PARADIGM pathway analysis of mRNASeq expression data - Thyroid Adenocarcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	247
Signaling events mediated by Stem cell factor receptor (c-Kit)	160
Signaling events regulated by Ret tyrosine kinase	149
TCGA08_retinoblastoma	139
Reelin signaling pathway	122
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	112
Wnt signaling	105
PDGFR-alpha signaling pathway	100
Noncanonical Wnt signaling pathway	99
IL4-mediated signaling events	91

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
Ephrin A reverse signaling	0.5082	247	1733	7	-0.52	0	1000	-1000	-0.03	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3292	160	12543	78	-0.8	0.24	1000	-1000	-0.071	-1000
Signaling events regulated by Ret tyrosine kinase	0.3066	149	12243	82	-0.46	0.013	1000	-1000	-0.079	-1000
TCGA08_retinoblastoma	0.2860	139	1118	8	-0.13	0.073	1000	-1000	-0.018	-1000
Reelin signaling pathway	0.2510	122	6841	56	-0.6	0.033	1000	-1000	-0.082	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2305	112	7677	68	-0.9	0.37	1000	-1000	-0.12	-1000
Wnt signaling	0.2160	105	735	7	-0.41	0.013	1000	-1000	-0.019	-1000
PDGFR-alpha signaling pathway	0.2058	100	4416	44	-0.51	0.033	1000	-1000	-0.062	-1000
Noncanonical Wnt signaling pathway	0.2037	99	2594	26	-0.41	0.013	1000	-1000	-0.079	-1000
IL4-mediated signaling events	0.1872	91	8297	91	-1.3	0.66	1000	-1000	-0.13	-1000
FOXA2 and FOXA3 transcription factor networks	0.1852	90	4181	46	-0.92	0.021	1000	-1000	-0.044	-1000
Nongenotropic Androgen signaling	0.1749	85	4452	52	-0.34	0.16	1000	-1000	-0.064	-1000
Signaling events mediated by the Hedgehog family	0.1667	81	4212	52	-0.38	0.2	1000	-1000	-0.082	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1605	78	4250	54	-0.6	0.028	1000	-1000	-0.093	-1000
Calcium signaling in the CD4+ TCR pathway	0.1564	76	2385	31	-0.53	0.013	1000	-1000	-0.082	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1481	72	2475	34	-0.17	0.013	1000	-1000	-0.067	-1000
Glypican 1 network	0.1296	63	3067	48	-0.38	0.028	1000	-1000	-0.042	-1000
Ephrin B reverse signaling	0.1276	62	3018	48	-0.31	0.19	1000	-1000	-0.068	-1000
Endothelins	0.1235	60	5798	96	-0.4	0.013	1000	-1000	-0.083	-1000
IGF1 pathway	0.1173	57	3249	57	-0.2	0.059	1000	-1000	-0.092	-1000
HIF-1-alpha transcription factor network	0.1132	55	4180	76	-0.57	0.042	1000	-1000	-0.099	-1000
Glucocorticoid receptor regulatory network	0.1111	54	6179	114	-0.57	0.37	1000	-1000	-0.07	-1000
TCR signaling in naïve CD8+ T cells	0.1111	54	5080	93	-0.2	0.089	1000	-1000	-0.075	-1000
IL23-mediated signaling events	0.1111	54	3299	60	-0.34	0.021	1000	-1000	-0.15	-1000
BMP receptor signaling	0.1070	52	4263	81	-0.58	0.026	1000	-1000	-0.085	-1000
Glypican 2 network	0.1049	51	207	4	-0.087	-0.01	1000	-1000	-0.022	-1000
Coregulation of Androgen receptor activity	0.0988	48	3664	76	-0.77	0.061	1000	-1000	-0.06	-1000
Arf6 signaling events	0.0967	47	2918	62	-0.32	0.021	1000	-1000	-0.061	-1000
Syndecan-1-mediated signaling events	0.0947	46	1590	34	-0.2	0.013	1000	-1000	-0.057	-1000
EPHB forward signaling	0.0926	45	3836	85	-0.31	0.15	1000	-1000	-0.094	-1000
IL12-mediated signaling events	0.0802	39	3420	87	-0.41	0.023	1000	-1000	-0.12	-1000
Signaling mediated by p38-alpha and p38-beta	0.0802	39	1751	44	-0.23	0.013	1000	-1000	-0.055	-1000
Hedgehog signaling events mediated by Gli proteins	0.0782	38	2522	65	-0.66	0.061	1000	-1000	-0.071	-1000
amb2 Integrin signaling	0.0782	38	3128	82	-0.24	0.013	1000	-1000	-0.081	-1000
IL6-mediated signaling events	0.0761	37	2799	75	-0.21	0.059	1000	-1000	-0.083	-1000
Syndecan-4-mediated signaling events	0.0741	36	2426	67	-0.24	0.013	1000	-1000	-0.088	-1000
Thromboxane A2 receptor signaling	0.0679	33	3506	105	-0.21	0.032	1000	-1000	-0.068	-1000
EGFR-dependent Endothelin signaling events	0.0658	32	679	21	-0.11	0.013	1000	-1000	-0.068	-1000
Osteopontin-mediated events	0.0638	31	1202	38	-0.26	0.013	1000	-1000	-0.092	-1000
FAS signaling pathway (CD95)	0.0617	30	1416	47	-0.26	0.029	1000	-1000	-0.047	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0597	29	2483	85	-0.28	0.013	1000	-1000	-0.08	-1000
Ras signaling in the CD4+ TCR pathway	0.0576	28	479	17	-0.095	0.013	1000	-1000	-0.046	-1000
Plasma membrane estrogen receptor signaling	0.0556	27	2354	86	-0.18	0.02	1000	-1000	-0.077	-1000
Regulation of Androgen receptor activity	0.0556	27	1893	70	-0.48	0.034	1000	-1000	-0.057	-1000
Syndecan-2-mediated signaling events	0.0535	26	1831	69	-0.22	0.038	1000	-1000	-0.059	-1000
Regulation of p38-alpha and p38-beta	0.0535	26	1414	54	-0.47	0.013	1000	-1000	-0.058	-1000
ErbB2/ErbB3 signaling events	0.0514	25	1675	65	-0.13	0.027	1000	-1000	-0.064	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0514	25	1323	52	-0.28	0.054	1000	-1000	-0.064	-1000
Visual signal transduction: Rods	0.0514	25	1340	52	-0.2	0.016	1000	-1000	-0.088	-1000
LPA receptor mediated events	0.0494	24	2527	102	-0.25	0.031	1000	-1000	-0.085	-1000
JNK signaling in the CD4+ TCR pathway	0.0473	23	404	17	-0.1	0.02	1000	-1000	-0.061	-1000
Integrins in angiogenesis	0.0473	23	1979	84	-0.24	0.033	1000	-1000	-0.099	-1000
BCR signaling pathway	0.0473	23	2364	99	-0.19	0.023	1000	-1000	-0.093	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0473	23	2033	88	-0.32	0.028	1000	-1000	-0.12	-1000
Signaling events mediated by PTP1B	0.0432	21	1664	76	-0.25	0.021	1000	-1000	-0.079	-1000
p75(NTR)-mediated signaling	0.0432	21	2701	125	-0.36	0.066	1000	-1000	-0.094	-1000
Effects of Botulinum toxin	0.0432	21	556	26	-0.16	0.019	1000	-1000	-0.059	-1000
IL27-mediated signaling events	0.0432	21	1111	51	-0.17	0.065	1000	-1000	-0.1	-1000
Regulation of nuclear SMAD2/3 signaling	0.0412	20	2767	136	-0.34	0.066	1000	-1000	-0.072	-1000
Aurora C signaling	0.0391	19	138	7	-0.059	0	1000	-1000	-0.042	-1000
Nectin adhesion pathway	0.0391	19	1205	63	-0.26	0.033	1000	-1000	-0.078	-1000
VEGFR1 specific signals	0.0391	19	1111	56	-0.07	0.041	1000	-1000	-0.077	-1000
Visual signal transduction: Cones	0.0370	18	715	38	-0.091	0.013	1000	-1000	-0.057	-1000
IL1-mediated signaling events	0.0370	18	1167	62	-0.12	0.066	1000	-1000	-0.093	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0370	18	2247	120	-0.31	0.042	1000	-1000	-0.076	-1000
FOXM1 transcription factor network	0.0370	18	952	51	-0.19	0.046	1000	-1000	-0.14	-1000
ErbB4 signaling events	0.0350	17	1239	69	-0.14	0.057	1000	-1000	-0.08	-1000
Fc-epsilon receptor I signaling in mast cells	0.0350	17	1741	97	-0.21	0.031	1000	-1000	-0.09	-1000
TCGA08_rtk_signaling	0.0350	17	459	26	-0.25	0.024	1000	-1000	-0.021	-1000
Insulin-mediated glucose transport	0.0329	16	525	32	-0.21	0.042	1000	-1000	-0.062	-1000
Aurora B signaling	0.0329	16	1094	67	-0.38	0.014	1000	-1000	-0.07	-1000
Syndecan-3-mediated signaling events	0.0309	15	550	35	-0.16	0.013	1000	-1000	-0.07	-1000
Rapid glucocorticoid signaling	0.0309	15	318	20	-0.092	0.015	1000	-1000	-0.033	-1000
LPA4-mediated signaling events	0.0288	14	178	12	-0.12	0.016	1000	-1000	-0.023	-1000
IFN-gamma pathway	0.0288	14	1014	68	-0.1	0.042	1000	-1000	-0.092	-1000
IL2 signaling events mediated by STAT5	0.0288	14	328	22	-0.067	0.039	1000	-1000	-0.045	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0288	14	467	33	-0.16	0.035	1000	-1000	-0.061	-1000
Class IB PI3K non-lipid kinase events	0.0288	14	42	3	-0.003	-1000	1000	-1000	-0.016	-1000
Presenilin action in Notch and Wnt signaling	0.0267	13	828	61	-0.21	0.043	1000	-1000	-0.081	-1000
Ceramide signaling pathway	0.0267	13	1012	76	-0.18	0.024	1000	-1000	-0.065	-1000
Signaling events mediated by HDAC Class III	0.0267	13	540	40	-0.35	0.024	1000	-1000	-0.041	-1000
IL2 signaling events mediated by PI3K	0.0267	13	795	58	-0.065	0.031	1000	-1000	-0.079	-1000
Insulin Pathway	0.0267	13	1021	74	-0.081	0.038	1000	-1000	-0.09	-1000
Signaling events mediated by PRL	0.0267	13	471	34	-0.11	0.013	1000	-1000	-0.037	-1000
a4b1 and a4b7 Integrin signaling	0.0226	11	59	5	-0.03	0.004	1000	-1000	-0.042	-1000
Cellular roles of Anthrax toxin	0.0226	11	438	39	-0.091	0.019	1000	-1000	-0.026	-1000
Regulation of Telomerase	0.0226	11	1164	102	-0.28	0.053	1000	-1000	-0.097	-1000
mTOR signaling pathway	0.0206	10	543	53	-0.044	0.021	1000	-1000	-0.057	-1000
Retinoic acid receptors-mediated signaling	0.0206	10	591	58	-0.12	0.033	1000	-1000	-0.073	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0206	10	478	45	-0.091	0.039	1000	-1000	-0.087	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0206	10	809	74	-0.18	0.086	1000	-1000	-0.092	-1000
Class I PI3K signaling events	0.0206	10	797	73	-0.25	0.023	1000	-1000	-0.074	-1000
Caspase cascade in apoptosis	0.0185	9	715	74	-0.091	0.029	1000	-1000	-0.054	-1000
BARD1 signaling events	0.0185	9	568	57	-0.033	0.054	1000	-1000	-0.058	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0185	9	827	83	-0.21	0.052	1000	-1000	-0.08	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0165	8	249	28	-0.18	0.031	1000	-1000	-0.051	-1000
Class I PI3K signaling events mediated by Akt	0.0165	8	556	68	-0.21	0.052	1000	-1000	-0.061	-1000
ceramide signaling pathway	0.0165	8	438	49	-0.091	0.031	1000	-1000	-0.045	-1000
S1P3 pathway	0.0165	8	364	42	-0.18	0.049	1000	-1000	-0.06	-1000
TRAIL signaling pathway	0.0144	7	377	48	-0.078	0.047	1000	-1000	-0.072	-1000
S1P1 pathway	0.0144	7	256	36	-0.037	0.032	1000	-1000	-0.059	-1000
Arf6 downstream pathway	0.0123	6	284	43	-0.18	0.093	1000	-1000	-0.045	-1000
Signaling events mediated by HDAC Class I	0.0123	6	675	104	-0.091	0.059	1000	-1000	-0.072	-1000
FoxO family signaling	0.0123	6	417	64	-0.21	0.16	1000	-1000	-0.071	-1000
Canonical NF-kappaB pathway	0.0103	5	225	39	-0.091	0.071	1000	-1000	-0.087	-1000
Circadian rhythm pathway	0.0103	5	127	22	-0.06	0.013	1000	-1000	-0.062	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0103	5	206	37	-0.031	0.039	1000	-1000	-0.059	-1000
EPO signaling pathway	0.0082	4	224	55	-0.037	0.062	1000	-1000	-0.099	-1000
Atypical NF-kappaB pathway	0.0082	4	149	31	-0.038	0.047	1000	-1000	-0.052	-1000
Canonical Wnt signaling pathway	0.0082	4	223	51	-0.047	0.068	1000	-1000	-0.058	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	4	533	125	-0.034	0.087	1000	-1000	-0.091	-1000
E-cadherin signaling in the nascent adherens junction	0.0082	4	379	76	-0.17	0.074	1000	-1000	-0.085	-1000
PLK1 signaling events	0.0062	3	317	85	-0.043	0.033	1000	-1000	-0.043	-1000
S1P5 pathway	0.0062	3	66	17	-0.017	0.022	1000	-1000	-0.06	-1000
HIF-2-alpha transcription factor network	0.0062	3	138	43	-0.2	0.2	1000	-1000	-0.081	-1000
Signaling mediated by p38-gamma and p38-delta	0.0062	3	48	15	0	0.032	1000	-1000	-0.033	-1000
Paxillin-dependent events mediated by a4b1	0.0062	3	130	36	-0.03	0.024	1000	-1000	-0.07	-1000
PDGFR-beta signaling pathway	0.0062	3	364	97	-0.18	0.064	1000	-1000	-0.087	-1000
S1P4 pathway	0.0062	3	90	25	-0.017	0.032	1000	-1000	-0.058	-1000
p38 MAPK signaling pathway	0.0062	3	144	44	-0.038	0.026	1000	-1000	-0.066	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0041	2	59	23	-0.036	0.049	1000	-1000	-0.076	-1000
Signaling events mediated by HDAC Class II	0.0041	2	180	75	-0.049	0.035	1000	-1000	-0.063	-1000
Aurora A signaling	0.0041	2	166	60	-0.049	0.038	1000	-1000	-0.057	-1000
E-cadherin signaling in keratinocytes	0.0041	2	115	43	-0.004	0.053	1000	-1000	-0.067	-1000
PLK2 and PLK4 events	0.0021	1	5	3	0.01	0.022	1000	-1000	-0.018	-1000
Arf6 trafficking events	0.0021	1	76	71	-0.02	0.046	1000	-1000	-0.077	-1000
TCGA08_p53	0.0000	0	0	7	-0.085	0.054	1000	-1000	-0.011	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.032	1000	-1000	-0.058	-1000
E-cadherin signaling events	0.0000	0	0	5	0	0.013	1000	-1000	-0.04	-1000
Arf1 pathway	0.0000	0	31	54	-0.005	0.036	1000	-1000	-0.041	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	-0.001	0.013	1000	-1000	-0.056	-1000
Total	NA	3998	221006	7203	-30	-990	131000	-131000	-9	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.43	0.31	-9999	-0.61	338	338
EFNA5	-0.12	0.3	-9999	-0.82	74	74
FYN	-0.38	0.3	-9999	-0.56	338	338
neuron projection morphogenesis	-0.43	0.31	-9999	-0.61	338	338
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.43	0.32	-9999	-0.62	338	338
EPHA5	-0.52	0.4	-9999	-0.82	307	307

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.21	0.22	-10000	0	-0.4	282	282
CRKL	-0.22	0.24	-10000	0	-0.42	275	275
HRAS	-0.19	0.21	-10000	0	-0.52	38	38
mol:PIP3	-0.22	0.22	-10000	0	-0.41	275	275
SPRED1	0.013	0	-10000	0	-10000	0	0
SPRED2	0.012	0.038	-10000	0	-0.82	1	1
GAB1	-0.24	0.25	-10000	0	-0.45	275	275
FOXO3	-0.19	0.22	-10000	0	-0.38	275	275
AKT1	-0.22	0.23	-10000	0	-0.42	275	275
BAD	-0.19	0.22	-10000	0	-0.38	275	275
megakaryocyte differentiation	-0.25	0.25	-10000	0	-0.45	283	283
GSK3B	-0.19	0.22	-10000	0	-0.38	275	275
RAF1	-0.15	0.18	-10000	0	-0.46	23	23
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.24	0.25	-10000	0	-0.45	275	275
STAT1	-0.59	0.59	-10000	0	-1.1	276	276
HRAS/SPRED1	-0.17	0.14	-10000	0	-0.45	25	25
cell proliferation	-0.24	0.25	-10000	0	-0.45	278	278
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.24	0.25	-10000	0	-0.45	275	275
HRAS/SPRED2	-0.17	0.15	-10000	0	-0.45	27	27
LYN/TEC/p62DOK	-0.23	0.21	-10000	0	-0.41	275	275
MAPK3	-0.094	0.13	-10000	0	-0.32	21	21
STAP1	-0.26	0.25	-10000	0	-0.47	275	275
GRAP2	-0.042	0.2	-10000	0	-0.78	34	34
JAK2	-0.51	0.45	-10000	0	-0.9	276	276
STAT1 (dimer)	-0.57	0.57	-10000	0	-1.1	276	276
mol:Gleevec	0.008	0.01	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.24	0.21	-10000	0	-0.42	278	278
actin filament polymerization	-0.23	0.24	-10000	0	-0.44	275	275
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.35	0.34	-10000	0	-0.64	275	275
PIK3R1	0.013	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.21	0.19	-10000	0	-0.37	274	274
PI3K	-0.22	0.24	-10000	0	-0.42	276	276
PTEN	0.012	0.038	-10000	0	-0.82	1	1
SCF/KIT/EPO/EPOR	-0.74	0.72	-10000	0	-1.4	275	275
MAPK8	-0.24	0.26	-10000	0	-0.46	278	278
STAT3 (dimer)	-0.23	0.24	-10000	0	-0.44	275	275
positive regulation of transcription	-0.075	0.11	-10000	0	-0.26	15	15
mol:GDP	-0.23	0.19	-10000	0	-0.55	42	42
PIK3C2B	-0.24	0.25	-10000	0	-0.45	275	275
CBL/CRKL	-0.2	0.22	-10000	0	-0.39	275	275
FER	-0.24	0.25	-10000	0	-0.45	276	276
SH2B3	-0.24	0.25	-10000	0	-0.45	275	275
PDPK1	-0.2	0.21	-10000	0	-0.37	276	276
SNAI2	-0.24	0.26	-10000	0	-0.46	276	276
positive regulation of cell proliferation	-0.41	0.42	-10000	0	-0.77	276	276
KITLG	-0.004	0.1	-10000	0	-0.86	7	7
cell motility	-0.41	0.42	-10000	0	-0.77	276	276
PTPN6	0.02	0.018	-10000	0	-10000	0	0
EPOR	-0.14	0.18	-10000	0	-0.67	2	2
STAT5A (dimer)	-0.33	0.35	-10000	0	-0.63	276	276
SOCS1	0.009	0.048	-10000	0	-0.42	5	5
cell migration	0.24	0.25	0.45	278	-10000	0	278
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.005	0.041	-10000	0	-0.33	7	7
VAV1	-0.013	0.1	-10000	0	-0.36	34	34
GRB10	-0.24	0.25	-10000	0	-0.45	275	275
PTPN11	0.02	0.039	-10000	0	-0.81	1	1
SCF/KIT	-0.26	0.26	-10000	0	-0.48	275	275
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.11	0.15	-10000	0	-0.35	21	21
CBL	0.013	0	-10000	0	-10000	0	0
KIT	-0.8	0.75	-10000	0	-1.5	275	275
MAP2K2	-0.11	0.15	-10000	0	-0.35	21	21
SHC/Grb2/SOS1	-0.23	0.21	-10000	0	-0.41	275	275
STAT5A	-0.35	0.36	-10000	0	-0.65	276	276
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.24	0.25	-10000	0	-0.45	276	276
SHC/GRAP2	-0.042	0.16	-10000	0	-0.63	31	31
PTPRO	-0.25	0.25	-10000	0	-0.46	283	283
SH2B2	-0.24	0.25	-10000	0	-0.45	275	275
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.24	0.25	-10000	0	-0.46	278	278
CREBBP	0.018	0.021	-10000	0	-10000	0	0
BCL2	-0.22	0.42	-10000	0	-1.6	35	35

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.09	0.069	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.26	0.2	-9999	-0.51	118	118
JUN	-0.32	0.31	-9999	-0.68	170	170
HRAS	0.012	0.021	-9999	-0.31	2	2
RET51/GFRalpha1/GDNF/GRB10	-0.39	0.32	-9999	-0.61	303	303
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.39	0.32	-9999	-0.61	303	303
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.3	0.25	-9999	-0.51	277	277
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.35	0.29	-9999	-0.55	303	303
GRB7	-0.042	0.12	-9999	-0.31	82	82
RET51/GFRalpha1/GDNF	-0.39	0.32	-9999	-0.61	303	303
MAPKKK cascade	-0.31	0.26	-9999	-0.49	303	303
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.35	0.31	-9999	-0.58	289	289
lamellipodium assembly	-0.24	0.18	-9999	-0.38	278	278
RET51/GFRalpha1/GDNF/SHC	-0.39	0.32	-9999	-0.61	303	303
PIK3CA	0.008	0.066	-9999	-0.82	3	3
RET9/GFRalpha1/GDNF/SHC	-0.29	0.25	-9999	-0.51	277	277
RET9/GFRalpha1/GDNF/Shank3	-0.29	0.25	-9999	-0.51	277	277
MAPK3	-0.32	0.29	-9999	-0.51	303	303
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.12	0.3	-9999	-0.82	76	76
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.31	0.29	-9999	-0.67	129	129
DOK5	-0.1	0.29	-9999	-0.82	66	66
GFRA1	-0.46	0.41	-9999	-0.82	278	278
MAPK8	-0.24	0.23	-9999	-0.59	91	91
HRAS/GTP	-0.36	0.3	-9999	-0.57	303	303
tube development	-0.27	0.24	-9999	-0.48	277	277
MAPK1	-0.32	0.29	-9999	-0.51	303	303
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.18	0.18	-9999	-0.34	277	277
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
PDLIM7	0.01	0.033	-9999	-0.31	5	5
RET51/GFRalpha1/GDNF/Dok6	-0.44	0.38	-9999	-0.67	314	314
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.39	0.32	-9999	-0.61	303	303
RET51/GFRalpha1/GDNF/Dok5	-0.46	0.39	-9999	-0.69	315	315
PRKCA	-0.028	0.18	-9999	-0.82	24	24
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
CREB1	-0.24	0.24	-9999	-0.43	277	277
PIK3R1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.18	0.18	-9999	-0.34	277	277
RET51/GFRalpha1/GDNF/Grb7	-0.42	0.33	-9999	-0.64	303	303
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.17	0.32	-9999	-0.64	136	136
DOK4	0.013	0.015	-9999	-0.31	1	1
JNK cascade	-0.31	0.3	-9999	-0.65	177	177
RET9/GFRalpha1/GDNF/FRS2	-0.29	0.25	-9999	-0.51	277	277
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.18	0.18	-9999	-0.34	277	277
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.25	0.24	-9999	-0.41	303	303
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.25	0.24	-9999	-0.41	303	303
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.29	0.31	-9999	-0.47	303	303
PI3K	-0.37	0.34	-9999	-0.62	278	278
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.27	0.24	-9999	-0.48	277	277
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.22	0.21	-9999	-0.38	277	277
RET51/GFRalpha1/GDNF/FRS2	-0.39	0.32	-9999	-0.61	303	303
GAB1	0.013	0	-9999	-10000	0	0
IRS1	-0.081	0.26	-9999	-0.82	55	55
IRS2	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.29	0.31	-9999	-0.47	303	303
RET51/GFRalpha1/GDNF/PKC alpha	-0.41	0.36	-9999	-0.64	305	305
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.002	0.041	-9999	-0.31	8	8
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.44	0.37	-9999	-0.67	314	314
Rac1/GTP	-0.29	0.23	-9999	-0.46	278	278
RET9/GFRalpha1/GDNF	-0.32	0.28	-9999	-0.56	277	277
GFRalpha1/GDNF	-0.37	0.32	-9999	-0.64	277	277

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.12	0.16	-10000	0	-0.32	202	202
CDKN2C	0.027	0.036	-10000	0	-0.32	2	2
CDKN2A	-0.13	0.16	-10000	0	-0.32	206	206
CCND2	0.07	0.073	0.17	141	-10000	0	141
RB1	-0.069	0.072	-10000	0	-0.17	141	141
CDK4	0.07	0.072	0.17	142	-10000	0	142
CDK6	0.073	0.077	0.18	141	-0.18	2	143
G1/S progression	0.061	0.08	0.17	141	-10000	0	141

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.001	0.013	-9999	-10000	0	0
VLDLR	-0.023	0.17	-9999	-0.82	21	21
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
ITGA3	0.01	0.033	-9999	-0.31	5	5
RELN/VLDLR/Fyn	-0.42	0.26	-9999	-0.57	361	361
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.009	0.062	-9999	-0.46	9	9
AKT1	-0.24	0.18	-9999	-0.33	362	362
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
RELN/LRP8/DAB1	-0.39	0.25	-9999	-0.53	360	360
LRPAP1/LRP8	-0.027	0.13	-9999	-0.63	21	21
RELN/LRP8/DAB1/Fyn	-0.37	0.24	-9999	-0.5	360	360
DAB1/alpha3/beta1 Integrin	-0.35	0.23	-9999	-0.84	36	36
long-term memory	-0.37	0.25	-9999	-0.49	362	362
DAB1/LIS1	-0.36	0.24	-9999	-0.48	365	365
DAB1/CRLK/C3G	-0.35	0.23	-9999	-0.88	32	32
PIK3CA	0.008	0.066	-9999	-0.82	3	3
DAB1/NCK2	-0.36	0.24	-9999	-0.48	365	365
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.023	0.16	-9999	-0.64	27	27
CDK5R1	0.012	0.021	-9999	-0.31	2	2
RELN	-0.6	0.37	-9999	-0.82	356	356
PIK3R1	0.013	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.42	0.26	-9999	-0.57	360	360
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.38	0.26	-9999	-0.51	362	362
MAPK8	-0.002	0.11	-9999	-0.82	9	9
RELN/VLDLR/DAB1	-0.39	0.25	-9999	-0.53	361	361
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.37	0.26	-9999	-0.5	365	365
RELN/LRP8	-0.42	0.26	-9999	-0.57	360	360
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.37	0.23	-9999	-0.5	360	360
PI3K	-0.004	0.049	-9999	-0.63	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.02	-9999	-10000	0	0
RAP1A	-0.31	0.23	-9999	-0.82	30	30
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.013	0	-9999	-10000	0	0
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.003	0.016	-9999	-0.31	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.16	0.14	-9999	-0.53	22	22
neuron adhesion	-0.28	0.23	-9999	-0.74	34	34
LRP8	-0.023	0.17	-9999	-0.82	21	21
GSK3B	-0.22	0.17	-9999	-0.62	18	18
RELN/VLDLR/DAB1/Fyn	-0.37	0.23	-9999	-0.5	361	361
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.26	0.18	-9999	-0.36	362	362
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.033	0.089	-9999	-0.33	20	20
neuron migration	-0.3	0.22	-9999	-0.42	357	357
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.16	0.14	-9999	-0.53	22	22
RELN/VLDLR	-0.4	0.27	-9999	-0.54	365	365

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.043	0.16	-10000	0	-0.54	33	33
NFATC2	-0.24	0.38	-10000	0	-0.81	124	124
NFATC3	-0.083	0.13	-10000	0	-10000	0	0
CD40LG	-0.74	0.57	-10000	0	-1.2	260	260
ITCH	0.051	0.015	-10000	0	-10000	0	0
CBLB	0.051	0.015	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.53	0.52	-10000	0	-1.2	142	142
JUNB	0.003	0.092	-10000	0	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.001	0.015	-10000	0	-0.34	1	1
T cell anergy	0.025	0.065	-10000	0	-0.49	1	1
TLE4	-0.25	0.44	-10000	0	-0.91	128	128
Jun/NFAT1-c-4/p21SNFT	-0.66	0.61	-10000	0	-1.2	237	237
AP-1/NFAT1-c-4	-0.9	0.79	-10000	0	-1.6	251	251
IKZF1	-0.18	0.34	-10000	0	-0.72	107	107
T-helper 2 cell differentiation	-0.32	0.35	-10000	0	-0.82	125	125
AP-1/NFAT1	-0.42	0.49	-10000	0	-0.9	214	214
CALM1	0.029	0.009	-10000	0	-10000	0	0
EGR2	-0.8	0.86	-10000	0	-1.7	223	223
EGR3	-0.58	0.75	-10000	0	-1.7	127	127
NFAT1/FOXP3	-0.22	0.33	-10000	0	-0.71	122	122
EGR1	-0.16	0.34	-10000	0	-0.82	103	103
JUN	-0.19	0.35	-10000	0	-0.83	109	109
EGR4	-0.035	0.18	-10000	0	-0.71	30	30
mol:Ca2+	0.016	0.01	-10000	0	-10000	0	0
GBP3	-0.17	0.32	-10000	0	-0.69	103	103
FOSL1	-0.028	0.12	-10000	0	-0.33	59	59
NFAT1-c-4/MAF/IRF4	-0.57	0.56	-10000	0	-1.1	224	224
DGKA	-0.16	0.3	-10000	0	-0.71	80	80
CREM	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.56	0.56	-10000	0	-1.1	236	236
CTLA4	-0.24	0.38	-10000	0	-0.82	111	111
NFAT1-c-4 (dimer)/EGR1	-0.64	0.67	-10000	0	-1.3	234	234
NFAT1-c-4 (dimer)/EGR4	-0.58	0.57	-10000	0	-1.1	238	238
FOS	-0.22	0.37	-10000	0	-0.83	129	129
IFNG	-0.43	0.54	-10000	0	-1.1	159	159
T cell activation	-0.44	0.43	-10000	0	-0.98	155	155
MAF	0.013	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	0.37	0.42	0.82	177	-10000	0	177
TNF	-0.6	0.58	-10000	0	-1.1	236	236
FASLG	-0.75	0.79	-10000	0	-1.5	242	242
TBX21	-0.038	0.18	-10000	0	-0.72	30	30
BATF3	-0.006	0.082	-10000	0	-0.33	27	27
PRKCQ	0.004	0.085	-10000	0	-0.82	5	5
PTPN1	-0.16	0.3	-10000	0	-0.68	91	91
NFAT1-c-4/ICER1	-0.55	0.56	-10000	0	-1.1	234	234
GATA3	-0.03	0.19	-10000	0	-0.78	27	27
T-helper 1 cell differentiation	-0.41	0.52	-10000	0	-1	160	160
IL2RA	-0.48	0.46	-10000	0	-1	152	152
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.3	-10000	0	-0.72	75	75
E2F1	-0.081	0.15	-10000	0	-0.3	152	152
PPARG	-0.003	0.11	-10000	0	-0.59	13	13
SLC3A2	-0.16	0.3	-10000	0	-0.75	67	67
IRF4	-0.1	0.23	-10000	0	-0.45	120	120
PTGS2	-0.71	0.57	-10000	0	-1.2	253	253
CSF2	-0.78	0.54	-10000	0	-1.2	265	265
JunB/Fra1/NFAT1-c-4	-0.54	0.54	-10000	0	-1.1	210	210
IL4	-0.33	0.37	-10000	0	-0.88	122	122
IL5	-0.69	0.54	-10000	0	-1.2	248	248
IL2	-0.45	0.44	-10000	0	-1	154	154
IL3	-0.097	0.062	-10000	0	-10000	0	0
RNF128	0.049	0.042	-10000	0	-0.88	1	1
NFATC1	-0.37	0.43	-10000	0	-0.82	177	177
CDK4	0.22	0.24	0.69	18	-10000	0	18
PTPRK	-0.16	0.3	-10000	0	-0.66	99	99
IL8	-0.72	0.55	-10000	0	-1.2	250	250
POU2F1	0.013	0.015	-10000	0	-0.31	1	1

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.47	302	302
FZD6	0.013	0	-9999	-10000	0	0
WNT6	0.005	0.049	-9999	-0.31	11	11
WNT4	-0.26	0.39	-9999	-0.81	162	162
FZD3	0.013	0	-9999	-10000	0	0
WNT5A	-0.005	0.12	-9999	-0.78	11	11
WNT11	-0.41	0.42	-9999	-0.82	249	249

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.26	0.39	-9999	-0.84	154	154
PDGF/PDGFRA/CRKL	-0.2	0.29	-9999	-0.63	154	154
positive regulation of JUN kinase activity	-0.15	0.22	-9999	-0.48	154	154
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.21	0.3	-9999	-0.64	154	154
AP1	-0.51	0.63	-9999	-1.5	136	136
mol:IP3	-0.2	0.31	-9999	-0.65	154	154
PLCG1	-0.2	0.31	-9999	-0.65	154	154
PDGF/PDGFRA/alphaV Integrin	-0.2	0.3	-9999	-0.63	155	155
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.2	0.31	-9999	-0.65	154	154
CAV3	-0.001	0.029	-9999	-0.31	4	4
CAV1	-0.009	0.14	-9999	-0.82	13	13
SHC/Grb2/SOS1	-0.15	0.23	-9999	-0.49	154	154
PDGF/PDGFRA/Shf	-0.2	0.29	-9999	-0.63	154	154
FOS	-0.46	0.61	-9999	-1.4	136	136
JUN	-0.17	0.29	-9999	-0.7	109	109
oligodendrocyte development	-0.2	0.3	-9999	-0.63	155	155
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
mol:DAG	-0.2	0.31	-9999	-0.65	154	154
PDGF/PDGFRA	-0.26	0.39	-9999	-0.84	154	154
actin cytoskeleton reorganization	-0.2	0.29	-9999	-0.63	154	154
SRF	0.033	0.012	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	-0.17	0.25	-9999	-0.54	157	157
PDGF/PDGFRA/Crk/C3G	-0.17	0.25	-9999	-0.54	154	154
JAK1	-0.19	0.3	-9999	-0.63	154	154
ELK1/SRF	-0.13	0.24	-9999	-0.49	154	154
SHB	0.013	0	-9999	-10000	0	0
SHF	0.013	0.015	-9999	-0.31	1	1
CSNK2A1	0.028	0.027	-9999	-10000	0	0
GO:0007205	-0.2	0.32	-9999	-0.66	154	154
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	-0.15	0.22	-9999	-0.48	154	154
PDGF/PDGFRA/SHB	-0.2	0.29	-9999	-0.63	154	154
PDGF/PDGFRA/Caveolin-1	-0.21	0.32	-9999	-0.66	157	157
ITGAV	0.01	0.054	-9999	-0.82	2	2
ELK1	-0.18	0.28	-9999	-0.6	154	154
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PDGF/PDGFRA/Crk	-0.2	0.29	-9999	-0.63	154	154
JAK-STAT cascade	-0.19	0.3	-9999	-0.63	154	154
cell proliferation	-0.2	0.29	-9999	-0.63	154	154

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.13	0.32	-9999	-0.82	83	83
GNB1/GNG2	-0.26	0.24	-9999	-0.6	124	124
mol:DAG	-0.21	0.24	-9999	-0.55	118	118
PLCG1	-0.22	0.25	-9999	-0.57	118	118
YES1	-0.25	0.27	-9999	-0.43	302	302
FZD3	0.013	0	-9999	-10000	0	0
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.24	0.22	-9999	-0.58	118	118
MAP3K7	-0.17	0.2	-9999	-0.45	116	116
mol:Ca2+	-0.2	0.23	-9999	-0.53	118	118
mol:IP3	-0.21	0.24	-9999	-0.55	118	118
NLK	-0.01	0.01	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.19	0.22	-9999	-0.48	129	129
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.28	0.28	-9999	-0.47	302	302
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.25	0.27	-9999	-0.62	125	125
GO:0007205	-0.21	0.23	-9999	-0.54	116	116
WNT6	0.005	0.049	-9999	-0.31	11	11
WNT4	-0.26	0.39	-9999	-0.81	162	162
NFAT1/CK1 alpha	-0.3	0.25	-9999	-0.62	150	150
GNG2	0.012	0.038	-9999	-0.82	1	1
WNT5A	-0.005	0.12	-9999	-0.78	11	11
WNT11	-0.41	0.42	-9999	-0.82	249	249
CDC42	-0.23	0.25	-9999	-0.59	123	123

×

IL4-mediated signaling events

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
BCL2L1	-0.59	0.44	-10000	0	-1.2	129	129
STAT6 (cleaved dimer)	-0.64	0.44	-10000	0	-1	251	251
IGHG1	-0.2	0.14	-10000	0	-0.36	22	22
IGHG3	-0.58	0.42	-10000	0	-0.96	221	221
AKT1	-0.32	0.26	-10000	0	-0.72	76	76
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.26	0.26	-10000	0	-0.75	55	55
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.35	0.28	-10000	0	-0.75	100	100
THY1	-0.59	0.44	-10000	0	-1.1	159	159
MYB	-0.008	0.12	-10000	0	-0.63	16	16
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.41	0.31	-10000	0	-0.74	167	167
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.32	0.26	-10000	0	-0.74	67	67
SP1	0.02	0.006	-10000	0	-10000	0	0
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
SOCS5	0.03	0.013	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.62	0.44	-10000	0	-1	231	231
SOCS1	-0.4	0.29	-10000	0	-0.74	118	118
SOCS3	-0.38	0.36	-10000	0	-1	69	69
FCER2	-0.58	0.42	-10000	0	-1	179	179
PARP14	0.013	0.004	-10000	0	-10000	0	0
CCL17	-0.66	0.48	-10000	0	-1.1	199	199
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.26	0.21	-10000	0	-0.66	49	49
T cell proliferation	-0.6	0.46	-10000	0	-1.1	183	183
IL4R/JAK1	-0.59	0.44	-10000	0	-1.1	163	163
EGR2	-0.93	0.73	-10000	0	-1.6	238	238
JAK2	-0.017	0.045	-10000	0	-0.86	1	1
JAK3	-0.065	0.14	-10000	0	-0.31	120	120
PIK3R1	0.013	0	-10000	0	-10000	0	0
JAK1	0.002	0.008	-10000	0	-10000	0	0
COL1A2	-0.19	0.15	-10000	0	-0.54	33	33
CCL26	-0.61	0.45	-10000	0	-1.1	169	169
IL4R	-0.63	0.47	-10000	0	-1.1	168	168
PTPN6	0.028	0.009	-10000	0	-10000	0	0
IL13RA2	-0.7	0.57	-10000	0	-1.3	174	174
IL13RA1	-0.016	0.024	-10000	0	-10000	0	0
IRF4	-0.34	0.48	-10000	0	-1.2	92	92
ARG1	-0.14	0.11	-10000	0	-10000	0	0
CBL	-0.38	0.3	-10000	0	-0.73	136	136
GTF3A	0.016	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
IL13RA1/JAK2	-0.024	0.045	-10000	0	-0.68	1	1
IRF4/BCL6	-0.31	0.44	-10000	0	-1.1	88	88
CD40LG	-0.12	0.3	-10000	0	-0.8	78	78
MAPK14	-0.39	0.32	-10000	0	-0.78	130	130
mitosis	-0.3	0.24	-10000	0	-0.67	76	76
STAT6	-0.67	0.51	-10000	0	-1.1	214	214
SPI1	0.002	0.071	-10000	0	-0.31	24	24
RPS6KB1	-0.29	0.24	-10000	0	-0.68	60	60
STAT6 (dimer)	-0.67	0.51	-10000	0	-1.1	214	214
STAT6 (dimer)/PARP14	-0.63	0.47	-10000	0	-1.1	197	197
mast cell activation	0.016	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.32	0.28	-10000	0	-0.73	82	82
FRAP1	-0.32	0.26	-10000	0	-0.72	76	76
LTA	-0.61	0.46	-10000	0	-1.1	169	169
FES	0.013	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.66	0.5	1.1	215	-10000	0	215
CCL11	-0.58	0.43	-10000	0	-1.1	161	161
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.32	0.27	-10000	0	-0.7	90	90
IL2RG	-0.043	0.19	-10000	0	-0.55	52	52
IL10	-0.61	0.47	-10000	0	-1.1	170	170
IRS1	-0.081	0.26	-10000	0	-0.82	55	55
IRS2	0.013	0	-10000	0	-10000	0	0
IL4	-0.14	0.096	-10000	0	-10000	0	0
IL5	-0.6	0.44	-10000	0	-1.1	161	161
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.48	0.33	-10000	0	-0.84	163	163
COL1A1	-0.26	0.24	-10000	0	-0.82	20	20
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.59	0.45	-10000	0	-1.2	128	128
IL2R gamma/JAK3	-0.08	0.18	-10000	0	-0.52	52	52
TFF3	-1.3	0.61	-10000	0	-1.6	393	393
ALOX15	-0.6	0.44	-10000	0	-1.1	159	159
MYBL1	0.013	0.015	-10000	0	-0.31	1	1
T-helper 2 cell differentiation	-0.51	0.36	-10000	0	-0.86	194	194
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.018	0.004	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.3	0.26	-10000	0	-0.71	66	66
mol:PI-3-4-5-P3	-0.32	0.26	-10000	0	-0.72	76	76
PI3K	-0.33	0.28	-10000	0	-0.77	76	76
DOK2	0	0.076	-10000	0	-0.38	16	16
ETS1	0.03	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.24	0.21	-10000	0	-0.65	48	48
ITGB3	-0.61	0.47	-10000	0	-1.2	156	156
PIGR	-0.64	0.5	-10000	0	-1.2	169	169
IGHE	0.051	0.035	-10000	0	-10000	0	0
MAPKKK cascade	-0.24	0.2	-10000	0	-0.64	48	48
BCL6	0.012	0.038	-10000	0	-0.82	1	1
OPRM1	-0.6	0.44	-10000	0	-1.1	155	155
RETNLB	-0.6	0.44	-10000	0	-1.1	159	159
SELP	-0.6	0.46	-10000	0	-1.1	151	151
AICDA	-0.58	0.42	-10000	0	-1.1	141	141

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.51	0.55	-9999	-1.1	203	203
PCK1	-0.34	0.5	-9999	-1.4	72	72
HNF4A	-0.67	0.66	-9999	-1.3	240	240
KCNJ11	-0.48	0.55	-9999	-1.1	189	189
AKT1	-0.04	0.12	-9999	-0.38	13	13
response to starvation	-0.018	0.034	-9999	-10000	0	0
DLK1	-0.49	0.54	-9999	-1.1	185	185
NKX2-1	-0.16	0.21	-9999	-10000	0	0
ACADM	-0.51	0.55	-9999	-1.1	205	205
TAT	-0.2	0.22	-9999	-0.63	20	20
CEBPB	0.013	0.005	-9999	-10000	0	0
CEBPA	0.005	0.085	-9999	-0.82	5	5
TTR	-0.19	0.22	-9999	-0.76	31	31
PKLR	-0.52	0.55	-9999	-1.1	186	186
APOA1	-0.92	0.89	-9999	-1.7	245	245
CPT1C	-0.53	0.55	-9999	-1.1	216	216
ALAS1	-0.16	0.21	-9999	-10000	0	0
TFRC	-0.26	0.3	-9999	-0.76	36	36
FOXF1	-0.011	0.093	-9999	-0.76	7	7
NF1	0.021	0.001	-9999	-10000	0	0
HNF1A (dimer)	0.015	0.007	-9999	-10000	0	0
CPT1A	-0.51	0.55	-9999	-1.1	190	190
HMGCS1	-0.51	0.55	-9999	-1.1	211	211
NR3C1	0.019	0.016	-9999	-10000	0	0
CPT1B	-0.51	0.55	-9999	-1.1	186	186
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.005	-9999	-10000	0	0
GCK	-0.66	0.7	-9999	-1.3	226	226
CREB1	0	0.053	-9999	-10000	0	0
IGFBP1	-0.18	0.2	-9999	-0.55	11	11
PDX1	-0.18	0.21	-9999	-0.61	1	1
UCP2	-0.51	0.55	-9999	-1.1	187	187
ALDOB	-0.48	0.54	-9999	-1.1	188	188
AFP	-0.048	0.11	-9999	-0.51	6	6
BDH1	-0.51	0.55	-9999	-1.1	192	192
HADH	-0.48	0.54	-9999	-1.1	184	184
F2	-0.63	0.64	-9999	-1.3	203	203
HNF1A	0.015	0.007	-9999	-10000	0	0
G6PC	-0.006	0.09	-9999	-10000	0	0
SLC2A2	-0.23	0.26	-9999	-0.65	3	3
INS	-0.008	0.018	-9999	-10000	0	0
FOXA1	-0.06	0.15	-9999	-0.54	13	13
FOXA3	-0.075	0.17	-9999	-0.49	35	35
FOXA2	-0.55	0.61	-9999	-1.2	204	204
ABCC8	-0.78	0.76	-9999	-1.4	258	258
ALB	-0.1	0.32	-9999	-1.3	30	30

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.21	0.25	-10000	0	-0.51	205	205
regulation of S phase of mitotic cell cycle	-0.13	0.18	-10000	0	-0.34	206	206
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
HRAS	0.011	0.021	-10000	0	-0.32	2	2
SHBG/T-DHT	-0.008	0.072	-10000	0	-0.56	8	8
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.012	0.001	-10000	0	-10000	0	0
MAP2K1	-0.17	0.24	-10000	0	-0.44	204	204
T-DHT/AR	-0.27	0.32	-10000	0	-0.64	204	204
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.005	128	128
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
mol:GDP	-0.26	0.31	-10000	0	-0.62	204	204
cell proliferation	-0.2	0.28	-10000	0	-0.65	88	88
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
FOS	-0.25	0.4	-10000	0	-0.89	129	129
mol:Ca2+	-0.027	0.031	-10000	0	-0.071	93	93
MAPK3	-0.18	0.26	-10000	0	-0.46	205	205
MAPK1	-0.084	0.13	-10000	0	-0.31	78	78
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	129	129
cAMP biosynthetic process	0.016	0.076	-10000	0	-0.53	8	8
GNG2	0.012	0.038	-10000	0	-0.82	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	129	129
HRAS/GTP	-0.2	0.23	-10000	0	-0.47	204	204
actin cytoskeleton reorganization	-0.003	0.035	-10000	0	-0.44	3	3
SRC	0.012	0.015	-10000	0	-0.32	1	1
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	129	129
PI3K	-0.003	0.043	-10000	0	-0.55	3	3
apoptosis	0.16	0.25	0.53	129	-10000	0	129
T-DHT/AR/PELP1	-0.23	0.28	-10000	0	-0.56	204	204
HRAS/GDP	-0.25	0.29	-10000	0	-0.59	205	205
CREB1	-0.18	0.28	-10000	0	-0.57	129	129
RAC1-CDC42/GTP	-0.003	0.035	-10000	0	-0.45	3	3
AR	-0.34	0.41	-10000	0	-0.83	204	204
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.18	0.24	-10000	0	-0.46	204	204
RAC1-CDC42/GDP	-0.24	0.28	-10000	0	-0.56	204	204
T-DHT/AR/PELP1/Src	-0.22	0.25	-10000	0	-0.51	204	204
MAP2K2	-0.17	0.24	-10000	0	-0.44	204	204
T-DHT/AR/PELP1/Src/PI3K	-0.13	0.19	-10000	0	-0.34	206	206
GNAZ	0.013	0	-10000	0	-10000	0	0
SHBG	0	0.11	-10000	0	-0.82	8	8
Gi family/GNB1/GNG2/GDP	-0.02	0.12	-10000	0	-0.55	16	16
mol:T-DHT	0	0.001	0.002	77	-0.003	50	127
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.009	0.043	-10000	0	-0.5	3	3
Gi family/GTP	-0.095	0.12	-10000	0	-0.48	17	17
CDC42	0.013	0	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.11	0.26	-10000	0	-0.69	36	36
IHH	-0.21	0.37	-10000	0	-0.84	122	122
SHH Np/Cholesterol/GAS1	-0.11	0.21	-10000	0	-0.52	98	98
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.11	0.21	0.51	98	-10000	0	98
SMO/beta Arrestin2	-0.098	0.24	-10000	0	-0.49	125	125
SMO	-0.11	0.26	-10000	0	-0.52	126	126
AKT1	-0.028	0.12	-10000	0	-0.66	2	2
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	-0.002	0.11	-10000	0	-0.82	9	9
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.11	0.25	-10000	0	-0.51	126	126
STIL	-0.08	0.2	-10000	0	-0.61	18	18
DHH N/PTCH2	-0.11	0.24	-10000	0	-0.64	81	81
DHH N/PTCH1	-0.1	0.23	-10000	0	-0.46	129	129
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
DHH	0.006	0.076	-10000	0	-0.82	4	4
PTHLH	-0.16	0.37	-10000	0	-1.2	36	36
determination of left/right symmetry	-0.11	0.25	-10000	0	-0.51	126	126
PIK3R1	0.013	0	-10000	0	-10000	0	0
skeletal system development	-0.16	0.37	-10000	0	-1.2	36	36
IHH N/Hhip	-0.38	0.4	-10000	0	-0.74	256	256
DHH N/Hhip	-0.25	0.31	-10000	0	-0.64	188	188
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.11	0.25	-10000	0	-0.51	126	126
pancreas development	-0.31	0.4	-10000	0	-0.82	188	188
HHAT	0.012	0.038	-10000	0	-0.82	1	1
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.15	0.33	-10000	0	-0.82	97	97
somite specification	-0.11	0.25	-10000	0	-0.51	126	126
SHH Np/Cholesterol/PTCH1	-0.09	0.21	-10000	0	-0.62	18	18
SHH Np/Cholesterol/PTCH2	-0.089	0.19	-10000	0	-0.52	80	80
SHH Np/Cholesterol/Megalin	-0.14	0.23	-10000	0	-0.52	128	128
SHH	0.007	0.05	-10000	0	-0.63	1	1
catabolic process	-0.12	0.25	-10000	0	-0.51	125	125
SMO/Vitamin D3	-0.094	0.22	-10000	0	-0.66	18	18
SHH Np/Cholesterol/Hhip	-0.2	0.25	-10000	0	-0.51	187	187
LRP2	-0.2	0.37	-10000	0	-0.82	127	127
receptor-mediated endocytosis	-0.2	0.24	-10000	0	-0.72	48	48
SHH Np/Cholesterol/BOC	-0.015	0.078	-10000	0	-0.52	10	10
SHH Np/Cholesterol/CDO	-0.15	0.23	-10000	0	-0.52	141	141
mesenchymal cell differentiation	0.2	0.24	0.51	187	-10000	0	187
mol:Vitamin D3	-0.09	0.21	-10000	0	-0.63	18	18
IHH N/PTCH2	-0.23	0.35	-10000	0	-0.67	179	179
CDON	-0.23	0.38	-10000	0	-0.82	140	140
IHH N/PTCH1	-0.12	0.25	-10000	0	-0.52	125	125
Megalin/LRPAP1	-0.16	0.28	-10000	0	-0.63	127	127
PTCH2	-0.12	0.31	-10000	0	-0.82	79	79
SHH Np/Cholesterol	-0.006	0.036	-10000	0	-0.51	1	1
PTCH1	-0.12	0.25	-10000	0	-0.52	125	125
HHIP	-0.31	0.4	-10000	0	-0.82	188	188

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	-0.023	0.17	-9999	-0.82	21	21
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.42	0.26	-9999	-0.57	360	360
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.013	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.37	0.26	-9999	-0.52	360	360
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	0.006	0.016	-9999	-0.31	1	1
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.1	0.29	-9999	-0.82	66	66
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.027	0.13	-9999	-0.63	21	21
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	0.012	0.021	-9999	-0.31	2	2
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	0.004	0.021	-9999	-0.31	2	2
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.42	0.26	-9999	-0.57	361	361
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.28	0.21	-9999	-0.73	17	17
MAP1B	0	0.005	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.32	0.23	-9999	-0.45	360	360
RELN	-0.6	0.37	-9999	-0.82	356	356
PAFAH/LIS1	-0.05	0.2	-9999	-0.55	66	66
LIS1/CLIP170	0.028	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.22	0.14	-9999	-0.55	17	17
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.25	0.19	-9999	-0.34	366	366
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.3	0.22	-9999	-0.42	360	360
LIS1/IQGAP1	0.028	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.024	0	-9999	-10000	0	0
PAFAH1B3	0.011	0.03	-9999	-0.31	4	4
PAFAH1B2	-0.002	0.11	-9999	-0.82	9	9
MAP1B/LIS1/Dynein heavy chain	0.027	0.003	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.28	0.17	-9999	-0.69	17	17
LRP8	-0.023	0.17	-9999	-0.82	21	21
NDEL1/Katanin 60	-0.28	0.21	-9999	-0.73	17	17
P39/CDK5	-0.32	0.23	-9999	-0.45	360	360
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.028	0	-9999	-10000	0	0
CDK5	-0.34	0.24	-9999	-0.48	360	360
PPP2R5D	0.013	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.36	0.23	-9999	-0.49	361	361
RELN/VLDLR	-0.4	0.27	-9999	-0.54	365	365
CDC42	0	0	-9999	-10000	0	0

×

Calcium 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
NFATC1	-0.011	0.081	-9999	-0.56	9	9
NFATC2	-0.1	0.22	-9999	-0.58	83	83
NFATC3	0	0.027	-9999	-10000	0	0
CD40LG	-0.44	0.41	-9999	-0.87	197	197
PTGS2	-0.42	0.4	-9999	-0.85	185	185
JUNB	0.003	0.092	-9999	-0.82	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.015	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.015	-9999	-10000	0	0
CALM1	0.008	0.008	-9999	-10000	0	0
JUN	-0.18	0.35	-9999	-0.83	109	109
mol:Ca2+	-0.01	0.012	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.004	-9999	-10000	0	0
FOSL1	-0.028	0.12	-9999	-0.33	59	59
CREM	0.013	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.26	0.28	-9999	-0.59	168	168
FOS	-0.22	0.37	-9999	-0.83	129	129
IFNG	-0.44	0.4	-9999	-0.85	203	203
AP-1/NFAT1-c-4	-0.53	0.51	-9999	-0.98	222	222
FASLG	-0.42	0.39	-9999	-0.83	189	189
NFAT1-c-4/ICER1	-0.11	0.2	-9999	-0.5	90	90
IL2RA	-0.41	0.38	-9999	-0.83	182	182
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.48	0.36	-9999	-0.77	254	254
JunB/Fra1/NFAT1-c-4	-0.13	0.2	-9999	-0.51	92	92
IL4	-0.4	0.36	-9999	-0.8	180	180
IL2	-0.012	0.026	-9999	-10000	0	0
IL3	-0.032	0.03	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.006	0.082	-9999	-0.33	27	27
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.013	0.015	-9999	-0.31	1	1

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.17	0.3	0.69	117	-10000	0	117
KIRREL	-0.068	0.24	-10000	0	-0.85	40	40
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.17	0.3	-10000	0	-0.69	117	117
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.13	0.24	-10000	0	-0.54	117	117
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.076	0.2	-10000	0	-0.41	117	117
FYN	-0.11	0.24	-10000	0	-0.51	117	117
mol:Ca2+	-0.13	0.24	-10000	0	-0.53	117	117
mol:DAG	-0.13	0.24	-10000	0	-0.54	117	117
NPHS2	-0.017	0.053	-10000	0	-0.9	1	1
mol:IP3	-0.13	0.24	-10000	0	-0.54	117	117
regulation of endocytosis	-0.12	0.21	-10000	0	-0.48	117	117
Nephrin/NEPH1/podocin/Cholesterol	-0.13	0.24	-10000	0	-0.55	117	117
establishment of cell polarity	-0.17	0.3	-10000	0	-0.69	117	117
Nephrin/NEPH1/podocin/NCK1-2	-0.12	0.22	-10000	0	-0.49	117	117
Nephrin/NEPH1/beta Arrestin2	-0.11	0.22	-10000	0	-0.48	117	117
NPHS1	-0.16	0.32	-10000	0	-0.83	90	90
Nephrin/NEPH1/podocin	-0.12	0.23	-10000	0	-0.51	117	117
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.13	0.24	-10000	0	-0.54	117	117
CD2AP	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.13	0.24	-10000	0	-0.54	117	117
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.11	0.24	-10000	0	-0.51	121	121
cytoskeleton organization	-0.1	0.26	-10000	0	-0.54	117	117
Nephrin/NEPH1	-0.13	0.24	-10000	0	-0.53	117	117
Nephrin/NEPH1/ZO-1	-0.14	0.26	-10000	0	-0.57	117	117

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	-0.001	0.026	-10000	0	-0.55	1	1
fibroblast growth factor receptor signaling pathway	-0.001	0.026	-10000	0	-0.54	1	1
LAMA1	-0.049	0.22	-10000	0	-0.81	37	37
PRNP	0.012	0.038	-10000	0	-0.82	1	1
GPC1/SLIT2	-0.097	0.23	-10000	0	-0.63	73	73
SMAD2	0.028	0.049	-10000	0	-0.49	3	3
GPC1/PrPc/Cu2+	-0.001	0.026	-10000	0	-0.55	1	1
GPC1/Laminin alpha1	-0.048	0.17	-10000	0	-0.63	36	36
TDGF1	-0.34	0.41	-10000	0	-0.82	204	204
CRIPTO/GPC1	-0.27	0.31	-10000	0	-0.63	204	204
APP/GPC1	0	0.009	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.21	0.28	-10000	0	-0.54	204	204
FLT1	0.012	0.038	-10000	0	-0.82	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.008	0.049	-10000	0	-0.55	3	3
SERPINC1	0.007	0.042	-10000	0	-0.31	8	8
FYN	-0.21	0.28	-10000	0	-0.54	204	204
FGR	-0.21	0.28	-10000	0	-0.54	204	204
positive regulation of MAPKKK cascade	-0.28	0.32	-10000	0	-0.62	206	206
SLIT2	-0.11	0.3	-10000	0	-0.8	76	76
GPC1/NRG	-0.061	0.18	-10000	0	-0.63	46	46
NRG1	-0.067	0.24	-10000	0	-0.8	48	48
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.005	0.059	-10000	0	-0.71	3	3
LYN	-0.21	0.28	-10000	0	-0.54	204	204
mol:Spermine	0.012	0.01	-10000	0	-10000	0	0
cell growth	-0.001	0.026	-10000	0	-0.54	1	1
BMP signaling pathway	-0.013	0.015	0.31	1	-10000	0	1
SRC	-0.21	0.28	-10000	0	-0.55	204	204
TGFBR1	0.005	0.051	-10000	0	-0.31	12	12
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.25	0.37	-10000	0	-0.69	184	184
GPC1	0.013	0.015	-10000	0	-0.31	1	1
TGFBR1 (dimer)	0.005	0.051	-10000	0	-0.31	12	12
VEGFA	0.008	0.066	-10000	0	-0.82	3	3
BLK	-0.38	0.38	-10000	0	-0.67	278	278
HCK	-0.22	0.28	-10000	0	-0.55	204	204
FGF2	0.013	0	-10000	0	-10000	0	0
FGFR1	0.012	0.038	-10000	0	-0.82	1	1
VEGFR1 homodimer	0.012	0.038	-10000	0	-0.82	1	1
TGFBR2	0.008	0.066	-10000	0	-0.82	3	3
cell death	0	0.009	-10000	0	-10000	0	0
ATIII/GPC1	-0.004	0.027	-10000	0	-10000	0	0
PLA2G2A/GPC1	-0.2	0.28	-10000	0	-0.63	135	135
LCK	-0.23	0.28	-10000	0	-0.55	209	209
neuron differentiation	-0.061	0.18	-10000	0	-0.63	46	46
PrPc/Cu2+	-0.001	0.029	-10000	0	-0.64	1	1
APP	0.013	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.008	0.065	-10000	0	-0.82	3	3

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.066	-10000	0	-0.83	3	3
EFNB1	-0.001	0.12	-10000	0	-0.63	17	17
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.25	0.25	-10000	0	-0.53	204	204
Ephrin B2/EPHB1-2	-0.2	0.25	-10000	0	-0.5	191	191
neuron projection morphogenesis	-0.24	0.23	-10000	0	-0.5	204	204
Ephrin B1/EPHB1-2/Tiam1	-0.27	0.27	-10000	0	-0.57	204	204
DNM1	-0.017	0.15	-10000	0	-0.8	18	18
cell-cell signaling	-0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.006	0.084	-10000	0	-0.8	5	5
YES1	-0.008	0.1	-10000	0	-1	5	5
Ephrin B1/EPHB1-2/NCK2	-0.19	0.25	-10000	0	-0.47	204	204
PI3K	0.004	0.11	-10000	0	-1.1	5	5
mol:GDP	-0.27	0.26	-10000	0	-0.56	204	204
ITGA2B	-0.074	0.26	-10000	0	-0.82	51	51
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.008	0.1	-10000	0	-1	5	5
MAP3K7	-0.011	0.086	-10000	0	-0.85	5	5
FGR	-0.01	0.1	-10000	0	-1	5	5
TIAM1	-0.17	0.16	-10000	0	-0.32	276	276
PIK3R1	0.013	0	-10000	0	-10000	0	0
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.043	0.21	-10000	0	-0.54	63	63
LYN	-0.008	0.1	-10000	0	-1	5	5
Ephrin B1/EPHB1-2/Src Family Kinases	-0.012	0.099	-10000	0	-0.98	5	5
Ephrin B1/EPHB1-2	-0.018	0.093	-10000	0	-0.92	5	5
SRC	-0.01	0.1	-10000	0	-1	5	5
ITGB3	-0.014	0.15	-10000	0	-0.82	16	16
EPHB1	-0.31	0.41	-10000	0	-0.82	189	189
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.086	0.23	-10000	0	-0.68	61	61
BLK	-0.065	0.14	-10000	0	-1.1	5	5
HCK	-0.011	0.1	-10000	0	-1	5	5
regulation of stress fiber formation	0.19	0.24	0.47	204	-10000	0	204
MAPK8	0.006	0.12	-10000	0	-0.78	10	10
Ephrin B1/EPHB1-2/RGS3	-0.19	0.25	-10000	0	-0.47	204	204
endothelial cell migration	-0.005	0.076	-10000	0	-0.74	5	5
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.006	0.098	-10000	0	-0.94	5	5
regulation of focal adhesion formation	0.19	0.24	0.47	204	-10000	0	204
chemotaxis	0.19	0.24	0.47	204	-10000	0	204
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
Rac1/GTP	-0.25	0.24	-10000	0	-0.52	204	204
angiogenesis	-0.018	0.092	-10000	0	-0.91	5	5
LCK	-0.013	0.11	-10000	0	-1.1	5	5

×

Endothelins

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
AKT1	-0.05	0.14	-9999	-0.53	10	10
PTK2B	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.13	0.28	-9999	-0.7	59	59
EDN1	-0.043	0.12	-9999	-0.74	7	7
EDN3	-0.4	0.42	-9999	-0.82	239	239
EDN2	-0.016	0.12	-9999	-0.4	34	34
HRAS/GDP	-0.1	0.24	-9999	-0.54	78	78
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.082	0.18	-9999	-0.39	90	90
ADCY4	-0.095	0.19	-9999	-0.5	68	68
ADCY5	-0.16	0.25	-9999	-0.56	114	114
ADCY6	-0.095	0.19	-9999	-0.5	68	68
ADCY7	-0.095	0.19	-9999	-0.5	68	68
ADCY1	-0.1	0.2	-9999	-0.52	70	70
ADCY2	-0.14	0.24	-9999	-0.55	102	102
ADCY3	-0.095	0.19	-9999	-0.5	68	68
ADCY8	-0.2	0.2	-9999	-0.54	94	94
ADCY9	-0.095	0.19	-9999	-0.5	68	68
arachidonic acid secretion	-0.17	0.32	-9999	-0.65	131	131
ETB receptor/Endothelin-1/Gq/GTP	-0.093	0.21	-9999	-0.43	115	115
GNAO1	-0.017	0.15	-9999	-0.72	20	20
HRAS	0.01	0.021	-9999	-0.31	2	2
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.16	-9999	-0.51	9	9
ETA receptor/Endothelin-1/Gs/GTP	-0.081	0.22	-9999	-0.53	69	69
mol:GTP	-0.003	0.009	-9999	-10000	0	0
COL3A1	-0.067	0.17	-9999	-0.5	38	38
EDNRB	0.004	0.087	-9999	-0.84	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
CYSLTR2	-0.16	0.24	-9999	-0.64	52	52
CYSLTR1	-0.059	0.17	-9999	-0.75	14	14
SLC9A1	-0.021	0.075	-9999	-0.3	6	6
mol:GDP	-0.12	0.25	-9999	-0.56	88	88
SLC9A3	-0.045	0.19	-9999	-0.79	20	20
RAF1	-0.15	0.3	-9999	-0.58	124	124
JUN	-0.28	0.51	-9999	-1.2	117	117
JAK2	-0.052	0.14	-9999	-0.54	10	10
mol:IP3	-0.11	0.22	-9999	-0.49	101	101
ETA receptor/Endothelin-1	-0.034	0.2	-9999	-0.52	19	19
PLCB1	0.009	0.039	-9999	-0.83	1	1
PLCB2	0.005	0.043	-9999	-0.32	8	8
ETA receptor/Endothelin-3	-0.33	0.34	-9999	-0.66	238	238
FOS	-0.26	0.48	-9999	-1	130	130
Gai/GDP	-0.003	0.13	-9999	-0.66	16	16
CRK	0.013	0.001	-9999	-10000	0	0
mol:Ca ++	-0.12	0.23	-9999	-0.6	51	51
BCAR1	0.013	0.002	-9999	-10000	0	0
PRKCB1	-0.11	0.22	-9999	-0.48	102	102
GNAQ	0.011	0.008	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNAL	-0.092	0.28	-9999	-0.82	61	61
Gs family/GDP	-0.18	0.25	-9999	-0.57	118	118
ETA receptor/Endothelin-1/Gq/GTP	-0.11	0.21	-9999	-0.45	101	101
MAPK14	-0.061	0.17	-9999	-0.46	33	33
TRPC6	-0.14	0.3	-9999	-0.75	58	58
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.82	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.073	0.18	-9999	-0.4	83	83
ETB receptor/Endothelin-2	-0.026	0.1	-9999	-0.64	11	11
ETB receptor/Endothelin-3	-0.32	0.32	-9999	-0.64	240	240
ETB receptor/Endothelin-1	-0.018	0.12	-9999	-0.63	11	11
MAPK3	-0.23	0.44	-9999	-0.89	136	136
MAPK1	-0.23	0.44	-9999	-0.89	135	135
Rac1/GDP	-0.1	0.24	-9999	-0.54	74	74
cAMP biosynthetic process	-0.14	0.21	-9999	-0.54	78	78
MAPK8	-0.17	0.34	-9999	-0.69	105	105
SRC	0.012	0.015	-9999	-0.32	1	1
ETB receptor/Endothelin-1/Gi/GTP	0.009	0.078	-9999	-0.36	7	7
p130Cas/CRK/Src/PYK2	-0.13	0.29	-9999	-0.62	91	91
mol:K +	0	0	-9999	-10000	0	0
G12/GDP	-0.1	0.24	-9999	-0.53	79	79
COL1A2	-0.036	0.16	-9999	-0.53	16	16
EntrezGene:2778	0	0	-9999	-10000	0	0
ETA receptor/Endothelin-2	-0.029	0.11	-9999	-0.63	8	8
mol:DAG	-0.11	0.22	-9999	-0.49	101	101
MAP2K2	-0.18	0.35	-9999	-0.69	138	138
MAP2K1	-0.18	0.35	-9999	-0.69	138	138
EDNRA	-0.037	0.098	-9999	-0.55	4	4
positive regulation of muscle contraction	-0.035	0.12	-9999	-0.49	8	8
Gq family/GDP	-0.19	0.29	-9999	-0.66	112	112
HRAS/GTP	-0.13	0.26	-9999	-0.57	94	94
PRKCH	-0.1	0.22	-9999	-0.51	83	83
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	-0.12	0.26	-9999	-0.55	98	98
PRKCB	-0.12	0.23	-9999	-0.52	89	89
PRKCE	-0.1	0.23	-9999	-0.52	84	84
PRKCD	-0.1	0.22	-9999	-0.51	83	83
PRKCG	-0.1	0.22	-9999	-0.51	83	83
regulation of vascular smooth muscle contraction	-0.3	0.56	-9999	-1.2	130	130
PRKCQ	-0.1	0.23	-9999	-0.51	86	86
PLA2G4A	-0.19	0.36	-9999	-0.72	131	131
GNA14	-0.18	0.36	-9999	-0.83	112	112
GNA15	-0.015	0.093	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA11	-0.005	0.11	-9999	-0.82	9	9
Rac1/GTP	-0.013	0.16	-9999	-0.53	8	8
MMP1	-0.098	0.16	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.013	0	-10000	0	-10000	0	0
PTK2	0.013	0	-10000	0	-10000	0	0
CRKL	-0.13	0.24	-10000	0	-0.45	156	156
GRB2/SOS1/SHC	0	0	-10000	0	-10000	0	0
HRAS	0.012	0.021	-10000	0	-0.31	2	2
IRS1/Crk	-0.13	0.24	-10000	0	-0.46	156	156
IGF-1R heterotetramer/IGF1/PTP1B	-0.13	0.22	-10000	0	-0.53	113	113
AKT1	-0.091	0.22	-10000	0	-0.78	15	15
BAD	-0.077	0.2	-10000	0	-0.71	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.13	0.24	-10000	0	-0.45	156	156
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.13	0.24	-10000	0	-0.46	156	156
RAF1	-0.068	0.19	-10000	0	-0.66	15	15
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.14	0.21	-10000	0	-0.46	113	113
YWHAZ	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.16	0.24	-10000	0	-0.5	156	156
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
RPS6KB1	-0.091	0.22	-10000	0	-0.78	15	15
GNB2L1	0.013	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.059	0.16	-10000	0	-0.54	15	15
PXN	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.12	0.19	-10000	0	-0.73	13	13
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.1	0.18	-10000	0	-0.42	113	113
IGF-1R heterotetramer	-0.019	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.15	0.22	-10000	0	-0.46	156	156
Crk/p130 Cas/Paxillin	-0.13	0.2	-10000	0	-0.44	113	113
IGF1R	-0.019	0.048	-10000	0	-10000	0	0
IGF1	-0.2	0.36	-10000	0	-0.82	119	119
IRS2/Crk	-0.11	0.23	-10000	0	-0.43	156	156
PI3K	-0.14	0.22	-10000	0	-0.47	114	114
apoptosis	0.059	0.18	0.58	15	-10000	0	15
HRAS/GDP	-0.001	0.014	-10000	0	-10000	0	0
PRKCD	-0.11	0.24	-10000	0	-0.53	113	113
RAF1/14-3-3 E	-0.05	0.17	-10000	0	-0.54	15	15
BAD/14-3-3	-0.063	0.19	-10000	0	-0.63	15	15
PRKCZ	-0.091	0.22	-10000	0	-0.78	15	15
Crk/p130 Cas/Paxillin/FAK1	-0.1	0.16	-10000	0	-0.64	15	15
PTPN1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.12	0.26	-10000	0	-0.57	113	113
BCAR1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.11	0.19	-10000	0	-0.46	113	113
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.13	0.24	-10000	0	-0.45	156	156
GRB10	0.013	0	-10000	0	-10000	0	0
PTPN11	-0.13	0.24	-10000	0	-0.46	156	156
IRS1	-0.15	0.25	-10000	0	-0.5	156	156
IRS2	-0.13	0.24	-10000	0	-0.45	156	156
IGF-1R heterotetramer/IGF1	-0.17	0.28	-10000	0	-0.66	113	113
GRB2	0.013	0	-10000	0	-10000	0	0
PDPK1	-0.1	0.23	-10000	0	-0.45	114	114
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKD1	-0.11	0.24	-10000	0	-0.53	114	114
SHC1	0.013	0	-10000	0	-10000	0	0

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.18	0.42	-9999	-0.96	51	51
HDAC7	0.015	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.28	0.34	-9999	-0.82	105	105
SMAD4	0.015	0.003	-9999	-10000	0	0
ID2	-0.18	0.42	-9999	-0.94	56	56
AP1	-0.29	0.45	-9999	-0.92	152	152
ABCG2	-0.19	0.42	-9999	-0.95	57	57
HIF1A	-0.008	0.068	-9999	-10000	0	0
TFF3	-0.57	0.52	-9999	-1	193	193
GATA2	0.014	0.015	-9999	-0.31	1	1
AKT1	-0.038	0.1	-9999	-10000	0	0
response to hypoxia	-0.059	0.11	-9999	-0.24	20	20
MCL1	-0.18	0.42	-9999	-0.96	50	50
NDRG1	-0.18	0.42	-9999	-0.95	54	54
SERPINE1	-0.2	0.43	-9999	-0.96	56	56
FECH	-0.18	0.42	-9999	-0.92	61	61
FURIN	-0.18	0.42	-9999	-0.93	58	58
NCOA2	-0.061	0.24	-9999	-0.82	44	44
EP300	-0.062	0.18	-9999	-0.33	112	112
HMOX1	-0.19	0.42	-9999	-0.93	62	62
BHLHE40	-0.19	0.43	-9999	-0.94	62	62
BHLHE41	-0.19	0.42	-9999	-1	46	46
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.017	0.036	-9999	-10000	0	0
ENG	0.042	0.092	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.82	109	109
RORA	-0.19	0.42	-9999	-0.98	50	50
ABCB1	-0.077	0.19	-9999	-1.4	8	8
TFRC	-0.19	0.42	-9999	-0.95	57	57
CXCR4	-0.18	0.42	-9999	-0.93	61	61
TF	-0.23	0.49	-9999	-1.1	83	83
CITED2	-0.22	0.47	-9999	-1	70	70
HIF1A/ARNT	-0.29	0.38	-9999	-1	66	66
LDHA	-0.039	0.049	-9999	-10000	0	0
ETS1	-0.18	0.42	-9999	-0.96	51	51
PGK1	-0.18	0.42	-9999	-0.99	44	44
NOS2	-0.2	0.43	-9999	-0.98	55	55
ITGB2	-0.19	0.42	-9999	-0.95	61	61
ALDOA	-0.18	0.42	-9999	-0.96	50	50
Cbp/p300/CITED2	-0.32	0.51	-9999	-1.1	103	103
FOS	-0.21	0.37	-9999	-0.82	129	129
HK2	-0.19	0.42	-9999	-0.94	58	58
SP1	0.022	0.008	-9999	-10000	0	0
GCK	-0.39	0.72	-9999	-1.5	136	136
HK1	-0.18	0.42	-9999	-0.94	56	56
NPM1	-0.18	0.42	-9999	-0.95	53	53
EGLN1	-0.18	0.42	-9999	-0.97	51	51
CREB1	0.022	0	-9999	-10000	0	0
PGM1	-0.18	0.42	-9999	-0.94	56	56
SMAD3	0.015	0.003	-9999	-10000	0	0
EDN1	-0.16	0.32	-9999	-0.73	67	67
IGFBP1	-0.2	0.42	-9999	-0.94	60	60
VEGFA	-0.16	0.38	-9999	-0.76	74	74
HIF1A/JAB1	-0.011	0.02	-9999	-10000	0	0
CP	-0.35	0.55	-9999	-1	147	147
CXCL12	-0.23	0.49	-9999	-1	84	84
COPS5	0.014	0.002	-9999	-10000	0	0
SMAD3/SMAD4	0	0.003	-9999	-10000	0	0
BNIP3	-0.18	0.42	-9999	-0.94	56	56
EGLN3	-0.2	0.44	-9999	-0.97	64	64
CA9	-0.2	0.42	-9999	-0.94	62	62
TERT	-0.2	0.42	-9999	-0.94	60	60
ENO1	-0.18	0.42	-9999	-0.94	56	56
PFKL	-0.18	0.42	-9999	-0.94	56	56
NCOA1	0.014	0	-9999	-10000	0	0
ADM	-0.22	0.44	-9999	-0.97	63	63
ARNT	-0.009	0.067	-9999	-10000	0	0
HNF4A	-0.026	0.065	-9999	-0.35	10	10
ADFP	-0.2	0.41	-9999	-0.92	66	66
SLC2A1	-0.15	0.38	-9999	-0.75	73	73
LEP	-0.2	0.42	-9999	-0.96	56	56
HIF1A/ARNT/Cbp/p300	-0.29	0.36	-9999	-0.86	105	105
EPO	-0.14	0.33	-9999	-0.91	28	28
CREBBP	-0.062	0.18	-9999	-0.32	126	126
HIF1A/ARNT/Cbp/p300/HDAC7	-0.28	0.34	-9999	-0.82	102	102
PFKFB3	-0.18	0.42	-9999	-0.93	63	63
NT5E	-0.19	0.43	-9999	-0.97	55	55

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.045	0.094	-10000	0	-10000	0	0
SMARCC2	0.013	0.014	-10000	0	-10000	0	0
SMARCC1	0.013	0.014	-10000	0	-10000	0	0
TBX21	-0.16	0.28	-10000	0	-0.86	46	46
SUMO2	0.014	0.013	-10000	0	-10000	0	0
STAT1 (dimer)	0.015	0.05	-10000	0	-0.31	11	11
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.001	0.1	-10000	0	-0.82	7	7
GR alpha/HSP90/FKBP51/HSP90	0.13	0.13	0.36	35	-0.49	7	42
PRL	-0.089	0.12	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.25	0.31	0.59	152	-0.49	21	173
RELA	-0.036	0.088	-10000	0	-10000	0	0
FGG	0.24	0.19	0.52	106	-10000	0	106
GR beta/TIF2	0.085	0.23	0.35	71	-0.56	44	115
IFNG	-0.5	0.51	-10000	0	-1	178	178
apoptosis	0.036	0.24	0.52	54	-0.56	2	56
CREB1	0.011	0.023	-10000	0	-10000	0	0
histone acetylation	-0.072	0.17	-10000	0	-0.42	55	55
BGLAP	-0.099	0.15	-10000	0	-0.52	15	15
GR/PKAc	0.13	0.1	0.36	25	-0.41	1	26
NF kappa B1 p50/RelA	-0.074	0.16	-10000	0	-0.45	32	32
SMARCD1	0.013	0.014	-10000	0	-10000	0	0
MDM2	0.12	0.094	0.27	102	-10000	0	102
GATA3	-0.027	0.19	-10000	0	-0.78	27	27
AKT1	0	0	-10000	0	-10000	0	0
CSF2	-0.21	0.16	-10000	0	-0.58	33	33
GSK3B	0.014	0.013	-10000	0	-10000	0	0
NR1I3	0.063	0.23	0.51	41	-0.78	4	45
CSN2	0.2	0.14	0.43	74	-10000	0	74
BRG1/BAF155/BAF170/BAF60A	0.017	0.049	-10000	0	-10000	0	0
NFATC1	0	0.11	-10000	0	-0.82	9	9
POU2F1	0.013	0.015	-10000	0	-0.3	1	1
CDKN1A	0.023	0.055	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.012	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	312	312
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.046	0.16	0.35	14	-0.48	14	28
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.074	0.44	0.49	42	-0.88	103	145
JUN	-0.33	0.3	-10000	0	-0.71	160	160
IL4	-0.13	0.18	-10000	0	-0.65	25	25
CDK5R1	0.012	0.022	-10000	0	-0.32	2	2
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.37	0.41	-10000	0	-0.82	185	185
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.13	0.12	0.35	31	-0.47	6	37
cortisol/GR alpha (monomer)	0.37	0.3	0.71	171	-10000	0	171
NCOA2	-0.062	0.24	-10000	0	-0.82	44	44
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.26	0.36	-10000	0	-0.85	129	129
AP-1/NFAT1-c-4	-0.56	0.48	-10000	0	-0.98	231	231
AFP	-0.22	0.22	-10000	0	-0.7	30	30
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.2	0.15	0.45	73	-10000	0	73
TP53	0.032	0.023	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.48	0.37	-10000	0	-0.82	189	189
KRT14	-0.24	0.18	-10000	0	-0.63	16	16
TBP	0.022	0.009	-10000	0	-10000	0	0
CREBBP	0.064	0.066	-10000	0	-10000	0	0
HDAC1	0.011	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.013	-10000	0	-10000	0	0
AP-1	-0.57	0.49	-10000	0	-0.98	232	232
MAPK14	0.014	0.012	-10000	0	-10000	0	0
MAPK10	0.013	0.04	-10000	0	-0.83	1	1
MAPK11	0.014	0.013	-10000	0	-10000	0	0
KRT5	-0.55	0.53	-10000	0	-1.2	162	162
interleukin-1 receptor activity	0.017	0.013	-10000	0	-10000	0	0
NCOA1	0.017	0.001	-10000	0	-10000	0	0
STAT1	0.015	0.05	-10000	0	-0.31	11	11
CGA	-0.13	0.16	-10000	0	-0.54	24	24
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.24	0.14	0.41	121	-10000	0	121
MAPK3	0.014	0.012	-10000	0	-10000	0	0
MAPK1	0.014	0.012	-10000	0	-10000	0	0
ICAM1	-0.26	0.27	-10000	0	-0.65	115	115
NFKB1	-0.038	0.097	-10000	0	-0.31	12	12
MAPK8	-0.19	0.2	-10000	0	-0.52	93	93
MAPK9	0.014	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.03	0.24	0.52	54	-0.58	2	56
BAX	0.028	0.032	-10000	0	-10000	0	0
POMC	-0.54	0.69	-10000	0	-1.5	138	138
EP300	0.065	0.067	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.33	0.24	0.6	165	-10000	0	165
proteasomal ubiquitin-dependent protein catabolic process	0.088	0.071	0.24	32	-10000	0	32
SGK1	0.1	0.24	-10000	0	-1.4	11	11
IL13	-0.3	0.25	-10000	0	-0.74	77	77
IL6	-0.41	0.54	-10000	0	-1.2	127	127
PRKACG	0.002	0.005	-10000	0	-10000	0	0
IL5	-0.26	0.2	-10000	0	-0.68	52	52
IL2	-0.36	0.27	-10000	0	-0.8	92	92
CDK5	0.013	0.007	-10000	0	-10000	0	0
PRKACB	0.012	0.038	-10000	0	-0.82	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.27	0.32	-10000	0	-0.74	99	99
CDK5R1/CDK5	0.007	0.023	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.032	0.12	-10000	0	-0.56	3	3
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	160	-10000	0	160
SMARCA4	0.013	0.014	-10000	0	-10000	0	0
chromatin remodeling	0.2	0.15	0.42	94	-10000	0	94
NF kappa B1 p50/RelA/Cbp	0.018	0.16	-10000	0	-0.52	5	5
JUN (dimer)	-0.33	0.3	-10000	0	-0.71	160	160
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.24	0.41	-10000	0	-1.1	82	82
NR3C1	0.22	0.19	0.5	111	-10000	0	111
NR4A1	-0.31	0.41	-10000	0	-0.76	206	206
TIF2/SUV420H1	-0.057	0.18	-10000	0	-0.63	44	44
MAPKKK cascade	0.036	0.24	0.52	54	-0.56	2	56
cortisol/GR alpha (dimer)/Src-1	0.32	0.24	0.6	163	-10000	0	163
PBX1	0.012	0.038	-10000	0	-0.82	1	1
POU1F1	0.007	0.008	-10000	0	-10000	0	0
SELE	-0.35	0.51	-10000	0	-1.2	105	105
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.2	0.15	0.43	90	-10000	0	90
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.31	0.22	0.56	160	-10000	0	160
mol:cortisol	0.21	0.19	0.4	188	-10000	0	188
MMP1	-0.22	0.15	-10000	0	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.12	0.23	-10000	0	-0.62	77	77
FYN	-0.11	0.35	-10000	0	-0.8	85	85
LAT/GRAP2/SLP76	-0.12	0.27	-10000	0	-0.66	87	87
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.054	0.22	-10000	0	-0.47	89	89
B2M	0.013	0.006	-10000	0	-10000	0	0
IKBKG	-0.031	0.05	-10000	0	-0.18	11	11
MAP3K8	0	0.11	-10000	0	-0.82	8	8
mol:Ca2+	-0.031	0.051	-10000	0	-0.12	107	107
integrin-mediated signaling pathway	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.1	0.33	-10000	0	-0.73	91	91
TRPV6	-0.18	0.34	-10000	0	-0.8	110	110
CD28	-0.043	0.19	-10000	0	-0.59	45	45
SHC1	-0.12	0.35	-10000	0	-0.8	86	86
receptor internalization	-0.14	0.38	-10000	0	-0.83	95	95
PRF1	-0.12	0.36	-10000	0	-0.89	73	73
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	-0.037	0.18	-10000	0	-0.38	88	88
LAT	-0.12	0.35	-10000	0	-0.81	86	86
EntrezGene:6955	0	0.003	-10000	0	-10000	0	0
CD3D	-0.096	0.27	-10000	0	-0.72	73	73
CD3E	-0.072	0.25	-10000	0	-0.76	54	54
CD3G	-0.15	0.33	-10000	0	-0.79	97	97
RASGRP2	0	0.031	-10000	0	-0.19	6	6
RASGRP1	-0.05	0.22	-10000	0	-0.47	91	91
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
RASSF5	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.011	0.068	-10000	0	-0.12	64	64
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.056	0.09	-10000	0	-0.25	64	64
PRKCA	-0.062	0.14	-10000	0	-0.32	84	84
GRAP2	-0.042	0.2	-10000	0	-0.78	34	34
mol:IP3	-0.051	0.23	0.28	84	-0.46	87	171
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.16	0.43	-10000	0	-0.97	83	83
ORAI1	0.089	0.16	0.39	102	-10000	0	102
CSK	-0.12	0.36	-10000	0	-0.82	86	86
B7 family/CD28	-0.2	0.35	-10000	0	-0.75	113	113
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.16	0.43	-10000	0	-0.96	91	91
PTPN6	-0.12	0.36	-10000	0	-0.84	85	85
VAV1	-0.12	0.35	-10000	0	-0.79	90	90
Monovalent TCR/CD3	-0.16	0.41	-10000	0	-0.74	121	121
CBL	0.013	0	-10000	0	-10000	0	0
LCK	-0.12	0.37	-10000	0	-0.83	87	87
PAG1	-0.12	0.36	-10000	0	-0.82	86	86
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.16	0.43	-10000	0	-0.96	90	90
CD80	-0.07	0.25	-10000	0	-0.81	49	49
CD86	-0.009	0.1	-10000	0	-0.42	24	24
PDK1/CARD11/BCL10/MALT1	-0.069	0.11	-10000	0	-0.29	71	71
HRAS	0.012	0.021	-10000	0	-0.31	2	2
GO:0035030	-0.11	0.3	-10000	0	-0.64	97	97
CD8A	-0.049	0.22	-10000	0	-0.83	36	36
CD8B	-0.092	0.27	-10000	0	-0.74	69	69
PTPRC	-0.034	0.18	-10000	0	-0.59	37	37
PDK1/PKC theta	-0.069	0.27	-10000	0	-0.6	87	87
CSK/PAG1	-0.11	0.35	-10000	0	-0.83	80	80
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.015	0.018	-10000	0	-10000	0	0
GRAP2/SLP76	-0.15	0.32	-10000	0	-0.78	90	90
STIM1	0.047	0.082	-10000	0	-10000	0	0
RAS family/GTP	0.008	0.092	-10000	0	-0.18	52	52
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.16	0.43	-10000	0	-0.93	95	95
mol:DAG	-0.071	0.18	-10000	0	-0.41	88	88
RAP1A/GDP	0.006	0.03	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.023	0.16	-10000	0	-0.64	27	27
cytotoxic T cell degranulation	-0.11	0.34	-10000	0	-0.81	77	77
RAP1A/GTP	-0.003	0.009	-10000	0	-0.07	5	5
mol:PI-3-4-5-P3	-0.074	0.26	-10000	0	-0.57	91	91
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.081	0.29	0.3	78	-0.62	88	166
NRAS	0.013	0	-10000	0	-10000	0	0
ZAP70	-0.022	0.16	-10000	0	-0.62	27	27
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.12	0.26	-10000	0	-0.63	88	88
MALT1	0.013	0	-10000	0	-10000	0	0
TRAF6	0.01	0.054	-10000	0	-0.82	2	2
CD8 heterodimer	-0.11	0.3	-10000	0	-0.77	74	74
CARD11	-0.072	0.17	-10000	0	-0.35	115	115
PRKCB	-0.059	0.13	-10000	0	-0.32	79	79
PRKCE	-0.052	0.12	-10000	0	-0.3	72	72
PRKCQ	-0.092	0.31	-10000	0	-0.7	88	88
LCP2	0.009	0.039	-10000	0	-0.31	7	7
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.04	0.19	-10000	0	-0.4	89	89
IKK complex	0.013	0.069	-10000	0	-0.12	38	38
RAS family/GDP	-0.005	0.01	-10000	0	-10000	0	0
MAP3K14	-0.017	0.14	-10000	0	-0.3	74	74
PDPK1	-0.048	0.21	-10000	0	-0.45	87	87
TCR/CD3/MHC I/CD8/Fyn	-0.17	0.46	-10000	0	-1.1	85	85

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.22	0.56	-10000	0	-1.3	76	76
IL23A	-0.23	0.57	-10000	0	-1.3	86	86
NF kappa B1 p50/RelA/I kappa B alpha	-0.3	0.48	-10000	0	-1.2	88	88
positive regulation of T cell mediated cytotoxicity	-0.26	0.62	-10000	0	-1.4	88	88
ITGA3	-0.21	0.52	-10000	0	-1.2	79	79
IL17F	-0.11	0.35	-10000	0	-0.75	73	73
IL12B	-0.001	0.1	-10000	0	-0.63	9	9
STAT1 (dimer)	-0.24	0.59	-10000	0	-1.3	87	87
CD4	-0.2	0.51	-10000	0	-1.2	82	82
IL23	-0.24	0.54	-10000	0	-1.2	83	83
IL23R	-0.005	0.1	-10000	0	-10000	0	0
IL1B	-0.24	0.6	-10000	0	-1.4	80	80
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.2	0.51	-10000	0	-1.2	82	82
TYK2	0.014	0.023	-10000	0	-10000	0	0
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
STAT3	0.013	0	-10000	0	-10000	0	0
IL18RAP	-0.027	0.17	-10000	0	-0.8	23	23
IL12RB1	-0.021	0.12	-10000	0	-0.37	44	44
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
IL12Rbeta1/TYK2	-0.009	0.093	-10000	0	-0.68	4	4
IL23R/JAK2	-0.002	0.13	-10000	0	-0.68	1	1
positive regulation of chronic inflammatory response	-0.26	0.62	-10000	0	-1.4	88	88
natural killer cell activation	0.001	0.009	0.036	1	-10000	0	1
JAK2	0.021	0.048	-10000	0	-0.86	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
NFKB1	0.011	0.038	-10000	0	-0.83	1	1
RELA	0.013	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.22	0.51	-10000	0	-1.1	85	85
ALOX12B	-0.22	0.52	-10000	0	-1.2	87	87
CXCL1	-0.23	0.54	-10000	0	-1.2	83	83
T cell proliferation	-0.26	0.62	-10000	0	-1.4	88	88
NFKBIA	0.013	0.004	-10000	0	-10000	0	0
IL17A	-0.063	0.28	-10000	0	-0.59	58	58
PI3K	-0.31	0.49	-10000	0	-1.2	88	88
IFNG	-0.02	0.055	-10000	0	-0.13	74	74
STAT3 (dimer)	-0.29	0.45	-10000	0	-1.2	86	86
IL18R1	-0.031	0.15	-10000	0	-0.43	47	47
IL23/IL23R/JAK2/TYK2/SOCS3	-0.1	0.33	-10000	0	-0.76	55	55
IL18/IL18R	-0.068	0.18	-10000	0	-0.56	47	47
macrophage activation	-0.015	0.018	-10000	0	-0.045	85	85
TNF	-0.28	0.63	-10000	0	-1.4	99	99
STAT3/STAT4	-0.32	0.5	-10000	0	-1.3	91	91
STAT4 (dimer)	-0.26	0.59	-10000	0	-1.3	91	91
IL18	-0.039	0.16	-10000	0	-0.41	58	58
IL19	-0.2	0.51	-10000	0	-1.2	77	77
STAT5A (dimer)	-0.24	0.59	-10000	0	-1.3	88	88
STAT1	0.006	0.049	-10000	0	-0.31	11	11
SOCS3	-0.034	0.19	-10000	0	-0.8	28	28
CXCL9	-0.3	0.64	-10000	0	-1.4	110	110
MPO	-0.2	0.52	-10000	0	-1.2	86	86
positive regulation of humoral immune response	-0.26	0.62	-10000	0	-1.4	88	88
IL23/IL23R/JAK2/TYK2	-0.3	0.75	-10000	0	-1.6	88	88
IL6	-0.34	0.66	-10000	0	-1.4	124	124
STAT5A	0.013	0	-10000	0	-10000	0	0
IL2	0.001	0.017	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.009	0.036	1	-10000	0	1
CD3E	-0.24	0.58	-10000	0	-1.3	92	92
keratinocyte proliferation	-0.26	0.62	-10000	0	-1.4	88	88
NOS2	-0.21	0.51	-10000	0	-1.2	77	77

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.27	0.33	-9999	-0.6	217	217
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.049	0.21	-9999	-0.7	42	42
SMAD9	-0.22	0.28	-9999	-0.59	165	165
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.096	0.2	-9999	-0.37	161	161
BMP7/USAG1	-0.33	0.32	-9999	-0.63	253	253
SMAD5/SKI	-0.085	0.2	-9999	-0.53	28	28
SMAD1	0.019	0.045	-9999	-10000	0	0
BMP2	-0.021	0.17	-9999	-0.82	20	20
SMAD1/SMAD1/SMAD4	-0.001	0.001	-9999	-10000	0	0
BMPR1A	0.013	0	-9999	-10000	0	0
BMPR1B	-0.26	0.39	-9999	-0.82	161	161
BMPR1A-1B/BAMBI	-0.19	0.26	-9999	-0.56	161	161
AHSG	-0.018	0.085	-9999	-0.31	37	37
CER1	0	0.003	-9999	-10000	0	0
BMP2-4/CER1	-0.04	0.14	-9999	-0.55	33	33
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.078	0.2	-9999	-0.63	32	32
BMP2-4 (homodimer)	-0.046	0.16	-9999	-0.63	33	33
RGMB	0.013	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.5	161	161
RGMA	-0.018	0.16	-9999	-0.82	18	18
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.089	0.19	-9999	-0.58	29	29
BMP2-4/USAG1	-0.32	0.3	-9999	-0.58	269	269
SMAD6/SMURF1/SMAD5	-0.085	0.2	-9999	-0.53	28	28
SOSTDC1	-0.42	0.42	-9999	-0.82	254	254
BMP7/BMPR2/BMPR1A-1B	-0.16	0.23	-9999	-0.5	161	161
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	0.013	0.015	-9999	-0.31	1	1
HFE2	0.001	0.033	-9999	-0.31	5	5
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.05	0.16	-9999	-0.56	42	42
SMAD5/SMAD5/SMAD4	-0.085	0.2	-9999	-0.53	28	28
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.094	0.14	-9999	-0.49	29	29
BMP7 (homodimer)	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.016	0.056	-9999	-0.4	1	1
SMAD1/SKI	0.026	0.043	-9999	-10000	0	0
SMAD6	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.052	0.15	-9999	-0.57	33	33
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.21	0.36	-9999	-0.73	143	143
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	-0.008	0.065	-9999	-0.55	7	7
BMPR1A-1B (homodimer)	-0.21	0.3	-9999	-0.63	161	161
CHRDL1	-0.58	0.38	-9999	-0.82	345	345
ENDOFIN/SMAD1	0.026	0.043	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.006	0.008	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.002	0.08	-9999	-0.37	19	19
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.42	0.28	-9999	-0.59	351	351
BMP2-4/GREM1	-0.18	0.28	-9999	-0.61	135	135
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.19	0.28	-9999	-0.55	165	165
SMAD1/SMAD6	0.026	0.043	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.013	0	-9999	-10000	0	0
BMP6	0.013	0.015	-9999	-0.31	1	1
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.067	0.16	-9999	-0.5	29	29
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.026	0.043	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.001	0.1	-9999	-0.82	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.2	0.32	-9999	-0.79	86	86
CHRD	-0.004	0.12	-9999	-0.82	10	10
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.095	0.2	-9999	-0.62	29	29
BMP4	-0.014	0.14	-9999	-0.64	20	20
FST	-0.2	0.36	-9999	-0.79	127	127
BMP2-4/NOG	-0.078	0.19	-9999	-0.55	65	65
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.15	0.22	-9999	-0.46	161	161

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.087	0.15	-9999	-0.31	149	149
GPC2	-0.01	0.083	-9999	-0.31	34	34
GPC2/Midkine	-0.076	0.11	-9999	-0.4	12	12
neuron projection morphogenesis	-0.076	0.11	-9999	-0.4	12	12

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	-0.015	0.064	-10000	0	-0.36	13	13
SVIL	-0.006	0.031	-10000	0	-10000	0	0
ZNF318	0.061	0.093	0.22	8	-0.82	1	9
JMJD2C	-0.064	0.069	-10000	0	-0.12	276	276
T-DHT/AR/Ubc9	-0.28	0.3	-10000	0	-0.62	204	204
CARM1	0.012	0.003	-10000	0	-10000	0	0
PRDX1	0.015	0.004	-10000	0	-10000	0	0
PELP1	0.02	0.011	-10000	0	-10000	0	0
CTNNB1	-0.002	0.023	-10000	0	-10000	0	0
AKT1	0.026	0.019	-10000	0	-10000	0	0
PTK2B	0.004	0.015	-10000	0	-10000	0	0
MED1	0.025	0.019	-10000	0	-10000	0	0
MAK	0.052	0.13	-10000	0	-0.8	6	6
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.01	0.061	-10000	0	-0.82	2	2
GSN	-0.006	0.03	-10000	0	-10000	0	0
NCOA2	-0.064	0.24	-10000	0	-0.82	44	44
NCOA6	-0.007	0.047	-10000	0	-0.82	1	1
DNA-PK	0.058	0.084	0.26	1	-10000	0	1
NCOA4	0.011	0.004	-10000	0	-10000	0	0
PIAS3	-0.002	0.023	-10000	0	-10000	0	0
cell proliferation	-0.011	0.15	-10000	0	-1.1	6	6
XRCC5	0.025	0.018	-10000	0	-10000	0	0
UBE3A	-0.016	0.047	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.31	0.33	-10000	0	-0.67	211	211
FHL2	-0.16	0.36	-10000	0	-1.3	39	39
RANBP9	-0.005	0.029	-10000	0	-10000	0	0
JMJD1A	0.002	0.037	-10000	0	-0.12	36	36
CDK6	0.009	0.066	-10000	0	-0.82	3	3
TGFB1I1	-0.006	0.031	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.3	0.3	-10000	0	-0.63	207	207
XRCC6	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR	-0.33	0.32	-10000	0	-0.64	230	230
CTDSP1	0.009	0.006	-10000	0	-10000	0	0
CTDSP2	0.046	0.05	-10000	0	-10000	0	0
BRCA1	-0.006	0.031	-10000	0	-10000	0	0
TCF4	0.035	0.034	-10000	0	-10000	0	0
CDKN2A	-0.11	0.16	-10000	0	-0.31	140	140
SRF	0.028	0.039	-10000	0	-10000	0	0
NKX3-1	-0.13	0.15	-10000	0	-1.3	4	4
KLK3	-0.44	0.71	-10000	0	-1.6	137	137
TMF1	0.006	0.054	-10000	0	-0.82	2	2
HNRNPA1	0.031	0.028	-10000	0	-10000	0	0
AOF2	-0.022	0.034	-10000	0	-0.075	137	137
APPL1	0.052	0.042	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.28	0.29	-10000	0	-0.61	204	204
AR	-0.38	0.42	-10000	0	-0.87	204	204
UBA3	0.009	0.006	-10000	0	-10000	0	0
PATZ1	0.031	0.028	-10000	0	-10000	0	0
PAWR	0.009	0.006	-10000	0	-10000	0	0
PRKDC	0.025	0.018	-10000	0	-10000	0	0
PA2G4	0.036	0.036	-10000	0	-10000	0	0
UBE2I	0.013	0	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.25	0.28	-10000	0	-0.57	204	204
RPS6KA3	-0.006	0.03	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.28	0.3	-10000	0	-0.62	204	204
LATS2	0.029	0.047	-10000	0	-0.82	1	1
T-DHT/AR/PRX1	-0.24	0.28	-10000	0	-0.56	204	204
Cyclin D3/CDK11 p58	0	0.003	-10000	0	-10000	0	0
VAV3	-0.012	0.094	-10000	0	-0.83	6	6
KLK2	-0.77	0.63	-10000	0	-1.3	275	275
CASP8	0.017	0.007	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.31	0.34	-10000	0	-0.67	210	210
TMPRSS2	-0.19	0.32	-10000	0	-1.2	35	35
CCND1	0.001	0.049	-10000	0	-0.31	11	11
PIAS1	-0.016	0.047	-10000	0	-10000	0	0
mol:T-DHT	-0.031	0.041	-10000	0	-0.082	162	162
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.036	0.077	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.28	0.3	-10000	0	-0.62	206	206
CMTM2	0.014	0.027	-10000	0	-0.31	3	3
SNURF	-0.032	0.19	-10000	0	-0.82	26	26
ZMIZ1	-0.013	0.051	-10000	0	-0.81	1	1
CCND3	0.014	0.002	-10000	0	-10000	0	0
TGIF1	0.031	0.028	-10000	0	-10000	0	0
FKBP4	-0.005	0.029	-10000	0	-10000	0	0

×

Arf6 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.043	0.11	-9999	-0.47	13	13
EGFR	0.006	0.076	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
USP6	0.011	0.026	-9999	-0.31	3	3
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.096	0.22	-9999	-0.63	72	72
ARRB2	-0.044	0.15	-9999	-0.45	59	59
mol:GTP	0.021	0.012	-9999	-10000	0	0
ARRB1	0.012	0.038	-9999	-0.82	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	0.01	0.054	-9999	-0.82	2	2
EGF	-0.11	0.29	-9999	-0.78	74	74
somatostatin receptor activity	0	0	-9999	-0.001	133	133
ARAP2	0.01	0.054	-9999	-0.82	2	2
mol:GDP	-0.12	0.15	-9999	-0.31	129	129
mol:PI-3-4-5-P3	0	0	-9999	-0.001	64	64
ITGA2B	-0.074	0.26	-9999	-0.82	51	51
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
ADAP1	0.013	0	-9999	-10000	0	0
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.17	0.24	-9999	-0.69	74	74
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.12	0.15	-9999	-0.31	134	134
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.083	0.19	-9999	-0.55	72	72
ADRB2	-0.009	0.14	-9999	-0.82	13	13
receptor agonist activity	0	0	-9999	0	137	137
actin filament binding	0	0	-9999	-0.001	131	131
SRC	0.013	0.015	-9999	-0.31	1	1
ITGB3	-0.014	0.15	-9999	-0.82	16	16
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	-9999	-0.001	120	120
ARF6/GDP	0.001	0.069	-9999	-0.32	3	3
ARF6/GDP/GULP/ACAP1	-0.19	0.2	-9999	-0.5	118	118
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.068	0.19	-9999	-0.54	61	61
ACAP1	0.001	0.075	-9999	-0.38	15	15
ACAP2	0.013	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.081	0.22	-9999	-0.68	59	59
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.11	0.3	-9999	-0.82	74	74
CYTH3	0.009	0.042	-9999	-0.64	2	2
CYTH2	0.008	0.002	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	110	110
endosomal lumen acidification	0	0	-9999	-0.001	137	137
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.14	0.32	-9999	-0.82	90	90
GNAQ/ARNO	0.009	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	19	19
MET	-0.11	0.16	-9999	-0.31	180	180
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.093	-9999	-0.33	37	37
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	130	130
GNA11	-0.002	0.11	-9999	-0.82	9	9
LHCGR	-0.098	0.27	-9999	-0.77	66	66
AGTR1	-0.32	0.41	-9999	-0.82	196	196
desensitization of G-protein coupled receptor protein signaling pathway	-0.081	0.22	-9999	-0.68	59	59
IPCEF1/ARNO	-0.056	0.16	-9999	-0.43	72	72
alphaIIb/beta3 Integrin	-0.086	0.23	-9999	-0.68	61	61

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.008	0.042	-9999	-0.31	8	8
CCL5	-0.045	0.21	-9999	-0.72	39	39
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.1	0.16	-9999	-0.49	48	48
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.092	0.16	-9999	-0.61	24	24
Syndecan-1/Syntenin	-0.092	0.16	-9999	-0.61	24	24
MAPK3	-0.069	0.14	-9999	-0.6	19	19
HGF/MET	-0.17	0.24	-9999	-0.69	74	74
TGFB1/TGF beta receptor Type II	0.008	0.042	-9999	-0.31	8	8
BSG	0.013	0.015	-9999	-0.31	1	1
keratinocyte migration	-0.091	0.15	-9999	-0.6	24	24
Syndecan-1/RANTES	-0.12	0.22	-9999	-0.66	53	53
Syndecan-1/CD147	-0.081	0.15	-9999	-0.62	21	21
Syndecan-1/Syntenin/PIP2	-0.099	0.14	-9999	-0.62	22	22
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.097	0.14	-9999	-0.57	24	24
MMP7	-0.18	0.22	-9999	-0.37	242	242
HGF	-0.11	0.3	-9999	-0.82	74	74
Syndecan-1/CASK	-0.1	0.16	-9999	-0.47	48	48
Syndecan-1/HGF/MET	-0.2	0.24	-9999	-0.65	87	87
regulation of cell adhesion	-0.059	0.14	-9999	-0.58	19	19
HPSE	-0.017	0.14	-9999	-0.51	28	28
positive regulation of cell migration	-0.1	0.16	-9999	-0.49	48	48
SDC1	-0.11	0.16	-9999	-0.49	48	48
Syndecan-1/Collagen	-0.1	0.16	-9999	-0.49	48	48
PPIB	0.013	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	180	180
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.082	0.24	-9999	-0.57	79	79
MAPK1	-0.069	0.14	-9999	-0.6	19	19
homophilic cell adhesion	-0.1	0.16	-9999	-0.48	48	48
MMP1	-0.14	0.16	-9999	-0.31	233	233

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.088	0.2	-10000	0	-0.56	76	76
cell-cell adhesion	0.15	0.19	0.55	10	-10000	0	10
Ephrin B/EPHB2/RasGAP	-0.014	0.068	-10000	0	-0.46	10	10
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.1	0.081	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.22	0.27	-10000	0	-0.55	189	189
HRAS/GDP	-0.14	0.17	-10000	0	-0.5	12	12
Ephrin B/EPHB1/GRB7	-0.21	0.25	-10000	0	-0.51	194	194
Endophilin/SYNJ1	0.025	0.072	-10000	0	-0.43	10	10
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.19	0.23	-10000	0	-0.47	194	194
endothelial cell migration	-0.003	0.037	-10000	0	-0.47	3	3
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.034	0.073	-10000	0	-0.43	10	10
HRAS	0.012	0.021	-10000	0	-0.31	2	2
RRAS	0.025	0.074	-10000	0	-0.44	10	10
DNM1	-0.017	0.15	-10000	0	-0.8	18	18
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.16	0.24	-10000	0	-0.45	194	194
lamellipodium assembly	-0.15	0.19	-10000	0	-0.55	10	10
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.11	0.18	-10000	0	-0.33	189	189
PIK3R1	0.013	0	-10000	0	-10000	0	0
EPHB2	0.008	0.066	-10000	0	-0.82	3	3
EPHB3	-0.19	0.16	-10000	0	-0.31	296	296
EPHB1	-0.31	0.41	-10000	0	-0.82	189	189
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.071	0.18	-10000	0	-0.51	7	7
Ephrin B/EPHB2	-0.014	0.07	-10000	0	-0.47	10	10
Ephrin B/EPHB3	-0.086	0.087	-10000	0	-0.57	7	7
JNK cascade	-0.15	0.24	-10000	0	-0.46	191	191
Ephrin B/EPHB1	-0.2	0.24	-10000	0	-0.48	194	194
RAP1/GDP	-0.055	0.16	-10000	0	-0.53	3	3
EFNB2	0.013	0	-10000	0	-10000	0	0
EFNB3	-0.01	0.12	-10000	0	-0.46	24	24
EFNB1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.2	0.25	-10000	0	-0.51	191	191
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.16	0.19	-10000	0	-0.58	10	10
Rap1/GTP	-0.15	0.19	-10000	0	-0.56	10	10
axon guidance	-0.088	0.2	-10000	0	-0.56	76	76
MAPK3	-0.08	0.16	-10000	0	-0.38	10	10
MAPK1	-0.08	0.16	-10000	0	-0.53	2	2
Rac1/GDP	-0.047	0.17	-10000	0	-0.46	7	7
actin cytoskeleton reorganization	-0.11	0.13	-10000	0	-0.55	3	3
CDC42/GDP	-0.047	0.17	-10000	0	-0.46	7	7
PI3K	-0.003	0.037	-10000	0	-0.47	3	3
EFNA5	-0.12	0.3	-10000	0	-0.82	74	74
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.029	0.055	-10000	0	-0.33	10	10
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.15	0.18	-10000	0	-0.54	11	11
PTK2	0.042	0.052	-10000	0	-10000	0	0
MAP4K4	-0.16	0.25	-10000	0	-0.46	191	191
SRC	0.013	0.015	-10000	0	-0.31	1	1
KALRN	0.013	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.071	0.18	-10000	0	-0.55	3	3
MAP2K1	-0.093	0.17	-10000	0	-0.41	10	10
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.2	0.24	-10000	0	-0.5	191	191
cell migration	-0.089	0.19	-10000	0	-0.44	10	10
NRAS	0.013	0	-10000	0	-10000	0	0
SYNJ1	0.026	0.073	-10000	0	-0.44	10	10
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.021	0.17	-10000	0	-0.45	60	60
HRAS/GTP	-0.17	0.2	-10000	0	-0.59	11	11
Ephrin B1/EPHB1-2	-0.2	0.25	-10000	0	-0.51	191	191
cell adhesion mediated by integrin	0.013	0.075	0.5	7	-10000	0	7
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.18	0.22	-10000	0	-0.44	196	196
RAC1-CDC42/GTP	-0.21	0.21	-10000	0	-0.49	146	146
RASA1	0.013	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.055	0.16	-10000	0	-0.53	3	3
ruffle organization	-0.12	0.22	-10000	0	-0.56	10	10
NCK1	0.013	0	-10000	0	-10000	0	0
receptor internalization	0.017	0.12	-10000	0	-0.46	25	25
Ephrin B/EPHB2/KALRN	-0.014	0.068	-10000	0	-0.46	10	10
ROCK1	-0.074	0.081	-10000	0	-10000	0	0
RAS family/GDP	-0.085	0.11	-10000	0	-0.52	3	3
Rac1/GTP	-0.16	0.2	-10000	0	-0.6	10	10
Ephrin B/EPHB1/Src/Paxillin	-0.11	0.18	-10000	0	-0.34	194	194

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.023	0.16	-10000	0	-0.47	27	27
TBX21	-0.12	0.44	-10000	0	-1.1	61	61
B2M	0.012	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.02	-10000	0	-10000	0	0
IL12RB1	-0.018	0.12	-10000	0	-0.37	44	44
GADD45B	-0.089	0.38	-10000	0	-1	52	52
IL12RB2	-0.017	0.16	-10000	0	-0.75	21	21
GADD45G	-0.072	0.34	-10000	0	-0.86	54	54
natural killer cell activation	0.003	0.022	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	-0.035	0.16	-10000	0	-0.41	58	58
IL2RA	-0.047	0.2	-10000	0	-0.58	49	49
IFNG	-0.11	0.28	-10000	0	-0.72	78	78
STAT3 (dimer)	-0.071	0.32	-10000	0	-0.74	65	65
HLA-DRB5	-0.041	0.13	-10000	0	-0.35	70	70
FASLG	-0.13	0.47	-10000	0	-1.2	64	64
NF kappa B2 p52/RelB	-0.17	0.32	-10000	0	-0.9	63	63
CD4	0.001	0.057	-10000	0	-0.32	15	15
SOCS1	0.009	0.048	-10000	0	-0.42	5	5
EntrezGene:6955	-0.007	0.015	-10000	0	-10000	0	0
CD3D	-0.1	0.27	-10000	0	-0.72	73	73
CD3E	-0.075	0.25	-10000	0	-0.75	54	54
CD3G	-0.15	0.33	-10000	0	-0.8	97	97
IL12Rbeta2/JAK2	-0.002	0.13	-10000	0	-0.64	19	19
CCL3	-0.1	0.43	-10000	0	-1.1	55	55
CCL4	-0.15	0.52	-10000	0	-1.4	63	63
HLA-A	0.011	0.022	-10000	0	-0.31	2	2
IL18/IL18R	-0.032	0.2	-10000	0	-0.57	46	46
NOS2	-0.086	0.34	-10000	0	-0.9	47	47
IL12/IL12R/TYK2/JAK2/SPHK2	-0.021	0.15	-10000	0	-0.44	27	27
IL1R1	-0.085	0.37	-10000	0	-0.95	54	54
IL4	0	0.027	-10000	0	-0.34	1	1
JAK2	0.014	0.044	-10000	0	-0.86	1	1
EntrezGene:6957	-0.006	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.24	0.56	-10000	0	-1.1	106	106
RAB7A	-0.039	0.29	-10000	0	-0.67	55	55
lysosomal transport	-0.034	0.28	-10000	0	-0.64	55	55
FOS	-0.41	0.65	-10000	0	-1.3	162	162
STAT4 (dimer)	-0.076	0.35	-10000	0	-0.83	61	61
STAT5A (dimer)	-0.22	0.36	-10000	0	-0.87	93	93
GZMA	-0.1	0.41	-10000	0	-1.1	55	55
GZMB	-0.099	0.39	-10000	0	-1	53	53
HLX	0.004	0.055	-10000	0	-0.31	14	14
LCK	-0.11	0.43	-10000	0	-0.98	69	69
TCR/CD3/MHC II/CD4	-0.19	0.35	-10000	0	-0.62	135	135
IL2/IL2R	-0.081	0.22	-10000	0	-0.67	47	47
MAPK14	-0.067	0.35	-10000	0	-0.8	64	64
CCR5	-0.096	0.41	-10000	0	-1.2	43	43
IL1B	-0.053	0.24	-10000	0	-0.83	40	40
STAT6	-0.003	0.11	-10000	0	-10000	0	0
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.049	-10000	0	-0.31	11	11
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
NFKB2	0.013	0	-10000	0	-10000	0	0
IL12B	-0.001	0.096	-10000	0	-0.58	10	10
CD8A	-0.05	0.22	-10000	0	-0.83	36	36
CD8B	-0.093	0.27	-10000	0	-0.73	69	69
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.023	0.16	0.46	27	-10000	0	27
IL2RB	-0.015	0.13	-10000	0	-0.51	26	26
proteasomal ubiquitin-dependent protein catabolic process	-0.064	0.32	-10000	0	-0.75	61	61
IL2RG	-0.047	0.19	-10000	0	-0.55	52	52
IL12	-0.057	0.22	-10000	0	-0.64	56	56
STAT5A	0.013	0	-10000	0	-10000	0	0
CD247	-0.026	0.16	-10000	0	-0.64	27	27
IL2	0.004	0.006	-10000	0	-10000	0	0
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.075	0.26	-10000	0	-0.8	54	54
IL12/IL12R/TYK2/JAK2	-0.12	0.48	-10000	0	-1.1	69	69
MAP2K3	-0.069	0.35	-10000	0	-0.79	64	64
RIPK2	0.013	0	-10000	0	-10000	0	0
MAP2K6	-0.076	0.36	-10000	0	-0.82	64	64
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.026	0.13	-10000	0	-0.4	44	44
IL18RAP	-0.023	0.18	-10000	0	-0.8	23	23
IL12Rbeta1/TYK2	-0.003	0.093	-10000	0	-0.64	4	4
EOMES	-0.14	0.43	-10000	0	-1.5	43	43
STAT1 (dimer)	-0.13	0.37	-10000	0	-0.77	94	94
T cell proliferation	-0.047	0.27	-10000	0	-0.61	58	58
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.027	0.15	-10000	0	-0.42	47	47
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.25	-10000	0	-0.69	61	61
ATF2	-0.069	0.33	-10000	0	-0.75	62	62

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.11	0.39	-9999	-1.3	43	43
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.035	0.11	-9999	-0.39	19	19
ATF2/c-Jun	-0.22	0.42	-9999	-0.96	112	112
MAPK11	-0.035	0.11	-9999	-0.39	19	19
MITF	-0.028	0.13	-9999	-0.4	43	43
MAPKAPK5	-0.028	0.13	-9999	-0.4	43	43
KRT8	-0.028	0.13	-9999	-0.48	19	19
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.048	0.17	-9999	-0.52	43	43
CEBPB	-0.028	0.13	-9999	-0.4	43	43
SLC9A1	-0.028	0.13	-9999	-0.4	43	43
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.07	0.19	-9999	-0.46	60	60
p38alpha-beta/MNK1	-0.025	0.14	-9999	-0.5	19	19
JUN	-0.21	0.42	-9999	-0.95	112	112
PPARGC1A	-0.23	0.25	-9999	-0.46	252	252
USF1	-0.028	0.13	-9999	-0.4	43	43
RAB5/GDP/GDI1	-0.038	0.084	-9999	-0.35	18	18
NOS2	-0.048	0.16	-9999	-0.66	8	8
DDIT3	-0.031	0.14	-9999	-0.41	43	43
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.012	0.11	-9999	-0.39	19	19
p38alpha-beta/HBP1	-0.025	0.14	-9999	-0.5	19	19
CREB1	-0.048	0.16	-9999	-0.46	43	43
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.015	0.12	-9999	-0.44	18	18
RPS6KA4	-0.028	0.13	-9999	-0.4	43	43
PLA2G4A	-0.049	0.2	-9999	-0.61	44	44
GDI1	-0.028	0.13	-9999	-0.4	43	43
TP53	-0.037	0.16	-9999	-0.5	43	43
RPS6KA5	-0.076	0.2	-9999	-0.46	86	86
ESR1	-0.065	0.21	-9999	-0.55	56	56
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.029	0.14	-9999	-0.4	44	44
MEF2A	-0.029	0.14	-9999	-0.4	44	44
EIF4EBP1	-0.048	0.16	-9999	-0.45	44	44
KRT19	-0.1	0.21	-9999	-0.55	55	55
ELK4	-0.028	0.13	-9999	-0.4	43	43
ATF6	-0.028	0.13	-9999	-0.4	43	43
ATF1	-0.049	0.16	-9999	-0.47	44	44
p38alpha-beta/MAPKAPK2	-0.025	0.14	-9999	-0.5	19	19
p38alpha-beta/MAPKAPK3	-0.025	0.14	-9999	-0.5	19	19

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.014	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.002	0.047	-9999	-1	1	1
forebrain development	-0.32	0.28	-9999	-0.56	254	254
GNAO1	-0.02	0.15	-9999	-0.72	20	20
SMO/beta Arrestin2	0.011	0.032	-9999	-0.63	1	1
SMO	0.006	0.038	-9999	-0.82	1	1
ARRB2	0.008	0.007	-9999	-10000	0	0
GLI3/SPOP	0.044	0.056	-9999	-10000	0	0
mol:GTP	-0.002	0.003	-9999	-10000	0	0
GSK3B	0.013	0	-9999	-10000	0	0
GNAI2	0.01	0.006	-9999	-10000	0	0
SIN3/HDAC complex	0.009	0.029	-9999	-0.5	1	1
GNAI1	0.008	0.039	-9999	-0.83	1	1
XPO1	0.008	0.008	-9999	-10000	0	0
GLI1/Su(fu)	-0.24	0.19	-9999	-0.51	134	134
SAP30	0.012	0.038	-9999	-0.82	1	1
mol:GDP	0.006	0.038	-9999	-0.82	1	1
MIM/GLI2A	-0.007	0.043	-9999	-0.31	1	1
IFT88	0.013	0	-9999	-10000	0	0
GNAI3	0.01	0.006	-9999	-10000	0	0
GLI2	0.033	0.062	-9999	-10000	0	0
GLI3	0.039	0.059	-9999	-0.3	13	13
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
SAP18	0.014	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.013	0	-9999	-10000	0	0
GNG2	0.012	0.038	-9999	-0.82	1	1
Gi family/GTP	0.008	0.071	-9999	-0.33	18	18
SIN3B	0.014	0.001	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.029	0.05	-9999	-10000	0	0
GLI2/Su(fu)	0.023	0.059	-9999	-10000	0	0
FOXA2	-0.66	0.66	-9999	-1.3	235	235
neural tube patterning	-0.32	0.28	-9999	-0.56	254	254
SPOP	0.013	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.018	0.022	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
CSNK1G3	0.013	0	-9999	-10000	0	0
MTSS1	-0.007	0.043	-9999	-0.31	1	1
embryonic limb morphogenesis	-0.32	0.28	-9999	-0.56	254	254
SUFU	0.016	0.021	-9999	-10000	0	0
LGALS3	-0.1	0.16	-9999	-0.31	173	173
catabolic process	0.061	0.069	-9999	-0.39	2	2
GLI3A/CBP	-0.2	0.2	-9999	-0.38	255	255
KIF3A	0.013	0	-9999	-10000	0	0
GLI1	-0.33	0.29	-9999	-0.57	254	254
RAB23	0.006	0.076	-9999	-0.82	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
IFT172	0.013	0	-9999	-10000	0	0
RBBP7	0.014	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.035	0.079	-9999	-0.4	1	1
GNAZ	0.01	0.006	-9999	-10000	0	0
RBBP4	0.009	0.065	-9999	-0.82	3	3
CSNK1G1	0.013	0	-9999	-10000	0	0
PIAS1	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GLI2/SPOP	0.038	0.058	-9999	-10000	0	0
STK36	0.008	0.008	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.013	0.063	-9999	-0.42	2	2
PTCH1	-0.28	0.27	-9999	-0.62	134	134
MIM/GLI1	-0.45	0.39	-9999	-0.76	247	247
CREBBP	-0.2	0.2	-9999	-0.38	255	255
Su(fu)/SIN3/HDAC complex	0.056	0.027	-9999	-10000	0	0

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.043	0.12	-9999	-0.46	28	28
alphaM/beta2 Integrin/GPIbA	-0.054	0.14	-9999	-0.51	35	35
alphaM/beta2 Integrin/proMMP-9	-0.092	0.19	-9999	-0.56	61	61
PLAUR	-0.088	0.15	-9999	-0.31	151	151
HMGB1	0.002	0.024	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.034	0.099	-9999	-0.43	20	20
AGER	-0.059	0.22	-9999	-0.8	37	37
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	-0.007	0.079	-9999	-0.31	30	30
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.12	0.19	-9999	-0.62	44	44
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.082	0.24	-9999	-0.57	79	79
CYR61	-0.24	0.38	-9999	-0.82	147	147
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.072	0.09	-9999	-0.46	8	8
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	-0.003	0.1	-9999	-0.59	13	13
MYH2	-0.1	0.12	-9999	-0.4	38	38
MST1R	0.001	0.096	-9999	-0.65	9	9
leukocyte activation during inflammatory response	-0.04	0.093	-9999	-0.46	10	10
APOB	-0.011	0.079	-9999	-0.31	31	31
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.001	0.1	-9999	-0.67	10	10
JAM3	0.013	0	-9999	-10000	0	0
GP1BA	-0.019	0.15	-9999	-0.63	24	24
alphaM/beta2 Integrin/CTGF	-0.11	0.22	-9999	-0.57	88	88
alphaM/beta2 Integrin	-0.095	0.11	-9999	-0.35	46	46
JAM3 homodimer	0.013	0	-9999	-10000	0	0
ICAM2	0.013	0	-9999	-10000	0	0
ICAM1	-0.083	0.15	-9999	-0.31	143	143
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.094	0.11	-9999	-0.35	46	46
cell adhesion	-0.053	0.14	-9999	-0.51	35	35
NFKB1	-0.13	0.3	-9999	-0.74	59	59
THY1	0.011	0.03	-9999	-0.31	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.014	0.051	-9999	-0.34	3	3
alphaM/beta2 Integrin/LRP/tPA	-0.034	0.1	-9999	-0.58	10	10
IL6	-0.23	0.46	-9999	-1.1	101	101
ITGB2	-0.018	0.086	-9999	-0.34	28	28
elevation of cytosolic calcium ion concentration	-0.14	0.16	-9999	-0.5	42	42
alphaM/beta2 Integrin/JAM2/JAM3	-0.031	0.1	-9999	-0.6	9	9
JAM2	0.006	0.077	-9999	-0.72	5	5
alphaM/beta2 Integrin/ICAM1	-0.068	0.12	-9999	-0.5	22	22
alphaM/beta2 Integrin/uPA/Plg	-0.098	0.12	-9999	-0.51	20	20
RhoA/GTP	-0.11	0.12	-9999	-0.42	40	40
positive regulation of phagocytosis	-0.07	0.12	-9999	-0.49	17	17
Ron/MSP	-0.011	0.077	-9999	-0.63	7	7
alphaM/beta2 Integrin/uPAR/uPA	-0.14	0.16	-9999	-0.5	42	42
alphaM/beta2 Integrin/uPAR	-0.084	0.13	-9999	-0.46	33	33
PLAU	-0.14	0.16	-9999	-0.31	225	225
PLAT	0.001	0.086	-9999	-0.48	12	12
actin filament polymerization	-0.1	0.11	-9999	-0.38	38	38
MST1	0.011	0.041	-9999	-0.57	2	2
alphaM/beta2 Integrin/lipoprotein(a)	-0.04	0.095	-9999	-0.51	8	8
TNF	-0.18	0.4	-9999	-0.98	79	79
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.11	0.13	-9999	-0.44	38	38
fibrinolysis	-0.097	0.12	-9999	-0.51	20	20
HCK	-0.008	0.08	-9999	-0.31	31	31
dendritic cell antigen processing and presentation	-0.094	0.11	-9999	-0.35	46	46
VTN	-0.069	0.24	-9999	-0.76	52	52
alphaM/beta2 Integrin/CYR61	-0.2	0.28	-9999	-0.59	154	154
LPA	-0.003	0.046	-9999	-0.31	10	10
LRP1	0.012	0.038	-9999	-0.82	1	1
cell migration	-0.088	0.2	-9999	-0.57	57	57
FN1	-0.22	0.15	-9999	-0.31	350	350
alphaM/beta2 Integrin/Thy1	-0.035	0.1	-9999	-0.42	21	21
MPO	-0.001	0.096	-9999	-0.65	9	9
KNG1	-0.014	0.077	-9999	-0.31	30	30
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.095	0.12	-9999	-0.39	37	37
ELA2	0	0	-9999	-10000	0	0
PLG	-0.003	0.035	-9999	-0.31	6	6
CTGF	-0.11	0.3	-9999	-0.82	71	71
alphaM/beta2 Integrin/Hck	-0.044	0.12	-9999	-0.47	30	30
ITGAM	-0.023	0.11	-9999	-0.39	30	30
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.045	0.13	-9999	-0.52	26	26
HP	-0.082	0.16	-9999	-0.34	131	131
leukocyte adhesion	-0.091	0.16	-9999	-0.61	26	26
SELP	-0.003	0.11	-9999	-0.59	13	13

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.057	0.21	-10000	0	-0.71	14	14
CRP	-0.063	0.22	-10000	0	-0.7	19	19
cell cycle arrest	-0.08	0.24	-10000	0	-0.73	32	32
TIMP1	-0.16	0.22	-10000	0	-0.59	44	44
IL6ST	-0.11	0.29	-10000	0	-0.82	69	69
Rac1/GDP	-0.088	0.25	-10000	0	-0.62	60	60
AP1	-0.19	0.32	-10000	0	-0.7	122	122
GAB2	0.014	0.001	-10000	0	-10000	0	0
TNFSF11	-0.099	0.23	-10000	0	-0.68	21	21
HSP90B1	0.022	0.043	-10000	0	-10000	0	0
GAB1	0.014	0	-10000	0	-10000	0	0
MAPK14	-0.099	0.3	-10000	0	-0.81	55	55
AKT1	0.053	0.057	-10000	0	-1.1	1	1
FOXO1	0.059	0.053	-10000	0	-0.98	1	1
MAP2K6	-0.1	0.29	-10000	0	-0.72	63	63
mol:GTP	0	0.001	-10000	0	-10000	0	0
MAP2K4	-0.076	0.24	-10000	0	-0.65	45	45
MITF	-0.09	0.26	-10000	0	-0.62	62	62
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.013	0	-10000	0	-10000	0	0
A2M	0.025	0.006	-10000	0	-10000	0	0
CEBPB	0.022	0.002	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.023	0.086	-10000	0	-0.49	1	1
STAT3	-0.093	0.25	-10000	0	-0.79	32	32
STAT1	-0.011	0.023	-10000	0	-10000	0	0
CEBPD	-0.057	0.21	-10000	0	-0.69	17	17
PIK3CA	0.01	0.066	-10000	0	-0.82	3	3
PI3K	0.019	0.051	-10000	0	-0.63	3	3
JUN	-0.18	0.35	-10000	0	-0.82	109	109
PIAS3/MITF	-0.078	0.25	-10000	0	-0.62	54	54
MAPK11	-0.099	0.3	-10000	0	-0.81	55	55
STAT3 (dimer)/FOXO1	-0.008	0.2	0.43	1	-0.58	22	23
GRB2/SOS1/GAB family	-0.11	0.2	-10000	0	-0.69	32	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.26	-10000	0	-0.56	84	84
GRB2	0.014	0	-10000	0	-10000	0	0
JAK2	0.012	0.038	-10000	0	-0.82	1	1
LBP	-0.061	0.2	-10000	0	-0.59	18	18
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.014	0.005	-10000	0	-10000	0	0
MYC	-0.072	0.27	-10000	0	-0.86	31	31
FGG	-0.066	0.22	-10000	0	-0.68	22	22
macrophage differentiation	-0.08	0.24	-10000	0	-0.73	32	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.18	0.29	-10000	0	-0.57	153	153
JUNB	-0.063	0.23	-10000	0	-0.75	25	25
FOS	-0.21	0.37	-10000	0	-0.82	129	129
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.1	0.28	-10000	0	-0.58	84	84
STAT1/PIAS1	-0.083	0.24	-10000	0	-0.55	67	67
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.061	-10000	0	-0.59	3	3
STAT3 (dimer)	-0.089	0.24	-10000	0	-0.76	32	32
PRKCD	-0.064	0.23	-10000	0	-0.64	39	39
IL6R	-0.015	0.15	-10000	0	-0.82	17	17
SOCS3	-0.12	0.37	-10000	0	-1	53	53
gp130 (dimer)/JAK1/JAK1/LMO4	-0.058	0.2	-10000	0	-0.55	69	69
Rac1/GTP	-0.11	0.24	-10000	0	-0.62	60	60
HCK	-0.008	0.08	-10000	0	-0.31	31	31
MAPKKK cascade	0.01	0.077	-10000	0	-0.98	1	1
bone resorption	-0.095	0.22	-10000	0	-0.64	23	23
IRF1	-0.057	0.21	-10000	0	-0.64	28	28
mol:GDP	-0.1	0.26	-10000	0	-0.62	67	67
SOS1	0.013	0.001	-10000	0	-10000	0	0
VAV1	-0.1	0.27	-10000	0	-0.64	67	67
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.11	0.3	-10000	0	-0.8	57	57
PTPN11	-0.011	0.059	-10000	0	-1.2	1	1
IL6/IL6RA	-0.15	0.29	-10000	0	-0.66	108	108
gp130 (dimer)/TYK2/TYK2/LMO4	-0.065	0.2	-10000	0	-0.55	69	69
gp130 (dimer)/JAK2/JAK2/LMO4	-0.066	0.2	-10000	0	-0.55	69	69
IL6	-0.17	0.33	-10000	0	-0.72	123	123
PIAS3	0.013	0	-10000	0	-10000	0	0
PTPRE	-0.083	0.15	-10000	0	-0.32	128	128
PIAS1	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.1	0.27	-10000	0	-0.46	137	137
LMO4	0.012	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.11	0.23	0.38	1	-0.78	32	33
MCL1	0.059	0.048	-10000	0	-0.88	1	1

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.081	0.063	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.13	0.18	-9999	-0.65	40	40
positive regulation of JNK cascade	-0.17	0.2	-9999	-0.61	69	69
Syndecan-4/ADAM12	-0.17	0.18	-9999	-0.65	41	41
CCL5	-0.045	0.21	-9999	-0.72	39	39
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
PLG	0	0.035	-9999	-0.31	4	4
ADAM12	-0.068	0.14	-9999	-0.31	121	121
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.065	0.045	-9999	-0.23	4	4
Syndecan-4/Laminin alpha1	-0.17	0.21	-9999	-0.68	49	49
Syndecan-4/CXCL12/CXCR4	-0.17	0.23	-9999	-0.65	69	69
Syndecan-4/Laminin alpha3	-0.15	0.19	-9999	-0.66	45	45
MDK	-0.087	0.15	-9999	-0.31	149	149
Syndecan-4/FZD7	-0.14	0.18	-9999	-0.64	42	42
Syndecan-4/Midkine	-0.18	0.19	-9999	-0.65	41	41
FZD7	0.006	0.076	-9999	-0.82	4	4
Syndecan-4/FGFR1/FGF	-0.13	0.16	-9999	-0.6	41	41
THBS1	-0.011	0.086	-9999	-0.31	36	36
integrin-mediated signaling pathway	-0.18	0.19	-9999	-0.66	40	40
positive regulation of MAPKKK cascade	-0.17	0.2	-9999	-0.61	69	69
Syndecan-4/TACI	-0.24	0.26	-9999	-0.64	120	120
CXCR4	0.012	0.021	-9999	-0.31	2	2
cell adhesion	-0.073	0.094	-9999	-0.44	24	24
Syndecan-4/Dynamin	-0.13	0.18	-9999	-0.65	40	40
Syndecan-4/TSP1	-0.14	0.18	-9999	-0.65	40	40
Syndecan-4/GIPC	-0.13	0.18	-9999	-0.65	40	40
Syndecan-4/RANTES	-0.16	0.22	-9999	-0.74	48	48
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.049	0.22	-9999	-0.81	37	37
LAMA3	-0.025	0.16	-9999	-0.59	31	31
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.013	0.18	-9999	-0.75	24	24
Syndecan-4/alpha-Actinin	-0.13	0.18	-9999	-0.65	40	40
TFPI	-0.035	0.2	-9999	-0.82	28	28
F2	-0.006	0.05	-9999	-0.31	12	12
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.17	0.21	-9999	-0.67	54	54
ACTN1	0.013	0.015	-9999	-0.31	1	1
TNC	-0.12	0.17	-9999	-0.82	4	4
Syndecan-4/CXCL12	-0.18	0.24	-9999	-0.68	70	70
FGF6	0	0.001	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.08	0.26	-9999	-0.82	54	54
TNFRSF13B	-0.19	0.35	-9999	-0.79	121	121
FGF2	0.013	0	-9999	-10000	0	0
FGFR1	0.012	0.038	-9999	-0.82	1	1
Syndecan-4/PI-4-5-P2	-0.14	0.18	-9999	-0.66	40	40
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.32	331	331
cell migration	-0.021	0.017	-9999	-10000	0	0
PRKCD	0.008	0.015	-9999	-10000	0	0
vasculogenesis	-0.14	0.17	-9999	-0.62	40	40
SDC4	-0.15	0.19	-9999	-0.7	40	40
Syndecan-4/Tenascin C	-0.19	0.2	-9999	-0.7	40	40
Syndecan-4/PI-4-5-P2/PKC alpha	-0.051	0.035	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.18	-9999	-0.65	40	40
MMP9	-0.084	0.24	-9999	-0.57	79	79
Rac1/GTP	-0.075	0.096	-9999	-0.46	24	24
cytoskeleton organization	-0.13	0.17	-9999	-0.62	40	40
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.16	0.21	-9999	-0.65	58	58

×

Thromboxane A2 receptor signaling

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
TGM2	-0.034	0.11	-10000	0	-0.32	67	67
GNB1/GNG2	-0.045	0.068	-10000	0	-0.2	48	48
AKT1	-0.014	0.1	-10000	0	-0.21	47	47
EGF	-0.11	0.29	-10000	0	-0.78	74	74
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.03	0.078	-10000	0	-0.65	2	2
mol:Ca2+	-0.045	0.15	-10000	0	-0.31	76	76
LYN	0.032	0.077	-10000	0	-0.65	2	2
RhoA/GTP	-0.031	0.045	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.045	0.16	-10000	0	-0.35	73	73
GNG2	0.012	0.038	-10000	0	-0.82	1	1
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.025	0.12	-10000	0	-0.54	11	11
G beta5/gamma2	-0.061	0.092	-10000	0	-0.27	48	48
PRKCH	-0.053	0.16	-10000	0	-0.36	74	74
DNM1	-0.017	0.15	-10000	0	-0.8	18	18
TXA2/TP beta/beta Arrestin3	-0.013	0.057	-10000	0	-0.3	17	17
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.025	0.17	-10000	0	-0.82	22	22
G12 family/GTP	-0.078	0.11	-10000	0	-0.31	73	73
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.013	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.019	0.1	0.36	16	-10000	0	16
mol:NADP	0.013	0	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.21	0.37	-10000	0	-0.82	131	131
mol:IP3	-0.06	0.18	-10000	0	-0.39	76	76
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.089	0.23	-10000	0	-0.53	76	76
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.098	0.2	-10000	0	-0.4	143	143
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.023	0.082	-10000	0	-0.65	2	2
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	0.003	0.092	-10000	0	-0.82	6	6
PRKCB1	-0.061	0.17	-10000	0	-0.39	76	76
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.086	0.23	-10000	0	-0.54	77	77
LCK	0.022	0.097	-10000	0	-0.55	7	7
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.02	0.091	-10000	0	-0.97	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.028	0.031	-10000	0	-0.38	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.019	0.09	-10000	0	-0.96	2	2
MAPK14	-0.02	0.11	-10000	0	-0.23	45	45
TGM2/GTP	-0.073	0.2	-10000	0	-0.43	76	76
MAPK11	-0.02	0.11	-10000	0	-0.23	47	47
ARHGEF1	-0.016	0.089	-10000	0	-0.19	17	17
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.058	0.18	-10000	0	-0.39	77	77
RAB11/GDP	0.013	0.001	-10000	0	-10000	0	0
ICAM1	-0.052	0.15	-10000	0	-0.3	82	82
cAMP biosynthetic process	-0.06	0.17	-10000	0	-0.36	76	76
Gq family/GTP/EBP50	-0.043	0.12	-10000	0	-0.25	119	119
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.031	0.077	-10000	0	-0.65	2	2
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.018	0.1	-10000	0	-0.31	16	16
VCAM1	-0.039	0.14	-10000	0	-0.3	76	76
TP beta/Gq family/GDP/G beta5/gamma2	-0.025	0.12	-10000	0	-0.54	11	11
platelet activation	-0.027	0.15	-10000	0	-0.3	72	72
PGI2/IP	-0.008	0.071	-10000	0	-0.64	6	6
PRKACA	-0.002	0.11	-10000	0	-0.43	26	26
Gq family/GDP/G beta5/gamma2	-0.027	0.12	-10000	0	-0.5	11	11
TXA2/TP beta/beta Arrestin2	-0.025	0.12	-10000	0	-0.66	17	17
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.006	0.11	-10000	0	-0.41	26	26
mol:DAG	-0.069	0.19	-10000	0	-0.43	76	76
EGFR	0.006	0.076	-10000	0	-0.82	4	4
TXA2/TP alpha	-0.083	0.22	-10000	0	-0.49	76	76
Gq family/GTP	-0.075	0.13	-10000	0	-0.3	119	119
YES1	0.032	0.077	-10000	0	-0.65	2	2
GNAI2/GTP	-0.017	0.078	-10000	0	-0.8	2	2
PGD2/DP	-0.029	0.13	-10000	0	-0.64	22	22
SLC9A3R1	0.012	0.021	-10000	0	-0.31	2	2
FYN	0.032	0.077	-10000	0	-0.65	2	2
mol:NO	0.013	0	-10000	0	-10000	0	0
GNA15	-0.013	0.093	-10000	0	-0.33	37	37
PGK/cGMP	-0.15	0.25	-10000	0	-0.56	131	131
RhoA/GDP	0.013	0.001	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.032	0.1	-10000	0	-0.66	6	6
NOS3	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.065	0.18	-10000	0	-0.4	79	79
PRKCB	-0.063	0.17	-10000	0	-0.38	77	77
PRKCE	-0.055	0.17	-10000	0	-0.38	74	74
PRKCD	-0.056	0.17	-10000	0	-0.39	74	74
PRKCG	-0.06	0.18	-10000	0	-0.4	74	74
muscle contraction	-0.075	0.22	-10000	0	-0.49	77	77
PRKCZ	-0.045	0.16	-10000	0	-0.35	73	73
ARR3	0.004	0.006	-10000	0	-10000	0	0
TXA2/TP beta	-0.02	0.092	-10000	0	-0.98	2	2
PRKCQ	-0.054	0.17	-10000	0	-0.36	77	77
MAPKKK cascade	-0.076	0.21	-10000	0	-0.47	77	77
SELE	-0.059	0.18	-10000	0	-0.43	74	74
TP beta/GNAI2/GDP/G beta/gamma	-0.019	0.095	-10000	0	-1.1	2	2
ROCK1	0.013	0	-10000	0	-10000	0	0
GNA14	-0.18	0.35	-10000	0	-0.82	112	112
chemotaxis	-0.099	0.26	-10000	0	-0.62	76	76
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	-0.002	0.11	-10000	0	-0.82	9	9
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin 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
HRAS	0.012	0.021	-9999	-0.31	2	2
EGFR	0.006	0.076	-9999	-0.82	4	4
EGF/EGFR	-0.076	0.17	-9999	-0.46	78	78
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.07	0.16	-9999	-0.46	72	72
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.01	0.046	-9999	-0.44	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
EGF/EGFR dimer/SHC	-0.083	0.19	-9999	-0.55	72	72
mol:GDP	-0.069	0.16	-9999	-0.46	72	72
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.003	0.087	-9999	-0.68	7	7
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.064	0.15	-9999	-0.42	72	72
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.065	0.15	-9999	-0.43	72	72
FRAP1	-0.034	0.17	-9999	-0.44	72	72
EGF/EGFR dimer	-0.096	0.22	-9999	-0.63	72	72
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.01	0.072	-9999	-0.63	6	6

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.034	0.15	-9999	-0.48	38	38
NF kappa B1 p50/RelA/I kappa B alpha	-0.056	0.12	-9999	-0.55	9	9
alphaV/beta3 Integrin/Osteopontin/Src	-0.067	0.15	-9999	-0.62	24	24
AP1	-0.26	0.35	-9999	-0.84	112	112
ILK	-0.034	0.16	-9999	-0.5	38	38
bone resorption	-0.048	0.16	-9999	-0.67	12	12
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.054	0.13	-9999	-0.46	38	38
ITGAV	0.01	0.054	-9999	-0.82	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.027	0.13	-9999	-0.63	21	21
alphaV/beta3 Integrin/Osteopontin	-0.072	0.16	-9999	-0.57	38	38
MAP3K1	-0.035	0.16	-9999	-0.51	38	38
JUN	-0.17	0.35	-9999	-0.82	109	109
MAPK3	-0.035	0.15	-9999	-0.47	38	38
MAPK1	-0.035	0.15	-9999	-0.47	38	38
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.032	0.17	-9999	-0.52	43	43
ITGB3	-0.014	0.15	-9999	-0.82	16	16
NFKBIA	-0.028	0.15	-9999	-0.46	38	38
FOS	-0.21	0.37	-9999	-0.82	129	129
CD44	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.11	0.18	-9999	-0.68	6	6
NF kappa B1 p50/RelA	-0.062	0.11	-9999	-0.55	8	8
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.023	0.13	-9999	-0.69	16	16
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.034	0.16	-9999	-0.51	38	38
VAV3	-0.029	0.16	-9999	-0.49	43	43
MAP3K14	-0.042	0.16	-9999	-0.51	38	38
ROCK2	-0.023	0.17	-9999	-0.82	21	21
SPP1	-0.082	0.2	-9999	-0.42	108	108
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.056	0.13	-9999	-0.44	43	43
MMP2	-0.18	0.29	-9999	-0.67	99	99

×

FAS signaling pathway (CD95)

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
SPTAN1	0.024	0.077	0.29	35	-10000	0	35
RFC1	0.024	0.077	0.29	35	-10000	0	35
PRKDC	0.024	0.077	0.29	35	-10000	0	35
RIPK1	0.014	0.004	-10000	0	-10000	0	0
CASP7	-0.013	0.044	0.2	3	-10000	0	3
FASLG/FAS/FADD/FAF1	-0.028	0.1	0.26	4	-0.37	32	36
MAP2K4	-0.023	0.16	-10000	0	-0.4	35	35
mol:ceramide	-0.022	0.14	-10000	0	-0.48	33	33
GSN	0.024	0.077	0.29	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 8	-0.019	0.13	-10000	0	-0.47	32	32
FAS	0.011	0.006	-10000	0	-10000	0	0
BID	-0.033	0.08	0.32	3	-10000	0	3
MAP3K1	0.004	0.097	-10000	0	-0.28	15	15
MAP3K7	0.01	0.006	-10000	0	-10000	0	0
RB1	0.023	0.078	0.29	34	-0.32	1	35
CFLAR	0.014	0.004	-10000	0	-10000	0	0
HGF/MET	-0.15	0.22	-10000	0	-0.62	76	76
ARHGDIB	0.021	0.081	0.29	35	-10000	0	35
FADD	0.011	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.024	0.077	-10000	0	-0.29	35	35
NFKB1	-0.053	0.093	-10000	0	-0.32	16	16
MAPK8	-0.058	0.22	-10000	0	-0.45	102	102
DFFA	0.024	0.077	0.29	35	-10000	0	35
DNA fragmentation during apoptosis	0.024	0.077	0.29	35	-10000	0	35
FAS/FADD/MET	-0.059	0.077	-10000	0	-10000	0	0
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.002	0.088	-10000	0	-0.39	20	20
FAF1	0.011	0.007	-10000	0	-10000	0	0
PARP1	0.024	0.077	0.29	35	-10000	0	35
DFFB	0.024	0.077	0.29	35	-10000	0	35
CHUK	-0.045	0.082	-10000	0	-0.73	1	1
FASLG	-0.058	0.22	-10000	0	-0.66	50	50
FAS/FADD	0	0.001	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	74	74
LMNA	0.022	0.07	0.26	35	-10000	0	35
CASP6	0.024	0.077	0.29	35	-10000	0	35
CASP10	0.011	0.006	-10000	0	-10000	0	0
CASP3	0.029	0.094	0.35	38	-10000	0	38
PTPN13	0.005	0.084	-10000	0	-0.82	5	5
CASP8	0.008	0.044	0.46	3	-10000	0	3
IL6	-0.26	0.56	-10000	0	-1.4	98	98
MET	-0.11	0.16	-10000	0	-0.31	180	180
ICAD/CAD	0.023	0.072	0.27	35	-10000	0	35
FASLG/FAS/FADD/FAF1/Caspase 10	-0.022	0.15	-10000	0	-0.49	33	33
activation of caspase activity by cytochrome c	-0.033	0.08	0.32	3	-10000	0	3
PAK2	0.024	0.077	0.29	35	-10000	0	35
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.075	0.098	-10000	0	-10000	0	0
CRKL	-0.032	0.11	-10000	0	-0.33	26	26
mol:PIP3	-0.019	0.033	0.69	1	-10000	0	1
AKT1	0.001	0.04	0.45	1	-0.53	2	3
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	-0.023	0.11	-10000	0	-10000	0	0
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
HGF/MET/SHIP2	-0.14	0.21	-10000	0	-0.6	74	74
MAP3K5	-0.019	0.11	-10000	0	-0.48	5	5
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.12	0.19	-10000	0	-0.55	74	74
AP1	-0.28	0.42	-10000	0	-0.87	152	152
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.26	0.4	-10000	0	-0.85	152	152
STAT3 (dimer)	-0.041	0.13	-10000	0	-0.34	74	74
GAB1/CRKL/SHP2/PI3K	-0.043	0.095	-10000	0	-0.7	2	2
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
CBL/CRK	-0.023	0.11	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1
ELK1	-0.049	0.062	-10000	0	-10000	0	0
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.04	0.073	-10000	0	-0.24	27	27
PAK1	0.009	0.038	0.42	1	-0.5	2	3
HGF/MET/RANBP10	-0.14	0.21	-10000	0	-0.6	74	74
HRAS	-0.06	0.16	-10000	0	-0.43	74	74
DOCK1	-0.026	0.12	-10000	0	-0.55	4	4
GAB1	-0.042	0.12	-10000	0	-0.3	74	74
CRK	-0.032	0.11	-10000	0	-0.33	26	26
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.11	0.21	-10000	0	-0.6	74	74
JUN	-0.17	0.35	-10000	0	-0.82	109	109
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.072	0.1	-10000	0	-0.29	74	74
PIK3R1	0.013	0	-10000	0	-10000	0	0
cell morphogenesis	-0.012	0.14	-10000	0	-0.65	2	2
GRB2/SHC	-0.039	0.097	-10000	0	-0.3	26	26
FOS	-0.21	0.37	-10000	0	-0.82	129	129
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.049	0.062	-10000	0	-10000	0	0
HGF/MET/MUC20	-0.14	0.21	-10000	0	-0.61	74	74
cell migration	-0.055	0.085	-10000	0	-0.3	26	26
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.013	0	-10000	0	-10000	0	0
MET/RANBP10	-0.075	0.098	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.052	0.14	-10000	0	-0.36	74	74
MET/MUC20	-0.079	0.1	-10000	0	-0.21	180	180
RAP1B	-0.013	0.1	-10000	0	-10000	0	0
RAP1A	-0.013	0.1	-10000	0	-10000	0	0
HGF/MET/RANBP9	-0.14	0.21	-10000	0	-0.6	74	74
RAF1	-0.049	0.16	-10000	0	-0.45	27	27
STAT3	-0.041	0.13	-10000	0	-0.34	74	74
cell proliferation	-0.049	0.18	-10000	0	-0.45	74	74
RPS6KB1	-0.015	0.04	-10000	0	-10000	0	0
MAPK3	-0.05	0.057	-10000	0	-10000	0	0
MAPK1	-0.05	0.057	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.007	0.13	-10000	0	-0.59	13	13
SRC	-0.041	0.13	-10000	0	-0.39	26	26
PI3K	-0.042	0.1	-10000	0	-0.32	29	29
MET/Glomulin	-0.059	0.094	-10000	0	-10000	0	0
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.038	0.14	-10000	0	-0.42	27	27
MET	-0.11	0.16	-10000	0	-0.31	180	180
MAP4K1	-0.028	0.12	-10000	0	-0.34	30	30
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.038	0.14	-10000	0	-0.42	27	27
BAD	0.009	0.038	0.42	1	-0.5	2	3
MAP2K4	-0.01	0.1	-10000	0	-0.43	5	5
SHP2/GRB2/SOS1/GAB1	-0.058	0.091	-10000	0	-0.38	1	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	-0.049	0.1	-10000	0	-0.26	74	74
PLCgamma1/PKC	0	0	-10000	0	-10000	0	0
HGF	-0.11	0.3	-10000	0	-0.82	74	74
RASA1	0.013	0	-10000	0	-10000	0	0
NCK1	0.013	0	-10000	0	-10000	0	0
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.042	0.11	-10000	0	-0.33	26	26
PDPK1	-0.009	0.044	0.52	1	-0.58	2	3
HGF/MET/SHIP	-0.15	0.21	-10000	0	-0.6	74	74

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.095	0.22	-9999	-0.54	44	44
MAP3K8	-0.003	0.11	-9999	-0.83	8	8
FOS	-0.059	0.17	-9999	-0.5	35	35
PRKCA	-0.031	0.18	-9999	-0.83	24	24
PTPN7	-0.044	0.17	-9999	-0.46	57	57
HRAS	0.011	0.021	-9999	-0.32	2	2
PRKCB	-0.03	0.13	-9999	-0.36	52	52
NRAS	0.013	0.002	-9999	-10000	0	0
RAS family/GTP	-0.001	0.009	-9999	-10000	0	0
MAPK3	-0.031	0.12	-9999	-0.42	28	28
MAP2K1	-0.027	0.16	-9999	-0.59	28	28
ELK1	0.008	0.011	-9999	-10000	0	0
BRAF	-0.046	0.14	-9999	-0.57	28	28
mol:GTP	-0.001	0.003	-9999	-0.006	128	128
MAPK1	-0.031	0.12	-9999	-0.52	17	17
RAF1	-0.046	0.14	-9999	-0.57	28	28
KRAS	0.013	0.002	-9999	-10000	0	0

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.036	0.12	-10000	0	-0.51	27	27
ER alpha/Gai/GDP/Gbeta gamma	0.005	0.15	-10000	0	-0.48	36	36
AKT1	-0.016	0.21	-10000	0	-0.86	26	26
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.015	0.21	-10000	0	-0.87	26	26
mol:Ca2+	-0.099	0.23	-10000	0	-0.5	114	114
IGF1R	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.072	0.18	-10000	0	-0.58	52	52
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.013	0.2	0.81	26	-10000	0	26
RhoA/GTP	-0.027	0.091	-10000	0	-0.41	24	24
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.037	0.13	-10000	0	-0.59	24	24
regulation of stress fiber formation	-0.013	0.12	0.47	4	-10000	0	4
E2/ERA-ERB (dimer)	-0.042	0.14	-10000	0	-0.57	27	27
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	-0.035	0.11	-10000	0	-0.51	24	24
pseudopodium formation	0.013	0.12	-10000	0	-0.47	4	4
E2/ER alpha (dimer)/PELP1	-0.038	0.12	-10000	0	-0.55	24	24
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.82	1	1
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
HRAS	0.012	0.021	-10000	0	-0.31	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.011	0.15	-10000	0	-0.58	26	26
E2/ER beta (dimer)	-0.005	0.058	-10000	0	-0.64	4	4
mol:GDP	-0.037	0.13	-10000	0	-0.56	27	27
mol:NADP	0.011	0.15	-10000	0	-0.58	26	26
PIK3R1	0.013	0	-10000	0	-10000	0	0
mol:IP3	-0.1	0.24	-10000	0	-0.52	114	114
IGF-1R heterotetramer	0.013	0	-10000	0	-10000	0	0
PLCB1	-0.11	0.24	-10000	0	-0.54	114	114
PLCB2	-0.11	0.25	-10000	0	-0.54	113	113
IGF1	-0.18	0.35	-10000	0	-0.8	119	119
mol:L-citrulline	0.011	0.15	-10000	0	-0.58	26	26
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.027	0.14	-10000	0	-0.78	16	16
JNK cascade	-0.005	0.058	-10000	0	-0.64	4	4
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	0.006	0.076	-10000	0	-0.82	4	4
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.049	0.19	-10000	0	-0.54	55	55
Gq family/GDP/Gbeta gamma	-0.055	0.17	-10000	0	-0.53	22	22
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.082	-10000	0	-0.36	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.037	0.13	-10000	0	-0.59	24	24
GNAZ	0.013	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.045	0.14	-10000	0	-0.64	24	24
STRN	-0.038	0.2	-10000	0	-0.82	30	30
GNAL	-0.092	0.28	-10000	0	-0.82	61	61
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	0.015	0.052	-10000	0	-0.55	4	4
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1
HBEGF	-0.005	0.16	-10000	0	-0.52	29	29
cAMP biosynthetic process	-0.09	0.19	-10000	0	-0.48	84	84
SRC	0.013	0.14	-10000	0	-0.5	25	25
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.032	0.12	-10000	0	-0.5	27	27
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-10000	0	-0.53	39	39
Gs family/GTP	-0.092	0.19	-10000	0	-0.49	84	84
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.009	-10000	0	-10000	0	0
vasodilation	0.012	0.14	-10000	0	-0.55	26	26
mol:DAG	-0.1	0.24	-10000	0	-0.52	114	114
Gs family/GDP/Gbeta gamma	-0.074	0.16	-10000	0	-0.41	84	84
MSN	0.012	0.12	-10000	0	-0.52	4	4
Gq family/GTP	-0.15	0.24	-10000	0	-0.57	113	113
mol:PI-3-4-5-P3	-0.013	0.2	-10000	0	-0.83	26	26
NRAS	0.013	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.012	0.14	0.55	26	-10000	0	26
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.034	0.12	-10000	0	-0.52	27	27
NOS3	0.01	0.16	-10000	0	-0.62	26	26
GNA11	-0.002	0.11	-10000	0	-0.82	9	9
MAPKKK cascade	-0.009	0.2	-10000	0	-0.55	52	52
E2/ER alpha (dimer)/PELP1/Src	-0.04	0.14	-10000	0	-0.62	24	24
ruffle organization	0.013	0.12	-10000	0	-0.47	4	4
ROCK2	0.002	0.13	-10000	0	-0.44	21	21
GNA14	-0.18	0.35	-10000	0	-0.82	112	112
GNA15	-0.013	0.093	-10000	0	-0.33	37	37
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.027	0.19	-10000	0	-0.52	46	46
MMP2	0.014	0.15	-10000	0	-0.49	29	29

×

Regulation of Androgen receptor activity

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
HDAC1	0.021	0.005	-9999	-10000	0	0
SMARCC1	0.013	0.014	-9999	-10000	0	0
REL	-0.033	0.2	-9999	-0.82	30	30
HDAC7	-0.031	0.14	-9999	-0.63	15	15
JUN	-0.18	0.35	-9999	-0.82	109	109
EP300	0.013	0.001	-9999	-10000	0	0
KAT2B	0.013	0.001	-9999	-10000	0	0
KAT5	0.014	0.001	-9999	-10000	0	0
MAPK14	-0.002	0.095	-9999	-0.64	10	10
FOXO1	0.012	0.001	-9999	-10000	0	0
T-DHT/AR	-0.044	0.15	-9999	-0.65	17	17
MAP2K6	-0.009	0.12	-9999	-0.78	11	11
BRM/BAF57	-0.001	0.003	-9999	-10000	0	0
MAP2K4	0.009	0.007	-9999	-10000	0	0
SMARCA2	0.009	0.007	-9999	-10000	0	0
PDE9A	0.011	0.057	-9999	-10000	0	0
NCOA2	-0.069	0.24	-9999	-0.83	44	44
CEBPA	0.006	0.084	-9999	-0.82	5	5
EHMT2	0.009	0.006	-9999	-10000	0	0
cell proliferation	-0.067	0.15	-9999	-0.54	15	15
NR0B1	-0.002	0.041	-9999	-0.31	8	8
EGR1	-0.17	0.34	-9999	-0.83	103	103
RXRs/9cRA	-0.13	0.059	-9999	-0.5	4	4
AR/RACK1/Src	-0.11	0.16	-9999	-0.66	17	17
AR/GR	-0.13	0.2	-9999	-0.37	126	126
GNB2L1	0.007	0.007	-9999	-10000	0	0
PKN1	0.013	0.001	-9999	-10000	0	0
RCHY1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.006	0.005	-9999	-10000	0	0
MAPK8	0	0.089	-9999	-0.64	9	9
T-DHT/AR/TIF2/CARM1	-0.12	0.23	-9999	-0.69	52	52
SRC	-0.003	0.11	-9999	-0.54	17	17
NR3C1	0.013	0	-9999	-10000	0	0
KLK3	-0.4	0.57	-9999	-1.3	139	139
APPBP2	0.013	0.004	-9999	-10000	0	0
TRIM24	0.009	0.007	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.053	0.14	-9999	-0.66	17	17
TMPRSS2	-0.06	0.32	-9999	-1.2	32	32
RXRG	-0.28	0.12	-9999	-0.32	430	430
mol:9cRA	-0.002	0.002	-9999	-10000	0	0
RXRA	0.012	0.001	-9999	-10000	0	0
RXRB	0.012	0.001	-9999	-10000	0	0
CARM1	0.007	0.007	-9999	-10000	0	0
NR2C2	-0.003	0.11	-9999	-0.82	9	9
KLK2	-0.48	0.43	-9999	-0.83	284	284
AR	-0.15	0.22	-9999	-0.38	206	206
SENP1	0.012	0.002	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
MDM2	0.022	0.014	-9999	-10000	0	0
SRY	0.009	0.015	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
MYST2	0.014	0.002	-9999	-10000	0	0
HOXB13	-0.015	0.054	-9999	-0.32	13	13
T-DHT/AR/RACK1/Src	-0.076	0.15	-9999	-0.66	17	17
positive regulation of transcription	0.013	0.015	-9999	-0.31	1	1
DNAJA1	0.013	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.005	-9999	-10000	0	0
NCOA1	0.013	0.009	-9999	-10000	0	0
SPDEF	-0.027	0.1	-9999	-0.32	53	53
T-DHT/AR/TIF2	-0.053	0.16	-9999	-0.45	46	46
T-DHT/AR/Hsp90	-0.055	0.14	-9999	-0.66	17	17
GSK3B	0.01	0.006	-9999	-10000	0	0
NR2C1	0.015	0.003	-9999	-10000	0	0
mol:T-DHT	-0.005	0.12	-9999	-0.57	17	17
SIRT1	0.011	0.038	-9999	-0.82	1	1
ZMIZ2	0.023	0.015	-9999	-10000	0	0
POU2F1	0.031	0.02	-9999	-0.3	1	1
T-DHT/AR/DAX-1	-0.074	0.14	-9999	-0.67	17	17
CREBBP	0.013	0.001	-9999	-10000	0	0
SMARCE1	0.009	0.007	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.12	0.1	-9999	-0.65	7	7
EPHB2	0.008	0.066	-9999	-0.82	3	3
Syndecan-2/TACI	-0.13	0.25	-9999	-0.56	118	118
LAMA1	-0.049	0.22	-9999	-0.81	37	37
Syndecan-2/alpha2 ITGB1	-0.072	0.11	-9999	-0.47	24	24
HRAS	0.012	0.021	-9999	-0.31	2	2
Syndecan-2/CASK	-0.008	0.066	-9999	-0.55	7	7
ITGA5	0.013	0	-9999	-10000	0	0
BAX	0.025	0.097	-9999	-0.75	1	1
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.007	0.059	-9999	-0.5	7	7
LAMA3	-0.025	0.16	-9999	-0.59	31	31
EZR	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.008	0.066	-9999	-0.82	3	3
Syndecan-2/MMP2	0.008	0.1	-9999	-0.58	13	13
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.079	0.099	-9999	-10000	0	0
dendrite morphogenesis	0.014	0.081	-9999	-0.54	10	10
Syndecan-2/GM-CSF	-0.11	0.099	-9999	-0.57	7	7
determination of left/right symmetry	0.012	0.078	-9999	-0.63	7	7
Syndecan-2/PKC delta	0.018	0.068	-9999	-0.54	7	7
GNB2L1	0.013	0	-9999	-10000	0	0
MAPK3	-0.087	0.092	-9999	-0.51	7	7
MAPK1	-0.087	0.092	-9999	-0.51	7	7
Syndecan-2/RACK1	-0.007	0.056	-9999	-0.47	7	7
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.012	0.078	-9999	-0.63	7	7
ITGA2	-0.12	0.16	-9999	-0.31	191	191
MAPK8	0.018	0.1	-9999	-0.55	16	16
Syndecan-2/alpha2/beta1 Integrin	-0.087	0.14	-9999	-0.51	40	40
Syndecan-2/Kininogen	-0.007	0.079	-9999	-0.55	7	7
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.031	0.058	-9999	-0.44	7	7
Syndecan-2/CASK/Protein 4.1	-0.007	0.06	-9999	-0.5	7	7
extracellular matrix organization	0.015	0.071	-9999	-0.54	7	7
actin cytoskeleton reorganization	-0.12	0.1	-9999	-0.65	7	7
Syndecan-2/Caveolin-2/Ras	-0.011	0.077	-9999	-0.55	9	9
Syndecan-2/Laminin alpha3	-0.008	0.13	-9999	-0.55	24	24
Syndecan-2/RasGAP	-0.007	0.053	-9999	-0.44	7	7
alpha5/beta1 Integrin	0	0	-9999	-10000	0	0
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.014	0.081	-9999	-0.55	10	10
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.057	-9999	-0.42	7	7
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.19	0.35	-9999	-0.79	121	121
RASA1	0.013	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.079	0.099	-9999	-10000	0	0
Syndecan-2/Synbindin	0.018	0.068	-9999	-0.54	7	7
TGFB1	0.008	0.042	-9999	-0.31	8	8
CASP3	0.027	0.063	-9999	-0.49	7	7
FN1	-0.22	0.15	-9999	-0.31	350	350
Syndecan-2/IL8	-0.037	0.12	-9999	-0.55	17	17
SDC2	0.012	0.078	-9999	-0.63	7	7
KNG1	-0.014	0.077	-9999	-0.31	30	30
Syndecan-2/Neurofibromin	0.018	0.068	-9999	-0.54	7	7
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.21	0.15	-9999	-0.31	329	329
Syndecan-2/TGFB1	0.015	0.071	-9999	-0.54	7	7
Syndecan-2/Syntenin/PI-4-5-P2	-0.007	0.06	-9999	-0.5	7	7
Syndecan-2/Ezrin	-0.007	0.059	-9999	-0.49	7	7
PRKACA	0.027	0.063	-9999	-0.49	7	7
angiogenesis	-0.037	0.12	-9999	-0.54	17	17
MMP2	-0.001	0.1	-9999	-0.67	10	10
IL8	-0.081	0.18	-9999	-0.36	124	124
calcineurin-NFAT signaling pathway	-0.12	0.25	-9999	-0.56	118	118

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.005	0.12	-9999	-0.78	11	11
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.15	0.15	-9999	-0.28	281	281
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	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	0.013	0	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
MAP3K12	0.013	0	-9999	-10000	0	0
FGR	0.011	0.03	-9999	-0.31	4	4
p38 alpha/TAB1	-0.047	0.068	-9999	-0.3	6	6
PRKG1	-0.21	0.37	-9999	-0.82	131	131
DUSP8	0.002	0.083	-9999	-0.82	4	4
PGK/cGMP/p38 alpha	-0.16	0.2	-9999	-0.47	134	134
apoptosis	-0.046	0.066	-9999	-0.29	6	6
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.12	0.31	-9999	-0.82	78	78
PAK1	0.013	0	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1/OSM/MEKK3/MKK3	0	0.006	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
RAC1	0.013	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	0.013	0.015	-9999	-0.31	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	-0.06	0.13	-9999	-0.37	15	15
BLK	-0.25	0.38	-9999	-0.76	164	164
HCK	-0.008	0.08	-9999	-0.31	31	31
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.013	0	-9999	-10000	0	0
DUSP10	0.01	0.043	-9999	-0.48	3	3
TRAF6/MEKK3	-0.002	0.033	-9999	-0.51	2	2
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.027	0.092	-9999	-0.34	5	5
positive regulation of innate immune response	-0.059	0.14	-9999	-0.41	12	12
LCK	-0.01	0.11	-9999	-0.44	25	25
p38alpha-beta/MKP7	-0.049	0.13	-9999	-0.47	5	5
p38alpha-beta/MKP5	-0.05	0.13	-9999	-0.48	7	7
PGK/cGMP	-0.17	0.28	-9999	-0.64	131	131
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.11	0.2	-9999	-0.49	74	74
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.47	0.41	-9999	-0.82	281	281

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.005	-9999	-10000	0	0
RAS family/GTP	-0.042	0.1	-9999	-0.38	21	21
NFATC4	-0.001	0.11	-9999	-0.34	17	17
ERBB2IP	0.014	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.013	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.047	0.13	-9999	-0.41	55	55
JUN	0.002	0.096	-9999	-0.27	12	12
HRAS	0.011	0.021	-9999	-0.32	2	2
DOCK7	-0.016	0.14	-9999	-0.38	58	58
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.056	0.16	-9999	-0.49	55	55
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.023	0.064	-9999	-0.32	3	3
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.026	0.15	-9999	-0.44	55	55
RAF1	-0.004	0.13	-9999	-0.4	21	21
ErbB2/ErbB3/neuregulin 2	-0.069	0.18	-9999	-0.52	64	64
STAT3	0	0.003	-9999	-10000	0	0
cell migration	0.022	0.083	-9999	-0.31	5	5
mol:PI-3-4-5-P3	0	0.002	-9999	-10000	0	0
cell proliferation	-0.13	0.33	-9999	-0.68	114	114
FOS	-0.11	0.28	-9999	-0.52	152	152
NRAS	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	-0.047	0.13	-9999	-0.41	55	55
MAPK3	-0.084	0.25	-9999	-0.5	111	111
MAPK1	-0.084	0.25	-9999	-0.5	110	110
JAK2	-0.014	0.14	-9999	-0.38	56	56
NF2	-0.002	0.006	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.016	0.13	-9999	-0.38	55	55
NRG1	-0.069	0.24	-9999	-0.8	48	48
GRB2/SOS1	0	0	-9999	-10000	0	0
MAPK8	-0.014	0.13	-9999	-0.35	63	63
MAPK9	-0.023	0.062	-9999	-0.26	2	2
ERBB2	0	0	-9999	-10000	0	0
ERBB3	-0.008	0.12	-9999	-0.74	12	12
SHC1	0.013	0.002	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
apoptosis	0.003	0.01	-9999	-10000	0	0
STAT3 (dimer)	0	0.003	-9999	-10000	0	0
RNF41	0.027	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.033	0.088	-9999	-0.38	2	2
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.057	0.2	-9999	-0.39	93	93
myelination	0.008	0.11	-9999	-0.32	25	25
PPP3CB	-0.012	0.13	-9999	-0.36	55	55
KRAS	0.013	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.025	0.11	-9999	-0.65	2	2
NRG2	-0.082	0.26	-9999	-0.8	57	57
mol:GDP	-0.016	0.13	-9999	-0.37	55	55
SOS1	0.013	0.001	-9999	-10000	0	0
MAP2K2	-0.006	0.14	-9999	-0.41	21	21
SRC	0.013	0.015	-9999	-0.31	1	1
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.015	0.14	-9999	-0.38	56	56
MAP2K1	-0.077	0.23	-9999	-0.58	33	33
heart morphogenesis	-0.047	0.13	-9999	-0.41	55	55
RAS family/GDP	-0.036	0.1	-9999	-0.64	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
PRKACA	-0.003	0.009	-9999	-10000	0	0
CHRNE	0.01	0.034	-9999	-0.13	17	17
HSP90AA1	0.013	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.047	0.13	-9999	-0.41	55	55
CDC42	0.013	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.038	0.038	-9999	-10000	0	0
VDR	0.013	0.015	-9999	-10000	0	0
FAM120B	0.013	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.059	0.11	-9999	-0.35	48	48
RXRs/LXRs/DNA/Oxysterols	-0.049	0.16	-9999	-0.46	58	58
MED1	0.013	0	-9999	-10000	0	0
mol:9cRA	0	0.017	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.022	0.083	-9999	-0.34	23	23
RXRs/NUR77	-0.26	0.25	-9999	-0.63	145	145
RXRs/PPAR	-0.055	0.065	-9999	-0.4	11	11
NCOR2	0.013	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-9999	-10000	0	0
RARs/VDR/DNA/Vit D3	-0.013	0.078	-9999	-0.48	13	13
RARA	0.013	0	-9999	-10000	0	0
NCOA1	0.013	0	-9999	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-9999	-10000	0	0
RARs/RARs/DNA/9cRA	-0.012	0.077	-9999	-0.48	13	13
RARG	0.013	0	-9999	-10000	0	0
RPS6KB1	0.054	0.031	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.022	0.083	-9999	-0.34	23	23
THRA	0.013	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0	0.01	-9999	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	-0.12	0.083	-9999	-0.53	5	5
NR1H4	0	0.036	-9999	-0.31	6	6
RXRs/LXRs/DNA	-0.098	0.093	-9999	-0.58	4	4
NR1H2	0.016	0.012	-9999	-10000	0	0
NR1H3	0.015	0.014	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.11	0.068	-9999	-0.52	4	4
NR4A1	-0.23	0.38	-9999	-0.82	143	143
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.048	0.049	-9999	-0.33	4	4
RXRG	-0.28	0.12	-9999	-0.32	430	430
RXR alpha/CCPG	0.021	0.01	-9999	-10000	0	0
RXRA	0.015	0.012	-9999	-10000	0	0
RXRB	0.015	0.014	-9999	-10000	0	0
THRB	-0.006	0.12	-9999	-0.82	11	11
PPARG	-0.003	0.11	-9999	-0.59	13	13
PPARD	0.013	0	-9999	-10000	0	0
TNF	-0.14	0.42	-9999	-1.3	58	58
mol:Oxysterols	0.001	0.016	-9999	-10000	0	0
cholesterol transport	-0.048	0.15	-9999	-0.46	58	58
PPARA	0.013	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.009	0.14	-9999	-0.82	13	13
RXRs/NUR77/BCL2	-0.19	0.2	-9999	-0.45	167	167
SREBF1	-0.038	0.14	-9999	-0.62	3	3
RXRs/RXRs/DNA/9cRA	-0.12	0.083	-9999	-0.53	5	5
ABCA1	-0.037	0.14	-9999	-0.62	3	3
RARs/THRs	-0.023	0.1	-9999	-0.48	23	23
RXRs/FXR	-0.12	0.072	-9999	-0.56	4	4
BCL2	-0.047	0.22	-9999	-0.82	35	35

×

Visual signal transduction: Rods

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	-0.001	0.017	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.001	0.011	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.018	0.071	-9999	-0.56	5	5
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.003	0.026	-9999	-0.31	3	3
GRK1	-0.067	0.24	-9999	-0.81	47	47
CNG Channel	-0.028	0.085	-9999	-0.51	9	9
mol:Na +	-0.023	0.081	-9999	-0.48	8	8
mol:ADP	-0.067	0.24	-9999	-0.81	47	47
RGS9-1/Gbeta5/R9AP	-0.091	0.21	-9999	-0.56	79	79
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.023	0.084	-9999	-0.53	5	5
CNGB1	0	0.062	-9999	-0.31	18	18
RDH5	-0.2	0.16	-9999	-0.31	315	315
SAG	0.002	0.015	-9999	-0.31	1	1
mol:Ca2+	0.016	0.088	-9999	-0.8	1	1
Na + (4 Units)	-0.021	0.075	-9999	-0.77	1	1
RGS9	-0.077	0.26	-9999	-0.8	54	54
GNB1/GNGT1	-0.003	0.026	-9999	-10000	0	0
GNAT1/GDP	-0.08	0.18	-9999	-0.49	79	79
GUCY2D	-0.011	0.11	-9999	-0.43	26	26
GNGT1	-0.005	0.04	-9999	-0.31	8	8
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.074	-9999	-0.48	5	5
mol:11-cis-retinal	-0.2	0.16	-9999	-0.31	315	315
mol:cGMP	-0.016	0.071	-9999	-0.48	9	9
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.13	0.099	-9999	-10000	0	0
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0.001	0.09	-9999	-0.57	10	10
Metarhodopsin II	-0.049	0.15	-9999	-0.52	46	46
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.017	0.075	-9999	-0.51	9	9
RGS9BP	-0.037	0.2	-9999	-0.82	29	29
Metarhodopsin II/Transducin	0.01	0.016	-9999	-10000	0	0
GCAP Family/Ca ++	-0.005	0.043	-9999	-0.52	3	3
PDE6A/B	-0.012	0.048	-9999	-10000	0	0
mol:Pi	-0.091	0.21	-9999	-0.56	79	79
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.003	0.024	-9999	-0.3	1	1
PDE6B	0.013	0	-9999	-10000	0	0
PDE6A	-0.008	0.077	-9999	-0.31	29	29
PDE6G	-0.017	0.12	-9999	-0.82	5	5
RHO	0.006	0.016	-9999	-0.31	1	1
PDE6	-0.092	0.18	-9999	-0.48	82	82
GUCA1A	0.004	0.03	-9999	-0.31	4	4
GC2/GCAP Family	-0.005	0.043	-9999	-0.52	3	3
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.008	0.067	-9999	-0.7	4	4

×

LPA receptor mediated events

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
GNB1/GNG2	-0.047	0.16	-9999	-0.54	41	41
NF kappa B1 p50/RelA/I kappa B alpha	-0.023	0.051	-9999	-0.6	1	1
AP1	-0.25	0.36	-9999	-0.68	178	178
mol:PIP3	-0.042	0.13	-9999	-0.64	8	8
AKT1	-0.029	0.098	-9999	-0.58	5	5
PTK2B	-0.001	0.087	-9999	-0.27	42	42
RHOA	0.031	0.047	-9999	-0.26	1	1
PIK3CB	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	0.005	0.073	-9999	-0.32	1	1
MAGI3	0.012	0.038	-9999	-0.82	1	1
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.016	0.14	-9999	-0.45	41	41
HRAS/GDP	-0.001	0.014	-9999	-0.21	2	2
positive regulation of microtubule depolymerization	0.008	0.089	-9999	-0.36	9	9
NF kappa B1 p50/RelA	-0.047	0.12	-9999	-0.55	13	13
endothelial cell migration	-0.03	0.21	-9999	-0.64	43	43
ADCY4	-0.017	0.2	-9999	-0.61	42	42
ADCY5	-0.049	0.22	-9999	-0.65	45	45
ADCY6	-0.017	0.2	-9999	-0.61	42	42
ADCY7	-0.017	0.2	-9999	-0.61	42	42
ADCY1	-0.02	0.2	-9999	-0.62	42	42
ADCY2	-0.041	0.22	-9999	-0.66	43	43
ADCY3	-0.017	0.2	-9999	-0.61	42	42
ADCY8	-0.059	0.2	-9999	-0.63	45	45
ADCY9	-0.017	0.2	-9999	-0.61	42	42
GSK3B	0.008	0.083	-9999	-0.3	13	13
arachidonic acid secretion	-0.01	0.19	-9999	-0.57	42	42
GNG2	0.012	0.038	-9999	-0.82	1	1
TRIP6	0.026	0.008	-9999	-10000	0	0
GNAO1	-0.043	0.21	-9999	-0.6	56	56
HRAS	0.012	0.021	-9999	-0.31	2	2
NFKBIA	0.01	0.079	-9999	-10000	0	0
GAB1	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.033	0.098	-9999	-0.97	5	5
JUN	-0.17	0.35	-9999	-0.82	109	109
LPA/LPA2/NHERF2	-0.001	0.007	-9999	-10000	0	0
TIAM1	-0.043	0.12	-9999	-1.2	5	5
PIK3R1	0.014	0.001	-9999	-10000	0	0
mol:IP3	0.004	0.074	-9999	-0.32	1	1
PLCB3	0.03	0.008	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	129	129
positive regulation of mitosis	-0.01	0.19	-9999	-0.57	42	42
LPA/LPA1-2-3	-0.053	0.16	-9999	-0.54	41	41
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	0.002	0.11	-9999	-0.35	41	41
GNAZ	-0.023	0.18	-9999	-0.57	43	43
EGFR/PI3K-beta/Gab1	-0.044	0.13	-9999	-0.68	8	8
positive regulation of dendritic cell cytokine production	-0.052	0.15	-9999	-0.54	41	41
LPA/LPA2/MAGI-3	-0.002	0.028	-9999	-0.59	1	1
ARHGEF1	-0.003	0.15	-9999	-0.49	41	41
GNAI2	-0.023	0.18	-9999	-0.57	43	43
GNAI3	-0.023	0.18	-9999	-0.57	43	43
GNAI1	-0.024	0.18	-9999	-0.57	44	44
LPA/LPA3	-0.01	0.043	-9999	-0.21	20	20
LPA/LPA2	-0.001	0.01	-9999	-10000	0	0
LPA/LPA1	-0.059	0.19	-9999	-0.66	43	43
HB-EGF/EGFR	-0.053	0.17	-9999	-0.54	46	46
HBEGF	-0.06	0.19	-9999	-0.62	42	42
mol:DAG	0.004	0.074	-9999	-0.32	1	1
cAMP biosynthetic process	-0.03	0.2	-9999	-0.56	55	55
NFKB1	0.012	0.038	-9999	-0.82	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
GNB1	0.014	0.001	-9999	-10000	0	0
LYN	0.01	0.079	-9999	-10000	0	0
GNAQ	0.019	0.028	-9999	-10000	0	0
LPAR2	0.013	0	-9999	-10000	0	0
LPAR3	-0.003	0.065	-9999	-0.31	20	20
LPAR1	-0.055	0.24	-9999	-0.84	41	41
IL8	-0.13	0.2	-9999	-0.46	69	69
PTK2	-0.012	0.16	-9999	-0.5	41	41
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.016	0.14	-9999	-0.45	41	41
EGFR	0.006	0.076	-9999	-0.82	4	4
PLCG1	-0.015	0.084	-9999	-0.29	13	13
PLD2	-0.012	0.16	-9999	-0.5	41	41
G12/G13	-0.047	0.15	-9999	-0.53	41	41
PI3K-beta	-0.034	0.12	-9999	-0.71	5	5
cell migration	-0.016	0.059	-9999	-0.25	10	10
SLC9A3R2	0.013	0	-9999	-10000	0	0
PXN	0.002	0.12	-9999	-0.36	41	41
HRAS/GTP	-0.012	0.19	-9999	-0.59	42	42
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.082	0.24	-9999	-0.57	79	79
PRKCE	0.007	0.076	-9999	-0.82	4	4
PRKCD	0.012	0.071	-9999	-10000	0	0
Gi(beta/gamma)	-0.011	0.19	-9999	-0.58	42	42
mol:LPA	0.003	0.018	-9999	-0.22	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.032	0.13	-9999	-0.45	41	41
MAPKKK cascade	-0.01	0.19	-9999	-0.57	42	42
contractile ring contraction involved in cytokinesis	0.031	0.047	-9999	-0.26	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.085	0.2	-9999	-0.44	112	112
GNA15	0.009	0.054	-9999	-0.43	1	1
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.008	0.091	-9999	-0.41	6	6
GNA11	0.011	0.067	-9999	-0.43	9	9
Rac1/GTP	-0.034	0.1	-9999	-1	5	5
MMP2	-0.031	0.21	-9999	-0.65	43	43

×

JNK signaling in the CD4+ TCR pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.054	0.16	-9999	-0.55	40	40
MAP4K1	-0.019	0.12	-9999	-0.41	37	37
MAP3K8	0	0.11	-9999	-0.82	8	8
PRKCB	-0.027	0.13	-9999	-0.36	52	52
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.014	0.11	-9999	-0.56	5	5
JUN	-0.1	0.24	-9999	-0.51	119	119
MAP3K7	0.014	0.11	-9999	-0.56	5	5
GRAP2	-0.042	0.2	-9999	-0.78	34	34
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.02	0.11	-9999	-0.52	7	7
LAT	0.006	0.077	-9999	-0.72	5	5
LCP2	0.009	0.039	-9999	-0.31	7	7
MAPK8	-0.001	0.14	-9999	-0.76	13	13
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.005	0.11	-9999	-0.37	32	32
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.05	0.15	-9999	-0.52	40	40

×

Integrins in angiogenesis

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.077	-9999	-0.73	5	5
alphaV beta3 Integrin	-0.02	0.11	-9999	-0.61	16	16
PTK2	0.014	0.16	-9999	-0.56	17	17
IGF1R	0.013	0	-9999	-10000	0	0
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	-0.025	0.1	-9999	-0.31	57	57
SRC	0.013	0.015	-9999	-0.31	1	1
CDKN1B	-0.064	0.18	-9999	-0.61	45	45
VEGFA	0.008	0.066	-9999	-0.82	3	3
ILK	-0.064	0.18	-9999	-0.61	45	45
ROCK1	0.013	0	-9999	-10000	0	0
AKT1	-0.059	0.17	-9999	-0.57	45	45
PTK2B	0.018	0.12	-9999	-0.52	21	21
alphaV/beta3 Integrin/JAM-A	-0.062	0.16	-9999	-0.49	60	60
CBL	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.021	0.11	-9999	-0.61	16	16
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.17	0.26	-9999	-0.54	156	156
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.002	0.11	-9999	-0.54	4	4
alphaV/beta3 Integrin/Syndecan-1	-0.021	0.11	-9999	-0.61	16	16
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.24	0.25	-9999	-0.62	115	115
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
alphaV/beta3 Integrin/Osteopontin	-0.072	0.16	-9999	-0.58	38	38
RPS6KB1	-0.21	0.24	-9999	-0.58	115	115
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.096	0.16	-9999	-0.78	16	16
GPR124	0.013	0	-9999	-10000	0	0
MAPK1	-0.096	0.16	-9999	-0.78	16	16
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.037	0.16	-9999	-0.63	28	28
cell adhesion	-0.031	0.11	-9999	-0.56	16	16
ANGPTL3	0.005	0.026	-9999	-0.31	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.007	0.068	-9999	-0.64	5	5
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.008	0.066	-9999	-0.82	3	3
ITGB3	-0.014	0.15	-9999	-0.82	16	16
IGF1	-0.18	0.35	-9999	-0.8	119	119
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.02	0.11	-9999	-0.6	16	16
apoptosis	0.01	0.053	-9999	-0.82	2	2
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.02	0.11	-9999	-0.61	16	16
VCL	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.04	0.14	-9999	-0.63	23	23
CSF1	0	0.11	-9999	-0.82	8	8
PIK3C2A	-0.066	0.18	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.055	0.14	-9999	-0.78	4	4
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.024	0.12	-9999	-0.56	21	21
FAK1/Vinculin	0.023	0.13	-9999	-0.49	9	9
alphaV beta3/Integrin/ppsTEM5	-0.02	0.11	-9999	-0.61	16	16
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.069	0.24	-9999	-0.76	52	52
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	0.013	0	-9999	-10000	0	0
F11R	0.024	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	-0.038	0.12	-9999	-0.61	16	16
alphaV/beta3 Integrin/TGFBR2	-0.023	0.12	-9999	-0.63	18	18
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.01	0.077	-9999	-0.55	9	9
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.019	0.1	-9999	-0.56	16	16
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.22	0.15	-9999	-0.31	350	350
alphaV/beta3 Integrin/Pyk2	-0.023	0.11	-9999	-0.53	21	21
SDC1	0.011	0.03	-9999	-0.31	4	4
VAV3	0.026	0.099	-9999	-0.53	14	14
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.081	0.26	-9999	-0.82	55	55
FAK1/Paxillin	0.023	0.13	-9999	-0.49	9	9
cell migration	0.033	0.12	-9999	-0.44	9	9
ITGAV	0.01	0.054	-9999	-0.82	2	2
PI3K	-0.058	0.16	-9999	-0.94	4	4
SPP1	-0.082	0.2	-9999	-0.42	108	108
KDR	0.008	0.066	-9999	-0.82	3	3
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.01	0.053	-9999	-0.82	2	2
COL4A3	-0.012	0.14	-9999	-0.82	15	15
angiogenesis	-0.086	0.18	-9999	-0.61	37	37
Rac1/GTP	-0.014	0.084	-9999	-0.48	14	14
EDIL3	-0.024	0.14	-9999	-0.43	41	41
cell proliferation	-0.023	0.12	-9999	-0.62	18	18

×

BCR signaling pathway

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
JUN	-0.11	0.18	-9999	-0.45	62	62
IKBKB	-0.018	0.071	-9999	-0.36	3	3
AKT1	-0.04	0.1	-9999	-0.27	21	21
IKBKG	-0.016	0.074	-9999	-0.33	5	5
CALM1	-0.034	0.085	-9999	-0.35	2	2
PIK3CA	0.008	0.066	-9999	-0.82	3	3
MAP3K1	-0.072	0.18	-9999	-0.65	16	16
MAP3K7	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.044	0.089	-9999	-0.38	2	2
DOK1	0.013	0	-9999	-10000	0	0
AP-1	-0.082	0.13	-9999	-0.28	108	108
LYN	0.013	0	-9999	-10000	0	0
BLNK	0.013	0	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
BCR complex	-0.17	0.24	-9999	-0.52	135	135
CD22	-0.15	0.22	-9999	-0.51	104	104
CAMK2G	-0.025	0.081	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	24	24
SHC/GRB2/SOS1	-0.095	0.15	-9999	-10000	0	0
GO:0007205	-0.045	0.09	-9999	-0.38	2	2
SYK	0.013	0	-9999	-10000	0	0
ELK1	-0.035	0.086	-9999	-0.36	2	2
NFATC1	-0.068	0.16	-9999	-0.55	19	19
B-cell antigen/BCR complex	-0.17	0.24	-9999	-0.52	135	135
PAG1/CSK	-0.001	0.029	-9999	-0.63	1	1
NFKBIB	0.002	0.028	-9999	-0.11	3	3
HRAS	-0.037	0.099	-9999	-0.35	2	2
NFKBIA	0.003	0.027	-9999	-0.11	3	3
NF-kappa-B/RelA/I kappa B beta	0.009	0.024	-9999	-0.2	1	1
RasGAP/Csk	-0.14	0.2	-9999	-0.49	94	94
mol:GDP	-0.04	0.083	-9999	-0.36	2	2
PTEN	0.012	0.038	-9999	-0.82	1	1
CD79B	-0.028	0.11	-9999	-0.31	62	62
NF-kappa-B/RelA/I kappa B alpha	0.009	0.024	-9999	-0.2	1	1
GRB2	0.013	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.085	0.18	-9999	-0.43	72	72
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	-0.051	0.087	-9999	-0.38	2	2
CSK	0.013	0	-9999	-10000	0	0
FOS	-0.14	0.21	-9999	-0.47	129	129
CHUK	-0.016	0.074	-9999	-0.35	4	4
IBTK	0.013	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.066	0.094	-9999	-0.49	8	8
PTPN6	-0.14	0.21	-9999	-0.6	51	51
RELA	0.013	0	-9999	-10000	0	0
BCL2A1	0.005	0.035	-9999	-0.13	18	18
VAV2	-0.13	0.18	-9999	-0.84	11	11
ubiquitin-dependent protein catabolic process	0.008	0.027	-9999	-0.11	3	3
BTK	-0.019	0.16	-9999	-1.2	8	8
CD19	-0.15	0.2	-9999	-0.45	98	98
MAP4K1	-0.019	0.12	-9999	-0.41	37	37
CD72	0.012	0.021	-9999	-0.31	2	2
PAG1	0.012	0.038	-9999	-0.82	1	1
MAPK14	-0.054	0.16	-9999	-0.52	16	16
SH3BP5	0.013	0	-9999	-10000	0	0
PIK3AP1	-0.034	0.088	-9999	-10000	0	0
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.06	0.17	-9999	-0.43	71	71
RAF1	-0.027	0.094	-9999	-10000	0	0
RasGAP/p62DOK/SHIP	-0.14	0.19	-9999	-0.47	93	93
CD79A	-0.19	0.3	-9999	-0.52	183	183
re-entry into mitotic cell cycle	-0.08	0.13	-9999	-0.28	108	108
RASA1	0.013	0	-9999	-10000	0	0
MAPK3	-0.008	0.083	-9999	-10000	0	0
MAPK1	-0.008	0.083	-9999	-10000	0	0
CD72/SHP1	-0.1	0.21	-9999	-0.58	46	46
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	-0.061	0.17	-9999	-0.53	24	24
actin cytoskeleton organization	-0.085	0.18	-9999	-0.68	11	11
NF-kappa-B/RelA	0.023	0.045	-9999	-0.2	1	1
Calcineurin	-0.035	0.059	-9999	-10000	0	0
PI3K	-0.13	0.16	-9999	-0.54	29	29
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.054	0.085	-9999	-0.34	2	2
SOS1	0.013	0	-9999	-10000	0	0
Bam32/HPK1	-0.11	0.24	-9999	-1	21	21
DAPP1	-0.13	0.26	-9999	-1.2	18	18
cytokine secretion	-0.063	0.15	-9999	-0.5	19	19
mol:DAG	-0.051	0.087	-9999	-0.38	2	2
PLCG2	0.013	0	-9999	-10000	0	0
MAP2K1	-0.017	0.089	-9999	-10000	0	0
B-cell antigen/BCR complex/FcgammaRIIB	-0.17	0.23	-9999	-0.58	94	94
mol:PI-3-4-5-P3	-0.095	0.12	-9999	-0.38	23	23
ETS1	-0.015	0.076	-9999	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.17	-9999	-0.46	74	74
B-cell antigen/BCR complex/LYN	-0.12	0.2	-9999	-0.49	81	81
MALT1	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
RAC1	-0.091	0.19	-9999	-0.75	11	11
B-cell antigen/BCR complex/LYN/SYK	-0.15	0.22	-9999	-0.55	81	81
CARD11	-0.074	0.12	-9999	-0.51	12	12
FCGR2B	-0.029	0.18	-9999	-0.82	23	23
PPP3CA	0.013	0	-9999	-10000	0	0
BCL10	0.013	0	-9999	-10000	0	0
IKK complex	0.001	0.035	-9999	-0.14	2	2
PTPRC	-0.033	0.17	-9999	-0.59	37	37
PDPK1	-0.043	0.1	-9999	-0.27	21	21
PPP3CB	0.013	0	-9999	-10000	0	0
PPP3CC	0.013	0	-9999	-10000	0	0
POU2F2	0.009	0.024	-9999	-0.089	1	1

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.01	0.22	-10000	0	-0.96	21	21
NCK1/PAK1/Dok-R	-0.028	0.091	-10000	0	-0.43	21	21
NCK1/Dok-R	-0.068	0.24	-10000	0	-1.2	21	21
PIK3CA	0.008	0.065	-10000	0	-0.82	3	3
mol:beta2-estradiol	-0.003	0.047	0.25	15	-10000	0	15
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.014	0.001	-10000	0	-10000	0	0
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.01	0.069	0.26	4	-0.33	11	15
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.06	0.23	-10000	0	-1.1	21	21
FN1	-0.22	0.15	-10000	0	-0.31	350	350
PLD2	0	0.27	-10000	0	-1.2	21	21
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
GRB14	-0.011	0.14	-10000	0	-0.82	14	14
ELK1	0.015	0.24	-10000	0	-1.1	21	21
GRB7	-0.042	0.12	-10000	0	-0.31	82	82
PAK1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.24	-10000	0	-1.2	21	21
CDKN1A	-0.011	0.17	-10000	0	-0.64	21	21
ITGA5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.068	0.24	-10000	0	-1.2	21	21
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	0.026	0.17	-10000	0	-0.69	21	21
PLG	-0.009	0.27	-10000	0	-1.2	21	21
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.009	0.21	-10000	0	-0.92	21	21
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
ANGPT2	-0.11	0.22	-10000	0	-0.72	25	25
BMX	-0.015	0.29	-10000	0	-1.3	21	21
ANGPT1	-0.039	0.29	-10000	0	-1.5	18	18
tube development	-0.018	0.19	-10000	0	-0.73	21	21
ANGPT4	-0.06	0.23	-10000	0	-0.74	48	48
response to hypoxia	0	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.019	0.3	-10000	0	-1.3	21	21
alpha5/beta1 Integrin	0	0	-10000	0	-10000	0	0
FGF2	0.012	0.001	-10000	0	-10000	0	0
STAT5A (dimer)	-0.021	0.21	-10000	0	-0.84	21	21
mol:L-citrulline	0.026	0.17	-10000	0	-0.69	21	21
AGTR1	-0.32	0.41	-10000	0	-0.82	196	196
MAPK14	-0.012	0.27	-10000	0	-1.2	21	21
Tie2/SHP2	-0.025	0.15	-10000	0	-1.4	5	5
TEK	0.016	0.17	-10000	0	-1.5	5	5
RPS6KB1	0.01	0.21	-10000	0	-0.92	21	21
Angiotensin II/AT1	-0.25	0.32	-10000	0	-0.64	196	196
Tie2/Ang1/GRB2	-0.005	0.28	-10000	0	-1.3	21	21
MAPK3	0.011	0.25	-10000	0	-1.1	21	21
MAPK1	0.011	0.25	-10000	0	-1.1	21	21
Tie2/Ang1/GRB7	-0.03	0.29	-10000	0	-1.3	21	21
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MAPK8	-0.008	0.29	-10000	0	-1.3	21	21
PI3K	-0.005	0.25	-10000	0	-1.1	21	21
FES	-0.011	0.27	-10000	0	-1.2	21	21
Crk/Dok-R	-0.068	0.24	-10000	0	-1.2	21	21
Tie2/Ang1/ABIN2	-0.005	0.28	-10000	0	-1.3	21	21
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.014	0.2	-10000	0	-0.84	21	21
STAT5A	0.014	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.01	0.21	-10000	0	-0.92	21	21
Tie2/Ang2	-0.04	0.24	-10000	0	-1	21	21
Tie2/Ang1	-0.012	0.3	-10000	0	-1.4	21	21
FOXO1	0.021	0.2	-10000	0	-0.85	21	21
ELF1	0.015	0.079	-10000	0	-0.85	4	4
ELF2	-0.004	0.27	-10000	0	-1.2	21	21
mol:Choline	0.003	0.26	-10000	0	-1.2	21	21
cell migration	-0.024	0.056	-10000	0	-0.25	9	9
FYN	-0.024	0.21	-10000	0	-0.84	21	21
DOK2	0	0.076	-10000	0	-0.38	16	16
negative regulation of cell cycle	-0.008	0.16	-10000	0	-0.58	21	21
ETS1	0.016	0.045	-10000	0	-10000	0	0
PXN	0.022	0.18	-10000	0	-0.74	21	21
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	0.022	0.19	-10000	0	-0.79	21	21
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.089	0.28	-10000	0	-0.78	64	64
MAPKKK cascade	0.003	0.26	-10000	0	-1.2	21	21
RASA1	0.013	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.009	0.28	-10000	0	-1.3	21	21
NCK1	0.013	0	-10000	0	-10000	0	0
vasculogenesis	0.028	0.15	-10000	0	-0.61	21	21
mol:Phosphatidic acid	0.003	0.26	-10000	0	-1.2	21	21
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.026	0.17	-10000	0	-0.69	21	21
Rac1/GTP	-0.051	0.18	-10000	0	-0.85	21	21
MMP2	-0.007	0.28	-10000	0	-1.3	21	21

×

Signaling events mediated by PTP1B

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
PDGFRB	0.012	0.038	-10000	0	-0.82	1	1
Jak2/Leptin Receptor	-0.023	0.096	-10000	0	-0.39	15	15
PTP1B/AKT1	-0.003	0.064	-10000	0	-0.31	4	4
FYN	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.012	0.071	-10000	0	-0.33	5	5
EGFR	0.005	0.076	-10000	0	-0.83	4	4
EGF/EGFR	-0.083	0.18	-10000	0	-0.5	72	72
CSF1	0	0.11	-10000	0	-0.82	8	8
AKT1	0.014	0.001	-10000	0	-10000	0	0
INSR	0.014	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.1	0.12	-10000	0	-0.46	19	19
Insulin Receptor/Insulin	-0.013	0.041	-10000	0	-10000	0	0
HCK	-0.008	0.08	-10000	0	-0.31	31	31
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.003	0.067	-10000	0	-0.36	2	2
EGF	-0.11	0.29	-10000	0	-0.79	74	74
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.017	0.099	-10000	0	-0.39	5	5
TXN	0.011	0.016	-10000	0	-0.32	1	1
PTP1B/IRS1/GRB2	-0.053	0.17	-10000	0	-0.5	56	56
cell migration	0.012	0.071	0.33	5	-10000	0	5
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.046	0.2	-10000	0	-0.61	47	47
ITGA2B	-0.075	0.26	-10000	0	-0.82	51	51
CSF1R	0.008	0.05	-10000	0	-0.4	6	6
Prolactin Receptor/Prolactin	-0.041	0.15	-10000	0	-0.64	27	27
FGR	0.011	0.03	-10000	0	-0.31	4	4
PTP1B/p130 Cas	-0.004	0.066	-10000	0	-0.32	4	4
Crk/p130 Cas	0.001	0.061	-10000	0	-0.35	2	2
DOK1	0.006	0.063	-10000	0	-0.37	1	1
JAK2	-0.012	0.089	-10000	0	-0.37	14	14
Jak2/Leptin Receptor/Leptin	-0.056	0.14	-10000	0	-0.58	28	28
PIK3R1	0.013	0	-10000	0	-10000	0	0
PTPN1	-0.012	0.071	-10000	0	-0.33	5	5
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.19	0.2	-10000	0	-0.34	279	279
SRC	0.012	0.03	-10000	0	-10000	0	0
ITGB3	-0.016	0.15	-10000	0	-0.83	16	16
CAT1/PTP1B	-0.09	0.15	-10000	0	-0.38	63	63
CAPN1	0.013	0.003	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.015	0.055	-10000	0	-0.61	3	3
mol:H2O2	0	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.055	0.15	-10000	0	-0.63	27	27
negative regulation of transcription	-0.011	0.089	-10000	0	-0.37	14	14
FCGR2A	-0.007	0.084	-10000	0	-0.33	28	28
FER	0.007	0.066	-10000	0	-0.83	3	3
alphaIIb/beta3 Integrin	-0.085	0.23	-10000	0	-0.68	61	61
BLK	-0.25	0.38	-10000	0	-0.76	164	164
Insulin Receptor/Insulin/Shc	0	0.001	-10000	0	-10000	0	0
RHOA	0.013	0.003	-10000	0	-10000	0	0
LEPR	0.004	0.086	-10000	0	-0.67	7	7
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.12	0.19	-10000	0	-0.45	65	65
PRL	0.001	0.016	-10000	0	-0.31	1	1
SOCS3	-0.07	0.35	-10000	0	-1.5	27	27
SPRY2	0.009	0.056	-10000	0	-0.66	3	3
Insulin Receptor/Insulin/IRS1	-0.063	0.18	-10000	0	-0.56	55	55
CSF1/CSF1R	-0.009	0.096	-10000	0	-0.52	10	10
Ras protein signal transduction	0.02	0.023	-10000	0	-10000	0	0
IRS1	-0.081	0.26	-10000	0	-0.82	55	55
INS	0	0.001	-10000	0	-10000	0	0
LEP	-0.007	0.065	-10000	0	-0.31	21	21
STAT5B	-0.007	0.07	-10000	0	-0.26	10	10
STAT5A	-0.007	0.07	-10000	0	-0.26	10	10
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.005	0.069	-10000	0	-0.35	5	5
CSN2	-0.007	0.056	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
LAT	0.002	0.066	-10000	0	-0.54	5	5
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	-0.01	0.11	-10000	0	-0.44	25	25
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.13	0.16	-10000	0	-0.31	213	213

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.003	0.04	-10000	0	-0.63	2	2
Necdin/E2F1	-0.069	0.12	-10000	0	-0.76	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.036	0.1	-10000	0	-0.49	20	20
NGF (dimer)/p75(NTR)/BEX1	-0.29	0.28	-10000	0	-0.57	230	230
NT-4/5 (dimer)/p75(NTR)	-0.075	0.18	-10000	0	-0.67	35	35
IKBKB	0.013	0	-10000	0	-10000	0	0
AKT1	-0.004	0.12	-10000	0	-0.49	23	23
IKBKG	0.013	0	-10000	0	-10000	0	0
BDNF	-0.013	0.14	-10000	0	-0.6	21	21
MGDIs/NGR/p75(NTR)/LINGO1	-0.05	0.12	-10000	0	-0.54	21	21
FURIN	0.013	0	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.058	0.14	-10000	0	-0.55	31	31
LINGO1	-0.003	0.072	-10000	0	-0.31	25	25
Sortilin/TRAF6/NRIF	-0.002	0.026	-10000	0	-0.4	2	2
proBDNF (dimer)	-0.013	0.14	-10000	0	-0.6	21	21
NTRK1	-0.002	0.061	-10000	0	-0.31	18	18
RTN4R	0.013	0	-10000	0	-10000	0	0
neuron apoptosis	-0.011	0.13	-10000	0	-0.48	29	29
IRAK1	0.013	0	-10000	0	-10000	0	0
SHC1	-0.021	0.13	-10000	0	-0.57	20	20
ARHGDIA	0.013	0	-10000	0	-10000	0	0
RhoA/GTP	0	0	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.04	0.11	-10000	0	-0.52	20	20
MAGEH1	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.045	0.12	-10000	0	-0.52	25	25
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.5	25	25
proNGF (dimer)	0.006	0.07	-10000	0	-0.57	6	6
MAGED1	0.013	0	-10000	0	-10000	0	0
APP	0.013	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.02	0.15	-10000	0	-0.64	25	25
ZNF274	0.013	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.037	0.1	-10000	0	-0.49	20	20
NGF	0.006	0.07	-10000	0	-0.57	6	6
cell cycle arrest	0.042	0.16	-10000	0	-0.47	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.008	0.086	-10000	0	-0.35	22	22
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.065	0.16	-10000	0	-0.58	37	37
NCSTN	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.047	0.12	-10000	0	-0.57	21	21
PSENEN	0.013	0	-10000	0	-10000	0	0
mol:ceramide	-0.01	0.12	-10000	0	-0.51	20	20
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.021	0.071	-10000	0	-0.44	2	2
p75(NTR)/beta APP	-0.051	0.13	-10000	0	-0.63	18	18
BEX1	-0.36	0.42	-10000	0	-0.82	215	215
mol:GDP	-0.032	0.13	-10000	0	-0.58	20	20
NGF (dimer)	-0.095	0.13	-10000	0	-0.51	30	30
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.043	0.11	-10000	0	-0.52	18	18
PIK3R1	0.013	0	-10000	0	-10000	0	0
RAC1/GTP	-0.039	0.11	-10000	0	-0.5	20	20
MYD88	0.013	0	-10000	0	-10000	0	0
CHUK	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.047	0.13	-10000	0	-0.57	21	21
RHOB	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.063	0.094	-10000	0	-10000	0	0
NT3 (dimer)	-0.05	0.2	-10000	0	-0.62	48	48
TP53	-0.006	0.13	-10000	0	-0.45	31	31
PRDM4	-0.011	0.12	-10000	0	-0.52	20	20
BDNF (dimer)	-0.13	0.16	-10000	0	-0.54	39	39
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
SORT1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.036	0.1	-10000	0	-0.48	20	20
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.042	0.12	-10000	0	-0.52	22	22
RHOC	0.013	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
MAPK10	0.023	0.12	-10000	0	-0.45	20	20
DIABLO	0.013	0	-10000	0	-10000	0	0
SMPD2	-0.011	0.12	-10000	0	-0.52	20	20
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.046	0.12	-10000	0	-0.57	20	20
PSEN1	0.013	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.029	-10000	0	-0.63	1	1
NT3 (dimer)/p75(NTR)	-0.096	0.2	-10000	0	-0.66	46	46
MAPK8	0.018	0.13	-10000	0	-0.46	20	20
MAPK9	0.023	0.12	-10000	0	-0.44	19	19
APAF1	0.012	0.038	-10000	0	-0.82	1	1
NTF3	-0.05	0.2	-10000	0	-0.62	48	48
NTF4	-0.02	0.16	-10000	0	-0.64	25	25
NDN	0.005	0.084	-10000	0	-0.82	5	5
RAC1/GDP	0	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.033	0.096	-10000	0	-0.45	21	21
p75 CTF/Sortilin/TRAF6/NRIF	-0.004	0.054	-10000	0	-0.66	3	3
RhoA-B-C/GTP	-0.046	0.12	-10000	0	-0.56	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.048	0.12	-10000	0	-0.48	31	31
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.053	0.13	-10000	0	-0.52	31	31
PRKACB	0.012	0.038	-10000	0	-0.82	1	1
proBDNF (dimer)/p75 ECD	-0.022	0.11	-10000	0	-0.63	14	14
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.68	35	35
BIRC2	0.013	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.066	0.17	0.24	185	-0.47	20	205
BAD	0.029	0.12	-10000	0	-0.44	20	20
RIPK2	0.013	0	-10000	0	-10000	0	0
NGFR	-0.062	0.19	-10000	0	-0.42	84	84
CYCS	-0.001	0.12	-10000	0	-0.48	20	20
ADAM17	0.01	0.054	-10000	0	-0.82	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.042	0.12	-10000	0	-0.52	22	22
BCL2L11	0.029	0.12	-10000	0	-0.44	20	20
BDNF (dimer)/p75(NTR)	-0.07	0.17	-10000	0	-0.63	31	31
PI3K	-0.043	0.12	-10000	0	-0.53	23	23
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.04	0.11	-10000	0	-0.52	20	20
NDNL2	0.013	0	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.056	0.14	-10000	0	-0.66	20	20
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.04	0.11	-10000	0	-0.52	20	20
TRAF6	0.01	0.054	-10000	0	-0.82	2	2
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
PLG	-0.003	0.035	-10000	0	-0.31	6	6
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.017	0.14	-10000	0	-0.49	31	31
SQSTM1	0.013	0	-10000	0	-10000	0	0
NGFRAP1	0.013	0	-10000	0	-10000	0	0
CASP3	0.03	0.11	-10000	0	-0.4	20	20
E2F1	-0.089	0.15	-10000	0	-0.31	152	152
CASP9	0.013	0	-10000	0	-10000	0	0
IKK complex	-0.014	0.059	-10000	0	-0.54	3	3
NGF (dimer)/TRKA	-0.013	0.064	-10000	0	-0.64	3	3
MMP7	-0.18	0.22	-10000	0	-0.37	242	242
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.038	0.11	-10000	0	-0.49	22	22
MMP3	-0.039	0.11	-10000	0	-0.31	67	67
APAF-1/Caspase 9	-0.041	0.11	-10000	0	-0.61	7	7

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.012	0	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.001	0.013	-9999	-10000	0	0
STXBP1	0.013	0	-9999	-10000	0	0
ACh/CHRNA1	-0.015	0.064	-9999	-0.23	9	9
RAB3GAP2/RIMS1/UNC13B	-0.001	0.01	-9999	-10000	0	0
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	0.01	0.021	-9999	-0.31	2	2
mol:ACh	-0.007	0.041	-9999	-0.15	29	29
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.014	0.044	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.015	0.063	-9999	-0.23	9	9
UNC13B	0.013	0	-9999	-10000	0	0
CHRNA1	-0.018	0.093	-9999	-0.31	44	44
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.11	0.16	-9999	-0.24	217	217
SNAP25	-0.032	0.097	-9999	-0.38	29	29
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.16	0.23	-9999	-0.38	217	217
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.019	0	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.014	0.044	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.042	-10000	0	-0.31	8	8
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.065	0.14	0.54	9	-10000	0	9
IL27/IL27R/JAK1	-0.12	0.19	-10000	0	-0.68	6	6
TBX21	-0.091	0.22	-10000	0	-0.66	30	30
IL12B	-0.005	0.091	-10000	0	-0.63	8	8
IL12A	-0.06	0.2	-10000	0	-0.64	51	51
IL6ST	-0.11	0.29	-10000	0	-0.83	69	69
IL27RA/JAK1	0.013	0.026	-10000	0	-10000	0	0
IL27	0.002	0.037	-10000	0	-0.32	6	6
TYK2	0.012	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.062	0.16	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.065	0.14	0.54	9	-10000	0	9
T cell proliferation during immune response	0.065	0.14	0.54	9	-10000	0	9
MAPKKK cascade	-0.065	0.14	-10000	0	-0.54	9	9
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.006	0.049	-10000	0	-0.32	11	11
IL12RB1	-0.022	0.12	-10000	0	-0.36	44	44
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.09	0.21	-10000	0	-0.66	27	27
IL27/IL27R/JAK2/TYK2	-0.065	0.15	-10000	0	-0.55	9	9
positive regulation of T cell mediated cytotoxicity	-0.065	0.14	-10000	0	-0.54	9	9
STAT1 (dimer)	-0.12	0.24	0.52	16	-0.8	12	28
JAK2	0.012	0.039	-10000	0	-0.84	1	1
JAK1	0.014	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.054	0.14	-10000	0	-0.54	7	7
T cell proliferation	-0.16	0.24	-10000	0	-0.62	59	59
IL12/IL12R/TYK2/JAK2	-0.055	0.17	-10000	0	-0.68	14	14
IL17A	-0.063	0.16	-10000	0	-10000	0	0
mast cell activation	0.065	0.14	0.54	9	-10000	0	9
IFNG	-0.02	0.048	-10000	0	-0.13	65	65
T cell differentiation	-0.005	0.008	-10000	0	-0.022	55	55
STAT3 (dimer)	-0.054	0.14	-10000	0	-0.54	7	7
STAT5A (dimer)	-0.054	0.14	-10000	0	-0.54	7	7
STAT4 (dimer)	-0.074	0.16	-10000	0	-0.52	21	21
STAT4	-0.025	0.14	-10000	0	-0.45	40	40
T cell activation	-0.012	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.063	0.18	-10000	0	-0.72	4	4
GATA3	-0.044	0.34	-10000	0	-1.5	25	25
IL18	-0.025	0.12	-10000	0	-0.64	11	11
positive regulation of mast cell cytokine production	-0.053	0.14	-10000	0	-0.53	7	7
IL27/EBI3	-0.097	0.12	-10000	0	-0.44	6	6
IL27RA	0.004	0.027	-10000	0	-10000	0	0
IL6	-0.17	0.33	-10000	0	-0.82	97	97
STAT5A	0.013	0	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-10000	0	0
IL2	0.002	0.013	-10000	0	-10000	0	0
IL1B	-0.042	0.18	-10000	0	-0.64	38	38
EBI3	-0.14	0.17	-10000	0	-0.32	232	232
TNF	-0.07	0.21	-10000	0	-0.6	64	64

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.015	-10000	0	-10000	0	0
HSPA8	0.004	0.076	-10000	0	-0.82	4	4
SMAD3/SMAD4/ER alpha	-0.053	0.14	-10000	0	-0.58	25	25
AKT1	0.008	0.011	-10000	0	-10000	0	0
GSC	-0.21	0.56	-10000	0	-1.6	71	71
NKX2-5	0.002	0.029	-10000	0	-0.31	4	4
muscle cell differentiation	0.026	0.051	0.44	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.005	0.08	-10000	0	-10000	0	0
SMAD4	-0.012	0.06	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.012	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.12	0.078	-10000	0	-0.55	5	5
SMAD3/SMAD4/VDR	0.01	0.044	-10000	0	-10000	0	0
MYC	0	0.14	-10000	0	-0.82	13	13
CDKN2B	-0.076	0.14	-10000	0	-10000	0	0
AP1	-0.26	0.51	-10000	0	-0.94	152	152
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.032	0.056	-10000	0	-0.71	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.001	0.063	-10000	0	-10000	0	0
SP3	0.016	0.002	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.011	0.074	-10000	0	-0.31	21	21
SMAD3/SMAD4/GR	-0.017	0.045	-10000	0	-10000	0	0
GATA3	-0.032	0.19	-10000	0	-0.78	27	27
SKI/SIN3/HDAC complex/NCoR1	0.04	0.029	-10000	0	-10000	0	0
MEF2C/TIF2	-0.045	0.17	-10000	0	-0.52	38	38
endothelial cell migration	-0.009	0.1	1.4	1	-10000	0	1
MAX	0.013	0.006	-10000	0	-10000	0	0
RBBP7	0.012	0.004	-10000	0	-10000	0	0
RBBP4	0.007	0.066	-10000	0	-0.82	3	3
RUNX2	-0.076	0.15	-10000	0	-0.32	129	129
RUNX3	-0.007	0.12	-10000	0	-0.6	16	16
RUNX1	-0.13	0.16	-10000	0	-0.31	213	213
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.013	0.006	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-10000	0	0
CDKN1A	0.023	0.073	-10000	0	-10000	0	0
KAT2B	0.016	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.038	0.094	-10000	0	-0.44	3	3
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.012	0.004	-10000	0	-10000	0	0
SERPINE1	0.009	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	-0.038	0.12	-10000	0	-0.59	18	18
SMAD3/SMAD4/ATF3	-0.16	0.26	-10000	0	-0.63	114	114
SAP30	0.01	0.038	-10000	0	-0.83	1	1
Cbp/p300/PIAS3	0.033	0.045	-10000	0	-10000	0	0
JUN	-0.25	0.5	-10000	0	-0.93	152	152
SMAD3/SMAD4/IRF7	-0.017	0.045	-10000	0	-10000	0	0
TFE3	0.019	0.006	-10000	0	-10000	0	0
COL1A2	-0.002	0.092	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.066	0.095	0.46	4	-10000	0	4
DLX1	-0.033	0.19	-10000	0	-0.82	27	27
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.22	0.4	-10000	0	-0.89	129	129
SMAD3/SMAD4/Max	-0.017	0.045	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.006	0.041	-10000	0	-0.55	2	2
ZBTB17	0.021	0.012	-10000	0	-10000	0	0
LAMC1	0.026	0.053	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	-0.017	0.043	-10000	0	-10000	0	0
IRF7	0.014	0.016	-10000	0	-0.31	1	1
ESR1	-0.05	0.19	-10000	0	-0.54	55	55
HNF4A	-0.003	0.045	-10000	0	-0.31	10	10
MEF2C	0.004	0.099	-10000	0	-1	1	1
SMAD2-3/SMAD4	-0.032	0.055	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.025	0.031	-10000	0	-10000	0	0
IGHV3OR16-13	-0.016	0.024	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.018	0.01	-10000	0	-10000	0	0
SKIL	0.012	0.038	-10000	0	-0.82	1	1
HDAC1	0.012	0.004	-10000	0	-10000	0	0
HDAC2	0.012	0.004	-10000	0	-10000	0	0
SNIP1	0.008	0.054	-10000	0	-0.82	2	2
GCN5L2	0.006	0.012	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.011	0.045	-10000	0	-10000	0	0
MSG1/HSC70	-0.18	0.1	-10000	0	-0.68	9	9
SMAD2	-0.003	0.04	-10000	0	-10000	0	0
SMAD3	-0.005	0.047	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.01	0.075	-10000	0	-0.36	13	13
SMAD2/SMAD2/SMAD4	0.014	0.028	-10000	0	-10000	0	0
NCOR1	0.012	0.004	-10000	0	-10000	0	0
NCOA2	-0.062	0.24	-10000	0	-0.82	44	44
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.018	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.014	0.077	-10000	0	-10000	0	0
IFNB1	0.014	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.006	0.099	-10000	0	-1	1	1
CITED1	-0.26	0.14	-10000	0	-0.32	403	403
SMAD2-3/SMAD4/ARC105	-0.022	0.046	-10000	0	-10000	0	0
RBL1	-0.007	0.13	-10000	0	-0.82	12	12
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.006	0.082	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.081	0.11	-10000	0	-0.49	14	14
SMAD7	-0.1	0.28	-10000	0	-0.59	101	101
MYC/MIZ-1	0.013	0.11	-10000	0	-0.63	13	13
SMAD3/SMAD4	0.064	0.1	0.31	42	-0.35	1	43
IL10	-0.026	0.19	-10000	0	-0.62	38	38
PIASy/HDAC complex	0.007	0.01	-10000	0	-10000	0	0
PIAS3	0.016	0.005	-10000	0	-10000	0	0
CDK2	0.018	0.011	-10000	0	-10000	0	0
IL5	-0.016	0.14	-10000	0	-0.5	26	26
CDK4	0.019	0.012	-10000	0	-10000	0	0
PIAS4	0.007	0.01	-10000	0	-10000	0	0
ATF3	-0.19	0.35	-10000	0	-0.79	121	121
SMAD3/SMAD4/SP1	-0.015	0.054	-10000	0	-10000	0	0
FOXG1	-0.003	0.072	-10000	0	-0.39	13	13
FOXO3	0.017	0.015	-10000	0	-10000	0	0
FOXO1	0.017	0.015	-10000	0	-10000	0	0
FOXO4	0.017	0.015	-10000	0	-10000	0	0
heart looping	0.004	0.098	-10000	0	-1	1	1
CEBPB	0.009	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.05	0.14	-10000	0	-0.6	27	27
MYOD1	-0.002	0.029	-10000	0	-0.31	4	4
SMAD3/SMAD4/HNF4	-0.024	0.052	-10000	0	-0.4	1	1
SMAD3/SMAD4/GATA3	-0.051	0.14	-10000	0	-0.54	30	30
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.038	-10000	0	-0.82	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.075	0.11	-10000	0	-0.55	11	11
SMAD3/SMAD4/SP1-3	0.006	0.056	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.015	0.022	-10000	0	-10000	0	0
SIN3B	0.012	0.004	-10000	0	-10000	0	0
SIN3A	0.012	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.017	0.095	-10000	0	-0.52	2	2
ITGB5	0.036	0.059	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.042	0.028	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.26	0.29	-10000	0	-0.6	204	204
AR	-0.34	0.41	-10000	0	-0.82	204	204
negative regulation of cell growth	-0.04	0.13	-10000	0	-0.46	8	8
SMAD3/SMAD4/MYOD	-0.023	0.049	-10000	0	-10000	0	0
E2F5	0.012	0.038	-10000	0	-0.82	1	1
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.013	0.066	-10000	0	-0.36	2	2
SMAD2-3/SMAD4/FOXO1-3a-4	0.001	0.067	-10000	0	-10000	0	0
TFDP1	0.012	0.038	-10000	0	-0.82	1	1
SMAD3/SMAD4/AP1	-0.27	0.51	-10000	0	-0.96	152	152
SMAD3/SMAD4/RUNX2	-0.066	0.096	-10000	0	-0.47	4	4
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.018	0.16	-10000	0	-0.82	18	18

×

Aurora C 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
INCENP	0.01	0.054	-9999	-0.82	2	2
Aurora C/Aurora B/INCENP	-0.039	0.077	-9999	-0.39	8	8
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.011	0.02	-9999	-10000	0	0
AURKB	-0.059	0.14	-9999	-0.31	107	107
AURKC	-0.001	0.067	-9999	-0.31	21	21

×

Nectin adhesion 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	0.012	0.038	-9999	-0.82	1	1
alphaV beta3 Integrin	-0.023	0.13	-9999	-0.7	16	16
PTK2	-0.04	0.15	-9999	-0.61	28	28
positive regulation of JNK cascade	-0.02	0.081	-9999	-0.34	28	28
CDC42/GDP	0.031	0.13	-9999	-0.47	28	28
Rac1/GDP	0.033	0.12	-9999	-0.46	28	28
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	-0.025	0.1	-9999	-0.43	28	28
nectin-3/I-afadin	-0.036	0.15	-9999	-0.63	28	28
RAPGEF1	0.024	0.14	-9999	-0.54	28	28
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0.16	-9999	-0.63	28	28
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
TLN1	0.019	0.075	-9999	-0.94	1	1
Rap1/GTP	-0.022	0.086	-9999	-0.37	28	28
IQGAP1	0.013	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	-0.036	0.15	-9999	-0.63	28	28
PVR	0.013	0	-9999	-10000	0	0
Necl-5(dimer)	0.013	0	-9999	-10000	0	0
mol:GDP	0.025	0.16	-9999	-0.59	28	28
MLLT4	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PI3K	-0.03	0.13	-9999	-0.51	29	29
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.033	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.021	0.085	-9999	-0.36	28	28
PVRL1	0.005	0.053	-9999	-0.31	13	13
PVRL3	-0.035	0.2	-9999	-0.82	28	28
PVRL2	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
CLDN1	-0.26	0.15	-9999	-0.33	396	396
JAM-A/CLDN1	-0.14	0.14	-9999	-0.58	38	38
SRC	-0.043	0.17	-9999	-0.72	28	28
ITGB3	-0.014	0.15	-9999	-0.82	16	16
nectin-1(dimer)/I-afadin/I-afadin	-0.005	0.033	-9999	-10000	0	0
FARP2	0.019	0.15	-9999	-0.58	28	28
RAC1	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.031	0.13	-9999	-0.55	28	28
nectin-1/I-afadin	-0.005	0.033	-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	-0.036	0.13	-9999	-0.55	28	28
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.013	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.02	0.081	-9999	-0.34	28	28
alphaV/beta3 Integrin/Talin	0.016	0.14	-9999	-0.61	16	16
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	0.011	0.08	-9999	-1	1	1
VAV2	0.018	0.15	-9999	-0.59	28	28
RAP1/GDP	-0.025	0.1	-9999	-0.43	28	28
ITGAV	0.01	0.054	-9999	-0.82	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.031	0.13	-9999	-0.55	28	28
nectin-3(dimer)/I-afadin/I-afadin	-0.036	0.15	-9999	-0.63	28	28
Rac1/GTP	-0.026	0.1	-9999	-0.44	28	28
PTPRM	-0.018	0.082	-9999	-0.32	28	28
E-cadherin/beta catenin/alpha catenin	-0.003	0.016	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.032	0.044	-9999	-0.93	1	1
VEGFR1 homodimer/NRP1	-0.002	0.042	-9999	-0.94	1	1
mol:DAG	-0.012	0.16	-9999	-0.49	49	49
VEGFR1 homodimer/NRP1/VEGFR 121	-0.005	0.068	-9999	-0.78	3	3
CaM/Ca2+	-0.004	0.15	-9999	-0.46	49	49
HIF1A	0.021	0.018	-9999	-0.38	1	1
GAB1	0.013	0	-9999	-10000	0	0
AKT1	0.009	0.16	-9999	-1.1	2	2
PLCG1	-0.012	0.16	-9999	-0.5	49	49
NOS3	0.017	0.15	-9999	-0.43	49	49
CBL	0.013	0	-9999	-10000	0	0
mol:NO	0.018	0.15	-9999	-0.42	49	49
FLT1	0.031	0.048	-9999	-1	1	1
PGF	-0.07	0.25	-9999	-0.81	49	49
VEGFR1 homodimer/NRP2/VEGFR121	-0.014	0.075	-9999	-0.77	3	3
CALM1	0.013	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
eNOS/Hsp90	0.025	0.14	-9999	-0.81	1	1
endothelial cell proliferation	-0.029	0.19	-9999	-0.52	50	50
mol:Ca2+	-0.011	0.16	-9999	-0.49	49	49
MAPK3	-0.017	0.18	-9999	-0.44	71	71
MAPK1	-0.017	0.18	-9999	-0.48	24	24
PIK3R1	0.013	0	-9999	-10000	0	0
PLGF homodimer	-0.07	0.25	-9999	-0.81	49	49
PRKACA	0.013	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.009	0.14	-9999	-0.82	13	13
VEGFA homodimer	0.008	0.065	-9999	-0.82	3	3
VEGFR1 homodimer/VEGFA homodimer	0.029	0.074	-9999	-0.82	3	3
platelet activating factor biosynthetic process	-0.009	0.17	-9999	-0.96	2	2
PI3K	-0.05	0.15	-9999	-0.47	51	51
PRKCA	-0.027	0.19	-9999	-0.47	71	71
PRKCB	-0.022	0.17	-9999	-0.47	53	53
VEGFR1 homodimer/PLGF homodimer	-0.025	0.18	-9999	-0.55	49	49
VEGFA	0.008	0.066	-9999	-0.82	3	3
VEGFB	0.013	0	-9999	-10000	0	0
mol:IP3	-0.012	0.16	-9999	-0.49	49	49
RASA1	0.041	0.041	-9999	-0.86	1	1
NRP2	-0.012	0.088	-9999	-0.31	38	38
VEGFR1 homodimer	0.031	0.048	-9999	-1	1	1
VEGFB homodimer	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.013	0.16	-9999	-0.8	4	4
PTPN11	0.012	0.038	-9999	-0.82	1	1
mol:PI-3-4-5-P3	-0.049	0.15	-9999	-0.46	51	51
mol:L-citrulline	0.018	0.15	-9999	-0.42	49	49
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.004	0.064	-9999	-0.73	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.005	0.067	-9999	-0.77	3	3
CD2AP	0.013	0	-9999	-10000	0	0
PI3K/GAB1	-0.047	0.14	-9999	-0.69	3	3
PDPK1	0.001	0.16	-9999	-0.45	51	51
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.006	0.084	-9999	-0.9	3	3
mol:NADP	0.018	0.15	-9999	-0.42	49	49
HSP90AA1	0.013	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.004	0.062	-9999	-0.71	3	3
VEGFR1 homodimer/NRP2	0.018	0.065	-9999	-0.93	1	1

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.017	0.087	-9999	-0.48	16	16
RGS9BP	-0.037	0.2	-9999	-0.82	29	29
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.067	0.24	-9999	-0.81	47	47
mol:Na +	-0.021	0.057	-9999	-10000	0	0
mol:ADP	-0.044	0.19	-9999	-0.64	46	46
GNAT2	0.009	0.022	-9999	-0.31	2	2
RGS9-1/Gbeta5/R9AP	-0.091	0.21	-9999	-0.56	79	79
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.011	-9999	-10000	0	0
GRK7	0.007	0.007	-9999	-10000	0	0
CNGB3	0.003	0.005	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.014	0.063	-9999	-0.3	2	2
Cone PDE6	-0.08	0.18	-9999	-0.48	79	79
Cone Metarhodopsin II	-0.049	0.15	-9999	-0.52	46	46
Na + (4 Units)	-0.025	0.057	-9999	-0.3	2	2
GNAT2/GDP	-0.079	0.18	-9999	-0.48	79	79
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.011	0.015	-9999	-10000	0	0
Cone Transducin	-0.018	0.091	-9999	-0.5	16	16
SLC24A2	-0.009	0.063	-9999	-0.31	20	20
GNB3/GNGT2	-0.022	0.11	-9999	-0.63	16	16
GNB3	-0.013	0.14	-9999	-0.79	16	16
GNAT2/GTP	-0.001	0.014	-9999	-0.21	2	2
CNGA3	-0.027	0.11	-9999	-0.31	60	60
ARR3	0.004	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.021	0.057	-9999	-10000	0	0
mol:Pi	-0.091	0.21	-9999	-0.56	79	79
Cone CNG Channel	-0.017	0.043	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.009	0.063	-9999	-0.31	20	20
RGS9	-0.077	0.26	-9999	-0.8	54	54
PDE6C	0.003	0.016	-9999	-0.31	1	1
GNGT2	0.01	0.046	-9999	-0.44	4	4
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.004	0.006	-9999	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.03	0.068	-9999	-0.32	8	8
IRAK/TOLLIP	0.029	0.004	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.12	0.25	-9999	-0.67	75	75
IL1A	-0.055	0.22	-9999	-0.79	41	41
IL1B	-0.033	0.18	-9999	-0.64	40	40
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.027	-9999	-0.43	2	2
IL1R2	-0.083	0.24	-9999	-0.59	77	77
IL1R1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.069	-9999	-0.3	1	1
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.005	0.084	-9999	-0.82	5	5
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.066	0.028	-9999	-10000	0	0
JUN	-0.072	0.22	-9999	-0.43	120	120
MAP3K7	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.068	0.14	-9999	-0.47	42	42
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.074	0.14	-9999	-0.51	38	38
PIK3R1	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.067	0.13	-9999	-0.48	38	38
IL1 beta fragment/IL1R1/IL1RAP	-0.078	0.15	-9999	-0.53	39	39
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.021	0.11	-9999	-0.51	17	17
IRAK1	0.023	0.004	-9999	-10000	0	0
IL1RN/IL1R1	-0.045	0.12	-9999	-0.63	11	11
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.013	0	-9999	-10000	0	0
TRAF6	0.01	0.054	-9999	-0.82	2	2
PI3K	-0.004	0.049	-9999	-0.63	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.088	-9999	-0.34	8	8
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.078	0.15	-9999	-0.53	39	39
IL1 beta/IL1R2	-0.1	0.23	-9999	-0.61	74	74
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.002	0.028	-9999	-0.44	2	2
NF kappa B1 p50/RelA	-0.058	0.12	-9999	-0.55	8	8
IRAK3	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.07	0.14	-9999	-0.48	44	44
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.016	0.1	-9999	-0.34	38	38
IL1 alpha/IL1R1/IL1RAP	-0.085	0.16	-9999	-0.55	41	41
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.022	0.035	-9999	-0.47	2	2
IL1RAP	-0.073	0.14	-9999	-0.31	128	128
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.054	0.12	-9999	-0.5	12	12
CASP1	0.008	0.059	-9999	-0.52	5	5
IL1RN/IL1R2	-0.11	0.22	-9999	-0.63	61	61
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.07	0.14	-9999	-0.5	39	39
TMEM189-UBE2V1	0.004	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.081	-9999	-0.34	4	4
PIK3CA	0.008	0.066	-9999	-0.82	3	3
IL1RN	-0.055	0.17	-9999	-0.38	85	85
TRAF6/TAK1/TAB1/TAB2	-0.002	0.03	-9999	-0.46	2	2
MAP2K6	0.022	0.074	-9999	-0.44	12	12

×

Neurotrophic factor-mediated Trk receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.065	0.082	-10000	0	-0.34	22	22
NT3 (dimer)/TRKC	-0.09	0.19	-10000	0	-0.68	40	40
NT3 (dimer)/TRKB	-0.086	0.18	-10000	0	-0.58	50	50
SHC/Grb2/SOS1/GAB1/PI3K	0.038	0.029	-10000	0	-0.33	3	3
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.013	0.14	-10000	0	-0.6	21	21
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
DYNLT1	0.013	0	-10000	0	-10000	0	0
NTRK1	-0.002	0.061	-10000	0	-0.31	18	18
NTRK2	0.005	0.084	-10000	0	-0.82	5	5
NTRK3	-0.056	0.17	-10000	0	-0.39	84	84
NT-4/5 (dimer)/TRKB	-0.068	0.16	-10000	0	-0.58	40	40
neuron apoptosis	0.04	0.092	0.42	15	-10000	0	15
SHC 2-3/Grb2	-0.043	0.1	-10000	0	-0.46	15	15
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.03	0.092	-10000	0	-0.64	6	6
SHC3	-0.047	0.1	-10000	0	-0.55	12	12
STAT3 (dimer)	0.018	0.024	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.087	0.18	-10000	0	-0.58	45	45
RIN/GDP	-0.009	0.063	-10000	0	-0.28	2	2
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.032	0.092	-10000	0	-0.44	19	19
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.026	0.044	-10000	0	-10000	0	0
MAGED1	0.013	0	-10000	0	-10000	0	0
PTPN11	0.012	0.038	-10000	0	-0.82	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.02	0.15	-10000	0	-0.64	25	25
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.019	0.082	-10000	0	-0.55	9	9
TRKA/NEDD4-2	-0.007	0.038	-10000	0	-10000	0	0
ELMO1	-0.31	0.41	-10000	0	-0.82	189	189
RhoG/GTP/ELMO1/DOCK1	-0.22	0.28	-10000	0	-0.56	190	190
NGF	0.006	0.07	-10000	0	-0.57	6	6
HRAS	0.012	0.021	-10000	0	-0.31	2	2
DOCK1	0.006	0.076	-10000	0	-0.82	4	4
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	0.002	0.005	-10000	0	-10000	0	0
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	-0.017	0.15	-10000	0	-0.8	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.2	0.23	-10000	0	-0.47	205	205
mol:GDP	-0.016	0.09	-10000	0	-0.4	4	4
NGF (dimer)	0.006	0.07	-10000	0	-0.57	6	6
RhoG/GDP	-0.25	0.31	-10000	0	-0.64	189	189
RIT1/GDP	-0.004	0.063	-10000	0	-0.28	2	2
TIAM1	-0.17	0.16	-10000	0	-0.32	276	276
PIK3R1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.022	0.11	-10000	0	-0.61	15	15
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.025	-10000	0	-0.55	1	1
SHC/GRB2/SOS1/GAB1	0	0	-10000	0	-10000	0	0
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.05	0.2	-10000	0	-0.62	48	48
RAP1/GDP	-0.018	0.042	-10000	0	-10000	0	0
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.013	0.14	-10000	0	-0.6	21	21
ubiquitin-dependent protein catabolic process	-0.01	0.053	-10000	0	-0.55	3	3
Schwann cell development	-0.042	0.032	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.042	0.017	-10000	0	-0.32	1	1
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.067	0.15	-10000	0	-0.47	52	52
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.007	0.037	-10000	0	-10000	0	0
STAT3	0.018	0.024	-10000	0	-10000	0	0
axon guidance	-0.064	0.14	-10000	0	-0.45	52	52
MAPK3	0.014	0.081	-10000	0	-0.5	9	9
MAPK1	0.014	0.081	-10000	0	-0.5	9	9
CDC42/GDP	-0.004	0.063	-10000	0	-0.28	2	2
NTF3	-0.05	0.2	-10000	0	-0.62	48	48
NTF4	-0.02	0.16	-10000	0	-0.64	25	25
NGF (dimer)/TRKA/FAIM	-0.01	0.053	-10000	0	-0.55	3	3
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
FRS3	0.013	0	-10000	0	-10000	0	0
FAIM	0.013	0	-10000	0	-10000	0	0
GAB1	0.013	0	-10000	0	-10000	0	0
RASGRF1	-0.13	0.11	-10000	0	-0.48	27	27
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.053	0.18	-10000	0	-0.59	39	39
RGS19	0.013	0	-10000	0	-10000	0	0
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.002	0.048	-10000	0	-0.42	1	1
Rac1/GDP	-0.004	0.063	-10000	0	-0.28	2	2
NGF (dimer)/TRKA/GRIT	-0.011	0.055	-10000	0	-0.56	3	3
neuron projection morphogenesis	0	0.095	-10000	0	-0.52	3	3
NGF (dimer)/TRKA/NEDD4-2	-0.01	0.053	-10000	0	-0.55	3	3
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.062	0.19	-10000	0	-0.42	84	84
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.079	-10000	0	-0.35	19	19
RAS family/GTP/PI3K	0.03	0.032	-10000	0	-0.37	3	3
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.021	-10000	0	-0.46	1	1
NRAS	0.013	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.013	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.01	0.057	-10000	0	-0.61	3	3
RASA1	0.013	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.007	0.038	-10000	0	-10000	0	0
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.02	0.1	-10000	0	-0.56	15	15
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.008	0.043	-10000	0	-0.47	3	3
MATK	-0.002	0.1	-10000	0	-0.82	6	6
NEDD4L	0.013	0	-10000	0	-10000	0	0
RAS family/GDP	-0.015	0.042	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.036	0.099	-10000	0	-0.45	23	23
Rac1/GTP	-0.19	0.15	-10000	0	-0.35	193	193
FRS2 family/SHP2/CRK family	-0.001	0.021	-10000	0	-0.46	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.046	0.35	-9999	-0.92	14	14
PLK1	0.043	0.07	-9999	-10000	0	0
BIRC5	0.024	0.12	-9999	-1.6	1	1
HSPA1B	0.045	0.35	-9999	-0.92	14	14
MAP2K1	0.032	0.038	-9999	-10000	0	0
BRCA2	0.04	0.36	-9999	-0.98	17	17
FOXM1	0.034	0.39	-9999	-0.99	22	22
XRCC1	0.046	0.35	-9999	-0.92	14	14
FOXM1B/p19	-0.098	0.31	-9999	-0.87	30	30
Cyclin D1/CDK4	0.033	0.34	-9999	-0.86	14	14
CDC2	0.039	0.37	-9999	-0.88	22	22
TGFA	0.016	0.35	-9999	-0.85	17	17
SKP2	0.038	0.37	-9999	-0.98	17	17
CCNE1	0.016	0.01	-9999	-10000	0	0
CKS1B	0.046	0.35	-9999	-0.92	14	14
RB1	-0.054	0.11	-9999	-1.2	1	1
FOXM1C/SP1	0.03	0.37	-9999	-0.97	21	21
AURKB	-0.004	0.12	-9999	-10000	0	0
CENPF	0.04	0.36	-9999	-0.95	14	14
CDK4	0.019	0.015	-9999	-10000	0	0
MYC	0.038	0.36	-9999	-0.92	21	21
CHEK2	0.032	0.038	-9999	-10000	0	0
ONECUT1	0.029	0.35	-9999	-0.88	17	17
CDKN2A	-0.13	0.16	-9999	-0.32	169	169
LAMA4	0.046	0.35	-9999	-0.92	14	14
FOXM1B/HNF6	0.022	0.37	-9999	-1	17	17
FOS	-0.19	0.66	-9999	-1.2	130	130
SP1	0.014	0.005	-9999	-10000	0	0
CDC25B	0.045	0.35	-9999	-0.92	14	14
response to radiation	0.015	0.035	-9999	-10000	0	0
CENPB	0.046	0.35	-9999	-0.92	14	14
CENPA	0.033	0.37	-9999	-0.96	19	19
NEK2	0.036	0.36	-9999	-0.94	17	17
HIST1H2BA	0.037	0.35	-9999	-0.92	14	14
CCNA2	0.01	0.047	-9999	-0.33	9	9
EP300	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.033	0.38	-9999	-1	14	14
CCNB2	0.042	0.36	-9999	-0.95	14	14
CCNB1	0.041	0.37	-9999	-0.96	14	14
ETV5	0.045	0.35	-9999	-0.92	15	15
ESR1	-0.005	0.44	-9999	-1.1	36	36
CCND1	0.035	0.34	-9999	-0.88	14	14
GSK3A	0.03	0.031	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.036	0.05	-9999	-10000	0	0
CDK2	0.016	0.01	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.017	0.041	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.13	0.23	-9999	-0.88	22	22
GAS1	-0.13	0.62	-9999	-1.2	105	105
MMP2	0.036	0.38	-9999	-1.1	17	17
RB1/FOXM1C	0.043	0.34	-9999	-0.93	14	14
CREBBP	0.013	0	-9999	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.013	0.093	-10000	0	-0.35	5	5
epithelial cell differentiation	-0.048	0.1	-10000	0	-0.47	11	11
ITCH	0.024	0.02	-10000	0	-10000	0	0
WWP1	0	0.079	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
EGFR	0.006	0.076	-10000	0	-0.82	4	4
PRL	0.001	0.015	-10000	0	-0.31	1	1
neuron projection morphogenesis	0.003	0.14	-10000	0	-0.51	10	10
PTPRZ1	-0.016	0.13	-10000	0	-0.82	11	11
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.059	0.13	-10000	0	-0.45	47	47
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.044	0.17	-10000	0	-0.53	48	48
ADAM17	0.02	0.058	-10000	0	-0.82	2	2
ErbB4/ErbB4	-0.01	0.1	-10000	0	-0.52	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.044	0.17	-10000	0	-0.56	37	37
NCOR1	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.068	0.15	-10000	0	-0.5	47	47
GRIN2B	-0.029	0.16	-10000	0	-0.47	47	47
ErbB4/ErbB2/betacellulin	-0.036	0.11	-10000	0	-0.63	13	13
STAT1	0.006	0.049	-10000	0	-0.31	11	11
HBEGF	-0.003	0.072	-10000	0	-0.31	25	25
PRLR	-0.047	0.2	-10000	0	-0.61	47	47
E4ICDs/ETO2	-0.005	0.091	-10000	0	-0.57	2	2
axon guidance	-0.001	0.087	-10000	0	-0.44	3	3
NEDD4	0.02	0.057	-10000	0	-0.81	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.045	0.15	-10000	0	-0.64	27	27
CBFA2T3	0.011	0.041	-10000	0	-0.57	2	2
ErbB4/ErbB2/HBEGF	-0.029	0.061	-10000	0	-0.58	2	2
MAPK3	-0.006	0.15	-10000	0	-0.53	11	11
STAT1 (dimer)	-0.007	0.09	-10000	0	-0.45	1	1
MAPK1	-0.006	0.15	-10000	0	-0.53	11	11
JAK2	0.012	0.038	-10000	0	-0.82	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.068	0.15	-10000	0	-0.5	47	47
NRG1	-0.036	0.2	-10000	0	-0.65	47	47
NRG3	-0.049	0.22	-10000	0	-0.82	36	36
NRG2	-0.082	0.26	-10000	0	-0.8	57	57
NRG4	0.007	0.039	-10000	0	-0.31	7	7
heart development	-0.001	0.087	-10000	0	-0.44	3	3
neural crest cell migration	-0.034	0.16	-10000	0	-0.49	47	47
ERBB2	0.028	0.043	-10000	0	-0.62	2	2
WWOX/E4ICDs	-0.005	0.093	-10000	0	-0.95	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.036	0.085	-10000	0	-0.66	4	4
apoptosis	0.057	0.14	0.46	37	-10000	0	37
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.066	0.19	-10000	0	-0.56	55	55
ErbB4/ErbB2/epiregulin	-0.078	0.087	-10000	0	-0.55	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.018	0.13	-10000	0	-0.64	14	14
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.061	0.12	-10000	0	-0.47	28	28
MDM2	0.001	0.087	-10000	0	-0.46	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.063	0.15	-10000	0	-0.5	47	47
STAT5A	0.007	0.082	-10000	0	-0.44	2	2
ErbB4/EGFR/neuregulin 1 beta	-0.072	0.16	-10000	0	-0.51	50	50
DLG4	0.013	0	-10000	0	-10000	0	0
GRB2/SHC	0	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.032	0.063	-10000	0	-0.43	1	1
STAT5A (dimer)	-0.05	0.11	-10000	0	-0.51	11	11
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.08	-10000	0	-0.44	2	2
LRIG1	0	0.11	-10000	0	-0.82	8	8
EREG	-0.14	0.16	-10000	0	-0.31	225	225
BTC	-0.009	0.14	-10000	0	-0.82	13	13
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.001	0.087	-10000	0	-0.44	3	3
ERBB4	-0.01	0.1	-10000	0	-0.52	1	1
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	-0.01	0.02	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.025	0.057	-10000	0	-0.51	2	2
glial cell differentiation	0.032	0.063	0.42	1	-10000	0	1
WWOX	0.012	0.038	-10000	0	-0.82	1	1
cell proliferation	-0.023	0.17	-10000	0	-0.46	54	54

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.013	0.015	-9999	-0.31	1	1
LAT2	-0.019	0.1	-9999	-0.38	5	5
AP1	-0.2	0.28	-9999	-0.63	127	127
mol:PIP3	-0.017	0.15	-9999	-0.52	14	14
IKBKB	0.002	0.093	-9999	-0.29	12	12
AKT1	-0.018	0.14	-9999	-0.59	6	6
IKBKG	0.002	0.093	-9999	-0.29	12	12
MS4A2	-0.066	0.14	-9999	-0.32	113	113
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.83	3	3
MAP3K1	0.01	0.1	-9999	-0.46	7	7
mol:Ca2+	-0.009	0.12	-9999	-0.38	14	14
LYN	0.01	0.007	-9999	-10000	0	0
CBLB	-0.011	0.09	-9999	-0.38	2	2
SHC1	0.013	0	-9999	-10000	0	0
RasGAP/p62DOK	-0.081	0.18	-9999	-0.5	78	78
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.003	0.071	-9999	-0.31	24	24
PLD2	-0.05	0.15	-9999	-0.45	42	42
PTPN13	-0.002	0.1	-9999	-0.59	5	5
PTPN11	0.011	0.04	-9999	-0.86	1	1
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.018	0.1	-9999	-0.37	4	4
SYK	0.01	0.007	-9999	-10000	0	0
GRB2	0.013	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.064	0.13	-9999	-0.54	14	14
LAT	-0.015	0.1	-9999	-0.43	8	8
PAK2	0.001	0.11	-9999	-0.51	8	8
NFATC2	-0.15	0.28	-9999	-0.76	83	83
HRAS	-0.008	0.12	-9999	-0.56	8	8
GAB2	0.013	0	-9999	-10000	0	0
PLA2G1B	0.031	0.017	-9999	-10000	0	0
Fc epsilon R1	-0.1	0.17	-9999	-0.51	54	54
Antigen/IgE/Fc epsilon R1	-0.092	0.16	-9999	-0.49	48	48
mol:GDP	-0.017	0.13	-9999	-0.54	12	12
JUN	-0.17	0.35	-9999	-0.82	109	109
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	129	129
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.045	0.08	-9999	-0.38	4	4
CHUK	0.002	0.093	-9999	-0.29	11	11
KLRG1	-0.023	0.11	-9999	-0.41	14	14
VAV1	-0.023	0.12	-9999	-0.49	9	9
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.011	0.09	-9999	-0.38	2	2
negative regulation of mast cell degranulation	-0.021	0.11	-9999	-0.4	11	11
BTK	-0.048	0.11	-9999	-0.61	11	11
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.049	0.19	-9999	-0.53	44	44
GAB2/PI3K/SHP2	-0.067	0.13	-9999	-0.66	6	6
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.019	0.096	-9999	-0.3	22	22
RAF1	0.018	0.021	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.11	0.2	-9999	-0.58	57	57
FCER1G	-0.009	0.083	-9999	-0.32	32	32
FCER1A	-0.078	0.23	-9999	-0.56	76	76
Antigen/IgE/Fc epsilon R1/Fyn	-0.082	0.14	-9999	-0.48	42	42
MAPK3	0.029	0.017	-9999	-10000	0	0
MAPK1	0.029	0.017	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAPK8	0.007	0.1	-9999	-0.69	9	9
DUSP1	-0.12	0.31	-9999	-0.82	78	78
NF-kappa-B/RelA	-0.019	0.044	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.005	0.084	-9999	-0.38	1	1
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.043	0.1	-9999	-0.63	7	7
FER	-0.014	0.099	-9999	-0.45	6	6
RELA	0.013	0	-9999	-10000	0	0
ITK	-0.074	0.18	-9999	-0.53	61	61
SOS1	0.013	0	-9999	-10000	0	0
PLCG1	-0.013	0.13	-9999	-0.57	10	10
cytokine secretion	-0.014	0.032	-9999	-10000	0	0
SPHK1	-0.015	0.094	-9999	-0.39	4	4
PTK2	-0.006	0.086	-9999	-0.39	1	1
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.067	0.14	-9999	-0.56	12	12
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.012	0.15	-9999	-0.5	13	13
MAP2K2	0.025	0.018	-9999	-10000	0	0
MAP2K1	0.025	0.018	-9999	-10000	0	0
MAP2K7	0.013	0	-9999	-10000	0	0
KLRG1/SHP2	-0.048	0.095	-9999	-0.45	11	11
MAP2K4	0.021	0.008	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.11	0.21	-9999	-0.62	54	54
mol:Choline	-0.049	0.15	-9999	-0.44	42	42
SHC/Grb2/SOS1	-0.032	0.066	-9999	-0.39	1	1
FYN	0.013	0	-9999	-10000	0	0
DOK1	0.013	0	-9999	-10000	0	0
PXN	0.003	0.082	-9999	-0.36	1	1
HCLS1	-0.013	0.094	-9999	-0.4	4	4
PRKCB	-0.011	0.12	-9999	-0.38	21	21
FCGR2B	-0.029	0.18	-9999	-0.82	23	23
IGHE	-0.001	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.021	0.11	-9999	-0.4	11	11
LCP2	0.009	0.039	-9999	-0.32	7	7
PLA2G4A	-0.042	0.16	-9999	-0.52	34	34
RASA1	0.013	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.049	0.15	-9999	-0.44	42	42
IKK complex	0.018	0.076	-9999	-0.23	2	2
WIPF1	0.013	0	-9999	-10000	0	0

×

TCGA08_rtk_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
PDGFRA	-0.25	0.39	-10000	0	-0.82	154	154
HRAS	0.012	0.021	-10000	0	-0.31	2	2
EGFR	0.006	0.076	-10000	0	-0.82	4	4
AKT	0.018	0.025	0.21	1	-10000	0	1
FOXO3	0.013	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
AKT3	0.013	0	-10000	0	-10000	0	0
FOXO4	0.013	0	-10000	0	-10000	0	0
MET	-0.11	0.16	-10000	0	-0.31	180	180
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PIK3CB	0.013	0	-10000	0	-10000	0	0
NRAS	0.013	0	-10000	0	-10000	0	0
PIK3CG	-0.011	0.13	-10000	0	-0.67	17	17
PIK3R3	0.012	0.038	-10000	0	-0.82	1	1
PIK3R2	0.013	0	-10000	0	-10000	0	0
NF1	0.013	0	-10000	0	-10000	0	0
RAS	-0.061	0.099	-10000	0	-0.26	43	43
ERBB2	0.013	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.024	0.024	0.19	1	-0.17	1	2
PI3K	-0.041	0.096	0.23	1	-0.22	49	50
PIK3R1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
FOXO	0.024	0.026	0.2	1	-10000	0	1
AKT2	0.013	0	-10000	0	-10000	0	0
PTEN	0.012	0.038	-10000	0	-0.82	1	1

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.004	0.076	-10000	0	-0.36	7	7
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.013	0	-10000	0	-10000	0	0
AKT2	0.013	0	-10000	0	-10000	0	0
STXBP4	0.012	0.038	-10000	0	-0.82	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.041	0.077	0.26	2	-10000	0	2
YWHAZ	0.013	0	-10000	0	-10000	0	0
CALM1	0.013	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.065	0.22	-10000	0	-0.63	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.025	-10000	0	-0.55	1	1
YWHAG	0.013	0	-10000	0	-10000	0	0
ASIP	-0.03	0.11	-10000	0	-0.31	62	62
PRKCI	0.013	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.013	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
TRIP10	0.013	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.038	0.1	-10000	0	-0.26	56	56
VAMP2	0.013	0	-10000	0	-10000	0	0
SLC2A4	0.042	0.081	0.26	2	-10000	0	2
STX4	0.013	0	-10000	0	-10000	0	0
GSK3B	0.028	0	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	312	312
LNPEP	-0.014	0.15	-10000	0	-0.82	16	16
YWHAE	0.013	0	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0	0.078	-9999	-10000	0	0
STMN1	-0.021	0.094	-9999	-0.39	1	1
Aurora B/RasGAP/Survivin	-0.025	0.11	-9999	-0.55	1	1
Chromosomal passenger complex/Cul3 protein complex	0.007	0.071	-9999	-0.29	14	14
BIRC5	-0.017	0.1	-9999	-0.33	42	42
DES	-0.38	0.3	-9999	-0.61	298	298
Aurora C/Aurora B/INCENP	-0.016	0.088	-9999	-0.48	4	4
Aurora B/TACC1	-0.021	0.081	-9999	-0.71	1	1
Aurora B/PP2A	-0.025	0.091	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.005	0.026	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.05	0.15	-9999	-0.39	60	60
Cul3 protein complex	-0.018	0.088	-9999	-0.55	12	12
KIF2C	0	0.042	-9999	-0.16	1	1
PEBP1	0.011	0.005	-9999	-10000	0	0
KIF20A	-0.043	0.12	-9999	-0.31	80	80
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.025	0.091	-9999	-10000	0	0
SEPT1	0.008	0.042	-9999	-0.31	8	8
SMC2	0.013	0	-9999	-10000	0	0
SMC4	0.013	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.007	0.045	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-9999	-10000	0	0
H3F3B	-0.007	0.055	-9999	-10000	0	0
AURKB	-0.05	0.14	-9999	-0.31	107	107
AURKC	-0.001	0.067	-9999	-0.31	21	21
CDCA8	0.01	0.027	-9999	-0.33	3	3
cytokinesis	-0.066	0.082	-9999	-0.43	5	5
Aurora B/Septin1	-0.027	0.1	-9999	-0.44	7	7
AURKA	0.012	0.002	-9999	-10000	0	0
INCENP	0.009	0.055	-9999	-0.84	2	2
KLHL13	-0.017	0.14	-9999	-0.55	26	26
BUB1	-0.1	0.16	-9999	-0.32	170	170
hSgo1/Aurora B/Survivin	-0.026	0.12	-9999	-0.44	18	18
EVI5	0.014	0.001	-9999	-10000	0	0
RhoA/GTP	-0.031	0.072	-9999	-0.36	3	3
SGOL1	0.001	0.062	-9999	-0.31	18	18
CENPA	-0.008	0.069	-9999	-0.24	6	6
NCAPG	-0.018	0.097	-9999	-0.31	47	47
Aurora B/HC8 Proteasome	-0.025	0.091	-9999	-10000	0	0
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.025	0.091	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.034	0.12	-9999	-0.31	71	71
NPM1	-0.012	0.048	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
KLHL9	0.013	0	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.025	0.091	-9999	-10000	0	0
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.035	0.08	-9999	-0.35	18	18
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.012	0.048	-9999	-10000	0	0
MYLK	-0.007	0.055	-9999	-10000	0	0
KIF23	-0.004	0.073	-9999	-0.32	25	25
VIM	-0.02	0.093	-9999	-10000	0	0
RACGAP1	0.013	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.012	0.048	-9999	-10000	0	0
Chromosomal passenger complex	-0.013	0.083	-9999	-0.26	18	18
Chromosomal passenger complex/EVI5	0.011	0.12	-9999	-0.48	6	6
TACC1	0.012	0.038	-9999	-0.82	1	1
PPP2R5D	0.013	0	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.042	0.12	-9999	-0.42	47	47
Syndecan-3/Neurocan	-0.035	0.12	-9999	-0.47	35	35
POMC	-0.16	0.34	-9999	-0.81	102	102
EGFR	0.006	0.076	-9999	-0.82	4	4
Syndecan-3/EGFR	-0.004	0.042	-9999	-0.46	4	4
AGRP	-0.004	0.059	-9999	-0.31	17	17
NCSTN	0.013	0	-9999	-10000	0	0
PSENEN	0.013	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
NCAN	-0.051	0.22	-9999	-0.77	39	39
long-term memory	0	0.005	-9999	-10000	0	0
Syndecan-3/IL8	-0.039	0.081	-9999	-0.46	10	10
PSEN1	0.013	0	-9999	-10000	0	0
Src/Cortactin	0	0.009	-9999	-10000	0	0
FYN	0.013	0	-9999	-10000	0	0
limb bud formation	-0.001	0.008	-9999	-10000	0	0
MC4R	0.001	0.039	-9999	-0.31	7	7
SRC	0.013	0.015	-9999	-0.31	1	1
PTN	-0.068	0.25	-9999	-0.81	48	48
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	-0.07	0.15	-9999	-0.61	3	3
Syndecan-3/AgRP	-0.005	0.023	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.006	0.025	-9999	-10000	0	0
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.038	0.08	-9999	-0.46	10	10
IL8	-0.081	0.18	-9999	-0.36	124	124
Syndecan-3/Fyn/Cortactin	-0.001	0.006	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.13	0.26	-9999	-0.64	99	99
Gamma Secretase	0	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.061	0.16	-10000	0	-0.48	62	62
MAPK9	0.009	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.007	0.054	-10000	0	-0.21	31	31
GNB1/GNG2	-0.001	0.025	-10000	0	-0.55	1	1
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0	-10000	0	-10000	0	0
Gs family/GTP	-0.065	0.17	-10000	0	-0.52	61	61
EntrezGene:2778	0	0	-10000	0	-10000	0	0
vasopressin secretion	0	0	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
glutamate secretion	0.015	0.039	0.12	61	-10000	0	61
GNAL	-0.092	0.28	-10000	0	-0.82	61	61
GNG2	0.012	0.038	-10000	0	-0.82	1	1
CRH	-0.013	0.079	-10000	0	-0.31	31	31
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0.063	-10000	0	-0.46	9	9
MAPK11	0.009	0	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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
ADCY4	0.016	0.052	-9999	-0.55	4	4
ADCY5	-0.058	0.2	-9999	-0.56	65	65
ADCY6	0.016	0.052	-9999	-0.55	4	4
ADCY7	0.016	0.052	-9999	-0.55	4	4
ADCY1	0.01	0.078	-9999	-0.57	8	8
ADCY2	-0.04	0.18	-9999	-0.57	46	46
ADCY3	0.016	0.052	-9999	-0.55	4	4
ADCY8	-0.12	0.099	-9999	-0.7	4	4
PRKCE	0.007	0.059	-9999	-0.64	4	4
ADCY9	0.016	0.052	-9999	-0.55	4	4
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.056	0.1	-9999	-0.37	31	31

×

IFN-gamma pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.027	0.16	-9999	-0.44	64	64
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.049	0.12	-9999	-0.75	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.01	0.037	-9999	-0.65	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.024	0.061	-9999	-0.3	2	2
CaM/Ca2+	-0.056	0.14	-9999	-0.4	64	64
RAP1A	0.013	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.02	0.16	-9999	-0.41	64	64
AKT1	-0.002	0.15	-9999	-0.62	3	3
MAP2K1	-0.005	0.15	-9999	-0.38	63	63
MAP3K11	-0.017	0.16	-9999	-0.41	64	64
IFNGR1	0.009	0.014	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.067	-9999	-0.64	1	1
Rap1/GTP	-0.041	0.1	-9999	-0.6	1	1
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.063	0.16	-9999	-0.46	63	63
CEBPB	0.017	0.18	-9999	-0.82	5	5
STAT3	0.013	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.059	0.15	-9999	-1.1	2	2
STAT1	-0.019	0.16	-9999	-0.41	64	64
CALM1	0.013	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.1	0.28	-9999	-0.72	78	78
PIK3CA	0.008	0.066	-9999	-0.82	3	3
STAT1 (dimer)/PIAS1	-0.01	0.15	-9999	-0.48	5	5
CEBPB/PTGES2/Cbp/p300	-0.035	0.082	-9999	-0.44	5	5
mol:Ca2+	-0.06	0.15	-9999	-0.43	64	64
MAPK3	0.01	0.14	-9999	-0.53	5	5
STAT1 (dimer)	-0.03	0.08	-9999	-0.42	2	2
MAPK1	0.01	0.14	-9999	-0.53	5	5
JAK2	0.008	0.042	-9999	-0.88	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.009	0.014	-9999	-10000	0	0
CAMK2D	0.013	0	-9999	-10000	0	0
DAPK1	0.015	0.18	-9999	-0.66	24	24
SMAD7	0.041	0.056	-9999	-10000	0	0
CBL/CRKL/C3G	-0.05	0.12	-9999	-0.76	1	1
PI3K	-0.056	0.14	-9999	-0.52	8	8
IFNG	-0.1	0.28	-9999	-0.72	78	78
apoptosis	0.013	0.13	-9999	-0.45	24	24
CAMK2G	0.013	0	-9999	-10000	0	0
STAT3 (dimer)	0.013	0	-9999	-10000	0	0
CAMK2A	-0.004	0.068	-9999	-0.31	22	22
CAMK2B	0.005	0.084	-9999	-0.82	5	5
FRAP1	0	0.14	-9999	-0.57	3	3
PRKCD	-0.002	0.15	-9999	-0.63	3	3
RAP1B	0.013	0	-9999	-10000	0	0
negative regulation of cell growth	-0.024	0.061	-9999	-0.3	2	2
PTPN2	0.013	0	-9999	-10000	0	0
EP300	0.014	0	-9999	-10000	0	0
IRF1	0.029	0.12	-9999	-0.47	2	2
STAT1 (dimer)/PIASy	-0.054	0.13	-9999	-0.48	5	5
SOCS1	0.001	0.074	-9999	-1.5	1	1
mol:GDP	-0.048	0.12	-9999	-0.71	1	1
CASP1	0.039	0.062	-9999	-0.35	2	2
PTGES2	0.013	0	-9999	-10000	0	0
IRF9	0.042	0.058	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.055	0.14	-9999	-0.5	8	8
RAP1/GDP	-0.041	0.1	-9999	-0.6	1	1
CBL	-0.017	0.16	-9999	-0.41	64	64
MAP3K1	-0.016	0.16	-9999	-0.41	64	64
PIAS1	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.024	0.061	-9999	-0.3	2	2
PTPN11	-0.027	0.16	-9999	-0.43	64	64
CREBBP	0.014	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.014	0.12	-9999	-0.44	30	30
CCNA2	0.007	0.044	-9999	-0.31	9	9
PIK3CA	0.009	0.066	-9999	-0.82	3	3
JAK3	-0.067	0.14	-9999	-0.31	120	120
PIK3R1	0.014	0	-9999	-10000	0	0
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.018	0.15	-9999	-0.56	19	19
SHC1	0.014	0	-9999	-10000	0	0
SP1	0.022	0	-9999	-10000	0	0
IL2RA	-0.043	0.25	-9999	-0.98	30	30
IL2RB	-0.014	0.13	-9999	-0.51	26	26
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.046	0.19	-9999	-0.55	52	52
G1/S transition of mitotic cell cycle	0.039	0.054	-9999	-0.59	3	3
PTPN11	0.012	0.038	-9999	-0.82	1	1
CCND2	0.033	0	-9999	-10000	0	0
LCK	-0.009	0.11	-9999	-0.44	25	25
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.005	0.006	-9999	-10000	0	0
CDK6	0.008	0.066	-9999	-0.82	3	3
CCND3	0.028	0.13	-9999	-0.64	7	7

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.16	0.34	-9999	-0.82	102	102
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.026	-9999	-0.31	3	3
TCEB1	0.013	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.023	-9999	-10000	0	0
HIF1A	0.022	0.024	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.004	0.041	-9999	-0.51	3	3
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.13	0.16	-9999	-0.31	208	208
ARNT/IPAS	-0.13	0.26	-9999	-0.63	102	102
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.013	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.023	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.012	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.023	-9999	-10000	0	0
PHD1-3/OS9	-0.018	0.088	-9999	-0.54	12	12
HIF1A/RACK1/Elongin B/Elongin C	-0.003	0.017	-9999	-10000	0	0
VHL	0.008	0.066	-9999	-0.82	3	3
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.023	-9999	-10000	0	0
EGLN3	-0.017	0.14	-9999	-0.51	28	28
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.01	0.054	-9999	-0.82	2	2
TP53	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.051	-9999	-0.6	3	3
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.032	0.074	-9999	-0.29	1	1

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.003	0.11	0.57	14	-10000	0	14
PI3K Class IB/PDE3B	-0.003	0.11	-10000	0	-0.57	14	14
PDE3B	-0.003	0.11	-10000	0	-0.57	14	14

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.018	0.12	-10000	0	-0.79	11	11
HDAC1	0.002	0.009	-10000	0	-10000	0	0
AES	0.012	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	0.001	0.1	-10000	0	-0.82	7	7
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.007	0.065	-10000	0	-0.82	3	3
AP1	-0.14	0.26	-10000	0	-0.49	162	162
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.006	0.12	-10000	0	-0.82	11	11
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.054	-10000	0	-0.34	1	1
NICD/RBPSUH	-0.017	0.11	-10000	0	-0.74	11	11
WIF1	-0.033	0.1	-10000	0	-10000	0	0
NOTCH1	-0.017	0.11	-10000	0	-0.77	11	11
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.01	0.085	-10000	0	-0.31	35	35
DKK1	-0.043	0.13	-10000	0	-0.82	2	2
beta catenin/beta TrCP1	0.036	0.037	-10000	0	-10000	0	0
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	0	0.036	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.024	0.037	-10000	0	-0.35	2	2
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.21	0.37	-10000	0	-0.82	129	129
JUN	-0.17	0.35	-10000	0	-0.82	109	109
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.029	0.04	0.24	13	-10000	0	13
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.037	0.12	-10000	0	-0.56	20	20
HNF1A	0.012	0.002	-10000	0	-10000	0	0
CTBP1	0.012	0.002	-10000	0	-10000	0	0
MYC	-0.015	0.25	-10000	0	-1.5	13	13
NKD1	-0.013	0.14	-10000	0	-0.73	17	17
FZD1	0.013	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.023	0.12	-10000	0	-0.62	18	18
apoptosis	-0.14	0.26	-10000	0	-0.48	162	162
Delta 1/NOTCHprecursor	-0.017	0.12	-10000	0	-0.76	11	11
DLL1	0.011	0.041	-10000	0	-0.57	2	2
PPARD	0.024	0.017	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.001	0.06	-10000	0	-1.1	1	1
DVL1	0.003	0.01	-10000	0	-10000	0	0
CSNK2A1	0.014	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.039	0.081	-10000	0	-0.63	2	2
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.002	-10000	0	-10000	0	0
NLK	0.015	0.008	-10000	0	-10000	0	0
CCND1	0.019	0.043	-10000	0	-10000	0	0
WNT1	0.01	0.021	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.043	0.051	-10000	0	-0.67	1	1
DKK2	-0.028	0.17	-10000	0	-0.65	30	30
NOTCH1 precursor/DVL1	-0.012	0.097	-10000	0	-0.65	11	11
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.024	0.12	-10000	0	-0.64	18	18
PPP2R5D	0.011	0.063	0.37	14	-10000	0	14
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.016	0.044	-10000	0	-10000	0	0
RBPJ	0.013	0.015	-10000	0	-0.31	1	1
CREBBP	0.017	0.004	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0	-10000	0	-10000	0	0
MAP4K4	-0.003	0.14	-10000	0	-0.7	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
PKC zeta/ceramide	-0.018	0.04	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.036	0.19	-10000	0	-0.68	35	35
BAX	-0.005	0.019	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AKT1	0.023	0.008	-10000	0	-10000	0	0
BAD	-0.017	0.04	-10000	0	-10000	0	0
SMPD1	-0.006	0.096	-10000	0	-0.26	58	58
RB1	-0.018	0.046	-10000	0	-0.5	1	1
FADD/Caspase 8	0.009	0.14	-10000	0	-0.66	11	11
MAP2K4	-0.009	0.038	-10000	0	-10000	0	0
NSMAF	0.013	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.011	0.05	-10000	0	-0.52	2	2
EGF	-0.11	0.29	-10000	0	-0.78	74	74
mol:ceramide	-0.028	0.043	-10000	0	-10000	0	0
MADD	0.013	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.023	0.03	-10000	0	-0.63	1	1
ASAH1	0.012	0.038	-10000	0	-0.82	1	1
negative regulation of cell cycle	-0.018	0.045	-10000	0	-0.49	1	1
cell proliferation	-0.1	0.16	-10000	0	-0.39	114	114
BID	-0.017	0.093	-10000	0	-0.4	11	11
MAP3K1	-0.017	0.04	-10000	0	-10000	0	0
EIF2A	0	0.036	-10000	0	-10000	0	0
TRADD	0.013	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
MAPK3	0.002	0.047	-10000	0	-0.47	2	2
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.002	0.047	-10000	0	-0.47	2	2
Cathepsin D/ceramide	-0.018	0.04	-10000	0	-10000	0	0
FADD	-0.003	0.14	-10000	0	-0.7	11	11
KSR1	-0.019	0.053	-10000	0	-0.55	2	2
MAPK8	-0.009	0.056	-10000	0	-0.31	9	9
PRKRA	-0.017	0.04	-10000	0	-10000	0	0
PDGFA	0.013	0	-10000	0	-10000	0	0
TRAF2	0.013	0	-10000	0	-10000	0	0
IGF1	-0.18	0.35	-10000	0	-0.8	119	119
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.028	0.042	-10000	0	-10000	0	0
CTSD	0.013	0.015	-10000	0	-0.31	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.029	-10000	0	-0.63	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.087	0.19	-10000	0	-0.42	114	114
PRKCD	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.023	0.03	-10000	0	-0.63	1	1
RelA/NF kappa B1	-0.001	0.029	-10000	0	-0.63	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.013	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.15	-10000	0	-0.75	11	11
TNFR1A/BAG4/TNF-alpha	-0.068	0.18	-10000	0	-0.55	59	59
mol:Sphingosine-1-phosphate	0.024	0	-10000	0	-10000	0	0
MAP2K1	-0.002	0.048	-10000	0	-0.49	2	2
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
CYCS	0.004	0.051	0.18	26	-10000	0	26
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
TNFR1A/BAG4	-0.001	0.029	-10000	0	-0.63	1	1
EIF2AK2	-0.009	0.038	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.067	0.18	-10000	0	-0.55	58	58
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.015	0.08	-10000	0	-0.33	11	11
MAP2K2	-0.002	0.048	-10000	0	-0.49	2	2
SMPD3	-0.012	0.12	-10000	0	-0.3	63	63
TNF	-0.091	0.27	-10000	0	-0.78	64	64
PKC zeta/PAR4	0	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.022	0.11	0.28	68	-10000	0	68
NF kappa B1/RelA/I kappa B alpha	-0.001	0.021	-10000	0	-0.46	1	1
AIFM1	0.003	0.051	0.18	26	-10000	0	26
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0	-10000	0	-10000	0	0
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.021	0.03	0.63	1	-10000	0	1
CDKN1A	-0.007	0.039	-10000	0	-10000	0	0
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
FOXO3	0	0.007	-10000	0	-10000	0	0
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.024	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	0.006	0.03	-10000	0	-0.31	4	4
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.011	0.02	-10000	0	-10000	0	0
PPARGC1A	-0.35	0.42	-10000	0	-0.82	211	211
FHL2	-0.054	0.23	-10000	0	-0.82	39	39
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.031	-10000	0	-0.63	1	1
HIST2H4A	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/FOXO3a	0.001	0.027	-10000	0	-0.56	1	1
SIRT1	0.001	0.04	-10000	0	-0.82	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.028	-10000	0	-0.55	1	1
SIRT1/Histone H1b	-0.005	0.051	-10000	0	-0.33	10	10
apoptosis	-0.001	0.028	0.54	1	-10000	0	1
SIRT1/PGC1A	-0.24	0.28	-10000	0	-0.56	211	211
p53/SIRT1	0.005	0.045	-10000	0	-0.63	1	1
SIRT1/FOXO4	0.001	0.028	-10000	0	-0.53	1	1
FOXO1/FHL2/SIRT1	-0.039	0.14	-10000	0	-0.51	40	40
HIST1H1E	0.015	0.054	-10000	0	-0.37	9	9
SIRT1/p300	0.001	0.031	-10000	0	-0.63	1	1
muscle cell differentiation	0	0.031	0.55	1	-10000	0	1
TP53	0.003	0.013	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.029	-10000	0	-0.55	1	1
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.001	0.036	-10000	0	-0.63	1	1
ACSS2	0.021	0.03	-10000	0	-0.63	1	1
SIRT1/PCAF/MYOD	0	0.031	-10000	0	-0.56	1	1

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.011	0.12	-10000	0	-0.88	2	2
UGCG	-0.04	0.17	-10000	0	-0.82	21	21
AKT1/mTOR/p70S6K/Hsp90/TERT	0.02	0.13	-10000	0	-0.41	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.019	0.17	-10000	0	-0.8	21	21
mol:DAG	0	0.004	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.059	0.14	-10000	0	-0.46	35	35
FRAP1	0.002	0.2	-10000	0	-0.49	50	50
FOXO3	0.02	0.16	-10000	0	-0.6	18	18
AKT1	0.01	0.18	-10000	0	-0.59	24	24
GAB2	0.013	0.004	-10000	0	-10000	0	0
SMPD1	-0.005	0.023	-10000	0	-10000	0	0
SGMS1	-0.005	0.023	-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	0.019	0.046	-10000	0	-0.56	3	3
CALM1	0.013	0	-10000	0	-10000	0	0
cell proliferation	-0.001	0.16	-10000	0	-0.47	31	31
EIF3A	0.013	0	-10000	0	-10000	0	0
PI3K	0.02	0.053	-10000	0	-0.64	3	3
RPS6KB1	0.017	0.041	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.004	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.012	5	5
JAK3	-0.065	0.14	-10000	0	-0.31	120	120
PIK3R1	0.015	0.005	-10000	0	-10000	0	0
JAK1	0.015	0.005	-10000	0	-10000	0	0
NFKB1	0.012	0.038	-10000	0	-0.82	1	1
MYC	0.007	0.22	-10000	0	-0.94	18	18
MYB	-0.016	0.2	-10000	0	-1.3	10	10
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.008	0.16	-10000	0	-0.55	25	25
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.038	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.009	0.16	-10000	0	-0.53	25	25
Rac1/GDP	0.024	0.043	-10000	0	-0.51	3	3
T cell proliferation	0.018	0.15	-10000	0	-0.51	21	21
SHC1	0.013	0.004	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.004	0.011	-10000	0	-0.051	16	16
PRKCZ	0.017	0.15	-10000	0	-0.54	21	21
NF kappa B1 p50/RelA	-0.058	0.14	-10000	0	-0.45	35	35
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.001	0.13	-10000	0	-0.6	11	11
HSP90AA1	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL2RA	-0.047	0.2	-10000	0	-0.58	49	49
IL2RB	-0.013	0.13	-10000	0	-0.51	26	26
TERT	0	0.033	-10000	0	-0.31	5	5
E2F1	-0.005	0.076	-10000	0	-0.45	10	10
SOS1	0.013	0.004	-10000	0	-10000	0	0
RPS6	0.013	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.005	0.024	16	-10000	0	16
PTPN11	0.011	0.038	-10000	0	-0.83	1	1
IL2RG	-0.045	0.19	-10000	0	-0.55	52	52
actin cytoskeleton organization	0.018	0.15	-10000	0	-0.51	21	21
GRB2	0.013	0.004	-10000	0	-10000	0	0
IL2	0.007	0.007	-10000	0	-10000	0	0
PIK3CA	0.01	0.066	-10000	0	-0.83	3	3
Rac1/GTP	0.031	0.043	-10000	0	-0.49	3	3
LCK	-0.008	0.11	-10000	0	-0.43	25	25
BCL2	-0.025	0.28	-10000	0	-0.82	47	47

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.053	0.14	-9999	-0.44	58	58
TC10/GTP	-0.004	0.038	-9999	-0.42	4	4
Insulin Receptor/Insulin/IRS1/Shp2	-0.059	0.17	-9999	-0.52	55	55
HRAS	0.012	0.021	-9999	-0.31	2	2
APS homodimer	0.013	0.015	-9999	-0.31	1	1
GRB14	-0.011	0.14	-9999	-0.82	14	14
FOXO3	-0.025	0.11	-9999	-0.72	11	11
AKT1	-0.01	0.16	-9999	-0.89	2	2
INSR	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	0.006	0.076	-9999	-0.82	4	4
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.038	0	-9999	-10000	0	0
CAV1	-0.042	0.18	-9999	-0.48	68	68
CBL/APS/CAP/Crk-II/C3G	-0.004	0.042	-9999	-0.46	4	4
Insulin Receptor/Insulin/IRS1/NCK2	-0.058	0.16	-9999	-0.51	55	55
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.053	0.15	-9999	-0.46	57	57
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.005	0.1	-9999	-10000	0	0
RPS6KB1	0	0.15	-9999	-0.76	2	2
PARD6A	0.013	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.054	0.13	-9999	-0.78	2	2
HRAS/GTP	-0.048	0.12	-9999	-0.5	3	3
Insulin Receptor	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.054	0.15	-9999	-0.48	55	55
PRKCI	-0.014	0.034	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.062	0.16	-9999	-0.43	71	71
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PI3K	-0.054	0.15	-9999	-0.46	57	57
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.014	-9999	-10000	0	0
AKT2	-0.01	0.16	-9999	-0.89	2	2
PRKCZ	-0.014	0.034	-9999	-10000	0	0
SH2B2	0.013	0.015	-9999	-0.31	1	1
SHC/SHIP	-0.026	0.16	-9999	-0.45	55	55
F2RL2	-0.081	0.16	-9999	-0.32	135	135
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.004	0.045	-9999	-0.5	4	4
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0	0	-9999	-10000	0	0
INPP5D	-0.036	0.16	-9999	-0.49	55	55
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.027	0.16	-9999	-1	11	11
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
IRS1	-0.081	0.26	-9999	-0.82	55	55
p62DOK/RasGAP	0	0	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	-0.036	0.16	-9999	-0.48	55	55
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.001	0.15	-9999	-0.64	4	4
PTPRA	0.015	0	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.01	0.054	-9999	-0.82	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.006	0.12	-9999	-0.33	55	55
Insulin Receptor/Insulin/IRS1	-0.059	0.16	-9999	-0.52	55	55
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.036	0.064	-9999	-0.47	3	3

×

Signaling events mediated by PRL

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
CCNE1	0.013	0	-9999	-10000	0	0
mol:Halofuginone	0.005	0.002	-9999	-10000	0	0
ITGA1	0.003	0.092	-9999	-0.82	6	6
CDKN1A	-0.013	0.088	-9999	-10000	0	0
PRL-3/alpha Tubulin	-0.016	0.055	-9999	-10000	0	0
mol:Ca2+	-0.013	0.11	-9999	-0.65	9	9
AGT	-0.019	0.13	-9999	-0.45	34	34
CCNA2	-0.062	0.2	-9999	-0.59	4	4
TUBA1B	0.013	0	-9999	-10000	0	0
EGR1	-0.11	0.27	-9999	-0.63	103	103
CDK2/Cyclin E1	0.004	0.077	-9999	-10000	0	0
MAPK3	0.006	0.061	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0	0	-9999	-10000	0	0
MAPK1	0.006	0.061	-9999	-10000	0	0
PTP4A1	-0.071	0.21	-9999	-0.48	103	103
PTP4A3	-0.013	0.089	-9999	-0.31	39	39
PTP4A2	0.013	0	-9999	-10000	0	0
ITGB1	0.006	0.061	-9999	-10000	0	0
SRC	0.013	0.015	-9999	-0.31	1	1
RAC1	-0.016	0.092	-9999	-0.25	13	13
Rab GGTase beta/Rab GGTase alpha	0	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.067	0.2	-9999	-0.59	4	4
RABGGTA	0.013	0	-9999	-10000	0	0
BCAR1	0.012	0.04	-9999	-10000	0	0
RHOC	-0.016	0.092	-9999	-10000	0	0
RHOA	-0.016	0.092	-9999	-10000	0	0
cell motility	-0.014	0.098	-9999	-0.26	13	13
PRL-1/alpha Tubulin	-0.061	0.2	-9999	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.09	-9999	-0.66	6	6
ROCK1	-0.015	0.099	-9999	-0.27	13	13
RABGGTB	0.013	0	-9999	-10000	0	0
CDK2	0.013	0	-9999	-10000	0	0
mitosis	-0.071	0.21	-9999	-0.48	103	103
ATF5	0	0.065	-9999	-0.31	20	20

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
ITGA4	0.004	0.069	-9999	-0.41	11	11
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.62	15	15
alpha4/beta1 Integrin	-0.006	0.049	-9999	-0.63	2	2

×

Cellular roles of Anthrax toxin

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
ANTXR1	-0.004	0.12	-10000	0	-0.82	10	10
ANTXR2	0.008	0.066	-10000	0	-0.82	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.016	-10000	0	-0.1	13	13
monocyte activation	-0.049	0.17	-10000	0	-0.48	62	62
MAP2K2	-0.001	0.007	-10000	0	-10000	0	0
MAP2K1	-0.002	0.014	-10000	0	-10000	0	0
MAP2K7	-0.002	0.014	-10000	0	-10000	0	0
MAP2K6	-0.013	0.073	-10000	0	-0.5	10	10
CYAA	0.003	0.081	-10000	0	-0.48	13	13
MAP2K4	-0.002	0.014	-10000	0	-10000	0	0
IL1B	-0.025	0.14	-10000	0	-0.47	40	40
Channel	-0.014	0.083	-10000	0	-0.51	13	13
NLRP1	-0.004	0.034	-10000	0	-0.49	2	2
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.019	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.016	0.1	13	-10000	0	13
MAPK3	-0.002	0.014	-10000	0	-10000	0	0
MAPK1	-0.002	0.014	-10000	0	-10000	0	0
PGR	-0.024	0.089	-10000	0	-0.47	16	16
PA/Cellular Receptors	-0.015	0.089	-10000	0	-0.55	13	13
apoptosis	-0.003	0.016	-10000	0	-0.1	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.004	0.08	-10000	0	-0.48	13	13
macrophage activation	0.019	0.015	-10000	0	-10000	0	0
TNF	-0.091	0.27	-10000	0	-0.78	64	64
VCAM1	-0.05	0.18	-10000	0	-0.49	62	62
platelet activation	-0.003	0.019	-10000	0	-10000	0	0
MAPKKK cascade	-0.013	0.024	0.11	10	-10000	0	10
IL18	-0.01	0.086	-10000	0	-0.42	14	14
negative regulation of macrophage activation	-0.003	0.016	-10000	0	-0.1	13	13
LEF	-0.003	0.017	-10000	0	-0.1	13	13
CASP1	-0.004	0.02	-10000	0	-0.22	2	2
mol:cAMP	-0.003	0.019	-10000	0	-10000	0	0
necrosis	-0.003	0.016	-10000	0	-0.1	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.013	0.079	-10000	0	-0.49	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.023	0.092	-9999	-0.51	1	1
RAD9A	0.013	0	-9999	-10000	0	0
AP1	-0.28	0.45	-9999	-0.92	152	152
IFNAR2	0.014	0.003	-9999	-10000	0	0
AKT1	-0.001	0.071	-9999	-0.29	24	24
ER alpha/Oestrogen	-0.044	0.14	-9999	-0.4	55	55
NFX1/SIN3/HDAC complex	0.047	0.026	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
SMG5	0.013	0	-9999	-10000	0	0
SMG6	0.013	0	-9999	-10000	0	0
SP3/HDAC2	0.007	0.011	-9999	-10000	0	0
TERT/c-Abl	-0.035	0.068	-9999	-0.48	1	1
SAP18	0.014	0	-9999	-10000	0	0
MRN complex	-0.003	0.043	-9999	-0.55	3	3
WT1	-0.025	0.1	-9999	-0.31	53	53
WRN	0.012	0.038	-9999	-0.82	1	1
SP1	0.015	0.003	-9999	-10000	0	0
SP3	0.014	0.002	-9999	-10000	0	0
TERF2IP	0.013	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.029	0.053	-9999	-10000	0	0
Mad/Max	0.006	0.01	-9999	-10000	0	0
TERT	-0.023	0.093	-9999	-0.52	1	1
CCND1	-0.015	0.092	-9999	-0.57	1	1
MAX	0.014	0.002	-9999	-10000	0	0
RBBP7	0.014	0	-9999	-10000	0	0
RBBP4	0.008	0.066	-9999	-0.82	3	3
TERF2	0	0.005	-9999	-10000	0	0
PTGES3	0.013	0	-9999	-10000	0	0
SIN3A	0.014	0	-9999	-10000	0	0
Telomerase/911	0.036	0.019	-9999	-10000	0	0
CDKN1B	-0.04	0.19	-9999	-0.52	63	63
RAD1	0.013	0	-9999	-10000	0	0
XRCC5	0.013	0	-9999	-10000	0	0
XRCC6	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.001	-9999	-10000	0	0
JUN	-0.17	0.35	-9999	-0.82	109	109
E6	0	0.001	-9999	-10000	0	0
HPV-16 E6/E6AP	0.003	0.006	-9999	-10000	0	0
FOS	-0.21	0.37	-9999	-0.82	129	129
IFN-gamma/IRF1	-0.086	0.21	-9999	-0.61	64	64
PARP2	0.013	0	-9999	-10000	0	0
BLM	0.013	0.015	-9999	-10000	0	0
Telomerase	0.014	0.072	-9999	-0.48	5	5
IRF1	0.018	0.015	-9999	-0.3	1	1
ESR1	-0.049	0.19	-9999	-0.54	55	55
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.025	-9999	-0.56	1	1
ubiquitin-dependent protein catabolic process	0.052	0.027	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.053	0.027	-9999	-10000	0	0
HDAC1	0.014	0	-9999	-10000	0	0
HDAC2	0.015	0.003	-9999	-10000	0	0
ATM	-0.001	0.026	-9999	-0.56	1	1
SMAD3	0.02	0.029	-9999	-10000	0	0
ABL1	0.013	0	-9999	-10000	0	0
MXD1	0.014	0.002	-9999	-10000	0	0
MRE11A	0.008	0.066	-9999	-0.82	3	3
HUS1	0.013	0	-9999	-10000	0	0
RPS6KB1	0.013	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.031	0.065	-9999	-10000	0	0
NR2F2	0.012	0.002	-9999	-10000	0	0
MAPK3	0.017	0.006	-9999	-10000	0	0
MAPK1	0.017	0.006	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.008	0.042	-9999	-0.31	8	8
NFKB1	0.012	0.038	-9999	-0.82	1	1
HNRNPC	0.013	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.025	-9999	-0.56	1	1
NBN	0.013	0	-9999	-10000	0	0
EGFR	0.007	0.076	-9999	-0.82	4	4
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.096	0.22	-9999	-0.63	72	72
MYC	-0.009	0.14	-9999	-0.82	13	13
IL2	0.006	0.007	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
TGFB1	0.008	0.042	-9999	-0.31	8	8
TRF2/BLM	0	0.009	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.018	0.078	-9999	-10000	0	0
SP1/HDAC2	0.022	0.007	-9999	-10000	0	0
PINX1	0.013	0	-9999	-10000	0	0
Telomerase/EST1A	-0.029	0.053	-9999	-10000	0	0
Smad3/Myc	0.009	0.097	-9999	-0.56	13	13
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.1	0.28	-9999	-0.71	78	78
Telomerase/PinX1	-0.029	0.053	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.021	0.037	-9999	-10000	0	0
SIN3B	0.014	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
Telomerase/EST1B	-0.029	0.053	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0.007	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.003	0.036	-9999	-0.45	3	3
TRF2/WRN	-0.001	0.027	-9999	-0.59	1	1
Telomerase/hnRNP C1/C2	-0.029	0.053	-9999	-10000	0	0
E2F1	-0.088	0.15	-9999	-0.31	152	152
ZNFX1	0.014	0	-9999	-10000	0	0
PIF1	0.002	0.089	-9999	-0.6	9	9
NCL	0.013	0	-9999	-10000	0	0
DKC1	0.013	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.013	0	-10000	0	-10000	0	0
mol:PIP3	-0.042	0.12	0.33	1	-0.36	57	58
FRAP1	0.008	0.026	-10000	0	-10000	0	0
AKT1	-0.035	0.1	0.25	1	-0.66	3	4
INSR	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.026	0.077	-10000	0	-0.51	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.007	0.022	-10000	0	-10000	0	0
TSC2	0.013	0	-10000	0	-10000	0	0
RHEB/GDP	-0.022	0.065	-10000	0	-0.46	3	3
TSC1	0.013	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.033	0.14	-10000	0	-0.42	55	55
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.009	0.027	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.013	0	-10000	0	-10000	0	0
RPS6KB1	0.01	0.06	-10000	0	-0.35	3	3
MAP3K5	0.011	0.021	-10000	0	-0.45	1	1
PIK3R1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.011	0.021	-10000	0	-0.45	1	1
mol:LY294002	0	0.001	0.001	1	-0.002	54	55
EIF4B	0.018	0.054	-10000	0	-0.34	2	2
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.013	0.039	-10000	0	-0.32	2	2
eIF4E/eIF4G1/eIF4A1	-0.001	0.008	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.023	0.14	-10000	0	-0.39	57	57
mTOR/RHEB/GTP/Raptor/GBL	0.021	0.04	0.18	1	-0.28	2	3
FKBP1A	0.013	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.022	0.064	-10000	0	-0.45	3	3
mol:Amino Acids	0	0.001	0.001	1	-0.002	54	55
FKBP12/Rapamycin	0	0.001	-10000	0	-10000	0	0
PDPK1	-0.039	0.12	0.26	1	-0.34	57	58
EIF4E	0.013	0	-10000	0	-10000	0	0
ASK1/PP5C	0.016	0.034	-10000	0	-0.62	1	1
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.028	0.083	-10000	0	-0.56	3	3
tumor necrosis factor receptor activity	0	0.001	0.002	54	-0.001	1	55
RPS6	0.013	0	-10000	0	-10000	0	0
PPP5C	0.013	0	-10000	0	-10000	0	0
EIF4G1	0.013	0	-10000	0	-10000	0	0
IRS1	-0.044	0.15	-10000	0	-0.46	55	55
INS	0	0	-10000	0	-10000	0	0
PTEN	0.011	0.038	-10000	0	-0.82	1	1
PDK2	-0.037	0.11	0.26	1	-0.32	57	58
EIF4EBP1	0.012	0.01	-10000	0	-10000	0	0
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PPP2R5D	0.015	0.025	-10000	0	-10000	0	0
peptide biosynthetic process	0.018	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
EIF4A1	0.013	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.004	1	-0.004	3	4
EEF2	0.018	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.019	0.008	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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
HDAC1	0.013	0	-10000	0	-10000	0	0
HDAC3	0.013	0	-10000	0	-10000	0	0
VDR	0.013	0.015	-10000	0	-10000	0	0
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.033	0.06	-10000	0	-0.34	6	6
KAT2B	0.013	0	-10000	0	-10000	0	0
MAPK14	0.013	0	-10000	0	-10000	0	0
AKT1	0.011	0.085	0.24	6	-0.41	14	20
RAR alpha/9cRA/Cyclin H	-0.024	0.095	-10000	0	-0.41	24	24
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.029	0.067	-10000	0	-0.38	7	7
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0.001	0.002	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.015	0.11	-10000	0	-0.72	9	9
NCOR2	0.013	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0	0.01	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.021	0.16	-10000	0	-0.62	27	27
NCOA2	-0.062	0.24	-10000	0	-0.82	44	44
NCOA3	0.013	0	-10000	0	-10000	0	0
NCOA1	0.013	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.013	0.015	-10000	0	-10000	0	0
RARG	0.014	0.002	-10000	0	-10000	0	0
RAR gamma1/9cRA	0	0	-10000	0	-10000	0	0
MAPK3	0.014	0.002	-10000	0	-10000	0	0
MAPK1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.11	-10000	0	-0.82	9	9
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.039	0.15	-10000	0	-0.66	24	24
RARA	0.006	0.093	-10000	0	-0.33	31	31
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0	0.14	-10000	0	-0.4	32	32
PRKCA	-0.025	0.18	-10000	0	-0.82	24	24
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.032	0.16	-10000	0	-0.64	27	27
RXRG	-0.12	0.11	-10000	0	-0.53	28	28
RXRA	0.012	0.095	-10000	0	-0.34	31	31
RXRB	0.003	0.1	-10000	0	-0.44	24	24
VDR/Vit D3/DNA	0	0.01	-10000	0	-10000	0	0
RBP1	-0.003	0.11	-10000	0	-0.65	12	12
CRBP1/9-cic-RA	-0.012	0.084	-10000	0	-0.5	12	12
RARB	-0.007	0.14	-10000	0	-0.82	13	13
PRKCG	0.008	0.022	-10000	0	-0.31	2	2
MNAT1	0.013	0	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.028	0.17	-10000	0	-0.67	27	27
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.009	0.14	-10000	0	-0.54	27	27
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.088	-10000	0	-0.49	7	7
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.032	0.16	-10000	0	-0.64	27	27
positive regulation of DNA binding	-0.023	0.089	-10000	0	-0.38	24	24
NRIP1	-0.027	0.15	-10000	0	-0.62	20	20
RXRs/RARs	-0.04	0.16	-10000	0	-0.64	27	27
RXRs/RXRs/DNA/9cRA	-0.051	0.15	-10000	0	-0.68	24	24
PRKACA	0.013	0	-10000	0	-10000	0	0
CDK7	0.013	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.013	0.054	-10000	0	-0.53	2	2
CCNH	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

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

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
BAG4	0.012	0.038	-9999	-0.82	1	1
Caspase 8 (4 units)	-0.021	0.06	-9999	-10000	0	0
NEF	-0.011	0.054	-9999	-10000	0	0
NFKBIA	0.009	0.029	-9999	-10000	0	0
BIRC3	-0.005	0.2	-9999	-0.81	26	26
CYCS	-0.005	0.1	-9999	-0.4	5	5
RIPK1	0.013	0	-9999	-10000	0	0
CD247	-0.035	0.18	-9999	-0.78	23	23
MAP2K7	0.025	0.079	-9999	-10000	0	0
protein ubiquitination	0.039	0.087	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
DAXX	0.013	0	-9999	-10000	0	0
FAS	0.013	0	-9999	-10000	0	0
BID	-0.014	0.1	-9999	-0.42	5	5
NF-kappa-B/RelA/I kappa B alpha	-0.022	0.08	-9999	-0.53	1	1
TRADD	0.013	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
CFLAR	0.013	0	-9999	-10000	0	0
FADD	0.013	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.022	0.081	-9999	-0.35	26	26
MAPK8	0.024	0.096	-9999	-0.42	9	9
APAF1	0.012	0.038	-9999	-0.82	1	1
TRAF1	0.013	0	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.011	0.095	-9999	-0.31	27	27
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.024	0.1	-9999	-0.36	11	11
CHUK	0.039	0.092	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.001	0.021	-9999	-0.46	1	1
TCRz/NEF	-0.057	0.17	-9999	-0.52	49	49
TNF	-0.091	0.27	-9999	-0.78	64	64
FASLG	-0.066	0.28	-9999	-0.84	49	49
NFKB1	0.007	0.048	-9999	-0.82	1	1
TNFR1A/BAG4/TNF-alpha	-0.068	0.18	-9999	-0.55	59	59
CASP6	-0.004	0.045	-9999	-10000	0	0
CASP7	0.03	0.17	-9999	-0.62	25	25
RELA	0.009	0.029	-9999	-10000	0	0
CASP2	0.013	0	-9999	-10000	0	0
CASP3	0.03	0.17	-9999	-0.62	25	25
TNFRSF1A	0.013	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.029	-9999	-0.63	1	1
CASP8	0.013	0	-9999	-10000	0	0
CASP9	0.013	0	-9999	-10000	0	0
MAP3K14	0.032	0.099	-9999	-0.37	2	2
APAF-1/Caspase 9	-0.046	0.12	-9999	-0.52	25	25
BCL2	-0.001	0.15	-9999	-0.41	41	41

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.033	0	-9999	-10000	0	0
epithelial cell differentiation	0	0	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
ENAH	0.071	0.009	-9999	-10000	0	0
EGFR	0.006	0.076	-9999	-0.82	4	4
EPHA2	0.011	0.026	-9999	-0.31	3	3
MYO6	0.041	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	0	0	-9999	-10000	0	0
AQP5	-0.04	0.13	-9999	-0.59	26	26
CTNND1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.04	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.038	0.074	-9999	-10000	0	0
EGF	-0.11	0.29	-9999	-0.78	74	74
NCKAP1	0.013	0	-9999	-10000	0	0
AQP3	-0.075	0.2	-9999	-0.59	61	61
cortical microtubule organization	0	0	-9999	-10000	0	0
GO:0000145	0.039	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GDP	0	0.005	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.001	0.01	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.049	0.032	-9999	-10000	0	0
PVRL2	0.013	0	-9999	-10000	0	0
ZYX	0.041	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.009	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.064	0.15	-9999	-0.43	72	72
RhoA/GDP	0	0	-9999	-10000	0	0
actin cytoskeleton organization	0.047	0	-9999	-10000	0	0
IGF-1R heterotetramer	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
IGF1R	0.013	0	-9999	-10000	0	0
IGF1	-0.18	0.35	-9999	-0.8	119	119
DIAPH1	0	0.002	-9999	-10000	0	0
Wnt receptor signaling pathway	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0	0.005	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
VCL	0.047	0	-9999	-10000	0	0
EFNA1	0.013	0	-9999	-10000	0	0
LPP	0.041	0.057	-9999	-0.43	7	7
Ephrin A1/EPHA2	-0.001	0.008	-9999	-10000	0	0
SEC6/SEC8	0	0	-9999	-10000	0	0
MGAT3	-0.038	0.075	-9999	-10000	0	0
HGF/MET	-0.1	0.16	-9999	-0.47	74	74
HGF	-0.11	0.3	-9999	-0.82	74	74
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.033	0	-9999	-10000	0	0
actin cable formation	0.086	0.02	-9999	-10000	0	0
KIAA1543	0.047	0.021	-9999	-0.42	1	1
KIFC3	0.041	0	-9999	-10000	0	0
NCK1	0.013	0	-9999	-10000	0	0
EXOC3	0.013	0	-9999	-10000	0	0
ACTN1	0.04	0.007	-9999	-10000	0	0
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
EXOC4	0.013	0	-9999	-10000	0	0
STX4	0.041	0	-9999	-10000	0	0
PIP5K1C	0.041	0	-9999	-10000	0	0
LIMA1	0.013	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
ROCK1	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.064	0.02	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.1	0.18	-9999	-0.43	113	113
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	-0.11	0.16	-9999	-0.31	180	180
PLEKHA7	0.04	0.022	-9999	-0.45	1	1
mol:GTP	-0.001	0.01	-9999	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.067	0	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	0.033	0	-9999	-10000	0	0
regulation of cell-cell adhesion	0.047	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.033	0	-9999	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	-0.001	0.034	0.3	1	-0.53	1	2
DAPP1	-0.053	0.14	-10000	0	-0.46	14	14
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.058	0.18	-10000	0	-0.49	31	31
mol:DAG	-0.005	0.096	-10000	0	-0.28	15	15
HRAS	0.013	0.021	-10000	0	-0.31	2	2
RAP1A	0.014	0.001	-10000	0	-10000	0	0
ARF5/GDP	0.023	0.035	-10000	0	-0.46	1	1
PLCG2	0.013	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
ARF5	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.014	0.27	1	-10000	0	1
ARF1/GTP	-0.001	0.022	0.28	1	-10000	0	1
RHOA	0.013	0	-10000	0	-10000	0	0
YES1	0.013	0	-10000	0	-10000	0	0
RAP1A/GTP	0	0.013	-10000	0	-10000	0	0
ADAP1	0	0.013	0.26	1	-10000	0	1
ARAP3	0	0.014	0.27	1	-10000	0	1
INPPL1	0.013	0	-10000	0	-10000	0	0
PREX1	0.013	0	-10000	0	-10000	0	0
ARHGEF6	0.012	0.038	-10000	0	-0.82	1	1
ARHGEF7	0.013	0	-10000	0	-10000	0	0
ARF1	0.013	0	-10000	0	-10000	0	0
NRAS	0.014	0.001	-10000	0	-10000	0	0
FYN	0.013	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
FGR	0.011	0.03	-10000	0	-0.31	4	4
mol:Ca2+	0.007	0.054	-10000	0	-10000	0	0
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.17	0.16	-10000	0	-0.32	276	276
ZAP70	-0.022	0.16	-10000	0	-0.62	27	27
mol:IP3	0.005	0.072	-10000	0	-10000	0	0
LYN	0.013	0	-10000	0	-10000	0	0
ARF1/GDP	0.023	0.035	-10000	0	-0.46	1	1
RhoA/GDP	-0.001	0.019	0.28	1	-10000	0	1
PDK1/Src/Hsp90	-0.003	0.036	-10000	0	-0.55	2	2
BLNK	0.013	0	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.038	0.038	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
PLEKHA2	0.023	0.041	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PTEN	-0.002	0.036	-10000	0	-0.8	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	0	0.015	0.3	1	-10000	0	1
RhoA/GTP	0	0.013	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.049	0.16	-10000	0	-0.61	13	13
BLK	-0.25	0.38	-10000	0	-0.76	164	164
PDPK1	0.01	0.054	-10000	0	-0.82	2	2
CYTH1	0	0.013	-10000	0	-10000	0	0
HCK	-0.008	0.08	-10000	0	-0.31	31	31
CYTH3	-0.002	0.034	0.26	1	-0.49	2	3
CYTH2	0	0.013	-10000	0	-10000	0	0
KRAS	0.014	0.001	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.014	0.095	-10000	0	-0.62	11	11
SGK1	-0.015	0.11	0.24	1	-0.69	11	12
INPP5D	-0.003	0.071	-10000	0	-0.31	24	24
mol:GDP	0.015	0.037	-10000	0	-0.49	1	1
SOS1	0.013	0	-10000	0	-10000	0	0
SYK	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.02	0.29	1	-10000	0	1
mol:PI-3-4-5-P3	0	0.018	0.36	1	-10000	0	1
ARAP3/RAP1A/GTP	0	0.013	-10000	0	-10000	0	0
VAV1	-0.013	0.1	-10000	0	-0.36	34	34
mol:PI-3-4-P2	0.013	0.049	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0	0.006	-10000	0	-10000	0	0
PLEKHA1	0.023	0.041	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.035	-10000	0	-0.46	1	1
LAT	0.006	0.077	-10000	0	-0.72	5	5
Rac1/GTP	-0.006	0.055	-10000	0	-0.47	2	2
ITK	-0.056	0.14	-10000	0	-0.44	60	60
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.014	0.13	-10000	0	-0.4	15	15
LCK	-0.01	0.11	-10000	0	-0.44	25	25
BTK	-0.013	0.061	-10000	0	-0.43	8	8

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.019	0.092	-10000	0	-0.46	12	12
ACTA1	0.01	0.12	-10000	0	-0.59	12	12
NUMA1	0.019	0.092	-10000	0	-0.46	12	12
SPTAN1	0.015	0.12	-10000	0	-0.61	11	11
LIMK1	0.015	0.12	-10000	0	-0.64	10	10
BIRC3	-0.036	0.19	-10000	0	-0.68	35	35
BIRC2	0.013	0	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
CASP10	0	0.12	-10000	0	-0.62	14	14
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0	-10000	0	-10000	0	0
PTK2	0.019	0.092	-10000	0	-0.46	12	12
DIABLO	0.013	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.015	0.11	-10000	0	-0.59	11	11
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.013	0	-10000	0	-10000	0	0
GSN	0.015	0.12	-10000	0	-0.64	10	10
MADD	0.013	0	-10000	0	-10000	0	0
TFAP2A	-0.057	0.22	-10000	0	-0.65	60	60
BID	-0.011	0.068	-10000	0	-0.31	12	12
MAP3K1	0.014	0.042	-10000	0	-0.23	3	3
TRADD	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.029	-10000	0	-0.63	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.012	0.12	-10000	0	-0.61	11	11
CASP9	0.013	0	-10000	0	-10000	0	0
DNA repair	-0.016	0.052	0.17	2	-0.23	22	24
neuron apoptosis	0.023	0.015	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.021	0.11	-10000	0	-0.61	10	10
APAF1	0.012	0.038	-10000	0	-0.82	1	1
CASP6	0.022	0.064	-10000	0	-0.4	5	5
TRAF2	0.013	0	-10000	0	-10000	0	0
ICAD/CAD	0.022	0.11	-10000	0	-0.61	10	10
CASP7	0.009	0.08	0.34	25	-10000	0	25
KRT18	0.017	0.018	-10000	0	-10000	0	0
apoptosis	0.026	0.11	-10000	0	-0.56	12	12
DFFA	0.015	0.12	-10000	0	-0.61	11	11
DFFB	0.015	0.12	-10000	0	-0.61	11	11
PARP1	0.016	0.052	0.23	22	-0.17	2	24
actin filament polymerization	-0.023	0.11	0.58	10	-10000	0	10
TNF	-0.091	0.27	-10000	0	-0.78	64	64
CYCS	0.005	0.045	-10000	0	-0.22	12	12
SATB1	0.029	0.061	-10000	0	-0.4	4	4
SLK	0.012	0.13	-10000	0	-0.64	13	13
p15 BID/BAX	-0.002	0.06	-10000	0	-0.35	4	4
CASP2	0.006	0.12	-10000	0	-0.46	11	11
JNK cascade	-0.014	0.042	0.23	3	-10000	0	3
CASP3	0.007	0.12	-10000	0	-0.62	12	12
LMNB2	0.021	0.076	-10000	0	-0.32	4	4
RIPK1	0.013	0	-10000	0	-10000	0	0
CASP4	0.013	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.028	0.11	-10000	0	-0.5	25	25
negative regulation of DNA binding	-0.056	0.22	-10000	0	-0.64	60	60
stress fiber formation	0.012	0.12	-10000	0	-0.62	13	13
GZMB	-0.013	0.14	-10000	0	-0.71	14	14
CASP1	0.016	0.032	-10000	0	-0.45	2	2
LMNB1	0.02	0.077	-10000	0	-0.32	4	4
APP	0.024	0.015	-10000	0	-10000	0	0
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.012	0	-10000	0	-10000	0	0
VIM	0.022	0.1	0.26	12	-0.51	10	22
LMNA	0.021	0.076	-10000	0	-0.32	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.003	0.12	-10000	0	-0.49	11	11
LRDD	0.013	0	-10000	0	-10000	0	0
SREBF1	0.014	0.12	-10000	0	-0.64	10	10
APAF-1/Caspase 9	0.005	0.042	-10000	0	-0.4	1	1
nuclear fragmentation during apoptosis	0.019	0.091	-10000	0	-0.46	12	12
CFL2	0.022	0.11	-10000	0	-0.6	10	10
GAS2	0.01	0.13	-10000	0	-0.58	16	16
positive regulation of apoptosis	0.023	0.079	-10000	0	-0.31	4	4
PRF1	-0.002	0.11	-10000	0	-0.72	10	10

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.032	0.14	-10000	0	-0.63	25	25
ATM	0.012	0.038	-10000	0	-0.82	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
ATR	0.012	0.038	-10000	0	-0.82	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.026	0.03	-10000	0	-0.44	2	2
protein ubiquitination	-0.025	0.1	-10000	0	-0.46	26	26
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	-0.003	0.043	-10000	0	-0.55	3	3
MRE11A	0.008	0.066	-10000	0	-0.82	3	3
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.002	0.012	-10000	0	-10000	0	0
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.013	0	-10000	0	-10000	0	0
CCNE1	0.013	0	-10000	0	-10000	0	0
CDK2/Cyclin E1	0	0	-10000	0	-10000	0	0
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.032	0.14	-10000	0	-0.63	25	25
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.013	0	-10000	0	-10000	0	0
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	-0.001	0.068	-10000	0	-0.31	22	22
DNA repair	0.054	0.099	-10000	0	-0.41	1	1
BRCA1/BARD1/ubiquitin	-0.032	0.14	-10000	0	-0.63	25	25
BARD1/DNA-PK	-0.026	0.11	-10000	0	-0.5	25	25
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.032	0.14	0.63	25	-10000	0	25
BRCA1/BARD1/CTIP/M/R/N Complex	0.021	0.089	-10000	0	-0.58	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/P53	-0.027	0.11	-10000	0	-0.5	26	26
BARD1/CSTF1/BRCA1	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BACH1	0.013	0	-10000	0	-10000	0	0
BARD1	-0.03	0.18	-10000	0	-0.82	25	25
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/UbcH7	-0.028	0.12	-10000	0	-0.55	25	25
BRCA1/BARD1/RAD51/PCNA	-0.026	0.11	-10000	0	-0.5	25	25
BARD1/DNA-PK/P53	-0.024	0.1	-10000	0	-0.46	25	25
BRCA1/BARD1/Ubiquitin	-0.032	0.14	-10000	0	-0.63	25	25
BRCA1/BARD1/CTIP	-0.027	0.11	-10000	0	-0.5	26	26
FA complex	0.038	0.024	-10000	0	-0.26	1	1
BARD1/EWS	-0.032	0.14	-10000	0	-0.63	25	25
RBBP8	0.023	0.03	-10000	0	-0.63	1	1
TP53	0.013	0	-10000	0	-10000	0	0
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.026	0.11	0.49	26	-10000	0	26
BRCA1/BARD1	-0.025	0.1	-10000	0	-0.46	26	26
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.033	0.14	-10000	0	-0.64	25	25
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.012	0.021	-10000	0	-0.31	2	2
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.032	0.14	-10000	0	-0.63	25	25
EWSR1	0.013	0	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.013	0	-10000	0	-10000	0	0
NFATC1	0.046	0.06	-10000	0	-0.38	8	8
NFATC2	-0.018	0.095	-10000	0	-0.29	26	26
NFATC3	0.018	0.012	-10000	0	-10000	0	0
YWHAE	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.011	0.092	-10000	0	-0.59	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	-0.002	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.026	0.097	-10000	0	-0.59	9	9
BCL2/BAX	-0.046	0.16	-10000	0	-0.63	35	35
CaM/Ca2+/Calcineurin A alpha-beta B1	0.006	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.006	0.01	-10000	0	-10000	0	0
BAX	0.013	0.015	-10000	0	-0.31	1	1
MAPK14	0.01	0.006	-10000	0	-10000	0	0
BAD	0.013	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.015	0.088	-10000	0	-0.57	4	4
Calcineurin A alpha-beta B1/BCL2	-0.047	0.22	-10000	0	-0.82	35	35
FKBP8	0.013	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.015	0.086	0.56	4	-10000	0	4
KPNB1	0.013	0	-10000	0	-10000	0	0
KPNA2	0.013	0	-10000	0	-10000	0	0
XPO1	0.013	0.001	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	312	312
MAP3K8	-0.004	0.11	-10000	0	-0.82	8	8
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.12	0.16	-10000	0	-0.49	22	22
CABIN1	0.011	0.093	-10000	0	-0.6	4	4
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
MAP3K1	0.013	0	-10000	0	-10000	0	0
CAMK4	-0.005	0.11	-10000	0	-0.54	16	16
mol:Ca2+	-0.005	0.009	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0	0	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.006	0.11	-10000	0	-0.82	9	9
MAPK9	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
FKBP1A	0.013	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.006	0.05	-10000	0	-10000	0	0
PRKCH	0.013	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.004	-10000	0	-10000	0	0
CASP3	0.01	0.006	-10000	0	-10000	0	0
PIM1	0.013	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.014	0.05	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	-0.004	0.047	-10000	0	-10000	0	0
PRKCB	-0.027	0.13	-10000	0	-0.36	52	52
PRKCE	0.006	0.076	-10000	0	-0.82	4	4
JNK2/NFAT4	0.022	0.014	-10000	0	-10000	0	0
BAD/BCL-XL	0	0	-10000	0	-10000	0	0
PRKCD	0.013	0	-10000	0	-10000	0	0
NUP214	0.013	0.001	-10000	0	-10000	0	0
PRKCZ	0.01	0.006	-10000	0	-10000	0	0
PRKCA	-0.028	0.18	-10000	0	-0.82	24	24
PRKCG	0.005	0.022	-10000	0	-0.31	2	2
PRKCQ	0.005	0.084	-10000	0	-0.82	5	5
FKBP38/BCL2	-0.045	0.16	-10000	0	-0.63	35	35
EP300	0.01	0.007	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
NFATc/JNK1	0.033	0.086	-10000	0	-0.4	9	9
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.01	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.011	0.071	-10000	0	-0.56	7	7
NFATc/ERK1	0.052	0.056	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.025	0.096	-10000	0	-0.58	9	9
NR4A1	-0.18	0.36	-10000	0	-0.73	144	144
GSK3B	0.01	0.006	-10000	0	-10000	0	0
positive T cell selection	0.018	0.012	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.036	0.062	-10000	0	-0.41	4	4
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
PRKACA	0.01	0.006	-10000	0	-10000	0	0
AKAP5	0.013	0	-10000	0	-10000	0	0
MEF2D	0.01	0.007	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.041	0.062	-10000	0	-10000	0	0
CREBBP	0.01	0.007	-10000	0	-10000	0	0
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

Sphingosine 1-phosphate (S1P) 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
SPHK2	0.013	0	-9999	-10000	0	0
SPHK1	0.006	0.049	-9999	-0.31	11	11
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.022	0.016	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.72	20	20
mol:Sphinganine-1-P	0.019	0.034	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.002	0.014	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.013	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.002	0.011	-9999	-10000	0	0
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
GNAI1	0.012	0.038	-9999	-0.82	1	1
S1P/S1P5/G12	-0.004	0.028	-9999	-0.49	1	1
S1P/S1P3/Gq	-0.048	0.15	-9999	-0.4	23	23
S1P/S1P4/Gi	0.031	0.068	-9999	-0.32	17	17
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.093	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.002	0.11	-9999	-0.82	9	9
ABCC1	0.013	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.024	0	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0	0	-10000	0	-10000	0	0
CDKN1B	0.039	0.016	-10000	0	-10000	0	0
CDKN1A	0.033	0.032	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.013	0	-10000	0	-10000	0	0
FOXO3	0.039	0.016	-10000	0	-10000	0	0
AKT1	-0.001	0.015	-10000	0	-0.28	1	1
BAD	0.013	0	-10000	0	-10000	0	0
AKT3	0.016	0.03	-10000	0	-0.45	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.039	0.016	-10000	0	-10000	0	0
AKT1/ASK1	-0.002	0.023	-10000	0	-0.43	1	1
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.012	0.038	-10000	0	-0.82	1	1
RAF1	0.013	0	-10000	0	-10000	0	0
JNK cascade	0.002	0.023	0.42	1	-10000	0	1
TSC1	0.039	0.016	-10000	0	-10000	0	0
YWHAZ	0.013	0	-10000	0	-10000	0	0
AKT1/RAF1	0.038	0.016	-10000	0	-10000	0	0
EP300	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.032	0.017	-10000	0	-0.28	1	1
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.039	0.016	-10000	0	-10000	0	0
YWHAQ	0.013	0	-10000	0	-10000	0	0
TBC1D4	-0.052	0.2	-10000	0	-0.55	66	66
MAP3K5	0.012	0.038	-10000	0	-0.82	1	1
MAPKAP1	0.013	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.035	-10000	0	-10000	0	0
YWHAH	0.013	0	-10000	0	-10000	0	0
AKT1S1	0.039	0.016	-10000	0	-10000	0	0
CASP9	0.039	0.016	-10000	0	-10000	0	0
YWHAB	0.013	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.045	0.015	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.003	0.036	-10000	0	-0.55	2	2
YWHAE	0.013	0	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
AKT2/p21CIP1	-0.005	0.03	-10000	0	-0.37	2	2
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.019	0.006	-10000	0	-10000	0	0
CHUK	0.039	0.016	-10000	0	-10000	0	0
BAD/BCL-XL	0.052	0.015	-10000	0	-10000	0	0
mTORC2	-0.001	0.023	-10000	0	-0.51	1	1
AKT2	0.016	0.03	-10000	0	-0.45	2	2
FOXO1-3a-4/14-3-3 family	0.025	0.041	-10000	0	-10000	0	0
PDPK1	0.01	0.054	-10000	0	-0.82	2	2
MDM2	0.039	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.038	0.016	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.051	0.015	-10000	0	-10000	0	0
TSC1/TSC2	0.046	0.016	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.011	-10000	0	-10000	0	0
glucose import	-0.06	0.21	-10000	0	-0.52	80	80
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.033	0.012	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.06	0.21	-10000	0	-0.53	80	80
GSK3A	0.039	0.016	-10000	0	-10000	0	0
FOXO1	0.039	0.016	-10000	0	-10000	0	0
GSK3B	0.039	0.016	-10000	0	-10000	0	0
SFN	-0.21	0.19	-10000	0	-0.34	312	312
G1/S transition of mitotic cell cycle	0.046	0.016	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	-0.001	0.052	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
KPNA1	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
YWHAG	0.013	0	-10000	0	-10000	0	0
RHEB	0.013	0	-10000	0	-10000	0	0
CREBBP	0.013	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.004	0.13	-10000	0	-0.56	11	11
BAG4	0.012	0.038	-10000	0	-0.82	1	1
BAD	0.017	0.046	-10000	0	-10000	0	0
NFKBIA	0.013	0	-10000	0	-10000	0	0
BIRC3	-0.037	0.19	-10000	0	-0.68	35	35
BAX	0.017	0.047	-10000	0	-0.22	1	1
EnzymeConsortium:3.1.4.12	0.004	0.034	-10000	0	-0.12	11	11
IKBKB	0.013	0.12	-10000	0	-0.52	11	11
MAP2K2	0.027	0.057	-10000	0	-0.37	2	2
MAP2K1	0.027	0.057	-10000	0	-0.37	2	2
SMPD1	0.01	0.034	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.013	0.13	-10000	0	-0.54	11	11
MAP2K4	0.024	0.047	-10000	0	-10000	0	0
protein ubiquitination	0.014	0.12	-10000	0	-0.53	11	11
EnzymeConsortium:2.7.1.37	0.031	0.062	-10000	0	-0.37	2	2
response to UV	0	0.001	-10000	0	-0.002	13	13
RAF1	0.022	0.057	-10000	0	-0.4	2	2
CRADD	0.014	0	-10000	0	-10000	0	0
mol:ceramide	0.01	0.048	-10000	0	-0.17	11	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.014	0	-10000	0	-10000	0	0
MAP3K1	0.017	0.047	-10000	0	-10000	0	0
TRADD	0.014	0	-10000	0	-10000	0	0
RELA/p50	0.013	0	-10000	0	-10000	0	0
MAPK3	0.03	0.056	-10000	0	-0.36	2	2
MAPK1	0.03	0.056	-10000	0	-0.36	2	2
p50/RELA/I-kappa-B-alpha	0	0	-10000	0	-10000	0	0
FADD	0.004	0.13	-10000	0	-0.56	11	11
KSR1	0.016	0.057	-10000	0	-0.43	2	2
MAPK8	0.023	0.077	-10000	0	-0.44	9	9
TRAF2	0.013	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.013	0.12	-10000	0	-0.52	11	11
TNF R/SODD	-0.001	0.029	-10000	0	-0.63	1	1
TNF	-0.091	0.27	-10000	0	-0.78	64	64
CYCS	0.027	0.056	0.16	29	-10000	0	29
IKBKG	0.013	0.12	-10000	0	-0.52	11	11
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.004	0.14	-10000	0	-0.45	25	25
RELA	0.013	0	-10000	0	-10000	0	0
RIPK1	0.013	0	-10000	0	-10000	0	0
AIFM1	0.027	0.056	0.16	29	-10000	0	29
TNF/TNF R/SODD	-0.068	0.18	-10000	0	-0.55	59	59
TNFRSF1A	0.013	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.02	0.033	-10000	0	-10000	0	0
NSMAF	0.005	0.13	-10000	0	-0.55	11	11
response to hydrogen peroxide	0	0.001	-10000	0	-0.002	13	13
BCL2	-0.047	0.22	-10000	0	-0.82	35	35

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.012	0.038	-9999	-0.82	1	1
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.026	0.058	-9999	-0.33	1	1
GNAO1	-0.015	0.15	-9999	-0.72	20	20
S1P/S1P3/G12/G13	0	0	-9999	-10000	0	0
AKT1	-0.005	0.029	-9999	-0.47	1	1
AKT3	0.049	0.05	-9999	-0.56	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
GNAI1	0.013	0.038	-9999	-0.82	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.015	0	-9999	-10000	0	0
S1PR2	0.01	0.033	-9999	-0.31	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.036	0.067	-9999	-0.32	16	16
MAPK3	0.042	0.064	-9999	-10000	0	0
MAPK1	0.042	0.064	-9999	-10000	0	0
JAK2	0.046	0.065	-9999	-0.43	1	1
CXCR4	0.042	0.065	-9999	-10000	0	0
FLT1	0.015	0.038	-9999	-0.82	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.042	0.064	-9999	-10000	0	0
S1P/S1P3/Gi	0.036	0.068	-9999	-0.32	16	16
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.01	0.052	-9999	-10000	0	0
VEGFA	0.011	0.066	-9999	-0.82	3	3
S1P/S1P2/Gi	0.03	0.068	-9999	-0.32	16	16
VEGFR1 homodimer/VEGFA homodimer	0.024	0.068	-9999	-0.8	3	3
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.065	0.17	-9999	-0.35	119	119
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	0.015	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
GNA14	-0.18	0.35	-9999	-0.82	112	112
GNA15	-0.013	0.093	-9999	-0.33	37	37
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.002	0.11	-9999	-0.82	9	9
Rac1/GTP	-0.01	0.052	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.008	0.067	-9999	-0.7	4	4
positive regulation of NF-kappaB transcription factor activity	-0.004	0.05	-9999	-0.63	3	3
MAP2K4	0.047	0.031	-9999	-0.3	3	3
IKBKB	0.013	0	-9999	-10000	0	0
TNFRSF10B	0.013	0	-9999	-10000	0	0
TNFRSF10A	0.008	0.066	-9999	-0.82	3	3
SMPD1	-0.002	0.023	-9999	-0.29	3	3
IKBKG	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.004	0.05	-9999	-0.63	3	3
TRAIL/TRAILR3	-0.06	0.1	-9999	-0.68	3	3
TRAIL/TRAILR1	-0.008	0.07	-9999	-0.63	6	6
TRAIL/TRAILR4	-0.004	0.05	-9999	-0.63	3	3
TRAIL/TRAILR1/DAP3/GTP	-0.007	0.056	-9999	-0.5	6	6
IKK complex	-0.002	0.017	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.02	0.052	-9999	-0.63	3	3
MAP3K1	-0.003	0.028	-9999	-0.32	3	3
TRAILR4 (trimer)	0.013	0	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.008	0.065	-9999	-0.82	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.035	0.041	-9999	-0.33	6	6
CFLAR	0.013	0	-9999	-10000	0	0
MAPK1	0.02	0.052	-9999	-0.63	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.006	0.051	-9999	-0.46	6	6
mol:ceramide	-0.002	0.023	-9999	-0.29	3	3
FADD	0.013	0	-9999	-10000	0	0
MAPK8	0.045	0.077	-9999	-0.47	9	9
TRAF2	0.013	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.077	0.15	-9999	-0.31	135	135
CHUK	0.013	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.007	0.061	-9999	-0.55	6	6
DAP3	0.013	0	-9999	-10000	0	0
CASP10	-0.005	0.046	-9999	-0.52	3	3
JNK cascade	-0.004	0.05	-9999	-0.63	3	3
TRAIL (trimer)	0.008	0.067	-9999	-0.7	4	4
TNFRSF10C	-0.078	0.15	-9999	-0.31	135	135
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.006	0.052	-9999	-0.47	6	6
TRAIL/TRAILR2/FADD	-0.004	0.043	-9999	-0.55	3	3
cell death	0.019	0.025	-9999	-0.29	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.037	0.029	-9999	-0.33	3	3
TRAILR2 (trimer)	0.013	0	-9999	-10000	0	0
CASP8	0.001	0.013	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.003	0.037	-9999	-0.46	3	3

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.008	0.077	-9999	-0.74	5	5
PDGFRB	0.012	0.038	-9999	-0.82	1	1
SPHK1	-0.008	0.022	-9999	-10000	0	0
mol:S1P	-0.009	0.026	-9999	-10000	0	0
S1P1/S1P/Gi	0.013	0.15	-9999	-0.67	11	11
GNAO1	-0.017	0.15	-9999	-0.73	20	20
PDGFB-D/PDGFRB/PLCgamma1	0.023	0.14	-9999	-0.57	11	11
PLCG1	0.02	0.14	-9999	-0.64	10	10
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.012	0.038	-9999	-0.82	1	1
GNAI2	0.013	0.005	-9999	-10000	0	0
GNAI3	0.013	0.005	-9999	-10000	0	0
GNAI1	0.012	0.038	-9999	-0.83	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.012	0.07	-9999	-0.64	5	5
S1P1/S1P	-0.016	0.064	-9999	-0.51	5	5
negative regulation of cAMP metabolic process	0.014	0.15	-9999	-0.65	11	11
MAPK3	0.006	0.2	-9999	-0.59	44	44
calcium-dependent phospholipase C activity	-0.001	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.008	0.066	-9999	-0.82	3	3
PLCB2	0.031	0.07	-9999	-0.44	5	5
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.052	-9999	-0.42	5	5
receptor internalization	-0.015	0.059	-9999	-0.47	5	5
PTGS2	-0.037	0.34	-9999	-1.1	44	44
Rac1/GTP	-0.013	0.052	-9999	-0.42	5	5
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	0.008	0.066	-9999	-0.82	3	3
negative regulation of T cell proliferation	0.014	0.15	-9999	-0.65	11	11
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.013	0.005	-9999	-10000	0	0
MAPK1	0.006	0.2	-9999	-0.59	44	44
S1P1/S1P/PDGFB-D/PDGFRB	0.032	0.086	-9999	-0.51	6	6
ABCC1	0.014	0.002	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.06	0.13	-10000	0	-10000	0	0
regulation of axonogenesis	-0.01	0.037	0.32	2	-10000	0	2
myoblast fusion	0.023	0.052	-10000	0	-10000	0	0
mol:GTP	-0.026	0.039	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.093	0.11	0.52	1	-10000	0	1
ARF1/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GM1	-0.011	0.033	-10000	0	-10000	0	0
mol:Choline	0.012	0.029	-10000	0	-10000	0	0
lamellipodium assembly	-0.002	0.064	-10000	0	-10000	0	0
MAPK3	-0.017	0.065	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.094	0.11	-10000	0	-0.52	1	1
ARF1	0.013	0	-10000	0	-10000	0	0
ARF6/GDP	-0.023	0.052	-10000	0	-10000	0	0
ARF1/GDP	0.005	0.059	-10000	0	-10000	0	0
ARF6	-0.001	0.023	-10000	0	-10000	0	0
RAB11A	0.013	0	-10000	0	-10000	0	0
TIAM1	-0.18	0.17	-10000	0	-0.32	276	276
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.017	0.065	-10000	0	-10000	0	0
actin filament bundle formation	0.025	0.038	-10000	0	-10000	0	0
KALRN	-0.005	0.051	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.025	0.038	-10000	0	-10000	0	0
NME1	0.011	0.007	-10000	0	-10000	0	0
Rac1/GDP	-0.025	0.038	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.026	0.039	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.002	0.064	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
liver development	-0.026	0.039	-10000	0	-10000	0	0
ARF6/GTP	-0.026	0.039	-10000	0	-10000	0	0
RhoA/GTP	-0.015	0.023	-10000	0	-10000	0	0
mol:GDP	-0.01	0.065	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	-0.01	0.014	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
PLD1	0.001	0.033	-10000	0	-10000	0	0
RAB11FIP3	0.013	0	-10000	0	-10000	0	0
tube morphogenesis	-0.002	0.064	-10000	0	-10000	0	0
ruffle organization	0.01	0.037	-10000	0	-0.32	2	2
regulation of epithelial cell migration	-0.026	0.039	-10000	0	-10000	0	0
PLD2	0.001	0.033	-10000	0	-10000	0	0
PIP5K1A	0.01	0.037	-10000	0	-0.33	2	2
mol:Phosphatidic acid	0.012	0.029	-10000	0	-10000	0	0
Rac1/GTP	-0.002	0.064	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.062	0.16	-9999	-0.5	59	59
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.049	0.14	-9999	-0.42	59	59
SUMO1	0.013	0	-9999	-10000	0	0
ZFPM1	0.013	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
FKBP3	0.013	0	-9999	-10000	0	0
Histones	-0.025	0.067	-9999	-10000	0	0
YY1/LSF	0.028	0.051	-9999	-0.53	4	4
SMG5	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.013	0.13	-9999	-0.37	58	58
I kappa B alpha/HDAC1	0	0.091	-9999	-10000	0	0
SAP18	0.013	0	-9999	-10000	0	0
RELA	-0.003	0.12	-9999	-0.32	58	58
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
HDAC3/TR2	0	0.091	-9999	-10000	0	0
NuRD/MBD3 Complex	0.049	0.02	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.002	0.11	-9999	-0.29	59	59
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
GATA1	0.009	0.006	-9999	-10000	0	0
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.059	0.022	-9999	-10000	0	0
RBBP7	0.013	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.008	0.066	-9999	-0.82	3	3
MAX	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NFKBIA	-0.008	0.1	-9999	-0.28	58	58
KAT2B	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.044	0.027	-9999	-10000	0	0
SIN3 complex	-0.001	0.022	-9999	-0.5	1	1
SMURF1	0.013	0	-9999	-10000	0	0
CHD3	0.013	0	-9999	-10000	0	0
SAP30	0.012	0.038	-9999	-0.82	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.013	0	-9999	-10000	0	0
YY1/HDAC3	0.014	0.085	-9999	-10000	0	0
YY1/HDAC2	0.033	0	-9999	-10000	0	0
YY1/HDAC1	0.033	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.049	0.02	-9999	-10000	0	0
PPARG	-0.061	0.16	-9999	-0.46	63	63
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0	0.091	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.013	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.053	0.022	-9999	-10000	0	0
HDAC1	0.013	0	-9999	-10000	0	0
HDAC3	-0.008	0.1	-9999	-10000	0	0
HDAC2	0.013	0	-9999	-10000	0	0
YY1	0.032	0	-9999	-10000	0	0
HDAC8	0.013	0	-9999	-10000	0	0
SMAD7	0.013	0	-9999	-10000	0	0
NCOR2	0.013	0	-9999	-10000	0	0
MXD1	0.013	0	-9999	-10000	0	0
STAT3	0.028	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.004	0.044	-9999	-0.48	4	4
YY1/SAP30/HDAC1	-0.001	0.022	-9999	-0.48	1	1
EP300	0.013	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.027	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.008	0.1	-9999	-0.28	58	58
histone deacetylation	0.049	0.02	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.085	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GATAD2B	0.013	0	-9999	-10000	0	0
GATAD2A	0.013	0	-9999	-10000	0	0
GATA2/HDAC3	-0.001	0.091	-9999	-10000	0	0
GATA1/HDAC1	0	0	-9999	-10000	0	0
GATA1/HDAC3	-0.01	0.09	-9999	-10000	0	0
CHD4	0.013	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.078	0.2	-9999	-0.63	58	58
SIN3/HDAC complex/Mad/Max	0.049	0.023	-9999	-10000	0	0
NuRD Complex	0.058	0.022	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.025	0.066	-9999	-10000	0	0
SIN3B	0.013	0	-9999	-10000	0	0
MTA2	0.013	0	-9999	-10000	0	0
SIN3A	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC1	0.032	0	-9999	-10000	0	0
HDAC complex	-0.003	0.039	-9999	-0.5	3	3
GATA1/Fog1	0	0	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.091	0.27	-9999	-0.78	64	64
negative regulation of cell growth	0.049	0.023	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.049	0.02	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.053	0.14	-9999	-0.44	58	58
SIN3/HDAC complex/NCoR1	0.046	0.026	-9999	-10000	0	0
TFCP2	0.006	0.076	-9999	-0.82	4	4
NR2C1	0.013	0	-9999	-10000	0	0
MBD3	0.013	0	-9999	-10000	0	0
MBD2	0.013	0	-9999	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.039	0.022	-9999	-10000	0	0
PLK1	0.11	0.11	-9999	-0.73	1	1
CDKN1B	0.15	0.048	-9999	-0.39	1	1
FOXO3	0.11	0.11	-9999	-0.62	3	3
KAT2B	0.025	0.01	-9999	-10000	0	0
FOXO1/SIRT1	0.009	0.038	-9999	-0.59	1	1
CAT	0.1	0.15	-9999	-1.4	3	3
CTNNB1	0.013	0	-9999	-10000	0	0
AKT1	0.028	0.011	-9999	-10000	0	0
FOXO1	0.042	0.015	-9999	-10000	0	0
MAPK10	0.043	0.026	-9999	-0.51	1	1
mol:GTP	0.002	0.001	-9999	-10000	0	0
FOXO4	0.11	0.063	-9999	-0.48	4	4
response to oxidative stress	0.015	0.013	-9999	-10000	0	0
FOXO3A/SIRT1	0.011	0.087	-9999	-0.72	3	3
XPO1	0.014	0	-9999	-10000	0	0
EP300	0.015	0.002	-9999	-10000	0	0
BCL2L11	0.041	0.027	-9999	-10000	0	0
FOXO1/SKP2	0.039	0.051	-9999	-0.5	4	4
mol:GDP	0.015	0.013	-9999	-10000	0	0
RAN	0.015	0.001	-9999	-10000	0	0
GADD45A	0.13	0.062	-9999	-0.72	1	1
YWHAQ	0.013	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.041	0.041	-9999	-10000	0	0
MST1	0.023	0.042	-9999	-0.55	2	2
CSNK1D	0.013	0	-9999	-10000	0	0
CSNK1E	0.013	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.009	0.064	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
MAPK8	0.035	0.072	-9999	-0.49	9	9
MAPK9	0.044	0.007	-9999	-10000	0	0
YWHAG	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
YWHAZ	0.013	0	-9999	-10000	0	0
SIRT1	0.006	0.042	-9999	-0.82	1	1
SOD2	0.16	0.073	-9999	-0.79	1	1
RBL2	0.11	0.15	-9999	-1.4	4	4
RAL/GDP	0.033	0.012	-9999	-10000	0	0
CHUK	0.025	0.01	-9999	-10000	0	0
Ran/GTP	0.015	0.002	-9999	-10000	0	0
CSNK1G2	0.013	0	-9999	-10000	0	0
RAL/GTP	0.043	0.01	-9999	-10000	0	0
CSNK1G1	0.013	0	-9999	-10000	0	0
FASLG	-0.068	0.4	-9999	-1.5	33	33
SKP2	0.006	0.076	-9999	-0.82	4	4
USP7	0.015	0.001	-9999	-10000	0	0
IKBKB	0.025	0.01	-9999	-10000	0	0
CCNB1	0.11	0.1	-9999	-0.73	1	1
FOXO1-3a-4/beta catenin	-0.003	0.05	-9999	-0.42	5	5
proteasomal ubiquitin-dependent protein catabolic process	0.039	0.05	-9999	-0.5	4	4
CSNK1A1	0.013	0	-9999	-10000	0	0
SGK1	0.006	0.13	-9999	-0.82	11	11
CSNK1G3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.003	-9999	-10000	0	0
ZFAND5	0.11	0.053	-9999	-0.47	1	1
SFN	-0.21	0.19	-9999	-0.34	312	312
CDK2	0.014	0.003	-9999	-10000	0	0
FOXO3A/14-3-3	0.017	0.062	-9999	-0.32	4	4
CREBBP	0.014	0.003	-9999	-10000	0	0
FBXO32	0.11	0.11	-9999	-0.73	1	1
BCL6	0.12	0.1	-9999	-0.94	2	2
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
YWHAH	0.013	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.017	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.071	0.056	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
RIP2/NOD2	-0.028	0.078	-9999	-0.63	2	2
NFKBIA	0.049	0.024	-9999	-0.47	1	1
BIRC2	0.013	0	-9999	-10000	0	0
IKBKB	0.013	0	-9999	-10000	0	0
RIPK2	0.013	0	-9999	-10000	0	0
IKBKG	-0.005	0.021	-9999	-10000	0	0
IKK complex/A20	-0.05	0.13	-9999	-0.64	2	2
NEMO/A20/RIP2	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
NEMO/ATM	0.042	0.039	-9999	-0.43	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.002	0.014	-9999	-10000	0	0
BCL10/MALT1/TRAF6	-0.002	0.035	-9999	-0.55	2	2
NOD2	-0.032	0.12	-9999	-0.33	64	64
NFKB1	0.015	0.038	-9999	-0.82	1	1
RELA	0.017	0	-9999	-10000	0	0
MALT1	0.013	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.012	0.038	-9999	-0.82	1	1
TNF/TNFR1A	-0.078	0.2	-9999	-0.63	58	58
TRAF6	0.01	0.054	-9999	-0.82	2	2
PRKCA	-0.028	0.18	-9999	-0.82	24	24
CHUK	0.013	0	-9999	-10000	0	0
UBE2D3	0.013	0	-9999	-10000	0	0
TNF	-0.091	0.27	-9999	-0.78	64	64
NF kappa B1 p50/RelA	-0.001	0.024	-9999	-0.53	1	1
BCL10	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.049	0.024	-9999	-0.47	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.017	0	-9999	-10000	0	0
TNFRSF1A	0.013	0	-9999	-10000	0	0
IKK complex	-0.003	0.016	-9999	-10000	0	0
CYLD	0.013	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.021	0.087	-9999	-0.54	1	1

×

Circadian rhythm 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
chromatin modification	-0.027	0.048	-9999	-0.63	1	1
CLOCK	-0.039	0.2	-9999	-0.83	29	29
TIMELESS/CRY2	-0.006	0.065	-9999	-10000	0	0
DEC1/BMAL1	-0.021	0.064	-9999	-10000	0	0
ATR	0.012	0.038	-9999	-0.82	1	1
NR1D1	-0.06	0.13	-9999	-10000	0	0
ARNTL	-0.02	0.096	-9999	-0.32	46	46
TIMELESS	-0.014	0.074	-9999	-10000	0	0
NPAS2	0.009	0.041	-9999	-0.56	2	2
CRY2	0.013	0	-9999	-10000	0	0
mol:CO	0.008	0.031	-9999	-10000	0	0
CHEK1	0.013	0	-9999	-10000	0	0
mol:HEME	-0.008	0.031	-9999	-10000	0	0
PER1	0.013	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	-0.03	0.15	-9999	-0.56	30	30
BMAL1/CLOCK	-0.056	0.15	-9999	-0.62	15	15
S phase of mitotic cell cycle	-0.027	0.048	-9999	-0.63	1	1
TIMELESS/CHEK1/ATR	-0.027	0.048	-9999	-0.64	1	1
mol:NADPH	-0.008	0.031	-9999	-10000	0	0
PER1/TIMELESS	-0.006	0.065	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0.015	-9999	-0.31	1	1

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.011	0.086	-9999	-0.44	14	14
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.006	0.076	-9999	-0.82	4	4
ITGA4	0.004	0.069	-9999	-0.41	11	11
alpha4/beta7 Integrin/MAdCAM1	-0.031	0.097	-9999	-0.5	16	16
EPO	0.002	0.039	-9999	-0.31	7	7
alpha4/beta7 Integrin	-0.03	0.12	-9999	-0.62	15	15
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.006	0.049	-9999	-0.63	2	2
EPO/EPOR (dimer)	-0.007	0.037	-9999	-10000	0	0
lamellipodium assembly	-0.002	0.038	-9999	-0.47	3	3
PIK3CA	0.008	0.066	-9999	-0.82	3	3
PI3K	-0.004	0.049	-9999	-0.63	3	3
ARF6	0.013	0	-9999	-10000	0	0
JAK2	0.024	0.048	-9999	-0.5	3	3
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
MADCAM1	-0.011	0.091	-9999	-0.35	29	29
cell adhesion	-0.031	0.097	-9999	-0.49	16	16
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.022	0.08	-9999	-0.56	7	7
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.014	0.082	-9999	-0.62	7	7
p130Cas/Crk/Dock1	0.039	0.081	-9999	-0.82	1	1
VCAM1	-0.001	0.099	-9999	-0.57	12	12
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.036	-9999	-0.5	2	2
BCAR1	0.03	0.076	-9999	-0.52	7	7
EPOR	0.007	0.046	-9999	-0.31	10	10
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.013	0	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.039	-9999	-0.48	3	3

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.053	0.1	-9999	-10000	0	0
CRKL	0.038	0.045	-9999	-0.53	1	1
mol:DAG	0.042	0.049	-9999	-10000	0	0
HRAS	0.062	0.042	-9999	-10000	0	0
MAPK8	0.021	0.086	-9999	-0.57	9	9
RAP1A	0.038	0.045	-9999	-0.53	1	1
GAB1	0.038	0.045	-9999	-0.53	1	1
MAPK14	0.03	0.031	-9999	-10000	0	0
EPO	0.005	0.038	-9999	-0.3	7	7
PLCG1	0.042	0.05	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.009	0.047	-9999	-0.32	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.037	0.13	-9999	-0.57	27	27
GAB1/SHC/GRB2/SOS1	-0.005	0.025	-9999	-0.46	1	1
EPO/EPOR (dimer)	0.013	0.042	-9999	-10000	0	0
IRS2	0.038	0.045	-9999	-0.53	1	1
STAT1	0.042	0.076	-9999	-10000	0	0
STAT5B	0.043	0.064	-9999	-10000	0	0
cell proliferation	0.028	0.081	-9999	-0.53	9	9
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.008	0.034	-9999	-10000	0	0
TEC	0.038	0.045	-9999	-0.53	1	1
SOCS3	-0.034	0.19	-9999	-0.8	28	28
STAT1 (dimer)	0.042	0.076	-9999	-10000	0	0
JAK2	0.013	0.039	-9999	-0.84	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.043	0.051	-9999	-0.57	1	1
EPO/EPOR	0.013	0.042	-9999	-10000	0	0
LYN	0.014	0.004	-9999	-10000	0	0
TEC/VAV2	0.046	0.044	-9999	-0.51	1	1
elevation of cytosolic calcium ion concentration	0.009	0.047	-9999	-0.32	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.028	0.036	-9999	-10000	0	0
mol:IP3	0.042	0.049	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.01	0.033	-9999	-0.48	1	1
SH2B3	0.014	0.005	-9999	-10000	0	0
NFKB1	0.029	0.039	-9999	-0.5	1	1
EPO/EPOR (dimer)/JAK2/SOCS3	-0.019	0.069	-9999	-0.29	28	28
PTPN6	0.031	0.047	-9999	-0.56	1	1
TEC/VAV2/GRB2	0.051	0.043	-9999	-0.49	1	1
EPOR	0.009	0.047	-9999	-0.32	10	10
INPP5D	-0.003	0.071	-9999	-0.31	24	24
mol:GDP	-0.005	0.025	-9999	-0.47	1	1
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.013	0	-9999	-10000	0	0
CRKL/CBL/C3G	0.051	0.043	-9999	-0.49	1	1
VAV2	0.038	0.045	-9999	-0.53	1	1
CBL	0.038	0.045	-9999	-0.53	1	1
SHC/Grb2/SOS1	-0.006	0.028	-9999	-0.49	1	1
STAT5A	0.043	0.064	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.053	0.097	-9999	-10000	0	0
LYN/PLCgamma2	0	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
BTK	0.021	0.088	-9999	-0.5	8	8
BCL2	0.004	0.28	-9999	-0.98	35	35

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0	0.009	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.008	0.14	-9999	-0.56	30	30
NF kappa B1 p50/RelA/I kappa B alpha	0.044	0.039	-9999	-0.42	1	1
NFKBIA	0.025	0.037	-9999	-0.28	6	6
MAPK14	0.013	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.027	0.026	-9999	-0.55	1	1
ARRB2	0.018	0	-9999	-10000	0	0
REL	-0.038	0.2	-9999	-0.82	30	30
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.026	0.027	-9999	-0.55	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.027	0.026	-9999	-0.55	1	1
PIK3CA	0.008	0.066	-9999	-0.82	3	3
NF kappa B1 p50 dimer	0.02	0.03	-9999	-0.63	1	1
PIK3R1	0.013	0	-9999	-10000	0	0
NFKB1	0.023	0.03	-9999	-0.63	1	1
RELA	0.013	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.031	0.038	-9999	-0.27	6	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.047	0.038	-9999	-0.4	1	1
SRC	0.013	0.015	-9999	-0.31	1	1
PI3K	-0.004	0.049	-9999	-0.63	3	3
NF kappa B1 p50/RelA	0.031	0.039	-9999	-0.27	6	6
IKBKB	0.013	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
SYK	0.013	0	-9999	-10000	0	0
I kappa B alpha/PIK3R1	0.03	0.035	-9999	-10000	0	0
cell death	-0.004	0.028	-9999	-0.38	1	1
NF kappa B1 p105/c-Rel	-0.008	0.14	-9999	-0.56	30	30
LCK	-0.01	0.11	-9999	-0.44	25	25
BCL3	0.013	0.015	-9999	-0.31	1	1

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.006	0.023	-10000	0	-10000	0	0
AES	0.005	0.02	-10000	0	-10000	0	0
FBXW11	0.013	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	0.013	0	-10000	0	-10000	0	0
DKK2	-0.028	0.17	-10000	0	-0.65	30	30
TLE1	0	0.066	-10000	0	-0.8	3	3
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.047	0.04	-10000	0	-10000	0	0
WIF1	-0.034	0.1	-10000	0	-10000	0	0
beta catenin/RanBP3	0.022	0.091	0.37	26	-10000	0	26
KREMEN2	-0.01	0.085	-10000	0	-0.31	35	35
DKK1	-0.043	0.13	-10000	0	-0.82	2	2
beta catenin/beta TrCP1	0.052	0.038	-10000	0	-10000	0	0
FZD1	0.014	0.001	-10000	0	-10000	0	0
AXIN2	-0.047	0.31	-10000	0	-1.6	18	18
AXIN1	0.014	0	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.006	0.019	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.063	0.044	-10000	0	-0.41	1	1
Axin1/APC/GSK3	0.007	0.031	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.018	-10000	0	-10000	0	0
HNF1A	0.006	0.021	-10000	0	-10000	0	0
CTBP1	0.006	0.021	-10000	0	-10000	0	0
MYC	-0.032	0.26	-10000	0	-1.6	13	13
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.037	0.12	-10000	0	-0.56	20	20
NKD1	-0.013	0.14	-10000	0	-0.73	17	17
TCF4	0.006	0.021	-10000	0	-10000	0	0
TCF3	0.006	0.021	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0	0.008	-10000	0	-10000	0	0
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.029	0.12	0.48	27	-10000	0	27
LEF1	-0.002	0.066	-10000	0	-0.42	9	9
DVL1	0.018	0.027	-10000	0	-10000	0	0
CSNK2A1	0.014	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.074	-10000	0	-0.5	3	3
DKK1/LRP6/Kremen 2	-0.039	0.081	-10000	0	-0.63	2	2
LRP6	0.014	0.001	-10000	0	-10000	0	0
CSNK1A1	0.006	0.023	-10000	0	-10000	0	0
NLK	0.014	0.004	-10000	0	-10000	0	0
CCND1	0	0.074	-10000	0	-0.64	2	2
WNT1	0.01	0.021	-10000	0	-10000	0	0
GSK3A	0.014	0.001	-10000	0	-10000	0	0
GSK3B	0.014	0	-10000	0	-10000	0	0
FRAT1	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.03	0.06	0.37	14	-10000	0	14
APC	0.039	0.026	-10000	0	-0.47	1	1
WNT1/LRP6/FZD1	0.035	0.036	-10000	0	-10000	0	0
CREBBP	0.006	0.021	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.023	0.13	-9999	-0.7	16	16
AKT1	0.085	0.085	-9999	-0.69	4	4
PTK2B	0.036	0.13	-9999	-0.94	5	5
VEGFR2 homodimer/Frs2	0.032	0.087	-9999	-1.1	3	3
CAV1	-0.009	0.14	-9999	-0.82	13	13
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.009	0.098	-9999	-0.87	5	5
endothelial cell proliferation	0.076	0.1	-9999	-0.63	4	4
mol:Ca2+	0.052	0.097	-9999	-0.72	6	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.008	0.093	-9999	-0.82	5	5
RP11-342D11.1	0.043	0.096	-9999	-0.73	6	6
CDH5	0.013	0	-9999	-10000	0	0
VEGFA homodimer	-0.006	0.063	-9999	-0.59	5	5
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0.008	0.066	-9999	-0.82	3	3
HRAS/GDP	-0.008	0.077	-9999	-0.76	4	4
SH2D2A	-0.033	0.18	-9999	-0.64	34	34
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.007	0.064	-9999	-0.72	3	3
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.034	0.14	-9999	-0.56	27	27
VEGFR1 homodimer	0.012	0.038	-9999	-0.82	1	1
SHC/GRB2/SOS1	-0.009	0.09	-9999	-1	3	3
GRB10	0.052	0.097	-9999	-1	3	3
PTPN11	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.008	0.089	-9999	-0.79	5	5
HRAS	0.012	0.021	-9999	-0.31	2	2
VEGF/Rho/ROCK1/Integrin Complex	0.04	0.079	-9999	-0.52	5	5
HIF1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.008	0.089	-9999	-0.8	5	5
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.084	-9999	-0.82	5	5
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.009	0.098	-9999	-0.87	5	5
mol:GDP	-0.008	0.082	-9999	-0.93	3	3
mol:NADP	0.078	0.062	-9999	-0.58	3	3
eNOS/Hsp90	0.08	0.058	-9999	-0.54	3	3
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.052	0.1	-9999	-0.75	6	6
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.013	0	-9999	-10000	0	0
VEGFA	0.011	0.065	-9999	-0.82	3	3
VEGFC	0.012	0.038	-9999	-0.82	1	1
FAK1/Vinculin	0.059	0.11	-9999	-0.68	7	7
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.025	0.13	-9999	-0.58	21	21
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.02	0.061	-9999	-0.65	3	3
mol:L-citrulline	0.078	0.062	-9999	-0.58	3	3
ITGAV	0.01	0.054	-9999	-0.82	2	2
PIK3CA	0.008	0.066	-9999	-0.82	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.008	0.093	-9999	-0.82	5	5
VEGFR2 homodimer/VEGFA homodimer	-0.011	0.11	-9999	-0.85	6	6
VEGFR2/3 heterodimer	0.027	0.12	-9999	-0.95	6	6
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.054	0.1	-9999	-0.77	6	6
VEGFR2 homodimer	0.031	0.096	-9999	-1.2	3	3
FLT1	0.012	0.038	-9999	-0.82	1	1
NEDD4	0.012	0.054	-9999	-0.82	2	2
MAPK3	0.044	0.1	-9999	-0.83	4	4
MAPK1	0.044	0.1	-9999	-0.83	4	4
VEGFA145/NRP2	-0.019	0.072	-9999	-0.63	3	3
VEGFR1/2 heterodimer	0.031	0.1	-9999	-1.2	3	3
KDR	0.031	0.096	-9999	-1.2	3	3
VEGFA165/NRP1/VEGFR2 homodimer	-0.017	0.1	-9999	-1.2	3	3
SRC	0.013	0.015	-9999	-0.31	1	1
platelet activating factor biosynthetic process	0.046	0.1	-9999	-1	3	3
PI3K	-0.01	0.089	-9999	-0.96	3	3
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.009	0.098	-9999	-0.87	5	5
FES	0.052	0.11	-9999	-1.1	3	3
GAB1	-0.008	0.087	-9999	-0.99	3	3
VEGFR2 homodimer/VEGFA homodimer/Src	-0.009	0.098	-9999	-0.87	5	5
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.07	0.09	-9999	-0.63	3	3
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.009	0.098	-9999	-0.87	5	5
PI3K/GAB1	0.087	0.079	-9999	-0.72	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.008	0.089	-9999	-1	3	3
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.012	0.11	-9999	-0.83	7	7
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.052	0.11	-9999	-1.1	3	3
actin cytoskeleton reorganization	-0.033	0.14	-9999	-0.55	27	27
PTK2	0.053	0.12	-9999	-0.76	7	7
EDG1	0.043	0.096	-9999	-0.73	6	6
mol:DAG	0.052	0.1	-9999	-0.75	6	6
CaM/Ca2+	-0.008	0.083	-9999	-0.94	3	3
MAP2K3	0.052	0.12	-9999	-1.1	3	3
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.01	0.1	-9999	-1.2	3	3
PLCG1	0.052	0.11	-9999	-1.1	3	3
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.009	0.094	-9999	-0.82	5	5
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.01	0.11	-9999	-0.94	5	5
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.009	0.098	-9999	-0.87	5	5
cell migration	0.083	0.094	-9999	-0.72	3	3
mol:PI-3-4-5-P3	-0.009	0.077	-9999	-0.82	3	3
FYN	0.013	0	-9999	-10000	0	0
VEGFB/NRP1	-0.008	0.084	-9999	-0.68	6	6
mol:NO	0.078	0.062	-9999	-0.58	3	3
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.008	0.077	-9999	-0.76	4	4
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.051	0.11	-9999	-1.2	3	3
VHL	0.008	0.066	-9999	-0.82	3	3
ITGB3	-0.014	0.15	-9999	-0.82	16	16
NOS3	0.08	0.071	-9999	-0.69	3	3
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.012	0.1	-9999	-0.72	8	8
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.035	0.15	-9999	-1.2	3	3
PRKCB	0.039	0.11	-9999	-0.94	3	3
VCL	0.013	0	-9999	-10000	0	0
VEGFA165/NRP1	0.042	0.1	-9999	-0.77	6	6
VEGFR1/2 heterodimer/VEGFA homodimer	-0.01	0.11	-9999	-0.94	5	5
VEGFA165/NRP2	-0.019	0.072	-9999	-0.63	3	3
MAPKKK cascade	-0.008	0.076	-9999	-0.85	3	3
NRP2	-0.012	0.088	-9999	-0.31	38	38
VEGFC homodimer	0.012	0.038	-9999	-0.82	1	1
NCK1	0.013	0	-9999	-10000	0	0
ROCK1	0.013	0	-9999	-10000	0	0
FAK1/Paxillin	0.059	0.11	-9999	-0.68	7	7
MAP3K13	0.044	0.13	-9999	-1.2	3	3
PDPK1	0.077	0.087	-9999	-0.74	4	4

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.044	0.007	-9999	-10000	0	0
KLHL20	-0.009	0.021	-9999	-10000	0	0
CYFIP2	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.074	0.009	-9999	-10000	0	0
ENAH	0.044	0.007	-9999	-10000	0	0
AP1M1	0.013	0	-9999	-10000	0	0
RAP1B	0.013	0	-9999	-10000	0	0
RAP1A	0.013	0	-9999	-10000	0	0
CTNNB1	0.013	0	-9999	-10000	0	0
CDC42/GTP	0	0.002	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.001	0.014	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.08	-9999	-0.5	12	12
RAPGEF1	0.058	0.006	-9999	-10000	0	0
CTNND1	0.013	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-9999	-10000	0	0
CRK	0.052	0.006	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0	0	-9999	-10000	0	0
alphaE/beta7 Integrin	-0.023	0.1	-9999	-0.63	12	12
IQGAP1	0.013	0	-9999	-10000	0	0
NCKAP1	0.013	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	0.045	0.002	-9999	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.016	-9999	-10000	0	0
MLLT4	0.013	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.08	0.072	-9999	-0.5	1	1
PI3K	-0.002	0.021	-9999	-10000	0	0
ARF6	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0	0	-9999	-10000	0	0
TIAM1	-0.17	0.16	-9999	-0.32	276	276
E-cadherin(dimer)/Ca2+	0	0	-9999	-10000	0	0
AKT1	-0.001	0.012	-9999	-10000	0	0
PIK3R1	0.013	0	-9999	-10000	0	0
CDH1	0.013	0	-9999	-10000	0	0
RhoA/GDP	0.074	0.009	-9999	-10000	0	0
actin cytoskeleton organization	-0.007	0.016	-9999	-10000	0	0
CDC42/GDP	0.074	0.009	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.027	0	-9999	-10000	0	0
ITGB7	-0.02	0.14	-9999	-0.51	31	31
RAC1	0.013	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
mol:GDP	0.072	0.01	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.013	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	0	0.002	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0
CTNNA1	0.013	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.013	0.032	-9999	-0.15	10	10
NME1	0.013	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.044	0.007	-9999	-10000	0	0
regulation of cell-cell adhesion	0	0.002	-9999	-10000	0	0
WASF2	0.002	0.008	-9999	-10000	0	0
Rap1/GTP	0	0.003	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.016	0.075	-9999	-0.46	12	12
CCND1	0.015	0.038	-9999	-0.18	10	10
VAV2	0.056	0.007	-9999	-10000	0	0
RAP1/GDP	0	0.004	-9999	-10000	0	0
adherens junction assembly	0.045	0.001	-9999	-10000	0	0
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.013	0	-9999	-10000	0	0
PIP5K1C	0.013	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.015	0.07	-9999	-0.44	12	12
E-cadherin/beta catenin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.044	0.009	-9999	-10000	0	0
PIK3CA	0.008	0.066	-9999	-0.82	3	3
Rac1/GTP	-0.017	0.033	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	0	0	-9999	-10000	0	0
ITGAE	0.013	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.01	0.018	-9999	-10000	0	0
BUB1B	0.017	0.028	-9999	-10000	0	0
PLK1	0.017	0.012	-9999	-0.098	3	3
PLK1S1	0.015	0.007	-9999	-10000	0	0
KIF2A	0.023	0.03	-9999	-0.59	1	1
regulation of mitotic centrosome separation	0.017	0.012	-9999	-0.098	3	3
GOLGA2	0.013	0	-9999	-10000	0	0
Hec1/SPC24	-0.002	0.076	-9999	-0.28	16	16
WEE1	0.022	0.011	-9999	-10000	0	0
cytokinesis	0.001	0.07	-9999	-0.31	3	3
PP2A-alpha B56	-0.018	0.059	-9999	-0.73	3	3
AURKA	0.016	0.009	-9999	-10000	0	0
PICH/PLK1	0.033	0.019	-9999	-10000	0	0
CENPE	0.019	0.049	-9999	-0.53	3	3
RhoA/GTP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.023	0.029	-9999	-0.58	1	1
PPP2CA	0.013	0	-9999	-10000	0	0
FZR1	0.013	0	-9999	-10000	0	0
TPX2	0.009	0.021	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
SPC24	-0.009	0.081	-9999	-0.31	32	32
FBXW11	0.013	0	-9999	-10000	0	0
CLSPN	0.005	0.035	-9999	-0.35	2	2
GORASP1	0.013	0	-9999	-10000	0	0
metaphase	0.001	0.001	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.009	0.007	-9999	-0.066	3	3
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.013	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.003	-9999	-10000	0	0
spindle elongation	0.017	0.012	-9999	-0.098	3	3
ODF2	0.013	0.001	-9999	-10000	0	0
BUB1	-0.027	0.068	-9999	-0.8	3	3
TPT1	0.015	0.007	-9999	-10000	0	0
CDC25C	0.011	0.023	-9999	-10000	0	0
CDC25B	0.012	0.026	-9999	-0.31	3	3
SGOL1	0.01	0.018	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
CCNB1/CDK1	0.005	0.013	-9999	-10000	0	0
CDC14B	0.005	0.067	-9999	-0.65	5	5
CDC20	0.009	0.039	-9999	-0.31	7	7
PLK1/PBIP1	0.002	0.023	-9999	-0.16	2	2
mitosis	0	0.002	-9999	-0.022	3	3
FBXO5	0.021	0.021	-9999	-0.4	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.034	0.12	-9999	-0.31	70	70
metaphase plate congression	0.015	0.007	-9999	-10000	0	0
ERCC6L	0.007	0.016	-9999	-10000	0	0
NLP/gamma Tubulin	0.013	0.009	-9999	-0.077	3	3
microtubule cytoskeleton organization	0.015	0.007	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0.001	-9999	-0.011	3	3
PPP1R12A	0.013	0	-9999	-10000	0	0
interphase	0	0.001	-9999	-0.011	3	3
PLK1/PRC1-2	0.004	0.061	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0	0.004	-9999	-10000	0	0
RAB1A	0.013	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.018	0.039	-9999	-0.48	3	3
mitotic prometaphase	0	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.034	-9999	-0.32	2	2
microtubule-based process	-0.005	0.065	-9999	-10000	0	0
Golgi organization	0.017	0.012	-9999	-0.098	3	3
Cohesin/SA2	-0.001	0.005	-9999	-10000	0	0
PPP1CB/MYPT1	0	0	-9999	-10000	0	0
KIF20A	-0.043	0.12	-9999	-0.31	84	84
APC/C/CDC20	0.021	0.024	-9999	-10000	0	0
PPP2R1A	0.013	0	-9999	-10000	0	0
chromosome segregation	0.002	0.023	-9999	-0.16	2	2
PRC1	0.013	0	-9999	-10000	0	0
ECT2	0.022	0.039	-9999	-0.56	2	2
C13orf34	0.018	0.04	-9999	-0.48	3	3
NUDC	0.015	0.007	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.017	0.027	-9999	-10000	0	0
spindle assembly	0.017	0.011	-9999	-0.092	3	3
spindle stabilization	0.015	0.007	-9999	-10000	0	0
APC/C/HCDH1	0.013	0.058	-9999	-0.56	5	5
MKLP2/PLK1	-0.005	0.065	-9999	-10000	0	0
CCNB1	0.014	0.001	-9999	-10000	0	0
PPP1CB	0.013	0	-9999	-10000	0	0
BTRC	0.013	0	-9999	-10000	0	0
ROCK2	0.001	0.11	-9999	-0.52	21	21
TUBG1	0.015	0.007	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.009	-9999	-10000	0	0
MLF1IP	0.007	0.034	-9999	-0.22	11	11
INCENP	0.009	0.054	-9999	-0.83	2	2

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.012	0.055	0.38	1	-10000	0	1
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.017	0.15	-10000	0	-0.72	20	20
RhoA/GTP	-0.012	0.056	-10000	0	-0.39	1	1
negative regulation of cAMP metabolic process	0.022	0.071	-10000	0	-0.33	17	17
GNAZ	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	0.007	0.054	-10000	0	-0.38	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	0.022	0.071	-10000	0	-0.34	17	17
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.82	1	1

×

HIF-2-alpha transcription factor network

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
MMP14	-0.001	0.023	-10000	0	-10000	0	0
oxygen homeostasis	0.016	0.011	-10000	0	-10000	0	0
TCEB2	0.011	0.026	-10000	0	-0.31	3	3
TCEB1	0.013	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.011	0.074	-10000	0	-0.7	4	4
EPO	0.18	0.14	-10000	0	-0.8	2	2
FIH (dimer)	0.029	0.011	-10000	0	-10000	0	0
APEX1	0.027	0.011	-10000	0	-10000	0	0
SERPINE1	0.18	0.17	-10000	0	-0.8	3	3
FLT1	-0.002	0.072	-10000	0	-1.6	1	1
ADORA2A	0.19	0.14	-10000	0	-0.86	2	2
germ cell development	0.19	0.14	-10000	0	-0.85	2	2
SLC11A2	0.19	0.15	-10000	0	-0.89	2	2
BHLHE40	0.18	0.16	-10000	0	-0.89	2	2
HIF1AN	0.029	0.011	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.003	0.076	-10000	0	-0.97	2	2
ETS1	0.03	0.002	-10000	0	-10000	0	0
CITED2	-0.09	0.32	-10000	0	-1.2	37	37
KDR	-0.007	0.11	-10000	0	-1.4	3	3
PGK1	0.19	0.15	-10000	0	-0.89	2	2
SIRT1	0.012	0.038	-10000	0	-0.82	1	1
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.2	0.16	-10000	0	-1.2	2	2
EPAS1	0.11	0.1	-10000	0	-0.63	3	3
SP1	0.022	0.002	-10000	0	-10000	0	0
ABCG2	0.19	0.16	-10000	0	-0.88	4	4
EFNA1	0.19	0.15	-10000	0	-0.89	2	2
FXN	0.19	0.14	-10000	0	-0.86	2	2
POU5F1	0.19	0.15	-10000	0	-0.9	2	2
neuron apoptosis	-0.2	0.16	1.1	2	-10000	0	2
EP300	0.013	0	-10000	0	-10000	0	0
EGLN3	-0.002	0.14	-10000	0	-0.5	28	28
EGLN2	0.029	0.011	-10000	0	-10000	0	0
EGLN1	0.025	0.056	-10000	0	-0.82	2	2
VHL/Elongin B/Elongin C	-0.004	0.048	-10000	0	-0.6	3	3
VHL	0.008	0.066	-10000	0	-0.82	3	3
ARNT	0.027	0.011	-10000	0	-10000	0	0
SLC2A1	0.19	0.14	-10000	0	-0.86	2	2
TWIST1	0.18	0.18	-10000	0	-0.65	11	11
ELK1	0.015	0.026	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.001	0.067	-10000	0	-0.76	2	2
VEGFA	0.19	0.16	-10000	0	-0.84	4	4
CREBBP	0.013	0	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.032	0	-9999	-10000	0	0
SNTA1	0.013	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.032	0.009	-9999	-10000	0	0
MAPK12	0.02	0.078	-9999	-0.48	11	11
CCND1	0.017	0.034	-9999	-0.25	1	1
p38 gamma/SNTA1	0.025	0.073	-9999	-0.46	10	10
MAP2K3	0.013	0	-9999	-10000	0	0
PKN1	0.013	0	-9999	-10000	0	0
G2/M transition checkpoint	0.02	0.077	-9999	-0.48	11	11
MAP2K6	0.013	0.083	-9999	-0.53	11	11
MAPT	0.024	0.045	-9999	-0.4	3	3
MAPK13	0.024	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.017	0.021	-9999	-0.45	1	1

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
Rac1/GDP	0.001	0.006	-10000	0	-10000	0	0
DOCK1	0.006	0.076	-10000	0	-0.82	4	4
ITGA4	0.004	0.069	-10000	0	-0.41	11	11
RAC1	0.013	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.03	0.12	-10000	0	-0.62	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.005	0.041	-10000	0	-0.55	2	2
alpha4/beta7 Integrin/Paxillin	-0.022	0.088	-10000	0	-0.5	14	14
lamellipodium assembly	-0.004	0.058	-10000	0	-0.54	5	5
PIK3CA	0.008	0.066	-10000	0	-0.82	3	3
PI3K	-0.004	0.049	-10000	0	-0.63	3	3
ARF6	0.013	0	-10000	0	-10000	0	0
TLN1	0.013	0	-10000	0	-10000	0	0
PXN	0.024	0	-10000	0	-10000	0	0
PIK3R1	0.013	0	-10000	0	-10000	0	0
ARF6/GTP	-0.004	0.03	-10000	0	-0.42	2	2
cell adhesion	-0.004	0.033	-10000	0	-0.46	2	2
CRKL/CBL	0	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.004	0.036	-10000	0	-0.5	2	2
ITGB1	0.013	0	-10000	0	-10000	0	0
ITGB7	-0.02	0.14	-10000	0	-0.51	31	31
ARF6/GDP	0.001	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.011	0.07	-10000	0	-0.53	7	7
p130Cas/Crk/Dock1	-0.004	0.049	-10000	0	-0.55	4	4
VCAM1	-0.001	0.099	-10000	0	-0.57	12	12
alpha4/beta1 Integrin/Paxillin/Talin	-0.004	0.033	-10000	0	-0.46	2	2
alpha4/beta1 Integrin/Paxillin/GIT1	-0.004	0.033	-10000	0	-0.46	2	2
BCAR1	0.013	0	-10000	0	-10000	0	0
mol:GDP	0.004	0.033	0.46	2	-10000	0	2
CBL	0.013	0	-10000	0	-10000	0	0
PRKACA	0.013	0	-10000	0	-10000	0	0
GIT1	0.013	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.004	0.033	-10000	0	-0.46	2	2
Rac1/GTP	-0.005	0.068	-10000	0	-0.63	5	5

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.001	0.04	-9999	-0.74	1	1
PDGFB-D/PDGFRB/SLAP	-0.002	0.03	-9999	-0.64	1	1
PDGFB-D/PDGFRB/APS/CBL	-0.001	0.026	-9999	-0.55	1	1
AKT1	0.059	0.044	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.024	0.051	-9999	-0.79	1	1
PIK3CA	0.008	0.066	-9999	-0.82	3	3
FGR	0.002	0.029	-9999	-0.56	1	1
mol:Ca2+	0.02	0.049	-9999	-0.82	1	1
MYC	0.018	0.15	-9999	-0.84	14	14
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	0.011	0.029	-9999	-0.45	1	1
LRP1/PDGFRB/PDGFB	-0.002	0.035	-9999	-0.55	2	2
GRB10	0.013	0	-9999	-10000	0	0
PTPN11	0.012	0.038	-9999	-0.82	1	1
GO:0007205	0.02	0.049	-9999	-0.85	1	1
PTEN	0.012	0.038	-9999	-0.82	1	1
GRB2	0.013	0	-9999	-10000	0	0
GRB7	-0.042	0.12	-9999	-0.31	82	82
PDGFB-D/PDGFRB/SHP2	-0.003	0.041	-9999	-0.64	2	2
PDGFB-D/PDGFRB/GRB10	-0.001	0.029	-9999	-0.64	1	1
cell cycle arrest	-0.002	0.03	-9999	-0.63	1	1
HRAS	0.012	0.021	-9999	-0.31	2	2
HIF1A	0.064	0.04	-9999	-10000	0	0
GAB1	0.013	0.064	-9999	-0.87	1	1
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.02	0.06	-9999	-0.78	1	1
PDGFB-D/PDGFRB	0.012	0.031	-9999	-0.57	1	1
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.029	-9999	-0.64	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.001	0.048	-9999	-0.75	1	1
positive regulation of MAPKKK cascade	-0.002	0.041	-9999	-0.64	2	2
PIK3R1	0.013	0	-9999	-10000	0	0
mol:IP3	0.02	0.05	-9999	-0.86	1	1
E5	0	0.001	-9999	-10000	0	0
CSK	0.013	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.036	0.084	-9999	-0.8	1	1
SHB	0.013	0	-9999	-10000	0	0
BLK	-0.18	0.28	-9999	-0.62	143	143
PTPN2	0.014	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.029	-9999	-0.64	1	1
BCAR1	0.013	0	-9999	-10000	0	0
VAV2	0.017	0.071	-9999	-0.87	1	1
CBL	0.013	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.001	0.029	-9999	-0.64	1	1
LCK	-0.008	0.088	-9999	-0.73	6	6
PDGFRB	0.012	0.038	-9999	-0.83	1	1
ACP1	0.013	0	-9999	-10000	0	0
HCK	0.005	0.035	-9999	-0.55	1	1
ABL1	0.009	0.061	-9999	-0.83	1	1
PDGFB-D/PDGFRB/CBL	0.009	0.068	-9999	-0.95	1	1
PTPN1	0.014	0.002	-9999	-10000	0	0
SNX15	0.013	0	-9999	-10000	0	0
STAT3	0.013	0	-9999	-10000	0	0
STAT1	0.006	0.049	-9999	-0.31	11	11
cell proliferation	0.02	0.13	-9999	-0.73	14	14
SLA	0.013	0.015	-9999	-0.31	1	1
actin cytoskeleton reorganization	0.052	0.025	-9999	-10000	0	0
SRC	0.005	0.029	-9999	-0.56	1	1
PI3K	-0.004	0.041	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.028	0.066	-9999	-0.7	1	1
SH2B2	0.013	0.015	-9999	-0.31	1	1
PLCgamma1/SPHK1	0.024	0.053	-9999	-0.83	1	1
LYN	0.006	0.029	-9999	-0.56	1	1
LRP1	0.012	0.038	-9999	-0.82	1	1
SOS1	0.013	0	-9999	-10000	0	0
STAT5B	0.013	0	-9999	-10000	0	0
STAT5A	0.013	0	-9999	-10000	0	0
NCK1-2/p130 Cas	0	0.021	-9999	-0.45	1	1
SPHK1	0.007	0.049	-9999	-0.31	11	11
EDG1	0.001	0.001	-9999	-10000	0	0
mol:DAG	0.02	0.05	-9999	-0.86	1	1
PLCG1	0.02	0.052	-9999	-0.9	1	1
NHERF/PDGFRB	-0.002	0.027	-9999	-0.55	1	1
YES1	0.003	0.028	-9999	-0.56	1	1
cell migration	-0.002	0.027	-9999	-0.54	1	1
SHC/Grb2/SOS1	0	0.021	-9999	-0.45	1	1
SLC9A3R2	0.013	0	-9999	-10000	0	0
SLC9A3R1	0.012	0.021	-9999	-0.31	2	2
NHERF1-2/PDGFRB/PTEN	-0.003	0.033	-9999	-0.5	2	2
FYN	0.006	0.029	-9999	-0.56	1	1
DOK1	0.034	0.025	-9999	-0.5	1	1
HRAS/GTP	-0.001	0.014	-9999	-10000	0	0
PDGFB	0.013	0	-9999	-10000	0	0
RAC1	0.027	0.09	-9999	-0.44	14	14
PRKCD	0.034	0.025	-9999	-0.51	1	1
FER	0.031	0.05	-9999	-0.51	4	4
MAPKKK cascade	-0.001	0.021	-9999	-0.44	1	1
RASA1	0.034	0.025	-9999	-0.51	1	1
NCK1	0.013	0	-9999	-10000	0	0
NCK2	0.013	0	-9999	-10000	0	0
p62DOK/Csk	0.017	0.03	-9999	-0.46	1	1
PDGFB-D/PDGFRB/SHB	-0.001	0.029	-9999	-0.64	1	1
chemotaxis	0.01	0.06	-9999	-0.79	1	1
STAT1-3-5/STAT1-3-5	-0.003	0.023	-9999	-0.43	1	1
Bovine Papilomavirus E5/PDGFRB	0.001	0.03	-9999	-0.65	1	1
PTPRJ	0.013	0	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.017	0.15	-9999	-0.72	20	20
CDC42/GTP	-0.011	0.054	-9999	-0.32	1	1
PLCG1	0.03	0.065	-9999	-0.33	1	1
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.011	0.053	-9999	-0.32	1	1
S1PR5	0.007	0.054	-9999	-0.38	8	8
S1PR4	0.01	0.033	-9999	-0.31	5	5
MAPK3	0.03	0.065	-9999	-0.31	17	17
MAPK1	0.03	0.065	-9999	-0.33	1	1
S1P/S1P5/Gi	0.022	0.071	-9999	-0.34	17	17
GNAI1	0.012	0.038	-9999	-0.82	1	1
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.004	0.032	-9999	-0.55	1	1
RHOA	0.032	0.016	-9999	-10000	0	0
S1P/S1P4/Gi	0.023	0.069	-9999	-0.33	17	17
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.013	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	-0.001	0.014	-9999	-10000	0	0
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.002	0.031	-9999	-0.39	3	3
TRAF2/ASK1	-0.001	0.025	-9999	-0.55	1	1
ATM	0.012	0.038	-9999	-0.82	1	1
MAP2K3	0.026	0.057	-9999	-0.53	2	2
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.025	0.078	-9999	-0.44	6	6
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.001	0.1	-9999	-0.67	10	10
TXN	0.009	0.006	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GADD45B	-0.014	0.15	-9999	-0.82	16	16
MAP3K1	0.013	0	-9999	-10000	0	0
MAP3K6	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0	-9999	-10000	0	0
MAP3K4	0.013	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.029	-9999	-0.63	1	1
TAK1/TAB family	-0.001	0.014	-9999	-0.22	2	2
RAC1/OSM/MEKK3	0	0.006	-9999	-10000	0	0
TRAF2	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.033	-9999	-0.47	1	1
TRAF6	0.007	0.03	-9999	-0.46	2	2
RAC1	0.013	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	0.005	0.084	-9999	-0.82	5	5
CCM2	0.013	0.015	-9999	-0.31	1	1
CaM/Ca2+/CAMKIIB	-0.006	0.056	-9999	-0.55	5	5
MAPK11	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.006	0.064	-9999	-0.6	5	5
OSM/MEKK3	0	0.009	-9999	-10000	0	0
TAOK1	-0.038	0.16	-9999	-0.46	57	57
TAOK2	0.017	0.021	-9999	-0.45	1	1
TAOK3	0.017	0.021	-9999	-0.45	1	1
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.012	0.038	-9999	-0.82	1	1
MAP3K10	0.013	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
TRX/ASK1	0.015	0.026	-9999	-0.55	1	1
GADD45/MTK1/MTK1	-0.023	0.1	-9999	-0.49	22	22

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.013	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.045	0	-9999	-10000	0	0
SMAD3/SMAD4	0.049	0.02	-9999	-0.39	1	1
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	-0.001	0.019	-9999	-0.42	1	1
PPM1A	0.013	0	-9999	-10000	0	0
CALM1	0.013	0	-9999	-10000	0	0
SMAD2/SMAD4	0.022	0	-9999	-10000	0	0
MAP3K1	0.013	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.036	0.15	-9999	-0.63	28	28
MAPK3	0.013	0	-9999	-10000	0	0
MAPK1	0.013	0	-9999	-10000	0	0
NUP214	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
CTDSP2	0.013	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
KPNB1	0.013	0	-9999	-10000	0	0
TGFBRAP1	-0.035	0.2	-9999	-0.82	28	28
UBE2I	0.013	0	-9999	-10000	0	0
NUP153	0.012	0.038	-9999	-0.82	1	1
KPNA2	0.013	0	-9999	-10000	0	0
PIAS4	0.013	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.022	-9999	-0.5	1	1
HDAC3	0.013	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC5	0	0	-9999	-10000	0	0
GATA2/HDAC5	0	0.009	-9999	-10000	0	0
HDAC5/BCL6/BCoR	-0.001	0.025	-9999	-0.55	1	1
HDAC9	-0.018	0.097	-9999	-0.31	47	47
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-9999	-10000	0	0
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	0	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.023	0	-9999	-10000	0	0
GATA2	0.013	0.015	-9999	-0.31	1	1
HDAC4/RFXANK	-0.001	0.013	-9999	-10000	0	0
BCOR	0.013	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.013	0	-9999	-10000	0	0
HDAC5	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.029	-9999	-0.63	1	1
Histones	0.035	0.024	-9999	-10000	0	0
ADRBK1	0.013	0	-9999	-10000	0	0
HDAC4	0.013	0	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
HDAC5/ANKRA2	0	0	-9999	-10000	0	0
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.013	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0	0	-9999	-10000	0	0
TUBA1B	0.013	0	-9999	-10000	0	0
HDAC6	0.013	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.013	-9999	-10000	0	0
CAMK4	-0.005	0.11	-9999	-0.54	16	16
Tubulin/HDAC6	-0.006	0.055	-9999	-0.55	5	5
SUMO1	0.013	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.013	0	-9999	-10000	0	0
GATA1	0.009	0.006	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
NR3C1	0.013	0	-9999	-10000	0	0
SUMO1/HDAC4	0.032	0	-9999	-10000	0	0
SRF	0.013	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.006	0.064	-9999	-0.63	5	5
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
RANGAP1	0.013	0	-9999	-10000	0	0
BCL6/BCoR	-0.001	0.029	-9999	-0.63	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.011	0.068	-9999	-0.55	7	7
HDAC4/ER alpha	-0.044	0.14	-9999	-0.63	24	24
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.035	0.024	-9999	-10000	0	0
cell motility	-0.006	0.055	-9999	-0.54	5	5
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.012	0.038	-9999	-0.82	1	1
HDAC4/CaMK II delta B	0.013	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	-0.049	0.19	-9999	-0.54	55	55
HDAC6/HDAC11	0	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.012	0.038	-9999	-0.82	1	1
RAN	0.013	0	-9999	-10000	0	0
HDAC4/MEF2C	-0.001	0.021	-9999	-0.46	1	1
GNG2	0.012	0.038	-9999	-0.82	1	1
NCOR2	0.013	0	-9999	-10000	0	0
TUBB2A	0.005	0.084	-9999	-0.82	5	5
HDAC11	0.013	0	-9999	-10000	0	0
HSP90AA1	0.013	0	-9999	-10000	0	0
RANBP2	0.013	0	-9999	-10000	0	0
ANKRA2	0.013	0	-9999	-10000	0	0
RFXANK	0.012	0.021	-9999	-0.31	2	2
nuclear import	0	0	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.028	0.007	-9999	-10000	0	0
BIRC5	-0.016	0.098	-9999	-0.33	42	42
NFKBIA	0.032	0.008	-9999	-10000	0	0
CPEB1	-0.049	0.22	-9999	-0.82	36	36
AKT1	0.032	0.008	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.003	0.011	-9999	-10000	0	0
NDEL1/TACC3	0.003	0.013	-9999	-10000	0	0
GADD45A	0.013	0	-9999	-10000	0	0
GSK3B	0.013	0.005	-9999	-10000	0	0
PAK1/Aurora A	0.028	0.007	-9999	-10000	0	0
MDM2	0.013	0	-9999	-10000	0	0
JUB	0.012	0.038	-9999	-0.82	1	1
TPX2	0.002	0.068	-9999	-10000	0	0
TP53	0.031	0.006	-9999	-10000	0	0
DLG7	0.021	0.008	-9999	-10000	0	0
AURKAIP1	0.012	0.021	-9999	-0.31	2	2
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.003	0.014	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.003	0.011	-9999	-10000	0	0
AURKA	0.026	0.011	-9999	-10000	0	0
AURKB	-0.014	0.027	-9999	-0.14	3	3
CDC25B	0.007	0.018	-9999	-10000	0	0
G2/M transition checkpoint	0.002	0.025	-9999	-0.5	1	1
mRNA polyadenylation	-0.035	0.13	-9999	-0.5	36	36
Aurora A/CPEB	-0.035	0.13	-9999	-0.5	36	36
Aurora A/TACC1/TRAP/chTOG	0.003	0.026	-9999	-0.47	1	1
BRCA1	0.013	0	-9999	-10000	0	0
centrosome duplication	0.028	0.007	-9999	-10000	0	0
regulation of centrosome cycle	0.002	0.011	-9999	-10000	0	0
spindle assembly	0.002	0.024	-9999	-0.46	1	1
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.01	0.036	-9999	-0.45	1	1
CENPA	-0.009	0.026	-9999	-0.26	3	3
Aurora A/PP2A	0.028	0.007	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.008	-9999	-10000	0	0
negative regulation of DNA binding	0.031	0.006	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.013	0	-9999	-10000	0	0
Ajuba/Aurora A	0.002	0.025	-9999	-0.5	1	1
mitotic prometaphase	0.005	0.01	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.011	-9999	-10000	0	0
TACC1	0.012	0.038	-9999	-0.82	1	1
TACC3	0.013	0.015	-9999	-0.31	1	1
Aurora A/Antizyme1	0.003	0.016	-9999	-10000	0	0
Aurora A/RasGAP	0.028	0.007	-9999	-10000	0	0
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.005	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.002	0.068	-9999	-10000	0	0
PPP2R5D	0.013	0	-9999	-10000	0	0
Aurora A/TPX2	0.019	0.05	-9999	-10000	0	0
PAK1	0.013	0	-9999	-10000	0	0
CKAP5	0.013	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.051	0.039	-10000	0	-0.44	3	3
adherens junction organization	0.041	0.037	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.053	0.057	-10000	0	-0.74	1	1
FMN1	0.022	0.11	-10000	0	-0.44	25	25
mol:IP3	-0.003	0.032	-10000	0	-0.41	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.04	0.012	-10000	0	-10000	0	0
CTNNB1	0.013	0	-10000	0	-10000	0	0
AKT1	0.049	0.035	-10000	0	-0.4	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.046	0.006	-10000	0	-10000	0	0
CTNND1	0.014	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.036	-10000	0	-0.49	2	2
VASP	0.047	0.011	-10000	0	-10000	0	0
ZYX	0.047	0.011	-10000	0	-10000	0	0
JUB	0.046	0.025	-10000	0	-0.43	1	1
EGFR(dimer)	0.042	0.048	-10000	0	-0.47	4	4
E-cadherin/beta catenin-gamma catenin	0	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.033	-10000	0	-0.43	3	3
PIK3CA	0.009	0.066	-10000	0	-0.82	3	3
PI3K	-0.003	0.034	-10000	0	-0.44	3	3
FYN	0.05	0.035	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.031	-10000	0	-0.4	3	3
JUP	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.001	-10000	0	-10000	0	0
mol:DAG	-0.003	0.032	-10000	0	-0.41	3	3
CDH1	0.013	0	-10000	0	-10000	0	0
RhoA/GDP	0.053	0.057	-10000	0	-0.74	1	1
establishment of polarity of embryonic epithelium	0.046	0.011	-10000	0	-10000	0	0
SRC	0.013	0.015	-10000	0	-0.31	1	1
RAC1	0.013	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
EGFR	0.006	0.076	-10000	0	-0.82	4	4
CASR	0.042	0.038	-10000	0	-0.38	3	3
RhoA/GTP	-0.002	0.028	-10000	0	-0.36	3	3
AKT2	0.049	0.035	-10000	0	-0.4	3	3
actin cable formation	0.029	0.1	-10000	0	-0.42	25	25
apoptosis	0.003	0.032	0.41	3	-10000	0	3
CTNNA1	0.014	0.001	-10000	0	-10000	0	0
mol:GDP	0.047	0.061	-10000	0	-0.48	6	6
PIP5K1A	0.045	0.037	-10000	0	-0.5	2	2
PLCG1	-0.003	0.033	-10000	0	-0.42	3	3
Rac1/GTP	-0.004	0.039	-10000	0	-0.42	4	4
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.01	0.033	-9999	-0.31	5	5
PLK4	0.013	0	-9999	-10000	0	0
regulation of centriole replication	0.022	0.023	-9999	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.02	0.16	-10000	0	-0.73	22	22
CLTC	0.034	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.029	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0	0	-10000	0	-10000	0	0
EXOC4	0.013	0	-10000	0	-10000	0	0
CD59	0.031	0	-10000	0	-10000	0	0
CPE	0.011	0.073	-10000	0	-0.56	8	8
CTNNB1	0.013	0	-10000	0	-10000	0	0
membrane fusion	0.028	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.013	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.035	0	-10000	0	-10000	0	0
TSHR	0.018	0.037	-10000	0	-0.56	2	2
INS	0.013	0	-10000	0	-10000	0	0
BIN1	0.013	0	-10000	0	-10000	0	0
mol:Choline	0.028	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.013	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
JUP	0.031	0	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.023	-10000	0	-0.5	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.031	0	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.013	0.015	-10000	0	-10000	0	0
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.013	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.046	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.013	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0	0	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.02	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0	0.008	-10000	0	-10000	0	0
ACAP1	0.027	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.025	0.001	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.002	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0	-10000	0	-10000	0	0
exocyst	0.046	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.02	0	-10000	0	-10000	0	0
clathrin coat assembly	0.034	0	-10000	0	-10000	0	0
IL2RA	0.011	0.07	-10000	0	-10000	0	0
VAMP3	0.02	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.016	0.077	-10000	0	-0.41	18	18
EXOC6	0.013	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.013	0	-10000	0	-10000	0	0
PIP5K1C	0.035	0	-10000	0	-10000	0	0
SDC1	0.03	0.008	-10000	0	-10000	0	0
ARF6/GDP	0.019	0	-10000	0	-10000	0	0
EXOC7	0.013	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.028	0	-10000	0	-10000	0	0
endocytosis	0.001	0.023	0.5	1	-10000	0	1
SCAMP2	0.013	0	-10000	0	-10000	0	0
ADRB2	0.028	0.077	-10000	0	-0.44	13	13
EXOC3	0.013	0	-10000	0	-10000	0	0
ASAP2	0.012	0.038	-10000	0	-0.82	1	1
Dynamin 2/GDP	0.027	0	-10000	0	-10000	0	0
KLC1	0.013	0	-10000	0	-10000	0	0
AVPR2	0.031	0.068	-10000	0	-0.44	10	10
RALA	0.013	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0	0	-10000	0	-10000	0	0

×

TCGA08_p53

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
CDKN2A	-0.085	0.11	-9999	-9999
TP53	-0.028	0.033	-9999	-9999
Senescence	-0.028	0.033	-9999	-9999
Apoptosis	-0.028	0.033	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.054	0.062	-9999	-9999
MDM4	0.013	0	-9999	-9999

×

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	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0.032	-9999	-9999
HDAC4	0.013	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.013	-9999	-9999
NPC/RanGAP1/SUMO1	0.018	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.031	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.013	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.013	-9999	-9999
SUMO1/HDAC4	0.032	-9999	-9999
SUMO1/HDAC1	0.032	-9999	-9999
RANGAP1	0.013	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.023	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.013	-9999	-9999
UBE2I	0.013	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.013	-9999	-9999
PIAS1	0.013	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

E-cadherin signaling events

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	0	-9999	-9999
E-cadherin/beta catenin	0	-9999	-9999
CTNNB1	0.013	-9999	-9999
JUP	0.013	-9999	-9999
CDH1	0.013	-9999	-9999

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0.001	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.021	0.015	-9999	-0.21	2	2
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.003	-9999	-10000	0	0
CLTB	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.027	0	-9999	-10000	0	0
CD4	0.003	0.057	-9999	-0.31	15	15
CLTA	0.013	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.002	0.027	-9999	-0.43	2	2
ARF1/GTP	-0.001	0.016	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.029	0	-9999	-10000	0	0
mol:Choline	-0.002	0.027	-9999	-0.42	2	2
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.014	0	-9999	-10000	0	0
DDEF1	-0.002	0.028	-9999	-0.43	2	2
ARF1/GDP	0	0.007	-9999	-10000	0	0
AP2M1	0.013	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.002	-9999	-10000	0	0
ARFIP2	0	0.005	-9999	-10000	0	0
COPA	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.027	0.008	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.013	0	-9999	-10000	0	0
ARF1/GTP/Membrin	-0.001	0.01	-9999	-10000	0	0
AP2A1	0.013	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.029	0	-9999	-10000	0	0
ARF1/GDP/Membrin	-0.001	0.009	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.004	-9999	-10000	0	0
CYTH2	0.014	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-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	0.036	0.014	-9999	-10000	0	0
PLD2	-0.002	0.027	-9999	-0.43	2	2
ARF-GAP1/v-SNARE	0.012	0	-9999	-10000	0	0
PIP5K1A	-0.002	0.028	-9999	-0.43	2	2
ARF1/GTP/Membrin/GBF1/p115	-0.001	0.015	-9999	-0.24	2	2
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.002	0.027	-9999	-0.42	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.012	0	-9999	-10000	0	0
GOSR2	-0.001	0.011	-9999	-10000	0	0
USO1	-0.001	0.011	-9999	-10000	0	0
GBF1	-0.001	0.011	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.003	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.027	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.013	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	0	0	-9999	-10000	0	0
NFKB1	0.012	0.038	-9999	-0.82	1	1
MAP3K14	0.013	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.001	0.029	-9999	-0.63	1	1
RELB	0.013	0	-9999	-10000	0	0
NFKB2	0.013	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.MK.A4N9	TCGA.MK.A4N7	TCGA.MK.A4N6	TCGA.L6.A4EU
109_MAP3K5	-0.28	-0.017	-0.017	-0.017
47_PPARGC1A	-0.82	-0.82	-0.82	0.013
105_BMP4	0.013	-0.31	0.013	0.013
105_BMP6	0.013	0.013	0.013	0.013
105_BMP7	0.013	0.013	0.013	0.013
105_BMP2	0.013	0.013	0.013	0.013
131_RELN/VLDLR	-0.5	-0.5	-0.5	-0.5
30_TGFB1/TGF beta receptor Type II	0.013	0.013	0.013	0.013
84_STAT5B	0.047	-0.097	0	-0.097
84_STAT5A	0.047	-0.097	0	-0.097