PARADIGM pathway analysis of mRNASeq expression data - Bladder Urothelial Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	155
Glypican 2 network	116
Aurora B signaling	108
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	86
Signaling events regulated by Ret tyrosine kinase	80
Signaling mediated by p38-alpha and p38-beta	72
Nongenotropic Androgen signaling	72
Signaling events mediated by the Hedgehog family	71
IL4-mediated signaling events	67
Endothelins	67

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	0.3799	155	7954	51	-0.87	0.016	1000	-1000	-0.13	-1000
Glypican 2 network	0.2843	116	465	4	-0.16	-0.13	1000	-1000	-0.011	-1000
Aurora B signaling	0.2647	108	7288	67	-0.51	0.016	1000	-1000	-0.052	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2108	86	5895	68	-0.73	0.36	1000	-1000	-0.09	-1000
Signaling events regulated by Ret tyrosine kinase	0.1961	80	6583	82	-0.31	0.016	1000	-1000	-0.072	-1000
Signaling mediated by p38-alpha and p38-beta	0.1765	72	3210	44	-0.25	0.016	1000	-1000	-0.044	-1000
Nongenotropic Androgen signaling	0.1765	72	3780	52	-0.26	0.14	1000	-1000	-0.05	-1000
Signaling events mediated by the Hedgehog family	0.1740	71	3702	52	-0.18	0.18	1000	-1000	-0.039	-1000
IL4-mediated signaling events	0.1642	67	6124	91	-0.78	0.55	1000	-1000	-0.11	-1000
Endothelins	0.1642	67	6474	96	-0.34	0.04	1000	-1000	-0.061	-1000
Reelin signaling pathway	0.1446	59	3326	56	-0.24	0.041	1000	-1000	-0.068	-1000
TCGA08_p53	0.1446	59	416	7	-0.18	0.081	1000	-1000	-0.016	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1422	58	4545	78	-0.26	0.088	1000	-1000	-0.056	-1000
Thromboxane A2 receptor signaling	0.1373	56	5953	105	-0.21	0.038	1000	-1000	-0.057	-1000
Aurora C signaling	0.1373	56	392	7	-0.22	0	1000	-1000	-0.026	-1000
PLK1 signaling events	0.1373	56	4827	85	-0.37	0.051	1000	-1000	-0.033	-1000
IGF1 pathway	0.1348	55	3142	57	-0.25	0.047	1000	-1000	-0.077	-1000
TCGA08_retinoblastoma	0.1324	54	433	8	-0.26	0.069	1000	-1000	-0.014	-1000
IL23-mediated signaling events	0.1275	52	3155	60	-0.61	0.016	1000	-1000	-0.11	-1000
Ephrin A reverse signaling	0.1225	50	350	7	-0.071	0	1000	-1000	-0.018	-1000
p75(NTR)-mediated signaling	0.1225	50	6318	125	-0.17	0.047	1000	-1000	-0.085	-1000
Plasma membrane estrogen receptor signaling	0.1225	50	4313	86	-0.26	0.13	1000	-1000	-0.071	-1000
Fc-epsilon receptor I signaling in mast cells	0.1201	49	4811	97	-0.2	0.041	1000	-1000	-0.076	-1000
HIF-1-alpha transcription factor network	0.1176	48	3712	76	-0.35	0.035	1000	-1000	-0.056	-1000
Rapid glucocorticoid signaling	0.1152	47	957	20	-0.24	0.037	1000	-1000	-0.015	-1000
Integrins in angiogenesis	0.1127	46	3877	84	-0.28	0.033	1000	-1000	-0.076	-1000
Syndecan-1-mediated signaling events	0.1078	44	1526	34	-0.28	0.016	1000	-1000	-0.04	-1000
Glypican 1 network	0.1078	44	2117	48	-0.25	0.036	1000	-1000	-0.021	-1000
IL6-mediated signaling events	0.1078	44	3321	75	-0.24	0.069	1000	-1000	-0.055	-1000
Ras signaling in the CD4+ TCR pathway	0.1078	44	760	17	-0.16	0.021	1000	-1000	-0.022	-1000
Glucocorticoid receptor regulatory network	0.1054	43	4986	114	-0.6	0.27	1000	-1000	-0.061	-1000
Calcium signaling in the CD4+ TCR pathway	0.1054	43	1361	31	-0.29	0.016	1000	-1000	-0.067	-1000
BMP receptor signaling	0.1029	42	3415	81	-0.32	0.053	1000	-1000	-0.08	-1000
amb2 Integrin signaling	0.1005	41	3441	82	-0.33	0.021	1000	-1000	-0.07	-1000
TCR signaling in naïve CD8+ T cells	0.1005	41	3828	93	-0.14	0.063	1000	-1000	-0.071	-1000
LPA receptor mediated events	0.0980	40	4095	102	-0.24	0.029	1000	-1000	-0.073	-1000
S1P1 pathway	0.0956	39	1405	36	-0.31	0.016	1000	-1000	-0.048	-1000
PDGFR-alpha signaling pathway	0.0931	38	1688	44	-0.34	0.033	1000	-1000	-0.049	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0931	38	4577	120	-0.32	0.18	1000	-1000	-0.067	-1000
S1P5 pathway	0.0907	37	633	17	-0.17	0.11	1000	-1000	-0.024	-1000
Visual signal transduction: Cones	0.0858	35	1361	38	-0.12	0.019	1000	-1000	-0.046	-1000
JNK signaling in the CD4+ TCR pathway	0.0858	35	598	17	-0.15	0.022	1000	-1000	-0.017	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0858	35	1826	52	-0.31	0.028	1000	-1000	-0.037	-1000
Osteopontin-mediated events	0.0833	34	1315	38	-0.19	0.017	1000	-1000	-0.074	-1000
LPA4-mediated signaling events	0.0784	32	393	12	-0.16	0.022	1000	-1000	-0.017	-1000
Aurora A signaling	0.0784	32	1947	60	-0.36	0.031	1000	-1000	-0.035	-1000
S1P4 pathway	0.0784	32	822	25	-0.17	0.032	1000	-1000	-0.03	-1000
Coregulation of Androgen receptor activity	0.0760	31	2376	76	-0.24	0.032	1000	-1000	-0.034	-1000
IL12-mediated signaling events	0.0760	31	2730	87	-0.42	0.037	1000	-1000	-0.1	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0760	31	1690	54	-0.2	0.031	1000	-1000	-0.083	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0760	31	2806	88	-0.23	0.041	1000	-1000	-0.093	-1000
BCR signaling pathway	0.0735	30	3065	99	-0.18	0.038	1000	-1000	-0.078	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0686	28	981	34	-0.053	0.016	1000	-1000	-0.049	-1000
S1P3 pathway	0.0686	28	1180	42	-0.17	0.032	1000	-1000	-0.024	-1000
Syndecan-2-mediated signaling events	0.0662	27	1904	69	-0.091	0.03	1000	-1000	-0.032	-1000
Arf6 signaling events	0.0662	27	1705	62	-0.24	0.03	1000	-1000	-0.044	-1000
Class IB PI3K non-lipid kinase events	0.0637	26	78	3	-0.022	-1000	1000	-1000	-0.008	-1000
Wnt signaling	0.0613	25	178	7	-0.06	0.016	1000	-1000	-0.019	-1000
Presenilin action in Notch and Wnt signaling	0.0588	24	1469	61	-0.19	0.045	1000	-1000	-0.064	-1000
FAS signaling pathway (CD95)	0.0588	24	1152	47	-0.56	0.02	1000	-1000	-0.023	-1000
Canonical Wnt signaling pathway	0.0539	22	1158	51	-0.19	0.081	1000	-1000	-0.038	-1000
Syndecan-4-mediated signaling events	0.0539	22	1531	67	-0.19	0.017	1000	-1000	-0.074	-1000
Visual signal transduction: Rods	0.0539	22	1185	52	-0.21	0.016	1000	-1000	-0.076	-1000
ErbB4 signaling events	0.0490	20	1439	69	-0.23	0.039	1000	-1000	-0.072	-1000
Noncanonical Wnt signaling pathway	0.0490	20	535	26	-0.092	0.016	1000	-1000	-0.04	-1000
ErbB2/ErbB3 signaling events	0.0466	19	1276	65	-0.23	0.027	1000	-1000	-0.056	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0466	19	533	28	-0.17	0.029	1000	-1000	-0.026	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0466	19	1693	85	-0.22	0.024	1000	-1000	-0.064	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0466	19	643	33	-0.28	0.047	1000	-1000	-0.041	-1000
FOXA2 and FOXA3 transcription factor networks	0.0441	18	832	46	-0.19	0.096	1000	-1000	-0.034	-1000
Effects of Botulinum toxin	0.0441	18	475	26	-0.076	0.016	1000	-1000	-0.053	-1000
Regulation of Androgen receptor activity	0.0392	16	1140	70	-0.21	0.03	1000	-1000	-0.049	-1000
Caspase cascade in apoptosis	0.0368	15	1157	74	-0.055	0.044	1000	-1000	-0.028	-1000
Cellular roles of Anthrax toxin	0.0368	15	592	39	-0.1	0.017	1000	-1000	-0.021	-1000
Hedgehog signaling events mediated by Gli proteins	0.0368	15	1002	65	-0.17	0.066	1000	-1000	-0.046	-1000
IL27-mediated signaling events	0.0368	15	794	51	-0.24	0.027	1000	-1000	-0.058	-1000
EGFR-dependent Endothelin signaling events	0.0368	15	334	21	-0.069	0.023	1000	-1000	-0.061	-1000
Nectin adhesion pathway	0.0343	14	922	63	-0.05	0.03	1000	-1000	-0.065	-1000
IL2 signaling events mediated by STAT5	0.0343	14	317	22	-0.12	0.069	1000	-1000	-0.028	-1000
Regulation of nuclear SMAD2/3 signaling	0.0294	12	1763	136	-0.2	0.069	1000	-1000	-0.066	-1000
Signaling events mediated by PTP1B	0.0294	12	926	76	-0.14	0.035	1000	-1000	-0.066	-1000
IL2 signaling events mediated by PI3K	0.0294	12	742	58	-0.21	0.058	1000	-1000	-0.063	-1000
Regulation of p38-alpha and p38-beta	0.0294	12	677	54	-0.16	0.042	1000	-1000	-0.046	-1000
Signaling events mediated by HDAC Class III	0.0270	11	459	40	-0.23	0.026	1000	-1000	-0.034	-1000
IL1-mediated signaling events	0.0270	11	700	62	-0.094	0.075	1000	-1000	-0.084	-1000
Syndecan-3-mediated signaling events	0.0270	11	385	35	-0.13	0.047	1000	-1000	-0.032	-1000
Regulation of Telomerase	0.0270	11	1125	102	-0.17	0.039	1000	-1000	-0.083	-1000
Insulin Pathway	0.0270	11	875	74	-0.26	0.042	1000	-1000	-0.076	-1000
Ceramide signaling pathway	0.0245	10	776	76	-0.24	0.046	1000	-1000	-0.028	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0245	10	878	83	-0.28	0.043	1000	-1000	-0.063	-1000
a4b1 and a4b7 Integrin signaling	0.0221	9	49	5	-0.003	0.01	1000	-1000	-0.025	-1000
Class I PI3K signaling events mediated by Akt	0.0221	9	645	68	-0.21	0.061	1000	-1000	-0.039	-1000
Ephrin B reverse signaling	0.0221	9	465	48	-0.053	0.02	1000	-1000	-0.064	-1000
Signaling events mediated by PRL	0.0221	9	319	34	-0.099	0.026	1000	-1000	-0.019	-1000
E-cadherin signaling events	0.0221	9	45	5	-0.004	0.018	1000	-1000	-0.021	-1000
BARD1 signaling events	0.0196	8	506	57	-0.17	0.045	1000	-1000	-0.053	-1000
IFN-gamma pathway	0.0196	8	561	68	-0.17	0.054	1000	-1000	-0.073	-1000
Signaling mediated by p38-gamma and p38-delta	0.0196	8	127	15	0	0.032	1000	-1000	-0.019	-1000
EPHB forward signaling	0.0196	8	761	85	-0.047	0.04	1000	-1000	-0.085	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0196	8	642	74	-0.24	0.077	1000	-1000	-0.078	-1000
PDGFR-beta signaling pathway	0.0196	8	843	97	-0.062	0.054	1000	-1000	-0.078	-1000
PLK2 and PLK4 events	0.0172	7	22	3	0.003	0.016	1000	-1000	-0.013	-1000
EPO signaling pathway	0.0172	7	423	55	-0.046	0.059	1000	-1000	-0.08	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0172	7	292	37	-0.027	0.036	1000	-1000	-0.044	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0172	7	341	45	-0.03	0.068	1000	-1000	-0.07	-1000
Arf6 trafficking events	0.0172	7	518	71	-0.41	0.05	1000	-1000	-0.063	-1000
TRAIL signaling pathway	0.0147	6	328	48	-0.01	0.051	1000	-1000	-0.048	-1000
Retinoic acid receptors-mediated signaling	0.0147	6	401	58	-0.079	0.033	1000	-1000	-0.061	-1000
TCGA08_rtk_signaling	0.0123	5	155	26	-0.065	0.048	1000	-1000	-0.016	-1000
E-cadherin signaling in the nascent adherens junction	0.0123	5	388	76	-0.02	0.058	1000	-1000	-0.075	-1000
Signaling events mediated by HDAC Class II	0.0098	4	317	75	-0.089	0.039	1000	-1000	-0.037	-1000
p38 MAPK signaling pathway	0.0098	4	176	44	-0.04	0.046	1000	-1000	-0.053	-1000
FoxO family signaling	0.0074	3	206	64	-0.06	0.097	1000	-1000	-0.04	-1000
Paxillin-dependent events mediated by a4b1	0.0074	3	115	36	-0.036	0.037	1000	-1000	-0.064	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0074	3	414	125	-0.05	0.097	1000	-1000	-0.08	-1000
Class I PI3K signaling events	0.0074	3	288	73	-0.06	0.042	1000	-1000	-0.055	-1000
Canonical NF-kappaB pathway	0.0049	2	105	39	-0.019	0.091	1000	-1000	-0.069	-1000
Circadian rhythm pathway	0.0049	2	54	22	-0.016	0.053	1000	-1000	-0.029	-1000
Insulin-mediated glucose transport	0.0049	2	66	32	-0.14	0.042	1000	-1000	-0.05	-1000
mTOR signaling pathway	0.0049	2	109	53	-0.008	0.04	1000	-1000	-0.054	-1000
ceramide signaling pathway	0.0049	2	115	49	-0.02	0.051	1000	-1000	-0.033	-1000
HIF-2-alpha transcription factor network	0.0049	2	122	43	-0.16	0.16	1000	-1000	-0.059	-1000
E-cadherin signaling in keratinocytes	0.0049	2	101	43	-0.046	0.048	1000	-1000	-0.057	-1000
Atypical NF-kappaB pathway	0.0025	1	47	31	0	0.055	1000	-1000	-0.022	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0025	1	39	27	-0.001	0.039	1000	-1000	-0.047	-1000
VEGFR1 specific signals	0.0025	1	102	56	-0.05	0.072	1000	-1000	-0.04	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	14	23	0.008	0.054	1000	-1000	-0.04	-1000
Arf6 downstream pathway	0.0000	0	17	43	-0.038	0.039	1000	-1000	-0.031	-1000
Signaling events mediated by HDAC Class I	0.0000	0	84	104	-0.032	0.066	1000	-1000	-0.058	-1000
Arf1 pathway	0.0000	0	6	54	0	0.04	1000	-1000	-0.03	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.047	1000	-1000	-0.018	-1000
Total	NA	3562	205923	7203	-24	-990	131000	-131000	-6.7	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.65	0.53	-9999	-1.1	209	209
PLK1	-0.13	0.18	-9999	-10000	0	0
BIRC5	-0.25	0.19	-9999	-1.5	1	1
HSPA1B	-0.65	0.53	-9999	-1.1	203	203
MAP2K1	-0.007	0.032	-9999	-10000	0	0
BRCA2	-0.66	0.54	-9999	-1.1	207	207
FOXM1	-0.87	0.76	-9999	-1.4	228	228
XRCC1	-0.65	0.53	-9999	-1.1	209	209
FOXM1B/p19	-0.77	0.52	-9999	-1.1	246	246
Cyclin D1/CDK4	-0.6	0.48	-9999	-0.99	208	208
CDC2	-0.7	0.56	-9999	-1.1	227	227
TGFA	-0.57	0.46	-9999	-0.94	208	208
SKP2	-0.66	0.53	-9999	-1.1	214	214
CCNE1	-0.073	0.19	-9999	-0.52	64	64
CKS1B	-0.66	0.53	-9999	-1.1	209	209
RB1	-0.26	0.16	-9999	-0.44	76	76
FOXM1C/SP1	-0.76	0.63	-9999	-1.2	228	228
AURKB	-0.16	0.19	-9999	-0.37	137	137
CENPF	-0.74	0.57	-9999	-1.2	231	231
CDK4	0.005	0.029	-9999	-0.51	1	1
MYC	-0.57	0.47	-9999	-0.95	212	212
CHEK2	-0.008	0.042	-9999	-0.56	1	1
ONECUT1	-0.63	0.51	-9999	-1	216	216
CDKN2A	-0.25	0.26	-9999	-0.5	205	205
LAMA4	-0.66	0.54	-9999	-1.1	209	209
FOXM1B/HNF6	-0.76	0.63	-9999	-1.3	214	214
FOS	-0.78	0.62	-9999	-1.2	232	232
SP1	0.016	0.001	-9999	-10000	0	0
CDC25B	-0.66	0.53	-9999	-1.1	215	215
response to radiation	-0.023	0.03	-9999	-10000	0	0
CENPB	-0.65	0.53	-9999	-1.1	209	209
CENPA	-0.74	0.57	-9999	-1.2	235	235
NEK2	-0.74	0.57	-9999	-1.2	229	229
HIST1H2BA	-0.66	0.53	-9999	-1.1	216	216
CCNA2	-0.13	0.23	-9999	-0.52	106	106
EP300	0.016	0	-9999	-10000	0	0
CCNB1/CDK1	-0.79	0.65	-9999	-1.3	217	217
CCNB2	-0.74	0.57	-9999	-1.2	223	223
CCNB1	-0.72	0.59	-9999	-1.2	217	217
ETV5	-0.66	0.53	-9999	-1.1	207	207
ESR1	-0.73	0.58	-9999	-1.2	229	229
CCND1	-0.61	0.5	-9999	-1	209	209
GSK3A	0.003	0.026	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.2	-9999	-0.37	144	144
CDK2	0.01	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.029	0.036	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.75	0.52	-9999	-1.2	229	229
GAS1	-0.78	0.57	-9999	-1.2	252	252
MMP2	-0.68	0.56	-9999	-1.1	207	207
RB1/FOXM1C	-0.65	0.53	-9999	-1.1	215	215
CREBBP	0.016	0	-9999	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.014	0.12	-9999	-0.51	23	23
GPC2	-0.16	0.25	-9999	-0.51	140	140
GPC2/Midkine	-0.13	0.2	-9999	-0.38	151	151
neuron projection morphogenesis	-0.13	0.2	-9999	-0.38	151	151

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.16	0.15	-9999	-0.32	152	152
STMN1	-0.18	0.23	-9999	-0.4	195	195
Aurora B/RasGAP/Survivin	-0.32	0.24	-9999	-0.45	297	297
Chromosomal passenger complex/Cul3 protein complex	-0.18	0.16	-9999	-0.35	146	146
BIRC5	-0.36	0.24	-9999	-0.51	293	293
DES	-0.51	0.37	-9999	-0.77	265	265
Aurora C/Aurora B/INCENP	-0.11	0.15	-9999	-0.27	194	194
Aurora B/TACC1	-0.12	0.16	-9999	-0.3	185	185
Aurora B/PP2A	-0.14	0.19	-9999	-0.35	184	184
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.021	0.045	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.25	0.29	-9999	-0.51	212	212
Cul3 protein complex	-0.061	0.17	-9999	-0.36	98	98
KIF2C	-0.12	0.1	-9999	-0.22	197	197
PEBP1	0.006	0.007	-9999	-10000	0	0
KIF20A	-0.37	0.23	-9999	-0.51	300	300
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.14	0.19	-9999	-0.35	184	184
SEPT1	0.01	0.053	-9999	-0.52	4	4
SMC2	0.014	0.026	-9999	-0.51	1	1
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.058	0.071	-9999	-10000	0	0
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.004	-9999	-10000	0	0
H3F3B	-0.068	0.1	-9999	-0.18	184	184
AURKB	-0.22	0.27	-9999	-0.51	184	184
AURKC	-0.001	0.092	-9999	-0.51	13	13
CDCA8	-0.13	0.23	-9999	-0.52	109	109
cytokinesis	-0.26	0.19	-9999	-0.41	223	223
Aurora B/Septin1	-0.24	0.19	-9999	-0.42	177	177
AURKA	-0.14	0.24	-9999	-0.51	124	124
INCENP	0.005	0.027	-9999	-0.53	1	1
KLHL13	-0.11	0.24	-9999	-0.57	88	88
BUB1	-0.088	0.21	-9999	-0.51	80	80
hSgo1/Aurora B/Survivin	-0.41	0.3	-9999	-0.53	317	317
EVI5	0.014	0.002	-9999	-10000	0	0
RhoA/GTP	-0.27	0.22	-9999	-0.46	206	206
SGOL1	-0.2	0.26	-9999	-0.51	172	172
CENPA	-0.18	0.15	-9999	-0.3	211	211
NCAPG	-0.22	0.26	-9999	-0.51	181	181
Aurora B/HC8 Proteasome	-0.14	0.19	-9999	-0.35	184	184
NCAPD2	0.014	0.026	-9999	-0.51	1	1
Aurora B/PP1-gamma	-0.14	0.19	-9999	-0.35	184	184
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.31	0.25	-9999	-0.51	253	253
NPM1	-0.067	0.085	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
KLHL9	-0.006	0.11	-9999	-0.57	15	15
mitotic prometaphase	-0.009	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.19	-9999	-0.35	184	184
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.3	0.24	-9999	-0.49	219	219
RhoA/GDP	0.012	0	-9999	-10000	0	0
NSUN2	-0.067	0.085	-9999	-10000	0	0
MYLK	-0.19	0.2	-9999	-0.32	257	257
KIF23	-0.25	0.26	-9999	-0.51	202	202
VIM	-0.15	0.2	-9999	-0.36	188	188
RACGAP1	0.006	0.052	-9999	-0.52	4	4
mitosis	0	0	-9999	-10000	0	0
NCL	-0.067	0.085	-9999	-10000	0	0
Chromosomal passenger complex	-0.2	0.17	-9999	-0.34	215	215
Chromosomal passenger complex/EVI5	-0.32	0.29	-9999	-0.57	202	202
TACC1	0.011	0.05	-9999	-0.57	3	3
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.001	0.11	-10000	0	-0.62	12	12
NFATC2	-0.12	0.28	-10000	0	-0.65	73	73
NFATC3	-0.093	0.13	-10000	0	-0.31	37	37
CD40LG	-0.55	0.55	-10000	0	-1	194	194
ITCH	0.024	0.089	-10000	0	-0.41	1	1
CBLB	0.025	0.086	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.38	0.44	-10000	0	-1.1	91	91
JUNB	0.008	0.064	-10000	0	-0.57	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.031	0.087	-10000	0	-0.28	43	43
T cell anergy	-0.015	0.14	-10000	0	-0.4	43	43
TLE4	-0.073	0.25	-10000	0	-0.62	50	50
Jun/NFAT1-c-4/p21SNFT	-0.46	0.56	-10000	0	-0.97	194	194
AP-1/NFAT1-c-4	-0.65	0.7	-10000	0	-1.2	199	199
IKZF1	-0.069	0.25	-10000	0	-0.64	43	43
T-helper 2 cell differentiation	-0.24	0.35	-10000	0	-0.88	74	74
AP-1/NFAT1	-0.2	0.28	-10000	0	-0.51	152	152
CALM1	0.013	0.056	-10000	0	-10000	0	0
EGR2	-0.51	0.73	-10000	0	-1.6	110	110
EGR3	-0.73	0.83	-10000	0	-1.5	201	201
NFAT1/FOXP3	-0.086	0.23	-10000	0	-0.54	59	59
EGR1	-0.13	0.25	-10000	0	-0.57	100	100
JUN	-0.013	0.12	-10000	0	-0.57	16	16
EGR4	-0.012	0.12	-10000	0	-0.55	19	19
mol:Ca2+	-0.004	0.061	-10000	0	-10000	0	0
GBP3	-0.062	0.22	-10000	0	-0.58	43	43
FOSL1	-0.024	0.15	-10000	0	-0.57	28	28
NFAT1-c-4/MAF/IRF4	-0.45	0.56	-10000	0	-0.94	203	203
DGKA	-0.057	0.21	-10000	0	-0.52	48	48
CREM	0.015	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.48	0.55	-10000	0	-0.96	202	202
CTLA4	-0.075	0.24	-10000	0	-0.71	34	34
NFAT1-c-4 (dimer)/EGR1	-0.51	0.62	-10000	0	-1.1	203	203
NFAT1-c-4 (dimer)/EGR4	-0.46	0.56	-10000	0	-0.95	204	204
FOS	-0.18	0.28	-10000	0	-0.58	129	129
IFNG	-0.26	0.31	-10000	0	-0.71	102	102
T cell activation	-0.26	0.32	-10000	0	-0.74	81	81
MAF	0	0.095	-10000	0	-0.57	11	11
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.36	0.5	0.78	201	-10000	0	201
TNF	-0.44	0.52	-10000	0	-0.95	184	184
FASLG	-0.69	0.8	-10000	0	-1.4	209	209
TBX21	-0.024	0.14	-10000	0	-0.57	24	24
BATF3	0.003	0.082	-10000	0	-0.54	9	9
PRKCQ	-0.04	0.17	-10000	0	-0.56	39	39
PTPN1	-0.057	0.21	-10000	0	-0.56	39	39
NFAT1-c-4/ICER1	-0.46	0.54	-10000	0	-0.94	202	202
GATA3	-0.025	0.15	-10000	0	-0.56	29	29
T-helper 1 cell differentiation	-0.23	0.32	-10000	0	-0.69	103	103
IL2RA	-0.38	0.42	-10000	0	-0.97	103	103
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.057	0.21	-10000	0	-0.54	42	42
E2F1	-0.1	0.22	-10000	0	-0.5	97	97
PPARG	-0.024	0.15	-10000	0	-0.56	28	28
SLC3A2	-0.057	0.21	-10000	0	-0.53	48	48
IRF4	-0.03	0.16	-10000	0	-0.56	32	32
PTGS2	-0.58	0.57	-10000	0	-1.1	202	202
CSF2	-0.57	0.53	-10000	0	-1	203	203
JunB/Fra1/NFAT1-c-4	-0.44	0.54	-10000	0	-0.93	202	202
IL4	-0.25	0.38	-10000	0	-0.96	71	71
IL5	-0.53	0.52	-10000	0	-1	191	191
IL2	-0.26	0.33	-10000	0	-0.76	79	79
IL3	-0.083	0.062	-10000	0	-10000	0	0
RNF128	-0.021	0.22	-10000	0	-0.62	46	46
NFATC1	-0.36	0.5	-10000	0	-0.78	201	201
CDK4	0.18	0.27	0.59	71	-10000	0	71
PTPRK	-0.057	0.22	-10000	0	-0.55	42	42
IL8	-0.56	0.55	-10000	0	-1.1	194	194
POU2F1	0.016	0.002	-10000	0	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.047	0.043	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.15	0.13	-9999	-0.39	33	33
JUN	-0.11	0.15	-9999	-0.44	24	24
HRAS	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.17	0.19	-9999	-0.33	233	233
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.007	0.068	-9999	-0.51	7	7
RAP1A/GDP	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.17	0.18	-9999	-0.32	229	229
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.17	0.17	-9999	-0.32	228	228
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.16	0.15	-9999	-0.52	15	15
GRB7	-0.012	0.12	-9999	-0.53	21	21
RET51/GFRalpha1/GDNF	-0.17	0.18	-9999	-0.32	229	229
MAPKKK cascade	-0.15	0.14	-9999	-0.5	14	14
BCAR1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.17	0.18	-9999	-0.33	230	230
lamellipodium assembly	-0.15	0.13	-9999	-0.37	33	33
RET51/GFRalpha1/GDNF/SHC	-0.17	0.18	-9999	-0.32	229	229
PIK3CA	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.17	0.17	-9999	-0.32	228	228
RET9/GFRalpha1/GDNF/Shank3	-0.17	0.17	-9999	-0.32	228	228
MAPK3	-0.13	0.16	-9999	-0.51	14	14
DOK1	0.014	0.026	-9999	-0.51	1	1
DOK6	-0.2	0.28	-9999	-0.57	148	148
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.16	0.18	-9999	-0.37	114	114
DOK5	-0.042	0.17	-9999	-0.56	40	40
GFRA1	-0.31	0.29	-9999	-0.57	228	228
MAPK8	-0.11	0.14	-9999	-0.44	15	15
HRAS/GTP	-0.17	0.16	-9999	-0.56	15	15
tube development	-0.15	0.16	-9999	-0.29	228	228
MAPK1	-0.13	0.16	-9999	-0.51	14	14
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.13	0.14	-9999	-0.25	228	228
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.26	0.25	-9999	-0.46	198	198
SHC1	0.014	0.026	-9999	-0.51	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.17	0.18	-9999	-0.32	231	231
RET51/GFRalpha1/GDNF/Dok5	-0.2	0.21	-9999	-0.36	241	241
PRKCA	0.008	0.064	-9999	-0.57	5	5
HRAS/GDP	0.012	0	-9999	-10000	0	0
CREB1	-0.15	0.17	-9999	-0.29	228	228
PIK3R1	0.014	0.029	-9999	-0.57	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.13	0.14	-9999	-0.25	228	228
RET51/GFRalpha1/GDNF/Grb7	-0.18	0.2	-9999	-0.34	235	235
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.009	0.12	-9999	-0.55	18	18
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	-0.11	0.14	-9999	-0.43	24	24
RET9/GFRalpha1/GDNF/FRS2	-0.17	0.17	-9999	-0.32	232	232
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.13	0.14	-9999	-0.25	228	228
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.13	0.15	-9999	-0.44	19	19
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.13	0.15	-9999	-0.44	16	16
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.13	0.16	-9999	-0.54	17	17
PI3K	-0.19	0.23	-9999	-0.58	34	34
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.15	0.16	-9999	-0.29	228	228
GRB10	0.008	0.064	-9999	-0.57	5	5
activation of MAPKK activity	-0.12	0.14	-9999	-0.4	17	17
RET51/GFRalpha1/GDNF/FRS2	-0.18	0.19	-9999	-0.33	230	230
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.001	0.09	-9999	-0.57	10	10
IRS2	-0.007	0.11	-9999	-0.57	16	16
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.13	0.16	-9999	-0.28	141	141
RET51/GFRalpha1/GDNF/PKC alpha	-0.17	0.19	-9999	-0.33	231	231
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.004	0.045	-9999	-0.51	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.18	0.19	-9999	-0.33	231	231
Rac1/GTP	-0.17	0.15	-9999	-0.45	33	33
RET9/GFRalpha1/GDNF	-0.19	0.19	-9999	-0.36	228	228
GFRalpha1/GDNF	-0.23	0.22	-9999	-0.42	228	228

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.25	0.51	-9999	-1.1	100	100
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	-0.058	0.15	-9999	-0.38	21	21
ATF2/c-Jun	-0.049	0.2	-9999	-0.68	25	25
MAPK11	-0.058	0.15	-9999	-0.38	21	21
MITF	-0.087	0.22	-9999	-0.39	123	123
MAPKAPK5	-0.059	0.18	-9999	-0.35	105	105
KRT8	-0.071	0.2	-9999	-0.38	108	108
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.088	0.22	-9999	-0.44	105	105
CEBPB	-0.06	0.18	-9999	-0.36	105	105
SLC9A1	-0.059	0.18	-9999	-0.35	105	105
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.055	0.19	-9999	-0.35	105	105
p38alpha-beta/MNK1	-0.056	0.18	-9999	-0.35	105	105
JUN	-0.048	0.2	-9999	-0.67	25	25
PPARGC1A	-0.22	0.28	-9999	-0.42	236	236
USF1	-0.059	0.18	-9999	-0.35	105	105
RAB5/GDP/GDI1	-0.068	0.11	-9999	-0.35	21	21
NOS2	-0.089	0.25	-9999	-0.74	26	26
DDIT3	-0.059	0.18	-9999	-0.35	105	105
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	-0.039	0.15	-9999	-0.4	21	21
p38alpha-beta/HBP1	-0.056	0.18	-9999	-0.49	21	21
CREB1	-0.063	0.2	-9999	-0.38	105	105
RAB5/GDP	0.012	0	-9999	-10000	0	0
EIF4E	-0.043	0.16	-9999	-0.43	21	21
RPS6KA4	-0.059	0.18	-9999	-0.35	105	105
PLA2G4A	-0.065	0.2	-9999	-0.53	35	35
GDI1	-0.059	0.18	-9999	-0.35	105	105
TP53	-0.079	0.22	-9999	-0.44	105	105
RPS6KA5	-0.069	0.2	-9999	-0.38	109	109
ESR1	-0.13	0.26	-9999	-0.42	155	155
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	-0.073	0.2	-9999	-0.37	115	115
MEF2A	-0.059	0.18	-9999	-0.35	105	105
EIF4EBP1	-0.065	0.2	-9999	-0.38	105	105
KRT19	-0.077	0.21	-9999	-0.38	114	114
ELK4	-0.059	0.18	-9999	-0.35	105	105
ATF6	-0.059	0.18	-9999	-0.35	105	105
ATF1	-0.063	0.2	-9999	-0.38	105	105
p38alpha-beta/MAPKAPK2	-0.056	0.18	-9999	-0.48	23	23
p38alpha-beta/MAPKAPK3	-0.056	0.18	-9999	-0.35	105	105

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.099	0.17	-10000	0	-0.31	152	152
regulation of S phase of mitotic cell cycle	-0.069	0.13	-10000	0	-0.25	149	149
GNAO1	-0.17	0.27	-10000	0	-0.57	129	129
HRAS	0.015	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.01	0.002	-10000	0	-10000	0	0
PELP1	0.015	0.002	-10000	0	-10000	0	0
AKT1	0.013	0.001	-10000	0	-10000	0	0
MAP2K1	-0.086	0.15	-10000	0	-0.35	55	55
T-DHT/AR	-0.15	0.21	-10000	0	-0.42	148	148
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	129	129
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	0.011	0.05	-10000	0	-0.57	3	3
mol:GDP	-0.16	0.21	-10000	0	-0.44	148	148
cell proliferation	-0.16	0.23	-10000	0	-0.45	130	130
PIK3CA	0.016	0	-10000	0	-10000	0	0
FOS	-0.26	0.4	-10000	0	-0.84	129	129
mol:Ca2+	-0.046	0.044	-10000	0	-0.085	193	193
MAPK3	-0.13	0.19	-10000	0	-0.48	55	55
MAPK1	-0.071	0.12	-10000	0	-0.22	129	129
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
mol:IP3	-0.001	0.002	-10000	0	-0.004	129	129
cAMP biosynthetic process	0.039	0.037	-10000	0	-10000	0	0
GNG2	0.007	0.07	-10000	0	-0.57	6	6
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	129	129
HRAS/GTP	-0.11	0.14	-10000	0	-0.29	148	148
actin cytoskeleton reorganization	-0.001	0.013	-10000	0	-0.27	1	1
SRC	0.015	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	129	129
PI3K	0.02	0.018	-10000	0	-0.35	1	1
apoptosis	0.14	0.22	0.45	129	-10000	0	129
T-DHT/AR/PELP1	-0.12	0.18	-10000	0	-0.35	148	148
HRAS/GDP	-0.15	0.2	-10000	0	-0.41	148	148
CREB1	-0.16	0.24	-10000	0	-0.48	129	129
RAC1-CDC42/GTP	-0.001	0.014	-10000	0	-0.27	1	1
AR	-0.2	0.28	-10000	0	-0.57	148	148
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	-0.088	0.15	-10000	0	-0.34	55	55
RAC1-CDC42/GDP	-0.14	0.19	-10000	0	-0.39	148	148
T-DHT/AR/PELP1/Src	-0.099	0.16	-10000	0	-0.32	148	148
MAP2K2	-0.086	0.15	-10000	0	-0.35	55	55
T-DHT/AR/PELP1/Src/PI3K	-0.07	0.14	-10000	0	-0.25	149	149
GNAZ	-0.11	0.24	-10000	0	-0.57	89	89
SHBG	0.015	0.003	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.16	0.25	-10000	0	-0.48	129	129
mol:T-DHT	0	0.001	-10000	0	-0.003	74	74
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	0.013	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.16	0.21	-10000	0	-0.41	137	137
CDC42	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.059	0.24	-10000	0	-0.63	49	49
IHH	-0.058	0.18	-10000	0	-0.52	52	52
SHH Np/Cholesterol/GAS1	-0.18	0.2	-10000	0	-0.34	221	221
LRPAP1	0.014	0.026	-10000	0	-0.51	1	1
dorsoventral neural tube patterning	0.18	0.2	0.34	221	-10000	0	221
SMO/beta Arrestin2	-0.05	0.17	-10000	0	-0.52	27	27
SMO	-0.061	0.18	-10000	0	-0.51	35	35
AKT1	-0.005	0.086	-10000	0	-0.34	5	5
ARRB2	0.016	0	-10000	0	-10000	0	0
BOC	-0.039	0.17	-10000	0	-0.57	38	38
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.06	0.18	-10000	0	-0.5	35	35
STIL	-0.15	0.22	-10000	0	-0.46	93	93
DHH N/PTCH2	-0.019	0.13	-10000	0	-0.42	38	38
DHH N/PTCH1	-0.037	0.16	-10000	0	-0.5	26	26
PIK3CA	0.016	0	-10000	0	-10000	0	0
DHH	-0.013	0.12	-10000	0	-0.57	19	19
PTHLH	-0.11	0.36	-10000	0	-1	49	49
determination of left/right symmetry	-0.06	0.18	-10000	0	-0.5	35	35
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
skeletal system development	-0.11	0.36	-10000	0	-1	49	49
IHH N/Hhip	-0.14	0.23	-10000	0	-0.48	121	121
DHH N/Hhip	-0.11	0.21	-10000	0	-0.42	121	121
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.06	0.18	-10000	0	-0.5	35	35
pancreas development	-0.14	0.26	-10000	0	-0.57	107	107
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	0.022	0.021	-10000	0	-0.41	1	1
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.12	0.25	-10000	0	-0.57	98	98
somite specification	-0.06	0.18	-10000	0	-0.5	35	35
SHH Np/Cholesterol/PTCH1	-0.12	0.19	-10000	0	-0.45	62	62
SHH Np/Cholesterol/PTCH2	-0.11	0.17	-10000	0	-0.32	163	163
SHH Np/Cholesterol/Megalin	-0.16	0.2	-10000	0	-0.35	198	198
SHH	-0.14	0.21	-10000	0	-0.41	150	150
catabolic process	-0.032	0.16	-10000	0	-0.52	20	20
SMO/Vitamin D3	-0.12	0.2	-10000	0	-0.46	66	66
SHH Np/Cholesterol/Hhip	-0.18	0.22	-10000	0	-0.38	212	212
LRP2	-0.094	0.21	-10000	0	-0.51	84	84
receptor-mediated endocytosis	-0.15	0.21	-10000	0	-0.46	91	91
SHH Np/Cholesterol/BOC	-0.13	0.18	-10000	0	-0.33	176	176
SHH Np/Cholesterol/CDO	-0.14	0.18	-10000	0	-0.33	194	194
mesenchymal cell differentiation	0.18	0.22	0.37	212	-10000	0	212
mol:Vitamin D3	-0.12	0.19	-10000	0	-0.45	62	62
IHH N/PTCH2	-0.043	0.15	-10000	0	-0.42	41	41
CDON	-0.066	0.2	-10000	0	-0.57	57	57
IHH N/PTCH1	-0.032	0.16	-10000	0	-0.53	20	20
Megalin/LRPAP1	-0.057	0.15	-10000	0	-0.36	85	85
PTCH2	-0.013	0.13	-10000	0	-0.57	20	20
SHH Np/Cholesterol	-0.11	0.16	-10000	0	-0.32	150	150
PTCH1	-0.033	0.16	-10000	0	-0.53	20	20
HHIP	-0.14	0.26	-10000	0	-0.57	107	107

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.56	-10000	0	-1.2	128	128
STAT6 (cleaved dimer)	-0.55	0.54	-10000	0	-1.2	151	151
IGHG1	-0.15	0.19	-10000	0	-0.39	51	51
IGHG3	-0.47	0.53	-10000	0	-1.1	140	140
AKT1	-0.21	0.31	-10000	0	-0.73	55	55
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.16	0.28	-10000	0	-0.73	41	41
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.32	-10000	0	-0.7	66	66
THY1	-0.48	0.56	-10000	0	-1.2	129	129
MYB	-0.058	0.18	-10000	0	-0.51	57	57
HMGA1	0.005	0.072	-10000	0	-0.51	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.39	-10000	0	-0.78	110	110
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.32	-10000	0	-0.68	70	70
SP1	0.023	0.009	-10000	0	-10000	0	0
INPP5D	0.006	0.076	-10000	0	-0.57	7	7
SOCS5	0.029	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.49	0.57	-10000	0	-1.2	135	135
SOCS1	-0.29	0.35	-10000	0	-0.75	104	104
SOCS3	-0.31	0.46	-10000	0	-1.3	53	53
FCER2	-0.72	0.73	-10000	0	-1.4	196	196
PARP14	0.01	0.014	-10000	0	-10000	0	0
CCL17	-0.51	0.55	-10000	0	-1.2	129	129
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.24	-10000	0	-0.64	35	35
T cell proliferation	-0.49	0.58	-10000	0	-1.2	134	134
IL4R/JAK1	-0.49	0.56	-10000	0	-1.2	129	129
EGR2	-0.67	0.72	-10000	0	-1.5	156	156
JAK2	-0.006	0.044	-10000	0	-0.61	1	1
JAK3	0.015	0.038	-10000	0	-0.52	2	2
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
JAK1	0.008	0.016	-10000	0	-10000	0	0
COL1A2	-0.2	0.4	-10000	0	-1.5	28	28
CCL26	-0.49	0.57	-10000	0	-1.2	131	131
IL4R	-0.52	0.6	-10000	0	-1.3	129	129
PTPN6	0.025	0.029	-10000	0	-0.5	1	1
IL13RA2	-0.51	0.58	-10000	0	-1.2	132	132
IL13RA1	-0.006	0.044	-10000	0	-0.61	1	1
IRF4	-0.24	0.47	-10000	0	-1.2	64	64
ARG1	-0.12	0.19	-10000	0	-0.9	7	7
CBL	-0.28	0.36	-10000	0	-0.73	106	106
GTF3A	0.024	0.005	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.01	0.057	-10000	0	-0.45	2	2
IRF4/BCL6	-0.19	0.43	-10000	0	-1.1	62	62
CD40LG	-0.051	0.18	-10000	0	-0.57	45	45
MAPK14	-0.29	0.41	-10000	0	-0.9	81	81
mitosis	-0.2	0.29	-10000	0	-0.68	55	55
STAT6	-0.58	0.7	-10000	0	-1.4	139	139
SPI1	0.002	0.092	-10000	0	-0.54	11	11
RPS6KB1	-0.19	0.28	-10000	0	-0.67	49	49
STAT6 (dimer)	-0.58	0.7	-10000	0	-1.4	139	139
STAT6 (dimer)/PARP14	-0.56	0.63	-10000	0	-1.2	155	155
mast cell activation	0.011	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.33	-10000	0	-0.78	54	54
FRAP1	-0.21	0.31	-10000	0	-0.73	55	55
LTA	-0.5	0.58	-10000	0	-1.2	127	127
FES	0.014	0.029	-10000	0	-0.57	1	1
T-helper 1 cell differentiation	0.55	0.65	1.3	139	-10000	0	139
CCL11	-0.51	0.59	-10000	0	-1.2	130	130
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.22	0.32	-10000	0	-0.75	53	53
IL2RG	-0.008	0.12	-10000	0	-0.54	19	19
IL10	-0.51	0.59	-10000	0	-1.3	127	127
IRS1	0.001	0.09	-10000	0	-0.57	10	10
IRS2	-0.007	0.11	-10000	0	-0.57	16	16
IL4	-0.1	0.13	-10000	0	-10000	0	0
IL5	-0.49	0.56	-10000	0	-1.2	122	122
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.38	0.42	-10000	0	-0.87	130	130
COL1A1	-0.17	0.32	-10000	0	-1.4	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.5	0.58	-10000	0	-1.2	124	124
IL2R gamma/JAK3	0	0.096	-10000	0	-0.42	19	19
TFF3	-0.65	0.7	-10000	0	-1.4	160	160
ALOX15	-0.53	0.57	-10000	0	-1.2	135	135
MYBL1	0.011	0.051	-10000	0	-0.51	4	4
T-helper 2 cell differentiation	-0.41	0.46	-10000	0	-0.95	135	135
SHC1	0.014	0.026	-10000	0	-0.51	1	1
CEBPB	0.016	0.032	-10000	0	-0.57	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.31	-10000	0	-0.67	68	68
mol:PI-3-4-5-P3	-0.21	0.31	-10000	0	-0.73	55	55
PI3K	-0.22	0.33	-10000	0	-0.8	53	53
DOK2	-0.006	0.11	-10000	0	-0.56	15	15
ETS1	0.027	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.15	0.23	-10000	0	-0.63	29	29
ITGB3	-0.54	0.64	-10000	0	-1.3	135	135
PIGR	-0.78	0.72	-10000	0	-1.4	208	208
IGHE	0.033	0.048	-10000	0	-0.22	1	1
MAPKKK cascade	-0.15	0.23	-10000	0	-0.62	29	29
BCL6	0.021	0.01	-10000	0	-10000	0	0
OPRM1	-0.49	0.55	-10000	0	-1.2	126	126
RETNLB	-0.49	0.56	-10000	0	-1.2	126	126
SELP	-0.62	0.7	-10000	0	-1.4	150	150
AICDA	-0.47	0.53	-10000	0	-1.1	126	126

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.009	0.23	-10000	0	-0.54	48	48
PTK2B	0.014	0.029	-10000	0	-0.57	1	1
mol:Ca2+	-0.013	0.22	-10000	0	-0.67	27	27
EDN1	0.04	0.12	-10000	0	-0.43	12	12
EDN3	-0.004	0.067	-10000	0	-0.51	7	7
EDN2	-0.055	0.18	-10000	0	-0.53	52	52
HRAS/GDP	-0.072	0.24	-10000	0	-0.49	73	73
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.028	0.19	-10000	0	-0.41	55	55
ADCY4	-0.15	0.26	-10000	0	-0.59	70	70
ADCY5	-0.3	0.33	-10000	0	-0.64	163	163
ADCY6	-0.15	0.26	-10000	0	-0.59	71	71
ADCY7	-0.15	0.26	-10000	0	-0.57	75	75
ADCY1	-0.16	0.26	-10000	0	-0.61	74	74
ADCY2	-0.26	0.31	-10000	0	-0.64	135	135
ADCY3	-0.15	0.26	-10000	0	-0.59	71	71
ADCY8	-0.16	0.26	-10000	0	-0.58	74	74
ADCY9	-0.15	0.27	-10000	0	-0.61	70	70
arachidonic acid secretion	-0.13	0.29	-10000	0	-0.5	115	115
ETB receptor/Endothelin-1/Gq/GTP	-0.041	0.19	-10000	0	-0.5	41	41
GNAO1	-0.17	0.27	-10000	0	-0.57	129	129
HRAS	0.013	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.039	0.26	0.26	135	-0.51	45	180
ETA receptor/Endothelin-1/Gs/GTP	-0.12	0.32	0.24	95	-0.6	77	172
mol:GTP	-0.001	0.006	-10000	0	-10000	0	0
COL3A1	-0.021	0.27	-10000	0	-0.64	47	47
EDNRB	-0.052	0.19	-10000	0	-0.57	47	47
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.014	0.24	-10000	0	-0.52	53	53
CYSLTR1	-0.03	0.28	-10000	0	-0.63	57	57
SLC9A1	-0.003	0.13	-10000	0	-0.33	26	26
mol:GDP	-0.085	0.25	-10000	0	-0.52	76	76
SLC9A3	-0.029	0.23	-10000	0	-0.61	42	42
RAF1	-0.13	0.28	-10000	0	-0.52	106	106
JUN	-0.035	0.29	-10000	0	-0.89	33	33
JAK2	-0.01	0.24	-10000	0	-0.55	46	46
mol:IP3	-0.05	0.21	-10000	0	-0.48	56	56
ETA receptor/Endothelin-1	0.029	0.31	0.29	177	-0.56	64	241
PLCB1	-0.004	0.099	-10000	0	-0.57	12	12
PLCB2	0.009	0.042	-10000	0	-0.57	2	2
ETA receptor/Endothelin-3	-0.04	0.2	-10000	0	-0.46	66	66
FOS	-0.28	0.48	-10000	0	-0.94	136	136
Gai/GDP	-0.26	0.41	-10000	0	-0.84	129	129
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.076	0.28	-10000	0	-0.59	74	74
BCAR1	0.016	0.001	-10000	0	-10000	0	0
PRKCB1	-0.051	0.2	-10000	0	-0.46	59	59
GNAQ	0.014	0.009	-10000	0	-10000	0	0
GNAZ	-0.11	0.24	-10000	0	-0.57	89	89
GNAL	-0.24	0.29	-10000	0	-0.57	178	178
Gs family/GDP	-0.22	0.25	-10000	0	-0.51	145	145
ETA receptor/Endothelin-1/Gq/GTP	-0.031	0.22	-10000	0	-0.48	50	50
MAPK14	-0.026	0.16	-10000	0	-0.48	33	33
TRPC6	-0.016	0.23	-10000	0	-0.71	27	27
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.05	-10000	0	-0.57	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.035	0.17	-10000	0	-0.46	42	42
ETB receptor/Endothelin-2	-0.076	0.19	-10000	0	-0.43	90	90
ETB receptor/Endothelin-3	-0.04	0.14	-10000	0	-0.41	54	54
ETB receptor/Endothelin-1	-0.011	0.17	-10000	0	-0.4	56	56
MAPK3	-0.24	0.42	-10000	0	-0.79	140	140
MAPK1	-0.24	0.42	-10000	0	-0.78	141	141
Rac1/GDP	-0.071	0.24	-10000	0	-0.48	73	73
cAMP biosynthetic process	-0.24	0.29	-10000	0	-0.52	178	178
MAPK8	-0.031	0.26	-10000	0	-0.69	37	37
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.11	0.22	-10000	0	-0.43	99	99
p130Cas/CRK/Src/PYK2	-0.064	0.24	-10000	0	-0.54	60	60
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.071	0.24	-10000	0	-0.48	73	73
COL1A2	-0.062	0.35	-10000	0	-0.96	43	43
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.081	0.22	-10000	0	-0.43	107	107
mol:DAG	-0.05	0.21	-10000	0	-0.48	56	56
MAP2K2	-0.18	0.33	-10000	0	-0.58	144	144
MAP2K1	-0.18	0.33	-10000	0	-0.58	144	144
EDNRA	-0.037	0.26	-10000	0	-0.64	59	59
positive regulation of muscle contraction	0	0.21	-10000	0	-0.48	44	44
Gq family/GDP	-0.13	0.2	-10000	0	-0.52	70	70
HRAS/GTP	-0.1	0.24	-10000	0	-0.5	83	83
PRKCH	-0.043	0.2	-10000	0	-0.49	50	50
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	-0.046	0.2	-10000	0	-0.48	56	56
PRKCB	-0.13	0.26	-10000	0	-0.5	111	111
PRKCE	-0.042	0.2	-10000	0	-0.49	49	49
PRKCD	-0.044	0.2	-10000	0	-0.48	52	52
PRKCG	-0.057	0.2	-10000	0	-0.48	57	57
regulation of vascular smooth muscle contraction	-0.34	0.56	-10000	0	-1.1	136	136
PRKCQ	-0.072	0.23	-10000	0	-0.5	70	70
PLA2G4A	-0.14	0.31	-10000	0	-0.55	115	115
GNA14	-0.069	0.2	-10000	0	-0.57	58	58
GNA15	0.011	0.05	-10000	0	-0.57	3	3
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.03	-10000	0	-0.57	1	1
Rac1/GTP	0.039	0.26	0.26	144	-0.51	45	189
MMP1	-0.19	0.23	-10000	0	-0.4	186	186

×

Reelin signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.003	0.086	-9999	-0.36	22	22
VLDLR	0.001	0.09	-9999	-0.57	10	10
CRKL	0.013	0.036	-9999	-0.51	2	2
LRPAP1	0.014	0.026	-9999	-0.51	1	1
FYN	0.011	0.05	-9999	-0.57	3	3
ITGA3	0.007	0.068	-9999	-0.51	7	7
RELN/VLDLR/Fyn	-0.11	0.18	-9999	-0.34	157	157
MAPK8IP1/MKK7/MAP3K11/JNK1	0.041	0.041	-9999	-10000	0	0
AKT1	-0.092	0.15	-9999	-0.42	29	29
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.07	0.2	-9999	-0.54	59	59
RELN/LRP8/DAB1	-0.19	0.23	-9999	-0.38	218	218
LRPAP1/LRP8	-0.048	0.15	-9999	-0.36	77	77
RELN/LRP8/DAB1/Fyn	-0.18	0.22	-9999	-0.38	176	176
DAB1/alpha3/beta1 Integrin	-0.17	0.19	-9999	-0.51	70	70
long-term memory	-0.23	0.27	-9999	-0.61	106	106
DAB1/LIS1	-0.18	0.19	-9999	-0.53	66	66
DAB1/CRLK/C3G	-0.17	0.19	-9999	-0.51	67	67
PIK3CA	0.016	0	-9999	-10000	0	0
DAB1/NCK2	-0.18	0.2	-9999	-0.54	66	66
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.12	0.24	-9999	-0.57	92	92
CDK5R1	-0.013	0.12	-9999	-0.51	22	22
RELN	-0.2	0.28	-9999	-0.57	147	147
PIK3R1	0.014	0.029	-9999	-0.57	1	1
RELN/LRP8/Fyn	-0.16	0.22	-9999	-0.38	191	191
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.24	0.27	-9999	-0.63	101	101
MAPK8	0.011	0.05	-9999	-0.57	3	3
RELN/VLDLR/DAB1	-0.15	0.2	-9999	-0.35	189	189
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.2	0.24	-9999	-0.41	196	196
RELN/LRP8	-0.16	0.22	-9999	-0.38	189	189
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.18	0.22	-9999	-0.57	63	63
PI3K	0.022	0.021	-9999	-0.41	1	1
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.017	0.049	-9999	-0.36	7	7
RAP1A	-0.13	0.2	-9999	-0.48	67	67
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.01	0.056	-9999	-0.55	4	4
CRLK/C3G	0.021	0.026	-9999	-0.36	2	2
GRIN2B	-0.011	0.09	-9999	-0.51	13	13
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.077	0.14	-9999	-0.32	58	58
neuron adhesion	-0.12	0.2	-9999	-0.44	71	71
LRP8	-0.082	0.2	-9999	-0.51	76	76
GSK3B	-0.079	0.15	-9999	-0.41	27	27
RELN/VLDLR/DAB1/Fyn	-0.13	0.19	-9999	-0.33	173	173
MAP3K11	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.11	0.16	-9999	-0.28	171	171
CDK5	0.016	0	-9999	-10000	0	0
MAPT	-0.022	0.16	-9999	-0.51	36	36
neuron migration	-0.13	0.21	-9999	-0.46	69	69
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.078	0.14	-9999	-0.32	58	58
RELN/VLDLR	-0.14	0.21	-9999	-0.36	163	163

×

TCGA08_p53

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
CDKN2A	-0.18	0.19	-10000	0	-0.37	205	205
TP53	-0.043	0.06	-10000	0	-10000	0	0
Senescence	-0.043	0.06	-10000	0	-10000	0	0
Apoptosis	-0.043	0.06	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.081	0.12	0.19	198	-0.32	13	211
MDM4	0.016	0	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.056	0.2	-10000	0	-0.4	91	91
CRKL	-0.059	0.2	-10000	0	-0.42	90	90
HRAS	-0.054	0.21	-10000	0	-0.46	46	46
mol:PIP3	-0.07	0.18	-10000	0	-0.4	90	90
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	-0.07	0.2	-10000	0	-0.44	90	90
FOXO3	-0.048	0.18	-10000	0	-0.38	90	90
AKT1	-0.061	0.2	-10000	0	-0.41	90	90
BAD	-0.048	0.18	-10000	0	-0.38	90	90
megakaryocyte differentiation	-0.075	0.21	-10000	0	-0.44	94	94
GSK3B	-0.048	0.18	-10000	0	-0.38	90	90
RAF1	-0.032	0.17	-10000	0	-0.41	32	32
SHC1	0.014	0.026	-10000	0	-0.51	1	1
STAT3	-0.07	0.2	-10000	0	-0.44	91	91
STAT1	-0.19	0.47	-10000	0	-1	98	98
HRAS/SPRED1	-0.034	0.17	-10000	0	-0.41	32	32
cell proliferation	-0.07	0.21	-10000	0	-0.44	90	90
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	-0.069	0.2	-10000	0	-0.44	91	91
HRAS/SPRED2	-0.034	0.17	-10000	0	-0.38	39	39
LYN/TEC/p62DOK	-0.084	0.18	-10000	0	-0.41	90	90
MAPK3	-0.007	0.13	-10000	0	-0.29	25	25
STAP1	-0.087	0.22	-10000	0	-0.46	91	91
GRAP2	-0.049	0.18	-10000	0	-0.57	45	45
JAK2	-0.2	0.37	-10000	0	-0.87	92	92
STAT1 (dimer)	-0.18	0.46	-10000	0	-0.98	98	98
mol:Gleevec	0.001	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.095	0.19	-10000	0	-0.42	93	93
actin filament polymerization	-0.071	0.2	-10000	0	-0.43	92	92
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.11	0.29	-10000	0	-0.62	92	92
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
CBL/CRKL/GRB2	-0.038	0.18	-10000	0	-0.37	90	90
PI3K	-0.053	0.2	-10000	0	-0.41	90	90
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.24	0.56	-10000	0	-1.3	91	91
MAPK8	-0.072	0.21	-10000	0	-0.45	90	90
STAT3 (dimer)	-0.068	0.2	-10000	0	-0.43	91	91
positive regulation of transcription	-0.001	0.11	-10000	0	-0.24	25	25
mol:GDP	-0.063	0.21	-10000	0	-0.41	99	99
PIK3C2B	-0.07	0.2	-10000	0	-0.44	90	90
CBL/CRKL	-0.047	0.19	-10000	0	-0.39	90	90
FER	-0.072	0.21	-10000	0	-0.45	90	90
SH2B3	-0.07	0.2	-10000	0	-0.44	91	91
PDPK1	-0.057	0.17	-10000	0	-0.37	90	90
SNAI2	-0.076	0.21	-10000	0	-0.45	91	91
positive regulation of cell proliferation	-0.13	0.34	-10000	0	-0.74	93	93
KITLG	0.009	0.068	-10000	0	-0.59	5	5
cell motility	-0.13	0.34	-10000	0	-0.74	93	93
PTPN6	0.017	0.029	-10000	0	-0.52	1	1
EPOR	-0.02	0.15	-10000	0	-0.56	2	2
STAT5A (dimer)	-0.1	0.29	-10000	0	-0.62	92	92
SOCS1	0.014	0.026	-10000	0	-0.51	1	1
cell migration	0.088	0.22	0.46	95	-10000	0	95
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.028	0.14	-10000	0	-0.51	31	31
VAV1	-0.01	0.12	-10000	0	-0.56	18	18
GRB10	-0.073	0.21	-10000	0	-0.45	90	90
PTPN11	0.017	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.082	0.22	-10000	0	-0.47	91	91
GO:0007205	0.003	0.011	-10000	0	-10000	0	0
MAP2K1	-0.014	0.14	-10000	0	-0.32	25	25
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-0.26	0.59	-10000	0	-1.4	90	90
MAP2K2	-0.014	0.14	-10000	0	-0.31	30	30
SHC/Grb2/SOS1	-0.084	0.18	-10000	0	-0.41	90	90
STAT5A	-0.1	0.3	-10000	0	-0.64	91	91
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	-0.074	0.21	-10000	0	-0.44	91	91
SHC/GRAP2	-0.025	0.14	-10000	0	-0.41	46	46
PTPRO	-0.077	0.21	-10000	0	-0.45	94	94
SH2B2	-0.073	0.21	-10000	0	-0.44	92	92
DOK1	0.014	0.026	-10000	0	-0.51	1	1
MATK	-0.09	0.22	-10000	0	-0.47	95	95
CREBBP	0.034	0.02	-10000	0	-10000	0	0
BCL2	-0.058	0.31	-10000	0	-1.4	16	16

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.013	0.12	-10000	0	-0.55	20	20
GNB1/GNG2	-0.08	0.089	-10000	0	-0.18	168	168
AKT1	-0.043	0.13	-10000	0	-0.2	115	115
EGF	-0.018	0.12	-10000	0	-0.51	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.036	0.056	-10000	0	-0.37	1	1
mol:Ca2+	-0.087	0.18	-10000	0	-0.3	166	166
LYN	0.037	0.053	-10000	0	-0.37	1	1
RhoA/GTP	-0.052	0.059	-10000	0	-0.13	34	34
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.1	0.21	-10000	0	-0.34	166	166
GNG2	0.007	0.07	-10000	0	-0.57	6	6
ARRB2	0.016	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.015	0.074	-10000	0	-0.38	5	5
G beta5/gamma2	-0.1	0.12	-10000	0	-0.24	168	168
PRKCH	-0.1	0.21	-10000	0	-0.34	166	166
DNM1	0	0.095	-10000	0	-0.57	11	11
TXA2/TP beta/beta Arrestin3	-0.008	0.04	-10000	0	-0.25	10	10
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.013	0.12	-10000	0	-0.57	19	19
G12 family/GTP	-0.13	0.14	-10000	0	-0.3	166	166
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.013	0.039	-10000	0	-0.54	2	2
RhoA/GTP/ROCK1	0.012	0.011	-10000	0	-10000	0	0
mol:GDP	0.038	0.12	0.3	14	-10000	0	14
mol:NADP	0.014	0.026	-10000	0	-0.51	1	1
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	-0.12	0.25	-10000	0	-0.57	94	94
mol:IP3	-0.12	0.22	-10000	0	-0.37	166	166
cell morphogenesis	0.011	0.011	-10000	0	-10000	0	0
PLCB2	-0.17	0.29	-10000	0	-0.5	166	166
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.002	0.098	-10000	0	-0.39	3	3
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.027	0.08	-10000	0	-0.4	6	6
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.014	0.029	-10000	0	-0.57	1	1
PRKCB1	-0.12	0.22	-10000	0	-0.37	166	166
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.014	0.026	-10000	0	-0.51	1	1
TXA2/TXA2-R family	-0.18	0.3	-10000	0	-0.53	166	166
LCK	0.034	0.063	-10000	0	-0.39	2	2
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.011	0.047	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.032	0.03	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.046	-10000	0	-10000	0	0
MAPK14	-0.055	0.15	-10000	0	-0.22	166	166
TGM2/GTP	-0.14	0.25	-10000	0	-0.42	166	166
MAPK11	-0.055	0.15	-10000	0	-0.23	115	115
ARHGEF1	-0.042	0.11	-10000	0	-0.18	106	106
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	-0.12	0.23	-10000	0	-0.39	166	166
RAB11/GDP	0.016	0.002	-10000	0	-10000	0	0
ICAM1	-0.08	0.17	-10000	0	-0.28	168	168
cAMP biosynthetic process	-0.11	0.21	-10000	0	-0.35	166	166
Gq family/GTP/EBP50	-0.005	0.088	-10000	0	-0.3	13	13
actin cytoskeleton reorganization	0.011	0.011	-10000	0	-10000	0	0
SRC	0.037	0.053	-10000	0	-0.37	1	1
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	0.035	0.075	-10000	0	-0.29	4	4
VCAM1	-0.09	0.19	-10000	0	-0.3	166	166
TP beta/Gq family/GDP/G beta5/gamma2	0.015	0.074	-10000	0	-0.38	5	5
platelet activation	-0.075	0.2	-10000	0	-0.3	166	166
PGI2/IP	0.01	0.021	-10000	0	-0.42	1	1
PRKACA	0.009	0.064	-10000	0	-0.27	20	20
Gq family/GDP/G beta5/gamma2	0.013	0.074	-10000	0	-0.36	5	5
TXA2/TP beta/beta Arrestin2	-0.015	0.087	-10000	0	-0.54	11	11
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.016	0.063	-10000	0	-0.25	21	21
mol:DAG	-0.13	0.24	-10000	0	-0.42	166	166
EGFR	-0.008	0.11	-10000	0	-0.54	17	17
TXA2/TP alpha	-0.16	0.28	-10000	0	-0.48	166	166
Gq family/GTP	-0.033	0.084	-10000	0	-0.23	61	61
YES1	0.037	0.053	-10000	0	-0.37	1	1
GNAI2/GTP	-0.011	0.047	-10000	0	-0.43	1	1
PGD2/DP	-0.01	0.09	-10000	0	-0.42	19	19
SLC9A3R1	-0.011	0.12	-10000	0	-0.51	21	21
FYN	0.036	0.059	-10000	0	-0.39	2	2
mol:NO	0.014	0.026	-10000	0	-0.51	1	1
GNA15	0.011	0.05	-10000	0	-0.57	3	3
PGK/cGMP	-0.066	0.16	-10000	0	-0.35	95	95
RhoA/GDP	0.016	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.022	0.1	-10000	0	-0.54	6	6
NOS3	0.014	0.026	-10000	0	-0.51	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	-0.1	0.21	-10000	0	-0.34	168	168
PRKCB	-0.15	0.24	-10000	0	-0.42	167	167
PRKCE	-0.098	0.21	-10000	0	-0.34	166	166
PRKCD	-0.12	0.22	-10000	0	-0.38	166	166
PRKCG	-0.12	0.23	-10000	0	-0.38	166	166
muscle contraction	-0.16	0.28	-10000	0	-0.49	166	166
PRKCZ	-0.099	0.21	-10000	0	-0.34	166	166
ARR3	0.003	0.006	-10000	0	-10000	0	0
TXA2/TP beta	0.012	0.063	-10000	0	-0.48	1	1
PRKCQ	-0.12	0.22	-10000	0	-0.36	166	166
MAPKKK cascade	-0.15	0.27	-10000	0	-0.46	166	166
SELE	-0.13	0.24	-10000	0	-0.41	168	168
TP beta/GNAI2/GDP/G beta/gamma	0.035	0.067	-10000	0	-0.47	1	1
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	-0.068	0.2	-10000	0	-0.57	58	58
chemotaxis	-0.21	0.35	-10000	0	-0.62	166	166
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.029	-10000	0	-0.57	1	1
Rac1/GTP	0.007	0.006	-10000	0	-10000	0	0

×

Aurora C signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.014	0.026	-9999	-0.51	1	1
Aurora C/Aurora B/INCENP	-0.11	0.15	-9999	-0.27	194	194
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.035	0.037	-9999	-10000	0	0
AURKB	-0.22	0.26	-9999	-0.51	184	184
AURKC	-0.001	0.092	-9999	-0.51	13	13

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	0.051	0.067	0.13	172	-10000	0	172
BUB1B	-0.082	0.12	-10000	0	-0.23	142	142
PLK1	-0.021	0.051	-10000	0	-0.11	82	82
PLK1S1	-0.004	0.027	-10000	0	-10000	0	0
KIF2A	-0.009	0.046	-10000	0	-0.18	1	1
regulation of mitotic centrosome separation	-0.021	0.051	-10000	0	-0.11	82	82
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.18	0.24	-10000	0	-0.41	195	195
WEE1	-0.017	0.055	-10000	0	-10000	0	0
cytokinesis	-0.14	0.11	-10000	0	-0.25	153	153
PP2A-alpha B56	0.017	0.04	-10000	0	-10000	0	0
AURKA	-0.02	0.049	-10000	0	-0.11	7	7
PICH/PLK1	-0.11	0.19	-10000	0	-0.37	115	115
CENPE	-0.068	0.14	-10000	0	-0.33	86	86
RhoA/GTP	0.012	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.009	0.046	-10000	0	-0.18	1	1
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.016	0	-10000	0	-10000	0	0
TPX2	-0.038	0.052	-10000	0	-0.1	111	111
PAK1	0.013	0.029	-10000	0	-0.58	1	1
SPC24	-0.18	0.25	-10000	0	-0.51	153	153
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.034	0.058	-10000	0	-0.13	69	69
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.011	80	80
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.01	0.026	-10000	0	-0.054	79	79
G2 phase of mitotic cell cycle	-0.002	0.003	-10000	0	-0.008	61	61
STAG2	0.013	0.041	-10000	0	-0.57	2	2
GRASP65/GM130/RAB1/GTP	0.006	0.011	-10000	0	-10000	0	0
spindle elongation	-0.021	0.051	-10000	0	-0.11	82	82
ODF2	0.013	0.003	-10000	0	-10000	0	0
BUB1	-0.017	0.036	-10000	0	-10000	0	0
TPT1	-0.004	0.027	-10000	0	-10000	0	0
CDC25C	-0.058	0.061	-10000	0	-0.14	80	80
CDC25B	0.006	0.063	-10000	0	-0.51	6	6
SGOL1	-0.051	0.067	-10000	0	-0.13	172	172
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.077	0.11	-10000	0	-0.24	91	91
CDC14B	0.011	0.022	-10000	0	-0.43	1	1
CDC20	-0.28	0.26	-10000	0	-0.51	231	231
PLK1/PBIP1	-0.033	0.063	-10000	0	-0.29	16	16
mitosis	-0.002	0.01	0.02	35	-0.017	46	81
FBXO5	-0.012	0.048	-10000	0	-0.23	3	3
CDC2	-0.003	0.006	-10000	0	-0.011	95	95
NDC80	-0.16	0.25	-10000	0	-0.51	135	135
metaphase plate congression	-0.008	0.033	-10000	0	-0.1	1	1
ERCC6L	-0.096	0.18	-10000	0	-0.38	87	87
NLP/gamma Tubulin	-0.006	0.027	-10000	0	-0.097	2	2
microtubule cytoskeleton organization	-0.004	0.026	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-10000	0	0
PPP1R12A	0.015	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.25	0.2	-10000	0	-0.34	302	302
GRASP65/GM130/RAB1/GTP/PLK1	0.009	0.04	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.014	0.049	-10000	0	-0.22	2	2
mitotic prometaphase	-0.003	0.003	-10000	0	-0.008	43	43
proteasomal ubiquitin-dependent protein catabolic process	-0.015	0.051	-10000	0	-0.3	1	1
microtubule-based process	-0.22	0.15	-10000	0	-0.3	300	300
Golgi organization	-0.021	0.051	-10000	0	-0.11	82	82
Cohesin/SA2	-0.026	0.039	-10000	0	-0.25	3	3
PPP1CB/MYPT1	0.018	0.009	-10000	0	-10000	0	0
KIF20A	-0.37	0.23	-10000	0	-0.51	300	300
APC/C/CDC20	-0.17	0.17	-10000	0	-0.32	231	231
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.032	0.062	-10000	0	-0.29	16	16
PRC1	-0.086	0.21	-10000	0	-0.51	79	79
ECT2	-0.038	0.11	-10000	0	-0.34	43	43
C13orf34	-0.011	0.046	-10000	0	-0.22	2	2
NUDC	-0.008	0.033	-10000	0	-0.11	1	1
regulation of attachment of spindle microtubules to kinetochore	-0.081	0.12	-10000	0	-0.23	142	142
spindle assembly	-0.012	0.04	-10000	0	-0.085	45	45
spindle stabilization	-0.004	0.026	-10000	0	-10000	0	0
APC/C/HCDH1	0.019	0.019	-10000	0	-0.35	1	1
MKLP2/PLK1	-0.22	0.15	-10000	0	-0.3	300	300
CCNB1	-0.17	0.25	-10000	0	-0.5	145	145
PPP1CB	0.015	0.001	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	-0.007	0.065	-10000	0	-0.43	7	7
TUBG1	-0.004	0.027	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.078	0.1	-10000	0	-0.24	91	91
MLF1IP	-0.006	0.073	-10000	0	-0.38	15	15
INCENP	0.014	0.026	-10000	0	-0.51	1	1

×

IGF1 pathway

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
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	-0.11	0.16	-10000	0	-0.29	185	185
GRB2/SOS1/SHC	0.031	0.016	-10000	0	-0.29	1	1
HRAS	0.016	0	-10000	0	-10000	0	0
IRS1/Crk	-0.11	0.16	-10000	0	-0.29	183	183
IGF-1R heterotetramer/IGF1/PTP1B	-0.14	0.16	-10000	0	-0.32	183	183
AKT1	-0.074	0.14	-10000	0	-0.45	10	10
BAD	-0.062	0.14	-10000	0	-0.42	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.11	0.16	-10000	0	-0.29	183	183
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.16	-10000	0	-0.29	183	183
RAF1	-0.054	0.13	-10000	0	-0.39	10	10
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.098	0.16	-10000	0	-0.51	9	9
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.18	-10000	0	-0.32	186	186
PIK3CA	0.016	0	-10000	0	-10000	0	0
RPS6KB1	-0.074	0.14	-10000	0	-0.45	10	10
GNB2L1	0.016	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.05	0.12	-10000	0	-0.34	10	10
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.12	-10000	0	-0.46	10	10
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.084	0.14	-10000	0	-0.51	3	3
IGF-1R heterotetramer	-0.022	0.064	-10000	0	-0.63	3	3
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.11	0.16	-10000	0	-0.29	183	183
Crk/p130 Cas/Paxillin	-0.087	0.15	-10000	0	-0.49	9	9
IGF1R	-0.022	0.064	-10000	0	-0.63	3	3
IGF1	-0.25	0.3	-10000	0	-0.58	182	182
IRS2/Crk	-0.11	0.18	-10000	0	-0.52	25	25
PI3K	-0.098	0.16	-10000	0	-0.51	10	10
apoptosis	0.047	0.12	0.36	10	-10000	0	10
HRAS/GDP	0.012	0	-10000	0	-10000	0	0
PRKCD	-0.14	0.21	-10000	0	-0.37	182	182
RAF1/14-3-3 E	-0.04	0.12	-10000	0	-0.34	11	11
BAD/14-3-3	-0.05	0.13	-10000	0	-0.38	10	10
PRKCZ	-0.076	0.14	-10000	0	-0.46	12	12
Crk/p130 Cas/Paxillin/FAK1	-0.08	0.093	-10000	0	-0.38	10	10
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.16	0.22	-10000	0	-0.4	183	183
BCAR1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.16	-10000	0	-0.44	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.11	0.16	-10000	0	-0.29	183	183
GRB10	0.008	0.064	-10000	0	-0.57	5	5
PTPN11	-0.11	0.16	-10000	0	-0.29	183	183
IRS1	-0.13	0.18	-10000	0	-0.32	186	186
IRS2	-0.12	0.18	-10000	0	-0.31	184	184
IGF-1R heterotetramer/IGF1	-0.18	0.23	-10000	0	-0.43	183	183
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	-0.086	0.15	-10000	0	-0.48	10	10
YWHAE	0.014	0.029	-10000	0	-0.57	1	1
PRKD1	-0.15	0.23	-10000	0	-0.4	182	182
SHC1	0.014	0.026	-10000	0	-0.51	1	1

×

TCGA08_retinoblastoma

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
CDKN2B	-0.029	0.15	-10000	0	-0.54	33	33
CDKN2C	0.039	0.045	-10000	0	-0.46	2	2
CDKN2A	-0.26	0.27	-10000	0	-0.52	205	205
CCND2	0.053	0.079	0.23	35	-0.15	9	44
RB1	-0.052	0.086	0.16	2	-0.24	34	36
CDK4	0.069	0.08	0.24	36	-10000	0	36
CDK6	0.06	0.086	0.25	34	-0.18	7	41
G1/S progression	0.052	0.086	0.24	34	-0.16	2	36

×

IL23-mediated signaling events

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
CCL2	-0.33	0.54	-10000	0	-1.2	84	84
IL23A	-0.29	0.46	-10000	0	-1.1	77	77
NF kappa B1 p50/RelA/I kappa B alpha	-0.32	0.39	-10000	0	-0.94	94	94
positive regulation of T cell mediated cytotoxicity	-0.31	0.5	-10000	0	-1.1	92	92
ITGA3	-0.27	0.44	-10000	0	-0.99	78	78
IL17F	-0.18	0.31	-10000	0	-0.66	76	76
IL12B	-0.014	0.1	-10000	0	-0.52	14	14
STAT1 (dimer)	-0.3	0.47	-10000	0	-1	88	88
CD4	-0.27	0.44	-10000	0	-1	73	73
IL23	-0.29	0.44	-10000	0	-1	77	77
IL23R	-0.029	0.089	-10000	0	-10000	0	0
IL1B	-0.3	0.49	-10000	0	-1.1	80	80
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.29	0.44	-10000	0	-0.99	79	79
TYK2	0.008	0.021	-10000	0	-10000	0	0
STAT4	-0.013	0.13	-10000	0	-0.57	20	20
STAT3	0.016	0	-10000	0	-10000	0	0
IL18RAP	-0.017	0.13	-10000	0	-0.57	21	21
IL12RB1	-0.032	0.15	-10000	0	-0.54	30	30
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.022	0.11	-10000	0	-0.4	30	30
IL23R/JAK2	-0.034	0.11	-10000	0	-0.47	1	1
positive regulation of chronic inflammatory response	-0.31	0.5	-10000	0	-1.1	92	92
natural killer cell activation	0.003	0.008	-10000	0	-10000	0	0
JAK2	0.013	0.04	-10000	0	-0.6	1	1
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
NFKB1	0.014	0.004	-10000	0	-10000	0	0
RELA	0.014	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.27	0.42	-10000	0	-0.96	78	78
ALOX12B	-0.28	0.44	-10000	0	-0.98	80	80
CXCL1	-0.33	0.52	-10000	0	-1.1	96	96
T cell proliferation	-0.31	0.5	-10000	0	-1.1	92	92
NFKBIA	0.014	0.004	-10000	0	-10000	0	0
IL17A	-0.12	0.25	-10000	0	-0.54	56	56
PI3K	-0.32	0.41	-10000	0	-0.97	92	92
IFNG	-0.017	0.035	0.1	1	-0.088	6	7
STAT3 (dimer)	-0.31	0.38	-10000	0	-0.94	86	86
IL18R1	0.009	0.05	-10000	0	-0.57	3	3
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.31	-10000	0	-0.7	62	62
IL18/IL18R	0.003	0.11	-10000	0	-0.37	27	27
macrophage activation	-0.018	0.017	-10000	0	-0.042	78	78
TNF	-0.29	0.46	-10000	0	-1	77	77
STAT3/STAT4	-0.33	0.42	-10000	0	-0.98	96	96
STAT4 (dimer)	-0.31	0.49	-10000	0	-1.1	89	89
IL18	0.005	0.07	-10000	0	-0.57	6	6
IL19	-0.28	0.44	-10000	0	-0.97	84	84
STAT5A (dimer)	-0.3	0.47	-10000	0	-1	87	87
STAT1	0.011	0.051	-10000	0	-0.51	4	4
SOCS3	-0.046	0.18	-10000	0	-0.57	43	43
CXCL9	-0.32	0.46	-10000	0	-1	81	81
MPO	-0.27	0.43	-10000	0	-0.98	77	77
positive regulation of humoral immune response	-0.31	0.5	-10000	0	-1.1	92	92
IL23/IL23R/JAK2/TYK2	-0.33	0.53	-10000	0	-1.1	90	90
IL6	-0.61	0.68	-10000	0	-1.3	199	199
STAT5A	0.014	0.029	-10000	0	-0.57	1	1
IL2	0.004	0.013	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.003	0.008	-10000	0	-10000	0	0
CD3E	-0.32	0.52	-10000	0	-1.2	85	85
keratinocyte proliferation	-0.31	0.5	-10000	0	-1.1	92	92
NOS2	-0.29	0.45	-10000	0	-0.99	87	87

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.047	0.14	-9999	-0.36	69	69
EFNA5	-0.006	0.11	-9999	-0.56	15	15
FYN	-0.035	0.13	-9999	-0.31	72	72
neuron projection morphogenesis	-0.047	0.14	-9999	-0.36	69	69
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.047	0.14	-9999	-0.36	69	69
EPHA5	-0.071	0.2	-9999	-0.57	56	56

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.023	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.12	0.21	-10000	0	-0.41	130	130
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.071	0.19	-10000	0	-0.5	34	34
NGF (dimer)/p75(NTR)/BEX1	-0.14	0.24	-10000	0	-0.42	148	148
NT-4/5 (dimer)/p75(NTR)	-0.1	0.21	-10000	0	-0.44	112	112
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.069	0.18	-10000	0	-0.56	23	23
IKBKG	0.016	0	-10000	0	-10000	0	0
BDNF	-0.096	0.23	-10000	0	-0.57	78	78
MGDIs/NGR/p75(NTR)/LINGO1	-0.12	0.2	-10000	0	-0.35	156	156
FURIN	0.014	0.026	-10000	0	-0.51	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.12	0.21	-10000	0	-0.39	150	150
LINGO1	-0.009	0.11	-10000	0	-0.51	19	19
Sortilin/TRAF6/NRIF	0	0	-10000	0	-10000	0	0
proBDNF (dimer)	-0.096	0.23	-10000	0	-0.57	78	78
NTRK1	0.005	0.068	-10000	0	-0.51	7	7
RTN4R	-0.064	0.19	-10000	0	-0.51	62	62
neuron apoptosis	-0.11	0.22	-10000	0	-0.52	61	61
IRAK1	0.016	0	-10000	0	-10000	0	0
SHC1	-0.1	0.21	-10000	0	-0.4	126	126
ARHGDIA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	0.012	0	-10000	0	-10000	0	0
Gamma Secretase	0.047	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.083	0.2	-10000	0	-0.36	121	121
MAGEH1	0.013	0.041	-10000	0	-0.57	2	2
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.12	0.24	-10000	0	-0.41	144	144
Mammalian IAPs/DIABLO	0.017	0.09	-10000	0	-0.32	23	23
proNGF (dimer)	-0.062	0.2	-10000	0	-0.57	54	54
MAGED1	0.016	0	-10000	0	-10000	0	0
APP	0.013	0.041	-10000	0	-0.57	2	2
NT-4/5 (dimer)	-0.023	0.14	-10000	0	-0.57	27	27
ZNF274	0.016	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.077	0.18	-10000	0	-0.34	121	121
NGF	-0.062	0.2	-10000	0	-0.57	54	54
cell cycle arrest	-0.083	0.17	-10000	0	-0.44	37	37
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.057	0.16	-10000	0	-0.5	23	23
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.077	0.18	-10000	0	-0.36	112	112
NCSTN	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.1	0.21	-10000	0	-0.39	128	128
PSENEN	0.016	0	-10000	0	-10000	0	0
mol:ceramide	-0.082	0.19	-10000	0	-0.35	121	121
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.037	0.14	-10000	0	-0.42	24	24
p75(NTR)/beta APP	-0.078	0.18	-10000	0	-0.41	96	96
BEX1	-0.042	0.17	-10000	0	-0.56	39	39
mol:GDP	-0.11	0.21	-10000	0	-0.4	126	126
NGF (dimer)	-0.09	0.17	-10000	0	-0.35	74	74
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.095	0.18	-10000	0	-0.35	98	98
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
RAC1/GTP	-0.087	0.18	-10000	0	-0.34	126	126
MYD88	0.016	0	-10000	0	-10000	0	0
CHUK	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.1	0.21	-10000	0	-0.4	128	128
RHOB	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.067	0.16	-10000	0	-0.36	97	97
NT3 (dimer)	-0.095	0.23	-10000	0	-0.57	77	77
TP53	-0.075	0.18	-10000	0	-0.54	23	23
PRDM4	-0.082	0.19	-10000	0	-0.36	121	121
BDNF (dimer)	-0.17	0.22	-10000	0	-0.42	130	130
PIK3CA	0.016	0	-10000	0	-10000	0	0
SORT1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.1	0.17	-10000	0	-0.5	34	34
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.082	0.19	-10000	0	-0.36	121	121
RHOC	0.016	0	-10000	0	-10000	0	0
XIAP	0.013	0.039	-10000	0	-0.54	2	2
MAPK10	-0.1	0.22	-10000	0	-0.53	58	58
DIABLO	0.016	0	-10000	0	-10000	0	0
SMPD2	-0.082	0.19	-10000	0	-0.36	121	121
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.1	0.21	-10000	0	-0.4	126	126
PSEN1	0.016	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.15	0.24	-10000	0	-0.46	149	149
MAPK8	-0.082	0.21	-10000	0	-0.52	48	48
MAPK9	-0.08	0.21	-10000	0	-0.52	48	48
APAF1	0.016	0	-10000	0	-10000	0	0
NTF3	-0.095	0.23	-10000	0	-0.57	77	77
NTF4	-0.023	0.14	-10000	0	-0.57	27	27
NDN	-0.055	0.19	-10000	0	-0.57	49	49
RAC1/GDP	0.012	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.093	0.15	-10000	0	-0.53	23	23
p75 CTF/Sortilin/TRAF6/NRIF	0.04	0.015	-10000	0	-0.26	1	1
RhoA-B-C/GTP	-0.1	0.21	-10000	0	-0.39	128	128
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.087	0.19	-10000	0	-0.57	23	23
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.2	-10000	0	-0.35	145	145
PRKACB	0.013	0.041	-10000	0	-0.57	2	2
proBDNF (dimer)/p75 ECD	-0.06	0.17	-10000	0	-0.41	78	78
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.02	0.14	-10000	0	-0.56	25	25
BIRC2	0.013	0.036	-10000	0	-0.51	2	2
neuron projection morphogenesis	-0.12	0.2	0.2	15	-0.4	113	128
BAD	-0.082	0.21	-10000	0	-0.49	55	55
RIPK2	0.016	0	-10000	0	-10000	0	0
NGFR	-0.12	0.25	-10000	0	-0.57	95	95
CYCS	-0.069	0.18	-10000	0	-0.48	32	32
ADAM17	0.014	0.026	-10000	0	-0.51	1	1
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.082	0.19	-10000	0	-0.36	121	121
BCL2L11	-0.082	0.21	-10000	0	-0.49	55	55
BDNF (dimer)/p75(NTR)	-0.15	0.24	-10000	0	-0.46	150	150
PI3K	-0.082	0.19	-10000	0	-0.36	122	122
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.082	0.19	-10000	0	-0.36	121	121
NDNL2	0.016	0	-10000	0	-10000	0	0
YWHAE	0.014	0.029	-10000	0	-0.57	1	1
PRKCI	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.13	0.24	-10000	0	-0.47	126	126
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.082	0.19	-10000	0	-0.36	121	121
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.05	-10000	0	-0.57	3	3
PLG	-0.003	0.056	-10000	0	-0.51	5	5
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.14	0.24	-10000	0	-0.48	102	102
SQSTM1	0.016	0	-10000	0	-10000	0	0
NGFRAP1	0.013	0.041	-10000	0	-0.57	2	2
CASP3	-0.074	0.2	-10000	0	-0.45	55	55
E2F1	-0.11	0.22	-10000	0	-0.51	97	97
CASP9	0.016	0	-10000	0	-10000	0	0
IKK complex	-0.076	0.13	-10000	0	-0.48	25	25
NGF (dimer)/TRKA	-0.042	0.15	-10000	0	-0.4	61	61
MMP7	-0.11	0.23	-10000	0	-0.52	99	99
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.069	0.18	-10000	0	-0.57	23	23
MMP3	-0.1	0.23	-10000	0	-0.55	84	84
APAF-1/Caspase 9	-0.082	0.13	-10000	0	-0.43	33	33

×

Plasma membrane estrogen receptor 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
GNB1/GNG2	-0.026	0.13	-10000	0	-0.29	77	77
ER alpha/Gai/GDP/Gbeta gamma	-0.19	0.34	-10000	0	-0.65	111	111
AKT1	-0.14	0.36	-10000	0	-0.89	73	73
PIK3CA	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.15	0.36	-10000	0	-0.92	73	73
mol:Ca2+	-0.042	0.18	-10000	0	-0.43	63	63
IGF1R	0.011	0.05	-10000	0	-0.57	3	3
E2/ER alpha (dimer)/Striatin	-0.045	0.14	-10000	0	-0.35	73	73
SHC1	0.014	0.026	-10000	0	-0.51	1	1
apoptosis	0.13	0.34	0.84	73	-10000	0	73
RhoA/GTP	-0.043	0.093	-10000	0	-0.47	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.17	0.25	-10000	0	-0.53	111	111
regulation of stress fiber formation	-0.01	0.1	0.39	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.046	0.14	-10000	0	-0.35	75	75
KRAS	0.014	0.026	-10000	0	-0.51	1	1
G13/GTP	-0.04	0.13	-10000	0	-0.32	73	73
pseudopodium formation	0.01	0.1	-10000	0	-0.39	4	4
E2/ER alpha (dimer)/PELP1	-0.045	0.14	-10000	0	-0.35	73	73
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.007	0.07	-10000	0	-0.57	6	6
GNAO1	-0.17	0.27	-10000	0	-0.57	129	129
HRAS	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.12	0.29	-10000	0	-0.68	74	74
E2/ER beta (dimer)	0.01	0.026	-10000	0	-0.37	2	2
mol:GDP	-0.071	0.15	-10000	0	-0.39	73	73
mol:NADP	-0.12	0.29	-10000	0	-0.68	74	74
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
mol:IP3	-0.045	0.19	-10000	0	-0.44	63	63
IGF-1R heterotetramer	0.011	0.05	-10000	0	-0.57	3	3
PLCB1	-0.053	0.19	-10000	0	-0.46	63	63
PLCB2	-0.046	0.18	-10000	0	-0.45	60	60
IGF1	-0.24	0.29	-10000	0	-0.57	182	182
mol:L-citrulline	-0.12	0.29	-10000	0	-0.68	74	74
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.26	0.41	-10000	0	-0.83	129	129
JNK cascade	0.01	0.026	-10000	0	-0.36	2	2
BCAR1	0.016	0	-10000	0	-10000	0	0
ESR2	0.013	0.036	-10000	0	-0.51	2	2
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	-0.089	0.22	-10000	0	-0.57	73	73
Gq family/GDP/Gbeta gamma	-0.002	0.11	-10000	0	-0.55	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.029	0.12	-10000	0	-0.3	47	47
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.17	0.25	-10000	0	-0.53	112	112
GNAZ	-0.11	0.24	-10000	0	-0.57	89	89
E2/ER alpha (dimer)	-0.065	0.16	-10000	0	-0.42	73	73
STRN	0.016	0	-10000	0	-10000	0	0
GNAL	-0.24	0.29	-10000	0	-0.57	178	178
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.02	0.022	-10000	0	-0.3	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.05	-10000	0	-0.57	3	3
HBEGF	-0.2	0.29	-10000	0	-0.6	113	113
cAMP biosynthetic process	-0.17	0.18	-10000	0	-0.33	209	209
SRC	-0.17	0.31	-10000	0	-0.61	111	111
PI3K	0.022	0.021	-10000	0	-0.41	1	1
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.064	0.13	-10000	0	-0.34	73	73
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.22	0.24	-10000	0	-0.49	153	153
Gs family/GTP	-0.17	0.19	-10000	0	-0.34	209	209
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.03	0.015	-10000	0	-0.26	1	1
vasodilation	-0.12	0.27	-10000	0	-0.64	74	74
mol:DAG	-0.045	0.19	-10000	0	-0.44	63	63
Gs family/GDP/Gbeta gamma	-0.15	0.18	-10000	0	-0.45	76	76
MSN	0.009	0.11	-10000	0	-0.43	4	4
Gq family/GTP	-0.056	0.19	-10000	0	-0.48	60	60
mol:PI-3-4-5-P3	-0.14	0.35	-10000	0	-0.87	73	73
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.12	0.27	0.64	74	-10000	0	74
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
RhoA/GDP	-0.066	0.14	-10000	0	-0.36	73	73
NOS3	-0.14	0.31	-10000	0	-0.73	74	74
GNA11	0.014	0.029	-10000	0	-0.57	1	1
MAPKKK cascade	-0.11	0.29	-10000	0	-0.7	73	73
E2/ER alpha (dimer)/PELP1/Src	-0.18	0.27	-10000	0	-0.57	111	111
ruffle organization	0.01	0.1	-10000	0	-0.39	4	4
ROCK2	0.001	0.11	-10000	0	-0.47	3	3
GNA14	-0.068	0.2	-10000	0	-0.57	58	58
GNA15	0.011	0.05	-10000	0	-0.57	3	3
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.22	0.29	-10000	0	-0.61	110	110
MMP2	-0.17	0.31	-10000	0	-0.64	101	101

×

Fc-epsilon receptor I signaling in mast cells

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.013	0.041	-9999	-0.57	2	2
LAT2	-0.1	0.2	-9999	-0.46	65	65
AP1	-0.2	0.23	-9999	-0.52	112	112
mol:PIP3	-0.12	0.24	-9999	-0.51	76	76
IKBKB	-0.076	0.15	-9999	-0.28	110	110
AKT1	-0.077	0.19	-9999	-0.44	59	59
IKBKG	-0.076	0.15	-9999	-0.29	109	109
MS4A2	-0.15	0.26	-9999	-0.57	115	115
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.002	-9999	-10000	0	0
MAP3K1	-0.071	0.19	-9999	-0.4	71	71
mol:Ca2+	-0.082	0.18	-9999	-0.37	76	76
LYN	0.014	0.006	-9999	-10000	0	0
CBLB	-0.099	0.19	-9999	-0.45	66	66
SHC1	0.014	0.026	-9999	-0.51	1	1
RasGAP/p62DOK	-0.069	0.16	-9999	-0.31	119	119
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.006	0.076	-9999	-0.57	7	7
PLD2	-0.12	0.21	-9999	-0.5	66	66
PTPN13	-0.098	0.2	-9999	-0.48	62	62
PTPN11	0.012	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.048	0.16	-9999	-0.34	56	56
SYK	0.008	0.06	-9999	-0.59	4	4
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.16	0.21	-9999	-0.53	77	77
LAT	-0.1	0.2	-9999	-0.45	67	67
PAK2	-0.089	0.21	-9999	-0.46	71	71
NFATC2	-0.16	0.26	-9999	-0.69	73	73
HRAS	-0.11	0.23	-9999	-0.5	73	73
GAB2	0.014	0.029	-9999	-0.57	1	1
PLA2G1B	0.041	0.023	-9999	-10000	0	0
Fc epsilon R1	-0.19	0.24	-9999	-0.43	179	179
Antigen/IgE/Fc epsilon R1	-0.17	0.22	-9999	-0.4	179	179
mol:GDP	-0.12	0.24	-9999	-0.54	74	74
JUN	-0.007	0.11	-9999	-0.57	16	16
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.029	-9999	-0.57	1	1
FOS	-0.17	0.27	-9999	-0.57	129	129
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.11	0.2	-9999	-0.38	123	123
CHUK	-0.076	0.15	-9999	-0.28	112	112
KLRG1	-0.097	0.18	-9999	-0.44	63	63
VAV1	-0.11	0.21	-9999	-0.47	74	74
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.099	0.19	-9999	-0.45	66	66
negative regulation of mast cell degranulation	-0.087	0.18	-9999	-0.42	66	66
BTK	-0.13	0.26	-9999	-0.58	72	72
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.15	0.27	-9999	-0.66	71	71
GAB2/PI3K/SHP2	-0.13	0.17	-9999	-0.48	59	59
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.12	0.22	-9999	-0.55	65	65
RAF1	0.03	0.027	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.18	0.24	-9999	-0.61	71	71
FCER1G	-0.004	0.11	-9999	-0.53	18	18
FCER1A	-0.14	0.26	-9999	-0.58	105	105
Antigen/IgE/Fc epsilon R1/Fyn	-0.16	0.21	-9999	-0.43	116	116
MAPK3	0.04	0.023	-9999	-10000	0	0
MAPK1	0.04	0.023	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.009	0.081	-9999	-0.59	3	3
DUSP1	-0.16	0.27	-9999	-0.57	119	119
NF-kappa-B/RelA	-0.062	0.071	-9999	-0.22	13	13
actin cytoskeleton reorganization	-0.1	0.2	-9999	-0.49	58	58
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.13	0.18	-9999	-0.46	68	68
FER	-0.1	0.2	-9999	-0.46	68	68
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.082	0.16	-9999	-0.52	46	46
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.12	0.24	-9999	-0.55	72	72
cytokine secretion	-0.045	0.051	-9999	-10000	0	0
SPHK1	-0.14	0.21	-9999	-0.47	83	83
PTK2	-0.11	0.21	-9999	-0.51	57	57
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.17	0.22	-9999	-0.55	78	78
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.11	0.23	-9999	-0.5	77	77
MAP2K2	0.036	0.024	-9999	-10000	0	0
MAP2K1	0.036	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.11	0.15	-9999	-0.4	63	63
MAP2K4	0.019	0.012	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.19	0.24	-9999	-0.49	125	125
mol:Choline	-0.12	0.21	-9999	-0.5	66	66
SHC/Grb2/SOS1	-0.11	0.16	-9999	-0.44	58	58
FYN	0.011	0.05	-9999	-0.57	3	3
DOK1	0.014	0.026	-9999	-0.51	1	1
PXN	-0.092	0.2	-9999	-0.47	57	57
HCLS1	-0.1	0.2	-9999	-0.46	66	66
PRKCB	-0.12	0.21	-9999	-0.41	116	116
FCGR2B	-0.027	0.15	-9999	-0.56	30	30
IGHE	-0.003	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.088	0.19	-9999	-0.43	66	66
LCP2	0.011	0.05	-9999	-0.57	3	3
PLA2G4A	-0.12	0.22	-9999	-0.5	74	74
RASA1	0.016	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.12	0.21	-9999	-0.5	66	66
IKK complex	-0.042	0.12	-9999	-0.22	66	66
WIPF1	-0.002	0.099	-9999	-0.57	12	12

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.18	0.44	-9999	-0.93	63	63
HDAC7	0.018	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.12	0.36	-9999	-0.77	54	54
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.19	0.45	-9999	-0.92	69	69
AP1	-0.12	0.23	-9999	-0.45	130	130
ABCG2	-0.2	0.46	-9999	-0.95	66	66
HIF1A	-0.012	0.084	-9999	-0.65	1	1
TFF3	-0.26	0.5	-9999	-0.98	93	93
GATA2	-0.009	0.12	-9999	-0.53	20	20
AKT1	-0.013	0.092	-9999	-10000	0	0
response to hypoxia	-0.036	0.098	-9999	-0.23	19	19
MCL1	-0.18	0.44	-9999	-0.93	63	63
NDRG1	-0.19	0.45	-9999	-0.93	67	67
SERPINE1	-0.19	0.45	-9999	-0.96	62	62
FECH	-0.18	0.44	-9999	-0.93	63	63
FURIN	-0.18	0.44	-9999	-0.94	62	62
NCOA2	-0.018	0.14	-9999	-0.57	24	24
EP300	-0.003	0.14	-9999	-0.33	26	26
HMOX1	-0.19	0.45	-9999	-0.94	63	63
BHLHE40	-0.19	0.45	-9999	-0.94	63	63
BHLHE41	-0.19	0.46	-9999	-0.96	64	64
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.012	0.092	-9999	-0.41	1	1
ENG	0.035	0.1	-9999	-10000	0	0
JUN	-0.006	0.11	-9999	-0.57	16	16
RORA	-0.19	0.45	-9999	-0.94	66	66
ABCB1	-0.2	0.4	-9999	-1.2	53	53
TFRC	-0.19	0.45	-9999	-0.95	63	63
CXCR4	-0.19	0.45	-9999	-0.97	61	61
TF	-0.22	0.47	-9999	-0.95	74	74
CITED2	-0.18	0.44	-9999	-0.94	62	62
HIF1A/ARNT	-0.19	0.52	-9999	-1	73	73
LDHA	-0.024	0.044	-9999	-10000	0	0
ETS1	-0.18	0.44	-9999	-0.94	62	62
PGK1	-0.18	0.44	-9999	-0.94	62	62
NOS2	-0.21	0.47	-9999	-0.97	70	70
ITGB2	-0.19	0.45	-9999	-0.96	63	63
ALDOA	-0.18	0.44	-9999	-0.94	61	61
Cbp/p300/CITED2	-0.17	0.47	-9999	-1	55	55
FOS	-0.17	0.27	-9999	-0.57	129	129
HK2	-0.18	0.45	-9999	-0.92	67	67
SP1	0.017	0.029	-9999	-10000	0	0
GCK	-0.079	0.4	-9999	-1.5	27	27
HK1	-0.18	0.44	-9999	-0.94	62	62
NPM1	-0.18	0.44	-9999	-0.93	63	63
EGLN1	-0.18	0.44	-9999	-0.94	62	62
CREB1	0.025	0	-9999	-10000	0	0
PGM1	-0.18	0.44	-9999	-0.93	63	63
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.055	0.23	-9999	-0.72	16	16
IGFBP1	-0.21	0.46	-9999	-0.94	73	73
VEGFA	-0.077	0.34	-9999	-0.71	34	34
HIF1A/JAB1	-0.007	0.042	-9999	-0.48	1	1
CP	-0.28	0.51	-9999	-0.98	97	97
CXCL12	-0.27	0.52	-9999	-1	97	97
COPS5	0.016	0.005	-9999	-10000	0	0
SMAD3/SMAD4	0.026	0.001	-9999	-10000	0	0
BNIP3	-0.19	0.45	-9999	-0.94	62	62
EGLN3	-0.19	0.45	-9999	-0.95	63	63
CA9	-0.35	0.5	-9999	-1	100	100
TERT	-0.28	0.49	-9999	-1	84	84
ENO1	-0.18	0.44	-9999	-0.93	63	63
PFKL	-0.18	0.44	-9999	-0.92	67	67
NCOA1	0.016	0.002	-9999	-10000	0	0
ADM	-0.19	0.45	-9999	-0.94	62	62
ARNT	-0.01	0.078	-9999	-10000	0	0
HNF4A	-0.041	0.16	-9999	-0.51	41	41
ADFP	-0.2	0.44	-9999	-0.9	73	73
SLC2A1	-0.08	0.35	-9999	-0.74	34	34
LEP	-0.22	0.48	-9999	-0.96	80	80
HIF1A/ARNT/Cbp/p300	-0.14	0.38	-9999	-0.8	55	55
EPO	-0.086	0.31	-9999	-0.81	13	13
CREBBP	-0.003	0.14	-9999	-0.33	26	26
HIF1A/ARNT/Cbp/p300/HDAC7	-0.12	0.36	-9999	-0.78	50	50
PFKFB3	-0.18	0.45	-9999	-0.95	60	60
NT5E	-0.21	0.48	-9999	-0.98	74	74

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	-0.12	0.16	-10000	0	-0.3	180	180
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.098	0.17	-10000	0	-0.37	114	114
GNB1/GNG2	0.016	0.044	-10000	0	-0.35	6	6
GNB1	0.016	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.14	0.17	-10000	0	-0.32	178	178
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	0.037	0.042	0.084	178	-10000	0	178
GNAL	-0.24	0.29	-10000	0	-0.57	178	178
GNG2	0.007	0.07	-10000	0	-0.57	6	6
CRH	-0.14	0.23	-10000	0	-0.51	114	114
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.007	0.031	-10000	0	-0.36	3	3
MAPK11	0.01	0	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.021	0.03	-9999	-0.41	2	2
alphaV beta3 Integrin	-0.13	0.23	-9999	-0.42	146	146
PTK2	-0.1	0.23	-9999	-0.54	68	68
IGF1R	0.011	0.05	-9999	-0.57	3	3
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.013	0.041	-9999	-0.57	2	2
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.13	0.28	-9999	-0.7	67	67
VEGFA	0.016	0	-9999	-10000	0	0
ILK	-0.13	0.28	-9999	-0.7	67	67
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.12	0.26	-9999	-0.65	67	67
PTK2B	0.007	0.11	-9999	-0.57	2	2
alphaV/beta3 Integrin/JAM-A	-0.15	0.26	-9999	-0.63	68	68
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.017	0.13	-9999	-0.35	50	50
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.18	-9999	-0.31	186	186
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.019	0.13	-9999	-0.43	18	18
alphaV/beta3 Integrin/Syndecan-1	-0.017	0.13	-9999	-0.34	53	53
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.26	0.29	-9999	-0.62	134	134
PI4 Kinase	0.023	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.14	0.18	-9999	-0.31	206	206
RPS6KB1	-0.21	0.29	-9999	-0.58	134	134
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.28	0.4	-9999	-0.78	146	146
GPR124	-0.05	0.18	-9999	-0.57	46	46
MAPK1	-0.28	0.4	-9999	-0.78	146	146
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
alphaV/beta3 Integrin/Tumstatin	-0.11	0.21	-9999	-0.38	144	144
cell adhesion	-0.032	0.12	-9999	-0.34	47	47
ANGPTL3	0.005	0.057	-9999	-0.51	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.03	0.026	-9999	-0.34	2	2
IGF-1R heterotetramer	0.011	0.05	-9999	-0.57	3	3
Rac1/GDP	0.012	0	-9999	-10000	0	0
TGFBR2	0.011	0.05	-9999	-0.57	3	3
ITGB3	-0.05	0.18	-9999	-0.57	46	46
IGF1	-0.24	0.29	-9999	-0.57	182	182
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.05	0.19	-9999	-0.45	69	69
apoptosis	0.014	0.029	-9999	-0.57	1	1
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.011	0.12	-9999	-0.34	46	46
VCL	0.014	0.029	-9999	-0.57	1	1
alphaV/beta3 Integrin/Del1	-0.06	0.2	-9999	-0.44	80	80
CSF1	-0.006	0.11	-9999	-0.57	15	15
PIK3C2A	-0.13	0.28	-9999	-0.7	67	67
PI4 Kinase/Pyk2	-0.14	0.2	-9999	-0.54	68	68
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0	0.11	-9999	-0.31	47	47
FAK1/Vinculin	-0.075	0.18	-9999	-0.41	69	69
alphaV beta3/Integrin/ppsTEM5	-0.05	0.19	-9999	-0.45	69	69
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.088	0.22	-9999	-0.56	73	73
BCAR1	0.016	0	-9999	-10000	0	0
FGF2	-0.18	0.28	-9999	-0.57	136	136
F11R	-0.12	0.21	-9999	-0.41	136	136
alphaV/beta3 Integrin/Lactadherin	-0.012	0.12	-9999	-0.35	47	47
alphaV/beta3 Integrin/TGFBR2	-0.013	0.13	-9999	-0.35	48	48
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.027	0.066	-9999	-0.3	16	16
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.009	0.11	-9999	-0.31	46	46
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.035	0.16	-9999	-0.53	38	38
alphaV/beta3 Integrin/Pyk2	0.008	0.11	-9999	-0.57	2	2
SDC1	0.006	0.076	-9999	-0.57	7	7
VAV3	0.027	0.073	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.001	0.09	-9999	-0.57	10	10
FAK1/Paxillin	-0.074	0.18	-9999	-0.41	68	68
cell migration	-0.059	0.17	-9999	-0.37	67	67
ITGAV	0.014	0.029	-9999	-0.57	1	1
PI3K	-0.16	0.21	-9999	-0.57	68	68
SPP1	-0.2	0.26	-9999	-0.51	165	165
KDR	0.013	0.041	-9999	-0.57	2	2
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.014	0.029	-9999	-0.57	1	1
COL4A3	-0.15	0.26	-9999	-0.57	116	116
angiogenesis	-0.27	0.4	-9999	-0.75	149	149
Rac1/GTP	0.033	0.067	-9999	-10000	0	0
EDIL3	-0.066	0.2	-9999	-0.57	57	57
cell proliferation	-0.013	0.12	-9999	-0.35	48	48

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0	-9999	-10000	0	0
CCL5	-0.03	0.15	-9999	-0.55	33	33
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.12	0.14	-9999	-0.35	59	59
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.11	0.13	-9999	-0.33	59	59
Syndecan-1/Syntenin	-0.11	0.13	-9999	-0.33	59	59
MAPK3	-0.083	0.12	-9999	-0.4	13	13
HGF/MET	-0.077	0.18	-9999	-0.4	96	96
TGFB1/TGF beta receptor Type II	0.016	0	-9999	-10000	0	0
BSG	0.016	0	-9999	-10000	0	0
keratinocyte migration	-0.11	0.13	-9999	-0.32	59	59
Syndecan-1/RANTES	-0.13	0.16	-9999	-0.38	73	73
Syndecan-1/CD147	-0.095	0.12	-9999	-0.38	20	20
Syndecan-1/Syntenin/PIP2	-0.1	0.12	-9999	-0.37	24	24
LAMA5	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.12	0.11	-9999	-0.31	59	59
MMP7	-0.11	0.23	-9999	-0.52	99	99
HGF	-0.12	0.24	-9999	-0.56	94	94
Syndecan-1/CASK	-0.12	0.13	-9999	-0.34	59	59
Syndecan-1/HGF/MET	-0.16	0.18	-9999	-0.45	75	75
regulation of cell adhesion	-0.073	0.12	-9999	-0.38	13	13
HPSE	-0.036	0.16	-9999	-0.51	40	40
positive regulation of cell migration	-0.12	0.14	-9999	-0.35	59	59
SDC1	-0.12	0.14	-9999	-0.36	59	59
Syndecan-1/Collagen	-0.12	0.14	-9999	-0.35	59	59
PPIB	0.016	0	-9999	-10000	0	0
MET	0.013	0.036	-9999	-0.51	2	2
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.13	0.23	-9999	-0.51	110	110
MAPK1	-0.083	0.12	-9999	-0.4	13	13
homophilic cell adhesion	-0.12	0.14	-9999	-0.35	59	59
MMP1	-0.28	0.26	-9999	-0.51	231	231

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.17	0.27	-10000	0	-0.49	157	157
fibroblast growth factor receptor signaling pathway	-0.17	0.27	-10000	0	-0.49	157	157
LAMA1	-0.091	0.21	-10000	0	-0.52	81	81
PRNP	0.001	0.09	-10000	0	-0.57	10	10
GPC1/SLIT2	-0.17	0.22	-10000	0	-0.41	185	185
SMAD2	0.036	0.032	-10000	0	-0.3	3	3
GPC1/PrPc/Cu2+	0.011	0.059	-10000	0	-0.34	11	11
GPC1/Laminin alpha1	-0.055	0.16	-10000	0	-0.37	81	81
TDGF1	0.005	0.045	-10000	0	-0.51	3	3
CRIPTO/GPC1	0.014	0.038	-10000	0	-0.36	4	4
APP/GPC1	0.02	0.035	-10000	0	-0.39	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	0.025	0.032	-10000	0	-0.29	4	4
FLT1	0.016	0	-10000	0	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	0.028	0.035	-10000	0	-0.33	4	4
SERPINC1	-0.026	0.14	-10000	0	-0.51	30	30
FYN	0.022	0.045	-10000	0	-0.32	7	7
FGR	0.023	0.041	-10000	0	-0.31	6	6
positive regulation of MAPKKK cascade	0.021	0.078	-10000	0	-0.43	3	3
SLIT2	-0.25	0.29	-10000	0	-0.57	185	185
GPC1/NRG	-0.072	0.18	-10000	0	-0.4	92	92
NRG1	-0.11	0.24	-10000	0	-0.56	91	91
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.031	0.016	-10000	0	-0.29	1	1
LYN	0.025	0.032	-10000	0	-0.29	4	4
mol:Spermine	0.012	0.019	-10000	0	-0.37	1	1
cell growth	-0.17	0.27	-10000	0	-0.49	157	157
BMP signaling pathway	-0.014	0.026	0.51	1	-10000	0	1
SRC	0.025	0.032	-10000	0	-0.29	4	4
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.25	0.29	-10000	0	-0.57	185	185
GPC1	0.014	0.026	-10000	0	-0.51	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	0.016	0	-10000	0	-10000	0	0
BLK	-0.024	0.12	-10000	0	-0.33	57	57
HCK	0.01	0.078	-10000	0	-0.32	21	21
FGF2	-0.18	0.28	-10000	0	-0.57	136	136
FGFR1	-0.12	0.24	-10000	0	-0.57	93	93
VEGFR1 homodimer	0.016	0	-10000	0	-10000	0	0
TGFBR2	0.011	0.05	-10000	0	-0.57	3	3
cell death	0.02	0.035	-10000	0	-0.39	3	3
ATIII/GPC1	-0.008	0.1	-10000	0	-0.36	31	31
PLA2G2A/GPC1	-0.17	0.22	-10000	0	-0.41	185	185
LCK	0.019	0.053	-10000	0	-0.31	10	10
neuron differentiation	-0.072	0.18	-10000	0	-0.4	92	92
PrPc/Cu2+	0.001	0.066	-10000	0	-0.42	10	10
APP	0.013	0.041	-10000	0	-0.57	2	2
TGFBR2 (dimer)	0.011	0.05	-10000	0	-0.57	3	3

×

IL6-mediated signaling events

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
BCL2L1	-0.056	0.23	-10000	0	-0.61	33	33
CRP	-0.067	0.24	-10000	0	-0.6	42	42
cell cycle arrest	-0.066	0.27	-10000	0	-0.64	50	50
TIMP1	-0.049	0.21	-10000	0	-0.54	27	27
IL6ST	-0.068	0.21	-10000	0	-0.57	61	61
Rac1/GDP	-0.13	0.26	-10000	0	-0.54	89	89
AP1	-0.057	0.18	-10000	0	-0.46	26	26
GAB2	0.017	0.03	-10000	0	-0.57	1	1
TNFSF11	-0.07	0.26	-10000	0	-0.7	30	30
HSP90B1	0.024	0.055	-10000	0	-0.56	1	1
GAB1	0.018	0.004	-10000	0	-10000	0	0
MAPK14	-0.17	0.31	-10000	0	-0.71	79	79
AKT1	0.063	0.022	-10000	0	-10000	0	0
FOXO1	0.068	0.025	-10000	0	-10000	0	0
MAP2K6	-0.16	0.28	-10000	0	-0.61	88	88
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	-0.095	0.26	-10000	0	-0.57	66	66
MITF	-0.16	0.28	-10000	0	-0.55	103	103
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.016	0	-10000	0	-10000	0	0
A2M	-0.1	0.42	-10000	0	-1.4	37	37
CEBPB	0.023	0.029	-10000	0	-0.57	1	1
GRB2/SOS1/GAB family/SHP2	-0.015	0.1	0.26	4	-0.55	2	6
STAT3	-0.078	0.28	-10000	0	-0.68	52	52
STAT1	-0.006	0.019	-10000	0	-10000	0	0
CEBPD	-0.058	0.24	-10000	0	-0.64	31	31
PIK3CA	0.018	0	-10000	0	-10000	0	0
PI3K	0.026	0.022	-10000	0	-0.41	1	1
JUN	-0.007	0.11	-10000	0	-0.57	16	16
PIAS3/MITF	-0.14	0.27	-10000	0	-0.54	96	96
MAPK11	-0.17	0.31	-10000	0	-0.71	79	79
STAT3 (dimer)/FOXO1	-0.032	0.25	-10000	0	-0.57	40	40
GRB2/SOS1/GAB family	-0.14	0.21	0.21	5	-0.57	57	62
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.16	0.27	-10000	0	-0.47	125	125
GRB2	0.018	0.004	-10000	0	-10000	0	0
JAK2	0.014	0.029	-10000	0	-0.57	1	1
LBP	-0.066	0.22	-10000	0	-0.54	28	28
PIK3R1	0.016	0.029	-10000	0	-0.57	1	1
JAK1	0.017	0.007	-10000	0	-10000	0	0
MYC	-0.08	0.3	-10000	0	-0.94	29	29
FGG	-0.081	0.25	-10000	0	-0.64	38	38
macrophage differentiation	-0.066	0.27	-10000	0	-0.64	50	50
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.19	0.23	-10000	0	-0.48	106	106
JUNB	-0.061	0.24	-10000	0	-0.69	27	27
FOS	-0.17	0.27	-10000	0	-0.57	129	129
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.16	0.27	-10000	0	-0.49	115	115
STAT1/PIAS1	-0.12	0.24	-10000	0	-0.53	69	69
GRB2/SOS1/GAB family/SHP2/PI3K	0.051	0.025	-10000	0	-10000	0	0
STAT3 (dimer)	-0.074	0.28	-10000	0	-0.67	49	49
PRKCD	-0.068	0.25	-10000	0	-0.55	62	62
IL6R	-0.033	0.16	-10000	0	-0.57	35	35
SOCS3	-0.21	0.42	-10000	0	-1.1	64	64
gp130 (dimer)/JAK1/JAK1/LMO4	-0.013	0.14	-10000	0	-0.34	62	62
Rac1/GTP	-0.12	0.26	-10000	0	-0.53	89	89
HCK	-0.008	0.11	-10000	0	-0.55	17	17
MAPKKK cascade	0.023	0.085	-10000	0	-0.85	1	1
bone resorption	-0.065	0.24	-10000	0	-0.64	34	34
IRF1	-0.056	0.23	-10000	0	-0.61	33	33
mol:GDP	-0.15	0.27	-10000	0	-0.55	95	95
SOS1	0.018	0.007	-10000	0	-10000	0	0
VAV1	-0.15	0.28	-10000	0	-0.56	95	95
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.2	0.34	-10000	0	-0.77	82	82
PTPN11	-0.004	0.018	-10000	0	-10000	0	0
IL6/IL6RA	-0.2	0.25	-10000	0	-0.45	194	194
gp130 (dimer)/TYK2/TYK2/LMO4	-0.019	0.14	-10000	0	-0.34	62	62
gp130 (dimer)/JAK2/JAK2/LMO4	-0.02	0.14	-10000	0	-0.34	62	62
IL6	-0.24	0.29	-10000	0	-0.57	184	184
PIAS3	0.016	0	-10000	0	-10000	0	0
PTPRE	0.005	0.046	-10000	0	-0.52	3	3
PIAS1	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.17	0.25	-10000	0	-0.35	210	210
LMO4	0.018	0.031	-10000	0	-0.57	1	1
STAT3 (dimer)/PIAS3	-0.14	0.23	-10000	0	-0.66	52	52
MCL1	0.069	0.021	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.13	0.24	-9999	-0.56	58	58
MAP3K8	0.008	0.05	-9999	-0.57	3	3
FOS	-0.094	0.18	-9999	-0.46	54	54
PRKCA	0.004	0.065	-9999	-0.57	5	5
PTPN7	-0.004	0.096	-9999	-0.55	12	12
HRAS	0.015	0.002	-9999	-10000	0	0
PRKCB	-0.16	0.26	-9999	-0.57	118	118
NRAS	0.015	0.002	-9999	-10000	0	0
RAS family/GTP	0.021	0.021	-9999	-0.28	1	1
MAPK3	-0.049	0.13	-9999	-0.54	10	10
MAP2K1	-0.12	0.23	-9999	-0.45	120	120
ELK1	0.01	0.01	-9999	-10000	0	0
BRAF	-0.11	0.22	-9999	-0.44	120	120
mol:GTP	-0.002	0.003	-9999	-0.005	128	128
MAPK1	-0.049	0.13	-9999	-0.54	10	10
RAF1	-0.11	0.22	-9999	-0.44	120	120
KRAS	0.014	0.026	-9999	-0.51	1	1

×

Glucocorticoid receptor regulatory network

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
PCK2	0.014	0.061	-10000	0	-10000	0	0
SMARCC2	0.015	0.015	-10000	0	-10000	0	0
SMARCC1	0.015	0.015	-10000	0	-10000	0	0
TBX21	-0.085	0.22	-10000	0	-0.78	30	30
SUMO2	0.012	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.021	0.051	-10000	0	-0.49	4	4
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	-0.009	0.12	-10000	0	-0.57	17	17
GR alpha/HSP90/FKBP51/HSP90	0.086	0.12	0.27	26	-0.38	3	29
PRL	-0.062	0.12	-10000	0	-0.73	1	1
cortisol/GR alpha (dimer)/TIF2	0.22	0.22	0.46	129	-0.41	2	131
RELA	-0.098	0.12	-10000	0	-0.26	60	60
FGG	0.16	0.22	0.43	69	-0.46	11	80
GR beta/TIF2	0.083	0.14	0.28	37	-0.34	23	60
IFNG	-0.33	0.26	-10000	0	-0.59	159	159
apoptosis	-0.067	0.18	0.42	4	-0.53	14	18
CREB1	0.014	0.031	-10000	0	-10000	0	0
histone acetylation	-0.011	0.14	0.49	1	-0.4	20	21
BGLAP	-0.042	0.11	-10000	0	-0.44	4	4
GR/PKAc	0.1	0.089	0.28	15	-10000	0	15
NF kappa B1 p50/RelA	-0.18	0.23	-10000	0	-0.45	139	139
SMARCD1	0.015	0.015	-10000	0	-10000	0	0
MDM2	0.09	0.087	0.24	32	-0.24	3	35
GATA3	-0.02	0.15	-10000	0	-0.56	29	29
AKT1	0.002	0.006	-10000	0	-10000	0	0
CSF2	-0.081	0.13	-10000	0	-0.48	3	3
GSK3B	0.012	0.007	-10000	0	-10000	0	0
NR1I3	-0.025	0.18	0.46	1	-0.52	4	5
CSN2	0.16	0.14	0.37	52	-10000	0	52
BRG1/BAF155/BAF170/BAF60A	0.039	0.052	-10000	0	-0.32	2	2
NFATC1	-0.01	0.12	-10000	0	-0.57	19	19
POU2F1	0.017	0.012	-10000	0	-10000	0	0
CDKN1A	0.034	0.1	-10000	0	-1.4	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.031	0.15	-10000	0	-0.51	36	36
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.076	0.13	0.27	19	-0.38	2	21
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.16	0.39	0.42	2	-0.83	100	102
JUN	-0.17	0.17	-10000	0	-0.44	77	77
IL4	-0.087	0.15	-10000	0	-0.53	21	21
CDK5R1	-0.014	0.12	-10000	0	-0.51	22	22
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.24	0.28	0.21	1	-0.54	154	155
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.097	0.11	0.28	20	-0.48	1	21
cortisol/GR alpha (monomer)	0.27	0.24	0.53	137	-10000	0	137
NCOA2	-0.019	0.14	-10000	0	-0.57	24	24
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.23	0.27	-10000	0	-0.62	129	129
AP-1/NFAT1-c-4	-0.41	0.32	-10000	0	-0.69	190	190
AFP	-0.14	0.15	-10000	0	-0.54	18	18
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.16	0.12	0.41	21	-10000	0	21
TP53	0.039	0.038	-10000	0	-0.5	2	2
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.36	0.38	-10000	0	-0.8	122	122
KRT14	-0.23	0.24	-10000	0	-0.7	29	29
TBP	0.026	0.011	-10000	0	-10000	0	0
CREBBP	0.07	0.089	0.32	2	-10000	0	2
HDAC1	0.014	0.007	-10000	0	-10000	0	0
HDAC2	0.02	0.014	-10000	0	-10000	0	0
AP-1	-0.41	0.32	-10000	0	-0.69	190	190
MAPK14	0.012	0.007	-10000	0	-10000	0	0
MAPK10	-0.042	0.17	-10000	0	-0.57	37	37
MAPK11	0.012	0.007	-10000	0	-10000	0	0
KRT5	-0.57	0.54	-10000	0	-1.1	178	178
interleukin-1 receptor activity	0.004	0.014	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.021	0.051	-10000	0	-0.49	4	4
CGA	-0.073	0.14	-10000	0	-0.55	8	8
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.16	0.35	70	-0.47	5	75
MAPK3	0.011	0.007	-10000	0	-10000	0	0
MAPK1	0.012	0.007	-10000	0	-10000	0	0
ICAM1	-0.24	0.26	-10000	0	-0.61	80	80
NFKB1	-0.098	0.12	-10000	0	-0.28	33	33
MAPK8	-0.13	0.14	-10000	0	-0.39	50	50
MAPK9	0.012	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.079	0.18	0.43	4	-0.56	14	18
BAX	0.04	0.034	-10000	0	-10000	0	0
POMC	-0.3	0.29	-10000	0	-0.52	201	201
EP300	0.07	0.089	0.3	3	-10000	0	3
cortisol/GR alpha (dimer)/p53	0.26	0.2	0.48	137	-10000	0	137
proteasomal ubiquitin-dependent protein catabolic process	0.062	0.069	0.22	7	-0.23	2	9
SGK1	0.084	0.3	-10000	0	-1.3	16	16
IL13	-0.24	0.22	-10000	0	-0.76	35	35
IL6	-0.6	0.6	-10000	0	-1.2	198	198
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.22	0.19	-10000	0	-0.7	22	22
IL2	-0.29	0.22	-10000	0	-0.61	79	79
CDK5	0.014	0.003	-10000	0	-10000	0	0
PRKACB	0.013	0.041	-10000	0	-0.57	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.35	0.45	-10000	0	-0.96	110	110
CDK5R1/CDK5	-0.004	0.085	-10000	0	-0.36	22	22
NF kappa B1 p50/RelA/PKAc	-0.11	0.18	-10000	0	-0.39	52	52
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.24	0.19	0.44	133	-10000	0	133
SMARCA4	0.015	0.015	-10000	0	-10000	0	0
chromatin remodeling	0.16	0.15	0.35	63	-0.44	7	70
NF kappa B1 p50/RelA/Cbp	-0.077	0.24	0.39	1	-0.48	41	42
JUN (dimer)	-0.17	0.17	-10000	0	-0.44	77	77
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.073	0.2	-10000	0	-0.64	33	33
NR3C1	0.15	0.15	0.37	67	-0.4	4	71
NR4A1	-0.31	0.3	-10000	0	-0.57	231	231
TIF2/SUV420H1	-0.002	0.1	-10000	0	-0.41	24	24
MAPKKK cascade	-0.067	0.18	0.42	4	-0.53	14	18
cortisol/GR alpha (dimer)/Src-1	0.25	0.2	0.47	129	-10000	0	129
PBX1	-0.009	0.12	-10000	0	-0.57	18	18
POU1F1	0.002	0.046	-10000	0	-0.5	3	3
SELE	-0.56	0.59	-10000	0	-1.2	181	181
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.15	0.35	63	-0.44	7	70
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.24	0.19	0.44	133	-10000	0	133
mol:cortisol	0.15	0.14	0.29	147	-0.21	2	149
MMP1	-0.26	0.19	-10000	0	-1.3	1	1

×

Calcium signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.084	-9999	-0.37	19	19
NFATC2	-0.059	0.14	-9999	-0.37	71	71
NFATC3	0.008	0.027	-9999	-10000	0	0
CD40LG	-0.26	0.33	-9999	-0.71	107	107
PTGS2	-0.29	0.36	-9999	-0.69	147	147
JUNB	0.008	0.064	-9999	-0.57	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.011	-9999	-10000	0	0
CALM1	0.012	0.008	-9999	-10000	0	0
JUN	-0.011	0.12	-9999	-0.58	16	16
mol:Ca2+	-0.008	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.003	0.004	-9999	-10000	0	0
FOSL1	-0.025	0.15	-9999	-0.57	28	28
CREM	0.015	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.13	0.17	-9999	-0.48	58	58
FOS	-0.18	0.28	-9999	-0.58	129	129
IFNG	-0.28	0.33	-9999	-0.66	130	130
AP-1/NFAT1-c-4	-0.29	0.37	-9999	-0.7	139	139
FASLG	-0.25	0.32	-9999	-0.69	100	100
NFAT1-c-4/ICER1	-0.071	0.16	-9999	-0.39	58	58
IL2RA	-0.25	0.33	-9999	-0.75	87	87
FKBP12/FK506	0.012	0	-9999	-10000	0	0
CSF2	-0.27	0.33	-9999	-0.7	111	111
JunB/Fra1/NFAT1-c-4	-0.1	0.16	-9999	-0.43	55	55
IL4	-0.24	0.3	-9999	-0.66	92	92
IL2	-0.009	0.019	-9999	-10000	0	0
IL3	-0.024	0.023	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	0.003	0.082	-9999	-0.54	9	9
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.002	-9999	-10000	0	0

×

BMP receptor signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.13	0.21	-9999	-0.53	47	47
SMAD6-7/SMURF1	0.028	0.038	-9999	-0.31	5	5
NOG	-0.026	0.14	-9999	-0.51	31	31
SMAD9	-0.15	0.25	-9999	-0.55	106	106
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.033	0.1	-9999	-0.28	29	29
BMP7/USAG1	-0.27	0.27	-9999	-0.48	234	234
SMAD5/SKI	-0.023	0.1	-9999	-0.36	6	6
SMAD1	0.046	0.021	-9999	-10000	0	0
BMP2	-0.046	0.18	-9999	-0.57	43	43
SMAD1/SMAD1/SMAD4	-0.002	0.019	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.063	0.19	-9999	-0.51	60	60
BMPR1A-1B/BAMBI	-0.051	0.16	-9999	-0.35	89	89
AHSG	-0.053	0.16	-9999	-0.51	46	46
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.034	0.14	-9999	-0.35	64	64
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.066	0.15	-9999	-0.38	34	34
BMP2-4 (homodimer)	-0.045	0.16	-9999	-0.41	64	64
RGMB	0.016	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.007	0.11	-9999	-0.3	7	7
RGMA	-0.16	0.27	-9999	-0.57	119	119
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.068	0.14	-9999	-0.36	40	40
BMP2-4/USAG1	-0.15	0.22	-9999	-0.38	178	178
SMAD6/SMURF1/SMAD5	-0.023	0.1	-9999	-0.36	6	6
SOSTDC1	-0.18	0.27	-9999	-0.57	137	137
BMP7/BMPR2/BMPR1A-1B	-0.12	0.2	-9999	-0.34	152	152
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.012	0.046	-9999	-0.53	3	3
HFE2	0.002	0.051	-9999	-0.51	4	4
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.061	0.18	-9999	-0.37	94	94
SMAD5/SMAD5/SMAD4	-0.023	0.1	-9999	-0.36	6	6
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.071	0.096	-9999	-0.36	24	24
BMP7 (homodimer)	-0.2	0.28	-9999	-0.57	147	147
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.029	0.12	-9999	-0.36	49	49
SMAD1/SKI	0.053	0.02	-9999	-10000	0	0
SMAD6	0.01	0.053	-9999	-0.52	4	4
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.068	0.17	-9999	-0.35	101	101
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.15	0.25	-9999	-0.54	121	121
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0.032	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.034	0.14	-9999	-0.36	60	60
CHRDL1	-0.32	0.29	-9999	-0.57	235	235
ENDOFIN/SMAD1	0.053	0.02	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.001	0.024	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	-0.041	0.17	-9999	-0.56	40	40
SMURF2	0.016	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.24	0.22	-9999	-0.39	259	259
BMP2-4/GREM1	-0.13	0.19	-9999	-0.33	179	179
SMAD7	0.014	0.029	-9999	-0.57	1	1
SMAD8A/SMAD8A/SMAD4	-0.13	0.24	-9999	-0.51	106	106
SMAD1/SMAD6	0.053	0.02	-9999	-10000	0	0
TAK1/SMAD6	0.023	0	-9999	-10000	0	0
BMP7	-0.2	0.28	-9999	-0.57	147	147
BMP6	0.012	0.046	-9999	-0.53	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.059	0.13	-9999	-0.34	40	40
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.053	0.02	-9999	-10000	0	0
SMAD7/SMURF1	0.022	0.021	-9999	-0.41	1	1
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.013	0.039	-9999	-0.54	2	2
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.097	0.18	-9999	-0.45	51	51
CHRD	-0.042	0.17	-9999	-0.57	40	40
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.083	0.15	-9999	-0.41	39	39
BMP4	-0.015	0.13	-9999	-0.56	22	22
FST	-0.029	0.15	-9999	-0.55	32	32
BMP2-4/NOG	-0.051	0.17	-9999	-0.38	82	82
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.11	0.18	-9999	-0.53	26	26

×

amb2 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.076	0.17	-9999	-0.46	58	58
alphaM/beta2 Integrin/GPIbA	-0.053	0.12	-9999	-0.41	39	39
alphaM/beta2 Integrin/proMMP-9	-0.13	0.18	-9999	-0.37	127	127
PLAUR	0.016	0	-9999	-10000	0	0
HMGB1	-0.003	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.046	0.12	-9999	-0.43	31	31
AGER	-0.011	0.069	-9999	-0.54	6	6
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	0.003	0.084	-9999	-0.56	9	9
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.11	0.14	-9999	-0.53	25	25
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.23	-9999	-0.51	110	110
CYR61	-0.15	0.26	-9999	-0.57	116	116
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.057	0.13	-9999	-0.48	24	24
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.24	-9999	-0.57	84	84
MYH2	-0.051	0.15	-9999	-0.45	26	26
MST1R	-0.02	0.14	-9999	-0.55	26	26
leukocyte activation during inflammatory response	-0.11	0.17	-9999	-0.36	114	114
APOB	-0.081	0.21	-9999	-0.56	66	66
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.036	0.17	-9999	-0.57	36	36
JAM3	-0.025	0.15	-9999	-0.57	28	28
GP1BA	0.002	0.078	-9999	-0.51	9	9
alphaM/beta2 Integrin/CTGF	-0.12	0.2	-9999	-0.44	100	100
alphaM/beta2 Integrin	-0.054	0.17	-9999	-0.53	29	29
JAM3 homodimer	-0.024	0.15	-9999	-0.57	28	28
ICAM2	0.014	0.029	-9999	-0.57	1	1
ICAM1	0.003	0.082	-9999	-0.51	10	10
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.053	0.16	-9999	-0.52	29	29
cell adhesion	-0.053	0.12	-9999	-0.41	39	39
NFKB1	-0.14	0.22	-9999	-0.61	26	26
THY1	0.012	0.045	-9999	-0.51	3	3
RhoA/GDP	0.012	0	-9999	-10000	0	0
Lipoprotein(a)	-0.076	0.17	-9999	-0.37	96	96
alphaM/beta2 Integrin/LRP/tPA	-0.033	0.16	-9999	-0.45	40	40
IL6	-0.33	0.42	-9999	-0.77	189	189
ITGB2	-0.025	0.11	-9999	-0.55	16	16
elevation of cytosolic calcium ion concentration	-0.071	0.13	-9999	-0.36	49	49
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.24	-9999	-0.44	126	126
JAM2	-0.14	0.26	-9999	-0.57	109	109
alphaM/beta2 Integrin/ICAM1	-0.046	0.16	-9999	-0.46	30	30
alphaM/beta2 Integrin/uPA/Plg	-0.065	0.15	-9999	-0.37	53	53
RhoA/GTP	-0.045	0.15	-9999	-0.47	26	26
positive regulation of phagocytosis	-0.066	0.16	-9999	-0.54	31	31
Ron/MSP	-0.024	0.13	-9999	-0.39	47	47
alphaM/beta2 Integrin/uPAR/uPA	-0.053	0.14	-9999	-0.37	49	49
alphaM/beta2 Integrin/uPAR	-0.046	0.12	-9999	-0.43	31	31
PLAU	-0.054	0.18	-9999	-0.51	54	54
PLAT	-0.013	0.12	-9999	-0.56	20	20
actin filament polymerization	-0.048	0.14	-9999	-0.43	26	26
MST1	-0.014	0.12	-9999	-0.51	23	23
alphaM/beta2 Integrin/lipoprotein(a)	-0.11	0.17	-9999	-0.36	114	114
TNF	-0.13	0.21	-9999	-0.56	25	25
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.085	0.15	-9999	-0.36	84	84
fibrinolysis	-0.079	0.14	-9999	-0.37	53	53
HCK	-0.008	0.11	-9999	-0.55	17	17
dendritic cell antigen processing and presentation	-0.053	0.16	-9999	-0.52	29	29
VTN	-0.088	0.22	-9999	-0.56	73	73
alphaM/beta2 Integrin/CYR61	-0.14	0.22	-9999	-0.46	124	124
LPA	-0.043	0.17	-9999	-0.56	38	38
LRP1	0.01	0.058	-9999	-0.57	4	4
cell migration	-0.12	0.21	-9999	-0.43	88	88
FN1	-0.035	0.16	-9999	-0.53	38	38
alphaM/beta2 Integrin/Thy1	-0.048	0.12	-9999	-0.42	34	34
MPO	0.011	0.037	-9999	-0.51	2	2
KNG1	0	0	-9999	-10000	0	0
RAP1/GDP	0.021	0	-9999	-10000	0	0
ROCK1	-0.034	0.14	-9999	-0.45	23	23
ELA2	0	0	-9999	-10000	0	0
PLG	-0.003	0.056	-9999	-0.51	5	5
CTGF	-0.1	0.24	-9999	-0.57	84	84
alphaM/beta2 Integrin/Hck	-0.059	0.16	-9999	-0.51	37	37
ITGAM	-0.035	0.13	-9999	-0.59	22	22
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.089	0.2	-9999	-0.4	101	101
HP	-0.049	0.17	-9999	-0.51	48	48
leukocyte adhesion	-0.17	0.21	-9999	-0.5	100	100
SELP	-0.1	0.24	-9999	-0.57	84	84

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.09	0.2	-10000	0	-0.55	59	59
FYN	-0.073	0.32	-10000	0	-0.74	65	65
LAT/GRAP2/SLP76	-0.099	0.24	-10000	0	-0.6	67	67
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.026	0.2	-10000	0	-0.46	61	61
B2M	0.016	0.005	-10000	0	-10000	0	0
IKBKG	-0.022	0.043	-10000	0	-0.13	26	26
MAP3K8	0.011	0.05	-10000	0	-0.57	3	3
mol:Ca2+	-0.022	0.038	-10000	0	-0.11	42	42
integrin-mediated signaling pathway	0.017	0.036	-10000	0	-0.35	4	4
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.063	0.3	-10000	0	-0.72	61	61
TRPV6	-0.11	0.22	-10000	0	-0.56	81	81
CD28	-0.01	0.12	-10000	0	-0.57	18	18
SHC1	-0.066	0.3	-10000	0	-0.72	60	60
receptor internalization	-0.077	0.31	-10000	0	-0.73	64	64
PRF1	-0.08	0.34	-10000	0	-0.94	43	43
KRAS	0.014	0.026	-10000	0	-0.51	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.009	0.16	-10000	0	-0.37	59	59
LAT	-0.066	0.3	-10000	0	-0.7	64	64
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.04	0.17	-10000	0	-0.57	39	39
CD3E	-0.045	0.18	-10000	0	-0.58	42	42
CD3G	-0.051	0.19	-10000	0	-0.57	46	46
RASGRP2	-0.039	0.081	-10000	0	-0.17	107	107
RASGRP1	-0.02	0.2	-10000	0	-0.46	61	61
HLA-A	0.014	0.03	-10000	0	-0.58	1	1
RASSF5	0.01	0.058	-10000	0	-0.57	4	4
RAP1A/GTP/RAPL	0.018	0.036	-10000	0	-0.35	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.008	0.069	-10000	0	-0.13	55	55
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.04	0.076	-10000	0	-0.22	49	49
PRKCA	-0.041	0.11	-10000	0	-0.28	59	59
GRAP2	-0.049	0.18	-10000	0	-0.57	45	45
mol:IP3	-0.042	0.2	0.23	69	-0.45	60	129
EntrezGene:6957	0	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.081	0.31	-10000	0	-0.73	61	61
ORAI1	0.063	0.12	0.31	81	-0.37	1	82
CSK	-0.069	0.3	-10000	0	-0.73	61	61
B7 family/CD28	-0.14	0.27	-10000	0	-0.69	64	64
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.092	0.35	-10000	0	-0.83	65	65
PTPN6	-0.073	0.3	-10000	0	-0.72	63	63
VAV1	-0.074	0.31	-10000	0	-0.72	66	66
Monovalent TCR/CD3	-0.07	0.26	-10000	0	-0.54	74	74
CBL	0.016	0	-10000	0	-10000	0	0
LCK	-0.079	0.32	-10000	0	-0.76	64	64
PAG1	-0.069	0.3	-10000	0	-0.73	61	61
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.093	0.35	-10000	0	-0.8	67	67
CD80	-0.054	0.18	-10000	0	-0.51	54	54
CD86	0.008	0.063	-10000	0	-0.56	5	5
PDK1/CARD11/BCL10/MALT1	-0.049	0.093	-10000	0	-0.26	57	57
HRAS	0.016	0	-10000	0	-10000	0	0
GO:0035030	-0.063	0.24	-10000	0	-0.56	64	64
CD8A	-0.041	0.18	-10000	0	-0.57	40	40
CD8B	-0.046	0.18	-10000	0	-0.57	44	44
PTPRC	-0.056	0.19	-10000	0	-0.57	50	50
PDK1/PKC theta	-0.037	0.25	-10000	0	-0.57	64	64
CSK/PAG1	-0.06	0.29	-10000	0	-0.71	59	59
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	0.021	0.025	-10000	0	-0.42	1	1
GRAP2/SLP76	-0.12	0.29	-10000	0	-0.71	67	67
STIM1	0.034	0.061	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.086	-10000	0	-0.17	43	43
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.087	0.34	-10000	0	-0.8	64	64
mol:DAG	-0.058	0.16	-10000	0	-0.4	61	61
RAP1A/GDP	0.005	0.03	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	0.004	0.081	-10000	0	-0.57	8	8
cytotoxic T cell degranulation	-0.073	0.31	-10000	0	-0.85	45	45
RAP1A/GTP	-0.017	0.027	-10000	0	-0.062	106	106
mol:PI-3-4-5-P3	-0.042	0.24	-10000	0	-0.57	61	61
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.065	0.26	0.24	68	-0.6	61	129
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.007	0.11	-10000	0	-0.57	16	16
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.096	0.23	-10000	0	-0.58	65	65
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.06	0.21	-10000	0	-0.53	62	62
CARD11	-0.001	0.095	-10000	0	-0.55	12	12
PRKCB	-0.085	0.15	-10000	0	-0.35	81	81
PRKCE	-0.039	0.11	-10000	0	-0.28	58	58
PRKCQ	-0.058	0.29	-10000	0	-0.66	66	66
LCP2	0.011	0.05	-10000	0	-0.57	3	3
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.016	0.17	-10000	0	-0.39	61	61
IKK complex	0.014	0.069	-10000	0	-0.12	51	51
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	0.005	0.13	-10000	0	-0.28	54	54
PDPK1	-0.02	0.19	-10000	0	-0.44	61	61
TCR/CD3/MHC I/CD8/Fyn	-0.11	0.38	-10000	0	-0.87	69	69

×

LPA receptor mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.015	0.13	-9999	-0.37	36	36
NF kappa B1 p50/RelA/I kappa B alpha	0.011	0.11	-9999	-0.33	11	11
AP1	-0.15	0.21	-9999	-0.56	61	61
mol:PIP3	-0.063	0.13	-9999	-0.46	26	26
AKT1	0.029	0.1	-9999	-0.39	10	10
PTK2B	-0.007	0.1	-9999	-0.27	34	34
RHOA	0.017	0.05	-9999	-0.26	1	1
PIK3CB	0.015	0.001	-9999	-10000	0	0
mol:Ca2+	0.002	0.097	-9999	-0.34	7	7
MAGI3	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.04	0.15	-9999	-0.36	59	59
HRAS/GDP	0.012	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.014	0.12	-9999	-0.28	50	50
NF kappa B1 p50/RelA	-0.053	0.12	-9999	-0.43	20	20
endothelial cell migration	-0.054	0.22	-9999	-0.56	60	60
ADCY4	-0.12	0.23	-9999	-0.48	92	92
ADCY5	-0.24	0.31	-9999	-0.58	159	159
ADCY6	-0.11	0.23	-9999	-0.47	92	92
ADCY7	-0.11	0.23	-9999	-0.47	92	92
ADCY1	-0.12	0.23	-9999	-0.48	95	95
ADCY2	-0.21	0.3	-9999	-0.55	142	142
ADCY3	-0.11	0.23	-9999	-0.47	92	92
ADCY8	-0.12	0.23	-9999	-0.48	92	92
ADCY9	-0.12	0.24	-9999	-0.49	93	93
GSK3B	0.002	0.096	-9999	-0.28	23	23
arachidonic acid secretion	-0.12	0.23	-9999	-0.48	94	94
GNG2	0.007	0.07	-9999	-0.57	6	6
TRIP6	0.024	0.022	-9999	-10000	0	0
GNAO1	-0.13	0.23	-9999	-0.41	154	154
HRAS	0.016	0	-9999	-10000	0	0
NFKBIA	0	0.12	-9999	-0.36	15	15
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.08	-9999	-0.92	3	3
JUN	-0.007	0.11	-9999	-0.57	16	16
LPA/LPA2/NHERF2	-0.007	0.035	-9999	-0.33	3	3
TIAM1	-0.005	0.094	-9999	-1.1	3	3
PIK3R1	0.014	0.029	-9999	-0.57	1	1
mol:IP3	0.001	0.098	-9999	-0.35	7	7
PLCB3	0.024	0.036	-9999	-0.29	3	3
FOS	-0.17	0.27	-9999	-0.57	129	129
positive regulation of mitosis	-0.12	0.23	-9999	-0.48	94	94
LPA/LPA1-2-3	-0.045	0.16	-9999	-0.36	66	66
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
stress fiber formation	-0.008	0.12	-9999	-0.35	24	24
GNAZ	-0.099	0.2	-9999	-0.38	130	130
EGFR/PI3K-beta/Gab1	-0.065	0.13	-9999	-0.48	26	26
positive regulation of dendritic cell cytokine production	-0.072	0.15	-9999	-0.36	66	66
LPA/LPA2/MAGI-3	-0.006	0.035	-9999	-0.33	3	3
ARHGEF1	0	0.12	-9999	-0.47	9	9
GNAI2	-0.02	0.14	-9999	-0.33	60	60
GNAI3	-0.02	0.14	-9999	-0.33	57	57
GNAI1	-0.023	0.14	-9999	-0.33	63	63
LPA/LPA3	-0.036	0.13	-9999	-0.41	38	38
LPA/LPA2	-0.004	0.046	-9999	-0.4	3	3
LPA/LPA1	-0.058	0.15	-9999	-0.4	60	60
HB-EGF/EGFR	-0.083	0.18	-9999	-0.33	126	126
HBEGF	-0.091	0.19	-9999	-0.38	119	119
mol:DAG	0.001	0.098	-9999	-0.35	7	7
cAMP biosynthetic process	-0.16	0.27	-9999	-0.5	131	131
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0.001	-9999	-10000	0	0
LYN	0	0.12	-9999	-0.36	15	15
GNAQ	-0.009	0.094	-9999	-0.29	35	35
LPAR2	0.012	0.045	-9999	-0.51	3	3
LPAR3	-0.039	0.17	-9999	-0.56	38	38
LPAR1	-0.039	0.17	-9999	-0.6	31	31
IL8	-0.12	0.23	-9999	-0.5	86	86
PTK2	-0.031	0.15	-9999	-0.34	60	60
Rac1/GDP	0.012	0	-9999	-10000	0	0
CASP3	-0.04	0.15	-9999	-0.36	59	59
EGFR	-0.008	0.11	-9999	-0.54	17	17
PLCG1	-0.019	0.11	-9999	-0.32	38	38
PLD2	-0.031	0.15	-9999	-0.34	60	60
G12/G13	-0.009	0.12	-9999	-0.36	31	31
PI3K-beta	-0.034	0.09	-9999	-0.45	10	10
cell migration	-0.019	0.054	-9999	-0.26	4	4
SLC9A3R2	0.016	0	-9999	-10000	0	0
PXN	-0.009	0.12	-9999	-0.36	24	24
HRAS/GTP	-0.12	0.24	-9999	-0.49	94	94
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.13	0.23	-9999	-0.51	110	110
PRKCE	0.016	0	-9999	-10000	0	0
PRKCD	0.009	0.094	-9999	-0.34	6	6
Gi(beta/gamma)	-0.11	0.23	-9999	-0.46	94	94
mol:LPA	-0.01	0.051	-9999	-0.19	29	29
TRIP6/p130 Cas/FAK1/Paxillin	-0.051	0.12	-9999	-0.48	17	17
MAPKKK cascade	-0.12	0.23	-9999	-0.48	94	94
contractile ring contraction involved in cytokinesis	0.017	0.049	-9999	-0.26	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.054	0.15	-9999	-0.32	90	90
GNA15	-0.011	0.098	-9999	-0.3	38	38
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	-0.015	0.12	-9999	-0.29	50	50
GNA11	-0.01	0.099	-9999	-0.31	35	35
Rac1/GTP	0.023	0.087	-9999	-0.99	3	3
MMP2	-0.054	0.22	-9999	-0.56	60	60

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.017	0.032	-9999	-0.41	2	2
PDGFRB	-0.002	0.091	-9999	-0.58	10	10
SPHK1	-0.035	0.061	-9999	-1.1	1	1
mol:S1P	-0.04	0.063	-9999	-0.66	2	2
S1P1/S1P/Gi	-0.19	0.27	-9999	-0.49	147	147
GNAO1	-0.17	0.27	-9999	-0.57	129	129
PDGFB-D/PDGFRB/PLCgamma1	-0.16	0.25	-9999	-0.51	99	99
PLCG1	-0.17	0.25	-9999	-0.46	147	147
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.002	0.091	-9999	-0.58	10	10
GNAI2	0.012	0.007	-9999	-10000	0	0
GNAI3	0.012	0.007	-9999	-10000	0	0
GNAI1	0.008	0.051	-9999	-0.58	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.015	0.028	-9999	-0.34	2	2
S1P1/S1P	-0.042	0.07	-9999	-0.42	4	4
negative regulation of cAMP metabolic process	-0.18	0.26	-9999	-0.48	147	147
MAPK3	-0.22	0.32	-9999	-0.6	145	145
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
KDR	0.012	0.041	-9999	-0.57	2	2
PLCB2	-0.014	0.081	-9999	-0.35	6	6
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.034	0.058	-9999	-0.35	4	4
receptor internalization	-0.04	0.066	-9999	-0.39	4	4
PTGS2	-0.31	0.47	-9999	-0.88	143	143
Rac1/GTP	-0.034	0.058	-9999	-0.35	4	4
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	0.015	0.003	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.18	0.26	-9999	-0.48	147	147
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.12	0.24	-9999	-0.57	89	89
MAPK1	-0.22	0.32	-9999	-0.6	145	145
S1P1/S1P/PDGFB-D/PDGFRB	-0.032	0.11	-9999	-0.43	11	11
ABCC1	0.011	0.037	-9999	-0.51	2	2

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.075	0.2	-9999	-0.59	56	56
PDGF/PDGFRA/CRKL	-0.042	0.15	-9999	-0.42	57	57
positive regulation of JUN kinase activity	-0.011	0.11	-9999	-0.31	24	24
CRKL	0.013	0.036	-9999	-0.51	2	2
PDGF/PDGFRA/Caveolin-3	-0.052	0.15	-9999	-0.42	58	58
AP1	-0.34	0.46	-9999	-1	129	129
mol:IP3	-0.05	0.16	-9999	-0.43	56	56
PLCG1	-0.05	0.16	-9999	-0.43	56	56
PDGF/PDGFRA/alphaV Integrin	-0.041	0.15	-9999	-0.42	56	56
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.05	0.16	-9999	-0.43	56	56
CAV3	0	0.044	-9999	-0.51	3	3
CAV1	-0.012	0.12	-9999	-0.57	19	19
SHC/Grb2/SOS1	-0.01	0.12	-9999	-0.31	24	24
PDGF/PDGFRA/Shf	-0.047	0.16	-9999	-0.43	60	60
FOS	-0.3	0.48	-9999	-0.99	129	129
JUN	-0.038	0.094	-9999	-0.48	16	16
oligodendrocyte development	-0.041	0.15	-9999	-0.42	56	56
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
mol:DAG	-0.05	0.16	-9999	-0.43	56	56
PDGF/PDGFRA	-0.075	0.2	-9999	-0.59	56	56
actin cytoskeleton reorganization	-0.04	0.15	-9999	-0.41	56	56
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.014	0.026	-9999	-0.51	1	1
PI3K	-0.023	0.13	-9999	-0.34	57	57
PDGF/PDGFRA/Crk/C3G	-0.023	0.13	-9999	-0.34	56	56
JAK1	-0.038	0.15	-9999	-0.41	56	56
ELK1/SRF	-0.009	0.12	-9999	-0.31	56	56
SHB	0.016	0	-9999	-10000	0	0
SHF	0.006	0.076	-9999	-0.57	7	7
CSNK2A1	0.022	0.028	-9999	-10000	0	0
GO:0007205	-0.054	0.16	-9999	-0.46	56	56
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.011	0.11	-9999	-0.31	24	24
PDGF/PDGFRA/SHB	-0.04	0.15	-9999	-0.41	56	56
PDGF/PDGFRA/Caveolin-1	-0.059	0.19	-9999	-0.47	64	64
ITGAV	0.014	0.029	-9999	-0.57	1	1
ELK1	-0.049	0.15	-9999	-0.41	56	56
PIK3CA	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.04	0.15	-9999	-0.41	56	56
JAK-STAT cascade	-0.038	0.15	-9999	-0.41	56	56
cell proliferation	-0.047	0.16	-9999	-0.43	60	60

×

Neurotrophic factor-mediated Trk 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
CRKL	0.013	0.036	-10000	0	-0.51	2	2
RAS family/GTP/Tiam1	-0.083	0.12	-10000	0	-0.27	49	49
NT3 (dimer)/TRKC	-0.26	0.27	-10000	0	-0.48	226	226
NT3 (dimer)/TRKB	-0.26	0.3	-10000	0	-0.48	230	230
SHC/Grb2/SOS1/GAB1/PI3K	0.043	0.016	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.096	0.23	-10000	0	-0.57	78	78
PIK3CA	0.016	0	-10000	0	-10000	0	0
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	0.005	0.068	-10000	0	-0.51	7	7
NTRK2	-0.22	0.28	-10000	0	-0.57	164	164
NTRK3	-0.27	0.29	-10000	0	-0.57	196	196
NT-4/5 (dimer)/TRKB	-0.22	0.27	-10000	0	-0.44	214	214
neuron apoptosis	0.18	0.25	0.52	121	-10000	0	121
SHC 2-3/Grb2	-0.2	0.28	-10000	0	-0.57	121	121
SHC1	0.014	0.026	-10000	0	-0.51	1	1
SHC2	-0.21	0.28	-10000	0	-0.64	101	101
SHC3	-0.21	0.26	-10000	0	-0.58	113	113
STAT3 (dimer)	0.011	0.061	-10000	0	-0.34	7	7
NT3 (dimer)/TRKA	-0.13	0.22	-10000	0	-0.39	154	154
RIN/GDP	-0.063	0.1	-10000	0	-0.24	32	32
GIPC1	0.016	0	-10000	0	-10000	0	0
KRAS	0.014	0.026	-10000	0	-0.51	1	1
DNAJA3	-0.1	0.16	-10000	0	-0.37	92	92
RIN/GTP	0	0.018	-10000	0	-0.37	1	1
CCND1	0.007	0.13	-10000	0	-0.52	21	21
MAGED1	0.016	0	-10000	0	-10000	0	0
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.023	0.14	-10000	0	-0.57	27	27
SHC/GRB2/SOS1	0.031	0.016	-10000	0	-0.29	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.049	0.17	-10000	0	-0.37	81	81
TRKA/NEDD4-2	0.015	0.049	-10000	0	-0.36	7	7
ELMO1	0.011	0.05	-10000	0	-0.57	3	3
RhoG/GTP/ELMO1/DOCK1	0.017	0.046	-10000	0	-0.43	4	4
NGF	-0.062	0.2	-10000	0	-0.57	54	54
HRAS	0.016	0	-10000	0	-10000	0	0
DOCK1	0.013	0.041	-10000	0	-0.57	2	2
GAB2	0.014	0.029	-10000	0	-0.57	1	1
RIT2	0	0.025	-10000	0	-0.51	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.007	0.068	-10000	0	-0.51	7	7
DNM1	0	0.095	-10000	0	-0.57	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.1	0.16	-10000	0	-0.36	94	94
mol:GDP	-0.094	0.15	-10000	0	-0.35	41	41
NGF (dimer)	-0.062	0.2	-10000	0	-0.57	54	54
RhoG/GDP	0.008	0.037	-10000	0	-0.42	3	3
RIT1/GDP	-0.057	0.1	-10000	0	-0.24	26	26
TIAM1	0.011	0.05	-10000	0	-0.57	3	3
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
BDNF (dimer)/TRKB	-0.18	0.24	-10000	0	-0.4	201	201
KIDINS220/CRKL/C3G	0.021	0.026	-10000	0	-0.36	2	2
SHC/RasGAP	0.022	0.019	-10000	0	-0.36	1	1
FRS2 family/SHP2	0.026	0.042	-10000	0	-0.29	7	7
SHC/GRB2/SOS1/GAB1	0.04	0.015	-10000	0	-10000	0	0
RIT1/GTP	0.012	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.095	0.23	-10000	0	-0.57	77	77
RAP1/GDP	-0.066	0.067	-10000	0	-0.23	3	3
KIDINS220/CRKL	0.013	0.036	-10000	0	-0.51	2	2
BDNF (dimer)	-0.096	0.23	-10000	0	-0.57	78	78
ubiquitin-dependent protein catabolic process	-0.024	0.13	-10000	0	-0.33	61	61
Schwann cell development	-0.054	0.037	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.035	0.038	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.044	0.022	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.32	0.28	-10000	0	-0.61	168	168
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
Rap1/GTP	-0.063	0.072	-10000	0	-10000	0	0
STAT3	0.011	0.061	-10000	0	-0.34	7	7
axon guidance	-0.31	0.26	-10000	0	-0.58	168	168
MAPK3	-0.035	0.15	-10000	0	-0.34	69	69
MAPK1	-0.035	0.15	-10000	0	-0.34	69	69
CDC42/GDP	-0.057	0.1	-10000	0	-0.24	30	30
NTF3	-0.095	0.23	-10000	0	-0.57	77	77
NTF4	-0.023	0.14	-10000	0	-0.57	27	27
NGF (dimer)/TRKA/FAIM	-0.024	0.13	-10000	0	-0.34	61	61
PI3K	0.022	0.021	-10000	0	-0.41	1	1
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.14	0.17	-10000	0	-0.38	96	96
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	-0.22	0.25	-10000	0	-0.43	228	228
RGS19	0.014	0.026	-10000	0	-0.51	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.01	0.073	-10000	0	-10000	0	0
Rac1/GDP	-0.057	0.1	-10000	0	-0.24	29	29
NGF (dimer)/TRKA/GRIT	-0.035	0.13	-10000	0	-0.34	61	61
neuron projection morphogenesis	-0.072	0.18	-10000	0	-0.51	28	28
NGF (dimer)/TRKA/NEDD4-2	-0.024	0.13	-10000	0	-0.34	61	61
MAP2K1	0.045	0.014	-10000	0	-10000	0	0
NGFR	-0.12	0.25	-10000	0	-0.57	95	95
NGF (dimer)/TRKA/GIPC/GAIP	-0.005	0.11	-10000	0	-0.33	19	19
RAS family/GTP/PI3K	0.035	0.016	-10000	0	-0.24	1	1
FRS2 family/SHP2/GRB2/SOS1	0.042	0.036	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0.023	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.05	-10000	0	-0.57	3	3
MAPKKK cascade	-0.13	0.24	-10000	0	-0.73	54	54
RASA1	0.016	0	-10000	0	-10000	0	0
TRKA/c-Abl	0.015	0.049	-10000	0	-0.36	7	7
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.16	0.22	-10000	0	-0.36	194	194
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.004	0.12	-10000	0	-0.55	2	2
MATK	-0.025	0.15	-10000	0	-0.56	29	29
NEDD4L	0.016	0	-10000	0	-10000	0	0
RAS family/GDP	-0.062	0.063	-10000	0	-0.23	2	2
NGF (dimer)/TRKA	-0.11	0.18	-10000	0	-0.36	123	123
Rac1/GTP	-0.11	0.11	-10000	0	-0.29	83	83
FRS2 family/SHP2/CRK family	0.041	0.041	-10000	0	-10000	0	0

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.11	0.15	0.42	59	-10000	0	59
GNAI2	0.016	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.008	0.064	-10000	0	-0.31	16	16
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.17	0.27	-10000	0	-0.57	129	129
RhoA/GTP	-0.09	0.18	-10000	0	-0.43	59	59
negative regulation of cAMP metabolic process	-0.11	0.19	-10000	0	-0.34	131	131
GNAZ	-0.11	0.24	-10000	0	-0.57	89	89
GNAI3	0.016	0	-10000	0	-10000	0	0
GNA12	0.016	0	-10000	0	-10000	0	0
S1PR5	-0.005	0.1	-10000	0	-0.52	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.11	0.19	-10000	0	-0.35	131	131
RhoA/GDP	0.012	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.05	-10000	0	-0.57	3	3

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.017	0.051	-9999	-0.27	12	12
RGS9BP	-0.009	0.12	-9999	-0.56	17	17
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0.025	-9999	-0.51	1	1
mol:Na +	-0.1	0.18	-9999	-0.34	136	136
mol:ADP	0.01	0.027	-9999	-0.36	2	2
GNAT2	0.007	0.052	-9999	-0.51	4	4
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.35	100	100
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.006	0.038	-9999	-0.3	6	6
GRK7	0.011	0.026	-9999	-0.51	1	1
CNGB3	-0.12	0.23	-9999	-0.51	108	108
Cone Metarhodopsin II/X-Arrestin	0.002	0.005	-9999	-10000	0	0
mol:Ca2+	-0.1	0.18	-9999	-0.32	147	147
Cone PDE6	-0.051	0.14	-9999	-0.3	94	94
Cone Metarhodopsin II	0.008	0.021	-9999	-0.28	2	2
Na + (4 Units)	-0.1	0.18	-9999	-0.32	147	147
GNAT2/GDP	-0.048	0.14	-9999	-0.29	97	97
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.007	0.035	-9999	-0.28	6	6
Cone Transducin	0.019	0.054	-9999	-0.29	12	12
SLC24A2	-0.017	0.12	-9999	-0.51	22	22
GNB3/GNGT2	0.015	0.059	-9999	-0.4	8	8
GNB3	0.01	0.056	-9999	-0.55	4	4
GNAT2/GTP	0.006	0.037	-9999	-0.37	4	4
CNGA3	-0.047	0.17	-9999	-0.57	40	40
ARR3	0.003	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.18	-9999	-0.34	136	136
mol:Pi	-0.062	0.17	-9999	-0.35	100	100
Cone CNG Channel	-0.094	0.14	-9999	-0.35	40	40
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.017	0.12	-9999	-0.51	22	22
RGS9	-0.11	0.24	-9999	-0.57	87	87
PDE6C	0.003	0.006	-9999	-10000	0	0
GNGT2	0.01	0.058	-9999	-0.57	4	4
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0	0.036	-9999	-0.51	2	2

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.01	0.14	-9999	-0.34	54	54
MAP4K1	-0.003	0.1	-9999	-0.56	13	13
MAP3K8	0.011	0.05	-9999	-0.57	3	3
PRKCB	-0.15	0.26	-9999	-0.57	118	118
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.013	0.036	-9999	-0.51	2	2
MAP3K1	0.015	0.11	-9999	-0.56	6	6
JUN	-0.15	0.29	-9999	-0.57	123	123
MAP3K7	0.015	0.11	-9999	-0.56	6	6
GRAP2	-0.049	0.18	-9999	-0.57	45	45
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	0.022	0.11	-9999	-0.52	7	7
LAT	0.014	0.026	-9999	-0.51	1	1
LCP2	0.011	0.05	-9999	-0.57	3	3
MAPK8	-0.15	0.3	-9999	-0.6	121	121
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.006	0.12	-9999	-0.28	46	46
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.001	0.13	-9999	-0.32	50	50

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.028	-9999	-10000	0	0
VDR	0.011	0.048	-9999	-0.55	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.011	0.13	-9999	-0.39	7	7
RXRs/LXRs/DNA/Oxysterols	0.007	0.12	-9999	-0.38	7	7
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.006	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.004	0.11	-9999	-0.5	7	7
RXRs/NUR77	-0.23	0.22	-9999	-0.37	273	273
RXRs/PPAR	-0.045	0.14	-9999	-0.37	17	17
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.009	0.035	-9999	-0.4	3	3
RARs/VDR/DNA/Vit D3	0.009	0.094	-9999	-0.29	35	35
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.048	-9999	-0.55	3	3
RARs/RARs/DNA/9cRA	0.004	0.088	-9999	-0.29	34	34
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	0.028	0.043	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.004	0.11	-9999	-0.5	7	7
THRA	0.016	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.009	0.035	-9999	-0.4	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	-0.044	0.15	-9999	-0.3	106	106
NR1H4	-0.12	0.23	-9999	-0.56	89	89
RXRs/LXRs/DNA	-0.014	0.15	-9999	-0.38	7	7
NR1H2	0.022	0.005	-9999	-10000	0	0
NR1H3	0.022	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.04	0.14	-9999	-0.28	108	108
NR4A1	-0.31	0.29	-9999	-0.57	230	230
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.079	0.16	-9999	-0.28	114	114
RXRG	-0.14	0.25	-9999	-0.56	107	107
RXR alpha/CCPG	0.026	0.022	-9999	-0.4	1	1
RXRA	0.02	0.029	-9999	-0.56	1	1
RXRB	0.022	0.005	-9999	-10000	0	0
THRB	-0.019	0.14	-9999	-0.57	24	24
PPARG	-0.024	0.15	-9999	-0.56	28	28
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.009	0.13	-9999	-0.48	5	5
mol:Oxysterols	0.006	0.007	-9999	-10000	0	0
cholesterol transport	0.007	0.12	-9999	-0.38	7	7
PPARA	0.013	0.041	-9999	-0.57	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.033	0.16	-9999	-0.57	34	34
RXRs/NUR77/BCL2	-0.2	0.2	-9999	-0.32	275	275
SREBF1	0.016	0.11	-9999	-0.47	2	2
RXRs/RXRs/DNA/9cRA	-0.044	0.15	-9999	-0.3	106	106
ABCA1	0.017	0.11	-9999	-0.46	1	1
RARs/THRs	0.002	0.12	-9999	-0.57	7	7
RXRs/FXR	-0.11	0.21	-9999	-0.35	157	157
BCL2	-0.007	0.11	-9999	-0.57	16	16

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.09	0.15	-9999	-0.33	31	31
NF kappa B1 p50/RelA/I kappa B alpha	-0.053	0.14	-9999	-0.47	6	6
alphaV/beta3 Integrin/Osteopontin/Src	-0.14	0.17	-9999	-0.35	166	166
AP1	-0.17	0.25	-9999	-0.52	102	102
ILK	-0.1	0.16	-9999	-0.46	11	11
bone resorption	-0.075	0.15	-9999	-0.48	18	18
PTK2B	0.014	0.029	-9999	-0.57	1	1
PYK2/p130Cas	-0.083	0.15	-9999	-0.51	6	6
ITGAV	0.017	0.03	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0	0.097	-9999	-0.4	22	22
alphaV/beta3 Integrin/Osteopontin	-0.15	0.16	-9999	-0.34	85	85
MAP3K1	-0.1	0.16	-9999	-0.3	82	82
JUN	-0.007	0.11	-9999	-0.57	16	16
MAPK3	-0.09	0.16	-9999	-0.34	41	41
MAPK1	-0.09	0.16	-9999	-0.34	41	41
Rac1/GDP	0.012	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.092	0.16	-9999	-0.46	12	12
ITGB3	-0.047	0.18	-9999	-0.56	46	46
NFKBIA	-0.073	0.15	-9999	-0.33	41	41
FOS	-0.17	0.27	-9999	-0.57	129	129
CD44	-0.006	0.11	-9999	-0.56	15	15
CHUK	0.016	0	-9999	-10000	0	0
PLAU	-0.09	0.18	-9999	-0.48	40	40
NF kappa B1 p50/RelA	-0.095	0.1	-9999	-0.45	6	6
BCAR1	0.016	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.035	0.13	-9999	-0.4	46	46
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.11	0.16	-9999	-0.33	38	38
VAV3	-0.097	0.16	-9999	-0.52	10	10
MAP3K14	-0.1	0.16	-9999	-0.34	49	49
ROCK2	0.006	0.076	-9999	-0.57	7	7
SPP1	-0.19	0.26	-9999	-0.5	165	165
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.082	0.14	-9999	-0.48	10	10
MMP2	-0.16	0.24	-9999	-0.55	72	72

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.021	0.026	-9999	-0.35	2	2
ADCY5	-0.16	0.18	-9999	-0.35	206	206
ADCY6	0.022	0	-9999	-10000	0	0
ADCY7	0.022	0	-9999	-10000	0	0
ADCY1	0.013	0.056	-9999	-0.31	12	12
ADCY2	-0.12	0.18	-9999	-0.35	153	153
ADCY3	0.022	0	-9999	-10000	0	0
ADCY8	0.011	0.031	-9999	-0.3	4	4
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.016	0.048	-9999	-0.35	7	7
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.062	0.094	-9999	-0.28	9	9

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.015	0.077	-9999	-10000	0	0
BIRC5	-0.36	0.24	-9999	-0.51	293	293
NFKBIA	-0.014	0.078	-9999	-10000	0	0
CPEB1	-0.26	0.29	-9999	-0.57	192	192
AKT1	-0.014	0.078	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.022	0.068	-9999	-0.4	1	1
NDEL1/TACC3	-0.023	0.1	-9999	-0.32	22	22
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.018	0.004	-9999	-10000	0	0
PAK1/Aurora A	-0.016	0.08	-9999	-0.47	1	1
MDM2	-0.001	0.092	-9999	-0.51	13	13
JUB	0.012	0.045	-9999	-0.51	3	3
TPX2	-0.18	0.19	-9999	-0.36	219	219
TP53	0	0.056	-9999	-10000	0	0
DLG7	-0.025	0.077	-9999	-10000	0	0
AURKAIP1	0.014	0.026	-9999	-0.51	1	1
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.025	0.11	-9999	-0.33	25	25
G2/M transition of mitotic cell cycle	-0.022	0.067	-9999	-0.4	1	1
AURKA	-0.029	0.096	-9999	-10000	0	0
AURKB	-0.049	0.06	-9999	-0.13	98	98
CDC25B	-0.007	0.07	-9999	-0.24	6	6
G2/M transition checkpoint	-0.023	0.071	-9999	-0.35	3	3
mRNA polyadenylation	-0.18	0.18	-9999	-0.36	192	192
Aurora A/CPEB	-0.18	0.18	-9999	-0.36	192	192
Aurora A/TACC1/TRAP/chTOG	0.005	0.072	-9999	-0.36	3	3
BRCA1	0.014	0.026	-9999	-0.51	1	1
centrosome duplication	-0.016	0.08	-9999	-0.47	1	1
regulation of centrosome cycle	-0.033	0.096	-9999	-0.32	22	22
spindle assembly	0.004	0.071	-9999	-0.35	3	3
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.18	0.15	-9999	-0.35	121	121
CENPA	-0.049	0.062	-9999	-0.14	98	98
Aurora A/PP2A	-0.015	0.077	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.004	0.06	-9999	-10000	0	0
negative regulation of DNA binding	0	0.055	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.023	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.023	0.071	-9999	-0.35	3	3
mitotic prometaphase	0.012	0.015	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.029	0.096	-9999	-10000	0	0
TACC1	0.011	0.05	-9999	-0.57	3	3
TACC3	-0.024	0.14	-9999	-0.51	31	31
Aurora A/Antizyme1	-0.004	0.07	-9999	-0.26	1	1
Aurora A/RasGAP	-0.015	0.077	-9999	-10000	0	0
OAZ1	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.004	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.031	0.018	-9999	-0.34	1	1
Importin alpha/Importin beta/TPX2	-0.18	0.19	-9999	-0.36	219	219
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.16	0.19	-9999	-0.34	177	177
PAK1	0.014	0.029	-9999	-0.57	1	1
CKAP5	0.016	0	-9999	-10000	0	0

×

S1P4 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.17	0.27	-9999	-0.57	129	129
CDC42/GTP	-0.088	0.18	-9999	-0.44	58	58
PLCG1	-0.091	0.18	-9999	-0.45	58	58
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0.023	0	-9999	-10000	0	0
cell migration	-0.11	0.16	-9999	-0.43	58	58
S1PR5	-0.005	0.1	-9999	-0.52	16	16
S1PR4	0.006	0.073	-9999	-0.54	7	7
MAPK3	-0.091	0.18	-9999	-0.45	58	58
MAPK1	-0.091	0.18	-9999	-0.45	58	58
S1P/S1P5/Gi	-0.11	0.19	-9999	-0.35	131	131
GNAI1	0.011	0.05	-9999	-0.57	3	3
CDC42/GDP	0.012	0	-9999	-10000	0	0
S1P/S1P5/G12	0.008	0.064	-9999	-0.31	16	16
RHOA	0.032	0.039	-9999	-0.28	4	4
S1P/S1P4/Gi	-0.1	0.2	-9999	-0.35	130	130
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.57	89	89
S1P/S1P4/G12/G13	0.025	0.042	-9999	-0.29	7	7
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.011	0.029	-10000	0	-0.5	1	1
SVIL	0.007	0.059	-10000	0	-0.57	4	4
ZNF318	0.023	0.033	-10000	0	-10000	0	0
JMJD2C	-0.002	0.025	-10000	0	-0.074	40	40
T-DHT/AR/Ubc9	-0.12	0.19	-10000	0	-0.37	148	148
CARM1	0.015	0.002	-10000	0	-10000	0	0
PRDX1	0.016	0.002	-10000	0	-10000	0	0
PELP1	0.017	0.005	-10000	0	-10000	0	0
CTNNB1	0.013	0.01	-10000	0	-10000	0	0
AKT1	0.018	0.009	-10000	0	-10000	0	0
PTK2B	0.012	0.03	-10000	0	-0.57	1	1
MED1	0.018	0.01	-10000	0	-10000	0	0
MAK	0.012	0.083	0.19	4	-0.5	9	13
response to oxidative stress	0	0.002	-10000	0	-10000	0	0
HIP1	0.01	0.043	-10000	0	-0.57	2	2
GSN	0.003	0.077	-10000	0	-0.57	7	7
NCOA2	-0.019	0.14	-10000	0	-0.57	24	24
NCOA6	0.012	0.029	-10000	0	-0.51	1	1
DNA-PK	0.032	0.036	-10000	0	-10000	0	0
NCOA4	0.015	0.001	-10000	0	-10000	0	0
PIAS3	0.013	0.01	-10000	0	-10000	0	0
cell proliferation	-0.02	0.051	-10000	0	-0.21	4	4
XRCC5	0.017	0.007	-10000	0	-10000	0	0
UBE3A	0.011	0.02	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.22	-10000	0	-0.4	160	160
FHL2	-0.023	0.13	-10000	0	-1.1	3	3
RANBP9	0.013	0.012	-10000	0	-10000	0	0
JMJD1A	-0.011	0.056	-10000	0	-0.12	83	83
CDK6	0	0.095	-10000	0	-0.57	11	11
TGFB1I1	-0.006	0.1	-10000	0	-0.57	13	13
T-DHT/AR/CyclinD1	-0.14	0.2	-10000	0	-0.38	160	160
XRCC6	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR	-0.12	0.21	-10000	0	-0.38	151	151
CTDSP1	0.015	0.003	-10000	0	-10000	0	0
CTDSP2	0.021	0.022	-10000	0	-10000	0	0
BRCA1	0.012	0.03	-10000	0	-0.53	1	1
TCF4	0.011	0.073	-10000	0	-0.57	6	6
CDKN2A	-0.24	0.26	-10000	0	-0.5	205	205
SRF	0.026	0.015	-10000	0	-10000	0	0
NKX3-1	-0.073	0.18	-10000	0	-0.41	50	50
KLK3	-0.052	0.3	-10000	0	-1.5	16	16
TMF1	0.015	0.003	-10000	0	-10000	0	0
HNRNPA1	0.018	0.012	-10000	0	-10000	0	0
AOF2	-0.003	0.015	-10000	0	-0.071	16	16
APPL1	0.031	0.02	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.12	0.19	-10000	0	-0.37	148	148
AR	-0.2	0.29	-10000	0	-0.58	148	148
UBA3	0.015	0.003	-10000	0	-10000	0	0
PATZ1	0.018	0.012	-10000	0	-10000	0	0
PAWR	0.013	0.029	-10000	0	-0.57	1	1
PRKDC	0.017	0.007	-10000	0	-10000	0	0
PA2G4	0.019	0.015	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.11	0.18	-10000	0	-0.34	148	148
RPS6KA3	0.013	0.014	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.12	0.19	-10000	0	-0.37	148	148
LATS2	0.017	0.031	-10000	0	-0.57	1	1
T-DHT/AR/PRX1	-0.11	0.18	-10000	0	-0.33	148	148
Cyclin D3/CDK11 p58	0.012	0.003	-10000	0	-10000	0	0
VAV3	0.003	0.078	-10000	0	-0.54	8	8
KLK2	-0.088	0.12	-10000	0	-0.47	20	20
CASP8	0.016	0.004	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.2	-10000	0	-0.35	159	159
TMPRSS2	-0.21	0.42	-10000	0	-1	81	81
CCND1	-0.013	0.12	-10000	0	-0.53	21	21
PIAS1	0.011	0.02	-10000	0	-10000	0	0
mol:T-DHT	-0.007	0.026	-10000	0	-0.071	36	36
CDC2L1	0	0.001	-10000	0	-10000	0	0
PIAS4	0.009	0.031	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.2	-10000	0	-0.38	154	154
CMTM2	0.01	0.058	-10000	0	-0.51	5	5
SNURF	-0.029	0.15	-10000	0	-0.57	30	30
ZMIZ1	0.011	0.022	-10000	0	-10000	0	0
CCND3	0.016	0.001	-10000	0	-10000	0	0
TGIF1	0.018	0.012	-10000	0	-10000	0	0
FKBP4	0.013	0.012	-10000	0	-10000	0	0

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.01	0.13	-10000	0	-0.35	23	23
TBX21	-0.13	0.49	-10000	0	-1.2	59	59
B2M	0.016	0.008	-10000	0	-10000	0	0
TYK2	0.018	0.022	-10000	0	-10000	0	0
IL12RB1	-0.023	0.15	-10000	0	-0.55	30	30
GADD45B	-0.07	0.38	-10000	0	-0.98	43	43
IL12RB2	-0.07	0.2	-10000	0	-0.51	68	68
GADD45G	-0.063	0.36	-10000	0	-0.93	41	41
natural killer cell activation	0.002	0.025	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.011	0.072	-10000	0	-0.57	6	6
IL2RA	-0.035	0.16	-10000	0	-0.54	37	37
IFNG	-0.091	0.21	-10000	0	-0.51	81	81
STAT3 (dimer)	-0.066	0.34	-10000	0	-0.76	63	63
HLA-DRB5	-0.025	0.14	-10000	0	-0.55	27	27
FASLG	-0.14	0.49	-10000	0	-1.1	66	66
NF kappa B2 p52/RelB	-0.19	0.38	-10000	0	-0.95	67	67
CD4	0.009	0.041	-10000	0	-0.57	2	2
SOCS1	0.014	0.026	-10000	0	-0.51	1	1
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.044	0.17	-10000	0	-0.57	39	39
CD3E	-0.049	0.18	-10000	0	-0.57	42	42
CD3G	-0.055	0.19	-10000	0	-0.57	46	46
IL12Rbeta2/JAK2	-0.039	0.15	-10000	0	-0.36	69	69
CCL3	-0.13	0.48	-10000	0	-1.2	60	60
CCL4	-0.16	0.53	-10000	0	-1.3	65	65
HLA-A	0.014	0.03	-10000	0	-0.57	1	1
IL18/IL18R	0.037	0.12	-10000	0	-0.38	27	27
NOS2	-0.1	0.41	-10000	0	-0.94	59	59
IL12/IL12R/TYK2/JAK2/SPHK2	-0.01	0.12	-10000	0	-0.35	22	22
IL1R1	-0.11	0.43	-10000	0	-1	57	57
IL4	0.001	0.025	-10000	0	-10000	0	0
JAK2	0.016	0.037	-10000	0	-0.58	1	1
EntrezGene:6957	-0.006	0.014	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.13	0.38	-10000	0	-0.85	69	69
RAB7A	-0.021	0.3	-10000	0	-0.74	37	37
lysosomal transport	-0.016	0.29	-10000	0	-0.69	38	38
FOS	-0.42	0.66	-10000	0	-1.2	153	153
STAT4 (dimer)	-0.062	0.39	-10000	0	-0.86	59	59
STAT5A (dimer)	-0.22	0.39	-10000	0	-0.89	82	82
GZMA	-0.16	0.53	-10000	0	-1.3	56	56
GZMB	-0.14	0.49	-10000	0	-1.2	60	60
HLX	0.014	0.026	-10000	0	-0.51	1	1
LCK	-0.13	0.48	-10000	0	-1.1	64	64
TCR/CD3/MHC II/CD4	-0.12	0.29	-10000	0	-0.63	68	68
IL2/IL2R	-0.015	0.14	-10000	0	-0.42	30	30
MAPK14	-0.05	0.36	-10000	0	-0.86	50	50
CCR5	-0.085	0.41	-10000	0	-1.1	44	44
IL1B	-0.031	0.16	-10000	0	-0.55	35	35
STAT6	-0.01	0.15	0.25	1	-0.31	38	39
STAT4	-0.013	0.13	-10000	0	-0.57	20	20
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.011	0.051	-10000	0	-0.51	4	4
NFKB1	0.016	0	-10000	0	-10000	0	0
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.005	0.096	-10000	0	-0.5	14	14
CD8A	-0.041	0.18	-10000	0	-0.57	40	40
CD8B	-0.046	0.18	-10000	0	-0.56	44	44
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.01	0.12	0.35	23	-10000	0	23
IL2RB	0.006	0.074	-10000	0	-0.55	7	7
proteasomal ubiquitin-dependent protein catabolic process	-0.049	0.35	-10000	0	-0.78	57	57
IL2RG	-0.01	0.12	-10000	0	-0.54	19	19
IL12	0.003	0.095	-10000	0	-0.36	21	21
STAT5A	0.014	0.029	-10000	0	-0.57	1	1
CD247	0	0.081	-10000	0	-0.56	8	8
IL2	0.004	0.007	-10000	0	-10000	0	0
SPHK2	0.014	0.026	-10000	0	-0.51	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.076	-10000	0	-0.5	8	8
IL12/IL12R/TYK2/JAK2	-0.15	0.55	-10000	0	-1.2	68	68
MAP2K3	-0.055	0.36	-10000	0	-0.84	53	53
RIPK2	0.016	0	-10000	0	-10000	0	0
MAP2K6	-0.058	0.37	-10000	0	-0.86	52	52
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.008	0.11	-10000	0	-0.57	14	14
IL18RAP	-0.011	0.13	-10000	0	-0.57	21	21
IL12Rbeta1/TYK2	-0.007	0.12	-10000	0	-0.4	30	30
EOMES	-0.063	0.3	-10000	0	-1.4	19	19
STAT1 (dimer)	-0.076	0.34	-10000	0	-0.72	67	67
T cell proliferation	-0.031	0.29	-10000	0	-0.64	52	52
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.015	0.052	-10000	0	-0.58	3	3
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.13	0.24	-10000	0	-0.7	48	48
ATF2	-0.035	0.34	-10000	0	-0.78	49	49

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.001	0.09	-9999	-0.57	10	10
LRPAP1	0.014	0.026	-9999	-0.51	1	1
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.22	-9999	-0.38	189	189
CaM/Ca2+	0.012	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.14	0.2	-9999	-0.36	146	146
IQGAP1/CaM	0.023	0	-9999	-10000	0	0
DAB1	-0.07	0.2	-9999	-0.54	59	59
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.051	0.17	-9999	-0.51	52	52
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.048	0.15	-9999	-0.36	77	77
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	-0.013	0.12	-9999	-0.51	22	22
LIS1/Poliovirus Protein 3A	0.02	0	-9999	-10000	0	0
CDK5R2	-0.023	0.13	-9999	-0.51	27	27
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.38	189	189
YWHAE	0.014	0.029	-9999	-0.57	1	1
NDEL1/14-3-3 E	-0.094	0.18	-9999	-0.43	45	45
MAP1B	-0.034	0.096	-9999	-0.31	45	45
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.2	-9999	-0.51	45	45
RELN	-0.2	0.28	-9999	-0.57	147	147
PAFAH/LIS1	-0.01	0.11	-9999	-0.29	52	52
LIS1/CLIP170	0.031	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.092	0.11	-9999	-0.35	34	34
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.18	-9999	-0.46	40	40
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.11	0.18	-9999	-0.44	55	55
LIS1/IQGAP1	0.031	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.026	0	-9999	-10000	0	0
PAFAH1B3	-0.014	0.12	-9999	-0.51	23	23
PAFAH1B2	0.016	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.006	0.067	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.083	0.17	-9999	-0.43	38	38
LRP8	-0.082	0.2	-9999	-0.51	76	76
NDEL1/Katanin 60	-0.093	0.18	-9999	-0.44	44	44
P39/CDK5	-0.12	0.2	-9999	-0.51	47	47
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0	-9999	-10000	0	0
CDK5	-0.12	0.19	-9999	-0.52	35	35
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.027	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.12	0.19	-9999	-0.55	28	28
RELN/VLDLR	-0.14	0.21	-9999	-0.36	163	163
CDC42	0	0	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	0.016	0.29	-10000	0	-0.82	42	42
NCK1/PAK1/Dok-R	-0.045	0.12	-10000	0	-0.41	42	42
NCK1/Dok-R	-0.028	0.34	-10000	0	-1	42	42
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.009	0.071	0.24	34	-10000	0	34
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.015	0.026	-10000	0	-0.5	1	1
Rac/GDP	0.012	0	-10000	0	-10000	0	0
F2	-0.019	0.15	0.25	33	-0.53	26	59
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.095	0.28	-10000	0	-0.93	42	42
FN1	-0.035	0.16	-10000	0	-0.53	38	38
PLD2	-0.026	0.34	-10000	0	-1	42	42
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.056	0.18	-10000	0	-0.51	56	56
ELK1	-0.008	0.31	-10000	0	-0.93	42	42
GRB7	-0.012	0.12	-10000	0	-0.53	21	21
PAK1	0.014	0.029	-10000	0	-0.57	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.12	0.32	-10000	0	-1	42	42
CDKN1A	0.022	0.21	-10000	0	-0.58	35	35
ITGA5	-0.007	0.11	-10000	0	-0.57	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.028	0.34	-10000	0	-1	42	42
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	0.037	0.22	-10000	0	-0.61	42	42
PLG	-0.035	0.34	-10000	0	-1	42	42
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.004	0.28	-10000	0	-0.81	42	42
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.015	0.029	-10000	0	-0.57	1	1
ANGPT2	-0.046	0.2	-10000	0	-0.6	28	28
BMX	-0.11	0.37	-10000	0	-1.1	42	42
ANGPT1	-0.06	0.37	-10000	0	-1.3	34	34
tube development	0.014	0.22	-10000	0	-0.61	40	40
ANGPT4	0.001	0.072	-10000	0	-0.5	8	8
response to hypoxia	-0.001	0.022	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.066	0.36	-10000	0	-1.1	42	42
alpha5/beta1 Integrin	0.006	0.084	-10000	0	-0.41	16	16
FGF2	-0.18	0.28	-10000	0	-0.57	136	136
STAT5A (dimer)	0.014	0.25	-10000	0	-0.69	39	39
mol:L-citrulline	0.037	0.22	-10000	0	-0.61	42	42
AGTR1	-0.23	0.29	-10000	0	-0.57	175	175
MAPK14	-0.024	0.34	-10000	0	-1	42	42
Tie2/SHP2	-0.039	0.17	-10000	0	-1.1	9	9
TEK	0.01	0.2	-10000	0	-1.2	9	9
RPS6KB1	0.014	0.28	-10000	0	-0.79	42	42
Angiotensin II/AT1	-0.17	0.21	-10000	0	-0.42	175	175
Tie2/Ang1/GRB2	-0.03	0.35	-10000	0	-1.1	42	42
MAPK3	-0.013	0.32	-10000	0	-0.95	42	42
MAPK1	-0.013	0.32	-10000	0	-0.95	42	42
Tie2/Ang1/GRB7	-0.045	0.36	-10000	0	-1.1	42	42
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.028	0.34	-10000	0	-1	42	42
PI3K	-0.004	0.32	-10000	0	-0.94	42	42
FES	-0.025	0.34	-10000	0	-1	42	42
Crk/Dok-R	-0.028	0.34	-10000	0	-1	42	42
Tie2/Ang1/ABIN2	-0.03	0.35	-10000	0	-1.1	42	42
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.023	0.26	-10000	0	-0.73	42	42
STAT5A	0.015	0.029	-10000	0	-0.57	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.014	0.28	-10000	0	-0.79	42	42
Tie2/Ang2	-0.007	0.28	-10000	0	-0.8	40	40
Tie2/Ang1	-0.037	0.37	-10000	0	-1.1	42	42
FOXO1	0.031	0.26	-10000	0	-0.73	42	42
ELF1	0.024	0.016	-10000	0	-10000	0	0
ELF2	-0.028	0.34	-10000	0	-1	42	42
mol:Choline	-0.022	0.33	-10000	0	-0.99	42	42
cell migration	-0.029	0.072	-10000	0	-0.23	43	43
FYN	0.007	0.25	-10000	0	-0.69	40	40
DOK2	-0.006	0.11	-10000	0	-0.56	15	15
negative regulation of cell cycle	0.026	0.2	-10000	0	-0.52	35	35
ETS1	0.007	0.068	-10000	0	-10000	0	0
PXN	0.031	0.24	-10000	0	-0.66	42	42
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	0.031	0.25	-10000	0	-0.69	42	42
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	-0.019	0.13	-10000	0	-0.5	21	21
MAPKKK cascade	-0.022	0.33	-10000	0	-0.99	42	42
RASA1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.029	0.35	-10000	0	-1.1	42	42
NCK1	0.016	0	-10000	0	-10000	0	0
vasculogenesis	0.041	0.2	-10000	0	-0.55	42	42
mol:Phosphatidic acid	-0.022	0.33	-10000	0	-0.99	42	42
mol:Angiotensin II	0.002	0.001	-10000	0	-10000	0	0
mol:NADP	0.037	0.22	-10000	0	-0.61	42	42
Rac1/GTP	-0.078	0.23	-10000	0	-0.74	42	42
MMP2	-0.051	0.36	-10000	0	-1.1	42	42

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.048	0.17	-10000	0	-0.41	53	53
IKBKB	-0.004	0.075	-10000	0	-0.25	9	9
AKT1	-0.043	0.12	-10000	0	-0.24	76	76
IKBKG	-0.002	0.078	-10000	0	-0.27	9	9
CALM1	-0.042	0.14	-10000	0	-0.42	32	32
PIK3CA	0.016	0	-10000	0	-10000	0	0
MAP3K1	-0.08	0.23	-10000	0	-0.53	67	67
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.053	0.14	-10000	0	-0.45	32	32
DOK1	0.014	0.026	-10000	0	-0.51	1	1
AP-1	-0.049	0.11	-10000	0	-0.24	61	61
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	-0.003	0.1	-10000	0	-0.57	13	13
SHC1	0.014	0.026	-10000	0	-0.51	1	1
BCR complex	-0.087	0.21	-10000	0	-0.46	92	92
CD22	-0.18	0.3	-10000	0	-0.7	80	80
CAMK2G	-0.031	0.13	-10000	0	-0.41	26	26
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.006	0.076	-10000	0	-0.57	7	7
SHC/GRB2/SOS1	-0.07	0.14	-10000	0	-0.48	25	25
GO:0007205	-0.054	0.15	-10000	0	-0.46	32	32
SYK	0.01	0.058	-10000	0	-0.57	4	4
ELK1	-0.043	0.14	-10000	0	-0.43	32	32
NFATC1	-0.092	0.23	-10000	0	-0.52	69	69
B-cell antigen/BCR complex	-0.087	0.21	-10000	0	-0.46	92	92
PAG1/CSK	0.023	0	-10000	0	-10000	0	0
NFKBIB	0.011	0.029	-10000	0	-10000	0	0
HRAS	-0.037	0.14	-10000	0	-0.4	33	33
NFKBIA	0.011	0.029	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.017	0.024	-10000	0	-10000	0	0
RasGAP/Csk	-0.058	0.2	-10000	0	-0.58	36	36
mol:GDP	-0.051	0.14	-10000	0	-0.44	32	32
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	-0.016	0.13	-10000	0	-0.55	23	23
NF-kappa-B/RelA/I kappa B alpha	0.017	0.024	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.11	0.24	-10000	0	-0.52	83	83
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
mol:IP3	-0.054	0.15	-10000	0	-0.47	32	32
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.12	0.19	-10000	0	-0.44	64	64
CHUK	-0.002	0.078	-10000	0	-0.27	9	9
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.053	0.12	-10000	0	-0.48	18	18
PTPN6	-0.13	0.3	-10000	0	-0.67	77	77
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	0.013	0.032	-10000	0	-0.099	21	21
VAV2	-0.14	0.28	-10000	0	-0.68	67	67
ubiquitin-dependent protein catabolic process	0.016	0.028	-10000	0	-10000	0	0
BTK	-0.059	0.26	0.35	5	-1.2	21	26
CD19	-0.18	0.28	-10000	0	-0.68	75	75
MAP4K1	-0.003	0.1	-10000	0	-0.56	13	13
CD72	-0.002	0.096	-10000	0	-0.51	14	14
PAG1	0.016	0	-10000	0	-10000	0	0
MAPK14	-0.057	0.2	-10000	0	-0.44	65	65
SH3BP5	0.014	0.029	-10000	0	-0.57	1	1
PIK3AP1	-0.05	0.17	-10000	0	-0.51	37	37
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.064	0.21	-10000	0	-0.44	83	83
RAF1	-0.027	0.13	-10000	0	-0.43	21	21
RasGAP/p62DOK/SHIP	-0.093	0.19	-10000	0	-0.59	37	37
CD79A	-0.11	0.24	-10000	0	-0.56	87	87
re-entry into mitotic cell cycle	-0.049	0.11	-10000	0	-0.24	61	61
RASA1	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.006	0.11	-10000	0	-0.41	14	14
MAPK1	-0.006	0.11	-10000	0	-0.41	14	14
CD72/SHP1	-0.12	0.28	-10000	0	-0.64	75	75
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.059	0.2	-10000	0	-0.44	66	66
actin cytoskeleton organization	-0.1	0.24	-10000	0	-0.56	65	65
NF-kappa-B/RelA	0.038	0.046	-10000	0	-10000	0	0
Calcineurin	-0.045	0.1	-10000	0	-0.47	14	14
PI3K	-0.15	0.21	-10000	0	-0.5	91	91
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.052	0.16	-10000	0	-0.46	36	36
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.1	0.28	-10000	0	-0.78	50	50
DAPP1	-0.14	0.3	-10000	0	-0.89	46	46
cytokine secretion	-0.083	0.21	-10000	0	-0.48	69	69
mol:DAG	-0.054	0.15	-10000	0	-0.47	32	32
PLCG2	0.009	0.06	-10000	0	-0.53	5	5
MAP2K1	-0.016	0.12	-10000	0	-0.46	14	14
B-cell antigen/BCR complex/FcgammaRIIB	-0.088	0.23	-10000	0	-0.46	100	100
mol:PI-3-4-5-P3	-0.11	0.14	-10000	0	-0.34	89	89
ETS1	-0.02	0.12	-10000	0	-0.47	14	14
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.05	0.18	-10000	0	-0.56	25	25
B-cell antigen/BCR complex/LYN	-0.12	0.26	-10000	0	-0.52	90	90
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.11	0.26	-10000	0	-0.61	65	65
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.27	-10000	0	-0.65	78	78
CARD11	-0.051	0.15	-10000	0	-0.43	38	38
FCGR2B	-0.027	0.15	-10000	0	-0.56	30	30
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.008	0.038	-10000	0	-0.096	2	2
PTPRC	-0.056	0.19	-10000	0	-0.57	50	50
PDPK1	-0.044	0.12	-10000	0	-0.25	52	52
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	0.016	0.027	-10000	0	-0.098	12	12

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.041	0.14	0.42	52	-10000	0	52
KIRREL	-0.053	0.19	-10000	0	-0.58	46	46
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.041	0.15	-10000	0	-0.42	52	52
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.016	0	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.044	0.12	-10000	0	-0.33	46	46
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.007	0.1	-10000	0	-0.28	46	46
FYN	-0.029	0.12	-10000	0	-0.32	47	47
mol:Ca2+	-0.048	0.11	-10000	0	-0.33	46	46
mol:DAG	-0.049	0.12	-10000	0	-0.33	46	46
NPHS2	-0.023	0.11	-10000	0	-0.52	19	19
mol:IP3	-0.049	0.12	-10000	0	-0.33	46	46
regulation of endocytosis	-0.018	0.11	-10000	0	-0.3	46	46
Nephrin/NEPH1/podocin/Cholesterol	-0.04	0.12	-10000	0	-0.31	66	66
establishment of cell polarity	-0.041	0.14	-10000	0	-0.42	52	52
Nephrin/NEPH1/podocin/NCK1-2	-0.013	0.12	-10000	0	-0.46	7	7
Nephrin/NEPH1/beta Arrestin2	-0.017	0.12	-10000	0	-0.3	46	46
NPHS1	-0.008	0.064	-10000	0	-0.5	6	6
Nephrin/NEPH1/podocin	-0.029	0.12	-10000	0	-0.32	47	47
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.044	0.12	-10000	0	-0.33	46	46
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.044	0.12	-10000	0	-0.33	46	46
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.025	0.12	-10000	0	-0.31	47	47
cytoskeleton organization	-0.007	0.12	-10000	0	-0.34	25	25
Nephrin/NEPH1	-0.027	0.1	-10000	0	-0.3	52	52
Nephrin/NEPH1/ZO-1	-0.042	0.11	-10000	0	-0.33	49	49

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.001	0.09	-9999	-0.57	10	10
mol:S1P	0.001	0.004	-9999	-10000	0	0
S1P1/S1P/Gi	-0.1	0.19	-9999	-0.39	95	95
GNAO1	-0.17	0.27	-9999	-0.57	129	129
S1P/S1P3/G12/G13	0.025	0.05	-9999	-0.3	9	9
AKT1	-0.035	0.16	-9999	-0.87	10	10
AKT3	-0.061	0.26	-9999	-1.2	16	16
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.001	0.09	-9999	-0.57	10	10
GNAI2	0.017	0.004	-9999	-10000	0	0
GNAI3	0.017	0.004	-9999	-10000	0	0
GNAI1	0.012	0.05	-9999	-0.57	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.004	0.085	-9999	-0.56	9	9
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.1	0.22	-9999	-0.51	67	67
MAPK3	-0.091	0.21	-9999	-0.48	67	67
MAPK1	-0.091	0.21	-9999	-0.48	67	67
JAK2	-0.092	0.22	-9999	-0.49	68	68
CXCR4	-0.097	0.22	-9999	-0.5	68	68
FLT1	0.019	0.003	-9999	-10000	0	0
RhoA/GDP	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.012	0	-9999	-10000	0	0
SRC	-0.091	0.21	-9999	-0.48	67	67
S1P/S1P3/Gi	-0.1	0.22	-9999	-0.52	67	67
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.089	0.2	-9999	-0.47	67	67
VEGFA	0.019	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	-0.097	0.19	-9999	-0.45	67	67
VEGFR1 homodimer/VEGFA homodimer	0.032	0.008	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.012	0.11	-9999	-0.26	66	66
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.57	89	89
G12/G13	0.023	0	-9999	-10000	0	0
GNA14	-0.068	0.2	-9999	-0.57	58	58
GNA15	0.011	0.05	-9999	-0.57	3	3
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.014	0.029	-9999	-0.57	1	1
Rac1/GTP	-0.089	0.2	-9999	-0.47	67	67

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.028	0.14	-9999	-0.33	64	64
EPHB2	-0.02	0.13	-9999	-0.51	28	28
Syndecan-2/TACI	-0.034	0.14	-9999	-0.35	66	66
LAMA1	-0.091	0.21	-9999	-0.52	81	81
Syndecan-2/alpha2 ITGB1	-0.034	0.15	-9999	-0.55	10	10
HRAS	0.016	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.008	0.093	-9999	-0.35	29	29
ITGA5	-0.007	0.11	-9999	-0.57	16	16
BAX	0.02	0.089	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.003	0.085	-9999	-0.3	29	29
LAMA3	-0.082	0.21	-9999	-0.54	72	72
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.01	0.058	-9999	-0.57	4	4
Syndecan-2/MMP2	-0.028	0.16	-9999	-0.42	52	52
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.018	0.047	-9999	-0.36	6	6
dendrite morphogenesis	-0.019	0.12	-9999	-0.32	56	56
Syndecan-2/GM-CSF	-0.057	0.15	-9999	-0.32	100	100
determination of left/right symmetry	-0.007	0.11	-9999	-0.41	29	29
Syndecan-2/PKC delta	0.003	0.094	-9999	-0.34	29	29
GNB2L1	0.016	0	-9999	-10000	0	0
MAPK3	-0.041	0.14	-9999	-0.33	29	29
MAPK1	-0.041	0.14	-9999	-0.33	29	29
Syndecan-2/RACK1	0.013	0.081	-9999	-0.28	29	29
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	-0.007	0.11	-9999	-0.41	29	29
ITGA2	0.008	0.064	-9999	-0.52	6	6
MAPK8	0.011	0.099	-9999	-0.33	32	32
Syndecan-2/alpha2/beta1 Integrin	-0.038	0.14	-9999	-0.53	9	9
Syndecan-2/Kininogen	-0.008	0.093	-9999	-0.35	29	29
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.021	0.077	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0.003	0.085	-9999	-0.31	29	29
extracellular matrix organization	0.003	0.094	-9999	-0.34	29	29
actin cytoskeleton reorganization	-0.028	0.14	-9999	-0.33	64	64
Syndecan-2/Caveolin-2/Ras	0.01	0.094	-9999	-0.31	32	32
Syndecan-2/Laminin alpha3	-0.057	0.16	-9999	-0.35	94	94
Syndecan-2/RasGAP	0.02	0.078	-9999	-10000	0	0
alpha5/beta1 Integrin	0.006	0.084	-9999	-0.41	16	16
PRKCD	0.016	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.019	0.12	-9999	-0.32	56	56
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.03	0.076	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.044	0.17	-9999	-0.56	40	40
RASA1	0.016	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.018	0.047	-9999	-0.36	6	6
Syndecan-2/Synbindin	0.003	0.094	-9999	-0.34	29	29
TGFB1	0.016	0	-9999	-10000	0	0
CASP3	0.014	0.086	-9999	-0.3	29	29
FN1	-0.035	0.16	-9999	-0.53	38	38
Syndecan-2/IL8	-0.051	0.16	-9999	-0.36	84	84
SDC2	-0.007	0.11	-9999	-0.41	29	29
KNG1	0	0	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.003	0.094	-9999	-0.34	29	29
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.082	0.2	-9999	-0.51	75	75
Syndecan-2/TGFB1	0.003	0.094	-9999	-0.34	29	29
Syndecan-2/Syntenin/PI-4-5-P2	0.003	0.085	-9999	-0.31	29	29
Syndecan-2/Ezrin	0.013	0.086	-9999	-0.3	29	29
PRKACA	0.014	0.086	-9999	-0.3	29	29
angiogenesis	-0.05	0.16	-9999	-0.36	84	84
MMP2	-0.036	0.17	-9999	-0.57	36	36
IL8	-0.07	0.21	-9999	-0.57	60	60
calcineurin-NFAT signaling pathway	-0.034	0.14	-9999	-0.35	66	66

×

Arf6 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.018	0.036	-9999	-0.35	4	4
ARNO/beta Arrestin1-2	-0.034	0.085	-9999	-0.37	1	1
EGFR	-0.008	0.11	-9999	-0.54	17	17
EPHA2	0.008	0.064	-9999	-0.57	5	5
USP6	0.016	0	-9999	-10000	0	0
IQSEC1	0.014	0.026	-9999	-0.51	1	1
EGFR/EGFR/EGF/EGF	-0.018	0.12	-9999	-0.37	42	42
ARRB2	0.012	0.014	-9999	-0.18	2	2
mol:GTP	0.016	0.031	-9999	-0.21	4	4
ARRB1	0.01	0.058	-9999	-0.57	4	4
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	0.002	0.068	-9999	-0.51	7	7
EGF	-0.018	0.12	-9999	-0.51	25	25
somatostatin receptor activity	0	0	-9999	-0.001	70	70
ARAP2	0.013	0.041	-9999	-0.57	2	2
mol:GDP	-0.071	0.12	-9999	-0.25	84	84
mol:PI-3-4-5-P3	0	0	-9999	-0.001	45	45
ITGA2B	-0.025	0.14	-9999	-0.51	31	31
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.057	-9999	-0.3	5	5
ADAP1	0.01	0.058	-9999	-0.57	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.077	0.18	-9999	-0.4	96	96
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.065	0.12	-9999	-0.26	71	71
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.004	0.1	-9999	-0.3	43	43
ADRB2	-0.059	0.2	-9999	-0.57	52	52
receptor agonist activity	0	0	-9999	0	81	81
actin filament binding	0	0	-9999	0	71	71
SRC	0.016	0	-9999	-10000	0	0
ITGB3	-0.05	0.18	-9999	-0.57	46	46
GNAQ	0.015	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	63	63
ARF6/GDP	0.009	0.096	-9999	-0.36	18	18
ARF6/GDP/GULP/ACAP1	-0.1	0.18	-9999	-0.42	74	74
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.02	0.13	-9999	-0.33	46	46
ACAP1	-0.014	0.13	-9999	-0.56	21	21
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0.004	0.021	-9999	-0.27	2	2
EFNA1	0.004	0.077	-9999	-0.51	9	9
HGF	-0.12	0.24	-9999	-0.56	94	94
CYTH3	0.013	0	-9999	-10000	0	0
CYTH2	0.01	0.002	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	50	50
endosomal lumen acidification	0	0	-9999	0	64	64
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.075	0.21	-9999	-0.57	63	63
GNAQ/ARNO	0.018	0.007	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	7	7
MET	0.013	0.036	-9999	-0.51	2	2
GNA14	-0.068	0.2	-9999	-0.57	58	58
GNA15	0.011	0.05	-9999	-0.57	3	3
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	66	66
GNA11	0.014	0.029	-9999	-0.57	1	1
LHCGR	0.001	0.036	-9999	-0.51	2	2
AGTR1	-0.24	0.29	-9999	-0.57	175	175
desensitization of G-protein coupled receptor protein signaling pathway	0.004	0.021	-9999	-0.27	2	2
IPCEF1/ARNO	-0.002	0.077	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.054	0.17	-9999	-0.41	72	72

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.022	0.14	0.57	26	-10000	0	26
PI3K Class IB/PDE3B	-0.022	0.14	-10000	0	-0.57	26	26
PDE3B	-0.022	0.14	-10000	0	-0.57	26	26

×

Wnt signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.038	0.14	-9999	-0.43	21	21
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.053	0.18	-9999	-0.52	52	52
WNT4	-0.025	0.15	-9999	-0.56	29	29
FZD3	0.011	0.05	-9999	-0.57	3	3
WNT5A	-0.007	0.11	-9999	-0.53	17	17
WNT11	-0.06	0.19	-9999	-0.53	56	56

×

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.004	0.031	-10000	0	-10000	0	0
HDAC1	0.014	0.011	-10000	0	-10000	0	0
AES	0.015	0.004	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.011	0.12	-10000	0	-0.55	19	19
LRP6/FZD1	0.021	0.028	-10000	0	-0.38	2	2
TLE1	0.011	0.05	-10000	0	-0.57	3	3
AP1	-0.097	0.19	-10000	0	-0.32	145	145
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.016	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.034	0.072	-10000	0	-10000	0	0
NICD/RBPSUH	0.04	0.001	-10000	0	-10000	0	0
WIF1	-0.12	0.24	-10000	0	-0.56	90	90
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.19	0.25	-10000	0	-0.51	158	158
DKK1	-0.085	0.22	-10000	0	-0.56	72	72
beta catenin/beta TrCP1	0.035	0.048	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	0.004	0.016	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.031	0.05	0.28	4	-10000	0	4
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.17	0.27	-10000	0	-0.57	129	129
JUN	-0.007	0.11	-10000	0	-0.57	16	16
MAP3K7	0.015	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.051	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.16	0.21	-10000	0	-0.35	208	208
HNF1A	0.009	0.058	-10000	0	-0.51	5	5
CTBP1	0.014	0.026	-10000	0	-0.5	1	1
MYC	-0.037	0.3	-10000	0	-1.4	18	18
NKD1	-0.028	0.15	-10000	0	-0.56	31	31
FZD1	0.013	0.039	-10000	0	-0.54	2	2
NOTCH1 precursor/Deltex homolog 1	0.026	0.062	-10000	0	-10000	0	0
apoptosis	-0.097	0.18	-10000	0	-0.32	145	145
Delta 1/NOTCHprecursor	0.036	0.035	-10000	0	-10000	0	0
DLL1	0.007	0.068	-10000	0	-0.55	6	6
PPARD	0.023	0.026	-10000	0	-10000	0	0
Gamma Secretase	0.045	0.011	-10000	0	-10000	0	0
APC	0.004	0.016	-10000	0	-10000	0	0
DVL1	0.011	0.032	-10000	0	-10000	0	0
CSNK2A1	0.016	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.21	-10000	0	-0.35	199	199
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.016	0.002	-10000	0	-10000	0	0
NLK	0.018	0.012	-10000	0	-10000	0	0
CCND1	-0.011	0.2	-10000	0	-1.5	7	7
WNT1	0.008	0.045	-10000	0	-0.51	3	3
Axin1/APC/beta catenin	0.045	0.034	-10000	0	-10000	0	0
DKK2	-0.1	0.22	-10000	0	-0.51	94	94
NOTCH1 precursor/DVL1	0.002	0.009	-10000	0	-10000	0	0
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.015	0.002	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.012	0.054	-10000	0	-10000	0	0
PPP2R5D	0.017	0.076	0.28	31	-10000	0	31
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.045	0.14	-10000	0	-0.31	81	81
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.018	0.006	-10000	0	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.012	0.05	0.24	16	-10000	0	16
RFC1	0.012	0.05	0.23	20	-10000	0	20
PRKDC	0.012	0.05	0.23	19	-10000	0	19
RIPK1	0.02	0.005	-10000	0	-10000	0	0
CASP7	-0.028	0.044	0.25	2	-10000	0	2
FASLG/FAS/FADD/FAF1	-0.035	0.081	0.22	5	-0.3	22	27
MAP2K4	-0.084	0.17	-10000	0	-0.44	21	21
mol:ceramide	-0.052	0.13	-10000	0	-0.38	28	28
GSN	0.006	0.063	0.24	18	-0.34	5	23
FASLG/FAS/FADD/FAF1/Caspase 8	-0.031	0.1	-10000	0	-0.35	24	24
FAS	0.001	0.071	-10000	0	-0.58	6	6
BID	0.003	0.038	0.3	4	-0.31	2	6
MAP3K1	-0.035	0.1	0.21	2	-0.25	15	17
MAP3K7	0.009	0.008	-10000	0	-10000	0	0
RB1	0.011	0.053	0.23	19	-0.34	1	20
CFLAR	0.02	0.005	-10000	0	-10000	0	0
HGF/MET	-0.061	0.16	-10000	0	-0.34	102	102
ARHGDIB	0.012	0.05	0.23	20	-10000	0	20
FADD	0.002	0.064	-10000	0	-0.52	6	6
actin filament polymerization	-0.006	0.063	0.33	5	-0.24	18	23
NFKB1	-0.095	0.1	-10000	0	-0.27	14	14
MAPK8	-0.16	0.25	-10000	0	-0.42	184	184
DFFA	0.012	0.05	0.23	19	-10000	0	19
DNA fragmentation during apoptosis	0.012	0.05	0.23	20	-10000	0	20
FAS/FADD/MET	0.007	0.064	-10000	0	-0.32	14	14
CFLAR/RIP1	0.012	0.011	-10000	0	-10000	0	0
FAIM3	0.007	0.077	-10000	0	-0.54	8	8
FAF1	0.01	0.009	-10000	0	-10000	0	0
PARP1	0.012	0.05	0.23	19	-10000	0	19
DFFB	0.012	0.05	0.23	20	-10000	0	20
CHUK	-0.082	0.089	-10000	0	-0.27	1	1
FASLG	-0.031	0.14	-10000	0	-0.56	28	28
FAS/FADD	0.002	0.07	-10000	0	-0.39	12	12
HGF	-0.12	0.24	-10000	0	-0.56	94	94
LMNA	0.011	0.047	0.22	16	-10000	0	16
CASP6	0.012	0.05	0.23	20	-10000	0	20
CASP10	0.009	0.008	-10000	0	-10000	0	0
CASP3	0.014	0.059	0.27	20	-10000	0	20
PTPN13	0.004	0.081	-10000	0	-0.57	8	8
CASP8	0.006	0.043	0.39	4	-10000	0	4
IL6	-0.56	0.67	-10000	0	-1.3	184	184
MET	0.013	0.036	-10000	0	-0.51	2	2
ICAD/CAD	0.011	0.047	0.22	16	-10000	0	16
FASLG/FAS/FADD/FAF1/Caspase 10	-0.053	0.13	-10000	0	-0.39	28	28
activation of caspase activity by cytochrome c	0.003	0.038	0.3	4	-0.31	2	6
PAK2	0.012	0.05	0.23	19	-10000	0	19
BCL2	-0.006	0.11	-10000	0	-0.57	16	16

×

Canonical Wnt signaling pathway

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
HDAC1	0.013	0.033	-10000	0	-10000	0	0
AES	0.019	0.025	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.019	0.029	-10000	0	-0.38	2	2
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.1	0.22	-10000	0	-0.51	94	94
TLE1	0.015	0.056	-10000	0	-0.57	3	3
MACF1	0.016	0	-10000	0	-10000	0	0
CTNNB1	0.039	0.078	0.27	5	-10000	0	5
WIF1	-0.12	0.24	-10000	0	-0.56	90	90
beta catenin/RanBP3	0.037	0.13	0.37	49	-10000	0	49
KREMEN2	-0.19	0.25	-10000	0	-0.51	158	158
DKK1	-0.085	0.22	-10000	0	-0.56	72	72
beta catenin/beta TrCP1	0.047	0.074	0.26	5	-10000	0	5
FZD1	0.013	0.039	-10000	0	-0.54	2	2
AXIN2	-0.092	0.37	-10000	0	-1.4	29	29
AXIN1	0.016	0.001	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.021	0.035	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.081	0.058	-10000	0	-0.32	1	1
Axin1/APC/GSK3	0.019	0.048	0.23	5	-10000	0	5
Axin1/APC/GSK3/beta catenin/Macf1	0.062	0.036	-10000	0	-10000	0	0
HNF1A	0.013	0.064	-10000	0	-0.51	5	5
CTBP1	0.018	0.036	-10000	0	-0.48	1	1
MYC	-0.064	0.32	-10000	0	-1.5	18	18
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.17	0.21	-10000	0	-0.35	208	208
NKD1	-0.028	0.15	-10000	0	-0.56	31	31
TCF4	0.011	0.073	-10000	0	-0.55	6	6
TCF3	0.019	0.026	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.03	0.035	-10000	0	-0.3	1	1
Ran/GTP	0.012	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.056	0.16	0.48	45	-10000	0	45
LEF1	0.011	0.072	-10000	0	-0.5	7	7
DVL1	0.059	0.038	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.065	0.089	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.21	-10000	0	-0.35	199	199
LRP6	0.016	0.001	-10000	0	-10000	0	0
CSNK1A1	0.018	0.031	-10000	0	-10000	0	0
NLK	0.015	0.005	-10000	0	-10000	0	0
CCND1	-0.038	0.22	-10000	0	-1.3	9	9
WNT1	0.008	0.045	-10000	0	-0.51	3	3
GSK3A	0.016	0.001	-10000	0	-10000	0	0
GSK3B	0.016	0.001	-10000	0	-10000	0	0
FRAT1	0.015	0	-10000	0	-10000	0	0
PPP2R5D	0.051	0.075	0.3	31	-10000	0	31
APC	0.041	0.031	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.07	0.089	0.24	79	-10000	0	79
CREBBP	0.019	0.026	-10000	0	-10000	0	0

×

Syndecan-4-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.003	0.11	-9999	-0.54	12	12
Syndecan-4/Syndesmos	-0.028	0.13	-9999	-0.55	10	10
positive regulation of JNK cascade	-0.098	0.18	-9999	-0.52	31	31
Syndecan-4/ADAM12	-0.052	0.15	-9999	-0.54	15	15
CCL5	-0.03	0.15	-9999	-0.55	33	33
Rac1/GDP	0.012	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.007	0.11	-9999	-0.57	16	16
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.003	0.057	-9999	-0.51	5	5
ADAM12	-0.036	0.16	-9999	-0.51	40	40
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.037	0.051	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.079	0.18	-9999	-0.55	24	24
Syndecan-4/CXCL12/CXCR4	-0.1	0.19	-9999	-0.56	31	31
Syndecan-4/Laminin alpha3	-0.075	0.17	-9999	-0.48	32	32
MDK	-0.014	0.12	-9999	-0.51	23	23
Syndecan-4/FZD7	-0.041	0.14	-9999	-0.48	17	17
Syndecan-4/Midkine	-0.042	0.14	-9999	-0.57	10	10
FZD7	-0.012	0.12	-9999	-0.57	19	19
Syndecan-4/FGFR1/FGF	-0.19	0.22	-9999	-0.56	81	81
THBS1	-0.003	0.1	-9999	-0.57	13	13
integrin-mediated signaling pathway	-0.054	0.16	-9999	-0.51	27	27
positive regulation of MAPKKK cascade	-0.098	0.18	-9999	-0.52	31	31
Syndecan-4/TACI	-0.058	0.15	-9999	-0.52	16	16
CXCR4	0.004	0.081	-9999	-0.57	8	8
cell adhesion	0.003	0.1	-9999	-0.4	16	16
Syndecan-4/Dynamin	-0.028	0.13	-9999	-0.55	10	10
Syndecan-4/TSP1	-0.037	0.14	-9999	-0.57	12	12
Syndecan-4/GIPC	-0.028	0.13	-9999	-0.55	10	10
Syndecan-4/RANTES	-0.05	0.16	-9999	-0.61	14	14
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.091	0.21	-9999	-0.52	81	81
LAMA3	-0.082	0.21	-9999	-0.54	72	72
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.017	0.069	-9999	-0.53	5	5
Syndecan-4/alpha-Actinin	-0.028	0.13	-9999	-0.55	10	10
TFPI	0.003	0.086	-9999	-0.57	9	9
F2	-0.031	0.14	-9999	-0.51	30	30
alpha5/beta1 Integrin	0.006	0.084	-9999	-0.41	16	16
positive regulation of cell adhesion	-0.11	0.2	-9999	-0.56	36	36
ACTN1	0.016	0	-9999	-10000	0	0
TNC	-0.043	0.17	-9999	-0.56	42	42
Syndecan-4/CXCL12	-0.11	0.18	-9999	-0.52	37	37
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.15	0.26	-9999	-0.57	114	114
TNFRSF13B	-0.044	0.17	-9999	-0.56	40	40
FGF2	-0.18	0.28	-9999	-0.57	136	136
FGFR1	-0.12	0.24	-9999	-0.57	93	93
Syndecan-4/PI-4-5-P2	-0.037	0.13	-9999	-0.56	10	10
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.034	0.16	-9999	-0.53	38	38
cell migration	-0.014	0.022	-9999	-10000	0	0
PRKCD	0.016	0.008	-9999	-10000	0	0
vasculogenesis	-0.036	0.13	-9999	-0.54	12	12
SDC4	-0.039	0.13	-9999	-0.59	10	10
Syndecan-4/Tenascin C	-0.056	0.17	-9999	-0.55	25	25
Syndecan-4/PI-4-5-P2/PKC alpha	-0.03	0.04	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.028	0.13	-9999	-0.55	10	10
MMP9	-0.13	0.23	-9999	-0.51	110	110
Rac1/GTP	0.003	0.11	-9999	-0.42	16	16
cytoskeleton organization	-0.027	0.12	-9999	-0.53	10	10
GIPC1	0.016	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.034	0.14	-9999	-0.59	13	13

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	0.004	0.037	-9999	-0.37	4	4
Metarhodopsin II/Arrestin	0.002	0.004	-9999	-10000	0	0
PDE6G/GNAT1/GTP	0.002	0.068	-9999	-0.3	19	19
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.005	0.051	-9999	-0.51	4	4
GRK1	0	0.025	-9999	-0.51	1	1
CNG Channel	-0.14	0.16	-9999	-0.48	45	45
mol:Na +	-0.16	0.16	-9999	-0.48	47	47
mol:ADP	0	0.025	-9999	-0.51	1	1
RGS9-1/Gbeta5/R9AP	-0.062	0.17	-9999	-0.35	100	100
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.16	0.16	-9999	-0.5	47	47
CNGB1	-0.21	0.26	-9999	-0.51	174	174
RDH5	0.014	0.029	-9999	-0.57	1	1
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.13	0.17	-9999	-0.46	47	47
Na + (4 Units)	-0.14	0.14	-9999	-0.45	47	47
RGS9	-0.11	0.24	-9999	-0.57	87	87
GNB1/GNGT1	0.003	0.081	-9999	-0.36	20	20
GNAT1/GDP	-0.05	0.14	-9999	-0.3	97	97
GUCY2D	-0.045	0.16	-9999	-0.51	45	45
GNGT1	-0.012	0.11	-9999	-0.51	20	20
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.003	0.094	-9999	-0.29	29	29
mol:11-cis-retinal	0.014	0.029	-9999	-0.57	1	1
mol:cGMP	-0.021	0.11	-9999	-0.45	4	4
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	0.013	0.022	-9999	-0.42	1	1
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.052	0.18	-9999	-0.54	50	50
Metarhodopsin II	0.002	0.015	-9999	-0.28	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.024	0.12	-9999	-0.48	4	4
RGS9BP	-0.009	0.12	-9999	-0.56	17	17
Metarhodopsin II/Transducin	0.011	0.035	-9999	-10000	0	0
GCAP Family/Ca ++	0.001	0.073	-9999	-0.28	24	24
PDE6A/B	-0.002	0.1	-9999	-0.41	23	23
mol:Pi	-0.062	0.17	-9999	-0.35	100	100
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.008	0.069	-9999	-0.26	24	24
PDE6B	-0.01	0.12	-9999	-0.57	18	18
PDE6A	0.007	0.063	-9999	-0.51	6	6
PDE6G	-0.004	0.098	-9999	-0.51	15	15
RHO	0.003	0.007	-9999	-10000	0	0
PDE6	-0.088	0.15	-9999	-0.56	16	16
GUCA1A	-0.015	0.12	-9999	-0.51	21	21
GC2/GCAP Family	0.002	0.073	-9999	-0.29	21	21
GUCA1C	0	0.025	-9999	-0.51	1	1
GUCA1B	0.012	0.046	-9999	-0.53	3	3

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.023	0.068	-9999	-0.31	13	13
epithelial cell differentiation	-0.042	0.087	-9999	-0.39	8	8
ITCH	0.017	0.027	-9999	-0.51	1	1
WWP1	0.034	0.029	-9999	-10000	0	0
FYN	0.011	0.05	-9999	-0.57	3	3
EGFR	-0.008	0.11	-9999	-0.54	17	17
PRL	-0.004	0.067	-9999	-0.51	7	7
neuron projection morphogenesis	0.01	0.12	-9999	-0.46	1	1
PTPRZ1	-0.17	0.26	-9999	-0.55	133	133
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.007	0.13	-9999	-0.43	2	2
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.036	0.14	-9999	-0.3	75	75
ADAM17	0.017	0.027	-9999	-0.51	1	1
ErbB4/ErbB4	0.033	0.036	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.004	0.06	-9999	-0.33	1	1
NCOR1	0.016	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.028	0.14	-9999	-0.34	15	15
GRIN2B	-0.031	0.14	-9999	-0.4	15	15
ErbB4/ErbB2/betacellulin	-0.006	0.12	-9999	-0.39	5	5
STAT1	0.011	0.051	-9999	-0.51	4	4
HBEGF	-0.003	0.1	-9999	-0.57	13	13
PRLR	-0.048	0.18	-9999	-0.53	47	47
E4ICDs/ETO2	0.023	0.067	-9999	-0.31	13	13
axon guidance	0.034	0.1	-9999	-0.29	8	8
NEDD4	0.017	0.03	-9999	-0.56	1	1
Prolactin receptor/Prolactin receptor/Prolactin	-0.037	0.13	-9999	-0.38	54	54
CBFA2T3	-0.003	0.1	-9999	-0.57	13	13
ErbB4/ErbB2/HBEGF	0.025	0.079	-9999	-0.37	4	4
MAPK3	0.002	0.12	-9999	-0.48	1	1
STAT1 (dimer)	0.031	0.042	-9999	-10000	0	0
MAPK1	0.002	0.12	-9999	-0.48	1	1
JAK2	0.014	0.029	-9999	-0.57	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.034	0.14	-9999	-0.35	16	16
NRG1	-0.069	0.18	-9999	-0.4	92	92
NRG3	-0.01	0.094	-9999	-0.51	14	14
NRG2	-0.23	0.29	-9999	-0.57	172	172
NRG4	-0.041	0.17	-9999	-0.57	39	39
heart development	0.034	0.1	-9999	-0.29	8	8
neural crest cell migration	-0.034	0.14	-9999	-0.35	16	16
ERBB2	0.015	0.071	-9999	-0.36	14	14
WWOX/E4ICDs	0.034	0.034	-9999	-0.31	1	1
SHC1	0.014	0.026	-9999	-0.51	1	1
ErbB4/EGFR/neuregulin 4	-0.003	0.12	-9999	-0.43	9	9
apoptosis	0.017	0.044	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.17	-9999	-0.32	172	172
ErbB4/ErbB2/epiregulin	-0.047	0.14	-9999	-0.39	15	15
ErbB4/ErbB4/betacellulin/betacellulin	-0.01	0.12	-9999	-0.32	50	50
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.037	0.095	-9999	-0.44	5	5
MDM2	0.029	0.063	-9999	-0.33	2	2
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.056	0.12	-9999	-0.29	75	75
STAT5A	0.039	0.1	-9999	-0.35	2	2
ErbB4/EGFR/neuregulin 1 beta	-0.038	0.14	-9999	-0.37	17	17
DLG4	0.014	0.029	-9999	-0.57	1	1
GRB2/SHC	0.022	0.019	-9999	-0.36	1	1
E4ICDs/TAB2/NCoR1	-0.004	0.017	-9999	-10000	0	0
STAT5A (dimer)	-0.043	0.093	-9999	-0.43	7	7
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.037	0.094	-9999	-0.31	1	1
LRIG1	-0.039	0.17	-9999	-0.57	38	38
EREG	-0.14	0.25	-9999	-0.54	111	111
BTC	-0.057	0.19	-9999	-0.57	50	50
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.032	0.1	-9999	-0.3	8	8
ERBB4	0.033	0.036	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
YAP1	-0.003	0.036	-9999	-0.69	1	1
GRB2	0.016	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.004	0.12	-9999	-0.44	10	10
glial cell differentiation	0.004	0.017	-9999	-10000	0	0
WWOX	0.014	0.029	-9999	-0.57	1	1
cell proliferation	-0.053	0.17	-9999	-0.44	33	33

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.087	0.22	-9999	-0.57	71	71
GNB1/GNG2	-0.022	0.13	-9999	-0.5	13	13
mol:DAG	-0.011	0.12	-9999	-0.45	13	13
PLCG1	-0.012	0.13	-9999	-0.46	13	13
YES1	-0.027	0.13	-9999	-0.5	13	13
FZD3	0.011	0.05	-9999	-0.57	3	3
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.012	0.13	-9999	-0.47	13	13
MAP3K7	-0.078	0.17	-9999	-0.38	60	60
mol:Ca2+	-0.011	0.12	-9999	-0.43	13	13
mol:IP3	-0.011	0.12	-9999	-0.45	13	13
NLK	-0.003	0.008	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.092	0.18	-9999	-0.42	61	61
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.038	0.14	-9999	-0.43	21	21
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.027	0.13	-9999	-0.5	13	13
GO:0007205	-0.011	0.12	-9999	-0.47	11	11
WNT6	-0.053	0.18	-9999	-0.52	52	52
WNT4	-0.025	0.15	-9999	-0.56	29	29
NFAT1/CK1 alpha	-0.052	0.16	-9999	-0.44	31	31
GNG2	0.007	0.07	-9999	-0.57	6	6
WNT5A	-0.007	0.11	-9999	-0.53	17	17
WNT11	-0.06	0.19	-9999	-0.53	56	56
CDC42	-0.017	0.13	-9999	-0.47	13	13

×

ErbB2/ErbB3 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.021	0.12	-9999	-0.47	7	7
NFATC4	-0.024	0.11	-9999	-0.37	11	11
ERBB2IP	0.016	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.016	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.043	0.13	-9999	-0.46	8	8
JUN	0.002	0.085	-9999	-0.33	2	2
HRAS	0.015	0.001	-9999	-10000	0	0
DOCK7	-0.036	0.12	-9999	-0.43	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.062	0.15	-9999	-0.32	81	81
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.022	0.003	-9999	-10000	0	0
MAPK10	-0.016	0.095	-9999	-0.26	17	17
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.046	0.14	-9999	-0.5	8	8
RAF1	-0.013	0.12	-9999	-0.42	9	9
ErbB2/ErbB3/neuregulin 2	-0.15	0.18	-9999	-0.33	185	185
STAT3	0.003	0.005	-9999	-10000	0	0
cell migration	-0.003	0.088	-9999	-0.22	18	18
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.093	0.24	-9999	-0.52	64	64
FOS	-0.13	0.27	-9999	-0.51	131	131
NRAS	0.015	0.001	-9999	-10000	0	0
mol:Ca2+	-0.043	0.13	-9999	-0.46	8	8
MAPK3	-0.058	0.19	-9999	-0.51	23	23
MAPK1	-0.058	0.19	-9999	-0.51	23	23
JAK2	-0.036	0.12	-9999	-0.43	8	8
NF2	-0.001	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.039	0.13	-9999	-0.28	81	81
NRG1	-0.11	0.24	-9999	-0.56	91	91
GRB2/SOS1	0.023	0.001	-9999	-10000	0	0
MAPK8	-0.032	0.12	-9999	-0.29	33	33
MAPK9	0.003	0.074	-9999	-0.21	8	8
ERBB2	-0.012	0.066	-9999	-0.37	13	13
ERBB3	-0.003	0.097	-9999	-0.56	12	12
SHC1	0.014	0.026	-9999	-0.51	1	1
RAC1	0.016	0	-9999	-10000	0	0
apoptosis	0.004	0.013	-9999	-10000	0	0
STAT3 (dimer)	0.022	0.006	-9999	-10000	0	0
RNF41	0.027	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.043	0.076	-9999	-0.3	8	8
ErbB2/ErbB2/HSP90 (dimer)	-0.01	0.054	-9999	-0.31	13	13
CHRNA1	-0.054	0.18	-9999	-0.39	47	47
myelination	-0.015	0.11	-9999	-0.35	11	11
PPP3CB	-0.033	0.12	-9999	-0.4	8	8
KRAS	0.014	0.026	-9999	-0.51	1	1
RAC1-CDC42/GDP	-0.017	0.12	-9999	-0.42	8	8
NRG2	-0.23	0.29	-9999	-0.57	172	172
mol:GDP	-0.039	0.13	-9999	-0.28	81	81
SOS1	0.015	0.001	-9999	-10000	0	0
MAP2K2	-0.009	0.12	-9999	-0.45	7	7
SRC	0.016	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.033	0.12	-9999	-0.43	8	8
MAP2K1	-0.071	0.19	-9999	-0.45	37	37
heart morphogenesis	-0.043	0.13	-9999	-0.46	8	8
RAS family/GDP	-0.021	0.12	-9999	-0.5	6	6
GRB2	0.015	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.012	0.026	-9999	-0.18	3	3
HSP90AA1	0.016	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.043	0.13	-9999	-0.46	8	8
CDC42	0.016	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.014	0.026	-9999	-0.51	1	1
SPHK1	-0.058	0.18	-9999	-0.51	57	57
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0.058	-9999	-0.29	1	1
GNAO1	-0.17	0.27	-9999	-0.57	129	129
mol:Sphinganine-1-P	-0.028	0.13	-9999	-0.36	58	58
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.029	0.042	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0.023	0	-9999	-10000	0	0
S1PR3	0.003	0.085	-9999	-0.56	9	9
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.017	0.041	-9999	-0.25	1	1
S1PR5	-0.005	0.1	-9999	-0.52	16	16
S1PR4	0.006	0.073	-9999	-0.54	7	7
GNAI1	0.011	0.05	-9999	-0.57	3	3
S1P/S1P5/G12	0.009	0.072	-9999	-0.28	16	16
S1P/S1P3/Gq	-0.013	0.12	-9999	-0.38	15	15
S1P/S1P4/Gi	-0.1	0.19	-9999	-0.45	67	67
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.57	89	89
GNA14	-0.068	0.2	-9999	-0.57	58	58
GNA15	0.011	0.05	-9999	-0.57	3	3
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.014	0.029	-9999	-0.57	1	1
ABCC1	0.013	0.036	-9999	-0.51	2	2

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.021	0.026	-9999	-0.36	2	2
CRKL	-0.008	0.1	-9999	-0.36	3	3
mol:PIP3	-0.021	0.006	-9999	-10000	0	0
AKT1	0.002	0.004	-9999	-10000	0	0
PTK2B	0.014	0.029	-9999	-0.57	1	1
RAPGEF1	0.001	0.097	-9999	-0.37	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.054	0.16	-9999	-0.33	96	96
MAP3K5	0.006	0.1	-9999	-0.38	6	6
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.039	0.14	-9999	-0.3	96	96
AP1	-0.11	0.2	-9999	-0.4	130	130
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.026	-9999	-0.51	1	1
apoptosis	-0.22	0.36	-9999	-0.75	130	130
STAT3 (dimer)	-0.013	0.12	-9999	-0.23	87	87
GAB1/CRKL/SHP2/PI3K	-0.035	0.068	-9999	-0.37	3	3
INPP5D	0.006	0.076	-9999	-0.57	7	7
CBL/CRK	0.003	0.095	-9999	-0.29	2	2
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	-0.004	0.016	-9999	-0.2	2	2
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.03	0.059	-9999	-0.39	1	1
PAK1	0.009	0.015	-9999	-0.29	1	1
HGF/MET/RANBP10	-0.054	0.16	-9999	-0.33	96	96
HRAS	-0.027	0.13	-9999	-0.38	1	1
DOCK1	-0.001	0.1	-9999	-0.4	3	3
GAB1	-0.016	0.1	-9999	-0.34	2	2
CRK	-0.007	0.098	-9999	-0.31	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.1	0.19	-9999	-0.47	87	87
JUN	-0.007	0.11	-9999	-0.57	16	16
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.032	0.092	-9999	-0.2	87	87
PIK3R1	0.014	0.029	-9999	-0.57	1	1
cell morphogenesis	0.014	0.12	-9999	-0.42	3	3
GRB2/SHC	-0.01	0.083	-9999	-0.32	2	2
FOS	-0.17	0.27	-9999	-0.57	129	129
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.004	0.016	-9999	-0.2	2	2
HGF/MET/MUC20	-0.065	0.16	-9999	-0.34	96	96
cell migration	-0.01	0.082	-9999	-0.32	2	2
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
MET/RANBP10	0.021	0.026	-9999	-0.36	2	2
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.02	0.12	-9999	-0.24	87	87
MET/MUC20	0.01	0.026	-9999	-0.37	2	2
RAP1B	0.009	0.092	-9999	-0.34	2	2
RAP1A	0.009	0.092	-9999	-0.34	2	2
HGF/MET/RANBP9	-0.054	0.16	-9999	-0.33	96	96
RAF1	-0.017	0.13	-9999	-0.35	1	1
STAT3	-0.013	0.12	-9999	-0.23	87	87
cell proliferation	-0.021	0.16	-9999	-0.32	87	87
RPS6KB1	-0.002	0.035	-9999	-0.16	1	1
MAPK3	-0.009	0.014	-9999	-10000	0	0
MAPK1	-0.009	0.014	-9999	-0.19	2	2
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.024	0.096	-9999	-0.34	7	7
SRC	-0.01	0.11	-9999	-0.46	1	1
PI3K	-0.01	0.085	-9999	-0.43	2	2
MET/Glomulin	0.013	0.023	-9999	-0.32	2	2
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	-0.008	0.12	-9999	-0.32	1	1
MET	0.013	0.036	-9999	-0.51	2	2
MAP4K1	-0.002	0.11	-9999	-0.37	6	6
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	-0.008	0.12	-9999	-0.32	1	1
BAD	0.01	0.005	-9999	-10000	0	0
MAP2K4	0.014	0.096	-9999	-0.34	6	6
SHP2/GRB2/SOS1/GAB1	-0.036	0.066	-9999	-0.29	1	1
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.02	0.085	-9999	-0.44	1	1
PLCgamma1/PKC	0.012	0	-9999	-10000	0	0
HGF	-0.12	0.24	-9999	-0.56	94	94
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
PTPRJ	0.014	0.029	-9999	-0.57	1	1
NCK/PLCgamma1	-0.012	0.092	-9999	-0.43	1	1
PDPK1	-0.008	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.06	0.17	-9999	-0.35	99	99

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.28	0.29	-9999	-0.57	206	206
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0.026	-9999	-0.51	1	1
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	0.036	0.015	-9999	-10000	0	0
HIF1A	0.027	0.016	-9999	-10000	0	0
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.046	0.014	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.25	0.26	-9999	-0.51	205	205
ARNT/IPAS	-0.2	0.22	-9999	-0.41	206	206
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.016	0	-9999	-10000	0	0
HIF1A/ARNT	0.036	0.015	-9999	-10000	0	0
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.031	0.016	-9999	-0.29	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.036	0.015	-9999	-10000	0	0
PHD1-3/OS9	0.034	0.047	-9999	-0.3	8	8
HIF1A/RACK1/Elongin B/Elongin C	0.047	0.018	-9999	-10000	0	0
VHL	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	0.036	0.015	-9999	-10000	0	0
EGLN3	0.004	0.081	-9999	-0.57	8	8
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.044	0.008	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.092	0.13	-9999	-0.28	8	8

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.015	0.25	-10000	0	-0.83	13	13
PCK1	-0.024	0.18	-10000	0	-0.73	7	7
HNF4A	-0.046	0.3	-10000	0	-0.99	18	18
KCNJ11	-0.04	0.32	-10000	0	-0.92	30	30
AKT1	0.018	0.11	-10000	0	-0.39	5	5
response to starvation	-0.004	0.019	-10000	0	-10000	0	0
DLK1	-0.053	0.33	-10000	0	-0.93	34	34
NKX2-1	0.096	0.23	0.66	12	-0.62	1	13
ACADM	-0.018	0.26	-10000	0	-0.81	18	18
TAT	-0.026	0.19	-10000	0	-0.71	12	12
CEBPB	0.012	0.031	-10000	0	-0.58	1	1
CEBPA	-0.002	0.093	-10000	0	-0.53	12	12
TTR	-0.094	0.24	-10000	0	-0.69	27	27
PKLR	-0.037	0.27	-10000	0	-0.85	17	17
APOA1	-0.026	0.3	-10000	0	-0.98	15	15
CPT1C	-0.02	0.26	-10000	0	-0.82	15	15
ALAS1	0.032	0.14	-10000	0	-10000	0	0
TFRC	-0.008	0.19	-10000	0	-0.63	6	6
FOXF1	-0.19	0.28	-10000	0	-0.56	148	148
NF1	0.024	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.022	0.075	-10000	0	-0.55	5	5
CPT1A	-0.017	0.25	-10000	0	-0.9	12	12
HMGCS1	-0.015	0.25	-10000	0	-0.83	13	13
NR3C1	-0.001	0.1	-10000	0	-0.57	12	12
CPT1B	-0.018	0.26	-10000	0	-0.89	13	13
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.014	0.042	-10000	0	-10000	0	0
GCK	-0.064	0.34	-10000	0	-0.91	39	39
CREB1	0.014	0.023	-10000	0	-10000	0	0
IGFBP1	-0.008	0.17	-10000	0	-0.57	14	14
PDX1	-0.075	0.22	-10000	0	-0.6	18	18
UCP2	-0.017	0.25	-10000	0	-0.78	17	17
ALDOB	-0.026	0.29	-10000	0	-0.86	21	21
AFP	-0.07	0.14	-10000	0	-0.47	22	22
BDH1	-0.015	0.25	-10000	0	-0.79	16	16
HADH	-0.006	0.26	-10000	0	-0.83	14	14
F2	-0.025	0.29	-10000	0	-0.96	16	16
HNF1A	-0.022	0.075	-10000	0	-0.55	5	5
G6PC	-0.031	0.12	-10000	0	-0.56	5	5
SLC2A2	-0.017	0.19	-10000	0	-0.67	11	11
INS	-0.006	0.028	-10000	0	-10000	0	0
FOXA1	-0.057	0.19	-10000	0	-0.57	45	45
FOXA3	-0.099	0.22	-10000	0	-0.51	81	81
FOXA2	-0.014	0.3	-10000	0	-0.86	20	20
ABCC8	-0.014	0.26	-10000	0	-0.86	14	14
ALB	-0.085	0.16	-10000	0	-0.46	28	28

×

Effects of Botulinum toxin

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.037	-9999	-0.37	4	4
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.003	0.08	-9999	-0.4	15	15
STXBP1	-0.007	0.11	-9999	-0.57	16	16
ACh/CHRNA1	-0.05	0.13	-9999	-0.33	71	71
RAB3GAP2/RIMS1/UNC13B	0.014	0.069	-9999	-0.34	15	15
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.012	0.11	-9999	-0.56	15	15
mol:ACh	-0.001	0.037	-9999	-0.12	30	30
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.03	0.084	-9999	-0.38	12	12
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.05	0.13	-9999	-0.33	71	71
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.076	0.2	-9999	-0.51	71	71
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.029	0.12	-9999	-0.38	42	42
SNAP25	-0.017	0.082	-9999	-0.26	39	39
VAMP2	0.008	0	-9999	-10000	0	0
SYT1	-0.043	0.17	-9999	-0.56	42	42
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.004	0.078	-9999	-0.34	20	20
STX1A/SNAP25 fragment 1/VAMP2	-0.03	0.084	-9999	-0.38	12	12

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.026	0.002	-9999	-10000	0	0
SMARCC1	0.012	0.014	-9999	-10000	0	0
REL	0.01	0.061	-9999	-0.54	5	5
HDAC7	-0.013	0.13	-9999	-0.37	6	6
JUN	-0.008	0.11	-9999	-0.57	16	16
EP300	0.016	0	-9999	-10000	0	0
KAT2B	0.014	0.029	-9999	-0.57	1	1
KAT5	0.016	0.001	-9999	-10000	0	0
MAPK14	0.016	0.053	-9999	-0.4	6	6
FOXO1	0.014	0.029	-9999	-0.57	1	1
T-DHT/AR	-0.019	0.14	-9999	-0.36	25	25
MAP2K6	0.005	0.07	-9999	-0.56	6	6
BRM/BAF57	0.022	0.007	-9999	-10000	0	0
MAP2K4	0.014	0.007	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.16	0.4	-9999	-1.2	49	49
NCOA2	-0.019	0.14	-9999	-0.57	24	24
CEBPA	0	0.09	-9999	-0.52	12	12
EHMT2	0.015	0.004	-9999	-10000	0	0
cell proliferation	0	0.15	-9999	-0.45	12	12
NR0B1	-0.035	0.14	-9999	-0.51	32	32
EGR1	-0.13	0.25	-9999	-0.57	100	100
RXRs/9cRA	-0.065	0.15	-9999	-0.31	107	107
AR/RACK1/Src	-0.015	0.087	-9999	-0.37	6	6
AR/GR	-0.074	0.15	-9999	-0.32	71	71
GNB2L1	0.016	0.001	-9999	-10000	0	0
PKN1	0.014	0.029	-9999	-0.57	1	1
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.019	0.04	-9999	-0.41	3	3
T-DHT/AR/TIF2/CARM1	-0.018	0.12	-9999	-0.39	19	19
SRC	0.028	0.056	-9999	-0.32	2	2
NR3C1	-0.002	0.099	-9999	-0.57	12	12
KLK3	-0.12	0.26	-9999	-0.93	28	28
APPBP2	0.013	0.008	-9999	-10000	0	0
TRIM24	0.011	0.045	-9999	-0.51	3	3
T-DHT/AR/TIP60	-0.009	0.091	-9999	-0.39	6	6
TMPRSS2	-0.21	0.45	-9999	-1.2	70	70
RXRG	-0.14	0.25	-9999	-0.57	107	107
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.029	-9999	-0.57	1	1
RXRB	0.015	0.001	-9999	-10000	0	0
CARM1	0.015	0.002	-9999	-10000	0	0
NR2C2	0.013	0.039	-9999	-0.54	2	2
KLK2	-0.024	0.14	-9999	-0.49	11	11
AR	-0.08	0.16	-9999	-0.28	149	149
SENP1	0.015	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0	0.092	-9999	-0.5	13	13
SRY	0	0.063	-9999	-0.51	6	6
GATA2	-0.011	0.12	-9999	-0.53	20	20
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.078	0.21	-9999	-0.56	65	65
T-DHT/AR/RACK1/Src	-0.002	0.09	-9999	-0.38	6	6
positive regulation of transcription	-0.011	0.12	-9999	-0.53	20	20
DNAJA1	0.013	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.024	-9999	-10000	0	0
NCOA1	0.02	0.006	-9999	-10000	0	0
SPDEF	-0.096	0.22	-9999	-0.54	81	81
T-DHT/AR/TIF2	0.004	0.091	-9999	-0.34	9	9
T-DHT/AR/Hsp90	-0.009	0.091	-9999	-0.39	6	6
GSK3B	0.015	0.005	-9999	-10000	0	0
NR2C1	0.016	0.002	-9999	-10000	0	0
mol:T-DHT	0.021	0.06	-9999	-0.31	8	8
SIRT1	0.016	0	-9999	-10000	0	0
ZMIZ2	0.017	0.007	-9999	-10000	0	0
POU2F1	0.018	0.041	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.049	0.11	-9999	-0.39	13	13
CREBBP	0.016	0.001	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

Caspase cascade in apoptosis

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
TOP1	-0.005	0.12	-10000	0	-0.36	33	33
ACTA1	-0.026	0.16	-10000	0	-0.48	35	35
NUMA1	-0.005	0.12	-10000	0	-0.36	33	33
SPTAN1	-0.021	0.16	-10000	0	-0.48	33	33
LIMK1	-0.021	0.16	-10000	0	-0.48	33	33
BIRC3	-0.02	0.14	-10000	0	-0.56	25	25
BIRC2	0.013	0.036	-10000	0	-0.51	2	2
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.036	0.17	-10000	0	-0.4	65	65
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0.039	-10000	0	-0.54	2	2
PTK2	-0.005	0.12	-10000	0	-0.36	33	33
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.02	0.16	-10000	0	-0.47	33	33
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.026	0.17	-10000	0	-0.5	35	35
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	0.017	0.048	-10000	0	-0.48	2	2
BID	-0.008	0.087	-10000	0	-0.24	40	40
MAP3K1	0.002	0.056	-10000	0	-0.2	10	10
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.023	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.021	0.16	-10000	0	-0.48	33	33
CASP9	0.016	0	-10000	0	-10000	0	0
DNA repair	-0.006	0.052	-10000	0	-0.2	12	12
neuron apoptosis	0.021	0.058	-10000	0	-0.77	2	2
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.01	0.15	-10000	0	-0.45	33	33
APAF1	0.016	0	-10000	0	-10000	0	0
CASP6	0.018	0.076	-10000	0	-0.35	3	3
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.012	0.15	-10000	0	-0.46	33	33
CASP7	0.009	0.078	0.31	22	-10000	0	22
KRT18	0.013	0.041	-10000	0	-0.64	1	1
apoptosis	-0.004	0.15	0.27	1	-0.47	26	27
DFFA	-0.021	0.16	-10000	0	-0.48	33	33
DFFB	-0.021	0.16	-10000	0	-0.48	33	33
PARP1	0.006	0.052	0.2	12	-10000	0	12
actin filament polymerization	0.012	0.15	0.44	33	-10000	0	33
TNF	-0.011	0.12	-10000	0	-0.51	21	21
CYCS	-0.001	0.066	-10000	0	-0.21	19	19
SATB1	0.016	0.09	-10000	0	-0.35	5	5
SLK	-0.021	0.16	-10000	0	-0.48	33	33
p15 BID/BAX	0.001	0.078	-10000	0	-0.3	10	10
CASP2	0.042	0.05	-10000	0	-10000	0	0
JNK cascade	-0.002	0.055	0.2	10	-10000	0	10
CASP3	-0.031	0.17	-10000	0	-0.51	33	33
LMNB2	0.04	0.045	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.014	0.026	-10000	0	-0.51	1	1
Mammalian IAPs/DIABLO	0.017	0.09	-10000	0	-0.32	23	23
negative regulation of DNA binding	0.017	0.048	-10000	0	-0.48	2	2
stress fiber formation	-0.02	0.16	-10000	0	-0.47	33	33
GZMB	-0.054	0.19	-10000	0	-0.48	65	65
CASP1	0.012	0.054	-10000	0	-0.33	10	10
LMNB1	0.039	0.046	-10000	0	-10000	0	0
APP	0.021	0.059	-10000	0	-0.78	2	2
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	-0.009	0.14	0.28	1	-0.43	33	34
LMNA	0.04	0.045	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.035	0.053	-10000	0	-10000	0	0
LRDD	0.016	0	-10000	0	-10000	0	0
SREBF1	-0.022	0.16	-10000	0	-0.48	33	33
APAF-1/Caspase 9	0.002	0.044	0.32	2	-10000	0	2
nuclear fragmentation during apoptosis	-0.005	0.12	-10000	0	-0.36	33	33
CFL2	-0.013	0.15	-10000	0	-0.45	33	33
GAS2	-0.055	0.19	-10000	0	-0.51	37	37
positive regulation of apoptosis	0.044	0.045	-10000	0	-10000	0	0
PRF1	-0.021	0.14	-10000	0	-0.54	27	27

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.01	0.058	-10000	0	-0.57	4	4
ANTXR2	-0.02	0.14	-10000	0	-0.57	25	25
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.005	0.019	-10000	0	-0.075	28	28
monocyte activation	-0.005	0.087	-10000	0	-0.41	17	17
MAP2K2	-0.002	0.007	-10000	0	-10000	0	0
MAP2K1	-0.004	0.015	-10000	0	-10000	0	0
MAP2K7	-0.004	0.015	-10000	0	-10000	0	0
MAP2K6	-0.009	0.04	-10000	0	-0.31	6	6
CYAA	-0.005	0.083	-10000	0	-0.31	28	28
MAP2K4	-0.004	0.015	-10000	0	-10000	0	0
IL1B	-0.014	0.091	-10000	0	-0.29	37	37
Channel	-0.004	0.089	-10000	0	-0.33	28	28
NLRP1	-0.009	0.043	-10000	0	-0.31	7	7
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.006	0.021	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.005	0.019	0.075	28	-10000	0	28
MAPK3	-0.004	0.015	-10000	0	-10000	0	0
MAPK1	-0.004	0.015	-10000	0	-10000	0	0
PGR	-0.1	0.15	-10000	0	-0.31	129	129
PA/Cellular Receptors	-0.005	0.097	-10000	0	-0.36	28	28
apoptosis	-0.005	0.019	-10000	0	-0.075	28	28
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.003	0.084	-10000	0	-0.31	28	28
macrophage activation	0.017	0.018	-10000	0	-10000	0	0
TNF	-0.011	0.12	-10000	0	-0.51	21	21
VCAM1	-0.005	0.088	-10000	0	-0.41	17	17
platelet activation	-0.006	0.021	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.022	0.12	2	-10000	0	2
IL18	0.006	0.057	-10000	0	-0.35	8	8
negative regulation of macrophage activation	-0.005	0.019	-10000	0	-0.075	28	28
LEF	-0.005	0.019	-10000	0	-0.076	28	28
CASP1	-0.009	0.037	-10000	0	-0.19	11	11
mol:cAMP	-0.006	0.021	-10000	0	-10000	0	0
necrosis	-0.005	0.019	-10000	0	-0.075	28	28
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.003	0.084	-10000	0	-0.31	28	28
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.001	-10000	0	-10000	0	0
HDAC2	0.016	0.001	-10000	0	-10000	0	0
GNB1/GNG2	0.004	0.095	-10000	0	-0.35	26	26
forebrain development	-0.09	0.25	-10000	0	-0.58	64	64
GNAO1	-0.17	0.27	-10000	0	-0.57	129	129
SMO/beta Arrestin2	0.001	0.096	-10000	0	-0.41	21	21
SMO	-0.015	0.13	-10000	0	-0.57	21	21
ARRB2	0.015	0.005	-10000	0	-10000	0	0
GLI3/SPOP	0.054	0.057	-10000	0	-10000	0	0
mol:GTP	0	0.002	-10000	0	-10000	0	0
GSK3B	0.016	0	-10000	0	-10000	0	0
GNAI2	0.016	0.002	-10000	0	-10000	0	0
SIN3/HDAC complex	0.04	0.002	-10000	0	-10000	0	0
GNAI1	0.011	0.05	-10000	0	-0.57	3	3
XPO1	0.016	0.007	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.094	0.2	-10000	0	-0.68	29	29
SAP30	0.016	0.001	-10000	0	-10000	0	0
mol:GDP	-0.015	0.13	-10000	0	-0.57	21	21
MIM/GLI2A	0.017	0.008	-10000	0	-10000	0	0
IFT88	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0.002	-10000	0	-10000	0	0
GLI2	0.022	0.075	-10000	0	-10000	0	0
GLI3	0.047	0.061	0.2	17	-0.24	12	29
CSNK1D	0.016	0	-10000	0	-10000	0	0
CSNK1E	0.016	0	-10000	0	-10000	0	0
SAP18	0.016	0.001	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.016	0	-10000	0	-10000	0	0
GNG2	0.007	0.07	-10000	0	-0.57	6	6
Gi family/GTP	-0.12	0.22	-10000	0	-0.49	78	78
SIN3B	0.016	0.001	-10000	0	-10000	0	0
SIN3A	0.016	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	0.066	0.042	-10000	0	-10000	0	0
GLI2/Su(fu)	0.027	0.088	-10000	0	-0.28	15	15
FOXA2	-0.056	0.12	-10000	0	-10000	0	0
neural tube patterning	-0.09	0.25	-10000	0	-0.58	64	64
SPOP	0.016	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.028	0.046	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
CSNK1G2	0.016	0	-10000	0	-10000	0	0
CSNK1G3	0.016	0	-10000	0	-10000	0	0
MTSS1	0.017	0.008	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.09	0.25	-10000	0	-0.58	64	64
SUFU	0.019	0.052	-10000	0	-10000	0	0
LGALS3	0.014	0.029	-10000	0	-0.57	1	1
catabolic process	0.059	0.076	-10000	0	-0.3	6	6
GLI3A/CBP	-0.029	0.13	-10000	0	-0.34	61	61
KIF3A	0.016	0	-10000	0	-10000	0	0
GLI1	-0.092	0.26	-10000	0	-0.6	64	64
RAB23	0.014	0.029	-10000	0	-0.57	1	1
CSNK1A1	0.016	0	-10000	0	-10000	0	0
IFT172	0.016	0	-10000	0	-10000	0	0
RBBP7	0.016	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.027	0.049	-10000	0	-0.29	1	1
GNAZ	-0.11	0.24	-10000	0	-0.57	89	89
RBBP4	0.016	0.001	-10000	0	-10000	0	0
CSNK1G1	0.016	0	-10000	0	-10000	0	0
PIAS1	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
GLI2/SPOP	0.028	0.07	-10000	0	-10000	0	0
STK36	0.016	0.006	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.097	0.21	-10000	0	-0.48	67	67
PTCH1	-0.072	0.22	-10000	0	-0.7	29	29
MIM/GLI1	-0.093	0.25	-10000	0	-0.63	52	52
CREBBP	-0.029	0.13	-10000	0	-0.34	61	61
Su(fu)/SIN3/HDAC complex	0.055	0.015	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.019	0.005	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.027	0.13	0.49	7	-10000	0	7
IL27/IL27R/JAK1	-0.054	0.16	-10000	0	-0.7	5	5
TBX21	-0.042	0.2	-10000	0	-0.53	32	32
IL12B	-0.009	0.095	-10000	0	-0.51	14	14
IL12A	0.005	0.053	-10000	0	-0.37	8	8
IL6ST	-0.074	0.21	-10000	0	-0.58	61	61
IL27RA/JAK1	0.016	0.037	-10000	0	-10000	0	0
IL27	-0.019	0.12	-10000	0	-0.51	23	23
TYK2	0.014	0.008	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.027	0.13	0.49	7	-10000	0	7
T cell proliferation during immune response	0.027	0.13	0.49	7	-10000	0	7
MAPKKK cascade	-0.027	0.13	-10000	0	-0.49	7	7
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.01	0.051	-10000	0	-0.5	4	4
IL12RB1	-0.025	0.14	-10000	0	-0.53	30	30
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.065	0.22	-10000	0	-0.51	46	46
IL27/IL27R/JAK2/TYK2	-0.027	0.13	-10000	0	-0.5	7	7
positive regulation of T cell mediated cytotoxicity	-0.027	0.13	-10000	0	-0.49	7	7
STAT1 (dimer)	-0.082	0.21	0.5	14	-0.65	20	34
JAK2	0.012	0.03	-10000	0	-0.57	1	1
JAK1	0.016	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.019	0.12	-10000	0	-0.52	5	5
T cell proliferation	-0.15	0.19	-10000	0	-0.51	41	41
IL12/IL12R/TYK2/JAK2	-0.001	0.086	-10000	0	-10000	0	0
IL17A	-0.12	0.15	-10000	0	-10000	0	0
mast cell activation	0.027	0.13	0.49	7	-10000	0	7
IFNG	-0.008	0.035	-10000	0	-0.079	27	27
T cell differentiation	-0.005	0.006	-10000	0	-0.018	44	44
STAT3 (dimer)	-0.019	0.12	-10000	0	-0.49	6	6
STAT5A (dimer)	-0.019	0.12	-10000	0	-0.52	5	5
STAT4 (dimer)	-0.034	0.14	-10000	0	-0.51	10	10
STAT4	-0.013	0.13	-10000	0	-0.57	20	20
T cell activation	-0.01	0.008	0.051	4	-10000	0	4
IL27R/JAK2/TYK2	-0.026	0.13	-10000	0	-0.61	2	2
GATA3	-0.071	0.35	-10000	0	-1.4	27	27
IL18	0.007	0.052	-10000	0	-0.42	6	6
positive regulation of mast cell cytokine production	-0.018	0.12	-10000	0	-0.48	6	6
IL27/EBI3	-0.014	0.11	-10000	0	-0.39	32	32
IL27RA	0.006	0.038	-10000	0	-10000	0	0
IL6	-0.24	0.29	-10000	0	-0.57	184	184
STAT5A	0.014	0.029	-10000	0	-0.57	1	1
monocyte differentiation	-0.001	0.002	-10000	0	-10000	0	0
IL2	0.004	0.022	-10000	0	-10000	0	0
IL1B	-0.022	0.12	-10000	0	-0.4	35	35
EBI3	-0.002	0.089	-10000	0	-0.53	11	11
TNF	-0.007	0.084	-10000	0	-0.37	21	21

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.008	0.11	-9999	-0.54	17	17
EGF/EGFR	-0.069	0.12	-9999	-0.29	69	69
EGF/EGFR dimer/SHC/GRB2/SOS1	0.016	0.09	-9999	-0.49	1	1
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.069	0.21	-9999	-0.57	59	59
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.018	0.12	-9999	-0.51	25	25
EGF/EGFR dimer/SHC	-0.004	0.1	-9999	-0.31	42	42
mol:GDP	-0.025	0.075	-9999	-0.48	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.005	0.076	-9999	-0.53	8	8
GRB2/SOS1	0.023	0	-9999	-10000	0	0
HRAS/GTP	-0.022	0.067	-9999	-0.45	1	1
SHC1	0.014	0.026	-9999	-0.51	1	1
HRAS/GDP	-0.023	0.069	-9999	-0.45	1	1
FRAP1	0.012	0.084	-9999	-0.47	1	1
EGF/EGFR dimer	-0.018	0.12	-9999	-0.37	42	42
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.047	0.16	-9999	-0.41	66	66

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.001	0.09	-9999	-0.57	10	10
alphaV beta3 Integrin	-0.026	0.14	-9999	-0.42	46	46
PTK2	-0.046	0.12	-9999	-0.44	29	29
positive regulation of JNK cascade	-0.023	0.078	-9999	-0.3	29	29
CDC42/GDP	0.028	0.12	-9999	-0.41	29	29
Rac1/GDP	0.03	0.12	-9999	-0.4	29	29
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.028	0.096	-9999	-0.37	29	29
nectin-3/I-afadin	-0.009	0.11	-9999	-0.4	31	31
RAPGEF1	0.02	0.14	-9999	-0.45	29	29
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.01	0.15	-9999	-0.52	29	29
PDGFB-D/PDGFRB	0.001	0.09	-9999	-0.57	10	10
TLN1	0.018	0.066	-9999	-0.32	6	6
Rap1/GTP	-0.023	0.082	-9999	-0.32	29	29
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.03	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.009	0.11	-9999	-0.4	31	31
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.021	0.15	-9999	-0.5	29	29
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.014	0.099	-9999	-0.57	1	1
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.022	0.021	-9999	-0.41	1	1
positive regulation of lamellipodium assembly	-0.025	0.084	-9999	-0.32	30	30
PVRL1	0.014	0.029	-9999	-0.57	1	1
PVRL3	-0.028	0.15	-9999	-0.56	31	31
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
CDH1	-0.004	0.11	-9999	-0.57	14	14
CLDN1	-0.019	0.14	-9999	-0.55	25	25
JAM-A/CLDN1	-0.006	0.12	-9999	-0.32	46	46
SRC	-0.047	0.15	-9999	-0.59	29	29
ITGB3	-0.05	0.18	-9999	-0.57	46	46
nectin-1(dimer)/I-afadin/I-afadin	0.022	0.021	-9999	-0.41	1	1
FARP2	0.016	0.14	-9999	-0.49	29	29
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.004	0.097	-9999	-0.34	31	31
nectin-1/I-afadin	0.022	0.021	-9999	-0.41	1	1
nectin-2/I-afadin	0.023	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.003	0.099	-9999	-0.34	32	32
CDC42/GTP/IQGAP1/filamentous actin	0.021	0	-9999	-10000	0	0
F11R	0.014	0.029	-9999	-0.57	1	1
positive regulation of filopodium formation	-0.023	0.078	-9999	-0.3	29	29
alphaV/beta3 Integrin/Talin	0.001	0.12	-9999	-0.46	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.023	0	-9999	-10000	0	0
PIP5K1C	0.01	0.07	-9999	-0.35	6	6
VAV2	0.012	0.15	-9999	-0.5	31	31
RAP1/GDP	-0.027	0.097	-9999	-0.37	29	29
ITGAV	0.014	0.029	-9999	-0.57	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.004	0.097	-9999	-0.34	31	31
nectin-3(dimer)/I-afadin/I-afadin	-0.009	0.11	-9999	-0.4	31	31
Rac1/GTP	-0.03	0.1	-9999	-0.39	30	30
PTPRM	0	0.077	-9999	-0.39	6	6
E-cadherin/beta catenin/alpha catenin	-0.009	0.052	-9999	-0.54	1	1
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.015	0.029	-9999	-0.57	1	1
ELF1	-0.001	0.086	-9999	-0.34	18	18
CCNA2	-0.12	0.23	-9999	-0.51	106	106
PIK3CA	0.017	0	-9999	-10000	0	0
JAK3	0.014	0.037	-9999	-0.51	2	2
PIK3R1	0.015	0.029	-9999	-0.57	1	1
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.062	0.098	-9999	-0.62	4	4
SHC1	0.015	0.026	-9999	-0.51	1	1
SP1	-0.003	0.098	-9999	-0.34	32	32
IL2RA	-0.019	0.19	-9999	-0.58	37	37
IL2RB	0.007	0.074	-9999	-0.55	7	7
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.009	0.12	-9999	-0.54	19	19
G1/S transition of mitotic cell cycle	-0.059	0.24	-9999	-0.76	37	37
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	-0.03	0.23	-9999	-0.8	32	32
LCK	0.008	0.068	-9999	-0.55	6	6
GRB2	0.017	0	-9999	-10000	0	0
IL2	0.005	0.007	-9999	-10000	0	0
CDK6	0	0.095	-9999	-0.57	11	11
CCND3	0.069	0.086	-9999	-0.56	3	3

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0.007	-10000	0	-10000	0	0
HSPA8	0.015	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.065	0.15	0.22	6	-0.38	69	75
AKT1	0.016	0.014	-10000	0	-10000	0	0
GSC	-0.005	0.085	-10000	0	-0.42	1	1
NKX2-5	-0.076	0.19	-10000	0	-0.5	65	65
muscle cell differentiation	0.051	0.088	0.4	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.049	0.096	-10000	0	-0.37	6	6
SMAD4	0.01	0.05	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.016	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.027	0.046	-10000	0	-0.29	8	8
SMAD3/SMAD4/VDR	-0.001	0.042	-10000	0	-0.43	2	2
MYC	-0.01	0.12	-10000	0	-0.57	18	18
CDKN2B	-0.009	0.25	-10000	0	-1.4	11	11
AP1	-0.054	0.21	-10000	0	-0.6	29	29
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.069	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.027	0.076	-10000	0	-0.33	6	6
SP3	0.019	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.1	0.22	-10000	0	-0.5	92	92
SMAD3/SMAD4/GR	-0.019	0.083	-10000	0	-0.43	12	12
GATA3	-0.028	0.15	-10000	0	-0.57	29	29
SKI/SIN3/HDAC complex/NCoR1	0.055	0.008	-10000	0	-10000	0	0
MEF2C/TIF2	-0.073	0.2	-10000	0	-0.55	39	39
endothelial cell migration	0.005	0.16	1.4	5	-10000	0	5
MAX	0.014	0.006	-10000	0	-10000	0	0
RBBP7	0.016	0.001	-10000	0	-10000	0	0
RBBP4	0.016	0.001	-10000	0	-10000	0	0
RUNX2	0.008	0.064	-10000	0	-0.52	6	6
RUNX3	-0.004	0.11	-10000	0	-0.57	14	14
RUNX1	0.016	0	-10000	0	-10000	0	0
CTBP1	0.014	0.026	-10000	0	-0.51	1	1
NR3C1	-0.003	0.099	-10000	0	-0.57	12	12
VDR	0.011	0.048	-10000	0	-0.55	3	3
CDKN1A	0.052	0.12	-10000	0	-1.4	2	2
KAT2B	0.014	0.029	-10000	0	-0.57	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.039	0.15	-10000	0	-0.37	29	29
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.016	0.001	-10000	0	-10000	0	0
SERPINE1	-0.007	0.17	-10000	0	-1.4	5	5
SMAD3/SMAD4/ATF2	-0.005	0.045	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.07	0.15	-10000	0	-0.39	72	72
SAP30	0.016	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.019	0.025	-10000	0	-10000	0	0
JUN	-0.054	0.21	-10000	0	-0.6	29	29
SMAD3/SMAD4/IRF7	-0.02	0.08	-10000	0	-0.38	8	8
TFE3	0.022	0.012	-10000	0	-10000	0	0
COL1A2	-0.042	0.26	-10000	0	-0.96	29	29
mesenchymal cell differentiation	0.01	0.058	0.32	6	-10000	0	6
DLX1	-0.04	0.16	-10000	0	-0.51	42	42
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	-0.16	0.28	-10000	0	-0.57	129	129
SMAD3/SMAD4/Max	-0.008	0.042	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.032	0.007	-10000	0	-10000	0	0
ZBTB17	0.016	0.012	-10000	0	-10000	0	0
LAMC1	0.046	0.06	-10000	0	-0.62	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.005	0.045	-10000	0	-10000	0	0
IRF7	-0.005	0.1	-10000	0	-0.52	15	15
ESR1	-0.087	0.22	-10000	0	-0.56	73	73
HNF4A	-0.04	0.16	-10000	0	-0.51	41	41
MEF2C	-0.068	0.19	-10000	0	-0.58	26	26
SMAD2-3/SMAD4	0.012	0.064	-10000	0	-0.32	1	1
Cbp/p300/Src-1	0.033	0.01	-10000	0	-10000	0	0
IGHV3OR16-13	-0.003	0.016	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0.005	-10000	0	-10000	0	0
SKIL	0.014	0.026	-10000	0	-0.51	1	1
HDAC1	0.016	0.001	-10000	0	-10000	0	0
HDAC2	0.016	0.001	-10000	0	-10000	0	0
SNIP1	0.016	0.001	-10000	0	-10000	0	0
GCN5L2	0	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.036	0.065	-10000	0	-0.33	1	1
MSG1/HSC70	0.014	0.053	-10000	0	-0.36	8	8
SMAD2	0.018	0.021	-10000	0	-10000	0	0
SMAD3	0.01	0.046	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.041	0.043	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.01	0.029	-10000	0	-0.34	1	1
NCOR1	0.016	0.001	-10000	0	-10000	0	0
NCOA2	-0.019	0.14	-10000	0	-0.57	24	24
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	0.012	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.061	0.091	-10000	0	-0.39	3	3
IFNB1	0.012	0.1	-10000	0	-0.47	10	10
SMAD3/SMAD4/MEF2C	-0.067	0.19	-10000	0	-0.57	27	27
CITED1	0.005	0.072	-10000	0	-0.51	8	8
SMAD2-3/SMAD4/ARC105	0.034	0.064	-10000	0	-10000	0	0
RBL1	0.013	0.036	-10000	0	-0.51	2	2
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.043	0.1	-10000	0	-0.49	11	11
RUNX1-3/PEBPB2	0.019	0.067	-10000	0	-0.34	14	14
SMAD7	-0.004	0.18	-10000	0	-0.55	16	16
MYC/MIZ-1	-0.007	0.093	-10000	0	-0.42	18	18
SMAD3/SMAD4	0.005	0.067	0.25	1	-0.4	5	6
IL10	-0.007	0.18	-10000	0	-0.6	25	25
PIASy/HDAC complex	0.015	0.006	-10000	0	-10000	0	0
PIAS3	0.016	0.003	-10000	0	-10000	0	0
CDK2	0.016	0.004	-10000	0	-10000	0	0
IL5	-0.001	0.12	-10000	0	-0.48	9	9
CDK4	0.015	0.026	-10000	0	-0.51	1	1
PIAS4	0.015	0.006	-10000	0	-10000	0	0
ATF3	-0.088	0.22	-10000	0	-0.57	72	72
SMAD3/SMAD4/SP1	0.028	0.093	-10000	0	-0.36	8	8
FOXG1	-0.067	0.18	-10000	0	-0.51	55	55
FOXO3	0.027	0.019	-10000	0	-10000	0	0
FOXO1	0.026	0.029	-10000	0	-0.42	1	1
FOXO4	0.026	0.027	-10000	0	-0.35	1	1
heart looping	-0.067	0.19	-10000	0	-0.57	26	26
CEBPB	0.014	0.03	-10000	0	-0.57	1	1
SMAD3/SMAD4/DLX1	-0.037	0.1	-10000	0	-0.34	23	23
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.036	0.1	-10000	0	-0.36	18	18
SMAD3/SMAD4/GATA3	-0.04	0.12	-10000	0	-0.41	22	22
SnoN/SIN3/HDAC complex/NCoR1	0.014	0.026	-10000	0	-0.51	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.026	0.085	-10000	0	-0.39	8	8
SMAD3/SMAD4/SP1-3	0.041	0.085	-10000	0	-0.37	1	1
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.017	0.037	-10000	0	-10000	0	0
SIN3B	0.016	0.001	-10000	0	-10000	0	0
SIN3A	0.016	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.073	0.18	-10000	0	-0.46	30	30
ITGB5	0.054	0.072	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.055	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.14	0.18	-10000	0	-0.36	148	148
AR	-0.2	0.28	-10000	0	-0.57	148	148
negative regulation of cell growth	0.009	0.098	-10000	0	-0.4	5	5
SMAD3/SMAD4/MYOD	-0.006	0.048	-10000	0	-10000	0	0
E2F5	0.012	0.046	-10000	0	-0.53	3	3
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.011	0.13	-10000	0	-0.4	8	8
SMAD2-3/SMAD4/FOXO1-3a-4	0.045	0.078	-10000	0	-0.34	11	11
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.054	0.21	-10000	0	-0.61	29	29
SMAD3/SMAD4/RUNX2	-0.01	0.058	-10000	0	-0.32	6	6
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.001	0.09	-10000	0	-0.57	10	10
Jak2/Leptin Receptor	-0.007	0.092	0.2	16	-0.35	9	25
PTP1B/AKT1	0.026	0.048	-10000	0	-0.24	2	2
FYN	0.011	0.05	-10000	0	-0.57	3	3
p210 bcr-abl/PTP1B	0.02	0.053	-10000	0	-0.25	3	3
EGFR	-0.007	0.11	-10000	0	-0.54	17	17
EGF/EGFR	-0.026	0.074	-10000	0	-0.28	18	18
CSF1	-0.006	0.11	-10000	0	-0.57	15	15
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.003	0.1	-10000	0	-0.29	26	26
Insulin Receptor/Insulin	-0.004	0.025	-10000	0	-10000	0	0
HCK	-0.008	0.11	-10000	0	-0.55	17	17
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	0.027	0.05	-10000	0	-0.25	2	2
EGF	-0.017	0.12	-10000	0	-0.5	25	25
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	0.023	0.068	-10000	0	-0.26	4	4
TXN	0.013	0.037	-10000	0	-0.51	2	2
PTP1B/IRS1/GRB2	0.028	0.071	-10000	0	-0.35	6	6
cell migration	-0.02	0.053	0.25	3	-10000	0	3
STAT3	0.015	0.001	-10000	0	-10000	0	0
PRLR	-0.046	0.18	-10000	0	-0.53	47	47
ITGA2B	-0.025	0.14	-10000	0	-0.51	31	31
CSF1R	-0.016	0.13	-10000	0	-0.56	22	22
Prolactin Receptor/Prolactin	-0.044	0.13	-10000	0	-0.38	54	54
FGR	0.013	0.041	-10000	0	-0.57	2	2
PTP1B/p130 Cas	0.027	0.05	-10000	0	-0.25	2	2
Crk/p130 Cas	0.035	0.049	-10000	0	-0.24	1	1
DOK1	0.029	0.062	-10000	0	-0.26	6	6
JAK2	0.011	0.072	-10000	0	-0.34	5	5
Jak2/Leptin Receptor/Leptin	-0.072	0.15	-10000	0	-0.43	44	44
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
PTPN1	0.02	0.054	-10000	0	-0.24	4	4
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.043	0.16	-10000	0	-0.51	45	45
SRC	0.028	0.023	-10000	0	-10000	0	0
ITGB3	-0.051	0.18	-10000	0	-0.57	46	46
CAT1/PTP1B	-0.001	0.11	-10000	0	-0.38	11	11
CAPN1	0.016	0.002	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	-0.001	0.024	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.071	0.15	-10000	0	-0.46	44	44
negative regulation of transcription	0.015	0.073	-10000	0	-0.34	5	5
FCGR2A	-0.001	0.093	-10000	0	-0.51	13	13
FER	0.012	0.05	-10000	0	-0.57	3	3
alphaIIb/beta3 Integrin	-0.056	0.17	-10000	0	-0.41	72	72
BLK	-0.06	0.19	-10000	0	-0.55	53	53
Insulin Receptor/Insulin/Shc	0.021	0.016	-10000	0	-0.3	1	1
RHOA	0.016	0.002	-10000	0	-10000	0	0
LEPR	-0.009	0.12	-10000	0	-0.56	18	18
BCAR1	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.022	0.13	-10000	0	-0.44	15	15
PRL	-0.002	0.067	-10000	0	-0.51	7	7
SOCS3	-0.14	0.43	-10000	0	-1.4	43	43
SPRY2	0.004	0.082	-10000	0	-0.57	8	8
Insulin Receptor/Insulin/IRS1	0.013	0.058	-10000	0	-0.35	10	10
CSF1/CSF1R	0.009	0.11	-10000	0	-0.38	19	19
Ras protein signal transduction	0.011	0.018	-10000	0	-10000	0	0
IRS1	0.001	0.09	-10000	0	-0.57	10	10
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.06	0.19	-10000	0	-0.55	52	52
STAT5B	0.022	0.055	-10000	0	-0.24	3	3
STAT5A	0.022	0.055	-10000	0	-0.26	2	2
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.02	0.071	-10000	0	-0.31	10	10
CSN2	-0.013	0.047	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
LAT	0.024	0.034	-10000	0	-0.39	1	1
YBX1	0.024	0.025	-10000	0	-0.49	1	1
LCK	0.007	0.068	-10000	0	-0.55	6	6
SHC1	0.014	0.026	-10000	0	-0.51	1	1
NOX4	-0.023	0.14	-10000	0	-0.5	30	30

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.054	0.079	-10000	0	-0.48	4	4
UGCG	-0.014	0.16	-10000	0	-0.66	23	23
AKT1/mTOR/p70S6K/Hsp90/TERT	0.024	0.12	-10000	0	-0.36	24	24
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.011	0.16	-10000	0	-0.65	23	23
mol:DAG	0	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.036	0.12	-10000	0	-0.43	25	25
FRAP1	0.046	0.17	-10000	0	-0.46	34	34
FOXO3	0.058	0.14	-10000	0	-0.46	20	20
AKT1	0.05	0.15	-10000	0	-0.46	26	26
GAB2	0.014	0.029	-10000	0	-0.57	1	1
SMPD1	0.023	0.028	-10000	0	-10000	0	0
SGMS1	0.023	0.028	-10000	0	-10000	0	0
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	0.023	0.019	-10000	0	-0.34	1	1
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	0.017	0.13	-10000	0	-0.32	40	40
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	0.027	0.023	-10000	0	-0.4	1	1
RPS6KB1	0.018	0.038	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.002	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.013	15	15
JAK3	0.016	0.037	-10000	0	-0.5	2	2
PIK3R1	0.017	0.029	-10000	0	-0.57	1	1
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	0.032	0.24	-10000	0	-0.94	21	21
MYB	-0.022	0.14	-10000	0	-1.3	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.052	0.12	-10000	0	-0.6	7	7
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.034	0.035	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.052	0.12	-10000	0	-0.58	7	7
Rac1/GDP	0.031	0.019	-10000	0	-0.3	1	1
T cell proliferation	0.056	0.11	-10000	0	-0.58	6	6
SHC1	0.014	0.026	-10000	0	-0.5	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.001	0.013	-10000	0	-0.031	57	57
PRKCZ	0.056	0.12	-10000	0	-0.61	6	6
NF kappa B1 p50/RelA	-0.024	0.12	-10000	0	-0.42	25	25
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.047	0.084	-10000	0	-0.44	9	9
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.035	0.16	-10000	0	-0.54	37	37
IL2RB	0.009	0.074	-10000	0	-0.55	7	7
TERT	-0.21	0.26	-10000	0	-0.51	176	176
E2F1	-0.01	0.088	-10000	0	-0.25	31	31
SOS1	0.016	0.004	-10000	0	-10000	0	0
RPS6	0.016	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.006	0.015	57	-10000	0	57
PTPN11	0.016	0.004	-10000	0	-10000	0	0
IL2RG	-0.007	0.12	-10000	0	-0.54	19	19
actin cytoskeleton organization	0.056	0.11	-10000	0	-0.58	6	6
GRB2	0.016	0.004	-10000	0	-10000	0	0
IL2	0.007	0.008	-10000	0	-10000	0	0
PIK3CA	0.018	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.039	0.02	-10000	0	-0.28	1	1
LCK	0.01	0.068	-10000	0	-0.55	6	6
BCL2	0.037	0.22	-10000	0	-0.8	21	21

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.021	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.007	0.069	-9999	-0.56	6	6
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.025	0.023	-9999	-0.21	1	1
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.011	0.05	-9999	-0.57	3	3
MAP3K12	0.014	0.029	-9999	-0.57	1	1
FGR	0.013	0.041	-9999	-0.57	2	2
p38 alpha/TAB1	-0.021	0.055	-9999	-0.27	12	12
PRKG1	-0.12	0.25	-9999	-0.57	94	94
DUSP8	-0.029	0.16	-9999	-0.57	31	31
PGK/cGMP/p38 alpha	-0.072	0.12	-9999	-0.27	96	96
apoptosis	-0.02	0.053	-9999	-0.26	12	12
RAL/GTP	0.02	0.016	-9999	-0.3	1	1
LYN	0.016	0	-9999	-10000	0	0
DUSP1	-0.16	0.27	-9999	-0.57	119	119
PAK1	0.014	0.029	-9999	-0.57	1	1
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.04	0.015	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.014	0.026	-9999	-0.51	1	1
RAC1-CDC42/GTP	0.021	0	-9999	-10000	0	0
MAPK11	0.027	0.099	-9999	-0.32	13	13
BLK	-0.06	0.19	-9999	-0.55	53	53
HCK	-0.008	0.11	-9999	-0.55	17	17
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.009	0.057	-9999	-0.51	5	5
TRAF6/MEKK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.031	0.082	-9999	-0.29	12	12
positive regulation of innate immune response	0.035	0.11	-9999	-0.36	13	13
LCK	0.007	0.068	-9999	-0.55	6	6
p38alpha-beta/MKP7	0.042	0.1	-9999	-0.34	13	13
p38alpha-beta/MKP5	0.039	0.11	-9999	-0.34	13	13
PGK/cGMP	-0.088	0.18	-9999	-0.42	94	94
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.035	0.18	-9999	-0.41	45	45
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.014	0.026	-9999	-0.51	1	1
PAK3	-0.006	0.087	-9999	-0.51	12	12

×

Signaling events mediated by HDAC Class III

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
EP300	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.005	0.1	0.36	31	-10000	0	31
CDKN1A	-0.004	0.053	-10000	0	-0.76	2	2
KAT2B	0.014	0.029	-10000	0	-0.57	1	1
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.014	0.029	-10000	0	-0.57	1	1
FOXO4	0.026	0.008	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.013	0.11	-10000	0	-0.51	18	18
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.012	0.021	-10000	0	-0.42	1	1
PPARGC1A	-0.23	0.29	-10000	0	-0.57	170	170
FHL2	0.011	0.05	-10000	0	-0.57	3	3
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.011	-10000	0	-10000	0	0
HIST2H4A	-0.005	0.1	-10000	0	-0.36	31	31
SIRT1/FOXO3a	0.001	0.01	-10000	0	-10000	0	0
SIRT1	0.001	0.014	0.2	2	-10000	0	2
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.01	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.009	0.033	0.16	2	-10000	0	2
apoptosis	-0.001	0.01	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.14	0.17	-10000	0	-0.35	170	170
p53/SIRT1	0.002	0.028	0.4	2	-10000	0	2
SIRT1/FOXO4	0.001	0.013	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.003	0.03	-10000	0	-0.29	4	4
HIST1H1E	0.011	0.047	-10000	0	-10000	0	0
SIRT1/p300	0.001	0.011	-10000	0	-10000	0	0
muscle cell differentiation	0	0.02	0.35	1	-10000	0	1
TP53	0.001	0.014	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.01	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.015	0.074	-10000	0	-0.36	18	18
ACSS2	0.023	0.021	-10000	0	-0.36	1	1
SIRT1/PCAF/MYOD	0.018	0.02	-10000	0	-0.35	1	1

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.018	0.006	-9999	-10000	0	0
PRKCZ	0.011	0.05	-9999	-0.57	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.017	0.048	-9999	-0.29	2	2
IRAK/TOLLIP	0.034	0.004	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.094	0.19	-9999	-0.39	115	115
IL1A	-0.089	0.22	-9999	-0.54	77	77
IL1B	-0.018	0.13	-9999	-0.4	43	43
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.021	-9999	-10000	0	0
IL1R2	-0.043	0.17	-9999	-0.52	45	45
IL1R1	0.014	0.029	-9999	-0.57	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.032	0.062	-9999	-0.4	1	1
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.014	0.029	-9999	-0.57	1	1
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.011	0	-9999	-10000	0	0
IKK complex/ELKS	0.075	0.01	-9999	-10000	0	0
JUN	0.034	0.067	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.013	0.11	-9999	-0.5	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.028	0.14	-9999	-0.32	39	39
PIK3R1	0.014	0.029	-9999	-0.57	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.018	0.13	-9999	-0.52	3	3
IL1 beta fragment/IL1R1/IL1RAP	-0.004	0.12	-9999	-0.33	30	30
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.039	0.042	-9999	-10000	0	0
IRAK1	0.027	0.005	-9999	-10000	0	0
IL1RN/IL1R1	0.008	0.08	-9999	-0.39	15	15
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	0.022	0.021	-9999	-0.41	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.023	0.067	-9999	-0.38	2	2
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.004	0.12	-9999	-0.33	30	30
IL1 beta/IL1R2	-0.043	0.16	-9999	-0.35	79	79
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.029	0.079	-9999	-0.45	4	4
IRAK3	-0.002	0.099	-9999	-0.57	12	12
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.013	0.11	-9999	-0.5	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.001	0.093	-9999	-0.5	1	1
IL1 alpha/IL1R1/IL1RAP	-0.043	0.15	-9999	-0.32	86	86
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.043	0.004	-9999	-10000	0	0
IL1RAP	0.002	0.085	-9999	-0.51	11	11
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.026	0.07	-9999	-0.41	4	4
CASP1	0.003	0.086	-9999	-0.57	9	9
IL1RN/IL1R2	-0.033	0.14	-9999	-0.38	57	57
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.006	0.11	-9999	-0.53	4	4
TMEM189-UBE2V1	0.008	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.016	0.076	-9999	-0.51	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
IL1RN	-0.004	0.1	-9999	-0.52	15	15
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.034	0.035	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.014	0.026	-9999	-0.51	1	1
Syndecan-3/Src/Cortactin	-0.028	0.13	-9999	-0.8	1	1
Syndecan-3/Neurocan	-0.008	0.048	-9999	-0.59	1	1
POMC	-0.006	0.11	-9999	-0.53	16	16
EGFR	-0.008	0.11	-9999	-0.54	17	17
Syndecan-3/EGFR	-0.012	0.059	-9999	-0.31	10	10
AGRP	0.004	0.045	-9999	-0.51	3	3
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.005	0.084	-9999	-0.51	11	11
long-term memory	0.034	0.048	-9999	-0.8	1	1
Syndecan-3/IL8	-0.042	0.11	-9999	-0.29	59	59
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0.022	0.019	-9999	-0.36	1	1
FYN	0.011	0.05	-9999	-0.57	3	3
limb bud formation	-0.002	0.03	-9999	-0.62	1	1
MC4R	-0.001	0.057	-9999	-0.51	5	5
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.13	0.25	-9999	-0.56	103	103
FGFR/FGF/Syndecan-3	-0.002	0.031	-9999	-0.62	1	1
neuron projection morphogenesis	-0.043	0.12	-9999	-0.6	2	2
Syndecan-3/AgRP	-0.003	0.035	-9999	-0.59	1	1
Syndecan-3/AgRP/MC4R	0.001	0.046	-9999	-0.57	1	1
Fyn/Cortactin	0.019	0.041	-9999	-0.4	4	4
SDC3	-0.002	0.031	-9999	-0.63	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.042	0.1	-9999	-0.28	59	59
IL8	-0.07	0.21	-9999	-0.57	60	60
Syndecan-3/Fyn/Cortactin	0.035	0.05	-9999	-0.84	1	1
Syndecan-3/CASK	-0.001	0.03	-9999	-0.6	1	1
alpha-MSH/MC4R	-0.004	0.087	-9999	-0.38	21	21
Gamma Secretase	0.047	0	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.13	0.2	-9999	-0.52	23	23
RAD9A	0.008	0.063	-9999	-0.51	6	6
AP1	-0.13	0.23	-9999	-0.45	130	130
IFNAR2	0.01	0.009	-9999	-10000	0	0
AKT1	-0.029	0.092	-9999	-0.24	40	40
ER alpha/Oestrogen	-0.069	0.16	-9999	-0.42	73	73
NFX1/SIN3/HDAC complex	0.032	0.029	-9999	-10000	0	0
EGF	-0.02	0.12	-9999	-0.51	25	25
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0.015	0.014	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.17	-9999	-0.51	17	17
SAP18	0.015	0.002	-9999	-10000	0	0
MRN complex	0.032	0	-9999	-10000	0	0
WT1	-0.061	0.17	-9999	-0.51	52	52
WRN	0.016	0	-9999	-10000	0	0
SP1	0.011	0.01	-9999	-10000	0	0
SP3	0.013	0.004	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.12	0.14	-9999	-0.54	8	8
Mad/Max	0.013	0.023	-9999	-0.37	1	1
TERT	-0.13	0.2	-9999	-0.54	21	21
CCND1	-0.13	0.23	-9999	-0.96	12	12
MAX	0.013	0.004	-9999	-10000	0	0
RBBP7	0.015	0.002	-9999	-10000	0	0
RBBP4	0.015	0.002	-9999	-10000	0	0
TERF2	0.015	0	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.015	0.002	-9999	-10000	0	0
Telomerase/911	0.024	0.038	-9999	-10000	0	0
CDKN1B	-0.024	0.13	-9999	-0.28	16	16
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	0.015	0.002	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.014	0.004	-9999	-10000	0	0
JUN	-0.009	0.11	-9999	-0.57	16	16
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.008	0.007	-9999	-10000	0	0
FOS	-0.17	0.27	-9999	-0.57	129	129
IFN-gamma/IRF1	-0.052	0.15	-9999	-0.34	81	81
PARP2	0.016	0	-9999	-10000	0	0
BLM	0	0.088	-9999	-0.51	12	12
Telomerase	-0.007	0.063	-9999	-0.41	1	1
IRF1	0.019	0.005	-9999	-10000	0	0
ESR1	-0.09	0.22	-9999	-0.57	73	73
KU/TER	0.023	0	-9999	-10000	0	0
ATM/TRF2	0.024	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.029	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.035	0.032	-9999	-10000	0	0
HDAC1	0.015	0.002	-9999	-10000	0	0
HDAC2	0.01	0.01	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.029	0.005	-9999	-10000	0	0
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.012	0.027	-9999	-0.52	1	1
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.13	0.17	-9999	-0.51	18	18
NR2F2	0.019	0.03	-9999	-0.57	1	1
MAPK3	0.011	0.01	-9999	-10000	0	0
MAPK1	0.011	0.01	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.017	0.002	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.016	0	-9999	-10000	0	0
EGFR	-0.009	0.11	-9999	-0.54	17	17
mol:Oestrogen	-0.002	0.003	-9999	-10000	0	0
EGF/EGFR	-0.026	0.12	-9999	-0.37	42	42
MYC	-0.016	0.12	-9999	-0.57	18	18
IL2	-0.001	0.013	-9999	-10000	0	0
KU	0.023	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.017	0.002	-9999	-10000	0	0
TRF2/BLM	-0.01	0.055	-9999	-0.33	12	12
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.19	-9999	-0.56	10	10
SP1/HDAC2	0.017	0.016	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.12	0.14	-9999	-0.54	8	8
Smad3/Myc	0.017	0.076	-9999	-0.34	18	18
911 complex	0.027	0.039	-9999	-0.29	6	6
IFNG	-0.087	0.21	-9999	-0.5	81	81
Telomerase/PinX1	-0.12	0.14	-9999	-0.54	8	8
Telomerase/AKT1/mTOR/p70S6K	-0.012	0.067	-9999	-10000	0	0
SIN3B	0.015	0.002	-9999	-10000	0	0
YWHAE	0.014	0.029	-9999	-0.57	1	1
Telomerase/EST1B	-0.12	0.14	-9999	-0.54	8	8
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.12	0.14	-9999	-0.54	8	8
E2F1	-0.11	0.22	-9999	-0.51	97	97
ZNFX1	0.015	0.002	-9999	-10000	0	0
PIF1	-0.029	0.15	-9999	-0.51	35	35
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.13	0.14	-9999	-0.54	6	6
TC10/GTP	-0.12	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	0.025	0.054	-9999	-0.31	10	10
HRAS	0.016	0	-9999	-10000	0	0
APS homodimer	0.009	0.057	-9999	-0.51	5	5
GRB14	-0.056	0.18	-9999	-0.51	56	56
FOXO3	-0.026	0.11	-9999	-0.58	16	16
AKT1	0.018	0.094	-9999	-0.44	2	2
INSR	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.042	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.008	0.064	-9999	-0.57	5	5
SORBS1	-0.26	0.29	-9999	-0.57	189	189
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.04	0	-9999	-10000	0	0
CAV1	0.009	0.093	-9999	-0.34	25	25
CBL/APS/CAP/Crk-II/C3G	-0.1	0.16	-9999	-0.27	189	189
Insulin Receptor/Insulin/IRS1/NCK2	0.025	0.054	-9999	-0.31	10	10
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.043	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.039	0.038	-9999	-10000	0	0
RPS6KB1	0.026	0.089	-9999	-0.4	2	2
PARD6A	0.014	0.029	-9999	-0.57	1	1
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.012	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.027	0.064	-9999	-0.4	2	2
HRAS/GTP	-0.01	0.044	-9999	-10000	0	0
Insulin Receptor	0.017	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.032	0.052	-9999	-10000	0	0
PRKCI	-0.008	0.028	-9999	-0.46	1	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.034	0.08	-9999	-0.48	2	2
SHC1	0.014	0.026	-9999	-0.51	1	1
negative regulation of MAPKKK cascade	0.001	0.01	-9999	-10000	0	0
PI3K	-0.007	0.044	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.012	0	-9999	-10000	0	0
AKT2	0.018	0.094	-9999	-0.44	2	2
PRKCZ	-0.011	0.049	-9999	-0.48	4	4
SH2B2	0.009	0.057	-9999	-0.51	5	5
SHC/SHIP	0.026	0.063	-9999	-0.27	17	17
F2RL2	-0.023	0.14	-9999	-0.54	28	28
TRIP10	0.014	0.029	-9999	-0.57	1	1
Insulin Receptor/Insulin/Shc	0.023	0.015	-9999	-0.28	1	1
TC10/GTP/CIP4/Exocyst	0.02	0.018	-9999	-0.35	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.04	0.014	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.12	0.17	-9999	-0.3	194	194
TC10/GDP	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.029	0.041	-9999	-0.31	6	6
INPP5D	0.018	0.064	-9999	-0.29	17	17
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.036	0.17	-9999	-0.88	16	16
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.001	0.09	-9999	-0.57	10	10
p62DOK/RasGAP	0.001	0.011	-9999	-10000	0	0
INS	0.004	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.018	0.064	-9999	-0.29	17	17
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.016	0.1	-9999	-0.39	5	5
PTPRA	0.017	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
TC10/GTP/CIP4	0.02	0.018	-9999	-0.35	1	1
PDPK1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.044	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.015	0.053	-9999	-0.32	10	10
Insulin Receptor/Insulin/IRS3	0.016	0	-9999	-10000	0	0
Par3/Par6	0.015	0.079	-9999	-0.28	17	17

×

Ceramide signaling 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
SPHK2	0.025	0.027	-10000	0	-0.36	2	2
MAP4K4	0.037	0.059	-10000	0	-10000	0	0
BAG4	0.016	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.005	0.034	-10000	0	-0.33	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.02	0.14	-10000	0	-0.56	25	25
BAX	0.002	0.009	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.022	0.007	-10000	0	-10000	0	0
BAD	-0.004	0.019	-10000	0	-10000	0	0
SMPD1	0.025	0.031	-10000	0	-10000	0	0
RB1	-0.005	0.024	-10000	0	-0.31	1	1
FADD/Caspase 8	0.046	0.063	-10000	0	-0.28	2	2
MAP2K4	0.004	0.018	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.023	-10000	0	-0.31	1	1
EGF	-0.018	0.12	-10000	0	-0.51	25	25
mol:ceramide	-0.015	0.02	0.14	2	-10000	0	2
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.026	0.019	-10000	0	-0.36	1	1
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.005	0.024	-10000	0	-0.31	1	1
cell proliferation	-0.086	0.13	-10000	0	-0.23	182	182
BID	0.03	0.041	-10000	0	-10000	0	0
MAP3K1	-0.004	0.019	0.14	2	-10000	0	2
EIF2A	0.012	0.017	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	0.016	0.022	-10000	0	-0.28	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.016	0.022	-10000	0	-0.28	1	1
Cathepsin D/ceramide	-0.003	0.019	0.13	2	-10000	0	2
FADD	0.034	0.066	-10000	0	-0.32	2	2
KSR1	-0.004	0.019	-10000	0	-10000	0	0
MAPK8	0.007	0.035	-10000	0	-0.24	6	6
PRKRA	-0.004	0.019	-10000	0	-10000	0	0
PDGFA	0.014	0.026	-10000	0	-0.51	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	-0.24	0.29	-10000	0	-0.57	182	182
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.015	0.02	0.14	2	-10000	0	2
CTSD	0.016	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.023	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.091	0.14	-10000	0	-0.24	182	182
PRKCD	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.05	-10000	0	-0.57	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.026	0.019	-10000	0	-0.36	1	1
RelA/NF kappa B1	0.023	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.029	-10000	0	-0.57	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.031	0.06	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.015	0.071	-10000	0	-0.29	21	21
mol:Sphingosine-1-phosphate	0.025	0.027	-10000	0	-0.36	2	2
MAP2K1	0.012	0.022	-10000	0	-0.29	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	0.006	0.035	0.16	16	-10000	0	16
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.023	0	-10000	0	-10000	0	0
EIF2AK2	0.004	0.018	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	0.015	0.071	-10000	0	-0.29	21	21
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.041	0.036	-10000	0	-10000	0	0
MAP2K2	0.012	0.022	-10000	0	-0.29	1	1
SMPD3	0.027	0.035	-10000	0	-10000	0	0
TNF	-0.011	0.12	-10000	0	-0.51	21	21
PKC zeta/PAR4	0.019	0.042	-10000	0	-0.41	4	4
mol:PHOSPHOCHOLINE	-0.002	0.037	0.14	22	-10000	0	22
NF kappa B1/RelA/I kappa B alpha	0.043	0.031	-10000	0	-0.27	4	4
AIFM1	0.006	0.035	0.16	16	-10000	0	16
BCL2	-0.007	0.11	-10000	0	-0.57	16	16

×

Role of Calcineurin-dependent NFAT signaling 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
BCL2L1	0.014	0.026	-10000	0	-0.51	1	1
NFATC1	0.035	0.078	-10000	0	-0.3	16	16
NFATC2	-0.024	0.075	-10000	0	-0.19	46	46
NFATC3	0.009	0.038	-10000	0	-0.4	3	3
YWHAE	0.014	0.029	-10000	0	-0.57	1	1
Calcineurin A alpha-beta B1/CABIN1	-0.045	0.14	-10000	0	-0.43	32	32
Exportin 1/Ran/NUP214	0.014	0.016	-10000	0	-10000	0	0
mol:DAG	-0.003	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.069	0.12	-10000	0	-0.4	35	35
BCL2/BAX	0.006	0.084	-10000	0	-0.41	16	16
CaM/Ca2+/Calcineurin A alpha-beta B1	0.003	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.003	0.01	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.007	0.008	-10000	0	-10000	0	0
BAD	0.016	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.039	0.14	-10000	0	-0.41	32	32
Calcineurin A alpha-beta B1/BCL2	-0.007	0.11	-10000	0	-0.57	16	16
FKBP8	0.016	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.039	0.14	0.4	32	-10000	0	32
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.011	0.051	-10000	0	-0.51	4	4
XPO1	0.015	0.001	-10000	0	-10000	0	0
SFN	-0.031	0.15	-10000	0	-0.51	36	36
MAP3K8	0.003	0.05	-10000	0	-0.57	3	3
NFAT4/CK1 alpha	-0.002	0.02	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.13	0.17	-10000	0	-0.38	46	46
CABIN1	-0.046	0.14	-10000	0	-0.43	32	32
CALM1	0.011	0.005	-10000	0	-10000	0	0
RAN	0.015	0.001	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0	0.094	-10000	0	-0.56	11	11
mol:Ca2+	-0.009	0.009	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.007	0.038	-10000	0	-0.36	4	4
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.003	0.05	-10000	0	-0.57	3	3
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.028	0.082	-10000	0	-0.34	3	3
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.01	0.014	-10000	0	-10000	0	0
CASP3	0.007	0.008	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.006	-10000	0	-10000	0	0
apoptosis	-0.005	0.024	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.036	0.036	-10000	0	-0.28	1	1
PRKCB	-0.15	0.26	-10000	0	-0.57	118	118
PRKCE	0.016	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.023	0.034	-10000	0	-0.36	3	3
BAD/BCL-XL	0.022	0.019	-10000	0	-0.36	1	1
PRKCD	0.016	0	-10000	0	-10000	0	0
NUP214	0.015	0.001	-10000	0	-10000	0	0
PRKCZ	0.003	0.05	-10000	0	-0.57	3	3
PRKCA	0.008	0.064	-10000	0	-0.57	5	5
PRKCG	-0.01	0.094	-10000	0	-0.51	14	14
PRKCQ	-0.04	0.17	-10000	0	-0.56	39	39
FKBP38/BCL2	0.006	0.084	-10000	0	-0.41	16	16
EP300	0.009	0.006	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.014	0.079	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.01	0.012	-10000	0	-10000	0	0
FKBP12/FK506	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.012	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0	0.06	-10000	0	-0.35	11	11
NFATc/ERK1	0.043	0.074	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.066	0.12	-10000	0	-0.39	35	35
NR4A1	-0.28	0.3	-10000	0	-0.54	230	230
GSK3B	0.007	0.008	-10000	0	-10000	0	0
positive T cell selection	0.009	0.038	-10000	0	-0.4	3	3
NFAT1/CK1 alpha	-0.034	0.049	-10000	0	-0.29	3	3
RCH1/ KPNB1	0.02	0.037	-10000	0	-0.36	4	4
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.007	0.008	-10000	0	-10000	0	0
AKAP5	0.011	0.051	-10000	0	-0.51	4	4
MEF2D	0.009	0.006	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.017	0.077	-10000	0	-10000	0	0
CREBBP	0.009	0.006	-10000	0	-10000	0	0
BCL2	-0.007	0.11	-10000	0	-0.57	16	16

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.008	0.064	-9999	-0.57	5	5
ITGA4	-0.003	0.1	-9999	-0.56	13	13
alpha4/beta7 Integrin	0.004	0.088	-9999	-0.4	18	18
alpha4/beta1 Integrin	0.01	0.075	-9999	-0.4	13	13

×

Class I PI3K signaling events mediated by Akt

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.026	0.019	-9999	-0.36	1	1
BAD/BCL-XL/YWHAZ	0.039	0.015	-9999	-10000	0	0
CDKN1B	0.043	0	-9999	-10000	0	0
CDKN1A	0.042	0.021	-9999	-0.26	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.043	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.016	0	-9999	-10000	0	0
AKT3	0.008	0.066	-9999	-0.34	14	14
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.042	0.013	-9999	-10000	0	0
AKT1/ASK1	0.041	0.014	-9999	-10000	0	0
BAD/YWHAZ	0.032	0	-9999	-10000	0	0
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.014	0.026	-9999	-0.51	1	1
JNK cascade	0.001	0.012	-9999	-10000	0	0
TSC1	0.043	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0.043	0.013	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
mol:GDP	0.036	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.043	0	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.028	0	-9999	-10000	0	0
MAP3K5	0.014	0.029	-9999	-0.57	1	1
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.044	0.026	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.043	0	-9999	-10000	0	0
CASP9	0.043	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.051	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.032	0	-9999	-10000	0	0
YWHAE	0.014	0.029	-9999	-0.57	1	1
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.001	0.017	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0	-9999	-10000	0	0
CHUK	0.043	0	-9999	-10000	0	0
BAD/BCL-XL	0.058	0.012	-9999	-10000	0	0
mTORC2	0.02	0	-9999	-10000	0	0
AKT2	0.02	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.061	0.03	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
MDM2	0.035	0.046	-9999	-10000	0	0
MAPKKK cascade	-0.042	0.013	-9999	-10000	0	0
MDM2/Cbp/p300	0.05	0.043	-9999	-10000	0	0
TSC1/TSC2	0.05	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.047	0.041	-9999	-10000	0	0
glucose import	-0.2	0.15	-9999	-0.3	294	294
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.037	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.21	0.15	-9999	-0.3	294	294
GSK3A	0.043	0	-9999	-10000	0	0
FOXO1	0.042	0.015	-9999	-0.26	1	1
GSK3B	0.043	0	-9999	-10000	0	0
SFN	-0.031	0.15	-9999	-0.51	36	36
G1/S transition of mitotic cell cycle	0.05	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.045	0.039	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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
EFNB2	0.013	0.036	-10000	0	-0.51	2	2
EPHB2	-0.02	0.13	-10000	0	-0.5	28	28
EFNB1	0.015	0.071	-10000	0	-0.41	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.035	0.1	-10000	0	-0.52	5	5
Ephrin B2/EPHB1-2	-0.016	0.12	-10000	0	-0.32	33	33
neuron projection morphogenesis	-0.04	0.094	-10000	0	-0.5	5	5
Ephrin B1/EPHB1-2/Tiam1	-0.007	0.12	-10000	0	-0.56	5	5
DNM1	0	0.095	-10000	0	-0.57	11	11
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.015	0.089	-10000	0	-0.61	8	8
YES1	-0.014	0.12	-10000	0	-0.86	8	8
Ephrin B1/EPHB1-2/NCK2	-0.004	0.12	-10000	0	-0.57	3	3
PI3K	0.016	0.092	-10000	0	-0.58	9	9
mol:GDP	-0.008	0.12	-10000	0	-0.55	5	5
ITGA2B	-0.024	0.14	-10000	0	-0.51	31	31
endothelial cell proliferation	0.018	0.023	-10000	0	-0.3	2	2
FYN	-0.015	0.12	-10000	0	-0.88	8	8
MAP3K7	-0.008	0.092	-10000	0	-0.65	8	8
FGR	-0.015	0.12	-10000	0	-0.87	8	8
TIAM1	0.011	0.05	-10000	0	-0.57	3	3
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.022	0.14	-10000	0	-0.54	13	13
LYN	-0.014	0.12	-10000	0	-0.86	8	8
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	0.11	-10000	0	-0.8	8	8
Ephrin B1/EPHB1-2	-0.015	0.099	-10000	0	-0.71	8	8
SRC	-0.014	0.12	-10000	0	-0.85	8	8
ITGB3	-0.05	0.18	-10000	0	-0.57	46	46
EPHB1	-0.03	0.16	-10000	0	-0.56	32	32
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.019	0.023	-10000	0	-0.3	2	2
alphaIIb/beta3 Integrin	-0.053	0.17	-10000	0	-0.41	72	72
BLK	-0.031	0.13	-10000	0	-0.86	8	8
HCK	-0.019	0.13	-10000	0	-0.88	8	8
regulation of stress fiber formation	0.005	0.12	0.56	3	-10000	0	3
MAPK8	0.02	0.097	-10000	0	-0.64	8	8
Ephrin B1/EPHB1-2/RGS3	-0.004	0.12	-10000	0	-0.57	3	3
endothelial cell migration	-0.007	0.079	-10000	0	-0.51	9	9
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.006	0.096	-10000	0	-0.68	8	8
regulation of focal adhesion formation	0.005	0.12	0.56	3	-10000	0	3
chemotaxis	0.005	0.12	0.56	3	-10000	0	3
PIK3CA	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	-0.041	0.096	-10000	0	-0.51	5	5
angiogenesis	-0.014	0.098	-10000	0	-0.71	8	8
LCK	-0.016	0.12	-10000	0	-0.85	8	8

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	-0.066	0.19	-9999	-0.51	64	64
mol:Halofuginone	0.006	0.001	-9999	-10000	0	0
ITGA1	0.016	0	-9999	-10000	0	0
CDKN1A	-0.001	0.08	-9999	-0.67	2	2
PRL-3/alpha Tubulin	0.023	0	-9999	-10000	0	0
mol:Ca2+	-0.056	0.14	-9999	-0.42	54	54
AGT	-0.061	0.2	-9999	-0.57	54	54
CCNA2	-0.099	0.18	-9999	-0.52	24	24
TUBA1B	0.016	0	-9999	-10000	0	0
EGR1	-0.077	0.18	-9999	-0.4	100	100
CDK2/Cyclin E1	-0.025	0.12	-9999	-0.41	15	15
MAPK3	0.026	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.023	0	-9999	-10000	0	0
MAPK1	0.026	0	-9999	-10000	0	0
PTP4A1	-0.039	0.14	-9999	-10000	0	0
PTP4A3	0.016	0	-9999	-10000	0	0
PTP4A2	0.016	0	-9999	-10000	0	0
ITGB1	0.026	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1	0.002	0.066	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.023	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.031	0.14	-9999	-0.52	2	2
RABGGTA	0.016	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.002	0.066	-9999	-10000	0	0
RHOA	0.002	0.066	-9999	-10000	0	0
cell motility	0.005	0.07	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.028	0.13	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.023	0	-9999	-10000	0	0
ROCK1	0.005	0.071	-9999	-10000	0	0
RABGGTB	0.016	0	-9999	-10000	0	0
CDK2	0.016	0	-9999	-10000	0	0
mitosis	-0.039	0.14	-9999	-10000	0	0
ATF5	0.011	0.051	-9999	-0.51	4	4

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.018	0.075	-9999	-0.36	15	15
E-cadherin/beta catenin	0.008	0.078	-9999	-0.41	14	14
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.013	0.041	-9999	-0.57	2	2
CDH1	-0.004	0.11	-9999	-0.57	14	14

×

BARD1 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
BARD1/CSTF1	0.013	0.067	-10000	0	-0.41	10	10
ATM	0.016	0	-10000	0	-10000	0	0
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.028	0.02	-10000	0	-10000	0	0
protein ubiquitination	-0.043	0.093	-10000	0	-0.52	1	1
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0.032	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0.032	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.045	0.037	-10000	0	-10000	0	0
FANCF	0.013	0.039	-10000	0	-0.54	2	2
BRCA1	0.014	0.026	-10000	0	-0.51	1	1
CCNE1	-0.066	0.19	-10000	0	-0.51	64	64
CDK2/Cyclin E1	-0.036	0.14	-10000	0	-0.36	64	64
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.012	0.069	-10000	0	-0.4	11	11
FANCE	0.014	0.026	-10000	0	-0.51	1	1
FANCC	0.014	0.026	-10000	0	-0.51	1	1
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.019	0.13	-10000	0	-0.51	27	27
DNA repair	-0.025	0.13	-10000	0	-0.39	6	6
BRCA1/BARD1/ubiquitin	0.012	0.069	-10000	0	-0.4	11	11
BARD1/DNA-PK	0.032	0.052	-10000	0	-0.3	10	10
FANCL	0.014	0.026	-10000	0	-0.51	1	1
mRNA polyadenylation	-0.013	0.066	0.41	10	-10000	0	10
BRCA1/BARD1/CTIP/M/R/N Complex	0.04	0.043	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	0.022	0.059	-10000	0	-0.33	11	11
BRCA1/BARD1/P53	0.031	0.054	-10000	0	-0.3	10	10
BARD1/CSTF1/BRCA1	0.022	0.059	-10000	0	-0.33	11	11
BRCA1/BACH1	0.014	0.026	-10000	0	-0.51	1	1
BARD1	0.001	0.09	-10000	0	-0.57	10	10
PCNA	0.014	0.026	-10000	0	-0.51	1	1
BRCA1/BARD1/UbcH5C	0.022	0.059	-10000	0	-0.33	11	11
BRCA1/BARD1/UbcH7	0.022	0.059	-10000	0	-0.33	11	11
BRCA1/BARD1/RAD51/PCNA	-0.074	0.15	-10000	0	-0.36	12	12
BARD1/DNA-PK/P53	0.039	0.049	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.012	0.069	-10000	0	-0.4	11	11
BRCA1/BARD1/CTIP	0.03	0.054	-10000	0	-0.3	10	10
FA complex	0.035	0.043	-10000	0	-10000	0	0
BARD1/EWS	0.013	0.067	-10000	0	-0.41	10	10
RBBP8	0.026	0	-10000	0	-10000	0	0
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.03	0.054	0.3	10	-10000	0	10
BRCA1/BARD1	-0.005	0.11	-10000	0	-0.53	1	1
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.001	0.066	-10000	0	-0.42	10	10
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.17	0.25	-10000	0	-0.51	145	145
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.012	0.069	-10000	0	-0.4	11	11
EWSR1	0.016	0	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.002	0.096	-9999	-0.25	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.013	0.036	-9999	-0.51	2	2
STAT1 (dimer)/Cbp/p300	0.036	0.092	-9999	-0.36	4	4
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.005	0.019	-9999	-0.34	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.031	0.062	-9999	-0.3	8	8
CaM/Ca2+	-0.035	0.069	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.005	0.099	-9999	-0.42	4	4
AKT1	0.021	0.084	-9999	-0.41	1	1
MAP2K1	0.017	0.087	-9999	-10000	0	0
MAP3K11	0.006	0.091	-9999	-10000	0	0
IFNGR1	0.013	0.009	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.19	-9999	-0.41	130	130
Rap1/GTP	-0.024	0.049	-9999	-0.32	1	1
CRKL/C3G	0.021	0.026	-9999	-0.36	2	2
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.005	0.1	-9999	-0.26	1	1
CEBPB	0.054	0.087	-9999	-0.36	4	4
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.006	0.097	-9999	-10000	0	0
STAT1	0.005	0.098	-9999	-0.42	4	4
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.087	0.2	-9999	-0.5	81	81
PIK3CA	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.014	0.094	-9999	-0.4	4	4
CEBPB/PTGES2/Cbp/p300	-0.009	0.025	-9999	-10000	0	0
mol:Ca2+	-0.004	0.094	-9999	-0.25	1	1
MAPK3	0.034	0.077	-9999	-10000	0	0
STAT1 (dimer)	-0.039	0.084	-9999	-0.42	8	8
MAPK1	0.034	0.077	-9999	-10000	0	0
JAK2	0.012	0.03	-9999	-0.56	1	1
PIK3R1	0.014	0.029	-9999	-0.57	1	1
JAK1	0.013	0.009	-9999	-10000	0	0
CAMK2D	0.013	0.041	-9999	-0.57	2	2
DAPK1	0.053	0.091	-9999	-0.62	4	4
SMAD7	0.02	0.06	-9999	-0.35	1	1
CBL/CRKL/C3G	0.02	0.087	-9999	-0.39	1	1
PI3K	-0.033	0.067	-9999	-0.44	1	1
IFNG	-0.088	0.2	-9999	-0.5	81	81
apoptosis	0.034	0.071	-9999	-0.44	4	4
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.17	0.27	-9999	-0.57	129	129
CAMK2B	-0.04	0.16	-9999	-0.51	43	43
FRAP1	0.02	0.08	-9999	-0.38	1	1
PRKCD	0.022	0.086	-9999	-0.41	1	1
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.031	0.062	-9999	-0.3	8	8
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
IRF1	0.05	0.079	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.009	0.094	-9999	-0.4	4	4
SOCS1	0.006	0.02	-9999	-10000	0	0
mol:GDP	-0.029	0.06	-9999	-0.37	1	1
CASP1	0.016	0.072	-9999	-0.29	10	10
PTGES2	0.016	0	-9999	-10000	0	0
IRF9	0.054	0.036	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.032	0.066	-9999	-0.43	1	1
RAP1/GDP	-0.024	0.049	-9999	-0.32	1	1
CBL	0.005	0.09	-9999	-10000	0	0
MAP3K1	0.007	0.091	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.031	0.062	-9999	-0.3	8	8
PTPN11	-0.004	0.094	-9999	-0.25	1	1
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.033	0.016	-9999	-0.29	1	1
SNTA1	0.016	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.001	0.098	-9999	-0.29	41	41
MAPK12	0.025	0.054	-9999	-0.27	13	13
CCND1	0.011	0.067	-9999	-0.45	7	7
p38 gamma/SNTA1	0.032	0.05	-9999	-0.27	5	5
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.014	0.029	-9999	-0.57	1	1
G2/M transition checkpoint	0.025	0.053	-9999	-0.27	13	13
MAP2K6	0.021	0.048	-9999	-0.32	8	8
MAPT	0.004	0.1	-9999	-0.31	35	35
MAPK13	0.026	0.019	-9999	-0.36	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.018	0.025	-9999	-0.34	2	2

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.014	0.1	-10000	0	-0.32	43	43
cell-cell adhesion	0.04	0.09	0.45	7	-10000	0	7
Ephrin B/EPHB2/RasGAP	0.01	0.1	-10000	0	-0.52	3	3
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
SHC1	0.014	0.026	-10000	0	-0.51	1	1
Ephrin B1/EPHB3	0.007	0.067	-10000	0	-0.31	18	18
Ephrin B1/EPHB1	-0.007	0.098	-10000	0	-0.34	32	32
HRAS/GDP	-0.025	0.084	-10000	0	-0.46	6	6
Ephrin B/EPHB1/GRB7	-0.01	0.13	-10000	0	-0.58	6	6
Endophilin/SYNJ1	0.009	0.095	-10000	0	-0.48	3	3
KRAS	0.014	0.026	-10000	0	-0.51	1	1
Ephrin B/EPHB1/Src	0.005	0.12	-10000	0	-0.59	5	5
endothelial cell migration	-0.002	0.021	-10000	0	-0.28	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	-0.012	0.12	-10000	0	-0.53	21	21
PAK1	0.012	0.1	-10000	0	-0.48	3	3
HRAS	0.016	0	-10000	0	-10000	0	0
RRAS	0.007	0.1	-10000	0	-0.51	4	4
DNM1	0	0.095	-10000	0	-0.57	11	11
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.004	0.11	-10000	0	-0.56	5	5
lamellipodium assembly	-0.04	0.09	-10000	0	-0.45	7	7
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.015	0.092	-10000	0	-0.44	4	4
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
EPHB2	-0.02	0.13	-10000	0	-0.51	28	28
EPHB3	-0.008	0.11	-10000	0	-0.51	18	18
EPHB1	-0.03	0.16	-10000	0	-0.56	32	32
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.099	-10000	0	-0.45	6	6
Ephrin B/EPHB2	0.001	0.1	-10000	0	-0.33	15	15
Ephrin B/EPHB3	0.007	0.095	-10000	0	-0.33	16	16
JNK cascade	0.001	0.11	-10000	0	-0.56	1	1
Ephrin B/EPHB1	-0.005	0.12	-10000	0	-0.32	41	41
RAP1/GDP	0.031	0.09	-10000	0	-0.42	4	4
EFNB2	0.013	0.036	-10000	0	-0.51	2	2
EFNB3	-0.015	0.13	-10000	0	-0.55	22	22
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.017	0.12	-10000	0	-0.29	60	60
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.04	0.092	-10000	0	-0.48	7	7
Rap1/GTP	-0.039	0.089	-10000	0	-0.45	7	7
axon guidance	-0.014	0.1	-10000	0	-0.32	43	43
MAPK3	0.031	0.083	-10000	0	-0.48	2	2
MAPK1	0.031	0.083	-10000	0	-0.48	2	2
Rac1/GDP	0.025	0.093	-10000	0	-0.41	6	6
actin cytoskeleton reorganization	-0.029	0.067	-10000	0	-0.36	6	6
CDC42/GDP	0.025	0.093	-10000	0	-0.41	6	6
PI3K	0.035	0.025	-10000	0	-0.28	1	1
EFNA5	-0.006	0.11	-10000	0	-0.56	15	15
Ephrin B2/EPHB4	0.02	0.022	-10000	0	-0.3	2	2
Ephrin B/EPHB2/Intersectin/N-WASP	0.02	0.069	-10000	0	-0.26	14	14
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.039	0.087	-10000	0	-0.44	7	7
PTK2	0.011	0.027	-10000	0	-10000	0	0
MAP4K4	0.001	0.11	-10000	0	-0.57	1	1
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.008	0.065	-10000	0	-0.53	6	6
Intersectin/N-WASP	0.023	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.037	0.1	-10000	0	-0.38	6	6
MAP2K1	0.023	0.087	-10000	0	-0.41	4	4
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.006	0.11	-10000	0	-0.3	28	28
cell migration	0.027	0.098	-10000	0	-0.45	4	4
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.009	0.097	-10000	0	-0.49	3	3
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.016	0.13	-10000	0	-0.49	10	10
HRAS/GTP	-0.043	0.098	-10000	0	-0.49	7	7
Ephrin B1/EPHB1-2	-0.016	0.11	-10000	0	-0.28	60	60
cell adhesion mediated by integrin	0.014	0.074	0.31	15	-10000	0	15
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.006	0.12	-10000	0	-0.52	7	7
RAC1-CDC42/GTP	-0.047	0.1	-10000	0	-0.44	13	13
RASA1	0.016	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.031	0.09	-10000	0	-0.42	4	4
ruffle organization	0.018	0.12	-10000	0	-0.45	7	7
NCK1	0.016	0	-10000	0	-10000	0	0
receptor internalization	0.009	0.1	-10000	0	-0.48	4	4
Ephrin B/EPHB2/KALRN	0.006	0.11	-10000	0	-0.52	3	3
ROCK1	0.016	0.061	-10000	0	-0.27	18	18
RAS family/GDP	-0.027	0.064	-10000	0	-0.39	4	4
Rac1/GTP	-0.042	0.095	-10000	0	-0.48	7	7
Ephrin B/EPHB1/Src/Paxillin	0.01	0.097	-10000	0	-0.44	5	5

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.027	0.051	-10000	0	-0.24	14	14
epithelial cell differentiation	-0.01	0.051	-10000	0	-0.28	14	14
CYFIP2	0	0.095	-10000	0	-0.57	11	11
ENAH	0.06	0.055	-10000	0	-0.32	1	1
EGFR	-0.008	0.11	-10000	0	-0.54	17	17
EPHA2	0.008	0.064	-10000	0	-0.57	5	5
MYO6	0.033	0.055	-10000	0	-10000	0	0
CTNNB1	0.016	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.022	0.06	-10000	0	-0.34	11	11
AQP5	-0.013	0.045	-10000	0	-0.35	1	1
CTNND1	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.033	0.054	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.017	0.086	-10000	0	-0.5	2	2
EGF	-0.018	0.12	-10000	0	-0.51	25	25
NCKAP1	0.016	0	-10000	0	-10000	0	0
AQP3	-0.096	0.2	-10000	0	-0.49	80	80
cortical microtubule organization	-0.01	0.051	-10000	0	-0.28	14	14
GO:0000145	0.031	0.052	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.026	0.058	-10000	0	-0.28	14	14
MLLT4	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.013	0.051	-10000	0	-0.45	1	1
ARF6	0.016	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.03	0.057	-10000	0	-0.3	5	5
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.045	0.055	-10000	0	-10000	0	0
PVRL2	0.016	0	-10000	0	-10000	0	0
ZYX	0.032	0.057	-10000	0	-10000	0	0
ARF6/GTP	-0.008	0.044	-10000	0	-10000	0	0
CDH1	-0.004	0.11	-10000	0	-0.57	14	14
EGFR/EGFR/EGF/EGF	-0.031	0.083	-10000	0	-0.5	3	3
RhoA/GDP	-0.009	0.047	-10000	0	-10000	0	0
actin cytoskeleton organization	0.039	0.055	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.011	0.05	-10000	0	-0.57	3	3
GIT1	0.016	0	-10000	0	-10000	0	0
IGF1R	0.011	0.05	-10000	0	-0.57	3	3
IGF1	-0.24	0.29	-10000	0	-0.57	182	182
DIAPH1	-0.014	0.094	-10000	0	-0.58	11	11
Wnt receptor signaling pathway	0.01	0.051	0.28	14	-10000	0	14
RHOA	0.016	0	-10000	0	-10000	0	0
RhoA/GTP	-0.013	0.051	-10000	0	-0.46	1	1
CTNNA1	0.016	0	-10000	0	-10000	0	0
VCL	0.039	0.056	-10000	0	-10000	0	0
EFNA1	0.004	0.077	-10000	0	-0.51	9	9
LPP	0.04	0.055	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.016	0.062	-10000	0	-0.53	1	1
SEC6/SEC8	-0.007	0.039	-10000	0	-10000	0	0
MGAT3	0.017	0.088	-10000	0	-0.51	2	2
HGF/MET	-0.066	0.11	-10000	0	-0.49	2	2
HGF	-0.12	0.24	-10000	0	-0.56	94	94
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.027	0.051	-10000	0	-0.24	14	14
actin cable formation	0.077	0.054	-10000	0	-10000	0	0
KIAA1543	0.031	0.095	-10000	0	-0.52	9	9
KIFC3	0.033	0.055	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
EXOC3	0.016	0	-10000	0	-10000	0	0
ACTN1	0.033	0.055	-10000	0	-10000	0	0
NCK1/GIT1	0.023	0	-10000	0	-10000	0	0
mol:GDP	-0.01	0.051	-10000	0	-0.28	14	14
EXOC4	0.016	0	-10000	0	-10000	0	0
STX4	0.033	0.055	-10000	0	-10000	0	0
PIP5K1C	0.033	0.055	-10000	0	-10000	0	0
LIMA1	0.016	0	-10000	0	-10000	0	0
ABI1	0.016	0	-10000	0	-10000	0	0
ROCK1	0.055	0.062	-10000	0	-0.39	1	1
adherens junction assembly	0.048	0.094	-10000	0	-0.5	9	9
IGF-1R heterotetramer/IGF1	-0.12	0.13	-10000	0	-0.53	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.023	0	-10000	0	-10000	0	0
MET	0.013	0.036	-10000	0	-0.51	2	2
PLEKHA7	0.033	0.06	-10000	0	-0.55	1	1
mol:GTP	0.028	0.056	-10000	0	-0.3	5	5
establishment of epithelial cell apical/basal polarity	0.061	0.05	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.027	0.051	-10000	0	-0.24	14	14
regulation of cell-cell adhesion	0.039	0.055	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.027	0.051	-10000	0	-0.24	14	14

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0	0.11	-9999	-0.52	10	10
PDGFB-D/PDGFRB/SLAP	-0.001	0.12	-9999	-0.5	19	19
PDGFB-D/PDGFRB/APS/CBL	0.018	0.067	-9999	-0.32	15	15
AKT1	0.049	0.067	-9999	-0.41	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.002	0.12	-9999	-0.56	10	10
PIK3CA	0.016	0	-9999	-10000	0	0
FGR	-0.011	0.069	-9999	-0.39	12	12
mol:Ca2+	0.016	0.1	-9999	-0.59	10	10
MYC	0.007	0.19	-9999	-0.75	22	22
SHC1	0.014	0.026	-9999	-0.51	1	1
HRAS/GDP	0.034	0.048	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0.018	0.069	-9999	-0.34	15	15
GRB10	0.008	0.064	-9999	-0.57	5	5
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.015	0.1	-9999	-0.6	10	10
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	-0.012	0.12	-9999	-0.53	21	21
PDGFB-D/PDGFRB/SHP2	0.012	0.067	-9999	-0.41	10	10
PDGFB-D/PDGFRB/GRB10	0.007	0.081	-9999	-0.41	15	15
cell cycle arrest	-0.001	0.12	-9999	-0.5	19	19
HRAS	0.016	0	-9999	-10000	0	0
HIF1A	0.054	0.063	-9999	-0.36	1	1
GAB1	0.012	0.11	-9999	-0.57	10	10
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.016	0.1	-9999	-0.51	10	10
PDGFB-D/PDGFRB	0.02	0.06	-9999	-0.35	10	10
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.012	0.067	-9999	-0.41	10	10
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.033	0.093	-9999	-0.48	10	10
positive regulation of MAPKKK cascade	0.012	0.067	-9999	-0.41	10	10
PIK3R1	0.014	0.029	-9999	-0.57	1	1
mol:IP3	0.016	0.1	-9999	-0.6	10	10
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.11	-9999	-0.39	31	31
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.062	0.18	-9999	-0.55	44	44
PTPN2	0.015	0.004	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.012	0.067	-9999	-0.41	10	10
BCAR1	0.016	0	-9999	-10000	0	0
VAV2	0.013	0.12	-9999	-0.55	12	12
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.011	0.074	-9999	-0.44	10	10
LCK	-0.014	0.091	-9999	-0.46	13	13
PDGFRB	0.001	0.092	-9999	-0.58	10	10
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.025	0.14	-9999	-0.62	18	18
ABL1	0.013	0.095	-9999	-0.51	10	10
PDGFB-D/PDGFRB/CBL	0.01	0.12	-9999	-0.64	10	10
PTPN1	0.015	0.004	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.011	0.051	-9999	-0.51	4	4
cell proliferation	0.011	0.17	-9999	-0.66	22	22
SLA	-0.004	0.11	-9999	-0.56	14	14
actin cytoskeleton reorganization	0.05	0.048	-9999	-10000	0	0
SRC	-0.007	0.059	-9999	-0.37	10	10
PI3K	-0.015	0.056	-9999	-0.46	1	1
PDGFB-D/PDGFRB/GRB7/SHC	0.004	0.094	-9999	-0.32	32	32
SH2B2	0.009	0.057	-9999	-0.51	5	5
PLCgamma1/SPHK1	-0.002	0.12	-9999	-0.58	10	10
LYN	-0.007	0.059	-9999	-0.37	10	10
LRP1	0.01	0.058	-9999	-0.57	4	4
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.014	0.029	-9999	-0.57	1	1
NCK1-2/p130 Cas	-0.001	0.044	-9999	-10000	0	0
SPHK1	-0.057	0.18	-9999	-0.5	57	57
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.016	0.1	-9999	-0.6	10	10
PLCG1	0.015	0.11	-9999	-0.62	10	10
NHERF/PDGFRB	0.005	0.09	-9999	-0.31	31	31
YES1	-0.007	0.059	-9999	-0.37	10	10
cell migration	0.005	0.09	-9999	-0.31	31	31
SHC/Grb2/SOS1	-0.001	0.045	-9999	-10000	0	0
SLC9A3R2	0.016	0	-9999	-10000	0	0
SLC9A3R1	-0.011	0.12	-9999	-0.51	21	21
NHERF1-2/PDGFRB/PTEN	0.016	0.082	-9999	-0.3	10	10
FYN	-0.011	0.071	-9999	-0.4	13	13
DOK1	0.028	0.055	-9999	-0.3	10	10
HRAS/GTP	0.012	0	-9999	-10000	0	0
PDGFB	0.014	0.026	-9999	-0.51	1	1
RAC1	0.018	0.14	-9999	-0.46	27	27
PRKCD	0.029	0.054	-9999	-0.31	10	10
FER	0.027	0.061	-9999	-0.31	13	13
MAPKKK cascade	-0.007	0.04	-9999	-10000	0	0
RASA1	0.029	0.054	-9999	-0.31	10	10
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.037	0.051	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.012	0.067	-9999	-0.41	10	10
chemotaxis	0.013	0.093	-9999	-0.5	10	10
STAT1-3-5/STAT1-3-5	-0.009	0.044	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0.067	-9999	-0.42	10	10
PTPRJ	0.014	0.029	-9999	-0.57	1	1

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.014	0.026	-9999	-0.51	1	1
PLK4	0.003	0.081	-9999	-0.51	10	10
regulation of centriole replication	0.016	0.062	-9999	-0.36	11	11

×

EPO signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.063	0.089	-9999	-0.42	3	3
CRKL	0.029	0.075	-9999	-0.29	3	3
mol:DAG	0.04	0.063	-9999	-0.28	1	1
HRAS	0.056	0.065	-9999	-10000	0	0
MAPK8	0.014	0.087	-9999	-0.34	6	6
RAP1A	0.03	0.073	-9999	-0.29	3	3
GAB1	0.03	0.073	-9999	-0.29	3	3
MAPK14	0.016	0.08	-9999	-0.28	3	3
EPO	-0.024	0.14	-9999	-0.5	31	31
PLCG1	0.041	0.064	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.072	-9999	-0.5	8	8
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.034	0.15	-9999	-0.39	46	46
GAB1/SHC/GRB2/SOS1	-0.015	0.044	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.009	0.11	-9999	-0.35	39	39
IRS2	0.018	0.094	-9999	-0.34	6	6
STAT1	0.046	0.08	-9999	-0.38	3	3
STAT5B	0.044	0.071	-9999	-0.34	3	3
cell proliferation	0.022	0.081	-9999	-0.41	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.018	0.052	-9999	-0.43	2	2
TEC	0.03	0.073	-9999	-0.29	3	3
SOCS3	-0.046	0.18	-9999	-0.57	43	43
STAT1 (dimer)	0.046	0.079	-9999	-0.37	3	3
JAK2	0.015	0.03	-9999	-0.56	1	1
PIK3R1	0.014	0.029	-9999	-0.57	1	1
EPO/EPOR (dimer)/JAK2	0.037	0.082	-9999	-0.3	4	4
EPO/EPOR	-0.009	0.11	-9999	-0.35	39	39
LYN	0.017	0.004	-9999	-10000	0	0
TEC/VAV2	0.038	0.074	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.072	-9999	-0.5	8	8
SHC1	0.014	0.026	-9999	-0.51	1	1
EPO/EPOR (dimer)/LYN	0.013	0.092	-9999	-0.27	39	39
mol:IP3	0.04	0.063	-9999	-0.28	1	1
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.027	0.099	-9999	-0.41	6	6
SH2B3	0.016	0.007	-9999	-10000	0	0
NFKB1	0.016	0.08	-9999	-0.28	3	3
EPO/EPOR (dimer)/JAK2/SOCS3	-0.035	0.082	-9999	-0.25	43	43
PTPN6	0.022	0.076	-9999	-0.3	4	4
TEC/VAV2/GRB2	0.045	0.072	-9999	-10000	0	0
EPOR	0.007	0.072	-9999	-0.5	8	8
INPP5D	0.006	0.076	-9999	-0.57	7	7
mol:GDP	-0.015	0.044	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.009	0.06	-9999	-0.53	5	5
CRKL/CBL/C3G	0.045	0.071	-9999	-10000	0	0
VAV2	0.029	0.076	-9999	-0.29	3	3
CBL	0.03	0.073	-9999	-0.29	3	3
SHC/Grb2/SOS1	-0.017	0.048	-9999	-10000	0	0
STAT5A	0.044	0.073	-9999	-0.34	3	3
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	0.059	0.094	-9999	-0.47	3	3
LYN/PLCgamma2	0.019	0.044	-9999	-0.38	5	5
PTPN11	0.016	0	-9999	-10000	0	0
BTK	0.013	0.1	-9999	-0.36	9	9
BCL2	0.041	0.19	-9999	-0.89	16	16

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.019	0.079	-9999	-0.35	17	17
CRKL	0.013	0.036	-9999	-0.51	2	2
Rac1/GDP	0.012	0	-9999	-10000	0	0
DOCK1	0.013	0.041	-9999	-0.57	2	2
ITGA4	-0.003	0.1	-9999	-0.56	13	13
alpha4/beta7 Integrin/MAdCAM1	0.014	0.091	-9999	-0.33	17	17
EPO	-0.027	0.14	-9999	-0.51	31	31
alpha4/beta7 Integrin	0.004	0.088	-9999	-0.4	18	18
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.01	0.075	-9999	-0.4	13	13
EPO/EPOR (dimer)	-0.015	0.11	-9999	-0.36	39	39
lamellipodium assembly	0.001	0.018	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.022	0.021	-9999	-0.41	1	1
ARF6	0.016	0	-9999	-10000	0	0
JAK2	0.011	0.077	-9999	-0.42	3	3
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
MADCAM1	-0.004	0.095	-9999	-0.51	14	14
cell adhesion	0.013	0.09	-9999	-0.33	17	17
CRKL/CBL	0.021	0.026	-9999	-0.36	2	2
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.013	0.1	-9999	-0.38	23	23
ITGB7	0.008	0.064	-9999	-0.57	5	5
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.004	0.11	-9999	-0.42	23	23
p130Cas/Crk/Dock1	0.036	0.093	-9999	-0.5	6	6
VCAM1	-0.011	0.12	-9999	-0.56	19	19
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.03	0.059	-9999	-0.3	12	12
BCAR1	0.022	0.098	-9999	-0.56	6	6
EPOR	0.005	0.072	-9999	-0.51	8	8
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0.001	0.018	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.016	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.015	0.064	-9999	-0.47	3	3
NEF	-0.007	0.048	-9999	-0.19	21	21
NFKBIA	0.013	0.026	-9999	-10000	0	0
BIRC3	0.014	0.15	-9999	-0.57	25	25
CYCS	0.034	0.084	-9999	-0.47	3	3
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.002	0.091	-9999	-0.56	8	8
MAP2K7	0.04	0.072	-9999	-0.52	2	2
protein ubiquitination	0.066	0.046	-9999	-0.34	1	1
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.007	0.07	-9999	-0.57	6	6
BID	0.026	0.088	-9999	-0.5	3	3
NF-kappa-B/RelA/I kappa B alpha	-0.016	0.064	-9999	-0.27	22	22
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.014	0.029	-9999	-0.57	1	1
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.008	0.063	-9999	-0.51	6	6
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.016	0.064	-9999	-0.27	22	22
MAPK8	0.045	0.072	-9999	-0.67	1	1
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.011	0.048	-9999	-0.55	3	3
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.02	0.091	-9999	-0.3	23	23
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.057	0.054	-9999	-0.45	1	1
CHUK	0.068	0.048	-9999	-0.37	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.037	0.057	-9999	-0.57	1	1
TCRz/NEF	-0.027	0.092	-9999	-0.32	36	36
TNF	-0.011	0.12	-9999	-0.51	21	21
FASLG	-0.019	0.17	-9999	-0.55	36	36
NFKB1	0.013	0.026	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	0.015	0.071	-9999	-0.29	21	21
CASP6	-0.01	0.043	-9999	-0.54	1	1
CASP7	0.051	0.15	-9999	-0.51	23	23
RELA	0.013	0.026	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	0.051	0.15	-9999	-0.51	23	23
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	0.023	0	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.063	0.051	-9999	-0.41	1	1
APAF-1/Caspase 9	-0.03	0.093	-9999	-0.37	24	24
BCL2	0.041	0.086	-9999	-0.5	2	2

×

Arf6 trafficking 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
SLC2A4	-0.41	0.26	-10000	0	-0.57	294	294
CLTC	0.037	0.009	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.03	0.01	-10000	0	-10000	0	0
Dynamin 2/GTP	0.028	0.014	-10000	0	-0.26	1	1
EXOC4	0.016	0	-10000	0	-10000	0	0
CD59	0.033	0.007	-10000	0	-10000	0	0
CPE	0.006	0.076	-10000	0	-0.35	18	18
CTNNB1	0.016	0	-10000	0	-10000	0	0
membrane fusion	0.03	0.011	-10000	0	-10000	0	0
CTNND1	0.036	0.014	-10000	0	-10000	0	0
DNM2	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.037	0.007	-10000	0	-10000	0	0
TSHR	0.013	0.042	-10000	0	-0.3	7	7
INS	0.014	0.003	-10000	0	-10000	0	0
BIN1	-0.062	0.2	-10000	0	-0.57	54	54
mol:Choline	0.03	0.011	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.021	0.016	-10000	0	-0.3	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0.027	0.014	-10000	0	-0.26	1	1
JUP	0.032	0.018	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.014	0.12	-10000	0	-0.31	54	54
ARF6/GTP	0.012	0	-10000	0	-10000	0	0
CDH1	0.025	0.042	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.012	0	-10000	0	-10000	0	0
MAPK8IP3	0.009	0.059	-10000	0	-0.52	5	5
positive regulation of endocytosis	0.012	0	-10000	0	-10000	0	0
EXOC2	0.016	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.05	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.016	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.004	0.024	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.022	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.017	0.037	-10000	0	-0.31	5	5
ACAP1	0.024	0.028	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.054	0.11	-10000	0	-0.27	2	2
clathrin heavy chain/ACAP1	0.042	0.012	-10000	0	-10000	0	0
JIP4/KLC1	0.03	0	-10000	0	-10000	0	0
EXOC1	0.016	0	-10000	0	-10000	0	0
exocyst	0.05	0	-10000	0	-10000	0	0
RALA/GTP	0.011	0.019	-10000	0	-0.37	1	1
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.021	0	-10000	0	-10000	0	0
receptor recycling	0.012	0	-10000	0	-10000	0	0
CTNNA1	0.036	0.014	-10000	0	-10000	0	0
NME1	0.021	0.016	-10000	0	-0.3	1	1
clathrin coat assembly	0.037	0.009	-10000	0	-10000	0	0
IL2RA	0.017	0.054	-10000	0	-10000	0	0
VAMP3	0.022	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.17	0.11	-10000	0	-0.28	16	16
EXOC6	0.016	0	-10000	0	-10000	0	0
PLD1	0.025	0.016	-10000	0	-0.28	1	1
PLD2	0.026	0.006	-10000	0	-10000	0	0
EXOC5	0.016	0	-10000	0	-10000	0	0
PIP5K1C	0.037	0.007	-10000	0	-10000	0	0
SDC1	0.029	0.031	-10000	0	-10000	0	0
ARF6/GDP	0.021	0.016	-10000	0	-0.3	1	1
EXOC7	0.016	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.005	0.024	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0.011	-10000	0	-10000	0	0
endocytosis	0.015	0.11	0.31	54	-10000	0	54
SCAMP2	0.016	0	-10000	0	-10000	0	0
ADRB2	0.005	0.1	-10000	0	-10000	0	0
EXOC3	0.016	0	-10000	0	-10000	0	0
ASAP2	0.016	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.029	0.014	-10000	0	-0.26	1	1
KLC1	0.016	0	-10000	0	-10000	0	0
AVPR2	0.013	0.091	-10000	0	-10000	0	0
RALA	0.014	0.026	-10000	0	-0.51	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.02	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.009	0.11	-10000	0	-0.51	19	19
positive regulation of NF-kappaB transcription factor activity	0	0.092	-10000	0	-0.36	24	24
MAP2K4	0.047	0.031	-10000	0	-10000	0	0
IKBKB	0.016	0	-10000	0	-10000	0	0
TNFRSF10B	0.016	0	-10000	0	-10000	0	0
TNFRSF10A	0.014	0.029	-10000	0	-0.57	1	1
SMPD1	0.016	0.033	-10000	0	-10000	0	0
IKBKG	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.008	0.064	-10000	0	-0.57	5	5
TRAIL/TRAILR2	0.006	0.08	-10000	0	-0.36	19	19
TRAIL/TRAILR3	-0.003	0.098	-10000	0	-0.36	28	28
TRAIL/TRAILR1	0.005	0.082	-10000	0	-0.36	20	20
TRAIL/TRAILR4	0	0.092	-10000	0	-0.37	24	24
TRAIL/TRAILR1/DAP3/GTP	0.016	0.064	-10000	0	-0.27	20	20
IKK complex	-0.005	0.02	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.012	0	-10000	0	-10000	0	0
MAPK3	0.009	0.08	-10000	0	-0.36	19	19
MAP3K1	0.04	0.033	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.008	0.064	-10000	0	-0.57	5	5
TRADD	0.016	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.014	0.029	-10000	0	-0.57	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.034	0.039	-10000	0	-10000	0	0
CFLAR	0.016	0	-10000	0	-10000	0	0
MAPK1	0.009	0.08	-10000	0	-0.36	19	19
TRAIL/TRAILR1/FADD/TRADD/RIP	0.029	0.068	-10000	0	-10000	0	0
mol:ceramide	0.016	0.033	-10000	0	-10000	0	0
FADD	0.008	0.063	-10000	0	-0.51	6	6
MAPK8	0.051	0.039	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.081	-10000	0	-0.53	9	9
CHUK	0.016	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.011	0.079	-10000	0	-0.29	26	26
DAP3	0.016	0	-10000	0	-10000	0	0
CASP10	-0.01	0.059	0.27	5	-10000	0	5
JNK cascade	0	0.092	-10000	0	-0.36	24	24
TRAIL (trimer)	-0.009	0.11	-10000	0	-0.51	19	19
TNFRSF10C	0.003	0.081	-10000	0	-0.53	9	9
TRAIL/TRAILR1/DAP3/GTP/FADD	0.02	0.068	-10000	0	-0.28	1	1
TRAIL/TRAILR2/FADD	0.012	0.077	-10000	0	-0.29	25	25
cell death	0.016	0.033	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.034	0.036	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.016	0	-10000	0	-10000	0	0
CASP8	0.004	0.021	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.03	0.066	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated 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
HDAC1	0.016	0	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
VDR	0.011	0.048	-10000	0	-0.55	3	3
Cbp/p300/PCAF	0.031	0.018	-10000	0	-0.34	1	1
EP300	0.016	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.033	0.062	-10000	0	-0.26	3	3
KAT2B	0.014	0.029	-10000	0	-0.57	1	1
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0.086	0.22	17	-0.26	27	44
RAR alpha/9cRA/Cyclin H	-0.007	0.038	-10000	0	-0.35	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.027	0.071	-10000	0	-0.29	3	3
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.017	0.053	-10000	0	-0.42	4	4
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.009	0.035	-10000	0	-0.4	3	3
RXRs/RARs/NRIP1/9cRA	0.013	0.1	-10000	0	-0.53	6	6
NCOA2	-0.019	0.14	-10000	0	-0.57	24	24
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.048	-10000	0	-0.55	3	3
RARG	0.017	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.022	0.001	-10000	0	-10000	0	0
MAPK3	0.017	0	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.013	0.05	-10000	0	-0.57	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.004	0.078	-10000	0	-0.46	6	6
RARA	0.023	0.047	-10000	0	-0.26	8	8
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.012	0.099	-10000	0	-0.44	7	7
PRKCA	0.012	0.065	-10000	0	-0.57	5	5
RXRs/RARs/NRIP1/9cRA/HDAC1	0	0.11	-10000	0	-0.56	6	6
RXRG	-0.079	0.16	-10000	0	-0.34	111	111
RXRA	0.031	0.047	-10000	0	-0.27	6	6
RXRB	0.019	0.058	-10000	0	-0.38	5	5
VDR/Vit D3/DNA	0.009	0.035	-10000	0	-0.4	3	3
RBP1	-0.023	0.14	-10000	0	-0.56	27	27
CRBP1/9-cic-RA	-0.016	0.1	-10000	0	-0.41	27	27
RARB	-0.03	0.16	-10000	0	-0.57	34	34
PRKCG	-0.006	0.094	-10000	0	-0.5	14	14
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.014	0.1	-10000	0	-0.52	6	6
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.018	0.095	-10000	0	-0.46	6	6
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.068	-10000	0	-0.32	4	4
RXRs/RARs/NRIP1/9cRA/HDAC3	0	0.11	-10000	0	-0.56	6	6
positive regulation of DNA binding	-0.006	0.037	-10000	0	-0.33	2	2
NRIP1	0.002	0.1	-10000	0	-0.69	3	3
RXRs/RARs	-0.008	0.11	-10000	0	-0.46	10	10
RXRs/RXRs/DNA/9cRA	-0.018	0.072	-10000	0	-0.5	5	5
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0.032	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.004	0.022	-10000	0	-10000	0	0
CCNH	0.016	0	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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
PDGFRA	-0.065	0.2	-10000	0	-0.57	56	56
HRAS	0.016	0	-10000	0	-10000	0	0
EGFR	-0.008	0.11	-10000	0	-0.54	17	17
AKT	0.032	0.06	-10000	0	-0.26	14	14
FOXO3	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
FOXO1	0.014	0.029	-10000	0	-0.57	1	1
AKT3	-0.004	0.11	-10000	0	-0.57	14	14
FOXO4	0.014	0.026	-10000	0	-0.51	1	1
MET	0.013	0.036	-10000	0	-0.51	2	2
PIK3CA	0.016	0	-10000	0	-10000	0	0
PIK3CB	0.016	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
PIK3CG	-0.006	0.11	-10000	0	-0.56	15	15
PIK3R3	0.016	0	-10000	0	-10000	0	0
PIK3R2	0.016	0	-10000	0	-10000	0	0
NF1	0.016	0	-10000	0	-10000	0	0
RAS	0.001	0.068	-10000	0	-0.26	6	6
ERBB2	-0.001	0.092	-10000	0	-0.51	13	13
proliferation/survival/translation	-0.035	0.031	0.19	2	-10000	0	2
PI3K	0.011	0.069	-10000	0	-0.22	12	12
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
KRAS	0.014	0.026	-10000	0	-0.51	1	1
FOXO	0.048	0.028	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
PTEN	0.016	0	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.031	0.091	-9999	-0.45	14	14
KLHL20	-0.013	0.039	-9999	-0.21	3	3
CYFIP2	0	0.095	-9999	-0.57	11	11
Rac1/GDP	0.058	0.059	-9999	-10000	0	0
ENAH	0.032	0.091	-9999	-0.45	14	14
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.006	0.032	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.029	-9999	-0.19	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.025	0.075	-9999	-0.32	18	18
RAPGEF1	0.046	0.08	-9999	-0.38	14	14
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.022	0.093	-9999	-0.47	14	14
CRK	0.04	0.086	-9999	-0.42	14	14
E-cadherin/gamma catenin/alpha catenin	0.016	0.075	-9999	-0.36	15	15
alphaE/beta7 Integrin	0.018	0.047	-9999	-0.41	5	5
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.03	0.001	-9999	-10000	0	0
DLG1	0.032	0.091	-9999	-0.45	14	14
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.024	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.027	0.032	-9999	-0.3	4	4
PI3K	-0.006	0.03	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.007	0.087	-9999	-0.43	15	15
TIAM1	0.011	0.05	-9999	-0.57	3	3
E-cadherin(dimer)/Ca2+	0.025	0.058	-9999	-0.28	14	14
AKT1	-0.003	0.017	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
CDH1	-0.004	0.11	-9999	-0.57	14	14
RhoA/GDP	0.058	0.059	-9999	-10000	0	0
actin cytoskeleton organization	0.04	0.045	-9999	-10000	0	0
CDC42/GDP	0.058	0.059	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.018	0.058	-9999	-0.27	15	15
ITGB7	0.008	0.064	-9999	-0.57	5	5
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.027	0.062	-9999	-0.3	14	14
E-cadherin/Ca2+/beta catenin/alpha catenin	0.016	0.058	-9999	-0.29	14	14
mol:GDP	0.054	0.066	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
JUP	0.013	0.041	-9999	-0.57	2	2
p120 catenin/RhoA/GDP	-0.006	0.048	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.021	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.023	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.026	0.056	-9999	-0.19	21	21
NME1	0.014	0.026	-9999	-0.51	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.032	0.091	-9999	-0.45	14	14
regulation of cell-cell adhesion	-0.005	0.029	-9999	-10000	0	0
WASF2	-0.005	0.015	-9999	-10000	0	0
Rap1/GTP	-0.007	0.037	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.03	0.077	-9999	-0.57	2	2
CCND1	0.03	0.068	-9999	-0.24	21	21
VAV2	0.041	0.099	-9999	-0.44	16	16
RAP1/GDP	0.055	0.052	-9999	-10000	0	0
adherens junction assembly	0.032	0.088	-9999	-0.43	14	14
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.038	0.074	-9999	-0.54	2	2
E-cadherin/beta catenin	-0.013	0.068	-9999	-0.38	14	14
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.03	0.091	-9999	-0.45	14	14
PIK3CA	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.02	0.062	-9999	-0.33	3	3
E-cadherin/beta catenin/alpha catenin	0.018	0.068	-9999	-0.34	14	14
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.087	-9999	-0.48	14	14

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.035	0.041	-10000	0	-0.3	6	6
HDAC3	0.016	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	0.02	0.005	-10000	0	-10000	0	0
GATA1/HDAC5	0.02	0.005	-10000	0	-10000	0	0
GATA2/HDAC5	0.004	0.086	-10000	0	-0.37	20	20
HDAC5/BCL6/BCoR	0.032	0	-10000	0	-10000	0	0
HDAC9	-0.025	0.15	-10000	0	-0.57	28	28
Glucocorticoid receptor/Hsp90/HDAC6	0.021	0.063	-10000	0	-0.34	12	12
HDAC4/ANKRA2	0.023	0	-10000	0	-10000	0	0
HDAC5/YWHAB	0.023	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-10000	0	-10000	0	0
GATA2	-0.011	0.12	-10000	0	-0.53	20	20
HDAC4/RFXANK	0.022	0.019	-10000	0	-0.36	1	1
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.016	0	-10000	0	-10000	0	0
HDAC5	0.016	0	-10000	0	-10000	0	0
GNB1/GNG2	0.017	0.052	-10000	0	-0.41	6	6
Histones	0.028	0.066	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.023	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.023	0	-10000	0	-10000	0	0
HDAC7	0.016	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.022	0.021	-10000	0	-0.41	1	1
TUBA1B	0.016	0	-10000	0	-10000	0	0
HDAC6	0.016	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.022	0.019	-10000	0	-0.36	1	1
CAMK4	0	0.094	-10000	0	-0.56	11	11
Tubulin/HDAC6	0.03	0.026	-10000	0	-0.34	2	2
SUMO1	0.016	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
GATA1	0.011	0.007	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.014	0.029	-10000	0	-0.57	1	1
NR3C1	-0.002	0.099	-10000	0	-0.57	12	12
SUMO1/HDAC4	0.036	0	-10000	0	-10000	0	0
SRF	0.016	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.023	0	-10000	0	-10000	0	0
Tubulin	0.021	0.03	-10000	0	-0.41	2	2
HDAC4/14-3-3 E	0.022	0.021	-10000	0	-0.41	1	1
GNB1	0.016	0	-10000	0	-10000	0	0
RANGAP1	0.016	0	-10000	0	-10000	0	0
BCL6/BCoR	0.023	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.032	0	-10000	0	-10000	0	0
HDAC4/SRF	0.022	0.059	-10000	0	-0.33	11	11
HDAC4/ER alpha	-0.054	0.16	-10000	0	-0.41	73	73
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.028	0.066	-10000	0	-10000	0	0
cell motility	0.03	0.026	-10000	0	-0.34	2	2
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.023	0	-10000	0	-10000	0	0
BCL6	0.016	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0.023	0	-10000	0	-10000	0	0
ESR1	-0.089	0.22	-10000	0	-0.57	73	73
HDAC6/HDAC11	0.018	0.046	-10000	0	-0.4	5	5
Ran/GTP/Exportin 1	0.039	0	-10000	0	-10000	0	0
NPC	0.009	0	-10000	0	-10000	0	0
MEF2C	-0.004	0.11	-10000	0	-0.57	14	14
RAN	0.016	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.036	0.058	-10000	0	-10000	0	0
GNG2	0.007	0.07	-10000	0	-0.57	6	6
NCOR2	0.016	0	-10000	0	-10000	0	0
TUBB2A	0.013	0.041	-10000	0	-0.57	2	2
HDAC11	0.009	0.063	-10000	0	-0.56	5	5
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RANBP2	0.016	0	-10000	0	-10000	0	0
ANKRA2	0.016	0	-10000	0	-10000	0	0
RFXANK	0.014	0.026	-10000	0	-0.51	1	1
nuclear import	-0.034	0.017	0.31	1	-10000	0	1

×

p38 MAPK signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.016	0.015	-9999	-0.3	1	1
TRAF2/ASK1	0.02	0.018	-9999	-0.35	1	1
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.041	0.023	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.046	0.037	-9999	-0.28	1	1
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.007	0.07	-9999	-0.57	6	6
TXN	0.009	0.014	-9999	-0.19	2	2
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	0.016	0	-9999	-10000	0	0
GADD45B	0	0.095	-9999	-0.57	11	11
MAP3K1	0.016	0	-9999	-10000	0	0
MAP3K6	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
MAP3K4	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.022	0.021	-9999	-0.41	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.03	0.015	-9999	-0.26	1	1
TRAF2	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.01	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.04	0.16	-9999	-0.51	43	43
CCM2	0.014	0.026	-9999	-0.51	1	1
CaM/Ca2+/CAMKIIB	-0.013	0.099	-9999	-0.3	43	43
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.002	0.091	-9999	-0.26	44	44
OSM/MEKK3	0.022	0.019	-9999	-0.36	1	1
TAOK1	0.019	0.018	-9999	-0.34	1	1
TAOK2	0.02	0	-9999	-10000	0	0
TAOK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.014	0.029	-9999	-0.57	1	1
MAP3K10	0.014	0.026	-9999	-0.51	1	1
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	0.017	0.021	-9999	-0.34	1	1
GADD45/MTK1/MTK1	0.024	0.067	-9999	-0.3	16	16

×

FoxO family signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.023	0.076	-9999	-10000	0	0
PLK1	-0.057	0.23	-9999	-0.61	9	9
CDKN1B	0.072	0.11	-9999	-0.32	1	1
FOXO3	-0.016	0.18	-9999	-0.5	10	10
KAT2B	0.012	0.034	-9999	-0.55	1	1
FOXO1/SIRT1	0.021	0.046	-9999	-10000	0	0
CAT	-0.005	0.17	-9999	-0.52	4	4
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	0.015	0.021	-9999	-10000	0	0
FOXO1	0.032	0.047	-9999	-0.29	1	1
MAPK10	0.012	0.096	-9999	-0.29	38	38
mol:GTP	0.003	0	-9999	-10000	0	0
FOXO4	0.093	0.066	-9999	-10000	0	0
response to oxidative stress	-0.001	0.024	-9999	-10000	0	0
FOXO3A/SIRT1	-0.06	0.12	-9999	-0.49	5	5
XPO1	0.017	0	-9999	-10000	0	0
EP300	0.016	0.006	-9999	-10000	0	0
BCL2L11	0.023	0.034	-9999	-10000	0	0
FOXO1/SKP2	0.03	0.063	-9999	-0.39	3	3
mol:GDP	-0.001	0.024	-9999	-10000	0	0
RAN	0.018	0	-9999	-10000	0	0
GADD45A	0.067	0.094	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.076	0.034	-9999	-10000	0	0
MST1	-0.016	0.12	-9999	-0.51	23	23
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.056	0.046	-9999	-0.34	1	1
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.039	0.033	-9999	-0.27	4	4
MAPK9	0.04	0.017	-9999	-0.25	1	1
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.014	0.029	-9999	-0.57	1	1
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.015	0.015	-9999	-10000	0	0
SOD2	0.077	0.12	-9999	-0.48	1	1
RBL2	0.031	0.14	-9999	-10000	0	0
RAL/GDP	0.025	0.025	-9999	-0.31	1	1
CHUK	0.014	0.019	-9999	-10000	0	0
Ran/GTP	0.017	0.001	-9999	-10000	0	0
CSNK1G2	0.016	0	-9999	-10000	0	0
RAL/GTP	0.036	0.022	-9999	-0.28	1	1
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.056	0.33	-9999	-1.4	21	21
SKP2	0.004	0.077	-9999	-0.51	9	9
USP7	0.018	0	-9999	-10000	0	0
IKBKB	0.014	0.019	-9999	-10000	0	0
CCNB1	-0.057	0.23	-9999	-0.61	8	8
FOXO1-3a-4/beta catenin	0.097	0.12	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.029	0.063	-9999	-0.38	3	3
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	-0.009	0.12	-9999	-0.57	16	16
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.03	0.001	-9999	-10000	0	0
ZFAND5	0.096	0.059	-9999	-10000	0	0
SFN	-0.031	0.15	-9999	-0.51	36	36
CDK2	0.015	0.009	-9999	-10000	0	0
FOXO3A/14-3-3	0.043	0.064	-9999	-0.36	2	2
CREBBP	0.015	0.009	-9999	-10000	0	0
FBXO32	-0.007	0.18	-9999	-0.72	4	4
BCL6	0.031	0.14	-9999	-0.46	1	1
RALB	0.017	0	-9999	-10000	0	0
RALA	0.016	0.026	-9999	-0.5	1	1
YWHAH	0.016	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0.036	-9999	-0.51	2	2
Rac1/GDP	0.002	0.01	-9999	-10000	0	0
DOCK1	0.013	0.041	-9999	-0.57	2	2
ITGA4	-0.003	0.1	-9999	-0.56	13	13
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.004	0.088	-9999	-0.4	18	18
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.02	0.064	-9999	-0.34	13	13
alpha4/beta7 Integrin/Paxillin	0.024	0.069	-9999	-0.3	17	17
lamellipodium assembly	0	0.028	-9999	-0.36	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0.022	0.021	-9999	-0.41	1	1
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.026	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
ARF6/GTP	-0.008	0.042	-9999	-10000	0	0
cell adhesion	0.036	0.055	-9999	-10000	0	0
CRKL/CBL	0.021	0.026	-9999	-0.36	2	2
alpha4/beta1 Integrin/Paxillin	0.029	0.059	-9999	-0.3	12	12
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.008	0.064	-9999	-0.57	5	5
ARF6/GDP	0.002	0.01	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.023	0.099	-9999	-0.57	6	6
p130Cas/Crk/Dock1	0.03	0.026	-9999	-0.34	2	2
VCAM1	-0.011	0.12	-9999	-0.56	19	19
alpha4/beta1 Integrin/Paxillin/Talin	0.037	0.056	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.037	0.056	-9999	-10000	0	0
BCAR1	0.016	0	-9999	-10000	0	0
mol:GDP	-0.036	0.055	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.037	0.056	-9999	-10000	0	0
Rac1/GTP	0	0.031	-9999	-0.4	1	1

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.026	0.14	-9999	-0.42	46	46
AKT1	0.095	0.061	-9999	-0.63	2	2
PTK2B	0.026	0.12	-9999	-0.57	5	5
VEGFR2 homodimer/Frs2	0.033	0.07	-9999	-0.76	2	2
CAV1	-0.012	0.12	-9999	-0.57	19	19
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.043	0.069	-9999	-0.73	2	2
endothelial cell proliferation	0.051	0.11	-9999	-0.56	3	3
mol:Ca2+	0.058	0.065	-9999	-0.71	2	2
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.056	0.055	-9999	-0.69	2	2
RP11-342D11.1	0.048	0.064	-9999	-0.72	2	2
CDH5	0.013	0.041	-9999	-0.57	2	2
VEGFA homodimer	0.041	0.015	-9999	-10000	0	0
SHC1	0.014	0.026	-9999	-0.51	1	1
SHC2	-0.021	0.14	-9999	-0.57	26	26
HRAS/GDP	-0.006	0.048	-9999	-0.6	2	2
SH2D2A	0.011	0.051	-9999	-0.51	4	4
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.005	0.045	-9999	-0.58	2	2
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.046	0.064	-9999	-0.73	2	2
VEGFR1 homodimer	0.016	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.006	0.054	-9999	-0.68	2	2
GRB10	0.054	0.094	-9999	-0.68	6	6
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.014	0.029	-9999	-0.57	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.005	0.066	-9999	-0.93	2	2
HRAS	0.016	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.031	0.085	-9999	-0.38	5	5
HIF1A	0.014	0.026	-9999	-0.51	1	1
FRS2	0.007	0.068	-9999	-0.51	7	7
oxygen and reactive oxygen species metabolic process	-0.004	0.049	-9999	-0.68	2	2
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.014	0.029	-9999	-0.57	1	1
Nck/Pak	0.022	0.021	-9999	-0.41	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.046	0.064	-9999	-0.73	2	2
mol:GDP	-0.006	0.052	-9999	-0.65	2	2
mol:NADP	0.085	0.049	-9999	-0.48	2	2
eNOS/Hsp90	0.088	0.046	-9999	-0.45	2	2
PIK3R1	0.014	0.029	-9999	-0.57	1	1
mol:IP3	0.058	0.065	-9999	-0.73	2	2
HIF1A/ARNT	0.022	0.019	-9999	-0.36	1	1
SHB	0.016	0	-9999	-10000	0	0
VEGFA	0.018	0.007	-9999	-10000	0	0
VEGFC	0.01	0.056	-9999	-0.55	4	4
FAK1/Vinculin	0.051	0.1	-9999	-0.65	3	3
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.019	0.12	-9999	-0.61	5	5
PTPN6	0.014	0.026	-9999	-0.51	1	1
EPAS1	0.025	0.027	-9999	-0.35	2	2
mol:L-citrulline	0.085	0.049	-9999	-0.48	2	2
ITGAV	0.014	0.029	-9999	-0.57	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.051	0.066	-9999	-0.69	2	2
VEGFR2 homodimer/VEGFA homodimer	0.052	0.07	-9999	-0.79	2	2
VEGFR2/3 heterodimer	0.037	0.068	-9999	-0.9	2	2
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	0.061	0.067	-9999	-0.74	2	2
VEGFR2 homodimer	0.037	0.064	-9999	-0.85	2	2
FLT1	0.016	0	-9999	-10000	0	0
NEDD4	0.016	0.03	-9999	-0.56	1	1
MAPK3	0.026	0.09	-9999	-0.61	3	3
MAPK1	0.026	0.09	-9999	-0.61	3	3
VEGFA145/NRP2	0.005	0.091	-9999	-0.41	19	19
VEGFR1/2 heterodimer	0.038	0.057	-9999	-0.76	2	2
KDR	0.037	0.064	-9999	-0.86	2	2
VEGFA165/NRP1/VEGFR2 homodimer	0.044	0.093	-9999	-0.66	3	3
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.03	0.089	-9999	-0.63	3	3
PI3K	0.083	0.072	-9999	-0.79	2	2
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.048	0.058	-9999	-0.73	2	2
FES	0.058	0.068	-9999	-0.74	2	2
GAB1	-0.005	0.053	-9999	-0.72	2	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.048	0.058	-9999	-0.73	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.076	0.071	-9999	-0.45	2	2
VEGFR2 homodimer/VEGFA homodimer/Yes	0.048	0.058	-9999	-0.73	2	2
PI3K/GAB1	0.097	0.063	-9999	-0.66	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.008	0.055	-9999	-0.66	2	2
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.041	0.072	-9999	-0.84	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	0.059	0.066	-9999	-0.74	2	2
actin cytoskeleton reorganization	0.045	0.064	-9999	-0.72	2	2
PTK2	0.045	0.11	-9999	-0.71	3	3
EDG1	0.048	0.064	-9999	-0.72	2	2
mol:DAG	0.058	0.065	-9999	-0.73	2	2
CaM/Ca2+	0.061	0.06	-9999	-0.66	2	2
MAP2K3	0.063	0.068	-9999	-0.7	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.056	0.096	-9999	-0.69	6	6
PLCG1	0.059	0.066	-9999	-0.74	2	2
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.056	0.055	-9999	-0.69	2	2
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.048	0.058	-9999	-0.73	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.048	0.059	-9999	-0.73	2	2
cell migration	0.078	0.094	-9999	-0.71	2	2
mol:PI-3-4-5-P3	0.081	0.066	-9999	-0.7	2	2
FYN	0.011	0.05	-9999	-0.57	3	3
VEGFB/NRP1	0.055	0.061	-9999	-0.68	2	2
mol:NO	0.085	0.049	-9999	-0.48	2	2
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.048	-9999	-0.61	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.056	0.096	-9999	-0.69	6	6
VHL	0.016	0	-9999	-10000	0	0
ITGB3	-0.05	0.18	-9999	-0.57	46	46
NOS3	0.087	0.054	-9999	-0.55	2	2
VEGFR2 homodimer/VEGFA homodimer/Sck	0.027	0.11	-9999	-0.73	3	3
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.061	0.073	-9999	-0.62	3	3
PRKCB	-0.024	0.16	-9999	-0.73	4	4
VCL	0.014	0.029	-9999	-0.57	1	1
VEGFA165/NRP1	0.049	0.064	-9999	-0.72	2	2
VEGFR1/2 heterodimer/VEGFA homodimer	0.048	0.058	-9999	-0.73	2	2
VEGFA165/NRP2	0.005	0.091	-9999	-0.41	19	19
MAPKKK cascade	0.079	0.081	-9999	-0.55	6	6
NRP2	-0.012	0.12	-9999	-0.57	19	19
VEGFC homodimer	0.01	0.056	-9999	-0.55	4	4
NCK1	0.016	0	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	0.052	0.1	-9999	-0.65	3	3
MAP3K13	0.056	0.072	-9999	-0.74	2	2
PDPK1	0.087	0.059	-9999	-0.6	2	2

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0.009	-9999	-10000	0	0
DAPP1	0.016	0.097	-9999	-0.45	7	7
Src family/SYK family/BLNK-LAT/BTK-ITK	0.011	0.15	-9999	-0.5	21	21
mol:DAG	0.034	0.085	-9999	-0.23	16	16
HRAS	0.017	0.001	-9999	-10000	0	0
RAP1A	0.016	0.001	-9999	-10000	0	0
ARF5/GDP	0.042	0.044	-9999	-10000	0	0
PLCG2	0.009	0.06	-9999	-0.53	5	5
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	0	0.01	-9999	-10000	0	0
ARF1/GTP	0	0.008	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	0	0.01	-9999	-10000	0	0
ADAP1	-0.003	0.027	-9999	-10000	0	0
ARAP3	0	0.01	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.011	0.05	-9999	-0.57	3	3
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0.001	-9999	-10000	0	0
FYN	0.011	0.05	-9999	-0.57	3	3
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.013	0.041	-9999	-0.57	2	2
mol:Ca2+	0.029	0.048	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.011	0.05	-9999	-0.57	3	3
ZAP70	-0.007	0.11	-9999	-0.56	16	16
mol:IP3	0.034	0.064	-9999	-0.2	3	3
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.042	0.044	-9999	-10000	0	0
RhoA/GDP	-0.002	0.01	-9999	-10000	0	0
PDK1/Src/Hsp90	0.032	0	-9999	-10000	0	0
BLNK	-0.003	0.1	-9999	-0.57	13	13
actin cytoskeleton reorganization	0.065	0.04	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.027	0.048	-9999	-0.34	7	7
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	0	0.009	-9999	-10000	0	0
RhoA/GTP	0	0.009	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	0.012	0.12	-9999	-0.46	13	13
BLK	-0.06	0.19	-9999	-0.55	53	53
PDPK1	0.016	0	-9999	-10000	0	0
CYTH1	0	0.009	-9999	-10000	0	0
HCK	-0.008	0.11	-9999	-0.55	17	17
CYTH3	0	0.009	-9999	-10000	0	0
CYTH2	0	0.009	-9999	-10000	0	0
KRAS	0.015	0.026	-9999	-0.5	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.032	0.096	-9999	-0.44	16	16
SGK1	-0.019	0.094	-9999	-0.48	16	16
INPP5D	0.006	0.076	-9999	-0.57	7	7
mol:GDP	0.034	0.046	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.01	0.058	-9999	-0.57	4	4
ARF6/GDP	-0.002	0.01	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.01	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0.01	-9999	-10000	0	0
VAV1	-0.01	0.12	-9999	-0.56	18	18
mol:PI-3-4-P2	0.019	0.056	-9999	-0.41	7	7
RAS family/GTP/PI3K Class I	0.036	0.012	-9999	-10000	0	0
PLEKHA1	0.027	0.048	-9999	-0.34	7	7
Rac1/GDP	0.042	0.044	-9999	-10000	0	0
LAT	0.014	0.026	-9999	-0.51	1	1
Rac1/GTP	0.036	0.057	-9999	-0.27	6	6
ITK	-0.029	0.081	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.034	0.11	-9999	-0.33	17	17
LCK	0.007	0.068	-9999	-0.55	6	6
BTK	-0.015	0.059	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.091	0.03	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.002	0.095	-9999	-0.36	27	27
NFKBIA	0.053	0	-9999	-10000	0	0
BIRC2	0.013	0.036	-9999	-0.51	2	2
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.016	0	-9999	-10000	0	0
IKBKG	-0.005	0.02	-9999	-10000	0	0
IKK complex/A20	-0.013	0.046	-9999	-10000	0	0
NEMO/A20/RIP2	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	0.051	0.032	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.021	0	-9999	-10000	0	0
IKK complex/ELKS	-0.003	0.013	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0.032	0	-9999	-10000	0	0
NOD2	-0.019	0.13	-9999	-0.51	27	27
NFKB1	0.02	0	-9999	-10000	0	0
RELA	0.02	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.021	0.026	-9999	-0.36	2	2
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	0.004	0.084	-9999	-0.36	21	21
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.008	0.064	-9999	-0.57	5	5
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	-0.011	0.12	-9999	-0.51	21	21
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.053	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	0.059	0.031	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.006	0.026	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.052	0.038	-10000	0	-10000	0	0
CLOCK	0.019	0.002	-10000	0	-10000	0	0
TIMELESS/CRY2	0.049	0.027	-10000	0	-10000	0	0
DEC1/BMAL1	0.007	0.057	-10000	0	-0.35	10	10
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.049	0.016	-10000	0	-10000	0	0
ARNTL	0.019	0.002	-10000	0	-10000	0	0
TIMELESS	0.048	0.029	-10000	0	-10000	0	0
NPAS2	0.017	0.041	-10000	0	-0.56	2	2
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.016	0.007	0.062	3	-10000	0	3
CHEK1	0.009	0.057	-10000	0	-0.51	5	5
mol:HEME	0.016	0.007	-10000	0	-0.062	3	3
PER1	-0.007	0.11	-10000	0	-0.57	16	16
BMAL/CLOCK/NPAS2	0.05	0.027	-10000	0	-0.33	2	2
BMAL1/CLOCK	0.051	0.039	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.052	0.038	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.053	0.039	-10000	0	-10000	0	0
mol:NADPH	0.016	0.007	-10000	0	-0.062	3	3
PER1/TIMELESS	0.036	0.07	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.01	0.079	-10000	0	-0.51	10	10

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.12	0.083	-10000	0	-0.39	4	4
CaM/Ca2+	0.012	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.13	0.12	0.22	1	-0.37	7	8
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.026	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0.032	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	0.005	0.051	-10000	0	-0.51	4	4
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.012	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.036	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.05	-10000	0	-0.57	3	3
TRIP10	0.014	0.029	-10000	0	-0.57	1	1
TC10/GTP/CIP4/Exocyst	0.02	0.018	-10000	0	-0.35	1	1
AS160/14-3-3	0.042	0.042	-10000	0	-0.3	1	1
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	-0.14	0.12	-10000	0	-0.41	7	7
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.03	0	-10000	0	-10000	0	0
SFN	-0.031	0.15	-10000	0	-0.51	36	36
LNPEP	0.016	0	-10000	0	-10000	0	0
YWHAE	0.014	0.029	-10000	0	-0.57	1	1

×

mTOR signaling 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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.008	0.046	-10000	0	-0.28	11	11
FRAP1	0.016	0.01	-10000	0	-10000	0	0
AKT1	0.026	0.043	-10000	0	-0.23	11	11
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.011	0	-10000	0	-10000	0	0
mol:GTP	-0.005	0.028	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.007	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.004	0.023	-10000	0	-10000	0	0
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.011	0.057	-10000	0	-0.35	10	10
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.029	0.023	-10000	0	-10000	0	0
MAP3K5	0.011	0.019	-10000	0	-0.38	1	1
PIK3R1	0.014	0.029	-10000	0	-0.57	1	1
apoptosis	0.011	0.019	-10000	0	-0.38	1	1
mol:LY294002	0	0	-10000	0	-0.001	10	10
EIF4B	0.035	0.022	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.039	0.02	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.002	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.02	0.054	-10000	0	-0.31	11	11
mTOR/RHEB/GTP/Raptor/GBL	0.034	0.016	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
RHEB/GTP	-0.004	0.023	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	10	10
FKBP12/Rapamycin	0.012	0.002	-10000	0	-10000	0	0
PDPK1	-0.007	0.041	-10000	0	-0.25	11	11
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.024	0.033	-10000	0	-0.62	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.02	0	-10000	0	-10000	0	0
TSC1/TSC2	0.04	0.037	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	10	-10000	0	10
RPS6	0.016	0	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.001	0.06	-10000	0	-0.38	10	10
INS	0	0	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.007	0.041	-10000	0	-0.25	11	11
EIF4EBP1	0.012	0.015	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
PPP2R5D	0.023	0.01	-10000	0	-10000	0	0
peptide biosynthetic process	0.02	0	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.02	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.02	0.013	-10000	0	-10000	0	0

×

ceramide 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
MAP4K4	0.039	0.073	-10000	0	-10000	0	0
BAG4	0.016	0	-10000	0	-10000	0	0
BAD	0.032	0.025	-10000	0	-10000	0	0
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.02	0.14	-10000	0	-0.56	25	25
BAX	0.032	0.025	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.014	0.019	-10000	0	-10000	0	0
IKBKB	0.046	0.07	-10000	0	-10000	0	0
MAP2K2	0.046	0.024	-10000	0	-10000	0	0
MAP2K1	0.046	0.024	-10000	0	-10000	0	0
SMPD1	0.021	0.019	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.045	0.076	-10000	0	-10000	0	0
MAP2K4	0.04	0.023	-10000	0	-10000	0	0
protein ubiquitination	0.048	0.071	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.051	0.025	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.04	0.026	-10000	0	-0.2	1	1
CRADD	0.016	0	-10000	0	-10000	0	0
mol:ceramide	0.025	0.026	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0.021	0	-10000	0	-10000	0	0
MADD	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.032	0.025	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
RELA/p50	0.016	0	-10000	0	-10000	0	0
MAPK3	0.049	0.024	-10000	0	-10000	0	0
MAPK1	0.049	0.024	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.023	0	-10000	0	-10000	0	0
FADD	0.036	0.079	-10000	0	-0.29	2	2
KSR1	0.033	0.024	-10000	0	-10000	0	0
MAPK8	0.044	0.032	-10000	0	-0.22	3	3
TRAF2	0.016	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.046	0.07	-10000	0	-10000	0	0
TNF R/SODD	0.023	0	-10000	0	-10000	0	0
TNF	-0.011	0.12	-10000	0	-0.5	21	21
CYCS	0.037	0.031	0.15	13	-10000	0	13
IKBKG	0.046	0.07	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.033	0.075	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AIFM1	0.037	0.031	0.15	13	-10000	0	13
TNF/TNF R/SODD	0.016	0.071	-10000	0	-0.29	21	21
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.031	0.021	-10000	0	-10000	0	0
NSMAF	0.04	0.07	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.007	0.11	-10000	0	-0.57	16	16

×

HIF-2-alpha transcription factor network

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
MMP14	0.008	0.024	-10000	0	-10000	0	0
oxygen homeostasis	0.01	0.017	-10000	0	-10000	0	0
TCEB2	0.014	0.026	-10000	0	-0.51	1	1
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.001	0.04	-10000	0	-10000	0	0
EPO	0.12	0.21	-10000	0	-0.69	2	2
FIH (dimer)	0.026	0.015	-10000	0	-10000	0	0
APEX1	0.025	0.017	-10000	0	-10000	0	0
SERPINE1	0.13	0.22	-10000	0	-0.71	6	6
FLT1	0.011	0.025	-10000	0	-10000	0	0
ADORA2A	0.13	0.2	-10000	0	-0.57	4	4
germ cell development	0.093	0.26	-10000	0	-0.72	6	6
SLC11A2	0.14	0.2	-10000	0	-0.58	4	4
BHLHE40	0.14	0.21	-10000	0	-0.65	5	5
HIF1AN	0.026	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.081	0.14	-10000	0	-10000	0	0
ETS1	0.034	0.006	-10000	0	-10000	0	0
CITED2	0.008	0.019	-10000	0	-10000	0	0
KDR	0.006	0.085	-10000	0	-1.2	2	2
PGK1	0.14	0.2	-10000	0	-0.58	4	4
SIRT1	0.016	0.002	-10000	0	-10000	0	0
response to hypoxia	0	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.22	-10000	0	-0.64	6	6
EPAS1	0.089	0.1	-10000	0	-0.28	3	3
SP1	0.025	0.003	-10000	0	-10000	0	0
ABCG2	0.13	0.23	-10000	0	-0.66	7	7
EFNA1	0.13	0.21	-10000	0	-0.6	5	5
FXN	0.13	0.2	-10000	0	-0.57	4	4
POU5F1	0.092	0.26	-10000	0	-0.76	6	6
neuron apoptosis	-0.16	0.22	0.63	6	-10000	0	6
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	0.015	0.083	-10000	0	-0.56	8	8
EGLN2	0.026	0.016	-10000	0	-10000	0	0
EGLN1	0.026	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.031	0.016	-10000	0	-0.29	1	1
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.025	0.017	-10000	0	-10000	0	0
SLC2A1	0.13	0.2	-10000	0	-0.57	4	4
TWIST1	0.07	0.3	-10000	0	-0.65	33	33
ELK1	0.025	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.008	0.061	-10000	0	-10000	0	0
VEGFA	0.14	0.2	-10000	0	-0.57	5	5
CREBBP	0.016	0	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.05	0.04	-10000	0	-0.37	1	1
adherens junction organization	0.038	0.064	-10000	0	-0.4	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.046	0.064	-10000	0	-0.36	2	2
FMN1	0.029	0.078	-10000	0	-0.52	2	2
mol:IP3	0.042	0.039	-10000	0	-0.38	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.032	0.062	-10000	0	-0.61	1	1
CTNNB1	0.016	0.002	-10000	0	-10000	0	0
AKT1	0.048	0.044	-10000	0	-0.42	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.034	0.085	-10000	0	-0.41	14	14
CTNND1	0.017	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.04	0.058	-10000	0	-0.56	1	1
VASP	0.04	0.059	-10000	0	-0.57	1	1
ZYX	0.039	0.061	-10000	0	-0.57	1	1
JUB	0.038	0.065	-10000	0	-0.52	2	2
EGFR(dimer)	0.028	0.082	-10000	0	-0.54	2	2
E-cadherin/beta catenin-gamma catenin	-0.012	0.066	-10000	0	-0.34	15	15
mol:PI-3-4-5-P3	0.04	0.046	-10000	0	-0.44	1	1
PIK3CA	0.017	0.001	-10000	0	-10000	0	0
PI3K	0.041	0.046	-10000	0	-0.45	1	1
FYN	0.046	0.056	-10000	0	-0.31	1	1
mol:Ca2+	0.041	0.038	-10000	0	-0.37	1	1
JUP	0.013	0.041	-10000	0	-0.57	2	2
PIK3R1	0.015	0.029	-10000	0	-0.57	1	1
mol:DAG	0.042	0.039	-10000	0	-0.38	1	1
CDH1	-0.005	0.11	-10000	0	-0.57	14	14
RhoA/GDP	0.046	0.064	-10000	0	-0.36	2	2
establishment of polarity of embryonic epithelium	0.04	0.058	-10000	0	-0.56	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	-0.008	0.11	-10000	0	-0.54	17	17
CASR	0.038	0.056	-10000	0	-0.35	1	1
RhoA/GTP	-0.005	0.026	-10000	0	-0.34	1	1
AKT2	0.048	0.044	-10000	0	-0.42	1	1
actin cable formation	0.036	0.076	-10000	0	-0.5	2	2
apoptosis	-0.046	0.043	0.4	1	-10000	0	1
CTNNA1	0.017	0.001	-10000	0	-10000	0	0
mol:GDP	0.039	0.068	-10000	0	-0.39	2	2
PIP5K1A	0.04	0.059	-10000	0	-0.57	1	1
PLCG1	0.042	0.04	-10000	0	-0.39	1	1
Rac1/GTP	-0.017	0.062	-10000	0	-0.49	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.022	0.021	-9999	-0.41	1	1
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.027	0.039	-9999	-0.32	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.051	0.031	-9999	-10000	0	0
NFKBIA	0.029	0.035	-9999	-0.21	8	8
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.031	0	-9999	-10000	0	0
ARRB2	0.02	0	-9999	-10000	0	0
REL	0.009	0.062	-9999	-0.54	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.03	0.018	-9999	-0.34	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.031	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.024	0	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
NFKB1	0.026	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.037	0.034	-9999	-0.21	4	4
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.055	0.03	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	0.022	0.021	-9999	-0.41	1	1
NF kappa B1 p50/RelA	0.037	0.034	-9999	-0.21	4	4
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.01	0.058	-9999	-0.57	4	4
I kappa B alpha/PIK3R1	0.035	0.04	-9999	-0.49	1	1
cell death	0.053	0.029	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.027	0.039	-9999	-0.32	5	5
LCK	0.007	0.068	-9999	-0.55	6	6
BCL3	0.014	0.029	-9999	-0.57	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.027	0.047	-9999	-0.23	13	13
HDAC4	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.033	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
SUMO1/HDAC4	0.036	0	-9999	-10000	0	0
SUMO1/HDAC1	0.036	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.031	0.052	-9999	-0.26	13	13
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.025	0	-9999	-10000	0	0
Ran/GTP	0.032	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	-0.001	0.092	-9999	-0.51	13	13
UBE2I	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
PIAS2	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.038	0.015	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.026	0.015	-9999	-0.28	1	1
mol:DAG	0.036	0.053	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.034	0.014	-9999	-10000	0	0
CaM/Ca2+	0.043	0.05	-9999	-10000	0	0
HIF1A	0.024	0.025	-9999	-0.49	1	1
GAB1	0.016	0	-9999	-10000	0	0
AKT1	0.059	0.044	-9999	-10000	0	0
PLCG1	0.036	0.053	-9999	-10000	0	0
NOS3	0.066	0.041	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
mol:NO	0.065	0.04	-9999	-10000	0	0
FLT1	0.035	0.019	-9999	-0.34	1	1
PGF	-0.001	0.092	-9999	-0.51	13	13
VEGFR1 homodimer/NRP2/VEGFR121	0.029	0.072	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
eNOS/Hsp90	0.072	0.039	-9999	-10000	0	0
endothelial cell proliferation	-0.022	0.13	-9999	-0.41	8	8
mol:Ca2+	0.036	0.053	-9999	-10000	0	0
MAPK3	0.046	0.057	-9999	-10000	0	0
MAPK1	0.046	0.057	-9999	-10000	0	0
PIK3R1	0.014	0.029	-9999	-0.57	1	1
PLGF homodimer	-0.001	0.092	-9999	-0.51	13	13
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.012	0.12	-9999	-0.57	19	19
VEGFA homodimer	0.016	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.038	0.015	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.052	0.055	-9999	-10000	0	0
PI3K	0.043	0.053	-9999	-10000	0	0
PRKCA	0.039	0.06	-9999	-10000	0	0
PRKCB	-0.05	0.15	-9999	-0.52	5	5
VEGFR1 homodimer/PLGF homodimer	0.027	0.059	-9999	-10000	0	0
VEGFA	0.016	0	-9999	-10000	0	0
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	0.036	0.053	-9999	-10000	0	0
RASA1	0.045	0.014	-9999	-10000	0	0
NRP2	-0.012	0.12	-9999	-0.57	19	19
VEGFR1 homodimer	0.035	0.018	-9999	-0.34	1	1
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.058	0.072	-9999	-0.41	1	1
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.041	0.052	-9999	-10000	0	0
mol:L-citrulline	0.065	0.04	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.053	0.013	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.045	0.014	-9999	-10000	0	0
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	0.049	0.05	-9999	-10000	0	0
PDPK1	0.048	0.049	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.045	0.014	-9999	-10000	0	0
mol:NADP	0.065	0.04	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.051	0.013	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.02	0.079	-9999	-0.33	19	19

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.016	0	-9999	-10000	0	0
SMAD3	0.048	0	-9999	-10000	0	0
SMAD3/SMAD4	0.054	0.007	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0.032	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.044	0.025	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.024	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.018	0.047	-9999	-0.41	5	5
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.008	0.064	-9999	-0.57	5	5
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	0.011	0.051	-9999	-0.51	4	4
PIAS4	0.016	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.05	0.005	-10000	0	-10000	0	0
regulation of axonogenesis	-0.034	0.013	-10000	0	-10000	0	0
myoblast fusion	-0.023	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.035	0.3	4	-10000	0	4
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.013	0.004	-10000	0	-10000	0	0
mol:Choline	0.033	0.019	-10000	0	-0.34	1	1
lamellipodium assembly	0	0.015	-10000	0	-10000	0	0
MAPK3	0.034	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.039	0.035	-10000	0	-0.31	4	4
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	0.023	0.014	-10000	0	-10000	0	0
ARF1/GDP	0.032	0.013	-10000	0	-10000	0	0
ARF6	0.015	0.002	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.014	0.05	-10000	0	-0.57	3	3
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.034	0.004	-10000	0	-10000	0	0
actin filament bundle formation	-0.03	0.011	-10000	0	-10000	0	0
KALRN	-0.003	0.032	-10000	0	-0.31	2	2
RAB11FIP3/RAB11A	0.023	0	-10000	0	-10000	0	0
RhoA/GDP	0.031	0.012	-10000	0	-10000	0	0
NME1	0.017	0.026	-10000	0	-0.5	1	1
Rac1/GDP	0.031	0.012	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0	0.015	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0	0.014	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.002	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.024	0.021	-10000	0	-0.4	1	1
RAB11FIP3	0.016	0	-10000	0	-10000	0	0
tube morphogenesis	0	0.015	-10000	0	-10000	0	0
ruffle organization	0.034	0.013	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.025	0.004	-10000	0	-10000	0	0
PIP5K1A	0.034	0.013	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.019	-10000	0	-0.34	1	1
Rac1/GTP	0	0.015	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.009	0.039	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.047	0.036	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.016	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	0.047	0.028	-9999	-10000	0	0
YY1/LSF	0.036	0.013	-9999	-10000	0	0
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.031	0.04	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.031	0.031	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.037	0.034	-9999	-10000	0	0
HDAC1/Smad7	0.031	0.018	-9999	-0.34	1	1
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	0.031	0.031	-9999	-10000	0	0
NuRD/MBD3 Complex	0.056	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.041	0.03	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.011	0.12	-9999	-0.53	20	20
GATA1	0.011	0.007	-9999	-10000	0	0
Mad/Max	0.022	0.019	-9999	-0.36	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.066	0.003	-9999	-10000	0	0
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	0.025	0.035	-9999	-10000	0	0
KAT2B	0.014	0.029	-9999	-0.57	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.051	0	-9999	-10000	0	0
SIN3 complex	0.04	0	-9999	-10000	0	0
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	0.016	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	0.044	0.031	-9999	-10000	0	0
YY1/HDAC2	0.036	0.013	-9999	-10000	0	0
YY1/HDAC1	0.036	0.013	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.056	0	-9999	-10000	0	0
PPARG	0.015	0.099	-9999	-0.44	8	8
HDAC8/hEST1B	0.032	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.031	0.031	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.031	0.018	-9999	-0.34	1	1
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.059	0	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.025	0.035	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.035	0.015	-9999	-0.28	1	1
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.014	0.029	-9999	-0.57	1	1
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.026	-9999	-0.51	1	1
STAT3	0.03	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.043	0.012	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.043	0.012	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.03	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.035	-9999	-10000	0	0
histone deacetylation	0.055	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.042	0.029	-9999	-10000	0	0
nuclear export	-0.032	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	0.016	0.072	-9999	-0.3	7	7
GATA1/HDAC1	0.02	0.005	-9999	-10000	0	0
GATA1/HDAC3	0.02	0.034	-9999	-10000	0	0
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.004	0.084	-9999	-0.36	21	21
SIN3/HDAC complex/Mad/Max	0.055	0.005	-9999	-10000	0	0
NuRD Complex	0.065	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.017	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0.036	0	-9999	-10000	0	0
HDAC complex	0.04	0	-9999	-10000	0	0
GATA1/Fog1	0.02	0.005	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0.032	0	-9999	-10000	0	0
TNF	-0.011	0.12	-9999	-0.51	21	21
negative regulation of cell growth	0.055	0.005	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.056	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.041	0.038	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.053	0	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.016	0	-9999	-10000	0	0
MBD2	0.016	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.024	0	-9999	-10000	0	0
AP2	0.023	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.03	0	-9999	-10000	0	0
CD4	0.013	0.041	-9999	-0.57	2	2
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.032	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.02	0	-9999	-10000	0	0
Rac/GTP	0.013	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.03	0	-9999	-10000	0	0
ARFIP2	0.014	0	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.03	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.022	0	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.032	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.022	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.012	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.04	0.017	-9999	-0.2	2	2
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.013	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.03	0.026	-9999	-0.34	2	2

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.023	-9999	-9999
FBXW11	0.016	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.016	-9999	-9999
CHUK	0.016	-9999	-9999
NF kappa B2 p100/RelB	0.047	-9999	-9999
NFKB1	0.016	-9999	-9999
MAP3K14	0.016	-9999	-9999
NF kappa B1 p50/RelB	0.023	-9999	-9999
RELB	0.016	-9999	-9999
NFKB2	0.016	-9999	-9999
NF kappa B2 p52/RelB	0.021	-9999	-9999
regulation of B cell activation	0.021	-9999	-9999

pid_entity	TCGA.ZF.AA5P	TCGA.ZF.AA5N	TCGA.ZF.AA5H	TCGA.ZF.AA58
109_MAP3K5	0.063	-0.15	-0.045	0.063
47_PPARGC1A	0.016	-2.9e-16	-0.57	-0.57
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0.016	0.016	-0.57	-0.57
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	0.04	0.03	0.04	-0.3
30_TGFB1/TGF beta receptor Type II	0.019	0.019	0.019	0.015
84_STAT5B	0.036	-0.12	0.051	0.031
84_STAT5A	0.036	-0.12	0.051	0.031