PARADIGM pathway analysis of mRNASeq expression data - Kidney Renal Clear Cell Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	347
HIF-1-alpha transcription factor network	192
Nephrin/Neph1 signaling in the kidney podocyte	170
TCR signaling in naïve CD8+ T cells	134
TCGA08_p53	132
Aurora B signaling	111
Syndecan-4-mediated signaling events	110
IL12-mediated signaling events	105
FOXA2 and FOXA3 transcription factor networks	103
Glypican 1 network	103

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
TCGA08_retinoblastoma	0.7229	347	2779	8	-0.85	0.22	1000	-1000	-0.034	-1000
HIF-1-alpha transcription factor network	0.4000	192	14611	76	-1.3	0.026	1000	-1000	-0.16	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3542	170	5804	34	-0.62	0.016	1000	-1000	-0.096	-1000
TCR signaling in naïve CD8+ T cells	0.2792	134	12504	93	-0.67	0.33	1000	-1000	-0.13	-1000
TCGA08_p53	0.2750	132	927	7	-0.66	0.31	1000	-1000	-0.02	-1000
Aurora B signaling	0.2313	111	7503	67	-0.42	0.016	1000	-1000	-0.098	-1000
Syndecan-4-mediated signaling events	0.2292	110	7430	67	-0.65	0.11	1000	-1000	-0.12	-1000
IL12-mediated signaling events	0.2188	105	9178	87	-0.72	0.17	1000	-1000	-0.16	-1000
FOXA2 and FOXA3 transcription factor networks	0.2146	103	4770	46	-1.3	0.025	1000	-1000	-0.11	-1000
Glypican 1 network	0.2146	103	4949	48	-0.57	0.045	1000	-1000	-0.07	-1000
FOXM1 transcription factor network	0.2146	103	5267	51	-0.83	0.04	1000	-1000	-0.18	-1000
PDGFR-alpha signaling pathway	0.1958	94	4159	44	-0.28	0.034	1000	-1000	-0.089	-1000
amb2 Integrin signaling	0.1667	80	6625	82	-0.57	0.016	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.1583	76	6975	91	-0.84	0.54	1000	-1000	-0.15	-1000
JNK signaling in the CD4+ TCR pathway	0.1521	73	1247	17	-0.43	0.016	1000	-1000	-0.097	-1000
EGFR-dependent Endothelin signaling events	0.1396	67	1420	21	-0.68	0.016	1000	-1000	-0.098	-1000
Caspase cascade in apoptosis	0.1375	66	4930	74	-0.33	0.16	1000	-1000	-0.081	-1000
Aurora C signaling	0.1354	65	460	7	-0.4	0.014	1000	-1000	-0.067	-1000
Glypican 2 network	0.1292	62	251	4	-0.12	-1000	1000	-1000	-0.057	-1000
HIF-2-alpha transcription factor network	0.1229	59	2564	43	-0.76	0.33	1000	-1000	-0.1	-1000
IL23-mediated signaling events	0.1229	59	3561	60	-0.41	0.021	1000	-1000	-0.18	-1000
Syndecan-1-mediated signaling events	0.1187	57	1969	34	-0.41	0.016	1000	-1000	-0.11	-1000
BMP receptor signaling	0.1187	57	4664	81	-0.7	0.016	1000	-1000	-0.14	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1125	54	1807	33	-0.83	0.016	1000	-1000	-0.095	-1000
VEGFR1 specific signals	0.1083	52	2927	56	-0.48	0.049	1000	-1000	-0.12	-1000
Signaling events mediated by the Hedgehog family	0.0979	47	2445	52	-0.45	0.12	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	0.0917	44	4276	97	-0.35	0.042	1000	-1000	-0.14	-1000
IL27-mediated signaling events	0.0833	40	2080	51	-0.61	0.074	1000	-1000	-0.12	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0813	39	2687	68	-0.55	0.067	1000	-1000	-0.17	-1000
Effects of Botulinum toxin	0.0792	38	999	26	-0.37	0.016	1000	-1000	-0.087	-1000
Calcium signaling in the CD4+ TCR pathway	0.0771	37	1150	31	-0.48	0.016	1000	-1000	-0.15	-1000
Ephrin A reverse signaling	0.0750	36	257	7	-0.058	0	1000	-1000	-0.045	-1000
Arf6 signaling events	0.0729	35	2190	62	-0.68	0.016	1000	-1000	-0.095	-1000
p75(NTR)-mediated signaling	0.0708	34	4348	125	-0.43	0.016	1000	-1000	-0.16	-1000
IL2 signaling events mediated by STAT5	0.0688	33	747	22	-0.47	0.038	1000	-1000	-0.066	-1000
S1P1 pathway	0.0667	32	1173	36	-0.38	0.018	1000	-1000	-0.1	-1000
IL2 signaling events mediated by PI3K	0.0667	32	1903	58	-0.46	0.033	1000	-1000	-0.11	-1000
LPA4-mediated signaling events	0.0625	30	360	12	-0.17	0.028	1000	-1000	-0.031	-1000
PLK1 signaling events	0.0604	29	2511	85	-0.4	0.016	1000	-1000	-0.083	-1000
BCR signaling pathway	0.0604	29	2903	99	-0.35	0.034	1000	-1000	-0.14	-1000
Regulation of Telomerase	0.0583	28	2857	102	-0.68	0.045	1000	-1000	-0.14	-1000
Coregulation of Androgen receptor activity	0.0563	27	2109	76	-0.94	0.033	1000	-1000	-0.069	-1000
Integrins in angiogenesis	0.0563	27	2277	84	-0.38	0.04	1000	-1000	-0.14	-1000
IL6-mediated signaling events	0.0542	26	1986	75	-0.28	0.078	1000	-1000	-0.11	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0521	25	1384	54	-0.66	0.031	1000	-1000	-0.15	-1000
Glucocorticoid receptor regulatory network	0.0521	25	2885	114	-0.41	0.15	1000	-1000	-0.1	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0479	23	1808	78	-0.32	0.046	1000	-1000	-0.1	-1000
Visual signal transduction: Rods	0.0437	21	1121	52	-0.28	0.016	1000	-1000	-0.12	-1000
Signaling events mediated by PTP1B	0.0417	20	1584	76	-0.68	0.048	1000	-1000	-0.12	-1000
Aurora A signaling	0.0417	20	1221	60	-0.24	0.054	1000	-1000	-0.1	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0417	20	1839	88	-0.32	0.079	1000	-1000	-0.15	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0396	19	2310	120	-0.17	0.15	1000	-1000	-0.11	-1000
Syndecan-2-mediated signaling events	0.0375	18	1299	69	-0.57	0.056	1000	-1000	-0.088	-1000
Reelin signaling pathway	0.0375	18	1015	56	-0.24	0.016	1000	-1000	-0.13	-1000
Endothelins	0.0375	18	1816	96	-0.35	0.089	1000	-1000	-0.11	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0375	18	831	45	-0.59	0.061	1000	-1000	-0.13	-1000
Regulation of nuclear SMAD2/3 signaling	0.0354	17	2432	136	-0.46	0.091	1000	-1000	-0.11	-1000
EPO signaling pathway	0.0333	16	918	55	-0.29	0.018	1000	-1000	-0.14	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0312	15	562	37	-0.3	0.022	1000	-1000	-0.11	-1000
Wnt signaling	0.0312	15	111	7	-0.073	0.016	1000	-1000	-0.087	-1000
S1P3 pathway	0.0312	15	649	42	-0.38	0.062	1000	-1000	-0.092	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0271	13	374	28	-0.14	0.024	1000	-1000	-0.088	-1000
Thromboxane A2 receptor signaling	0.0271	13	1415	105	-0.68	0.069	1000	-1000	-0.11	-1000
Ceramide signaling pathway	0.0271	13	1043	76	-0.68	0.23	1000	-1000	-0.093	-1000
FoxO family signaling	0.0271	13	888	64	-0.57	0.12	1000	-1000	-0.11	-1000
LPA receptor mediated events	0.0271	13	1405	102	-0.39	0.062	1000	-1000	-0.13	-1000
Class I PI3K signaling events	0.0271	13	961	73	-0.48	0.036	1000	-1000	-0.11	-1000
PLK2 and PLK4 events	0.0250	12	38	3	-0.014	0.01	1000	-1000	-0.034	-1000
Presenilin action in Notch and Wnt signaling	0.0250	12	760	61	-0.19	0.092	1000	-1000	-0.11	-1000
IFN-gamma pathway	0.0250	12	821	68	-0.38	0.017	1000	-1000	-0.14	-1000
FAS signaling pathway (CD95)	0.0250	12	603	47	-0.45	0.031	1000	-1000	-0.068	-1000
Canonical Wnt signaling pathway	0.0250	12	627	51	-0.19	0.096	1000	-1000	-0.078	-1000
E-cadherin signaling events	0.0250	12	62	5	-0.023	0.016	1000	-1000	-0.07	-1000
Regulation of Androgen receptor activity	0.0229	11	800	70	-0.97	0.04	1000	-1000	-0.1	-1000
ErbB4 signaling events	0.0208	10	730	69	-0.18	0.11	1000	-1000	-0.13	-1000
Noncanonical Wnt signaling pathway	0.0208	10	270	26	-0.12	0.016	1000	-1000	-0.14	-1000
S1P5 pathway	0.0208	10	174	17	-0.14	0.045	1000	-1000	-0.084	-1000
Nongenotropic Androgen signaling	0.0208	10	554	52	-0.17	0.074	1000	-1000	-0.085	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0208	10	1338	125	-0.4	0.044	1000	-1000	-0.15	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0208	10	762	74	-0.68	0.1	1000	-1000	-0.15	-1000
a4b1 and a4b7 Integrin signaling	0.0187	9	48	5	-0.022	0.016	1000	-1000	-0.056	-1000
S1P4 pathway	0.0187	9	249	25	-0.14	0.035	1000	-1000	-0.08	-1000
TCGA08_rtk_signaling	0.0167	8	214	26	-0.28	0.041	1000	-1000	-0.031	-1000
Visual signal transduction: Cones	0.0146	7	301	38	-0.036	0.016	1000	-1000	-0.099	-1000
Canonical NF-kappaB pathway	0.0125	6	256	39	-0.2	0.074	1000	-1000	-0.13	-1000
Signaling events mediated by PRL	0.0125	6	219	34	-0.056	0.049	1000	-1000	-0.082	-1000
ErbB2/ErbB3 signaling events	0.0104	5	333	65	-0.13	0.061	1000	-1000	-0.098	-1000
Insulin-mediated glucose transport	0.0104	5	168	32	-0.079	0.067	1000	-1000	-0.095	-1000
Signaling events mediated by HDAC Class III	0.0104	5	208	40	-0.065	0.032	1000	-1000	-0.066	-1000
IL1-mediated signaling events	0.0104	5	363	62	-0.096	0.062	1000	-1000	-0.15	-1000
Signaling events regulated by Ret tyrosine kinase	0.0104	5	483	82	-0.059	0.032	1000	-1000	-0.13	-1000
Ephrin B reverse signaling	0.0104	5	274	48	-0.022	0.034	1000	-1000	-0.1	-1000
Syndecan-3-mediated signaling events	0.0104	5	188	35	-0.04	0.016	1000	-1000	-0.096	-1000
Arf6 trafficking events	0.0104	5	366	71	-0.13	0.05	1000	-1000	-0.12	-1000
Class IB PI3K non-lipid kinase events	0.0104	5	15	3	-0.007	0.007	1000	-1000	-0.033	-1000
p38 MAPK signaling pathway	0.0104	5	252	44	-0.11	0.051	1000	-1000	-0.094	-1000
Arf6 downstream pathway	0.0083	4	198	43	-0.034	0.034	1000	-1000	-0.059	-1000
Signaling mediated by p38-gamma and p38-delta	0.0083	4	72	15	0	0.037	1000	-1000	-0.065	-1000
E-cadherin signaling in the nascent adherens junction	0.0083	4	375	76	-0.026	0.068	1000	-1000	-0.12	-1000
Ras signaling in the CD4+ TCR pathway	0.0083	4	73	17	-0.037	0.055	1000	-1000	-0.06	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0063	3	316	85	-0.037	0.081	1000	-1000	-0.12	-1000
EPHB forward signaling	0.0063	3	301	85	-0.073	0.075	1000	-1000	-0.14	-1000
BARD1 signaling events	0.0042	2	167	57	-0.18	0.044	1000	-1000	-0.11	-1000
Osteopontin-mediated events	0.0042	2	88	38	-0.029	0.1	1000	-1000	-0.16	-1000
Cellular roles of Anthrax toxin	0.0042	2	103	39	-0.023	0.028	1000	-1000	-0.043	-1000
ceramide signaling pathway	0.0042	2	121	49	-0.12	0.054	1000	-1000	-0.077	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0042	2	109	52	-0.029	0.092	1000	-1000	-0.095	-1000
Paxillin-dependent events mediated by a4b1	0.0042	2	98	36	-0.031	0.031	1000	-1000	-0.11	-1000
Regulation of p38-alpha and p38-beta	0.0042	2	133	54	-0.04	0.074	1000	-1000	-0.088	-1000
Insulin Pathway	0.0042	2	173	74	-0.034	0.057	1000	-1000	-0.14	-1000
Plasma membrane estrogen receptor signaling	0.0042	2	247	86	-0.16	0.076	1000	-1000	-0.12	-1000
PDGFR-beta signaling pathway	0.0042	2	235	97	-0.057	0.09	1000	-1000	-0.13	-1000
E-cadherin signaling in keratinocytes	0.0042	2	112	43	-0.3	0.056	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class II	0.0021	1	102	75	-0.026	0.051	1000	-1000	-0.087	-1000
Circadian rhythm pathway	0.0021	1	25	22	-0.019	0.066	1000	-1000	-0.11	-1000
Hedgehog signaling events mediated by Gli proteins	0.0021	1	119	65	-0.062	0.093	1000	-1000	-0.092	-1000
Class I PI3K signaling events mediated by Akt	0.0021	1	81	68	-0.079	0.061	1000	-1000	-0.1	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0021	1	154	83	-0.079	0.081	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class I	0.0021	1	162	104	-0.029	0.064	1000	-1000	-0.1	-1000
Retinoic acid receptors-mediated signaling	0.0021	1	93	58	-0.022	0.065	1000	-1000	-0.11	-1000
Atypical NF-kappaB pathway	0.0021	1	37	31	-0.024	0.036	1000	-1000	-0.1	-1000
IGF1 pathway	0.0021	1	93	57	-0.068	0.073	1000	-1000	-0.14	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0	0.063	1000	-1000	-0.098	-1000
mTOR signaling pathway	0.0000	0	32	53	-0.005	0.046	1000	-1000	-0.082	-1000
Nectin adhesion pathway	0.0000	0	28	63	-0.015	0.082	1000	-1000	-0.13	-1000
TRAIL signaling pathway	0.0000	0	19	48	-0.002	0.072	1000	-1000	-0.11	-1000
Signaling mediated by p38-alpha and p38-beta	0.0000	0	42	44	-0.043	0.052	1000	-1000	-0.075	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.088	-1000
Rapid glucocorticoid signaling	0.0000	0	10	20	-0.005	0.016	1000	-1000	-0.062	-1000
Arf1 pathway	0.0000	0	25	54	-0.011	0.035	1000	-1000	-0.082	-1000
Alternative NF-kappaB pathway	0.0000	0	8	13	-0.006	0.016	1000	-1000	-0.1	-1000
Total	NA	3866	203837	7203	-41	-990	131000	-131000	-14	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.009	0.089	-10000	0	-0.88	5	5
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.85	0.16	-10000	0	-0.88	463	463
CCND2	0.18	0.046	0.19	462	-10000	0	462
RB1	-0.2	0.048	-10000	0	-0.21	462	462
CDK4	0.22	0.05	0.22	462	-10000	0	462
CDK6	0.2	0.052	0.21	462	-0.18	1	463
G1/S progression	0.2	0.052	0.21	462	-10000	0	462

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.98	0.53	-9999	-1.3	293	293
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.9	286	286
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.98	0.53	-9999	-1.3	301	301
AP1	-0.012	0.081	-9999	-0.57	10	10
ABCG2	-0.98	0.53	-9999	-1.3	301	301
HIF1A	-0.1	0.048	-9999	-10000	0	0
TFF3	-0.99	0.53	-9999	-1.3	303	303
GATA2	0.003	0.1	-9999	-0.76	9	9
AKT1	-0.094	0.052	-9999	-10000	0	0
response to hypoxia	-0.13	0.058	-9999	-10000	0	0
MCL1	-0.98	0.53	-9999	-1.3	302	302
NDRG1	-0.98	0.53	-9999	-1.3	292	292
SERPINE1	-1	0.56	-9999	-1.4	279	279
FECH	-0.98	0.53	-9999	-1.3	303	303
FURIN	-0.98	0.53	-9999	-1.3	293	293
NCOA2	0.005	0.07	-9999	-0.76	4	4
EP300	-0.1	0.074	-9999	-0.34	6	6
HMOX1	-0.99	0.55	-9999	-1.3	304	304
BHLHE40	-0.98	0.53	-9999	-1.3	302	302
BHLHE41	-1.1	0.58	-9999	-1.5	290	290
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.077	0.046	-9999	-10000	0	0
ENG	-0.056	0.055	-9999	-10000	0	0
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.98	0.53	-9999	-1.3	293	293
ABCB1	-0.3	0.42	-9999	-1.3	63	63
TFRC	-0.98	0.53	-9999	-1.3	292	292
CXCR4	-1.1	0.6	-9999	-1.5	297	297
TF	-1	0.58	-9999	-1.4	301	301
CITED2	-0.98	0.53	-9999	-1.3	300	300
HIF1A/ARNT	-1.3	0.85	-9999	-1.8	313	313
LDHA	-0.085	0.064	-9999	-0.86	2	2
ETS1	-0.98	0.53	-9999	-1.3	293	293
PGK1	-0.98	0.53	-9999	-1.3	293	293
NOS2	-0.98	0.53	-9999	-1.3	302	302
ITGB2	-1	0.57	-9999	-1.4	301	301
ALDOA	-0.98	0.53	-9999	-1.3	291	291
Cbp/p300/CITED2	-0.98	0.53	-9999	-1.4	275	275
FOS	0	0.11	-9999	-0.76	10	10
HK2	-1.2	0.58	-9999	-1.5	362	362
SP1	0.021	0.029	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.2	9	9
HK1	-0.98	0.53	-9999	-1.4	278	278
NPM1	-0.98	0.53	-9999	-1.3	293	293
EGLN1	-0.98	0.53	-9999	-1.3	302	302
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.98	0.53	-9999	-1.3	293	293
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.092	0.17	-9999	-0.8	19	19
IGFBP1	-1	0.57	-9999	-1.4	298	298
VEGFA	-0.77	0.41	-9999	-1.1	218	218
HIF1A/JAB1	-0.052	0.026	-9999	-10000	0	0
CP	-1.2	0.59	-9999	-1.5	357	357
CXCL12	-0.98	0.53	-9999	-1.3	296	296
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.98	0.53	-9999	-1.3	293	293
EGLN3	-1.3	0.51	-9999	-1.5	375	375
CA9	-1.3	0.47	-9999	-1.5	390	390
TERT	-1	0.55	-9999	-1.4	310	310
ENO1	-0.98	0.53	-9999	-1.4	275	275
PFKL	-0.98	0.53	-9999	-1.4	278	278
NCOA1	0.014	0.004	-9999	-10000	0	0
ADM	-1	0.57	-9999	-1.4	306	306
ARNT	-0.1	0.046	-9999	-10000	0	0
HNF4A	-0.046	0.22	-9999	-0.76	41	41
ADFP	-0.99	0.53	-9999	-1.3	306	306
SLC2A1	-0.63	0.33	-9999	-0.97	152	152
LEP	-1	0.55	-9999	-1.4	310	310
HIF1A/ARNT/Cbp/p300	-0.7	0.33	-9999	-0.92	289	289
EPO	-0.61	0.39	-9999	-1.1	170	170
CREBBP	-0.1	0.074	-9999	-0.35	5	5
HIF1A/ARNT/Cbp/p300/HDAC7	-0.75	0.38	-9999	-0.99	289	289
PFKFB3	-0.98	0.53	-9999	-1.3	302	302
NT5E	-0.98	0.53	-9999	-1.3	291	291

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.49	0.26	0.63	374	-10000	0	374
KIRREL	-0.049	0.078	-10000	0	-0.84	4	4
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.5	0.26	-10000	0	-0.63	374	374
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.54	0.31	-10000	0	-0.86	209	209
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.42	0.25	-10000	0	-0.67	209	209
FYN	-0.51	0.3	-10000	0	-0.81	209	209
mol:Ca2+	-0.53	0.31	-10000	0	-0.84	209	209
mol:DAG	-0.54	0.31	-10000	0	-0.85	209	209
NPHS2	-0.42	0.39	-10000	0	-0.82	231	231
mol:IP3	-0.54	0.31	-10000	0	-0.85	209	209
regulation of endocytosis	-0.48	0.28	-10000	0	-0.76	209	209
Nephrin/NEPH1/podocin/Cholesterol	-0.55	0.32	-10000	0	-0.66	398	398
establishment of cell polarity	-0.49	0.26	-10000	0	-0.63	374	374
Nephrin/NEPH1/podocin/NCK1-2	-0.5	0.3	-10000	0	-0.8	209	209
Nephrin/NEPH1/beta Arrestin2	-0.49	0.29	-10000	0	-0.78	209	209
NPHS1	-0.62	0.33	-10000	0	-0.8	374	374
Nephrin/NEPH1/podocin	-0.52	0.3	-10000	0	-0.82	209	209
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	-0.54	0.31	-10000	0	-0.86	209	209
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.54	0.31	-10000	0	-0.86	209	209
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.5	0.3	-10000	0	-0.8	209	209
cytoskeleton organization	-0.54	0.32	-10000	0	-0.86	209	209
Nephrin/NEPH1	-0.37	0.2	-10000	0	-0.47	374	374
Nephrin/NEPH1/ZO-1	-0.4	0.22	-10000	0	-0.51	374	374

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.34	0.33	-10000	0	-0.7	212	212
FYN	-0.42	0.5	-10000	0	-0.95	216	216
LAT/GRAP2/SLP76	-0.37	0.39	-10000	0	-0.77	217	217
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.26	0.29	-10000	0	-0.54	222	222
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.081	0.071	-10000	0	-0.19	31	31
MAP3K8	0.012	0.057	-10000	0	-0.86	2	2
mol:Ca2+	-0.12	0.045	-10000	0	-0.14	319	319
integrin-mediated signaling pathway	-0.018	0.1	-10000	0	-0.58	15	15
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.42	0.45	-10000	0	-0.87	227	227
TRPV6	-0.67	0.26	-10000	0	-0.77	417	417
CD28	-0.06	0.24	-10000	0	-0.87	37	37
SHC1	-0.45	0.49	-10000	0	-0.95	224	224
receptor internalization	-0.53	0.57	-10000	0	-1.1	231	231
PRF1	-0.5	0.6	-10000	0	-1.1	207	207
KRAS	0.016	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.19	0.22	-10000	0	-0.42	210	210
LAT	-0.52	0.54	-10000	0	-1	238	238
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	216	216
CD3E	-0.37	0.44	-10000	0	-0.88	205	205
CD3G	-0.33	0.43	-10000	0	-0.87	186	186
RASGRP2	-0.023	0.029	-10000	0	-0.14	2	2
RASGRP1	-0.24	0.28	-10000	0	-0.51	214	214
HLA-A	0.006	0.041	-10000	0	-0.88	1	1
RASSF5	-0.012	0.15	-10000	0	-0.86	15	15
RAP1A/GTP/RAPL	-0.018	0.1	-10000	0	-0.59	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.038	0.082	-10000	0	-0.14	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.15	0.13	-10000	0	-0.34	85	85
PRKCA	-0.14	0.17	-10000	0	-0.31	198	198
GRAP2	-0.046	0.22	-10000	0	-0.86	34	34
mol:IP3	-0.16	0.34	0.26	154	-0.5	210	364
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.54	0.64	-10000	0	-1.1	230	230
ORAI1	0.33	0.13	0.38	416	-10000	0	416
CSK	-0.47	0.51	-10000	0	-0.99	223	223
B7 family/CD28	-0.53	0.52	-10000	0	-1	227	227
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.58	0.63	-10000	0	-1.2	226	226
PTPN6	-0.45	0.53	-10000	0	-1	214	214
VAV1	-0.5	0.54	-10000	0	-1	232	232
Monovalent TCR/CD3	-0.46	0.54	-10000	0	-1	219	219
CBL	0.016	0	-10000	0	-10000	0	0
LCK	-0.45	0.53	-10000	0	-1	220	220
PAG1	-0.47	0.51	-10000	0	-0.99	224	224
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.55	0.64	-10000	0	-1.2	222	222
CD80	-0.19	0.37	-10000	0	-0.87	108	108
CD86	-0.13	0.32	-10000	0	-0.87	76	76
PDK1/CARD11/BCL10/MALT1	-0.18	0.16	-10000	0	-0.42	93	93
HRAS	0.016	0	-10000	0	-10000	0	0
GO:0035030	-0.36	0.42	-10000	0	-0.78	227	227
CD8A	-0.4	0.44	-10000	0	-0.87	225	225
CD8B	-0.31	0.43	-10000	0	-0.88	174	174
PTPRC	-0.091	0.28	-10000	0	-0.87	54	54
PDK1/PKC theta	-0.33	0.36	-10000	0	-0.7	221	221
CSK/PAG1	-0.45	0.5	-10000	0	-0.96	220	220
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.031	-10000	0	-0.68	1	1
GRAP2/SLP76	-0.44	0.44	-10000	0	-0.9	222	222
STIM1	0.18	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.065	0.11	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.6	0.66	-10000	0	-1.2	231	231
mol:DAG	-0.21	0.26	-10000	0	-0.46	218	218
RAP1A/GDP	-0.014	0.035	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	159	159
cytotoxic T cell degranulation	-0.46	0.56	-10000	0	-1	212	212
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.32	0.35	-10000	0	-0.67	224	224
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.27	0.44	0.3	102	-0.71	218	320
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.48	0.44	-10000	0	-0.87	272	272
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.39	0.35	-10000	0	-0.75	222	222
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.52	0.56	-10000	0	-1.1	230	230
CARD11	-0.17	0.36	-10000	0	-0.86	101	101
PRKCB	-0.14	0.17	-10000	0	-0.31	208	208
PRKCE	-0.14	0.17	-10000	0	-0.31	198	198
PRKCQ	-0.4	0.43	-10000	0	-0.82	226	226
LCP2	-0.043	0.22	-10000	0	-0.86	32	32
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.21	0.24	-10000	0	-0.45	220	220
IKK complex	-0.029	0.084	-10000	0	-10000	0	0
RAS family/GDP	-0.012	0.011	-10000	0	-10000	0	0
MAP3K14	-0.13	0.18	-10000	0	-0.32	158	158
PDPK1	-0.24	0.27	-10000	0	-0.51	217	217
TCR/CD3/MHC I/CD8/Fyn	-0.57	0.66	-10000	0	-1.3	219	219

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.66	0.13	-10000	0	-0.68	463	463
TP53	-0.17	0.037	-10000	0	-10000	0	0
Senescence	-0.17	0.036	-10000	0	-10000	0	0
Apoptosis	-0.17	0.036	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.31	0.06	0.33	463	-10000	0	463
MDM4	0.014	0.04	-10000	0	-0.86	1	1

×

Aurora B signaling

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
Condensin I complex	-0.25	0.32	-9999	-0.68	154	154
STMN1	-0.3	0.35	-9999	-0.66	229	229
Aurora B/RasGAP/Survivin	-0.41	0.48	-9999	-0.87	233	233
Chromosomal passenger complex/Cul3 protein complex	-0.17	0.23	-9999	-0.49	138	138
BIRC5	-0.25	0.41	-9999	-0.89	140	140
DES	-0.38	0.34	-9999	-0.6	276	276
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	230	230
Aurora B/TACC1	-0.27	0.3	-9999	-0.58	229	229
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	229	229
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.074	0.091	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.42	0.5	-9999	-0.9	233	233
Cul3 protein complex	-0.015	0.084	-9999	-0.48	15	15
KIF2C	-0.16	0.18	-9999	-0.32	218	218
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.4	0.44	-9999	-0.87	228	228
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	229	229
SEPT1	-0.1	0.3	-9999	-0.86	63	63
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.19	0.24	-9999	-0.46	168	168
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.004	-9999	-10000	0	0
H3F3B	-0.17	0.21	-9999	-0.39	229	229
AURKB	-0.41	0.44	-9999	-0.87	229	229
AURKC	0.014	0.04	-9999	-0.86	1	1
CDCA8	-0.026	0.17	-9999	-0.9	18	18
cytokinesis	-0.35	0.37	-9999	-0.74	203	203
Aurora B/Septin1	-0.37	0.42	-9999	-0.83	197	197
AURKA	0.001	0.099	-9999	-0.87	6	6
INCENP	0.007	0.009	-9999	-10000	0	0
KLHL13	-0.008	0.14	-9999	-0.76	15	15
BUB1	-0.4	0.44	-9999	-0.87	223	223
hSgo1/Aurora B/Survivin	-0.4	0.49	-9999	-0.85	234	234
EVI5	0.009	0.008	-9999	-10000	0	0
RhoA/GTP	-0.32	0.34	-9999	-0.71	187	187
SGOL1	-0.015	0.16	-9999	-0.86	17	17
CENPA	-0.3	0.35	-9999	-0.63	236	236
NCAPG	-0.29	0.42	-9999	-0.86	167	167
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	229	229
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	229	229
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.14	0.34	-9999	-0.86	84	84
NPM1	-0.22	0.24	-9999	-0.47	229	229
RASA1	0.016	0	-9999	-10000	0	0
KLHL9	0.016	0	-9999	-10000	0	0
mitotic prometaphase	-0.01	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.3	0.34	-9999	-0.66	229	229
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.35	0.38	-9999	-0.78	191	191
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.22	0.24	-9999	-0.47	229	229
MYLK	-0.17	0.21	-9999	-0.39	229	229
KIF23	-0.008	0.11	-9999	-0.88	8	8
VIM	-0.35	0.41	-9999	-0.74	241	241
RACGAP1	0.003	0.058	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.22	0.24	-9999	-0.47	229	229
Chromosomal passenger complex	-0.36	0.41	-9999	-0.75	232	232
Chromosomal passenger complex/EVI5	-0.37	0.48	-9999	-0.94	168	168
TACC1	0.016	0	-9999	-10000	0	0
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

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.056	0.14	-9999	-0.54	37	37
Syndecan-4/Syndesmos	-0.47	0.4	-9999	-0.85	218	218
positive regulation of JNK cascade	-0.54	0.38	-9999	-0.85	263	263
Syndecan-4/ADAM12	-0.58	0.5	-9999	-1	241	241
CCL5	-0.36	0.44	-9999	-0.86	206	206
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.052	0.24	-9999	-0.86	37	37
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.38	0.37	-9999	-0.73	256	256
ADAM12	-0.23	0.4	-9999	-0.86	135	135
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	-0.1	0.071	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.48	0.4	-9999	-0.86	221	221
Syndecan-4/CXCL12/CXCR4	-0.6	0.43	-9999	-0.94	263	263
Syndecan-4/Laminin alpha3	-0.47	0.4	-9999	-0.85	221	221
MDK	-0.052	0.24	-9999	-0.86	37	37
Syndecan-4/FZD7	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/Midkine	-0.5	0.42	-9999	-0.89	229	229
FZD7	0.014	0.035	-9999	-0.76	1	1
Syndecan-4/FGFR1/FGF	-0.44	0.34	-9999	-0.77	220	220
THBS1	0.014	0.035	-9999	-0.76	1	1
integrin-mediated signaling pathway	-0.45	0.36	-9999	-0.8	222	222
positive regulation of MAPKKK cascade	-0.54	0.38	-9999	-0.85	263	263
Syndecan-4/TACI	-0.51	0.43	-9999	-0.9	229	229
CXCR4	-0.3	0.42	-9999	-0.86	170	170
cell adhesion	-0.009	0.12	-9999	-0.46	19	19
Syndecan-4/Dynamin	-0.47	0.4	-9999	-0.85	218	218
Syndecan-4/TSP1	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/GIPC	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/RANTES	-0.65	0.46	-9999	-1	272	272
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.007	0.13	-9999	-0.77	14	14
LAMA3	0.007	0.089	-9999	-0.86	5	5
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.067	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.47	0.4	-9999	-0.85	218	218
TFPI	0	0.11	-9999	-0.82	9	9
F2	-0.32	0.43	-9999	-0.87	182	182
alpha5/beta1 Integrin	-0.051	0.18	-9999	-0.67	37	37
positive regulation of cell adhesion	-0.46	0.39	-9999	-0.82	224	224
ACTN1	0.014	0.04	-9999	-0.86	1	1
TNC	0	0.11	-9999	-0.76	10	10
Syndecan-4/CXCL12	-0.47	0.4	-9999	-0.85	222	222
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	0.003	0.099	-9999	-0.76	8	8
TNFRSF13B	-0.065	0.25	-9999	-0.86	43	43
FGF2	0.009	0.073	-9999	-0.78	4	4
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.48	0.39	-9999	-0.86	218	218
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.043	0.23	-9999	-0.83	37	37
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.047	-9999	-0.85	1	1
vasculogenesis	-0.44	0.37	-9999	-0.8	219	219
SDC4	-0.52	0.44	-9999	-0.94	218	218
Syndecan-4/Tenascin C	-0.48	0.39	-9999	-0.85	222	222
Syndecan-4/PI-4-5-P2/PKC alpha	-0.08	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.47	0.4	-9999	-0.85	218	218
MMP9	-0.39	0.44	-9999	-0.86	223	223
Rac1/GTP	-0.018	0.12	-9999	-0.48	19	19
cytoskeleton organization	-0.44	0.37	-9999	-0.8	218	218
GIPC1	0.014	0.035	-9999	-0.76	1	1
Syndecan-4/TFPI	-0.48	0.4	-9999	-0.85	223	223

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.17	0.26	-10000	0	-0.62	77	77
TBX21	-0.56	0.68	-10000	0	-1.2	210	210
B2M	0.01	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.021	-10000	0	-10000	0	0
IL12RB1	-0.28	0.43	-10000	0	-0.91	152	152
GADD45B	-0.31	0.43	-10000	0	-0.81	156	156
IL12RB2	-0.11	0.31	-10000	0	-0.88	67	67
GADD45G	-0.32	0.44	-10000	0	-0.82	163	163
natural killer cell activation	-0.01	0.03	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.002	0.099	-10000	0	-0.87	6	6
IL2RA	-0.16	0.35	-10000	0	-0.86	96	96
IFNG	-0.39	0.44	-10000	0	-0.86	220	220
STAT3 (dimer)	-0.39	0.47	-10000	0	-0.86	209	209
HLA-DRB5	-0.04	0.22	-10000	0	-0.86	31	31
FASLG	-0.62	0.7	-10000	0	-1.3	226	226
NF kappa B2 p52/RelB	-0.53	0.54	-10000	0	-1.1	206	206
CD4	0	0.12	-10000	0	-0.86	9	9
SOCS1	0.007	0.089	-10000	0	-0.86	5	5
EntrezGene:6955	-0.002	0.01	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	216	216
CD3E	-0.36	0.44	-10000	0	-0.87	205	205
CD3G	-0.33	0.43	-10000	0	-0.87	186	186
IL12Rbeta2/JAK2	-0.083	0.25	-10000	0	-0.69	67	67
CCL3	-0.5	0.63	-10000	0	-1.2	190	190
CCL4	-0.52	0.67	-10000	0	-1.3	184	184
HLA-A	0.008	0.041	-10000	0	-0.87	1	1
IL18/IL18R	-0.15	0.31	-10000	0	-0.6	153	153
NOS2	-0.38	0.5	-10000	0	-0.92	181	181
IL12/IL12R/TYK2/JAK2/SPHK2	-0.17	0.26	-10000	0	-0.57	92	92
IL1R1	-0.46	0.6	-10000	0	-1.1	199	199
IL4	0.014	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.021	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.72	0.83	-10000	0	-1.5	238	238
RAB7A	-0.25	0.37	-10000	0	-0.74	80	80
lysosomal transport	-0.24	0.36	-10000	0	-0.69	90	90
FOS	-0.38	0.5	-10000	0	-0.94	191	191
STAT4 (dimer)	-0.42	0.53	-10000	0	-0.98	193	193
STAT5A (dimer)	-0.66	0.62	-10000	0	-1.2	239	239
GZMA	-0.58	0.71	-10000	0	-1.3	210	210
GZMB	-0.54	0.68	-10000	0	-1.2	201	201
HLX	-0.083	0.28	-10000	0	-0.86	54	54
LCK	-0.53	0.7	-10000	0	-1.2	207	207
TCR/CD3/MHC II/CD4	-0.38	0.47	-10000	0	-0.88	212	212
IL2/IL2R	-0.44	0.42	-10000	0	-0.71	292	292
MAPK14	-0.32	0.44	-10000	0	-0.82	161	161
CCR5	-0.49	0.6	-10000	0	-1.1	207	207
IL1B	0.005	0.082	-10000	0	-0.86	4	4
STAT6	-0.086	0.15	-10000	0	-10000	0	0
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.014	0.04	-10000	0	-0.86	1	1
NFKB1	0.016	0	-10000	0	-10000	0	0
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.095	0.3	-10000	0	-0.9	57	57
CD8A	-0.4	0.44	-10000	0	-0.87	225	225
CD8B	-0.31	0.43	-10000	0	-0.87	174	174
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.17	0.26	0.6	78	-10000	0	78
IL2RB	-0.47	0.44	-10000	0	-0.86	263	263
proteasomal ubiquitin-dependent protein catabolic process	-0.38	0.48	-10000	0	-0.88	191	191
IL2RG	-0.045	0.22	-10000	0	-0.86	33	33
IL12	-0.072	0.24	-10000	0	-0.72	58	58
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	159	159
IL2	-0.008	0.12	-10000	0	-0.86	10	10
SPHK2	0.012	0.05	-10000	0	-0.76	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.047	-10000	0	-0.92	1	1
IL12/IL12R/TYK2/JAK2	-0.6	0.79	-10000	0	-1.4	207	207
MAP2K3	-0.32	0.44	-10000	0	-0.8	181	181
RIPK2	0.014	0.04	-10000	0	-0.86	1	1
MAP2K6	-0.32	0.44	-10000	0	-0.8	181	181
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.011	0.069	-10000	0	-0.86	3	3
IL18RAP	-0.25	0.41	-10000	0	-0.87	143	143
IL12Rbeta1/TYK2	-0.21	0.35	-10000	0	-0.72	152	152
EOMES	-0.31	0.38	-10000	0	-0.74	205	205
STAT1 (dimer)	-0.46	0.51	-10000	0	-0.95	226	226
T cell proliferation	-0.28	0.37	-10000	0	-0.68	170	170
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.82	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.38	0.33	-10000	0	-0.76	178	178
ATF2	-0.28	0.41	-10000	0	-0.76	156	156

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.45	0.48	-10000	0	-1.2	98	98
PCK1	-0.94	0.72	-10000	0	-1.5	252	252
HNF4A	-0.59	0.58	-10000	0	-1.4	124	124
KCNJ11	-0.45	0.51	-10000	0	-1.3	91	91
AKT1	-0.17	0.18	-10000	0	-10000	0	0
response to starvation	-0.02	0.039	-10000	0	-10000	0	0
DLK1	-0.56	0.58	-10000	0	-1.3	150	150
NKX2-1	-0.048	0.21	0.58	1	-0.82	3	4
ACADM	-0.45	0.48	-10000	0	-1.2	93	93
TAT	-0.52	0.35	-10000	0	-0.9	166	166
CEBPB	-0.026	0.14	-10000	0	-0.92	12	12
CEBPA	-0.019	0.12	-10000	0	-0.9	9	9
TTR	-0.91	0.48	-10000	0	-1.2	293	293
PKLR	-0.51	0.56	-10000	0	-1.3	115	115
APOA1	-0.56	0.57	-10000	0	-1.4	109	109
CPT1C	-0.45	0.48	-10000	0	-1.2	104	104
ALAS1	-0.17	0.2	-10000	0	-10000	0	0
TFRC	-0.63	0.42	-10000	0	-1	185	185
FOXF1	-0.004	0.12	-10000	0	-0.84	10	10
NF1	0.025	0.001	-10000	0	-10000	0	0
HNF1A (dimer)	-0.001	0.083	-10000	0	-0.81	4	4
CPT1A	-0.45	0.48	-10000	0	-1.2	94	94
HMGCS1	-0.45	0.48	-10000	0	-1.2	98	98
NR3C1	0.003	0.067	-10000	0	-0.97	1	1
CPT1B	-0.47	0.5	-10000	0	-1.3	96	96
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.017	0.005	-10000	0	-10000	0	0
GCK	-0.46	0.49	-10000	0	-1.2	91	91
CREB1	-0.027	0.065	-10000	0	-10000	0	0
IGFBP1	-0.32	0.42	-10000	0	-1	111	111
PDX1	-0.19	0.22	-10000	0	-1.1	5	5
UCP2	-0.45	0.48	-10000	0	-1.2	94	94
ALDOB	-0.95	0.63	-10000	0	-1.3	337	337
AFP	-0.74	0.51	-10000	0	-0.99	310	310
BDH1	-0.6	0.57	-10000	0	-1.2	175	175
HADH	-0.44	0.49	-10000	0	-1.2	88	88
F2	-0.66	0.62	-10000	0	-1.4	162	162
HNF1A	-0.001	0.083	-10000	0	-0.81	4	4
G6PC	-0.81	0.66	-10000	0	-1.5	227	227
SLC2A2	-0.32	0.47	-10000	0	-1.7	41	41
INS	0.01	0.055	-10000	0	-10000	0	0
FOXA1	-0.4	0.41	-10000	0	-1	133	133
FOXA3	-0.62	0.38	-10000	0	-0.93	264	264
FOXA2	-0.52	0.57	-10000	0	-1.4	105	105
ABCC8	-0.45	0.49	-10000	0	-1.2	95	95
ALB	-1.3	0.49	-10000	0	-1.4	420	420

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.005	0.051	-10000	0	-0.5	5	5
fibroblast growth factor receptor signaling pathway	-0.005	0.051	-10000	0	-0.5	5	5
LAMA1	-0.007	0.13	-10000	0	-0.77	14	14
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.57	99	99
SMAD2	0.045	0.022	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.023	-10000	0	-0.5	1	1
GPC1/Laminin alpha1	-0.018	0.1	-10000	0	-0.58	15	15
TDGF1	-0.57	0.33	-10000	0	-0.76	364	364
CRIPTO/GPC1	-0.43	0.25	-10000	0	-0.57	364	364
APP/GPC1	-0.002	0.037	-10000	0	-0.57	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.36	0.22	-10000	0	-0.48	364	364
FLT1	0.008	0.08	-10000	0	-0.86	4	4
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.022	-10000	0	-0.48	1	1
SERPINC1	-0.066	0.24	-10000	0	-0.77	49	49
FYN	-0.36	0.22	-10000	0	-0.48	364	364
FGR	-0.36	0.23	-10000	0	-0.49	364	364
positive regulation of MAPKKK cascade	-0.37	0.25	-10000	0	-0.5	364	364
SLIT2	-0.14	0.31	-10000	0	-0.76	98	98
GPC1/NRG	-0.014	0.089	-10000	0	-0.57	12	12
NRG1	-0.002	0.12	-10000	0	-0.76	11	11
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.26	0.3	-10000	0	-0.59	216	216
LYN	-0.36	0.22	-10000	0	-0.48	364	364
mol:Spermine	0.014	0.027	-10000	0	-0.58	1	1
cell growth	-0.005	0.051	-10000	0	-0.5	5	5
BMP signaling pathway	-0.014	0.035	0.76	1	-10000	0	1
SRC	-0.36	0.22	-10000	0	-0.48	364	364
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.075	0.26	-10000	0	-0.86	47	47
GPC1	0.014	0.035	-10000	0	-0.76	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.38	0.44	-10000	0	-0.86	215	215
BLK	-0.4	0.26	-10000	0	-0.52	369	369
HCK	-0.39	0.25	-10000	0	-0.51	373	373
FGF2	0.009	0.073	-10000	0	-0.78	4	4
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.008	0.08	-10000	0	-0.86	4	4
TGFBR2	0.016	0	-10000	0	-10000	0	0
cell death	-0.002	0.037	-10000	0	-0.57	2	2
ATIII/GPC1	-0.061	0.18	-10000	0	-0.58	50	50
PLA2G2A/GPC1	-0.067	0.2	-10000	0	-0.66	48	48
LCK	-0.39	0.24	-10000	0	-0.51	372	372
neuron differentiation	-0.014	0.089	-10000	0	-0.57	12	12
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.035	-10000	0	-0.76	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.2	0.68	-10000	0	-1.2	116	116
PLK1	-0.11	0.41	-10000	0	-0.8	124	124
BIRC5	-0.14	0.43	-10000	0	-0.79	140	140
HSPA1B	-0.2	0.68	-10000	0	-1.2	119	119
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.21	0.69	-10000	0	-1.2	121	121
FOXM1	-0.39	1	-10000	0	-1.9	128	128
XRCC1	-0.2	0.68	-10000	0	-1.2	119	119
FOXM1B/p19	-0.5	0.5	0.51	1	-1.2	130	131
Cyclin D1/CDK4	-0.2	0.61	-10000	0	-1.1	114	114
CDC2	-0.23	0.73	-10000	0	-1.3	128	128
TGFA	-0.17	0.61	-10000	0	-1.1	106	106
SKP2	-0.2	0.68	-10000	0	-1.2	119	119
CCNE1	0.004	0.1	-10000	0	-0.88	6	6
CKS1B	-0.2	0.68	-10000	0	-1.2	119	119
RB1	-0.2	0.26	-10000	0	-0.7	86	86
FOXM1C/SP1	-0.3	0.78	-10000	0	-1.4	130	130
AURKB	-0.26	0.47	-10000	0	-0.77	204	204
CENPF	-0.22	0.72	-10000	0	-1.3	124	124
CDK4	0.02	0.022	-10000	0	-10000	0	0
MYC	-0.16	0.61	-10000	0	-1	116	116
CHEK2	0.038	0.064	-10000	0	-0.91	1	1
ONECUT1	-0.2	0.66	-10000	0	-1.2	120	120
CDKN2A	-0.83	0.16	-10000	0	-0.86	463	463
LAMA4	-0.29	0.7	-10000	0	-1.2	131	131
FOXM1B/HNF6	-0.29	0.8	-10000	0	-1.5	120	120
FOS	-0.21	0.69	-10000	0	-1.2	121	121
SP1	0.017	0.005	-10000	0	-10000	0	0
CDC25B	-0.2	0.69	-10000	0	-1.2	119	119
response to radiation	0.013	0.05	-10000	0	-10000	0	0
CENPB	-0.2	0.68	-10000	0	-1.2	114	114
CENPA	-0.3	0.78	-10000	0	-1.3	152	152
NEK2	-0.26	0.76	-10000	0	-1.4	133	133
HIST1H2BA	-0.21	0.68	-10000	0	-1.2	119	119
CCNA2	-0.16	0.36	-10000	0	-0.88	96	96
EP300	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.29	0.82	-10000	0	-1.5	126	126
CCNB2	-0.26	0.76	-10000	0	-1.4	128	128
CCNB1	-0.23	0.73	-10000	0	-1.3	122	122
ETV5	-0.2	0.68	-10000	0	-1.2	119	119
ESR1	-0.2	0.68	-10000	0	-1.2	120	120
CCND1	-0.19	0.64	-10000	0	-1.1	116	116
GSK3A	0.036	0.042	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.084	0.29	-10000	0	-0.64	96	96
CDK2	0.015	0.016	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.44	0.59	-10000	0	-1.3	133	133
GAS1	-0.24	0.71	-10000	0	-1.2	133	133
MMP2	-0.2	0.68	-10000	0	-1.2	119	119
RB1/FOXM1C	-0.22	0.68	-10000	0	-1.2	116	116
CREBBP	0.016	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.38	-9999	-0.76	184	184
PDGF/PDGFRA/CRKL	-0.21	0.27	-9999	-0.55	184	184
positive regulation of JUN kinase activity	-0.16	0.2	-9999	-0.46	7	7
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.22	0.27	-9999	-0.56	185	185
AP1	-0.16	0.24	-9999	-1.3	10	10
mol:IP3	-0.2	0.29	-9999	-0.57	184	184
PLCG1	-0.2	0.29	-9999	-0.57	184	184
PDGF/PDGFRA/alphaV Integrin	-0.21	0.27	-9999	-0.55	184	184
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.29	-9999	-0.56	184	184
CAV3	0.003	0.04	-9999	-0.86	1	1
CAV1	-0.05	0.23	-9999	-0.86	36	36
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.46	7	7
PDGF/PDGFRA/Shf	-0.21	0.27	-9999	-0.55	185	185
FOS	-0.12	0.26	-9999	-1.2	10	10
JUN	-0.013	0.017	-9999	-10000	0	0
oligodendrocyte development	-0.21	0.27	-9999	-0.55	184	184
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
mol:DAG	-0.2	0.29	-9999	-0.57	184	184
PDGF/PDGFRA	-0.28	0.38	-9999	-0.76	184	184
actin cytoskeleton reorganization	-0.21	0.27	-9999	-0.55	184	184
SRF	0.034	0.009	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
PI3K	-0.18	0.23	-9999	-0.46	184	184
PDGF/PDGFRA/Crk/C3G	-0.18	0.23	-9999	-0.46	184	184
JAK1	-0.19	0.28	-9999	-0.55	184	184
ELK1/SRF	-0.15	0.2	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.035	-9999	-0.76	1	1
CSNK2A1	0.017	0.022	-9999	-10000	0	0
GO:0007205	-0.2	0.3	-9999	-0.58	184	184
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.2	-9999	-0.46	7	7
PDGF/PDGFRA/SHB	-0.21	0.27	-9999	-0.55	184	184
PDGF/PDGFRA/Caveolin-1	-0.26	0.3	-9999	-0.59	212	212
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.27	-9999	-0.5	184	184
PIK3CA	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.21	0.27	-9999	-0.55	184	184
JAK-STAT cascade	-0.19	0.28	-9999	-0.55	184	184
cell proliferation	-0.21	0.27	-9999	-0.55	185	185

×

amb2 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.15	0.29	-9999	-0.67	105	105
alphaM/beta2 Integrin/GPIbA	-0.14	0.28	-9999	-0.66	102	102
alphaM/beta2 Integrin/proMMP-9	-0.4	0.43	-9999	-0.76	254	254
PLAUR	-0.028	0.19	-9999	-0.86	24	24
HMGB1	0.015	0.013	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.14	0.28	-9999	-0.67	101	101
AGER	-0.13	0.33	-9999	-0.86	79	79
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.048	0.23	-9999	-0.86	35	35
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.23	0.34	-9999	-0.66	158	158
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
CYR61	0.008	0.079	-9999	-0.76	5	5
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.26	0.21	-9999	-0.57	112	112
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.02	0.16	-9999	-0.76	22	22
MYH2	-0.35	0.26	-9999	-0.65	172	172
MST1R	0.006	0.088	-9999	-0.78	6	6
leukocyte activation during inflammatory response	-0.28	0.35	-9999	-0.64	210	210
APOB	-0.27	0.41	-9999	-0.86	158	158
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.007	0.089	-9999	-0.86	5	5
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.035	-9999	-0.76	1	1
alphaM/beta2 Integrin/CTGF	-0.15	0.29	-9999	-0.67	105	105
alphaM/beta2 Integrin	-0.31	0.25	-9999	-0.54	216	216
JAM3 homodimer	0.016	0	-9999	-10000	0	0
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	-0.003	0.13	-9999	-0.86	10	10
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.31	0.25	-9999	-0.53	216	216
cell adhesion	-0.14	0.28	-9999	-0.66	102	102
NFKB1	-0.18	0.37	-9999	-0.95	58	58
THY1	0.014	0.035	-9999	-0.76	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.2	0.28	-9999	-0.6	159	159
alphaM/beta2 Integrin/LRP/tPA	-0.14	0.27	-9999	-0.62	103	103
IL6	-0.2	0.41	-9999	-0.91	91	91
ITGB2	-0.17	0.36	-9999	-0.86	99	99
elevation of cytosolic calcium ion concentration	-0.16	0.3	-9999	-0.63	119	119
alphaM/beta2 Integrin/JAM2/JAM3	-0.13	0.26	-9999	-0.61	101	101
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.14	0.28	-9999	-0.84	39	39
alphaM/beta2 Integrin/uPA/Plg	-0.37	0.34	-9999	-0.8	126	126
RhoA/GTP	-0.38	0.27	-9999	-0.68	179	179
positive regulation of phagocytosis	-0.26	0.27	-9999	-0.71	100	100
Ron/MSP	-0.016	0.098	-9999	-0.63	12	12
alphaM/beta2 Integrin/uPAR/uPA	-0.16	0.3	-9999	-0.64	119	119
alphaM/beta2 Integrin/uPAR	-0.17	0.32	-9999	-0.7	116	116
PLAU	0.004	0.093	-9999	-0.76	7	7
PLAT	-0.004	0.12	-9999	-0.76	12	12
actin filament polymerization	-0.34	0.24	-9999	-0.62	172	172
MST1	0.005	0.098	-9999	-0.86	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.29	0.36	-9999	-0.65	210	210
TNF	-0.15	0.34	-9999	-0.85	62	62
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.15	0.29	-9999	-0.66	108	108
fibrinolysis	-0.36	0.34	-9999	-0.79	126	126
HCK	-0.034	0.2	-9999	-0.86	27	27
dendritic cell antigen processing and presentation	-0.31	0.25	-9999	-0.53	216	216
VTN	-0.11	0.29	-9999	-0.77	76	76
alphaM/beta2 Integrin/CYR61	-0.15	0.29	-9999	-0.66	106	106
LPA	0.002	0.069	-9999	-0.86	3	3
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.37	0.41	-9999	-0.7	255	255
FN1	-0.052	0.24	-9999	-0.86	37	37
alphaM/beta2 Integrin/Thy1	-0.14	0.29	-9999	-0.67	101	101
MPO	-0.013	0.15	-9999	-0.86	15	15
KNG1	-0.57	0.33	-9999	-0.76	363	363
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.34	0.26	-9999	-0.64	168	168
ELA2	0	0	-9999	-10000	0	0
PLG	-0.4	0.38	-9999	-0.76	256	256
CTGF	0.006	0.086	-9999	-0.76	6	6
alphaM/beta2 Integrin/Hck	-0.17	0.35	-9999	-0.77	105	105
ITGAM	-0.02	0.17	-9999	-0.87	19	19
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.35	-9999	-0.7	126	126
HP	-0.21	0.38	-9999	-0.86	121	121
leukocyte adhesion	-0.18	0.27	-9999	-0.78	57	57
SELP	-0.02	0.16	-9999	-0.76	22	22

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.48	-10000	0	-1.2	110	110
STAT6 (cleaved dimer)	-0.59	0.5	-10000	0	-1.1	181	181
IGHG1	-0.17	0.19	-10000	0	-0.62	14	14
IGHG3	-0.48	0.46	-10000	0	-1	148	148
AKT1	-0.28	0.34	-10000	0	-0.82	83	83
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.25	0.32	-10000	0	-0.81	85	85
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.79	63	63
THY1	-0.48	0.49	-10000	0	-1.2	108	108
MYB	-0.22	0.39	-10000	0	-0.86	130	130
HMGA1	0.014	0.04	-10000	0	-0.86	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.4	0.43	-10000	0	-0.96	124	124
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.8	63	63
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.008	0.08	-10000	0	-0.86	4	4
SOCS5	0.026	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.48	-10000	0	-1.1	170	170
SOCS1	-0.33	0.34	-10000	0	-0.79	85	85
SOCS3	-0.3	0.35	-10000	0	-0.94	59	59
FCER2	-0.42	0.44	-10000	0	-1.1	84	84
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.51	0.51	-10000	0	-1.2	118	118
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.23	0.28	-10000	0	-0.77	54	54
T cell proliferation	-0.51	0.52	-10000	0	-1.2	127	127
IL4R/JAK1	-0.48	0.48	-10000	0	-1.1	114	114
EGR2	-0.49	0.5	-10000	0	-1.2	116	116
JAK2	0.008	0.023	-10000	0	-10000	0	0
JAK3	-0.17	0.36	-10000	0	-0.87	102	102
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.007	0.016	-10000	0	-10000	0	0
COL1A2	-0.22	0.31	-10000	0	-0.9	64	64
CCL26	-0.49	0.49	-10000	0	-1.2	116	116
IL4R	-0.51	0.52	-10000	0	-1.2	115	115
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.55	0.56	-10000	0	-1.3	138	138
IL13RA1	0.008	0.023	-10000	0	-10000	0	0
IRF4	-0.28	0.44	-10000	0	-1	116	116
ARG1	-0.17	0.27	-10000	0	-0.79	44	44
CBL	-0.36	0.4	-10000	0	-0.93	112	112
GTF3A	0.011	0.03	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.006	0.044	-10000	0	-10000	0	0
IRF4/BCL6	-0.28	0.39	-10000	0	-0.95	110	110
CD40LG	-0.09	0.31	-10000	0	-0.92	57	57
MAPK14	-0.36	0.4	-10000	0	-0.95	105	105
mitosis	-0.27	0.32	-10000	0	-0.77	81	81
STAT6	-0.55	0.56	-10000	0	-1.2	137	137
SPI1	-0.097	0.3	-10000	0	-0.86	64	64
RPS6KB1	-0.25	0.31	-10000	0	-0.77	68	68
STAT6 (dimer)	-0.56	0.56	-10000	0	-1.2	137	137
STAT6 (dimer)/PARP14	-0.51	0.52	-10000	0	-1.2	121	121
mast cell activation	0.012	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.31	0.37	-10000	0	-0.89	96	96
FRAP1	-0.28	0.34	-10000	0	-0.82	83	83
LTA	-0.61	0.56	-10000	0	-1.3	156	156
FES	0.012	0.05	-10000	0	-0.76	2	2
T-helper 1 cell differentiation	0.54	0.54	1.2	138	-10000	0	138
CCL11	-0.7	0.61	-10000	0	-1.3	218	218
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.3	0.35	-10000	0	-0.83	98	98
IL2RG	-0.04	0.22	-10000	0	-0.86	33	33
IL10	-0.5	0.51	-10000	0	-1.2	119	119
IRS1	0.012	0.05	-10000	0	-0.76	2	2
IRS2	0.001	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.13	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.1	114	114
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.38	-10000	0	-0.87	108	108
COL1A1	-0.41	0.44	-10000	0	-0.92	185	185
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.49	-10000	0	-1.2	101	101
IL2R gamma/JAK3	-0.17	0.37	-10000	0	-0.84	105	105
TFF3	-0.5	0.51	-10000	0	-1.2	121	121
ALOX15	-0.49	0.49	-10000	0	-1.1	115	115
MYBL1	-0.052	0.24	-10000	0	-0.86	37	37
T-helper 2 cell differentiation	-0.43	0.42	-10000	0	-0.95	128	128
SHC1	0.014	0.04	-10000	0	-0.86	1	1
CEBPB	-0.002	0.14	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.3	-10000	0	-0.77	67	67
mol:PI-3-4-5-P3	-0.28	0.34	-10000	0	-0.82	83	83
PI3K	-0.3	0.36	-10000	0	-0.89	85	85
DOK2	-0.035	0.21	-10000	0	-0.86	28	28
ETS1	0.028	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.28	-10000	0	-0.74	60	60
ITGB3	-0.48	0.49	-10000	0	-1.2	113	113
PIGR	-0.84	0.71	-10000	0	-1.5	249	249
IGHE	0.028	0.093	0.28	17	-0.37	4	21
MAPKKK cascade	-0.21	0.27	-10000	0	-0.72	59	59
BCL6	0.012	0.006	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	107	107
RETNLB	-0.49	0.48	-10000	0	-1.2	107	107
SELP	-0.51	0.53	-10000	0	-1.2	113	113
AICDA	-0.62	0.55	-10000	0	-1.2	175	175

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.43	0.55	-9999	-0.93	221	221
MAP4K1	-0.35	0.43	-9999	-0.86	197	197
MAP3K8	0.012	0.057	-9999	-0.86	2	2
PRKCB	0.007	0.085	-9999	-0.82	5	5
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	-0.16	0.3	-9999	-0.62	121	121
JUN	0.001	0.076	-9999	-0.53	4	4
MAP3K7	-0.16	0.3	-9999	-0.62	121	121
GRAP2	-0.046	0.22	-9999	-0.86	34	34
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.14	0.29	-9999	-0.59	121	121
LAT	-0.25	0.4	-9999	-0.86	143	143
LCP2	-0.043	0.22	-9999	-0.86	32	32
MAPK8	-0.011	0.081	-9999	-0.57	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.21	0.3	-9999	-0.67	121	121
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.41	0.52	-9999	-1.2	121	121

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EGF/EGFR	-0.39	0.17	-9999	-0.87	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.37	0.14	-9999	-0.91	9	9
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.012	0.057	-9999	-0.86	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.68	0.23	-9999	-0.76	432	432
EGF/EGFR dimer/SHC	-0.45	0.16	-9999	-0.5	433	433
mol:GDP	-0.37	0.14	-9999	-0.89	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.017	0.17	-9999	-0.86	18	18
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.34	0.13	-9999	-0.82	9	9
SHC1	0.014	0.04	-9999	-0.86	1	1
HRAS/GDP	-0.34	0.13	-9999	-0.83	9	9
FRAP1	-0.35	0.13	-9999	-0.86	9	9
EGF/EGFR dimer	-0.52	0.19	-9999	-0.58	433	433
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.028	0.13	-9999	-0.66	20	20

×

Caspase cascade in apoptosis

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
TOP1	-0.13	0.27	-10000	0	-0.5	154	154
ACTA1	-0.19	0.36	-10000	0	-0.68	155	155
NUMA1	-0.13	0.27	-10000	0	-0.5	154	154
SPTAN1	-0.19	0.36	-10000	0	-0.68	154	154
LIMK1	-0.19	0.36	-10000	0	-0.68	155	155
BIRC3	-0.12	0.32	-10000	0	-0.86	74	74
BIRC2	0.011	0.007	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.28	0.47	-10000	0	-0.88	168	168
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0.007	-10000	0	-10000	0	0
PTK2	-0.13	0.27	-10000	0	-0.5	154	154
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.35	-10000	0	-0.66	154	154
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.19	0.36	-10000	0	-0.81	100	100
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.3	0.28	-10000	0	-0.54	263	263
BID	-0.09	0.17	-10000	0	-0.37	100	100
MAP3K1	-0.043	0.11	-10000	0	-0.22	73	73
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.19	0.36	-10000	0	-0.68	152	152
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.012	0.095	-10000	0	-0.21	33	33
neuron apoptosis	0.011	0.046	-10000	0	-0.62	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.17	0.35	-10000	0	-0.65	154	154
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.05	0.16	-10000	0	-0.39	27	27
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.17	0.35	-10000	0	-0.77	100	100
CASP7	0.051	0.13	0.34	74	-10000	0	74
KRT18	-0.002	0.047	-10000	0	-0.3	2	2
apoptosis	-0.17	0.33	-10000	0	-0.7	104	104
DFFA	-0.19	0.36	-10000	0	-0.68	154	154
DFFB	-0.19	0.36	-10000	0	-0.68	154	154
PARP1	-0.013	0.095	0.21	33	-10000	0	33
actin filament polymerization	0.16	0.33	0.72	100	-10000	0	100
TNF	0.002	0.11	-10000	0	-0.81	8	8
CYCS	-0.068	0.13	-10000	0	-0.28	100	100
SATB1	-0.037	0.15	-10000	0	-0.48	3	3
SLK	-0.19	0.36	-10000	0	-0.68	154	154
p15 BID/BAX	-0.073	0.16	-10000	0	-10000	0	0
CASP2	0.031	0.09	-10000	0	-0.43	1	1
JNK cascade	0.043	0.11	0.22	73	-10000	0	73
CASP3	-0.21	0.38	-10000	0	-0.72	154	154
LMNB2	0.011	0.086	-10000	0	-0.39	4	4
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.081	0.19	-10000	0	-0.52	74	74
negative regulation of DNA binding	-0.29	0.28	-10000	0	-0.54	263	263
stress fiber formation	-0.18	0.35	-10000	0	-0.66	154	154
GZMB	-0.33	0.51	-10000	0	-0.99	168	168
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.008	0.091	-10000	0	-0.37	7	7
APP	0.011	0.046	-10000	0	-0.62	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	-0.17	0.31	-10000	0	-0.67	106	106
LMNA	0.011	0.086	-10000	0	-0.39	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.03	0.074	-10000	0	-0.41	7	7
LRDD	0.003	0.1	-10000	0	-0.85	7	7
SREBF1	-0.19	0.36	-10000	0	-0.68	155	155
APAF-1/Caspase 9	-0.009	0.063	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.13	0.26	-10000	0	-0.49	154	154
CFL2	-0.17	0.34	-10000	0	-0.75	100	100
GAS2	-0.2	0.36	-10000	0	-0.68	157	157
positive regulation of apoptosis	0.015	0.087	-10000	0	-0.38	4	4
PRF1	-0.22	0.39	-10000	0	-0.86	126	126

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.26	0.27	-9999	-0.53	230	230
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.065	0.068	-9999	-10000	0	0
AURKB	-0.4	0.44	-9999	-0.86	229	229
AURKC	0.014	0.04	-9999	-0.86	1	1

×

Glypican 2 network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.052	0.24	-9999	-0.86	37	37
GPC2	-0.083	0.28	-9999	-0.86	54	54
GPC2/Midkine	-0.12	0.29	-9999	-0.74	80	80
neuron projection morphogenesis	-0.12	0.29	-9999	-0.74	80	80

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.027	0.083	-10000	0	-0.73	6	6
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.014	0.035	-10000	0	-0.76	1	1
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.23	0.14	-10000	0	-0.55	3	3
EPO	-0.4	0.41	-10000	0	-0.9	132	132
FIH (dimer)	0.014	0.02	-10000	0	-10000	0	0
APEX1	0.013	0.014	-10000	0	-10000	0	0
SERPINE1	-0.34	0.4	-10000	0	-0.92	102	102
FLT1	-0.017	0.073	-10000	0	-0.76	4	4
ADORA2A	-0.3	0.34	-10000	0	-0.82	68	68
germ cell development	-0.4	0.44	-10000	0	-0.89	183	183
SLC11A2	-0.28	0.34	-10000	0	-0.81	68	68
BHLHE40	-0.28	0.34	-10000	0	-0.81	68	68
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.52	200	200
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.02	0.024	-10000	0	-10000	0	0
KDR	-0.014	0.068	-10000	0	-1.4	1	1
PGK1	-0.28	0.34	-10000	0	-0.81	68	68
SIRT1	0.012	0.007	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.34	0.41	-10000	0	-1	68	68
EPAS1	-0.27	0.19	-10000	0	-0.44	202	202
SP1	0.026	0.005	-10000	0	-10000	0	0
ABCG2	-0.29	0.34	-10000	0	-0.81	69	69
EFNA1	-0.29	0.34	-10000	0	-0.81	69	69
FXN	-0.3	0.34	-10000	0	-0.82	68	68
POU5F1	-0.42	0.47	-10000	0	-0.95	183	183
neuron apoptosis	0.33	0.39	0.96	68	-10000	0	68
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	-0.76	0.29	-10000	0	-0.87	424	424
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.022	-10000	0	-0.48	1	1
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.31	0.36	-10000	0	-0.89	74	74
TWIST1	-0.3	0.34	-10000	0	-0.83	71	71
ELK1	0.026	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.5	142	142
VEGFA	-0.46	0.48	-10000	0	-0.93	221	221
CREBBP	0.016	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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
CCL2	-0.26	0.48	-10000	0	-1	68	68
IL23A	-0.24	0.48	-10000	0	-1.1	58	58
NF kappa B1 p50/RelA/I kappa B alpha	-0.33	0.39	-10000	0	-1	80	80
positive regulation of T cell mediated cytotoxicity	-0.29	0.53	-10000	0	-1.1	88	88
ITGA3	-0.25	0.47	-10000	0	-1.1	60	60
IL17F	-0.15	0.35	-10000	0	-0.74	35	35
IL12B	-0.088	0.3	-10000	0	-0.89	57	57
STAT1 (dimer)	-0.29	0.5	-10000	0	-1.1	86	86
CD4	-0.26	0.48	-10000	0	-1.1	64	64
IL23	-0.28	0.49	-10000	0	-1.1	73	73
IL23R	-0.012	0.15	-10000	0	-0.8	9	9
IL1B	-0.26	0.49	-10000	0	-1.1	65	65
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.25	0.48	-10000	0	-1	69	69
TYK2	0.016	0.025	-10000	0	-10000	0	0
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0.001	-10000	0	-10000	0	0
IL18RAP	-0.26	0.41	-10000	0	-0.88	143	143
IL12RB1	-0.27	0.43	-10000	0	-0.89	152	152
PIK3CA	0.016	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.21	0.34	-10000	0	-0.7	152	152
IL23R/JAK2	-0.011	0.16	-10000	0	-0.79	8	8
positive regulation of chronic inflammatory response	-0.29	0.53	-10000	0	-1.1	88	88
natural killer cell activation	0.002	0.012	0.063	9	-10000	0	9
JAK2	0.021	0.035	-10000	0	-10000	0	0
PIK3R1	0.016	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0.009	-10000	0	-10000	0	0
RELA	0.01	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.27	0.47	-10000	0	-1	74	74
ALOX12B	-0.31	0.51	-10000	0	-1.1	79	79
CXCL1	-0.3	0.53	-10000	0	-1.2	80	80
T cell proliferation	-0.29	0.53	-10000	0	-1.1	88	88
NFKBIA	0.01	0.009	-10000	0	-10000	0	0
IL17A	-0.1	0.29	-10000	0	-0.6	8	8
PI3K	-0.34	0.4	-10000	0	-1	88	88
IFNG	-0.054	0.069	0.14	3	-0.12	208	211
STAT3 (dimer)	-0.32	0.38	-10000	0	-1	80	80
IL18R1	-0.003	0.1	-10000	0	-0.82	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	-0.19	0.38	-10000	0	-0.8	79	79
IL18/IL18R	-0.2	0.29	-10000	0	-0.62	153	153
macrophage activation	-0.017	0.018	-10000	0	-0.045	11	11
TNF	-0.26	0.49	-10000	0	-1.1	65	65
STAT3/STAT4	-0.37	0.44	-10000	0	-1.1	96	96
STAT4 (dimer)	-0.32	0.54	-10000	0	-1.2	86	86
IL18	-0.002	0.097	-10000	0	-0.86	6	6
IL19	-0.26	0.47	-10000	0	-1	65	65
STAT5A (dimer)	-0.29	0.5	-10000	0	-1.1	85	85
STAT1	0.014	0.04	-10000	0	-0.86	1	1
SOCS3	0.012	0.057	-10000	0	-0.86	2	2
CXCL9	-0.41	0.6	-10000	0	-1.1	150	150
MPO	-0.26	0.48	-10000	0	-1.1	65	65
positive regulation of humoral immune response	-0.29	0.53	-10000	0	-1.1	88	88
IL23/IL23R/JAK2/TYK2	-0.31	0.55	-10000	0	-1.2	88	88
IL6	-0.3	0.53	-10000	0	-1.2	84	84
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.017	0.12	-10000	0	-0.86	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.063	9	-10000	0	9
CD3E	-0.4	0.6	-10000	0	-1.1	150	150
keratinocyte proliferation	-0.29	0.53	-10000	0	-1.1	88	88
NOS2	-0.26	0.48	-10000	0	-1	71	71

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.089	-9999	-0.86	5	5
CCL5	-0.36	0.44	-9999	-0.86	206	206
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.21	0.23	-9999	-0.59	79	79
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.22	-9999	-0.56	79	79
Syndecan-1/Syntenin	-0.19	0.22	-9999	-0.56	79	79
MAPK3	-0.16	0.2	-9999	-0.7	13	13
HGF/MET	-0.034	0.15	-9999	-0.67	24	24
TGFB1/TGF beta receptor Type II	0.007	0.089	-9999	-0.86	5	5
BSG	0.016	0	-9999	-10000	0	0
keratinocyte migration	-0.19	0.21	-9999	-0.55	79	79
Syndecan-1/RANTES	-0.41	0.34	-9999	-0.69	250	250
Syndecan-1/CD147	-0.2	0.18	-9999	-0.57	53	53
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	79	79
LAMA5	0.014	0.035	-9999	-0.76	1	1
positive regulation of cell-cell adhesion	-0.2	0.18	-9999	-0.53	79	79
MMP7	-0.12	0.3	-9999	-0.77	83	83
HGF	-0.021	0.17	-9999	-0.81	21	21
Syndecan-1/CASK	-0.2	0.22	-9999	-0.57	79	79
Syndecan-1/HGF/MET	-0.22	0.22	-9999	-0.59	88	88
regulation of cell adhesion	-0.14	0.19	-9999	-0.67	13	13
HPSE	0.012	0.05	-9999	-0.76	2	2
positive regulation of cell migration	-0.21	0.23	-9999	-0.59	79	79
SDC1	-0.22	0.23	-9999	-0.6	79	79
Syndecan-1/Collagen	-0.21	0.23	-9999	-0.59	79	79
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
MAPK1	-0.16	0.2	-9999	-0.7	13	13
homophilic cell adhesion	-0.21	0.22	-9999	-0.59	79	79
MMP1	-0.15	0.34	-9999	-0.83	95	95

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.6	0.32	-9999	-0.87	253	253
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.32	-9999	-0.85	78	78
SMAD9	-0.064	0.084	-9999	-0.58	9	9
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.18	0.17	-9999	-0.52	17	17
BMP7/USAG1	-0.7	0.35	-9999	-0.81	416	416
SMAD5/SKI	-0.17	0.16	-9999	-0.5	13	13
SMAD1	0.002	0.042	-9999	-10000	0	0
BMP2	0.009	0.073	-9999	-0.78	4	4
SMAD1/SMAD1/SMAD4	0	0	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.51	0.36	-9999	-0.76	328	328
BMPR1A-1B/BAMBI	-0.34	0.23	-9999	-0.49	330	330
AHSG	-0.009	0.12	-9999	-0.86	9	9
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.005	0.052	-9999	-0.52	5	5
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.11	-9999	-0.5	16	16
BMP2-4 (homodimer)	-0.006	0.06	-9999	-0.59	5	5
RGMB	0.012	0.057	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.52	1	1
RGMA	0.008	0.079	-9999	-0.76	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.17	0.14	-9999	-0.57	17	17
BMP2-4/USAG1	-0.31	0.24	-9999	-0.49	306	306
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	13	13
SOSTDC1	-0.48	0.37	-9999	-0.76	305	305
BMP7/BMPR2/BMPR1A-1B	-0.59	0.31	-9999	-0.87	235	235
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.009	0.07	-9999	-0.76	4	4
HFE2	-0.017	0.16	-9999	-0.86	16	16
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.016	0.094	-9999	-0.54	14	14
SMAD5/SMAD5/SMAD4	-0.17	0.16	-9999	-0.5	13	13
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.1	-9999	-0.51	13	13
BMP7 (homodimer)	-0.51	0.36	-9999	-0.76	323	323
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.017	0.1	-9999	-0.64	13	13
SMAD1/SKI	0.012	0.039	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.016	0.093	-9999	-0.55	14	14
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.18	0.34	-9999	-0.77	118	118
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.39	0.26	-9999	-0.57	328	328
CHRDL1	-0.39	0.38	-9999	-0.76	253	253
ENDOFIN/SMAD1	0.012	0.039	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.005	0.003	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	0.008	0.079	-9999	-0.76	5	5
SMURF2	0.016	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.26	0.25	-9999	-0.49	255	255
BMP2-4/GREM1	-0.13	0.22	-9999	-0.5	121	121
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.037	0.089	-9999	-0.54	9	9
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.51	0.36	-9999	-0.76	323	323
BMP6	0.009	0.07	-9999	-0.76	4	4
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.12	0.13	-9999	-0.46	17	17
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.012	0.039	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.21	0.18	-9999	-0.6	56	56
CHRD	-0.001	0.12	-9999	-0.79	10	10
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.17	0.13	-9999	-0.58	17	17
BMP4	0.014	0.035	-9999	-0.76	1	1
FST	-0.072	0.25	-9999	-0.78	53	53
BMP2-4/NOG	-0.096	0.21	-9999	-0.56	82	82
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.56	0.29	-9999	-0.83	235	235

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.008	0.14	-9999	-0.79	14	14
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0.035	-9999	-0.76	1	1
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.045	-9999	-10000	0	0
HIF1A	-0.098	0.036	-9999	-10000	0	0
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.018	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.16	-9999	-0.86	463	463
ARNT/IPAS	-0.017	0.1	-9999	-0.6	14	14
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.014	0.04	-9999	-0.86	1	1
HIF1A/ARNT	-0.08	0.045	-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	-0.002	0.034	-9999	-0.53	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.045	-9999	-10000	0	0
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	423	423
HIF1A/RACK1/Elongin B/Elongin C	-0.065	0.036	-9999	-0.5	2	2
VHL	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.045	-9999	-10000	0	0
EGLN3	-0.76	0.28	-9999	-0.86	424	424
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	-0.001	0.013	-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	-0.56	0.11	-9999	-0.57	463	463

×

VEGFR1 specific signals

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.006	0.062	-9999	-0.68	4	4
VEGFR1 homodimer/NRP1	-0.006	0.063	-9999	-0.69	4	4
mol:DAG	-0.26	0.29	-9999	-0.52	269	269
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	216	216
CaM/Ca2+	-0.27	0.24	-9999	-0.92	4	4
HIF1A	0.023	0.032	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.22	0.2	-9999	-0.89	3	3
PLCG1	-0.27	0.29	-9999	-0.52	269	269
NOS3	-0.18	0.24	-9999	-0.87	3	3
CBL	0.016	0	-9999	-10000	0	0
mol:NO	-0.17	0.23	-9999	-0.81	3	3
FLT1	0.034	0.074	-9999	-0.78	4	4
PGF	-0.48	0.44	-9999	-0.86	268	268
VEGFR1 homodimer/NRP2/VEGFR121	-0.24	0.27	-9999	-1	6	6
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
eNOS/Hsp90	-0.16	0.23	-9999	-0.78	3	3
endothelial cell proliferation	-0.2	0.25	-9999	-0.86	5	5
mol:Ca2+	-0.26	0.28	-9999	-0.51	269	269
MAPK3	-0.21	0.26	-9999	-0.94	3	3
MAPK1	-0.21	0.26	-9999	-0.94	3	3
PIK3R1	0.016	0	-9999	-10000	0	0
PLGF homodimer	-0.48	0.44	-9999	-0.86	268	268
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.05	0.23	-9999	-0.86	36	36
VEGFA homodimer	-0.38	0.44	-9999	-0.86	215	215
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	216	216
platelet activating factor biosynthetic process	-0.2	0.25	-9999	-0.9	3	3
PI3K	-0.27	0.24	-9999	-0.94	4	4
PRKCA	-0.24	0.27	-9999	-0.89	4	4
PRKCB	-0.24	0.27	-9999	-0.92	6	6
VEGFR1 homodimer/PLGF homodimer	-0.32	0.29	-9999	-0.58	269	269
VEGFA	-0.38	0.44	-9999	-0.86	215	215
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.52	269	269
RASA1	0.049	0.061	-9999	-0.62	4	4
NRP2	0.003	0.11	-9999	-0.86	7	7
VEGFR1 homodimer	0.034	0.074	-9999	-0.77	4	4
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.19	0.26	-9999	-0.81	28	28
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.27	0.24	-9999	-0.92	4	4
mol:L-citrulline	-0.17	0.23	-9999	-0.81	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.22	0.25	-9999	-0.95	4	4
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.24	0.27	-9999	-1	4	4
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.99	3	3
PDPK1	-0.22	0.26	-9999	-0.96	3	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-1	4	4
mol:NADP	-0.17	0.23	-9999	-0.81	3	3
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.22	0.24	-9999	-0.92	4	4
VEGFR1 homodimer/NRP2	-0.014	0.091	-9999	-0.61	11	11

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.25	0.26	-10000	0	-0.75	31	31
IHH	-0.1	0.24	-10000	0	-0.83	45	45
SHH Np/Cholesterol/GAS1	-0.038	0.13	-10000	0	-0.46	39	39
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.037	0.13	0.46	39	-10000	0	39
SMO/beta Arrestin2	-0.15	0.16	-10000	0	-0.6	33	33
SMO	-0.14	0.19	-10000	0	-0.64	32	32
AKT1	-0.042	0.091	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
BOC	0.016	0	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.14	0.19	-10000	0	-0.63	32	32
STIL	-0.098	0.17	-10000	0	-0.68	10	10
DHH N/PTCH2	-0.045	0.16	-10000	0	-0.64	34	34
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.63	35	35
PIK3CA	0.016	0	-10000	0	-10000	0	0
DHH	-0.001	0.11	-10000	0	-0.76	10	10
PTHLH	-0.45	0.41	-10000	0	-0.74	301	301
determination of left/right symmetry	-0.14	0.19	-10000	0	-0.63	32	32
PIK3R1	0.016	0	-10000	0	-10000	0	0
skeletal system development	-0.44	0.4	-10000	0	-0.74	301	301
IHH N/Hhip	-0.21	0.32	-10000	0	-0.66	149	149
DHH N/Hhip	-0.16	0.26	-10000	0	-0.59	127	127
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.14	0.19	-10000	0	-0.63	32	32
pancreas development	-0.18	0.34	-10000	0	-0.77	119	119
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.033	0.19	-10000	0	-0.76	30	30
somite specification	-0.14	0.19	-10000	0	-0.63	32	32
SHH Np/Cholesterol/PTCH1	-0.14	0.15	-10000	0	-0.56	35	35
SHH Np/Cholesterol/PTCH2	-0.036	0.13	-10000	0	-0.53	25	25
SHH Np/Cholesterol/Megalin	-0.048	0.15	-10000	0	-0.5	46	46
SHH	0.018	0.087	-10000	0	-0.58	10	10
catabolic process	-0.16	0.2	-10000	0	-0.66	31	31
SMO/Vitamin D3	-0.14	0.15	-10000	0	-0.59	35	35
SHH Np/Cholesterol/Hhip	-0.12	0.21	-10000	0	-0.47	125	125
LRP2	-0.05	0.22	-10000	0	-0.76	41	41
receptor-mediated endocytosis	-0.16	0.18	-10000	0	-0.78	19	19
SHH Np/Cholesterol/BOC	-0.009	0.065	-10000	0	-0.46	10	10
SHH Np/Cholesterol/CDO	-0.072	0.18	-10000	0	-0.53	65	65
mesenchymal cell differentiation	0.12	0.21	0.46	125	-10000	0	125
mol:Vitamin D3	-0.11	0.18	-10000	0	-0.57	35	35
IHH N/PTCH2	-0.087	0.22	-10000	0	-0.62	67	67
CDON	-0.087	0.28	-10000	0	-0.86	56	56
IHH N/PTCH1	-0.16	0.2	-10000	0	-0.67	31	31
Megalin/LRPAP1	-0.049	0.16	-10000	0	-0.57	41	41
PTCH2	-0.028	0.19	-10000	0	-0.86	24	24
SHH Np/Cholesterol	-0.01	0.067	-10000	0	-0.47	10	10
PTCH1	-0.16	0.2	-10000	0	-0.66	31	31
HHIP	-0.18	0.34	-10000	0	-0.77	119	119

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.016	0	-9999	-10000	0	0
LAT2	-0.17	0.24	-9999	-0.71	62	62
AP1	-0.16	0.21	-9999	-0.57	80	80
mol:PIP3	-0.24	0.34	-9999	-0.71	141	141
IKBKB	-0.093	0.17	-9999	-0.34	77	77
AKT1	-0.18	0.22	-9999	-0.73	23	23
IKBKG	-0.093	0.17	-9999	-0.34	75	75
MS4A2	-0.18	0.36	-9999	-0.86	102	102
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.008	-9999	-10000	0	0
MAP3K1	-0.13	0.27	-9999	-0.58	93	93
mol:Ca2+	-0.17	0.24	-9999	-0.49	129	129
LYN	0.011	0.009	-9999	-10000	0	0
CBLB	-0.12	0.16	-9999	-0.54	24	24
SHC1	0.014	0.04	-9999	-0.86	1	1
RasGAP/p62DOK	-0.001	0.024	-9999	-0.53	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
PLD2	-0.19	0.29	-9999	-0.92	23	23
PTPN13	-0.076	0.16	-9999	-0.48	21	21
PTPN11	0.014	0.007	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.051	0.17	-9999	-0.41	5	5
SYK	0.007	0.051	-9999	-0.77	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.31	0.32	-9999	-0.77	137	137
LAT	-0.27	0.3	-9999	-0.66	155	155
PAK2	-0.16	0.3	-9999	-0.64	110	110
NFATC2	-0.07	0.085	-9999	-0.64	1	1
HRAS	-0.19	0.33	-9999	-0.71	118	118
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.042	0.027	-9999	-10000	0	0
Fc epsilon R1	-0.27	0.33	-9999	-0.63	207	207
Antigen/IgE/Fc epsilon R1	-0.26	0.31	-9999	-0.59	207	207
mol:GDP	-0.22	0.36	-9999	-0.78	125	125
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.008	-9999	-10000	0	0
FOS	0	0.11	-9999	-0.76	10	10
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.14	0.17	-9999	-0.58	24	24
CHUK	-0.093	0.17	-9999	-0.34	76	76
KLRG1	-0.13	0.16	-9999	-0.55	24	24
VAV1	-0.24	0.31	-9999	-0.71	131	131
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.16	-9999	-0.54	24	24
negative regulation of mast cell degranulation	-0.12	0.16	-9999	-0.55	26	26
BTK	-0.19	0.24	-9999	-0.64	91	91
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.18	0.22	-9999	-0.58	86	86
GAB2/PI3K/SHP2	-0.2	0.24	-9999	-0.83	23	23
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.13	0.16	-9999	-0.56	24	24
RAF1	0.028	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.33	0.4	-9999	-1.1	86	86
FCER1G	-0.19	0.37	-9999	-0.87	107	107
FCER1A	-0.025	0.16	-9999	-0.78	21	21
Antigen/IgE/Fc epsilon R1/Fyn	-0.24	0.29	-9999	-0.56	195	195
MAPK3	0.041	0.026	-9999	-10000	0	0
MAPK1	0.041	0.026	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.012	0.072	-9999	-10000	0	0
DUSP1	0.014	0.04	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.072	0.075	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.082	0.16	-9999	-0.48	24	24
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.23	0.3	-9999	-0.74	110	110
FER	-0.12	0.16	-9999	-0.55	25	25
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.16	0.2	-9999	-0.43	159	159
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.21	0.37	-9999	-0.77	125	125
cytokine secretion	-0.053	0.054	-9999	-10000	0	0
SPHK1	-0.16	0.22	-9999	-0.66	57	57
PTK2	-0.086	0.17	-9999	-0.5	23	23
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.26	0.32	-9999	-0.77	112	112
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.2	0.32	-9999	-0.68	112	112
MAP2K2	0.036	0.032	-9999	-0.43	1	1
MAP2K1	0.037	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.12	0.15	-9999	-0.53	24	24
MAP2K4	0.017	0.016	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.35	0.42	-9999	-0.74	221	221
mol:Choline	-0.19	0.29	-9999	-0.89	23	23
SHC/Grb2/SOS1	-0.11	0.14	-9999	-0.51	19	19
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.07	0.16	-9999	-0.48	14	14
HCLS1	-0.14	0.19	-9999	-0.66	32	32
PRKCB	-0.15	0.23	-9999	-0.48	118	118
FCGR2B	-0.16	0.35	-9999	-0.86	97	97
IGHE	-0.006	0.011	-9999	-10000	0	0
KLRG1/SHIP	-0.12	0.16	-9999	-0.57	26	26
LCP2	-0.044	0.22	-9999	-0.87	32	32
PLA2G4A	-0.13	0.16	-9999	-0.55	26	26
RASA1	0.016	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.19	0.29	-9999	-0.89	23	23
IKK complex	-0.051	0.13	-9999	-0.29	1	1
WIPF1	0.016	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.008	0.09	-10000	0	-0.86	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.074	0.2	0.65	23	-0.44	3	26
IL27/IL27R/JAK1	-0.079	0.35	0.58	1	-0.86	50	51
TBX21	-0.21	0.41	0.5	1	-0.76	142	143
IL12B	-0.096	0.28	-10000	0	-0.87	57	57
IL12A	0.008	0.033	-10000	0	-0.69	1	1
IL6ST	-0.005	0.11	-10000	0	-0.77	10	10
IL27RA/JAK1	0.009	0.063	-10000	0	-0.7	1	1
IL27	-0.044	0.21	-10000	0	-0.88	29	29
TYK2	0.011	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.024	0.13	-10000	0	-0.74	2	2
T-helper 2 cell differentiation	0.074	0.2	0.65	23	-0.44	3	26
T cell proliferation during immune response	0.074	0.2	0.65	23	-0.44	3	26
MAPKKK cascade	-0.074	0.2	0.44	3	-0.65	23	26
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.015	0.041	-10000	0	-0.87	1	1
IL12RB1	-0.27	0.41	-10000	0	-0.87	152	152
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.16	0.35	0.5	1	-0.71	88	89
IL27/IL27R/JAK2/TYK2	-0.076	0.2	0.44	3	-0.66	23	26
positive regulation of T cell mediated cytotoxicity	-0.074	0.2	0.44	3	-0.65	23	26
STAT1 (dimer)	-0.062	0.5	0.54	108	-0.99	62	170
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
T cell proliferation	-0.12	0.25	0.4	1	-0.71	46	47
IL12/IL12R/TYK2/JAK2	-0.18	0.27	-10000	0	-0.55	141	141
IL17A	-0.024	0.13	-10000	0	-0.74	2	2
mast cell activation	0.074	0.2	0.65	23	-0.44	3	26
IFNG	-0.041	0.066	0.13	3	-0.11	220	223
T cell differentiation	-0.011	0.011	0.03	3	-0.026	131	134
STAT3 (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
STAT5A (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.76	41	43
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
T cell activation	-0.012	0.007	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.037	0.094	-10000	0	-0.71	1	1
GATA3	-0.61	0.69	-10000	0	-1.3	230	230
IL18	0.005	0.077	-10000	0	-0.68	6	6
positive regulation of mast cell cytokine production	-0.078	0.17	0.38	3	-0.62	21	24
IL27/EBI3	-0.13	0.33	-10000	0	-0.83	80	80
IL27RA	-0.003	0.065	-10000	0	-0.76	1	1
IL6	-0.087	0.28	-10000	0	-0.83	59	59
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0	0.091	-10000	0	-0.6	10	10
IL1B	0.009	0.061	-10000	0	-0.66	4	4
EBI3	-0.12	0.32	-10000	0	-0.88	71	71
TNF	0.003	0.083	-10000	0	-0.63	8	8

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.19	0.36	-10000	0	-1.1	67	67
NFATC2	-0.081	0.23	-10000	0	-0.66	26	26
NFATC3	-0.023	0.064	-10000	0	-10000	0	0
CD40LG	-0.25	0.46	-10000	0	-1.1	63	63
ITCH	0.054	0.059	-10000	0	-10000	0	0
CBLB	0.054	0.059	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.55	0.57	-10000	0	-1.1	206	206
JUNB	0.013	0.05	-10000	0	-0.76	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.059	-10000	0	-10000	0	0
T cell anergy	0.024	0.094	-10000	0	-10000	0	0
TLE4	-0.031	0.17	-10000	0	-0.83	3	3
Jun/NFAT1-c-4/p21SNFT	-0.24	0.28	-10000	0	-1	23	23
AP-1/NFAT1-c-4	-0.31	0.37	-10000	0	-1.1	43	43
IKZF1	-0.14	0.37	-10000	0	-0.89	89	89
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.72	108	108
AP-1/NFAT1	-0.094	0.16	-10000	0	-0.64	12	12
CALM1	0.028	0.037	-10000	0	-10000	0	0
EGR2	-0.11	0.28	-10000	0	-1.4	7	7
EGR3	-0.11	0.28	-10000	0	-1.5	6	6
NFAT1/FOXP3	-0.29	0.41	-10000	0	-0.95	110	110
EGR1	0.006	0.093	-10000	0	-0.76	7	7
JUN	0.005	0.022	-10000	0	-10000	0	0
EGR4	0.007	0.069	-10000	0	-0.86	3	3
mol:Ca2+	0.007	0.041	-10000	0	-10000	0	0
GBP3	-0.034	0.18	-10000	0	-0.84	5	5
FOSL1	-0.026	0.19	-10000	0	-0.86	23	23
NFAT1-c-4/MAF/IRF4	-0.28	0.36	-10000	0	-0.91	95	95
DGKA	-0.034	0.18	-10000	0	-1.1	4	4
CREM	0.014	0.005	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.21	-10000	0	-1.1	5	5
CTLA4	-0.43	0.59	-10000	0	-1	215	215
NFAT1-c-4 (dimer)/EGR1	-0.17	0.23	-10000	0	-1.2	7	7
NFAT1-c-4 (dimer)/EGR4	-0.17	0.22	-10000	0	-1.2	6	6
FOS	-0.011	0.11	-10000	0	-0.77	10	10
IFNG	-0.5	0.52	-10000	0	-1	220	220
T cell activation	-0.052	0.22	-10000	0	-0.83	15	15
MAF	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.067	0.2	0.91	3	-10000	0	3
TNF	-0.097	0.27	-10000	0	-1.1	11	11
FASLG	-0.35	0.47	-10000	0	-1	35	35
TBX21	-0.3	0.44	-10000	0	-0.93	156	156
BATF3	-0.058	0.24	-10000	0	-0.86	40	40
PRKCQ	-0.032	0.12	-10000	0	-0.76	12	12
PTPN1	-0.031	0.17	-10000	0	-0.76	4	4
NFAT1-c-4/ICER1	-0.17	0.21	-10000	0	-1.2	4	4
GATA3	-0.35	0.39	-10000	0	-0.76	230	230
T-helper 1 cell differentiation	-0.49	0.5	-10000	0	-0.99	220	220
IL2RA	-0.39	0.46	-10000	0	-1.1	120	120
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.031	0.17	-10000	0	-0.76	4	4
E2F1	-0.074	0.28	-10000	0	-0.86	54	54
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.031	0.17	-10000	0	-0.76	4	4
IRF4	-0.19	0.37	-10000	0	-0.86	114	114
PTGS2	-0.22	0.4	-10000	0	-1.1	37	37
CSF2	-0.22	0.4	-10000	0	-1.1	35	35
JunB/Fra1/NFAT1-c-4	-0.18	0.22	-10000	0	-0.92	11	11
IL4	-0.36	0.29	-10000	0	-0.76	104	104
IL5	-0.21	0.38	-10000	0	-1	29	29
IL2	-0.053	0.22	-10000	0	-0.85	15	15
IL3	-0.051	0.049	-10000	0	-10000	0	0
RNF128	0.032	0.16	-10000	0	-0.8	18	18
NFATC1	-0.067	0.2	-10000	0	-0.91	3	3
CDK4	0.038	0.18	-10000	0	-10000	0	0
PTPRK	-0.031	0.17	-10000	0	-0.76	4	4
IL8	-0.23	0.42	-10000	0	-1.1	40	40
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.008	0.069	-9999	-0.66	5	5
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.019	0.11	-9999	-0.67	14	14
STXBP1	0.014	0.035	-9999	-0.76	1	1
ACh/CHRNA1	-0.28	0.32	-9999	-0.63	212	212
RAB3GAP2/RIMS1/UNC13B	-0.017	0.097	-9999	-0.58	14	14
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	-0.014	0.15	-9999	-0.86	14	14
mol:ACh	-0.008	0.053	-9999	-0.13	71	71
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.037	0.099	-9999	-0.62	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.28	0.31	-9999	-0.63	212	212
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.37	0.44	-9999	-0.86	212	212
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.088	0.21	-9999	-0.54	81	81
SNAP25	-0.038	0.12	-9999	-0.33	68	68
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.12	0.29	-9999	-0.76	81	81
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.007	0.062	-9999	-0.56	6	6
STX1A/SNAP25 fragment 1/VAMP2	-0.037	0.099	-9999	-0.62	4	4

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.015	0.047	-9999	-10000	0	0
NFATC2	-0.016	0.055	-9999	-0.63	1	1
NFATC3	-0.015	0.047	-9999	-10000	0	0
CD40LG	-0.32	0.43	-9999	-0.95	101	101
PTGS2	-0.3	0.39	-9999	-0.86	94	94
JUNB	0.012	0.05	-9999	-0.76	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.021	0.018	-9999	-10000	0	0
CaM/Ca2+	-0.021	0.018	-9999	-10000	0	0
CALM1	0.005	0.013	-9999	-10000	0	0
JUN	0.006	0.013	-9999	-10000	0	0
mol:Ca2+	-0.021	0.019	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.003	-9999	-10000	0	0
FOSL1	-0.026	0.19	-9999	-0.86	23	23
CREM	0.015	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.75	32	32
FOS	-0.011	0.11	-9999	-0.77	10	10
IFNG	-0.45	0.52	-9999	-0.99	211	211
AP-1/NFAT1-c-4	-0.42	0.41	-9999	-1.1	94	94
FASLG	-0.48	0.52	-9999	-0.99	216	216
NFAT1-c-4/ICER1	-0.081	0.075	-9999	-0.56	1	1
IL2RA	-0.35	0.45	-9999	-0.96	116	116
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.3	0.39	-9999	-0.86	92	92
JunB/Fra1/NFAT1-c-4	-0.095	0.12	-9999	-0.58	17	17
IL4	-0.29	0.37	-9999	-0.83	90	90
IL2	-0.013	0.11	-9999	-0.77	10	10
IL3	-0.029	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.058	0.24	-9999	-0.86	40	40
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.057	0.17	-9999	-0.54	51	51
EFNA5	-0.057	0.23	-9999	-0.76	45	45
FYN	-0.027	0.16	-9999	-0.49	51	51
neuron projection morphogenesis	-0.057	0.17	-9999	-0.54	51	51
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.058	0.17	-9999	-0.54	51	51
EPHA5	-0.009	0.11	-9999	-0.86	8	8

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.045	-9999	-0.5	4	4
ARNO/beta Arrestin1-2	-0.017	0.061	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EPHA2	0.014	0.035	-9999	-0.76	1	1
USP6	0.014	0.04	-9999	-0.86	1	1
IQSEC1	0.015	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.52	0.19	-9999	-0.58	433	433
ARRB2	-0.012	0.1	-9999	-0.39	33	33
mol:GTP	-0.011	0.048	-9999	-0.24	2	2
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.089	0.28	-9999	-0.86	57	57
EGF	-0.68	0.23	-9999	-0.76	432	432
somatostatin receptor activity	0	0	-9999	-0.001	12	12
ARAP2	0.014	0.035	-9999	-0.76	1	1
mol:GDP	-0.056	0.094	-9999	-0.34	21	21
mol:PI-3-4-5-P3	0	0	-9999	-0.001	10	10
ITGA2B	-0.012	0.15	-9999	-0.86	15	15
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.002	0.031	-9999	-0.52	1	1
ADAP1	0.009	0.07	-9999	-0.76	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.034	0.15	-9999	-0.67	24	24
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.086	0.09	-9999	-0.35	17	17
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.45	0.16	-9999	-0.5	433	433
ADRB2	0.012	0.05	-9999	-0.76	2	2
receptor agonist activity	0	0	-9999	0	12	12
actin filament binding	0	0	-9999	-0.001	16	16
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
GNAQ	0.015	0.003	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	10	10
ARF6/GDP	-0.068	0.14	-9999	-0.39	5	5
ARF6/GDP/GULP/ACAP1	-0.23	0.26	-9999	-0.54	185	185
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.017	0.092	-9999	-0.52	14	14
ACAP1	-0.32	0.43	-9999	-0.86	184	184
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.041	0.15	-9999	-0.59	33	33
EFNA1	0.014	0.04	-9999	-0.86	1	1
HGF	-0.021	0.17	-9999	-0.81	21	21
CYTH3	0.015	0	-9999	-10000	0	0
CYTH2	0.01	0.001	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	-0.001	10	10
endosomal lumen acidification	0	0	-9999	-0.001	17	17
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.012	0.14	-9999	-0.76	17	17
GNAQ/ARNO	0.004	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	-10000	0	0
MET	0.006	0.089	-9999	-0.86	5	5
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	11	11
GNA11	0.012	0.05	-9999	-0.76	2	2
LHCGR	-0.052	0.22	-9999	-0.86	32	32
AGTR1	-0.026	0.18	-9999	-0.76	26	26
desensitization of G-protein coupled receptor protein signaling pathway	-0.04	0.15	-9999	-0.59	33	33
IPCEF1/ARNO	-0.35	0.13	-9999	-0.82	8	8
alphaIIb/beta3 Integrin	-0.022	0.12	-9999	-0.66	16	16

×

p75(NTR)-mediated 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
Sortilin/TRAF6	-0.001	0.026	-9999	-0.57	1	1
Necdin/E2F1	-0.078	0.22	-9999	-0.68	55	55
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.088	0.22	-9999	-0.98	11	11
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.32	-9999	-0.58	233	233
NT-4/5 (dimer)/p75(NTR)	-0.06	0.19	-9999	-0.67	43	43
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.04	0.23	-9999	-0.96	11	11
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.11	0.31	-9999	-0.86	68	68
MGDIs/NGR/p75(NTR)/LINGO1	-0.077	0.21	-9999	-0.62	60	60
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.13	0.26	-9999	-0.63	96	96
LINGO1	-0.021	0.18	-9999	-0.86	20	20
Sortilin/TRAF6/NRIF	-0.001	0.015	-9999	-10000	0	0
proBDNF (dimer)	-0.11	0.3	-9999	-0.86	68	68
NTRK1	-0.047	0.21	-9999	-0.76	38	38
RTN4R	0.003	0.1	-9999	-0.85	7	7
neuron apoptosis	-0.073	0.24	-9999	-0.7	33	33
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.071	0.26	-9999	-0.65	76	76
ARHGDIA	0.014	0.035	-9999	-0.76	1	1
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.094	0.23	-9999	-0.6	74	74
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.097	0.23	-9999	-0.6	75	75
Mammalian IAPs/DIABLO	-0.081	0.19	-9999	-0.52	74	74
proNGF (dimer)	-0.072	0.26	-9999	-0.86	48	48
MAGED1	0.014	0.04	-9999	-0.86	1	1
APP	0.014	0.035	-9999	-0.76	1	1
NT-4/5 (dimer)	-0.004	0.089	-9999	-0.86	5	5
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.089	0.22	-9999	-0.56	74	74
NGF	-0.072	0.26	-9999	-0.86	48	48
cell cycle arrest	-0.022	0.27	-9999	-0.58	74	74
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.05	0.12	-9999	-0.57	11	11
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.052	0.17	-9999	-0.58	43	43
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.1	0.25	-9999	-0.65	75	75
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.054	0.24	-9999	-0.59	74	74
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.039	0.094	-9999	-0.44	11	11
p75(NTR)/beta APP	-0.054	0.18	-9999	-0.66	39	39
BEX1	-0.27	0.37	-9999	-0.76	177	177
mol:GDP	-0.082	0.26	-9999	-0.66	75	75
NGF (dimer)	-0.36	0.31	-9999	-0.85	84	84
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.071	0.2	-9999	-0.57	60	60
PIK3R1	0.016	0	-9999	-10000	0	0
RAC1/GTP	-0.09	0.22	-9999	-0.58	75	75
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.1	0.25	-9999	-0.65	75	75
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.075	0.21	-9999	-0.67	54	54
NT3 (dimer)	0.006	0.09	-9999	-0.79	6	6
TP53	-0.051	0.24	-9999	-0.91	11	11
PRDM4	-0.055	0.24	-9999	-0.6	74	74
BDNF (dimer)	-0.43	0.37	-9999	-0.89	134	134
PIK3CA	0.016	0	-9999	-10000	0	0
SORT1	0.014	0.035	-9999	-0.76	1	1
activation of caspase activity	-0.087	0.21	-9999	-0.96	11	11
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.094	0.23	-9999	-0.6	74	74
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.032	0.22	-9999	-0.64	28	28
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.055	0.24	-9999	-0.6	74	74
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.1	0.25	-9999	-0.65	76	76
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.06	0.19	-9999	-0.66	44	44
MAPK8	-0.029	0.22	-9999	-0.64	26	26
MAPK9	-0.029	0.22	-9999	-0.64	26	26
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.006	0.09	-9999	-0.79	6	6
NTF4	-0.004	0.089	-9999	-0.86	5	5
NDN	0.011	0.061	-9999	-0.76	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.08	0.2	-9999	-0.91	11	11
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.02	-9999	-10000	0	0
RhoA-B-C/GTP	-0.1	0.24	-9999	-0.64	75	75
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.11	0.23	-9999	-0.98	11	11
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.12	0.24	-9999	-0.58	94	94
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.094	0.23	-9999	-0.66	68	68
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	74	74
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.001	0.26	-9999	-0.56	58	58
BAD	-0.018	0.21	-9999	-0.6	27	27
RIPK2	0.014	0.04	-9999	-0.86	1	1
NGFR	-0.054	0.24	-9999	-0.86	38	38
CYCS	-0.043	0.23	-9999	-0.97	11	11
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.094	0.23	-9999	-0.6	75	75
BCL2L11	-0.017	0.21	-9999	-0.6	27	27
BDNF (dimer)/p75(NTR)	-0.14	0.3	-9999	-0.72	96	96
PI3K	-0.093	0.23	-9999	-0.6	74	74
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.094	0.23	-9999	-0.6	74	74
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.12	0.28	-9999	-0.75	75	75
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.095	0.23	-9999	-0.6	75	75
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.061	-9999	-0.76	3	3
PLG	-0.4	0.38	-9999	-0.76	256	256
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.14	0.25	-9999	-0.72	46	46
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.011	0.19	-9999	-0.54	27	27
E2F1	-0.083	0.28	-9999	-0.86	54	54
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.076	0.15	-9999	-0.6	14	14
NGF (dimer)/TRKA	-0.11	0.24	-9999	-0.64	84	84
MMP7	-0.12	0.3	-9999	-0.77	83	83
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.088	0.22	-9999	-0.98	11	11
MMP3	-0.075	0.26	-9999	-0.86	46	46
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.69	13	13

×

IL2 signaling events mediated by STAT5

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.044	0.14	-9999	-10000	0	0
CCNA2	-0.16	0.35	-9999	-0.86	96	96
PIK3CA	0.017	0	-9999	-10000	0	0
JAK3	-0.17	0.36	-9999	-0.86	102	102
PIK3R1	0.017	0	-9999	-10000	0	0
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.11	0.25	-9999	-0.66	56	56
SHC1	0.015	0.04	-9999	-0.86	1	1
SP1	0.024	0.023	-9999	-10000	0	0
IL2RA	-0.12	0.33	-9999	-0.78	96	96
IL2RB	-0.47	0.44	-9999	-0.86	263	263
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.044	0.22	-9999	-0.86	33	33
G1/S transition of mitotic cell cycle	-0.049	0.2	-9999	-0.49	38	38
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.053	-9999	-0.78	2	2
LCK	-0.023	0.18	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.008	0.12	-9999	-0.86	10	10
CDK6	0.014	0.035	-9999	-0.76	1	1
CCND3	-0.084	0.21	-9999	-0.67	27	27

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	215	215
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.031	0.1	-9999	-0.36	40	40
mol:S1P	-0.024	0.095	-9999	-0.37	15	15
S1P1/S1P/Gi	-0.047	0.14	-9999	-0.49	14	14
GNAO1	0.011	0.078	-9999	-0.84	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.088	-9999	-0.67	1	1
PLCG1	-0.028	0.13	-9999	-0.49	8	8
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.004	-9999	-10000	0	0
GNAI2	0.018	0.005	-9999	-10000	0	0
GNAI3	0.015	0.006	-9999	-10000	0	0
GNAI1	0.01	0.062	-9999	-0.76	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.25	0.3	-9999	-0.58	215	215
S1P1/S1P	-0.21	0.21	-9999	-0.61	23	23
negative regulation of cAMP metabolic process	-0.045	0.14	-9999	-0.48	14	14
MAPK3	-0.038	0.17	-9999	-0.64	13	13
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.013	0.035	-9999	-0.76	1	1
PLCB2	-0.2	0.26	-9999	-0.67	56	56
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.17	-9999	-0.51	21	21
receptor internalization	-0.2	0.2	-9999	-0.4	217	217
PTGS2	-0.049	0.24	-9999	-0.99	25	25
Rac1/GTP	-0.17	0.17	-9999	-0.51	21	21
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	215	215
negative regulation of T cell proliferation	-0.045	0.14	-9999	-0.48	14	14
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.01	0.062	-9999	-0.76	3	3
MAPK1	-0.038	0.17	-9999	-0.64	13	13
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.62	22	22
ABCC1	0.015	0.005	-9999	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.13	0.24	-10000	0	-0.78	34	34
UGCG	-0.022	0.031	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.086	0.2	-10000	0	-0.48	55	55
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.008	0.045	-10000	0	-10000	0	0
mol:DAG	-0.004	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.11	0.17	-10000	0	-0.55	36	36
FRAP1	-0.09	0.23	-10000	0	-0.61	48	48
FOXO3	-0.081	0.22	-10000	0	-0.63	37	37
AKT1	-0.098	0.24	-10000	0	-0.64	50	50
GAB2	0.015	0.005	-10000	0	-10000	0	0
SMPD1	-0.022	0.031	-10000	0	-10000	0	0
SGMS1	-0.022	0.031	-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	0.029	0.006	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.023	0.096	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
RPS6KB1	-0.029	0.088	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.006	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.17	0.36	-10000	0	-0.86	102	102
PIK3R1	0.019	0.004	-10000	0	-10000	0	0
JAK1	0.019	0.004	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	-0.08	0.23	-10000	0	-0.65	35	35
MYB	-0.19	0.34	-10000	0	-0.73	130	130
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.13	0.26	-10000	0	-0.68	61	61
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.037	0.064	-10000	0	-0.45	1	1
mol:PI-3-4-5-P3	-0.12	0.25	-10000	0	-0.65	61	61
Rac1/GDP	0	0	-10000	0	-10000	0	0
T cell proliferation	-0.1	0.24	-10000	0	-0.59	63	63
SHC1	0.013	0.04	-10000	0	-0.86	1	1
RAC1	0.015	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.008	0.026	-10000	0	-0.051	130	130
PRKCZ	-0.11	0.25	-10000	0	-0.62	63	63
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.58	27	27
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.16	0.27	-10000	0	-0.58	102	102
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.16	0.35	-10000	0	-0.86	96	96
IL2RB	-0.46	0.44	-10000	0	-0.86	263	263
TERT	-0.12	0.31	-10000	0	-0.86	70	70
E2F1	-0.1	0.2	-10000	0	-0.37	161	161
SOS1	0.014	0.006	-10000	0	-10000	0	0
RPS6	0.014	0.04	-10000	0	-0.86	1	1
mol:cAMP	0.004	0.013	0.025	130	-10000	0	130
PTPN11	0.015	0.005	-10000	0	-10000	0	0
IL2RG	-0.042	0.22	-10000	0	-0.86	33	33
actin cytoskeleton organization	-0.1	0.24	-10000	0	-0.59	63	63
GRB2	0.014	0.006	-10000	0	-10000	0	0
IL2	-0.006	0.12	-10000	0	-0.86	10	10
PIK3CA	0.018	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.021	-10000	0	-10000	0	0
LCK	-0.021	0.18	-10000	0	-0.85	22	22
BCL2	-0.056	0.18	-10000	0	-0.55	18	18

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.028	0	-9999	-10000	0	0
ADCY5	0.007	0.1	-9999	-0.5	19	19
ADCY6	0.028	0	-9999	-10000	0	0
ADCY7	0.008	0.11	-9999	-0.59	15	15
ADCY1	0.017	0.074	-9999	-0.52	9	9
ADCY2	-0.13	0.26	-9999	-0.58	122	122
ADCY3	0.028	0	-9999	-10000	0	0
ADCY8	-0.17	0.28	-9999	-0.59	149	149
PRKCE	0.015	0	-9999	-10000	0	0
ADCY9	0.028	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.089	0.17	-9999	-0.51	46	46

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0	0.058	0.29	17	-10000	0	17
BUB1B	-0.025	0.13	-10000	0	-0.51	24	24
PLK1	-0.014	0.06	-10000	0	-0.2	10	10
PLK1S1	0	0.031	-10000	0	-10000	0	0
KIF2A	-0.004	0.072	-10000	0	-0.6	3	3
regulation of mitotic centrosome separation	-0.014	0.059	-10000	0	-0.2	10	10
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.19	0.34	-10000	0	-0.72	121	121
WEE1	-0.003	0.057	-10000	0	-0.3	5	5
cytokinesis	-0.22	0.27	-10000	0	-0.5	228	228
PP2A-alpha B56	-0.15	0.16	-10000	0	-10000	0	0
AURKA	-0.003	0.046	-10000	0	-0.3	6	6
PICH/PLK1	-0.047	0.17	-10000	0	-0.84	18	18
CENPE	-0.068	0.21	-10000	0	-0.63	59	59
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.004	0.071	-10000	0	-0.6	3	3
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.035	-10000	0	-0.76	1	1
TPX2	-0.053	0.12	-10000	0	-0.26	120	120
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.082	0.28	-10000	0	-0.86	53	53
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.027	0.097	-10000	0	-0.28	56	56
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.004	0.01	-10000	0	-0.02	124	124
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.031	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0.001	0.002	-10000	0	-0.014	6	6
STAG2	0.016	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.009	0.013	-10000	0	-10000	0	0
spindle elongation	-0.014	0.059	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.18	0.19	-10000	0	-0.46	9	9
TPT1	0	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	224	224
CDC25B	0.006	0.091	-10000	0	-0.88	5	5
SGOL1	0	0.058	-10000	0	-0.29	17	17
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.025	0.11	-10000	0	-0.74	9	9
CDC14B	0.016	0.002	-10000	0	-10000	0	0
CDC20	-0.058	0.24	-10000	0	-0.86	40	40
PLK1/PBIP1	-0.04	0.11	-10000	0	-0.61	15	15
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.001	0.045	-10000	0	-10000	0	0
CDC2	-0.001	0.004	-10000	0	-0.023	9	9
NDC80	-0.18	0.36	-10000	0	-0.86	104	104
metaphase plate congression	-0.006	0.042	-10000	0	-10000	0	0
ERCC6L	-0.039	0.17	-10000	0	-0.82	18	18
NLP/gamma Tubulin	-0.004	0.035	-10000	0	-0.12	5	5
microtubule cytoskeleton organization	0	0.031	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.016	0.002	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.27	0.29	-10000	0	-0.57	228	228
GRASP65/GM130/RAB1/GTP/PLK1	-0.014	0.027	-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	0.006	0.039	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	117	117
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.043	-10000	0	-10000	0	0
microtubule-based process	-0.26	0.31	-10000	0	-0.58	228	228
Golgi organization	-0.014	0.059	-10000	0	-0.2	10	10
Cohesin/SA2	-0.025	0.046	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.4	0.44	-10000	0	-0.86	228	228
APC/C/CDC20	-0.048	0.18	-10000	0	-0.64	40	40
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.04	0.11	-10000	0	-0.6	15	15
PRC1	0.005	0.098	-10000	0	-0.86	6	6
ECT2	-0.001	0.054	-10000	0	-10000	0	0
C13orf34	0.002	0.043	-10000	0	-10000	0	0
NUDC	-0.006	0.042	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.025	0.12	-10000	0	-0.51	24	24
spindle assembly	-0.008	0.048	-10000	0	-0.16	8	8
spindle stabilization	0	0.031	-10000	0	-10000	0	0
APC/C/HCDH1	-0.001	0.023	-10000	0	-0.5	1	1
MKLP2/PLK1	-0.26	0.31	-10000	0	-0.59	228	228
CCNB1	0.001	0.11	-10000	0	-0.88	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.005	0.046	-10000	0	-0.47	1	1
TUBG1	0	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.027	0.1	-10000	0	-0.71	9	9
MLF1IP	-0.009	0.12	-10000	0	-0.69	15	15
INCENP	0.008	0.008	-10000	0	-10000	0	0

×

BCR signaling 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
JUN	-0.057	0.17	-10000	0	-0.42	32	32
IKBKB	-0.025	0.1	-10000	0	-10000	0	0
AKT1	-0.026	0.12	-10000	0	-0.3	3	3
IKBKG	-0.025	0.11	-10000	0	-10000	0	0
CALM1	-0.044	0.1	-10000	0	-0.5	3	3
PIK3CA	0.016	0	-10000	0	-10000	0	0
MAP3K1	-0.12	0.25	-10000	0	-0.64	66	66
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.057	0.11	-10000	0	-0.5	4	4
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.012	0.09	-10000	0	-10000	0	0
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.035	-10000	0	-0.76	1	1
SHC1	0.014	0.04	-10000	0	-0.86	1	1
BCR complex	-0.17	0.3	-10000	0	-0.68	123	123
CD22	-0.16	0.24	-10000	0	-0.68	51	51
CAMK2G	-0.031	0.1	-10000	0	-0.5	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.008	0.08	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.11	0.19	-10000	0	-0.85	4	4
GO:0007205	-0.057	0.11	-10000	0	-0.51	4	4
SYK	0.013	0.05	-10000	0	-0.76	2	2
ELK1	-0.044	0.11	-10000	0	-0.51	3	3
NFATC1	-0.075	0.2	-10000	0	-0.5	62	62
B-cell antigen/BCR complex	-0.17	0.3	-10000	0	-0.68	123	123
PAG1/CSK	-0.003	0.043	-10000	0	-0.67	2	2
NFKBIB	0.004	0.038	-10000	0	-10000	0	0
HRAS	-0.039	0.12	-10000	0	-0.52	3	3
NFKBIA	0.005	0.038	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.013	0.031	-10000	0	-10000	0	0
RasGAP/Csk	-0.22	0.33	-10000	0	-1	47	47
mol:GDP	-0.052	0.1	0.29	1	-0.52	3	4
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	0.01	0.069	-10000	0	-0.86	3	3
NF-kappa-B/RelA/I kappa B alpha	0.013	0.031	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.083	0.22	-10000	0	-0.57	59	59
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.068	0.11	-10000	0	-0.52	4	4
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.04	0.11	-10000	0	-0.5	5	5
CHUK	-0.025	0.11	-10000	0	-0.3	1	1
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.13	0.2	-10000	0	-0.56	59	59
PTPN6	-0.14	0.22	-10000	0	-0.68	39	39
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.012	0.069	-10000	0	-0.14	103	103
VAV2	-0.17	0.29	-10000	0	-0.8	69	69
ubiquitin-dependent protein catabolic process	0.01	0.037	-10000	0	-10000	0	0
BTK	-0.086	0.17	0.46	1	-0.42	96	97
CD19	-0.2	0.33	-10000	0	-0.9	73	73
MAP4K1	-0.35	0.43	-10000	0	-0.86	197	197
CD72	-0.2	0.38	-10000	0	-0.86	116	116
PAG1	0.012	0.057	-10000	0	-0.86	2	2
MAPK14	-0.089	0.22	-10000	0	-0.53	58	58
SH3BP5	0.014	0.035	-10000	0	-0.76	1	1
PIK3AP1	-0.04	0.11	-10000	0	-0.55	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.12	0.24	-10000	0	-0.6	67	67
RAF1	-0.026	0.12	-10000	0	-0.54	2	2
RasGAP/p62DOK/SHIP	-0.22	0.32	-10000	0	-0.97	48	48
CD79A	-0.21	0.38	-10000	0	-0.86	123	123
re-entry into mitotic cell cycle	-0.012	0.09	-10000	0	-10000	0	0
RASA1	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.002	0.1	-10000	0	-10000	0	0
MAPK1	-0.002	0.1	-10000	0	-10000	0	0
CD72/SHP1	-0.24	0.33	-10000	0	-0.83	96	96
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.089	0.22	-10000	0	-0.53	58	58
actin cytoskeleton organization	-0.1	0.26	-10000	0	-0.67	63	63
NF-kappa-B/RelA	0.034	0.058	-10000	0	-10000	0	0
Calcineurin	-0.044	0.071	-10000	0	-10000	0	0
PI3K	-0.14	0.22	-10000	0	-0.61	60	60
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.064	0.1	-10000	0	-0.55	4	4
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.28	0.32	-10000	0	-0.74	129	129
DAPP1	-0.11	0.19	-10000	0	-0.61	36	36
cytokine secretion	-0.069	0.19	-10000	0	-0.47	62	62
mol:DAG	-0.068	0.11	-10000	0	-0.52	4	4
PLCG2	0.002	0.11	-10000	0	-0.82	8	8
MAP2K1	-0.014	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.26	0.38	-10000	0	-0.73	173	173
mol:PI-3-4-5-P3	-0.1	0.15	-10000	0	-0.43	38	38
ETS1	-0.019	0.093	-10000	0	-0.44	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.22	-10000	0	-0.98	3	3
B-cell antigen/BCR complex/LYN	-0.14	0.22	-10000	0	-0.58	69	69
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.11	0.28	-10000	0	-0.73	63	63
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.25	-10000	0	-0.76	37	37
CARD11	-0.15	0.26	-10000	0	-0.61	102	102
FCGR2B	-0.16	0.35	-10000	0	-0.86	97	97
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.004	0.047	-10000	0	-10000	0	0
PTPRC	-0.083	0.28	-10000	0	-0.86	54	54
PDPK1	-0.062	0.1	-10000	0	-0.3	3	3
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	-0.001	0.059	-10000	0	-0.14	64	64

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.24	0.28	-9999	-0.83	74	74
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.012	0.082	-9999	-0.57	10	10
IFNAR2	0.014	0.007	-9999	-10000	0	0
AKT1	0.014	0.069	-9999	-0.43	10	10
ER alpha/Oestrogen	-0.002	0.038	-9999	-0.59	2	2
NFX1/SIN3/HDAC complex	0.045	0.052	-9999	-10000	0	0
EGF	-0.68	0.23	-9999	-0.76	432	432
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.22	0.26	-9999	-0.78	71	71
SAP18	0.013	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.36	0.39	-9999	-0.76	229	229
WRN	0.016	0	-9999	-10000	0	0
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.19	0.23	-9999	-0.72	60	60
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.25	0.29	-9999	-0.88	71	71
CCND1	-0.22	0.27	-9999	-0.77	83	83
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.013	0.006	-9999	-10000	0	0
RBBP4	0.013	0.006	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.013	0.006	-9999	-10000	0	0
Telomerase/911	0	0.025	-9999	-10000	0	0
CDKN1B	-0.23	0.3	-9999	-0.55	220	220
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	-0.016	0.16	-9999	-0.86	16	16
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.014	0.006	-9999	-10000	0	0
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.002	0.11	-9999	-0.76	10	10
IFN-gamma/IRF1	-0.3	0.32	-9999	-0.65	220	220
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.004	0.13	-9999	-0.86	11	11
Telomerase	-0.016	0.16	-9999	-0.4	38	38
IRF1	0.016	0.041	-9999	-0.86	1	1
ESR1	0.01	0.05	-9999	-0.76	2	2
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.051	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.006	0.031	-9999	-10000	0	0
HDAC1	0.013	0.006	-9999	-10000	0	0
HDAC2	0.015	0.007	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.024	0.07	-9999	-0.66	5	5
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.006	-9999	-10000	0	0
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	-0.18	0.25	-9999	-0.73	68	68
NR2F2	0.006	0.013	-9999	-10000	0	0
MAPK3	0.008	0.099	-9999	-0.67	10	10
MAPK1	0.008	0.099	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.007	0.089	-9999	-0.86	5	5
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	-0.001	0.12	-9999	-0.85	9	9
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.52	0.19	-9999	-0.58	433	433
MYC	-0.015	0.16	-9999	-0.87	16	16
IL2	-0.009	0.13	-9999	-0.87	10	10
KU	0	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.007	0.089	-9999	-0.86	5	5
TRF2/BLM	-0.014	0.094	-9999	-0.63	11	11
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.22	0.26	-9999	-0.78	69	69
SP1/HDAC2	0.006	0.013	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.19	0.23	-9999	-0.7	68	68
Smad3/Myc	-0.018	0.12	-9999	-0.6	20	20
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.85	220	220
Telomerase/PinX1	-0.19	0.23	-9999	-0.7	68	68
Telomerase/AKT1/mTOR/p70S6K	-0.014	0.08	-9999	-0.46	4	4
SIN3B	0.013	0.006	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.19	0.23	-9999	-0.71	65	65
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	-0.19	0.23	-9999	-0.7	68	68
E2F1	-0.085	0.28	-9999	-0.87	54	54
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.13	0.33	-9999	-0.86	79	79
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

×

Coregulation of Androgen receptor activity

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
NRIP1	0.013	0.038	-9999	-0.8	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.022	-9999	-10000	0	0
JMJD2C	0	0.02	-9999	-0.11	15	15
T-DHT/AR/Ubc9	-0.077	0.11	-9999	-0.56	22	22
CARM1	0.015	0.003	-9999	-10000	0	0
PRDX1	0.016	0.001	-9999	-10000	0	0
PELP1	0.016	0.003	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
AKT1	0.017	0.006	-9999	-10000	0	0
PTK2B	0.015	0.003	-9999	-10000	0	0
MED1	0.013	0.009	-9999	-10000	0	0
MAK	0.016	0.022	-9999	-10000	0	0
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.013	0.038	-9999	-0.8	1	1
GSN	0.015	0.007	-9999	-10000	0	0
NCOA2	0.009	0.07	-9999	-0.76	4	4
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.026	-9999	-10000	0	0
NCOA4	0.015	0.002	-9999	-10000	0	0
PIAS3	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.027	0.026	-9999	-10000	0	0
XRCC5	0.016	0.005	-9999	-10000	0	0
UBE3A	0.014	0.012	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.15	-9999	-0.6	35	35
FHL2	-0.037	0.098	-9999	-1.2	3	3
RANBP9	0.016	0.003	-9999	-10000	0	0
JMJD1A	-0.12	0.054	-9999	-0.14	419	419
CDK6	0.014	0.035	-9999	-0.76	1	1
TGFB1I1	0.013	0.041	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.16	-9999	-0.6	42	42
XRCC6	0.016	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.6	22	22
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.015	0.017	-9999	-10000	0	0
BRCA1	0.015	0.007	-9999	-10000	0	0
TCF4	0.014	0.013	-9999	-10000	0	0
CDKN2A	-0.83	0.16	-9999	-0.86	463	463
SRF	0.027	0.01	-9999	-10000	0	0
NKX3-1	-0.19	0.068	-9999	-10000	0	0
KLK3	0.025	0.14	-9999	-0.7	18	18
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.012	-9999	-10000	0	0
AOF2	-0.001	0.01	-9999	-10000	0	0
APPL1	0.033	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.076	0.11	-9999	-0.55	22	22
AR	-0.068	0.16	-9999	-0.8	22	22
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.014	0.012	-9999	-10000	0	0
PAWR	0.014	0.035	-9999	-0.76	1	1
PRKDC	0.016	0.005	-9999	-10000	0	0
PA2G4	0.014	0.012	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.1	-9999	-0.51	22	22
RPS6KA3	0.015	0.007	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.078	0.11	-9999	-0.56	22	22
LATS2	0.014	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.068	0.1	-9999	-0.51	22	22
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.007	0.13	-9999	-0.76	14	14
KLK2	-0.082	0.14	-9999	-0.81	15	15
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.063	0.12	-9999	-0.54	24	24
TMPRSS2	-0.94	0.35	-9999	-1.1	419	419
CCND1	-0.021	0.18	-9999	-0.86	20	20
PIAS1	0.014	0.012	-9999	-10000	0	0
mol:T-DHT	-0.062	0.026	-9999	-0.072	412	412
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.013	0.018	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.11	-9999	-0.57	22	22
CMTM2	-0.001	0.12	-9999	-0.86	9	9
SNURF	-0.011	0.14	-9999	-0.76	16	16
ZMIZ1	-0.032	0.021	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.014	0.012	-9999	-10000	0	0
FKBP4	0.016	0.003	-9999	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	215	215
alphaV beta3 Integrin	-0.005	0.051	-9999	-0.5	5	5
PTK2	-0.14	0.23	-9999	-0.55	47	47
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.014	0.04	-9999	-0.86	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.086	0.2	-9999	-0.53	76	76
VEGFA	-0.38	0.44	-9999	-0.86	215	215
ILK	-0.086	0.2	-9999	-0.53	76	76
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.079	0.18	-9999	-0.5	68	68
PTK2B	-0.19	0.27	-9999	-0.48	215	215
alphaV/beta3 Integrin/JAM-A	-0.069	0.16	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.48	220	220
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.068	-9999	-0.52	7	7
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.15	-9999	-0.48	45	45
alphaV/beta3 Integrin/Syndecan-1	-0.006	0.054	-9999	-0.48	6	6
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-9999	-0.88	3	3
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.004	0.044	-9999	-0.48	4	4
RPS6KB1	-0.042	0.13	-9999	-0.8	3	3
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.04	0.085	-9999	-0.62	3	3
GPR124	0.012	0.057	-9999	-0.86	2	2
MAPK1	-0.04	0.085	-9999	-0.62	3	3
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.055	0.15	-9999	-0.48	54	54
cell adhesion	-0.17	0.18	-9999	-0.84	1	1
ANGPTL3	-0.34	0.38	-9999	-0.76	219	219
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	215	215
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
IGF1	0.003	0.11	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.003	0.043	-9999	-0.54	3	3
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.001	0.022	-9999	-0.48	1	1
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.014	0.085	-9999	-0.52	13	13
CSF1	0.016	0	-9999	-10000	0	0
PIK3C2A	-0.086	0.2	-9999	-0.53	76	76
PI4 Kinase/Pyk2	-0.24	0.25	-9999	-0.76	45	45
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	215	215
FAK1/Vinculin	-0.11	0.19	-9999	-0.55	2	2
alphaV beta3/Integrin/ppsTEM5	-0.003	0.043	-9999	-0.55	3	3
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.11	0.29	-9999	-0.77	76	76
BCAR1	0.014	0.035	-9999	-0.76	1	1
FGF2	0.009	0.073	-9999	-0.78	4	4
F11R	0.026	0.057	-9999	-0.59	4	4
alphaV/beta3 Integrin/Lactadherin	-0.002	0.034	-9999	-0.53	2	2
alphaV/beta3 Integrin/TGFBR2	-0.001	0.022	-9999	-0.48	1	1
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.001	0.02	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.001	0.02	-9999	-0.45	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.052	0.24	-9999	-0.86	37	37
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.89	1	1
SDC1	0.008	0.079	-9999	-0.76	5	5
VAV3	0.04	0.08	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
FAK1/Paxillin	-0.11	0.19	-9999	-0.55	2	2
cell migration	-0.088	0.18	-9999	-0.53	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.061	0.14	-9999	-10000	0	0
SPP1	0.011	0.061	-9999	-0.76	3	3
KDR	0.014	0.035	-9999	-0.76	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	-0.07	0.24	-9999	-0.76	53	53
angiogenesis	0.005	0.14	-9999	-0.8	1	1
Rac1/GTP	-0.011	0.063	-9999	-10000	0	0
EDIL3	-0.005	0.13	-9999	-0.8	12	12
cell proliferation	-0.001	0.022	-9999	-0.48	1	1

×

IL6-mediated signaling 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
BCL2L1	-0.14	0.31	-9999	-0.76	42	42
CRP	-0.2	0.4	-9999	-0.9	91	91
cell cycle arrest	-0.18	0.36	-9999	-0.79	80	80
TIMP1	-0.15	0.34	-9999	-0.77	70	70
IL6ST	-0.004	0.11	-9999	-0.75	10	10
Rac1/GDP	-0.14	0.26	-9999	-0.6	84	84
AP1	0.026	0.1	-9999	-0.48	1	1
GAB2	0.012	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.38	-9999	-0.84	79	79
HSP90B1	0.005	0.092	-9999	-10000	0	0
GAB1	0.013	0.007	-9999	-10000	0	0
MAPK14	0.023	0.13	-9999	-0.71	3	3
AKT1	0.061	0.032	-9999	-10000	0	0
FOXO1	0.078	0.016	-9999	-10000	0	0
MAP2K6	-0.011	0.13	-9999	-0.66	4	4
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.28	-9999	-0.67	62	62
MITF	-0.02	0.14	-9999	-0.72	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	0.028	0.005	-9999	-10000	0	0
CEBPB	0.001	0.14	-9999	-0.86	12	12
GRB2/SOS1/GAB family/SHP2	0.003	0.07	-9999	-10000	0	0
STAT3	-0.19	0.38	-9999	-0.84	80	80
STAT1	-0.006	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.32	-9999	-0.75	45	45
PIK3CA	0.018	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.013	0.13	-9999	-0.68	2	2
MAPK11	0.023	0.13	-9999	-0.71	3	3
STAT3 (dimer)/FOXO1	-0.068	0.28	-9999	-0.63	23	23
GRB2/SOS1/GAB family	-0.044	0.1	-9999	-0.64	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.033	0.15	-9999	-0.63	10	10
GRB2	0.013	0.007	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	-0.27	0.45	-9999	-0.89	141	141
PIK3R1	0.017	0	-9999	-10000	0	0
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.33	-9999	-0.79	49	49
FGG	-0.28	0.44	-9999	-0.88	125	125
macrophage differentiation	-0.18	0.36	-9999	-0.79	80	80
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.066	0.17	-9999	-0.55	24	24
JUNB	-0.14	0.31	-9999	-0.77	35	35
FOS	-0.006	0.11	-9999	-0.76	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.03	0.15	-9999	-0.44	20	20
STAT1/PIAS1	-0.043	0.16	-9999	-0.51	13	13
GRB2/SOS1/GAB family/SHP2/PI3K	0.023	0.035	-9999	-10000	0	0
STAT3 (dimer)	-0.19	0.38	-9999	-0.84	80	80
PRKCD	-0.15	0.31	-9999	-0.73	55	55
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.038	0.12	-9999	-0.78	2	2
gp130 (dimer)/JAK1/JAK1/LMO4	-0.008	0.07	-9999	-0.48	10	10
Rac1/GTP	-0.18	0.24	-9999	-0.62	89	89
HCK	-0.036	0.2	-9999	-0.87	27	27
MAPKKK cascade	0.028	0.061	-9999	-10000	0	0
bone resorption	-0.18	0.36	-9999	-0.79	79	79
IRF1	-0.14	0.32	-9999	-0.77	39	39
mol:GDP	-0.15	0.27	-9999	-0.61	94	94
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.28	-9999	-0.62	94	94
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.003	0.12	-9999	-0.66	2	2
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.079	0.21	-9999	-0.64	59	59
gp130 (dimer)/TYK2/TYK2/LMO4	-0.008	0.069	-9999	-0.48	10	10
gp130 (dimer)/JAK2/JAK2/LMO4	-0.008	0.069	-9999	-0.48	10	10
IL6	-0.092	0.28	-9999	-0.84	59	59
PIAS3	0.016	0	-9999	-10000	0	0
PTPRE	0.017	0.017	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.015	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.03	0.13	-9999	-0.54	3	3
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.3	-9999	-0.78	71	71
MCL1	0.077	0.015	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.23	-9999	-0.49	160	160
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.12	0.23	-9999	-0.52	5	5
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.009	0.13	-9999	-0.86	11	11
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.66	0.38	-9999	-0.86	366	366
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	-0.001	0.03	-9999	-0.67	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.1	0.29	-9999	-0.86	61	61
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.18	0.24	-9999	-0.5	169	169
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.14	0.17	-9999	-0.6	15	15
MAP1B	-0.001	0.021	-9999	-0.33	2	2
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.18	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.76	159	159
PAFAH/LIS1	-0.44	0.24	-9999	-0.58	366	366
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.1	0.12	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.14	-9999	-0.7	1	1
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.14	0.19	-9999	-0.65	15	15
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.031	0	-9999	-10000	0	0
PAFAH1B3	0.014	0.035	-9999	-0.76	1	1
PAFAH1B2	0.016	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.001	0.013	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.16	-9999	-0.56	15	15
LRP8	0.014	0.04	-9999	-0.86	1	1
NDEL1/Katanin 60	-0.14	0.17	-9999	-0.6	15	15
P39/CDK5	-0.18	0.23	-9999	-0.87	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.096	0.22	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.15	0.2	-9999	-0.91	1	1
RELN/VLDLR	-0.15	0.21	-9999	-0.52	5	5
CDC42	0	0	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.018	0.11	-10000	0	-1.4	1	1
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.018	0	-10000	0	-10000	0	0
TBX21	-0.25	0.41	-10000	0	-0.82	159	159
SUMO2	0.01	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.024	0.056	-10000	0	-1.2	1	1
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	0.003	0.1	-10000	0	-0.85	7	7
GR alpha/HSP90/FKBP51/HSP90	0.05	0.13	0.39	5	-0.59	7	12
PRL	-0.01	0.11	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.58	72	-0.71	1	73
RELA	0.006	0.075	-10000	0	-10000	0	0
FGG	-0.16	0.43	0.59	11	-0.73	141	152
GR beta/TIF2	0.054	0.14	0.44	5	-0.56	5	10
IFNG	-0.41	0.44	-10000	0	-0.83	218	218
apoptosis	-0.098	0.22	-10000	0	-0.81	2	2
CREB1	-0.017	0.11	-10000	0	-0.4	5	5
histone acetylation	0.018	0.13	0.39	7	-0.39	7	14
BGLAP	-0.004	0.12	-10000	0	-0.57	2	2
GR/PKAc	0.061	0.1	0.39	3	-0.6	1	4
NF kappa B1 p50/RelA	0.015	0.14	-10000	0	-0.54	5	5
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.044	0.093	0.36	5	-10000	0	5
GATA3	-0.35	0.39	-10000	0	-0.75	230	230
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.026	0.16	-10000	0	-0.73	14	14
GSK3B	0.01	0.008	-10000	0	-10000	0	0
NR1I3	-0.06	0.22	-10000	0	-0.89	8	8
CSN2	0.038	0.19	0.52	3	-0.66	1	4
BRG1/BAF155/BAF170/BAF60A	0	0.004	-10000	0	-10000	0	0
NFATC1	0.018	0.005	-10000	0	-10000	0	0
POU2F1	0.02	0.005	-10000	0	-10000	0	0
CDKN1A	0.05	0.055	-10000	0	-0.72	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	-0.079	0.27	-10000	0	-0.84	53	53
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.005	0.21	0.38	2	-0.61	19	21
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.057	0.22	-10000	0	-0.89	7	7
JUN	-0.22	0.25	-10000	0	-0.63	73	73
IL4	-0.02	0.12	-10000	0	-0.58	2	2
CDK5R1	0.012	0.007	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.26	0.31	2	-0.67	80	82
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.056	0.12	0.38	4	-0.6	4	8
cortisol/GR alpha (monomer)	0.14	0.34	0.67	81	-0.81	1	82
NCOA2	0.009	0.07	-10000	0	-0.76	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.05	0.13	-10000	0	-0.82	10	10
AP-1/NFAT1-c-4	-0.32	0.34	-10000	0	-0.82	92	92
AFP	-0.37	0.57	-10000	0	-1.4	107	107
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.079	0.15	0.53	6	-0.62	1	7
TP53	0.044	0.022	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.24	0.41	-10000	0	-1.2	59	59
KRT14	-0.13	0.29	-10000	0	-0.85	60	60
TBP	0.029	0.001	-10000	0	-10000	0	0
CREBBP	0.042	0.076	-10000	0	-10000	0	0
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.011	0.014	-10000	0	-10000	0	0
AP-1	-0.32	0.34	-10000	0	-0.83	92	92
MAPK14	0.009	0.008	-10000	0	-10000	0	0
MAPK10	0	0.079	-10000	0	-0.77	5	5
MAPK11	0.01	0.008	-10000	0	-10000	0	0
KRT5	-0.25	0.38	-10000	0	-0.93	88	88
interleukin-1 receptor activity	0	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.056	-10000	0	-1.2	1	1
CGA	-0.13	0.38	-10000	0	-1.2	50	50
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.086	0.15	0.46	31	-10000	0	31
MAPK3	0.008	0.008	-10000	0	-10000	0	0
MAPK1	0.009	0.008	-10000	0	-10000	0	0
ICAM1	-0.042	0.22	-10000	0	-0.8	20	20
NFKB1	0.006	0.075	-10000	0	-10000	0	0
MAPK8	-0.14	0.19	-10000	0	-0.53	35	35
MAPK9	0.009	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.1	0.23	-10000	0	-0.86	2	2
BAX	0.052	0.029	-10000	0	-10000	0	0
POMC	-0.033	0.17	-10000	0	-0.92	4	4
EP300	0.042	0.077	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.15	0.29	0.6	74	-0.7	1	75
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.071	0.29	1	-10000	0	1
SGK1	0.099	0.094	-10000	0	-10000	0	0
IL13	-0.35	0.28	-10000	0	-0.8	87	87
IL6	-0.11	0.37	-10000	0	-0.98	63	63
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.28	0.21	-10000	0	-0.66	57	57
IL2	-0.17	0.25	-10000	0	-0.85	25	25
CDK5	0.012	0.007	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.071	0.29	-10000	0	-0.88	42	42
CDK5R1/CDK5	0	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.027	0.099	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.55	69	-0.65	1	70
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.097	0.15	0.42	29	-10000	0	29
NF kappa B1 p50/RelA/Cbp	0.062	0.13	-10000	0	-10000	0	0
JUN (dimer)	-0.21	0.25	-10000	0	-0.62	73	73
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.055	0.22	-10000	0	-0.84	21	21
NR3C1	0.075	0.19	0.52	28	-0.95	1	29
NR4A1	-0.002	0.14	-10000	0	-0.74	17	17
TIF2/SUV420H1	-0.005	0.052	-10000	0	-0.57	4	4
MAPKKK cascade	-0.098	0.22	-10000	0	-0.81	2	2
cortisol/GR alpha (dimer)/Src-1	0.14	0.29	0.58	77	-0.8	1	78
PBX1	0	0.12	-10000	0	-0.76	12	12
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.086	0.35	-10000	0	-1.2	34	34
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.097	0.15	0.42	29	-10000	0	29
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.55	69	-0.65	1	70
mol:cortisol	0.057	0.2	0.44	49	-10000	0	49
MMP1	-0.23	0.4	-10000	0	-0.99	95	95

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.17	0.27	-10000	0	-0.53	89	89
CRKL	0.019	0.11	-10000	0	-0.68	4	4
HRAS	-0.045	0.18	-10000	0	-0.51	41	41
mol:PIP3	-0.002	0.1	-10000	0	-0.45	18	18
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	0.007	0.12	-10000	0	-0.5	18	18
FOXO3	0.025	0.1	-10000	0	-0.6	4	4
AKT1	0.015	0.11	-10000	0	-0.45	18	18
BAD	0.024	0.1	-10000	0	-0.6	4	4
megakaryocyte differentiation	-0.066	0.21	-10000	0	-0.52	53	53
GSK3B	0.025	0.1	-10000	0	-0.6	4	4
RAF1	-0.012	0.16	-10000	0	-0.51	4	4
SHC1	0.014	0.04	-10000	0	-0.86	1	1
STAT3	0.008	0.12	-10000	0	-0.5	18	18
STAT1	-0.014	0.23	-10000	0	-1	18	18
HRAS/SPRED1	-0.068	0.12	-10000	0	-0.42	20	20
cell proliferation	0.008	0.12	-10000	0	-0.48	18	18
PIK3CA	0.016	0	-10000	0	-10000	0	0
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.009	0.12	-10000	0	-0.49	18	18
HRAS/SPRED2	-0.068	0.12	-10000	0	-0.42	20	20
LYN/TEC/p62DOK	-0.017	0.099	-10000	0	-0.67	4	4
MAPK3	0.011	0.12	-10000	0	-0.37	2	2
STAP1	-0.32	0.22	-10000	0	-0.43	365	365
GRAP2	-0.046	0.22	-10000	0	-0.86	34	34
JAK2	-0.066	0.18	-10000	0	-0.91	18	18
STAT1 (dimer)	-0.012	0.23	-10000	0	-1	18	18
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.22	-10000	0	-0.56	46	46
actin filament polymerization	0.003	0.13	-10000	0	-0.48	23	23
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.3	0.23	-10000	0	-0.86	27	27
PIK3R1	0.016	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.012	0.09	-10000	0	-0.59	4	4
PI3K	-0.017	0.1	-10000	0	-0.68	4	4
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.33	-10000	0	-1.3	20	20
MAPK8	0.008	0.12	-10000	0	-0.5	18	18
STAT3 (dimer)	0.008	0.12	-10000	0	-0.48	18	18
positive regulation of transcription	0.014	0.1	-10000	0	-0.31	1	1
mol:GDP	-0.12	0.2	-10000	0	-0.62	44	44
PIK3C2B	0.008	0.12	-10000	0	-0.5	18	18
CBL/CRKL	0.027	0.11	-10000	0	-0.62	4	4
FER	0.007	0.12	-10000	0	-0.51	19	19
SH2B3	0.008	0.12	-10000	0	-0.5	18	18
PDPK1	0.009	0.098	-10000	0	-0.57	4	4
SNAI2	0.007	0.12	-10000	0	-0.52	18	18
positive regulation of cell proliferation	0.001	0.18	-10000	0	-0.79	18	18
KITLG	0	0.11	-10000	0	-0.78	9	9
cell motility	0.001	0.18	-10000	0	-0.79	18	18
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.041	0.07	-10000	0	-10000	0	0
STAT5A (dimer)	0.005	0.16	-10000	0	-0.65	19	19
SOCS1	0.007	0.089	-10000	0	-0.86	5	5
cell migration	0.046	0.19	0.5	66	-10000	0	66
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.3	0.42	-10000	0	-0.86	172	172
VAV1	-0.2	0.38	-10000	0	-0.86	119	119
GRB10	0.007	0.12	-10000	0	-0.5	18	18
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.034	0.11	-10000	0	-0.51	20	20
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.005	0.13	-10000	0	-0.42	2	2
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-0.007	0.27	-10000	0	-1.1	25	25
MAP2K2	0.004	0.13	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.018	0.1	-10000	0	-0.67	4	4
STAT5A	0.004	0.16	-10000	0	-0.67	19	19
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.007	0.12	-10000	0	-0.5	18	18
SHC/GRAP2	-0.048	0.17	-10000	0	-0.66	35	35
PTPRO	-0.068	0.21	-10000	0	-0.53	53	53
SH2B2	0.002	0.13	-10000	0	-0.49	23	23
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.047	0.2	-10000	0	-0.51	66	66
CREBBP	0.045	0.012	-10000	0	-10000	0	0
BCL2	0.043	0.067	-10000	0	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.069	-9999	-0.68	5	5
Metarhodopsin II/Arrestin	-0.019	0.1	-9999	-0.6	15	15
PDE6G/GNAT1/GTP	-0.012	0.079	-9999	-0.56	10	10
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.002	0.089	-9999	-0.86	5	5
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.11	0.21	-9999	-0.92	11	11
mol:Na +	-0.11	0.21	-9999	-0.82	18	18
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	33	33
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.22	-9999	-0.86	18	18
CNGB1	-0.005	0.11	-9999	-0.86	8	8
RDH5	0	0.12	-9999	-0.83	9	9
SAG	0.002	0.006	-9999	-10000	0	0
mol:Ca2+	-0.074	0.22	-9999	-0.78	18	18
Na + (4 Units)	-0.1	0.19	-9999	-0.75	18	18
RGS9	-0.005	0.13	-9999	-0.82	12	12
GNB1/GNGT1	-0.22	0.32	-9999	-0.67	161	161
GNAT1/GDP	-0.035	0.12	-9999	-0.47	28	28
GUCY2D	-0.028	0.18	-9999	-0.86	22	22
GNGT1	-0.28	0.41	-9999	-0.86	161	161
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.036	0.14	-9999	-0.58	26	26
mol:11-cis-retinal	0	0.12	-9999	-0.83	9	9
mol:cGMP	-0.039	0.14	-9999	-0.53	24	24
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.033	0.14	-9999	-0.66	24	24
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.13	0.3	-9999	-0.76	91	91
Metarhodopsin II	-0.017	0.096	-9999	-0.55	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.041	0.14	-9999	-0.55	34	34
RGS9BP	-0.019	0.16	-9999	-0.76	21	21
Metarhodopsin II/Transducin	-0.11	0.16	-9999	-0.62	9	9
GCAP Family/Ca ++	-0.016	0.098	-9999	-0.56	14	14
PDE6A/B	-0.035	0.15	-9999	-0.67	25	25
mol:Pi	-0.035	0.13	-9999	-0.5	33	33
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.26	-9999	-0.55	162	162
PDE6B	0.008	0.079	-9999	-0.76	5	5
PDE6A	-0.025	0.18	-9999	-0.86	21	21
PDE6G	0.007	0.081	-9999	-0.78	5	5
RHO	-0.017	0.15	-9999	-0.86	15	15
PDE6	-0.056	0.16	-9999	-0.84	8	8
GUCA1A	-0.01	0.12	-9999	-0.86	9	9
GC2/GCAP Family	-0.016	0.098	-9999	-0.57	13	13
GUCA1C	0.001	0.05	-9999	-0.76	2	2
GUCA1B	0.008	0.08	-9999	-0.86	4	4

×

Signaling events mediated by PTP1B

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
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.045	0.099	-10000	0	-0.56	4	4
PTP1B/AKT1	-0.031	0.045	-10000	0	-0.42	2	2
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.048	0.051	-10000	0	-0.37	5	5
EGFR	-0.015	0.12	-10000	0	-0.87	9	9
EGF/EGFR	-0.38	0.14	-10000	0	-0.42	431	431
CSF1	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.048	0.086	-10000	0	-0.46	15	15
Insulin Receptor/Insulin	-0.011	0.031	-10000	0	-10000	0	0
HCK	-0.034	0.2	-10000	0	-0.86	27	27
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.034	0.049	-10000	0	-0.45	2	2
EGF	-0.68	0.23	-10000	0	-0.76	432	432
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	39	39
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.031	0.046	-10000	0	-0.44	4	4
cell migration	0.048	0.051	0.37	5	-10000	0	5
STAT3	0.015	0.003	-10000	0	-10000	0	0
PRLR	-0.09	0.24	-10000	0	-0.76	57	57
ITGA2B	-0.025	0.15	-10000	0	-0.86	15	15
CSF1R	0.003	0.11	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.068	0.19	-10000	0	-0.58	57	57
FGR	0.01	0.069	-10000	0	-0.86	3	3
PTP1B/p130 Cas	-0.036	0.05	-10000	0	-0.43	3	3
Crk/p130 Cas	-0.03	0.04	-10000	0	-0.42	2	2
DOK1	-0.018	0.044	-10000	0	-0.38	2	2
JAK2	-0.05	0.11	-10000	0	-0.42	14	14
Jak2/Leptin Receptor/Leptin	-0.051	0.13	-10000	0	-0.7	3	3
PIK3R1	0.016	0	-10000	0	-10000	0	0
PTPN1	-0.048	0.051	-10000	0	-0.37	5	5
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.007	0.13	-10000	0	-0.76	14	14
SRC	0	0.02	-10000	0	-10000	0	0
ITGB3	0	0.035	-10000	0	-0.76	1	1
CAT1/PTP1B	-0.24	0.14	-10000	0	-0.56	40	40
CAPN1	0.002	0.005	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0.011	0.029	-10000	0	-10000	0	0
mol:H2O2	-0.007	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.033	0.12	-10000	0	-0.66	3	3
negative regulation of transcription	-0.049	0.11	-10000	0	-0.41	14	14
FCGR2A	-0.025	0.18	-10000	0	-0.86	22	22
FER	0	0.035	-10000	0	-0.77	1	1
alphaIIb/beta3 Integrin	-0.022	0.12	-10000	0	-0.66	16	16
BLK	-0.04	0.21	-10000	0	-0.86	30	30
Insulin Receptor/Insulin/Shc	-0.001	0.027	-10000	0	-0.59	1	1
RHOA	0.002	0.005	-10000	0	-10000	0	0
LEPR	0.014	0.004	-10000	0	-10000	0	0
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.23	0.16	-10000	0	-0.56	55	55
PRL	0	0.002	-10000	0	-10000	0	0
SOCS3	0.028	0.051	-10000	0	-0.74	2	2
SPRY2	0.001	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.032	-10000	0	-0.5	2	2
CSF1/CSF1R	-0.037	0.071	-10000	0	-0.51	9	9
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.012	0.05	-10000	0	-0.76	2	2
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.073	0.26	-10000	0	-0.86	46	46
STAT5B	-0.043	0.065	-10000	0	-0.46	4	4
STAT5A	-0.043	0.065	-10000	0	-0.46	4	4
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.035	0.048	-10000	0	-0.45	2	2
CSN2	-0.006	0.067	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
LAT	-0.11	0.17	-10000	0	-0.35	144	144
YBX1	0.003	0.008	-10000	0	-10000	0	0
LCK	-0.024	0.18	-10000	0	-0.85	22	22
SHC1	0.014	0.04	-10000	0	-0.86	1	1
NOX4	-0.007	0.078	-10000	0	-0.77	5	5

×

Aurora A signaling

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
Aurora A/GADD45A	0.02	0.046	-9999	-10000	0	0
BIRC5	-0.24	0.4	-9999	-0.86	140	140
NFKBIA	0.048	0.041	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.77	94	94
AKT1	0.048	0.041	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.018	0.042	-9999	-10000	0	0
NDEL1/TACC3	0.016	0.078	-9999	-0.74	4	4
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.014	0.019	-9999	-10000	0	0
PAK1/Aurora A	0.02	0.046	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.012	0.05	-9999	-0.76	2	2
TPX2	-0.14	0.3	-9999	-0.67	120	120
TP53	0.025	0.037	-9999	-10000	0	0
DLG7	0.02	0.045	-9999	-0.29	6	6
AURKAIP1	0.012	0.05	-9999	-0.76	2	2
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.017	0.082	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
AURKA	0.027	0.056	-9999	-0.34	6	6
AURKB	-0.14	0.15	-9999	-0.29	229	229
CDC25B	0.018	0.064	-9999	-0.58	2	2
G2/M transition checkpoint	0.016	0.051	-9999	-0.45	2	2
mRNA polyadenylation	-0.073	0.19	-9999	-0.45	94	94
Aurora A/CPEB	-0.074	0.19	-9999	-0.46	94	94
Aurora A/TACC1/TRAP/chTOG	-0.003	0.024	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.02	0.046	-9999	-10000	0	0
regulation of centrosome cycle	-0.007	0.068	-9999	-0.73	4	4
spindle assembly	-0.003	0.024	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.14	0.21	-9999	-0.71	6	6
CENPA	-0.12	0.14	-9999	-0.3	160	160
Aurora A/PP2A	0.02	0.046	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.054	0.036	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.037	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
Ajuba/Aurora A	0.016	0.051	-9999	-0.45	2	2
mitotic prometaphase	0.038	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.056	-9999	-0.34	6	6
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.008	0.08	-9999	-0.86	4	4
Aurora A/Antizyme1	0.02	0.053	-9999	-10000	0	0
Aurora A/RasGAP	0.02	0.046	-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	0.014	0.019	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.3	-9999	-0.67	120	120
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.092	0.25	-9999	-0.52	120	120
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	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	-0.081	0.31	-10000	0	-0.91	26	26
NCK1/PAK1/Dok-R	-0.081	0.1	-10000	0	-0.42	24	24
NCK1/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
PIK3CA	0.002	0.005	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.007	0.034	0.28	6	-10000	0	6
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.006	0.041	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.32	0.42	-10000	0	-0.86	182	182
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.053	0.22	-10000	0	-0.97	26	26
FN1	-0.052	0.24	-10000	0	-0.86	37	37
PLD2	0.038	0.29	-10000	0	-1.1	26	26
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.029	0.18	-10000	0	-0.76	28	28
ELK1	0.066	0.26	-10000	0	-0.98	26	26
GRB7	0.004	0.093	-10000	0	-0.76	7	7
PAK1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.29	-10000	0	-1	40	40
CDKN1A	-0.11	0.31	-10000	0	-0.68	19	19
ITGA5	-0.052	0.24	-10000	0	-0.86	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.046	0.26	-10000	0	-0.66	26	26
PLG	-0.19	0.35	-10000	0	-1.3	26	26
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.2	-10000	0	-0.85	26	26
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.009	-10000	0	-10000	0	0
ANGPT2	-0.21	0.38	-10000	0	-0.65	151	151
BMX	-0.04	0.34	-10000	0	-1.1	26	26
ANGPT1	0.079	0.19	-10000	0	-1.3	6	6
tube development	-0.13	0.34	-10000	0	-0.74	22	22
ANGPT4	-0.021	0.16	-10000	0	-0.87	16	16
response to hypoxia	-0.002	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.049	0.31	-10000	0	-1.2	26	26
alpha5/beta1 Integrin	-0.051	0.18	-10000	0	-0.67	37	37
FGF2	0.011	0.075	-10000	0	-0.78	4	4
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	23	23
mol:L-citrulline	-0.046	0.26	-10000	0	-0.66	26	26
AGTR1	-0.037	0.17	-10000	0	-0.76	26	26
MAPK14	0.002	0.3	-10000	0	-1.2	26	26
Tie2/SHP2	-0.058	0.25	-10000	0	-1.1	25	25
TEK	-0.049	0.28	-10000	0	-1.2	25	25
RPS6KB1	-0.043	0.28	-10000	0	-0.87	26	26
Angiotensin II/AT1	-0.044	0.13	-10000	0	-0.59	26	26
Tie2/Ang1/GRB2	-0.027	0.29	-10000	0	-1.1	26	26
MAPK3	0.05	0.27	-10000	0	-1	26	26
MAPK1	0.05	0.27	-10000	0	-1	26	26
Tie2/Ang1/GRB7	-0.032	0.3	-10000	0	-1.2	26	26
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.038	0.29	-10000	0	-1.1	26	26
PI3K	-0.066	0.32	-10000	0	-1.1	26	26
FES	-0.004	0.31	-10000	0	-1.1	27	27
Crk/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
Tie2/Ang1/ABIN2	-0.027	0.29	-10000	0	-1.1	26	26
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.07	0.29	-10000	0	-0.8	26	26
STAT5A	0.016	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.043	0.28	-10000	0	-0.87	26	26
Tie2/Ang2	-0.19	0.4	-10000	0	-0.99	28	28
Tie2/Ang1	0.03	0.32	-10000	0	-1.2	26	26
FOXO1	-0.1	0.31	-10000	0	-0.81	26	26
ELF1	0.025	0.013	-10000	0	-10000	0	0
ELF2	0.034	0.3	-10000	0	-1.1	26	26
mol:Choline	0.041	0.28	-10000	0	-1	26	26
cell migration	-0.055	0.071	-10000	0	-10000	0	0
FYN	-0.15	0.36	-10000	0	-0.86	22	22
DOK2	-0.035	0.21	-10000	0	-0.86	28	28
negative regulation of cell cycle	-0.094	0.3	-10000	0	-0.6	22	22
ETS1	0.029	0.033	-10000	0	-10000	0	0
PXN	-0.022	0.25	-10000	0	-0.7	26	26
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.057	0.28	-10000	0	-0.75	26	26
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.009	0.11	-10000	0	-0.8	8	8
MAPKKK cascade	0.041	0.28	-10000	0	-1	26	26
RASA1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.001	0.3	-10000	0	-1.1	26	26
NCK1	0.016	0	-10000	0	-10000	0	0
vasculogenesis	-0.038	0.24	-10000	0	-0.58	26	26
mol:Phosphatidic acid	0.041	0.28	-10000	0	-1	26	26
mol:Angiotensin II	-0.017	0.022	-10000	0	-10000	0	0
mol:NADP	-0.046	0.26	-10000	0	-0.66	26	26
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	26	26
MMP2	0.033	0.3	-10000	0	-1.1	26	26

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.014	0.057	-10000	0	-0.62	1	1
NT3 (dimer)/TRKC	-0.039	0.15	-10000	0	-0.61	31	31
NT3 (dimer)/TRKB	-0.14	0.25	-10000	0	-0.55	125	125
SHC/Grb2/SOS1/GAB1/PI3K	-0.001	0.012	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.11	0.31	-10000	0	-0.86	68	68
PIK3CA	0.016	0	-10000	0	-10000	0	0
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.047	0.21	-10000	0	-0.76	38	38
NTRK2	-0.13	0.3	-10000	0	-0.76	91	91
NTRK3	-0.028	0.18	-10000	0	-0.76	27	27
NT-4/5 (dimer)/TRKB	-0.14	0.26	-10000	0	-0.56	123	123
neuron apoptosis	0.15	0.19	0.58	46	-10000	0	46
SHC 2-3/Grb2	-0.16	0.21	-10000	0	-0.65	46	46
SHC1	0.014	0.04	-10000	0	-0.86	1	1
SHC2	-0.1	0.15	-10000	0	-0.5	35	35
SHC3	-0.17	0.25	-10000	0	-0.64	86	86
STAT3 (dimer)	0.011	0.07	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.09	0.21	-10000	0	-0.56	78	78
RIN/GDP	0.048	0.063	-10000	0	-0.31	2	2
GIPC1	0.014	0.035	-10000	0	-0.76	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.075	0.15	-10000	0	-0.63	15	15
RIN/GTP	-0.001	0.031	-10000	0	-0.68	1	1
CCND1	0.007	0.16	-10000	0	-0.78	20	20
MAGED1	0.014	0.04	-10000	0	-0.86	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.004	0.089	-10000	0	-0.86	5	5
SHC/GRB2/SOS1	-0.001	0.026	-10000	0	-0.58	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.16	0.28	-10000	0	-0.6	124	124
TRKA/NEDD4-2	-0.046	0.16	-10000	0	-0.58	38	38
ELMO1	0.012	0.057	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.002	0.038	-10000	0	-0.59	2	2
NGF	-0.072	0.26	-10000	0	-0.86	48	48
HRAS	0.016	0	-10000	0	-10000	0	0
DOCK1	0.016	0	-10000	0	-10000	0	0
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.002	0.04	-10000	0	-0.86	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
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	-0.075	0.15	-10000	0	-0.6	17	17
mol:GDP	0.062	0.085	-10000	0	-0.52	1	1
NGF (dimer)	-0.072	0.26	-10000	0	-0.86	48	48
RhoG/GDP	-0.003	0.044	-10000	0	-0.68	2	2
RIT1/GDP	0.055	0.062	-10000	0	-0.32	1	1
TIAM1	0.014	0.035	-10000	0	-0.76	1	1
PIK3R1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.17	0.27	-10000	0	-0.56	147	147
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.001	0.03	-10000	0	-0.67	1	1
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.001	0.024	-10000	0	-0.52	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	0.006	0.09	-10000	0	-0.79	6	6
RAP1/GDP	-0.008	0.03	-10000	0	-10000	0	0
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.11	0.3	-10000	0	-0.86	68	68
ubiquitin-dependent protein catabolic process	-0.096	0.21	-10000	0	-0.55	84	84
Schwann cell development	-0.027	0.033	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-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	-0.15	0.24	-10000	0	-0.83	28	28
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.052	0.08	-10000	0	-10000	0	0
STAT3	0.011	0.07	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.77	28	28
MAPK3	-0.11	0.27	-10000	0	-0.59	90	90
MAPK1	-0.11	0.27	-10000	0	-0.59	90	90
CDC42/GDP	0.055	0.062	-10000	0	-0.32	1	1
NTF3	0.006	0.09	-10000	0	-0.79	6	6
NTF4	-0.004	0.089	-10000	0	-0.86	5	5
NGF (dimer)/TRKA/FAIM	-0.096	0.21	-10000	0	-0.55	84	84
PI3K	0	0	-10000	0	-10000	0	0
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	-0.086	0.17	-10000	0	-0.61	25	25
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0.001	0.14	-10000	0	-0.52	31	31
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.068	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.062	-10000	0	-0.32	1	1
NGF (dimer)/TRKA/GRIT	-0.098	0.22	-10000	0	-0.56	84	84
neuron projection morphogenesis	-0.027	0.15	-10000	0	-0.54	15	15
NGF (dimer)/TRKA/NEDD4-2	-0.097	0.21	-10000	0	-0.55	84	84
MAP2K1	0.053	0.024	-10000	0	-0.48	1	1
NGFR	-0.054	0.24	-10000	0	-0.86	38	38
NGF (dimer)/TRKA/GIPC/GAIP	-0.056	0.12	-10000	0	-0.6	2	2
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0	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	0.061	-10000	0	-0.76	3	3
MAPKKK cascade	-0.1	0.19	-10000	0	-0.61	45	45
RASA1	0.016	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.045	0.16	-10000	0	-0.57	38	38
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.16	0.25	-10000	0	-0.6	67	67
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.083	0.18	-10000	0	-0.88	3	3
MATK	-0.078	0.27	-10000	0	-0.86	51	51
NEDD4L	0.014	0.035	-10000	0	-0.76	1	1
RAS family/GDP	-0.007	0.029	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.081	0.16	-10000	0	-0.48	40	40
Rac1/GTP	-0.047	0.086	-10000	0	-0.41	6	6
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.045	0.15	-9999	-0.58	37	37
EPHB2	0.001	0.11	-9999	-0.78	9	9
Syndecan-2/TACI	-0.052	0.16	-9999	-0.58	43	43
LAMA1	-0.007	0.13	-9999	-0.77	14	14
Syndecan-2/alpha2 ITGB1	-0.007	0.056	-9999	-0.49	5	5
HRAS	0.016	0	-9999	-10000	0	0
Syndecan-2/CASK	0	0	-9999	-10000	0	0
ITGA5	-0.052	0.24	-9999	-0.86	37	37
BAX	0.056	0	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
LAMA3	0.007	0.089	-9999	-0.86	5	5
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.003	0.11	-9999	-0.86	7	7
Syndecan-2/MMP2	-0.006	0.059	-9999	-0.58	5	5
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.002	0.037	-9999	-0.57	2	2
dendrite morphogenesis	-0.009	0.069	-9999	-0.51	9	9
Syndecan-2/GM-CSF	-0.017	0.097	-9999	-0.58	14	14
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.026	-9999	-0.58	1	1
GNB2L1	0.014	0.04	-9999	-0.86	1	1
MAPK3	0.022	0.095	-9999	-0.52	14	14
MAPK1	0.022	0.095	-9999	-0.52	14	14
Syndecan-2/RACK1	-0.001	0.023	-9999	-0.5	1	1
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.027	0	-9999	-10000	0	0
ITGA2	0.012	0.05	-9999	-0.76	2	2
MAPK8	0.048	0	-9999	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	-0.014	0.079	-9999	-0.66	2	2
Syndecan-2/Kininogen	-0.37	0.21	-9999	-0.49	363	363
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.049	0.024	-9999	-0.47	1	1
Syndecan-2/CASK/Protein 4.1	0	0	-9999	-10000	0	0
extracellular matrix organization	-0.006	0.058	-9999	-0.58	5	5
actin cytoskeleton reorganization	-0.044	0.15	-9999	-0.58	37	37
Syndecan-2/Caveolin-2/Ras	-0.008	0.063	-9999	-0.53	7	7
Syndecan-2/Laminin alpha3	-0.006	0.059	-9999	-0.58	5	5
Syndecan-2/RasGAP	-0.001	0.021	-9999	-0.47	1	1
alpha5/beta1 Integrin	-0.051	0.18	-9999	-0.67	37	37
PRKCD	0.014	0.04	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.069	-9999	-0.51	9	9
GO:0007205	0.005	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.001	0.02	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.065	0.25	-9999	-0.86	43	43
RASA1	0.016	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.002	0.037	-9999	-0.57	2	2
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.089	-9999	-0.86	5	5
CASP3	0.043	0.026	-9999	-0.52	1	1
FN1	-0.052	0.24	-9999	-0.86	37	37
Syndecan-2/IL8	-0.036	0.14	-9999	-0.56	31	31
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.57	0.33	-9999	-0.76	363	363
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.018	0.15	-9999	-0.86	14	14
Syndecan-2/TGFB1	-0.006	0.059	-9999	-0.58	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-2/Ezrin	0	0	-9999	-10000	0	0
PRKACA	0.045	0	-9999	-10000	0	0
angiogenesis	-0.036	0.14	-9999	-0.56	31	31
MMP2	0.007	0.089	-9999	-0.86	5	5
IL8	-0.04	0.21	-9999	-0.85	31	31
calcineurin-NFAT signaling pathway	-0.052	0.16	-9999	-0.58	43	43

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.014	0.04	-9999	-0.86	1	1
RELN/VLDLR/Fyn	-0.16	0.23	-9999	-0.58	4	4
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.003	0.042	-9999	-0.83	1	1
AKT1	-0.066	0.16	-9999	-0.56	1	1
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.009	0.13	-9999	-0.86	11	11
RELN/LRP8/DAB1	-0.16	0.22	-9999	-0.46	170	170
LRPAP1/LRP8	-0.001	0.03	-9999	-0.67	1	1
RELN/LRP8/DAB1/Fyn	-0.15	0.21	-9999	-0.52	16	16
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.83	1	1
long-term memory	-0.21	0.25	-9999	-0.89	22	22
DAB1/LIS1	-0.14	0.19	-9999	-0.86	1	1
DAB1/CRLK/C3G	-0.13	0.18	-9999	-0.83	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
DAB1/NCK2	-0.14	0.19	-9999	-0.87	1	1
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.11	0.3	-9999	-0.84	68	68
CDK5R1	0.016	0	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.76	159	159
PIK3R1	0.016	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.16	0.23	-9999	-0.49	160	160
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.26	-9999	-0.9	22	22
MAPK8	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.46	169	169
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.88	2	2
RELN/LRP8	-0.16	0.23	-9999	-0.49	160	160
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.15	0.21	-9999	-0.91	2	2
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.001	0.03	-9999	-0.67	1	1
RAP1A	-0.12	0.16	-9999	-0.76	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.012	0.05	-9999	-0.76	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.008	0.057	-9999	-0.86	2	2
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.028	0.12	-9999	-0.54	2	2
neuron adhesion	-0.05	0.2	-9999	-0.71	1	1
LRP8	0.014	0.04	-9999	-0.86	1	1
GSK3B	-0.052	0.15	-9999	-0.53	1	1
RELN/VLDLR/DAB1/Fyn	-0.15	0.21	-9999	-0.53	15	15
MAP3K11	0.014	0.035	-9999	-0.76	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.15	-9999	-0.6	1	1
CDK5	0.016	0	-9999	-10000	0	0
MAPT	0.015	0.087	-9999	-0.71	6	6
neuron migration	-0.059	0.21	-9999	-0.61	1	1
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.058	0.1	-9999	-0.55	2	2
RELN/VLDLR	-0.15	0.21	-9999	-0.52	5	5

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.002	0.22	-10000	0	-0.56	18	18
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.086	0.12	-10000	0	-0.76	2	2
EDN1	-0.04	0.2	-10000	0	-0.74	20	20
EDN3	-0.02	0.16	-10000	0	-0.86	16	16
EDN2	-0.088	0.28	-10000	0	-0.82	59	59
HRAS/GDP	0.055	0.16	-10000	0	-0.66	8	8
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.022	0.15	-10000	0	-0.49	13	13
ADCY4	0.005	0.17	-10000	0	-0.74	3	3
ADCY5	-0.012	0.2	-10000	0	-0.7	12	12
ADCY6	0.005	0.17	-10000	0	-0.74	3	3
ADCY7	-0.011	0.2	-10000	0	-0.73	7	7
ADCY1	-0.003	0.18	-10000	0	-0.65	6	6
ADCY2	-0.13	0.27	-10000	0	-0.69	30	30
ADCY3	0.005	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.28	-10000	0	-0.72	37	37
ADCY9	0.005	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.081	0.15	-10000	0	-0.54	8	8
ETB receptor/Endothelin-1/Gq/GTP	0.034	0.11	-10000	0	-0.48	11	11
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.019	0.22	0.38	65	-0.52	18	83
ETA receptor/Endothelin-1/Gs/GTP	-0.018	0.21	0.36	65	-0.5	18	83
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.051	0.35	-10000	0	-0.95	51	51
EDNRB	0.006	0.071	-10000	0	-0.79	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.049	0.31	-10000	0	-0.76	46	46
CYSLTR1	0.002	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.016	0.12	-10000	0	-0.39	2	2
mol:GDP	0.048	0.18	-10000	0	-0.7	9	9
SLC9A3	-0.35	0.3	-10000	0	-0.54	301	301
RAF1	0.051	0.16	-10000	0	-0.67	9	9
JUN	0.089	0.12	-10000	0	-0.57	1	1
JAK2	0.002	0.22	-10000	0	-0.56	18	18
mol:IP3	0.019	0.17	-10000	0	-0.57	15	15
ETA receptor/Endothelin-1	-0.034	0.28	0.45	65	-0.57	53	118
PLCB1	0.005	0.093	-10000	0	-0.76	7	7
PLCB2	-0.078	0.27	-10000	0	-0.86	52	52
ETA receptor/Endothelin-3	-0.024	0.16	-10000	0	-0.68	18	18
FOS	0.065	0.2	-10000	0	-0.88	12	12
Gai/GDP	0.039	0.071	-10000	0	-0.63	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.001	0.24	-10000	0	-0.76	15	15
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
PRKCB1	0.021	0.16	-10000	0	-0.54	15	15
GNAQ	0.02	0.003	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
Gs family/GDP	-0.042	0.1	-10000	0	-0.61	9	9
ETA receptor/Endothelin-1/Gq/GTP	0.044	0.14	-10000	0	-0.49	10	10
MAPK14	0.026	0.13	-10000	0	-0.6	7	7
TRPC6	0.086	0.13	-10000	0	-0.81	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.016	0.14	-10000	0	-0.53	12	12
ETB receptor/Endothelin-2	-0.085	0.21	-10000	0	-0.63	62	62
ETB receptor/Endothelin-3	-0.03	0.13	-10000	0	-0.66	19	19
ETB receptor/Endothelin-1	-0.037	0.17	-10000	0	-0.62	20	20
MAPK3	0.065	0.19	-10000	0	-0.72	14	14
MAPK1	0.065	0.19	-10000	0	-0.72	14	14
Rac1/GDP	0.055	0.16	-10000	0	-0.73	6	6
cAMP biosynthetic process	-0.063	0.19	-10000	0	-0.62	13	13
MAPK8	0.081	0.13	-10000	0	-0.59	2	2
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.005	0.085	-10000	0	-0.58	3	3
p130Cas/CRK/Src/PYK2	0.076	0.17	-10000	0	-0.72	6	6
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.055	0.16	-10000	0	-0.69	7	7
COL1A2	-0.11	0.34	-10000	0	-0.88	67	67
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.08	0.23	-10000	0	-0.63	61	61
mol:DAG	0.019	0.17	-10000	0	-0.57	15	15
MAP2K2	0.061	0.17	-10000	0	-0.69	9	9
MAP2K1	0.062	0.17	-10000	0	-0.69	8	8
EDNRA	-0.011	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.014	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.031	0.14	-10000	0	-0.7	13	13
HRAS/GTP	0.039	0.17	-10000	0	-0.7	9	9
PRKCH	0.031	0.16	-10000	0	-0.68	7	7
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.031	0.16	-10000	0	-0.65	8	8
PRKCB	0.025	0.18	-10000	0	-0.69	13	13
PRKCE	0.03	0.16	-10000	0	-0.6	10	10
PRKCD	0.03	0.16	-10000	0	-0.65	8	8
PRKCG	0.006	0.19	-10000	0	-0.71	16	16
regulation of vascular smooth muscle contraction	0.065	0.22	-10000	0	-1	12	12
PRKCQ	0.019	0.18	-10000	0	-0.73	9	9
PLA2G4A	0.081	0.16	-10000	0	-0.59	8	8
GNA14	0.009	0.093	-10000	0	-0.76	7	7
GNA15	-0.003	0.14	-10000	0	-0.86	12	12
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.016	0.05	-10000	0	-0.76	2	2
Rac1/GTP	-0.019	0.22	0.38	65	-0.52	18	83
MMP1	-0.14	0.37	-10000	0	-0.86	95	95

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.016	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.1	0.092	-9999	-10000	0	0
NEF	-0.06	0.085	-9999	-10000	0	0
NFKBIA	0.001	0.045	-9999	-10000	0	0
BIRC3	-0.07	0.31	-9999	-0.79	74	74
CYCS	-0.082	0.14	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.38	0.48	-9999	-1.1	159	159
MAP2K7	-0.044	0.11	-9999	-10000	0	0
protein ubiquitination	0.06	0.072	-9999	-0.45	1	1
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.016	0	-9999	-10000	0	0
BID	-0.097	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.05	0.12	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.05	0.12	-9999	-10000	0	0
MAPK8	-0.031	0.1	-9999	-10000	0	0
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.014	0.04	-9999	-0.86	1	1
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.14	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.012	0.059	-9999	-10000	0	0
CHUK	0.061	0.076	-9999	-0.49	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.41	0.45	-9999	-1	159	159
TNF	0.002	0.11	-9999	-0.81	8	8
FASLG	-0.59	0.61	-9999	-1.1	264	264
NFKB1	0.001	0.045	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.009	0.068	-9999	-0.53	8	8
CASP6	-0.05	0.052	-9999	-10000	0	0
CASP7	-0.063	0.21	-9999	-0.55	51	51
RELA	0.001	0.045	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.063	0.21	-9999	-0.55	51	51
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.053	0.082	-9999	-0.53	3	3
APAF-1/Caspase 9	-0.13	0.18	-9999	-0.56	51	51
BCL2	-0.019	0.097	-9999	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.015	0.01	-10000	0	-10000	0	0
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.025	0.083	-10000	0	-0.51	2	2
AKT1	0.02	0.006	-10000	0	-10000	0	0
GSC	-0.024	0.22	-10000	0	-0.76	39	39
NKX2-5	-0.048	0.22	-10000	0	-0.86	32	32
muscle cell differentiation	0.033	0.11	0.57	10	-10000	0	10
SMAD2-3/SMAD4/SP1	0.035	0.079	-10000	0	-10000	0	0
SMAD4	0.032	0.03	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.005	0.034	-10000	0	-0.56	1	1
SMAD3/SMAD4/VDR	0.012	0.05	-10000	0	-10000	0	0
MYC	-0.028	0.16	-10000	0	-0.86	16	16
CDKN2B	0.056	0.086	-10000	0	-0.67	5	5
AP1	0.061	0.071	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.011	0.046	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.039	0.069	-10000	0	-0.45	4	4
SP3	0.02	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.051	0.24	-10000	0	-0.88	36	36
SMAD3/SMAD4/GR	0.009	0.045	-10000	0	-0.6	1	1
GATA3	-0.35	0.38	-10000	0	-0.75	230	230
SKI/SIN3/HDAC complex/NCoR1	0.056	0.042	-10000	0	-10000	0	0
MEF2C/TIF2	-0.068	0.18	-10000	0	-0.79	17	17
endothelial cell migration	0.091	0.26	0.74	65	-10000	0	65
MAX	0.008	0.02	-10000	0	-10000	0	0
RBBP7	0.015	0.005	-10000	0	-10000	0	0
RBBP4	0.015	0.005	-10000	0	-10000	0	0
RUNX2	-0.008	0.14	-10000	0	-0.86	13	13
RUNX3	-0.37	0.44	-10000	0	-0.86	210	210
RUNX1	-0.048	0.23	-10000	0	-0.86	35	35
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.006	0.045	-10000	0	-0.87	1	1
VDR	0.011	0.061	-10000	0	-0.76	3	3
CDKN1A	0.083	0.077	-10000	0	-0.64	2	2
KAT2B	0.014	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.048	0.17	-10000	0	-0.61	36	36
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.005	-10000	0	-10000	0	0
SERPINE1	-0.093	0.26	-10000	0	-0.74	65	65
SMAD3/SMAD4/ATF2	0.009	0.031	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.003	0.06	-10000	0	-0.5	5	5
SAP30	-0.014	0.16	-10000	0	-0.86	16	16
Cbp/p300/PIAS3	0.008	0.029	-10000	0	-10000	0	0
JUN	0.077	0.067	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.01	0.11	-10000	0	-0.56	16	16
TFE3	0.022	0.011	-10000	0	-10000	0	0
COL1A2	-0.098	0.26	-10000	0	-0.75	64	64
mesenchymal cell differentiation	0.007	0.1	0.59	13	-10000	0	13
DLX1	-0.46	0.44	-10000	0	-0.86	260	260
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.009	0.11	-10000	0	-0.74	10	10
SMAD3/SMAD4/Max	0.01	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	-0.002	0.047	-10000	0	-0.73	2	2
LAMC1	0.072	0.042	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.031	-10000	0	-10000	0	0
IRF7	-0.011	0.16	-10000	0	-0.85	16	16
ESR1	0.005	0.054	-10000	0	-0.76	2	2
HNF4A	-0.05	0.22	-10000	0	-0.76	41	41
MEF2C	-0.002	0.22	-10000	0	-0.81	18	18
SMAD2-3/SMAD4	0.006	0.032	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.006	0.021	-10000	0	-10000	0	0
IGHV3OR16-13	-0.051	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.008	-10000	0	-10000	0	0
SKIL	0.016	0	-10000	0	-10000	0	0
HDAC1	0.015	0.005	-10000	0	-10000	0	0
HDAC2	0.015	0.005	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.011	0.037	-10000	0	-10000	0	0
MSG1/HSC70	0.003	0.033	-10000	0	-0.67	1	1
SMAD2	0.022	0.019	-10000	0	-10000	0	0
SMAD3	0.033	0.027	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.064	0.03	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.025	0.02	-10000	0	-10000	0	0
NCOR1	0.015	0.005	-10000	0	-10000	0	0
NCOA2	0.009	0.07	-10000	0	-0.76	4	4
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.038	0.15	-10000	0	-0.67	27	27
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.086	-10000	0	-10000	0	0
IFNB1	0.047	0.1	-10000	0	-0.54	2	2
SMAD3/SMAD4/MEF2C	-0.02	0.2	-10000	0	-0.77	17	17
CITED1	0.012	0.04	-10000	0	-0.86	1	1
SMAD2-3/SMAD4/ARC105	0.008	0.031	-10000	0	-10000	0	0
RBL1	0.016	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.078	0.064	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.29	0.32	-10000	0	-0.61	231	231
SMAD7	0.052	0.08	-10000	0	-10000	0	0
MYC/MIZ-1	-0.024	0.12	-10000	0	-0.65	18	18
SMAD3/SMAD4	-0.018	0.12	-10000	0	-10000	0	0
IL10	-0.2	0.32	-10000	0	-1	31	31
PIASy/HDAC complex	0.018	0.01	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.17	0.26	-10000	0	-0.76	15	15
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.018	0.01	-10000	0	-10000	0	0
ATF3	0.008	0.079	-10000	0	-0.76	5	5
SMAD3/SMAD4/SP1	-0.012	0.054	-10000	0	-10000	0	0
FOXG1	-0.026	0.17	-10000	0	-0.87	19	19
FOXO3	0.037	0.008	-10000	0	-10000	0	0
FOXO1	0.037	0.008	-10000	0	-10000	0	0
FOXO4	0.037	0.008	-10000	0	-10000	0	0
heart looping	-0.001	0.22	-10000	0	-0.79	18	18
CEBPB	-0.004	0.14	-10000	0	-0.87	12	12
SMAD3/SMAD4/DLX1	-0.32	0.29	-10000	0	-0.58	260	260
MYOD1	-0.043	0.2	-10000	0	-0.86	27	27
SMAD3/SMAD4/HNF4	-0.034	0.14	-10000	0	-0.5	41	41
SMAD3/SMAD4/GATA3	-0.24	0.26	-10000	0	-0.49	221	221
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.24	0.28	-10000	0	-0.69	44	44
SMAD3/SMAD4/SP1-3	-0.006	0.044	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.012	0.051	-10000	0	-10000	0	0
SIN3B	0.015	0.005	-10000	0	-10000	0	0
SIN3A	0.015	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.073	0.22	-10000	0	-0.62	55	55
ITGB5	0.085	0.066	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.041	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.014	0.11	-10000	0	-0.5	22	22
AR	-0.02	0.16	-10000	0	-0.76	22	22
negative regulation of cell growth	0.063	0.069	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.025	0.14	-10000	0	-0.6	27	27
E2F5	0.016	0	-10000	0	-10000	0	0
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.036	0.14	-10000	0	-0.62	12	12
SMAD2-3/SMAD4/FOXO1-3a-4	0.074	0.044	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.01	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.007	0.1	-10000	0	-0.59	13	13
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

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.022	0.18	-9999	-10000	0	0
CRKL	-0.097	0.22	-9999	-10000	0	0
mol:DAG	-0.13	0.17	-9999	-10000	0	0
HRAS	-0.11	0.15	-9999	-10000	0	0
MAPK8	-0.14	0.26	-9999	-10000	0	0
RAP1A	-0.097	0.22	-9999	-10000	0	0
GAB1	-0.097	0.22	-9999	-10000	0	0
MAPK14	-0.14	0.26	-9999	-10000	0	0
EPO	-0.29	0.42	-9999	-0.85	172	172
PLCG1	-0.13	0.17	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.019	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.2	0.27	-9999	-0.55	172	172
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.65	172	172
IRS2	-0.11	0.23	-9999	-0.88	2	2
STAT1	-0.068	0.21	-9999	-10000	0	0
STAT5B	-0.073	0.21	-9999	-10000	0	0
cell proliferation	-0.12	0.24	-9999	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.12	0.15	-9999	-0.71	1	1
TEC	-0.097	0.22	-9999	-10000	0	0
SOCS3	0.012	0.057	-9999	-0.86	2	2
STAT1 (dimer)	-0.066	0.21	-9999	-10000	0	0
JAK2	0.006	0.018	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	-0.1	0.24	-9999	-10000	0	0
EPO/EPOR	-0.23	0.32	-9999	-0.65	172	172
LYN	0.018	0.001	-9999	-10000	0	0
TEC/VAV2	-0.084	0.22	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.019	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
EPO/EPOR (dimer)/LYN	-0.16	0.28	-9999	-0.54	172	172
mol:IP3	-0.13	0.17	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.14	0.18	-9999	-0.79	3	3
SH2B3	0.006	0.018	-9999	-10000	0	0
NFKB1	-0.14	0.26	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.11	0.15	-9999	-0.53	2	2
PTPN6	-0.11	0.23	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.13	0.17	-9999	-10000	0	0
EPOR	0.007	0.019	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
mol:GDP	-0.12	0.16	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.002	0.11	-9999	-0.82	8	8
CRKL/CBL/C3G	-0.13	0.17	-9999	-10000	0	0
VAV2	-0.097	0.22	-9999	-10000	0	0
CBL	-0.097	0.22	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.13	0.17	-9999	-10000	0	0
STAT5A	-0.073	0.21	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.048	0.21	-9999	-10000	0	0
LYN/PLCgamma2	-0.01	0.081	-9999	-0.63	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.29	-9999	-0.88	27	27
BCL2	-0.022	0.18	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.017	0.093	-9999	-0.52	16	16
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
alpha4/beta7 Integrin/MAdCAM1	-0.026	0.11	-9999	-0.52	24	24
EPO	-0.3	0.42	-9999	-0.86	172	172
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.67	16	16
EPO/EPOR (dimer)	-0.24	0.32	-9999	-0.67	172	172
lamellipodium assembly	0.003	0.013	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
JAK2	-0.13	0.17	-9999	-0.66	7	7
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
MADCAM1	-0.002	0.11	-9999	-0.86	8	8
cell adhesion	-0.026	0.11	-9999	-0.52	24	24
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.01	0.14	-9999	-0.54	26	26
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.036	0.14	-9999	-0.58	30	30
p130Cas/Crk/Dock1	-0.028	0.11	-9999	-0.84	2	2
VCAM1	-0.011	0.15	-9999	-0.84	15	15
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.017	0.094	-9999	-0.52	16	16
BCAR1	0.022	0.14	-9999	-0.93	2	2
EPOR	0.016	0	-9999	-10000	0	0
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	0.003	0.013	-9999	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.063	0.13	-9999	-0.61	7	7
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.01	0.15	-9999	-0.86	14	14
WNT4	-0.073	0.25	-9999	-0.76	55	55
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.061	-9999	-0.76	3	3
WNT11	-0.037	0.2	-9999	-0.77	32	32

×

S1P3 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.04	0.045	-9999	-10000	0	0
GNAO1	0.011	0.078	-9999	-0.84	4	4
S1P/S1P3/G12/G13	-0.001	0.02	-9999	-0.44	1	1
AKT1	-0.002	0.013	-9999	-10000	0	0
AKT3	-0.024	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	0.013	0.061	-9999	-0.76	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.035	-9999	-0.76	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.054	0.049	-9999	-0.54	1	1
MAPK3	0.062	0.047	-9999	-0.51	1	1
MAPK1	0.062	0.047	-9999	-0.51	1	1
JAK2	-0.025	0.13	-9999	-0.48	2	2
CXCR4	-0.13	0.26	-9999	-0.47	171	171
FLT1	0.012	0.08	-9999	-0.86	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.062	0.047	-9999	-0.51	1	1
S1P/S1P3/Gi	0.054	0.05	-9999	-0.55	1	1
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.036	-9999	-0.49	1	1
VEGFA	-0.38	0.44	-9999	-0.86	215	215
S1P/S1P2/Gi	0.049	0.043	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	216	216
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.009	0.072	-9999	-0.6	1	1
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.061	-9999	-0.76	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.012	0.05	-9999	-0.76	2	2
Rac1/GTP	-0.005	0.036	-9999	-0.49	1	1

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.05	-9999	-0.76	2	2
SPHK1	-0.058	0.24	-9999	-0.86	40	40
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.001	0.095	-9999	-0.31	42	42
GNAO1	0.009	0.078	-9999	-0.84	4	4
mol:Sphinganine-1-P	-0.03	0.2	-9999	-0.66	42	42
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.017	0.056	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.014	0.035	-9999	-0.76	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.023	0.075	-9999	-0.29	2	2
S1PR5	-0.14	0.33	-9999	-0.86	82	82
S1PR4	-0.03	0.2	-9999	-0.86	25	25
GNAI1	0.011	0.061	-9999	-0.76	3	3
S1P/S1P5/G12	-0.11	0.21	-9999	-0.54	82	82
S1P/S1P3/Gq	-0.023	0.085	-9999	-0.45	14	14
S1P/S1P4/Gi	0.024	0.097	-9999	-0.39	11	11
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.012	0.05	-9999	-0.76	2	2
ABCC1	0.016	0	-9999	-10000	0	0

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.003	0.12	-10000	0	-0.86	9	9
GNB1/GNG2	-0.034	0.062	-10000	0	-0.22	11	11
AKT1	0.056	0.1	-10000	0	-0.25	1	1
EGF	-0.68	0.23	-10000	0	-0.76	432	432
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.034	0.082	-10000	0	-0.61	2	2
mol:Ca2+	0.043	0.14	-10000	0	-0.33	21	21
LYN	-0.032	0.073	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.037	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.15	-10000	0	-0.39	11	11
GNG2	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.03	0.077	-10000	0	-0.43	7	7
G beta5/gamma2	-0.045	0.081	-10000	0	-0.3	12	12
PRKCH	0.044	0.15	-10000	0	-0.4	14	14
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
TXA2/TP beta/beta Arrestin3	-0.013	0.042	-10000	0	-0.32	2	2
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.12	0.32	-10000	0	-0.86	76	76
G12 family/GTP	-0.042	0.089	-10000	0	-0.32	19	19
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.016	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.1	0.31	9	-10000	0	9
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	0	0.11	-10000	0	-0.76	10	10
mol:IP3	0.04	0.17	-10000	0	-0.42	21	21
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.031	0.21	-10000	0	-0.59	21	21
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.056	0.13	-10000	0	-0.61	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.054	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.014	0.04	-10000	0	-0.86	1	1
PRKCB1	0.039	0.16	-10000	0	-0.38	35	35
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.038	0.21	-10000	0	-0.53	37	37
LCK	-0.049	0.12	-10000	0	-0.6	12	12
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.043	0.099	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.027	0.037	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.043	0.098	-10000	0	-10000	0	0
MAPK14	0.055	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.039	0.19	-10000	0	-0.49	21	21
MAPK11	0.055	0.11	-10000	0	-0.31	1	1
ARHGEF1	0.043	0.087	-10000	0	-0.33	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.046	0.16	-10000	0	-0.39	37	37
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.046	0.13	-10000	0	-0.36	15	15
cAMP biosynthetic process	0.037	0.16	-10000	0	-0.39	21	21
Gq family/GTP/EBP50	0.027	0.059	-10000	0	-0.47	1	1
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.032	0.073	-10000	0	-10000	0	0
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.089	0.11	-10000	0	-0.41	15	15
VCAM1	0.044	0.14	-10000	0	-0.34	26	26
TP beta/Gq family/GDP/G beta5/gamma2	0.03	0.077	-10000	0	-0.43	7	7
platelet activation	0.069	0.15	-10000	0	-0.34	11	11
PGI2/IP	-0.001	0.031	-10000	0	-0.68	1	1
PRKACA	-0.055	0.13	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.025	0.078	-10000	0	-0.43	7	7
TXA2/TP beta/beta Arrestin2	-0.013	0.059	-10000	0	-0.41	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.02	0.13	-10000	0	-10000	0	0
mol:DAG	0.039	0.18	-10000	0	-0.43	35	35
EGFR	-0.001	0.12	-10000	0	-0.85	9	9
TXA2/TP alpha	0.036	0.2	-10000	0	-0.54	24	24
Gq family/GTP	-0.004	0.054	-10000	0	-0.3	6	6
YES1	-0.032	0.073	-10000	0	-10000	0	0
GNAI2/GTP	-0.037	0.085	-10000	0	-10000	0	0
PGD2/DP	-0.11	0.25	-10000	0	-0.68	76	76
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.032	0.073	-10000	0	-10000	0	0
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	-0.006	0.14	-10000	0	-0.86	12	12
PGK/cGMP	-0.01	0.071	-10000	0	-0.5	10	10
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.049	0.11	-10000	0	-0.71	1	1
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.044	0.15	-10000	0	-0.4	15	15
PRKCB	0.042	0.16	-10000	0	-0.43	18	18
PRKCE	0.046	0.15	-10000	0	-0.4	15	15
PRKCD	0.043	0.16	-10000	0	-0.4	19	19
PRKCG	0.032	0.18	-10000	0	-0.5	24	24
muscle contraction	0.045	0.2	-10000	0	-0.49	37	37
PRKCZ	0.051	0.15	-10000	0	-0.37	21	21
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.042	0.096	-10000	0	-10000	0	0
PRKCQ	0.038	0.16	-10000	0	-0.43	18	18
MAPKKK cascade	0.038	0.19	-10000	0	-0.49	23	23
SELE	0.039	0.15	-10000	0	-0.41	34	34
TP beta/GNAI2/GDP/G beta/gamma	-0.04	0.093	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.004	0.093	-10000	0	-0.76	7	7
chemotaxis	0.039	0.23	-10000	0	-0.61	36	36
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.012	0.05	-10000	0	-0.76	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.028	0.039	-10000	0	-0.57	2	2
MAP4K4	0.025	0.094	-10000	0	-0.48	1	1
BAG4	0.016	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.1	0.047	-10000	0	-0.49	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.12	0.32	-10000	0	-0.86	74	74
BAX	-0.043	0.018	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.047	0.008	-10000	0	-10000	0	0
BAD	-0.099	0.035	-10000	0	-0.27	1	1
SMPD1	0.026	0.043	-10000	0	-0.28	1	1
RB1	-0.098	0.036	-10000	0	-10000	0	0
FADD/Caspase 8	0.04	0.088	-10000	0	-10000	0	0
MAP2K4	-0.082	0.034	-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	-0.086	0.058	-10000	0	-0.59	4	4
EGF	-0.68	0.23	-10000	0	-0.76	432	432
mol:ceramide	-0.12	0.038	0.2	1	-10000	0	1
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.031	0	-10000	0	-10000	0	0
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.097	0.036	-10000	0	-10000	0	0
cell proliferation	-0.055	0.064	-10000	0	-0.45	11	11
BID	-0.012	0.066	-10000	0	-10000	0	0
MAP3K1	-0.098	0.036	-10000	0	-10000	0	0
EIF2A	-0.068	0.033	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.066	0.053	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.066	0.053	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.099	0.034	-10000	0	-10000	0	0
FADD	0.025	0.094	-10000	0	-0.48	1	1
KSR1	-0.1	0.061	-10000	0	-0.63	4	4
MAPK8	-0.077	0.037	-10000	0	-0.35	2	2
PRKRA	-0.098	0.036	-10000	0	-10000	0	0
PDGFA	0.016	0	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.003	0.11	-10000	0	-0.86	7	7
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.12	0.038	0.2	1	-10000	0	1
CTSD	0.014	0.035	-10000	0	-0.76	1	1
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.058	0.07	-10000	0	-0.49	11	11
PRKCD	0.014	0.04	-10000	0	-0.86	1	1
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.031	0	-10000	0	-10000	0	0
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.035	-10000	0	-0.76	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.035	0.078	-10000	0	-0.51	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.068	-10000	0	-0.53	8	8
mol:Sphingosine-1-phosphate	0.028	0.039	-10000	0	-0.57	2	2
MAP2K1	-0.072	0.055	-10000	0	-0.55	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	-0.064	0.023	-10000	0	-10000	0	0
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0	0	-10000	0	-10000	0	0
EIF2AK2	-0.082	0.034	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.009	0.068	-10000	0	-0.53	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.036	-10000	0	-10000	0	0
MAP2K2	-0.073	0.054	-10000	0	-0.55	4	4
SMPD3	0.026	0.053	-10000	0	-0.33	2	2
TNF	0.002	0.11	-10000	0	-0.81	8	8
PKC zeta/PAR4	-0.005	0.052	-10000	0	-0.57	4	4
mol:PHOSPHOCHOLINE	0.23	0.085	0.26	432	-10000	0	432
NF kappa B1/RelA/I kappa B alpha	-0.003	0.036	-10000	0	-10000	0	0
AIFM1	-0.064	0.023	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

FoxO family signaling

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
G6PC	-0.57	0.68	-9999	-1.3	224	224
PLK1	-0.13	0.37	-9999	-0.79	89	89
CDKN1B	0.062	0.16	-9999	-10000	0	0
FOXO3	-0.042	0.23	-9999	-0.75	6	6
KAT2B	0.013	0.02	-9999	-10000	0	0
FOXO1/SIRT1	-0.14	0.21	-9999	-10000	0	0
CAT	-0.028	0.21	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	-0.008	0.038	-9999	-10000	0	0
FOXO1	-0.16	0.23	-9999	-0.41	224	224
MAPK10	0.032	0.052	-9999	-0.44	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.045	-9999	-10000	0	0
response to oxidative stress	-0.029	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.028	0.2	-9999	-0.6	5	5
XPO1	0.017	0	-9999	-10000	0	0
EP300	-0.004	0.027	-9999	-10000	0	0
BCL2L11	0.011	0.043	-9999	-10000	0	0
FOXO1/SKP2	-0.14	0.21	-9999	-0.4	3	3
mol:GDP	-0.029	0.045	-9999	-10000	0	0
RAN	0.018	0.001	-9999	-10000	0	0
GADD45A	0.12	0.097	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.034	0.084	-9999	-10000	0	0
MST1	0.002	0.1	-9999	-0.88	6	6
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.046	0.093	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.038	0.019	-9999	-10000	0	0
MAPK9	0.037	0.019	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.037	0.028	-9999	-10000	0	0
SOD2	0.013	0.21	-9999	-0.71	6	6
RBL2	0.022	0.16	-9999	-10000	0	0
RAL/GDP	0.008	0.023	-9999	-10000	0	0
CHUK	0.013	0.02	-9999	-10000	0	0
Ran/GTP	0.015	0.006	-9999	-10000	0	0
CSNK1G2	0.014	0.035	-9999	-0.76	1	1
RAL/GTP	0.024	0.026	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.36	0.39	-9999	-0.73	252	252
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.018	0.001	-9999	-10000	0	0
IKBKB	0.013	0.02	-9999	-10000	0	0
CCNB1	-0.034	0.23	-9999	-0.98	8	8
FOXO1-3a-4/beta catenin	-0.071	0.1	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-9999	-0.4	3	3
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.013	0.02	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.019	0.016	-9999	-10000	0	0
ZFAND5	0.11	0.042	-9999	-10000	0	0
SFN	-0.079	0.27	-9999	-0.84	53	53
CDK2	-0.018	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.013	0.097	-9999	-10000	0	0
CREBBP	-0.018	0.041	-9999	-10000	0	0
FBXO32	-0.03	0.22	-9999	-0.95	3	3
BCL6	0.022	0.16	-9999	-10000	0	0
RALB	0.018	0	-9999	-10000	0	0
RALA	0.018	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

LPA receptor mediated 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
GNB1/GNG2	-0.02	0.089	-9999	-0.43	20	20
NF kappa B1 p50/RelA/I kappa B alpha	-0.007	0.035	-9999	-10000	0	0
AP1	-0.029	0.098	-9999	-10000	0	0
mol:PIP3	-0.026	0.091	-9999	-10000	0	0
AKT1	-0.013	0.055	-9999	-10000	0	0
PTK2B	0.034	0.058	-9999	-10000	0	0
RHOA	0.036	0.037	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.051	0.054	-9999	-0.48	1	1
MAGI3	0.011	0.061	-9999	-0.76	3	3
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.021	0.085	-9999	-0.38	24	24
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.046	0.071	-9999	-0.39	4	4
NF kappa B1 p50/RelA	-0.018	0.072	-9999	-10000	0	0
endothelial cell migration	0.008	0.13	-9999	-0.54	25	25
ADCY4	0.033	0.12	-9999	-0.48	22	22
ADCY5	0.024	0.13	-9999	-0.5	24	24
ADCY6	0.033	0.12	-9999	-0.48	22	22
ADCY7	0.027	0.12	-9999	-0.48	22	22
ADCY1	0.029	0.12	-9999	-0.48	22	22
ADCY2	-0.015	0.14	-9999	-0.52	22	22
ADCY3	0.033	0.12	-9999	-0.48	22	22
ADCY8	-0.026	0.14	-9999	-0.49	22	22
ADCY9	0.033	0.12	-9999	-0.48	22	22
GSK3B	0.043	0.055	-9999	-10000	0	0
arachidonic acid secretion	0.04	0.11	-9999	-0.44	20	20
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0	0.003	-9999	-10000	0	0
GNAO1	0.009	0.12	-9999	-0.49	24	24
HRAS	0.016	0	-9999	-10000	0	0
NFKBIA	0.062	0.063	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0	0.04	-9999	-0.86	1	1
JUN	0.016	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.002	0.024	-9999	-0.49	1	1
TIAM1	-0.001	0.047	-9999	-1	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
mol:IP3	0.052	0.055	-9999	-0.5	1	1
PLCB3	0.037	0.024	-9999	-0.44	1	1
FOS	0	0.11	-9999	-0.76	10	10
positive regulation of mitosis	0.04	0.11	-9999	-0.44	20	20
LPA/LPA1-2-3	-0.025	0.1	-9999	-0.52	4	4
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
stress fiber formation	0.04	0.076	-9999	-10000	0	0
GNAZ	0.01	0.12	-9999	-0.49	23	23
EGFR/PI3K-beta/Gab1	-0.027	0.094	-9999	-10000	0	0
positive regulation of dendritic cell cytokine production	-0.025	0.1	-9999	-0.52	4	4
LPA/LPA2/MAGI-3	-0.004	0.04	-9999	-0.49	3	3
ARHGEF1	0.031	0.096	-9999	-0.49	1	1
GNAI2	0.014	0.11	-9999	-0.48	20	20
GNAI3	0.014	0.11	-9999	-0.48	20	20
GNAI1	0.01	0.12	-9999	-0.49	23	23
LPA/LPA3	-0.007	0.062	-9999	-0.67	4	4
LPA/LPA2	-0.001	0.012	-9999	-10000	0	0
LPA/LPA1	-0.027	0.12	-9999	-0.56	20	20
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	229	229
HBEGF	-0.29	0.35	-9999	-0.67	223	223
mol:DAG	0.052	0.055	-9999	-0.5	1	1
cAMP biosynthetic process	0.021	0.12	-9999	-0.46	21	21
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.062	0.063	-9999	-10000	0	0
GNAQ	-0.004	0.037	-9999	-0.4	4	4
LPAR2	0.016	0	-9999	-10000	0	0
LPAR3	0.002	0.08	-9999	-0.86	4	4
LPAR1	-0.012	0.15	-9999	-0.74	20	20
IL8	-0.074	0.2	-9999	-0.49	40	40
PTK2	0.025	0.1	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.021	0.086	-9999	-0.38	24	24
EGFR	-0.001	0.12	-9999	-0.85	9	9
PLCG1	0.019	0.056	-9999	-0.41	4	4
PLD2	0.025	0.1	-9999	-10000	0	0
G12/G13	-0.02	0.089	-9999	-10000	0	0
PI3K-beta	-0.015	0.064	-9999	-10000	0	0
cell migration	-0.008	0.033	-9999	-10000	0	0
SLC9A3R2	0.014	0.035	-9999	-0.76	1	1
PXN	0.04	0.077	-9999	-10000	0	0
HRAS/GTP	-0.025	0.098	-9999	-0.46	20	20
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
PRKCE	0.015	0.004	-9999	-10000	0	0
PRKCD	0.059	0.057	-9999	-10000	0	0
Gi(beta/gamma)	-0.025	0.097	-9999	-0.45	22	22
mol:LPA	0.004	0.022	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.018	0.081	-9999	-10000	0	0
MAPKKK cascade	0.04	0.11	-9999	-0.44	20	20
contractile ring contraction involved in cytokinesis	0.036	0.037	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.01	0.062	-9999	-0.41	11	11
GNA15	-0.014	0.076	-9999	-0.43	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.047	0.072	-9999	-0.41	3	3
GNA11	-0.006	0.044	-9999	-0.39	6	6
Rac1/GTP	0	0.042	-9999	-0.92	1	1
MMP2	0.008	0.13	-9999	-0.54	25	25

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0	-9999	-10000	0	0
DAPP1	0.029	0.12	-9999	-0.54	9	9
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.15	0.26	-9999	-0.74	52	52
mol:DAG	-0.076	0.15	-9999	-0.32	56	56
HRAS	0.017	0	-9999	-10000	0	0
RAP1A	0.017	0	-9999	-10000	0	0
ARF5/GDP	0.017	0.075	-9999	-10000	0	0
PLCG2	0.002	0.11	-9999	-0.82	8	8
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	0	0	-9999	-10000	0	0
ADAP1	-0.003	0.034	-9999	-10000	0	0
ARAP3	0	0	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.01	0.069	-9999	-0.86	3	3
mol:Ca2+	-0.025	0.078	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.014	0.035	-9999	-0.76	1	1
ZAP70	-0.48	0.44	-9999	-0.86	272	272
mol:IP3	-0.041	0.11	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.017	0.075	-9999	-10000	0	0
RhoA/GDP	-0.003	0.006	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.014	0.035	-9999	-0.76	1	1
actin cytoskeleton reorganization	0.044	0.082	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.036	0.056	-9999	-0.57	4	4
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.21	0.24	-9999	-0.56	129	129
BLK	-0.04	0.21	-9999	-0.86	30	30
PDPK1	0.016	0	-9999	-10000	0	0
CYTH1	0	0	-9999	-10000	0	0
HCK	-0.034	0.2	-9999	-0.86	27	27
CYTH3	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
KRAS	0.017	0	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
SGK1	0	0	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
mol:GDP	0.009	0.079	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.012	0.05	-9999	-0.76	2	2
ARF6/GDP	-0.003	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0	-9999	-10000	0	0
VAV1	-0.2	0.38	-9999	-0.86	119	119
mol:PI-3-4-P2	0.025	0.063	-9999	-0.67	4	4
RAS family/GTP/PI3K Class I	0	0	-9999	-10000	0	0
PLEKHA1	0.036	0.056	-9999	-0.57	4	4
Rac1/GDP	0.017	0.075	-9999	-10000	0	0
LAT	-0.25	0.4	-9999	-0.86	143	143
Rac1/GTP	-0.003	0.1	-9999	-10000	0	0
ITK	-0.15	0.22	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.12	0.21	-9999	-0.46	71	71
LCK	-0.024	0.18	-9999	-0.85	22	22
BTK	-0.094	0.18	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.014	0.16	-9999	-0.86	16	16
PLK4	0.01	0.069	-9999	-0.86	3	3
regulation of centriole replication	0.003	0.14	-9999	-0.67	19	19

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-10000	0	-10000	0	0
HDAC1	0.003	0.011	-10000	0	-10000	0	0
AES	0.003	0.007	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.054	0.22	-10000	0	-0.76	43	43
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.015	0.002	-10000	0	-10000	0	0
AP1	-0.097	0.16	-10000	0	-0.91	3	3
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	0.012	0.067	-10000	0	-0.45	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.003	0.094	-10000	0	-0.77	7	7
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.081	0.27	-10000	0	-0.86	52	52
DKK1	-0.016	0.16	-10000	0	-0.84	18	18
beta catenin/beta TrCP1	0.084	0.085	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	-0.011	0.035	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.008	0.047	-10000	0	-10000	0	0
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	0	0.11	-10000	0	-0.76	10	10
JUN	0.016	0	-10000	0	-10000	0	0
MAP3K7	0.002	0.008	-10000	0	-10000	0	0
CTNNB1	0.08	0.092	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.091	0.21	-10000	0	-0.57	76	76
HNF1A	-0.003	0.069	-10000	0	-0.76	4	4
CTBP1	0.003	0.007	-10000	0	-10000	0	0
MYC	-0.016	0.14	-10000	0	-0.73	16	16
NKD1	-0.19	0.34	-10000	0	-0.76	127	127
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.036	0.11	-10000	0	-10000	0	0
apoptosis	-0.096	0.16	-10000	0	-0.35	117	117
Delta 1/NOTCHprecursor	0	0	-10000	0	-10000	0	0
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.007	0.024	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.011	0.035	-10000	0	-10000	0	0
DVL1	-0.006	0.034	-10000	0	-0.48	2	2
CSNK2A1	0.015	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.083	0.22	-10000	0	-0.62	64	64
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
NLK	0.004	0.014	-10000	0	-10000	0	0
CCND1	-0.021	0.15	-10000	0	-0.73	20	20
WNT1	-0.029	0.19	-10000	0	-0.86	24	24
Axin1/APC/beta catenin	0.081	0.051	-10000	0	-10000	0	0
DKK2	-0.029	0.19	-10000	0	-0.83	25	25
NOTCH1 precursor/DVL1	-0.003	0.024	-10000	0	-10000	0	0
GSK3B	0.012	0.007	-10000	0	-10000	0	0
FRAT1	0.002	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.036	0.11	-10000	0	-10000	0	0
PPP2R5D	0.092	0.16	0.36	126	-10000	0	126
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.033	0.12	-10000	0	-0.52	25	25
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.2	0.22	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.16	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.028	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.11	0.091	-9999	-0.37	1	1
CaM/Ca2+	-0.18	0.2	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.18	0.2	-9999	-1	1	1
AKT1	-0.16	0.17	-9999	-10000	0	0
MAP2K1	-0.13	0.22	-9999	-10000	0	0
MAP3K11	-0.15	0.23	-9999	-0.81	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.28	0.29	-9999	-0.75	109	109
Rap1/GTP	-0.13	0.14	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.21	0.23	-9999	-10000	0	0
CEBPB	-0.07	0.2	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.2	0.22	-9999	-0.8	4	4
STAT1	-0.15	0.24	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.38	0.43	-9999	-0.85	220	220
PIK3CA	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.076	0.085	-9999	-0.47	1	1
mol:Ca2+	-0.2	0.21	-9999	-10000	0	0
MAPK3	-0.091	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.091	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
JAK1	0.001	0.019	-9999	-10000	0	0
CAMK2D	0.016	0	-9999	-10000	0	0
DAPK1	-0.025	0.15	-9999	-0.63	2	2
SMAD7	-0.023	0.082	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.17	0.19	-9999	-10000	0	0
IFNG	-0.38	0.44	-9999	-0.86	220	220
apoptosis	-0.038	0.12	-9999	-0.44	2	2
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.26	0.37	-9999	-0.76	168	168
CAMK2B	-0.11	0.28	-9999	-0.76	75	75
FRAP1	-0.11	0.2	-9999	-10000	0	0
PRKCD	-0.14	0.2	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.11	0.091	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
IRF1	-0.059	0.19	-9999	-0.66	3	3
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.012	0.079	-9999	-0.73	5	5
mol:GDP	-0.16	0.17	-9999	-10000	0	0
CASP1	-0.023	0.082	-9999	-10000	0	0
PTGES2	0.013	0.05	-9999	-0.76	2	2
IRF9	0.017	0.076	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.18	-9999	-10000	0	0
RAP1/GDP	-0.13	0.14	-9999	-10000	0	0
CBL	-0.15	0.23	-9999	-10000	0	0
MAP3K1	-0.15	0.23	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.11	0.091	-9999	-0.37	1	1
PTPN11	-0.17	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.013	0.045	-10000	0	-10000	0	0
RFC1	0.013	0.045	-10000	0	-10000	0	0
PRKDC	0.013	0.045	-10000	0	-10000	0	0
RIPK1	0.013	0.005	-10000	0	-10000	0	0
CASP7	-0.023	0.068	0.25	5	-10000	0	5
FASLG/FAS/FADD/FAF1	-0.14	0.16	-10000	0	-0.35	21	21
MAP2K4	-0.089	0.16	-10000	0	-0.42	21	21
mol:ceramide	-0.16	0.2	-10000	0	-0.48	30	30
GSN	0.013	0.045	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.18	0.18	-10000	0	-0.44	21	21
FAS	0.015	0.006	-10000	0	-10000	0	0
BID	0.02	0.07	-10000	0	-10000	0	0
MAP3K1	-0.037	0.1	-10000	0	-10000	0	0
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
RB1	0.013	0.045	-10000	0	-10000	0	0
CFLAR	0.013	0.005	-10000	0	-10000	0	0
HGF/MET	-0.036	0.15	-10000	0	-0.58	30	30
ARHGDIB	0.013	0.045	-10000	0	-10000	0	0
FADD	0.015	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.045	-10000	0	-10000	0	0
NFKB1	-0.065	0.071	-10000	0	-10000	0	0
MAPK8	-0.086	0.18	-10000	0	-0.51	21	21
DFFA	0.013	0.045	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.013	0.045	-10000	0	-10000	0	0
FAS/FADD/MET	-0.006	0.058	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.052	0.24	-10000	0	-0.86	37	37
FAF1	0.015	0.006	-10000	0	-10000	0	0
PARP1	0.013	0.045	-10000	0	-10000	0	0
DFFB	0.013	0.045	-10000	0	-10000	0	0
CHUK	-0.052	0.06	-10000	0	-10000	0	0
FASLG	-0.45	0.44	-10000	0	-0.87	252	252
FAS/FADD	0	0	-10000	0	-10000	0	0
HGF	-0.021	0.17	-10000	0	-0.81	21	21
LMNA	0.011	0.049	-10000	0	-0.52	1	1
CASP6	0.013	0.045	-10000	0	-10000	0	0
CASP10	0.015	0.006	-10000	0	-10000	0	0
CASP3	0.015	0.052	-10000	0	-10000	0	0
PTPN13	0.004	0.093	-10000	0	-0.76	7	7
CASP8	0.031	0.11	0.4	37	-10000	0	37
IL6	-0.12	0.32	-10000	0	-0.92	59	59
MET	0.007	0.089	-10000	0	-0.86	5	5
ICAD/CAD	0.013	0.045	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.16	0.2	-10000	0	-0.49	30	30
activation of caspase activity by cytochrome c	0.02	0.07	-10000	0	-10000	0	0
PAK2	0.013	0.045	-10000	0	-10000	0	0
BCL2	0.016	0.001	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.018	-10000	0	-10000	0	0
AES	0.004	0.016	-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	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.029	0.19	-10000	0	-0.83	25	25
TLE1	0.004	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.003	-10000	0	-10000	0	0
CTNNB1	0.051	0.1	-10000	0	-10000	0	0
WIF1	-0.009	0.093	-10000	0	-0.77	7	7
beta catenin/RanBP3	0.004	0.11	0.36	19	-10000	0	19
KREMEN2	-0.081	0.27	-10000	0	-0.86	52	52
DKK1	-0.016	0.16	-10000	0	-0.84	18	18
beta catenin/beta TrCP1	0.057	0.094	-10000	0	-10000	0	0
FZD1	0.015	0.005	-10000	0	-10000	0	0
AXIN2	0.012	0.081	-10000	0	-1.4	1	1
AXIN1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.018	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.074	0.065	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.04	0.084	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.002	0.071	-10000	0	-0.75	4	4
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.005	0.14	-10000	0	-0.75	16	16
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.091	0.21	-10000	0	-0.57	76	76
NKD1	-0.19	0.34	-10000	0	-0.76	127	127
TCF4	0.005	0.017	-10000	0	-10000	0	0
TCF3	0.005	0.016	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.026	0.11	-10000	0	-0.52	24	24
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.018	0.1	0.57	2	-10000	0	2
LEF1	-0.023	0.15	-10000	0	-0.87	15	15
DVL1	0.004	0.036	-10000	0	-10000	0	0
CSNK2A1	0.015	0.003	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.083	0.071	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.083	0.22	-10000	0	-0.62	64	64
LRP6	0.016	0.003	-10000	0	-10000	0	0
CSNK1A1	0.005	0.018	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.01	0.16	-10000	0	-0.75	20	20
WNT1	-0.03	0.19	-10000	0	-0.86	24	24
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.015	0.005	-10000	0	-10000	0	0
FRAT1	0.014	0.005	-10000	0	-10000	0	0
PPP2R5D	0.096	0.16	0.36	126	-10000	0	126
APC	-0.019	0.11	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.013	0.067	0.28	7	-10000	0	7
CREBBP	0.005	0.016	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.022	0.11	-9999	-0.51	21	21
E-cadherin/beta catenin	-0.023	0.11	-9999	-0.57	19	19
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.011	0.061	-9999	-0.76	3	3
CDH1	-0.015	0.15	-9999	-0.76	19	19

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.031	0.002	-9999	-10000	0	0
SMARCC1	0.027	0.009	-9999	-10000	0	0
REL	0.01	0.05	-9999	-0.76	2	2
HDAC7	-0.097	0.08	-9999	-0.67	2	2
JUN	0.015	0.003	-9999	-10000	0	0
EP300	0.015	0.003	-9999	-10000	0	0
KAT2B	0.015	0.003	-9999	-10000	0	0
KAT5	0.016	0	-9999	-10000	0	0
MAPK14	0.001	0.041	-9999	-0.61	2	2
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.082	-9999	-0.72	2	2
MAP2K6	-0.001	0.051	-9999	-0.78	2	2
BRM/BAF57	0	0	-9999	-10000	0	0
MAP2K4	0.002	0.006	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.12	0.13	-9999	-1.3	4	4
NCOA2	0.009	0.07	-9999	-0.76	4	4
CEBPA	-0.001	0.12	-9999	-0.86	9	9
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.089	0.089	-9999	-0.52	2	2
NR0B1	-0.05	0.21	-9999	-0.86	30	30
EGR1	0.004	0.093	-9999	-0.76	7	7
RXRs/9cRA	-0.005	0.049	-9999	-0.54	4	4
AR/RACK1/Src	-0.013	0.054	-9999	-0.59	1	1
AR/GR	0.003	0.081	-9999	-0.77	2	2
GNB2L1	0.014	0.04	-9999	-0.86	1	1
PKN1	0.015	0.003	-9999	-10000	0	0
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.004	0.011	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.014	0.065	-9999	-0.58	2	2
SRC	0.005	0.038	-9999	-10000	0	0
NR3C1	0.014	0.04	-9999	-0.86	1	1
KLK3	-0.05	0.18	-9999	-0.72	21	21
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.024	0.044	-9999	-0.59	2	2
TMPRSS2	-0.97	0.37	-9999	-1.1	419	419
RXRG	0.006	0.08	-9999	-0.87	4	4
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.016	0.001	-9999	-10000	0	0
RXRB	0.016	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.016	0.001	-9999	-10000	0	0
KLK2	-0.018	0.12	-9999	-0.62	15	15
AR	-0.008	0.08	-9999	-0.4	11	11
SENP1	0.016	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.013	0.009	-9999	-10000	0	0
SRY	0.002	0.007	-9999	-10000	0	0
GATA2	0.001	0.1	-9999	-0.76	9	9
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.17	0.35	-9999	-0.86	96	96
T-DHT/AR/RACK1/Src	-0.013	0.052	-9999	-0.6	1	1
positive regulation of transcription	0.001	0.1	-9999	-0.76	9	9
DNAJA1	0.002	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.002	-9999	-10000	0	0
NCOA1	0.024	0.005	-9999	-10000	0	0
SPDEF	-0.18	0.37	-9999	-0.87	108	108
T-DHT/AR/TIF2	0.024	0.044	-9999	-10000	0	0
T-DHT/AR/Hsp90	-0.025	0.043	-9999	-0.58	2	2
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.009	0.042	-9999	-0.51	2	2
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.013	0.009	-9999	-10000	0	0
POU2F1	0.004	0.014	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.063	0.14	-9999	-0.59	24	24
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.07	-10000	0	-10000	0	0
epithelial cell differentiation	-0.047	0.11	-10000	0	-10000	0	0
ITCH	0.056	0.018	-10000	0	-10000	0	0
WWP1	-0.098	0.066	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	-0.001	0.12	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.016	0.074	-10000	0	-10000	0	0
PTPRZ1	-0.088	0.26	-10000	0	-0.77	61	61
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.051	0.065	-10000	0	-0.55	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.086	-10000	0	-0.56	7	7
ADAM17	0.056	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.084	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.64	10	10
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.068	-10000	0	-0.52	7	7
GRIN2B	-0.054	0.085	-10000	0	-0.58	2	2
ErbB4/ErbB2/betacellulin	-0.14	0.17	-10000	0	-0.52	69	69
STAT1	0.014	0.04	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.076	0.25	-10000	0	-0.76	57	57
E4ICDs/ETO2	-0.11	0.079	-10000	0	-0.7	2	2
axon guidance	-0.015	0.071	-10000	0	-10000	0	0
NEDD4	0.056	0.018	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.069	0.19	-10000	0	-0.58	57	57
CBFA2T3	0.012	0.057	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.065	0.038	-10000	0	-0.52	1	1
MAPK3	-0.027	0.076	-10000	0	-10000	0	0
STAT1 (dimer)	-0.11	0.072	-10000	0	-0.54	1	1
MAPK1	-0.027	0.076	-10000	0	-10000	0	0
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.075	0.073	-10000	0	-0.52	8	8
NRG1	0.041	0.094	-10000	0	-0.57	11	11
NRG3	-0.003	0.13	-10000	0	-0.86	10	10
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
NRG4	-0.059	0.23	-10000	0	-0.78	44	44
heart development	-0.015	0.071	-10000	0	-10000	0	0
neural crest cell migration	-0.074	0.072	-10000	0	-0.52	8	8
ERBB2	0.052	0.042	-10000	0	-0.57	2	2
WWOX/E4ICDs	-0.11	0.075	-10000	0	-0.7	1	1
SHC1	0.014	0.04	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.15	0.15	-10000	0	-0.57	49	49
apoptosis	0.11	0.062	0.39	7	-10000	0	7
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.089	-10000	0	-0.53	10	10
ErbB4/ErbB2/epiregulin	-0.098	0.13	-10000	0	-0.57	31	31
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.19	-10000	0	-0.6	76	76
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.12	0.14	-10000	0	-10000	0	0
MDM2	-0.11	0.073	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.051	0.068	-10000	0	-0.51	7	7
STAT5A	-0.003	0.066	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.083	0.096	-10000	0	-0.56	15	15
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.03	-10000	0	-0.67	1	1
E4ICDs/TAB2/NCoR1	-0.11	0.047	-10000	0	-10000	0	0
STAT5A (dimer)	-0.05	0.12	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.005	0.063	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.04	0.21	-10000	0	-0.86	30	30
BTC	-0.11	0.28	-10000	0	-0.76	76	76
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.015	0.071	-10000	0	-10000	0	0
ERBB4	-0.14	0.085	-10000	0	-10000	0	0
STAT5B	0.016	0	-10000	0	-10000	0	0
YAP1	-0.034	0.016	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.11	0.14	-10000	0	-0.53	36	36
glial cell differentiation	0.1	0.047	-10000	0	-10000	0	0
WWOX	0.014	0.04	-10000	0	-0.86	1	1
cell proliferation	-0.076	0.16	-10000	0	-0.62	9	9

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.014	0.04	-9999	-0.86	1	1
GNB1/GNG2	-0.054	0.11	-9999	-0.54	7	7
mol:DAG	0.011	0.13	-9999	-0.49	7	7
PLCG1	0.011	0.13	-9999	-0.51	7	7
YES1	-0.01	0.14	-9999	-0.57	7	7
FZD3	0.016	0	-9999	-10000	0	0
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.049	0.1	-9999	-0.51	7	7
MAP3K7	-0.1	0.22	-9999	-0.56	44	44
mol:Ca2+	0.011	0.13	-9999	-0.47	7	7
mol:IP3	0.011	0.13	-9999	-0.49	7	7
NLK	-0.008	0.01	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.12	0.24	-9999	-0.62	44	44
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.063	0.13	-9999	-0.61	7	7
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.01	0.14	-9999	-0.57	7	7
GO:0007205	0.012	0.13	-9999	-0.48	7	7
WNT6	-0.01	0.15	-9999	-0.86	14	14
WNT4	-0.073	0.25	-9999	-0.76	55	55
NFAT1/CK1 alpha	-0.048	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.061	-9999	-0.76	3	3
WNT11	-0.037	0.2	-9999	-0.77	32	32
CDC42	0.002	0.14	-9999	-0.54	7	7

×

S1P5 pathway

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
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.045	0.092	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	82	82
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.009	0.078	-9999	-0.84	4	4
RhoA/GTP	-0.046	0.094	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.052	0.11	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	82	82
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
GNAI1	0.011	0.061	-9999	-0.76	3	3

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.02	0.093	-10000	0	-0.45	22	22
regulation of S phase of mitotic cell cycle	-0.013	0.063	-10000	0	-10000	0	0
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.05	0.15	-10000	0	-0.51	47	47
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.049	0.088	-10000	0	-10000	0	0
T-DHT/AR	-0.027	0.12	-10000	0	-0.58	22	22
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	10	10
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
mol:GDP	-0.025	0.11	-10000	0	-0.55	22	22
cell proliferation	0.074	0.1	-10000	0	-0.66	2	2
PIK3CA	0.016	0	-10000	0	-10000	0	0
FOS	0.06	0.14	-10000	0	-0.83	10	10
mol:Ca2+	-0.003	0.014	-10000	0	-0.11	4	4
MAPK3	0.066	0.096	-10000	0	-0.58	2	2
MAPK1	0.046	0.051	-10000	0	-0.3	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	10	10
cAMP biosynthetic process	-0.045	0.15	-10000	0	-0.49	47	47
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	10	10
HRAS/GTP	-0.018	0.083	-10000	0	-0.45	2	2
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.016	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	10	10
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	-0.064	0.087	0.4	10	-10000	0	10
T-DHT/AR/PELP1	-0.023	0.1	-10000	0	-0.5	22	22
HRAS/GDP	-0.023	0.11	-10000	0	-0.51	22	22
CREB1	0.064	0.092	-10000	0	-0.43	10	10
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.02	0.16	-10000	0	-0.76	22	22
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.037	0.09	-10000	0	-0.45	2	2
RAC1-CDC42/GDP	-0.022	0.1	-10000	0	-0.48	22	22
T-DHT/AR/PELP1/Src	-0.02	0.094	-10000	0	-0.45	22	22
MAP2K2	0.048	0.09	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.013	0.063	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
SHBG	-0.061	0.23	-10000	0	-0.76	47	47
Gi family/GNB1/GNG2/GDP	-0.008	0.045	-10000	0	-0.45	2	2
mol:T-DHT	0	0	-10000	0	-0.004	8	8
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.17	0.31	-10000	0	-0.68	129	129
Gi family/GTP	-0.013	0.06	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.051	0.19	-9999	-0.69	2	2
PTK2B	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.003	0.044	-9999	-0.84	1	1
CAV1	-0.05	0.23	-9999	-0.86	36	36
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.23	0.25	-9999	-1.3	1	1
endothelial cell proliferation	-0.037	0.19	-9999	-0.69	1	1
mol:Ca2+	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.21	0.24	-9999	-1.2	1	1
RP11-342D11.1	-0.17	0.26	-9999	-1.1	1	1
CDH5	0.014	0.04	-9999	-0.86	1	1
VEGFA homodimer	-0.23	0.26	-9999	-0.52	215	215
SHC1	0.014	0.04	-9999	-0.86	1	1
SHC2	0.009	0.075	-9999	-0.81	4	4
HRAS/GDP	-0.17	0.18	-9999	-0.91	1	1
SH2D2A	-0.28	0.42	-9999	-0.86	164	164
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.14	0.15	-9999	-0.79	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.4	0.34	-9999	-1	65	65
VEGFR1 homodimer	0.008	0.08	-9999	-0.86	4	4
SHC/GRB2/SOS1	-0.18	0.21	-9999	-1.1	1	1
GRB10	-0.16	0.26	-9999	-1.1	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.2	0.22	-9999	-1	2	2
HRAS	0.016	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.084	0.094	-9999	-0.58	1	1
HIF1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.21	0.23	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.23	0.25	-9999	-1.3	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.061	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.05	0.18	-9999	-0.57	1	1
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	-0.16	0.27	-9999	-1.1	1	1
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.37	0.44	-9999	-0.86	215	215
VEGFC	0.014	0.04	-9999	-0.86	1	1
FAK1/Vinculin	-0.1	0.22	-9999	-1	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.21	0.24	-9999	-1.2	1	1
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	0.026	0.039	-9999	-0.73	1	1
mol:L-citrulline	-0.061	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.22	0.25	-9999	-1.3	1	1
VEGFR2/3 heterodimer	-0.003	0.044	-9999	-0.84	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer	0.043	0.052	-9999	-0.74	2	2
FLT1	0.008	0.08	-9999	-0.86	4	4
NEDD4	0.018	0.001	-9999	-10000	0	0
MAPK3	-0.14	0.25	-9999	-0.76	2	2
MAPK1	-0.14	0.25	-9999	-0.76	2	2
VEGFA145/NRP2	-0.3	0.33	-9999	-0.67	220	220
VEGFR1/2 heterodimer	-0.007	0.067	-9999	-0.62	5	5
KDR	0.044	0.053	-9999	-0.74	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.21	0.23	-9999	-1.2	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.14	0.25	-9999	-0.78	2	2
PI3K	-0.16	0.18	-9999	-0.82	4	4
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.23	0.25	-9999	-1.3	1	1
FES	-0.16	0.27	-9999	-1	2	2
GAB1	-0.16	0.19	-9999	-0.82	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.23	0.25	-9999	-1.3	1	1
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	-0.081	0.2	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.23	0.25	-9999	-1.3	1	1
PI3K/GAB1	-0.051	0.19	-9999	-0.69	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.2	0.22	-9999	-1.2	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.004	0.046	-9999	-0.78	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.16	0.27	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.4	0.33	-9999	-1	65	65
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.27	-9999	-1.1	1	1
CaM/Ca2+	-0.18	0.21	-9999	-1	1	1
MAP2K3	-0.14	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.21	0.23	-9999	-1.2	1	1
PLCG1	-0.16	0.27	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.21	0.24	-9999	-1.2	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.23	0.25	-9999	-1.3	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.23	0.25	-9999	-1.3	1	1
cell migration	-0.05	0.2	-9999	-0.77	1	1
mol:PI-3-4-5-P3	-0.15	0.17	-9999	-0.74	4	4
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.19	0.21	-9999	-1	1	1
mol:NO	-0.061	0.19	-9999	-0.62	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.17	0.18	-9999	-0.92	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.21	0.23	-9999	-1.2	1	1
VHL	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
NOS3	-0.071	0.2	-9999	-0.73	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.23	0.26	-9999	-1.1	3	3
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.14	0.25	-9999	-1	1	1
PRKCB	-0.14	0.26	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.21	0.24	-9999	-1.2	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.23	0.26	-9999	-1.1	4	4
VEGFA165/NRP2	-0.3	0.33	-9999	-0.67	220	220
MAPKKK cascade	-0.16	0.18	-9999	-0.92	1	1
NRP2	0.003	0.11	-9999	-0.86	7	7
VEGFC homodimer	0.014	0.04	-9999	-0.86	1	1
NCK1	0.016	0	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.1	0.22	-9999	-1	1	1
MAP3K13	-0.16	0.27	-9999	-1.2	1	1
PDPK1	-0.068	0.2	-9999	-0.71	2	2

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.012	0.058	-9999	-10000	0	0
epithelial cell differentiation	-0.016	0.08	-9999	-10000	0	0
CYFIP2	0.003	0.099	-9999	-0.76	8	8
ENAH	0.08	0.064	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EPHA2	0.014	0.035	-9999	-0.76	1	1
MYO6	0.033	0.099	-9999	-0.8	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.062	-9999	-0.48	8	8
AQP5	-0.17	0.24	-9999	-0.53	147	147
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.035	0.084	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.12	-9999	-0.85	1	1
EGF	-0.68	0.23	-9999	-0.76	432	432
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.051	0.16	-9999	-0.58	35	35
cortical microtubule organization	-0.016	0.08	-9999	-10000	0	0
GO:0000145	0.035	0.08	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.081	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GDP	-0.013	0.062	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.002	0.031	-9999	-0.52	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.052	0.084	-9999	-0.59	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.035	0.085	-9999	-10000	0	0
ARF6/GTP	-0.002	0.028	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
EGFR/EGFR/EGF/EGF	-0.35	0.15	-9999	-0.79	26	26
RhoA/GDP	-0.015	0.074	-9999	-10000	0	0
actin cytoskeleton organization	0.042	0.094	-9999	-0.73	2	2
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
IGF1	0.003	0.11	-9999	-0.86	7	7
DIAPH1	-0.011	0.09	-9999	-0.7	8	8
Wnt receptor signaling pathway	0.016	0.08	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.063	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.042	0.096	-9999	-0.76	2	2
EFNA1	0.014	0.04	-9999	-0.86	1	1
LPP	0.045	0.089	-9999	-0.81	1	1
Ephrin A1/EPHA2	-0.016	0.075	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.063	-9999	-10000	0	0
MGAT3	0.019	0.12	-9999	-0.88	1	1
HGF/MET	-0.037	0.13	-9999	-0.96	4	4
HGF	-0.021	0.17	-9999	-0.81	21	21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.012	0.059	-9999	-10000	0	0
actin cable formation	0.1	0.07	-9999	-10000	0	0
KIAA1543	0.037	0.13	-9999	-0.87	6	6
KIFC3	0.034	0.087	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.034	0.093	-9999	-0.88	1	1
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.016	0.08	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.035	0.085	-9999	-10000	0	0
PIP5K1C	0.035	0.085	-9999	-10000	0	0
LIMA1	0.016	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
ROCK1	-0.012	0.054	-9999	-10000	0	0
adherens junction assembly	0.059	0.13	-9999	-0.8	7	7
IGF-1R heterotetramer/IGF1	-0.021	0.087	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PLEKHA7	0.032	0.1	-9999	-0.8	3	3
mol:GTP	-0.002	0.031	-9999	-0.52	1	1
establishment of epithelial cell apical/basal polarity	0.072	0.076	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.058	-9999	-10000	0	0
regulation of cell-cell adhesion	0.042	0.094	-9999	-0.73	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.012	0.059	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.67	16	16

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.009	0.078	-9999	-0.84	4	4
CDC42/GTP	-0.017	0.061	-9999	-10000	0	0
PLCG1	0.035	0.078	-9999	-10000	0	0
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	0	-9999	-10000	0	0
cell migration	-0.017	0.06	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	82	82
S1PR4	-0.03	0.2	-9999	-0.86	25	25
MAPK3	0.035	0.078	-9999	-10000	0	0
MAPK1	0.035	0.078	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
GNAI1	0.011	0.061	-9999	-0.76	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	82	82
RHOA	0.016	0.12	-9999	-0.49	25	25
S1P/S1P4/Gi	-0.02	0.07	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
S1P/S1P4/G12/G13	-0.028	0.12	-9999	-0.53	25	25
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.38	-9999	-0.76	184	184
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
AKT	0.036	0.03	-9999	-10000	0	0
FOXO3	0.016	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
FOXO4	0.016	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PIK3CA	0.016	0	-9999	-10000	0	0
PIK3CB	0.016	0	-9999	-10000	0	0
NRAS	0.016	0	-9999	-10000	0	0
PIK3CG	0.01	0.069	-9999	-0.86	3	3
PIK3R3	0.016	0	-9999	-10000	0	0
PIK3R2	0.016	0	-9999	-10000	0	0
NF1	0.016	0	-9999	-10000	0	0
RAS	-0.041	0.099	-9999	-0.38	5	5
ERBB2	0.012	0.05	-9999	-0.76	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.022	0.092	-9999	-0.28	6	6
PIK3R1	0.016	0	-9999	-10000	0	0
KRAS	0.016	0	-9999	-10000	0	0
FOXO	0.041	0.034	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.028	0.12	-9999	-0.51	26	26
RGS9BP	-0.019	0.16	-9999	-0.76	21	21
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.012	0.085	-9999	-0.59	10	10
mol:ADP	0.013	0.033	-9999	-0.68	1	1
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	33	33
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.027	-9999	-0.59	1	1
GRK7	0.01	0.041	-9999	-0.86	1	1
CNGB3	-0.008	0.11	-9999	-0.86	8	8
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.12	-9999	-0.65	14	14
Cone PDE6	-0.033	0.12	-9999	-0.57	6	6
Cone Metarhodopsin II	-0.001	0.025	-9999	-0.56	1	1
Na + (4 Units)	-0.019	0.12	-9999	-0.65	14	14
GNAT2/GDP	-0.03	0.11	-9999	-0.5	7	7
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.045	-9999	-0.54	3	3
Cone Transducin	-0.029	0.12	-9999	-0.54	26	26
SLC24A2	-0.01	0.1	-9999	-0.86	7	7
GNB3/GNGT2	-0.036	0.15	-9999	-0.67	26	26
GNB3	-0.033	0.2	-9999	-0.86	26	26
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.001	0.057	-9999	-0.86	2	2
ARR3	0.004	0.007	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.012	0.085	-9999	-0.6	10	10
mol:Pi	-0.035	0.13	-9999	-0.5	33	33
Cone CNG Channel	-0.013	0.085	-9999	-0.66	3	3
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.1	-9999	-0.86	7	7
RGS9	-0.005	0.13	-9999	-0.82	12	12
PDE6C	0.003	0.057	-9999	-0.86	2	2
GNGT2	0.016	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.04	-9999	-0.86	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
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	0.074	0.074	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.16	0.29	-9999	-0.67	118	118
NFKBIA	0.065	0	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.014	0.04	-9999	-0.86	1	1
IKBKG	-0.049	0.086	-9999	-10000	0	0
IKK complex/A20	-0.043	0.082	-9999	-0.59	2	2
NEMO/A20/RIP2	0.014	0.04	-9999	-0.86	1	1
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	-0.044	0.077	-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	0	-9999	-10000	0	0
IKK complex/ELKS	-0.036	0.063	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.2	0.38	-9999	-0.86	118	118
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	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	-0.01	0.079	-9999	-0.62	8	8
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
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	0.065	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	-0.04	0.071	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.037	0.065	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.005	0.098	-10000	0	-0.86	6	6
mol:Halofuginone	0.007	0.001	-10000	0	-10000	0	0
ITGA1	0.016	0	-10000	0	-10000	0	0
CDKN1A	0.041	0.031	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.024	0.12	-10000	0	-0.67	17	17
mol:Ca2+	-0.021	0.17	0.41	17	-0.66	26	43
AGT	-0.03	0.19	-10000	0	-0.83	26	26
CCNA2	-0.056	0.23	-10000	0	-0.89	4	4
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.024	0.071	-10000	0	-0.56	7	7
CDK2/Cyclin E1	-0.008	0.055	-10000	0	-0.47	6	6
MAPK3	0.006	0.13	-10000	0	-0.67	17	17
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.13	-10000	0	-0.67	17	17
PTP4A1	0.045	0.057	-10000	0	-10000	0	0
PTP4A3	-0.015	0.16	-10000	0	-0.86	17	17
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.006	0.13	-10000	0	-0.67	17	17
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.032	0.06	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.002	0.037	-10000	0	-0.57	2	2
PRL-1/ATF-5	0.045	0.068	-10000	0	-10000	0	0
RABGGTA	0.012	0.05	-10000	0	-0.76	2	2
BCAR1	0.013	0.08	0.41	17	-0.59	1	18
RHOC	0.032	0.06	-10000	0	-10000	0	0
RHOA	0.032	0.06	-10000	0	-10000	0	0
cell motility	0.038	0.062	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.049	0.053	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.12	-10000	0	-0.67	17	17
ROCK1	0.038	0.062	-10000	0	-10000	0	0
RABGGTB	0.016	0	-10000	0	-10000	0	0
CDK2	0.016	0	-10000	0	-10000	0	0
mitosis	0.045	0.057	-10000	0	-10000	0	0
ATF5	0.01	0.069	-10000	0	-0.86	3	3

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.029	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.012	0.065	-10000	0	-0.71	2	2
NFATC4	0.027	0.072	-10000	0	-0.46	1	1
ERBB2IP	0.008	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.016	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.016	0.074	-10000	0	-0.65	1	1
JUN	0.038	0.077	-10000	0	-0.41	1	1
HRAS	0.015	0.001	-10000	0	-10000	0	0
DOCK7	0.022	0.085	-10000	0	-0.61	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.02	0.099	-10000	0	-0.89	2	2
AKT1	0.016	0.002	-10000	0	-10000	0	0
BAD	0.027	0.024	-10000	0	-0.5	1	1
MAPK10	-0.01	0.043	-10000	0	-0.4	1	1
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.017	0.08	-10000	0	-0.73	1	1
RAF1	0.042	0.087	-10000	0	-0.66	2	2
ErbB2/ErbB3/neuregulin 2	-0.022	0.1	-10000	0	-0.49	21	21
STAT3	0	0.002	-10000	0	-10000	0	0
cell migration	0.061	0.052	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.088	0.26	-10000	0	-0.6	6	6
FOS	-0.036	0.19	-10000	0	-0.5	11	11
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.074	-10000	0	-0.65	1	1
MAPK3	-0.057	0.21	-10000	0	-0.55	5	5
MAPK1	-0.057	0.21	-10000	0	-0.55	5	5
JAK2	0.022	0.085	-10000	0	-0.61	1	1
NF2	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.008	0.088	-10000	0	-0.83	2	2
NRG1	-0.009	0.12	-10000	0	-0.76	11	11
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.027	0.078	-10000	0	-0.45	1	1
MAPK9	-0.007	0.034	-10000	0	-10000	0	0
ERBB2	-0.002	0.038	-10000	0	-0.59	2	2
ERBB3	-0.005	0.1	-10000	0	-0.76	9	9
SHC1	0.007	0.041	-10000	0	-0.86	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.002	0.016	0.34	1	-10000	0	1
STAT3 (dimer)	0	0.002	-10000	0	-10000	0	0
RNF41	0.038	0.005	-10000	0	-10000	0	0
FRAP1	0.015	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.01	0.048	-10000	0	-0.4	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.032	-10000	0	-0.5	2	2
CHRNA1	-0.13	0.28	-10000	0	-0.45	212	212
myelination	0.054	0.068	-10000	0	-0.45	1	1
PPP3CB	0.022	0.08	-10000	0	-0.56	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.013	0.068	-10000	0	-0.73	2	2
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
mol:GDP	0.008	0.087	-10000	0	-0.82	2	2
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.048	0.09	-10000	0	-0.72	1	1
SRC	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.021	0.084	-10000	0	-0.61	1	1
MAP2K1	-0.039	0.18	-10000	0	-0.56	5	5
heart morphogenesis	-0.016	0.074	-10000	0	-0.65	1	1
RAS family/GDP	-0.012	0.065	-10000	0	-0.71	2	2
GRB2	0.009	0.008	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.021	0.024	-10000	0	-0.24	1	1
HSP90AA1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.016	0.002	-10000	0	-10000	0	0
nervous system development	-0.016	0.074	-10000	0	-0.65	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.006	0.036	-10000	0	-10000	0	0
CaM/Ca2+	0	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	0.065	0.091	0.32	32	-0.36	2	34
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	0.031	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	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	-0.066	0.25	-10000	0	-0.86	43	43
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.044	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
TRIP10	0.016	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.022	0.062	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	0.067	0.094	0.33	32	-0.4	2	34
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.035	0	-10000	0	-10000	0	0
SFN	-0.079	0.27	-10000	0	-0.84	53	53
LNPEP	0.014	0.035	-10000	0	-0.76	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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
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	-0.026	0.032	0.67	1	-10000	0	1
CDKN1A	-0.003	0.042	-10000	0	-0.65	2	2
KAT2B	0.016	0	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.031	0	-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	0.1	-10000	0	-0.86	7	7
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.018	0.16	-10000	0	-0.67	27	27
PPARGC1A	-0.065	0.24	-10000	0	-0.76	50	50
FHL2	0.011	0.061	-10000	0	-0.76	3	3
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.008	-10000	0	-10000	0	0
HIST2H4A	0.026	0.032	-10000	0	-0.67	1	1
SIRT1/FOXO3a	0	0.007	-10000	0	-10000	0	0
SIRT1	0.001	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	0	0.015	-10000	0	-10000	0	0
apoptosis	-0.001	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.052	0.15	-10000	0	-0.5	50	50
p53/SIRT1	0.002	0.024	0.38	2	-10000	0	2
SIRT1/FOXO4	0.001	0.009	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.002	0.036	-10000	0	-0.45	3	3
HIST1H1E	0.029	0.015	-10000	0	-0.3	1	1
SIRT1/p300	0.001	0.008	-10000	0	-10000	0	0
muscle cell differentiation	0.032	0.13	0.57	27	-10000	0	27
TP53	0.001	0.011	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.008	-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	-0.009	0.081	-10000	0	-0.67	7	7
ACSS2	0.028	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.032	0.13	-10000	0	-0.58	27	27

×

IL1-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.061	-9999	-0.76	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.023	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.09	0.22	-9999	-0.62	69	69
IL1A	-0.008	0.14	-9999	-0.86	12	12
IL1B	0.025	0.062	-9999	-0.64	4	4
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.029	-9999	-10000	0	0
IL1R2	-0.082	0.26	-9999	-0.8	58	58
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.002	0.019	-9999	-10000	0	0
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.016	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.042	0.047	-9999	-10000	0	0
JUN	0.062	0.025	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.006	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.015	0.088	-9999	-0.52	14	14
PIK3R1	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.014	0.082	-9999	-0.5	1	1
IL1 beta fragment/IL1R1/IL1RAP	-0.006	0.057	-9999	-0.51	6	6
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.053	0.027	-9999	-10000	0	0
IRAK1	0.031	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.024	0.12	-9999	-0.67	17	17
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	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.025	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.006	0.057	-9999	-0.51	6	6
IL1 beta/IL1R2	-0.067	0.18	-9999	-0.52	62	62
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.005	0.044	-9999	-10000	0	0
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.006	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.046	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.017	0.097	-9999	-0.58	14	14
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	0	-9999	-10000	0	0
IL1RAP	0.012	0.057	-9999	-0.86	2	2
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.004	0.04	-9999	-10000	0	0
CASP1	0.016	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.096	0.23	-9999	-0.63	73	73
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.006	0.053	-9999	-0.49	5	5
TMEM189-UBE2V1	0.007	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.031	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
IL1RN	-0.015	0.16	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.044	0.028	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.011	0.035	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.032	0.091	-9999	-0.49	4	4
JUN	0.032	0.1	-9999	-0.53	4	4
HRAS	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.048	0.15	-9999	-0.71	9	9
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.048	0.15	-9999	-0.71	9	9
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	-0.038	0.13	-9999	-0.54	10	10
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.042	0.14	-9999	-0.85	4	4
GRB7	0.004	0.093	-9999	-0.76	7	7
RET51/GFRalpha1/GDNF	-0.048	0.15	-9999	-0.71	9	9
MAPKKK cascade	-0.037	0.12	-9999	-0.72	4	4
BCAR1	0.014	0.035	-9999	-0.76	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.035	0.12	-9999	-0.47	36	36
lamellipodium assembly	-0.03	0.085	-9999	-0.44	4	4
RET51/GFRalpha1/GDNF/SHC	-0.049	0.15	-9999	-0.69	10	10
PIK3CA	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.034	0.12	-9999	-0.47	35	35
RET9/GFRalpha1/GDNF/Shank3	-0.033	0.12	-9999	-0.47	34	34
MAPK3	0.011	0.14	-9999	-0.79	4	4
DOK1	0.016	0	-9999	-10000	0	0
DOK6	0	0.11	-9999	-0.76	10	10
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.039	0.12	-9999	-0.75	4	4
DOK5	-0.005	0.13	-9999	-0.77	13	13
GFRA1	-0.035	0.19	-9999	-0.77	31	31
MAPK8	0.021	0.11	-9999	-0.56	4	4
HRAS/GTP	-0.042	0.14	-9999	-0.85	4	4
tube development	-0.031	0.11	-9999	-0.5	6	6
MAPK1	0.011	0.14	-9999	-0.79	4	4
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.022	0.078	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.008	0.08	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.053	0.17	-9999	-0.9	10	10
SHC1	0.014	0.04	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.048	0.15	-9999	-0.71	9	9
RET51/GFRalpha1/GDNF/Dok5	-0.059	0.19	-9999	-0.84	15	15
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.028	0.093	-9999	-0.53	4	4
PIK3R1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.022	0.079	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.054	0.17	-9999	-0.82	12	12
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.011	0.14	-9999	-0.77	16	16
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.032	0.1	-9999	-0.52	4	4
RET9/GFRalpha1/GDNF/FRS2	-0.033	0.12	-9999	-0.54	6	6
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	-0.022	0.079	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.031	0.099	-9999	-0.61	4	4
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.031	0.099	-9999	-0.61	4	4
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.033	0.11	-9999	-0.76	4	4
PI3K	-0.045	0.13	-9999	-0.74	4	4
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.031	0.11	-9999	-0.5	6	6
GRB10	0.016	0	-9999	-10000	0	0
activation of MAPKK activity	-0.028	0.089	-9999	-0.53	4	4
RET51/GFRalpha1/GDNF/FRS2	-0.048	0.15	-9999	-0.71	9	9
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
IRS2	0.001	0.11	-9999	-0.86	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.033	0.11	-9999	-0.76	4	4
RET51/GFRalpha1/GDNF/PKC alpha	-0.048	0.15	-9999	-0.71	9	9
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.001	0.069	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.049	0.16	-9999	-0.71	9	9
Rac1/GTP	-0.036	0.1	-9999	-0.54	4	4
RET9/GFRalpha1/GDNF	-0.037	0.13	-9999	-0.52	34	34
GFRalpha1/GDNF	-0.042	0.15	-9999	-0.6	34	34

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0.001	0.11	-10000	0	-0.78	9	9
EFNB1	0.018	0.095	-10000	0	-0.67	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.018	0.092	-10000	0	-0.76	2	2
Ephrin B2/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
neuron projection morphogenesis	-0.017	0.088	-10000	0	-0.72	2	2
Ephrin B1/EPHB1-2/Tiam1	-0.02	0.1	-10000	0	-0.53	14	14
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.025	0.086	-10000	0	-0.68	7	7
YES1	-0.013	0.11	-10000	0	-0.9	7	7
Ephrin B1/EPHB1-2/NCK2	-0.019	0.094	-10000	0	-0.51	13	13
PI3K	-0.009	0.083	-10000	0	-0.68	7	7
mol:GDP	-0.019	0.099	-10000	0	-0.52	14	14
ITGA2B	-0.012	0.15	-10000	0	-0.86	15	15
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.013	0.11	-10000	0	-0.9	7	7
MAP3K7	-0.01	0.087	-10000	0	-0.72	7	7
FGR	-0.013	0.11	-10000	0	-0.9	7	7
TIAM1	0.014	0.035	-10000	0	-0.76	1	1
PIK3R1	0.016	0	-10000	0	-10000	0	0
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.019	0.12	-10000	0	-0.65	8	8
LYN	-0.013	0.11	-10000	0	-0.9	7	7
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.1	-10000	0	-0.85	7	7
Ephrin B1/EPHB1-2	-0.014	0.095	-10000	0	-0.79	7	7
SRC	-0.013	0.11	-10000	0	-0.9	7	7
ITGB3	0.014	0.035	-10000	0	-0.76	1	1
EPHB1	0.012	0.054	-10000	0	-0.81	2	2
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.022	0.12	-10000	0	-0.66	16	16
BLK	-0.02	0.11	-10000	0	-0.89	7	7
HCK	-0.019	0.12	-10000	0	-0.94	7	7
regulation of stress fiber formation	0.019	0.093	0.5	13	-10000	0	13
MAPK8	0.034	0.082	-10000	0	-0.64	7	7
Ephrin B1/EPHB1-2/RGS3	-0.019	0.094	-10000	0	-0.83	1	1
endothelial cell migration	-0.007	0.075	-10000	0	-0.62	7	7
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.008	0.1	-10000	0	-0.86	7	7
regulation of focal adhesion formation	0.019	0.093	0.5	13	-10000	0	13
chemotaxis	0.019	0.093	0.81	1	-10000	0	1
PIK3CA	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	-0.018	0.09	-10000	0	-0.75	2	2
angiogenesis	-0.014	0.094	-10000	0	-0.78	7	7
LCK	-0.018	0.11	-10000	0	-0.92	7	7

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.07	-9999	-0.44	1	1
Syndecan-3/Neurocan	-0.011	0.072	-9999	-0.48	11	11
POMC	0.014	0.035	-9999	-0.76	1	1
EGFR	-0.001	0.12	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.01	0.068	-9999	-0.47	10	10
AGRP	0.006	0.05	-9999	-0.76	2	2
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	-0.007	0.12	-9999	-0.86	10	10
long-term memory	-0.001	0.017	-9999	-10000	0	0
Syndecan-3/IL8	-0.032	0.12	-9999	-0.48	32	32
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.001	0.019	-9999	-0.43	1	1
MC4R	-0.01	0.11	-9999	-0.86	8	8
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.76	17	17
FGFR/FGF/Syndecan-3	-0.001	0.02	-9999	-0.43	1	1
neuron projection morphogenesis	-0.022	0.089	-9999	-10000	0	0
Syndecan-3/AgRP	-0.003	0.032	-9999	-0.41	3	3
Syndecan-3/AgRP/MC4R	-0.01	0.067	-9999	-0.47	8	8
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.02	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.031	0.12	-9999	-0.47	32	32
IL8	-0.04	0.21	-9999	-0.85	31	31
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.019	-9999	-0.41	1	1
alpha-MSH/MC4R	-0.012	0.089	-9999	-0.66	9	9
Gamma Secretase	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.003	0.12	-9999	-0.82	11	11
CLTC	0.044	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.037	0	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
CD59	0.04	0	-9999	-10000	0	0
CPE	0	0.12	-9999	-0.58	20	20
CTNNB1	0.016	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	0.044	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.045	0	-9999	-10000	0	0
TSHR	-0.048	0.2	-9999	-0.59	57	57
INS	0.017	0.001	-9999	-10000	0	0
BIN1	0.016	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.025	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.038	0.022	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.028	0.055	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	-0.05	0.23	-9999	-0.86	36	36
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.016	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.006	0.03	-9999	-10000	0	0
positive regulation of phagocytosis	0.025	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.044	0.16	-9999	-0.59	36	36
ACAP1	-0.019	0.024	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.033	0.012	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.043	0.011	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.016	0	-9999	-10000	0	0
exocyst	0	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0.044	0	-9999	-10000	0	0
NME1	0.025	0	-9999	-10000	0	0
clathrin coat assembly	0.043	0	-9999	-10000	0	0
IL2RA	-0.015	0.11	-9999	-10000	0	0
VAMP3	0.025	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.06	-9999	-0.43	6	6
EXOC6	0.016	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.016	0	-9999	-10000	0	0
PIP5K1C	0.045	0	-9999	-10000	0	0
SDC1	0.037	0.029	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
EXOC7	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.006	0.031	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.016	0	-9999	-10000	0	0
ADRB2	0.05	0.028	-9999	-10000	0	0
EXOC3	0.016	0	-9999	-10000	0	0
ASAP2	0.016	0	-9999	-10000	0	0
Dynamin 2/GDP	0	0	-9999	-10000	0	0
KLC1	0.016	0	-9999	-10000	0	0
AVPR2	-0.13	0.21	-9999	-0.38	200	200
RALA	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.026	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.007	0.081	0.78	5	-10000	0	5
PI3K Class IB/PDE3B	0.007	0.081	-10000	0	-0.78	5	5
PDE3B	0.007	0.081	-10000	0	-0.78	5	5

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.038	0.042	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.051	0.041	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.004	0.13	-9999	-0.86	11	11
TXN	0.011	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	0.016	0	-9999	-10000	0	0
GADD45B	0.016	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
MAP3K6	0.014	0.035	-9999	-0.76	1	1
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	-0.001	0.026	-9999	-0.57	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.003	0.011	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.11	0.28	-9999	-0.76	75	75
CCM2	0.016	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.079	0.18	-9999	-0.5	75	75
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.071	0.16	-9999	-0.45	75	75
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.02	0.035	-9999	-0.42	3	3
TAOK2	0.023	0	-9999	-10000	0	0
TAOK3	0.023	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	0.016	0	-9999	-10000	0	0
MAP3K10	0.014	0.035	-9999	-0.76	1	1
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	0	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.011	0.073	-9999	-0.5	10	10

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.021	0.17	-10000	0	-0.72	24	24
regulation of axonogenesis	-0.034	0.032	-10000	0	-10000	0	0
myoblast fusion	0.016	0.069	0.32	24	-10000	0	24
mol:GTP	-0.01	0.043	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.041	0.46	1	-10000	0	1
ARF1/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GM1	0.007	0.035	-10000	0	-10000	0	0
mol:Choline	0.033	0.03	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.072	-10000	0	-0.33	24	24
MAPK3	0.024	0.068	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.041	-10000	0	-0.46	1	1
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.07	-10000	0	-0.32	24	24
ARF1/GDP	-0.014	0.062	-10000	0	-10000	0	0
ARF6	0.009	0.024	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.016	0.035	-10000	0	-0.76	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.024	0.068	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.012	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.026	-10000	0	-0.57	1	1
RhoA/GDP	-0.014	0.062	-10000	0	-10000	0	0
NME1	0.017	0.004	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.062	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.016	0.073	-10000	0	-0.33	24	24
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.01	0.043	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.043	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.016	0.07	-10000	0	-0.32	24	24
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.03	-10000	0	-0.47	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.021	0.035	-10000	0	-10000	0	0
RAB11FIP3	0.014	0.035	-10000	0	-0.76	1	1
tube morphogenesis	-0.016	0.072	-10000	0	-0.33	24	24
ruffle organization	0.034	0.032	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.043	-10000	0	-10000	0	0
PLD2	0.021	0.035	-10000	0	-10000	0	0
PIP5K1A	0.034	0.032	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.03	-10000	0	-10000	0	0
Rac1/GTP	-0.016	0.073	-10000	0	-0.33	24	24

×

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	0.036	0.055	-9999	-0.5	5	5
SNTA1	0.012	0.053	-9999	-0.81	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.037	0.048	-9999	-0.48	4	4
MAPK12	0.03	0.083	-9999	-0.51	9	9
CCND1	0.013	0.07	-9999	-0.28	20	20
p38 gamma/SNTA1	0.034	0.088	-9999	-0.52	10	10
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.016	0	-9999	-10000	0	0
G2/M transition checkpoint	0.03	0.082	-9999	-0.51	9	9
MAP2K6	0.031	0.037	-9999	-0.48	2	2
MAPT	0.033	0.068	-9999	-0.46	6	6
MAPK13	0.026	0.055	-9999	-0.57	4	4
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.022	0.019	-9999	-0.39	1	1

×

E-cadherin signaling in the nascent adherens junction

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.02	0.1	-9999	-0.52	19	19
KLHL20	-0.013	0.045	-9999	-0.33	1	1
CYFIP2	0.003	0.099	-9999	-0.76	8	8
Rac1/GDP	0.068	0.076	-9999	-10000	0	0
ENAH	-0.02	0.1	-9999	-0.52	19	19
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	0.015	0.003	-9999	-10000	0	0
CDC42/GTP	-0.01	0.047	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.037	-9999	-0.22	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.085	-9999	-10000	0	0
RAPGEF1	0.055	0.099	-9999	-10000	0	0
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.021	0.11	-9999	-0.54	19	19
CRK	0.043	0.11	-9999	-0.48	19	19
E-cadherin/gamma catenin/alpha catenin	-0.022	0.11	-9999	-0.51	21	21
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	-0.02	0.1	-9999	-0.52	19	19
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.033	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.001	0.02	-9999	-0.45	1	1
PI3K	-0.009	0.043	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.026	0.12	-9999	-0.59	21	21
TIAM1	0.014	0.035	-9999	-0.76	1	1
E-cadherin(dimer)/Ca2+	-0.016	0.08	-9999	-10000	0	0
AKT1	-0.005	0.024	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
RhoA/GDP	0.068	0.075	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.033	-9999	-0.23	1	1
CDC42/GDP	0.068	0.075	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.068	-9999	-0.33	21	21
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.017	0.085	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.083	-9999	-0.42	19	19
mol:GDP	0.064	0.087	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.061	-9999	-0.76	3	3
p120 catenin/RhoA/GDP	-0.012	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	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	0.035	0.066	-9999	-0.26	20	20
NME1	0.016	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.02	0.1	-9999	-0.52	19	19
regulation of cell-cell adhesion	-0.008	0.041	-9999	-10000	0	0
WASF2	-0.005	0.019	-9999	-10000	0	0
Rap1/GTP	-0.011	0.054	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.088	-9999	-0.83	1	1
CCND1	-0.017	0.068	-9999	-0.33	20	20
VAV2	0.05	0.1	-9999	-10000	0	0
RAP1/GDP	-0.011	0.056	-9999	-10000	0	0
adherens junction assembly	0.033	0.11	-9999	-0.5	19	19
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	-0.017	0.083	-9999	-0.79	1	1
E-cadherin/beta catenin	-0.018	0.09	-9999	-0.46	19	19
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.02	0.1	-9999	-0.52	19	19
PIK3CA	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.021	0.073	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.019	0.095	-9999	-0.48	19	19
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.022	0.11	-9999	-0.56	19	19

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.051	0.11	-9999	-0.65	4	4
MAP3K8	0.012	0.057	-9999	-0.86	2	2
FOS	0.043	0.1	-9999	-0.55	4	4
PRKCA	0.017	0.003	-9999	-10000	0	0
PTPN7	-0.037	0.21	-9999	-0.86	30	30
HRAS	0.016	0.002	-9999	-10000	0	0
PRKCB	0.008	0.086	-9999	-0.83	5	5
NRAS	0.016	0.002	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.031	0.082	-9999	-0.52	2	2
MAP2K1	0.055	0.057	-9999	-0.48	5	5
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.005	0.045	-9999	-0.44	5	5
mol:GTP	0	0.001	-9999	-0.006	10	10
MAPK1	0.031	0.082	-9999	-0.52	2	2
RAF1	-0.005	0.045	-9999	-0.46	4	4
KRAS	0.016	0.002	-9999	-10000	0	0

×

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

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
MET/RANBP9	-0.007	0.068	-9999	-0.67	5	5
CRKL	0.041	0.065	-9999	-0.46	2	2
mol:PIP3	-0.03	0.003	-9999	-10000	0	0
AKT1	0.001	0.002	-9999	-10000	0	0
PTK2B	0.016	0	-9999	-10000	0	0
RAPGEF1	0.05	0.062	-9999	-0.43	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.029	0.13	-9999	-0.58	24	24
MAP3K5	-0.024	0.12	-9999	-0.39	2	2
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.026	0.12	-9999	-0.6	14	14
AP1	-0.012	0.076	-9999	-0.52	10	10
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
apoptosis	0.006	0.1	-9999	-0.7	10	10
STAT3 (dimer)	0.042	0.075	-9999	-0.51	2	2
GAB1/CRKL/SHP2/PI3K	-0.009	0.043	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
CBL/CRK	0.048	0.062	-9999	-0.43	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	0.031	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.039	-9999	-0.34	2	2
PAK1	0.011	0.002	-9999	-10000	0	0
HGF/MET/RANBP10	-0.029	0.13	-9999	-0.58	24	24
HRAS	0.032	0.095	-9999	-0.72	2	2
DOCK1	0.05	0.062	-9999	-0.43	2	2
GAB1	0.031	0.068	-9999	-0.49	2	2
CRK	0.041	0.065	-9999	-0.46	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.1	-9999	-0.55	12	12
JUN	0.016	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.013	0.061	-9999	-0.4	5	5
PIK3R1	0.016	0	-9999	-10000	0	0
cell morphogenesis	0.081	0.074	-9999	-10000	0	0
GRB2/SHC	-0.012	0.058	-9999	-0.54	3	3
FOS	0	0.11	-9999	-0.76	10	10
GLMN	0	0	-9999	-10000	0	0
cell motility	0	0.031	-9999	-0.29	5	5
HGF/MET/MUC20	-0.03	0.13	-9999	-0.59	24	24
cell migration	-0.012	0.057	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
MET/RANBP10	-0.007	0.068	-9999	-0.67	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.069	-9999	-0.57	2	2
MET/MUC20	-0.007	0.069	-9999	-0.68	5	5
RAP1B	0.058	0.059	-9999	-10000	0	0
RAP1A	0.058	0.059	-9999	-10000	0	0
HGF/MET/RANBP9	-0.029	0.13	-9999	-0.58	24	24
RAF1	0.042	0.09	-9999	-0.66	2	2
STAT3	-0.014	0.063	-9999	-0.52	2	2
cell proliferation	0.055	0.099	-9999	-0.64	3	3
RPS6KB1	-0.004	0.02	-9999	-10000	0	0
MAPK3	-0.006	0.028	-9999	-0.27	5	5
MAPK1	-0.006	0.028	-9999	-0.27	5	5
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.014	0.093	-9999	-10000	0	0
SRC	0.043	0.076	-9999	-0.54	2	2
PI3K	-0.011	0.05	-9999	-0.46	2	2
MET/Glomulin	0.009	0.064	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.051	0.085	-9999	-0.6	2	2
MET	0.007	0.089	-9999	-0.86	5	5
MAP4K1	-0.037	0.12	-9999	-0.4	11	11
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.05	0.087	-9999	-0.6	2	2
BAD	0.01	0.02	-9999	-0.43	1	1
MAP2K4	-0.012	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.057	-9999	-0.57	2	2
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	-0.012	0.055	-9999	-0.49	2	2
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.021	0.17	-9999	-0.81	21	21
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.012	0.054	-9999	-0.48	2	2
PDPK1	-0.013	0.003	-9999	-10000	0	0
HGF/MET/SHIP	-0.034	0.14	-9999	-0.6	27	27

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.057	0.16	-10000	0	-0.5	54	54
cell-cell adhesion	0.01	0.064	0.64	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	-0.011	0.073	-10000	0	-0.83	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
SHC1	0.014	0.04	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.014	0.082	-10000	0	-0.5	13	13
Ephrin B1/EPHB1	-0.002	0.035	-10000	0	-0.54	2	2
HRAS/GDP	-0.005	0.04	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.011	0.066	-10000	0	-0.49	1	1
Endophilin/SYNJ1	0.04	0.076	-10000	0	-0.76	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.005	0.046	-10000	0	-0.49	1	1
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.004	0.093	-10000	0	-0.76	7	7
PAK1	0.051	0.077	-10000	0	-0.78	1	1
HRAS	0.016	0	-10000	0	-10000	0	0
RRAS	0.04	0.077	-10000	0	-0.78	1	1
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.047	0.05	-10000	0	-0.46	1	1
lamellipodium assembly	-0.01	0.064	-10000	0	-0.64	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.004	0.03	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
EPHB2	0.001	0.11	-10000	0	-0.78	9	9
EPHB3	-0.005	0.13	-10000	0	-0.77	13	13
EPHB1	0.012	0.053	-10000	0	-0.81	2	2
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	0	0.051	-10000	0	-10000	0	0
Ephrin B/EPHB2	-0.012	0.075	-10000	0	-0.61	3	3
Ephrin B/EPHB3	-0.015	0.082	-10000	0	-0.67	2	2
JNK cascade	0.043	0.075	-10000	0	-0.8	1	1
Ephrin B/EPHB1	-0.005	0.048	-10000	0	-0.5	1	1
RAP1/GDP	0	0.045	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.009	0.07	-10000	0	-0.76	4	4
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.011	0.071	-10000	0	-0.72	2	2
Rap1/GTP	-0.01	0.064	-10000	0	-0.66	2	2
axon guidance	-0.057	0.16	-10000	0	-0.5	54	54
MAPK3	0.068	0.033	-10000	0	-10000	0	0
MAPK1	0.068	0.033	-10000	0	-10000	0	0
Rac1/GDP	0	0.048	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.008	0.048	-10000	0	-0.45	1	1
CDC42/GDP	0	0.048	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.057	0.23	-10000	0	-0.76	45	45
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.008	0.051	-10000	0	-0.61	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.01	0.063	-10000	0	-0.63	2	2
PTK2	0.002	0.016	-10000	0	-10000	0	0
MAP4K4	0.043	0.076	-10000	0	-0.82	1	1
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.008	0.051	-10000	0	-0.5	2	2
MAP2K1	0.059	0.035	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.011	0.075	-10000	0	-0.61	4	4
cell migration	0.07	0.038	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.04	0.077	-10000	0	-0.78	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.073	0.23	-10000	0	-0.78	2	2
HRAS/GTP	-0.011	0.07	-10000	0	-0.7	2	2
Ephrin B1/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
cell adhesion mediated by integrin	0.008	0.055	0.49	4	-10000	0	4
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.012	0.076	-10000	0	-0.77	2	2
RAC1-CDC42/GTP	-0.018	0.092	-10000	0	-0.87	3	3
RASA1	0.016	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0	0.045	-10000	0	-10000	0	0
ruffle organization	0.075	0.078	-10000	0	-0.66	2	2
NCK1	0.016	0	-10000	0	-10000	0	0
receptor internalization	0.041	0.1	-10000	0	-0.73	1	1
Ephrin B/EPHB2/KALRN	-0.011	0.073	-10000	0	-0.6	3	3
ROCK1	0.021	0.079	-10000	0	-0.45	13	13
RAS family/GDP	-0.008	0.047	-10000	0	-10000	0	0
Rac1/GTP	-0.011	0.069	-10000	0	-0.7	2	2
Ephrin B/EPHB1/Src/Paxillin	-0.004	0.032	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.004	0.045	-10000	0	-0.57	3	3
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	0.035	0	-10000	0	-10000	0	0
protein ubiquitination	-0.008	0.062	-10000	0	-10000	0	0
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.035	0.069	-10000	0	-0.52	1	1
FANCF	0.016	0	-10000	0	-10000	0	0
BRCA1	0.016	0	-10000	0	-10000	0	0
CCNE1	0.005	0.098	-10000	0	-0.86	6	6
CDK2/Cyclin E1	-0.008	0.074	-10000	0	-0.67	6	6
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.045	-10000	0	-0.57	3	3
FANCE	0.014	0.04	-10000	0	-0.86	1	1
FANCC	0.016	0	-10000	0	-10000	0	0
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.18	0.36	-10000	0	-0.86	105	105
DNA repair	0.044	0.13	-10000	0	-0.67	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.045	-10000	0	-0.57	3	3
BARD1/DNA-PK	-0.003	0.034	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.045	0.57	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	-0.002	0.022	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.003	0.038	-10000	0	-10000	0	0
BRCA1/BARD1/P53	-0.003	0.034	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.003	0.038	-10000	0	-10000	0	0
BRCA1/BACH1	0.016	0	-10000	0	-10000	0	0
BARD1	0.011	0.061	-10000	0	-0.76	3	3
PCNA	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.003	0.038	-10000	0	-0.48	3	3
BRCA1/BARD1/UbcH7	-0.003	0.038	-10000	0	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	-0.016	0.088	-10000	0	-10000	0	0
BARD1/DNA-PK/P53	-0.003	0.032	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.045	-10000	0	-0.57	3	3
BRCA1/BARD1/CTIP	-0.003	0.034	-10000	0	-10000	0	0
FA complex	-0.059	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.045	-10000	0	-0.57	3	3
RBBP8	0.031	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	0.003	0.034	-10000	0	-10000	0	0
BRCA1/BARD1	-0.009	0.062	-10000	0	-10000	0	0
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.046	-10000	0	-0.58	3	3
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.006	0.14	-10000	0	-0.86	12	12
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.045	-10000	0	-0.57	3	3
EWSR1	0.016	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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
IKK alpha homodimer	-0.007	0.055	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.046	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.044	-9999	-0.56	3	3
AP1	-0.013	0.074	-9999	-0.68	3	3
ILK	0.066	0.047	-9999	-10000	0	0
bone resorption	-0.022	0.096	-9999	-0.77	2	2
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.005	0.044	-9999	-10000	0	0
ITGAV	0.022	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.029	0.14	-9999	-0.66	21	21
alphaV/beta3 Integrin/Osteopontin	-0.004	0.043	-9999	-0.48	4	4
MAP3K1	0.066	0.047	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.078	0.07	-9999	-10000	0	0
MAPK1	0.078	0.07	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.079	0.047	-9999	-10000	0	0
ITGB3	0.021	0.036	-9999	-0.76	1	1
NFKBIA	0.091	0.07	-9999	-10000	0	0
FOS	0	0.11	-9999	-0.76	10	10
CD44	-0.021	0.18	-9999	-0.86	20	20
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.092	0.16	-9999	-1.1	7	7
NF kappa B1 p50/RelA	-0.008	0.048	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.062	0.055	-9999	-10000	0	0
VAV3	0.059	0.097	-9999	-0.8	1	1
MAP3K14	0.064	0.071	-9999	-0.5	4	4
ROCK2	0.014	0.035	-9999	-0.76	1	1
SPP1	0.018	0.061	-9999	-0.75	3	3
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.014	0.073	-9999	-0.73	1	1
MMP2	0.1	0.11	-9999	-0.73	5	5

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.016	0	-10000	0	-10000	0	0
ANTXR2	0.014	0.035	-10000	0	-0.76	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.095	1	1
monocyte activation	0.005	0.087	-10000	0	-0.36	22	22
MAP2K2	-0.002	0.037	-10000	0	-0.8	1	1
MAP2K1	0	0.003	-10000	0	-10000	0	0
MAP2K7	0	0.003	-10000	0	-10000	0	0
MAP2K6	-0.002	0.029	-10000	0	-0.44	2	2
CYAA	0.021	0.021	-10000	0	-0.43	1	1
MAP2K4	0	0.003	-10000	0	-10000	0	0
IL1B	0.018	0.052	-10000	0	-0.48	4	4
Channel	-0.001	0.021	-10000	0	-0.46	1	1
NLRP1	-0.006	0.053	-10000	0	-0.53	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.095	1	-10000	0	1
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
PGR	-0.015	0.081	-10000	0	-0.45	16	16
PA/Cellular Receptors	-0.001	0.023	-10000	0	-0.5	1	1
apoptosis	0	0.004	-10000	0	-0.095	1	1
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.001	0.019	-10000	0	-0.43	1	1
macrophage activation	0.028	0.004	-10000	0	-10000	0	0
TNF	0.002	0.11	-10000	0	-0.81	8	8
VCAM1	-0.016	0.084	-10000	0	-0.36	22	22
platelet activation	0	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.023	0.009	-10000	0	-10000	0	0
IL18	0.016	0.063	-10000	0	-0.51	6	6
negative regulation of macrophage activation	0	0.004	-10000	0	-0.095	1	1
LEF	0	0.004	-10000	0	-0.095	1	1
CASP1	-0.003	0.024	-10000	0	-0.23	5	5
mol:cAMP	0	0.005	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.095	1	1
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.02	-10000	0	-0.43	1	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.027	0.1	-9999	-10000	0	0
BAG4	0.016	0	-9999	-10000	0	0
BAD	0.031	0.041	-9999	-0.4	1	1
NFKBIA	0.016	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	74	74
BAX	0.032	0.037	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.028	-9999	-0.099	1	1
IKBKB	0.037	0.097	-9999	-10000	0	0
MAP2K2	0.046	0.055	-9999	-0.38	4	4
MAP2K1	0.047	0.052	-9999	-0.38	4	4
SMPD1	0.019	0.028	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.038	0.098	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.04	0.098	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.053	-9999	-0.38	4	4
response to UV	0.001	0	-9999	-10000	0	0
RAF1	0.039	0.054	-9999	-0.42	4	4
CRADD	0.016	0.002	-9999	-10000	0	0
mol:ceramide	0.022	0.038	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.016	0.002	-9999	-10000	0	0
MAP3K1	0.032	0.037	-9999	-10000	0	0
TRADD	0.016	0.002	-9999	-10000	0	0
RELA/p50	0.016	0	-9999	-10000	0	0
MAPK3	0.05	0.052	-9999	-0.37	4	4
MAPK1	0.05	0.052	-9999	-0.37	4	4
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.027	0.1	-9999	-10000	0	0
KSR1	0.029	0.057	-9999	-0.45	4	4
MAPK8	0.05	0.034	-9999	-10000	0	0
TRAF2	0.016	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.037	0.097	-9999	-10000	0	0
TNF R/SODD	0	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
CYCS	0.033	0.037	-9999	-10000	0	0
IKBKG	0.037	0.097	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.017	0.1	-9999	-0.44	1	1
RELA	0.016	0	-9999	-10000	0	0
RIPK1	0.016	0.001	-9999	-10000	0	0
AIFM1	0.033	0.037	-9999	-10000	0	0
TNF/TNF R/SODD	-0.009	0.068	-9999	-0.53	8	8
TNFRSF1A	0.016	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.03	-9999	-10000	0	0
NSMAF	0.028	0.099	-9999	-10000	0	0
response to hydrogen peroxide	0.001	0	-9999	-10000	0	0
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.006	0.075	-9999	-0.73	5	5
VDR	0.011	0.061	-9999	-0.76	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.076	0.052	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.086	0.065	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.009	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.072	-9999	-10000	0	0
RXRs/NUR77	-0.018	0.091	-9999	-10000	0	0
RXRs/PPAR	0.058	0.031	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.004	0.046	-9999	-0.58	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.042	-9999	-10000	0	0
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.061	-9999	-0.76	3	3
RARs/RARs/DNA/9cRA	-0.001	0.027	-9999	-0.42	2	2
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.036	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.072	-9999	-10000	0	0
THRA	0.014	0.035	-9999	-0.76	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.004	0.046	-9999	-0.58	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	-0.003	0.055	-9999	-0.5	4	4
NR1H4	-0.01	0.14	-9999	-0.76	16	16
RXRs/LXRs/DNA	0.008	0.059	-9999	-10000	0	0
NR1H2	0.023	0.036	-9999	-0.75	1	1
NR1H3	0.025	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.055	-9999	-10000	0	0
NR4A1	-0.01	0.14	-9999	-0.76	16	16
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.069	-9999	-0.42	2	2
RXRG	0.014	0.08	-9999	-0.85	4	4
RXR alpha/CCPG	0	0.004	-9999	-10000	0	0
RXRA	0.024	0.004	-9999	-10000	0	0
RXRB	0.025	0.006	-9999	-10000	0	0
THRB	-0.029	0.18	-9999	-0.76	28	28
PPARG	0.016	0	-9999	-10000	0	0
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.083	0.13	-9999	-0.88	8	8
mol:Oxysterols	0.009	0.008	-9999	-10000	0	0
cholesterol transport	0.086	0.064	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.012	0.05	-9999	-0.76	2	2
RXRs/NUR77/BCL2	-0.012	0.06	-9999	-10000	0	0
SREBF1	0.092	0.068	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.059	-9999	-0.5	4	4
ABCA1	0.091	0.074	-9999	-0.66	2	2
RARs/THRs	-0.026	0.099	-9999	-10000	0	0
RXRs/FXR	-0.018	0.092	-9999	-0.51	1	1
BCL2	0.016	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.002	0.013	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.1	-9999	-0.58	16	16
alpha4/beta7 Integrin/Paxillin	-0.017	0.094	-9999	-0.52	16	16
lamellipodium assembly	0.002	0.022	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.031	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.015	0.079	-9999	-10000	0	0
cell adhesion	-0.016	0.086	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.017	0.094	-9999	-0.52	16	16
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ARF6/GDP	0.002	0.013	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.031	0.12	-9999	-0.98	1	1
p130Cas/Crk/Dock1	-0.001	0.022	-9999	-0.48	1	1
VCAM1	-0.011	0.15	-9999	-0.84	15	15
alpha4/beta1 Integrin/Paxillin/Talin	-0.016	0.087	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.016	0.087	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
mol:GDP	0.016	0.086	-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	-0.016	0.087	-9999	-10000	0	0
Rac1/GTP	0.002	0.023	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	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	0.012	0.05	-9999	-0.76	2	2
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.007	0.039	-9999	-10000	0	0
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	0.016	0	-9999	-10000	0	0
MAP3K12	0.016	0	-9999	-10000	0	0
FGR	0.01	0.069	-9999	-0.86	3	3
p38 alpha/TAB1	-0.012	0.039	-9999	-0.31	2	2
PRKG1	0	0.11	-9999	-0.76	10	10
DUSP8	0.014	0.035	-9999	-0.76	1	1
PGK/cGMP/p38 alpha	-0.018	0.059	-9999	-0.52	1	1
apoptosis	-0.012	0.037	-9999	-0.3	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
DUSP1	0.014	0.04	-9999	-0.86	1	1
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-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	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.057	0.084	-9999	-0.42	2	2
BLK	-0.04	0.21	-9999	-0.86	30	30
HCK	-0.034	0.2	-9999	-0.86	27	27
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.012	0.057	-9999	-0.86	2	2
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.057	0.067	-9999	-0.34	2	2
positive regulation of innate immune response	0.068	0.091	-9999	-0.44	2	2
LCK	-0.024	0.18	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.074	0.088	-9999	-10000	0	0
p38alpha-beta/MKP5	0.072	0.092	-9999	-10000	0	0
PGK/cGMP	-0.012	0.083	-9999	-0.58	10	10
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.073	0.09	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.01	0.14	-9999	-0.83	14	14

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.007	0.055	-9999	-10000	0	0
TC10/GTP	-0.005	0.048	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.002	0.029	-9999	-10000	0	0
HRAS	0.016	0	-9999	-10000	0	0
APS homodimer	0.007	0.089	-9999	-0.86	5	5
GRB14	-0.029	0.18	-9999	-0.76	28	28
FOXO3	-0.003	0.012	-9999	-10000	0	0
AKT1	-0.02	0.082	-9999	-0.67	1	1
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
SORBS1	0.014	0.035	-9999	-0.76	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.006	0.15	-9999	-0.51	36	36
CBL/APS/CAP/Crk-II/C3G	-0.006	0.053	-9999	-0.49	5	5
Insulin Receptor/Insulin/IRS1/NCK2	-0.002	0.029	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.025	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.019	-9999	-10000	0	0
RPS6KB1	0.057	0.093	-9999	-0.6	1	1
PARD6A	0.011	0.061	-9999	-0.76	3	3
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.018	0.071	-9999	-0.62	1	1
HRAS/GTP	-0.006	0.051	-9999	-0.74	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.003	0.035	-9999	-10000	0	0
PRKCI	-0.005	0.019	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.022	0.09	-9999	-0.74	1	1
SHC1	0.014	0.04	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	0	0.003	-9999	-10000	0	0
PI3K	-0.002	0.026	-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	0	-9999	-10000	0	0
AKT2	-0.02	0.082	-9999	-0.67	1	1
PRKCZ	-0.009	0.059	-9999	-0.7	3	3
SH2B2	0.007	0.089	-9999	-0.86	5	5
SHC/SHIP	-0.007	0.061	-9999	-0.87	1	1
F2RL2	-0.034	0.2	-9999	-0.86	27	27
TRIP10	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.025	-9999	-0.55	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.023	-9999	-0.5	1	1
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	-0.006	0.057	-9999	-0.51	6	6
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.025	-9999	-0.54	1	1
INPP5D	0.031	0.065	-9999	-0.62	4	4
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.001	0.005	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
p62DOK/RasGAP	0	0.003	-9999	-10000	0	0
INS	0.005	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	0.031	0.064	-9999	-0.61	4	4
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.037	0.14	-9999	-0.69	4	4
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.002	0.023	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.03	-9999	-0.46	2	2
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.031	0.12	-9999	-0.5	27	27

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.008	0.058	-10000	0	-0.5	4	4
ER alpha/Gai/GDP/Gbeta gamma	0.056	0.049	-10000	0	-10000	0	0
AKT1	0.05	0.053	-10000	0	-0.75	2	2
PIK3CA	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.045	0.053	-10000	0	-0.76	2	2
mol:Ca2+	-0.01	0.18	-10000	0	-0.69	9	9
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.003	0.039	-10000	0	-0.5	3	3
SHC1	0.014	0.04	-10000	0	-0.86	1	1
apoptosis	-0.05	0.05	0.71	2	-10000	0	2
RhoA/GTP	-0.001	0.023	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.006	0.039	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.071	0.027	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.009	0.07	-10000	0	-0.54	8	8
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.002	0.029	-10000	0	-0.46	2	2
pseudopodium formation	0.071	0.027	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.002	0.032	-10000	0	-0.5	2	2
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.066	0.051	-10000	0	-0.47	2	2
E2/ER beta (dimer)	-0.008	0.072	-10000	0	-0.65	6	6
mol:GDP	-0.007	0.052	-10000	0	-0.49	2	2
mol:NADP	0.066	0.051	-10000	0	-0.47	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.013	0.19	-10000	0	-0.73	9	9
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.021	0.094	-10000	0	-0.8	3	3
PLCB2	-0.065	0.16	-10000	0	-0.48	59	59
IGF1	0.003	0.11	-10000	0	-0.86	7	7
mol:L-citrulline	0.066	0.051	-10000	0	-0.47	2	2
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.047	-10000	0	-0.63	1	1
JNK cascade	-0.008	0.072	-10000	0	-0.64	6	6
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
ESR2	0.005	0.094	-10000	0	-0.83	6	6
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.012	0.05	-10000	0	-0.76	2	2
Gq family/GDP/Gbeta gamma	-0.014	0.072	-10000	0	-0.6	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.053	0.027	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.006	0.04	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
E2/ER alpha (dimer)	-0.002	0.038	-10000	0	-0.58	2	2
STRN	0.014	0.035	-10000	0	-0.76	1	1
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.018	0.065	-10000	0	-0.56	6	6
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
HBEGF	-0.037	0.14	-10000	0	-0.51	5	5
cAMP biosynthetic process	-0.007	0.056	-10000	0	-0.44	8	8
SRC	0.065	0.047	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.006	0.045	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.009	0.05	-10000	0	-10000	0	0
Gs family/GTP	-0.007	0.057	-10000	0	-0.45	8	8
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.065	0.049	-10000	0	-0.45	2	2
mol:DAG	-0.013	0.19	-10000	0	-0.73	9	9
Gs family/GDP/Gbeta gamma	-0.005	0.041	-10000	0	-10000	0	0
MSN	0.073	0.029	-10000	0	-10000	0	0
Gq family/GTP	-0.017	0.08	-10000	0	-0.5	9	9
mol:PI-3-4-5-P3	0.045	0.051	-10000	0	-0.73	2	2
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.065	0.049	0.45	2	-10000	0	2
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.048	-10000	0	-0.46	2	2
NOS3	0.067	0.053	-10000	0	-0.49	2	2
GNA11	0.012	0.05	-10000	0	-0.76	2	2
MAPKKK cascade	0.076	0.052	-10000	0	-0.57	2	2
E2/ER alpha (dimer)/PELP1/Src	-0.005	0.039	-10000	0	-0.48	2	2
ruffle organization	0.071	0.027	-10000	0	-10000	0	0
ROCK2	-0.002	0.026	-10000	0	-10000	0	0
GNA14	0.004	0.093	-10000	0	-0.76	7	7
GNA15	-0.006	0.14	-10000	0	-0.86	12	12
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.16	0.25	-10000	0	-0.66	7	7
MMP2	0.068	0.074	-10000	0	-0.64	2	2

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	-0.036	0.12	-9999	-0.46	16	16
PDGFB-D/PDGFRB/SLAP	-0.029	0.14	-9999	-0.67	21	21
PDGFB-D/PDGFRB/APS/CBL	-0.006	0.059	-9999	-0.58	5	5
AKT1	-0.001	0.013	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.013	0.14	-9999	-0.48	16	16
PIK3CA	0.016	0	-9999	-10000	0	0
FGR	-0.004	0.03	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.045	0.13	-9999	-0.57	16	16
SHC1	0.014	0.04	-9999	-0.86	1	1
HRAS/GDP	0	0.002	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.038	0.042	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.004	0.093	-9999	-0.76	7	7
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	-0.029	0.14	-9999	-0.67	21	21
HRAS	0.016	0	-9999	-10000	0	0
HIF1A	0.09	0.017	-9999	-10000	0	0
GAB1	0.033	0.077	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.036	0.083	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.012	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.038	0.12	-9999	-0.51	9	9
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	0.039	0.042	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.004	0.007	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.069	-9999	-0.58	7	7
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.087	-9999	-10000	0	0
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
VAV2	0.036	0.088	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	-0.02	0.088	-9999	-0.62	3	3
PDGFRB	0.016	0.006	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.021	0.083	-9999	-10000	0	0
ABL1	0.033	0.061	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.033	0.072	-9999	-10000	0	0
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.014	0.04	-9999	-0.86	1	1
cell proliferation	0.045	0.12	-9999	-0.51	16	16
SLA	-0.023	0.18	-9999	-0.86	21	21
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	-0.001	0.013	-9999	-10000	0	0
PI3K	-0.001	0.015	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.008	0.064	-9999	-0.5	8	8
SH2B2	0.007	0.089	-9999	-0.86	5	5
PLCgamma1/SPHK1	0.012	0.14	-9999	-0.5	16	16
LYN	-0.001	0.013	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.017	-9999	-10000	0	0
SPHK1	-0.057	0.24	-9999	-0.86	40	40
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.039	0.042	-9999	-10000	0	0
PLCG1	0.039	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.022	-9999	-0.49	1	1
YES1	-0.001	0.013	-9999	-10000	0	0
cell migration	-0.001	0.022	-9999	-0.48	1	1
SHC/Grb2/SOS1	-0.001	0.021	-9999	-10000	0	0
SLC9A3R2	0.014	0.035	-9999	-0.76	1	1
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.02	-9999	-10000	0	0
FYN	-0.001	0.013	-9999	-10000	0	0
DOK1	0.044	0.009	-9999	-10000	0	0
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	0.046	0.1	-9999	-0.52	1	1
PRKCD	0.042	0.029	-9999	-0.53	1	1
FER	0.042	0.026	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.021	-9999	-10000	0	0
RASA1	0.043	0.014	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.033	0.06	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.021	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.06	0.046	-10000	0	-0.46	1	1
adherens junction organization	0.041	0.078	-10000	0	-0.68	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.06	-10000	0	-10000	0	0
FMN1	0.025	0.12	-10000	0	-0.67	1	1
mol:IP3	-0.007	0.035	-10000	0	-0.48	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.013	0.065	-10000	0	-0.72	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.056	0.052	-10000	0	-0.51	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.11	-10000	0	-0.56	15	15
CTNND1	0.017	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.046	0.071	-10000	0	-0.65	1	1
VASP	0.046	0.072	-10000	0	-0.67	1	1
ZYX	0.046	0.072	-10000	0	-0.67	1	1
JUB	0.044	0.077	-10000	0	-0.67	1	1
EGFR(dimer)	-0.021	0.084	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.021	0.1	-10000	0	-0.49	21	21
mol:PI-3-4-5-P3	-0.009	0.043	-10000	0	-0.55	1	1
PIK3CA	0.017	0.001	-10000	0	-10000	0	0
PI3K	-0.009	0.044	-10000	0	-0.56	1	1
FYN	-0.24	0.13	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.034	-10000	0	-0.47	1	1
JUP	-0.004	0.06	-10000	0	-0.76	3	3
PIK3R1	0.017	0.001	-10000	0	-10000	0	0
mol:DAG	-0.007	0.035	-10000	0	-0.48	1	1
CDH1	-0.03	0.15	-10000	0	-0.76	19	19
RhoA/GDP	-0.013	0.06	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.046	0.071	-10000	0	-0.65	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	-0.001	0.12	-10000	0	-0.85	9	9
CASR	-0.3	0.15	-10000	0	-0.53	14	14
RhoA/GTP	-0.006	0.03	-10000	0	-10000	0	0
AKT2	0.056	0.052	-10000	0	-0.51	1	1
actin cable formation	0.035	0.11	-10000	0	-0.64	1	1
apoptosis	0.008	0.038	0.5	1	-10000	0	1
CTNNA1	0.017	0.004	-10000	0	-10000	0	0
mol:GDP	-0.014	0.066	-10000	0	-0.49	1	1
PIP5K1A	0.046	0.072	-10000	0	-0.67	1	1
PLCG1	-0.007	0.036	-10000	0	-0.5	1	1
Rac1/GTP	-0.019	0.076	-10000	0	-0.61	1	1
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.02	-10000	0	-10000	0	0
HDAC3	0.016	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	-0.025	0.13	-10000	0	-0.67	18	18
GATA1/HDAC5	-0.026	0.13	-10000	0	-0.66	19	19
GATA2/HDAC5	-0.012	0.081	-10000	0	-0.57	10	10
HDAC5/BCL6/BCoR	-0.001	0.022	-10000	0	-0.48	1	1
HDAC9	0.016	0	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.026	-10000	0	-0.58	1	1
HDAC4/ANKRA2	0	0	-10000	0	-10000	0	0
HDAC5/YWHAB	-0.001	0.026	-10000	0	-0.57	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-10000	0	-10000	0	0
GATA2	0.001	0.1	-10000	0	-0.76	9	9
HDAC4/RFXANK	0	0	-10000	0	-10000	0	0
BCOR	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.014	0.035	-10000	0	-0.76	1	1
HDAC5	0.014	0.035	-10000	0	-0.76	1	1
GNB1/GNG2	0	0	-10000	0	-10000	0	0
Histones	-0.003	0.042	-10000	0	-0.85	1	1
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	-0.001	0.026	-10000	0	-0.57	1	1
HDAC4/Ubc9	0	0	-10000	0	-10000	0	0
HDAC7	0.016	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.026	-10000	0	-0.57	1	1
TUBA1B	0.016	0	-10000	0	-10000	0	0
HDAC6	0.016	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.026	-10000	0	-0.57	1	1
CAMK4	0.012	0.05	-10000	0	-0.76	2	2
Tubulin/HDAC6	-0.001	0.022	-10000	0	-0.48	1	1
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	-0.02	0.17	-10000	0	-0.86	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.016	0	-10000	0	-10000	0	0
NR3C1	0.014	0.04	-10000	0	-0.86	1	1
SUMO1/HDAC4	0	0	-10000	0	-10000	0	0
SRF	0.016	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0	0	-10000	0	-10000	0	0
Tubulin	-0.001	0.026	-10000	0	-0.57	1	1
HDAC4/14-3-3 E	0	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
RANGAP1	0.016	0	-10000	0	-10000	0	0
BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-10000	0	-10000	0	0
HDAC4/SRF	-0.002	0.031	-10000	0	-0.48	2	2
HDAC4/ER alpha	-0.002	0.037	-10000	0	-0.57	2	2
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.051	0.045	-10000	0	-0.84	1	1
cell motility	-0.001	0.022	-10000	0	-0.48	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.016	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	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	0	-10000	0	-10000	0	0
ESR1	0.012	0.05	-10000	0	-0.76	2	2
HDAC6/HDAC11	-0.002	0.037	-10000	0	-0.57	2	2
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0.016	0	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
NCOR2	0.016	0	-10000	0	-10000	0	0
TUBB2A	0.014	0.035	-10000	0	-0.76	1	1
HDAC11	0.012	0.05	-10000	0	-0.76	2	2
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	0.016	0	-10000	0	-10000	0	0
nuclear import	0.001	0.018	0.4	1	-10000	0	1

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.014	-10000	0	-10000	0	0
CLOCK	0.02	0.002	-10000	0	-10000	0	0
TIMELESS/CRY2	0.057	0.022	-10000	0	-10000	0	0
DEC1/BMAL1	-0.001	0.03	-10000	0	-0.66	1	1
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.055	0.064	-10000	0	-1.3	1	1
ARNTL	0.02	0.002	-10000	0	-10000	0	0
TIMELESS	0.057	0.025	-10000	0	-10000	0	0
NPAS2	0.006	0.1	-10000	0	-0.75	9	9
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.007	0.14	1	-10000	0	1
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.007	-10000	0	-0.14	1	1
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.045	0.072	-10000	0	-0.47	9	9
BMAL1/CLOCK	0.066	0.048	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.014	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.014	-10000	0	-10000	0	0
mol:NADPH	0.019	0.007	-10000	0	-0.14	1	1
PER1/TIMELESS	0.057	0.022	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.001	0.04	-10000	0	-0.86	1	1

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.022	-9999	-0.48	1	1
forebrain development	0.056	0.093	-9999	-0.5	2	2
GNAO1	0.009	0.078	-9999	-0.84	4	4
SMO/beta Arrestin2	-0.002	0.04	-9999	-0.62	2	2
SMO	0.015	0.036	-9999	-0.76	1	1
ARRB2	0.014	0.04	-9999	-0.86	1	1
GLI3/SPOP	0.062	0.021	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.004	-9999	-10000	0	0
SIN3/HDAC complex	-0.017	0.094	-9999	-0.52	16	16
GNAI1	0.011	0.061	-9999	-0.76	3	3
XPO1	0.019	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.013	0.061	-9999	-10000	0	0
SAP30	-0.014	0.16	-9999	-0.86	16	16
mol:GDP	0.015	0.036	-9999	-0.76	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.035	-9999	-0.76	1	1
GNAI3	0.016	0.004	-9999	-10000	0	0
GLI2	0.058	0.032	-9999	-10000	0	0
GLI3	0.056	0.023	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0.035	-9999	-0.76	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.045	0.052	-9999	-0.56	1	1
SIN3B	0.015	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.058	0.043	-9999	-10000	0	0
GLI2/Su(fu)	0.075	0.038	-9999	-10000	0	0
FOXA2	-0.062	0.23	-9999	-0.85	35	35
neural tube patterning	0.056	0.093	-9999	-0.5	2	2
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.014	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.014	0.035	-9999	-0.76	1	1
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.023	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	0.056	0.093	-9999	-0.5	2	2
SUFU	0.038	0.022	-9999	-10000	0	0
LGALS3	-0.003	0.13	-9999	-0.86	10	10
catabolic process	0.093	0.029	-9999	-10000	0	0
GLI3A/CBP	0.018	0.052	-9999	-10000	0	0
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.056	0.094	-9999	-0.51	2	2
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.012	0.079	-9999	-0.55	10	10
GNAZ	0.011	0.061	-9999	-0.76	3	3
RBBP4	0.016	0.001	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.061	0.03	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.041	0.051	-9999	-0.49	1	1
PTCH1	0.063	0.1	-9999	-1.1	1	1
MIM/GLI1	0.053	0.15	-9999	-0.6	2	2
CREBBP	0.018	0.052	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.058	0.045	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.031	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.001	0.02	-9999	-10000	0	0
CDKN1B	0.051	0	-9999	-10000	0	0
CDKN1A	0.049	0.033	-9999	-0.47	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.051	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.014	0.035	-9999	-0.76	1	1
AKT3	0.023	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.051	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	-0.001	0.022	-9999	-0.48	1	1
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.016	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.051	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.051	0	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.034	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.042	0.051	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.051	0	-9999	-10000	0	0
CASP9	0.051	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.058	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.029	-9999	-0.45	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0	-9999	-10000	0	0
CHUK	0.051	0	-9999	-10000	0	0
BAD/BCL-XL	-0.001	0.016	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.023	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.061	0.057	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
MDM2	0.051	0	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0	-9999	-10000	0	0
TSC1/TSC2	0.06	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
glucose import	0.031	0.079	-9999	-0.48	11	11
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.031	0.079	-9999	-0.48	11	11
GSK3A	0.051	0	-9999	-10000	0	0
FOXO1	0.051	0	-9999	-10000	0	0
GSK3B	0.051	0	-9999	-10000	0	0
SFN	-0.079	0.27	-9999	-0.84	53	53
G1/S transition of mitotic cell cycle	0.06	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.038	0.077	-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

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.076	0.028	-10000	0	-10000	0	0
NFATC2	0.054	0.029	-10000	0	-10000	0	0
NFATC3	0.028	0.042	-10000	0	-0.49	3	3
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.034	0.067	-10000	0	-0.47	3	3
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.011	0.053	-10000	0	-0.53	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+	0	0.001	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0.003	-10000	0	-10000	0	0
BAD	0.014	0.035	-10000	0	-0.76	1	1
CABIN1/MEF2D	0.039	0.064	-10000	0	-0.44	3	3
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.035	-10000	0	-0.76	1	1
activation-induced cell death of T cells	-0.039	0.063	0.43	3	-10000	0	3
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.016	0	-10000	0	-10000	0	0
XPO1	0.015	0.003	-10000	0	-10000	0	0
SFN	-0.079	0.27	-10000	0	-0.84	53	53
MAP3K8	0.012	0.057	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.002	0.025	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.011	0.057	-10000	0	-10000	0	0
CABIN1	0.034	0.068	-10000	0	-0.47	3	3
CALM1	0.016	0.003	-10000	0	-10000	0	0
RAN	0.015	0.003	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0.012	0.05	-10000	0	-0.76	2	2
mol:Ca2+	0.001	0.004	-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	-0.005	0.052	-10000	0	-0.57	4	4
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0.003	-10000	0	-10000	0	0
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	-0.002	0.029	-10000	0	-10000	0	0
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0	0	-10000	0	-10000	0	0
CASP3	0.016	0.003	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.01	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.073	-10000	0	-0.54	1	1
PRKCB	0.007	0.085	-10000	0	-0.82	5	5
PRKCE	0.016	0	-10000	0	-10000	0	0
JNK2/NFAT4	-0.003	0.035	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.001	0.026	-10000	0	-0.57	1	1
PRKCD	0.014	0.04	-10000	0	-0.86	1	1
NUP214	0.015	0.003	-10000	0	-10000	0	0
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.027	0.17	-10000	0	-0.86	19	19
PRKCQ	-0.004	0.12	-10000	0	-0.76	12	12
FKBP38/BCL2	-0.001	0.026	-10000	0	-0.57	1	1
EP300	0.016	0.003	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.081	0.03	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.001	0.023	-10000	0	-0.51	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.032	-10000	0	-0.5	2	2
NFATc/ERK1	0.081	0.027	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.011	0.053	-10000	0	-0.53	2	2
NR4A1	0.071	0.14	-10000	0	-0.68	16	16
GSK3B	0.016	0.003	-10000	0	-10000	0	0
positive T cell selection	0.028	0.042	-10000	0	-0.49	3	3
NFAT1/CK1 alpha	-0.002	0.015	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0.003	-10000	0	-10000	0	0
AKAP5	0.009	0.07	-10000	0	-0.76	4	4
MEF2D	0.016	0.003	-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	0.08	0.03	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.007	0.056	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.044	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.061	-9999	-0.76	3	3
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	-0.003	0.023	-9999	-10000	0	0
YY1/LSF	0	0	-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	-0.005	0.042	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.004	0.028	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.046	0.042	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0.064	0.011	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.049	0.038	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.001	0.1	-9999	-0.76	9	9
GATA1	-0.02	0.17	-9999	-0.86	18	18
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.008	0.037	-9999	-0.44	1	1
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	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	-0.004	0.033	-9999	-10000	0	0
KAT2B	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.007	0.036	-9999	-10000	0	0
SIN3 complex	-0.017	0.094	-9999	-0.52	16	16
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.014	0.16	-9999	-0.86	16	16
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	-0.003	0.024	-9999	-10000	0	0
YY1/HDAC2	0	0	-9999	-10000	0	0
YY1/HDAC1	0	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.064	0	-9999	-10000	0	0
PPARG	-0.006	0.049	-9999	-10000	0	0
HDAC8/hEST1B	0	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)	-0.004	0.028	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.009	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	-0.004	0.033	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.041	0	-9999	-10000	0	0
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.035	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	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.017	0.091	-9999	-0.51	16	16
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.033	-9999	-10000	0	0
histone deacetylation	0.064	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.025	-9999	-10000	0	0
nuclear export	0	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	-0.012	0.065	-9999	-0.43	9	9
GATA1/HDAC1	-0.025	0.13	-9999	-0.67	18	18
GATA1/HDAC3	-0.023	0.1	-9999	-0.52	18	18
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.01	0.079	-9999	-0.62	8	8
SIN3/HDAC complex/Mad/Max	0.057	0.038	-9999	-10000	0	0
NuRD Complex	0	0.008	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.023	-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	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.029	0.13	-9999	-0.65	21	21
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
negative regulation of cell growth	0.057	0.038	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.064	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.047	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	-0.005	0.027	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.014	0.035	-9999	-0.76	1	1
MBD2	0.016	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.061	-10000	0	-0.76	3	3
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.016	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.058	0.026	-10000	0	-10000	0	0
KAT2B	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
AKT1	0.031	0.037	0.24	1	-0.31	2	3
RAR alpha/9cRA/Cyclin H	-0.007	0.035	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.054	0.028	-10000	0	-10000	0	0
CDC2	0.001	0.001	-10000	0	-10000	0	0
response to UV	0.002	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.008	0.038	-10000	0	-10000	0	0
NCOR2	0.016	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	-0.004	0.046	-10000	0	-0.58	3	3
RXRs/RARs/NRIP1/9cRA	0.065	0.079	-10000	0	-0.52	1	1
NCOA2	0.009	0.07	-10000	0	-0.76	4	4
NCOA3	0.016	0	-10000	0	-10000	0	0
NCOA1	0.016	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.011	0.061	-10000	0	-0.76	3	3
RARG	0.017	0.001	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.017	0.001	-10000	0	-10000	0	0
MAPK1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.017	0.001	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.017	0.071	-10000	0	-10000	0	0
RARA	0.027	0.055	-10000	0	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.052	0.04	-10000	0	-10000	0	0
PRKCA	0.021	0.001	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.057	0.08	-10000	0	-0.57	1	1
RXRG	0.014	0.088	-10000	0	-0.38	23	23
RXRA	0.038	0.052	-10000	0	-10000	0	0
RXRB	0.019	0.08	-10000	0	-0.37	19	19
VDR/Vit D3/DNA	-0.004	0.046	-10000	0	-0.58	3	3
RBP1	0.01	0.067	-10000	0	-0.83	3	3
CRBP1/9-cic-RA	-0.004	0.051	-10000	0	-0.65	3	3
RARB	0.016	0.05	-10000	0	-0.76	2	2
PRKCG	-0.022	0.17	-10000	0	-0.86	19	19
MNAT1	0.016	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.056	0.08	-10000	0	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.063	0.071	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.041	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.057	0.08	-10000	0	-0.57	1	1
positive regulation of DNA binding	-0.007	0.033	-10000	0	-10000	0	0
NRIP1	0.055	0.091	-10000	0	-1.2	1	1
RXRs/RARs	0.048	0.078	-10000	0	-0.41	1	1
RXRs/RXRs/DNA/9cRA	-0.015	0.07	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
CDK7	0.016	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.005	0.024	-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

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.003	0.043	-9999	-0.67	2	2
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.002	0.031	-9999	-0.49	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.037	-9999	-10000	0	0
NFKBIA	0.027	0.058	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0	-9999	-10000	0	0
ARRB2	0.022	0.019	-9999	-0.39	1	1
REL	0.012	0.05	-9999	-0.76	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.002	0.037	-9999	-0.58	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.027	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
NFKB1	0.031	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.036	0.057	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.008	0.036	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.011	0.046	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.012	0.05	-9999	-0.76	2	2
I kappa B alpha/PIK3R1	0.034	0.054	-9999	-10000	0	0
cell death	-0.008	0.034	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.002	0.031	-9999	-0.49	2	2
LCK	-0.024	0.18	-9999	-0.85	22	22
BCL3	0.012	0.057	-9999	-0.86	2	2

×

IGF1 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.016	0	-9999	-10000	0	0
PTK2	0.016	0	-9999	-10000	0	0
CRKL	0.029	0.058	-9999	-0.41	7	7
GRB2/SOS1/SHC	-0.001	0.026	-9999	-0.58	1	1
HRAS	0.016	0	-9999	-10000	0	0
IRS1/Crk	-0.007	0.053	-9999	-0.41	7	7
IGF-1R heterotetramer/IGF1/PTP1B	-0.008	0.062	-9999	-0.52	7	7
AKT1	0.057	0.051	-9999	-10000	0	0
BAD	0.065	0.052	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.029	0.058	-9999	-0.41	7	7
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.053	-9999	-10000	0	0
RAF1	0.07	0.046	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.007	0.05	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.008	0.059	-9999	-0.45	7	7
PIK3CA	0.016	0	-9999	-10000	0	0
RPS6KB1	0.057	0.051	-9999	-10000	0	0
GNB2L1	0.014	0.04	-9999	-0.86	1	1
positive regulation of MAPKKK cascade	0.061	0.041	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.007	0.047	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.007	0.054	-9999	-0.51	1	1
IGF-1R heterotetramer	0.015	0.012	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.053	-9999	-0.41	7	7
Crk/p130 Cas/Paxillin	-0.007	0.049	-9999	-10000	0	0
IGF1R	0.015	0.012	-9999	-10000	0	0
IGF1	0.003	0.1	-9999	-0.85	7	7
IRS2/Crk	-0.015	0.079	-9999	-0.49	8	8
PI3K	-0.007	0.049	-9999	-10000	0	0
apoptosis	-0.068	0.046	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.049	0.061	-9999	-0.82	1	1
RAF1/14-3-3 E	0.073	0.041	-9999	-10000	0	0
BAD/14-3-3	0.071	0.049	-9999	-10000	0	0
PRKCZ	0.054	0.061	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.005	0.036	-9999	-10000	0	0
PTPN1	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.041	0.052	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.008	0.06	-9999	-0.55	1	1
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
IRS1/NCK2	-0.007	0.053	-9999	-0.41	7	7
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.029	0.058	-9999	-10000	0	0
IRS1	0.018	0.062	-9999	-0.45	7	7
IRS2	0.019	0.091	-9999	-0.52	8	8
IGF-1R heterotetramer/IGF1	-0.01	0.079	-9999	-0.66	7	7
GRB2	0.016	0	-9999	-10000	0	0
PDPK1	0.047	0.053	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKD1	0.05	0.049	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0.016	-9999	-9999
SMAD2	0.019	-9999	-9999
SMAD3	0.057	-9999	-9999
SMAD3/SMAD4	0.063	-9999	-9999
SMAD4/Ubc9/PIASy	0	-9999	-9999
SMAD2/SMAD2/SMAD4	0	-9999	-9999
PPM1A	0.016	-9999	-9999
CALM1	0.016	-9999	-9999
SMAD2/SMAD4	0.027	-9999	-9999
MAP3K1	0.016	-9999	-9999
TRAP-1/SMAD4	0	-9999	-9999
MAPK3	0.016	-9999	-9999
MAPK1	0.016	-9999	-9999
NUP214	0.016	-9999	-9999
CTDSP1	0.016	-9999	-9999
CTDSP2	0.016	-9999	-9999
CTDSPL	0.016	-9999	-9999
KPNB1	0.016	-9999	-9999
TGFBRAP1	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
NUP153	0.016	-9999	-9999
KPNA2	0.016	-9999	-9999
PIAS4	0.016	-9999	-9999

×

mTOR signaling 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	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	-0.001	0.021	-10000	0	-10000	0	0
FRAP1	0.021	0.004	-10000	0	-10000	0	0
AKT1	-0.001	0.016	-10000	0	-10000	0	0
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.012	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.003	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.01	-10000	0	-10000	0	0
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.019	0.027	-10000	0	-0.39	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.038	0.01	-10000	0	-10000	0	0
MAP3K5	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.014	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	2	2
EIF4B	0.046	0.009	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.018	-10000	0	-0.37	1	1
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.001	0.022	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.044	0.007	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.009	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.002	2	2
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.018	-10000	0	-10000	0	0
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.003	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.023	0	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.013	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.002	2	-10000	0	2
RPS6	0.014	0.04	-10000	0	-0.86	1	1
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.01	0.028	-10000	0	-0.43	2	2
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0	0.001	-10000	0	-10000	0	0
PDK2	-0.001	0.018	-10000	0	-10000	0	0
EIF4EBP1	-0.005	0.094	-10000	0	-0.46	20	20
PIK3CA	0.016	0	-10000	0	-10000	0	0
PPP2R5D	0.03	0.004	-10000	0	-10000	0	0
peptide biosynthetic process	0.023	0.001	-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	0.001	0	-10000	0	-10000	0	0
EEF2	0.023	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.005	0.084	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.57	1	1
PTK2	0	0.008	-9999	-10000	0	0
positive regulation of JNK cascade	-0.001	0.014	-9999	-10000	0	0
CDC42/GDP	0.08	0.012	-9999	-10000	0	0
Rac1/GDP	0.082	0.011	-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	-0.001	0.017	-9999	-0.36	1	1
nectin-3/I-afadin	0	0	-9999	-10000	0	0
RAPGEF1	0.078	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.071	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	0.047	0	-9999	-10000	0	0
Rap1/GTP	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.082	0.013	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	0	0.001	-9999	-10000	0	0
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	0.016	0	-9999	-10000	0	0
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
CLDN1	0.01	0.067	-9999	-0.83	3	3
JAM-A/CLDN1	-0.003	0.039	-9999	-0.52	2	2
SRC	0	0.003	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.072	0.029	-9999	-0.54	1	1
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	0	-9999	-10000	0	0
nectin-1/I-afadin	0	0	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.016	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.001	0.014	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.001	0.017	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
VAV2	0.072	0.006	-9999	-10000	0	0
RAP1/GDP	0	0.005	-9999	-10000	0	0
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
Rac1/GTP	0	0.001	-9999	-10000	0	0
PTPRM	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.074	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.014	0.035	-9999	-0.76	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.026	-9999	-0.57	1	1
MAP2K4	0.064	0.017	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.016	0	-9999	-10000	0	0
TNFRSF10A	0.014	0.035	-9999	-0.76	1	1
SMPD1	-0.001	0.012	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR3	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR1	-0.002	0.037	-9999	-0.57	2	2
TRAIL/TRAILR4	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.029	-9999	-0.45	2	2
IKK complex	-0.001	0.008	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.03	0.027	-9999	-0.57	1	1
MAP3K1	-0.001	0.014	-9999	-10000	0	0
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.035	-9999	-0.76	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.019	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
MAPK1	0.03	0.027	-9999	-0.57	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.026	-9999	-10000	0	0
mol:ceramide	-0.001	0.012	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.072	0.016	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.031	-9999	-0.48	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.001	0.024	-9999	-0.46	1	1
JNK cascade	-0.001	0.026	-9999	-0.57	1	1
TRAIL (trimer)	0.014	0.035	-9999	-0.76	1	1
TNFRSF10C	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.027	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.001	0.022	-9999	-0.48	1	1
cell death	-0.001	0.012	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.013	-9999	-10000	0	0
TRAILR2 (trimer)	0.016	0	-9999	-10000	0	0
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.001	0.018	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.007	0.26	-9999	-1.1	25	25
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.023	0.073	-9999	-10000	0	0
ATF2/c-Jun	0.046	0.056	-9999	-10000	0	0
MAPK11	0.023	0.073	-9999	-10000	0	0
MITF	0.045	0.088	-9999	-10000	0	0
MAPKAPK5	0.045	0.088	-9999	-10000	0	0
KRT8	0.044	0.09	-9999	-10000	0	0
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.033	0.11	-9999	-10000	0	0
CEBPB	0.034	0.11	-9999	-10000	0	0
SLC9A1	0.045	0.088	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.052	0.087	-9999	-10000	0	0
p38alpha-beta/MNK1	-0.018	0.07	-9999	-10000	0	0
JUN	0.047	0.056	-9999	-10000	0	0
PPARGC1A	-0.001	0.16	-9999	-0.75	2	2
USF1	0.045	0.088	-9999	-10000	0	0
RAB5/GDP/GDI1	-0.013	0.049	-9999	-10000	0	0
NOS2	0.041	0.12	-9999	-0.79	6	6
DDIT3	0.042	0.094	-9999	-10000	0	0
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.049	0.076	-9999	-0.48	1	1
p38alpha-beta/HBP1	-0.018	0.07	-9999	-10000	0	0
CREB1	0.05	0.092	-9999	-10000	0	0
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.049	0.075	-9999	-10000	0	0
RPS6KA4	0.045	0.088	-9999	-10000	0	0
PLA2G4A	0.045	0.087	-9999	-10000	0	0
GDI1	0.045	0.088	-9999	-10000	0	0
TP53	0.047	0.11	-9999	-10000	0	0
RPS6KA5	0.045	0.088	-9999	-10000	0	0
ESR1	0.043	0.092	-9999	-10000	0	0
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.045	0.088	-9999	-10000	0	0
MEF2A	0.045	0.088	-9999	-10000	0	0
EIF4EBP1	0.045	0.094	-9999	-10000	0	0
KRT19	-0.043	0.21	-9999	-0.91	8	8
ELK4	0.045	0.088	-9999	-10000	0	0
ATF6	0.045	0.088	-9999	-10000	0	0
ATF1	0.05	0.092	-9999	-10000	0	0
p38alpha-beta/MAPKAPK2	-0.018	0.07	-9999	-10000	0	0
p38alpha-beta/MAPKAPK3	-0.018	0.07	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.016	-9999	-9999
NPC/RanGAP1/SUMO1	0	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.039	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.016	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.016	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.016	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.016	-9999	-9999
PIAS1	0.016	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0	-9999	-10000	0	0
MAPK9	0.011	0	-9999	-10000	0	0
adrenocorticotropin secretion	-0.003	0.07	-9999	-0.68	5	5
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0	-9999	-10000	0	0
Gs family/GTP	0	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	-0.005	0.088	-9999	-0.86	5	5
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.011	0	-9999	-10000	0	0
MAPK11	0.011	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	-0.001	0.024	-9999	-0.53	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.028	0	-9999	-10000	0	0
AP2	0	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	0	-9999	-10000	0	0
CD4	-0.001	0.12	-9999	-0.86	9	9
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.014	0.027	-9999	-0.58	1	1
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	-0.001	0.022	-9999	-0.48	1	1
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	-0.001	0.022	-9999	-0.47	1	1
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.02	-9999	-0.43	1	1
ARFIP2	0	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	0.035	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	0	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.001	0.011	-9999	-10000	0	0
ARF1/GDP/Membrin	0	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	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	-0.004	0.029	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.014	0.027	-9999	-0.58	1	1
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	0.014	0.027	-9999	-0.58	1	1
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	-0.011	0.078	-9999	-0.58	9	9

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.006	0.061	-9999	-0.67	4	4
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.044	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAP3K14	0.008	0.08	-9999	-0.86	4	4
NF kappa B1 p50/RelB	0	0	-9999	-10000	0	0
RELB	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.EU.5906	TCGA.EU.5905	TCGA.EU.5904	TCGA.DV.5576
109_MAP3K5	0.074	0.074	0.074	0.074
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	-0.76	0	-0.76	0.016
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	0	-0.44	0	0
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.016	0.015
84_STAT5B	-0.032	-0.031	0.025	0.06
84_STAT5A	-0.032	-0.031	0.025	0.06