	4	6
JAK1	0.004	0.028	-10000	0	-0.39	3	3
STAT2 (dimer)	0.024	0.1	0.41	8	-0.46	4	12
T cell proliferation	-0.01	0.1	0.44	2	-0.51	6	8
IL12/IL12R/TYK2/JAK2	0.034	0.082	0.44	5	-10000	0	5
IL17A	-0.074	0.14	-10000	0	-0.55	18	18
mast cell activation	-0.007	0.093	0.51	4	-0.4	2	6
IFNG	0.011	0.048	0.21	28	-10000	0	28
T cell differentiation	0	0.005	0.022	26	-0.024	2	28
STAT3 (dimer)	0.005	0.092	0.35	2	-0.46	7	9
STAT5A (dimer)	0.006	0.089	0.35	2	-0.49	4	6
STAT4 (dimer)	0.009	0.085	0.35	2	-0.46	4	6
STAT4	0.007	0.013	0.22	2	-10000	0	2
T cell activation	-0.001	0.013	0.12	2	-0.19	2	4
IL27R/JAK2/TYK2	0.01	0.1	0.4	2	-1	2	4
GATA3	-0.001	0.036	-10000	0	-10000	0	0
IL18	0.035	0.077	0.2	103	-10000	0	103
positive regulation of mast cell cytokine production	0.005	0.091	0.35	2	-0.46	7	9
IL27/EBI3	0.013	0.021	0.16	1	-10000	0	1
IL27RA	0.002	0.078	-10000	0	-1.2	2	2
IL6	-0.023	0.11	0.22	4	-0.38	46	50
STAT5A	0	0.049	-10000	0	-0.38	9	9
monocyte differentiation	0.001	0.003	0.015	3	-10000	0	3
IL2	-0.003	0.042	0.46	2	-0.42	2	4
IL1B	0.012	0.05	0.2	38	-10000	0	38
EBI3	0.008	0.012	-10000	0	-10000	0	0
TNF	-0.001	0.009	0.2	1	-10000	0	1

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	0.008	0.018	0.22	4	-10000	0	4
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.006	0	-10000	0	-10000	0	0
TCEB1	0.006	0	-10000	0	-10000	0	0
HIF1A/p53	-0.017	0.066	-10000	0	-0.23	6	6
HIF1A	-0.001	0.024	-10000	0	-0.19	3	3
COPS5	0.02	0.053	0.22	37	-10000	0	37
VHL/Elongin B/Elongin C/RBX1/CUL2	0.03	0.037	-10000	0	-0.19	1	1
FIH (dimer)	0.006	0	-10000	0	-10000	0	0
CDKN2A	0.13	0.11	0.22	317	-10000	0	317
ARNT/IPAS	0.009	0.001	-10000	0	-10000	0	0
HIF1AN	0.006	0	-10000	0	-10000	0	0
GNB2L1	0.006	0	-10000	0	-10000	0	0
HIF1A/ARNT	0.005	0.026	-10000	0	-10000	0	0
CUL2	0.026	0.066	0.22	55	-0.38	1	56
OS9	0.006	0.016	-10000	0	-0.38	1	1
RACK1/Elongin B/Elongin C	0.013	0	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.005	0.026	-10000	0	-10000	0	0
PHD1-3/OS9	0.013	0.056	-10000	0	-0.2	26	26
HIF1A/RACK1/Elongin B/Elongin C	0.011	0.025	-10000	0	-10000	0	0
VHL	0.007	0.016	0.22	3	-10000	0	3
HSP90AA1	0.006	0	-10000	0	-10000	0	0
HIF1A/JAB1	0.014	0.044	0.2	8	-10000	0	8
EGLN3	0	0.096	0.22	30	-0.38	25	55
EGLN2	0.006	0	-10000	0	-10000	0	0
EGLN1	0.006	0	-10000	0	-10000	0	0
TP53	-0.045	0.13	0.22	3	-0.38	76	79
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.018	0.032	-10000	0	-10000	0	0
ARNT	0.007	0.009	0.22	1	-10000	0	1
ARD1A	0.01	0.03	0.22	11	-10000	0	11
RBX1	0.006	0	-10000	0	-10000	0	0
HIF1A/p19ARF	0.079	0.071	0.2	19	-10000	0	19

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.002	0.015	0.17	4	-10000	0	4
RAS family/GTP	0.058	0.097	0.3	33	-0.22	1	34
NFATC4	-0.013	0.047	0.19	1	-0.27	1	2
ERBB2IP	0.004	0.023	-10000	0	-0.38	2	2
HSP90 (dimer)	0.006	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.01	0.065	0.28	7	-0.23	6	13
JUN	0.001	0.096	0.38	18	-10000	0	18
HRAS	0.005	0.005	-10000	0	-10000	0	0
DOCK7	-0.006	0.064	0.23	8	-0.33	1	9
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.002	0.058	0.19	2	-0.2	32	34
AKT1	-0.002	0.009	0.2	1	-10000	0	1
BAD	-0.003	0.007	0.17	1	-10000	0	1
MAPK10	-0.009	0.041	0.17	2	-0.16	5	7
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.011	0.07	0.3	7	-0.26	4	11
RAF1	0.053	0.11	0.37	29	-10000	0	29
ErbB2/ErbB3/neuregulin 2	-0.002	0.058	0.15	10	-0.21	32	42
STAT3	-0.012	0.13	-10000	0	-0.92	12	12
cell migration	-0.006	0.044	0.17	6	-0.17	1	7
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.042	0.21	0.57	25	-0.5	14	39
FOS	-0.063	0.24	0.53	28	-0.46	110	138
NRAS	0.099	0.11	0.22	245	-10000	0	245
mol:Ca2+	-0.01	0.065	0.28	7	-0.23	6	13
MAPK3	-0.046	0.2	0.52	25	-0.52	26	51
MAPK1	-0.017	0.18	0.51	26	-0.46	5	31
JAK2	-0.015	0.057	0.19	5	-0.25	3	8
NF2	0	0.013	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.003	0.058	-10000	0	-0.22	28	28
NRG1	0.005	0.011	0.23	1	-10000	0	1
GRB2/SOS1	0.009	0.012	-10000	0	-0.27	1	1
MAPK8	-0.01	0.065	0.24	6	-0.24	25	31
MAPK9	-0.007	0.039	0.16	5	-0.18	1	6
ERBB2	-0.004	0.035	0.23	7	-0.27	4	11
ERBB3	-0.011	0.092	0.22	10	-0.39	29	39
SHC1	0.005	0.004	-10000	0	-10000	0	0
RAC1	0.006	0.016	-10000	0	-0.38	1	1
apoptosis	0.003	0.011	-10000	0	-0.19	1	1
STAT3 (dimer)	-0.012	0.13	-10000	0	-0.9	12	12
RNF41	-0.003	0.016	0.15	6	-10000	0	6
FRAP1	-0.003	0.007	0.17	1	-10000	0	1
RAC1-CDC42/GTP	-0.018	0.034	-10000	0	-0.17	8	8
ErbB2/ErbB2/HSP90 (dimer)	-0.005	0.027	0.16	7	-0.23	4	11
CHRNA1	-0.012	0.17	0.53	28	-0.38	1	29
myelination	-0.014	0.046	0.19	1	-0.27	1	2
PPP3CB	-0.014	0.052	0.18	5	-0.31	1	6
KRAS	0.029	0.068	0.22	62	-10000	0	62
RAC1-CDC42/GDP	0.002	0.052	-10000	0	-0.2	27	27
NRG2	0.006	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.057	-10000	0	-0.22	28	28
SOS1	0.014	0.04	0.22	20	-10000	0	20
MAP2K2	0.004	0.12	0.38	22	-0.32	5	27
SRC	0.006	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	-0.014	0.054	0.2	2	-0.33	1	3
MAP2K1	0.032	0.16	0.5	26	-0.41	2	28
heart morphogenesis	-0.01	0.065	0.28	7	-0.23	6	13
RAS family/GDP	0.076	0.095	0.27	45	-0.21	2	47
GRB2	0.005	0.017	-10000	0	-0.39	1	1
PRKACA	0.002	0.006	-10000	0	-10000	0	0
CHRNE	0.003	0.033	0.28	4	-10000	0	4
HSP90AA1	0.006	0	-10000	0	-10000	0	0
activation of caspase activity	0.002	0.009	-10000	0	-0.2	1	1
nervous system development	-0.01	0.065	0.28	7	-0.23	6	13
CDC42	0.006	0	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.013	0.073	-10000	0	-0.4	18	18
KLHL20	-0.044	0.077	0.32	1	-0.29	9	10
CYFIP2	-0.001	0.051	-10000	0	-0.38	10	10
Rac1/GDP	-0.015	0.05	-10000	0	-0.25	19	19
ENAH	-0.014	0.074	-10000	0	-0.41	17	17
AP1M1	0.007	0.016	0.22	3	-10000	0	3
RAP1B	0.007	0.026	0.22	5	-0.38	1	6
RAP1A	0.007	0.009	0.22	1	-10000	0	1
CTNNB1	0.006	0.009	0.22	1	-10000	0	1
CDC42/GTP	-0.018	0.035	-10000	0	-0.21	6	6
ABI1/Sra1/Nap1	-0.035	0.051	-10000	0	-0.15	21	21
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.008	0.045	-10000	0	-0.21	21	21
RAPGEF1	-0.016	0.064	-10000	0	-0.36	17	17
CTNND1	0.006	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.011	0.075	-10000	0	-0.4	19	19
CRK	-0.015	0.069	-10000	0	-0.39	17	17
E-cadherin/gamma catenin/alpha catenin	-0.002	0.06	-10000	0	-0.25	31	31
alphaE/beta7 Integrin	0.007	0.026	-10000	0	-0.27	5	5
IQGAP1	0.005	0.025	0.22	1	-0.38	2	3
NCKAP1	0.01	0.028	0.22	10	-10000	0	10
Rap1/GTP/I-afadin	0.006	0.041	0.14	6	-0.2	19	25
DLG1	-0.003	0.082	-10000	0	-0.39	19	19
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.04	-10000	0	-0.17	10	10
MLLT4	-0.006	0.068	-10000	0	-0.38	18	18
ARF6/GTP/NME1/Tiam1	0.018	0.033	0.14	33	-0.2	2	35
PI3K	-0.029	0.05	-10000	0	-0.22	10	10
ARF6	0.005	0.016	-10000	0	-0.38	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	-0.006	0.068	-10000	0	-0.29	29	29
TIAM1	0.006	0.021	0.22	2	-0.38	1	3
E-cadherin(dimer)/Ca2+	0.007	0.037	-10000	0	-0.19	19	19
AKT1	-0.018	0.031	-10000	0	-0.15	4	4
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
CDH1	-0.006	0.067	-10000	0	-0.38	17	17
RhoA/GDP	-0.013	0.05	-10000	0	-0.25	19	19
actin cytoskeleton organization	-0.032	0.058	0.27	1	-0.22	7	8
CDC42/GDP	-0.012	0.049	-10000	0	-0.25	19	19
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.009	0.054	-10000	0	-0.23	31	31
ITGB7	0.003	0.038	0.22	1	-0.38	5	6
RAC1	0.005	0.016	-10000	0	-0.38	1	1
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.008	0.04	-10000	0	-0.2	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin	0.004	0.037	0.13	1	-0.19	19	20
mol:GDP	-0.016	0.055	-10000	0	-0.29	19	19
CDC42/GTP/IQGAP1	0.008	0.014	-10000	0	-0.22	2	2
JUP	-0.004	0.063	-10000	0	-0.38	15	15
p120 catenin/RhoA/GDP	-0.012	0.051	-10000	0	-0.26	18	18
RAC1/GTP/IQGAP1	0.007	0.017	-10000	0	-0.22	3	3
PIP5K1C/AP1M1	0.009	0.001	-10000	0	-10000	0	0
RHOA	0.005	0.023	-10000	0	-0.38	2	2
CDC42	0.006	0	-10000	0	-10000	0	0
CTNNA1	0.005	0.023	-10000	0	-0.38	2	2
positive regulation of S phase of mitotic cell cycle	-0.046	0.081	0.37	1	-0.18	144	145
NME1	0.018	0.049	0.22	31	-10000	0	31
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.013	0.073	-10000	0	-0.41	17	17
regulation of cell-cell adhesion	-0.016	0.031	-10000	0	-0.19	6	6
WASF2	-0.038	0.045	-10000	0	-0.13	47	47
Rap1/GTP	-0.017	0.041	-10000	0	-0.24	6	6
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.004	0.058	-10000	0	-0.21	35	35
CCND1	-0.057	0.1	0.41	1	-0.22	145	146
VAV2	-0.019	0.088	-10000	0	-0.45	20	20
RAP1/GDP	-0.011	0.046	-10000	0	-0.22	18	18
adherens junction assembly	-0.013	0.071	-10000	0	-0.4	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.007	0.009	0.22	1	-10000	0	1
PIP5K1C	0.006	0	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0	0.055	-10000	0	-0.26	9	9
E-cadherin/beta catenin	-0.006	0.051	-10000	0	-0.29	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.014	0.073	-10000	0	-0.39	19	19
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
Rac1/GTP	-0.068	0.12	0.42	1	-0.37	20	21
E-cadherin/beta catenin/alpha catenin	0.004	0.043	-10000	0	-0.23	19	19
ITGAE	0.006	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.012	0.076	-10000	0	-0.41	19	19

×

Canonical NF-kappaB pathway

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
FBXW11	0.004	0.015	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.07	0.23	4	-0.31	2	6
ERC1	0.008	0.029	0.22	7	-0.38	1	8
RIP2/NOD2	0.007	0.004	-10000	0	-10000	0	0
NFKBIA	-0.023	0.08	-10000	0	-0.47	16	16
BIRC2	0.037	0.075	0.22	81	-10000	0	81
IKBKB	0.007	0.016	0.22	3	-10000	0	3
RIPK2	0.065	0.096	0.22	156	-10000	0	156
IKBKG	0.039	0.053	0.2	1	-10000	0	1
IKK complex/A20	0.03	0.051	0.26	1	-10000	0	1
NEMO/A20/RIP2	0.065	0.096	0.22	156	-10000	0	156
XPO1	0.026	0.062	0.22	52	-10000	0	52
NEMO/ATM	0.051	0.064	0.26	22	-10000	0	22
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.006	0	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.008	0.002	-10000	0	-10000	0	0
IKK complex/ELKS	0.007	0.009	-10000	0	-10000	0	0
BCL10/MALT1/TRAF6	0.012	0.003	-10000	0	-10000	0	0
NOD2	0.007	0.009	0.22	1	-10000	0	1
NFKB1	-0.004	0.059	-10000	0	-0.41	11	11
RELA	0.002	0.028	-10000	0	-0.39	2	2
MALT1	0.017	0.047	0.22	29	-10000	0	29
cIAP1/UbcH5C	0.008	0.003	-10000	0	-10000	0	0
ATM	0.014	0.04	0.22	20	-10000	0	20
TNF/TNFR1A	-0.003	0.057	-10000	0	-0.27	25	25
TRAF6	0.007	0.013	0.22	2	-10000	0	2
PRKCA	0.005	0.044	0.22	7	-0.38	5	12
CHUK	0.011	0.031	0.22	12	-10000	0	12
UBE2D3	0.006	0	-10000	0	-10000	0	0
TNF	0.007	0.009	0.22	1	-10000	0	1
NF kappa B1 p50/RelA	0.002	0.059	-10000	0	-0.26	26	26
BCL10	0.006	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.023	0.08	-10000	0	-0.46	16	16
beta TrCP1/SCF ubiquitin ligase complex	0.004	0.016	-10000	0	-10000	0	0
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
IKK complex	0.049	0.053	0.23	8	-10000	0	8
CYLD	0.006	0	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.04	0.045	0.28	1	-10000	0	1

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.003	0.058	-10000	0	-0.38	13	13
GNB1/GNG2	0.035	0.054	0.19	19	-10000	0	19
mol:DAG	0.027	0.054	0.18	20	-10000	0	20
PLCG1	0.028	0.055	0.18	20	-10000	0	20
YES1	0.032	0.062	0.21	22	-0.2	7	29
FZD3	0.031	0.08	0.22	72	-0.38	4	76
FZD6	0.022	0.06	0.22	43	-0.38	1	44
G protein	0.032	0.053	-10000	0	-10000	0	0
MAP3K7	0.021	0.054	0.18	21	-10000	0	21
mol:Ca2+	0.027	0.053	0.18	20	-10000	0	20
mol:IP3	0.027	0.054	0.18	20	-10000	0	20
NLK	0.011	0.012	-10000	0	-10000	0	0
GNB1	0.006	0.016	-10000	0	-0.38	1	1
CAMK2A	0.021	0.053	0.17	20	-10000	0	20
MAP3K7IP1	0.006	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	0.034	0.061	0.22	19	-0.21	7	26
CSNK1A1	0.007	0.009	0.22	1	-10000	0	1
GNAS	0.029	0.058	0.2	19	-0.2	7	26
GO:0007205	0.023	0.055	0.18	20	-10000	0	20
WNT6	0.006	0.016	-10000	0	-0.38	1	1
WNT4	0.006	0	-10000	0	-10000	0	0
NFAT1/CK1 alpha	0.031	0.06	0.2	3	-0.34	1	4
GNG2	0.004	0.034	0.22	1	-0.38	4	5
WNT5A	0.006	0.029	0.22	4	-0.38	2	6
WNT11	0.026	0.062	0.22	52	-10000	0	52
CDC42	0.028	0.059	0.2	22	-10000	0	22

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.002	0.058	-10000	0	-0.29	21	21
FBXW11	0.006	0	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.002	0.034	-10000	0	-0.23	11	11
NF kappa B1 p50/RelA/I kappa B alpha	-0.003	0.048	-10000	0	-0.35	4	4
NFKBIA	-0.005	0.039	-10000	0	-0.2	20	20
MAPK14	0.007	0.009	0.22	1	-10000	0	1
NF kappa B1 p105/p50	0.002	0.034	-10000	0	-0.23	11	11
ARRB2	0.003	0.006	0.15	1	-10000	0	1
REL	0.006	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	-0.006	0.055	-10000	0	-0.23	32	32
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.002	0.036	-10000	0	-0.23	13	13
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
NF kappa B1 p50 dimer	-0.008	0.039	0.18	3	-0.27	11	14
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
NFKB1	-0.008	0.04	0.2	3	-0.27	11	14
RELA	0.005	0.023	-10000	0	-0.38	2	2
positive regulation of anti-apoptosis	-0.001	0.029	-10000	0	-0.18	8	8
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.002	0.047	-10000	0	-0.34	4	4
SRC	0.006	0	-10000	0	-10000	0	0
PI3K	-0.022	0.083	-10000	0	-0.27	56	56
NF kappa B1 p50/RelA	-0.001	0.029	-10000	0	-0.18	8	8
IKBKB	0.007	0.016	0.22	3	-10000	0	3
beta TrCP1/SCF ubiquitin ligase complex	0.006	0	-10000	0	-10000	0	0
SYK	0.003	0.043	0.22	3	-0.38	6	9
I kappa B alpha/PIK3R1	-0.022	0.071	-10000	0	-0.19	81	81
cell death	-0.002	0.046	-10000	0	-0.33	4	4
NF kappa B1 p105/c-Rel	0.002	0.034	-10000	0	-0.23	11	11
LCK	0.006	0	-10000	0	-10000	0	0
BCL3	-0.008	0.074	-10000	0	-0.38	21	21

×

Calcium signaling in the CD4+ TCR 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.047	0.25	2	-0.22	18	20
NFATC2	-0.015	0.057	0.25	2	-0.23	28	30
NFATC3	-0.01	0.046	0.25	2	-0.22	17	19
CD40LG	-0.055	0.13	0.69	2	-0.5	2	4
PTGS2	-0.068	0.17	0.55	7	-0.55	19	26
JUNB	-0.097	0.17	-10000	0	-0.38	151	151
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.007	0.047	-10000	0	-0.26	18	18
CaM/Ca2+	-0.007	0.047	-10000	0	-0.26	18	18
CALM1	-0.007	0.068	-10000	0	-0.38	18	18
JUN	0.007	0.041	0.22	9	-0.39	3	12
mol:Ca2+	-0.001	0.008	0.074	2	-10000	0	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.005	-10000	0	-10000	0	0
FOSL1	0.006	0	-10000	0	-10000	0	0
CREM	0.007	0.009	0.22	1	-10000	0	1
Jun/NFAT1-c-4/p21SNFT	-0.031	0.055	-10000	0	-0.29	4	4
FOS	-0.066	0.16	0.22	8	-0.38	110	118
IFNG	-0.05	0.14	0.55	13	-0.5	2	15
AP-1/NFAT1-c-4	-0.032	0.15	-10000	0	-0.43	19	19
FASLG	-0.055	0.13	0.69	2	-0.5	2	4
NFAT1-c-4/ICER1	-0.019	0.062	-10000	0	-0.26	4	4
IL2RA	-0.054	0.14	0.72	3	-0.5	2	5
FKBP12/FK506	0.005	0	-10000	0	-10000	0	0
CSF2	-0.055	0.13	0.69	2	-0.5	2	4
JunB/Fra1/NFAT1-c-4	-0.064	0.1	-10000	0	-0.3	36	36
IL4	-0.055	0.13	0.69	2	-0.5	2	4
IL2	-0.002	0.009	-10000	0	-10000	0	0
IL3	-0.005	0.015	-10000	0	-10000	0	0
FKBP1A	0.006	0	-10000	0	-10000	0	0
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.007	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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
JUN	-0.008	0.067	-10000	0	-0.29	18	18
IKBKB	0.004	0.047	0.19	1	-0.22	2	3
AKT1	-0.019	0.069	0.18	7	-0.19	16	23
IKBKG	0.001	0.041	-10000	0	-0.19	1	1
CALM1	-0.016	0.07	-10000	0	-0.27	25	25
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
MAP3K1	-0.008	0.09	-10000	0	-0.41	17	17
MAP3K7	0.01	0.028	0.22	10	-10000	0	10
mol:Ca2+	-0.01	0.065	-10000	0	-0.28	21	21
DOK1	0.006	0.016	-10000	0	-0.38	1	1
AP-1	-0.023	0.059	0.17	4	-0.2	20	24
LYN	-0.007	0.07	-10000	0	-0.38	19	19
BLNK	-0.013	0.085	-10000	0	-0.38	28	28
SHC1	0.006	0	-10000	0	-10000	0	0
BCR complex	0.009	0.001	-10000	0	-10000	0	0
CD22	-0.055	0.11	0.2	2	-0.41	23	25
CAMK2G	-0.016	0.066	-10000	0	-0.26	25	25
CSNK2A1	0.006	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.023	0.055	-10000	0	-0.21	43	43
GO:0007205	-0.01	0.066	-10000	0	-0.28	21	21
SYK	0.003	0.043	0.22	3	-0.38	6	9
ELK1	-0.01	0.063	-10000	0	-0.27	21	21
NFATC1	-0.012	0.074	0.2	1	-0.31	21	22
B-cell antigen/BCR complex	0.009	0.001	-10000	0	-10000	0	0
PAG1/CSK	0.009	0.001	-10000	0	-10000	0	0
NFKBIB	0.002	0.025	-10000	0	-0.13	13	13
HRAS	-0.011	0.061	-10000	0	-0.27	19	19
NFKBIA	0.003	0.023	-10000	0	-0.13	10	10
NF-kappa-B/RelA/I kappa B beta	0.003	0.026	-10000	0	-0.14	13	13
RasGAP/Csk	0.025	0.035	-10000	0	-0.19	4	4
mol:GDP	-0.01	0.063	-10000	0	-0.27	21	21
PTEN	-0.001	0.054	-10000	0	-0.38	11	11
CD79B	0.006	0	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.003	0.025	-10000	0	-0.13	13	13
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PI3K/BCAP/CD19	-0.044	0.13	-10000	0	-0.37	47	47
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.01	0.066	-10000	0	-0.29	21	21
CSK	0.006	0	-10000	0	-10000	0	0
FOS	-0.041	0.094	-10000	0	-0.3	32	32
CHUK	0.003	0.044	-10000	0	-0.19	2	2
IBTK	0.009	0.024	0.22	7	-10000	0	7
CARD11/BCL10/MALT1/TAK1	0.004	0.063	-10000	0	-0.24	19	19
PTPN6	-0.052	0.11	0.21	3	-0.4	23	26
RELA	0.005	0.023	-10000	0	-0.39	2	2
BCL2A1	0.002	0.021	0.1	1	-0.13	3	4
VAV2	-0.013	0.096	0.24	1	-0.42	21	22
ubiquitin-dependent protein catabolic process	0.002	0.025	-10000	0	-0.13	13	13
BTK	0.009	0.029	-10000	0	-10000	0	0
CD19	-0.015	0.089	0.2	2	-0.42	19	21
MAP4K1	0.007	0.013	0.22	2	-10000	0	2
CD72	0.006	0	-10000	0	-10000	0	0
PAG1	0.007	0.013	0.22	2	-10000	0	2
MAPK14	-0.007	0.08	-10000	0	-0.35	17	17
SH3BP5	0.004	0.028	-10000	0	-0.38	3	3
PIK3AP1	-0.011	0.071	-10000	0	-0.32	21	21
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.011	0.08	-10000	0	-0.33	25	25
RAF1	-0.012	0.058	-10000	0	-0.25	19	19
RasGAP/p62DOK/SHIP	0.013	0.019	-10000	0	-0.18	5	5
CD79A	0.009	0.024	0.22	7	-10000	0	7
re-entry into mitotic cell cycle	-0.023	0.058	0.17	4	-0.19	23	27
RASA1	0.004	0.028	-10000	0	-0.38	3	3
MAPK3	-0.026	0.067	-10000	0	-0.29	12	12
MAPK1	-0.012	0.051	-10000	0	-0.28	7	7
CD72/SHP1	-0.049	0.11	0.23	1	-0.38	22	23
NFKB1	-0.001	0.054	-10000	0	-0.39	11	11
MAPK8	-0.007	0.078	-10000	0	-0.34	17	17
actin cytoskeleton organization	-0.012	0.086	0.22	1	-0.37	21	22
NF-kappa-B/RelA	0.004	0.058	-10000	0	-0.25	16	16
Calcineurin	-0.009	0.065	-10000	0	-0.24	25	25
PI3K	-0.057	0.09	-10000	0	-0.28	44	44
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.012	0.073	-10000	0	-0.33	21	21
SOS1	0.014	0.04	0.22	20	-10000	0	20
Bam32/HPK1	-0.004	0.1	-10000	0	-0.49	17	17
DAPP1	-0.011	0.11	-10000	0	-0.55	17	17
cytokine secretion	-0.011	0.07	0.2	1	-0.3	21	22
mol:DAG	-0.01	0.066	-10000	0	-0.29	21	21
PLCG2	0.006	0	-10000	0	-10000	0	0
MAP2K1	-0.012	0.055	-10000	0	-0.3	8	8
B-cell antigen/BCR complex/FcgammaRIIB	0.012	0.011	-10000	0	-0.23	1	1
mol:PI-3-4-5-P3	-0.036	0.078	0.2	5	-0.23	28	33
ETS1	-0.015	0.064	-10000	0	-0.25	25	25
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.002	0.07	-10000	0	-0.22	46	46
B-cell antigen/BCR complex/LYN	-0.013	0.094	0.21	2	-0.44	19	21
MALT1	0.017	0.047	0.22	29	-10000	0	29
TRAF6	0.007	0.013	0.22	2	-10000	0	2
RAC1	-0.014	0.091	0.23	1	-0.39	21	22
B-cell antigen/BCR complex/LYN/SYK	-0.05	0.099	-10000	0	-0.34	24	24
CARD11	-0.01	0.063	-10000	0	-0.27	21	21
FCGR2B	0.019	0.055	0.22	36	-0.38	1	37
PPP3CA	0.004	0.033	-10000	0	-0.38	4	4
BCL10	0.006	0	-10000	0	-10000	0	0
IKK complex	0.005	0.025	0.11	4	-10000	0	4
PTPRC	-0.006	0.13	0.22	49	-0.38	45	94
PDPK1	-0.021	0.064	0.16	7	-0.17	19	26
PPP3CB	0.006	0	-10000	0	-10000	0	0
PPP3CC	0.006	0	-10000	0	-10000	0	0
POU2F2	0.001	0.019	-10000	0	-0.13	3	3

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.001	0.096	0.51	13	-10000	0	13
regulation of axonogenesis	-0.021	0.047	0.34	1	-0.17	17	18
myoblast fusion	-0.002	0.052	0.33	1	-0.29	13	14
mol:GTP	0.011	0.03	0.18	13	-0.33	1	14
regulation of calcium-dependent cell-cell adhesion	-0.012	0.039	0.21	2	-0.24	13	15
ARF1/GTP	-0.006	0.063	-10000	0	-0.24	37	37
mol:GM1	0.006	0.027	0.17	13	-0.26	1	14
mol:Choline	0.012	0.045	0.16	49	-0.22	1	50
lamellipodium assembly	0.001	0.053	0.29	13	-0.42	1	14
MAPK3	-0.01	0.088	0.33	13	-0.24	52	65
ARF6/GTP/NME1/Tiam1	0.013	0.039	0.24	13	-0.21	2	15
ARF1	-0.02	0.098	-10000	0	-0.38	38	38
ARF6/GDP	0.002	0.052	0.29	13	-0.33	1	14
ARF1/GDP	-0.01	0.068	0.25	11	-0.22	37	48
ARF6	0.011	0.026	-10000	0	-0.49	1	1
RAB11A	0.006	0	-10000	0	-10000	0	0
TIAM1	0.005	0.023	0.22	2	-0.39	1	3
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.013	0.051	0.32	14	-0.24	2	16
actin filament bundle formation	0.003	0.028	0.23	3	-10000	0	3
KALRN	-0.003	0.025	0.18	1	-0.3	1	2
RAB11FIP3/RAB11A	0.009	0	-10000	0	-10000	0	0
RhoA/GDP	-0.003	0.028	-10000	0	-0.23	3	3
NME1	0.016	0.05	0.22	31	-10000	0	31
Rac1/GDP	-0.002	0.027	-10000	0	-0.25	2	2
substrate adhesion-dependent cell spreading	0.011	0.03	0.18	13	-0.33	1	14
cortical actin cytoskeleton organization	0.001	0.053	0.29	13	-0.42	1	14
RAC1	0.006	0.016	-10000	0	-0.38	1	1
liver development	0.011	0.03	0.18	13	-0.33	1	14
ARF6/GTP	0.011	0.03	0.18	13	-0.33	1	14
RhoA/GTP	0.009	0.02	-10000	0	-0.25	3	3
mol:GDP	0.004	0.057	0.34	13	-0.33	1	14
ARF6/GTP/RAB11FIP3/RAB11A	0.017	0.023	0.15	13	-0.22	1	14
RHOA	0.005	0.023	-10000	0	-0.38	2	2
PLD1	0.019	0.05	0.18	49	-0.26	1	50
RAB11FIP3	0.006	0	-10000	0	-10000	0	0
tube morphogenesis	0.001	0.053	0.29	13	-0.42	1	14
ruffle organization	0.021	0.047	0.17	17	-0.34	1	18
regulation of epithelial cell migration	0.011	0.03	0.18	13	-0.33	1	14
PLD2	0.008	0.027	0.17	13	-0.26	1	14
PIP5K1A	0.021	0.048	0.17	17	-0.34	1	18
mol:Phosphatidic acid	0.012	0.045	0.16	49	-0.22	1	50
Rac1/GTP	0.001	0.054	0.29	13	-0.43	1	14

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.009	0	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.006	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.028	0.065	0.22	57	-10000	0	57
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.001	0.043	-10000	0	-0.38	7	7
RAC1-CDC42/GTP/PAK family	-0.047	0.085	-10000	0	-0.18	156	156
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.011	0.031	0.22	12	-10000	0	12
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.006	0	-10000	0	-10000	0	0
FYN	-0.039	0.13	0.22	1	-0.38	67	68
MAP3K12	0.006	0	-10000	0	-10000	0	0
FGR	0.006	0	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.014	0.057	-10000	0	-0.25	4	4
PRKG1	0.007	0.009	0.22	1	-10000	0	1
DUSP8	0.006	0	-10000	0	-10000	0	0
PGK/cGMP/p38 alpha	-0.019	0.051	0.12	1	-0.25	4	5
apoptosis	-0.014	0.055	-10000	0	-0.24	4	4
RAL/GTP	0.008	0.01	-10000	0	-0.22	1	1
LYN	-0.007	0.07	-10000	0	-0.38	19	19
DUSP1	-0.12	0.18	0.22	1	-0.38	179	180
PAK1	0.012	0.041	0.22	18	-0.38	1	19
SRC	0.006	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.014	0.023	-10000	0	-0.2	6	6
TRAF6	0.007	0.013	0.22	2	-10000	0	2
RAC1	0.006	0.016	-10000	0	-0.38	1	1
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.006	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.008	0.01	-10000	0	-0.22	1	1
MAPK11	-0.023	0.078	0.18	1	-0.25	22	23
BLK	0.007	0.009	0.22	1	-10000	0	1
HCK	0.007	0.009	0.22	1	-10000	0	1
MAP2K3	0.003	0.037	-10000	0	-0.38	5	5
DUSP16	0.008	0.02	0.22	5	-10000	0	5
DUSP10	0.017	0.047	0.22	28	-10000	0	28
TRAF6/MEKK3	0.008	0	-10000	0	-10000	0	0
MAP3K7IP1	0.006	0	-10000	0	-10000	0	0
MAPK14	-0.016	0.06	-10000	0	-0.27	4	4
positive regulation of innate immune response	-0.026	0.084	-10000	0	-0.27	22	22
LCK	0.006	0	-10000	0	-10000	0	0
p38alpha-beta/MKP7	-0.022	0.084	0.22	3	-0.26	22	25
p38alpha-beta/MKP5	-0.017	0.085	-10000	0	-0.26	21	21
PGK/cGMP	0.005	0	-10000	0	-10000	0	0
PAK2	0.007	0.013	0.22	2	-10000	0	2
p38alpha-beta/MKP1	-0.069	0.12	-10000	0	-0.33	53	53
CDC42	0.006	0	-10000	0	-10000	0	0
RALB	0.006	0.016	-10000	0	-0.38	1	1
RALA	0.007	0.009	0.22	1	-10000	0	1
PAK3	-0.1	0.18	0.22	3	-0.38	164	167

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.033	0.1	-10000	0	-0.28	83	83
AKT1	-0.042	0.12	0.39	1	-0.41	5	6
PTK2B	-0.066	0.13	0.26	6	-0.36	53	59
VEGFR2 homodimer/Frs2	-0.051	0.11	0.27	2	-0.31	7	9
CAV1	-0.062	0.15	0.22	3	-0.38	101	104
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.039	0.11	0.28	1	-0.34	7	8
endothelial cell proliferation	-0.04	0.1	0.35	1	-0.36	5	6
mol:Ca2+	-0.052	0.1	0.32	1	-0.41	7	8
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.038	0.1	-10000	0	-0.33	9	9
RP11-342D11.1	-0.052	0.1	0.32	1	-0.41	7	8
CDH5	0.006	0	-10000	0	-10000	0	0
VEGFA homodimer	0.022	0.036	-10000	0	-0.21	3	3
SHC1	0.006	0	-10000	0	-10000	0	0
SHC2	-0.013	0.085	-10000	0	-0.38	28	28
HRAS/GDP	-0.041	0.088	-10000	0	-0.35	8	8
SH2D2A	0.006	0	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.034	0.1	0.31	1	-0.35	8	9
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.043	0.11	-10000	0	-0.34	7	7
VEGFR1 homodimer	0.006	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.031	0.1	-10000	0	-0.38	8	8
GRB10	-0.053	0.1	0.48	1	-0.41	7	8
PTPN11	0.006	0	-10000	0	-10000	0	0
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PAK1	0.012	0.041	0.22	18	-0.38	1	19
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.034	0.1	-10000	0	-0.32	8	8
HRAS	0.006	0	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.049	0.12	0.28	1	-0.34	45	46
HIF1A	0.004	0.028	-10000	0	-0.38	3	3
FRS2	0.013	0.038	0.22	18	-10000	0	18
oxygen and reactive oxygen species metabolic process	-0.038	0.1	-10000	0	-0.33	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.006	0	-10000	0	-10000	0	0
Nck/Pak	0.008	0.012	-10000	0	-0.27	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.067	0.13	-10000	0	-0.38	27	27
mol:GDP	-0.041	0.092	-10000	0	-0.37	8	8
mol:NADP	-0.037	0.087	0.31	1	-0.33	3	4
eNOS/Hsp90	-0.034	0.085	0.29	1	-0.32	3	4
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
mol:IP3	-0.052	0.1	0.33	1	-0.42	7	8
HIF1A/ARNT	0.008	0.02	-10000	0	-0.27	3	3
SHB	0.006	0	-10000	0	-10000	0	0
VEGFA	0.017	0.05	0.22	30	-10000	0	30
VEGFC	-0.008	0.074	-10000	0	-0.38	21	21
FAK1/Vinculin	-0.057	0.14	0.31	2	-0.38	47	49
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.005	0.023	-10000	0	-0.38	2	2
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.055	0.15	0.3	6	-0.37	53	59
PTPN6	0.006	0	-10000	0	-10000	0	0
EPAS1	-0.098	0.18	-10000	0	-0.39	152	152
mol:L-citrulline	-0.037	0.087	0.31	1	-0.33	3	4
ITGAV	0.017	0.06	0.22	35	-0.38	3	38
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.034	0.1	0.27	1	-0.33	8	9
VEGFR2 homodimer/VEGFA homodimer	-0.043	0.12	-10000	0	-0.45	7	7
VEGFR2/3 heterodimer	-0.056	0.11	0.27	2	-0.31	7	9
VEGFB	0.001	0.046	-10000	0	-0.38	8	8
MAPK11	-0.054	0.11	0.39	1	-0.43	7	8
VEGFR2 homodimer	-0.076	0.12	0.4	2	-0.36	7	9
FLT1	0.006	0	-10000	0	-10000	0	0
NEDD4	0.006	0.018	0.22	3	-10000	0	3
MAPK3	-0.057	0.1	0.3	1	-0.39	7	8
MAPK1	-0.049	0.094	0.3	1	-0.38	7	8
VEGFA145/NRP2	0.008	0.007	-10000	0	-10000	0	0
VEGFR1/2 heterodimer	-0.056	0.11	0.27	2	-0.31	7	9
KDR	-0.076	0.12	0.4	2	-0.36	7	9
VEGFA165/NRP1/VEGFR2 homodimer	-0.032	0.11	0.26	5	-0.41	7	12
SRC	0.006	0	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.054	0.098	0.32	1	-0.39	7	8
PI3K	-0.036	0.13	0.42	1	-0.44	5	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.032	0.12	0.28	5	-0.34	7	12
FES	-0.054	0.1	0.33	1	-0.42	7	8
GAB1	-0.051	0.11	-10000	0	-0.4	9	9
VEGFR2 homodimer/VEGFA homodimer/Src	-0.043	0.11	-10000	0	-0.34	7	7
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
SOS1	0.014	0.04	0.22	20	-10000	0	20
ARNT	0.007	0.009	0.22	1	-10000	0	1
eNOS/Caveolin-1	-0.058	0.11	0.29	1	-0.37	16	17
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.04	0.11	-10000	0	-0.34	7	7
PI3K/GAB1	-0.051	0.14	0.39	1	-0.41	26	27
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.017	0.11	0.26	11	-0.32	7	18
PRKACA	0.006	0	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.056	0.11	-10000	0	-0.34	14	14
HSP90AA1	0.006	0	-10000	0	-10000	0	0
CDC42	-0.054	0.1	0.33	1	-0.42	7	8
actin cytoskeleton reorganization	-0.043	0.11	-10000	0	-0.34	7	7
PTK2	-0.063	0.15	0.32	2	-0.4	48	50
EDG1	-0.058	0.12	0.32	1	-0.55	13	14
mol:DAG	-0.052	0.1	0.33	1	-0.42	7	8
CaM/Ca2+	-0.056	0.095	-10000	0	-0.37	13	13
MAP2K3	-0.052	0.1	0.46	1	-0.39	9	10
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.038	0.11	-10000	0	-0.42	7	7
PLCG1	-0.053	0.1	0.33	1	-0.42	7	8
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.037	0.1	-10000	0	-0.32	7	7
IQGAP1	0.005	0.025	0.22	1	-0.38	2	3
YES1	0.011	0.031	0.22	12	-10000	0	12
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.043	0.11	-10000	0	-0.34	7	7
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.043	0.11	-10000	0	-0.34	7	7
cell migration	-0.056	0.14	0.29	2	-0.36	47	49
mol:PI-3-4-5-P3	-0.034	0.12	0.41	1	-0.41	5	6
FYN	-0.039	0.13	0.22	1	-0.38	67	68
VEGFB/NRP1	-0.053	0.099	0.22	2	-0.4	11	13
mol:NO	-0.037	0.087	0.31	1	-0.33	3	4
PXN	-0.002	0.056	-10000	0	-0.38	12	12
HRAS/GTP	-0.055	0.078	-10000	0	-0.35	8	8
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.041	0.11	-10000	0	-0.42	7	7
VHL	0.007	0.016	0.22	3	-10000	0	3
ITGB3	-0.045	0.14	0.22	13	-0.38	82	95
NOS3	-0.041	0.094	0.32	1	-0.37	3	4
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.053	0.12	-10000	0	-0.36	14	14
RAC1	0.006	0.016	-10000	0	-0.38	1	1
PRKCA	-0.05	0.098	0.31	1	-0.38	8	9
PRKCB	-0.049	0.095	0.31	1	-0.39	7	8
VCL	0.007	0.016	0.22	3	-10000	0	3
VEGFA165/NRP1	-0.051	0.1	0.32	1	-0.41	7	8
VEGFR1/2 heterodimer/VEGFA homodimer	-0.043	0.11	-10000	0	-0.34	7	7
VEGFA165/NRP2	0.008	0.007	-10000	0	-10000	0	0
MAPKKK cascade	-0.045	0.093	0.4	1	-0.37	6	7
NRP2	0.017	0.047	0.22	28	-10000	0	28
VEGFC homodimer	-0.008	0.074	-10000	0	-0.38	21	21
NCK1	0.024	0.059	0.22	47	-10000	0	47
ROCK1	0.007	0.009	0.22	1	-10000	0	1
FAK1/Paxillin	-0.061	0.15	0.31	2	-0.38	51	53
MAP3K13	-0.052	0.1	0.38	2	-0.42	7	9
PDPK1	-0.037	0.11	0.38	1	-0.38	5	6

×

E-cadherin signaling events

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
E-cadherin/beta catenin-gamma catenin	0	0.059	-10000	0	-0.25	29	29
E-cadherin/beta catenin	0.001	0.048	-10000	0	-0.27	17	17
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
JUP	-0.004	0.063	-10000	0	-0.38	15	15
CDH1	-0.005	0.067	-10000	0	-0.38	17	17

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.003	0.008	-10000	0	-10000	0	0
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.009	0.064	-10000	0	-0.24	38	38
AP2	-0.01	0.071	-10000	0	-0.27	40	40
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.006	0.012	-10000	0	-0.23	1	1
CLTB	0.006	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	-0.011	0.056	-10000	0	-0.22	38	38
CD4	0.009	0.039	0.22	12	-0.38	2	14
CLTA	0.006	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.006	-10000	0	-10000	0	0
ARFGAP1	-0.002	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.002	0.039	-10000	0	-10000	0	0
ARF1/GTP	-0.011	0.054	-10000	0	-0.21	38	38
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.011	0.047	-10000	0	-0.19	38	38
mol:Choline	0.002	0.038	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	-0.02	0.1	-10000	0	-0.39	38	38
DDEF1	0.001	0.036	-10000	0	-10000	0	0
ARF1/GDP	0.004	0.009	-10000	0	-10000	0	0
AP2M1	0.007	0.016	0.22	3	-10000	0	3
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.016	0.049	-10000	0	-0.2	39	39
Rac/GTP	0.003	0.013	-10000	0	-0.28	1	1
ARF1/GTP/GGA3/ARF-GAP1	-0.005	0.048	-10000	0	-0.18	38	38
ARFIP2	0.004	0.007	-10000	0	-10000	0	0
COPA	0.007	0.013	0.22	2	-10000	0	2
RAC1	0.006	0.016	-10000	0	-0.38	1	1
ARF1/GTP/coatomer protein complex	-0.007	0.051	0.14	1	-0.2	35	36
ARF1/GTP/ARHGAP10	-0.011	0.057	-10000	0	-0.22	38	38
GGA3	0.006	0	-10000	0	-10000	0	0
ARF1/GTP/Membrin	-0.008	0.05	-10000	0	-0.19	38	38
AP2A1	-0.021	0.1	-10000	0	-0.38	40	40
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.009	0.047	-10000	0	-0.18	38	38
ARF1/GDP/Membrin	-0.007	0.047	-10000	0	-0.18	38	38
Arfaptin 2/Rac/GDP	0.007	0.011	-10000	0	-0.22	1	1
CYTH2	-0.002	0.006	-10000	0	-10000	0	0
ARF1/GTP/GGA3	-0.008	0.058	-10000	0	-0.22	38	38
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.004	0.011	-10000	0	-0.27	1	1
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	-0.017	0.065	-10000	0	-0.31	7	7
PLD2	0.002	0.038	-10000	0	-10000	0	0
ARF-GAP1/v-SNARE	-0.002	0	-10000	0	-10000	0	0
PIP5K1A	0.002	0.039	-10000	0	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	-0.01	0.05	-10000	0	-0.19	38	38
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.002	0.038	-10000	0	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	-0.002	0	-10000	0	-10000	0	0
GOSR2	0.004	0.019	-10000	0	-10000	0	0
USO1	0.003	0.031	-10000	0	-0.39	2	2
GBF1	0	0.043	-10000	0	-0.4	5	5
ARF1/GTP/Arfaptin 2	-0.008	0.058	-10000	0	-0.22	38	38
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.061	-10000	0	-0.23	40	40

×

Ephrin A reverse 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
MAPKKK cascade	0.007	0.017	-10000	0	-0.22	3	3
EFNA5	0.006	0.035	0.22	5	-0.38	3	8
FYN	-0.027	0.068	0.14	5	-0.21	68	73
neuron projection morphogenesis	0.007	0.017	-10000	0	-0.22	3	3
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.007	0.017	-10000	0	-0.22	3	3
EPHA5	0.006	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.003	0.037	-10000	0	-0.38	5	5
HDAC4	0.006	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.004	0.028	-10000	0	-0.14	1	1
CDKN1A	-0.026	0.15	-10000	0	-0.59	35	35
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.006	0	-10000	0	-10000	0	0
FOXO3	-0.001	0.035	0.34	4	-0.18	7	11
FOXO1	0	0.049	-10000	0	-0.38	9	9
FOXO4	-0.003	0.044	-10000	0	-0.3	11	11
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.006	0	-10000	0	-10000	0	0
TAT	0.006	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.002	0	-10000	0	-10000	0	0
PPARGC1A	0.008	0.02	0.22	5	-10000	0	5
FHL2	0.007	0.009	0.22	1	-10000	0	1
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.016	0.027	0.13	31	-10000	0	31
HIST2H4A	0.004	0.028	0.14	1	-10000	0	1
SIRT1/FOXO3a	0.011	0.038	0.22	5	-10000	0	5
SIRT1	0.015	0.039	0.18	31	-10000	0	31
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.019	0.025	0.14	1	-10000	0	1
SIRT1/Histone H1b	0.009	0.05	-10000	0	-0.26	11	11
apoptosis	-0.019	0.025	-10000	0	-0.14	1	1
SIRT1/PGC1A	0.015	0.026	0.12	31	-10000	0	31
p53/SIRT1	-0.008	0.13	0.35	31	-0.27	72	103
SIRT1/FOXO4	0.008	0.049	-10000	0	-0.26	11	11
FOXO1/FHL2/SIRT1	0.014	0.034	-10000	0	-0.2	6	6
HIST1H1E	-0.002	0.047	-10000	0	-0.3	11	11
SIRT1/p300	0.013	0.038	0.15	1	-0.27	5	6
muscle cell differentiation	-0.003	0.028	-10000	0	-0.12	31	31
TP53	-0.034	0.14	0.18	33	-0.39	72	105
KU70/SIRT1/BAX	0.019	0.025	0.14	1	-10000	0	1
CREBBP	0.001	0.046	-10000	0	-0.38	8	8
MEF2D	0.006	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.016	0.027	0.15	1	-10000	0	1
ACSS2	0.002	0.031	-10000	0	-0.27	1	1
SIRT1/PCAF/MYOD	0.003	0.028	0.12	31	-10000	0	31

×

EPO 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
BCL2L1	0.001	0.13	0.51	2	-0.51	2	4
CRKL	-0.018	0.041	0.22	2	-10000	0	2
mol:DAG	-0.021	0.072	0.28	2	-0.3	13	15
HRAS	-0.017	0.044	0.22	2	-0.26	1	3
MAPK8	-0.015	0.039	0.2	1	-0.22	15	16
RAP1A	-0.018	0.041	0.22	2	-10000	0	2
GAB1	-0.019	0.044	0.22	2	-0.21	4	6
MAPK14	-0.016	0.042	0.36	1	-0.22	17	18
EPO	0.003	0.011	-10000	0	-10000	0	0
PLCG1	-0.021	0.073	0.29	2	-0.3	13	15
EPOR/TRPC2/IP3 Receptors	0.004	0.019	0.21	3	-10000	0	3
RAPGEF1	0.006	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.005	0.035	0.21	1	-0.24	9	10
GAB1/SHC/GRB2/SOS1	-0.003	0.046	-10000	0	-0.27	1	1
EPO/EPOR (dimer)	0.005	0.018	0.23	1	-10000	0	1
IRS2	-0.018	0.041	0.22	2	-10000	0	2
STAT1	0.037	0.11	0.41	2	-0.42	5	7
STAT5B	-0.034	0.098	0.35	2	-0.43	8	10
cell proliferation	-0.015	0.037	0.32	1	-0.2	15	16
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.039	0.061	-10000	0	-0.26	11	11
TEC	0	0.061	0.3	2	-10000	0	2
SOCS3	0.001	0.051	0.22	2	-0.38	9	11
STAT1 (dimer)	0.037	0.11	0.41	2	-0.42	5	7
JAK2	0.001	0.036	0.2	2	-0.39	4	6
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
EPO/EPOR (dimer)/JAK2	0.002	0.054	0.35	3	-10000	0	3
EPO/EPOR	0.005	0.018	0.23	1	-10000	0	1
LYN	-0.01	0.07	-10000	0	-0.38	19	19
TEC/VAV2	-0.003	0.06	0.3	2	-10000	0	2
elevation of cytosolic calcium ion concentration	0.004	0.019	0.21	3	-10000	0	3
SHC1	0.006	0	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.001	0.051	0.27	2	-0.24	18	20
mol:IP3	-0.021	0.072	0.28	2	-0.3	13	15
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.036	0.066	0.24	1	-0.28	10	11
SH2B3	0.003	0.01	-10000	0	-10000	0	0
NFKB1	-0.02	0.058	0.2	1	-0.29	21	22
EPO/EPOR (dimer)/JAK2/SOCS3	-0.001	0.03	-10000	0	-0.2	12	12
PTPN6	-0.017	0.043	0.23	2	-0.18	4	6
TEC/VAV2/GRB2	0.008	0.059	0.4	1	-10000	0	1
EPOR	0.004	0.019	0.21	3	-10000	0	3
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.003	0.047	-10000	0	-0.27	1	1
SOS1	0.014	0.04	0.22	20	-10000	0	20
PLCG2	0.006	0	-10000	0	-10000	0	0
CRKL/CBL/C3G	-0.005	0.044	0.27	1	-10000	0	1
VAV2	-0.019	0.043	0.22	2	-10000	0	2
CBL	-0.018	0.041	0.22	2	-10000	0	2
SHC/Grb2/SOS1	-0.004	0.041	0.16	1	-10000	0	1
STAT5A	-0.033	0.099	0.35	2	-0.43	10	12
GRB2	0.006	0.016	-10000	0	-0.38	1	1
STAT5 (dimer)	-0.047	0.14	0.48	2	-0.37	77	79
LYN/PLCgamma2	-0.003	0.05	-10000	0	-0.27	19	19
PTPN11	0.006	0	-10000	0	-10000	0	0
BTK	-0.012	0.051	0.23	3	-10000	0	3
BCL2	-0.06	0.28	0.51	2	-0.76	73	75

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	0.11	0.22	0.67	2	-10000	0	2
PCK1	0.14	0.22	0.58	40	-0.86	4	44
HNF4A	0.14	0.25	0.75	6	-10000	0	6
KCNJ11	0.12	0.23	0.65	1	-10000	0	1
AKT1	0.089	0.14	0.4	5	-10000	0	5
response to starvation	0.017	0.029	-10000	0	-10000	0	0
DLK1	0.13	0.25	0.79	14	-10000	0	14
NKX2-1	0.08	0.15	-10000	0	-10000	0	0
ACADM	0.11	0.22	0.64	4	-10000	0	4
TAT	0.11	0.16	0.53	2	-10000	0	2
CEBPB	0.005	0.035	0.22	1	-0.38	4	5
CEBPA	0.007	0.007	-10000	0	-10000	0	0
TTR	0.099	0.13	0.91	2	-10000	0	2
PKLR	0.11	0.22	0.64	1	-10000	0	1
APOA1	0.18	0.31	0.79	38	-10000	0	38
CPT1C	0.12	0.22	0.7	10	-10000	0	10
ALAS1	0.076	0.16	0.88	2	-10000	0	2
TFRC	0.19	0.28	0.78	50	-10000	0	50
FOXF1	0.006	0	-10000	0	-10000	0	0
NF1	-0.008	0.081	0.2	4	-0.38	24	28
HNF1A (dimer)	0.007	0.025	-10000	0	-0.33	3	3
CPT1A	0.11	0.22	0.64	1	-0.81	1	2
HMGCS1	0.13	0.24	0.7	14	-10000	0	14
NR3C1	-0.001	0.059	-10000	0	-0.38	13	13
CPT1B	0.11	0.22	0.59	3	-10000	0	3
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.007	0.01	-10000	0	-0.23	1	1
GCK	0.11	0.22	0.59	3	-10000	0	3
CREB1	0.032	0.071	0.19	52	-0.31	5	57
IGFBP1	0.082	0.14	-10000	0	-10000	0	0
PDX1	0.082	0.16	-10000	0	-1.1	1	1
UCP2	0.023	0.36	0.64	1	-0.81	52	53
ALDOB	0.12	0.23	0.65	1	-10000	0	1
AFP	0.033	0.052	0.45	1	-10000	0	1
BDH1	0.11	0.22	0.69	2	-0.81	1	3
HADH	0.079	0.3	0.65	1	-0.83	25	26
F2	0.15	0.26	0.78	3	-10000	0	3
HNF1A	0.007	0.025	-10000	0	-0.33	3	3
G6PC	0.037	0.065	-10000	0	-10000	0	0
SLC2A2	0.095	0.17	-10000	0	-10000	0	0
INS	0.003	0.016	-10000	0	-0.19	2	2
FOXA1	0.009	0.032	0.48	1	-0.39	2	3
FOXA3	0.081	0.11	0.37	23	-10000	0	23
FOXA2	0.17	0.3	0.84	13	-10000	0	13
ABCC8	0.12	0.23	0.65	1	-10000	0	1
ALB	0.033	0.053	0.44	2	-10000	0	2

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.005	0.04	0.17	22	-10000	0	22
GNAI2	0.006	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.004	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
RhoA/GTP	0.005	0.041	-10000	0	-0.17	22	22
negative regulation of cAMP metabolic process	0.003	0.044	0.18	1	-0.19	20	21
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
GNAI3	0.017	0.047	0.22	29	-10000	0	29
GNA12	0.006	0	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.003	0.044	0.18	1	-0.19	20	21
RhoA/GDP	0.004	0.016	-10000	0	-0.27	2	2
RHOA	0.005	0.023	-10000	0	-0.38	2	2
GNAI1	0	0.063	0.22	7	-0.38	13	20

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.003	0.032	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	0.002	0.016	-10000	0	-10000	0	0
mol:DAG	-0.004	0.021	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.013	0.034	-10000	0	-10000	0	0
CaM/Ca2+	0	0.04	-10000	0	-10000	0	0
HIF1A	0.007	0.029	-10000	0	-0.39	3	3
GAB1	0.004	0.033	-10000	0	-0.38	4	4
AKT1	-0.001	0.089	-10000	0	-0.37	1	1
PLCG1	-0.004	0.021	-10000	0	-10000	0	0
NOS3	-0.002	0.052	-10000	0	-10000	0	0
CBL	0.006	0	-10000	0	-10000	0	0
mol:NO	-0.002	0.051	-10000	0	-10000	0	0
FLT1	0.003	0.02	-10000	0	-10000	0	0
PGF	0.006	0	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.024	0.046	0.28	3	-10000	0	3
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
eNOS/Hsp90	0.001	0.051	-10000	0	-10000	0	0
endothelial cell proliferation	-0.004	0.03	0.26	1	-10000	0	1
mol:Ca2+	-0.004	0.021	-10000	0	-10000	0	0
MAPK3	-0.022	0.06	0.25	1	-0.36	1	2
MAPK1	-0.006	0.031	0.25	1	-10000	0	1
PIK3R1	-0.038	0.12	-10000	0	-0.38	64	64
PLGF homodimer	0.006	0	-10000	0	-10000	0	0
PRKACA	0.006	0	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.062	0.15	0.22	3	-0.38	101	104
VEGFA homodimer	0.018	0.048	0.22	30	-10000	0	30
VEGFR1 homodimer/VEGFA homodimer	0.015	0.038	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.022	0.059	0.24	1	-0.35	1	2
PI3K	0.02	0.091	-10000	0	-0.37	1	1
PRKCA	-0.005	0.031	0.27	1	-10000	0	1
PRKCB	-0.004	0.019	-10000	0	-10000	0	0
VEGFR1 homodimer/PLGF homodimer	0.007	0.017	-10000	0	-10000	0	0
VEGFA	0.018	0.048	0.22	30	-10000	0	30
VEGFB	0.001	0.046	-10000	0	-0.38	8	8
mol:IP3	-0.004	0.021	-10000	0	-10000	0	0
RASA1	-0.009	0.031	-10000	0	-10000	0	0
NRP2	0.017	0.047	0.22	28	-10000	0	28
VEGFR1 homodimer	0.003	0.02	-10000	0	-10000	0	0
VEGFB homodimer	0.001	0.046	-10000	0	-0.38	8	8
NCK1	0.024	0.059	0.22	47	-10000	0	47
eNOS/Caveolin-1	-0.024	0.086	-10000	0	-0.37	5	5
PTPN11	0.006	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.019	0.089	-10000	0	-0.37	1	1
mol:L-citrulline	-0.002	0.051	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.021	0.037	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.029	0.053	0.28	5	-10000	0	5
CD2AP	0.007	0.031	0.22	5	-0.38	2	7
PI3K/GAB1	0.02	0.088	-10000	0	-0.36	1	1
PDPK1	0.002	0.082	-10000	0	-0.35	1	1
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.018	0.034	-10000	0	-10000	0	0
mol:NADP	-0.002	0.051	-10000	0	-10000	0	0
HSP90AA1	0.006	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.02	0.036	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP2	0.014	0.037	-10000	0	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.012	0.11	0.79	2	-0.85	1	3
NCK1/PAK1/Dok-R	-0.019	0.046	-10000	0	-0.41	1	1
NCK1/Dok-R	0.018	0.062	-10000	0	-0.87	1	1
PIK3CA	0.056	0.091	0.22	131	-10000	0	131
mol:beta2-estradiol	-0.002	0.018	-10000	0	-0.16	7	7
RELA	0.005	0.023	-10000	0	-0.38	2	2
SHC1	0.006	0.004	-10000	0	-10000	0	0
Rac/GDP	0.004	0.011	-10000	0	-0.27	1	1
F2	0.003	0.028	0.23	1	-0.29	2	3
TNIP2	0.007	0.009	0.22	1	-10000	0	1
NF kappa B/RelA	0.005	0.053	-10000	0	-0.82	1	1
FN1	0.074	0.12	0.22	201	-0.38	13	214
PLD2	0.001	0.06	0.72	1	-0.89	1	2
PTPN11	0.006	0	-10000	0	-10000	0	0
GRB14	0.015	0.042	0.22	22	-10000	0	22
ELK1	-0.009	0.063	0.64	1	-0.84	1	2
GRB7	0.006	0.035	0.22	5	-0.38	3	8
PAK1	0.012	0.041	0.22	18	-0.38	1	19
Tie2/Ang1/alpha5/beta1 Integrin	0.05	0.09	-10000	0	-0.85	1	1
CDKN1A	-0.042	0.2	0.57	6	-0.76	36	42
ITGA5	0.008	0.018	0.22	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0.007	0.053	-10000	0	-0.87	1	1
CRK	0.006	0	-10000	0	-10000	0	0
mol:NO	-0.01	0.098	0.57	4	-0.64	1	5
PLG	-0.002	0.064	0.72	1	-0.89	1	2
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.001	0.094	0.7	2	-0.8	1	3
GRB2	0.006	0.016	-10000	0	-0.38	1	1
PIK3R1	-0.038	0.12	-10000	0	-0.39	64	64
ANGPT2	0	0.082	0.58	8	-10000	0	8
BMX	0.001	0.06	0.72	1	-0.89	1	2
ANGPT1	0.007	0.051	0.56	2	-10000	0	2
tube development	-0.034	0.13	0.56	7	-0.66	1	8
ANGPT4	0.006	0.01	0.22	1	-10000	0	1
response to hypoxia	0	0.007	0.11	1	-10000	0	1
Tie2/Ang1/GRB14	0.011	0.064	0.65	1	-0.91	1	2
alpha5/beta1 Integrin	0.009	0.001	-10000	0	-10000	0	0
FGF2	0.006	0.005	-10000	0	-10000	0	0
STAT5A (dimer)	-0.029	0.16	0.79	2	-0.58	36	38
mol:L-citrulline	-0.01	0.098	0.57	4	-0.64	1	5
AGTR1	0.006	0.008	-10000	0	-10000	0	0
MAPK14	0	0.077	0.86	1	-1	1	2
Tie2/SHP2	0.001	0.054	-10000	0	-0.96	1	1
TEK	0	0.068	0.73	1	-1	1	2
RPS6KB1	-0.006	0.1	0.74	2	-0.82	1	3
Angiotensin II/AT1	0.006	0.018	0.15	8	-10000	0	8
Tie2/Ang1/GRB2	0.005	0.059	0.65	1	-0.91	1	2
MAPK3	-0.016	0.075	0.66	1	-0.84	1	2
MAPK1	-0.001	0.057	0.66	1	-0.84	1	2
Tie2/Ang1/GRB7	0.005	0.052	-10000	0	-0.91	1	1
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MAPK8	0.002	0.061	0.72	1	-0.89	1	2
PI3K	-0.008	0.11	0.78	2	-0.96	1	3
FES	-0.002	0.077	0.86	1	-1	1	2
Crk/Dok-R	0.008	0.051	-10000	0	-0.87	1	1
Tie2/Ang1/ABIN2	0.006	0.059	0.65	1	-0.91	1	2
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.011	0.11	0.78	2	-0.76	1	3
STAT5A	-0.001	0.049	-10000	0	-0.38	9	9
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.003	0.11	0.74	2	-0.82	1	3
Tie2/Ang2	-0.021	0.13	0.86	2	-0.87	1	3
Tie2/Ang1	0.003	0.065	0.82	1	-0.94	1	2
FOXO1	-0.017	0.12	0.8	2	-0.77	1	3
ELF1	0.002	0.044	0.21	1	-0.38	7	8
ELF2	0.003	0.062	0.79	1	-0.9	1	2
mol:Choline	0.001	0.059	0.71	1	-0.87	1	2
cell migration	-0.011	0.029	-10000	0	-0.23	1	1
FYN	-0.037	0.14	0.57	7	-0.75	1	8
DOK2	0.007	0.009	0.22	1	-10000	0	1
negative regulation of cell cycle	-0.036	0.18	0.56	6	-0.68	36	42
ETS1	0.009	0.03	0.22	4	-0.4	1	5
PXN	0	0.1	0.71	2	-0.68	1	3
ITGB1	0.007	0.016	0.22	3	-10000	0	3
NOS3	-0.011	0.1	0.75	2	-0.72	1	3
RAC1	0.006	0.016	-10000	0	-0.38	1	1
TNF	0.009	0.021	0.21	2	-10000	0	2
MAPKKK cascade	0.001	0.059	0.71	1	-0.87	1	2
RASA1	0.004	0.028	-10000	0	-0.38	3	3
Tie2/Ang1/Shc	0.007	0.061	0.69	1	-0.91	1	2
NCK1	0.024	0.059	0.22	47	-10000	0	47
vasculogenesis	-0.008	0.093	0.49	7	-0.57	1	8
mol:Phosphatidic acid	0.001	0.059	0.71	1	-0.87	1	2
mol:Angiotensin II	0.001	0.008	-10000	0	-10000	0	0
mol:NADP	-0.01	0.098	0.57	4	-0.64	1	5
Rac1/GTP	-0.013	0.079	-10000	0	-0.76	1	1
MMP2	-0.027	0.098	0.72	1	-0.89	1	2

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.007	0.016	0.22	3	-10000	0	3
ITGB7	0.003	0.038	0.22	1	-0.38	5	6
ITGA4	0.017	0.047	0.22	29	-10000	0	29
alpha4/beta7 Integrin	0.007	0.024	-10000	0	-0.27	4	4
alpha4/beta1 Integrin	0.009	0.002	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.004	0.008	0.2	1	-10000	0	1
BAD/BCL-XL/YWHAZ	0.01	0.005	-10000	0	-10000	0	0
CDKN1B	0.026	0.051	0.25	1	-10000	0	1
CDKN1A	0.015	0.061	-10000	0	-10000	0	0
FRAP1	0.006	0	-10000	0	-10000	0	0
PRKDC	0.048	0.085	0.22	110	-10000	0	110
FOXO3	0.023	0.053	-10000	0	-10000	0	0
AKT1	0.028	0.05	-10000	0	-10000	0	0
BAD	0.006	0	-10000	0	-10000	0	0
AKT3	-0.16	0.14	0.15	4	-0.27	337	341
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.025	0.048	-10000	0	-10000	0	0
AKT1/ASK1	0.026	0.047	-10000	0	-10000	0	0
BAD/YWHAZ	0.013	0	-10000	0	-10000	0	0
RICTOR	0.009	0.024	0.22	7	-10000	0	7
RAF1	0.006	0	-10000	0	-10000	0	0
JNK cascade	-0.004	0.018	-10000	0	-10000	0	0
TSC1	0.025	0.048	-10000	0	-10000	0	0
YWHAZ	0.006	0	-10000	0	-10000	0	0
AKT1/RAF1	0.03	0.045	-10000	0	-10000	0	0
EP300	0.003	0.037	-10000	0	-0.38	5	5
mol:GDP	0.027	0.05	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.025	0.048	-10000	0	-10000	0	0
YWHAQ	0.006	0	-10000	0	-10000	0	0
TBC1D4	0.001	0.017	0.16	2	-10000	0	2
MAP3K5	0.002	0.044	0.22	1	-0.38	7	8
MAPKAP1	0.006	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.014	0.033	0.2	3	-10000	0	3
YWHAH	0.005	0.03	0.22	1	-0.38	3	4
AKT1S1	0.025	0.048	-10000	0	-10000	0	0
CASP9	0.025	0.048	-10000	0	-10000	0	0
YWHAB	0.007	0.009	0.22	1	-10000	0	1
p27Kip1/KPNA1	0.028	0.048	0.23	1	-10000	0	1
GBL	0.006	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.013	0	-10000	0	-10000	0	0
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
SRC	0.006	0	-10000	0	-10000	0	0
AKT2/p21CIP1	0.013	0.059	0.19	4	-10000	0	4
KIAA1303	0.006	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.028	-10000	0	-10000	0	0
CHUK	0.028	0.052	0.25	4	-10000	0	4
BAD/BCL-XL	0.029	0.043	-10000	0	-10000	0	0
mTORC2	0.018	0.014	-10000	0	-10000	0	0
AKT2	0.004	0.017	0.15	7	-10000	0	7
FOXO1-3a-4/14-3-3 family	0.022	0.045	-10000	0	-10000	0	0
PDPK1	0.006	0	-10000	0	-10000	0	0
MDM2	0.026	0.049	-10000	0	-10000	0	0
MAPKKK cascade	-0.029	0.045	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.026	0.054	-10000	0	-0.33	2	2
TSC1/TSC2	0.023	0.046	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.052	-10000	0	-0.32	2	2
glucose import	0	0.015	0.14	2	-10000	0	2
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.027	0.038	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	0	0.015	0.14	2	-10000	0	2
GSK3A	0.023	0.051	-10000	0	-10000	0	0
FOXO1	0.022	0.053	-10000	0	-10000	0	0
GSK3B	0.025	0.048	-10000	0	-10000	0	0
SFN	0.013	0.039	0.22	19	-10000	0	19
G1/S transition of mitotic cell cycle	0.021	0.049	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.011	0.036	-10000	0	-0.31	4	4
PRKACA	0.006	0	-10000	0	-10000	0	0
KPNA1	0.007	0.013	0.22	2	-10000	0	2
HSP90AA1	0.006	0	-10000	0	-10000	0	0
YWHAG	0.004	0.033	-10000	0	-0.38	4	4
RHEB	0.017	0.047	0.22	28	-10000	0	28
CREBBP	0.001	0.046	-10000	0	-0.38	8	8

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.003	0.074	-10000	0	-0.31	27	27
Ran/GTP/Exportin 1/HDAC1	-0.004	0.001	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.015	0.089	-10000	0	-0.36	27	27
SUMO1	0.006	0	-10000	0	-10000	0	0
ZFPM1	0.006	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.003	0.005	-10000	0	-10000	0	0
FKBP3	0.01	0.027	0.22	9	-10000	0	9
Histones	0.027	0.058	0.26	8	-10000	0	8
YY1/LSF	0.015	0.062	0.16	53	-0.25	13	66
SMG5	0.007	0.016	0.22	3	-10000	0	3
RAN	0.006	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.011	0.066	-10000	0	-0.25	36	36
I kappa B alpha/HDAC1	-0.001	0.07	-10000	0	-0.4	10	10
SAP18	0.006	0.016	-10000	0	-0.38	1	1
RELA	-0.01	0.061	-10000	0	-0.28	13	13
HDAC1/Smad7	0.012	0.003	-10000	0	-10000	0	0
RANGAP1	0.006	0	-10000	0	-10000	0	0
HDAC3/TR2	0.005	0.035	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.011	0.042	0.26	1	-10000	0	1
NF kappa B1 p50/RelA	-0.01	0.068	-10000	0	-0.39	10	10
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.004	0.034	0.22	1	-0.38	4	5
GATA1	0.006	0	-10000	0	-10000	0	0
Mad/Max	0.009	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.013	0.042	0.25	1	-10000	0	1
RBBP7	0.006	0.019	0.22	1	-0.38	1	2
NPC	0.004	0	-10000	0	-10000	0	0
RBBP4	0.015	0.042	0.22	22	-10000	0	22
MAX	0.006	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.006	0	-10000	0	-10000	0	0
NFKBIA	-0.012	0.074	-10000	0	-0.39	16	16
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.014	0.039	0.19	14	-10000	0	14
SIN3 complex	0.016	0.011	-10000	0	-0.2	1	1
SMURF1	0.006	0	-10000	0	-10000	0	0
CHD3	0.001	0.046	-10000	0	-0.38	8	8
SAP30	0.006	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.002	0.04	-10000	0	-0.38	6	6
YY1/HDAC3	-0.005	0.044	-10000	0	-0.38	3	3
YY1/HDAC2	0.005	0.046	0.16	13	-0.25	12	25
YY1/HDAC1	0.009	0.051	0.16	27	-0.26	10	37
NuRD/MBD2 Complex (MeCP1)	0.011	0.042	0.26	1	-10000	0	1
PPARG	-0.011	0.067	-10000	0	-0.28	30	30
HDAC8/hEST1B	0.012	0.004	-10000	0	-10000	0	0
UBE2I	0.006	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.006	0	-10000	0	-10000	0	0
TNFRSF1A	-0.011	0.08	-10000	0	-0.38	25	25
HDAC3/SMRT (N-CoR2)	-0.002	0.041	-10000	0	-0.22	8	8
MBD3L2	0.006	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.012	0.003	-10000	0	-10000	0	0
CREBBP	0.001	0.046	-10000	0	-0.38	8	8
NuRD/MBD3/MBD3L2 Complex	0.013	0.044	0.27	1	-10000	0	1
HDAC1	0.017	0.047	0.22	28	-10000	0	28
HDAC3	-0.003	0.034	-10000	0	-10000	0	0
HDAC2	0.011	0.036	0.22	13	-0.38	1	14
YY1	-0.003	0.044	-10000	0	-0.3	11	11
HDAC8	0.023	0.058	0.22	44	-10000	0	44
SMAD7	0.006	0	-10000	0	-10000	0	0
NCOR2	0	0.049	-10000	0	-0.38	9	9
MXD1	0.006	0	-10000	0	-10000	0	0
STAT3	-0.008	0.066	-10000	0	-0.31	22	22
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.007	0.013	0.22	2	-10000	0	2
YY1/LSF/HDAC1	0.024	0.066	0.29	6	-0.23	13	19
YY1/SAP30/HDAC1	0.012	0.047	-10000	0	-0.24	10	10
EP300	0.003	0.037	-10000	0	-0.38	5	5
STAT3 (dimer non-phopshorylated)	-0.008	0.066	-10000	0	-0.31	22	22
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.073	-10000	0	-0.39	16	16
histone deacetylation	0.011	0.041	0.21	2	-10000	0	2
STAT3 (dimer non-phopshorylated)/HDAC3	-0.009	0.06	-10000	0	-0.42	5	5
nuclear export	-0.012	0.003	-10000	0	-10000	0	0
PRKACA	0.006	0	-10000	0	-10000	0	0
GATAD2B	0.006	0.016	-10000	0	-0.38	1	1
GATAD2A	0.006	0.016	-10000	0	-0.38	1	1
GATA2/HDAC3	0	0.036	-10000	0	-0.2	4	4
GATA1/HDAC1	0.009	0.002	-10000	0	-10000	0	0
GATA1/HDAC3	0.001	0.032	-10000	0	-10000	0	0
CHD4	0.007	0.016	0.22	3	-10000	0	3
TNF-alpha/TNFR1A	-0.003	0.057	-10000	0	-0.27	25	25
SIN3/HDAC complex/Mad/Max	0.014	0.035	0.17	14	-10000	0	14
NuRD Complex	0.013	0.044	0.27	1	-10000	0	1
positive regulation of chromatin silencing	0.026	0.056	0.25	8	-10000	0	8
SIN3B	0.007	0.009	0.22	1	-10000	0	1
MTA2	0.006	0	-10000	0	-10000	0	0
SIN3A	0.006	0	-10000	0	-10000	0	0
XPO1	0.026	0.062	0.22	52	-10000	0	52
SUMO1/HDAC1	0.016	0.029	0.2	1	-10000	0	1
HDAC complex	0.023	0.034	-10000	0	-0.2	2	2
GATA1/Fog1	0.009	0	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.011	0.011	-10000	0	-0.23	1	1
TNF	0.007	0.009	0.22	1	-10000	0	1
negative regulation of cell growth	0.014	0.035	0.17	14	-10000	0	14
NuRD/MBD2/PRMT5 Complex	0.011	0.042	0.26	1	-10000	0	1
Ran/GTP/Exportin 1	0.021	0.035	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.016	0.08	-10000	0	-0.34	27	27
SIN3/HDAC complex/NCoR1	0.012	0.041	0.19	14	-10000	0	14
TFCP2	0.025	0.07	0.22	54	-0.38	3	57
NR2C1	0.012	0.033	0.22	14	-10000	0	14
MBD3	0.006	0	-10000	0	-10000	0	0
MBD2	0.006	0	-10000	0	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	-0.003	0.024	0.32	1	-0.13	3	4
KIRREL	0.009	0.043	0.2	22	-0.42	1	23
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.003	0.024	0.13	3	-0.32	1	4
PLCG1	0.009	0.022	0.22	6	-10000	0	6
ARRB2	0.006	0	-10000	0	-10000	0	0
WASL	0.006	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.012	0.033	-10000	0	-0.22	1	1
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.014	0.038	0.2	1	-0.24	1	2
FYN	-0.016	0.054	0.21	1	-0.15	64	65
mol:Ca2+	0.008	0.025	0.12	4	-0.25	1	5
mol:DAG	0.012	0.032	-10000	0	-0.25	1	1
NPHS2	0.003	0.014	-10000	0	-10000	0	0
mol:IP3	0.012	0.032	-10000	0	-0.25	1	1
regulation of endocytosis	0	0.055	0.21	1	-0.34	1	2
Nephrin/NEPH1/podocin/Cholesterol	0.005	0.023	0.12	3	-0.25	1	4
establishment of cell polarity	0.003	0.024	0.13	3	-0.32	1	4
Nephrin/NEPH1/podocin/NCK1-2	0.026	0.046	-10000	0	-0.23	1	1
Nephrin/NEPH1/beta Arrestin2	0	0.056	0.22	1	-0.34	1	2
NPHS1	0.003	0.02	0.2	3	-10000	0	3
Nephrin/NEPH1/podocin	-0.002	0.058	0.23	1	-0.15	64	65
TJP1	0.006	0.021	0.22	2	-0.38	1	3
NCK1	0.024	0.059	0.22	47	-10000	0	47
NCK2	0.006	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.013	0.033	-10000	0	-0.25	1	1
CD2AP	0.007	0.031	0.22	5	-0.38	2	7
Nephrin/NEPH1/podocin/GRB2	0.012	0.035	-10000	0	-0.26	2	2
GRB2	0.006	0.016	-10000	0	-0.38	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.004	0.03	0.18	2	-0.23	1	3
cytoskeleton organization	0.005	0.039	0.22	1	-0.24	2	3
Nephrin/NEPH1	0.004	0.017	0.11	3	-0.22	1	4
Nephrin/NEPH1/ZO-1	0.007	0.023	0.12	3	-0.26	2	5

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.047	0.22	28	-10000	0	28
HDAC2	0.011	0.036	0.22	13	-0.38	1	14
GNB1/GNG2	0.009	0.023	-10000	0	-0.23	5	5
forebrain development	-0.005	0.082	-10000	0	-0.44	8	8
GNAO1	0.005	0.036	0.22	6	-0.38	3	9
SMO/beta Arrestin2	0.008	0.007	-10000	0	-10000	0	0
SMO	0.005	0.006	-10000	0	-10000	0	0
ARRB2	0.005	0.004	-10000	0	-10000	0	0
GLI3/SPOP	0.006	0.044	-10000	0	-0.39	1	1
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
GSK3B	0.006	0	-10000	0	-10000	0	0
GNAI2	0.005	0.005	-10000	0	-10000	0	0
SIN3/HDAC complex	0.017	0.011	-10000	0	-0.2	1	1
GNAI1	-0.001	0.064	0.22	7	-0.38	13	20
XPO1	0.024	0.062	0.22	52	-10000	0	52
GLI1/Su(fu)	-0.007	0.075	-10000	0	-0.43	7	7
SAP30	0.006	0.001	-10000	0	-10000	0	0
mol:GDP	0.005	0.006	-10000	0	-10000	0	0
MIM/GLI2A	0.003	0.034	0.22	6	-10000	0	6
IFT88	-0.001	0.054	-10000	0	-0.38	11	11
GNAI3	0.016	0.048	0.22	29	-10000	0	29
GLI2	0.004	0.003	-10000	0	-10000	0	0
GLI3	0.002	0.046	-10000	0	-0.26	9	9
CSNK1D	0.006	0	-10000	0	-10000	0	0
CSNK1E	0.006	0	-10000	0	-10000	0	0
SAP18	0.006	0.016	-10000	0	-0.38	1	1
embryonic digit morphogenesis	-0.001	0.054	-10000	0	-0.38	11	11
GNG2	0.004	0.034	0.22	1	-0.38	4	5
Gi family/GTP	0	0.045	0.19	1	-0.21	4	5
SIN3B	0.007	0.009	0.22	1	-10000	0	1
SIN3A	0.006	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	0.005	0.042	-10000	0	-0.36	1	1
GLI2/Su(fu)	0.006	0.01	-10000	0	-10000	0	0
FOXA2	-0.05	0.23	-10000	0	-0.96	33	33
neural tube patterning	-0.005	0.082	-10000	0	-0.44	8	8
SPOP	0.006	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.007	0.013	-10000	0	-10000	0	0
GNB1	0.006	0.016	-10000	0	-0.38	1	1
CSNK1G2	0.006	0	-10000	0	-10000	0	0
CSNK1G3	0.006	0	-10000	0	-10000	0	0
MTSS1	0.003	0.034	0.22	6	-10000	0	6
embryonic limb morphogenesis	-0.005	0.082	-10000	0	-0.44	8	8
SUFU	0.003	0.013	-10000	0	-10000	0	0
LGALS3	-0.04	0.13	-10000	0	-0.38	68	68
catabolic process	0.009	0.037	-10000	0	-0.3	1	1
GLI3A/CBP	0.001	0.047	-10000	0	-0.39	8	8
KIF3A	0.008	0.02	0.22	5	-10000	0	5
GLI1	-0.005	0.083	-10000	0	-0.45	8	8
RAB23	0.006	0	-10000	0	-10000	0	0
CSNK1A1	0.007	0.009	0.22	1	-10000	0	1
IFT172	0.005	0.023	-10000	0	-0.38	2	2
RBBP7	0.006	0.019	0.22	1	-0.38	1	2
Su(fu)/Galectin3	-0.018	0.068	-10000	0	-0.22	7	7
GNAZ	0.001	0.04	-10000	0	-0.39	6	6
RBBP4	0.015	0.042	0.22	22	-10000	0	22
CSNK1G1	0.006	0	-10000	0	-10000	0	0
PIAS1	0.007	0.009	0.22	1	-10000	0	1
PRKACA	0.006	0	-10000	0	-10000	0	0
GLI2/SPOP	0.008	0.003	-10000	0	-10000	0	0
STK36	0.006	0.017	0.22	3	-10000	0	3
Gi family/GNB1/GNG2/GDP	0.001	0.047	0.27	1	-0.22	2	3
PTCH1	-0.015	0.15	-10000	0	-1	10	10
MIM/GLI1	-0.013	0.12	-10000	0	-0.44	31	31
CREBBP	0.001	0.047	-10000	0	-0.39	8	8
Su(fu)/SIN3/HDAC complex	0.016	0.037	0.23	2	-10000	0	2

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.006	0.036	0.22	6	-0.38	3	9
CDC42/GTP	0.006	0.039	-10000	0	-0.19	3	3
PLCG1	0.003	0.044	0.17	1	-0.18	20	21
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.006	0	-10000	0	-10000	0	0
GNAI3	0.017	0.047	0.22	29	-10000	0	29
G12/G13	0.009	0.012	-10000	0	-0.27	1	1
cell migration	0.006	0.039	-10000	0	-0.18	3	3
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.014	0.067	0.17	1	-0.19	48	49
MAPK1	0.001	0.043	0.17	1	-0.19	4	5
S1P/S1P5/Gi	0.003	0.044	0.18	1	-0.19	20	21
GNAI1	0	0.063	0.22	7	-0.38	13	20
CDC42/GDP	0.005	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.004	0	-10000	0	-10000	0	0
RHOA	-0.005	0.014	-10000	0	-0.19	3	3
S1P/S1P4/Gi	0.003	0.044	0.18	1	-0.19	20	21
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.002	0.04	-10000	0	-0.38	6	6
S1P/S1P4/G12/G13	0.008	0.009	-10000	0	-0.2	1	1
GNA12	0.006	0	-10000	0	-10000	0	0
GNA13	0.006	0.016	-10000	0	-0.38	1	1
CDC42	0.006	0	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.003	0.025	0.14	1	-0.19	9	10
TRAF2/ASK1	0.006	0.026	-10000	0	-0.22	7	7
ATM	0.014	0.04	0.22	20	-10000	0	20
MAP2K3	0.002	0.043	-10000	0	-0.32	4	4
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.012	0.045	0.18	1	-0.22	10	11
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.007	0.024	0.22	4	-0.38	1	5
TXN	-0.014	0.062	-10000	0	-0.27	31	31
CALM1	-0.006	0.068	-10000	0	-0.38	18	18
GADD45A	0.024	0.059	0.22	46	-10000	0	46
GADD45B	0.008	0.02	0.22	5	-10000	0	5
MAP3K1	0.004	0.033	-10000	0	-0.38	4	4
MAP3K6	0.006	0	-10000	0	-10000	0	0
MAP3K7	0.01	0.028	0.22	10	-10000	0	10
MAP3K4	0.006	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.006	0.031	-10000	0	-0.27	7	7
TAK1/TAB family	0.004	0.025	-10000	0	-0.33	2	2
RAC1/OSM/MEKK3	0.012	0.009	-10000	0	-0.2	1	1
TRAF2	0.006	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.003	0.033	-10000	0	-0.27	5	5
TRAF6	0.002	0.02	0.15	3	-0.27	2	5
RAC1	0.006	0.016	-10000	0	-0.38	1	1
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.006	0	-10000	0	-10000	0	0
CCM2	0.006	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.001	0.041	-10000	0	-0.22	18	18
MAPK11	0.006	0	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.003	0.045	0.14	1	-0.2	25	26
OSM/MEKK3	0.009	0	-10000	0	-10000	0	0
TAOK1	0.008	0.031	0.15	22	-0.27	1	23
TAOK2	0.008	0.028	0.15	20	-10000	0	20
TAOK3	0.008	0.028	0.15	20	-10000	0	20
MAP3K7IP1	0.006	0	-10000	0	-10000	0	0
MAPK14	0.007	0.009	0.22	1	-10000	0	1
MAP3K7IP2	0.005	0.025	0.22	1	-0.38	2	3
MAP3K5	0.002	0.044	0.22	1	-0.38	7	8
MAP3K10	0.006	0	-10000	0	-10000	0	0
MAP3K3	0.006	0	-10000	0	-10000	0	0
TRX/ASK1	-0.01	0.062	0.16	1	-0.24	36	37
GADD45/MTK1/MTK1	0.024	0.033	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.013	0.03	-10000	0	-0.2	10	10
HDAC3	0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.004	0.001	-10000	0	-10000	0	0
GATA1/HDAC4	0.009	0	-10000	0	-10000	0	0
GATA1/HDAC5	0.007	0.026	-10000	0	-0.27	5	5
GATA2/HDAC5	0.005	0.035	-10000	0	-0.27	9	9
HDAC5/BCL6/BCoR	0.004	0.044	-10000	0	-0.23	20	20
HDAC9	0.015	0.042	0.22	22	-10000	0	22
Glucocorticoid receptor/Hsp90/HDAC6	0.007	0.036	-10000	0	-0.23	13	13
HDAC4/ANKRA2	0.009	0.012	-10000	0	-0.27	1	1
HDAC5/YWHAB	0.007	0.026	-10000	0	-0.27	5	5
NPC/RanGAP1/SUMO1/Ubc9	0.003	0.005	-10000	0	-10000	0	0
GATA2	0.004	0.034	0.22	1	-0.38	4	5
HDAC4/RFXANK	0.009	0.001	-10000	0	-10000	0	0
BCOR	0.007	0.009	0.22	1	-10000	0	1
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.006	0	-10000	0	-10000	0	0
HDAC5	0.003	0.037	-10000	0	-0.38	5	5
GNB1/GNG2	0.007	0.026	-10000	0	-0.27	5	5
Histones	0.007	0.027	0.18	1	-0.21	4	5
ADRBK1	0.006	0	-10000	0	-10000	0	0
HDAC4	0.006	0	-10000	0	-10000	0	0
XPO1	0.026	0.062	0.22	52	-10000	0	52
HDAC5/ANKRA2	0.006	0.029	-10000	0	-0.27	6	6
HDAC4/Ubc9	0.009	0	-10000	0	-10000	0	0
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.006	0.029	-10000	0	-0.27	6	6
TUBA1B	0.006	0	-10000	0	-10000	0	0
HDAC6	0.008	0.02	0.22	5	-10000	0	5
HDAC5/RFXANK	0.007	0.026	-10000	0	-0.27	5	5
CAMK4	0.01	0.027	0.22	9	-10000	0	9
Tubulin/HDAC6	0.013	0.001	-10000	0	-10000	0	0
SUMO1	0.006	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.007	0.009	0.22	1	-10000	0	1
GATA1	0.006	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.006	0.016	-10000	0	-0.38	1	1
NR3C1	-0.003	0.058	-10000	0	-0.38	13	13
SUMO1/HDAC4	0.01	0.001	-10000	0	-10000	0	0
SRF	0.002	0.04	-10000	0	-0.38	6	6
HDAC4/YWHAB	0.009	0	-10000	0	-10000	0	0
Tubulin	0.009	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.009	0.012	-10000	0	-0.27	1	1
GNB1	0.006	0.016	-10000	0	-0.38	1	1
RANGAP1	0.006	0	-10000	0	-10000	0	0
BCL6/BCoR	0.002	0.045	-10000	0	-0.27	15	15
HDAC4/HDAC3/SMRT (N-CoR2)	0.009	0.03	-10000	0	-0.23	9	9
HDAC4/SRF	0.01	0.024	-10000	0	-0.23	6	6
HDAC4/ER alpha	-0.021	0.086	-10000	0	-0.27	61	61
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.007	0.027	0.18	1	-0.2	4	5
cell motility	0.013	0.001	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.006	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.005	0	-10000	0	-10000	0	0
BCL6	-0.004	0.063	-10000	0	-0.38	15	15
HDAC4/CaMK II delta B	0.006	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0.009	0.001	-10000	0	-10000	0	0
ESR1	-0.036	0.12	-10000	0	-0.38	61	61
HDAC6/HDAC11	0.009	0.001	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.021	0.035	-10000	0	-10000	0	0
NPC	0.004	0	-10000	0	-10000	0	0
MEF2C	-0.005	0.067	-10000	0	-0.38	17	17
RAN	0.006	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.009	0.044	-10000	0	-0.19	26	26
GNG2	0.004	0.034	0.22	1	-0.38	4	5
NCOR2	0	0.049	-10000	0	-0.38	9	9
TUBB2A	0.006	0	-10000	0	-10000	0	0
HDAC11	0.006	0	-10000	0	-10000	0	0
HSP90AA1	0.006	0	-10000	0	-10000	0	0
RANBP2	0.007	0.013	0.22	2	-10000	0	2
ANKRA2	0.006	0.019	0.22	1	-0.38	1	2
RFXANK	0.008	0.018	0.22	4	-10000	0	4
nuclear import	-0.005	0.026	0.24	6	-10000	0	6

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.006	0.046	-10000	0	-0.2	26	26
MAP4K1	0.007	0.013	0.22	2	-10000	0	2
MAP3K8	0.006	0	-10000	0	-10000	0	0
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0.006	0	-10000	0	-10000	0	0
CRKL	0.006	0	-10000	0	-10000	0	0
MAP3K1	-0.008	0.044	-10000	0	-10000	0	0
JUN	0.002	0.025	0.16	1	-0.18	3	4
MAP3K7	-0.005	0.045	-10000	0	-10000	0	0
GRAP2	0.006	0	-10000	0	-10000	0	0
CRK	0.006	0	-10000	0	-10000	0	0
MAP2K4	-0.009	0.046	-10000	0	-10000	0	0
LAT	0.006	0	-10000	0	-10000	0	0
LCP2	-0.013	0.085	-10000	0	-0.38	28	28
MAPK8	0.002	0.016	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.005	0.044	-10000	0	-0.21	26	26
LAT/GRAP2/SLP76/HPK1/HIP-55	0.009	0.044	-10000	0	-0.19	26	26

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.009	0.022	-10000	0	-0.22	6	6
PI3K Class IB/PDE3B	0.009	0.022	0.22	6	-10000	0	6
PDE3B	0.009	0.022	0.22	6	-10000	0	6

×

Arf6 trafficking events

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
SLC2A4	0.006	0	-10000	0	-10000	0	0
CLTC	0.01	0.033	-10000	0	-0.52	1	1
calcium ion-dependent exocytosis	0.006	0.023	-10000	0	-0.22	2	2
Dynamin 2/GTP	0.005	0.01	0.14	1	-0.2	1	2
EXOC4	0.009	0.024	0.22	7	-10000	0	7
CD59	0.007	0.029	-10000	0	-0.47	1	1
CPE	-0.009	0.062	0.16	23	-0.23	32	55
CTNNB1	0.007	0.009	0.22	1	-10000	0	1
membrane fusion	0.006	0.023	-10000	0	-0.22	2	2
CTNND1	0.002	0.031	-10000	0	-0.19	1	1
DNM2	0.007	0.009	0.22	1	-10000	0	1
mol:PI-4-5-P2	0.007	0.023	-10000	0	-0.36	1	1
TSHR	0.002	0.03	0.16	18	-0.22	1	19
INS	0.006	0.008	-10000	0	-10000	0	0
BIN1	0.005	0.023	-10000	0	-0.38	2	2
mol:Choline	0.006	0.023	-10000	0	-0.22	2	2
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.038	0.16	31	-0.22	1	32
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.006	0.016	-10000	0	-0.38	1	1
mol:Ca2+	0.005	0.01	0.14	1	-0.2	1	2
JUP	0.003	0.039	-10000	0	-0.47	1	1
ASAP2/amphiphysin II	0.007	0.015	-10000	0	-0.2	3	3
ARF6/GTP	0.004	0.011	-10000	0	-0.27	1	1
CDH1	0.003	0.039	-10000	0	-0.47	1	1
clathrin-independent pinocytosis	0.004	0.011	-10000	0	-0.27	1	1
MAPK8IP3	0.006	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.004	0.011	-10000	0	-0.27	1	1
EXOC2	0.01	0.03	0.22	11	-10000	0	11
substrate adhesion-dependent cell spreading	0.01	0.022	0.2	1	-10000	0	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.007	0.009	0.22	1	-10000	0	1
regulation of calcium-dependent cell-cell adhesion	-0.004	0.029	0.44	1	-10000	0	1
positive regulation of phagocytosis	-0.004	0.009	-10000	0	-0.22	1	1
ARF6/GTP/JIP3	0.008	0.01	-10000	0	-0.22	1	1
ACAP1	0.006	0.02	-10000	0	-0.2	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.008	0.028	-10000	0	-0.47	1	1
clathrin heavy chain/ACAP1	0.01	0.031	-10000	0	-0.44	1	1
JIP4/KLC1	0.013	0.014	0.14	4	-0.2	1	5
EXOC1	0.008	0.02	0.22	5	-10000	0	5
exocyst	0.01	0.023	0.2	1	-10000	0	1
RALA/GTP	0.005	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.008	0.01	-10000	0	-0.22	1	1
receptor recycling	0.004	0.011	-10000	0	-0.27	1	1
CTNNA1	0.001	0.033	0.13	1	-0.19	3	4
NME1	0.005	0.038	0.16	31	-0.22	1	32
clathrin coat assembly	0.01	0.033	-10000	0	-0.51	1	1
IL2RA	0.008	0.029	-10000	0	-0.47	1	1
VAMP3	-0.004	0.009	-10000	0	-0.22	1	1
GLUT4/clathrin heavy chain/ACAP1	0.01	0.026	-10000	0	-0.42	1	1
EXOC6	0.007	0.013	0.22	2	-10000	0	2
PLD1	0.009	0.029	-10000	0	-0.24	1	1
PLD2	0.002	0.012	-10000	0	-0.19	2	2
EXOC5	0.007	0.009	0.22	1	-10000	0	1
PIP5K1C	0.007	0.023	-10000	0	-0.36	1	1
SDC1	0.008	0.029	-10000	0	-0.47	1	1
ARF6/GDP	0.012	0.033	0.14	31	-0.22	1	32
EXOC7	0.006	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.011	0.039	-10000	0	-0.45	1	1
mol:Phosphatidic acid	0.006	0.023	-10000	0	-0.22	2	2
endocytosis	-0.007	0.015	0.2	3	-10000	0	3
SCAMP2	0.006	0.016	-10000	0	-0.38	1	1
ADRB2	0.009	0.032	-10000	0	-0.49	1	1
EXOC3	0.007	0.009	0.22	1	-10000	0	1
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.014	0.032	0.14	32	-0.2	1	33
KLC1	0.007	0.016	0.22	3	-10000	0	3
AVPR2	0.009	0.032	-10000	0	-0.49	1	1
RALA	0.007	0.009	0.22	1	-10000	0	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.008	0.038	-10000	0	-0.43	1	1

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.009	0.001	-10000	0	-10000	0	0
FBXW11	0.006	0	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.006	0	-10000	0	-10000	0	0
CHUK	0.011	0.031	0.22	12	-10000	0	12
NF kappa B2 p100/RelB	0.02	0.023	-10000	0	-0.19	3	3
NFKB1	-0.001	0.054	-10000	0	-0.38	11	11
MAP3K14	0.006	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelB	0.003	0.043	-10000	0	-0.27	14	14
RELB	0.004	0.028	-10000	0	-0.38	3	3
NFKB2	0.006	0	-10000	0	-10000	0	0
NF kappa B2 p52/RelB	0.007	0.017	-10000	0	-0.22	3	3
regulation of B cell activation	0.007	0.017	-10000	0	-0.22	3	3

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.006	0	-10000	0	-10000	0	0
GNAT1/GTP	0.005	0	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.009	0	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.009	0.001	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.006	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.007	0.031	-10000	0	-0.18	15	15
mol:Na +	0.008	0.03	-10000	0	-0.18	15	15
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.01	0.026	-10000	0	-0.23	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.011	0.032	-10000	0	-0.18	15	15
CNGB1	0.006	0	-10000	0	-10000	0	0
RDH5	0.01	0.03	0.22	11	-10000	0	11
SAG	0.006	0	-10000	0	-10000	0	0
mol:Ca2+	-0.013	0.027	-10000	0	-10000	0	0
Na + (4 Units)	0.006	0.029	-10000	0	-0.17	15	15
RGS9	0.007	0.009	0.22	1	-10000	0	1
GNB1/GNGT1	0.009	0.012	-10000	0	-0.27	1	1
GNAT1/GDP	0.013	0.023	-10000	0	-0.19	7	7
GUCY2D	0.006	0	-10000	0	-10000	0	0
GNGT1	0.01	0.027	0.22	9	-10000	0	9
GUCY2F	0.006	0	-10000	0	-10000	0	0
GNB5	0.001	0.043	-10000	0	-0.38	7	7
mol:GMP (4 units)	0.006	0.011	-10000	0	-10000	0	0
mol:11-cis-retinal	0.01	0.03	0.22	11	-10000	0	11
mol:cGMP	0.014	0.008	-10000	0	-10000	0	0
GNB1	0.006	0.016	-10000	0	-0.38	1	1
Rhodopsin	0.009	0.001	-10000	0	-10000	0	0
SLC24A1	0.006	0	-10000	0	-10000	0	0
CNGA1	-0.004	0.063	-10000	0	-0.38	15	15
Metarhodopsin II	0.004	0	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.017	0.008	-10000	0	-10000	0	0
RGS9BP	0.006	0	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.005	0.016	-10000	0	-0.21	1	1
GCAP Family/Ca ++	0.013	0.008	-10000	0	-10000	0	0
PDE6A/B	0.009	0.001	-10000	0	-10000	0	0
mol:Pi	0.01	0.026	-10000	0	-0.23	7	7
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.014	0.018	-10000	0	-0.2	1	1
PDE6B	0.007	0.009	0.22	1	-10000	0	1
PDE6A	0.007	0.009	0.22	1	-10000	0	1
PDE6G	0.007	0.013	0.22	2	-10000	0	2
RHO	0.006	0	-10000	0	-10000	0	0
PDE6	0.017	0.024	-10000	0	-0.18	7	7
GUCA1A	0.006	0	-10000	0	-10000	0	0
GC2/GCAP Family	0.017	0.008	-10000	0	-10000	0	0
GUCA1C	0.007	0.013	0.22	2	-10000	0	2
GUCA1B	0.006	0	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.047	0.22	28	-10000	0	28
Ran/GTP/Exportin 1/HDAC4	-0.004	0.001	-10000	0	-10000	0	0
MDM2/SUMO1	0.01	0.014	-10000	0	-0.18	1	1
HDAC4	0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.004	0.001	-10000	0	-10000	0	0
SUMO1	0.006	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.002	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	0.013	0.038	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.006	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.007	0.013	0.22	2	-10000	0	2
SUMO1/HDAC4	0.01	0.001	-10000	0	-10000	0	0
SUMO1/HDAC1	0.016	0.029	0.2	1	-10000	0	1
RANGAP1	0.006	0	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.02	0.024	-10000	0	-0.2	1	1
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.003	0.005	-10000	0	-10000	0	0
Ran/GTP	0.006	0.005	-10000	0	-10000	0	0
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.007	0.024	0.22	4	-0.38	1	5
UBE2I	0.006	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.015	0.033	-10000	0	-10000	0	0
NPC	0.004	0	-10000	0	-10000	0	0
PIAS2	0.011	0.031	0.22	12	-10000	0	12
PIAS1	0.007	0.009	0.22	1	-10000	0	1
EntrezGene:9972	0	0	-10000	0	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.01	0.02	0.13	1	-0.19	5	6
MAPK9	0.001	0.013	0.15	1	-0.27	1	2
adrenocorticotropin secretion	-0.002	0.008	0.2	1	-10000	0	1
GNB1/GNG2	0.006	0.022	-10000	0	-0.22	5	5
GNB1	0.006	0.016	-10000	0	-0.38	1	1
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.002	0.006	0.15	1	-10000	0	1
Gs family/GTP	0.004	0	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0	0	-10000	0	-10000	0	0
GNAL	0.006	0	-10000	0	-10000	0	0
GNG2	0.004	0.034	0.22	1	-0.38	4	5
CRH	0.007	0.009	0.22	1	-10000	0	1
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.003	0.014	0.15	5	-10000	0	5
MAPK11	0.001	0	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.011	0	-10000	0	-10000	0	0
RGS9BP	0.006	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.008	0	-10000	0	-10000	0	0
mol:ADP	-0.002	0	-10000	0	-10000	0	0
GNAT2	0.006	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.01	0.026	-10000	0	-0.23	7	7
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.009	0	-10000	0	-10000	0	0
GRK7	0.006	0	-10000	0	-10000	0	0
CNGB3	0.006	0	-10000	0	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.005	0	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0	-10000	0	-10000	0	0
Cone PDE6	0.016	0.024	-10000	0	-0.19	7	7
Cone Metarhodopsin II	0.004	0	-10000	0	-10000	0	0
Na + (4 Units)	0.012	0	-10000	0	-10000	0	0
GNAT2/GDP	0.013	0.023	-10000	0	-0.19	7	7
GNB5	0.001	0.043	-10000	0	-0.38	7	7
mol:GMP (4 units)	-0.004	0	-10000	0	-10000	0	0
Cone Transducin	0.012	0	-10000	0	-10000	0	0
SLC24A2	0.006	0	-10000	0	-10000	0	0
GNB3/GNGT2	0.009	0	-10000	0	-10000	0	0
GNB3	0.006	0	-10000	0	-10000	0	0
GNAT2/GTP	0.005	0	-10000	0	-10000	0	0
CNGA3	0.006	0	-10000	0	-10000	0	0
ARR3	0.006	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.009	0	-10000	0	-10000	0	0
mol:Pi	0.01	0.026	-10000	0	-0.23	7	7
Cone CNG Channel	0.015	0	-10000	0	-10000	0	0
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.006	0	-10000	0	-10000	0	0
RGS9	0.007	0.009	0.22	1	-10000	0	1
PDE6C	0.006	0	-10000	0	-10000	0	0
GNGT2	0.006	0	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.006	0	-10000	0	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.007	0.013	0.22	2	-9999	2
GPC2	0.006	0	-10000	0	-9999	0
GPC2/Midkine	0.009	0.001	-10000	0	-9999	0
neuron projection morphogenesis	0.009	0.001	-10000	0	-9999	0

pid_entity	TCGA.61.2614	TCGA.61.2613	TCGA.61.2612	TCGA.61.2113
109_MAP3K5	0.0039	0.0039	0.0039	0.0039
47_PPARGC1A	0.0063	0.0063	0.0063	0.0063
105_BMP4	0.0063	0.0063	0.0063	0.0063
105_BMP6	0.0063	0.0063	0.0063	0.0063
105_BMP7	0.22	0.0063	0.0063	0.0063
105_BMP2	0.0063	0.0063	0.0063	0.0063
131_RELN/VLDLR	0.016	0.016	0.016	0.14
30_TGFB1/TGF beta receptor Type II	0.0062	0.0062	0.0062	0.0062
84_STAT5B	-0.048	-0.048	-0.048	0.068
84_STAT5A	-0.048	-0.048	-0.048	0.068