PARADIGM pathway analysis of mRNASeq expression and copy number 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)	171
Signaling events regulated by Ret tyrosine kinase	144
Reelin signaling pathway	122
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	112
Wnt signaling	102
PDGFR-alpha signaling pathway	94
FOXA2 and FOXA3 transcription factor networks	91
Noncanonical Wnt signaling pathway	89
Nongenotropic Androgen signaling	88

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	0.4930	247	1732	7	-0.42	0	1000	-1000	-0.005	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.3413	171	13374	78	-0.75	0.24	1000	-1000	-0.038	-1000
Signaling events regulated by Ret tyrosine kinase	0.2874	144	11818	82	-0.37	0.027	1000	-1000	-0.061	-1000
Reelin signaling pathway	0.2435	122	6849	56	-0.46	0.061	1000	-1000	-0.047	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.2236	112	7636	68	-0.73	0.35	1000	-1000	-0.074	-1000
Wnt signaling	0.2036	102	718	7	-0.33	0.014	1000	-1000	-0.021	-1000
PDGFR-alpha signaling pathway	0.1876	94	4164	44	-0.4	0.043	1000	-1000	-0.034	-1000
FOXA2 and FOXA3 transcription factor networks	0.1816	91	4227	46	-0.84	0.031	1000	-1000	-0.066	-1000
Noncanonical Wnt signaling pathway	0.1776	89	2314	26	-0.33	0.027	1000	-1000	-0.042	-1000
Nongenotropic Androgen signaling	0.1756	88	4598	52	-0.26	0.19	1000	-1000	-0.032	-1000
Signaling events mediated by the Hedgehog family	0.1517	76	3971	52	-0.29	0.14	1000	-1000	-0.039	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.1337	67	2292	34	-0.1	0.027	1000	-1000	-0.042	-1000
Calcium signaling in the CD4+ TCR pathway	0.1317	66	2074	31	-0.36	0.027	1000	-1000	-0.05	-1000
IGF1 pathway	0.1297	65	3731	57	-0.14	0.063	1000	-1000	-0.042	-1000
Endothelins	0.1257	63	6118	96	-0.32	0.029	1000	-1000	-0.046	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.1238	62	3365	54	-0.46	0.039	1000	-1000	-0.065	-1000
IL4-mediated signaling events	0.1238	62	5688	91	-1.2	0.57	1000	-1000	-0.076	-1000
Glypican 1 network	0.1238	62	3016	48	-0.3	0.052	1000	-1000	-0.028	-1000
HIF-1-alpha transcription factor network	0.1138	57	4368	76	-0.49	0.041	1000	-1000	-0.062	-1000
Ephrin B reverse signaling	0.1058	53	2567	48	-0.24	0.12	1000	-1000	-0.041	-1000
IL23-mediated signaling events	0.1038	52	3136	60	-0.26	0.027	1000	-1000	-0.04	-1000
Coregulation of Androgen receptor activity	0.1018	51	3880	76	-0.68	0.076	1000	-1000	-0.017	-1000
Glucocorticoid receptor regulatory network	0.0978	49	5646	114	-0.45	0.26	1000	-1000	-0.053	-1000
BMP receptor signaling	0.0958	48	3966	81	-0.45	0.052	1000	-1000	-0.051	-1000
TCR signaling in naïve CD8+ T cells	0.0958	48	4494	93	-0.16	0.046	1000	-1000	-0.048	-1000
Arf6 signaling events	0.0918	46	2856	62	-0.26	0.061	1000	-1000	-0.036	-1000
EPHB forward signaling	0.0898	45	3867	85	-0.24	0.11	1000	-1000	-0.075	-1000
IL12-mediated signaling events	0.0818	41	3600	87	-0.36	0.029	1000	-1000	-0.068	-1000
Signaling mediated by p38-alpha and p38-beta	0.0778	39	1757	44	-0.22	0.027	1000	-1000	-0.028	-1000
Thromboxane A2 receptor signaling	0.0719	36	3849	105	-0.16	0.047	1000	-1000	-0.046	-1000
IL6-mediated signaling events	0.0639	32	2414	75	-0.15	0.054	1000	-1000	-0.038	-1000
Hedgehog signaling events mediated by Gli proteins	0.0619	31	2078	65	-0.58	0.064	1000	-1000	-0.045	-1000
EGFR-dependent Endothelin signaling events	0.0619	31	666	21	-0.076	0.038	1000	-1000	-0.048	-1000
Ras signaling in the CD4+ TCR pathway	0.0599	30	518	17	-0.1	0.041	1000	-1000	-0.022	-1000
Osteopontin-mediated events	0.0499	25	963	38	-0.15	0.043	1000	-1000	-0.04	-1000
Regulation of p38-alpha and p38-beta	0.0499	25	1393	54	-0.36	0.065	1000	-1000	-0.05	-1000
Regulation of Androgen receptor activity	0.0499	25	1800	70	-0.45	0.036	1000	-1000	-0.061	-1000
ErbB2/ErbB3 signaling events	0.0479	24	1594	65	-0.17	0.037	1000	-1000	-0.052	-1000
Syndecan-1-mediated signaling events	0.0479	24	830	34	-0.079	0.027	1000	-1000	-0.048	-1000
FAS signaling pathway (CD95)	0.0479	24	1167	47	-0.2	0.042	1000	-1000	-0.03	-1000
Plasma membrane estrogen receptor signaling	0.0479	24	2130	86	-0.14	0.049	1000	-1000	-0.059	-1000
BCR signaling pathway	0.0459	23	2306	99	-0.1	0.048	1000	-1000	-0.057	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0439	22	1897	85	-0.22	0.14	1000	-1000	-0.045	-1000
Syndecan-4-mediated signaling events	0.0439	22	1512	67	-0.16	0.039	1000	-1000	-0.051	-1000
IFN-gamma pathway	0.0419	21	1430	68	-0.17	0.035	1000	-1000	-0.055	-1000
LPA receptor mediated events	0.0419	21	2193	102	-0.15	0.035	1000	-1000	-0.069	-1000
Ceramide signaling pathway	0.0399	20	1549	76	-0.15	0.075	1000	-1000	-0.033	-1000
Signaling events mediated by PRL	0.0399	20	685	34	-0.087	0.04	1000	-1000	-0.04	-1000
Fc-epsilon receptor I signaling in mast cells	0.0379	19	1904	97	-0.15	0.044	1000	-1000	-0.055	-1000
Integrins in angiogenesis	0.0359	18	1515	84	-0.14	0.056	1000	-1000	-0.045	-1000
IL27-mediated signaling events	0.0359	18	943	51	-0.11	0.045	1000	-1000	-0.058	-1000
Insulin Pathway	0.0359	18	1339	74	-0.054	0.065	1000	-1000	-0.045	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0359	18	1649	88	-0.26	0.039	1000	-1000	-0.062	-1000
ceramide signaling pathway	0.0339	17	862	49	-0.055	0.039	1000	-1000	-0.034	-1000
Signaling events mediated by PTP1B	0.0319	16	1274	76	-0.19	0.039	1000	-1000	-0.033	-1000
amb2 Integrin signaling	0.0319	16	1345	82	-0.19	0.035	1000	-1000	-0.032	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0319	16	848	52	-0.18	0.057	1000	-1000	-0.037	-1000
mTOR signaling pathway	0.0299	15	799	53	-0.042	0.03	1000	-1000	-0.04	-1000
VEGFR1 specific signals	0.0299	15	881	56	-0.045	0.058	1000	-1000	-0.051	-1000
FOXM1 transcription factor network	0.0299	15	791	51	-0.22	0.052	1000	-1000	-0.069	-1000
LPA4-mediated signaling events	0.0279	14	178	12	-0.054	0.004	1000	-1000	-0.023	-1000
Regulation of nuclear SMAD2/3 signaling	0.0279	14	1984	136	-0.26	0.053	1000	-1000	-0.03	-1000
Visual signal transduction: Cones	0.0279	14	550	38	-0.043	0.042	1000	-1000	-0.017	-1000
JNK signaling in the CD4+ TCR pathway	0.0279	14	247	17	-0.084	0.026	1000	-1000	-0.032	-1000
p75(NTR)-mediated signaling	0.0279	14	1791	125	-0.28	0.071	1000	-1000	-0.064	-1000
Caspase cascade in apoptosis	0.0259	13	975	74	-0.056	0.046	1000	-1000	-0.043	-1000
Nectin adhesion pathway	0.0259	13	866	63	-0.11	0.073	1000	-1000	-0.048	-1000
Signaling events mediated by HDAC Class III	0.0259	13	557	40	-0.28	0.046	1000	-1000	-0.02	-1000
IL1-mediated signaling events	0.0259	13	838	62	-0.077	0.062	1000	-1000	-0.044	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0259	13	587	45	-0.056	0.076	1000	-1000	-0.051	-1000
Rapid glucocorticoid signaling	0.0259	13	266	20	-0.061	0.034	1000	-1000	-0.01	-1000
Presenilin action in Notch and Wnt signaling	0.0240	12	755	61	-0.15	0.07	1000	-1000	-0.051	-1000
IL2 signaling events mediated by PI3K	0.0240	12	751	58	-0.059	0.048	1000	-1000	-0.033	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0240	12	1542	120	-0.24	0.074	1000	-1000	-0.054	-1000
Cellular roles of Anthrax toxin	0.0220	11	458	39	-0.056	0.027	1000	-1000	-0.025	-1000
Syndecan-3-mediated signaling events	0.0220	11	393	35	-0.11	0.07	1000	-1000	-0.031	-1000
Visual signal transduction: Rods	0.0220	11	596	52	-0.073	0.046	1000	-1000	-0.03	-1000
ErbB4 signaling events	0.0200	10	738	69	-0.052	0.037	1000	-1000	-0.055	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0200	10	300	28	-0.14	0.056	1000	-1000	-0.022	-1000
Syndecan-2-mediated signaling events	0.0200	10	704	69	-0.16	0.05	1000	-1000	-0.032	-1000
S1P1 pathway	0.0200	10	379	36	-0.054	0.027	1000	-1000	-0.036	-1000
TCGA08_rtk_signaling	0.0200	10	261	26	-0.18	0.045	1000	-1000	-0.008	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0200	10	748	74	-0.13	0.068	1000	-1000	-0.069	-1000
BARD1 signaling events	0.0180	9	544	57	-0.04	0.051	1000	-1000	-0.05	-1000
TCGA08_p53	0.0180	9	67	7	-0.025	0.025	1000	-1000	-0.008	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0160	8	668	83	-0.17	0.05	1000	-1000	-0.035	-1000
Retinoic acid receptors-mediated signaling	0.0160	8	506	58	-0.037	0.054	1000	-1000	-0.049	-1000
Class I PI3K signaling events	0.0160	8	594	73	-0.19	0.05	1000	-1000	-0.038	-1000
Regulation of Telomerase	0.0160	8	866	102	-0.19	0.071	1000	-1000	-0.041	-1000
S1P3 pathway	0.0160	8	363	42	-0.14	0.048	1000	-1000	-0.039	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0140	7	246	33	-0.11	0.055	1000	-1000	-0.04	-1000
Class IB PI3K non-lipid kinase events	0.0140	7	21	3	-0.015	0.015	1000	-1000	-0.005	-1000
a4b1 and a4b7 Integrin signaling	0.0120	6	32	5	0.004	0.034	1000	-1000	-0.001	-1000
PLK1 signaling events	0.0120	6	538	85	-0.006	0.049	1000	-1000	-0.038	-1000
IL2 signaling events mediated by STAT5	0.0120	6	134	22	-0.033	0.033	1000	-1000	-0.043	-1000
TCGA08_retinoblastoma	0.0120	6	54	8	-0.035	0.031	1000	-1000	-0.003	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0100	5	656	125	-0.008	0.07	1000	-1000	-0.053	-1000
PDGFR-beta signaling pathway	0.0100	5	494	97	-0.15	0.079	1000	-1000	-0.053	-1000
Aurora B signaling	0.0100	5	384	67	-0.32	0.1	1000	-1000	-0.036	-1000
Insulin-mediated glucose transport	0.0080	4	150	32	-0.085	0.05	1000	-1000	-0.031	-1000
Class I PI3K signaling events mediated by Akt	0.0080	4	291	68	-0.085	0.05	1000	-1000	-0.036	-1000
Signaling events mediated by HDAC Class I	0.0080	4	510	104	-0.056	0.063	1000	-1000	-0.029	-1000
Atypical NF-kappaB pathway	0.0080	4	128	31	-0.018	0.04	1000	-1000	-0.027	-1000
Canonical Wnt signaling pathway	0.0080	4	226	51	-0.037	0.065	1000	-1000	-0.051	-1000
Effects of Botulinum toxin	0.0080	4	125	26	-0.067	0.048	1000	-1000	-0.015	-1000
S1P4 pathway	0.0080	4	122	25	-0.003	0.047	1000	-1000	-0.031	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0060	3	71	23	-0.016	0.049	1000	-1000	-0.028	-1000
Canonical NF-kappaB pathway	0.0060	3	149	39	-0.056	0.061	1000	-1000	-0.035	-1000
Circadian rhythm pathway	0.0060	3	81	22	-0.017	0.04	1000	-1000	-0.032	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0060	3	137	37	0	0.063	1000	-1000	-0.034	-1000
S1P5 pathway	0.0060	3	56	17	-0.007	0.032	1000	-1000	-0.018	-1000
HIF-2-alpha transcription factor network	0.0060	3	132	43	-0.16	0.16	1000	-1000	-0.048	-1000
FoxO family signaling	0.0060	3	245	64	-0.085	0.1	1000	-1000	-0.058	-1000
Signaling mediated by p38-gamma and p38-delta	0.0060	3	53	15	-0.005	0.027	1000	-1000	-0.029	-1000
E-cadherin signaling in keratinocytes	0.0060	3	146	43	-0.03	0.051	1000	-1000	-0.038	-1000
p38 MAPK signaling pathway	0.0060	3	168	44	-0.032	0.049	1000	-1000	-0.026	-1000
Aurora A signaling	0.0040	2	128	60	-0.025	0.055	1000	-1000	-0.025	-1000
EPO signaling pathway	0.0040	2	162	55	-0.015	0.059	1000	-1000	-0.033	-1000
TRAIL signaling pathway	0.0040	2	109	48	-0.014	0.074	1000	-1000	-0.041	-1000
Paxillin-dependent events mediated by a4b1	0.0040	2	98	36	-0.053	0.055	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class II	0.0020	1	87	75	-0.036	0.074	1000	-1000	-0.03	-1000
E-cadherin signaling in the nascent adherens junction	0.0020	1	135	76	-0.059	0.066	1000	-1000	-0.067	-1000
Arf6 trafficking events	0.0020	1	84	71	-0.048	0.05	1000	-1000	-0.039	-1000
PLK2 and PLK4 events	0.0000	0	0	3	0.016	0.027	1000	-1000	-0.015	-1000
Arf6 downstream pathway	0.0000	0	9	43	-0.061	0.045	1000	-1000	-0.032	-1000
Aurora C signaling	0.0000	0	4	7	-0.007	0.046	1000	-1000	-0.016	-1000
Glypican 2 network	0.0000	0	3	4	-0.02	0.016	1000	-1000	0.002	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	14	27	0	0.066	1000	-1000	-0.037	-1000
E-cadherin signaling events	0.0000	0	0	5	0.026	0.051	1000	-1000	0.002	-1000
Arf1 pathway	0.0000	0	24	54	-0.001	0.052	1000	-1000	-0.022	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.072	1000	-1000	-0.003	-1000
Total	NA	3450	199224	7203	-22	8.1	131000	-131000	-5.1	-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	-0.32	0.26	-9999	-0.48	339	339
EFNA5	-0.071	0.24	-9999	-0.67	69	69
FYN	-0.3	0.24	-9999	-0.45	333	333
neuron projection morphogenesis	-0.32	0.26	-9999	-0.48	339	339
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.32	0.26	-9999	-0.48	339	339
EPHA5	-0.42	0.33	-9999	-0.67	313	313

×

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	-0.22	0.21	0.38	1	-0.39	279	280
CRKL	-0.23	0.22	-10000	0	-0.41	285	285
HRAS	-0.2	0.19	-10000	0	-0.36	231	231
mol:PIP3	-0.2	0.2	-10000	0	-0.39	259	259
SPRED1	0.027	0.004	-10000	0	-10000	0	0
SPRED2	0.025	0.032	-10000	0	-0.67	1	1
GAB1	-0.24	0.24	-10000	0	-0.44	286	286
FOXO3	-0.19	0.21	0.37	2	-0.37	272	274
AKT1	-0.21	0.22	0.29	2	-0.39	278	280
BAD	-0.19	0.2	0.28	2	-0.37	270	272
megakaryocyte differentiation	-0.24	0.23	-10000	0	-0.43	295	295
GSK3B	-0.19	0.21	0.32	2	-0.37	271	273
RAF1	-0.16	0.16	0.35	1	-0.34	86	87
SHC1	0.025	0.008	-10000	0	-10000	0	0
STAT3	-0.24	0.23	-10000	0	-0.44	281	281
STAT1	-0.6	0.56	-10000	0	-1.1	289	289
HRAS/SPRED1	-0.16	0.16	-10000	0	-0.34	91	91
cell proliferation	-0.24	0.24	-10000	0	-0.44	289	289
PIK3CA	0.022	0.055	-10000	0	-0.68	3	3
TEC	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	-0.23	0.23	-10000	0	-0.42	286	286
HRAS/SPRED2	-0.16	0.16	-10000	0	-0.35	72	72
LYN/TEC/p62DOK	-0.21	0.24	-10000	0	-0.41	284	284
MAPK3	-0.11	0.12	0.26	5	-0.29	19	24
STAP1	-0.25	0.24	-10000	0	-0.44	287	287
GRAP2	-0.02	0.15	-10000	0	-0.56	33	33
JAK2	-0.5	0.48	-10000	0	-0.89	289	289
STAT1 (dimer)	-0.58	0.54	-10000	0	-1	289	289
mol:Gleevec	0.008	0.011	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.21	0.24	-10000	0	-0.42	269	269
actin filament polymerization	-0.24	0.23	-10000	0	-0.43	284	284
LYN	0.027	0.005	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.34	0.32	0.35	1	-0.61	287	288
PIK3R1	0.026	0.005	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.19	0.21	-10000	0	-0.38	270	270
PI3K	-0.21	0.24	-10000	0	-0.41	283	283
PTEN	0.026	0.018	-10000	0	-0.36	1	1
SCF/KIT/EPO/EPOR	-0.71	0.66	-10000	0	-1.3	287	287
MAPK8	-0.25	0.24	-10000	0	-0.44	289	289
STAT3 (dimer)	-0.23	0.23	-10000	0	-0.43	280	280
positive regulation of transcription	-0.086	0.11	0.3	7	-0.24	18	25
mol:GDP	-0.2	0.2	-10000	0	-0.38	240	240
PIK3C2B	-0.23	0.23	-10000	0	-0.43	279	279
CBL/CRKL	-0.21	0.22	-10000	0	-0.39	283	283
FER	-0.24	0.24	-10000	0	-0.44	285	285
SH2B3	-0.24	0.23	-10000	0	-0.44	287	287
PDPK1	-0.19	0.2	0.3	3	-0.36	253	256
SNAI2	-0.24	0.24	-10000	0	-0.44	286	286
positive regulation of cell proliferation	-0.42	0.4	-10000	0	-0.74	289	289
KITLG	-0.018	0.094	-10000	0	-0.71	8	8
cell motility	-0.42	0.4	-10000	0	-0.74	289	289
PTPN6	0.039	0.014	-10000	0	-10000	0	0
EPOR	-0.16	0.19	-10000	0	-0.87	9	9
STAT5A (dimer)	-0.34	0.33	-10000	0	-0.61	287	287
SOCS1	0.023	0.035	-10000	0	-0.67	1	1
cell migration	0.24	0.23	0.43	281	-10000	0	281
SOS1	0.027	0.005	-10000	0	-10000	0	0
EPO	-0.008	0.031	-10000	0	-10000	0	0
VAV1	0.011	0.061	-10000	0	-0.57	3	3
GRB10	-0.24	0.23	-10000	0	-0.44	284	284
PTPN11	0.034	0.033	-10000	0	-0.66	1	1
SCF/KIT	-0.25	0.25	-10000	0	-0.46	287	287
GO:0007205	0.011	0.013	-10000	0	-10000	0	0
MAP2K1	-0.13	0.13	0.27	3	-0.3	30	33
CBL	0.027	0.005	-10000	0	-10000	0	0
KIT	-0.75	0.68	-10000	0	-1.3	287	287
MAP2K2	-0.12	0.13	0.28	2	-0.31	25	27
SHC/Grb2/SOS1	-0.2	0.23	-10000	0	-0.42	249	249
STAT5A	-0.35	0.34	-10000	0	-0.63	287	287
GRB2	0.026	0.007	-10000	0	-10000	0	0
response to radiation	-0.24	0.24	-10000	0	-0.43	286	286
SHC/GRAP2	-0.001	0.11	-10000	0	-0.39	33	33
PTPRO	-0.25	0.23	-10000	0	-0.44	295	295
SH2B2	-0.24	0.23	-10000	0	-0.44	284	284
DOK1	0.027	0.005	-10000	0	-10000	0	0
MATK	-0.24	0.23	-10000	0	-0.44	280	280
CREBBP	-0.043	0.077	-10000	0	-10000	0	0
BCL2	-0.22	0.4	-10000	0	-1.5	42	42

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.061	0.097	-10000	0	-0.67	6	6
Crk/p130 Cas/Paxillin	-0.22	0.19	-10000	0	-0.38	254	254
JUN	-0.26	0.26	-10000	0	-0.56	165	165
HRAS	0.026	0.011	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.26	0.29	-10000	0	-0.49	287	287
RAP1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.027	0.005	-10000	0	-10000	0	0
RAP1A/GDP	0.02	0.004	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.26	0.29	-10000	0	-0.49	290	290
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.007	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.2	0.22	-10000	0	-0.41	265	265
RHOA	0.027	0.003	-10000	0	-10000	0	0
RAP1A/GTP	-0.24	0.26	-10000	0	-0.44	285	285
GRB7	0.001	0.056	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF	-0.26	0.29	-10000	0	-0.49	283	283
MAPKKK cascade	-0.23	0.24	-10000	0	-0.42	282	282
BCAR1	0.026	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.25	0.27	-10000	0	-0.46	289	289
lamellipodium assembly	-0.19	0.18	-10000	0	-0.35	258	258
RET51/GFRalpha1/GDNF/SHC	-0.26	0.29	-10000	0	-0.49	277	277
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
RET9/GFRalpha1/GDNF/SHC	-0.2	0.22	-10000	0	-0.39	271	271
RET9/GFRalpha1/GDNF/Shank3	-0.21	0.21	-10000	0	-0.4	276	276
MAPK3	-0.24	0.23	-10000	0	-0.42	282	282
DOK1	0.027	0.005	-10000	0	-10000	0	0
DOK6	-0.083	0.26	-10000	0	-0.67	78	78
PXN	0.027	0.005	-10000	0	-10000	0	0
neurite development	-0.26	0.25	-10000	0	-0.53	168	168
DOK5	-0.067	0.24	-10000	0	-0.67	67	67
GFRA1	-0.37	0.34	-10000	0	-0.67	281	281
MAPK8	-0.2	0.2	-10000	0	-0.36	242	242
HRAS/GTP	-0.26	0.28	-10000	0	-0.47	289	289
tube development	-0.19	0.2	-10000	0	-0.38	258	258
MAPK1	-0.24	0.23	0.32	3	-0.42	284	287
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.15	0.16	-10000	0	-0.3	258	258
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
PDLIM7	0.026	0.011	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.3	0.34	-10000	0	-0.54	300	300
SHC1	0.025	0.008	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.26	0.29	-10000	0	-0.49	289	289
RET51/GFRalpha1/GDNF/Dok5	-0.31	0.34	-10000	0	-0.55	303	303
PRKCA	0.002	0.13	-10000	0	-0.67	17	17
HRAS/GDP	0.019	0.008	-10000	0	-10000	0	0
CREB1	-0.19	0.21	-10000	0	-0.38	254	254
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.14	0.16	-10000	0	-0.29	242	242
RET51/GFRalpha1/GDNF/Grb7	-0.27	0.29	-10000	0	-0.49	287	287
mol:GDP	0	0	-10000	0	-10000	0	0
RET	-0.1	0.26	-10000	0	-0.66	85	85
DOK4	0.026	0.009	-10000	0	-10000	0	0
JNK cascade	-0.25	0.25	-10000	0	-0.56	156	156
RET9/GFRalpha1/GDNF/FRS2	-0.2	0.22	-10000	0	-0.4	272	272
SHANK3	0.02	0.013	-10000	0	-10000	0	0
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.15	0.16	-10000	0	-0.3	243	243
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.2	0.21	-10000	0	-0.35	286	286
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.2	0.21	-10000	0	-0.35	291	291
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.22	0.26	-10000	0	-0.4	276	276
PI3K	-0.3	0.29	-10000	0	-0.55	260	260
SOS1	0.027	0.005	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.19	0.21	-10000	0	-0.38	258	258
GRB10	0.026	0.006	-10000	0	-10000	0	0
activation of MAPKK activity	-0.18	0.18	-10000	0	-0.32	267	267
RET51/GFRalpha1/GDNF/FRS2	-0.26	0.29	-10000	0	-0.49	290	290
GAB1	0.027	0.004	-10000	0	-10000	0	0
IRS1	-0.054	0.22	-10000	0	-0.67	58	58
IRS2	0.026	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.22	0.26	-10000	0	-0.4	274	274
RET51/GFRalpha1/GDNF/PKC alpha	-0.27	0.3	-10000	0	-0.5	288	288
GRB2	0.026	0.007	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
GDNF	-0.007	0.024	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.31	0.32	-10000	0	-0.54	304	304
Rac1/GTP	-0.23	0.22	-10000	0	-0.42	258	258
RET9/GFRalpha1/GDNF	-0.23	0.23	-10000	0	-0.44	279	279
GFRalpha1/GDNF	-0.27	0.27	-10000	0	-0.5	279	279

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.037	0.015	-10000	0	-10000	0	0
VLDLR	-0.004	0.14	-10000	0	-0.66	21	21
CRKL	0.02	0.012	-10000	0	-10000	0	0
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
ITGA3	0.025	0.015	-10000	0	-10000	0	0
RELN/VLDLR/Fyn	-0.3	0.23	-10000	0	-0.45	351	351
MAPK8IP1/MKK7/MAP3K11/JNK1	0.061	0.067	-10000	0	-0.38	9	9
AKT1	-0.2	0.15	-10000	0	-0.3	336	336
MAP2K7	0.025	0.008	-10000	0	-10000	0	0
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0
DAB1	0.006	0.023	-10000	0	-10000	0	0
RELN/LRP8/DAB1	-0.28	0.22	-10000	0	-0.42	340	340
LRPAP1/LRP8	0.017	0.11	-10000	0	-0.51	20	20
RELN/LRP8/DAB1/Fyn	-0.26	0.22	-10000	0	-0.4	339	339
DAB1/alpha3/beta1 Integrin	-0.25	0.21	-10000	0	-0.39	311	311
long-term memory	-0.26	0.23	-10000	0	-0.4	339	339
DAB1/LIS1	-0.26	0.22	-10000	0	-0.4	331	331
DAB1/CRLK/C3G	-0.25	0.21	-10000	0	-0.39	288	288
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
DAB1/NCK2	-0.26	0.22	-10000	0	-0.4	338	338
ARHGEF2	0.025	0.007	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.001	0.12	-10000	0	-0.67	16	16
CDK5R1	0.025	0.014	-10000	0	-10000	0	0
RELN	-0.46	0.32	-10000	0	-0.67	343	343
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RELN/LRP8/Fyn	-0.3	0.24	-10000	0	-0.45	347	347
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.27	0.24	-10000	0	-0.42	339	339
MAPK8	0.013	0.095	-10000	0	-0.64	10	10
RELN/VLDLR/DAB1	-0.28	0.22	-10000	0	-0.42	342	342
ITGB1	0.027	0.004	-10000	0	-10000	0	0
MAP1B	-0.28	0.21	-10000	0	-0.41	341	341
RELN/LRP8	-0.3	0.24	-10000	0	-0.46	339	339
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.26	0.22	-10000	0	-0.41	339	339
PI3K	0.036	0.043	-10000	0	-0.51	3	3
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.037	0.015	-10000	0	-10000	0	0
RAP1A	-0.24	0.2	0.49	3	-0.67	25	28
PAFAH1B1	0.026	0.007	-10000	0	-10000	0	0
MAPK8IP1	0.027	0.005	-10000	0	-10000	0	0
CRLK/C3G	0.028	0.019	-10000	0	-10000	0	0
GRIN2B	-0.005	0.02	-10000	0	-10000	0	0
NCK2	0.027	0.005	-10000	0	-10000	0	0
neuron differentiation	-0.14	0.13	-10000	0	-0.43	37	37
neuron adhesion	-0.22	0.21	0.44	10	-0.64	25	35
LRP8	-0.002	0.14	-10000	0	-0.67	20	20
GSK3B	-0.19	0.14	-10000	0	-0.43	31	31
RELN/VLDLR/DAB1/Fyn	-0.26	0.21	-10000	0	-0.4	340	340
MAP3K11	0.027	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.21	0.16	-10000	0	-0.31	340	340
CDK5	0.026	0.006	-10000	0	-10000	0	0
MAPT	0.052	0.17	0.82	20	-0.61	3	23
neuron migration	-0.26	0.19	-10000	0	-0.41	171	171
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.14	0.13	-10000	0	-0.43	37	37
RELN/VLDLR	-0.29	0.24	-10000	0	-0.43	342	342

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	-0.011	0.11	-10000	0	-0.41	20	20
NFATC2	-0.23	0.33	-10000	0	-0.72	126	126
NFATC3	-0.083	0.14	-10000	0	-0.29	96	96
CD40LG	-0.63	0.55	-10000	0	-1.1	275	275
ITCH	0.038	0.016	-10000	0	-10000	0	0
CBLB	0.039	0.016	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.46	0.52	-10000	0	-1.2	132	132
JUNB	0.02	0.057	-10000	0	-0.6	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.042	0.018	-10000	0	-0.32	1	1
T cell anergy	0.007	0.073	0.4	5	-0.47	1	6
TLE4	-0.22	0.36	-10000	0	-0.8	110	110
Jun/NFAT1-c-4/p21SNFT	-0.56	0.58	-10000	0	-1.1	238	238
AP-1/NFAT1-c-4	-0.72	0.73	-10000	0	-1.3	263	263
IKZF1	-0.17	0.28	-10000	0	-0.67	80	80
T-helper 2 cell differentiation	-0.28	0.33	-10000	0	-0.85	96	96
AP-1/NFAT1	-0.32	0.41	-10000	0	-0.73	209	209
CALM1	0.038	0.012	-10000	0	-0.19	1	1
EGR2	-0.73	0.78	-10000	0	-1.5	237	237
EGR3	-0.53	0.68	-10000	0	-1.5	135	135
NFAT1/FOXP3	-0.17	0.28	-10000	0	-0.58	131	131
EGR1	-0.12	0.28	-10000	0	-0.68	101	101
JUN	-0.14	0.28	-10000	0	-0.67	108	108
EGR4	-0.016	0.15	-10000	0	-0.66	24	24
mol:Ca2+	0.012	0.009	-10000	0	-10000	0	0
GBP3	-0.16	0.26	-10000	0	-0.59	101	101
FOSL1	0.005	0.055	-10000	0	-0.36	1	1
NFAT1-c-4/MAF/IRF4	-0.49	0.55	-10000	0	-0.99	241	241
DGKA	-0.16	0.25	-10000	0	-0.6	84	84
CREM	0.027	0.004	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.5	0.55	-10000	0	-1	242	242
CTLA4	-0.2	0.31	-10000	0	-0.7	104	104
NFAT1-c-4 (dimer)/EGR1	-0.56	0.63	-10000	0	-1.1	235	235
NFAT1-c-4 (dimer)/EGR4	-0.52	0.55	-10000	0	-1	242	242
FOS	-0.16	0.3	-10000	0	-0.68	125	125
IFNG	-0.38	0.5	-10000	0	-1.1	127	127
T cell activation	-0.39	0.39	0.42	1	-0.83	185	186
MAF	0.026	0.006	-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	0.35	0.4	0.73	229	-10000	0	229
TNF	-0.55	0.54	-10000	0	-1	256	256
FASLG	-0.7	0.75	-10000	0	-1.4	249	249
TBX21	-0.02	0.15	-10000	0	-0.69	22	22
BATF3	0.018	0.043	-10000	0	-0.67	1	1
PRKCQ	0.017	0.074	-10000	0	-0.62	6	6
PTPN1	-0.16	0.25	-10000	0	-0.63	76	76
NFAT1-c-4/ICER1	-0.49	0.54	-10000	0	-1	238	238
GATA3	-0.007	0.15	-10000	0	-0.64	25	25
T-helper 1 cell differentiation	-0.36	0.48	-10000	0	-1.1	127	127
IL2RA	-0.42	0.46	-10000	0	-1.1	132	132
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.16	0.25	-10000	0	-0.62	77	77
E2F1	-0.013	0.07	-10000	0	-10000	0	0
PPARG	0.016	0.083	-10000	0	-0.67	7	7
SLC3A2	-0.16	0.25	-10000	0	-0.62	76	76
IRF4	-0.048	0.18	-10000	0	-0.66	37	37
PTGS2	-0.61	0.54	0.51	1	-1.1	258	259
CSF2	-0.62	0.52	-10000	0	-1.1	262	262
JunB/Fra1/NFAT1-c-4	-0.46	0.53	-10000	0	-0.97	233	233
IL4	-0.3	0.35	-10000	0	-0.92	92	92
IL5	-0.6	0.52	-10000	0	-1	261	261
IL2	-0.4	0.4	0.42	1	-0.85	184	185
IL3	-0.071	0.089	-10000	0	-0.86	2	2
RNF128	0.035	0.037	-10000	0	-0.75	1	1
NFATC1	-0.35	0.41	-10000	0	-0.74	229	229
CDK4	0.24	0.25	0.58	100	-10000	0	100
PTPRK	-0.16	0.25	-10000	0	-0.56	108	108
IL8	-0.61	0.53	0.51	1	-1	264	265
POU2F1	0.025	0.01	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.23	0.24	-9999	-0.4	301	301
FZD6	0.027	0.005	-9999	-10000	0	0
WNT6	0.02	0.027	-9999	-10000	0	0
WNT4	-0.19	0.32	-9999	-0.67	156	156
FZD3	0.027	0.005	-9999	-10000	0	0
WNT5A	0.014	0.094	-9999	-0.67	9	9
WNT11	-0.33	0.35	-9999	-0.67	252	252

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.2	0.32	-10000	0	-0.69	149	149
PDGF/PDGFRA/CRKL	-0.14	0.24	-10000	0	-0.5	148	148
positive regulation of JUN kinase activity	-0.072	0.2	-10000	0	-0.4	129	129
CRKL	0.02	0.012	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.14	0.24	-10000	0	-0.52	147	147
AP1	-0.4	0.54	-10000	0	-1.2	135	135
mol:IP3	-0.16	0.24	-10000	0	-0.53	147	147
PLCG1	-0.16	0.24	-10000	0	-0.53	147	147
PDGF/PDGFRA/alphaV Integrin	-0.14	0.25	-10000	0	-0.51	149	149
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0
CRK	0.026	0.007	-10000	0	-10000	0	0
mol:Ca2+	-0.16	0.24	-10000	0	-0.52	147	147
CAV3	-0.011	0.019	-10000	0	-10000	0	0
CAV1	0.014	0.094	-10000	0	-0.67	9	9
SHC/Grb2/SOS1	-0.072	0.2	-10000	0	-0.4	129	129
PDGF/PDGFRA/Shf	-0.14	0.24	-10000	0	-0.51	148	148
FOS	-0.39	0.52	0.31	1	-1.2	135	136
JUN	-0.15	0.22	-10000	0	-0.57	106	106
oligodendrocyte development	-0.14	0.25	-10000	0	-0.51	149	149
GRB2	0.026	0.007	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:DAG	-0.16	0.24	-10000	0	-0.53	147	147
PDGF/PDGFRA	-0.2	0.32	-10000	0	-0.69	149	149
actin cytoskeleton reorganization	-0.13	0.24	-10000	0	-0.5	148	148
SRF	0.025	0.013	-10000	0	-10000	0	0
SHC1	0.025	0.008	-10000	0	-10000	0	0
PI3K	-0.095	0.22	-10000	0	-0.43	148	148
PDGF/PDGFRA/Crk/C3G	-0.094	0.22	-10000	0	-0.43	140	140
JAK1	-0.15	0.24	-10000	0	-0.51	148	148
ELK1/SRF	-0.12	0.19	0.32	1	-0.41	141	142
SHB	0.025	0.007	-10000	0	-10000	0	0
SHF	0.027	0.008	-10000	0	-10000	0	0
CSNK2A1	0.043	0.024	-10000	0	-10000	0	0
GO:0007205	-0.17	0.25	-10000	0	-0.54	148	148
SOS1	0.027	0.005	-10000	0	-10000	0	0
Ras protein signal transduction	-0.072	0.2	-10000	0	-0.4	129	129
PDGF/PDGFRA/SHB	-0.14	0.24	-10000	0	-0.5	148	148
PDGF/PDGFRA/Caveolin-1	-0.14	0.26	-10000	0	-0.52	150	150
ITGAV	0.024	0.045	-10000	0	-0.67	2	2
ELK1	-0.16	0.22	-10000	0	-0.49	145	145
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
PDGF/PDGFRA/Crk	-0.13	0.24	-10000	0	-0.5	146	146
JAK-STAT cascade	-0.15	0.24	-10000	0	-0.51	148	148
cell proliferation	-0.13	0.24	-10000	0	-0.51	148	148

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.47	0.49	-10000	0	-0.97	204	204
PCK1	-0.3	0.44	-10000	0	-1.4	59	59
HNF4A	-0.61	0.6	-10000	0	-1.2	234	234
KCNJ11	-0.45	0.47	-10000	0	-1	171	171
AKT1	-0.065	0.14	-10000	0	-0.45	12	12
response to starvation	-0.018	0.042	-10000	0	-0.49	2	2
DLK1	-0.45	0.47	-10000	0	-0.99	179	179
NKX2-1	-0.18	0.19	0.29	1	-0.39	176	177
ACADM	-0.47	0.48	-10000	0	-0.94	217	217
TAT	-0.18	0.2	-10000	0	-0.69	1	1
CEBPB	0.027	0.005	-10000	0	-10000	0	0
CEBPA	0.019	0.07	-10000	0	-0.67	5	5
TTR	-0.14	0.22	0.68	6	-0.76	21	27
PKLR	-0.46	0.48	-10000	0	-0.96	203	203
APOA1	-0.84	0.83	-10000	0	-1.7	234	234
CPT1C	-0.47	0.49	-10000	0	-0.97	210	210
ALAS1	-0.16	0.19	-10000	0	-0.63	1	1
TFRC	-0.23	0.27	-10000	0	-0.88	18	18
FOXF1	0.02	0.063	-10000	0	-0.67	4	4
NF1	0.031	0.008	-10000	0	-10000	0	0
HNF1A (dimer)	0.028	0.008	-10000	0	-10000	0	0
CPT1A	-0.47	0.48	-10000	0	-1	192	192
HMGCS1	-0.47	0.48	-10000	0	-1	168	168
NR3C1	0.031	0.012	-10000	0	-10000	0	0
CPT1B	-0.47	0.48	-10000	0	-0.96	209	209
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.027	0.006	-10000	0	-10000	0	0
GCK	-0.59	0.62	-10000	0	-1.2	220	220
CREB1	0.009	0.066	-10000	0	-0.24	16	16
IGFBP1	-0.16	0.18	-10000	0	-10000	0	0
PDX1	-0.18	0.19	-10000	0	-0.61	3	3
UCP2	-0.47	0.48	-10000	0	-1	192	192
ALDOB	-0.44	0.47	-10000	0	-1	170	170
AFP	-0.017	0.085	-10000	0	-10000	0	0
BDH1	-0.47	0.48	-10000	0	-1	189	189
HADH	-0.44	0.47	-10000	0	-1	170	170
F2	-0.58	0.58	-10000	0	-1.2	215	215
HNF1A	0.028	0.008	-10000	0	-10000	0	0
G6PC	-0.001	0.067	-10000	0	-10000	0	0
SLC2A2	-0.22	0.23	-10000	0	-0.56	1	1
INS	-0.025	0.053	-10000	0	-0.68	3	3
FOXA1	-0.009	0.096	-10000	0	-0.32	28	28
FOXA3	-0.027	0.12	-10000	0	-0.39	18	18
FOXA2	-0.5	0.54	-10000	0	-1.1	194	194
ABCC8	-0.7	0.66	-10000	0	-1.3	251	251
ALB	-0.058	0.27	-10000	0	-1.1	30	30

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.092	0.26	-10000	0	-0.67	84	84
GNB1/GNG2	-0.2	0.23	-10000	0	-0.53	115	115
mol:DAG	-0.19	0.2	-10000	0	-0.49	112	112
PLCG1	-0.19	0.21	-10000	0	-0.51	112	112
YES1	-0.22	0.22	-10000	0	-0.53	121	121
FZD3	0.027	0.005	-10000	0	-10000	0	0
FZD6	0.027	0.005	-10000	0	-10000	0	0
G protein	-0.19	0.22	-10000	0	-0.51	112	112
MAP3K7	-0.16	0.17	0.28	2	-0.42	109	111
mol:Ca2+	-0.18	0.2	-10000	0	-0.47	112	112
mol:IP3	-0.19	0.2	-10000	0	-0.49	112	112
NLK	0	0.054	-10000	0	-0.81	2	2
GNB1	0.026	0.006	-10000	0	-10000	0	0
CAMK2A	-0.17	0.19	0.29	2	-0.45	110	112
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.23	0.24	-10000	0	-0.4	301	301
CSNK1A1	0.026	0.006	-10000	0	-10000	0	0
GNAS	-0.22	0.22	-10000	0	-0.53	121	121
GO:0007205	-0.18	0.2	-10000	0	-0.48	112	112
WNT6	0.02	0.027	-10000	0	-10000	0	0
WNT4	-0.19	0.32	-10000	0	-0.67	156	156
NFAT1/CK1 alpha	-0.24	0.24	-10000	0	-0.55	141	141
GNG2	0.025	0.032	-10000	0	-0.67	1	1
WNT5A	0.014	0.094	-10000	0	-0.67	9	9
WNT11	-0.33	0.35	-10000	0	-0.67	252	252
CDC42	-0.2	0.21	-10000	0	-0.51	116	116

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.008	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.14	0.22	-10000	0	-0.4	199	199
regulation of S phase of mitotic cell cycle	-0.1	0.16	-10000	0	-0.29	200	200
GNAO1	0.004	0.12	-10000	0	-0.67	15	15
HRAS	0.025	0.011	-10000	0	-10000	0	0
SHBG/T-DHT	0.009	0.061	-10000	0	-0.44	9	9
PELP1	0.025	0.007	-10000	0	-10000	0	0
AKT1	0.009	0.002	-10000	0	-10000	0	0
MAP2K1	-0.14	0.2	0.45	5	-0.37	195	200
T-DHT/AR	-0.2	0.26	-10000	0	-0.5	206	206
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.004	-10000	0	-0.005	128	128
GNAI2	0.027	0.003	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.025	0.032	-10000	0	-0.68	1	1
mol:GDP	-0.21	0.26	-10000	0	-0.52	203	203
cell proliferation	-0.2	0.26	0.46	11	-0.51	149	160
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
FOS	-0.26	0.37	0.45	9	-0.79	145	154
mol:Ca2+	-0.026	0.029	-10000	0	-0.066	105	105
MAPK3	-0.16	0.24	0.5	12	-0.49	99	111
MAPK1	-0.18	0.22	0.31	4	-0.42	173	177
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	128	128
cAMP biosynthetic process	0.016	0.071	0.26	10	-0.41	9	19
GNG2	0.025	0.032	-10000	0	-0.67	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	128	128
HRAS/GTP	-0.14	0.2	-10000	0	-0.38	195	195
actin cytoskeleton reorganization	0.037	0.033	-10000	0	-0.36	3	3
SRC	0.026	0.01	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	128	128
PI3K	0.033	0.038	-10000	0	-0.44	3	3
apoptosis	0.19	0.25	0.51	151	-0.41	7	158
T-DHT/AR/PELP1	-0.16	0.23	-10000	0	-0.44	204	204
HRAS/GDP	-0.2	0.26	-10000	0	-0.5	202	202
CREB1	-0.21	0.27	0.42	7	-0.56	151	158
RAC1-CDC42/GTP	0.047	0.035	-10000	0	-0.37	3	3
AR	-0.26	0.34	-10000	0	-0.67	206	206
GNB1	0.026	0.006	-10000	0	-10000	0	0
RAF1	-0.14	0.21	0.5	6	-0.38	195	201
RAC1-CDC42/GDP	-0.17	0.26	-10000	0	-0.48	201	201
T-DHT/AR/PELP1/Src	-0.14	0.22	-10000	0	-0.41	195	195
MAP2K2	-0.14	0.19	0.43	2	-0.37	191	193
T-DHT/AR/PELP1/Src/PI3K	-0.1	0.16	-10000	0	-0.3	200	200
GNAZ	0.02	0.012	-10000	0	-10000	0	0
SHBG	0.013	0.094	-10000	0	-0.67	9	9
Gi family/GNB1/GNG2/GDP	-0.032	0.099	-10000	0	-0.46	16	16
mol:T-DHT	0	0.003	0.001	59	-0.005	67	126
RAC1	0.026	0.006	-10000	0	-10000	0	0
GNRH1	0.006	0.033	-10000	0	-0.51	2	2
Gi family/GTP	-0.087	0.11	-10000	0	-0.3	48	48
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.087	0.21	-10000	0	-0.62	30	30
IHH	-0.15	0.31	-10000	0	-0.7	119	119
SHH Np/Cholesterol/GAS1	-0.053	0.16	-10000	0	-0.4	84	84
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.053	0.16	0.39	84	-10000	0	84
SMO/beta Arrestin2	-0.073	0.2	-10000	0	-0.52	16	16
SMO	-0.094	0.21	-10000	0	-0.44	113	113
AKT1	-0.015	0.1	-10000	0	-0.61	2	2
ARRB2	0.026	0.007	-10000	0	-10000	0	0
BOC	0.016	0.088	-10000	0	-0.67	8	8
ADRBK1	0.027	0.005	-10000	0	-10000	0	0
heart looping	-0.093	0.2	-10000	0	-0.43	113	113
STIL	-0.064	0.16	-10000	0	-0.49	14	14
DHH N/PTCH2	-0.05	0.2	-10000	0	-0.51	80	80
DHH N/PTCH1	-0.075	0.19	-10000	0	-0.38	120	120
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
DHH	0.021	0.063	-10000	0	-0.67	4	4
PTHLH	-0.14	0.31	-10000	0	-1	32	32
determination of left/right symmetry	-0.093	0.2	-10000	0	-0.43	113	113
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
skeletal system development	-0.13	0.3	-10000	0	-1	32	32
IHH N/Hhip	-0.29	0.33	-10000	0	-0.59	258	258
DHH N/Hhip	-0.17	0.27	-10000	0	-0.51	190	190
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.093	0.2	-10000	0	-0.43	113	113
pancreas development	-0.25	0.33	-10000	0	-0.67	189	189
HHAT	0.024	0.032	-10000	0	-0.67	1	1
PI3K	0.036	0.043	-10000	0	-0.51	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.1	0.26	-10000	0	-0.63	95	95
somite specification	-0.093	0.2	-10000	0	-0.43	113	113
SHH Np/Cholesterol/PTCH1	-0.069	0.16	-10000	0	-0.5	13	13
SHH Np/Cholesterol/PTCH2	-0.043	0.15	-10000	0	-0.38	79	79
SHH Np/Cholesterol/Megalin	-0.081	0.18	-10000	0	-0.38	126	126
SHH	-0.005	0.029	-10000	0	-0.51	1	1
catabolic process	-0.092	0.2	-10000	0	-0.42	124	124
SMO/Vitamin D3	-0.074	0.18	-10000	0	-0.55	12	12
SHH Np/Cholesterol/Hhip	-0.14	0.2	-10000	0	-0.39	189	189
LRP2	-0.16	0.3	-10000	0	-0.66	131	131
receptor-mediated endocytosis	-0.14	0.21	-10000	0	-0.6	41	41
SHH Np/Cholesterol/BOC	0.014	0.056	-10000	0	-0.37	9	9
SHH Np/Cholesterol/CDO	-0.095	0.18	-10000	0	-0.38	145	145
mesenchymal cell differentiation	0.14	0.2	0.39	189	-10000	0	189
mol:Vitamin D3	-0.063	0.17	-10000	0	-0.5	13	13
IHH N/PTCH2	-0.17	0.29	-10000	0	-0.53	176	176
CDON	-0.18	0.32	-10000	0	-0.67	146	146
IHH N/PTCH1	-0.09	0.21	-10000	0	-0.42	124	124
Megalin/LRPAP1	-0.1	0.24	-10000	0	-0.5	131	131
PTCH2	-0.084	0.26	-10000	0	-0.67	79	79
SHH Np/Cholesterol	0.009	0.023	-10000	0	-0.4	1	1
PTCH1	-0.093	0.2	-10000	0	-0.42	124	124
HHIP	-0.25	0.33	-10000	0	-0.67	189	189

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.1	0.25	0.53	115	-10000	0	115
KIRREL	-0.046	0.2	-10000	0	-0.69	41	41
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.1	0.25	-10000	0	-0.54	111	111
PLCG1	0.027	0.005	-10000	0	-10000	0	0
ARRB2	0.026	0.007	-10000	0	-10000	0	0
WASL	0.026	0.006	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.057	0.21	-10000	0	-0.44	105	105
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.058	0.16	-10000	0	-0.35	103	103
FYN	-0.063	0.2	0.28	26	-0.41	105	131
mol:Ca2+	-0.056	0.2	-10000	0	-0.43	104	104
mol:DAG	-0.056	0.2	-10000	0	-0.43	104	104
NPHS2	-0.005	0.054	-10000	0	-0.74	1	1
mol:IP3	-0.056	0.2	-10000	0	-0.43	104	104
regulation of endocytosis	-0.05	0.18	-10000	0	-0.39	103	103
Nephrin/NEPH1/podocin/Cholesterol	-0.068	0.2	-10000	0	-0.43	106	106
establishment of cell polarity	-0.1	0.25	-10000	0	-0.53	115	115
Nephrin/NEPH1/podocin/NCK1-2	-0.04	0.2	-10000	0	-0.4	105	105
Nephrin/NEPH1/beta Arrestin2	-0.05	0.18	-10000	0	-0.39	103	103
NPHS1	-0.1	0.26	-10000	0	-0.68	84	84
Nephrin/NEPH1/podocin	-0.061	0.19	-10000	0	-0.41	106	106
TJP1	0.027	0.004	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
NCK2	0.027	0.005	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.055	0.2	-10000	0	-0.44	104	104
CD2AP	0.027	0.003	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.055	0.2	-10000	0	-0.44	102	102
GRB2	0.026	0.007	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.078	0.2	0.28	21	-0.41	107	128
cytoskeleton organization	-0.082	0.2	-10000	0	-0.45	102	102
Nephrin/NEPH1	-0.072	0.19	-10000	0	-0.41	109	109
Nephrin/NEPH1/ZO-1	-0.069	0.21	-10000	0	-0.46	106	106

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.01	0.068	-9999	-0.45	9	9
NFATC2	-0.08	0.17	-9999	-0.45	84	84
NFATC3	-0.002	0.031	-9999	-10000	0	0
CD40LG	-0.34	0.37	-9999	-0.76	184	184
PTGS2	-0.31	0.35	-9999	-0.73	171	171
JUNB	0.02	0.057	-9999	-0.6	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.007	0.024	-9999	-10000	0	0
CaM/Ca2+	0.007	0.024	-9999	-10000	0	0
CALM1	0.017	0.021	-9999	-10000	0	0
JUN	-0.14	0.29	-9999	-0.67	108	108
mol:Ca2+	-0.008	0.02	-9999	-0.18	4	4
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.011	-9999	-10000	0	0
FOSL1	0.005	0.055	-9999	-0.36	1	1
CREM	0.027	0.004	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.18	0.25	-9999	-0.47	163	163
FOS	-0.16	0.3	-9999	-0.68	125	125
IFNG	-0.34	0.36	-9999	-0.75	185	185
AP-1/NFAT1-c-4	-0.36	0.45	-9999	-0.86	176	176
FASLG	-0.32	0.35	-9999	-0.73	171	171
NFAT1-c-4/ICER1	-0.08	0.17	-9999	-0.41	91	91
IL2RA	-0.32	0.34	-9999	-0.72	170	170
FKBP12/FK506	0.02	0.004	-9999	-10000	0	0
CSF2	-0.33	0.32	-9999	-0.7	172	172
JunB/Fra1/NFAT1-c-4	-0.071	0.18	-9999	-0.4	86	86
IL4	-0.31	0.32	-9999	-0.69	166	166
IL2	0.003	0.071	-9999	-1	2	2
IL3	-0.009	0.054	-9999	-0.92	1	1
FKBP1A	0.027	0.005	-9999	-10000	0	0
BATF3	0.018	0.043	-9999	-0.67	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.025	0.01	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.027	0.005	-10000	0	-10000	0	0
PTK2	0.026	0.006	-10000	0	-10000	0	0
CRKL	-0.1	0.18	-10000	0	-0.36	151	151
GRB2/SOS1/SHC	0.048	0.02	-10000	0	-10000	0	0
HRAS	0.026	0.011	-10000	0	-10000	0	0
IRS1/Crk	-0.091	0.19	-10000	0	-0.36	148	148
IGF-1R heterotetramer/IGF1/PTP1B	-0.064	0.2	-10000	0	-0.43	107	107
AKT1	-0.089	0.17	-10000	0	-0.36	106	106
BAD	-0.087	0.16	-10000	0	-0.34	106	106
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.097	0.18	-10000	0	-0.36	148	148
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.088	0.19	-10000	0	-0.37	152	152
RAF1	-0.068	0.15	0.39	1	-0.54	17	18
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.062	0.19	-10000	0	-0.35	145	145
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.096	0.21	-10000	0	-0.39	153	153
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
RPS6KB1	-0.088	0.17	-10000	0	-0.36	103	103
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.058	0.14	0.32	6	-0.45	16	22
PXN	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.038	0.011	-10000	0	-10000	0	0
HRAS/GTP	-0.07	0.16	-10000	0	-0.35	99	99
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.028	0.17	-10000	0	-0.35	97	97
IGF-1R heterotetramer	-0.008	0.058	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.077	0.2	-10000	0	-0.36	152	152
Crk/p130 Cas/Paxillin	-0.056	0.19	-10000	0	-0.34	147	147
IGF1R	-0.008	0.058	-10000	0	-10000	0	0
IGF1	-0.14	0.29	-10000	0	-0.69	108	108
IRS2/Crk	-0.085	0.18	-10000	0	-0.35	146	146
PI3K	-0.065	0.2	-10000	0	-0.35	152	152
apoptosis	0.063	0.15	0.5	15	-0.32	2	17
HRAS/GDP	0.019	0.008	-10000	0	-10000	0	0
PRKCD	-0.09	0.2	-10000	0	-0.45	107	107
RAF1/14-3-3 E	-0.044	0.14	0.33	3	-0.46	17	20
BAD/14-3-3	-0.067	0.16	0.35	3	-0.54	15	18
PRKCZ	-0.087	0.17	0.25	1	-0.36	105	106
Crk/p130 Cas/Paxillin/FAK1	-0.057	0.16	-10000	0	-0.54	15	15
PTPN1	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.093	0.21	-10000	0	-0.47	108	108
BCAR1	0.026	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.042	0.18	-10000	0	-0.38	104	104
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
IRS1/NCK2	-0.087	0.19	-10000	0	-0.36	152	152
GRB10	0.026	0.006	-10000	0	-10000	0	0
PTPN11	-0.098	0.19	-10000	0	-0.36	152	152
IRS1	-0.11	0.2	-10000	0	-0.39	153	153
IRS2	-0.098	0.18	-10000	0	-0.36	152	152
IGF-1R heterotetramer/IGF1	-0.1	0.23	-10000	0	-0.54	108	108
GRB2	0.026	0.007	-10000	0	-10000	0	0
PDPK1	-0.089	0.18	-10000	0	-0.34	149	149
YWHAE	0.026	0.007	-10000	0	-10000	0	0
PRKD1	-0.09	0.19	-10000	0	-0.45	107	107
SHC1	0.025	0.008	-10000	0	-10000	0	0

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.03	0.094	-10000	0	-0.45	9	9
PTK2B	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.15	0.28	0.47	1	-0.68	71	72
EDN1	-0.004	0.099	-10000	0	-0.56	8	8
EDN3	-0.31	0.35	-10000	0	-0.67	236	236
EDN2	0.011	0.082	-10000	0	-0.67	6	6
HRAS/GDP	-0.11	0.23	0.45	3	-0.49	91	94
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.075	0.15	-10000	0	-0.34	87	87
ADCY4	-0.071	0.15	0.35	1	-0.41	66	67
ADCY5	-0.12	0.2	0.35	1	-0.45	112	113
ADCY6	-0.069	0.15	0.35	1	-0.4	65	66
ADCY7	-0.068	0.15	0.35	1	-0.4	65	66
ADCY1	-0.072	0.15	0.35	1	-0.42	67	68
ADCY2	-0.1	0.18	-10000	0	-0.44	92	92
ADCY3	-0.07	0.15	0.35	1	-0.4	69	70
ADCY8	-0.1	0.16	0.35	1	-0.44	69	70
ADCY9	-0.068	0.15	0.35	1	-0.4	65	66
arachidonic acid secretion	-0.19	0.32	0.36	11	-0.6	153	164
ETB receptor/Endothelin-1/Gq/GTP	-0.084	0.18	-10000	0	-0.37	122	122
GNAO1	0.004	0.12	-10000	0	-0.67	15	15
HRAS	0.025	0.011	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.029	0.11	-10000	0	-0.4	8	8
ETA receptor/Endothelin-1/Gs/GTP	-0.028	0.18	-10000	0	-0.42	70	70
mol:GTP	-0.003	0.009	-10000	0	-10000	0	0
COL3A1	-0.036	0.1	-10000	0	-0.48	9	9
EDNRB	0.015	0.079	-10000	0	-0.68	6	6
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.07	0.15	-10000	0	-0.6	23	23
CYSLTR1	-0.038	0.13	-10000	0	-0.67	15	15
SLC9A1	0	0.055	-10000	0	-0.27	9	9
mol:GDP	-0.12	0.24	0.44	4	-0.51	94	98
SLC9A3	-0.055	0.21	0.37	1	-0.71	34	35
RAF1	-0.16	0.28	0.44	3	-0.55	138	141
JUN	-0.29	0.49	0.46	1	-1.1	128	129
JAK2	-0.031	0.098	-10000	0	-0.44	13	13
mol:IP3	-0.1	0.2	-10000	0	-0.42	118	118
ETA receptor/Endothelin-1	0.011	0.13	-10000	0	-0.46	17	17
PLCB1	0.024	0.032	-10000	0	-0.68	1	1
PLCB2	0.02	0.025	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.24	0.28	-10000	0	-0.52	237	237
FOS	-0.27	0.44	0.4	7	-0.98	131	138
Gai/GDP	-0.011	0.15	-10000	0	-0.65	22	22
CRK	0.025	0.007	-10000	0	-10000	0	0
mol:Ca ++	-0.1	0.19	-10000	0	-0.48	59	59
BCAR1	0.026	0.006	-10000	0	-10000	0	0
PRKCB1	-0.11	0.2	-10000	0	-0.41	120	120
GNAQ	0.015	0.022	-10000	0	-10000	0	0
GNAZ	0.02	0.012	-10000	0	-10000	0	0
GNAL	-0.061	0.23	-10000	0	-0.66	64	64
Gs family/GDP	-0.15	0.25	0.28	1	-0.53	115	116
ETA receptor/Endothelin-1/Gq/GTP	-0.09	0.18	-10000	0	-0.37	113	113
MAPK14	-0.071	0.15	-10000	0	-0.35	79	79
TRPC6	-0.16	0.3	0.47	1	-0.73	69	70
GNAI2	0.027	0.003	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.025	0.032	-10000	0	-0.67	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.073	0.16	-10000	0	-0.36	88	88
ETB receptor/Endothelin-2	0.02	0.087	-10000	0	-0.51	12	12
ETB receptor/Endothelin-3	-0.23	0.28	-10000	0	-0.51	239	239
ETB receptor/Endothelin-1	0.014	0.1	-10000	0	-0.55	11	11
MAPK3	-0.24	0.41	0.38	9	-0.85	137	146
MAPK1	-0.29	0.44	0.6	1	-0.96	136	137
Rac1/GDP	-0.11	0.22	0.37	1	-0.48	87	88
cAMP biosynthetic process	-0.076	0.18	0.47	10	-0.45	62	72
MAPK8	-0.19	0.36	0.48	1	-0.72	110	111
SRC	0.026	0.009	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.003	0.076	-10000	0	-0.34	12	12
p130Cas/CRK/Src/PYK2	-0.15	0.29	0.44	7	-0.55	129	136
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.11	0.22	0.37	1	-0.48	87	88
COL1A2	-0.007	0.11	-10000	0	-0.59	7	7
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.012	0.085	-10000	0	-0.53	7	7
mol:DAG	-0.1	0.2	-10000	0	-0.42	118	118
MAP2K2	-0.19	0.34	0.39	12	-0.67	138	150
MAP2K1	-0.2	0.34	0.43	3	-0.68	143	146
EDNRA	0.001	0.073	-10000	0	-0.37	5	5
positive regulation of muscle contraction	-0.024	0.08	-10000	0	-0.41	6	6
Gq family/GDP	-0.15	0.28	0.38	1	-0.55	129	130
HRAS/GTP	-0.14	0.24	0.48	2	-0.51	107	109
PRKCH	-0.11	0.2	-10000	0	-0.45	93	93
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	-0.12	0.22	-10000	0	-0.47	101	101
PRKCB	-0.11	0.2	-10000	0	-0.45	98	98
PRKCE	-0.11	0.2	-10000	0	-0.46	94	94
PRKCD	-0.11	0.2	-10000	0	-0.45	93	93
PRKCG	-0.1	0.2	-10000	0	-0.45	89	89
regulation of vascular smooth muscle contraction	-0.32	0.52	0.65	2	-1.2	130	132
PRKCQ	-0.11	0.2	-10000	0	-0.45	96	96
PLA2G4A	-0.21	0.35	0.37	10	-0.67	153	163
GNA14	-0.14	0.29	-10000	0	-0.64	120	120
GNA15	0.007	0.052	-10000	0	-0.67	1	1
GNA12	0.026	0.006	-10000	0	-10000	0	0
GNA11	0.008	0.085	-10000	0	-0.64	8	8
Rac1/GTP	0.029	0.11	-10000	0	-0.4	8	8
MMP1	-0.035	0.08	0.62	2	-10000	0	2

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.027	0.005	-10000	0	-10000	0	0
VLDLR	-0.004	0.14	-10000	0	-0.66	21	21
LRPAP1	0.027	0.004	-10000	0	-10000	0	0
NUDC	0.027	0.005	-10000	0	-10000	0	0
RELN/LRP8	-0.3	0.24	-10000	0	-0.46	339	339
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
KATNA1	0.027	0.004	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.28	0.21	-10000	0	-0.42	335	335
IQGAP1/CaM	0.039	0.008	-10000	0	-10000	0	0
DAB1	0.006	0.023	-10000	0	-10000	0	0
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
PLA2G7	-0.062	0.23	-10000	0	-0.67	63	63
CALM1	0.027	0.005	-10000	0	-10000	0	0
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.017	0.11	-10000	0	-0.51	20	20
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.027	0.005	-10000	0	-10000	0	0
CDK5R1	0.025	0.014	-10000	0	-10000	0	0
LIS1/Poliovirus Protein 3A	0.012	0.003	-10000	0	-10000	0	0
CDK5R2	0.001	0.023	-10000	0	-10000	0	0
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.31	0.23	-10000	0	-0.46	342	342
YWHAE	0.026	0.007	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.21	0.19	0.42	3	-0.59	17	20
MAP1B	0.007	0.002	-10000	0	-10000	0	0
RAC1	0.017	0.005	-10000	0	-10000	0	0
p35/CDK5	-0.24	0.19	-10000	0	-0.38	323	323
RELN	-0.46	0.32	-10000	0	-0.67	343	343
PAFAH/LIS1	-0.027	0.15	-10000	0	-0.43	63	63
LIS1/CLIP170	0.031	0.009	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.18	0.15	-10000	0	-0.48	16	16
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.2	0.17	-10000	0	-0.46	50	50
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.23	0.18	0.64	1	-0.58	22	23
LIS1/IQGAP1	0.031	0.009	-10000	0	-10000	0	0
RHOA	0.017	0.005	-10000	0	-10000	0	0
PAFAH1B1	0.016	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.024	0.016	-10000	0	-10000	0	0
PAFAH1B2	0.016	0.084	-10000	0	-0.64	8	8
MAP1B/LIS1/Dynein heavy chain	0.031	0.012	-10000	0	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.2	0.18	0.32	2	-0.57	17	19
LRP8	-0.002	0.14	-10000	0	-0.67	20	20
NDEL1/Katanin 60	-0.21	0.18	0.33	2	-0.58	18	20
P39/CDK5	-0.25	0.19	-10000	0	-0.38	332	332
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.031	0.01	-10000	0	-10000	0	0
CDK5	-0.27	0.19	-10000	0	-0.39	335	335
PPP2R5D	0.027	0.003	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.027	0.008	-10000	0	-10000	0	0
CSNK2A1	0.027	0.005	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.26	0.21	-10000	0	-0.4	331	331
RELN/VLDLR	-0.29	0.24	-10000	0	-0.43	342	342
CDC42	0.017	0.005	-10000	0	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.52	0.4	-10000	0	-1.1	89	89
STAT6 (cleaved dimer)	-0.53	0.41	-10000	0	-0.95	176	176
IGHG1	-0.18	0.13	-10000	0	-0.41	6	6
IGHG3	-0.51	0.38	-10000	0	-0.9	175	175
AKT1	-0.27	0.28	0.62	2	-0.82	60	62
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.23	0.29	-10000	0	-1	48	48
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.31	0.3	-10000	0	-0.77	95	95
THY1	-0.52	0.4	-10000	0	-1.1	82	82
MYB	0.01	0.1	-10000	0	-0.65	11	11
HMGA1	0.027	0.003	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.35	0.31	-10000	0	-0.78	104	104
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.28	0.28	-10000	0	-0.89	51	51
SP1	0.03	0.012	-10000	0	-10000	0	0
INPP5D	0.019	0.034	-10000	0	-10000	0	0
SOCS5	0.041	0.018	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.52	0.41	-10000	0	-1	133	133
SOCS1	-0.36	0.26	-10000	0	-0.72	78	78
SOCS3	-0.32	0.33	0.6	2	-1	56	58
FCER2	-0.56	0.46	-10000	0	-0.97	213	213
PARP14	0.026	0.009	-10000	0	-10000	0	0
CCL17	-0.55	0.42	-10000	0	-1.1	108	108
GRB2	0.026	0.007	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.2	-10000	0	-0.7	40	40
T cell proliferation	-0.51	0.41	-10000	0	-1.1	103	103
IL4R/JAK1	-0.52	0.4	-10000	0	-1.1	92	92
EGR2	-0.86	0.68	-10000	0	-1.5	238	238
JAK2	-0.033	0.041	-10000	0	-0.39	2	2
JAK3	-0.012	0.067	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	0.003	0.021	-10000	0	-10000	0	0
COL1A2	-0.16	0.15	-10000	0	-1.2	3	3
CCL26	-0.52	0.4	-10000	0	-1.1	95	95
IL4R	-0.55	0.43	-10000	0	-1.2	91	91
PTPN6	0.04	0.012	-10000	0	-10000	0	0
IL13RA2	-0.62	0.53	-10000	0	-1.4	125	125
IL13RA1	-0.031	0.033	-10000	0	-10000	0	0
IRF4	-0.31	0.5	-10000	0	-1.1	109	109
ARG1	-0.13	0.13	-10000	0	-0.73	4	4
CBL	-0.33	0.29	-10000	0	-0.8	82	82
GTF3A	0.024	0.019	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
IL13RA1/JAK2	-0.038	0.047	-10000	0	-0.25	1	1
IRF4/BCL6	-0.28	0.46	-10000	0	-1	109	109
CD40LG	-0.081	0.24	-10000	0	-0.64	77	77
MAPK14	-0.34	0.32	-10000	0	-0.88	81	81
mitosis	-0.26	0.26	0.62	2	-0.77	61	63
STAT6	-0.58	0.48	-10000	0	-1.1	145	145
SPI1	0.022	0.035	-10000	0	-10000	0	0
RPS6KB1	-0.25	0.25	0.71	3	-0.72	57	60
STAT6 (dimer)	-0.59	0.48	-10000	0	-1.1	145	145
STAT6 (dimer)/PARP14	-0.55	0.44	-10000	0	-1.1	139	139
mast cell activation	0.015	0.01	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.28	0.3	-10000	0	-0.97	54	54
FRAP1	-0.28	0.28	0.62	2	-0.82	61	63
LTA	-0.53	0.4	-10000	0	-1.1	87	87
FES	0.027	0.004	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.57	0.46	1.1	151	-10000	0	151
CCL11	-0.5	0.38	-10000	0	-1	105	105
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.28	0.3	-10000	0	-0.91	61	61
IL2RG	-0.01	0.14	-10000	0	-0.62	21	21
IL10	-0.53	0.42	-10000	0	-1.2	85	85
IRS1	-0.054	0.22	-10000	0	-0.67	58	58
IRS2	0.026	0.006	-10000	0	-10000	0	0
IL4	-0.12	0.09	-10000	0	-10000	0	0
IL5	-0.52	0.4	-10000	0	-1.1	91	91
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.45	0.35	-10000	0	-0.91	111	111
COL1A1	-0.22	0.24	-10000	0	-1	26	26
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.52	0.42	-10000	0	-1.2	71	71
IL2R gamma/JAK3	-0.021	0.12	-10000	0	-0.48	20	20
TFF3	-1.2	0.58	-10000	0	-1.4	402	402
ALOX15	-0.52	0.4	-10000	0	-1.1	88	88
MYBL1	0.026	0.008	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.45	0.35	-10000	0	-0.9	110	110
SHC1	0.025	0.008	-10000	0	-10000	0	0
CEBPB	0.03	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.28	0.28	-10000	0	-0.88	50	50
mol:PI-3-4-5-P3	-0.28	0.28	0.62	2	-0.83	60	62
PI3K	-0.29	0.3	0.67	1	-0.9	60	61
DOK2	0.019	0.052	-10000	0	-0.67	2	2
ETS1	0.039	0.017	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.2	0.19	-10000	0	-0.69	34	34
ITGB3	-0.53	0.43	-10000	0	-1.2	95	95
PIGR	-0.55	0.45	-10000	0	-1.2	100	100
IGHE	0.047	0.044	0.24	9	-10000	0	9
MAPKKK cascade	-0.2	0.19	0.59	1	-0.68	34	35
BCL6	0.026	0.032	-10000	0	-0.67	1	1
OPRM1	-0.53	0.4	-10000	0	-1.1	92	92
RETNLB	-0.53	0.4	-10000	0	-1.1	86	86
SELP	-0.52	0.41	-10000	0	-1.2	84	84
AICDA	-0.51	0.38	-10000	0	-1.1	77	77

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.052	0.025	-9999	-0.44	1	1
fibroblast growth factor receptor signaling pathway	0.052	0.025	-9999	-0.44	1	1
LAMA1	-0.021	0.18	-9999	-0.66	34	34
PRNP	0.025	0.032	-9999	-0.67	1	1
GPC1/SLIT2	-0.042	0.19	-9999	-0.5	74	74
SMAD2	0.016	0.038	-9999	-0.4	3	3
GPC1/PrPc/Cu2+	0.034	0.023	-9999	-0.44	1	1
GPC1/Laminin alpha1	0.002	0.14	-9999	-0.5	34	34
TDGF1	-0.27	0.34	-9999	-0.67	212	212
CRIPTO/GPC1	-0.19	0.27	-9999	-0.5	212	212
APP/GPC1	0.038	0.011	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	-0.17	0.22	-9999	-0.44	210	210
FLT1	0.024	0.032	-9999	-0.67	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.047	0.042	-9999	-0.43	3	3
SERPINC1	0.019	0.023	-9999	-10000	0	0
FYN	-0.17	0.23	-9999	-0.44	210	210
FGR	-0.17	0.22	-9999	-0.43	210	210
positive regulation of MAPKKK cascade	-0.23	0.26	-9999	-0.52	204	204
SLIT2	-0.077	0.25	-9999	-0.67	74	74
GPC1/NRG	-0.008	0.15	-9999	-0.5	43	43
NRG1	-0.033	0.19	-9999	-0.66	43	43
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.047	0.053	-9999	-0.57	3	3
LYN	-0.17	0.22	-9999	-0.44	208	208
mol:Spermine	0.009	0.004	-9999	-10000	0	0
cell growth	0.052	0.025	-9999	-0.44	1	1
BMP signaling pathway	-0.026	0.009	-9999	-10000	0	0
SRC	-0.17	0.22	-9999	-0.44	209	209
TGFBR1	0.021	0.025	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.18	0.3	-9999	-0.67	132	132
GPC1	0.026	0.009	-9999	-10000	0	0
TGFBR1 (dimer)	0.021	0.025	-9999	-10000	0	0
VEGFA	0.023	0.054	-9999	-0.67	3	3
BLK	-0.3	0.3	-9999	-0.54	281	281
HCK	-0.18	0.22	-9999	-0.44	210	210
FGF2	0.027	0.004	-9999	-10000	0	0
FGFR1	0.025	0.032	-9999	-0.67	1	1
VEGFR1 homodimer	0.024	0.032	-9999	-0.67	1	1
TGFBR2	0.023	0.054	-9999	-0.67	3	3
cell death	0.038	0.011	-9999	-10000	0	0
ATIII/GPC1	0.034	0.02	-9999	-10000	0	0
PLA2G2A/GPC1	-0.12	0.24	-9999	-0.51	131	131
LCK	-0.18	0.22	-9999	-0.44	215	215
neuron differentiation	-0.008	0.15	-9999	-0.49	43	43
PrPc/Cu2+	0.019	0.024	-9999	-0.51	1	1
APP	0.026	0.006	-9999	-10000	0	0
TGFBR2 (dimer)	0.023	0.054	-9999	-0.67	3	3

×

HIF-1-alpha transcription factor network

Figure S19. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S19. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.21	0.33	-10000	0	-0.79	63	63
HDAC7	0.028	0.006	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.24	0.4	-10000	0	-0.81	110	110
SMAD4	0.028	0.005	-10000	0	-10000	0	0
ID2	-0.2	0.35	0.62	3	-0.83	52	55
AP1	-0.19	0.37	-10000	0	-0.72	149	149
ABCG2	-0.2	0.35	0.61	1	-0.84	54	55
HIF1A	-0.021	0.073	-10000	0	-0.35	1	1
TFF3	-0.49	0.43	0.62	3	-0.91	181	184
GATA2	0.028	0.01	-10000	0	-10000	0	0
AKT1	-0.054	0.11	-10000	0	-0.28	11	11
response to hypoxia	-0.071	0.11	-10000	0	-0.23	95	95
MCL1	-0.19	0.34	0.61	3	-0.83	50	53
NDRG1	-0.2	0.34	0.6	2	-0.82	53	55
SERPINE1	-0.2	0.34	0.61	1	-0.84	50	51
FECH	-0.2	0.35	0.61	4	-0.82	54	58
FURIN	-0.2	0.35	0.61	4	-0.82	55	59
NCOA2	-0.036	0.2	-10000	0	-0.67	45	45
EP300	-0.1	0.18	-10000	0	-0.35	157	157
HMOX1	-0.21	0.33	0.62	2	-0.83	52	54
BHLHE40	-0.2	0.35	0.62	2	-0.82	56	58
BHLHE41	-0.2	0.35	0.61	1	-0.83	52	53
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.029	0.1	-10000	0	-10000	0	0
ENG	0.01	0.091	0.47	3	-10000	0	3
JUN	-0.12	0.29	-10000	0	-0.67	107	107
RORA	-0.2	0.35	0.61	4	-0.84	53	57
ABCB1	-0.052	0.16	-10000	0	-1.2	8	8
TFRC	-0.2	0.35	0.62	2	-0.84	54	56
CXCR4	-0.2	0.35	0.62	3	-0.82	53	56
TF	-0.24	0.4	0.62	2	-0.92	82	84
CITED2	-0.22	0.39	0.61	3	-0.92	67	70
HIF1A/ARNT	-0.22	0.38	-10000	0	-0.91	54	54
LDHA	-0.033	0.11	-10000	0	-0.7	8	8
ETS1	-0.2	0.35	0.62	3	-0.82	53	56
PGK1	-0.2	0.34	0.61	1	-0.83	52	53
NOS2	-0.2	0.35	0.61	2	-0.83	52	54
ITGB2	-0.2	0.35	0.62	3	-0.83	53	56
ALDOA	-0.2	0.34	0.61	1	-0.82	53	54
Cbp/p300/CITED2	-0.3	0.46	-10000	0	-0.98	116	116
FOS	-0.15	0.3	-10000	0	-0.67	125	125
HK2	-0.2	0.35	0.62	3	-0.82	55	58
SP1	0.032	0.017	-10000	0	-10000	0	0
GCK	-0.4	0.64	-10000	0	-1.4	137	137
HK1	-0.2	0.35	0.62	3	-0.82	55	58
NPM1	-0.2	0.34	0.61	1	-0.83	51	52
EGLN1	-0.19	0.34	0.61	3	-0.83	50	53
CREB1	0.033	0.006	-10000	0	-10000	0	0
PGM1	-0.2	0.35	0.61	3	-0.82	55	58
SMAD3	0.028	0.004	-10000	0	-10000	0	0
EDN1	-0.19	0.29	0.5	1	-0.7	74	75
IGFBP1	-0.2	0.34	0.61	1	-0.83	52	53
VEGFA	-0.2	0.35	-10000	0	-0.71	102	102
HIF1A/JAB1	0.003	0.058	-10000	0	-10000	0	0
CP	-0.32	0.46	0.62	2	-0.92	140	142
CXCL12	-0.24	0.4	0.62	3	-0.93	76	79
COPS5	0.027	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4	0.041	0.008	-10000	0	-10000	0	0
BNIP3	-0.2	0.35	0.62	3	-0.82	54	57
EGLN3	-0.21	0.35	-10000	0	-0.84	58	58
CA9	-0.2	0.35	0.6	2	-0.82	59	61
TERT	-0.2	0.34	0.6	1	-0.83	51	52
ENO1	-0.2	0.35	0.61	3	-0.82	55	58
PFKL	-0.2	0.35	0.62	3	-0.83	52	55
NCOA1	0.027	0.005	-10000	0	-10000	0	0
ADM	-0.21	0.36	0.62	3	-0.83	57	60
ARNT	-0.015	0.071	-10000	0	-0.31	2	2
HNF4A	-0.015	0.058	-10000	0	-0.22	4	4
ADFP	-0.21	0.33	-10000	0	-0.79	63	63
SLC2A1	-0.2	0.35	-10000	0	-0.71	99	99
LEP	-0.2	0.34	0.61	1	-0.84	51	52
HIF1A/ARNT/Cbp/p300	-0.26	0.41	-10000	0	-0.83	117	117
EPO	-0.14	0.28	-10000	0	-0.89	23	23
CREBBP	-0.081	0.17	-10000	0	-0.33	133	133
HIF1A/ARNT/Cbp/p300/HDAC7	-0.23	0.4	-10000	0	-0.82	107	107
PFKFB3	-0.2	0.35	0.62	3	-0.82	55	58
NT5E	-0.2	0.36	0.61	3	-0.83	56	59

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.026	0.006	-10000	0	-10000	0	0
EPHB2	0.021	0.055	-10000	0	-0.68	3	3
EFNB1	-0.002	0.085	-10000	0	-0.49	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.11	0.22	-10000	0	-0.4	184	184
Ephrin B2/EPHB1-2	-0.12	0.22	-10000	0	-0.4	181	181
neuron projection morphogenesis	-0.12	0.21	-10000	0	-0.38	184	184
Ephrin B1/EPHB1-2/Tiam1	-0.13	0.23	-10000	0	-0.42	186	186
DNM1	0.004	0.11	-10000	0	-0.63	15	15
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	-0.002	0.094	0.41	1	-0.65	8	9
YES1	0.004	0.11	-10000	0	-0.89	7	7
Ephrin B1/EPHB1-2/NCK2	-0.12	0.22	-10000	0	-0.39	185	185
PI3K	0.024	0.11	-10000	0	-0.83	7	7
mol:GDP	-0.13	0.23	-10000	0	-0.42	186	186
ITGA2B	-0.041	0.2	-10000	0	-0.67	48	48
endothelial cell proliferation	0.033	0.01	-10000	0	-10000	0	0
FYN	0.003	0.11	-10000	0	-0.86	8	8
MAP3K7	-0.011	0.088	-10000	0	-0.68	8	8
FGR	0.002	0.11	-10000	0	-0.85	8	8
TIAM1	-0.059	0.081	-10000	0	-0.67	1	1
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RGS3	0.025	0.008	-10000	0	-10000	0	0
cell adhesion	-0.027	0.16	-10000	0	-0.43	57	57
LYN	0.003	0.11	-10000	0	-0.86	8	8
Ephrin B1/EPHB1-2/Src Family Kinases	-0.006	0.1	-10000	0	-0.81	8	8
Ephrin B1/EPHB1-2	-0.01	0.092	-10000	0	-0.77	7	7
SRC	0.002	0.11	-10000	0	-0.85	8	8
ITGB3	0.011	0.1	-10000	0	-0.65	11	11
EPHB1	-0.24	0.34	-10000	0	-0.67	188	188
EPHB4	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.034	0.011	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.025	0.18	-10000	0	-0.53	55	55
BLK	-0.049	0.14	-10000	0	-0.92	8	8
HCK	0.002	0.11	-10000	0	-0.85	8	8
regulation of stress fiber formation	0.12	0.21	0.38	185	-10000	0	185
MAPK8	-0.006	0.12	0.36	5	-0.67	12	17
Ephrin B1/EPHB1-2/RGS3	-0.12	0.21	-10000	0	-0.38	185	185
endothelial cell migration	-0.006	0.083	0.4	2	-0.62	7	9
NCK2	0.027	0.005	-10000	0	-10000	0	0
PTPN13	0.024	0.091	-10000	0	-0.79	6	6
regulation of focal adhesion formation	0.12	0.21	0.38	185	-10000	0	185
chemotaxis	0.12	0.21	0.38	185	-10000	0	185
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
Rac1/GTP	-0.12	0.22	-10000	0	-0.39	184	184
angiogenesis	-0.011	0.094	-10000	0	-0.73	8	8
LCK	0	0.12	-10000	0	-0.9	8	8

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.18	0.53	-10000	0	-1.3	77	77
IL23A	-0.2	0.54	-10000	0	-1.2	96	96
NF kappa B1 p50/RelA/I kappa B alpha	-0.16	0.54	-10000	0	-1.2	83	83
positive regulation of T cell mediated cytotoxicity	-0.22	0.61	-10000	0	-1.3	92	92
ITGA3	-0.17	0.5	-10000	0	-1.2	76	76
IL17F	-0.094	0.33	0.64	2	-0.74	76	78
IL12B	0.003	0.097	-10000	0	-0.7	7	7
STAT1 (dimer)	-0.2	0.58	-10000	0	-1.3	89	89
CD4	-0.17	0.49	-10000	0	-1.2	76	76
IL23	-0.19	0.52	-10000	0	-1.2	95	95
IL23R	0.006	0.1	-10000	0	-0.82	2	2
IL1B	-0.21	0.56	-10000	0	-1.3	85	85
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.16	0.5	-10000	0	-1.2	75	75
TYK2	0.016	0.035	-10000	0	-10000	0	0
STAT4	0.004	0.099	-10000	0	-0.59	11	11
STAT3	0.026	0.007	-10000	0	-10000	0	0
IL18RAP	-0.012	0.15	-10000	0	-0.68	23	23
IL12RB1	-0.004	0.089	-10000	0	-0.66	6	6
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
IL12Rbeta1/TYK2	0.011	0.078	-10000	0	-0.51	6	6
IL23R/JAK2	0.013	0.13	-10000	0	-0.72	2	2
positive regulation of chronic inflammatory response	-0.22	0.61	-10000	0	-1.3	92	92
natural killer cell activation	0.001	0.009	-10000	0	-0.046	2	2
JAK2	0.016	0.051	-10000	0	-0.38	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.005	-10000	0	-10000	0	0
RELA	0.027	0.006	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.17	0.49	-10000	0	-1.1	96	96
ALOX12B	-0.17	0.49	-10000	0	-1.2	78	78
CXCL1	-0.18	0.52	-10000	0	-1.2	83	83
T cell proliferation	-0.22	0.61	-10000	0	-1.3	92	92
NFKBIA	0.027	0.006	-10000	0	-10000	0	0
IL17A	-0.051	0.26	-10000	0	-0.57	67	67
PI3K	-0.18	0.55	-10000	0	-1.2	84	84
IFNG	-0.015	0.053	0.12	1	-0.13	67	68
STAT3 (dimer)	-0.16	0.51	-10000	0	-1.2	79	79
IL18R1	-0.002	0.096	-10000	0	-0.59	10	10
IL23/IL23R/JAK2/TYK2/SOCS3	-0.089	0.34	-10000	0	-0.79	66	66
IL18/IL18R	-0.004	0.15	-10000	0	-0.48	37	37
macrophage activation	-0.008	0.021	-10000	0	-0.044	97	97
TNF	-0.24	0.6	-10000	0	-1.4	94	94
STAT3/STAT4	-0.19	0.55	-10000	0	-1.2	86	86
STAT4 (dimer)	-0.21	0.58	-10000	0	-1.3	90	90
IL18	-0.009	0.11	-10000	0	-0.65	11	11
IL19	-0.16	0.5	-10000	0	-1.2	73	73
STAT5A (dimer)	-0.2	0.57	-10000	0	-1.3	88	88
STAT1	0.023	0.023	-10000	0	-10000	0	0
SOCS3	-0.001	0.13	-10000	0	-0.67	19	19
CXCL9	-0.26	0.62	-10000	0	-1.4	109	109
MPO	-0.17	0.5	-10000	0	-1.2	81	81
positive regulation of humoral immune response	-0.22	0.61	-10000	0	-1.3	92	92
IL23/IL23R/JAK2/TYK2	-0.26	0.74	-10000	0	-1.6	92	92
IL6	-0.26	0.62	-10000	0	-1.3	112	112
STAT5A	0.026	0.007	-10000	0	-10000	0	0
IL2	0.003	0.03	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.001	0.009	-10000	0	-0.046	2	2
CD3E	-0.2	0.55	-10000	0	-1.3	85	85
keratinocyte proliferation	-0.22	0.61	-10000	0	-1.3	92	92
NOS2	-0.17	0.49	-10000	0	-1.2	75	75

×

Coregulation of Androgen receptor activity

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
NRIP1	-0.006	0.053	-10000	0	-10000	0	0
SVIL	-0.003	0.048	-10000	0	-10000	0	0
ZNF318	0.076	0.087	0.22	56	-0.67	1	57
JMJD2C	-0.066	0.067	-10000	0	-0.12	285	285
T-DHT/AR/Ubc9	-0.23	0.24	-10000	0	-0.49	209	209
CARM1	0.023	0.009	-10000	0	-10000	0	0
PRDX1	0.029	0.006	-10000	0	-10000	0	0
PELP1	0.032	0.013	-10000	0	-10000	0	0
CTNNB1	0.002	0.04	-10000	0	-10000	0	0
AKT1	0.038	0.021	-10000	0	-10000	0	0
PTK2B	0.007	0.032	-10000	0	-10000	0	0
MED1	0.037	0.021	-10000	0	-10000	0	0
MAK	0.067	0.12	0.26	3	-0.65	7	10
response to oxidative stress	0.002	0.004	-10000	0	-10000	0	0
HIP1	-0.006	0.064	-10000	0	-0.67	2	2
GSN	-0.001	0.045	-10000	0	-10000	0	0
NCOA2	-0.039	0.2	-10000	0	-0.68	45	45
NCOA6	-0.003	0.054	-10000	0	-0.67	1	1
DNA-PK	0.074	0.078	-10000	0	-10000	0	0
NCOA4	0.026	0.005	-10000	0	-10000	0	0
PIAS3	0.003	0.038	-10000	0	-10000	0	0
cell proliferation	-0.003	0.15	-10000	0	-0.81	10	10
XRCC5	0.037	0.018	-10000	0	-10000	0	0
UBE3A	-0.012	0.063	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.25	0.26	-10000	0	-0.52	217	217
FHL2	-0.13	0.33	-10000	0	-1.1	43	43
RANBP9	-0.001	0.046	-10000	0	-10000	0	0
JMJD1A	-0.006	0.032	-10000	0	-0.13	30	30
CDK6	0.023	0.055	-10000	0	-0.67	3	3
TGFB1I1	-0.003	0.047	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	-0.24	0.24	-10000	0	-0.49	218	218
XRCC6	0.028	0.023	-10000	0	-10000	0	0
T-DHT/AR	-0.28	0.26	-10000	0	-0.53	234	234
CTDSP1	0.012	0.023	-10000	0	-10000	0	0
CTDSP2	0.058	0.052	-10000	0	-10000	0	0
BRCA1	-0.003	0.047	-10000	0	-10000	0	0
TCF4	0.048	0.035	-10000	0	-10000	0	0
CDKN2A	0.003	0.083	-10000	0	-10000	0	0
SRF	0.035	0.051	-10000	0	-10000	0	0
NKX3-1	-0.12	0.1	-10000	0	-0.21	240	240
KLK3	-0.39	0.65	-10000	0	-1.4	142	142
TMF1	0.017	0.046	-10000	0	-0.67	2	2
HNRNPA1	0.044	0.029	-10000	0	-10000	0	0
AOF2	-0.02	0.033	-10000	0	-0.072	142	142
APPL1	0.042	0.042	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.22	0.24	-10000	0	-0.48	208	208
AR	-0.31	0.34	-10000	0	-0.71	206	206
UBA3	0.013	0.023	-10000	0	-10000	0	0
PATZ1	0.033	0.031	-10000	0	-10000	0	0
PAWR	0.02	0.015	-10000	0	-10000	0	0
PRKDC	0.037	0.018	-10000	0	-10000	0	0
PA2G4	0.049	0.037	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.2	0.22	-10000	0	-0.46	203	203
RPS6KA3	-0.003	0.046	-10000	0	-10000	0	0
T-DHT/AR/ARA70	-0.23	0.24	-10000	0	-0.5	206	206
LATS2	0.041	0.043	-10000	0	-0.67	1	1
T-DHT/AR/PRX1	-0.2	0.22	-10000	0	-0.44	204	204
Cyclin D3/CDK11 p58	0.022	0.005	-10000	0	-10000	0	0
VAV3	-0.005	0.084	-10000	0	-0.68	6	6
KLK2	-0.68	0.55	-10000	0	-1.1	291	291
CASP8	0.031	0.009	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.24	0.27	-10000	0	-0.53	209	209
TMPRSS2	-0.16	0.27	-10000	0	-1.1	33	33
CCND1	0.013	0.031	-10000	0	-10000	0	0
PIAS1	-0.012	0.063	-10000	0	-10000	0	0
mol:T-DHT	-0.034	0.04	-10000	0	-0.079	184	184
CDC2L1	0.001	0.002	-10000	0	-10000	0	0
PIAS4	-0.031	0.09	-10000	0	-0.22	1	1
T-DHT/AR/CDK6	-0.23	0.24	-10000	0	-0.49	208	208
CMTM2	0.029	0.012	-10000	0	-10000	0	0
SNURF	-0.015	0.16	-10000	0	-0.65	29	29
ZMIZ1	-0.025	0.057	-10000	0	-0.67	1	1
CCND3	0.028	0.004	-10000	0	-10000	0	0
TGIF1	0.044	0.029	-10000	0	-10000	0	0
FKBP4	-0.002	0.046	-10000	0	-10000	0	0

×

Glucocorticoid receptor regulatory network

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
PCK2	0.084	0.087	0.36	1	-10000	0	1
SMARCC2	0.026	0.018	-10000	0	-10000	0	0
SMARCC1	0.026	0.018	-10000	0	-10000	0	0
TBX21	-0.12	0.24	0.32	2	-0.66	55	57
SUMO2	0.024	0.018	-10000	0	-10000	0	0
STAT1 (dimer)	0.03	0.024	-10000	0	-10000	0	0
FKBP4	0.027	0.005	-10000	0	-10000	0	0
FKBP5	0.019	0.072	-10000	0	-0.62	6	6
GR alpha/HSP90/FKBP51/HSP90	0.12	0.11	0.33	51	-0.42	4	55
PRL	-0.062	0.1	-10000	0	-0.4	1	1
cortisol/GR alpha (dimer)/TIF2	0.18	0.29	0.54	144	-0.46	20	164
RELA	-0.026	0.098	-10000	0	-0.28	21	21
FGG	0.16	0.2	0.47	104	-10000	0	104
GR beta/TIF2	0.073	0.2	0.33	69	-0.45	45	114
IFNG	-0.36	0.48	-10000	0	-1.2	106	106
apoptosis	-0.015	0.23	0.5	36	-0.52	21	57
CREB1	0.026	0.014	-10000	0	-10000	0	0
histone acetylation	-0.074	0.16	-10000	0	-0.43	57	57
BGLAP	-0.077	0.13	-10000	0	-0.49	12	12
GR/PKAc	0.11	0.1	0.36	25	-0.34	1	26
NF kappa B1 p50/RelA	-0.044	0.17	-10000	0	-0.46	37	37
SMARCD1	0.026	0.018	-10000	0	-10000	0	0
MDM2	0.085	0.097	0.24	102	-10000	0	102
GATA3	-0.004	0.15	-10000	0	-0.64	25	25
AKT1	0.021	0.004	-10000	0	-10000	0	0
CSF2	-0.12	0.14	-10000	0	-0.56	17	17
GSK3B	0.025	0.018	-10000	0	-10000	0	0
NR1I3	0.003	0.23	0.51	33	-0.58	10	43
CSN2	0.13	0.16	0.4	87	-10000	0	87
BRG1/BAF155/BAF170/BAF60A	0.063	0.054	-10000	0	-0.31	7	7
NFATC1	0.016	0.094	-10000	0	-0.67	9	9
POU2F1	0.026	0.01	-10000	0	-10000	0	0
CDKN1A	0.026	0.034	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.013	-10000	0	-10000	0	0
SFN	-0.085	0.13	-10000	0	-0.67	15	15
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.12	0.14	0.34	45	-0.37	12	57
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.12	0.4	0.48	27	-0.83	103	130
JUN	-0.24	0.27	-10000	0	-0.56	171	171
IL4	-0.1	0.16	-10000	0	-0.64	20	20
CDK5R1	0.025	0.015	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.26	0.31	-10000	0	-0.66	154	154
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.12	0.11	0.36	32	-0.38	4	36
cortisol/GR alpha (monomer)	0.26	0.3	0.63	156	-10000	0	156
NCOA2	-0.037	0.2	-10000	0	-0.67	45	45
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.18	0.3	-10000	0	-0.69	126	126
AP-1/NFAT1-c-4	-0.38	0.41	-10000	0	-0.75	233	233
AFP	-0.17	0.21	-10000	0	-0.64	33	33
SUV420H1	0.027	0.005	-10000	0	-10000	0	0
IRF1	0.14	0.14	0.45	49	-10000	0	49
TP53	0.041	0.015	-10000	0	-10000	0	0
PPP5C	0.025	0.008	-10000	0	-10000	0	0
KRT17	-0.29	0.34	-10000	0	-0.72	136	136
KRT14	-0.085	0.12	-10000	0	-0.49	6	6
TBP	0.034	0.007	-10000	0	-10000	0	0
CREBBP	0.036	0.046	-10000	0	-0.26	10	10
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC2	0.03	0.005	-10000	0	-10000	0	0
AP-1	-0.38	0.41	-10000	0	-0.75	233	233
MAPK14	0.027	0.016	-10000	0	-10000	0	0
MAPK10	0.025	0.035	-10000	0	-0.68	1	1
MAPK11	0.017	0.019	-10000	0	-10000	0	0
KRT5	-0.37	0.49	-10000	0	-1	144	144
interleukin-1 receptor activity	0.003	0.003	-10000	0	-10000	0	0
NCOA1	0.029	0.005	-10000	0	-10000	0	0
STAT1	0.03	0.024	-10000	0	-10000	0	0
CGA	-0.095	0.14	-10000	0	-0.52	14	14
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.094	0.12	0.35	35	-10000	0	35
MAPK3	0.025	0.016	-10000	0	-10000	0	0
MAPK1	0.02	0.017	-10000	0	-10000	0	0
ICAM1	-0.16	0.24	-10000	0	-0.64	73	73
NFKB1	-0.025	0.096	-10000	0	-0.28	14	14
MAPK8	-0.14	0.18	-10000	0	-0.44	95	95
MAPK9	0.027	0.013	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.02	0.24	0.5	33	-0.55	21	54
BAX	0.04	0.093	0.85	5	-10000	0	5
POMC	-0.45	0.63	-10000	0	-1.4	131	131
EP300	0.027	0.044	-10000	0	-0.26	8	8
cortisol/GR alpha (dimer)/p53	0.23	0.25	0.55	151	-10000	0	151
proteasomal ubiquitin-dependent protein catabolic process	0.08	0.13	0.33	85	-10000	0	85
SGK1	0.013	0.21	0.51	1	-1.3	10	11
IL13	-0.21	0.25	-10000	0	-0.7	61	61
IL6	-0.28	0.48	-10000	0	-1.1	110	110
PRKACG	-0.009	0.016	-10000	0	-10000	0	0
IL5	-0.18	0.2	-10000	0	-0.65	43	43
IL2	-0.25	0.28	-10000	0	-0.6	146	146
CDK5	0.027	0.008	-10000	0	-10000	0	0
PRKACB	0.025	0.032	-10000	0	-0.67	1	1
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
IL8	-0.18	0.29	-10000	0	-0.67	86	86
CDK5R1/CDK5	0.038	0.02	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.002	0.14	-10000	0	-0.4	18	18
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.23	0.23	0.52	154	-10000	0	154
SMARCA4	0.025	0.018	-10000	0	-10000	0	0
chromatin remodeling	0.14	0.15	0.37	105	-0.44	1	106
NF kappa B1 p50/RelA/Cbp	-0.006	0.16	-10000	0	-0.43	23	23
JUN (dimer)	-0.24	0.27	-10000	0	-0.56	171	171
YWHAH	0.02	0.012	-10000	0	-10000	0	0
VIPR1	-0.22	0.36	-10000	0	-0.88	102	102
NR3C1	0.16	0.19	0.44	113	-10000	0	113
NR4A1	-0.26	0.36	-10000	0	-0.66	211	211
TIF2/SUV420H1	-0.011	0.16	-10000	0	-0.51	45	45
MAPKKK cascade	-0.015	0.23	0.5	36	-0.52	21	57
cortisol/GR alpha (dimer)/Src-1	0.23	0.25	0.55	147	-10000	0	147
PBX1	0.025	0.032	-10000	0	-0.67	1	1
POU1F1	0.005	0.022	-10000	0	-10000	0	0
SELE	-0.25	0.45	-10000	0	-1.1	88	88
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.14	0.15	0.37	102	-0.44	1	103
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.23	0.23	0.52	154	-10000	0	154
mol:cortisol	0.14	0.19	0.37	157	-10000	0	157
MMP1	-0.1	0.14	-10000	0	-0.87	10	10

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.16	0.3	-10000	0	-0.48	211	211
SMAD6-7/SMURF1	0.052	0.014	-10000	0	-10000	0	0
NOG	-0.02	0.17	-10000	0	-0.67	30	30
SMAD9	-0.18	0.27	-10000	0	-0.54	169	169
SMAD4	0.027	0.004	-10000	0	-10000	0	0
SMAD5	-0.084	0.17	-10000	0	-0.44	31	31
BMP7/USAG1	-0.24	0.27	-10000	0	-0.51	250	250
SMAD5/SKI	-0.069	0.17	0.31	3	-0.43	31	34
SMAD1	-0.037	0.094	-10000	0	-0.66	1	1
BMP2	0.001	0.13	-10000	0	-0.67	18	18
SMAD1/SMAD1/SMAD4	-0.022	0.085	-10000	0	-0.53	1	1
BMPR1A	0.027	0.005	-10000	0	-10000	0	0
BMPR1B	-0.21	0.33	-10000	0	-0.67	164	164
BMPR1A-1B/BAMBI	-0.11	0.24	-10000	0	-0.44	164	164
AHSG	-0.005	0.042	-10000	0	-10000	0	0
CER1	-0.014	0.009	-10000	0	-10000	0	0
BMP2-4/CER1	0.014	0.12	-10000	0	-0.44	29	29
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.066	0.16	-10000	0	-0.54	29	29
BMP2-4 (homodimer)	0.006	0.13	-10000	0	-0.51	29	29
RGMB	0.026	0.006	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.088	0.22	-10000	0	-0.4	163	163
RGMA	0.001	0.13	-10000	0	-0.66	19	19
SMURF1	0.026	0.006	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.079	0.16	-10000	0	-0.46	34	34
BMP2-4/USAG1	-0.22	0.26	-10000	0	-0.46	263	263
SMAD6/SMURF1/SMAD5	-0.068	0.17	0.32	1	-0.43	27	28
SOSTDC1	-0.33	0.35	-10000	0	-0.67	250	250
BMP7/BMPR2/BMPR1A-1B	-0.088	0.22	-10000	0	-0.4	161	161
SKI	0.026	0.006	-10000	0	-10000	0	0
BMP6 (homodimer)	0.026	0.014	-10000	0	-10000	0	0
HFE2	-0.003	0.022	-10000	0	-10000	0	0
ZFYVE16	0.027	0.005	-10000	0	-10000	0	0
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
BMP2-4/CHRD	0.015	0.14	-10000	0	-0.45	38	38
SMAD5/SMAD5/SMAD4	-0.067	0.17	0.31	3	-0.42	31	34
MAPK1	0.02	0.012	-10000	0	-10000	0	0
TAK1/TAB family	-0.054	0.15	-10000	0	-0.42	29	29
BMP7 (homodimer)	0.027	0.005	-10000	0	-10000	0	0
NUP214	0.025	0.008	-10000	0	-10000	0	0
BMP6/FETUA	0.026	0.034	-10000	0	-10000	0	0
SMAD1/SKI	-0.027	0.1	0.34	1	-0.48	2	3
SMAD6	0.027	0.004	-10000	0	-10000	0	0
CTDSP2	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/FETUA	0.022	0.12	-10000	0	-0.45	29	29
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.14	0.29	-10000	0	-0.66	114	114
BMPR2 (homodimer)	0.027	0.005	-10000	0	-10000	0	0
GADD34/PP1CA	0.046	0.047	-10000	0	-0.44	4	4
BMPR1A-1B (homodimer)	-0.14	0.26	-10000	0	-0.51	164	164
CHRDL1	-0.45	0.32	-10000	0	-0.66	341	341
ENDOFIN/SMAD1	-0.029	0.098	-10000	0	-0.62	1	1
SMAD6-7/SMURF1/SMAD1	-0.013	0.1	-10000	0	-0.58	1	1
SMAD6/SMURF1	0.026	0.006	-10000	0	-10000	0	0
BAMBI	0.019	0.052	-10000	0	-0.67	2	2
SMURF2	0.026	0.007	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.3	0.25	-10000	0	-0.46	332	332
BMP2-4/GREM1	-0.079	0.24	-10000	0	-0.47	125	125
SMAD7	0.027	0.004	-10000	0	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.17	0.26	-10000	0	-0.52	162	162
SMAD1/SMAD6	-0.028	0.096	-10000	0	-0.62	1	1
TAK1/SMAD6	0.039	0.01	-10000	0	-10000	0	0
BMP7	0.027	0.005	-10000	0	-10000	0	0
BMP6	0.026	0.014	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.058	0.13	-10000	0	-0.4	31	31
PPM1A	0.027	0.005	-10000	0	-10000	0	0
SMAD1/SMURF2	-0.026	0.097	0.31	1	-0.48	2	3
SMAD7/SMURF1	0.038	0.01	-10000	0	-10000	0	0
CTDSPL	0.027	0.003	-10000	0	-10000	0	0
PPP1CA	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.026	0.007	-10000	0	-10000	0	0
CTDSP1	0.027	0.005	-10000	0	-10000	0	0
PPP1R15A	0.02	0.063	-10000	0	-0.67	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.16	0.26	-10000	0	-0.64	88	88
CHRD	0.013	0.099	-10000	0	-0.67	10	10
BMPR2	0.027	0.005	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.08	0.16	-10000	0	-0.49	32	32
BMP4	0.008	0.11	-10000	0	-0.65	12	12
FST	-0.14	0.29	-10000	0	-0.67	112	112
BMP2-4/NOG	-0.006	0.16	-10000	0	-0.44	58	58
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.073	0.21	-10000	0	-0.38	158	158

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.057	0.24	0.29	20	-0.6	70	90
FYN	-0.1	0.32	0.46	1	-0.78	74	75
LAT/GRAP2/SLP76	-0.084	0.25	-10000	0	-0.63	76	76
IKBKB	0.027	0.005	-10000	0	-10000	0	0
AKT1	-0.062	0.21	0.56	9	-0.48	75	84
B2M	0.027	0.006	-10000	0	-10000	0	0
IKBKG	-0.016	0.057	0.14	3	-0.16	34	37
MAP3K8	0.018	0.079	-10000	0	-0.63	7	7
mol:Ca2+	-0.03	0.042	0.092	5	-0.11	102	107
integrin-mediated signaling pathway	0.034	0.01	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.11	0.3	0.51	4	-0.73	78	82
TRPV6	-0.1	0.35	0.99	20	-0.68	103	123
CD28	-0.014	0.15	-10000	0	-0.65	25	25
SHC1	-0.1	0.32	0.3	21	-0.79	73	94
receptor internalization	-0.13	0.34	-10000	0	-0.8	86	86
PRF1	-0.11	0.33	-10000	0	-0.88	64	64
KRAS	0.027	0.005	-10000	0	-10000	0	0
GRB2	0.026	0.007	-10000	0	-10000	0	0
COT/AKT1	-0.046	0.16	0.44	5	-0.38	77	82
LAT	-0.11	0.31	0.3	4	-0.79	75	79
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.048	0.21	-10000	0	-0.64	52	52
CD3E	-0.03	0.19	-10000	0	-0.63	42	42
CD3G	-0.096	0.26	-10000	0	-0.65	88	88
RASGRP2	-0.004	0.033	0.094	3	-0.18	12	15
RASGRP1	-0.051	0.22	0.56	11	-0.47	75	86
HLA-A	0	0.006	0.063	2	-10000	0	2
RASSF5	0.025	0.008	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.034	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.017	0.14	0.35	29	-0.13	38	67
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.048	0.085	-10000	0	-0.25	60	60
PRKCA	-0.035	0.12	-10000	0	-0.29	73	73
GRAP2	-0.02	0.15	-10000	0	-0.56	33	33
mol:IP3	-0.033	0.21	0.26	72	-0.45	72	144
EntrezGene:6957	0	0.005	0.045	2	-10000	0	2
TCR/CD3/MHC I/CD8	-0.13	0.35	-10000	0	-0.88	73	73
ORAI1	0.046	0.21	0.7	2	-0.78	16	18
CSK	-0.11	0.32	-10000	0	-0.81	74	74
B7 family/CD28	-0.11	0.35	-10000	0	-0.79	82	82
CHUK	0.027	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.14	0.38	-10000	0	-0.91	82	82
PTPN6	-0.12	0.32	0.24	1	-0.82	74	75
VAV1	-0.11	0.31	0.31	1	-0.79	74	75
Monovalent TCR/CD3	-0.11	0.31	-10000	0	-0.61	107	107
CBL	0.027	0.005	-10000	0	-10000	0	0
LCK	-0.11	0.33	-10000	0	-0.82	74	74
PAG1	-0.11	0.32	-10000	0	-0.82	74	74
RAP1A	0.027	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.14	0.38	-10000	0	-0.92	80	80
CD80	-0.043	0.21	-10000	0	-0.67	49	49
CD86	0.013	0.077	-10000	0	-0.68	5	5
PDK1/CARD11/BCL10/MALT1	-0.042	0.11	-10000	0	-0.29	61	61
HRAS	0.026	0.011	-10000	0	-10000	0	0
GO:0035030	-0.1	0.26	-10000	0	-0.6	90	90
CD8A	-0.025	0.18	-10000	0	-0.66	38	38
CD8B	-0.052	0.22	-10000	0	-0.65	55	55
PTPRC	-0.009	0.14	-10000	0	-0.68	20	20
PDK1/PKC theta	-0.076	0.26	0.61	12	-0.59	75	87
CSK/PAG1	-0.11	0.31	-10000	0	-0.79	74	74
SOS1	0.027	0.005	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.012	-10000	0	-10000	0	0
GRAP2/SLP76	-0.1	0.3	-10000	0	-0.76	76	76
STIM1	0.019	0.16	1.2	2	-0.9	9	11
RAS family/GTP	0.008	0.098	0.23	25	-0.19	42	67
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.14	0.38	-10000	0	-0.88	86	86
mol:DAG	-0.059	0.16	0.15	5	-0.4	74	79
RAP1A/GDP	0.008	0.059	0.19	17	-0.066	11	28
PLCG1	0.027	0.005	-10000	0	-10000	0	0
CD247	-0.001	0.13	-10000	0	-0.68	17	17
cytotoxic T cell degranulation	-0.1	0.31	-10000	0	-0.8	70	70
RAP1A/GTP	-0.001	0.012	-10000	0	-0.067	11	11
mol:PI-3-4-5-P3	-0.083	0.24	0.54	8	-0.58	78	86
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.051	0.26	0.28	65	-0.59	74	139
NRAS	0.027	0.005	-10000	0	-10000	0	0
ZAP70	0	0.13	-10000	0	-0.66	17	17
GRB2/SOS1	0.038	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.082	0.24	-10000	0	-0.59	76	76
MALT1	0.027	0.004	-10000	0	-10000	0	0
TRAF6	0.024	0.045	-10000	0	-0.67	2	2
CD8 heterodimer	-0.057	0.24	-10000	0	-0.6	73	73
CARD11	-0.019	0.12	-10000	0	-0.67	11	11
PRKCB	-0.032	0.12	-10000	0	-0.3	67	67
PRKCE	-0.031	0.12	-10000	0	-0.28	71	71
PRKCQ	-0.095	0.29	0.59	9	-0.69	75	84
LCP2	0.024	0.021	-10000	0	-10000	0	0
BCL10	0.027	0.005	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.049	0.18	0.54	9	-0.4	75	84
IKK complex	0.018	0.13	0.41	23	-0.13	13	36
RAS family/GDP	-0.005	0.011	-10000	0	-10000	0	0
MAP3K14	-0.035	0.12	0.27	4	-0.29	64	68
PDPK1	-0.059	0.2	0.53	11	-0.45	76	87
TCR/CD3/MHC I/CD8/Fyn	-0.16	0.41	-10000	0	-1	80	80

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.035	0.009	-10000	0	-10000	0	0
ARNO/beta Arrestin1-2	-0.017	0.15	-10000	0	-0.71	12	12
EGFR	0.019	0.07	-10000	0	-0.67	5	5
EPHA2	0.026	0.013	-10000	0	-10000	0	0
USP6	0.025	0.014	-10000	0	-10000	0	0
IQSEC1	0.027	0.004	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.045	0.2	-10000	0	-0.5	76	76
ARRB2	-0.037	0.13	-10000	0	-0.39	62	62
mol:GTP	0.024	0.037	0.17	20	-10000	0	20
ARRB1	0.025	0.032	-10000	0	-0.67	1	1
FBXO8	0.027	0.004	-10000	0	-10000	0	0
TSHR	0.024	0.045	-10000	0	-0.68	2	2
EGF	-0.076	0.25	-10000	0	-0.67	72	72
somatostatin receptor activity	0	0.001	0.002	14	-0.001	145	159
ARAP2	0.025	0.036	-10000	0	-0.52	2	2
mol:GDP	-0.11	0.14	0.27	5	-0.3	121	126
mol:PI-3-4-5-P3	0	0	0.002	11	-0.001	71	82
ITGA2B	-0.041	0.2	-10000	0	-0.67	48	48
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.025	-10000	0	-10000	0	0
ADAP1	0.026	0.006	-10000	0	-10000	0	0
KIF13B	0.027	0.005	-10000	0	-10000	0	0
HGF/MET	-0.078	0.19	-10000	0	-0.52	70	70
PXN	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	-0.11	0.16	0.51	8	-0.29	151	159
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.022	0.18	-10000	0	-0.44	76	76
ADRB2	0.011	0.1	-10000	0	-0.67	11	11
receptor agonist activity	0	0	0.001	19	0	153	172
actin filament binding	0	0	0.002	15	-0.001	146	161
SRC	0.026	0.008	-10000	0	-10000	0	0
ITGB3	0.011	0.1	-10000	0	-0.65	11	11
GNAQ	0.025	0.008	-10000	0	-10000	0	0
EFA6/PI-4-5-P2	0	0.001	0.004	17	-0.001	90	107
ARF6/GDP	-0.006	0.088	0.25	2	-0.42	9	11
ARF6/GDP/GULP/ACAP1	-0.14	0.19	-10000	0	-0.42	112	112
alphaIIb/beta3 Integrin/paxillin/GIT1	0.011	0.16	-10000	0	-0.42	55	55
ACAP1	0.019	0.045	-10000	0	-0.52	2	2
ACAP2	0.027	0.004	-10000	0	-10000	0	0
LHCGR/beta Arrestin2	-0.053	0.19	-10000	0	-0.56	62	62
EFNA1	0.025	0.008	-10000	0	-10000	0	0
HGF	-0.073	0.24	-10000	0	-0.67	70	70
CYTH3	0.006	0.033	-10000	0	-0.51	2	2
CYTH2	-0.008	0.15	-10000	0	-0.94	13	13
NCK1	0.027	0.003	-10000	0	-10000	0	0
fibronectin binding	0	0	0.001	23	0	113	136
endosomal lumen acidification	0	0	0.002	6	-0.001	146	152
microtubule-based process	0	0	-10000	0	0	7	7
GULP1	-0.093	0.26	-10000	0	-0.65	88	88
GNAQ/ARNO	0.005	0.14	-10000	0	-0.86	13	13
mol:Phosphatidic acid	0	0	0.001	12	-10000	0	12
PIP3-E	0	0	0.001	10	0	17	27
MET	-0.03	0.074	-10000	0	-10000	0	0
GNA14	-0.14	0.29	-10000	0	-0.64	120	120
GNA15	0.013	0.05	-10000	0	-0.67	1	1
GIT1	0.026	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0.001	0.003	15	-0.001	123	138
GNA11	0.014	0.084	-10000	0	-0.64	8	8
LHCGR	-0.078	0.23	-10000	0	-0.67	62	62
AGTR1	-0.26	0.34	-10000	0	-0.67	201	201
desensitization of G-protein coupled receptor protein signaling pathway	-0.052	0.19	-10000	0	-0.56	62	62
IPCEF1/ARNO	-0.035	0.18	-10000	0	-0.75	13	13
alphaIIb/beta3 Integrin	-0.025	0.18	-10000	0	-0.53	55	55

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.034	0.17	-10000	0	-0.44	71	71
cell-cell adhesion	0.11	0.16	0.32	164	-10000	0	164
Ephrin B/EPHB2/RasGAP	0.065	0.06	-10000	0	-0.38	7	7
ITSN1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
SHC1	0.025	0.008	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.026	0.048	-10000	0	-10000	0	0
Ephrin B1/EPHB1	-0.14	0.23	-10000	0	-0.43	186	186
HRAS/GDP	-0.079	0.16	-10000	0	-0.36	12	12
Ephrin B/EPHB1/GRB7	-0.099	0.23	-10000	0	-0.4	178	178
Endophilin/SYNJ1	0.023	0.073	0.44	6	-0.35	7	13
KRAS	0.027	0.005	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.096	0.22	-10000	0	-0.38	179	179
endothelial cell migration	0.052	0.037	-10000	0	-0.37	3	3
GRB2	0.026	0.007	-10000	0	-10000	0	0
GRB7	0.001	0.056	-10000	0	-10000	0	0
PAK1	0.024	0.075	0.47	5	-0.35	7	12
HRAS	0.026	0.011	-10000	0	-10000	0	0
RRAS	0.02	0.067	0.44	4	-0.36	6	10
DNM1	0.005	0.12	-10000	0	-0.62	16	16
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.12	0.19	-10000	0	-0.37	178	178
lamellipodium assembly	-0.11	0.16	-10000	0	-0.32	164	164
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.085	0.16	-10000	0	-0.3	161	161
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
EPHB2	0.022	0.055	-10000	0	-0.67	3	3
EPHB3	-0.067	0.075	-10000	0	-10000	0	0
EPHB1	-0.24	0.34	-10000	0	-0.67	188	188
EPHB4	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	-0.071	0.13	-10000	0	-0.38	13	13
Ephrin B/EPHB2	0.051	0.056	-10000	0	-0.38	7	7
Ephrin B/EPHB3	0.057	0.055	-10000	0	-0.43	4	4
JNK cascade	-0.12	0.19	-10000	0	-0.38	176	176
Ephrin B/EPHB1	-0.11	0.21	-10000	0	-0.38	180	180
RAP1/GDP	-0.046	0.14	-10000	0	-0.37	5	5
EFNB2	0.026	0.006	-10000	0	-10000	0	0
EFNB3	0.015	0.068	-10000	0	-0.67	4	4
EFNB1	0.026	0.007	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.12	0.22	-10000	0	-0.4	181	181
RAP1B	0.027	0.005	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.084	0.18	-10000	0	-0.38	20	20
Rap1/GTP	-0.1	0.17	-10000	0	-0.44	7	7
axon guidance	-0.034	0.17	-10000	0	-0.44	71	71
MAPK3	-0.081	0.14	-10000	0	-0.46	9	9
MAPK1	-0.079	0.13	-10000	0	-0.43	11	11
Rac1/GDP	-0.057	0.13	-10000	0	-0.38	5	5
actin cytoskeleton reorganization	-0.079	0.12	-10000	0	-0.34	3	3
CDC42/GDP	-0.054	0.14	0.4	2	-0.38	5	7
PI3K	0.057	0.039	-10000	0	-0.38	3	3
EFNA5	-0.071	0.24	-10000	0	-0.67	69	69
Ephrin B2/EPHB4	0.034	0.011	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.026	0.044	-10000	0	-0.36	3	3
CDC42	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.1	0.16	-10000	0	-0.42	7	7
PTK2	0.043	0.098	0.67	10	-10000	0	10
MAP4K4	-0.12	0.19	-10000	0	-0.38	176	176
SRC	0.026	0.008	-10000	0	-10000	0	0
KALRN	0.027	0.003	-10000	0	-10000	0	0
Intersectin/N-WASP	0.038	0.01	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.076	0.14	0.32	5	-10000	0	5
MAP2K1	-0.082	0.15	-10000	0	-0.4	17	17
WASL	0.026	0.006	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.11	0.22	-10000	0	-0.4	176	176
cell migration	-0.083	0.18	0.58	4	-0.48	13	17
NRAS	0.027	0.005	-10000	0	-10000	0	0
SYNJ1	0.023	0.074	0.45	6	-0.36	7	13
PXN	0.027	0.005	-10000	0	-10000	0	0
TF	-0.024	0.13	0.47	3	-0.37	52	55
HRAS/GTP	-0.092	0.19	-10000	0	-0.34	173	173
Ephrin B1/EPHB1-2	-0.12	0.22	-10000	0	-0.39	187	187
cell adhesion mediated by integrin	-0.007	0.073	0.39	4	-0.37	8	12
RAC1	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	-0.096	0.2	-10000	0	-0.36	176	176
RAC1-CDC42/GTP	-0.14	0.16	-10000	0	-0.37	131	131
RASA1	0.027	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.048	0.14	-10000	0	-0.37	5	5
ruffle organization	-0.1	0.18	0.58	6	-0.48	1	7
NCK1	0.027	0.003	-10000	0	-10000	0	0
receptor internalization	0.002	0.085	0.41	3	-0.37	17	20
Ephrin B/EPHB2/KALRN	0.065	0.06	-10000	0	-0.38	7	7
ROCK1	-0.025	0.044	-10000	0	-10000	0	0
RAS family/GDP	-0.073	0.1	-10000	0	-0.34	2	2
Rac1/GTP	-0.11	0.17	-10000	0	-0.34	164	164
Ephrin B/EPHB1/Src/Paxillin	-0.091	0.16	-10000	0	-0.3	181	181

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.029	0.14	-10000	0	-0.37	44	44
TBX21	-0.12	0.43	-10000	0	-1.1	62	62
B2M	0.023	0.018	-10000	0	-10000	0	0
TYK2	0.019	0.03	-10000	0	-10000	0	0
IL12RB1	0	0.088	-10000	0	-0.64	6	6
GADD45B	-0.096	0.39	-10000	0	-1	61	61
IL12RB2	-0.003	0.13	-10000	0	-0.66	17	17
GADD45G	-0.092	0.36	-10000	0	-0.95	53	53
natural killer cell activation	0.001	0.02	0.047	10	-0.04	36	46
RELB	0.026	0.007	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
IL18	-0.003	0.11	-10000	0	-0.66	11	11
IL2RA	-0.017	0.16	-10000	0	-0.64	28	28
IFNG	-0.073	0.23	-10000	0	-0.67	62	62
STAT3 (dimer)	-0.081	0.32	-10000	0	-0.78	64	64
HLA-DRB5	-0.005	0.01	-10000	0	-0.022	105	105
FASLG	-0.14	0.46	-10000	0	-1.2	64	64
NF kappa B2 p52/RelB	-0.1	0.39	-10000	0	-0.94	67	67
CD4	0.011	0.036	-10000	0	-10000	0	0
SOCS1	0.023	0.035	-10000	0	-0.67	1	1
EntrezGene:6955	-0.007	0.015	-10000	0	-0.029	139	139
CD3D	-0.061	0.2	-10000	0	-0.64	52	52
CD3E	-0.043	0.18	-10000	0	-0.62	42	42
CD3G	-0.11	0.26	-10000	0	-0.66	88	88
IL12Rbeta2/JAK2	0.012	0.11	-10000	0	-0.47	19	19
CCL3	-0.12	0.42	-10000	0	-1.2	55	55
CCL4	-0.15	0.49	-10000	0	-1.3	63	63
HLA-A	-0.001	0.01	-10000	0	-0.036	30	30
IL18/IL18R	0.027	0.16	-10000	0	-0.48	37	37
NOS2	-0.088	0.36	-10000	0	-1	47	47
IL12/IL12R/TYK2/JAK2/SPHK2	-0.029	0.14	-10000	0	-0.38	40	40
IL1R1	-0.1	0.38	-10000	0	-1	53	53
IL4	0	0.034	-10000	0	-10000	0	0
JAK2	0.018	0.04	-10000	0	-0.38	2	2
EntrezGene:6957	-0.006	0.014	-10000	0	-0.027	132	132
TCR/CD3/MHC I/CD8	-0.21	0.49	-10000	0	-1.1	96	96
RAB7A	-0.057	0.3	-10000	0	-0.76	53	53
lysosomal transport	-0.051	0.29	-10000	0	-0.71	53	53
FOS	-0.36	0.61	-10000	0	-1.2	163	163
STAT4 (dimer)	-0.085	0.36	-10000	0	-0.84	70	70
STAT5A (dimer)	-0.14	0.41	-10000	0	-0.95	79	79
GZMA	-0.12	0.4	-10000	0	-1.2	50	50
GZMB	-0.11	0.39	-10000	0	-1.1	49	49
HLX	0.022	0.025	-10000	0	-10000	0	0
LCK	-0.13	0.43	-10000	0	-1.1	65	65
TCR/CD3/MHC II/CD4	-0.14	0.26	-10000	0	-0.42	163	163
IL2/IL2R	-0.007	0.17	-10000	0	-0.55	37	37
MAPK14	-0.085	0.37	0.46	1	-0.89	67	68
CCR5	-0.095	0.4	-10000	0	-1.2	42	42
IL1B	-0.025	0.18	-10000	0	-0.71	32	32
STAT6	-0.007	0.11	-10000	0	-0.36	10	10
STAT4	0.004	0.099	-10000	0	-0.59	11	11
STAT3	0.026	0.007	-10000	0	-10000	0	0
STAT1	0.023	0.023	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
NFKB2	0.027	0.004	-10000	0	-10000	0	0
IL12B	0.004	0.09	-10000	0	-0.68	7	7
CD8A	-0.028	0.18	-10000	0	-0.66	38	38
CD8B	-0.055	0.21	-10000	0	-0.65	55	55
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.029	0.14	0.37	44	-10000	0	44
IL2RB	0.004	0.09	-10000	0	-0.58	10	10
proteasomal ubiquitin-dependent protein catabolic process	-0.072	0.33	-10000	0	-0.76	70	70
IL2RG	-0.012	0.14	-10000	0	-0.63	21	21
IL12	-0.037	0.18	-10000	0	-0.53	58	58
STAT5A	0.026	0.007	-10000	0	-10000	0	0
CD247	-0.013	0.13	-10000	0	-0.68	17	17
IL2	-0.003	0.02	-10000	0	-10000	0	0
SPHK2	0.025	0.007	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.055	0.22	-10000	0	-0.68	53	53
IL12/IL12R/TYK2/JAK2	-0.14	0.51	-10000	0	-1.2	67	67
MAP2K3	-0.086	0.37	-10000	0	-0.9	64	64
RIPK2	0.027	0.005	-10000	0	-10000	0	0
MAP2K6	-0.093	0.38	-10000	0	-0.89	69	69
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.005	0.011	-10000	0	-0.026	114	114
IL18RAP	-0.006	0.15	-10000	0	-0.68	23	23
IL12Rbeta1/TYK2	0.019	0.076	-10000	0	-0.49	6	6
EOMES	-0.13	0.4	-10000	0	-1.3	49	49
STAT1 (dimer)	-0.12	0.36	-10000	0	-0.8	87	87
T cell proliferation	-0.051	0.27	-10000	0	-0.62	65	65
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.005	0.096	-10000	0	-0.58	10	10
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.068	0.28	-10000	0	-0.66	70	70
ATF2	-0.088	0.34	0.44	1	-0.79	71	72

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.083	0.32	-10000	0	-1.2	39	39
MKNK1	0.027	0.005	-10000	0	-10000	0	0
MAPK14	-0.016	0.11	-10000	0	-0.35	33	33
ATF2/c-Jun	-0.2	0.36	-10000	0	-0.79	123	123
MAPK11	-0.011	0.095	-10000	0	-0.35	27	27
MITF	-0.022	0.12	-10000	0	-0.42	36	36
MAPKAPK5	-0.018	0.11	-10000	0	-0.41	32	32
KRT8	-0.018	0.11	-10000	0	-0.41	32	32
MAPKAPK3	0.027	0.003	-10000	0	-10000	0	0
MAPKAPK2	0.025	0.008	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.027	0.15	-10000	0	-0.49	36	36
CEBPB	-0.02	0.12	-10000	0	-0.41	34	34
SLC9A1	-0.022	0.12	-10000	0	-0.41	37	37
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.074	0.19	-10000	0	-0.44	80	80
p38alpha-beta/MNK1	-0.009	0.13	-10000	0	-0.41	32	32
JUN	-0.2	0.35	-10000	0	-0.79	123	123
PPARGC1A	-0.22	0.25	-10000	0	-0.45	254	254
USF1	-0.023	0.12	-10000	0	-0.41	37	37
RAB5/GDP/GDI1	-0.034	0.1	-10000	0	-0.32	34	34
NOS2	-0.027	0.12	-10000	0	-0.53	6	6
DDIT3	-0.019	0.11	-10000	0	-0.41	32	32
RAB5A	0.027	0.004	-10000	0	-10000	0	0
HSPB1	-0.015	0.092	0.37	2	-0.34	30	32
p38alpha-beta/HBP1	-0.005	0.12	-10000	0	-0.42	26	26
CREB1	-0.054	0.16	-10000	0	-0.47	41	41
RAB5/GDP	0.02	0.003	-10000	0	-10000	0	0
EIF4E	-0.024	0.1	-10000	0	-0.38	25	25
RPS6KA4	-0.02	0.12	-10000	0	-0.42	34	34
PLA2G4A	-0.05	0.16	-10000	0	-0.48	49	49
GDI1	-0.018	0.12	-10000	0	-0.43	31	31
TP53	-0.031	0.13	-10000	0	-0.5	31	31
RPS6KA5	-0.062	0.18	-10000	0	-0.45	77	77
ESR1	-0.049	0.19	-10000	0	-0.54	50	50
HBP1	0.026	0.006	-10000	0	-10000	0	0
MEF2C	-0.019	0.12	-10000	0	-0.41	33	33
MEF2A	-0.024	0.12	-10000	0	-0.42	38	38
EIF4EBP1	-0.053	0.15	-10000	0	-0.46	42	42
KRT19	-0.051	0.16	-10000	0	-0.49	44	44
ELK4	-0.023	0.12	-10000	0	-0.41	37	37
ATF6	-0.023	0.12	-10000	0	-0.41	37	37
ATF1	-0.052	0.15	-10000	0	-0.47	39	39
p38alpha-beta/MAPKAPK2	-0.01	0.12	-10000	0	-0.41	32	32
p38alpha-beta/MAPKAPK3	-0.009	0.13	-10000	0	-0.42	32	32

×

Thromboxane A2 receptor 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
TGM2	0.005	0.053	-10000	0	-10000	0	0
GNB1/GNG2	-0.032	0.065	-10000	0	-0.19	67	67
AKT1	0.014	0.13	0.41	23	-0.23	5	28
EGF	-0.076	0.25	-10000	0	-0.67	72	72
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.02	0.086	0.36	14	-0.5	2	16
mol:Ca2+	-0.014	0.15	0.4	16	-0.3	68	84
LYN	0.02	0.085	0.36	13	-0.5	2	15
RhoA/GTP	-0.008	0.054	-10000	0	-0.15	2	2
mol:PGI2	0	0.001	-10000	0	-10000	0	0
SYK	-0.015	0.17	0.43	19	-0.34	67	86
GNG2	0.025	0.032	-10000	0	-0.68	1	1
ARRB2	0.026	0.007	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.032	0.12	0.27	1	-0.59	12	13
G beta5/gamma2	-0.042	0.089	-10000	0	-0.25	67	67
PRKCH	-0.021	0.17	0.44	15	-0.36	68	83
DNM1	0.005	0.12	-10000	0	-0.62	16	16
TXA2/TP beta/beta Arrestin3	-0.009	0.12	-10000	0	-0.49	24	24
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.002	0.14	-10000	0	-0.67	20	20
G12 family/GTP	-0.033	0.12	-10000	0	-0.31	65	65
ADRBK1	0.027	0.005	-10000	0	-10000	0	0
ADRBK2	0.02	0.012	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.036	0.007	-10000	0	-10000	0	0
mol:GDP	0.047	0.14	0.39	37	-0.35	7	44
mol:NADP	0.026	0.006	-10000	0	-10000	0	0
RAB11A	0.027	0.004	-10000	0	-10000	0	0
PRKG1	-0.16	0.31	-10000	0	-0.67	136	136
mol:IP3	-0.024	0.18	0.45	14	-0.38	68	82
cell morphogenesis	0.036	0.007	-10000	0	-10000	0	0
PLCB2	-0.045	0.22	0.45	12	-0.52	68	80
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.077	0.17	0.36	10	-0.33	140	150
mol:PDG2	0	0.001	-10000	0	-10000	0	0
HCK	0.015	0.081	0.35	11	-0.5	2	13
RHOA	0.027	0.003	-10000	0	-10000	0	0
PTGIR	0.02	0.063	-10000	0	-0.68	4	4
PRKCB1	-0.024	0.17	0.43	14	-0.38	68	82
GNAQ	0.025	0.008	-10000	0	-10000	0	0
mol:L-citrulline	0.026	0.006	-10000	0	-10000	0	0
TXA2/TXA2-R family	-0.042	0.23	0.49	14	-0.54	68	82
LCK	0.016	0.098	0.36	14	-0.53	5	19
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.027	0.081	-10000	0	-0.68	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.031	0.033	-10000	0	-0.36	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.032	0.081	-10000	0	-0.67	2	2
MAPK14	-0.003	0.12	0.35	21	-0.23	61	82
TGM2/GTP	-0.041	0.18	0.34	6	-0.43	63	69
MAPK11	-0.006	0.13	0.38	20	-0.23	50	70
ARHGEF1	-0.014	0.073	0.17	1	-0.19	37	38
GNAI2	0.027	0.003	-10000	0	-10000	0	0
JNK cascade	-0.021	0.18	0.43	19	-0.39	68	87
RAB11/GDP	0.027	0.006	-10000	0	-10000	0	0
ICAM1	-0.013	0.14	0.38	19	-0.29	69	88
cAMP biosynthetic process	-0.025	0.17	0.43	16	-0.36	63	79
Gq family/GTP/EBP50	-0.046	0.12	0.24	2	-0.23	120	122
actin cytoskeleton reorganization	0.036	0.007	-10000	0	-10000	0	0
SRC	0.018	0.08	0.35	11	-0.5	2	13
GNB5	0.027	0.004	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
EGF/EGFR	-0.019	0.13	0.43	17	-0.29	14	31
VCAM1	-0.01	0.15	0.37	19	-0.3	69	88
TP beta/Gq family/GDP/G beta5/gamma2	-0.032	0.12	0.27	1	-0.59	12	13
platelet activation	-0.002	0.17	0.45	24	-0.3	64	88
PGI2/IP	0.015	0.048	-10000	0	-0.51	4	4
PRKACA	0.005	0.079	-10000	0	-0.35	21	21
Gq family/GDP/G beta5/gamma2	-0.032	0.12	0.28	1	-0.54	13	14
TXA2/TP beta/beta Arrestin2	0.006	0.1	-10000	0	-0.54	16	16
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.001	0.079	-10000	0	-0.35	19	19
mol:DAG	-0.029	0.19	0.45	14	-0.43	68	82
EGFR	0.019	0.07	-10000	0	-0.67	5	5
TXA2/TP alpha	-0.041	0.22	0.52	13	-0.49	63	76
Gq family/GTP	-0.066	0.13	0.22	2	-0.28	123	125
YES1	0.022	0.088	0.37	15	-0.5	2	17
GNAI2/GTP	0.009	0.069	-10000	0	-0.6	2	2
PGD2/DP	-0.002	0.1	-10000	0	-0.51	20	20
SLC9A3R1	0.026	0.007	-10000	0	-10000	0	0
FYN	0.024	0.089	0.36	17	-0.5	2	19
mol:NO	0.026	0.006	-10000	0	-10000	0	0
GNA15	0.013	0.05	-10000	0	-0.67	1	1
PGK/cGMP	-0.092	0.21	-10000	0	-0.43	135	135
RhoA/GDP	0.027	0.004	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.04	0.091	-10000	0	-0.48	6	6
NOS3	0.026	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	-0.024	0.18	0.44	17	-0.38	70	87
PRKCB	-0.023	0.18	0.44	17	-0.37	67	84
PRKCE	-0.027	0.16	0.37	12	-0.37	69	81
PRKCD	-0.025	0.17	0.43	13	-0.38	68	81
PRKCG	-0.024	0.18	0.44	15	-0.39	66	81
muscle contraction	-0.034	0.22	0.5	15	-0.49	68	83
PRKCZ	-0.014	0.17	0.43	19	-0.34	65	84
ARR3	-0.002	0.02	-10000	0	-10000	0	0
TXA2/TP beta	0.016	0.08	-10000	0	-0.32	18	18
PRKCQ	-0.024	0.17	0.41	14	-0.36	69	83
MAPKKK cascade	-0.034	0.21	0.46	16	-0.46	68	84
SELE	-0.027	0.18	0.37	19	-0.42	69	88
TP beta/GNAI2/GDP/G beta/gamma	0.039	0.089	-10000	0	-0.8	2	2
ROCK1	0.027	0.005	-10000	0	-10000	0	0
GNA14	-0.14	0.29	-10000	0	-0.64	120	120
chemotaxis	-0.049	0.26	0.58	10	-0.61	69	79
GNA12	0.026	0.006	-10000	0	-10000	0	0
GNA13	0.026	0.007	-10000	0	-10000	0	0
GNA11	0.015	0.084	-10000	0	-0.64	8	8
Rac1/GTP	0.019	0.005	-10000	0	-10000	0	0

×

IL6-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
BCL2L1	0.003	0.19	0.6	5	-0.59	18	23
CRP	0.005	0.2	0.58	9	-0.6	18	27
cell cycle arrest	-0.011	0.2	0.49	6	-0.64	26	32
TIMP1	-0.037	0.22	0.6	3	-0.67	25	28
IL6ST	-0.065	0.24	-10000	0	-0.67	66	66
Rac1/GDP	-0.043	0.2	0.31	1	-0.53	45	46
AP1	-0.11	0.27	-10000	0	-0.6	92	92
GAB2	0.027	0.005	-10000	0	-10000	0	0
TNFSF11	-0.009	0.19	0.63	4	-0.6	17	21
HSP90B1	0.043	0.052	-10000	0	-0.64	1	1
GAB1	0.028	0.004	-10000	0	-10000	0	0
MAPK14	-0.082	0.24	-10000	0	-0.71	46	46
AKT1	0.04	0.06	-10000	0	-0.98	1	1
FOXO1	0.04	0.058	-10000	0	-0.91	1	1
MAP2K6	-0.074	0.23	0.25	1	-0.61	52	53
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.029	0.19	0.34	5	-0.54	37	42
MITF	-0.063	0.21	-10000	0	-0.56	47	47
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.025	0.008	-10000	0	-10000	0	0
A2M	0.026	0.07	-10000	0	-1.1	2	2
CEBPB	0.033	0.006	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.009	0.093	-10000	0	-0.49	6	6
STAT3	-0.021	0.21	0.51	4	-0.68	26	30
STAT1	0.01	0.097	-10000	0	-0.92	5	5
CEBPD	0	0.19	0.5	7	-0.56	25	32
PIK3CA	0.024	0.055	-10000	0	-0.67	3	3
PI3K	0.038	0.043	-10000	0	-0.51	3	3
JUN	-0.12	0.29	-10000	0	-0.67	107	107
PIAS3/MITF	-0.048	0.2	-10000	0	-0.57	40	40
MAPK11	-0.084	0.23	-10000	0	-0.72	43	43
STAT3 (dimer)/FOXO1	0.018	0.16	0.38	1	-0.52	19	20
GRB2/SOS1/GAB family	-0.025	0.2	-10000	0	-0.61	26	26
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.068	0.21	-10000	0	-0.37	128	128
GRB2	0.026	0.007	-10000	0	-10000	0	0
JAK2	0.024	0.025	-10000	0	-0.36	2	2
LBP	0.008	0.18	0.59	8	-0.51	15	23
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
JAK1	0.027	0.013	-10000	0	-10000	0	0
MYC	-0.013	0.24	0.52	7	-0.78	28	35
FGG	-0.006	0.19	0.68	3	-0.6	19	22
macrophage differentiation	-0.011	0.2	0.49	6	-0.64	26	32
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.065	0.25	-10000	0	-0.46	129	129
JUNB	-0.001	0.21	0.6	3	-0.68	20	23
FOS	-0.15	0.3	-10000	0	-0.67	125	125
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.062	0.22	-10000	0	-0.41	108	108
STAT1/PIAS1	-0.034	0.2	-10000	0	-0.51	46	46
GRB2/SOS1/GAB family/SHP2/PI3K	0.038	0.062	-10000	0	-0.55	3	3
STAT3 (dimer)	-0.015	0.21	0.55	3	-0.67	26	29
PRKCD	-0.017	0.19	0.4	7	-0.56	29	36
IL6R	0.003	0.12	-10000	0	-0.67	16	16
SOCS3	-0.095	0.31	0.43	2	-0.95	43	45
gp130 (dimer)/JAK1/JAK1/LMO4	-0.006	0.17	-10000	0	-0.44	64	64
Rac1/GTP	-0.04	0.2	-10000	0	-0.55	42	42
HCK	0.016	0.039	-10000	0	-10000	0	0
MAPKKK cascade	0.026	0.1	-10000	0	-0.61	5	5
bone resorption	-0.008	0.18	0.63	4	-0.56	19	23
IRF1	0.003	0.19	0.61	7	-0.59	17	24
mol:GDP	-0.061	0.2	0.25	1	-0.54	50	51
SOS1	0.027	0.005	-10000	0	-10000	0	0
VAV1	-0.062	0.2	0.25	1	-0.55	50	51
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.078	0.24	-10000	0	-0.71	48	48
PTPN11	0.014	0.074	-10000	0	-0.87	3	3
IL6/IL6RA	-0.07	0.22	-10000	0	-0.52	92	92
gp130 (dimer)/TYK2/TYK2/LMO4	-0.009	0.16	-10000	0	-0.41	66	66
gp130 (dimer)/JAK2/JAK2/LMO4	-0.012	0.17	-10000	0	-0.43	66	66
IL6	-0.095	0.26	-10000	0	-0.68	81	81
PIAS3	0.026	0.007	-10000	0	-10000	0	0
PTPRE	-0.025	0.078	-10000	0	-0.68	1	1
PIAS1	0.027	0.004	-10000	0	-10000	0	0
RAC1	0.027	0.006	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.069	0.21	-10000	0	-0.38	126	126
LMO4	0.028	0.016	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.017	0.21	-10000	0	-0.68	25	25
MCL1	0.054	0.072	-10000	0	-0.82	1	1

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.028	0.004	-10000	0	-10000	0	0
GNB1/GNG2	0.045	0.042	-10000	0	-0.82	1	1
forebrain development	-0.3	0.28	0.41	2	-0.59	181	183
GNAO1	0.002	0.12	-10000	0	-0.67	15	15
SMO/beta Arrestin2	0.015	0.036	-10000	0	-0.51	1	1
SMO	0.015	0.034	-10000	0	-0.67	1	1
ARRB2	0.021	0.008	-10000	0	-10000	0	0
GLI3/SPOP	0.036	0.075	-10000	0	-0.37	3	3
mol:GTP	-0.002	0.005	-10000	0	-10000	0	0
GSK3B	0.027	0.003	-10000	0	-10000	0	0
GNAI2	0.025	0.005	-10000	0	-10000	0	0
SIN3/HDAC complex	0.064	0.033	-10000	0	-0.4	1	1
GNAI1	0.023	0.032	-10000	0	-0.68	1	1
XPO1	0.016	0.019	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.21	0.21	-10000	0	-0.49	135	135
SAP30	0.026	0.032	-10000	0	-0.67	1	1
mol:GDP	0.015	0.034	-10000	0	-0.67	1	1
MIM/GLI2A	-0.031	0.067	-10000	0	-10000	0	0
IFT88	0.026	0.007	-10000	0	-10000	0	0
GNAI3	0.025	0.006	-10000	0	-10000	0	0
GLI2	0	0.079	0.28	2	-0.38	7	9
GLI3	0.027	0.078	0.28	3	-0.36	5	8
CSNK1D	0.026	0.007	-10000	0	-10000	0	0
CSNK1E	0.02	0.012	-10000	0	-10000	0	0
SAP18	0.027	0.007	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.026	0.007	-10000	0	-10000	0	0
GNG2	0.025	0.032	-10000	0	-0.67	1	1
Gi family/GTP	-0.016	0.069	-10000	0	-0.3	17	17
SIN3B	0.026	0.008	-10000	0	-10000	0	0
SIN3A	0.028	0.004	-10000	0	-10000	0	0
GLI3/Su(fu)	0.037	0.067	-10000	0	-0.48	2	2
GLI2/Su(fu)	0.01	0.075	-10000	0	-0.49	3	3
FOXA2	-0.58	0.62	-10000	0	-1.2	242	242
neural tube patterning	-0.3	0.28	0.41	2	-0.59	181	183
SPOP	0.026	0.007	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.035	0.03	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
CSNK1G2	0.025	0.008	-10000	0	-10000	0	0
CSNK1G3	0.026	0.006	-10000	0	-10000	0	0
MTSS1	-0.031	0.067	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.3	0.28	0.41	2	-0.59	181	183
SUFU	0.019	0.016	-10000	0	-0.24	1	1
LGALS3	-0.023	0.077	-10000	0	-0.67	1	1
catabolic process	0.032	0.1	-10000	0	-0.49	5	5
GLI3A/CBP	-0.17	0.2	-10000	0	-0.38	245	245
KIF3A	0.026	0.006	-10000	0	-10000	0	0
GLI1	-0.3	0.28	0.41	2	-0.61	180	182
RAB23	0.022	0.063	-10000	0	-0.67	4	4
CSNK1A1	0.026	0.006	-10000	0	-10000	0	0
IFT172	0.027	0.005	-10000	0	-10000	0	0
RBBP7	0.026	0.008	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.019	0.052	-10000	0	-0.33	2	2
GNAZ	0.018	0.012	-10000	0	-10000	0	0
RBBP4	0.025	0.045	-10000	0	-0.67	2	2
CSNK1G1	0.027	0.004	-10000	0	-10000	0	0
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
GLI2/SPOP	0.011	0.081	-10000	0	-0.36	7	7
STK36	0.016	0.019	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.01	0.054	-10000	0	-0.34	4	4
PTCH1	-0.27	0.26	0.58	2	-0.59	133	135
MIM/GLI1	-0.42	0.37	-10000	0	-0.72	249	249
CREBBP	-0.17	0.2	-10000	0	-0.38	245	245
Su(fu)/SIN3/HDAC complex	0.036	0.068	-10000	0	-0.53	5	5

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.026	0.011	-9999	-10000	0	0
EGFR	0.019	0.07	-9999	-0.67	5	5
EGF/EGFR	-0.017	0.15	-9999	-0.37	78	78
EGF/EGFR dimer/SHC/GRB2/SOS1	0.003	0.16	-9999	-0.38	70	70
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.024	0.035	-9999	-0.67	1	1
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.076	0.25	-9999	-0.67	72	72
EGF/EGFR dimer/SHC	-0.025	0.18	-9999	-0.44	73	73
mol:GDP	-0.002	0.16	-9999	-0.38	70	70
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.019	0.071	-9999	-0.67	5	5
GRB2/SOS1	0.038	0.011	-9999	-10000	0	0
HRAS/GTP	-0.014	0.14	-9999	-0.35	70	70
SHC1	0.025	0.008	-9999	-10000	0	0
HRAS/GDP	-0.001	0.15	-9999	-0.36	70	70
FRAP1	-0.052	0.13	-9999	-0.36	70	70
EGF/EGFR dimer	-0.045	0.2	-9999	-0.5	76	76
SOS1	0.027	0.005	-9999	-10000	0	0
GRB2	0.026	0.007	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.032	0.062	-9999	-0.51	6	6

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.1	0.22	-10000	0	-0.42	132	132
MAP3K8	0.015	0.079	-10000	0	-0.63	7	7
FOS	-0.075	0.17	0.3	2	-0.44	59	61
PRKCA	-0.008	0.13	-10000	0	-0.68	17	17
PTPN7	-0.023	0.13	-10000	0	-0.67	18	18
HRAS	0.025	0.011	-10000	0	-10000	0	0
PRKCB	-0.003	0.081	-10000	0	-0.68	5	5
NRAS	0.026	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.022	-10000	0	-10000	0	0
MAPK3	-0.012	0.12	-10000	0	-0.47	22	22
MAP2K1	-0.015	0.13	-10000	0	-0.53	22	22
ELK1	0.013	0.025	-10000	0	-10000	0	0
BRAF	-0.011	0.11	-10000	0	-0.52	21	21
mol:GTP	-0.002	0.004	-10000	0	-0.007	128	128
MAPK1	-0.1	0.2	-10000	0	-0.5	64	64
RAF1	-0.011	0.11	-10000	0	-0.52	21	21
KRAS	0.026	0.005	-10000	0	-10000	0	0

×

Osteopontin-mediated 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
IKK alpha homodimer	0.001	0.11	-10000	0	-0.38	31	31
NF kappa B1 p50/RelA/I kappa B alpha	0.01	0.11	0.35	3	-0.51	2	5
alphaV/beta3 Integrin/Osteopontin/Src	-0.003	0.12	-10000	0	-0.5	25	25
AP1	-0.14	0.3	-10000	0	-0.7	89	89
ILK	-0.006	0.11	-10000	0	-0.4	30	30
bone resorption	-0.007	0.13	-10000	0	-0.54	7	7
PTK2B	0.027	0.005	-10000	0	-10000	0	0
PYK2/p130Cas	0.043	0.11	-10000	0	-0.37	31	31
ITGAV	0.026	0.045	-10000	0	-0.67	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.013	0.12	-10000	0	-0.5	24	24
alphaV/beta3 Integrin/Osteopontin	0.027	0.13	-10000	0	-0.44	31	31
MAP3K1	-0.007	0.11	-10000	0	-0.4	31	31
JUN	-0.12	0.29	-10000	0	-0.67	107	107
MAPK3	-0.022	0.099	-10000	0	-0.37	31	31
MAPK1	-0.023	0.095	-10000	0	-0.37	30	30
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.018	0.12	-10000	0	-0.4	37	37
ITGB3	0.013	0.1	-10000	0	-0.64	11	11
NFKBIA	-0.018	0.094	-10000	0	-0.37	29	29
FOS	-0.15	0.3	-10000	0	-0.67	125	125
CD44	0.027	0.005	-10000	0	-10000	0	0
CHUK	0.027	0.004	-10000	0	-10000	0	0
PLAU	-0.039	0.11	0.52	3	-0.61	1	4
NF kappa B1 p50/RelA	0.022	0.1	-10000	0	-0.51	2	2
BCAR1	0.026	0.006	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
alphaV beta3 Integrin	0.028	0.088	-10000	0	-0.54	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.007	0.11	-10000	0	-0.4	31	31
VAV3	-0.015	0.12	0.4	1	-0.39	35	36
MAP3K14	-0.013	0.11	-10000	0	-0.4	31	31
ROCK2	-0.006	0.15	-10000	0	-0.66	24	24
SPP1	-0.028	0.15	-10000	0	-0.67	23	23
RAC1	0.026	0.006	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.11	-10000	0	-0.36	34	34
MMP2	-0.13	0.24	-10000	0	-0.56	91	91

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.035	0.01	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.027	0.003	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.011	0.099	-10000	0	-0.67	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.026	0.007	-10000	0	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.12	0.13	-10000	0	-0.25	256	256
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.027	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.026	0.007	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
MAP3K12	0.027	0.005	-10000	0	-10000	0	0
FGR	0.025	0.015	-10000	0	-10000	0	0
p38 alpha/TAB1	-0.044	0.068	-10000	0	-0.28	10	10
PRKG1	-0.16	0.31	-10000	0	-0.67	136	136
DUSP8	0.019	0.065	-10000	0	-0.67	4	4
PGK/cGMP/p38 alpha	-0.11	0.18	-10000	0	-0.37	132	132
apoptosis	-0.042	0.065	-10000	0	-0.27	10	10
RAL/GTP	0.036	0.008	-10000	0	-10000	0	0
LYN	0.027	0.005	-10000	0	-10000	0	0
DUSP1	-0.084	0.26	-10000	0	-0.67	78	78
PAK1	0.027	0.005	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.065	0.02	-10000	0	-10000	0	0
TRAF6	0.024	0.045	-10000	0	-0.67	2	2
RAC1	0.026	0.006	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.026	0.011	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.035	0.01	-10000	0	-10000	0	0
MAPK11	-0.054	0.16	0.44	16	-0.33	30	46
BLK	-0.19	0.31	-10000	0	-0.67	148	148
HCK	0.017	0.039	-10000	0	-10000	0	0
MAP2K3	0.026	0.007	-10000	0	-10000	0	0
DUSP16	0.027	0.005	-10000	0	-10000	0	0
DUSP10	0.023	0.034	-10000	0	-0.67	1	1
TRAF6/MEKK3	0.031	0.029	-10000	0	-0.4	2	2
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	-0.011	0.12	0.38	16	-0.32	8	24
positive regulation of innate immune response	-0.043	0.17	0.46	19	-0.47	8	27
LCK	0.012	0.082	-10000	0	-0.67	6	6
p38alpha-beta/MKP7	-0.045	0.14	0.34	9	-0.46	7	16
p38alpha-beta/MKP5	-0.037	0.15	0.46	12	-0.45	7	19
PGK/cGMP	-0.12	0.23	-10000	0	-0.5	136	136
PAK2	0.027	0.004	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.097	0.18	0.31	4	-0.46	47	51
CDC42	0.027	0.005	-10000	0	-10000	0	0
RALB	0.027	0.005	-10000	0	-10000	0	0
RALA	0.026	0.006	-10000	0	-10000	0	0
PAK3	-0.36	0.34	-10000	0	-0.66	279	279

×

Regulation of Androgen receptor activity

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
HDAC1	0.009	0.013	-10000	0	-10000	0	0
SMARCC1	0.011	0.013	-10000	0	-10000	0	0
REL	-0.012	0.17	-10000	0	-0.66	32	32
HDAC7	-0.07	0.12	-10000	0	-0.53	16	16
JUN	-0.12	0.29	-10000	0	-0.67	107	107
EP300	0.02	0.012	-10000	0	-10000	0	0
KAT2B	0.027	0.004	-10000	0	-10000	0	0
KAT5	0.027	0.005	-10000	0	-10000	0	0
MAPK14	-0.015	0.075	-10000	0	-0.52	10	10
FOXO1	0.025	0.007	-10000	0	-10000	0	0
T-DHT/AR	-0.068	0.13	-10000	0	-0.53	19	19
MAP2K6	0.004	0.1	-10000	0	-0.68	10	10
BRM/BAF57	0.017	0.033	-10000	0	-10000	0	0
MAP2K4	0.019	0.014	-10000	0	-10000	0	0
SMARCA2	0.013	0.022	-10000	0	-10000	0	0
PDE9A	0.015	0.066	-10000	0	-0.59	1	1
NCOA2	-0.043	0.2	-10000	0	-0.68	45	45
CEBPA	0.019	0.07	-10000	0	-0.67	5	5
EHMT2	0.025	0.005	-10000	0	-10000	0	0
cell proliferation	-0.082	0.2	0.57	20	-0.49	20	40
NR0B1	-0.008	0.023	-10000	0	-10000	0	0
EGR1	-0.13	0.28	-10000	0	-0.68	101	101
RXRs/9cRA	0.017	0.072	-10000	0	-0.4	4	4
AR/RACK1/Src	-0.13	0.15	0.33	2	-0.56	18	20
AR/GR	-0.12	0.18	0.28	2	-0.34	149	151
GNB2L1	0.022	0.008	-10000	0	-10000	0	0
PKN1	0.025	0.008	-10000	0	-10000	0	0
RCHY1	0.027	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	-0.005	0.007	-10000	0	-0.011	179	179
MAPK8	-0.014	0.071	-10000	0	-0.52	9	9
T-DHT/AR/TIF2/CARM1	-0.13	0.19	0.34	3	-0.58	47	50
SRC	-0.044	0.088	0.24	1	-0.46	16	17
NR3C1	0.026	0.006	-10000	0	-10000	0	0
KLK3	-0.36	0.55	0.38	2	-1.2	143	145
APPBP2	0.024	0.012	-10000	0	-10000	0	0
TRIM24	0.013	0.021	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.07	0.13	0.32	7	-0.57	16	23
TMPRSS2	-0.043	0.28	-10000	0	-1.1	30	30
RXRG	-0.11	0.076	-10000	0	-0.67	4	4
mol:9cRA	-0.002	0.003	-10000	0	-0.011	10	10
RXRA	0.024	0.008	-10000	0	-10000	0	0
RXRB	0.026	0.004	-10000	0	-10000	0	0
CARM1	0.02	0.009	-10000	0	-10000	0	0
NR2C2	0.012	0.099	-10000	0	-0.68	10	10
KLK2	-0.45	0.38	0.34	2	-0.77	287	289
AR	-0.14	0.18	-10000	0	-0.35	198	198
SENP1	0.025	0.005	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
MDM2	0.036	0.016	-10000	0	-10000	0	0
SRY	0.009	0.015	0.031	142	-10000	0	142
GATA2	0.027	0.008	-10000	0	-10000	0	0
MYST2	0.001	0.002	-10000	0	-10000	0	0
HOXB13	-0.011	0.034	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.1	0.13	0.33	4	-0.57	16	20
positive regulation of transcription	0.027	0.008	-10000	0	-10000	0	0
DNAJA1	0.024	0.014	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.008	-10000	0	-10000	0	0
NCOA1	0.018	0.022	-10000	0	-10000	0	0
SPDEF	-0.003	0.049	-10000	0	-10000	0	0
T-DHT/AR/TIF2	-0.092	0.15	0.28	2	-0.45	48	50
T-DHT/AR/Hsp90	-0.071	0.13	0.33	7	-0.56	16	23
GSK3B	0.025	0.007	-10000	0	-10000	0	0
NR2C1	0.028	0.006	-10000	0	-10000	0	0
mol:T-DHT	-0.038	0.092	0.26	1	-0.49	16	17
SIRT1	0.025	0.032	-10000	0	-0.67	1	1
ZMIZ2	0.036	0.017	-10000	0	-10000	0	0
POU2F1	0.032	0.036	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.075	0.13	0.32	6	-0.57	16	22
CREBBP	0.026	0.006	-10000	0	-10000	0	0
SMARCE1	0.012	0.022	-10000	0	-10000	0	0

×

ErbB2/ErbB3 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.005	0.007	-10000	0	-10000	0	0
RAS family/GTP	0.005	0.12	-10000	0	-0.37	18	18
NFATC4	-0.018	0.087	0.28	4	-0.29	9	13
ERBB2IP	0.027	0.007	-10000	0	-10000	0	0
HSP90 (dimer)	0.027	0.005	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.014	0.11	-10000	0	-0.35	39	39
JUN	-0.005	0.094	0.34	10	-0.4	1	11
HRAS	0.025	0.011	-10000	0	-10000	0	0
DOCK7	-0.024	0.1	-10000	0	-0.34	38	38
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.004	0.12	-10000	0	-0.4	41	41
AKT1	0.007	0.006	-10000	0	-10000	0	0
BAD	0.005	0.004	-10000	0	-10000	0	0
MAPK10	-0.008	0.065	0.25	4	-0.3	2	6
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.015	0.12	-10000	0	-0.38	39	39
RAF1	-0.011	0.12	0.32	9	-0.39	18	27
ErbB2/ErbB3/neuregulin 2	-0.025	0.14	-10000	0	-0.41	60	60
STAT3	0.028	0.069	-10000	0	-0.84	3	3
cell migration	0.007	0.11	0.39	20	-0.28	4	24
mol:PI-3-4-5-P3	0	0.004	-10000	0	-10000	0	0
cell proliferation	-0.15	0.32	0.35	1	-0.68	117	118
FOS	-0.12	0.26	0.35	6	-0.5	152	158
NRAS	0.026	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.014	0.11	-10000	0	-0.35	39	39
MAPK3	-0.077	0.24	0.38	3	-0.52	87	90
MAPK1	-0.17	0.3	0.36	1	-0.64	119	120
JAK2	-0.024	0.098	-10000	0	-0.34	38	38
NF2	-0.011	0.11	-10000	0	-0.62	16	16
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.011	0.11	-10000	0	-0.34	41	41
NRG1	-0.034	0.19	-10000	0	-0.66	43	43
GRB2/SOS1	0.037	0.011	-10000	0	-10000	0	0
MAPK8	-0.019	0.11	-10000	0	-0.33	46	46
MAPK9	-0.009	0.062	0.23	3	-10000	0	3
ERBB2	-0.017	0.006	-10000	0	-10000	0	0
ERBB3	0.016	0.079	-10000	0	-0.63	7	7
SHC1	0.025	0.007	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
apoptosis	0.001	0.014	-10000	0	-10000	0	0
STAT3 (dimer)	0.028	0.067	-10000	0	-0.82	3	3
RNF41	0	0.008	-10000	0	-10000	0	0
FRAP1	0.002	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.017	0.076	-10000	0	-0.25	37	37
ErbB2/ErbB2/HSP90 (dimer)	0.014	0.013	-10000	0	-10000	0	0
CHRNA1	-0.075	0.19	0.33	1	-0.4	99	100
myelination	-0.008	0.14	0.52	17	-0.31	1	18
PPP3CB	-0.021	0.094	-10000	0	-0.32	37	37
KRAS	0.026	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.021	0.1	-10000	0	-0.3	40	40
NRG2	-0.052	0.22	-10000	0	-0.67	54	54
mol:GDP	-0.011	0.11	-10000	0	-0.34	41	41
SOS1	0.026	0.005	-10000	0	-10000	0	0
MAP2K2	-0.026	0.12	0.31	5	-0.38	20	25
SRC	0.026	0.008	-10000	0	-10000	0	0
mol:cAMP	0	0.003	-10000	0	-10000	0	0
PTPN11	-0.022	0.1	0.25	1	-0.34	39	40
MAP2K1	-0.073	0.23	0.36	1	-0.58	37	38
heart morphogenesis	-0.014	0.11	-10000	0	-0.35	39	39
RAS family/GDP	0.017	0.11	-10000	0	-0.38	14	14
GRB2	0.025	0.007	-10000	0	-10000	0	0
PRKACA	-0.011	0.12	-10000	0	-0.65	18	18
CHRNE	0.008	0.037	0.18	12	-0.23	1	13
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	-0.007	0.006	-10000	0	-10000	0	0
nervous system development	-0.014	0.11	-10000	0	-0.35	39	39
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.024	0.017	-10000	0	-10000	0	0
CCL5	-0.016	0.16	-10000	0	-0.67	28	28
SDCBP	0.027	0.005	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.039	0.13	-10000	0	-0.41	42	42
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	-0.033	0.14	-10000	0	-0.48	29	29
Syndecan-1/Syntenin	-0.031	0.14	0.25	1	-0.53	23	24
MAPK3	-0.031	0.12	-10000	0	-0.51	19	19
HGF/MET	-0.078	0.19	-10000	0	-0.52	70	70
TGFB1/TGF beta receptor Type II	0.024	0.017	-10000	0	-10000	0	0
BSG	0.025	0.008	-10000	0	-10000	0	0
keratinocyte migration	-0.033	0.14	-10000	0	-0.47	29	29
Syndecan-1/RANTES	-0.051	0.19	-10000	0	-0.56	47	47
Syndecan-1/CD147	-0.016	0.14	-10000	0	-0.52	22	22
Syndecan-1/Syntenin/PIP2	-0.031	0.14	-10000	0	-0.52	23	23
LAMA5	0.027	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	-0.031	0.13	-10000	0	-0.5	23	23
MMP7	-0.079	0.16	-10000	0	-0.66	26	26
HGF	-0.073	0.24	-10000	0	-0.67	70	70
Syndecan-1/CASK	-0.046	0.13	-10000	0	-0.41	45	45
Syndecan-1/HGF/MET	-0.076	0.2	-10000	0	-0.5	73	73
regulation of cell adhesion	-0.033	0.11	-10000	0	-0.49	19	19
HPSE	0.01	0.094	-10000	0	-0.64	9	9
positive regulation of cell migration	-0.039	0.13	-10000	0	-0.41	42	42
SDC1	-0.039	0.13	-10000	0	-0.42	42	42
Syndecan-1/Collagen	-0.039	0.13	-10000	0	-0.41	42	42
PPIB	0.027	0.004	-10000	0	-10000	0	0
MET	-0.029	0.074	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
MMP9	-0.043	0.2	-10000	0	-0.67	42	42
MAPK1	-0.032	0.12	-10000	0	-0.5	21	21
homophilic cell adhesion	-0.039	0.13	-10000	0	-0.4	43	43
MMP1	-0.045	0.075	-10000	0	-10000	0	0

×

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	0.013	0.062	0.24	32	-10000	0	32
RFC1	0.015	0.064	0.24	35	-10000	0	35
PRKDC	0.017	0.071	0.26	37	-10000	0	37
RIPK1	0.029	0.005	-10000	0	-10000	0	0
CASP7	-0.003	0.095	-10000	0	-0.74	6	6
FASLG/FAS/FADD/FAF1	-0.015	0.096	0.24	5	-0.34	33	38
MAP2K4	-0.027	0.16	0.32	2	-0.49	26	28
mol:ceramide	-0.02	0.13	-10000	0	-0.43	35	35
GSN	0.013	0.062	0.24	32	-10000	0	32
FASLG/FAS/FADD/FAF1/Caspase 8	-0.02	0.12	-10000	0	-0.43	33	33
FAS	0.02	0.018	-10000	0	-10000	0	0
BID	-0.017	0.036	0.26	4	-10000	0	4
MAP3K1	-0.008	0.12	0.27	3	-0.41	18	21
MAP3K7	0.026	0.005	-10000	0	-10000	0	0
RB1	0.014	0.066	0.25	33	-10000	0	33
CFLAR	0.028	0.006	-10000	0	-10000	0	0
HGF/MET	-0.02	0.19	-10000	0	-0.47	73	73
ARHGDIB	0.016	0.069	0.25	38	-10000	0	38
FADD	0.02	0.018	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.062	-10000	0	-0.24	32	32
NFKB1	-0.015	0.098	-10000	0	-0.57	3	3
MAPK8	-0.063	0.22	0.4	2	-0.47	93	95
DFFA	0.015	0.065	0.24	36	-10000	0	36
DNA fragmentation during apoptosis	0.015	0.065	0.24	36	-10000	0	36
FAS/FADD/MET	0.039	0.044	-10000	0	-10000	0	0
CFLAR/RIP1	0.042	0.01	-10000	0	-10000	0	0
FAIM3	0.016	0.061	-10000	0	-0.67	3	3
FAF1	0.019	0.02	-10000	0	-10000	0	0
PARP1	0.019	0.082	0.29	36	-10000	0	36
DFFB	0.015	0.065	0.24	36	-10000	0	36
CHUK	-0.015	0.089	-10000	0	-0.62	2	2
FASLG	-0.034	0.18	-10000	0	-0.68	33	33
FAS/FADD	0.029	0.026	-10000	0	-10000	0	0
HGF	-0.073	0.24	-10000	0	-0.67	70	70
LMNA	0.014	0.07	0.26	28	-10000	0	28
CASP6	0.015	0.064	0.24	35	-10000	0	35
CASP10	0.02	0.018	-10000	0	-10000	0	0
CASP3	0.019	0.08	0.3	37	-10000	0	37
PTPN13	0.019	0.077	-10000	0	-0.67	6	6
CASP8	-0.012	0.034	0.4	3	-10000	0	3
IL6	-0.2	0.5	-10000	0	-1.3	91	91
MET	-0.029	0.074	-10000	0	-10000	0	0
ICAD/CAD	0.014	0.06	0.23	27	-10000	0	27
FASLG/FAS/FADD/FAF1/Caspase 10	-0.02	0.14	-10000	0	-0.43	35	35
activation of caspase activity by cytochrome c	-0.017	0.036	0.26	4	-10000	0	4
PAK2	0.015	0.065	0.24	36	-10000	0	36
BCL2	-0.026	0.18	-10000	0	-0.67	38	38

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.04	0.1	-10000	0	-0.41	22	22
ER alpha/Gai/GDP/Gbeta gamma	-0.004	0.14	-10000	0	-0.54	22	22
AKT1	-0.012	0.2	-10000	0	-0.78	28	28
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.008	0.2	-10000	0	-0.81	27	27
mol:Ca2+	-0.098	0.19	-10000	0	-0.43	120	120
IGF1R	0.027	0.004	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.019	0.15	-10000	0	-0.46	49	49
SHC1	0.025	0.008	-10000	0	-10000	0	0
apoptosis	0.01	0.18	0.74	28	-10000	0	28
RhoA/GTP	0.006	0.071	-10000	0	-0.34	17	17
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	0.005	0.13	-10000	0	-0.54	20	20
regulation of stress fiber formation	0.009	0.088	0.36	5	-0.28	1	6
E2/ERA-ERB (dimer)	0.007	0.11	-10000	0	-0.45	23	23
KRAS	0.027	0.005	-10000	0	-10000	0	0
G13/GTP	0.01	0.085	-10000	0	-0.37	21	21
pseudopodium formation	-0.009	0.088	0.28	1	-0.36	5	6
E2/ER alpha (dimer)/PELP1	0.01	0.093	-10000	0	-0.41	21	21
GRB2	0.026	0.007	-10000	0	-10000	0	0
GNG2	0.025	0.032	-10000	0	-0.67	1	1
GNAO1	0.004	0.12	-10000	0	-0.67	15	15
HRAS	0.026	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.01	0.15	0.47	7	-0.59	22	29
E2/ER beta (dimer)	0.017	0.041	-10000	0	-0.51	3	3
mol:GDP	0.003	0.11	-10000	0	-0.47	23	23
mol:NADP	0.01	0.15	0.47	7	-0.59	22	29
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.1	0.2	-10000	0	-0.44	120	120
IGF-1R heterotetramer	0.027	0.004	-10000	0	-10000	0	0
PLCB1	-0.1	0.21	-10000	0	-0.45	121	121
PLCB2	-0.1	0.21	-10000	0	-0.46	121	121
IGF1	-0.13	0.29	-10000	0	-0.67	108	108
mol:L-citrulline	0.01	0.15	0.47	7	-0.59	22	29
RHOA	0.027	0.003	-10000	0	-10000	0	0
Gai/GDP	0.005	0.14	-10000	0	-0.67	20	20
JNK cascade	0.017	0.041	-10000	0	-0.51	3	3
BCAR1	0.026	0.006	-10000	0	-10000	0	0
ESR2	0.023	0.055	-10000	0	-0.67	3	3
GNAQ	0.025	0.008	-10000	0	-10000	0	0
ESR1	-0.014	0.15	-10000	0	-0.65	23	23
Gq family/GDP/Gbeta gamma	-0.059	0.19	-10000	0	-0.65	28	28
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.02	0.097	-10000	0	-0.64	5	5
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.003	0.13	-10000	0	-0.55	19	19
GNAZ	0.02	0.012	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.01	0.11	-10000	0	-0.49	23	23
STRN	-0.016	0.17	-10000	0	-0.66	31	31
GNAL	-0.061	0.23	-10000	0	-0.66	64	64
PELP1	0.026	0.007	-10000	0	-10000	0	0
MAPK11	0.01	0.035	-10000	0	-0.43	3	3
GNAI2	0.027	0.003	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNAI1	0.025	0.032	-10000	0	-0.67	1	1
HBEGF	-0.019	0.14	0.41	2	-0.55	20	22
cAMP biosynthetic process	-0.041	0.16	-10000	0	-0.38	78	78
SRC	-0.004	0.13	-10000	0	-0.61	13	13
PI3K	0.036	0.043	-10000	0	-0.51	3	3
GNB1	0.026	0.006	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.031	0.11	-10000	0	-0.46	19	19
SOS1	0.027	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.069	0.16	-10000	0	-0.5	30	30
Gs family/GTP	-0.036	0.16	-10000	0	-0.39	78	78
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.049	0.015	-10000	0	-10000	0	0
vasodilation	0.011	0.15	0.46	7	-0.56	22	29
mol:DAG	-0.1	0.2	-10000	0	-0.44	120	120
Gs family/GDP/Gbeta gamma	-0.026	0.14	-10000	0	-0.45	23	23
MSN	-0.011	0.094	0.29	1	-0.39	5	6
Gq family/GTP	-0.1	0.22	-10000	0	-0.48	122	122
mol:PI-3-4-5-P3	-0.006	0.19	-10000	0	-0.77	27	27
NRAS	0.027	0.005	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.011	0.15	0.56	22	-0.46	7	29
GRB2/SOS1	0.038	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.021	0.11	-10000	0	-0.44	23	23
NOS3	0.004	0.15	0.49	2	-0.63	22	24
GNA11	0.015	0.084	-10000	0	-0.64	8	8
MAPKKK cascade	-0.015	0.18	0.37	1	-0.59	29	30
E2/ER alpha (dimer)/PELP1/Src	0.001	0.14	-10000	0	-0.57	20	20
ruffle organization	-0.009	0.088	0.28	1	-0.36	5	6
ROCK2	-0.004	0.11	0.36	5	-0.36	19	24
GNA14	-0.14	0.29	-10000	0	-0.64	120	120
GNA15	0.013	0.05	-10000	0	-0.67	1	1
GNA13	0.026	0.007	-10000	0	-10000	0	0
MMP9	-0.034	0.16	-10000	0	-0.58	25	25
MMP2	-0.004	0.13	0.34	1	-0.59	14	15

×

BCR signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.067	0.18	0.43	10	-0.42	44	54
IKBKB	0.01	0.12	0.48	16	-0.32	7	23
AKT1	-0.001	0.17	0.55	25	-0.24	15	40
IKBKG	-0.001	0.13	0.47	15	-0.32	18	33
CALM1	-0.022	0.093	0.39	3	-0.4	8	11
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
MAP3K1	-0.015	0.17	0.45	12	-0.53	21	33
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.093	0.32	2	-0.4	9	11
DOK1	0.027	0.005	-10000	0	-10000	0	0
AP-1	-0.058	0.15	0.5	12	-0.27	96	108
LYN	0.027	0.005	-10000	0	-10000	0	0
BLNK	0.027	0.004	-10000	0	-10000	0	0
SHC1	0.025	0.008	-10000	0	-10000	0	0
BCR complex	-0.072	0.18	-10000	0	-0.5	67	67
CD22	-0.07	0.18	-10000	0	-0.42	83	83
CAMK2G	-0.019	0.09	0.34	4	-0.37	8	12
CSNK2A1	0.027	0.005	-10000	0	-10000	0	0
INPP5D	0.019	0.034	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.04	0.12	-10000	0	-0.34	56	56
GO:0007205	-0.025	0.095	0.32	2	-0.42	9	11
SYK	0.025	0.008	-10000	0	-10000	0	0
ELK1	-0.019	0.093	0.31	4	-0.42	7	11
NFATC1	-0.04	0.14	0.36	6	-0.44	23	29
B-cell antigen/BCR complex	-0.072	0.18	-10000	0	-0.5	67	67
PAG1/CSK	0.038	0.027	-10000	0	-0.51	1	1
NFKBIB	0.019	0.044	0.19	13	-0.13	6	19
HRAS	-0.017	0.099	0.35	5	-0.34	9	14
NFKBIA	0.019	0.044	0.19	13	-0.12	8	21
NF-kappa-B/RelA/I kappa B beta	0.024	0.04	0.2	12	-10000	0	12
RasGAP/Csk	-0.028	0.18	-10000	0	-0.4	74	74
mol:GDP	-0.023	0.093	0.29	2	-0.4	10	12
PTEN	0.026	0.018	-10000	0	-0.36	1	1
CD79B	0.006	0.052	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	0.024	0.04	0.2	12	-10000	0	12
GRB2	0.026	0.007	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.038	0.16	0.44	4	-0.48	20	24
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.024	0.092	0.32	2	-0.4	8	10
CSK	0.027	0.008	-10000	0	-10000	0	0
FOS	-0.098	0.18	0.47	8	-0.37	126	134
CHUK	0.007	0.1	0.42	14	-0.33	8	22
IBTK	0.027	0.004	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.013	0.11	-10000	0	-0.45	11	11
PTPN6	-0.065	0.16	-10000	0	-0.49	41	41
RELA	0.027	0.005	-10000	0	-10000	0	0
BCL2A1	0.014	0.036	0.16	6	-0.12	11	17
VAV2	-0.057	0.16	-10000	0	-0.63	16	16
ubiquitin-dependent protein catabolic process	0.022	0.043	0.19	13	-0.12	6	19
BTK	-0.038	0.24	-10000	0	-0.98	30	30
CD19	-0.062	0.16	-10000	0	-0.4	68	68
MAP4K1	0.008	0.079	-10000	0	-0.67	5	5
CD72	0.024	0.016	-10000	0	-10000	0	0
PAG1	0.025	0.032	-10000	0	-0.67	1	1
MAPK14	-0.008	0.15	0.42	14	-0.46	20	34
SH3BP5	0.027	0.004	-10000	0	-10000	0	0
PIK3AP1	-0.017	0.094	-10000	0	-0.45	8	8
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.049	0.18	-10000	0	-0.42	79	79
RAF1	-0.015	0.097	0.34	7	-0.39	4	11
RasGAP/p62DOK/SHIP	-0.008	0.17	-10000	0	-0.39	74	74
CD79A	-0.1	0.23	-10000	0	-0.66	68	68
re-entry into mitotic cell cycle	-0.057	0.15	0.5	12	-0.26	97	109
RASA1	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.004	0.1	0.4	14	-0.4	2	16
MAPK1	-0.01	0.09	0.38	8	-0.39	2	10
CD72/SHP1	-0.047	0.17	0.31	1	-0.53	27	28
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.014	0.16	0.46	13	-0.49	21	34
actin cytoskeleton organization	-0.045	0.14	0.34	2	-0.52	16	18
NF-kappa-B/RelA	0.048	0.073	0.34	13	-0.22	1	14
Calcineurin	0.008	0.091	-10000	0	-0.41	4	4
PI3K	-0.063	0.14	-10000	0	-0.45	25	25
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.019	0.098	-10000	0	-0.44	10	10
SOS1	0.027	0.005	-10000	0	-10000	0	0
Bam32/HPK1	-0.025	0.22	-10000	0	-0.91	21	21
DAPP1	-0.045	0.25	-10000	0	-1.1	20	20
cytokine secretion	-0.037	0.13	0.36	6	-0.41	23	29
mol:DAG	-0.024	0.092	0.32	2	-0.4	8	10
PLCG2	0.026	0.006	-10000	0	-10000	0	0
MAP2K1	-0.013	0.092	0.34	6	-0.45	2	8
B-cell antigen/BCR complex/FcgammaRIIB	-0.057	0.19	-10000	0	-0.44	83	83
mol:PI-3-4-5-P3	-0.053	0.099	-10000	0	-0.36	16	16
ETS1	-0.015	0.086	0.34	5	-0.39	5	10
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.013	0.16	-10000	0	-0.38	64	64
B-cell antigen/BCR complex/LYN	-0.05	0.17	-10000	0	-0.42	69	69
MALT1	0.027	0.004	-10000	0	-10000	0	0
TRAF6	0.024	0.045	-10000	0	-0.67	2	2
RAC1	-0.049	0.15	0.36	1	-0.56	16	17
B-cell antigen/BCR complex/LYN/SYK	-0.04	0.19	-10000	0	-0.45	66	66
CARD11	-0.036	0.12	0.34	5	-0.44	18	23
FCGR2B	-0.009	0.15	-10000	0	-0.67	24	24
PPP3CA	0.027	0.004	-10000	0	-10000	0	0
BCL10	0.027	0.005	-10000	0	-10000	0	0
IKK complex	0.019	0.095	0.43	18	-0.13	6	24
PTPRC	-0.008	0.14	-10000	0	-0.67	20	20
PDPK1	-0.029	0.087	0.23	11	-0.25	17	28
PPP3CB	0.027	0.005	-10000	0	-10000	0	0
PPP3CC	0.027	0.005	-10000	0	-10000	0	0
POU2F2	0.019	0.033	0.16	14	-10000	0	14

×

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

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
MET/RANBP9	-0.005	0.058	-10000	0	-10000	0	0
CRKL	-0.013	0.091	0.36	2	-0.42	1	3
mol:PIP3	-0.002	0.017	0.34	1	-10000	0	1
AKT1	0.003	0.056	0.37	2	-0.45	3	5
PTK2B	0.027	0.005	-10000	0	-10000	0	0
RAPGEF1	0.002	0.1	0.4	9	-0.4	1	10
RANBP10	0.026	0.006	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
HGF/MET/SHIP2	-0.015	0.18	-10000	0	-0.46	68	68
MAP3K5	0.011	0.12	0.44	13	-0.4	6	19
HGF/MET/CIN85/CBL/ENDOPHILINS	0.002	0.17	-10000	0	-0.42	66	66
AP1	-0.18	0.33	-10000	0	-0.65	149	149
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.025	0.008	-10000	0	-10000	0	0
apoptosis	-0.22	0.4	0.38	1	-0.81	150	151
STAT3 (dimer)	-0.019	0.1	-10000	0	-0.52	1	1
GAB1/CRKL/SHP2/PI3K	0.027	0.11	0.34	1	-0.5	3	4
INPP5D	0.019	0.034	-10000	0	-10000	0	0
CBL/CRK	0.016	0.11	0.5	7	-0.41	1	8
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.027	0.005	-10000	0	-10000	0	0
PTEN	0.026	0.018	-10000	0	-0.36	1	1
ELK1	0.035	0.14	0.42	29	-0.26	2	31
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.006	0.068	-10000	0	-0.24	5	5
PAK1	0.006	0.058	0.35	5	-0.4	2	7
HGF/MET/RANBP10	-0.015	0.18	-10000	0	-0.45	70	70
HRAS	-0.02	0.13	-10000	0	-0.55	3	3
DOCK1	0.001	0.11	0.42	10	-0.4	4	14
GAB1	-0.011	0.097	0.26	1	-0.35	4	5
CRK	-0.006	0.098	0.37	2	-0.43	1	3
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.044	0.19	-10000	0	-0.51	70	70
JUN	-0.12	0.29	-10000	0	-0.67	107	107
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.031	0.086	-10000	0	-0.24	68	68
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
cell morphogenesis	-0.007	0.13	0.45	7	-0.51	3	10
GRB2/SHC	0.004	0.085	-10000	0	-0.28	1	1
FOS	-0.15	0.3	-10000	0	-0.67	125	125
GLMN	0.004	0.001	-10000	0	-10000	0	0
cell motility	0.035	0.14	0.42	29	-0.26	2	31
HGF/MET/MUC20	-0.065	0.16	-10000	0	-0.45	70	70
cell migration	0.004	0.084	-10000	0	-0.27	1	1
GRB2	0.026	0.007	-10000	0	-10000	0	0
CBL	0.027	0.005	-10000	0	-10000	0	0
MET/RANBP10	-0.005	0.057	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.016	0.11	-10000	0	-0.3	64	64
MET/MUC20	-0.017	0.048	-10000	0	-10000	0	0
RAP1B	0.012	0.13	0.54	13	-0.37	1	14
RAP1A	0.009	0.11	0.39	12	-0.37	1	13
HGF/MET/RANBP9	-0.014	0.18	-10000	0	-0.45	70	70
RAF1	-0.018	0.12	-10000	0	-0.46	3	3
STAT3	-0.02	0.11	-10000	0	-0.52	1	1
cell proliferation	-0.023	0.15	-10000	0	-0.39	60	60
RPS6KB1	0	0.034	-10000	0	-0.22	2	2
MAPK3	-0.022	0.1	0.52	12	-10000	0	12
MAPK1	0.14	0.29	0.61	134	-10000	0	134
RANBP9	0.027	0.003	-10000	0	-10000	0	0
MAPK8	0.024	0.17	0.55	20	-0.6	9	29
SRC	-0.021	0.1	-10000	0	-0.3	25	25
PI3K	0.003	0.094	-10000	0	-0.25	29	29
MET/Glomulin	-0.007	0.045	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
MAP2K1	-0.01	0.13	0.37	4	-0.46	2	6
MET	-0.029	0.074	-10000	0	-10000	0	0
MAP4K1	0.007	0.12	0.46	8	-0.43	6	14
PTK2	0.026	0.006	-10000	0	-10000	0	0
MAP2K2	-0.006	0.12	0.43	2	-0.44	1	3
BAD	0.006	0.058	0.35	5	-0.4	2	7
MAP2K4	0.021	0.14	0.5	20	-0.4	4	24
SHP2/GRB2/SOS1/GAB1	0.018	0.098	-10000	0	-0.36	1	1
INPPL1	0.027	0.005	-10000	0	-10000	0	0
PXN	0.027	0.005	-10000	0	-10000	0	0
SH3KBP1	0.026	0.007	-10000	0	-10000	0	0
HGS	-0.028	0.077	-10000	0	-0.22	65	65
PLCgamma1/PKC	0.02	0.004	-10000	0	-10000	0	0
HGF	-0.073	0.24	-10000	0	-0.67	70	70
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
PTPRJ	0.027	0.005	-10000	0	-10000	0	0
NCK/PLCgamma1	0.003	0.099	-10000	0	-0.24	67	67
PDPK1	-0.001	0.048	-10000	0	-0.48	3	3
HGF/MET/SHIP	-0.018	0.18	-10000	0	-0.46	70	70

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.01	0.1	-10000	0	-0.81	6	6
Syndecan-4/Syndesmos	-0.041	0.16	-10000	0	-0.54	42	42
positive regulation of JNK cascade	-0.054	0.19	-10000	0	-0.56	44	44
Syndecan-4/ADAM12	-0.053	0.16	-10000	0	-0.55	42	42
CCL5	-0.016	0.16	-10000	0	-0.67	28	28
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
DNM2	0.025	0.008	-10000	0	-10000	0	0
ITGA5	0.027	0.005	-10000	0	-10000	0	0
SDCBP	0.027	0.005	-10000	0	-10000	0	0
PLG	0.007	0.031	-10000	0	-10000	0	0
ADAM12	-0.011	0.067	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.026	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.058	0.03	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.063	0.18	-10000	0	-0.58	41	41
Syndecan-4/CXCL12/CXCR4	-0.057	0.2	-10000	0	-0.6	44	44
Syndecan-4/Laminin alpha3	-0.052	0.17	-10000	0	-0.57	40	40
MDK	-0.02	0.076	-10000	0	-0.67	1	1
Syndecan-4/FZD7	-0.041	0.16	-10000	0	-0.55	42	42
Syndecan-4/Midkine	-0.053	0.16	-10000	0	-0.56	41	41
FZD7	0.022	0.051	-10000	0	-0.52	4	4
Syndecan-4/FGFR1/FGF	-0.014	0.16	-10000	0	-0.51	40	40
THBS1	0.012	0.046	-10000	0	-10000	0	0
integrin-mediated signaling pathway	-0.059	0.16	-10000	0	-0.55	42	42
positive regulation of MAPKKK cascade	-0.054	0.19	-10000	0	-0.56	44	44
Syndecan-4/TACI	-0.13	0.21	-10000	0	-0.62	40	40
CXCR4	0.026	0.013	-10000	0	-10000	0	0
cell adhesion	-0.009	0.066	0.2	5	-0.31	17	22
Syndecan-4/Dynamin	-0.041	0.16	-10000	0	-0.55	41	41
Syndecan-4/TSP1	-0.045	0.16	-10000	0	-0.55	42	42
Syndecan-4/GIPC	-0.041	0.16	-10000	0	-0.55	41	41
Syndecan-4/RANTES	-0.061	0.2	-10000	0	-0.66	42	42
ITGB1	0.027	0.004	-10000	0	-10000	0	0
LAMA1	-0.021	0.18	-10000	0	-0.66	34	34
LAMA3	-0.001	0.13	-10000	0	-0.67	16	16
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	0.019	0.19	0.76	21	-0.62	17	38
Syndecan-4/alpha-Actinin	-0.04	0.16	-10000	0	-0.55	41	41
TFPI	-0.012	0.16	-10000	0	-0.66	28	28
F2	0.01	0.03	-10000	0	-10000	0	0
alpha5/beta1 Integrin	0.039	0.009	-10000	0	-10000	0	0
positive regulation of cell adhesion	-0.075	0.18	-10000	0	-0.58	41	41
ACTN1	0.027	0.008	-10000	0	-10000	0	0
TNC	-0.033	0.096	-10000	0	-0.67	5	5
Syndecan-4/CXCL12	-0.077	0.2	-10000	0	-0.62	44	44
FGF6	-0.016	0.005	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
CXCL12	-0.047	0.22	-10000	0	-0.67	53	53
TNFRSF13B	-0.16	0.29	-10000	0	-0.67	121	121
FGF2	0.027	0.004	-10000	0	-10000	0	0
FGFR1	0.025	0.032	-10000	0	-0.67	1	1
Syndecan-4/PI-4-5-P2	-0.051	0.16	-10000	0	-0.55	42	42
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.086	0.07	-10000	0	-0.22	2	2
cell migration	-0.027	0.012	-10000	0	-10000	0	0
PRKCD	0.026	0.022	-10000	0	-10000	0	0
vasculogenesis	-0.043	0.16	-10000	0	-0.53	42	42
SDC4	-0.051	0.16	-10000	0	-0.58	42	42
Syndecan-4/Tenascin C	-0.061	0.17	-10000	0	-0.58	42	42
Syndecan-4/PI-4-5-P2/PKC alpha	-0.046	0.023	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.04	0.16	-10000	0	-0.55	42	42
MMP9	-0.043	0.2	-10000	0	-0.67	42	42
Rac1/GTP	-0.009	0.068	0.2	5	-0.32	17	22
cytoskeleton organization	-0.039	0.15	-10000	0	-0.52	42	42
GIPC1	0.025	0.008	-10000	0	-10000	0	0
Syndecan-4/TFPI	-0.059	0.18	-10000	0	-0.57	43	43

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.009	0.14	-10000	0	-0.36	62	62
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.02	0.012	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.001	0.12	-10000	0	-0.44	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.035	0.053	-10000	0	-0.29	1	1
antigen processing and presentation of peptide antigen via MHC class I	0.008	0.072	-10000	0	-0.24	4	4
CaM/Ca2+	0.013	0.14	-10000	0	-0.33	62	62
RAP1A	0.027	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.013	0.13	-10000	0	-0.34	62	62
AKT1	-0.017	0.12	0.38	5	-0.38	7	12
MAP2K1	-0.025	0.12	0.29	2	-0.32	59	61
MAP3K11	-0.022	0.13	0.3	5	-0.34	62	67
IFNGR1	0.02	0.026	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	0.017	0.074	-10000	0	-0.44	2	2
Rap1/GTP	-0.02	0.095	-10000	0	-0.36	1	1
CRKL/C3G	0.028	0.019	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.016	0.15	-10000	0	-0.37	61	61
CEBPB	-0.059	0.19	0.52	6	-0.56	29	35
STAT3	0.026	0.007	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.016	0.16	-10000	0	-0.71	6	6
STAT1	-0.023	0.13	0.3	5	-0.34	62	67
CALM1	0.027	0.005	-10000	0	-10000	0	0
IFN-gamma (dimer)	-0.066	0.23	-10000	0	-0.67	62	62
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
STAT1 (dimer)/PIAS1	-0.006	0.13	0.3	4	-0.33	58	62
CEBPB/PTGES2/Cbp/p300	-0.024	0.12	-10000	0	-0.39	14	14
mol:Ca2+	0.006	0.14	-10000	0	-0.35	62	62
MAPK3	-0.009	0.12	-10000	0	-0.65	4	4
STAT1 (dimer)	0.017	0.098	-10000	0	-0.34	3	3
MAPK1	-0.17	0.31	0.44	1	-0.67	122	123
JAK2	0.017	0.036	-10000	0	-0.38	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
JAK1	0.02	0.025	-10000	0	-10000	0	0
CAMK2D	0.027	0.004	-10000	0	-10000	0	0
DAPK1	-0.041	0.18	0.48	9	-0.6	27	36
SMAD7	0.018	0.065	0.33	9	-10000	0	9
CBL/CRKL/C3G	-0.009	0.12	0.3	2	-0.36	5	7
PI3K	0.011	0.14	-10000	0	-0.34	62	62
IFNG	-0.067	0.23	-10000	0	-0.68	62	62
apoptosis	-0.038	0.15	0.56	4	-0.46	36	40
CAMK2G	0.027	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	0.026	0.007	-10000	0	-10000	0	0
CAMK2A	0.011	0.035	-10000	0	-10000	0	0
CAMK2B	0.019	0.07	-10000	0	-0.67	5	5
FRAP1	-0.024	0.11	0.37	5	-0.35	7	12
PRKCD	-0.013	0.13	0.42	9	-0.38	7	16
RAP1B	0.027	0.005	-10000	0	-10000	0	0
negative regulation of cell growth	0.008	0.072	-10000	0	-0.24	4	4
PTPN2	0.027	0.004	-10000	0	-10000	0	0
EP300	0.02	0.013	-10000	0	-10000	0	0
IRF1	-0.015	0.086	-10000	0	-10000	0	0
STAT1 (dimer)/PIASy	-0.012	0.12	0.3	2	-0.32	55	57
SOCS1	0.018	0.12	-10000	0	-1	6	6
mol:GDP	-0.01	0.11	0.28	2	-0.34	5	7
CASP1	0.016	0.064	0.35	6	-0.32	2	8
PTGES2	0.025	0.008	-10000	0	-10000	0	0
IRF9	-0.001	0.058	0.35	1	-10000	0	1
mol:PI-3-4-5-P3	-0.002	0.13	-10000	0	-0.33	62	62
RAP1/GDP	-0.006	0.1	-10000	0	-0.36	1	1
CBL	-0.022	0.13	0.29	6	-0.34	62	68
MAP3K1	-0.023	0.12	0.3	2	-0.34	60	62
PIAS1	0.027	0.004	-10000	0	-10000	0	0
PIAS4	0.025	0.008	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	0.008	0.072	-10000	0	-0.24	4	4
PTPN11	-0.026	0.13	-10000	0	-0.36	62	62
CREBBP	0.027	0.006	-10000	0	-10000	0	0
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.019	0.12	-10000	0	-0.42	33	33
NF kappa B1 p50/RelA/I kappa B alpha	0.011	0.087	0.42	1	-10000	0	1
AP1	-0.15	0.3	-10000	0	-0.55	157	157
mol:PIP3	-0.011	0.091	-10000	0	-0.35	30	30
AKT1	0.032	0.097	0.34	4	-0.57	2	6
PTK2B	-0.009	0.085	0.26	1	-0.36	12	13
RHOA	0.014	0.042	0.25	1	-10000	0	1
PIK3CB	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.072	0.27	8	-10000	0	8
MAGI3	0.025	0.032	-10000	0	-0.67	1	1
RELA	0.027	0.005	-10000	0	-10000	0	0
apoptosis	-0.008	0.1	-10000	0	-0.35	36	36
HRAS/GDP	0.019	0.008	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0	0.099	0.35	11	-0.37	9	20
NF kappa B1 p50/RelA	-0.019	0.1	-10000	0	-0.43	9	9
endothelial cell migration	-0.015	0.15	-10000	0	-0.52	33	33
ADCY4	-0.029	0.14	-10000	0	-0.52	35	35
ADCY5	-0.054	0.16	-10000	0	-0.54	39	39
ADCY6	-0.029	0.14	-10000	0	-0.52	35	35
ADCY7	-0.029	0.15	-10000	0	-0.52	35	35
ADCY1	-0.031	0.15	-10000	0	-0.51	37	37
ADCY2	-0.049	0.17	-10000	0	-0.54	39	39
ADCY3	-0.029	0.15	-10000	0	-0.53	34	34
ADCY8	-0.037	0.15	-10000	0	-0.52	36	36
ADCY9	-0.029	0.15	-10000	0	-0.52	35	35
GSK3B	-0.007	0.084	0.37	2	-0.34	12	14
arachidonic acid secretion	-0.029	0.14	-10000	0	-0.43	48	48
GNG2	0.025	0.032	-10000	0	-0.67	1	1
TRIP6	0.024	0.01	-10000	0	-10000	0	0
GNAO1	-0.024	0.15	-10000	0	-0.47	46	46
HRAS	0.026	0.011	-10000	0	-10000	0	0
NFKBIA	-0.005	0.095	0.46	5	-0.49	1	6
GAB1	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.015	0.18	-10000	0	-0.79	22	22
JUN	-0.12	0.29	-10000	0	-0.67	107	107
LPA/LPA2/NHERF2	0.035	0.017	-10000	0	-10000	0	0
TIAM1	0	0.21	-10000	0	-0.93	23	23
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.012	0.065	0.32	1	-10000	0	1
PLCB3	0.027	0.034	-10000	0	-10000	0	0
FOS	-0.15	0.3	-10000	0	-0.67	125	125
positive regulation of mitosis	-0.029	0.14	-10000	0	-0.43	48	48
LPA/LPA1-2-3	0.019	0.12	-10000	0	-0.41	29	29
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.026	0.006	-10000	0	-10000	0	0
stress fiber formation	0.002	0.1	0.45	2	-0.39	12	14
GNAZ	-0.015	0.12	-10000	0	-0.44	33	33
EGFR/PI3K-beta/Gab1	-0.001	0.099	-10000	0	-0.36	30	30
positive regulation of dendritic cell cytokine production	0.018	0.11	-10000	0	-0.4	29	29
LPA/LPA2/MAGI-3	0.035	0.027	-10000	0	-0.45	1	1
ARHGEF1	0.006	0.1	0.36	3	-0.39	23	26
GNAI2	-0.012	0.12	-10000	0	-0.45	33	33
GNAI3	-0.011	0.12	-10000	0	-0.42	37	37
GNAI1	-0.011	0.12	-10000	0	-0.44	34	34
LPA/LPA3	0.015	0.025	-10000	0	-10000	0	0
LPA/LPA2	0.02	0.013	-10000	0	-10000	0	0
LPA/LPA1	-0.015	0.14	-10000	0	-0.47	40	40
HB-EGF/EGFR	-0.022	0.14	-10000	0	-0.44	44	44
HBEGF	-0.038	0.14	-10000	0	-0.49	42	42
mol:DAG	-0.012	0.065	0.32	1	-10000	0	1
cAMP biosynthetic process	-0.035	0.17	0.42	10	-0.46	49	59
NFKB1	0.027	0.004	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
GNB1	0.026	0.006	-10000	0	-10000	0	0
LYN	-0.007	0.091	0.36	6	-0.49	1	7
GNAQ	0.016	0.015	-10000	0	-10000	0	0
LPAR2	0.025	0.008	-10000	0	-10000	0	0
LPAR3	0.013	0.034	-10000	0	-10000	0	0
LPAR1	-0.022	0.18	-10000	0	-0.62	38	38
IL8	-0.084	0.17	0.36	1	-0.47	40	41
PTK2	-0.002	0.1	-10000	0	-0.4	25	25
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
CASP3	-0.008	0.1	-10000	0	-0.36	36	36
EGFR	0.019	0.07	-10000	0	-0.67	5	5
PLCG1	-0.013	0.064	-10000	0	-0.28	4	4
PLD2	-0.002	0.1	-10000	0	-0.39	24	24
G12/G13	0.022	0.12	-10000	0	-0.4	32	32
PI3K-beta	0.006	0.087	-10000	0	-0.68	2	2
cell migration	0.019	0.072	-10000	0	-0.27	9	9
SLC9A3R2	0.026	0.006	-10000	0	-10000	0	0
PXN	0	0.098	0.27	1	-0.4	12	13
HRAS/GTP	-0.028	0.15	-10000	0	-0.45	47	47
RAC1	0.026	0.006	-10000	0	-10000	0	0
MMP9	-0.043	0.2	-10000	0	-0.67	42	42
PRKCE	0.02	0.07	-10000	0	-0.68	5	5
PRKCD	-0.008	0.085	0.37	7	-10000	0	7
Gi(beta/gamma)	-0.023	0.14	-10000	0	-0.51	33	33
mol:LPA	0.002	0.017	-10000	0	-0.19	2	2
TRIP6/p130 Cas/FAK1/Paxillin	0.019	0.11	-10000	0	-0.42	15	15
MAPKKK cascade	-0.029	0.14	-10000	0	-0.43	48	48
contractile ring contraction involved in cytokinesis	0.017	0.047	0.27	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.068	0.15	-10000	0	-0.35	109	109
GNA15	0.013	0.027	-10000	0	-0.36	1	1
GNA12	0.026	0.006	-10000	0	-10000	0	0
GNA13	0.026	0.007	-10000	0	-10000	0	0
MAPT	-0.003	0.094	0.33	8	-0.38	9	17
GNA11	0.012	0.046	-10000	0	-0.33	8	8
Rac1/GTP	0.014	0.19	-10000	0	-0.84	21	21
MMP2	-0.015	0.15	-10000	0	-0.53	33	33

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.016	0.005	-10000	0	-10000	0	0
MAP4K4	-0.014	0.12	-10000	0	-0.49	16	16
BAG4	0.025	0.032	-10000	0	-0.67	1	1
PKC zeta/ceramide	-0.02	0.097	-10000	0	-0.28	37	37
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	-0.01	0.15	-10000	0	-0.62	25	25
BAX	-0.013	0.075	-10000	0	-0.34	20	20
RIPK1	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.028	0.14	0.79	16	-10000	0	16
BAD	-0.033	0.088	0.18	1	-0.39	16	17
SMPD1	-0.011	0.089	0.27	6	-0.23	61	67
RB1	-0.033	0.09	0.19	1	-0.38	19	20
FADD/Caspase 8	-0.005	0.12	-10000	0	-0.52	13	13
MAP2K4	-0.02	0.072	0.21	2	-0.37	8	10
NSMAF	0.027	0.005	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.024	0.083	-10000	0	-0.41	12	12
EGF	-0.076	0.25	-10000	0	-0.67	72	72
mol:ceramide	-0.038	0.098	-10000	0	-0.3	39	39
MADD	0.027	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.016	0.024	-10000	0	-0.51	1	1
ASAH1	0.025	0.032	-10000	0	-0.67	1	1
negative regulation of cell cycle	-0.033	0.089	0.19	1	-0.37	19	20
cell proliferation	-0.059	0.15	-10000	0	-0.33	104	104
BID	-0.15	0.28	-10000	0	-0.6	127	127
MAP3K1	-0.028	0.079	0.19	1	-0.28	27	28
EIF2A	-0.03	0.078	-10000	0	-0.45	10	10
TRADD	0.026	0.006	-10000	0	-10000	0	0
CRADD	0.027	0.005	-10000	0	-10000	0	0
MAPK3	-0.014	0.07	-10000	0	-0.35	10	10
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.043	0.086	-10000	0	-0.38	13	13
Cathepsin D/ceramide	-0.019	0.093	-10000	0	-0.27	37	37
FADD	-0.013	0.12	-10000	0	-0.5	15	15
KSR1	-0.027	0.087	0.18	7	-0.43	13	20
MAPK8	-0.019	0.091	-10000	0	-0.37	20	20
PRKRA	-0.035	0.091	-10000	0	-0.36	21	21
PDGFA	0.026	0.006	-10000	0	-10000	0	0
TRAF2	0.025	0.009	-10000	0	-10000	0	0
IGF1	-0.13	0.29	-10000	0	-0.67	108	108
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.037	0.097	-10000	0	-0.29	39	39
CTSD	0.026	0.009	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.039	0.008	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.063	0.16	-10000	0	-0.35	104	104
PRKCD	0.027	0.003	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.016	0.024	-10000	0	-0.51	1	1
RelA/NF kappa B1	0.039	0.008	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.027	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.013	0.12	-10000	0	-0.47	19	19
TNFR1A/BAG4/TNF-alpha	-0.003	0.16	-10000	0	-0.44	57	57
mol:Sphingosine-1-phosphate	0.016	0.005	-10000	0	-10000	0	0
MAP2K1	-0.023	0.078	-10000	0	-0.38	12	12
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
CYCS	-0.006	0.072	0.17	25	-0.24	18	43
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.038	0.026	-10000	0	-0.51	1	1
EIF2AK2	-0.032	0.084	-10000	0	-0.47	11	11
TNF-alpha/TNFR1A/FAN	-0.002	0.16	-10000	0	-0.44	56	56
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.012	0.088	-10000	0	-0.48	7	7
MAP2K2	-0.015	0.068	-10000	0	-0.4	6	6
SMPD3	-0.016	0.1	-10000	0	-0.26	65	65
TNF	-0.056	0.22	-10000	0	-0.67	56	56
PKC zeta/PAR4	0.038	0.011	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.016	0.11	0.25	70	-0.25	17	87
NF kappa B1/RelA/I kappa B alpha	0.075	0.024	-10000	0	-10000	0	0
AIFM1	-0.01	0.082	0.17	25	-0.28	22	47
BCL2	-0.026	0.18	-10000	0	-0.67	38	38

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.025	0.007	-10000	0	-10000	0	0
mol:Halofuginone	0.004	0.001	-10000	0	-10000	0	0
ITGA1	0.017	0.083	-10000	0	-0.67	7	7
CDKN1A	-0.007	0.071	-10000	0	-0.61	1	1
PRL-3/alpha Tubulin	0.028	0.035	-10000	0	-10000	0	0
mol:Ca2+	-0.024	0.082	0.24	5	-0.52	11	16
AGT	0.003	0.11	-10000	0	-0.67	11	11
CCNA2	-0.067	0.15	-10000	0	-0.37	100	100
TUBA1B	0.027	0.005	-10000	0	-10000	0	0
EGR1	-0.087	0.21	-10000	0	-0.5	101	101
CDK2/Cyclin E1	0.018	0.077	-10000	0	-0.54	1	1
MAPK3	0.008	0.027	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.04	0.007	-10000	0	-10000	0	0
MAPK1	0.007	0.023	-10000	0	-10000	0	0
PTP4A1	-0.07	0.16	-10000	0	-0.39	101	101
PTP4A3	0.013	0.043	-10000	0	-10000	0	0
PTP4A2	0.027	0.005	-10000	0	-10000	0	0
ITGB1	0.008	0.028	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
RAC1	-0.011	0.082	-10000	0	-0.37	8	8
Rab GGTase beta/Rab GGTase alpha	0.039	0.009	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.054	0.16	-10000	0	-0.37	99	99
RABGGTA	0.027	0.005	-10000	0	-10000	0	0
BCAR1	-0.012	0.014	-10000	0	-10000	0	0
RHOC	-0.011	0.083	-10000	0	-0.4	7	7
RHOA	-0.011	0.081	-10000	0	-0.61	2	2
cell motility	-0.004	0.096	0.3	5	-0.4	7	12
PRL-1/alpha Tubulin	-0.05	0.16	-10000	0	-0.36	101	101
PRL-3/alpha1 Integrin	0.02	0.074	-10000	0	-0.52	7	7
ROCK1	-0.005	0.093	0.3	3	-0.4	7	10
RABGGTB	0.027	0.005	-10000	0	-10000	0	0
CDK2	0.027	0.005	-10000	0	-10000	0	0
mitosis	-0.07	0.16	-10000	0	-0.39	101	101
ATF5	0.02	0.029	-10000	0	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

Figure S49. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S49. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.026	0.009	-10000	0	-10000	0	0
LAT2	-0.003	0.066	-10000	0	-0.29	1	1
AP1	-0.12	0.26	-10000	0	-0.55	107	107
mol:PIP3	0.027	0.17	0.61	21	-0.41	12	33
IKBKB	0.039	0.17	0.58	28	-0.27	6	34
AKT1	-0.007	0.12	0.32	26	-0.43	8	34
IKBKG	0.041	0.17	0.62	28	-0.26	7	35
MS4A2	-0.015	0.064	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.023	0.055	-10000	0	-0.68	3	3
MAP3K1	0.023	0.11	0.44	13	-0.4	7	20
mol:Ca2+	0.033	0.16	0.52	29	-0.32	11	40
LYN	0.027	0.011	-10000	0	-10000	0	0
CBLB	-0.001	0.063	-10000	0	-0.27	1	1
SHC1	0.025	0.008	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.021	0.16	-10000	0	-0.4	78	78
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.019	0.034	-10000	0	-10000	0	0
PLD2	-0.009	0.13	0.32	34	-0.37	30	64
PTPN13	0.012	0.13	0.53	1	-0.63	13	14
PTPN11	0.023	0.036	-10000	0	-0.7	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.031	0.16	0.62	21	-0.37	6	27
SYK	0.025	0.012	-10000	0	-10000	0	0
GRB2	0.026	0.007	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.001	0.11	-10000	0	-0.37	28	28
LAT	-0.004	0.069	-10000	0	-0.33	4	4
PAK2	0.017	0.1	0.32	8	-0.42	9	17
NFATC2	-0.11	0.23	-10000	0	-0.61	84	84
HRAS	0.012	0.099	0.24	2	-0.43	10	12
GAB2	0.027	0.005	-10000	0	-10000	0	0
PLA2G1B	0.006	0.096	-10000	0	-0.68	7	7
Fc epsilon R1	0.005	0.13	-10000	0	-0.45	32	32
Antigen/IgE/Fc epsilon R1	0.009	0.12	-10000	0	-0.41	32	32
mol:GDP	0.003	0.11	-10000	0	-0.46	14	14
JUN	-0.12	0.29	-10000	0	-0.67	107	107
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
FOS	-0.15	0.3	-10000	0	-0.67	125	125
Antigen/IgE/Fc epsilon R1/LYN/SYK	0.003	0.069	-10000	0	-0.26	8	8
CHUK	0.036	0.16	0.58	26	-0.26	7	33
KLRG1	-0.007	0.077	-10000	0	-0.31	13	13
VAV1	-0.005	0.073	0.21	1	-0.36	6	7
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.001	0.063	-10000	0	-10000	0	0
negative regulation of mast cell degranulation	0.006	0.08	-10000	0	-0.3	10	10
BTK	-0.006	0.12	-10000	0	-0.53	18	18
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.018	0.15	-10000	0	-0.47	41	41
GAB2/PI3K/SHP2	-0.029	0.098	-10000	0	-0.38	29	29
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.001	0.072	-10000	0	-0.27	28	28
RAF1	0.014	0.085	-10000	0	-0.85	4	4
Fc epsilon R1/FcgammaRIIB/SHIP	0.019	0.17	-10000	0	-0.5	42	42
FCER1G	0.018	0.035	-10000	0	-10000	0	0
FCER1A	-0.033	0.18	-10000	0	-0.68	33	33
Antigen/IgE/Fc epsilon R1/Fyn	0.025	0.12	-10000	0	-0.38	32	32
MAPK3	0.019	0.091	-10000	0	-0.7	6	6
MAPK1	-0.014	0.11	-10000	0	-0.72	7	7
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	0.001	0.18	-10000	0	-0.63	31	31
DUSP1	-0.084	0.26	-10000	0	-0.67	78	78
NF-kappa-B/RelA	0.015	0.048	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.014	0.13	0.37	1	-0.71	10	11
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	0.023	0.098	-10000	0	-0.47	7	7
FER	-0.004	0.071	-10000	0	-0.38	4	4
RELA	0.027	0.005	-10000	0	-10000	0	0
ITK	-0.042	0.15	-10000	0	-0.47	54	54
SOS1	0.027	0.005	-10000	0	-10000	0	0
PLCG1	0.011	0.12	0.4	8	-0.51	10	18
cytokine secretion	0.005	0.03	-10000	0	-10000	0	0
SPHK1	-0.001	0.065	0.27	1	-0.28	2	3
PTK2	0.014	0.13	0.37	1	-0.75	10	11
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.006	0.11	-10000	0	-0.38	27	27
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0.035	0.18	0.64	21	-0.41	11	32
MAP2K2	0.019	0.09	-10000	0	-0.79	4	4
MAP2K1	0.01	0.083	-10000	0	-0.76	5	5
MAP2K7	0.025	0.008	-10000	0	-10000	0	0
KLRG1/SHP2	-0.001	0.082	-10000	0	-0.34	10	10
MAP2K4	-0.005	0.19	-10000	0	-0.84	24	24
Fc epsilon R1/FcgammaRIIB	0.007	0.18	-10000	0	-0.53	42	42
mol:Choline	-0.009	0.13	0.32	34	-0.37	30	64
SHC/Grb2/SOS1	0.037	0.076	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
DOK1	0.027	0.005	-10000	0	-10000	0	0
PXN	0.018	0.13	0.46	3	-0.67	10	13
HCLS1	-0.002	0.064	-10000	0	-0.28	2	2
PRKCB	0.036	0.18	0.62	26	-0.34	12	38
FCGR2B	-0.009	0.15	-10000	0	-0.67	24	24
IGHE	0.001	0.011	-10000	0	-10000	0	0
KLRG1/SHIP	0.006	0.082	-10000	0	-0.31	10	10
LCP2	0.024	0.021	-10000	0	-10000	0	0
PLA2G4A	-0.023	0.12	-10000	0	-0.42	31	31
RASA1	0.027	0.005	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.009	0.13	0.32	34	-0.37	30	64
IKK complex	0.044	0.18	0.61	30	-0.21	2	32
WIPF1	0.027	0.005	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.033	0.07	-10000	0	-0.58	6	6
alphaV beta3 Integrin	0.039	0.081	-10000	0	-0.48	11	11
PTK2	0.013	0.14	0.41	11	-0.5	11	22
IGF1R	0.027	0.004	-10000	0	-10000	0	0
PI4KB	0.025	0.007	-10000	0	-10000	0	0
MFGE8	0.009	0.05	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
CDKN1B	-0.027	0.16	-10000	0	-0.54	45	45
VEGFA	0.023	0.054	-10000	0	-0.67	3	3
ILK	-0.027	0.16	-10000	0	-0.53	46	46
ROCK1	0.027	0.005	-10000	0	-10000	0	0
AKT1	-0.029	0.15	-10000	0	-0.5	45	45
PTK2B	0.012	0.09	0.36	1	-0.42	16	17
alphaV/beta3 Integrin/JAM-A	0.007	0.14	-10000	0	-0.4	51	51
CBL	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.036	0.08	-10000	0	-0.46	11	11
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.088	0.24	-10000	0	-0.44	152	152
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.001	0.092	-10000	0	-0.41	5	5
alphaV/beta3 Integrin/Syndecan-1	0.04	0.081	-10000	0	-0.48	11	11
PI4KA	0.02	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.093	0.23	-10000	0	-0.43	152	152
PI4 Kinase	0.028	0.019	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
alphaV/beta3 Integrin/Osteopontin	0.02	0.13	-10000	0	-0.43	35	35
RPS6KB1	-0.14	0.19	0.42	2	-0.4	152	154
TLN1	0.025	0.007	-10000	0	-10000	0	0
MAPK3	-0.051	0.13	-10000	0	-0.64	12	12
GPR124	0.027	0.005	-10000	0	-10000	0	0
MAPK1	-0.06	0.14	-10000	0	-0.57	20	20
PXN	0.027	0.005	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	0.028	0.12	-10000	0	-0.52	20	20
cell adhesion	0.03	0.078	-10000	0	-0.46	10	10
ANGPTL3	0.007	0.024	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.047	0.064	-10000	0	-0.5	6	6
IGF-1R heterotetramer	0.027	0.004	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
TGFBR2	0.023	0.054	-10000	0	-0.67	3	3
ITGB3	0.011	0.1	-10000	0	-0.65	11	11
IGF1	-0.13	0.29	-10000	0	-0.67	108	108
RAC1	0.026	0.006	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	0.039	0.081	-10000	0	-0.47	11	11
apoptosis	0.024	0.044	-10000	0	-0.67	2	2
CD47	0.027	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0.04	0.081	-10000	0	-0.48	11	11
VCL	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	0.032	0.1	-10000	0	-0.48	18	18
CSF1	0.015	0.088	-10000	0	-0.67	8	8
PIK3C2A	-0.028	0.17	-10000	0	-0.53	47	47
PI4 Kinase/Pyk2	-0.014	0.12	-10000	0	-0.36	42	42
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.048	0.097	-10000	0	-0.45	16	16
FAK1/Vinculin	0.024	0.12	0.39	9	-0.41	9	18
alphaV beta3/Integrin/ppsTEM5	0.04	0.081	-10000	0	-0.48	11	11
RHOA	0.027	0.003	-10000	0	-10000	0	0
VTN	-0.038	0.2	-10000	0	-0.67	44	44
BCAR1	0.026	0.006	-10000	0	-10000	0	0
FGF2	0.027	0.004	-10000	0	-10000	0	0
F11R	0.016	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.041	0.082	-10000	0	-0.48	11	11
alphaV/beta3 Integrin/TGFBR2	0.037	0.086	-10000	0	-0.44	14	14
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.056	0.072	-10000	0	-0.44	9	9
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.036	0.075	-10000	0	-0.44	11	11
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	-0.085	0.069	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Pyk2	0.034	0.089	-10000	0	-0.42	16	16
SDC1	0.026	0.015	-10000	0	-10000	0	0
VAV3	0.009	0.08	-10000	0	-0.43	14	14
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
IRS1	-0.054	0.22	-10000	0	-0.67	58	58
FAK1/Paxillin	0.022	0.12	0.35	8	-0.41	9	17
cell migration	0.018	0.11	0.34	6	-0.41	6	12
ITGAV	0.024	0.045	-10000	0	-0.67	2	2
PI3K	0.016	0.14	-10000	0	-0.38	52	52
SPP1	-0.031	0.15	-10000	0	-0.67	23	23
KDR	0.021	0.063	-10000	0	-0.67	4	4
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.024	0.045	-10000	0	-0.67	2	2
COL4A3	0.008	0.11	-10000	0	-0.63	14	14
angiogenesis	-0.054	0.15	-10000	0	-0.52	32	32
Rac1/GTP	0.021	0.075	-10000	0	-0.4	14	14
EDIL3	0.005	0.095	-10000	0	-0.67	8	8
cell proliferation	0.037	0.086	-10000	0	-0.44	14	14

×

IL27-mediated signaling events

Figure S51. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S51. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.026	0.017	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.045	0.13	0.47	16	-10000	0	16
IL27/IL27R/JAK1	-0.015	0.17	-10000	0	-0.48	12	12
TBX21	-0.066	0.18	0.39	6	-0.57	29	35
IL12B	0.004	0.085	-10000	0	-0.68	7	7
IL12A	-0.049	0.16	-10000	0	-0.5	53	53
IL6ST	-0.072	0.24	-10000	0	-0.68	66	66
IL27RA/JAK1	0.02	0.054	0.55	1	-10000	0	1
IL27	0.011	0.028	-10000	0	-10000	0	0
TYK2	0.019	0.02	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.04	0.13	-10000	0	-0.49	3	3
T-helper 2 cell differentiation	0.045	0.13	0.47	16	-10000	0	16
T cell proliferation during immune response	0.045	0.13	0.47	16	-10000	0	16
MAPKKK cascade	-0.045	0.13	-10000	0	-0.47	16	16
STAT3	0.026	0.007	-10000	0	-10000	0	0
STAT2	0.027	0.005	-10000	0	-10000	0	0
STAT1	0.023	0.023	-10000	0	-10000	0	0
IL12RB1	0.004	0.082	-10000	0	-0.62	6	6
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.057	0.19	0.48	13	-0.56	25	38
IL27/IL27R/JAK2/TYK2	-0.046	0.13	-10000	0	-0.47	16	16
positive regulation of T cell mediated cytotoxicity	-0.045	0.13	-10000	0	-0.47	16	16
STAT1 (dimer)	-0.026	0.22	0.52	12	-0.6	17	29
JAK2	0.019	0.031	-10000	0	-0.36	2	2
JAK1	0.027	0.008	-10000	0	-10000	0	0
STAT2 (dimer)	-0.033	0.14	-10000	0	-0.46	15	15
T cell proliferation	-0.11	0.19	-10000	0	-0.45	87	87
IL12/IL12R/TYK2/JAK2	-0.073	0.24	-10000	0	-0.84	30	30
IL17A	-0.04	0.13	-10000	0	-0.49	3	3
mast cell activation	0.045	0.13	0.47	16	-10000	0	16
IFNG	-0.016	0.051	0.092	5	-0.13	69	74
T cell differentiation	-0.004	0.008	0.014	1	-0.022	65	66
STAT3 (dimer)	-0.032	0.14	-10000	0	-0.45	15	15
STAT5A (dimer)	-0.032	0.14	-10000	0	-0.46	14	14
STAT4 (dimer)	-0.039	0.15	0.32	1	-0.44	24	25
STAT4	0.004	0.099	-10000	0	-0.59	11	11
T cell activation	-0.008	0.005	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.025	0.15	-10000	0	-0.45	15	15
GATA3	-0.058	0.3	-10000	0	-1.4	25	25
IL18	-0.012	0.077	-10000	0	-0.49	11	11
positive regulation of mast cell cytokine production	-0.032	0.13	-10000	0	-0.44	15	15
IL27/EBI3	-0.031	0.06	-10000	0	-0.26	1	1
IL27RA	0	0.024	-10000	0	-10000	0	0
IL6	-0.096	0.26	-10000	0	-0.67	81	81
STAT5A	0.026	0.007	-10000	0	-10000	0	0
monocyte differentiation	-0.001	0.003	-10000	0	-0.023	2	2
IL2	-0.011	0.018	-10000	0	-10000	0	0
IL1B	-0.027	0.13	-10000	0	-0.51	32	32
EBI3	-0.052	0.075	-10000	0	-0.37	1	1
TNF	-0.053	0.16	-10000	0	-0.51	56	56

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.004	0.14	-10000	0	-0.37	62	62
TC10/GTP	0.041	0.042	-10000	0	-0.35	4	4
Insulin Receptor/Insulin/IRS1/Shp2	0	0.16	-10000	0	-0.42	60	60
HRAS	0.026	0.011	-10000	0	-10000	0	0
APS homodimer	0.024	0.033	-10000	0	-0.67	1	1
GRB14	0.006	0.12	-10000	0	-0.67	15	15
FOXO3	0.002	0.12	-10000	0	-0.65	14	14
AKT1	-0.028	0.14	0.34	6	-0.34	70	76
INSR	0.027	0.01	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.05	0.036	-10000	0	-0.34	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.026	0.006	-10000	0	-10000	0	0
SORBS1	0.021	0.063	-10000	0	-0.67	4	4
CRK	0.026	0.007	-10000	0	-10000	0	0
PTPN1	0.016	0.039	-10000	0	-0.34	2	2
CAV1	-0.035	0.14	-10000	0	-0.38	68	68
CBL/APS/CAP/Crk-II/C3G	0.065	0.052	-10000	0	-0.38	4	4
Insulin Receptor/Insulin/IRS1/NCK2	0.002	0.16	-10000	0	-0.41	60	60
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.005	0.14	-10000	0	-0.37	62	62
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.007	0.1	-10000	0	-0.45	7	7
RPS6KB1	-0.032	0.12	0.3	3	-0.32	63	66
PARD6A	0.026	0.006	-10000	0	-10000	0	0
CBL	0.027	0.005	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.018	0.036	-10000	0	-0.52	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.011	0.13	-10000	0	-0.33	65	65
HRAS/GTP	-0.024	0.11	-10000	0	-0.34	46	46
Insulin Receptor	0.027	0.01	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.015	0.14	-10000	0	-0.39	47	47
PRKCI	0.012	0.075	-10000	0	-0.49	5	5
Insulin Receptor/Insulin/GRB14/PDK1	-0.026	0.14	-10000	0	-0.36	71	71
SHC1	0.025	0.008	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.045	0.046	-10000	0	-0.43	2	2
PI3K	0.004	0.15	-10000	0	-0.38	62	62
NCK2	0.027	0.005	-10000	0	-10000	0	0
RHOQ	0.027	0.005	-10000	0	-10000	0	0
mol:H2O2	0.001	0.008	-10000	0	-10000	0	0
HRAS/GDP	0.019	0.008	-10000	0	-10000	0	0
AKT2	-0.03	0.14	0.38	7	-0.34	70	77
PRKCZ	0.013	0.074	-10000	0	-0.51	5	5
SH2B2	0.024	0.033	-10000	0	-0.67	1	1
SHC/SHIP	-0.013	0.13	0.3	1	-0.37	50	51
F2RL2	-0.018	0.085	-10000	0	-0.67	3	3
TRIP10	0.025	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.039	0.037	-10000	0	-0.37	3	3
TC10/GTP/CIP4/Exocyst	0.034	0.011	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.062	0.041	-10000	0	-0.34	2	2
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0
RASA1	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
CBL/APS/CAP/Crk-II	0.059	0.049	-10000	0	-0.4	4	4
TC10/GDP	0.02	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.053	0.041	-10000	0	-0.37	3	3
INPP5D	-0.031	0.14	0.31	1	-0.39	60	61
SOS1	0.027	0.005	-10000	0	-10000	0	0
SGK1	-0.013	0.15	-10000	0	-0.83	15	15
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
IRS1	-0.054	0.22	-10000	0	-0.67	58	58
p62DOK/RasGAP	0.046	0.046	-10000	0	-0.44	2	2
INS	0.015	0.054	-10000	0	-0.67	3	3
mol:PI-3-4-P2	-0.031	0.14	0.31	1	-0.38	60	61
GRB2	0.026	0.007	-10000	0	-10000	0	0
EIF4EBP1	-0.032	0.12	0.36	3	-0.32	61	64
PTPRA	0.028	0.008	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
TC10/GTP/CIP4	0.034	0.011	-10000	0	-10000	0	0
PDPK1	0.023	0.045	-10000	0	-0.67	2	2
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.009	0.1	-10000	0	-0.3	47	47
Insulin Receptor/Insulin/IRS1	-0.012	0.15	-10000	0	-0.41	60	60
Insulin Receptor/Insulin/IRS3	0.03	0.043	-10000	0	-0.5	3	3
Par3/Par6	0.058	0.039	-10000	0	-0.38	2	2

×

Angiopoietin receptor Tie2-mediated signaling

Figure S53. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S53. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.012	0.2	-10000	0	-0.94	20	20
NCK1/PAK1/Dok-R	-0.028	0.088	-10000	0	-0.43	20	20
NCK1/Dok-R	-0.003	0.25	-10000	0	-1.1	21	21
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
mol:beta2-estradiol	0	0.045	0.23	18	-10000	0	18
RELA	0.027	0.005	-10000	0	-10000	0	0
SHC1	0.026	0.008	-10000	0	-10000	0	0
Rac/GDP	0.02	0.004	-10000	0	-10000	0	0
F2	-0.012	0.056	0.27	13	-10000	0	13
TNIP2	0.027	0.004	-10000	0	-10000	0	0
NF kappa B/RelA	0.011	0.23	-10000	0	-1.1	20	20
FN1	-0.085	0.069	-10000	0	-10000	0	0
PLD2	-0.024	0.25	-10000	0	-1.2	20	20
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
GRB14	0.006	0.12	-10000	0	-0.67	15	15
ELK1	-0.024	0.22	-10000	0	-1	20	20
GRB7	0.001	0.056	-10000	0	-10000	0	0
PAK1	0.027	0.005	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	0.007	0.25	-10000	0	-1.1	20	20
CDKN1A	-0.022	0.16	0.49	4	-0.63	20	24
ITGA5	0.027	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.004	0.25	-10000	0	-1.1	21	21
CRK	0.026	0.007	-10000	0	-10000	0	0
mol:NO	0.011	0.17	0.57	8	-0.67	20	28
PLG	-0.031	0.25	-10000	0	-1.2	20	20
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.011	0.19	-10000	0	-0.89	20	20
GRB2	0.026	0.007	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
ANGPT2	-0.1	0.2	0.42	1	-0.78	17	18
BMX	-0.034	0.26	-10000	0	-1.2	20	20
ANGPT1	-0.043	0.26	-10000	0	-1.3	18	18
tube development	-0.037	0.17	0.46	3	-0.73	20	23
ANGPT4	-0.034	0.2	-10000	0	-0.67	42	42
response to hypoxia	-0.004	0.015	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.027	0.27	-10000	0	-1.2	20	20
alpha5/beta1 Integrin	0.039	0.009	-10000	0	-10000	0	0
FGF2	0.026	0.004	-10000	0	-10000	0	0
STAT5A (dimer)	-0.037	0.19	-10000	0	-0.83	20	20
mol:L-citrulline	0.011	0.17	0.57	8	-0.67	20	28
AGTR1	-0.26	0.34	-10000	0	-0.67	201	201
MAPK14	-0.026	0.25	-10000	0	-1.2	20	20
Tie2/SHP2	-0.003	0.18	-10000	0	-1.2	8	8
TEK	0.005	0.19	-10000	0	-1.4	8	8
RPS6KB1	-0.006	0.2	0.51	2	-0.89	20	22
Angiotensin II/AT1	-0.19	0.26	-10000	0	-0.5	201	201
Tie2/Ang1/GRB2	-0.016	0.26	-10000	0	-1.2	20	20
MAPK3	-0.02	0.22	-10000	0	-1.1	20	20
MAPK1	-0.029	0.22	-10000	0	-1.1	20	20
Tie2/Ang1/GRB7	-0.016	0.26	-10000	0	-1.2	20	20
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MAPK8	-0.032	0.26	-10000	0	-1.2	20	20
PI3K	-0.02	0.23	-10000	0	-1.1	20	20
FES	-0.027	0.25	-10000	0	-1.2	20	20
Crk/Dok-R	-0.003	0.25	-10000	0	-1.1	21	21
Tie2/Ang1/ABIN2	-0.015	0.26	-10000	0	-1.2	20	20
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.003	0.19	0.5	4	-0.83	20	24
STAT5A	0.026	0.007	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.01	0.2	0.48	1	-0.9	20	21
Tie2/Ang2	-0.056	0.22	-10000	0	-1	20	20
Tie2/Ang1	-0.027	0.28	-10000	0	-1.3	20	20
FOXO1	0	0.19	0.56	4	-0.84	20	24
ELF1	0.028	0.053	-10000	0	-0.59	3	3
ELF2	-0.023	0.24	-10000	0	-1.2	20	20
mol:Choline	-0.021	0.23	-10000	0	-1.1	20	20
cell migration	-0.014	0.055	-10000	0	-0.24	20	20
FYN	-0.046	0.19	0.53	1	-0.84	20	21
DOK2	0.019	0.052	-10000	0	-0.67	2	2
negative regulation of cell cycle	-0.019	0.15	0.45	6	-0.57	20	26
ETS1	0.026	0.047	-10000	0	-0.24	13	13
PXN	0.003	0.18	0.59	5	-0.73	20	25
ITGB1	0.027	0.004	-10000	0	-10000	0	0
NOS3	0.004	0.19	0.58	7	-0.78	20	27
RAC1	0.026	0.006	-10000	0	-10000	0	0
TNF	-0.056	0.23	-10000	0	-0.59	71	71
MAPKKK cascade	-0.021	0.23	-10000	0	-1.1	20	20
RASA1	0.027	0.005	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.017	0.26	-10000	0	-1.2	20	20
NCK1	0.027	0.003	-10000	0	-10000	0	0
vasculogenesis	0.014	0.16	0.52	10	-0.6	20	30
mol:Phosphatidic acid	-0.021	0.23	-10000	0	-1.1	20	20
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.011	0.17	0.57	8	-0.67	20	28
Rac1/GTP	-0.004	0.18	-10000	0	-0.83	20	20
MMP2	-0.029	0.26	-10000	0	-1.2	20	20

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.015	0.12	-10000	0	-0.44	20	20
BAG4	0.025	0.032	-10000	0	-0.67	1	1
BAD	0.007	0.065	0.34	9	-10000	0	9
NFKBIA	0.027	0.005	-10000	0	-10000	0	0
BIRC3	-0.01	0.15	-10000	0	-0.62	25	25
BAX	0.013	0.07	0.25	23	-10000	0	23
EnzymeConsortium:3.1.4.12	0.002	0.039	0.16	10	-0.1	17	27
IKBKB	-0.013	0.12	0.29	1	-0.45	15	16
MAP2K2	0.018	0.094	0.34	23	-0.3	2	25
MAP2K1	0.011	0.083	0.32	19	-0.3	2	21
SMPD1	0.005	0.045	0.24	7	-0.13	4	11
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.01	0.12	-10000	0	-0.45	20	20
MAP2K4	0.017	0.096	0.35	26	-10000	0	26
protein ubiquitination	-0.011	0.12	0.32	4	-0.43	18	22
EnzymeConsortium:2.7.1.37	0.018	0.11	0.38	25	-0.31	2	27
response to UV	0	0.002	0.006	27	-0.002	3	30
RAF1	0.012	0.085	0.31	21	-0.32	2	23
CRADD	0.027	0.005	-10000	0	-10000	0	0
mol:ceramide	0.005	0.059	0.22	12	-0.15	16	28
I-kappa-B-alpha/RELA/p50/ubiquitin	0.036	0.008	-10000	0	-10000	0	0
MADD	0.027	0.005	-10000	0	-10000	0	0
MAP3K1	0.01	0.076	0.31	18	-0.16	10	28
TRADD	0.026	0.006	-10000	0	-10000	0	0
RELA/p50	0.027	0.005	-10000	0	-10000	0	0
MAPK3	0.018	0.088	0.34	19	-0.29	2	21
MAPK1	-0.005	0.09	0.33	16	-0.27	4	20
p50/RELA/I-kappa-B-alpha	0.039	0.009	-10000	0	-10000	0	0
FADD	-0.014	0.12	-10000	0	-0.44	19	19
KSR1	0.01	0.08	0.28	23	-0.33	2	25
MAPK8	0.011	0.11	0.38	22	-0.35	9	31
TRAF2	0.025	0.009	-10000	0	-10000	0	0
response to radiation	0	0.001	0.006	13	-10000	0	13
CHUK	-0.014	0.12	0.33	1	-0.42	20	21
TNF R/SODD	0.038	0.026	-10000	0	-0.51	1	1
TNF	-0.055	0.22	-10000	0	-0.68	56	56
CYCS	0.02	0.08	0.26	25	-0.18	1	26
IKBKG	-0.012	0.12	0.32	2	-0.42	18	20
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.015	0.13	-10000	0	-0.41	29	29
RELA	0.027	0.005	-10000	0	-10000	0	0
RIPK1	0.027	0.003	-10000	0	-10000	0	0
AIFM1	0.018	0.079	0.25	25	-0.18	2	27
TNF/TNF R/SODD	-0.003	0.16	-10000	0	-0.44	57	57
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
response to heat	0	0.001	0.006	13	-10000	0	13
CASP8	0.009	0.13	-10000	0	-0.72	14	14
NSMAF	-0.014	0.12	-10000	0	-0.44	19	19
response to hydrogen peroxide	0	0.002	0.006	27	-0.002	3	30
BCL2	-0.026	0.18	-10000	0	-0.67	38	38

×

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	0.025	0.032	-10000	0	-0.67	1	1
Jak2/Leptin Receptor	-0.006	0.12	0.26	4	-0.37	31	35
PTP1B/AKT1	0.006	0.071	0.32	2	-0.28	6	8
FYN	0.027	0.004	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0	0.082	0.31	11	-0.28	9	20
EGFR	0.013	0.072	-10000	0	-0.68	5	5
EGF/EGFR	-0.035	0.16	0.24	1	-0.39	74	75
CSF1	0.015	0.088	-10000	0	-0.67	8	8
AKT1	0.027	0.006	-10000	0	-10000	0	0
INSR	0.026	0.008	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.004	0.11	0.32	6	-0.32	21	27
Insulin Receptor/Insulin	0.015	0.072	-10000	0	-0.35	4	4
HCK	0.017	0.039	-10000	0	-10000	0	0
CRK	0.026	0.007	-10000	0	-10000	0	0
TYK2	0.008	0.093	0.31	21	-0.29	5	26
EGF	-0.076	0.25	-10000	0	-0.67	72	72
YES1	0.027	0.005	-10000	0	-10000	0	0
CAV1	-0.004	0.11	0.4	12	-0.32	10	22
TXN	0.024	0.011	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.029	0.14	-10000	0	-0.38	57	57
cell migration	0	0.082	0.28	9	-0.31	11	20
STAT3	0.026	0.007	-10000	0	-10000	0	0
PRLR	-0.014	0.16	-10000	0	-0.67	25	25
ITGA2B	-0.042	0.21	-10000	0	-0.67	48	48
CSF1R	0.024	0.035	-10000	0	-0.67	1	1
Prolactin Receptor/Prolactin	0.001	0.12	-10000	0	-0.51	25	25
FGR	0.025	0.015	-10000	0	-10000	0	0
PTP1B/p130 Cas	0.006	0.073	0.28	3	-0.27	8	11
Crk/p130 Cas	0.013	0.071	-10000	0	-0.29	4	4
DOK1	0.012	0.087	0.36	12	-0.32	4	16
JAK2	-0.012	0.12	0.31	7	-0.37	35	42
Jak2/Leptin Receptor/Leptin	-0.007	0.13	-10000	0	-0.49	20	20
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
PTPN1	0	0.083	0.31	11	-0.28	9	20
LYN	0.027	0.005	-10000	0	-10000	0	0
CDH2	-0.073	0.12	-10000	0	-0.63	14	14
SRC	0.023	0.057	0.32	1	-0.39	5	6
ITGB3	0.01	0.1	-10000	0	-0.65	11	11
CAT1/PTP1B	-0.06	0.16	0.4	14	-0.36	45	59
CAPN1	0.027	0.006	-10000	0	-10000	0	0
CSK	0.027	0.008	-10000	0	-10000	0	0
PI3K	0.021	0.082	-10000	0	-0.42	6	6
mol:H2O2	-0.001	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	-0.007	0.13	-10000	0	-0.52	19	19
negative regulation of transcription	-0.01	0.12	0.31	7	-0.36	35	42
FCGR2A	0.017	0.045	-10000	0	-0.67	1	1
FER	0.021	0.055	-10000	0	-0.68	3	3
alphaIIb/beta3 Integrin	-0.026	0.18	-10000	0	-0.53	55	55
BLK	-0.19	0.31	-10000	0	-0.67	148	148
Insulin Receptor/Insulin/Shc	0.039	0.04	-10000	0	-0.42	3	3
RHOA	0.028	0.006	-10000	0	-10000	0	0
LEPR	0.021	0.06	-10000	0	-0.54	5	5
BCAR1	0.026	0.006	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.026	0.007	-10000	0	-10000	0	0
mol:NADPH	0	0.005	-10000	0	-10000	0	0
TRPV6	-0.09	0.18	0.38	3	-0.47	42	45
PRL	-0.006	0.019	-10000	0	-10000	0	0
SOCS3	-0.038	0.3	-10000	0	-1.3	26	26
SPRY2	0.022	0.046	-10000	0	-0.68	2	2
Insulin Receptor/Insulin/IRS1	-0.016	0.16	-10000	0	-0.45	60	60
CSF1/CSF1R	0.008	0.095	0.28	1	-0.46	10	11
Ras protein signal transduction	0.026	0.11	0.46	26	-10000	0	26
IRS1	-0.054	0.22	-10000	0	-0.67	58	58
INS	0.007	0.055	-10000	0	-0.67	3	3
LEP	0.009	0.033	-10000	0	-10000	0	0
STAT5B	0.001	0.091	0.29	11	-0.28	14	25
STAT5A	0.001	0.091	0.29	11	-0.28	14	25
GRB2	0.026	0.007	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.073	0.28	1	-0.3	9	10
CSN2	0.001	0.062	0.81	1	-10000	0	1
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
LAT	0.02	0.073	0.32	1	-0.45	8	9
YBX1	0.033	0.007	-10000	0	-10000	0	0
LCK	0.012	0.082	-10000	0	-0.67	6	6
SHC1	0.025	0.008	-10000	0	-10000	0	0
NOX4	-0.041	0.077	-10000	0	-10000	0	0

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	0.01	0.1	-10000	0	-0.52	11	11
alphaM/beta2 Integrin/GPIbA	0.001	0.12	-10000	0	-0.49	18	18
alphaM/beta2 Integrin/proMMP-9	-0.023	0.17	-10000	0	-0.5	44	44
PLAUR	-0.023	0.071	-10000	0	-10000	0	0
HMGB1	0.009	0.035	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.015	0.085	-10000	0	-0.57	5	5
AGER	-0.037	0.18	-10000	0	-0.7	32	32
RAP1A	0.027	0.005	-10000	0	-10000	0	0
SELPLG	0.016	0.039	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.032	0.19	-10000	0	-0.47	55	55
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	-0.043	0.2	-10000	0	-0.67	42	42
CYR61	-0.18	0.32	-10000	0	-0.67	144	144
TLN1	0.025	0.007	-10000	0	-10000	0	0
Rap1/GTP	-0.001	0.087	-10000	0	-0.37	9	9
RHOA	0.027	0.003	-10000	0	-10000	0	0
P-selectin oligomer	0.015	0.078	-10000	0	-0.67	6	6
MYH2	-0.031	0.097	-10000	0	-0.41	9	9
MST1R	0.02	0.065	-10000	0	-0.67	4	4
leukocyte activation during inflammatory response	0.014	0.081	-10000	0	-0.49	5	5
APOB	0.006	0.04	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.017	0.079	-10000	0	-0.63	7	7
JAM3	0.027	0.005	-10000	0	-10000	0	0
GP1BA	0.002	0.12	-10000	0	-0.63	15	15
alphaM/beta2 Integrin/CTGF	-0.051	0.19	-10000	0	-0.47	76	76
alphaM/beta2 Integrin	-0.024	0.089	-10000	0	-0.35	16	16
JAM3 homodimer	0.027	0.005	-10000	0	-10000	0	0
ICAM2	0.026	0.007	-10000	0	-10000	0	0
ICAM1	-0.011	0.065	-10000	0	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.024	0.089	-10000	0	-0.37	14	14
cell adhesion	0.001	0.12	-10000	0	-0.49	18	18
NFKB1	-0.11	0.26	0.33	1	-0.5	129	130
THY1	0.026	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	0.021	0.028	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.026	0.095	-10000	0	-0.48	9	9
IL6	-0.19	0.38	-10000	0	-0.96	88	88
ITGB2	-0.001	0.058	-10000	0	-0.46	2	2
elevation of cytosolic calcium ion concentration	-0.02	0.11	-10000	0	-0.52	5	5
alphaM/beta2 Integrin/JAM2/JAM3	0.026	0.094	-10000	0	-0.47	9	9
JAM2	0.021	0.063	-10000	0	-0.67	4	4
alphaM/beta2 Integrin/ICAM1	0.034	0.1	-10000	0	-0.52	8	8
alphaM/beta2 Integrin/uPA/Plg	0.009	0.098	-10000	0	-0.52	5	5
RhoA/GTP	-0.026	0.1	-10000	0	-0.36	19	19
positive regulation of phagocytosis	-0.007	0.096	-10000	0	-0.49	7	7
Ron/MSP	0.034	0.056	-10000	0	-0.51	5	5
alphaM/beta2 Integrin/uPAR/uPA	-0.02	0.11	-10000	0	-0.52	5	5
alphaM/beta2 Integrin/uPAR	0.007	0.094	-10000	0	-0.55	5	5
PLAU	-0.045	0.077	-10000	0	-10000	0	0
PLAT	0.02	0.058	-10000	0	-0.67	3	3
actin filament polymerization	-0.029	0.095	-10000	0	-0.4	9	9
MST1	0.026	0.032	-10000	0	-0.67	1	1
alphaM/beta2 Integrin/lipoprotein(a)	0.018	0.083	-10000	0	-0.5	5	5
TNF	-0.16	0.35	-10000	0	-0.92	73	73
RAP1B	0.027	0.005	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.004	0.099	-10000	0	-0.51	6	6
fibrinolysis	0.008	0.097	-10000	0	-0.52	5	5
HCK	0.017	0.039	-10000	0	-10000	0	0
dendritic cell antigen processing and presentation	-0.024	0.089	-10000	0	-0.37	14	14
VTN	-0.038	0.2	-10000	0	-0.67	44	44
alphaM/beta2 Integrin/CYR61	-0.12	0.23	-10000	0	-0.47	146	146
LPA	-0.005	0.026	-10000	0	-10000	0	0
LRP1	0.025	0.032	-10000	0	-0.67	1	1
cell migration	-0.031	0.16	-10000	0	-0.49	45	45
FN1	-0.085	0.069	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Thy1	0.016	0.086	-10000	0	-0.56	5	5
MPO	0.012	0.078	-10000	0	-0.67	6	6
KNG1	-0.005	0.038	-10000	0	-10000	0	0
RAP1/GDP	0.035	0.009	-10000	0	-10000	0	0
ROCK1	-0.024	0.098	-10000	0	-0.43	7	7
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.014	0.02	-10000	0	-10000	0	0
CTGF	-0.078	0.25	-10000	0	-0.66	76	76
alphaM/beta2 Integrin/Hck	0.011	0.092	-10000	0	-0.51	6	6
ITGAM	-0.005	0.081	-10000	0	-0.62	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.02	0.1	-10000	0	-0.52	10	10
HP	-0.023	0.098	-10000	0	-0.67	6	6
leukocyte adhesion	-0.025	0.16	-10000	0	-0.46	35	35
SELP	0.015	0.078	-10000	0	-0.67	6	6

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.04	0.12	0.89	7	-10000	0	7
VDR	0.026	0.009	-10000	0	-10000	0	0
FAM120B	0.027	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.006	0.11	-10000	0	-0.41	8	8
RXRs/LXRs/DNA/Oxysterols	-0.01	0.15	-10000	0	-0.42	51	51
MED1	0.026	0.007	-10000	0	-10000	0	0
mol:9cRA	-0.001	0.018	-10000	0	-0.14	1	1
RARs/THRs/DNA/Src-1	0.02	0.069	-10000	0	-0.3	21	21
RXRs/NUR77	-0.091	0.24	-10000	0	-0.45	136	136
RXRs/PPAR	-0.021	0.081	-10000	0	-0.38	11	11
NCOR2	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.006	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.049	0.074	-10000	0	-0.39	13	13
RARA	0.026	0.007	-10000	0	-10000	0	0
NCOA1	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.009	-10000	0	-10000	0	0
RARs/RARs/DNA/9cRA	0.032	0.071	-10000	0	-0.37	14	14
RARG	0.027	0.005	-10000	0	-10000	0	0
RPS6KB1	0.051	0.12	0.56	27	-10000	0	27
RARs/THRs/DNA/SMRT	0.021	0.069	-10000	0	-0.3	21	21
THRA	0.026	0.007	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.02	0.006	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.036	0.097	-10000	0	-0.44	5	5
NR1H4	-0.004	0.022	-10000	0	-10000	0	0
RXRs/LXRs/DNA	0.057	0.12	-10000	0	-0.5	4	4
NR1H2	0.022	0.024	-10000	0	-10000	0	0
NR1H3	0.023	0.026	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.048	0.08	-10000	0	-0.45	3	3
NR4A1	-0.18	0.32	-10000	0	-0.67	146	146
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.003	0.054	-10000	0	-0.31	3	3
RXRG	-0.11	0.077	-10000	0	-0.7	4	4
RXR alpha/CCPG	0.032	0.025	-10000	0	-10000	0	0
RXRA	0.021	0.025	-10000	0	-10000	0	0
RXRB	0.023	0.026	-10000	0	-10000	0	0
THRB	0.014	0.095	-10000	0	-0.64	10	10
PPARG	0.016	0.083	-10000	0	-0.67	7	7
PPARD	0.027	0.003	-10000	0	-10000	0	0
TNF	-0.097	0.37	-10000	0	-1.1	57	57
mol:Oxysterols	0	0.016	-10000	0	-10000	0	0
cholesterol transport	-0.009	0.15	-10000	0	-0.42	51	51
PPARA	0.02	0.012	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.007	0.12	-10000	0	-0.67	14	14
RXRs/NUR77/BCL2	-0.11	0.17	-10000	0	-0.34	157	157
SREBF1	-0.011	0.14	-10000	0	-0.53	7	7
RXRs/RXRs/DNA/9cRA	0.037	0.097	-10000	0	-0.44	5	5
ABCA1	-0.01	0.14	-10000	0	-0.59	4	4
RARs/THRs	0.056	0.098	-10000	0	-0.4	20	20
RXRs/FXR	0.047	0.085	-10000	0	-0.48	3	3
BCL2	-0.026	0.18	-10000	0	-0.67	38	38

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.027	0.005	-10000	0	-10000	0	0
mol:PIP3	-0.03	0.11	-10000	0	-0.33	58	58
FRAP1	0.01	0.047	0.33	4	-0.42	1	5
AKT1	-0.026	0.096	-10000	0	-0.28	55	55
INSR	0.025	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.024	0.037	-10000	0	-0.43	3	3
mol:GTP	0.004	0.089	-10000	0	-0.42	3	3
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0.007	0.036	-10000	0	-0.24	1	1
TSC2	0.026	0.006	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.074	-10000	0	-0.39	3	3
TSC1	0.025	0.008	-10000	0	-10000	0	0
Insulin Receptor/IRS1	-0.023	0.13	-10000	0	-0.38	59	59
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.016	0.044	-10000	0	-0.27	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.027	0.004	-10000	0	-10000	0	0
RPS6KB1	0.019	0.098	0.37	20	-0.37	3	23
MAP3K5	0.006	0.028	0.18	1	-0.22	6	7
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
apoptosis	0.006	0.029	0.18	1	-0.21	7	8
mol:LY294002	0	0.001	0.001	1	-0.002	72	73
EIF4B	0.024	0.11	0.46	21	-0.32	3	24
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.027	0.069	0.35	5	-0.31	3	8
eIF4E/eIF4G1/eIF4A1	0.016	0.024	-10000	0	-0.25	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.007	0.13	-10000	0	-0.36	59	59
mTOR/RHEB/GTP/Raptor/GBL	0.004	0.047	0.28	3	-0.24	2	5
FKBP1A	0.027	0.005	-10000	0	-10000	0	0
RHEB/GTP	0.012	0.08	-10000	0	-0.38	3	3
mol:Amino Acids	0	0.001	0.001	1	-0.002	72	73
FKBP12/Rapamycin	0.02	0.004	-10000	0	-10000	0	0
PDPK1	-0.032	0.11	-10000	0	-0.32	57	57
EIF4E	0.027	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.026	0.074	-10000	0	-0.5	8	8
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.018	0.008	-10000	0	-10000	0	0
TSC1/TSC2	0.006	0.096	0.28	1	-0.46	3	4
tumor necrosis factor receptor activity	0	0.001	0.002	72	-0.001	1	73
RPS6	0.025	0.008	-10000	0	-10000	0	0
PPP5C	0.025	0.008	-10000	0	-10000	0	0
EIF4G1	0.027	0.004	-10000	0	-10000	0	0
IRS1	-0.042	0.14	-10000	0	-0.37	67	67
INS	-0.02	0.051	-10000	0	-0.67	3	3
PTEN	0.025	0.018	-10000	0	-0.36	1	1
PDK2	-0.029	0.1	0.22	3	-0.31	55	58
EIF4EBP1	0.016	0.096	-10000	0	-0.93	5	5
PIK3CA	0.023	0.055	-10000	0	-0.68	3	3
PPP2R5D	0.02	0.074	0.38	14	-0.38	1	15
peptide biosynthetic process	0.011	0.034	-10000	0	-0.39	3	3
RHEB	0.026	0.006	-10000	0	-10000	0	0
EIF4A1	0.026	0.007	-10000	0	-10000	0	0
mol:Rapamycin	0	0.002	0.009	19	-0.003	3	22
EEF2	0.011	0.034	-10000	0	-0.39	3	3
eIF4E/4E-BP1	0.03	0.088	-10000	0	-0.83	5	5

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.033	0.04	-10000	0	-0.82	1	1
VEGFR1 homodimer/NRP1	0.015	0.038	-10000	0	-0.82	1	1
mol:DAG	-0.022	0.13	-10000	0	-0.4	51	51
VEGFR1 homodimer/NRP1/VEGFR 121	0.028	0.059	-10000	0	-0.64	3	3
CaM/Ca2+	-0.006	0.13	-10000	0	-0.38	51	51
HIF1A	0.033	0.019	-10000	0	-0.37	1	1
GAB1	0.027	0.004	-10000	0	-10000	0	0
AKT1	-0.02	0.14	-10000	0	-0.7	4	4
PLCG1	-0.022	0.13	-10000	0	-0.4	51	51
NOS3	-0.012	0.12	-10000	0	-0.53	3	3
CBL	0.027	0.005	-10000	0	-10000	0	0
mol:NO	-0.007	0.12	0.47	3	-0.5	3	6
FLT1	0.02	0.042	-10000	0	-0.91	1	1
PGF	-0.045	0.21	-10000	0	-0.67	51	51
VEGFR1 homodimer/NRP2/VEGFR121	0.045	0.062	-10000	0	-0.64	3	3
CALM1	0.027	0.005	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
eNOS/Hsp90	0.005	0.12	-10000	0	-0.74	1	1
endothelial cell proliferation	-0.037	0.15	0.36	2	-0.43	49	51
mol:Ca2+	-0.022	0.13	-10000	0	-0.4	51	51
MAPK3	-0.038	0.13	0.36	2	-0.99	1	3
MAPK1	-0.042	0.13	-10000	0	-0.41	12	12
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
PLGF homodimer	-0.044	0.21	-10000	0	-0.67	51	51
PRKACA	0.025	0.008	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.014	0.094	-10000	0	-0.67	9	9
VEGFA homodimer	0.023	0.054	-10000	0	-0.67	3	3
VEGFR1 homodimer/VEGFA homodimer	0.031	0.063	-10000	0	-0.68	3	3
platelet activating factor biosynthetic process	-0.041	0.12	-10000	0	-0.96	1	1
PI3K	0.015	0.14	-10000	0	-0.39	52	52
PRKCA	-0.039	0.14	-10000	0	-0.38	65	65
PRKCB	-0.034	0.13	-10000	0	-0.38	54	54
VEGFR1 homodimer/PLGF homodimer	-0.014	0.15	-10000	0	-0.44	51	51
VEGFA	0.023	0.054	-10000	0	-0.67	3	3
VEGFB	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	-0.022	0.13	-10000	0	-0.4	51	51
RASA1	0.02	0.038	-10000	0	-0.76	1	1
NRP2	0.014	0.043	-10000	0	-10000	0	0
VEGFR1 homodimer	0.02	0.042	-10000	0	-0.91	1	1
VEGFB homodimer	0.027	0.005	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.002	0.14	0.55	4	-0.62	4	8
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
mol:PI-3-4-5-P3	0.013	0.14	-10000	0	-0.38	52	52
mol:L-citrulline	-0.007	0.12	0.47	3	-0.5	3	6
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.058	0.062	-10000	0	-0.61	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.045	0.061	-10000	0	-0.64	3	3
CD2AP	0.027	0.003	-10000	0	-10000	0	0
PI3K/GAB1	0.025	0.14	-10000	0	-0.37	52	52
PDPK1	-0.017	0.13	0.34	3	-0.38	47	50
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.044	0.074	-10000	0	-0.75	3	3
mol:NADP	-0.007	0.12	0.47	3	-0.5	3	6
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.056	0.06	-10000	0	-0.6	3	3
VEGFR1 homodimer/NRP2	0.026	0.047	-10000	0	-0.82	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.017	0.31	0.78	2	-0.92	12	14
PLK1	0.029	0.095	-10000	0	-0.82	5	5
BIRC5	0.025	0.1	-10000	0	-0.93	4	4
HSPA1B	-0.023	0.31	-10000	0	-0.92	12	12
MAP2K1	0.025	0.045	-10000	0	-10000	0	0
BRCA2	-0.025	0.32	0.79	1	-0.97	16	17
FOXM1	-0.048	0.34	-10000	0	-0.95	23	23
XRCC1	-0.014	0.31	-10000	0	-0.89	13	13
FOXM1B/p19	-0.047	0.33	-10000	0	-0.87	29	29
Cyclin D1/CDK4	0	0.29	-10000	0	-0.83	11	11
CDC2	-0.026	0.32	0.61	1	-0.85	23	24
TGFA	-0.014	0.29	-10000	0	-0.8	14	14
SKP2	-0.019	0.32	0.78	2	-0.92	19	21
CCNE1	0.027	0.01	-10000	0	-10000	0	0
CKS1B	-0.023	0.31	-10000	0	-0.82	23	23
RB1	0.026	0.19	-10000	0	-0.72	7	7
FOXM1C/SP1	-0.029	0.33	-10000	0	-0.92	23	23
AURKB	0.009	0.13	-10000	0	-0.83	9	9
CENPF	-0.012	0.31	0.78	1	-0.91	12	13
CDK4	0.027	0.019	-10000	0	-10000	0	0
MYC	-0.029	0.31	-10000	0	-0.86	23	23
CHEK2	0.02	0.04	-10000	0	-10000	0	0
ONECUT1	-0.012	0.3	-10000	0	-0.82	17	17
CDKN2A	-0.033	0.073	-10000	0	-10000	0	0
LAMA4	-0.023	0.31	-10000	0	-0.91	13	13
FOXM1B/HNF6	-0.019	0.32	-10000	0	-0.93	17	17
FOS	-0.22	0.59	0.78	2	-1.2	129	131
SP1	0.027	0.009	-10000	0	-10000	0	0
CDC25B	-0.018	0.31	0.79	1	-0.93	11	12
response to radiation	0.006	0.026	-10000	0	-10000	0	0
CENPB	-0.018	0.31	0.79	1	-0.92	12	13
CENPA	-0.032	0.32	-10000	0	-0.89	22	22
NEK2	-0.012	0.31	0.78	1	-0.93	11	12
HIST1H2BA	-0.029	0.31	-10000	0	-0.91	13	13
CCNA2	0.026	0.022	-10000	0	-10000	0	0
EP300	0.02	0.012	-10000	0	-10000	0	0
CCNB1/CDK1	-0.034	0.33	-10000	0	-0.96	18	18
CCNB2	-0.025	0.31	-10000	0	-0.92	12	12
CCNB1	-0.024	0.32	0.66	2	-0.89	18	20
ETV5	-0.023	0.31	-10000	0	-0.86	17	17
ESR1	-0.059	0.38	-10000	0	-1.1	28	28
CCND1	-0.006	0.29	0.58	1	-0.84	12	13
GSK3A	0.022	0.038	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	0.052	0.043	-10000	0	-10000	0	0
CDK2	0.028	0.008	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.009	0.032	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.036	0.31	-10000	0	-0.87	21	21
GAS1	-0.17	0.55	0.79	1	-1.2	99	100
MMP2	-0.024	0.34	0.78	2	-1.1	14	16
RB1/FOXM1C	-0.005	0.29	-10000	0	-0.89	11	11
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

Figure S61. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S61. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.002	0.044	-10000	0	-0.44	5	5
ADCY5	-0.054	0.15	-10000	0	-0.44	66	66
ADCY6	0.002	0.044	-10000	0	-0.44	5	5
ADCY7	0.002	0.044	-10000	0	-0.44	5	5
ADCY1	-0.002	0.065	-10000	0	-0.49	8	8
ADCY2	-0.038	0.13	-10000	0	-0.44	46	46
ADCY3	0.002	0.044	-10000	0	-0.44	5	5
ADCY8	-0.05	0.054	-10000	0	-0.49	5	5
PRKCE	0.004	0.052	-10000	0	-0.51	5	5
ADCY9	0.002	0.044	-10000	0	-0.44	5	5
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.035	0.096	0.34	7	-0.36	16	23

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.025	0.025	0.37	1	-10000	0	1
HSPA8	0.02	0.057	-10000	0	-0.6	4	4
SMAD3/SMAD4/ER alpha	-0.002	0.13	-10000	0	-0.48	21	21
AKT1	0.026	0.007	-10000	0	-10000	0	0
GSC	-0.17	0.49	-10000	0	-1.4	67	67
NKX2-5	0.002	0.002	-10000	0	-10000	0	0
muscle cell differentiation	-0.012	0.081	0.38	1	-10000	0	1
SMAD2-3/SMAD4/SP1	0.037	0.096	-10000	0	-0.31	1	1
SMAD4	-0.006	0.071	-10000	0	-0.26	1	1
CBFB	0.026	0.006	-10000	0	-10000	0	0
SAP18	0.025	0.007	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.034	0.072	-10000	0	-0.44	3	3
SMAD3/SMAD4/VDR	0.048	0.074	-10000	0	-10000	0	0
MYC	0.012	0.1	-10000	0	-0.65	12	12
CDKN2B	-0.021	0.11	-10000	0	-0.47	3	3
AP1	-0.19	0.41	-10000	0	-0.76	150	150
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.029	0.063	-10000	0	-0.51	3	3
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.01	0.035	-10000	0	-10000	0	0
SP3	0.029	0.005	-10000	0	-10000	0	0
CREB1	0.027	0.005	-10000	0	-10000	0	0
FOXH1	0.005	0.053	-10000	0	-0.23	1	1
SMAD3/SMAD4/GR	0.021	0.079	-10000	0	-10000	0	0
GATA3	-0.01	0.15	-10000	0	-0.63	25	25
SKI/SIN3/HDAC complex/NCoR1	0.028	0.041	-10000	0	-0.65	1	1
MEF2C/TIF2	-0.026	0.15	0.32	3	-0.4	42	45
endothelial cell migration	-0.022	0.079	1.3	1	-10000	0	1
MAX	0.026	0.005	-10000	0	-10000	0	0
RBBP7	0.025	0.007	-10000	0	-10000	0	0
RBBP4	0.024	0.045	-10000	0	-0.67	2	2
RUNX2	-0.015	0.08	-10000	0	-0.67	2	2
RUNX3	0.009	0.1	-10000	0	-0.67	11	11
RUNX1	-0.04	0.076	-10000	0	-10000	0	0
CTBP1	0.027	0.004	-10000	0	-10000	0	0
NR3C1	0.026	0.006	-10000	0	-10000	0	0
VDR	0.026	0.009	-10000	0	-10000	0	0
CDKN1A	0.019	0.047	-10000	0	-10000	0	0
KAT2B	0.029	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.014	0.12	-10000	0	-0.29	37	37
DCP1A	0.027	0.003	-10000	0	-10000	0	0
SKI	0.026	0.006	-10000	0	-10000	0	0
SERPINE1	0.022	0.079	-10000	0	-1.3	1	1
SMAD3/SMAD4/ATF2	0.003	0.13	-10000	0	-0.46	23	23
SMAD3/SMAD4/ATF3	-0.079	0.24	-10000	0	-0.51	109	109
SAP30	0.025	0.032	-10000	0	-0.68	1	1
Cbp/p300/PIAS3	0.048	0.044	-10000	0	-10000	0	0
JUN	-0.2	0.4	0.3	1	-0.76	150	151
SMAD3/SMAD4/IRF7	0.025	0.08	-10000	0	-10000	0	0
TFE3	0.03	0.009	-10000	0	-10000	0	0
COL1A2	0.026	0.064	-10000	0	-1.1	1	1
mesenchymal cell differentiation	-0.014	0.097	0.34	5	-10000	0	5
DLX1	-0.009	0.15	-10000	0	-0.65	26	26
TCF3	0.025	0.008	-10000	0	-10000	0	0
FOS	-0.17	0.33	-10000	0	-0.73	125	125
SMAD3/SMAD4/Max	0.02	0.08	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.042	0.036	-10000	0	-0.42	1	1
ZBTB17	0.028	0.006	-10000	0	-10000	0	0
LAMC1	0.012	0.06	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.022	0.08	-10000	0	-0.25	3	3
IRF7	0.027	0.01	-10000	0	-10000	0	0
ESR1	-0.015	0.15	-10000	0	-0.65	23	23
HNF4A	-0.009	0.024	-10000	0	-10000	0	0
MEF2C	-0.006	0.1	0.38	4	-0.88	1	5
SMAD2-3/SMAD4	0.012	0.095	-10000	0	-0.29	2	2
Cbp/p300/Src-1	0.046	0.035	-10000	0	-10000	0	0
IGHV3OR16-13	0.001	0.034	-10000	0	-0.34	3	3
TGIF2/HDAC complex	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.029	0.011	-10000	0	-10000	0	0
SKIL	0.026	0.032	-10000	0	-0.67	1	1
HDAC1	0.026	0.005	-10000	0	-10000	0	0
HDAC2	0.027	0.004	-10000	0	-10000	0	0
SNIP1	0.024	0.032	-10000	0	-0.67	1	1
GCN5L2	0.004	0.013	0.2	1	-10000	0	1
SMAD3/SMAD4/TFE3	0.03	0.08	-10000	0	-0.27	1	1
MSG1/HSC70	-0.068	0.07	-10000	0	-0.47	8	8
SMAD2	0.012	0.047	-10000	0	-10000	0	0
SMAD3	0.005	0.06	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.067	-10000	0	-0.34	9	9
SMAD2/SMAD2/SMAD4	0.004	0.036	0.23	3	-10000	0	3
NCOR1	0.025	0.007	-10000	0	-10000	0	0
NCOA2	-0.037	0.2	-10000	0	-0.67	45	45
NCOA1	0.027	0.005	-10000	0	-10000	0	0
MYOD/E2A	0.029	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.046	0.094	-10000	0	-10000	0	0
IFNB1	0	0.058	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.01	0.11	-10000	0	-0.61	2	2
CITED1	-0.1	0.081	-10000	0	-0.61	5	5
SMAD2-3/SMAD4/ARC105	0.013	0.085	-10000	0	-10000	0	0
RBL1	0.014	0.094	-10000	0	-0.67	9	9
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.012	0.035	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	0.043	0.077	-10000	0	-0.43	11	11
SMAD7	-0.087	0.25	-10000	0	-0.52	106	106
MYC/MIZ-1	0.028	0.083	-10000	0	-0.49	12	12
SMAD3/SMAD4	0.022	0.11	0.3	26	-0.52	1	27
IL10	-0.03	0.15	-10000	0	-0.52	35	35
PIASy/HDAC complex	0.018	0.02	-10000	0	-10000	0	0
PIAS3	0.027	0.008	-10000	0	-10000	0	0
CDK2	0.03	0.011	-10000	0	-10000	0	0
IL5	-0.022	0.11	-10000	0	-0.4	24	24
CDK4	0.031	0.011	-10000	0	-10000	0	0
PIAS4	0.018	0.02	-10000	0	-10000	0	0
ATF3	-0.13	0.29	-10000	0	-0.67	110	110
SMAD3/SMAD4/SP1	0.033	0.083	-10000	0	-0.29	1	1
FOXG1	0.007	0.043	-10000	0	-0.68	1	1
FOXO3	0.015	0.008	-10000	0	-10000	0	0
FOXO1	0.014	0.009	-10000	0	-10000	0	0
FOXO4	0.014	0.008	-10000	0	-10000	0	0
heart looping	-0.006	0.1	0.38	4	-0.86	1	5
CEBPB	0.026	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.003	0.14	-10000	0	-0.49	24	24
MYOD1	-0.013	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	0.016	0.081	-10000	0	-0.26	4	4
SMAD3/SMAD4/GATA3	0	0.14	-10000	0	-0.41	35	35
SnoN/SIN3/HDAC complex/NCoR1	0.026	0.032	-10000	0	-0.67	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.028	0.12	-10000	0	-0.48	10	10
SMAD3/SMAD4/SP1-3	0.053	0.081	-10000	0	-10000	0	0
MED15	0.02	0.012	-10000	0	-10000	0	0
SP1	0.03	0.015	-10000	0	-10000	0	0
SIN3B	0.025	0.008	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.022	0.11	-10000	0	-0.28	23	23
ITGB5	0.015	0.06	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.031	0.034	-10000	0	-0.49	1	1
SMAD3/SMAD4/AR	-0.18	0.26	-10000	0	-0.48	200	200
AR	-0.26	0.34	-10000	0	-0.66	206	206
negative regulation of cell growth	-0.022	0.12	-10000	0	-0.36	12	12
SMAD3/SMAD4/MYOD	0.016	0.08	-10000	0	-10000	0	0
E2F5	0.025	0.032	-10000	0	-0.67	1	1
E2F4	0.026	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.027	0.096	-10000	0	-0.33	2	2
SMAD2-3/SMAD4/FOXO1-3a-4	0.013	0.036	-10000	0	-10000	0	0
TFDP1	0.025	0.018	-10000	0	-0.36	1	1
SMAD3/SMAD4/AP1	-0.18	0.43	-10000	0	-0.78	150	150
SMAD3/SMAD4/RUNX2	0.015	0.097	-10000	0	-0.34	5	5
TGIF2	0.027	0.005	-10000	0	-10000	0	0
TGIF1	0.027	0.005	-10000	0	-10000	0	0
ATF2	-0.002	0.14	-10000	0	-0.66	21	21

×

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	0.03	0.074	-9999	-0.38	15	15
RGS9BP	-0.015	0.16	-9999	-0.66	29	29
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.038	0.2	-9999	-0.65	46	46
mol:Na +	0.017	0.034	-9999	-10000	0	0
mol:ADP	-0.043	0.15	-9999	-0.5	45	45
GNAT2	0.016	0.02	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.022	0.18	-9999	-0.45	71	71
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.028	0.01	-9999	-10000	0	0
GRK7	0.005	0.022	-9999	-10000	0	0
CNGB3	-0.008	0.017	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.014	0.005	-9999	-10000	0	0
mol:Ca2+	-0.01	0.029	-9999	-10000	0	0
Cone PDE6	-0.003	0.16	-9999	-0.4	70	70
Cone Metarhodopsin II	-0.01	0.12	-9999	-0.4	45	45
Na + (4 Units)	0.022	0.039	-9999	-10000	0	0
GNAT2/GDP	-0.008	0.16	-9999	-0.39	68	68
GNB5	0.027	0.004	-9999	-10000	0	0
mol:GMP (4 units)	-0.003	0.022	-9999	-10000	0	0
Cone Transducin	0.033	0.079	-9999	-0.4	15	15
SLC24A2	-0.008	0.031	-9999	-10000	0	0
GNB3/GNGT2	0.021	0.094	-9999	-0.51	15	15
GNB3	0.007	0.12	-9999	-0.67	14	14
GNAT2/GTP	0.017	0.008	-9999	-10000	0	0
CNGA3	0.007	0.052	-9999	-10000	0	0
ARR3	-0.002	0.02	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.017	0.034	-9999	-10000	0	0
mol:Pi	-0.022	0.18	-9999	-0.45	71	71
Cone CNG Channel	0.042	0.034	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.008	0.031	-9999	-10000	0	0
RGS9	-0.039	0.2	-9999	-0.67	45	45
PDE6C	-0.005	0.02	-9999	-10000	0	0
GNGT2	0.023	0.035	-9999	-0.67	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.003	0.02	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.018	0.12	-10000	0	-0.45	25	25
MAP4K1	0.008	0.079	-10000	0	-0.67	5	5
MAP3K8	0.018	0.079	-10000	0	-0.63	7	7
PRKCB	0.007	0.08	-10000	0	-0.67	5	5
DBNL	0.026	0.006	-10000	0	-10000	0	0
CRKL	0.02	0.012	-10000	0	-10000	0	0
MAP3K1	0.002	0.081	-10000	0	-0.41	9	9
JUN	-0.084	0.21	0.37	1	-0.51	56	57
MAP3K7	0.002	0.081	-10000	0	-0.41	9	9
GRAP2	-0.02	0.15	-10000	0	-0.56	33	33
CRK	0.026	0.007	-10000	0	-10000	0	0
MAP2K4	-0.003	0.097	0.34	3	-0.37	17	20
LAT	0.021	0.058	-10000	0	-0.6	4	4
LCP2	0.024	0.021	-10000	0	-10000	0	0
MAPK8	-0.007	0.15	-10000	0	-0.62	25	25
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.005	0.085	-10000	0	-0.34	25	25
LAT/GRAP2/SLP76/HPK1/HIP-55	0.026	0.12	-10000	0	-0.44	23	23

×

p75(NTR)-mediated 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
Sortilin/TRAF6	0.037	0.036	-10000	0	-0.51	2	2
Necdin/E2F1	-0.002	0.078	-10000	0	-0.55	5	5
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.057	0.091	-10000	0	-0.4	16	16
NGF (dimer)/p75(NTR)/BEX1	-0.18	0.25	-10000	0	-0.44	227	227
NT-4/5 (dimer)/p75(NTR)	-0.012	0.14	-10000	0	-0.52	30	30
IKBKB	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.005	0.097	0.36	1	-0.4	19	20
IKBKG	0.025	0.008	-10000	0	-10000	0	0
BDNF	0.008	0.1	-10000	0	-0.67	11	11
MGDIs/NGR/p75(NTR)/LINGO1	0.022	0.092	-10000	0	-0.45	16	16
FURIN	0.027	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	0.026	0.11	-10000	0	-0.42	27	27
LINGO1	0.02	0.032	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.031	0.028	-10000	0	-0.35	2	2
proBDNF (dimer)	0.008	0.1	-10000	0	-0.67	11	11
NTRK1	0.01	0.031	-10000	0	-10000	0	0
RTN4R	0.02	0.012	-10000	0	-10000	0	0
neuron apoptosis	0.023	0.13	0.46	10	-0.56	3	13
IRAK1	0.025	0.008	-10000	0	-10000	0	0
SHC1	-0.006	0.09	-10000	0	-0.46	15	15
ARHGDIA	0.026	0.007	-10000	0	-10000	0	0
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.07	0.03	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.047	0.092	-10000	0	-0.43	16	16
MAGEH1	0.026	0.007	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.045	0.1	-10000	0	-0.42	20	20
Mammalian IAPs/DIABLO	0.046	0.094	-10000	0	-0.39	20	20
proNGF (dimer)	0.021	0.056	-10000	0	-0.67	3	3
MAGED1	0.026	0.007	-10000	0	-10000	0	0
APP	0.026	0.006	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.002	0.12	-10000	0	-0.65	15	15
ZNF274	0.025	0.007	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	0.012	0.085	-10000	0	-0.4	16	16
NGF	0.022	0.056	-10000	0	-0.67	3	3
cell cycle arrest	0.057	0.14	0.46	16	-0.38	16	32
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.016	0.069	-10000	0	-0.32	18	18
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.018	0.13	-10000	0	-0.45	32	32
NCSTN	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	0.034	0.097	-10000	0	-0.46	17	17
PSENEN	0.026	0.007	-10000	0	-10000	0	0
mol:ceramide	0.003	0.092	-10000	0	-0.42	16	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.019	0.059	-10000	0	-0.38	4	4
p75(NTR)/beta APP	0.005	0.1	-10000	0	-0.51	16	16
BEX1	-0.28	0.35	-10000	0	-0.67	218	218
mol:GDP	-0.018	0.088	-10000	0	-0.44	18	18
NGF (dimer)	0.036	0.11	-10000	0	-0.41	27	27
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.034	0.09	-10000	0	-0.41	16	16
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
RAC1/GTP	0.03	0.083	-10000	0	-0.4	16	16
MYD88	0.027	0.003	-10000	0	-10000	0	0
CHUK	0.027	0.004	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.034	0.098	-10000	0	-0.46	17	17
RHOB	0.027	0.005	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.004	0.055	-10000	0	-10000	0	0
NT3 (dimer)	-0.016	0.15	-10000	0	-0.67	25	25
TP53	-0.003	0.099	0.35	1	-0.36	25	26
PRDM4	0.001	0.09	-10000	0	-0.42	16	16
BDNF (dimer)	-0.011	0.14	-10000	0	-0.44	34	34
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
SORT1	0.027	0.005	-10000	0	-10000	0	0
activation of caspase activity	0.051	0.088	-10000	0	-0.4	16	16
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.047	0.097	-10000	0	-0.43	18	18
RHOC	0.027	0.005	-10000	0	-10000	0	0
XIAP	0.026	0.007	-10000	0	-10000	0	0
MAPK10	0.015	0.11	0.34	16	-0.4	14	30
DIABLO	0.027	0.005	-10000	0	-10000	0	0
SMPD2	0.003	0.092	-10000	0	-0.42	16	16
APH1B	0.027	0.004	-10000	0	-10000	0	0
APH1A	0.025	0.007	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	0.035	0.095	-10000	0	-0.46	16	16
PSEN1	0.027	0.005	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.037	0.026	-10000	0	-0.51	1	1
NT3 (dimer)/p75(NTR)	-0.026	0.15	-10000	0	-0.51	40	40
MAPK8	0.01	0.12	0.35	14	-0.41	15	29
MAPK9	0.011	0.1	0.34	10	-0.39	13	23
APAF1	0.025	0.032	-10000	0	-0.67	1	1
NTF3	-0.017	0.16	-10000	0	-0.67	25	25
NTF4	0.002	0.12	-10000	0	-0.65	15	15
NDN	0.02	0.07	-10000	0	-0.67	5	5
RAC1/GDP	0.02	0.004	-10000	0	-10000	0	0
RhoA-B-C/GDP	0.052	0.085	-10000	0	-0.38	17	17
p75 CTF/Sortilin/TRAF6/NRIF	0.06	0.052	-10000	0	-0.52	3	3
RhoA-B-C/GTP	0.033	0.097	-10000	0	-0.46	17	17
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.048	0.11	-10000	0	-0.38	26	26
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.039	0.11	-10000	0	-0.4	27	27
PRKACB	0.025	0.032	-10000	0	-0.67	1	1
proBDNF (dimer)/p75 ECD	0.023	0.089	-10000	0	-0.51	13	13
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.01	0.15	-10000	0	-0.62	25	25
BIRC2	0.027	0.005	-10000	0	-10000	0	0
neuron projection morphogenesis	0.071	0.14	0.48	12	-0.43	12	24
BAD	0.027	0.14	0.44	25	-0.4	15	40
RIPK2	0.027	0.005	-10000	0	-10000	0	0
NGFR	-0.016	0.13	-10000	0	-0.67	16	16
CYCS	0.008	0.1	0.36	12	-0.4	16	28
ADAM17	0.024	0.045	-10000	0	-0.67	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.046	0.097	-10000	0	-0.43	18	18
BCL2L11	0.027	0.14	0.44	25	-0.4	15	40
BDNF (dimer)/p75(NTR)	-0.009	0.13	-10000	0	-0.51	27	27
PI3K	0.046	0.099	-10000	0	-0.43	19	19
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.049	0.092	-10000	0	-0.43	16	16
NDNL2	0.027	0.004	-10000	0	-10000	0	0
YWHAE	0.026	0.007	-10000	0	-10000	0	0
PRKCI	0.027	0.003	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	0.002	0.11	-10000	0	-0.51	18	18
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.047	0.092	-10000	0	-0.43	16	16
TRAF6	0.024	0.045	-10000	0	-0.67	2	2
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
PLG	-0.014	0.02	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.005	0.099	-10000	0	-0.4	26	26
SQSTM1	0.026	0.006	-10000	0	-10000	0	0
NGFRAP1	0.026	0.007	-10000	0	-10000	0	0
CASP3	0.031	0.14	0.44	26	-0.37	15	41
E2F1	-0.019	0.07	-10000	0	-10000	0	0
CASP9	0.027	0.005	-10000	0	-10000	0	0
IKK complex	0.051	0.074	-10000	0	-0.46	3	3
NGF (dimer)/TRKA	0.027	0.05	-10000	0	-0.51	3	3
MMP7	-0.079	0.16	-10000	0	-0.66	26	26
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.055	0.096	-10000	0	-0.4	18	18
MMP3	-0.018	0.049	-10000	0	-10000	0	0
APAF-1/Caspase 9	-0.014	0.095	-10000	0	-0.58	5	5

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.02	0.088	0.32	5	-0.42	12	17
ACTA1	0.008	0.1	0.34	6	-0.48	12	18
NUMA1	0.016	0.097	0.3	4	-0.48	13	17
SPTAN1	0.006	0.1	0.37	5	-0.49	11	16
LIMK1	0.012	0.11	0.45	8	-0.51	10	18
BIRC3	-0.01	0.15	-10000	0	-0.62	25	25
BIRC2	0.027	0.005	-10000	0	-10000	0	0
BAX	0.025	0.01	-10000	0	-10000	0	0
CASP10	-0.011	0.089	-10000	0	-0.54	12	12
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.026	0.007	-10000	0	-10000	0	0
PTK2	0.014	0.099	0.39	2	-0.46	14	16
DIABLO	0.027	0.005	-10000	0	-10000	0	0
apoptotic nuclear changes	0.006	0.1	0.35	6	-0.48	11	17
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.027	0.005	-10000	0	-10000	0	0
GSN	0.006	0.1	0.37	5	-0.48	12	17
MADD	0.027	0.005	-10000	0	-10000	0	0
TFAP2A	-0.042	0.22	-10000	0	-0.61	62	62
BID	-0.012	0.061	-10000	0	-0.32	12	12
MAP3K1	0.018	0.042	0.27	3	-10000	0	3
TRADD	0.026	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.038	0.026	-10000	0	-0.51	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.009	0.11	0.45	8	-0.51	10	18
CASP9	0.027	0.006	-10000	0	-10000	0	0
DNA repair	-0.017	0.063	0.42	4	-0.21	19	23
neuron apoptosis	0.009	0.11	-10000	0	-0.55	15	15
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.016	0.11	0.35	4	-0.51	13	17
APAF1	0.025	0.032	-10000	0	-0.67	1	1
CASP6	0.02	0.086	0.39	1	-0.59	4	5
TRAF2	0.025	0.009	-10000	0	-10000	0	0
ICAD/CAD	0.012	0.11	0.4	14	-0.5	10	24
CASP7	0.007	0.097	0.31	22	-0.45	8	30
KRT18	0.021	0.04	-10000	0	-0.44	2	2
apoptosis	0.016	0.1	0.48	4	-0.46	11	15
DFFA	0.008	0.1	0.36	6	-0.49	11	17
DFFB	0.009	0.1	0.36	6	-0.49	11	17
PARP1	0.017	0.064	0.21	19	-0.43	4	23
actin filament polymerization	-0.017	0.12	0.47	10	-0.54	11	21
TNF	-0.056	0.22	-10000	0	-0.67	56	56
CYCS	-0.001	0.048	0.24	3	-0.22	10	13
SATB1	0.02	0.085	0.52	2	-0.55	4	6
SLK	0.004	0.1	0.46	3	-0.48	13	16
p15 BID/BAX	-0.011	0.07	-10000	0	-0.34	8	8
CASP2	-0.014	0.1	0.21	4	-0.37	18	22
JNK cascade	-0.018	0.041	-10000	0	-0.27	3	3
CASP3	0.005	0.1	0.38	4	-0.5	12	16
LMNB2	0.006	0.11	0.36	9	-0.41	12	21
RIPK1	0.027	0.003	-10000	0	-10000	0	0
CASP4	0.027	0.005	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.046	0.094	-10000	0	-0.4	20	20
negative regulation of DNA binding	-0.041	0.22	-10000	0	-0.6	62	62
stress fiber formation	0.004	0.1	0.46	3	-0.47	13	16
GZMB	-0.007	0.1	-10000	0	-0.61	12	12
CASP1	0.015	0.026	-10000	0	-0.39	2	2
LMNB1	0.02	0.087	0.33	11	-0.3	3	14
APP	0.009	0.11	-10000	0	-0.56	15	15
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
response to stress	0	0.001	-10000	0	-10000	0	0
CASP8	0.009	0.002	-10000	0	-10000	0	0
VIM	0.017	0.095	0.45	3	-0.46	10	13
LMNA	0.015	0.097	0.35	11	-0.4	6	17
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.013	0.11	-10000	0	-0.28	59	59
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.014	0.11	0.43	9	-0.53	9	18
APAF-1/Caspase 9	0.013	0.063	-10000	0	-0.55	4	4
nuclear fragmentation during apoptosis	0.016	0.096	0.29	5	-0.47	13	18
CFL2	0.017	0.12	0.54	11	-0.49	10	21
GAS2	0.002	0.1	0.36	4	-0.47	14	18
positive regulation of apoptosis	0.016	0.1	0.36	9	-0.36	9	18
PRF1	0.015	0.089	-10000	0	-0.68	8	8

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.025	0.032	-10000	0	-0.67	1	1
alphaV beta3 Integrin	0.025	0.089	-10000	0	-0.52	12	12
PTK2	0.008	0.15	-10000	0	-0.55	27	27
positive regulation of JNK cascade	0.013	0.099	-10000	0	-0.33	32	32
CDC42/GDP	0.029	0.14	0.44	1	-0.44	34	35
Rac1/GDP	0.029	0.14	-10000	0	-0.45	30	30
RAP1B	0.027	0.005	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.022	0.12	-10000	0	-0.4	32	32
nectin-3/I-afadin	0.007	0.13	-10000	0	-0.51	30	30
RAPGEF1	0.011	0.14	0.35	2	-0.51	29	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.008	0.16	-10000	0	-0.58	30	30
PDGFB-D/PDGFRB	0.025	0.032	-10000	0	-0.67	1	1
TLN1	-0.005	0.061	-10000	0	-0.79	1	1
Rap1/GTP	0.01	0.097	-10000	0	-0.36	29	29
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.014	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.007	0.13	-10000	0	-0.51	30	30
PVR	0.026	0.007	-10000	0	-10000	0	0
Necl-5(dimer)	0.026	0.007	-10000	0	-10000	0	0
mol:GDP	0.015	0.17	0.47	1	-0.55	36	37
MLLT4	0.027	0.004	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
PI3K	0.049	0.12	-10000	0	-0.42	29	29
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.037	0.02	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.008	0.11	-10000	0	-0.35	30	30
PVRL1	0.023	0.025	-10000	0	-10000	0	0
PVRL3	-0.016	0.17	-10000	0	-0.66	31	31
PVRL2	0.026	0.007	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
CDH1	0.026	0.006	-10000	0	-10000	0	0
CLDN1	-0.11	0.095	-10000	0	-0.61	10	10
JAM-A/CLDN1	0.037	0.13	-10000	0	-0.42	35	35
SRC	0.004	0.17	-10000	0	-0.64	31	31
ITGB3	0.011	0.1	-10000	0	-0.65	11	11
nectin-1(dimer)/I-afadin/I-afadin	0.037	0.02	-10000	0	-10000	0	0
FARP2	0.018	0.16	-10000	0	-0.54	35	35
RAC1	0.026	0.006	-10000	0	-10000	0	0
CTNNA1	0.026	0.006	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.022	0.12	-10000	0	-0.44	30	30
nectin-1/I-afadin	0.037	0.02	-10000	0	-10000	0	0
nectin-2/I-afadin	0.038	0.011	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.035	0.009	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.024	0.12	-10000	0	-0.44	30	30
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.008	-10000	0	-10000	0	0
F11R	0.025	0.007	-10000	0	-10000	0	0
positive regulation of filopodium formation	0.013	0.099	-10000	0	-0.33	32	32
alphaV/beta3 Integrin/Talin	0.023	0.11	-10000	0	-0.55	11	11
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
PIP5K1C	-0.003	0.066	-10000	0	-0.83	1	1
VAV2	-0.002	0.19	0.37	1	-0.59	34	35
RAP1/GDP	0.033	0.13	0.28	2	-0.42	31	33
ITGAV	0.024	0.045	-10000	0	-0.67	2	2
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.022	0.12	-10000	0	-0.44	30	30
nectin-3(dimer)/I-afadin/I-afadin	0.007	0.13	-10000	0	-0.51	30	30
Rac1/GTP	0.014	0.14	-10000	0	-0.44	30	30
PTPRM	0	0.073	-10000	0	-0.27	29	29
E-cadherin/beta catenin/alpha catenin	0.073	0.027	-10000	0	-10000	0	0
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.02	0.012	-10000	0	-10000	0	0
HDAC4	0.027	0.005	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.013	0.024	0.51	1	-10000	0	1
CDKN1A	-0.006	0.012	-10000	0	-10000	0	0
KAT2B	0.027	0.004	-10000	0	-10000	0	0
BAX	0.025	0.01	-10000	0	-10000	0	0
FOXO3	-0.004	0.007	-10000	0	-10000	0	0
FOXO1	0.026	0.007	-10000	0	-10000	0	0
FOXO4	0.014	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.02	0.012	-10000	0	-10000	0	0
TAT	0.011	0.025	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.008	0.01	-10000	0	-10000	0	0
PPARGC1A	-0.28	0.35	-10000	0	-0.67	220	220
FHL2	-0.028	0.19	-10000	0	-0.67	39	39
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.026	0.03	-10000	0	-0.51	1	1
HIST2H4A	0.013	0.024	-10000	0	-0.51	1	1
SIRT1/FOXO3a	0.039	0.053	-10000	0	-0.43	1	1
SIRT1	0.022	0.032	-10000	0	-0.68	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.046	0.028	-10000	0	-0.44	1	1
SIRT1/Histone H1b	-0.006	0.07	-10000	0	-0.3	12	12
apoptosis	-0.036	0.033	0.44	1	-10000	0	1
SIRT1/PGC1A	-0.18	0.24	-10000	0	-0.44	220	220
p53/SIRT1	0.028	0.027	-10000	0	-0.51	1	1
SIRT1/FOXO4	-0.004	0.064	-10000	0	-0.31	4	4
FOXO1/FHL2/SIRT1	0.009	0.12	-10000	0	-0.4	40	40
HIST1H1E	0.008	0.047	-10000	0	-0.34	8	8
SIRT1/p300	0.026	0.03	-10000	0	-0.51	1	1
muscle cell differentiation	-0.029	0.028	0.44	1	-10000	0	1
TP53	0.023	0.006	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.037	0.033	-10000	0	-0.44	1	1
CREBBP	0.026	0.006	-10000	0	-10000	0	0
MEF2D	0.025	0.007	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.031	0.029	-10000	0	-0.51	1	1
ACSS2	0.014	0.024	-10000	0	-0.51	1	1
SIRT1/PCAF/MYOD	0.029	0.028	-10000	0	-0.45	1	1

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.02	0.004	-9999	-10000	0	0
PRKCZ	0.026	0.006	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.027	0.005	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.016	0.06	-9999	-0.38	2	2
IRAK/TOLLIP	0.03	0.011	-9999	-10000	0	0
IKBKB	0.027	0.005	-9999	-10000	0	0
IKBKG	0.025	0.008	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.054	0.21	-9999	-0.53	73	73
IL1A	-0.029	0.18	-9999	-0.67	37	37
IL1B	-0.02	0.13	-9999	-0.51	33	33
IRAK/TRAF6/p62/Atypical PKCs	0.062	0.037	-9999	-0.36	2	2
IL1R2	-0.044	0.19	-9999	-0.66	42	42
IL1R1	0.027	0.005	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.008	0.049	-9999	-10000	0	0
TOLLIP	0.027	0.005	-9999	-10000	0	0
TICAM2	0.019	0.07	-9999	-0.67	5	5
MAP3K3	0.026	0.007	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.018	0.002	-9999	-10000	0	0
IKK complex/ELKS	0.038	0.059	-9999	-10000	0	0
JUN	-0.077	0.16	-9999	-0.37	111	111
MAP3K7	0.027	0.004	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.042	0.12	-9999	-0.38	32	32
IL1 alpha/IL1R1/IL1RAP/MYD88	0.036	0.13	-9999	-0.41	36	36
PIK3R1	0.027	0.005	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.047	0.12	-9999	-0.39	36	36
IL1 beta fragment/IL1R1/IL1RAP	0.018	0.12	-9999	-0.42	32	32
NFKB1	0.027	0.004	-9999	-10000	0	0
MAPK8	-0.003	0.086	-9999	-0.44	16	16
IRAK1	0.016	0.005	-9999	-10000	0	0
IL1RN/IL1R1	0.01	0.087	-9999	-0.48	11	11
IRAK4	0.027	0.005	-9999	-10000	0	0
PRKCI	0.027	0.003	-9999	-10000	0	0
TRAF6	0.024	0.045	-9999	-0.67	2	2
PI3K	0.036	0.043	-9999	-0.51	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.015	0.066	-9999	-0.38	3	3
CHUK	0.027	0.004	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.018	0.12	-9999	-0.42	32	32
IL1 beta/IL1R2	-0.042	0.18	-9999	-0.48	66	66
IRAK/TRAF6/TAK1/TAB1/TAB2	0.036	0.028	-9999	-0.36	2	2
NF kappa B1 p50/RelA	0.029	0.11	-9999	-0.36	32	32
IRAK3	0.027	0.005	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.04	0.12	-9999	-0.39	34	34
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.007	0.084	-9999	-0.29	36	36
IL1 alpha/IL1R1/IL1RAP	0.02	0.13	-9999	-0.44	36	36
RELA	0.027	0.005	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.026	0.006	-9999	-10000	0	0
MYD88	0.027	0.003	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.043	0.032	-9999	-0.38	2	2
IL1RAP	-0.013	0.068	-9999	-10000	0	0
UBE2N	0.027	0.005	-9999	-10000	0	0
IRAK/TRAF6	0.009	0.1	-9999	-0.38	11	11
CASP1	0.022	0.047	-9999	-0.67	2	2
IL1RN/IL1R2	-0.042	0.17	-9999	-0.54	47	47
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.032	0.12	-9999	-0.4	32	32
TMEM189-UBE2V1	0	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.012	0.07	-9999	-0.36	2	2
PIK3CA	0.023	0.054	-9999	-0.67	3	3
IL1RN	-0.011	0.11	-9999	-0.65	11	11
TRAF6/TAK1/TAB1/TAB2	0.037	0.027	-9999	-0.37	2	2
MAP2K6	0.01	0.06	-9999	-0.36	12	12

×

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

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
BAG4	0.025	0.032	-10000	0	-0.67	1	1
Caspase 8 (4 units)	0.023	0.09	-10000	0	-0.44	5	5
NEF	-0.014	0.067	-10000	0	-0.25	29	29
NFKBIA	0.021	0.032	-10000	0	-10000	0	0
BIRC3	-0.004	0.15	-10000	0	-0.65	23	23
CYCS	-0.008	0.093	-10000	0	-0.37	10	10
RIPK1	0.027	0.003	-10000	0	-10000	0	0
CD247	-0.014	0.15	-10000	0	-0.77	17	17
MAP2K7	-0.001	0.16	-10000	0	-0.61	24	24
protein ubiquitination	0.009	0.099	0.36	6	-0.35	5	11
CRADD	0.027	0.005	-10000	0	-10000	0	0
DAXX	0.027	0.003	-10000	0	-10000	0	0
FAS	0.027	0.005	-10000	0	-10000	0	0
BID	-0.01	0.098	0.22	1	-0.33	25	26
NF-kappa-B/RelA/I kappa B alpha	0.043	0.079	-10000	0	-0.33	18	18
TRADD	0.026	0.006	-10000	0	-10000	0	0
MAP3K5	0.026	0.032	-10000	0	-0.67	1	1
CFLAR	0.027	0.005	-10000	0	-10000	0	0
FADD	0.027	0.005	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.043	0.079	-10000	0	-0.33	18	18
MAPK8	-0.005	0.16	0.35	1	-0.58	24	25
APAF1	0.025	0.032	-10000	0	-0.67	1	1
TRAF1	0.025	0.008	-10000	0	-10000	0	0
TRAF2	0.025	0.009	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.001	0.098	-10000	0	-0.32	35	35
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0	0.11	-10000	0	-0.37	19	19
CHUK	0.005	0.098	0.28	3	-0.38	5	8
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.076	0.029	-10000	0	-0.38	1	1
TCRz/NEF	-0.022	0.15	-10000	0	-0.45	46	46
TNF	-0.056	0.22	-10000	0	-0.67	56	56
FASLG	-0.048	0.23	-10000	0	-0.77	41	41
NFKB1	0.021	0.033	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.003	0.16	-10000	0	-0.44	57	57
CASP6	0.039	0.096	-10000	0	-0.66	5	5
CASP7	0.01	0.15	0.39	2	-0.57	26	28
RELA	0.021	0.033	-10000	0	-10000	0	0
CASP2	0.026	0.006	-10000	0	-10000	0	0
CASP3	0.01	0.15	0.35	1	-0.56	26	27
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
TNFR1A/BAG4	0.038	0.026	-10000	0	-0.51	1	1
CASP8	0.027	0.005	-10000	0	-10000	0	0
CASP9	0.027	0.005	-10000	0	-10000	0	0
MAP3K14	0.003	0.1	-10000	0	-0.4	7	7
APAF-1/Caspase 9	-0.002	0.12	-10000	0	-0.48	22	22
BCL2	-0.027	0.16	0.34	1	-0.56	24	25

×

Rapid glucocorticoid 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.007	0.14	-10000	0	-0.37	62	62
MAPK9	0.008	0.002	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.004	0.022	-10000	0	-10000	0	0
GNB1/GNG2	0.034	0.023	-10000	0	-0.44	1	1
GNB1	0.026	0.006	-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	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.035	0.14	-10000	0	-0.39	64	64
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	0.012	0.032	0.096	64	-10000	0	64
GNAL	-0.061	0.23	-10000	0	-0.66	64	64
GNG2	0.025	0.032	-10000	0	-0.67	1	1
CRH	0	0.039	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.055	-10000	0	-0.38	10	10
MAPK11	0.006	0.004	-10000	0	-10000	0	0

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.006	0.14	-10000	0	-0.69	11	11
HDAC1	0.024	0.008	-10000	0	-10000	0	0
AES	0.024	0.008	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
DTX1	0.024	0.045	-10000	0	-0.67	2	2
LRP6/FZD1	0.039	0.009	-10000	0	-10000	0	0
TLE1	0.02	0.055	-10000	0	-0.68	3	3
AP1	-0.13	0.24	-10000	0	-0.49	139	139
NCSTN	0.026	0.007	-10000	0	-10000	0	0
ADAM10	0.011	0.1	-10000	0	-0.67	11	11
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.029	0.075	-10000	0	-0.55	4	4
NICD/RBPSUH	0.006	0.13	-10000	0	-0.64	11	11
WIF1	-0.015	0.047	-10000	0	-10000	0	0
NOTCH1	-0.003	0.13	-10000	0	-0.69	10	10
PSENEN	0.026	0.007	-10000	0	-10000	0	0
KREMEN2	0.016	0.037	-10000	0	-10000	0	0
DKK1	-0.001	0.07	-10000	0	-0.67	2	2
beta catenin/beta TrCP1	0.046	0.048	0.29	2	-10000	0	2
APH1B	0.027	0.004	-10000	0	-10000	0	0
APH1A	0.026	0.007	-10000	0	-10000	0	0
AXIN1	-0.006	0.082	0.38	1	-0.55	4	5
CtBP/CBP/TCF1/TLE1/AES	0.019	0.031	-10000	0	-0.29	3	3
PSEN1	0.027	0.005	-10000	0	-10000	0	0
FOS	-0.15	0.3	-10000	0	-0.67	125	125
JUN	-0.12	0.29	-10000	0	-0.67	107	107
MAP3K7	0.026	0.004	-10000	0	-10000	0	0
CTNNB1	0.038	0.063	0.31	11	-10000	0	11
MAPK3	0.026	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.034	0.096	-10000	0	-0.44	19	19
HNF1A	0.026	0.005	-10000	0	-10000	0	0
CTBP1	0.026	0.005	-10000	0	-10000	0	0
MYC	-0.017	0.25	-10000	0	-1.2	19	19
NKD1	0.006	0.11	-10000	0	-0.68	13	13
FZD1	0.026	0.006	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	0.006	0.14	-10000	0	-0.64	13	13
apoptosis	-0.13	0.24	-10000	0	-0.48	139	139
Delta 1/NOTCHprecursor	0.006	0.14	-10000	0	-0.67	11	11
DLL1	0.025	0.032	-10000	0	-0.67	1	1
PPARD	0.022	0.081	-10000	0	-0.84	4	4
Gamma Secretase	0.07	0.03	-10000	0	-10000	0	0
APC	0	0.074	0.33	2	-0.55	3	5
DVL1	0.025	0.01	-10000	0	-10000	0	0
CSNK2A1	0.027	0.005	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.048	0.044	-10000	0	-0.47	2	2
LRP6	0.027	0.005	-10000	0	-10000	0	0
CSNK1A1	0.027	0.006	-10000	0	-10000	0	0
NLK	0.014	0.007	-10000	0	-10000	0	0
CCND1	0.01	0.13	-10000	0	-0.85	10	10
WNT1	0.018	0.022	-10000	0	-10000	0	0
Axin1/APC/beta catenin	0.045	0.095	0.42	12	-0.61	1	13
DKK2	-0.004	0.14	-10000	0	-0.66	20	20
NOTCH1 precursor/DVL1	0.013	0.12	-10000	0	-0.59	11	11
GSK3B	0.027	0.003	-10000	0	-10000	0	0
FRAT1	0.026	0.005	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	0.006	0.14	-10000	0	-0.66	13	13
PPP2R5D	0.027	0.062	0.33	13	-0.38	3	16
MAPK1	0.02	0.012	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.064	0.018	-10000	0	-10000	0	0
RBPJ	0.027	0.008	-10000	0	-10000	0	0
CREBBP	0.028	0.008	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.002	0.1	-10000	0	-0.61	8	8
UGCG	-0.059	0.22	-10000	0	-0.64	58	58
AKT1/mTOR/p70S6K/Hsp90/TERT	0.013	0.14	0.42	5	-0.41	22	27
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.059	0.22	-10000	0	-0.62	60	60
mol:DAG	-0.009	0.12	-10000	0	-0.77	12	12
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.17	-10000	0	-0.43	50	50
FRAP1	-0.017	0.2	0.44	2	-0.5	51	53
FOXO3	-0.003	0.17	0.44	2	-0.61	22	24
AKT1	-0.008	0.18	-10000	0	-0.66	23	23
GAB2	0.027	0.006	-10000	0	-10000	0	0
SMPD1	0.01	0.085	-10000	0	-0.77	5	5
SGMS1	0.002	0.11	-10000	0	-0.64	12	12
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	0.007	0.036	-10000	0	-0.45	3	3
CALM1	0.027	0.005	-10000	0	-10000	0	0
cell proliferation	-0.03	0.19	0.33	5	-0.52	42	47
EIF3A	0.027	0.004	-10000	0	-10000	0	0
PI3K	0.039	0.044	-10000	0	-0.51	3	3
RPS6KB1	0.016	0.067	-10000	0	-0.82	2	2
mol:sphingomyelin	-0.009	0.12	-10000	0	-0.77	12	12
natural killer cell activation	0	0.002	-10000	0	-0.012	4	4
JAK3	-0.01	0.066	-10000	0	-10000	0	0
PIK3R1	0.028	0.006	-10000	0	-10000	0	0
JAK1	0.029	0.006	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
MYC	-0.006	0.21	0.47	4	-0.92	18	22
MYB	0.002	0.19	-10000	0	-1.2	11	11
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.005	0.15	-10000	0	-0.55	23	23
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.043	0.067	-10000	0	-0.74	2	2
mol:PI-3-4-5-P3	-0.004	0.14	-10000	0	-0.53	23	23
Rac1/GDP	0.023	0.036	-10000	0	-0.41	3	3
T cell proliferation	-0.004	0.13	-10000	0	-0.52	20	20
SHC1	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.01	-10000	0	-0.066	11	11
PRKCZ	-0.005	0.14	-10000	0	-0.54	20	20
NF kappa B1 p50/RelA	0.01	0.17	-10000	0	-0.5	28	28
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0	0.11	-10000	0	-0.49	16	16
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
IL2RA	-0.017	0.16	-10000	0	-0.64	28	28
IL2RB	0.005	0.09	-10000	0	-0.58	10	10
TERT	-0.006	0.023	-10000	0	-10000	0	0
E2F1	0.022	0.07	-10000	0	-0.43	11	11
SOS1	0.027	0.005	-10000	0	-10000	0	0
RPS6	0.025	0.008	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.005	0.031	11	-10000	0	11
PTPN11	0.025	0.032	-10000	0	-0.68	1	1
IL2RG	-0.01	0.14	-10000	0	-0.63	21	21
actin cytoskeleton organization	-0.004	0.13	-10000	0	-0.52	20	20
GRB2	0.026	0.007	-10000	0	-10000	0	0
IL2	0.018	0.013	-10000	0	-10000	0	0
PIK3CA	0.025	0.055	-10000	0	-0.68	3	3
Rac1/GTP	0.048	0.042	-10000	0	-0.39	3	3
LCK	0.014	0.082	-10000	0	-0.67	6	6
BCL2	-0.042	0.27	0.47	4	-0.79	51	55

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.02	0.012	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.003	0.065	-10000	0	-0.38	2	2
NT3 (dimer)/TRKC	-0.022	0.14	-10000	0	-0.5	37	37
NT3 (dimer)/TRKB	0.005	0.14	-10000	0	-0.44	44	44
SHC/Grb2/SOS1/GAB1/PI3K	0.03	0.028	-10000	0	-0.29	3	3
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0
BDNF	0.008	0.1	-10000	0	-0.67	11	11
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
DYNLT1	0.027	0.004	-10000	0	-10000	0	0
NTRK1	0.01	0.031	-10000	0	-10000	0	0
NTRK2	0.019	0.065	-10000	0	-0.61	5	5
NTRK3	-0.013	0.12	-10000	0	-0.65	13	13
NT-4/5 (dimer)/TRKB	0.013	0.13	-10000	0	-0.45	34	34
neuron apoptosis	-0.011	0.11	0.38	18	-10000	0	18
SHC 2-3/Grb2	0.011	0.12	-10000	0	-0.42	18	18
SHC1	0.025	0.008	-10000	0	-10000	0	0
SHC2	0.001	0.1	-10000	0	-0.55	10	10
SHC3	-0.005	0.12	-10000	0	-0.42	28	28
STAT3 (dimer)	0.03	0.015	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	0.003	0.14	-10000	0	-0.45	37	37
RIN/GDP	-0.005	0.078	0.3	7	-0.27	3	10
GIPC1	0.025	0.008	-10000	0	-10000	0	0
KRAS	0.027	0.005	-10000	0	-10000	0	0
DNAJA3	-0.005	0.071	-10000	0	-0.38	15	15
RIN/GTP	0.013	0.004	-10000	0	-10000	0	0
CCND1	0.02	0.018	-10000	0	-10000	0	0
MAGED1	0.026	0.007	-10000	0	-10000	0	0
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.002	0.12	-10000	0	-0.65	15	15
SHC/GRB2/SOS1	0.048	0.02	-10000	0	-10000	0	0
GRB2	0.026	0.007	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	0.038	0.064	-10000	0	-0.44	7	7
TRKA/NEDD4-2	0.031	0.024	-10000	0	-10000	0	0
ELMO1	-0.24	0.34	-10000	0	-0.67	190	190
RhoG/GTP/ELMO1/DOCK1	-0.15	0.24	-10000	0	-0.44	190	190
NGF	0.022	0.056	-10000	0	-0.67	3	3
HRAS	0.026	0.011	-10000	0	-10000	0	0
DOCK1	0.023	0.054	-10000	0	-0.67	3	3
GAB2	0.027	0.005	-10000	0	-10000	0	0
RIT2	-0.009	0.016	-10000	0	-10000	0	0
RIT1	0.025	0.007	-10000	0	-10000	0	0
FRS2	0.027	0.005	-10000	0	-10000	0	0
DNM1	0.005	0.12	-10000	0	-0.62	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.007	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.12	0.19	-10000	0	-0.35	189	189
mol:GDP	-0.014	0.1	0.35	8	-0.4	4	12
NGF (dimer)	0.021	0.056	-10000	0	-0.67	3	3
RhoG/GDP	-0.18	0.26	-10000	0	-0.51	190	190
RIT1/GDP	-0.003	0.076	0.3	7	-0.27	3	10
TIAM1	-0.059	0.081	-10000	0	-0.67	1	1
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	0.036	0.087	-10000	0	-0.45	15	15
KIDINS220/CRKL/C3G	0.028	0.019	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2	0.053	0.025	-10000	0	-0.44	1	1
SHC/GRB2/SOS1/GAB1	0.061	0.026	-10000	0	-10000	0	0
RIT1/GTP	0.019	0.006	-10000	0	-10000	0	0
NT3 (dimer)	-0.016	0.15	-10000	0	-0.67	25	25
RAP1/GDP	-0.005	0.057	-10000	0	-0.23	3	3
KIDINS220/CRKL	0.02	0.012	-10000	0	-10000	0	0
BDNF (dimer)	0.008	0.1	-10000	0	-0.67	11	11
ubiquitin-dependent protein catabolic process	0.045	0.043	-10000	0	-0.44	3	3
Schwann cell development	-0.031	0.028	-10000	0	-10000	0	0
EHD4	0.027	0.004	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.065	0.02	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.02	0.037	-10000	0	-0.28	1	1
RAP1B	0.027	0.005	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CDC42/GTP	-0.008	0.12	-10000	0	-0.35	45	45
ABL1	0.025	0.008	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.038	0.011	-10000	0	-10000	0	0
Rap1/GTP	-0.008	0.1	-10000	0	-0.49	7	7
STAT3	0.03	0.015	-10000	0	-10000	0	0
axon guidance	-0.016	0.11	-10000	0	-0.34	46	46
MAPK3	0.018	0.069	-10000	0	-0.4	7	7
MAPK1	0.01	0.063	-10000	0	-0.4	7	7
CDC42/GDP	-0.001	0.078	0.3	7	-0.27	3	10
NTF3	-0.017	0.16	-10000	0	-0.67	25	25
NTF4	0.002	0.12	-10000	0	-0.65	15	15
NGF (dimer)/TRKA/FAIM	0.046	0.043	-10000	0	-0.44	3	3
PI3K	0.036	0.043	-10000	0	-0.51	3	3
FRS3	0.027	0.003	-10000	0	-10000	0	0
FAIM	0.027	0.003	-10000	0	-10000	0	0
GAB1	0.027	0.004	-10000	0	-10000	0	0
RASGRF1	-0.043	0.083	-10000	0	-0.4	19	19
SOS1	0.027	0.005	-10000	0	-10000	0	0
MCF2L	-0.028	0.12	-10000	0	-0.44	36	36
RGS19	0.026	0.009	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.07	-10000	0	-0.59	1	1
Rac1/GDP	-0.005	0.067	0.22	1	-0.26	2	3
NGF (dimer)/TRKA/GRIT	0.025	0.043	-10000	0	-0.44	3	3
neuron projection morphogenesis	0.024	0.088	-10000	0	-0.7	2	2
NGF (dimer)/TRKA/NEDD4-2	0.045	0.043	-10000	0	-0.44	3	3
MAP2K1	0.04	0.058	0.36	4	-10000	0	4
NGFR	-0.016	0.13	-10000	0	-0.67	16	16
NGF (dimer)/TRKA/GIPC/GAIP	0.016	0.07	-10000	0	-0.34	15	15
RAS family/GTP/PI3K	0.027	0.027	-10000	0	-0.3	3	3
FRS2 family/SHP2/GRB2/SOS1	0.074	0.032	-10000	0	-0.38	1	1
NRAS	0.027	0.005	-10000	0	-10000	0	0
GRB2/SOS1	0.038	0.011	-10000	0	-10000	0	0
PRKCI	0.027	0.003	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
MAPKKK cascade	0.021	0.074	-10000	0	-0.54	6	6
RASA1	0.027	0.005	-10000	0	-10000	0	0
TRKA/c-Abl	0.03	0.025	-10000	0	-10000	0	0
SQSTM1	0.026	0.006	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.047	0.083	-10000	0	-0.41	14	14
NGF (dimer)/TRKA/p62/Atypical PKCs	0.068	0.046	-10000	0	-0.38	3	3
MATK	0.015	0.069	-10000	0	-0.61	5	5
NEDD4L	0.027	0.004	-10000	0	-10000	0	0
RAS family/GDP	-0.02	0.042	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.003	0.077	-10000	0	-0.39	16	16
Rac1/GTP	-0.11	0.12	-10000	0	-0.32	46	46
FRS2 family/SHP2/CRK family	0.057	0.043	-10000	0	-0.38	1	1

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.014	0.091	-10000	0	-0.61	10	10
ANTXR2	0.023	0.054	-10000	0	-0.67	3	3
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.013	-10000	0	-0.082	13	13
monocyte activation	-0.035	0.16	-10000	0	-0.44	62	62
MAP2K2	-0.008	0.11	-10000	0	-0.54	22	22
MAP2K1	-0.001	0.012	-10000	0	-10000	0	0
MAP2K7	-0.001	0.012	-10000	0	-10000	0	0
MAP2K6	-0.009	0.056	0.11	1	-0.39	10	11
CYAA	-0.007	0.057	-10000	0	-0.38	11	11
MAP2K4	-0.001	0.012	-10000	0	-10000	0	0
IL1B	-0.021	0.094	0.18	1	-0.35	34	35
Channel	0.024	0.066	-10000	0	-0.37	13	13
NLRP1	-0.002	0.027	0.11	1	-0.38	2	3
CALM1	0.027	0.005	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.011	0.028	-10000	0	-0.51	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.013	0.082	13	-10000	0	13
MAPK3	-0.001	0.012	-10000	0	-10000	0	0
MAPK1	-0.001	0.012	-10000	0	-10000	0	0
PGR	-0.012	0.055	-10000	0	-0.32	13	13
PA/Cellular Receptors	0.025	0.072	-10000	0	-0.4	13	13
apoptosis	-0.002	0.013	-10000	0	-0.082	13	13
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.024	0.062	-10000	0	-0.35	13	13
macrophage activation	-0.001	0.011	-10000	0	-10000	0	0
TNF	-0.056	0.22	-10000	0	-0.67	56	56
VCAM1	-0.036	0.16	-10000	0	-0.44	62	62
platelet activation	0.011	0.028	-10000	0	-0.51	1	1
MAPKKK cascade	-0.003	0.029	0.17	2	-0.13	8	10
IL18	-0.009	0.06	-10000	0	-0.33	13	13
negative regulation of macrophage activation	-0.002	0.013	-10000	0	-0.082	13	13
LEF	-0.002	0.013	-10000	0	-0.082	13	13
CASP1	0.001	0.018	-10000	0	-0.097	14	14
mol:cAMP	0.011	0.029	-10000	0	-0.52	1	1
necrosis	-0.002	0.013	-10000	0	-0.082	13	13
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.024	0.063	-10000	0	-0.35	13	13
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.027	0.005	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	0.026	0.12	-9999	-0.34	36	36
Syndecan-3/Neurocan	0.004	0.095	-9999	-0.36	28	28
POMC	-0.11	0.28	-9999	-0.66	101	101
EGFR	0.019	0.07	-9999	-0.67	5	5
Syndecan-3/EGFR	0.027	0.044	-9999	-0.33	6	6
AGRP	0.003	0.035	-9999	-10000	0	0
NCSTN	0.025	0.007	-9999	-10000	0	0
PSENEN	0.026	0.007	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.027	0.004	-9999	-10000	0	0
APH1A	0.025	0.007	-9999	-10000	0	0
NCAN	-0.026	0.17	-9999	-0.66	34	34
long-term memory	0.051	0.029	-9999	-10000	0	0
Syndecan-3/IL8	0.029	0.066	-9999	-0.36	11	11
PSEN1	0.027	0.005	-9999	-10000	0	0
Src/Cortactin	0.039	0.01	-9999	-10000	0	0
FYN	0.027	0.004	-9999	-10000	0	0
limb bud formation	0.015	0.006	-9999	-10000	0	0
MC4R	0	0.028	-9999	-10000	0	0
SRC	0.026	0.008	-9999	-10000	0	0
PTN	-0.038	0.2	-9999	-0.67	45	45
FGFR/FGF/Syndecan-3	0.015	0.006	-9999	-10000	0	0
neuron projection morphogenesis	-0.023	0.13	-9999	-0.45	3	3
Syndecan-3/AgRP	0.031	0.023	-9999	-0.31	1	1
Syndecan-3/AgRP/MC4R	0.045	0.03	-9999	-10000	0	0
Fyn/Cortactin	0.039	0.008	-9999	-10000	0	0
SDC3	0.015	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0.029	0.065	-9999	-0.36	11	11
IL8	-0.026	0.12	-9999	-0.67	11	11
Syndecan-3/Fyn/Cortactin	0.052	0.03	-9999	-10000	0	0
Syndecan-3/CASK	0.011	0.023	-9999	-0.3	1	1
alpha-MSH/MC4R	-0.077	0.22	-9999	-0.5	100	100
Gamma Secretase	0.07	0.03	-9999	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.027	0.004	-10000	0	-10000	0	0
GNAT1/GTP	0.014	0.009	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.026	0.009	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.02	0.049	-10000	0	-0.44	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	-0.001	0.023	-10000	0	-10000	0	0
GRK1	-0.038	0.2	-10000	0	-0.65	46	46
CNG Channel	0.036	0.061	-10000	0	-0.38	8	8
mol:Na +	0.028	0.072	-10000	0	-0.39	10	10
mol:ADP	-0.038	0.2	-10000	0	-0.65	46	46
RGS9-1/Gbeta5/R9AP	-0.022	0.18	-10000	0	-0.45	71	71
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.041	0.075	-10000	0	-0.4	10	10
CNGB1	0.016	0.034	-10000	0	-10000	0	0
RDH5	-0.073	0.074	-10000	0	-10000	0	0
SAG	-0.009	0.018	-10000	0	-10000	0	0
mol:Ca2+	-0.009	0.1	0.5	11	-0.38	9	20
Na + (4 Units)	0.021	0.067	-10000	0	-0.37	10	10
RGS9	-0.039	0.2	-10000	0	-0.67	45	45
GNB1/GNGT1	0.029	0.014	-10000	0	-10000	0	0
GNAT1/GDP	-0.01	0.16	-10000	0	-0.39	70	70
GUCY2D	0.013	0.077	-10000	0	-0.62	6	6
GNGT1	-0.015	0.014	-10000	0	-10000	0	0
GUCY2F	-0.013	0.01	-10000	0	-10000	0	0
GNB5	0.027	0.004	-10000	0	-10000	0	0
mol:GMP (4 units)	0.014	0.044	-10000	0	-0.38	3	3
mol:11-cis-retinal	-0.072	0.073	-10000	0	-10000	0	0
mol:cGMP	0.032	0.057	-10000	0	-0.4	6	6
GNB1	0.026	0.006	-10000	0	-10000	0	0
Rhodopsin	-0.043	0.057	-10000	0	-10000	0	0
SLC24A1	0.027	0.004	-10000	0	-10000	0	0
CNGA1	0.017	0.078	-10000	0	-0.67	6	6
Metarhodopsin II	-0.009	0.12	-10000	0	-0.4	44	44
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.045	0.065	-10000	0	-0.41	8	8
RGS9BP	-0.015	0.16	-10000	0	-0.66	29	29
Metarhodopsin II/Transducin	0.013	0.007	-10000	0	-10000	0	0
GCAP Family/Ca ++	0.038	0.038	-10000	0	-0.41	3	3
PDE6A/B	0.031	0.028	-10000	0	-10000	0	0
mol:Pi	-0.022	0.18	-10000	0	-0.45	71	71
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.037	0.016	-10000	0	-10000	0	0
PDE6B	0.027	0.004	-10000	0	-10000	0	0
PDE6A	0.012	0.037	-10000	0	-10000	0	0
PDE6G	0.01	0.072	-10000	0	-0.67	4	4
RHO	0.006	0.023	-10000	0	-10000	0	0
PDE6	0.004	0.17	-10000	0	-0.39	71	71
GUCA1A	0.005	0.025	-10000	0	-10000	0	0
GC2/GCAP Family	0.046	0.037	-10000	0	-0.42	2	2
GUCA1C	-0.016	0.002	-10000	0	-10000	0	0
GUCA1B	0.023	0.055	-10000	0	-0.67	3	3

×

ErbB4 signaling 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
ErbB4/ErbB4/HBEGF/HBEGF	-0.002	0.086	-10000	0	-0.41	1	1
epithelial cell differentiation	-0.004	0.098	-10000	0	-0.41	7	7
ITCH	0.037	0.019	-10000	0	-10000	0	0
WWP1	-0.009	0.07	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
EGFR	0.019	0.07	-10000	0	-0.67	5	5
PRL	-0.012	0.014	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.018	0.11	0.34	3	-0.48	5	8
PTPRZ1	0.002	0.1	-10000	0	-0.67	10	10
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.002	0.13	-10000	0	-0.51	6	6
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.037	0.13	-10000	0	-0.42	42	42
ADAM17	0.033	0.049	-10000	0	-0.67	2	2
ErbB4/ErbB4	-0.015	0.088	-10000	0	-0.46	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.029	0.14	-10000	0	-0.45	33	33
NCOR1	0.026	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.025	0.13	-10000	0	-0.4	41	41
GRIN2B	-0.034	0.12	-10000	0	-0.51	8	8
ErbB4/ErbB2/betacellulin	0	0.11	-10000	0	-0.5	14	14
STAT1	0.023	0.023	-10000	0	-10000	0	0
HBEGF	0.018	0.035	-10000	0	-10000	0	0
PRLR	-0.015	0.15	-10000	0	-0.67	25	25
E4ICDs/ETO2	-0.002	0.086	-10000	0	-0.48	2	2
axon guidance	-0.006	0.071	-10000	0	-0.47	1	1
NEDD4	0.034	0.048	-10000	0	-0.66	2	2
Prolactin receptor/Prolactin receptor/Prolactin	0.001	0.12	-10000	0	-0.51	25	25
CBFA2T3	0.024	0.034	-10000	0	-0.67	1	1
ErbB4/ErbB2/HBEGF	0.01	0.073	-10000	0	-0.45	2	2
MAPK3	-0.013	0.12	-10000	0	-0.48	6	6
STAT1 (dimer)	-0.001	0.086	-10000	0	-0.41	1	1
MAPK1	-0.016	0.11	-10000	0	-0.5	5	5
JAK2	0.024	0.025	-10000	0	-0.36	2	2
ErbB4/ErbB2/neuregulin 1 beta	-0.03	0.12	-10000	0	-0.4	38	38
NRG1	-0.025	0.15	-10000	0	-0.52	43	43
NRG3	-0.021	0.17	-10000	0	-0.65	35	35
NRG2	-0.052	0.22	-10000	0	-0.67	54	54
NRG4	0.021	0.021	-10000	0	-10000	0	0
heart development	-0.006	0.071	-10000	0	-0.47	1	1
neural crest cell migration	-0.03	0.12	-10000	0	-0.39	38	38
ERBB2	0.019	0.035	-10000	0	-0.5	2	2
WWOX/E4ICDs	-0.003	0.089	-10000	0	-0.78	1	1
SHC1	0.025	0.008	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.008	0.097	-10000	0	-0.49	5	5
apoptosis	0.022	0.13	0.41	32	-10000	0	32
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.049	0.16	-10000	0	-0.44	56	56
ErbB4/ErbB2/epiregulin	0.01	0.085	-10000	0	-0.42	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.015	0.12	-10000	0	-0.52	16	16
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.005	0.12	-10000	0	-0.37	24	24
MDM2	-0.013	0.078	-10000	0	-0.41	1	1
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.021	0.13	-10000	0	-0.4	41	41
STAT5A	-0.001	0.072	-10000	0	-0.45	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.027	0.14	-10000	0	-0.41	44	44
DLG4	0.026	0.007	-10000	0	-10000	0	0
GRB2/SHC	0.035	0.014	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.002	0.076	-10000	0	-0.38	1	1
STAT5A (dimer)	0.005	0.11	-10000	0	-0.45	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.006	0.073	-10000	0	-0.45	1	1
LRIG1	0.017	0.084	-10000	0	-0.64	8	8
EREG	-0.052	0.072	-10000	0	-10000	0	0
BTC	0.004	0.12	-10000	0	-0.67	16	16
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.006	0.07	-10000	0	-0.48	1	1
ERBB4	-0.015	0.088	-10000	0	-0.46	1	1
STAT5B	0.026	0.007	-10000	0	-10000	0	0
YAP1	0.005	0.066	-10000	0	-0.47	8	8
GRB2	0.026	0.007	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.01	0.072	-10000	0	-0.43	2	2
glial cell differentiation	0.002	0.076	0.38	1	-10000	0	1
WWOX	0.025	0.032	-10000	0	-0.67	1	1
cell proliferation	-0.024	0.14	-10000	0	-0.59	8	8

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.025	0.007	-9999	-10000	0	0
SPHK1	0.022	0.024	-9999	-10000	0	0
GNAI2	0.027	0.003	-9999	-10000	0	0
mol:S1P	0.017	0.008	-9999	-10000	0	0
GNAO1	0.004	0.12	-9999	-0.67	15	15
mol:Sphinganine-1-P	0.014	0.015	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.056	0.028	-9999	-10000	0	0
GNAI3	0.027	0.005	-9999	-10000	0	0
G12/G13	0.038	0.011	-9999	-10000	0	0
S1PR3	0.025	0.008	-9999	-10000	0	0
S1PR2	0.024	0.014	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.01	0.018	-9999	-0.2	2	2
S1PR5	0.023	0.034	-9999	-0.67	1	1
S1PR4	0.023	0.02	-9999	-10000	0	0
GNAI1	0.025	0.032	-9999	-0.67	1	1
S1P/S1P5/G12	0.043	0.031	-9999	-0.38	1	1
S1P/S1P3/Gq	-0.056	0.16	-9999	-0.3	134	134
S1P/S1P4/Gi	0.003	0.079	-9999	-0.32	17	17
GNAQ	0.025	0.008	-9999	-10000	0	0
GNAZ	0.02	0.012	-9999	-10000	0	0
GNA14	-0.14	0.29	-9999	-0.64	120	120
GNA15	0.013	0.05	-9999	-0.67	1	1
GNA12	0.026	0.006	-9999	-10000	0	0
GNA13	0.026	0.007	-9999	-10000	0	0
GNA11	0.015	0.084	-9999	-0.64	8	8
ABCC1	0.026	0.006	-9999	-10000	0	0

×

Syndecan-2-mediated signaling events

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
Syndecan-2/Fibronectin	-0.038	0.06	-10000	0	-0.4	6	6
EPHB2	0.022	0.055	-10000	0	-0.67	3	3
Syndecan-2/TACI	-0.089	0.2	-10000	0	-0.44	121	121
LAMA1	-0.021	0.18	-10000	0	-0.66	34	34
Syndecan-2/alpha2 ITGB1	0.042	0.092	-10000	0	-0.38	19	19
HRAS	0.026	0.011	-10000	0	-10000	0	0
Syndecan-2/CASK	0.007	0.043	-10000	0	-0.33	7	7
ITGA5	0.027	0.005	-10000	0	-10000	0	0
BAX	0.003	0.065	-10000	0	-0.46	1	1
EPB41	0.027	0.005	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.024	0.041	-10000	0	-0.39	4	4
LAMA3	-0.001	0.13	-10000	0	-0.67	16	16
EZR	0.027	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.023	0.045	-10000	0	-0.67	2	2
Syndecan-2/MMP2	0.021	0.071	-10000	0	-0.48	9	9
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	-0.008	0.059	-10000	0	-10000	0	0
dendrite morphogenesis	0.023	0.057	-10000	0	-0.43	7	7
Syndecan-2/GM-CSF	-0.035	0.057	-10000	0	-0.45	4	4
determination of left/right symmetry	0.01	0.05	-10000	0	-0.39	7	7
Syndecan-2/PKC delta	0.026	0.045	-10000	0	-0.43	4	4
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
MAPK3	-0.032	0.049	-10000	0	-0.41	4	4
MAPK1	-0.026	0.048	-10000	0	-0.41	4	4
Syndecan-2/RACK1	0.038	0.041	-10000	0	-0.38	4	4
NF1	0.026	0.007	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0.01	0.05	-10000	0	-0.39	7	7
ITGA2	-0.034	0.075	-10000	0	-10000	0	0
MAPK8	0.004	0.074	-10000	0	-0.42	14	14
Syndecan-2/alpha2/beta1 Integrin	0.032	0.12	-10000	0	-0.42	32	32
Syndecan-2/Kininogen	0.016	0.05	-10000	0	-0.44	4	4
ITGB1	0.027	0.004	-10000	0	-10000	0	0
SRC	0.022	0.045	0.35	1	-0.36	4	5
Syndecan-2/CASK/Protein 4.1	0.023	0.041	-10000	0	-0.4	4	4
extracellular matrix organization	0.024	0.044	-10000	0	-0.43	4	4
actin cytoskeleton reorganization	-0.038	0.059	-10000	0	-0.4	6	6
Syndecan-2/Caveolin-2/Ras	0.039	0.05	-10000	0	-0.39	6	6
Syndecan-2/Laminin alpha3	0.009	0.094	-10000	0	-0.43	20	20
Syndecan-2/RasGAP	0.05	0.042	-10000	0	-0.36	4	4
alpha5/beta1 Integrin	0.039	0.009	-10000	0	-10000	0	0
PRKCD	0.027	0.003	-10000	0	-10000	0	0
Syndecan-2 dimer	0.023	0.058	-10000	0	-0.43	7	7
GO:0007205	0.003	0.001	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.04	0.042	-10000	0	-0.35	4	4
RHOA	0.027	0.003	-10000	0	-10000	0	0
SDCBP	0.027	0.005	-10000	0	-10000	0	0
TNFRSF13B	-0.16	0.29	-10000	0	-0.67	121	121
RASA1	0.027	0.005	-10000	0	-10000	0	0
alpha2/beta1 Integrin	-0.008	0.059	-10000	0	-10000	0	0
Syndecan-2/Synbindin	0.026	0.044	-10000	0	-0.43	4	4
TGFB1	0.024	0.017	-10000	0	-10000	0	0
CASP3	0.018	0.044	-10000	0	-0.4	4	4
FN1	-0.085	0.069	-10000	0	-10000	0	0
Syndecan-2/IL8	-0.005	0.087	-10000	0	-0.4	18	18
SDC2	0.01	0.05	-10000	0	-0.39	7	7
KNG1	-0.005	0.038	-10000	0	-10000	0	0
Syndecan-2/Neurofibromin	0.026	0.043	-10000	0	-0.43	4	4
TRAPPC4	0.027	0.005	-10000	0	-10000	0	0
CSF2	-0.082	0.067	-10000	0	-10000	0	0
Syndecan-2/TGFB1	0.024	0.044	-10000	0	-0.43	4	4
Syndecan-2/Syntenin/PI-4-5-P2	0.024	0.041	-10000	0	-0.4	4	4
Syndecan-2/Ezrin	0.042	0.043	-10000	0	-0.4	4	4
PRKACA	0.017	0.041	-10000	0	-0.4	4	4
angiogenesis	-0.005	0.087	-10000	0	-0.39	18	18
MMP2	0.017	0.079	-10000	0	-0.63	7	7
IL8	-0.026	0.12	-10000	0	-0.67	11	11
calcineurin-NFAT signaling pathway	-0.089	0.2	-10000	0	-0.44	121	121

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.03	0.071	-10000	0	-0.57	6	6
PDGFRB	0.025	0.032	-10000	0	-0.68	1	1
SPHK1	0.01	0.059	-10000	0	-0.86	2	2
mol:S1P	0.008	0.057	-10000	0	-0.79	2	2
S1P1/S1P/Gi	-0.007	0.12	-10000	0	-0.4	39	39
GNAO1	0.002	0.12	-10000	0	-0.68	15	15
PDGFB-D/PDGFRB/PLCgamma1	-0.005	0.12	-10000	0	-0.38	30	30
PLCG1	-0.007	0.12	-10000	0	-0.39	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.032	-10000	0	-0.68	1	1
GNAI2	0.025	0.012	-10000	0	-10000	0	0
GNAI3	0.025	0.013	-10000	0	-10000	0	0
GNAI1	0.023	0.033	-10000	0	-0.68	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.001	0.058	-10000	0	-0.5	6	6
S1P1/S1P	0.004	0.07	-10000	0	-0.45	7	7
negative regulation of cAMP metabolic process	-0.006	0.12	-10000	0	-0.39	39	39
MAPK3	-0.019	0.16	-10000	0	-0.58	33	33
calcium-dependent phospholipase C activity	-0.001	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.02	0.004	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
KDR	0.021	0.063	-10000	0	-0.68	4	4
PLCB2	0.014	0.077	0.4	5	-0.4	7	12
RAC1	0.026	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.01	0.06	-10000	0	-0.38	7	7
receptor internalization	0.004	0.065	-10000	0	-0.42	7	7
PTGS2	-0.054	0.29	0.64	3	-0.98	41	44
Rac1/GTP	0.011	0.059	-10000	0	-0.38	7	7
RHOA	0.027	0.003	-10000	0	-10000	0	0
VEGFA	0.023	0.055	-10000	0	-0.67	3	3
negative regulation of T cell proliferation	-0.006	0.12	-10000	0	-0.39	39	39
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.019	0.015	-10000	0	-10000	0	0
MAPK1	-0.02	0.17	-10000	0	-0.6	34	34
S1P1/S1P/PDGFB-D/PDGFRB	0.012	0.08	-10000	0	-0.44	8	8
ABCC1	0.026	0.006	-10000	0	-10000	0	0

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.18	0.32	-10000	0	-0.67	150	150
HRAS	0.026	0.011	-10000	0	-10000	0	0
EGFR	0.019	0.07	-10000	0	-0.67	5	5
AKT	0.015	0.084	0.32	10	-10000	0	10
FOXO3	0.027	0.004	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
FOXO1	0.026	0.007	-10000	0	-10000	0	0
AKT3	0.025	0.008	-10000	0	-10000	0	0
FOXO4	0.026	0.007	-10000	0	-10000	0	0
MET	-0.029	0.074	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
PIK3CB	0.027	0.003	-10000	0	-10000	0	0
NRAS	0.027	0.005	-10000	0	-10000	0	0
PIK3CG	0.005	0.12	-10000	0	-0.67	14	14
PIK3R3	0.027	0.005	-10000	0	-10000	0	0
PIK3R2	0.025	0.008	-10000	0	-10000	0	0
NF1	0.026	0.007	-10000	0	-10000	0	0
RAS	-0.031	0.087	-10000	0	-0.2	41	41
ERBB2	0.026	0.007	-10000	0	-10000	0	0
proliferation/survival/translation	-0.038	0.06	0.32	7	-0.2	1	8
PI3K	-0.016	0.099	0.39	8	-0.25	13	21
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
KRAS	0.027	0.005	-10000	0	-10000	0	0
FOXO	0.045	0.059	0.31	8	-10000	0	8
AKT2	0.026	0.007	-10000	0	-10000	0	0
PTEN	0.026	0.018	-10000	0	-0.36	1	1

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.029	0.009	-10000	0	-10000	0	0
epithelial cell differentiation	0.055	0.016	-10000	0	-10000	0	0
CYFIP2	0.026	0.006	-10000	0	-10000	0	0
ENAH	0.022	0.078	0.46	11	-10000	0	11
EGFR	0.019	0.07	-10000	0	-0.67	5	5
EPHA2	0.026	0.013	-10000	0	-10000	0	0
MYO6	0.031	0.065	0.42	11	-10000	0	11
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.053	0.013	-10000	0	-10000	0	0
AQP5	0.001	0.11	-10000	0	-0.53	19	19
CTNND1	0.027	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.024	0.046	0.38	7	-10000	0	7
regulation of calcium-dependent cell-cell adhesion	-0.011	0.054	0.39	5	-10000	0	5
EGF	-0.076	0.25	-10000	0	-0.67	72	72
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
AQP3	-0.041	0.17	-10000	0	-0.53	49	49
cortical microtubule organization	0.055	0.016	-10000	0	-10000	0	0
GO:0000145	0.012	0.046	0.37	7	-10000	0	7
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.061	0.017	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GDP	0.006	0.004	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.061	0.025	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.013	0.031	-10000	0	-10000	0	0
PVRL2	0.026	0.007	-10000	0	-10000	0	0
ZYX	0.021	0.021	-10000	0	-10000	0	0
ARF6/GTP	0.067	0.028	-10000	0	-10000	0	0
CDH1	0.026	0.006	-10000	0	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.011	0.14	-10000	0	-0.36	74	74
RhoA/GDP	0.057	0.016	-10000	0	-10000	0	0
actin cytoskeleton organization	0.021	0.05	0.38	8	-10000	0	8
IGF-1R heterotetramer	0.027	0.004	-10000	0	-10000	0	0
GIT1	0.026	0.007	-10000	0	-10000	0	0
IGF1R	0.027	0.004	-10000	0	-10000	0	0
IGF1	-0.13	0.29	-10000	0	-0.67	108	108
DIAPH1	0.05	0.05	-10000	0	-10000	0	0
Wnt receptor signaling pathway	-0.055	0.016	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
RhoA/GTP	0.006	0.004	-10000	0	-10000	0	0
CTNNA1	0.026	0.006	-10000	0	-10000	0	0
VCL	0.021	0.051	0.39	8	-10000	0	8
EFNA1	0.025	0.008	-10000	0	-10000	0	0
LPP	0.011	0.06	0.35	4	-0.36	8	12
Ephrin A1/EPHA2	0.047	0.019	-10000	0	-10000	0	0
SEC6/SEC8	0.014	0.006	-10000	0	-10000	0	0
MGAT3	-0.011	0.055	0.4	5	-10000	0	5
HGF/MET	-0.006	0.14	-10000	0	-0.38	64	64
HGF	-0.073	0.24	-10000	0	-0.67	70	70
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.029	0.009	-10000	0	-10000	0	0
actin cable formation	0.068	0.13	0.48	31	-0.33	1	32
KIAA1543	0.013	0.052	0.37	8	-0.35	1	9
KIFC3	0.021	0.023	-10000	0	-10000	0	0
NCK1	0.027	0.003	-10000	0	-10000	0	0
EXOC3	0.026	0.007	-10000	0	-10000	0	0
ACTN1	0.024	0.038	0.36	4	-10000	0	4
NCK1/GIT1	0.038	0.01	-10000	0	-10000	0	0
mol:GDP	0.055	0.016	-10000	0	-10000	0	0
EXOC4	0.026	0.006	-10000	0	-10000	0	0
STX4	0.021	0.023	-10000	0	-10000	0	0
PIP5K1C	0.024	0.047	0.38	7	-10000	0	7
LIMA1	0.027	0.005	-10000	0	-10000	0	0
ABI1	0.027	0.004	-10000	0	-10000	0	0
ROCK1	0.045	0.1	0.44	22	-10000	0	22
adherens junction assembly	0.027	0.085	0.46	12	-0.56	1	13
IGF-1R heterotetramer/IGF1	-0.036	0.16	-10000	0	-0.36	102	102
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.038	0.011	-10000	0	-10000	0	0
MET	-0.029	0.074	-10000	0	-10000	0	0
PLEKHA7	0.026	0.052	0.38	8	-0.37	1	9
mol:GTP	0.059	0.024	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.033	0.067	0.48	7	-10000	0	7
cortical actin cytoskeleton stabilization	0.029	0.009	-10000	0	-10000	0	0
regulation of cell-cell adhesion	0.021	0.05	0.38	8	-10000	0	8
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.029	0.009	-10000	0	-10000	0	0

×

BARD1 signaling events

Figure S84. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S84. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.012	0.12	-10000	0	-0.47	27	27
ATM	0.025	0.032	-10000	0	-0.67	1	1
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
PRKDC	0.027	0.005	-10000	0	-10000	0	0
ATR	0.026	0.032	-10000	0	-0.67	1	1
UBE2L3	0.02	0.012	-10000	0	-10000	0	0
FANCD2	0.023	0.026	-10000	0	-0.38	2	2
protein ubiquitination	0.044	0.096	-10000	0	-0.38	21	21
XRCC5	0.027	0.005	-10000	0	-10000	0	0
XRCC6	0.02	0.012	-10000	0	-10000	0	0
M/R/N Complex	0.051	0.034	-10000	0	-0.44	2	2
MRE11A	0.024	0.045	-10000	0	-0.67	2	2
DNA-PK	0.04	0.026	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.008	0.12	-10000	0	-0.49	23	23
FANCF	0.027	0.005	-10000	0	-10000	0	0
BRCA1	0.026	0.007	-10000	0	-10000	0	0
CCNE1	0.025	0.007	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.037	0.012	-10000	0	-10000	0	0
FANCG	0.025	0.007	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.011	0.12	-10000	0	-0.46	27	27
FANCE	0.027	0.003	-10000	0	-10000	0	0
FANCC	0.025	0.008	-10000	0	-10000	0	0
NBN	0.027	0.005	-10000	0	-10000	0	0
FANCA	0.02	0.031	-10000	0	-10000	0	0
DNA repair	0.018	0.09	0.41	2	-0.49	4	6
BRCA1/BARD1/ubiquitin	0.011	0.12	-10000	0	-0.46	27	27
BARD1/DNA-PK	0.028	0.1	-10000	0	-0.4	23	23
FANCL	0.027	0.005	-10000	0	-10000	0	0
mRNA polyadenylation	-0.011	0.12	0.47	27	-10000	0	27
BRCA1/BARD1/CTIP/M/R/N Complex	0.014	0.075	-10000	0	-0.48	1	1
BRCA1/BACH1/BARD1/TopBP1	0.028	0.1	-10000	0	-0.42	24	24
BRCA1/BARD1/P53	0.042	0.1	-10000	0	-0.4	22	22
BARD1/CSTF1/BRCA1	0.028	0.1	-10000	0	-0.44	21	21
BRCA1/BACH1	0.026	0.007	-10000	0	-10000	0	0
BARD1	-0.011	0.15	-10000	0	-0.63	28	28
PCNA	0.027	0.005	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.028	0.1	-10000	0	-0.44	21	21
BRCA1/BARD1/UbcH7	0.017	0.1	-10000	0	-0.43	22	22
BRCA1/BARD1/RAD51/PCNA	0.043	0.1	-10000	0	-0.41	21	21
BARD1/DNA-PK/P53	0.037	0.098	-10000	0	-0.38	21	21
BRCA1/BARD1/Ubiquitin	0.011	0.12	-10000	0	-0.46	27	27
BRCA1/BARD1/CTIP	0.023	0.096	-10000	0	-0.4	22	22
FA complex	0.028	0.033	-10000	0	-10000	0	0
BARD1/EWS	0.002	0.12	-10000	0	-0.48	26	26
RBBP8	0.016	0.024	-10000	0	-0.51	1	1
TP53	0.026	0.007	-10000	0	-10000	0	0
TOPBP1	0.027	0.003	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.04	0.099	0.4	22	-10000	0	22
BRCA1/BARD1	0.05	0.099	-10000	0	-0.38	21	21
CSTF1	0.027	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.008	0.12	-10000	0	-0.47	28	28
CDK2	0.027	0.005	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.026	0.011	-10000	0	-10000	0	0
RAD50	0.026	0.006	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.011	0.12	-10000	0	-0.46	27	27
EWSR1	0.02	0.012	-10000	0	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.025	0.043	-10000	0	-10000	0	0
TP53	-0.009	0.039	-10000	0	-0.18	22	22
Senescence	-0.009	0.038	-10000	0	-0.18	22	22
Apoptosis	-0.009	0.038	-10000	0	-0.18	22	22
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.011	0.025	0.35	1	-10000	0	1
MDM4	0.025	0.008	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.027	0.005	-10000	0	-10000	0	0
NFATC1	0.037	0.094	0.46	9	-0.38	9	18
NFATC2	-0.022	0.097	0.28	9	-0.27	31	40
NFATC3	0.018	0.011	-10000	0	-10000	0	0
YWHAE	0.026	0.007	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.007	0.086	0.28	1	-0.4	10	11
Exportin 1/Ran/NUP214	0.047	0.018	-10000	0	-10000	0	0
mol:DAG	-0.002	0.003	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.004	0.098	-10000	0	-0.44	9	9
BCL2/BAX	-0.003	0.14	-10000	0	-0.48	38	38
CaM/Ca2+/Calcineurin A alpha-beta B1	0.008	0.02	-10000	0	-10000	0	0
CaM/Ca2+	0.008	0.02	-10000	0	-10000	0	0
BAX	0.025	0.01	-10000	0	-10000	0	0
MAPK14	0.025	0.005	-10000	0	-10000	0	0
BAD	0.027	0.005	-10000	0	-10000	0	0
CABIN1/MEF2D	0.006	0.091	0.4	2	-0.39	10	12
Calcineurin A alpha-beta B1/BCL2	-0.026	0.18	-10000	0	-0.66	38	38
FKBP8	0.025	0.008	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.006	0.09	0.38	10	-0.39	2	12
KPNB1	0.026	0.007	-10000	0	-10000	0	0
KPNA2	0.026	0.007	-10000	0	-10000	0	0
XPO1	0.026	0.005	-10000	0	-10000	0	0
SFN	-0.085	0.13	-10000	0	-0.67	15	15
MAP3K8	0.016	0.079	-10000	0	-0.63	7	7
NFAT4/CK1 alpha	0.019	0.029	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.073	0.17	-10000	0	-0.34	109	109
CABIN1	-0.007	0.084	0.28	1	-0.4	9	10
CALM1	0.023	0.009	-10000	0	-10000	0	0
RAN	0.026	0.005	-10000	0	-10000	0	0
MAP3K1	0.027	0.005	-10000	0	-10000	0	0
CAMK4	0.013	0.085	-10000	0	-0.67	7	7
mol:Ca2+	-0.004	0.009	-10000	0	-10000	0	0
MAPK3	0.026	0.006	-10000	0	-10000	0	0
YWHAH	0.02	0.012	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.036	0.012	-10000	0	-10000	0	0
YWHAB	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.011	0.095	-10000	0	-0.64	10	10
MAPK9	0.026	0.006	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
FKBP1A	0.027	0.005	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.022	0.086	0.37	2	-0.47	3	5
PRKCH	0.027	0.005	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.013	0.031	-10000	0	-10000	0	0
CASP3	0.025	0.005	-10000	0	-10000	0	0
PIM1	0.027	0.003	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.011	0.012	-10000	0	-10000	0	0
apoptosis	0.009	0.044	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.003	0.054	-10000	0	-0.32	5	5
PRKCB	0.007	0.08	-10000	0	-0.67	5	5
PRKCE	0.02	0.07	-10000	0	-0.67	5	5
JNK2/NFAT4	0.031	0.026	-10000	0	-10000	0	0
BAD/BCL-XL	0.039	0.009	-10000	0	-10000	0	0
PRKCD	0.027	0.003	-10000	0	-10000	0	0
NUP214	0.025	0.008	-10000	0	-10000	0	0
PRKCZ	0.024	0.007	-10000	0	-10000	0	0
PRKCA	0.002	0.13	-10000	0	-0.67	17	17
PRKCG	0.005	0.023	-10000	0	-10000	0	0
PRKCQ	0.019	0.072	-10000	0	-0.62	6	6
FKBP38/BCL2	-0.003	0.14	-10000	0	-0.48	38	38
EP300	0.01	0.02	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.027	0.005	-10000	0	-10000	0	0
NFATc/JNK1	0.039	0.1	0.41	7	-0.38	11	18
CaM/Ca2+/FKBP38	0.019	0.025	-10000	0	-10000	0	0
FKBP12/FK506	0.02	0.004	-10000	0	-10000	0	0
CSNK1A1	0.005	0.02	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.013	0.062	-10000	0	-0.45	7	7
NFATc/ERK1	0.044	0.08	0.44	3	-0.41	4	7
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.008	0.1	-10000	0	-0.45	9	9
NR4A1	-0.17	0.29	-10000	0	-0.61	148	148
GSK3B	0.024	0.007	-10000	0	-10000	0	0
positive T cell selection	0.018	0.011	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.023	0.072	-10000	0	-0.31	10	10
RCH1/ KPNB1	0.038	0.01	-10000	0	-10000	0	0
YWHAQ	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.023	0.008	-10000	0	-10000	0	0
AKAP5	0.027	0.005	-10000	0	-10000	0	0
MEF2D	0.014	0.021	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
NFATc/p38 alpha	0.05	0.093	0.43	10	-0.41	4	14
CREBBP	0.013	0.022	-10000	0	-10000	0	0
BCL2	-0.026	0.18	-10000	0	-0.67	38	38

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	0.026	0.006	-10000	0	-10000	0	0
VDR	0.026	0.009	-10000	0	-10000	0	0
Cbp/p300/PCAF	0.04	0.026	-10000	0	-10000	0	0
EP300	0.02	0.012	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.003	0.07	-10000	0	-0.31	10	10
KAT2B	0.027	0.004	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.014	0.083	0.25	14	-0.36	14	28
RAR alpha/9cRA/Cyclin H	0.035	0.097	-10000	0	-0.38	18	18
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.013	0.066	0.25	1	-0.35	8	9
CDC2	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.011	0.097	-10000	0	-0.57	10	10
NCOR2	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.02	0.006	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.003	0.13	-10000	0	-0.55	21	21
NCOA2	-0.037	0.2	-10000	0	-0.67	45	45
NCOA3	0.027	0.005	-10000	0	-10000	0	0
NCOA1	0.027	0.005	-10000	0	-10000	0	0
VDR/VDR/DNA	0.026	0.009	-10000	0	-10000	0	0
RARG	0.027	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.034	0.011	-10000	0	-10000	0	0
MAPK3	0.027	0.006	-10000	0	-10000	0	0
MAPK1	0.02	0.012	-10000	0	-10000	0	0
MAPK8	0.014	0.095	-10000	0	-0.64	10	10
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.009	0.12	-10000	0	-0.54	18	18
RARA	0.005	0.075	-10000	0	-0.31	24	24
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.015	0.13	-10000	0	-0.48	25	25
PRKCA	0.004	0.13	-10000	0	-0.67	17	17
RXRs/RARs/NRIP1/9cRA/HDAC1	0.011	0.14	0.4	4	-0.54	23	27
RXRG	-0.028	0.079	-10000	0	-0.4	21	21
RXRA	0.007	0.075	-10000	0	-0.31	21	21
RXRB	0.009	0.074	-10000	0	-0.38	17	17
VDR/Vit D3/DNA	0.02	0.006	-10000	0	-10000	0	0
RBP1	0.013	0.094	-10000	0	-0.67	9	9
CRBP1/9-cic-RA	0.01	0.071	-10000	0	-0.51	9	9
RARB	0.009	0.12	-10000	0	-0.67	14	14
PRKCG	0.022	0.014	-10000	0	-10000	0	0
MNAT1	0.027	0.005	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.006	0.13	-10000	0	-0.58	21	21
RXRs/RARs/SMRT(N-CoR2)/9cRA	0	0.12	-10000	0	-0.49	21	21
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.09	0.36	3	-0.42	11	14
RXRs/RARs/NRIP1/9cRA/HDAC3	0.012	0.14	0.42	5	-0.54	22	27
positive regulation of DNA binding	0.023	0.088	-10000	0	-0.36	19	19
NRIP1	0.012	0.13	0.5	1	-0.72	5	6
RXRs/RARs	0.005	0.13	-10000	0	-0.54	23	23
RXRs/RXRs/DNA/9cRA	-0.011	0.12	-10000	0	-0.55	19	19
PRKACA	0.025	0.008	-10000	0	-10000	0	0
CDK7	0.027	0.005	-10000	0	-10000	0	0
TFIIH	0.054	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.047	0.068	-10000	0	-0.42	3	3
CCNH	0.027	0.005	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.05	0.018	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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
ARF5/GTP	0.026	0.046	0.29	10	-0.35	1	11
DAPP1	-0.037	0.13	0.33	4	-0.47	12	16
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.052	0.17	0.29	7	-0.48	27	34
mol:DAG	-0.016	0.095	0.35	11	-0.25	14	25
HRAS	0.027	0.012	-10000	0	-10000	0	0
RAP1A	0.028	0.007	-10000	0	-10000	0	0
ARF5/GDP	0.035	0.064	0.35	1	-0.35	4	5
PLCG2	0.026	0.006	-10000	0	-10000	0	0
PLCG1	0.027	0.005	-10000	0	-10000	0	0
ARF5	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.048	0.3	10	-10000	0	10
ARF1/GTP	0.004	0.017	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
YES1	0.027	0.005	-10000	0	-10000	0	0
RAP1A/GTP	0.019	0.017	-10000	0	-10000	0	0
ADAP1	0	0.045	0.29	10	-10000	0	10
ARAP3	0	0.047	0.3	10	-10000	0	10
INPPL1	0.027	0.005	-10000	0	-10000	0	0
PREX1	0.027	0.005	-10000	0	-10000	0	0
ARHGEF6	0.025	0.019	-10000	0	-0.36	1	1
ARHGEF7	0.026	0.006	-10000	0	-10000	0	0
ARF1	0.025	0.008	-10000	0	-10000	0	0
NRAS	0.028	0.007	-10000	0	-10000	0	0
FYN	0.027	0.004	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
FGR	0.025	0.015	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.065	0.3	10	-10000	0	10
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.059	0.081	-10000	0	-0.67	1	1
ZAP70	0	0.13	-10000	0	-0.66	17	17
mol:IP3	-0.013	0.069	0.24	12	-0.21	4	16
LYN	0.027	0.005	-10000	0	-10000	0	0
ARF1/GDP	0.034	0.073	0.32	6	-0.35	6	12
RhoA/GDP	0.039	0.044	0.35	2	-10000	0	2
PDK1/Src/Hsp90	0.05	0.034	-10000	0	-0.44	2	2
BLNK	0.027	0.004	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.034	0.076	0.4	10	-10000	0	10
SRC	0.026	0.008	-10000	0	-10000	0	0
PLEKHA2	0.005	0.016	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
PTEN	0.023	0.021	-10000	0	-0.34	1	1
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.025	0.039	0.29	9	-10000	0	9
RhoA/GTP	0.025	0.042	0.3	9	-10000	0	9
Src family/SYK family/BLNK-LAT	-0.045	0.14	-10000	0	-0.44	24	24
BLK	-0.19	0.31	-10000	0	-0.67	148	148
PDPK1	0.023	0.045	-10000	0	-0.67	2	2
CYTH1	0.002	0.054	0.31	12	-10000	0	12
HCK	0.017	0.039	-10000	0	-10000	0	0
CYTH3	-0.002	0.049	0.29	10	-0.36	1	11
CYTH2	0.003	0.057	0.31	14	-10000	0	14
KRAS	0.028	0.007	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.017	0.089	-10000	0	-0.54	10	10
SGK1	0.018	0.098	-10000	0	-0.59	10	10
INPP5D	0.019	0.034	-10000	0	-10000	0	0
mol:GDP	0.026	0.08	0.3	12	-0.33	8	20
SOS1	0.027	0.005	-10000	0	-10000	0	0
SYK	0.025	0.008	-10000	0	-10000	0	0
ARF6/GDP	0.03	0.051	0.29	8	-10000	0	8
mol:PI-3-4-5-P3	-0.007	0.015	-10000	0	-10000	0	0
ARAP3/RAP1A/GTP	0.019	0.017	-10000	0	-10000	0	0
VAV1	0.011	0.061	-10000	0	-0.57	3	3
mol:PI-3-4-P2	0.012	0.021	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.044	0.029	0.33	1	-10000	0	1
PLEKHA1	0.005	0.016	-10000	0	-10000	0	0
Rac1/GDP	0.034	0.065	0.35	1	-0.34	5	6
LAT	0.021	0.058	-10000	0	-0.6	4	4
Rac1/GTP	0.017	0.059	0.27	1	-0.48	3	4
ITK	-0.039	0.12	0.28	9	-0.36	48	57
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.028	0.12	0.38	9	-0.36	15	24
LCK	0.012	0.082	-10000	0	-0.67	6	6
BTK	-0.005	0.067	0.3	13	-0.36	6	19

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.002	0.099	0.49	5	-10000	0	5
RAD9A	0.027	0.005	-10000	0	-10000	0	0
AP1	-0.19	0.37	-10000	0	-0.72	149	149
IFNAR2	0.027	0.006	-10000	0	-10000	0	0
AKT1	0.008	0.053	-10000	0	-0.24	20	20
ER alpha/Oestrogen	-0.009	0.11	-10000	0	-0.48	23	23
NFX1/SIN3/HDAC complex	0.032	0.036	-10000	0	-0.49	1	1
EGF	-0.075	0.24	-10000	0	-0.67	72	72
SMG5	0.025	0.007	-10000	0	-10000	0	0
SMG6	0.026	0.007	-10000	0	-10000	0	0
SP3/HDAC2	0.041	0.008	-10000	0	-10000	0	0
TERT/c-Abl	-0.003	0.081	0.47	1	-10000	0	1
SAP18	0.026	0.007	-10000	0	-10000	0	0
MRN complex	0.051	0.034	-10000	0	-0.44	2	2
WT1	0.007	0.048	-10000	0	-10000	0	0
WRN	0.025	0.032	-10000	0	-0.67	1	1
SP1	0.028	0.006	-10000	0	-10000	0	0
SP3	0.027	0.005	-10000	0	-10000	0	0
TERF2IP	0.026	0.006	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.012	0.081	-10000	0	-10000	0	0
Mad/Max	0.04	0.009	-10000	0	-10000	0	0
TERT	-0.002	0.1	0.5	5	-10000	0	5
CCND1	0.001	0.1	0.53	6	-10000	0	6
MAX	0.027	0.005	-10000	0	-10000	0	0
RBBP7	0.026	0.007	-10000	0	-10000	0	0
RBBP4	0.024	0.045	-10000	0	-0.67	2	2
TERF2	0.024	0.009	-10000	0	-10000	0	0
PTGES3	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
Telomerase/911	0.027	0.057	-10000	0	-10000	0	0
CDKN1B	-0.029	0.15	-10000	0	-0.42	57	57
RAD1	0.026	0.006	-10000	0	-10000	0	0
XRCC5	0.027	0.005	-10000	0	-10000	0	0
XRCC6	0.02	0.012	-10000	0	-10000	0	0
SAP30	0.026	0.032	-10000	0	-0.67	1	1
TRF2/PARP2	0.038	0.011	-10000	0	-10000	0	0
UBE3A	0.028	0.004	-10000	0	-10000	0	0
JUN	-0.12	0.29	-10000	0	-0.67	107	107
E6	0	0	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.021	0.003	-10000	0	-10000	0	0
FOS	-0.15	0.3	-10000	0	-0.67	125	125
IFN-gamma/IRF1	-0.023	0.18	-10000	0	-0.48	62	62
PARP2	0.027	0.005	-10000	0	-10000	0	0
BLM	0.027	0.008	-10000	0	-10000	0	0
Telomerase	0.016	0.1	0.27	1	-0.48	12	13
IRF1	0.03	0.009	-10000	0	-10000	0	0
ESR1	-0.013	0.15	-10000	0	-0.65	23	23
KU/TER	0.029	0.019	-10000	0	-10000	0	0
ATM/TRF2	0.038	0.025	-10000	0	-0.46	1	1
ubiquitin-dependent protein catabolic process	0.038	0.039	-10000	0	-0.33	3	3
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.038	0.04	-10000	0	-0.34	3	3
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC2	0.028	0.004	-10000	0	-10000	0	0
ATM	0.009	0.023	-10000	0	-0.48	1	1
SMAD3	0.015	0.011	-10000	0	-10000	0	0
ABL1	0.025	0.008	-10000	0	-10000	0	0
MXD1	0.027	0.005	-10000	0	-10000	0	0
MRE11A	0.024	0.045	-10000	0	-0.67	2	2
HUS1	0.026	0.006	-10000	0	-10000	0	0
RPS6KB1	0.026	0.007	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.017	0.08	-10000	0	-10000	0	0
NR2F2	0.026	0.004	-10000	0	-10000	0	0
MAPK3	0.002	0.013	-10000	0	-10000	0	0
MAPK1	0.002	0.011	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.024	0.017	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
HNRNPC	0.027	0.005	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.009	0.023	-10000	0	-0.48	1	1
NBN	0.027	0.005	-10000	0	-10000	0	0
EGFR	0.02	0.07	-10000	0	-0.67	5	5
mol:Oestrogen	0	0	-10000	0	-10000	0	0
EGF/EGFR	-0.044	0.2	-10000	0	-0.5	76	76
MYC	0.011	0.1	-10000	0	-0.65	12	12
IL2	0.02	0.009	-10000	0	-10000	0	0
KU	0.029	0.019	-10000	0	-10000	0	0
RAD50	0.026	0.006	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
TGFB1	0.024	0.017	-10000	0	-10000	0	0
TRF2/BLM	0.038	0.012	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.002	0.084	0.5	2	-10000	0	2
SP1/HDAC2	0.042	0.01	-10000	0	-10000	0	0
PINX1	0.027	0.005	-10000	0	-10000	0	0
Telomerase/EST1A	0.012	0.08	-10000	0	-10000	0	0
Smad3/Myc	0.018	0.068	-10000	0	-0.42	11	11
911 complex	0.052	0.015	-10000	0	-10000	0	0
IFNG	-0.062	0.23	-10000	0	-0.67	62	62
Telomerase/PinX1	0.011	0.081	-10000	0	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	0.015	0.061	0.37	1	-0.42	2	3
SIN3B	0.026	0.008	-10000	0	-10000	0	0
YWHAE	0.026	0.007	-10000	0	-10000	0	0
Telomerase/EST1B	0.01	0.078	-10000	0	-10000	0	0
response to DNA damage stimulus	0.003	0.019	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.071	0.036	-10000	0	-0.38	2	2
TRF2/WRN	0.037	0.026	-10000	0	-0.48	1	1
Telomerase/hnRNP C1/C2	0.012	0.082	-10000	0	-10000	0	0
E2F1	-0.018	0.071	-10000	0	-10000	0	0
ZNFX1	0.027	0.005	-10000	0	-10000	0	0
PIF1	0.017	0.078	-10000	0	-0.67	6	6
NCL	0.027	0.005	-10000	0	-10000	0	0
DKC1	0.025	0.008	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

S1P3 pathway

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
PDGFRB	0.025	0.032	-9999	-0.67	1	1
mol:S1P	0.001	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.013	0.053	-9999	-0.26	16	16
GNAO1	0.005	0.12	-9999	-0.67	15	15
S1P/S1P3/G12/G13	0.048	0.02	-9999	-10000	0	0
AKT1	0.023	0.041	-9999	-0.35	3	3
AKT3	0.019	0.067	-9999	-0.51	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.025	0.032	-9999	-0.67	1	1
GNAI2	0.029	0.004	-9999	-10000	0	0
GNAI3	0.028	0.005	-9999	-10000	0	0
GNAI1	0.026	0.032	-9999	-0.67	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.026	0.008	-9999	-10000	0	0
S1PR2	0.024	0.014	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.006	0.07	-9999	-0.3	15	15
MAPK3	0.003	0.065	-9999	-0.4	3	3
MAPK1	0.014	0.058	-9999	-0.38	3	3
JAK2	0.006	0.067	-9999	-0.4	3	3
CXCR4	0.003	0.064	-9999	-0.4	3	3
FLT1	0.027	0.032	-9999	-0.67	1	1
RhoA/GDP	0.02	0.003	-9999	-10000	0	0
Rac1/GDP	0.02	0.004	-9999	-10000	0	0
SRC	0.003	0.063	-9999	-0.34	3	3
S1P/S1P3/Gi	0.006	0.07	-9999	-0.3	15	15
RAC1	0.026	0.006	-9999	-10000	0	0
RhoA/GTP	0.01	0.073	-9999	-0.38	3	3
VEGFA	0.025	0.055	-9999	-0.67	3	3
S1P/S1P2/Gi	0.004	0.074	-9999	-0.32	16	16
VEGFR1 homodimer/VEGFA homodimer	0.04	0.057	-9999	-0.64	3	3
RHOA	0.027	0.003	-9999	-10000	0	0
S1P/S1P3/Gq	-0.057	0.15	-9999	-0.31	122	122
GNAQ	0.025	0.008	-9999	-10000	0	0
GNAZ	0.021	0.013	-9999	-10000	0	0
G12/G13	0.038	0.011	-9999	-10000	0	0
GNA14	-0.14	0.29	-9999	-0.64	120	120
GNA15	0.013	0.05	-9999	-0.67	1	1
GNA12	0.026	0.006	-9999	-10000	0	0
GNA13	0.026	0.007	-9999	-10000	0	0
GNA11	0.015	0.084	-9999	-0.64	8	8
Rac1/GTP	0.01	0.072	-9999	-0.38	3	3

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

Figure S91. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S91. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.11	0.28	-10000	0	-0.67	97	97
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.025	0.014	-10000	0	-10000	0	0
TCEB1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/p53	0.033	0.039	0.35	1	-10000	0	1
HIF1A	0.009	0.024	-10000	0	-10000	0	0
COPS5	0.027	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.054	0.052	-10000	0	-0.39	3	3
FIH (dimer)	0.027	0.004	-10000	0	-10000	0	0
CDKN2A	-0.032	0.074	-10000	0	-10000	0	0
ARNT/IPAS	-0.067	0.21	-10000	0	-0.49	97	97
HIF1AN	0.027	0.004	-10000	0	-10000	0	0
GNB2L1	0.026	0.006	-10000	0	-10000	0	0
HIF1A/ARNT	0.032	0.048	0.31	7	-10000	0	7
CUL2	0.027	0.004	-10000	0	-10000	0	0
OS9	0.027	0.005	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.052	0.015	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.033	0.038	0.28	1	-10000	0	1
PHD1-3/OS9	0.05	0.073	-10000	0	-0.4	11	11
HIF1A/RACK1/Elongin B/Elongin C	0.055	0.039	-10000	0	-10000	0	0
VHL	0.023	0.054	-10000	0	-0.67	3	3
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
HIF1A/JAB1	0.036	0.047	0.34	4	-10000	0	4
EGLN3	0.006	0.1	-10000	0	-0.67	10	10
EGLN2	0.026	0.007	-10000	0	-10000	0	0
EGLN1	0.024	0.032	-10000	0	-0.67	1	1
TP53	0.026	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.026	0.075	-10000	0	-0.57	6	6
ARNT	0.025	0.007	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.02	0.012	-10000	0	-10000	0	0
HIF1A/p19ARF	0.037	0.052	0.33	5	-10000	0	5

×

Class IB PI3K non-lipid kinase 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
cAMP biosynthetic process	-0.015	0.08	0.63	7	-10000	0	7
PI3K Class IB/PDE3B	0.015	0.08	-10000	0	-0.63	7	7
PDE3B	0.015	0.08	-10000	0	-0.63	7	7

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.004	-9999	-10000	0	0
ITGB7	0.004	0.11	-9999	-0.65	12	12
ITGA4	0.02	0.058	-9999	-0.67	3	3
alpha4/beta7 Integrin	0.016	0.095	-9999	-0.51	14	14
alpha4/beta1 Integrin	0.034	0.046	-9999	-0.51	3	3

×

PLK1 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
regulation of centriole-centriole cohesion	-0.006	0.016	0.12	1	-0.13	3	4
BUB1B	0.014	0.031	0.18	10	-0.15	1	11
PLK1	0.012	0.03	0.16	13	-0.1	1	14
PLK1S1	0.015	0.026	0.18	9	-10000	0	9
KIF2A	0.018	0.067	0.32	20	-0.39	1	21
regulation of mitotic centrosome separation	0.012	0.03	0.16	13	-0.1	1	14
GOLGA2	0.025	0.008	-10000	0	-10000	0	0
Hec1/SPC24	0.033	0.036	-10000	0	-10000	0	0
WEE1	0.022	0.046	0.29	5	-0.34	2	7
cytokinesis	0.011	0.062	0.27	8	-0.26	2	10
PP2A-alpha B56	0.048	0.095	-10000	0	-0.55	9	9
AURKA	0.014	0.023	0.17	7	-10000	0	7
PICH/PLK1	0.02	0.015	-10000	0	-10000	0	0
CENPE	0.01	0.051	0.26	10	-0.39	3	13
RhoA/GTP	0.02	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.018	0.067	0.32	20	-0.38	1	21
PPP2CA	0.026	0.006	-10000	0	-10000	0	0
FZR1	0.025	0.008	-10000	0	-10000	0	0
TPX2	0.015	0.027	0.17	11	-10000	0	11
PAK1	0.026	0.005	-10000	0	-10000	0	0
SPC24	0.015	0.037	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
CLSPN	0.012	0.029	0.14	1	-0.29	3	4
GORASP1	0.027	0.004	-10000	0	-10000	0	0
metaphase	0.001	0.006	0.023	27	-10000	0	27
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.006	0.018	0.095	14	-0.05	1	15
G2 phase of mitotic cell cycle	0	0.004	0.02	12	-10000	0	12
STAG2	0.026	0.007	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.024	0.03	-10000	0	-0.41	2	2
spindle elongation	0.012	0.03	0.16	13	-0.1	1	14
ODF2	0.025	0.008	-10000	0	-10000	0	0
BUB1	0.022	0.099	-10000	0	-0.56	13	13
TPT1	0.004	0.045	0.14	4	-0.18	24	28
CDC25C	0.019	0.025	0.2	5	-10000	0	5
CDC25B	0.027	0.011	-10000	0	-10000	0	0
SGOL1	0.006	0.016	0.13	3	-0.12	1	4
RHOA	0.027	0.003	-10000	0	-10000	0	0
CCNB1/CDK1	0.042	0.015	-10000	0	-10000	0	0
CDC14B	0.003	0.045	-10000	0	-0.38	6	6
CDC20	0.025	0.019	-10000	0	-10000	0	0
PLK1/PBIP1	0.01	0.019	0.14	3	-10000	0	3
mitosis	-0.001	0.003	0.019	4	-10000	0	4
FBXO5	0.013	0.037	0.21	9	-0.34	1	10
CDC2	0.002	0.001	0.01	1	-10000	0	1
NDC80	0.009	0.049	-10000	0	-10000	0	0
metaphase plate congression	0.014	0.025	0.14	1	-0.24	3	4
ERCC6L	0.025	0.014	-10000	0	-10000	0	0
NLP/gamma Tubulin	0.011	0.027	0.14	15	-10000	0	15
microtubule cytoskeleton organization	0.004	0.045	0.14	4	-0.18	24	28
G2/M transition DNA damage checkpoint	0	0.004	0.019	15	-10000	0	15
PPP1R12A	0.027	0.005	-10000	0	-10000	0	0
interphase	0	0.004	0.019	15	-10000	0	15
PLK1/PRC1-2	0.038	0.027	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP/PLK1	0.049	0.021	-10000	0	-10000	0	0
RAB1A	0.027	0.005	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.009	0.027	0.14	14	-10000	0	14
mitotic prometaphase	0	0.004	0.027	7	-10000	0	7
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.026	-10000	0	-10000	0	0
microtubule-based process	0.013	0.031	-10000	0	-10000	0	0
Golgi organization	0.012	0.03	0.16	13	-0.1	1	14
Cohesin/SA2	0.021	0.02	0.18	3	-10000	0	3
PPP1CB/MYPT1	0.04	0.009	-10000	0	-10000	0	0
KIF20A	0.005	0.054	-10000	0	-10000	0	0
APC/C/CDC20	0.025	0.024	0.18	2	-10000	0	2
PPP2R1A	0.025	0.007	-10000	0	-10000	0	0
chromosome segregation	0.01	0.019	0.14	3	-10000	0	3
PRC1	0.027	0.004	-10000	0	-10000	0	0
ECT2	0.01	0.041	0.22	8	-0.4	2	10
C13orf34	0.01	0.026	0.14	13	-0.081	1	14
NUDC	0.014	0.025	0.14	1	-0.24	3	4
regulation of attachment of spindle microtubules to kinetochore	0.014	0.031	0.18	10	-0.14	1	11
spindle assembly	0.014	0.037	0.17	18	-10000	0	18
spindle stabilization	0.015	0.026	0.18	9	-10000	0	9
APC/C/HCDH1	0.019	0.041	-10000	0	-0.32	6	6
MKLP2/PLK1	0.013	0.032	-10000	0	-10000	0	0
CCNB1	0.028	0.006	-10000	0	-10000	0	0
PPP1CB	0.027	0.005	-10000	0	-10000	0	0
BTRC	0.027	0.004	-10000	0	-10000	0	0
ROCK2	-0.006	0.11	0.22	2	-0.41	32	34
TUBG1	0.015	0.028	0.18	9	-0.16	2	11
G2/M transition of mitotic cell cycle	0.013	0.01	-10000	0	-10000	0	0
MLF1IP	0.007	0.012	-10000	0	-10000	0	0
INCENP	0.024	0.045	-10000	0	-0.68	2	2

×

IL2 signaling events mediated by STAT5

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
GAB2	0.027	0.005	-10000	0	-10000	0	0
ELF1	0.004	0.1	-10000	0	-0.39	29	29
CCNA2	0.025	0.02	-10000	0	-10000	0	0
PIK3CA	0.024	0.054	-10000	0	-0.67	3	3
JAK3	-0.012	0.066	-10000	0	-10000	0	0
PIK3R1	0.027	0.006	-10000	0	-10000	0	0
JAK1	0.027	0.005	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.003	0.13	-10000	0	-0.59	16	16
SHC1	0.026	0.008	-10000	0	-10000	0	0
SP1	0.033	0.006	-10000	0	-10000	0	0
IL2RA	-0.033	0.21	-10000	0	-0.87	28	28
IL2RB	0.004	0.09	-10000	0	-0.58	10	10
SOS1	0.027	0.005	-10000	0	-10000	0	0
IL2RG	-0.011	0.14	-10000	0	-0.63	21	21
G1/S transition of mitotic cell cycle	0.03	0.063	0.42	5	-0.5	3	8
PTPN11	0.026	0.032	-10000	0	-0.67	1	1
CCND2	0.024	0.005	-10000	0	-10000	0	0
LCK	0.013	0.082	-10000	0	-0.67	6	6
GRB2	0.026	0.007	-10000	0	-10000	0	0
IL2	0.02	0.006	-10000	0	-10000	0	0
CDK6	0.022	0.055	-10000	0	-0.67	3	3
CCND3	0.007	0.12	-10000	0	-0.59	9	9

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.035	0.077	-10000	0	-10000	0	0
CDKN2C	0.031	0.02	-10000	0	-10000	0	0
CDKN2A	-0.032	0.077	-10000	0	-10000	0	0
CCND2	0.011	0.024	-10000	0	-10000	0	0
RB1	-0.016	0.049	0.32	2	-0.24	14	16
CDK4	0.015	0.042	0.26	10	-10000	0	10
CDK6	0.017	0.044	0.26	10	-0.16	1	11
G1/S progression	0.017	0.051	0.24	15	-0.32	2	17

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.025	0.089	-10000	0	-0.52	12	12
AKT1	0.04	0.09	0.37	3	-0.58	7	10
PTK2B	0.017	0.11	0.35	1	-0.8	5	6
VEGFR2 homodimer/Frs2	0.032	0.083	-10000	0	-0.88	4	4
CAV1	0.014	0.094	-10000	0	-0.67	9	9
CALM1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.047	0.094	-10000	0	-0.74	6	6
endothelial cell proliferation	0.054	0.14	0.57	19	-0.55	6	25
mol:Ca2+	0.023	0.09	-10000	0	-0.64	7	7
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.061	0.092	-10000	0	-0.77	5	5
RP11-342D11.1	0.012	0.089	-10000	0	-0.64	7	7
CDH5	0.026	0.006	-10000	0	-10000	0	0
VEGFA homodimer	0.059	0.058	-10000	0	-0.49	4	4
SHC1	0.025	0.008	-10000	0	-10000	0	0
SHC2	0.021	0.055	-10000	0	-0.67	3	3
HRAS/GDP	0.04	0.079	-10000	0	-0.64	5	5
SH2D2A	-0.008	0.14	-10000	0	-0.67	21	21
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.058	0.095	-10000	0	-0.65	4	4
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.025	0.13	-10000	0	-0.46	27	27
VEGFR1 homodimer	0.024	0.032	-10000	0	-0.67	1	1
SHC/GRB2/SOS1	0.066	0.095	-10000	0	-0.81	4	4
GRB10	0.024	0.089	-10000	0	-0.86	4	4
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
GRB2	0.026	0.007	-10000	0	-10000	0	0
PAK1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.07	0.092	-10000	0	-0.84	4	4
HRAS	0.026	0.011	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.028	0.065	-10000	0	-0.44	5	5
HIF1A	0.027	0.005	-10000	0	-10000	0	0
FRS2	0.027	0.005	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.059	0.089	-10000	0	-0.75	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.018	0.077	-10000	0	-0.67	6	6
Nck/Pak	0.039	0.008	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.048	0.094	-10000	0	-0.74	6	6
mol:GDP	0.052	0.086	-10000	0	-0.76	4	4
mol:NADP	0.041	0.097	0.46	7	-0.48	6	13
eNOS/Hsp90	0.044	0.079	-10000	0	-0.5	4	4
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.023	0.093	-10000	0	-0.66	7	7
HIF1A/ARNT	0.037	0.012	-10000	0	-10000	0	0
SHB	0.025	0.007	-10000	0	-10000	0	0
VEGFA	0.025	0.054	-10000	0	-0.67	3	3
VEGFC	0.026	0.032	-10000	0	-0.67	1	1
FAK1/Vinculin	0.04	0.1	0.33	1	-0.69	6	7
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.048	0.12	-10000	0	-0.52	16	16
PTPN6	0.027	0.005	-10000	0	-10000	0	0
EPAS1	0.031	0.056	-10000	0	-0.53	4	4
mol:L-citrulline	0.041	0.097	0.46	7	-0.48	6	13
ITGAV	0.024	0.045	-10000	0	-0.67	2	2
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.059	0.092	-10000	0	-0.77	5	5
VEGFR2 homodimer/VEGFA homodimer	0.05	0.11	-10000	0	-0.73	7	7
VEGFR2/3 heterodimer	0.027	0.11	-10000	0	-0.84	7	7
VEGFB	0.027	0.005	-10000	0	-10000	0	0
MAPK11	0.006	0.098	0.38	1	-0.7	7	8
VEGFR2 homodimer	0.019	0.09	-10000	0	-0.97	4	4
FLT1	0.024	0.032	-10000	0	-0.67	1	1
NEDD4	0.026	0.045	-10000	0	-0.67	2	2
MAPK3	0.002	0.091	0.38	1	-0.73	5	6
MAPK1	-0.003	0.091	0.38	1	-0.74	5	6
VEGFA145/NRP2	0.027	0.054	-10000	0	-0.51	3	3
VEGFR1/2 heterodimer	0.03	0.093	-10000	0	-0.96	4	4
KDR	0.019	0.091	-10000	0	-0.98	4	4
VEGFA165/NRP1/VEGFR2 homodimer	0.054	0.099	-10000	0	-0.67	7	7
SRC	0.026	0.008	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	0.011	0.11	0.38	11	-0.76	5	16
PI3K	0.042	0.098	-10000	0	-0.78	5	5
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.048	0.094	-10000	0	-0.74	6	6
FES	0.024	0.096	-10000	0	-0.73	6	6
GAB1	0.03	0.093	-10000	0	-0.77	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	0.047	0.095	-10000	0	-0.74	6	6
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
ARNT	0.025	0.007	-10000	0	-10000	0	0
eNOS/Caveolin-1	0.04	0.09	0.4	1	-0.54	5	6
VEGFR2 homodimer/VEGFA homodimer/Yes	0.047	0.095	-10000	0	-0.74	6	6
PI3K/GAB1	0.051	0.085	-10000	0	-0.62	5	5
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.07	0.092	-10000	0	-0.68	6	6
PRKACA	0.025	0.008	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.04	0.11	-10000	0	-0.74	8	8
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
CDC42	0.023	0.096	-10000	0	-0.68	7	7
actin cytoskeleton reorganization	0.025	0.13	-10000	0	-0.46	27	27
PTK2	0.025	0.1	0.32	1	-0.75	6	7
EDG1	0.012	0.089	-10000	0	-0.64	7	7
mol:DAG	0.023	0.093	-10000	0	-0.66	7	7
CaM/Ca2+	0.036	0.086	-10000	0	-0.6	7	7
MAP2K3	0.009	0.1	0.37	1	-0.9	4	5
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.052	0.1	-10000	0	-0.94	4	4
PLCG1	0.023	0.096	-10000	0	-0.68	7	7
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.058	0.093	-10000	0	-0.7	6	6
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
YES1	0.027	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.046	0.1	-10000	0	-0.79	6	6
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.047	0.094	-10000	0	-0.74	6	6
cell migration	0.047	0.084	0.34	1	-0.66	4	5
mol:PI-3-4-5-P3	0.042	0.086	-10000	0	-0.68	5	5
FYN	0.027	0.004	-10000	0	-10000	0	0
VEGFB/NRP1	0.028	0.085	-10000	0	-0.61	7	7
mol:NO	0.041	0.097	0.46	7	-0.48	6	13
PXN	0.027	0.005	-10000	0	-10000	0	0
HRAS/GTP	0.021	0.075	-10000	0	-0.64	5	5
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.044	0.1	-10000	0	-0.94	4	4
VHL	0.023	0.054	-10000	0	-0.67	3	3
ITGB3	0.011	0.1	-10000	0	-0.65	11	11
NOS3	0.04	0.1	0.47	7	-0.55	6	13
VEGFR2 homodimer/VEGFA homodimer/Sck	0.041	0.1	-10000	0	-0.65	8	8
RAC1	0.026	0.006	-10000	0	-10000	0	0
PRKCA	0.003	0.12	0.36	1	-0.48	19	20
PRKCB	0.007	0.094	0.36	1	-0.56	9	10
VCL	0.027	0.005	-10000	0	-10000	0	0
VEGFA165/NRP1	0.03	0.095	-10000	0	-0.67	7	7
VEGFR1/2 heterodimer/VEGFA homodimer	0.044	0.1	-10000	0	-0.78	6	6
VEGFA165/NRP2	0.027	0.054	-10000	0	-0.51	3	3
MAPKKK cascade	0.054	0.091	0.36	2	-0.71	4	6
NRP2	0.014	0.043	-10000	0	-10000	0	0
VEGFC homodimer	0.025	0.032	-10000	0	-0.67	1	1
NCK1	0.027	0.003	-10000	0	-10000	0	0
ROCK1	0.027	0.005	-10000	0	-10000	0	0
FAK1/Paxillin	0.041	0.1	-10000	0	-0.69	6	6
MAP3K13	0.016	0.12	-10000	0	-0.53	15	15
PDPK1	0.028	0.081	-10000	0	-0.67	5	5

×

PDGFR-beta 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
S1P1/Sphingosine-1-phosphate	0.025	0.052	0.31	1	-0.67	1	2
PDGFB-D/PDGFRB/SLAP	0.038	0.027	-10000	0	-0.51	1	1
PDGFB-D/PDGFRB/APS/CBL	0.051	0.034	-10000	0	-0.43	2	2
AKT1	0.03	0.087	0.5	11	-10000	0	11
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.029	0.054	0.34	1	-0.71	1	2
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
FGR	0.018	0.045	0.36	1	-0.54	2	3
mol:Ca2+	0.034	0.082	0.41	13	-0.74	1	14
MYC	0.03	0.18	0.57	19	-0.77	14	33
SHC1	0.025	0.008	-10000	0	-10000	0	0
HRAS/GDP	0.035	0.025	-10000	0	-0.38	1	1
LRP1/PDGFRB/PDGFB	0.038	0.04	-10000	0	-0.44	2	2
GRB10	0.026	0.006	-10000	0	-10000	0	0
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
GO:0007205	0.034	0.083	0.41	13	-0.76	1	14
PTEN	0.026	0.018	-10000	0	-0.36	1	1
GRB2	0.026	0.007	-10000	0	-10000	0	0
GRB7	0.001	0.056	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SHP2	0.037	0.036	-10000	0	-0.51	2	2
PDGFB-D/PDGFRB/GRB10	0.038	0.027	-10000	0	-0.51	1	1
cell cycle arrest	0.037	0.027	-10000	0	-0.51	1	1
HRAS	0.026	0.011	-10000	0	-10000	0	0
HIF1A	0.024	0.084	0.48	11	-10000	0	11
GAB1	0.029	0.094	0.45	11	-0.56	2	13
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.034	0.11	0.51	15	-0.7	1	16
PDGFB-D/PDGFRB	0.054	0.029	-10000	0	-0.46	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.038	0.027	-10000	0	-0.51	1	1
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.033	0.053	-10000	0	-0.67	1	1
positive regulation of MAPKKK cascade	0.037	0.036	-10000	0	-0.51	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
mol:IP3	0.034	0.083	0.41	13	-0.76	1	14
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.025	0.011	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.017	0.052	-10000	0	-0.57	1	1
SHB	0.025	0.007	-10000	0	-10000	0	0
BLK	-0.15	0.26	-10000	0	-0.56	144	144
PTPN2	0.028	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.038	0.026	-10000	0	-0.49	1	1
BCAR1	0.026	0.006	-10000	0	-10000	0	0
VAV2	0.034	0.11	0.49	14	-0.57	3	17
CBL	0.027	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.038	0.027	-10000	0	-0.51	1	1
LCK	0.011	0.08	-10000	0	-0.65	6	6
PDGFRB	0.026	0.033	-10000	0	-0.68	1	1
ACP1	0.027	0.005	-10000	0	-10000	0	0
HCK	0.024	0.031	-10000	0	-0.44	1	1
ABL1	0.026	0.097	0.42	14	-0.59	2	16
PDGFB-D/PDGFRB/CBL	0.023	0.083	0.45	4	-0.64	2	6
PTPN1	0.028	0.005	-10000	0	-10000	0	0
SNX15	0.027	0.005	-10000	0	-10000	0	0
STAT3	0.026	0.007	-10000	0	-10000	0	0
STAT1	0.023	0.023	-10000	0	-10000	0	0
cell proliferation	0.032	0.17	0.54	20	-0.68	14	34
SLA	0.026	0.009	-10000	0	-10000	0	0
actin cytoskeleton reorganization	0.034	0.027	-10000	0	-0.37	1	1
SRC	0.019	0.035	-10000	0	-0.4	2	2
PI3K	0.012	0.034	-10000	0	-0.35	4	4
PDGFB-D/PDGFRB/GRB7/SHC	0.049	0.028	-10000	0	-0.31	1	1
SH2B2	0.024	0.033	-10000	0	-0.67	1	1
PLCgamma1/SPHK1	0.029	0.055	0.34	1	-0.74	1	2
LYN	0.018	0.035	-10000	0	-0.44	2	2
LRP1	0.025	0.032	-10000	0	-0.67	1	1
SOS1	0.027	0.005	-10000	0	-10000	0	0
STAT5B	0.026	0.007	-10000	0	-10000	0	0
STAT5A	0.026	0.007	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.079	0.032	-10000	0	-0.38	1	1
SPHK1	0.023	0.023	-10000	0	-10000	0	0
EDG1	0.001	0.005	-10000	0	-10000	0	0
mol:DAG	0.034	0.083	0.41	13	-0.76	1	14
PLCG1	0.034	0.084	0.44	11	-0.79	1	12
NHERF/PDGFRB	0.05	0.028	-10000	0	-0.44	1	1
YES1	0.015	0.056	0.37	1	-0.51	4	5
cell migration	0.05	0.028	-10000	0	-0.44	1	1
SHC/Grb2/SOS1	0.072	0.035	-10000	0	-10000	0	0
SLC9A3R2	0.026	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.026	0.007	-10000	0	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.062	0.033	-10000	0	-0.4	1	1
FYN	0.016	0.05	-10000	0	-0.44	4	4
DOK1	0.024	0.029	-10000	0	-0.41	1	1
HRAS/GTP	0.019	0.008	-10000	0	-10000	0	0
PDGFB	0.02	0.012	-10000	0	-10000	0	0
RAC1	0.039	0.14	0.54	20	-0.46	12	32
PRKCD	0.024	0.031	-10000	0	-0.42	1	1
FER	0.02	0.043	-10000	0	-0.42	4	4
MAPKKK cascade	0.016	0.056	0.37	1	-10000	0	1
RASA1	0.023	0.028	-10000	0	-0.42	1	1
NCK1	0.027	0.003	-10000	0	-10000	0	0
NCK2	0.027	0.005	-10000	0	-10000	0	0
p62DOK/Csk	0.039	0.03	-10000	0	-0.38	1	1
PDGFB-D/PDGFRB/SHB	0.036	0.028	-10000	0	-0.51	1	1
chemotaxis	0.026	0.095	0.42	14	-0.56	2	16
STAT1-3-5/STAT1-3-5	0.064	0.029	-10000	0	-0.37	1	1
Bovine Papilomavirus E5/PDGFRB	0.019	0.025	-10000	0	-0.52	1	1
PTPRJ	0.027	0.005	-10000	0	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.017	0.041	-10000	0	-0.26	1	1
STMN1	0.001	0.042	-10000	0	-10000	0	0
Aurora B/RasGAP/Survivin	0.053	0.051	-10000	0	-0.44	1	1
Chromosomal passenger complex/Cul3 protein complex	0.014	0.05	-10000	0	-0.25	11	11
BIRC5	0.017	0.048	-10000	0	-0.68	1	1
DES	-0.32	0.3	-10000	0	-0.57	289	289
Aurora C/Aurora B/INCENP	0.054	0.044	-10000	0	-0.45	2	2
Aurora B/TACC1	0.029	0.043	-10000	0	-0.5	1	1
Aurora B/PP2A	0.02	0.05	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.011	0.007	-10000	0	-10000	0	0
mitotic metaphase/anaphase transition	-0.001	0.002	-10000	0	-10000	0	0
NDC80	-0.008	0.06	-10000	0	-10000	0	0
Cul3 protein complex	0.038	0.072	-10000	0	-0.44	10	10
KIF2C	0.015	0.028	-10000	0	-0.47	1	1
PEBP1	0.027	0.006	-10000	0	-10000	0	0
KIF20A	0.004	0.054	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.02	0.05	-10000	0	-10000	0	0
SEPT1	0.024	0.021	-10000	0	-10000	0	0
SMC2	0.025	0.008	-10000	0	-10000	0	0
SMC4	0.027	0.003	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.017	0.079	0.28	2	-0.54	8	10
PSMA3	0.027	0.005	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.002	-10000	0	-10000	0	0
H3F3B	0.011	0.017	-10000	0	-10000	0	0
AURKB	0.001	0.066	-10000	0	-10000	0	0
AURKC	0.02	0.03	-10000	0	-10000	0	0
CDCA8	0.027	0.016	-10000	0	-10000	0	0
cytokinesis	-0.018	0.054	-10000	0	-0.36	4	4
Aurora B/Septin1	0.045	0.066	-10000	0	-0.36	3	3
AURKA	0.026	0.005	-10000	0	-10000	0	0
INCENP	0.026	0.046	-10000	0	-0.68	2	2
KLHL13	0.006	0.1	-10000	0	-0.62	12	12
BUB1	-0.028	0.079	-10000	0	-0.68	1	1
hSgo1/Aurora B/Survivin	0.048	0.055	-10000	0	-0.4	1	1
EVI5	0.028	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.05	0.047	-10000	0	-10000	0	0
SGOL1	0.021	0.029	-10000	0	-10000	0	0
CENPA	0.018	0.041	0.2	2	-0.22	6	8
NCAPG	0.013	0.045	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.02	0.05	-10000	0	-10000	0	0
NCAPD2	0.027	0.005	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.019	0.05	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
NCAPH	0.005	0.054	-10000	0	-10000	0	0
NPM1	0.012	0.041	-10000	0	-0.3	7	7
RASA1	0.027	0.005	-10000	0	-10000	0	0
KLHL9	0.025	0.008	-10000	0	-10000	0	0
mitotic prometaphase	0.001	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.05	-10000	0	-10000	0	0
PPP1CC	0.027	0.005	-10000	0	-10000	0	0
Centraspindlin	0.043	0.048	-10000	0	-10000	0	0
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
NSUN2	0.011	0.043	-10000	0	-0.31	4	4
MYLK	0.01	0.025	-10000	0	-0.41	1	1
KIF23	0.021	0.034	-10000	0	-10000	0	0
VIM	0	0.04	-10000	0	-10000	0	0
RACGAP1	0.028	0.006	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.006	0.072	-10000	0	-0.47	7	7
Chromosomal passenger complex	0.015	0.036	-10000	0	-0.26	3	3
Chromosomal passenger complex/EVI5	0.1	0.069	-10000	0	-0.42	3	3
TACC1	0.025	0.032	-10000	0	-0.67	1	1
PPP2R5D	0.027	0.003	-10000	0	-10000	0	0
CUL3	0.027	0.005	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.03	0.1	-10000	0	-0.5	7	7
CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
AKT1	0.027	0.005	-10000	0	-10000	0	0
AKT2	0.026	0.007	-10000	0	-10000	0	0
STXBP4	0.024	0.032	-10000	0	-0.67	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.024	0.1	0.33	7	-0.47	7	14
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
YWHAQ	0.027	0.005	-10000	0	-10000	0	0
TBC1D4	-0.053	0.18	-10000	0	-0.49	67	67
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.02	0.012	-10000	0	-10000	0	0
YWHAB	0.027	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.05	0.027	-10000	0	-0.44	1	1
YWHAG	0.026	0.006	-10000	0	-10000	0	0
ASIP	0.005	0.05	-10000	0	-10000	0	0
PRKCI	0.027	0.003	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.02	0.004	-10000	0	-10000	0	0
RHOQ	0.027	0.005	-10000	0	-10000	0	0
GYS1	0.017	0.012	0.25	1	-10000	0	1
PRKCZ	0.026	0.006	-10000	0	-10000	0	0
TRIP10	0.025	0.008	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.034	0.011	-10000	0	-10000	0	0
AS160/14-3-3	-0.035	0.094	-10000	0	-0.35	15	15
VAMP2	0.026	0.007	-10000	0	-10000	0	0
SLC2A4	0.022	0.11	0.33	6	-0.53	7	13
STX4	0.026	0.006	-10000	0	-10000	0	0
GSK3B	0.024	0.008	-10000	0	-10000	0	0
SFN	-0.085	0.13	-10000	0	-0.67	15	15
LNPEP	0.004	0.12	-10000	0	-0.67	16	16
YWHAE	0.026	0.007	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0.005	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.044	0.016	-10000	0	-10000	0	0
CDKN1B	0.022	0.024	-10000	0	-10000	0	0
CDKN1A	0.021	0.025	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.027	0.005	-10000	0	-10000	0	0
FOXO3	0.022	0.024	-10000	0	-10000	0	0
AKT1	0.022	0.023	-10000	0	-10000	0	0
BAD	0.027	0.005	-10000	0	-10000	0	0
AKT3	0.014	0.026	-10000	0	-0.39	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.022	0.026	-10000	0	-10000	0	0
AKT1/ASK1	0.038	0.036	-10000	0	-0.33	1	1
BAD/YWHAZ	0.05	0.018	-10000	0	-10000	0	0
RICTOR	0.025	0.032	-10000	0	-0.67	1	1
RAF1	0.027	0.004	-10000	0	-10000	0	0
JNK cascade	-0.036	0.035	0.32	1	-10000	0	1
TSC1	0.021	0.025	-10000	0	-10000	0	0
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
AKT1/RAF1	0.041	0.035	-10000	0	-10000	0	0
EP300	0.02	0.012	-10000	0	-10000	0	0
mol:GDP	0.022	0.023	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.022	0.023	-10000	0	-10000	0	0
YWHAQ	0.027	0.005	-10000	0	-10000	0	0
TBC1D4	-0.046	0.15	-10000	0	-0.43	64	64
MAP3K5	0.026	0.032	-10000	0	-0.67	1	1
MAPKAP1	0.025	0.008	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.011	0.075	0.4	4	-0.32	8	12
YWHAH	0.02	0.012	-10000	0	-10000	0	0
AKT1S1	0.027	0.038	-10000	0	-10000	0	0
CASP9	0.024	0.031	-10000	0	-10000	0	0
YWHAB	0.027	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.045	0.048	0.36	6	-10000	0	6
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.05	0.034	-10000	0	-0.44	2	2
YWHAE	0.026	0.007	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
AKT2/p21CIP1	0.022	0.029	-10000	0	-0.36	1	1
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.011	-10000	0	-10000	0	0
CHUK	0.022	0.024	-10000	0	-10000	0	0
BAD/BCL-XL	0.046	0.034	-10000	0	-10000	0	0
mTORC2	0.03	0.023	-10000	0	-0.4	1	1
AKT2	0.014	0.026	-10000	0	-0.39	2	2
FOXO1-3a-4/14-3-3 family	0.02	0.079	0.37	8	-0.37	2	10
PDPK1	0.023	0.045	-10000	0	-0.67	2	2
MDM2	0.023	0.025	-10000	0	-10000	0	0
MAPKKK cascade	-0.041	0.035	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.039	0.034	-10000	0	-10000	0	0
TSC1/TSC2	0.023	0.039	0.44	1	-10000	0	1
proteasomal ubiquitin-dependent protein catabolic process	0.037	0.033	-10000	0	-10000	0	0
glucose import	-0.057	0.16	0.21	5	-0.42	78	83
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.026	0.029	0.24	1	-10000	0	1
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.059	0.16	-10000	0	-0.42	78	78
GSK3A	0.026	0.037	-10000	0	-10000	0	0
FOXO1	0.021	0.025	-10000	0	-10000	0	0
GSK3B	0.022	0.024	-10000	0	-10000	0	0
SFN	-0.085	0.13	-10000	0	-0.67	15	15
G1/S transition of mitotic cell cycle	0.029	0.044	0.32	2	-10000	0	2
p27Kip1/14-3-3 family	0.015	0.054	-10000	0	-0.34	5	5
PRKACA	0.025	0.008	-10000	0	-10000	0	0
KPNA1	0.027	0.003	-10000	0	-10000	0	0
HSP90AA1	0.027	0.005	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
RHEB	0.026	0.006	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.006	0.16	-10000	0	-0.44	56	56
Ran/GTP/Exportin 1/HDAC1	0.007	0.002	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.018	0.14	-10000	0	-0.38	55	55
SUMO1	0.027	0.005	-10000	0	-10000	0	0
ZFPM1	0.026	0.007	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.009	-10000	0	-10000	0	0
FKBP3	0.027	0.005	-10000	0	-10000	0	0
Histones	0.036	0.083	-10000	0	-10000	0	0
YY1/LSF	0.006	0.065	-10000	0	-0.43	4	4
SMG5	0.025	0.007	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.007	0.11	-10000	0	-0.31	54	54
I kappa B alpha/HDAC1	0.011	0.08	-10000	0	-10000	0	0
SAP18	0.026	0.007	-10000	0	-10000	0	0
RELA	-0.016	0.11	-10000	0	-0.32	56	56
HDAC1/Smad7	0.052	0.016	-10000	0	-10000	0	0
RANGAP1	0.02	0.012	-10000	0	-10000	0	0
HDAC3/TR2	0.012	0.08	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.031	0.037	-10000	0	-0.44	2	2
NF kappa B1 p50/RelA	-0.024	0.12	0.32	1	-0.43	15	16
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.027	0.008	-10000	0	-10000	0	0
GATA1	0.012	0.021	-10000	0	-10000	0	0
Mad/Max	0.039	0.008	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.035	0.067	-10000	0	-0.49	5	5
RBBP7	0.026	0.007	-10000	0	-10000	0	0
NPC	0.016	0.003	-10000	0	-10000	0	0
RBBP4	0.024	0.045	-10000	0	-0.67	2	2
MAX	0.027	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
NFKBIA	-0.003	0.083	-10000	0	-10000	0	0
KAT2B	0.027	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.029	0.034	-10000	0	-0.55	1	1
SIN3 complex	0.061	0.032	-10000	0	-0.4	1	1
SMURF1	0.026	0.006	-10000	0	-10000	0	0
CHD3	0.026	0.007	-10000	0	-10000	0	0
SAP30	0.026	0.032	-10000	0	-0.67	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.026	0.007	-10000	0	-10000	0	0
YY1/HDAC3	-0.008	0.079	-10000	0	-10000	0	0
YY1/HDAC2	0.009	0.054	-10000	0	-0.28	1	1
YY1/HDAC1	0.009	0.054	-10000	0	-0.28	1	1
NuRD/MBD2 Complex (MeCP1)	0.032	0.031	-10000	0	-0.4	1	1
PPARG	-0.021	0.14	-10000	0	-0.39	60	60
HDAC8/hEST1B	0.046	0.021	-10000	0	-10000	0	0
UBE2I	0.026	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.012	0.08	-10000	0	-10000	0	0
MBD3L2	-0.015	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.051	0.015	-10000	0	-10000	0	0
CREBBP	0.026	0.006	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.036	0.061	-10000	0	-0.45	4	4
HDAC1	0.027	0.005	-10000	0	-10000	0	0
HDAC3	-0.003	0.083	-10000	0	-10000	0	0
HDAC2	0.027	0.004	-10000	0	-10000	0	0
YY1	0.019	0.012	-10000	0	-10000	0	0
HDAC8	0.026	0.007	-10000	0	-10000	0	0
SMAD7	0.027	0.004	-10000	0	-10000	0	0
NCOR2	0.027	0.005	-10000	0	-10000	0	0
MXD1	0.027	0.005	-10000	0	-10000	0	0
STAT3	0.018	0.012	-10000	0	-10000	0	0
NFKB1	0.027	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.027	0.005	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.019	0.066	-10000	0	-0.4	4	4
YY1/SAP30/HDAC1	0.021	0.058	-10000	0	-0.31	1	1
EP300	0.02	0.012	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.018	0.012	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.003	0.082	-10000	0	-10000	0	0
histone deacetylation	0.038	0.034	-10000	0	-0.39	1	1
STAT3 (dimer non-phopshorylated)/HDAC3	0.003	0.074	-10000	0	-0.3	1	1
nuclear export	-0.046	0.021	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
GATAD2B	0.025	0.007	-10000	0	-10000	0	0
GATAD2A	0.025	0.008	-10000	0	-10000	0	0
GATA2/HDAC3	0.012	0.08	-10000	0	-10000	0	0
GATA1/HDAC1	0.035	0.013	-10000	0	-10000	0	0
GATA1/HDAC3	0.009	0.079	-10000	0	-10000	0	0
CHD4	0.027	0.005	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.024	0.17	-10000	0	-0.51	56	56
SIN3/HDAC complex/Mad/Max	0.032	0.034	-10000	0	-0.49	1	1
NuRD Complex	0.042	0.052	-10000	0	-0.49	2	2
positive regulation of chromatin silencing	0.034	0.081	-10000	0	-10000	0	0
SIN3B	0.025	0.008	-10000	0	-10000	0	0
MTA2	0.027	0.005	-10000	0	-10000	0	0
SIN3A	0.027	0.004	-10000	0	-10000	0	0
XPO1	0.027	0.005	-10000	0	-10000	0	0
SUMO1/HDAC1	0.014	0.057	-10000	0	-0.27	2	2
HDAC complex	0.063	0.036	-10000	0	-0.4	2	2
GATA1/Fog1	0.034	0.014	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.053	0.014	-10000	0	-10000	0	0
TNF	-0.056	0.22	-10000	0	-0.67	56	56
negative regulation of cell growth	0.036	0.035	-10000	0	-0.48	1	1
NuRD/MBD2/PRMT5 Complex	0.032	0.031	-10000	0	-0.4	1	1
Ran/GTP/Exportin 1	0.017	0.052	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.03	0.14	-10000	0	-0.4	56	56
SIN3/HDAC complex/NCoR1	0.031	0.044	-10000	0	-0.45	2	2
TFCP2	0.021	0.063	-10000	0	-0.67	4	4
NR2C1	0.027	0.005	-10000	0	-10000	0	0
MBD3	0.025	0.008	-10000	0	-10000	0	0
MBD2	0.027	0.004	-10000	0	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.037	0.013	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.003	0.11	-10000	0	-0.44	30	30
NF kappa B1 p50/RelA/I kappa B alpha	0.036	0.038	-10000	0	-10000	0	0
NFKBIA	0.014	0.029	-10000	0	-0.24	5	5
MAPK14	0.027	0.003	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.032	0.008	-10000	0	-10000	0	0
ARRB2	0.016	0.005	-10000	0	-10000	0	0
REL	-0.018	0.17	-10000	0	-0.66	32	32
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.03	0.011	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.032	0.008	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
NF kappa B1 p50 dimer	0.025	0.023	0.25	5	-10000	0	5
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
NFKB1	0.017	0.003	-10000	0	-10000	0	0
RELA	0.027	0.005	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.02	0.038	-10000	0	-0.31	5	5
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.04	0.039	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
PI3K	0.036	0.043	-10000	0	-0.51	3	3
NF kappa B1 p50/RelA	0.021	0.038	-10000	0	-0.31	5	5
IKBKB	0.027	0.005	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-10000	0	-10000	0	0
SYK	0.025	0.008	-10000	0	-10000	0	0
I kappa B alpha/PIK3R1	0.028	0.038	-10000	0	-0.23	4	4
cell death	0.038	0.038	-10000	0	-10000	0	0
NF kappa B1 p105/c-Rel	0.003	0.11	-10000	0	-0.44	30	30
LCK	0.012	0.082	-10000	0	-0.67	6	6
BCL3	0.025	0.01	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.022	0.25	1	-10000	0	1
AES	0.025	0.018	-10000	0	-10000	0	0
FBXW11	0.026	0.006	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.039	0.009	-10000	0	-10000	0	0
SMAD4	0.027	0.004	-10000	0	-10000	0	0
DKK2	-0.004	0.14	-10000	0	-0.66	20	20
TLE1	0.021	0.056	-10000	0	-0.66	3	3
MACF1	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.048	0.088	0.46	16	-10000	0	16
WIF1	-0.015	0.047	-10000	0	-10000	0	0
beta catenin/RanBP3	0.03	0.084	0.38	24	-10000	0	24
KREMEN2	0.016	0.037	-10000	0	-10000	0	0
DKK1	-0.001	0.07	-10000	0	-0.67	2	2
beta catenin/beta TrCP1	0.048	0.045	0.38	2	-10000	0	2
FZD1	0.027	0.006	-10000	0	-10000	0	0
AXIN2	-0.029	0.3	0.62	12	-1.4	18	30
AXIN1	0.026	0.007	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.03	0.066	-10000	0	-0.51	2	2
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.04	0.094	0.3	1	-0.55	4	5
Axin1/APC/GSK3	0.034	0.045	0.34	4	-10000	0	4
Axin1/APC/GSK3/beta catenin/Macf1	0.034	0.029	0.32	1	-10000	0	1
HNF1A	0.027	0.02	0.23	1	-10000	0	1
CTBP1	0.027	0.02	0.24	1	-10000	0	1
MYC	-0.037	0.24	0.53	6	-1.4	14	20
RANBP3	0.025	0.008	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.034	0.096	-10000	0	-0.44	19	19
NKD1	0.007	0.11	-10000	0	-0.67	13	13
TCF4	0.027	0.019	0.22	1	-10000	0	1
TCF3	0.025	0.02	0.23	1	-10000	0	1
WNT1/LRP6/FZD1/Axin1	0.065	0.02	-10000	0	-10000	0	0
Ran/GTP	0.02	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.021	0.12	0.49	22	-10000	0	22
LEF1	0.022	0.049	0.22	1	-0.63	2	3
DVL1	0.028	0.016	-10000	0	-10000	0	0
CSNK2A1	0.027	0.005	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.039	0.11	-10000	0	-0.52	9	9
DKK1/LRP6/Kremen 2	0.049	0.044	-10000	0	-0.47	2	2
LRP6	0.027	0.005	-10000	0	-10000	0	0
CSNK1A1	0.026	0.019	-10000	0	-10000	0	0
NLK	0.026	0.008	-10000	0	-10000	0	0
CCND1	-0.011	0.082	0.58	2	-0.69	2	4
WNT1	0.022	0.018	-10000	0	-10000	0	0
GSK3A	0.026	0.008	-10000	0	-10000	0	0
GSK3B	0.027	0.004	-10000	0	-10000	0	0
FRAT1	0.027	0.005	-10000	0	-10000	0	0
PPP2R5D	0.031	0.058	0.33	13	-0.32	2	15
APC	0.022	0.039	0.36	3	-0.39	1	4
WNT1/LRP6/FZD1	0.032	0.021	-10000	0	-10000	0	0
CREBBP	0.027	0.02	0.23	1	-10000	0	1

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.009	0.002	-10000	0	-10000	0	0
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.036	0.013	-10000	0	-10000	0	0
STXBP1	0.025	0.008	-10000	0	-10000	0	0
ACh/CHRNA1	0.009	0.044	-10000	0	-0.24	4	4
RAB3GAP2/RIMS1/UNC13B	0.048	0.02	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.021	0.018	-10000	0	-10000	0	0
mol:ACh	0.002	0.044	0.14	20	-0.14	22	42
RAB3GAP2	0.025	0.008	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	0.031	0.055	-10000	0	-10000	0	0
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.009	0.044	-10000	0	-0.24	4	4
UNC13B	0.025	0.008	-10000	0	-10000	0	0
CHRNA1	0.008	0.052	-10000	0	-0.67	1	1
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.041	0.11	-10000	0	-0.48	25	25
SNAP25	-0.015	0.075	-10000	0	-0.34	25	25
VAMP2	0.006	0.001	-10000	0	-10000	0	0
SYT1	-0.067	0.16	-10000	0	-0.67	24	24
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.024	0.009	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.031	0.055	-10000	0	-10000	0	0

×

S1P4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.004	0.12	-10000	0	-0.67	15	15
CDC42/GTP	0.008	0.074	-10000	0	-0.31	14	14
PLCG1	-0.002	0.067	-10000	0	-0.32	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.027	0.003	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
G12/G13	0.038	0.011	-10000	0	-10000	0	0
cell migration	0.007	0.073	-10000	0	-0.3	14	14
S1PR5	0.023	0.034	-10000	0	-0.67	1	1
S1PR4	0.023	0.02	-10000	0	-10000	0	0
MAPK3	-0.003	0.068	-10000	0	-0.5	3	3
MAPK1	0.009	0.06	-10000	0	-0.32	14	14
S1P/S1P5/Gi	-0.001	0.074	-10000	0	-0.33	16	16
GNAI1	0.025	0.032	-10000	0	-0.67	1	1
CDC42/GDP	0.02	0.004	-10000	0	-10000	0	0
S1P/S1P5/G12	0.032	0.025	-10000	0	-0.44	1	1
RHOA	0.035	0.07	0.41	12	-10000	0	12
S1P/S1P4/Gi	0	0.073	-10000	0	-0.32	17	17
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.02	0.012	-10000	0	-10000	0	0
S1P/S1P4/G12/G13	0.047	0.018	-10000	0	-10000	0	0
GNA12	0.026	0.006	-10000	0	-10000	0	0
GNA13	0.026	0.007	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.027	0.004	-9999	-10000	0	0
SMAD2	-0.016	0.044	-9999	-0.24	1	1
SMAD3	0.021	0.016	-9999	-10000	0	0
SMAD3/SMAD4	0.032	0.05	-9999	-0.41	5	5
SMAD4/Ubc9/PIASy	0.049	0.019	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.027	0.064	-9999	-0.42	1	1
PPM1A	0.027	0.005	-9999	-10000	0	0
CALM1	0.027	0.005	-9999	-10000	0	0
SMAD2/SMAD4	-0.004	0.055	-9999	-0.43	1	1
MAP3K1	0.027	0.005	-9999	-10000	0	0
TRAP-1/SMAD4	0.006	0.13	-9999	-0.49	31	31
MAPK3	0.026	0.006	-9999	-10000	0	0
MAPK1	0.02	0.012	-9999	-10000	0	0
NUP214	0.025	0.008	-9999	-10000	0	0
CTDSP1	0.027	0.005	-9999	-10000	0	0
CTDSP2	0.027	0.005	-9999	-10000	0	0
CTDSPL	0.027	0.003	-9999	-10000	0	0
KPNB1	0.026	0.007	-9999	-10000	0	0
TGFBRAP1	-0.016	0.17	-9999	-0.66	31	31
UBE2I	0.026	0.007	-9999	-10000	0	0
NUP153	0.026	0.032	-9999	-0.67	1	1
KPNA2	0.026	0.007	-9999	-10000	0	0
PIAS4	0.025	0.008	-9999	-10000	0	0

×

Canonical NF-kappaB 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.029	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.05	0.064	0.38	1	-10000	0	1
ERC1	0.027	0.005	-10000	0	-10000	0	0
RIP2/NOD2	0.021	0.053	-10000	0	-0.51	2	2
NFKBIA	0.022	0.014	-10000	0	-10000	0	0
BIRC2	0.027	0.005	-10000	0	-10000	0	0
IKBKB	0.027	0.005	-10000	0	-10000	0	0
RIPK2	0.027	0.005	-10000	0	-10000	0	0
IKBKG	0.034	0.025	-10000	0	-10000	0	0
IKK complex/A20	0.017	0.14	-10000	0	-0.48	5	5
NEMO/A20/RIP2	0.027	0.005	-10000	0	-10000	0	0
XPO1	0.027	0.005	-10000	0	-10000	0	0
NEMO/ATM	0.035	0.072	-10000	0	-0.56	1	1
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.036	0.008	-10000	0	-10000	0	0
IKK complex/ELKS	0.046	0.065	-10000	0	-0.38	1	1
BCL10/MALT1/TRAF6	0.051	0.034	-10000	0	-0.44	2	2
NOD2	0.003	0.067	-10000	0	-0.67	2	2
NFKB1	0.03	0.004	-10000	0	-10000	0	0
RELA	0.029	0.005	-10000	0	-10000	0	0
MALT1	0.027	0.004	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.039	0.008	-10000	0	-10000	0	0
ATM	0.025	0.032	-10000	0	-0.67	1	1
TNF/TNFR1A	-0.024	0.17	-10000	0	-0.51	56	56
TRAF6	0.024	0.045	-10000	0	-0.67	2	2
PRKCA	0.002	0.13	-10000	0	-0.67	17	17
CHUK	0.027	0.004	-10000	0	-10000	0	0
UBE2D3	0.027	0.004	-10000	0	-10000	0	0
TNF	-0.056	0.22	-10000	0	-0.67	56	56
NF kappa B1 p50/RelA	0.061	0.016	-10000	0	-10000	0	0
BCL10	0.027	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.013	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.029	0.006	-10000	0	-10000	0	0
TNFRSF1A	0.027	0.005	-10000	0	-10000	0	0
IKK complex	0.05	0.07	-10000	0	-0.4	1	1
CYLD	0.026	0.006	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.045	0.098	-10000	0	-0.47	2	2

×

Circadian rhythm 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
chromatin modification	0.039	0.042	-9999	-0.45	1	1
CLOCK	-0.017	0.17	-9999	-0.67	32	32
TIMELESS/CRY2	0.026	0.036	-9999	-10000	0	0
DEC1/BMAL1	0.016	0.039	-9999	-10000	0	0
ATR	0.026	0.032	-9999	-0.67	1	1
NR1D1	-0.001	0.042	-9999	-10000	0	0
ARNTL	0.01	0.049	-9999	-10000	0	0
TIMELESS	0.01	0.032	-9999	-10000	0	0
NPAS2	0.027	0.019	-9999	-0.36	1	1
CRY2	0.027	0.005	-9999	-10000	0	0
mol:CO	-0.004	0.009	-9999	-10000	0	0
CHEK1	0.027	0.005	-9999	-10000	0	0
mol:HEME	0.004	0.009	-9999	-10000	0	0
PER1	0.026	0.007	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.023	0.13	-9999	-0.44	32	32
BMAL1/CLOCK	-0.005	0.11	-9999	-0.44	13	13
S phase of mitotic cell cycle	0.039	0.042	-9999	-0.45	1	1
TIMELESS/CHEK1/ATR	0.04	0.043	-9999	-10000	0	0
mol:NADPH	0.004	0.009	-9999	-10000	0	0
PER1/TIMELESS	0.026	0.034	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.012	0.013	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.07	-9999	-0.38	14	14
CRKL	0.02	0.012	-9999	-10000	0	0
Rac1/GDP	0.02	0.004	-9999	-10000	0	0
DOCK1	0.023	0.054	-9999	-0.67	3	3
ITGA4	0.02	0.058	-9999	-0.67	3	3
alpha4/beta7 Integrin/MAdCAM1	0.044	0.089	-9999	-0.41	16	16
EPO	0.004	0.027	-9999	-10000	0	0
alpha4/beta7 Integrin	0.016	0.095	-9999	-0.51	14	14
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.026	0.007	-9999	-10000	0	0
alpha4/beta1 Integrin	0.034	0.046	-9999	-0.51	3	3
EPO/EPOR (dimer)	0.03	0.021	-9999	-10000	0	0
lamellipodium assembly	0.02	0.037	-9999	-0.4	3	3
PIK3CA	0.023	0.054	-9999	-0.67	3	3
PI3K	0.036	0.043	-9999	-0.51	3	3
ARF6	0.027	0.005	-9999	-10000	0	0
JAK2	0.022	0.045	-9999	-0.51	3	3
PXN	0.027	0.005	-9999	-10000	0	0
PIK3R1	0.027	0.005	-9999	-10000	0	0
MADCAM1	0.004	0.064	-9999	-0.67	3	3
cell adhesion	0.043	0.088	-9999	-0.4	16	16
CRKL/CBL	0.029	0.019	-9999	-10000	0	0
ITGB1	0.027	0.004	-9999	-10000	0	0
SRC	0.016	0.065	-9999	-0.45	7	7
ITGB7	0.004	0.11	-9999	-0.65	12	12
RAC1	0.026	0.006	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.045	0.068	-9999	-0.49	7	7
p130Cas/Crk/Dock1	0.035	0.065	-9999	-0.37	10	10
VCAM1	0.018	0.071	-9999	-0.67	5	5
RHOA	0.027	0.003	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.063	0.038	-9999	-0.4	2	2
BCAR1	0.008	0.061	-9999	-0.43	7	7
EPOR	0.024	0.017	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.027	0.005	-9999	-10000	0	0
GIT1	0.026	0.007	-9999	-10000	0	0
Rac1/GTP	0.02	0.038	-9999	-0.41	3	3

×

S1P5 pathway

Figure S111. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S111. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.007	0.074	0.47	3	-10000	0	3
GNAI2	0.027	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.032	0.025	-10000	0	-0.44	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.004	0.12	-10000	0	-0.67	15	15
RhoA/GTP	0.007	0.075	-10000	0	-0.48	3	3
negative regulation of cAMP metabolic process	-0.001	0.074	-10000	0	-0.32	16	16
GNAZ	0.02	0.012	-10000	0	-10000	0	0
GNAI3	0.027	0.005	-10000	0	-10000	0	0
GNA12	0.026	0.006	-10000	0	-10000	0	0
S1PR5	0.023	0.034	-10000	0	-0.67	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.001	0.074	-10000	0	-0.33	16	16
RhoA/GDP	0.02	0.003	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
GNAI1	0.025	0.032	-10000	0	-0.67	1	1

×

HIF-2-alpha transcription factor network

Figure S112. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S112. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.015	0.034	-10000	0	-10000	0	0
oxygen homeostasis	0.011	0.009	-10000	0	-10000	0	0
TCEB2	0.025	0.014	-10000	0	-10000	0	0
TCEB1	0.027	0.005	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.1	0.087	-10000	0	-0.54	3	3
EPO	0.12	0.11	-10000	0	-0.91	1	1
FIH (dimer)	0.037	0.012	-10000	0	-10000	0	0
APEX1	0.035	0.015	-10000	0	-10000	0	0
SERPINE1	0.12	0.12	-10000	0	-0.67	3	3
FLT1	-0.002	0.12	-10000	0	-0.72	8	8
ADORA2A	0.1	0.12	0.43	1	-0.72	2	3
germ cell development	0.13	0.11	-10000	0	-0.71	2	2
SLC11A2	0.12	0.11	-10000	0	-0.75	2	2
BHLHE40	0.13	0.11	-10000	0	-0.75	2	2
HIF1AN	0.037	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	0.11	0.096	-10000	0	-0.66	2	2
ETS1	0.038	0.015	-10000	0	-10000	0	0
CITED2	-0.036	0.31	-10000	0	-1.1	39	39
KDR	0.004	0.13	-10000	0	-1	6	6
PGK1	0.12	0.11	-10000	0	-0.75	2	2
SIRT1	0.026	0.032	-10000	0	-0.67	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.14	-10000	0	-0.95	2	2
EPAS1	0.061	0.069	-10000	0	-0.46	2	2
SP1	0.032	0.007	-10000	0	-10000	0	0
ABCG2	0.12	0.13	-10000	0	-0.78	4	4
EFNA1	0.13	0.11	-10000	0	-0.75	2	2
FXN	0.12	0.12	0.51	2	-0.72	2	4
POU5F1	0.13	0.11	-10000	0	-0.75	2	2
neuron apoptosis	-0.16	0.13	0.89	2	-10000	0	2
EP300	0.02	0.012	-10000	0	-10000	0	0
EGLN3	0.016	0.1	-10000	0	-0.66	10	10
EGLN2	0.035	0.014	-10000	0	-10000	0	0
EGLN1	0.034	0.035	-10000	0	-0.68	1	1
VHL/Elongin B/Elongin C	0.05	0.042	-10000	0	-0.46	3	3
VHL	0.023	0.054	-10000	0	-0.67	3	3
ARNT	0.034	0.015	-10000	0	-10000	0	0
SLC2A1	0.14	0.12	0.47	6	-0.72	2	8
TWIST1	0.12	0.14	0.44	2	-0.57	8	10
ELK1	0.022	0.036	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.089	0.098	-10000	0	-0.63	1	1
VEGFA	0.12	0.12	-10000	0	-0.7	4	4
CREBBP	0.026	0.006	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.025	0.11	0.66	10	-10000	0	10
PLK1	0.07	0.12	0.6	2	-0.71	1	3
CDKN1B	0.074	0.09	0.47	3	-0.4	1	4
FOXO3	0.067	0.11	-10000	0	-0.63	4	4
KAT2B	0.032	0.019	-10000	0	-10000	0	0
FOXO1/SIRT1	0.019	0.056	0.42	2	-0.4	1	3
CAT	0.063	0.13	-10000	0	-1.4	2	2
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
AKT1	0.034	0.02	-10000	0	-10000	0	0
FOXO1	0.017	0.08	0.44	11	-10000	0	11
MAPK10	0.033	0.032	0.2	10	-0.41	1	11
mol:GTP	0.002	0.001	-10000	0	-10000	0	0
FOXO4	0.069	0.085	0.49	9	-0.51	3	12
response to oxidative stress	0.01	0.012	-10000	0	-10000	0	0
FOXO3A/SIRT1	0.087	0.087	-10000	0	-0.79	2	2
XPO1	0.027	0.005	-10000	0	-10000	0	0
EP300	0.021	0.013	-10000	0	-10000	0	0
BCL2L11	0.027	0.099	-10000	0	-0.66	8	8
FOXO1/SKP2	0.016	0.055	-10000	0	-0.44	3	3
mol:GDP	0.01	0.012	-10000	0	-10000	0	0
RAN	0.028	0.006	-10000	0	-10000	0	0
GADD45A	0.1	0.091	0.46	6	-0.54	4	10
YWHAQ	0.027	0.005	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0	0.1	-10000	0	-0.48	7	7
MST1	0.031	0.036	-10000	0	-0.66	1	1
CSNK1D	0.026	0.007	-10000	0	-10000	0	0
CSNK1E	0.02	0.012	-10000	0	-10000	0	0
FOXO4/14-3-3 family	-0.008	0.11	-10000	0	-0.56	9	9
YWHAB	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.027	0.062	-10000	0	-0.39	9	9
MAPK9	0.031	0.018	-10000	0	-10000	0	0
YWHAG	0.026	0.006	-10000	0	-10000	0	0
YWHAE	0.026	0.007	-10000	0	-10000	0	0
YWHAZ	0.027	0.005	-10000	0	-10000	0	0
SIRT1	0.026	0.037	-10000	0	-0.67	1	1
SOD2	0.1	0.1	0.56	10	-0.62	2	12
RBL2	0.078	0.15	0.57	1	-1	5	6
RAL/GDP	0.046	0.015	-10000	0	-10000	0	0
CHUK	0.032	0.019	-10000	0	-10000	0	0
Ran/GTP	0.023	0.005	-10000	0	-10000	0	0
CSNK1G2	0.025	0.008	-10000	0	-10000	0	0
RAL/GTP	0.05	0.016	-10000	0	-10000	0	0
CSNK1G1	0.027	0.004	-10000	0	-10000	0	0
FASLG	-0.07	0.38	-10000	0	-1.4	39	39
SKP2	0.022	0.055	-10000	0	-0.67	3	3
USP7	0.028	0.006	-10000	0	-10000	0	0
IKBKB	0.032	0.02	-10000	0	-10000	0	0
CCNB1	0.07	0.11	0.6	2	-0.63	2	4
FOXO1-3a-4/beta catenin	0.1	0.099	0.44	7	-0.42	4	11
proteasomal ubiquitin-dependent protein catabolic process	0.015	0.055	-10000	0	-0.43	3	3
CSNK1A1	0.026	0.006	-10000	0	-10000	0	0
SGK1	0.018	0.1	-10000	0	-0.67	10	10
CSNK1G3	0.026	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.041	0.01	-10000	0	-10000	0	0
ZFAND5	0.077	0.11	0.6	13	-0.44	2	15
SFN	-0.085	0.13	-10000	0	-0.67	15	15
CDK2	0.027	0.005	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.009	0.099	-10000	0	-0.47	10	10
CREBBP	0.026	0.006	-10000	0	-10000	0	0
FBXO32	0.067	0.11	0.59	1	-0.71	1	2
BCL6	0.084	0.12	0.57	1	-0.82	4	5
RALB	0.028	0.005	-10000	0	-10000	0	0
RALA	0.027	0.006	-10000	0	-10000	0	0
YWHAH	0.02	0.012	-10000	0	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.009	0.003	-10000	0	-10000	0	0
SNTA1	0.027	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	0.009	0.004	-10000	0	-10000	0	0
MAPK12	-0.004	0.053	-10000	0	-0.39	9	9
CCND1	0.004	0.037	-10000	0	-0.33	4	4
p38 gamma/SNTA1	0.018	0.065	-10000	0	-0.38	10	10
MAP2K3	0.026	0.007	-10000	0	-10000	0	0
PKN1	0.025	0.008	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.005	0.056	-10000	0	-0.39	10	10
MAP2K6	-0.003	0.062	-10000	0	-0.44	10	10
MAPT	0.009	0.052	0.32	7	-0.37	3	10
MAPK13	0.016	0.005	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.008	0.002	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.028	0.041	0.29	3	-0.38	3	6
adherens junction organization	0.021	0.04	0.25	4	-10000	0	4
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.036	0.052	-10000	0	-0.36	7	7
FMN1	0.008	0.082	-10000	0	-0.35	24	24
mol:IP3	0.028	0.032	-10000	0	-0.33	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.029	0.022	-10000	0	-10000	0	0
CTNNB1	0.027	0.005	-10000	0	-10000	0	0
AKT1	0.033	0.035	0.25	1	-0.32	3	4
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.036	0.028	-10000	0	-10000	0	0
CTNND1	0.028	0.007	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.023	0.032	-10000	0	-0.38	2	2
VASP	0.025	0.018	-10000	0	-10000	0	0
ZYX	0.026	0.021	-10000	0	-10000	0	0
JUB	0.025	0.02	-10000	0	-10000	0	0
EGFR(dimer)	0.039	0.048	-10000	0	-0.36	5	5
E-cadherin/beta catenin-gamma catenin	0.051	0.016	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.048	0.038	0.25	1	-0.34	3	4
PIK3CA	0.025	0.055	-10000	0	-0.68	3	3
PI3K	0.05	0.039	0.26	1	-0.35	3	4
FYN	0.026	0.036	0.29	3	-0.29	3	6
mol:Ca2+	0.027	0.032	-10000	0	-0.32	3	3
JUP	0.026	0.007	-10000	0	-10000	0	0
PIK3R1	0.027	0.007	-10000	0	-10000	0	0
mol:DAG	0.028	0.032	-10000	0	-0.33	3	3
CDH1	0.026	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.037	0.053	-10000	0	-0.36	7	7
establishment of polarity of embryonic epithelium	0.025	0.018	-10000	0	-10000	0	0
SRC	0.026	0.008	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
EGFR	0.019	0.07	-10000	0	-0.67	5	5
CASR	0.018	0.031	-10000	0	-0.32	3	3
RhoA/GTP	0.039	0.032	-10000	0	-0.3	3	3
AKT2	0.031	0.033	-10000	0	-0.32	3	3
actin cable formation	0.006	0.078	-10000	0	-0.34	23	23
apoptosis	-0.03	0.043	0.36	3	-0.32	4	7
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
mol:GDP	0.022	0.052	-10000	0	-0.38	7	7
PIP5K1A	0.023	0.033	-10000	0	-0.39	2	2
PLCG1	0.028	0.033	-10000	0	-0.34	3	3
Rac1/GTP	0.048	0.047	-10000	0	-0.33	5	5
homophilic cell adhesion	0.001	0.005	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.019	0.03	-10000	0	-0.32	3	3
TRAF2/ASK1	0.032	0.024	-10000	0	-0.44	1	1
ATM	0.025	0.032	-10000	0	-0.67	1	1
MAP2K3	0.036	0.094	0.42	15	-0.38	3	18
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.025	0.095	0.34	14	-0.4	7	21
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.014	0.084	-10000	0	-0.67	7	7
TXN	0.008	0.003	-10000	0	-10000	0	0
CALM1	0.027	0.005	-10000	0	-10000	0	0
GADD45A	0.027	0.005	-10000	0	-10000	0	0
GADD45B	0.006	0.11	-10000	0	-0.61	15	15
MAP3K1	0.027	0.005	-10000	0	-10000	0	0
MAP3K6	0.027	0.005	-10000	0	-10000	0	0
MAP3K7	0.027	0.004	-10000	0	-10000	0	0
MAP3K4	0.027	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.038	0.026	-10000	0	-0.51	1	1
TAK1/TAB family	0.011	0.033	-10000	0	-0.19	3	3
RAC1/OSM/MEKK3	0.049	0.015	-10000	0	-10000	0	0
TRAF2	0.025	0.009	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.036	0.055	-10000	0	-0.33	2	2
TRAF6	0.007	0.026	-10000	0	-0.4	2	2
RAC1	0.026	0.006	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.019	0.07	-10000	0	-0.67	5	5
CCM2	0.026	0.011	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.031	0.048	-10000	0	-0.44	5	5
MAPK11	0.02	0.013	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.045	0.056	-10000	0	-0.48	5	5
OSM/MEKK3	0.037	0.014	-10000	0	-10000	0	0
TAOK1	-0.032	0.13	-10000	0	-0.4	57	57
TAOK2	0.015	0.019	-10000	0	-0.39	1	1
TAOK3	0.016	0.019	-10000	0	-0.39	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.027	0.003	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.026	0.032	-10000	0	-0.67	1	1
MAP3K10	0.026	0.007	-10000	0	-10000	0	0
MAP3K3	0.026	0.007	-10000	0	-10000	0	0
TRX/ASK1	0.017	0.037	-10000	0	-0.43	1	1
GADD45/MTK1/MTK1	0.038	0.091	-10000	0	-0.4	18	18

×

Aurora A signaling

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
Aurora A/GADD45A	0.03	0.025	-10000	0	-10000	0	0
BIRC5	0.015	0.047	-10000	0	-0.67	1	1
NFKBIA	0.015	0.022	0.25	3	-10000	0	3
CPEB1	-0.025	0.18	-10000	0	-0.65	38	38
AKT1	0.015	0.024	0.25	4	-10000	0	4
NDEL1	0.026	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0.027	0.021	-10000	0	-10000	0	0
NDEL1/TACC3	0.044	0.024	-10000	0	-10000	0	0
GADD45A	0.027	0.005	-10000	0	-10000	0	0
GSK3B	0.027	0.009	-10000	0	-10000	0	0
PAK1/Aurora A	0.03	0.025	-10000	0	-10000	0	0
MDM2	0.027	0.005	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.008	0.028	-10000	0	-10000	0	0
TP53	0.026	0.012	-10000	0	-10000	0	0
DLG7	0.013	0.011	-10000	0	-10000	0	0
AURKAIP1	0.026	0.011	-10000	0	-10000	0	0
ARHGEF7	0.026	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.047	0.024	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.027	0.021	-10000	0	-10000	0	0
AURKA	0.021	0.016	-10000	0	-10000	0	0
AURKB	0.012	0.023	-10000	0	-0.16	3	3
CDC25B	0.021	0.012	-10000	0	-10000	0	0
G2/M transition checkpoint	0.01	0.018	-10000	0	-10000	0	0
mRNA polyadenylation	-0.003	0.11	-10000	0	-0.4	34	34
Aurora A/CPEB	-0.003	0.11	-10000	0	-0.4	34	34
Aurora A/TACC1/TRAP/chTOG	0.055	0.038	-10000	0	-0.38	1	1
BRCA1	0.026	0.007	-10000	0	-10000	0	0
centrosome duplication	0.03	0.024	-10000	0	-10000	0	0
regulation of centrosome cycle	0.043	0.023	-10000	0	-10000	0	0
spindle assembly	0.053	0.038	-10000	0	-0.37	1	1
TDRD7	0.025	0.008	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.055	0.033	-10000	0	-0.36	1	1
CENPA	0.015	0.033	-10000	0	-0.25	7	7
Aurora A/PP2A	0.03	0.024	-10000	0	-10000	0	0
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.022	0.02	-10000	0	-10000	0	0
negative regulation of DNA binding	0.026	0.012	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.037	0.012	-10000	0	-10000	0	0
RASA1	0.027	0.005	-10000	0	-10000	0	0
Ajuba/Aurora A	0.01	0.019	-10000	0	-10000	0	0
mitotic prometaphase	-0.004	0.011	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.021	0.016	-10000	0	-10000	0	0
TACC1	0.025	0.032	-10000	0	-0.67	1	1
TACC3	0.026	0.011	-10000	0	-10000	0	0
Aurora A/Antizyme1	0.046	0.02	-10000	0	-10000	0	0
Aurora A/RasGAP	0.03	0.024	-10000	0	-10000	0	0
OAZ1	0.025	0.008	-10000	0	-10000	0	0
RAN	0.027	0.005	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.025	0.01	-10000	0	-10000	0	0
GIT1	0.026	0.007	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.05	0.018	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.008	0.028	-10000	0	-10000	0	0
PPP2R5D	0.027	0.003	-10000	0	-10000	0	0
Aurora A/TPX2	0.018	0.031	-10000	0	-10000	0	0
PAK1	0.027	0.005	-10000	0	-10000	0	0
CKAP5	0.027	0.005	-10000	0	-10000	0	0

×

EPO 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.031	0.099	-10000	0	-10000	0	0
CRKL	0.014	0.048	0.46	3	-10000	0	3
mol:DAG	0.028	0.048	-10000	0	-10000	0	0
HRAS	0.034	0.064	0.35	6	-10000	0	6
MAPK8	0.013	0.069	-10000	0	-0.44	9	9
RAP1A	0.023	0.063	0.49	5	-10000	0	5
GAB1	0.021	0.054	0.46	3	-10000	0	3
MAPK14	0.021	0.033	-10000	0	-10000	0	0
EPO	0.018	0.023	-10000	0	-10000	0	0
PLCG1	0.028	0.048	-10000	0	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.023	0.022	-10000	0	-10000	0	0
RAPGEF1	0.025	0.008	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.027	0.093	-10000	0	-0.41	19	19
GAB1/SHC/GRB2/SOS1	0.047	0.045	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.03	0.028	-10000	0	-10000	0	0
IRS2	0.02	0.055	0.5	3	-10000	0	3
STAT1	0.029	0.072	-10000	0	-10000	0	0
STAT5B	0.027	0.061	-10000	0	-10000	0	0
cell proliferation	0.012	0.077	0.34	7	-0.41	9	16
GAB1/SHIP/PIK3R1/SHP2/SHC	0.036	0.042	-10000	0	-0.41	1	1
TEC	0.021	0.054	0.46	3	-10000	0	3
SOCS3	-0.001	0.13	-10000	0	-0.67	19	19
STAT1 (dimer)	0.029	0.071	-10000	0	-10000	0	0
JAK2	0.026	0.027	-10000	0	-0.34	2	2
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.059	0.054	-10000	0	-10000	0	0
EPO/EPOR	0.03	0.028	-10000	0	-10000	0	0
LYN	0.025	0.014	-10000	0	-10000	0	0
TEC/VAV2	0.032	0.042	-10000	0	-10000	0	0
elevation of cytosolic calcium ion concentration	0.023	0.022	-10000	0	-10000	0	0
SHC1	0.025	0.008	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.049	0.032	-10000	0	-10000	0	0
mol:IP3	0.028	0.048	-10000	0	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.043	0.047	-10000	0	-10000	0	0
SH2B3	0.028	0.008	-10000	0	-10000	0	0
NFKB1	0.021	0.033	-10000	0	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	0.002	0.057	-10000	0	-0.26	18	18
PTPN6	0.022	0.048	0.31	1	-10000	0	1
TEC/VAV2/GRB2	0.042	0.045	-10000	0	-10000	0	0
EPOR	0.023	0.022	-10000	0	-10000	0	0
INPP5D	0.019	0.034	-10000	0	-10000	0	0
mol:GDP	0.046	0.045	-10000	0	-10000	0	0
SOS1	0.027	0.005	-10000	0	-10000	0	0
PLCG2	0.026	0.006	-10000	0	-10000	0	0
CRKL/CBL/C3G	0.03	0.043	-10000	0	-10000	0	0
VAV2	0.023	0.059	0.47	5	-10000	0	5
CBL	0.022	0.056	0.45	4	-10000	0	4
SHC/Grb2/SOS1	0.035	0.039	-10000	0	-10000	0	0
STAT5A	0.027	0.061	-10000	0	-10000	0	0
GRB2	0.026	0.007	-10000	0	-10000	0	0
STAT5 (dimer)	0.039	0.097	-10000	0	-0.42	1	1
LYN/PLCgamma2	0.039	0.011	-10000	0	-10000	0	0
PTPN11	0.025	0.032	-10000	0	-0.67	1	1
BTK	0.01	0.059	-10000	0	-0.36	6	6
BCL2	-0.015	0.26	-10000	0	-0.9	37	37

×

TRAIL signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.023	0.055	-10000	0	-0.67	3	3
positive regulation of NF-kappaB transcription factor activity	0.036	0.043	-10000	0	-0.51	3	3
MAP2K4	0.027	0.046	-10000	0	-0.44	1	1
IKBKB	0.027	0.005	-10000	0	-10000	0	0
TNFRSF10B	0.027	0.005	-10000	0	-10000	0	0
TNFRSF10A	0.023	0.055	-10000	0	-0.67	3	3
SMPD1	0.015	0.03	-10000	0	-0.34	3	3
IKBKG	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.027	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR2	0.036	0.043	-10000	0	-0.51	3	3
TRAIL/TRAILR3	0.004	0.067	-10000	0	-0.51	3	3
TRAIL/TRAILR1	0.033	0.061	-10000	0	-0.51	6	6
TRAIL/TRAILR4	0.036	0.043	-10000	0	-0.51	3	3
TRAIL/TRAILR1/DAP3/GTP	0.042	0.052	-10000	0	-0.4	6	6
IKK complex	0.025	0.051	-10000	0	-0.4	2	2
RIPK1	0.027	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.019	0.006	-10000	0	-10000	0	0
MAPK3	0.013	0.041	-10000	0	-0.51	3	3
MAP3K1	0.027	0.047	-10000	0	-0.37	4	4
TRAILR4 (trimer)	0.027	0.005	-10000	0	-10000	0	0
TRADD	0.026	0.006	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.023	0.054	-10000	0	-0.67	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.028	0.043	-10000	0	-0.33	6	6
CFLAR	0.027	0.005	-10000	0	-10000	0	0
MAPK1	0.01	0.041	-10000	0	-0.5	3	3
TRAIL/TRAILR1/FADD/TRADD/RIP	0.071	0.054	-10000	0	-0.38	6	6
mol:ceramide	0.015	0.03	-10000	0	-0.34	3	3
FADD	0.027	0.005	-10000	0	-10000	0	0
MAPK8	0.016	0.071	0.28	1	-0.36	10	11
TRAF2	0.025	0.009	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.014	0.068	-10000	0	-10000	0	0
CHUK	0.027	0.004	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.047	0.055	-10000	0	-0.44	6	6
DAP3	0.025	0.008	-10000	0	-10000	0	0
CASP10	0.01	0.04	-10000	0	-0.43	3	3
JNK cascade	0.036	0.043	-10000	0	-0.51	3	3
TRAIL (trimer)	0.023	0.055	-10000	0	-0.67	3	3
TNFRSF10C	-0.014	0.068	-10000	0	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	0.053	0.052	-10000	0	-0.38	6	6
TRAIL/TRAILR2/FADD	0.05	0.04	-10000	0	-0.43	3	3
cell death	0.015	0.03	-10000	0	-0.34	3	3
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.03	0.035	-10000	0	-0.37	3	3
TRAILR2 (trimer)	0.027	0.005	-10000	0	-10000	0	0
CASP8	0.011	0.032	-10000	0	-0.58	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.074	0.041	-10000	0	-0.38	3	3

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.02	0.012	-10000	0	-10000	0	0
Rac1/GDP	0.024	0.009	-10000	0	-10000	0	0
DOCK1	0.023	0.054	-10000	0	-0.67	3	3
ITGA4	0.02	0.058	-10000	0	-0.67	3	3
RAC1	0.026	0.006	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.016	0.095	-10000	0	-0.51	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.026	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.048	0.042	-10000	0	-0.44	3	3
alpha4/beta7 Integrin/Paxillin	0.032	0.077	-10000	0	-0.41	14	14
lamellipodium assembly	0.025	0.063	-10000	0	-0.53	5	5
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
PI3K	0.036	0.043	-10000	0	-0.51	3	3
ARF6	0.027	0.005	-10000	0	-10000	0	0
TLN1	0.025	0.007	-10000	0	-10000	0	0
PXN	0.016	0.005	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
ARF6/GTP	0.053	0.035	-10000	0	-0.35	2	2
cell adhesion	0.051	0.04	-10000	0	-0.37	3	3
CRKL/CBL	0.029	0.019	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.042	0.038	-10000	0	-0.4	3	3
ITGB1	0.027	0.004	-10000	0	-10000	0	0
ITGB7	0.004	0.11	-10000	0	-0.65	12	12
ARF6/GDP	0.024	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.05	0.064	-10000	0	-0.43	7	7
p130Cas/Crk/Dock1	0.048	0.041	-10000	0	-0.44	3	3
VCAM1	0.018	0.071	-10000	0	-0.67	5	5
alpha4/beta1 Integrin/Paxillin/Talin	0.052	0.041	-10000	0	-0.37	3	3
alpha4/beta1 Integrin/Paxillin/GIT1	0.055	0.037	-10000	0	-0.38	2	2
BCAR1	0.026	0.006	-10000	0	-10000	0	0
mol:GDP	-0.053	0.036	0.38	2	-10000	0	2
CBL	0.027	0.005	-10000	0	-10000	0	0
PRKACA	0.025	0.008	-10000	0	-10000	0	0
GIT1	0.026	0.007	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.052	0.041	-10000	0	-0.37	3	3
Rac1/GTP	0.026	0.071	-10000	0	-0.61	5	5

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.063	0.03	-9999	-0.39	1	1
HDAC3	0.026	0.006	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.007	0.002	-9999	-10000	0	0
GATA1/HDAC4	0.035	0.012	-9999	-10000	0	0
GATA1/HDAC5	0.034	0.013	-9999	-10000	0	0
GATA2/HDAC5	0.038	0.011	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0.049	0.028	-9999	-0.44	1	1
HDAC9	0.012	0.045	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0.051	0.016	-9999	-10000	0	0
HDAC4/ANKRA2	0.039	0.01	-9999	-10000	0	0
HDAC5/YWHAB	0.038	0.01	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.013	0.009	-9999	-10000	0	0
GATA2	0.027	0.008	-9999	-10000	0	0
HDAC4/RFXANK	0.037	0.014	-9999	-10000	0	0
BCOR	0.026	0.007	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.02	0.013	-9999	-10000	0	0
HDAC5	0.026	0.007	-9999	-10000	0	0
GNB1/GNG2	0.037	0.027	-9999	-0.51	1	1
Histones	0.008	0.048	-9999	-10000	0	0
ADRBK1	0.027	0.005	-9999	-10000	0	0
HDAC4	0.027	0.005	-9999	-10000	0	0
XPO1	0.027	0.005	-9999	-10000	0	0
HDAC5/ANKRA2	0.038	0.011	-9999	-10000	0	0
HDAC4/Ubc9	0.038	0.011	-9999	-10000	0	0
HDAC7	0.027	0.005	-9999	-10000	0	0
HDAC5/14-3-3 E	0.038	0.011	-9999	-10000	0	0
TUBA1B	0.027	0.005	-9999	-10000	0	0
HDAC6	0.026	0.007	-9999	-10000	0	0
HDAC5/RFXANK	0.036	0.015	-9999	-10000	0	0
CAMK4	0.013	0.085	-9999	-0.67	7	7
Tubulin/HDAC6	0.047	0.048	-9999	-0.4	5	5
SUMO1	0.027	0.005	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.027	0.005	-9999	-10000	0	0
GATA1	0.012	0.021	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.026	0.007	-9999	-10000	0	0
NR3C1	0.026	0.006	-9999	-10000	0	0
SUMO1/HDAC4	0.014	0.058	-9999	-0.29	1	1
SRF	0.027	0.003	-9999	-10000	0	0
HDAC4/YWHAB	0.039	0.009	-9999	-10000	0	0
Tubulin	0.034	0.055	-9999	-0.51	5	5
HDAC4/14-3-3 E	0.038	0.011	-9999	-10000	0	0
GNB1	0.026	0.006	-9999	-10000	0	0
RANGAP1	0.02	0.012	-9999	-10000	0	0
BCL6/BCoR	0.037	0.027	-9999	-0.51	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.052	0.014	-9999	-10000	0	0
HDAC4/SRF	0.046	0.06	-9999	-0.44	7	7
HDAC4/ER alpha	0.008	0.11	-9999	-0.51	21	21
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.008	0.048	-9999	-10000	0	0
cell motility	0.046	0.048	-9999	-0.4	5	5
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
HDAC7/HDAC3	0.039	0.009	-9999	-10000	0	0
BCL6	0.026	0.032	-9999	-0.67	1	1
HDAC4/CaMK II delta B	0.027	0.005	-9999	-10000	0	0
Hsp90/HDAC6	0.037	0.012	-9999	-10000	0	0
ESR1	-0.014	0.15	-9999	-0.65	23	23
HDAC6/HDAC11	0.038	0.011	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.017	0.052	-9999	-10000	0	0
NPC	0.016	0.003	-9999	-10000	0	0
MEF2C	0.025	0.032	-9999	-0.67	1	1
RAN	0.027	0.005	-9999	-10000	0	0
HDAC4/MEF2C	0.074	0.031	-9999	-0.38	1	1
GNG2	0.025	0.032	-9999	-0.67	1	1
NCOR2	0.027	0.005	-9999	-10000	0	0
TUBB2A	0.02	0.07	-9999	-0.67	5	5
HDAC11	0.027	0.004	-9999	-10000	0	0
HSP90AA1	0.027	0.005	-9999	-10000	0	0
RANBP2	0.027	0.005	-9999	-10000	0	0
ANKRA2	0.027	0.005	-9999	-10000	0	0
RFXANK	0.025	0.012	-9999	-10000	0	0
nuclear import	-0.036	0.011	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.03	0.029	-10000	0	-10000	0	0
KLHL20	0.013	0.051	0.2	1	-10000	0	1
CYFIP2	0.026	0.006	-10000	0	-10000	0	0
Rac1/GDP	0.039	0.042	0.26	1	-10000	0	1
ENAH	0.028	0.027	-10000	0	-10000	0	0
AP1M1	0.025	0.008	-10000	0	-10000	0	0
RAP1B	0.027	0.005	-10000	0	-10000	0	0
RAP1A	0.027	0.005	-10000	0	-10000	0	0
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
CDC42/GTP	0.035	0.016	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.032	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.055	0.072	-10000	0	-0.4	11	11
RAPGEF1	0.026	0.033	-10000	0	-10000	0	0
CTNND1	0.027	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.033	0.034	-10000	0	-10000	0	0
CRK	0.026	0.026	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	0.051	0.016	-10000	0	-10000	0	0
alphaE/beta7 Integrin	0.021	0.084	-10000	0	-0.51	11	11
IQGAP1	0.027	0.004	-10000	0	-10000	0	0
NCKAP1	0.027	0.005	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.05	0.014	-10000	0	-10000	0	0
DLG1	0.029	0.033	-10000	0	-10000	0	0
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.008	0.016	-10000	0	-10000	0	0
MLLT4	0.027	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.053	0.03	-10000	0	-0.4	1	1
PI3K	0.017	0.022	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.038	0.011	-10000	0	-10000	0	0
TIAM1	-0.059	0.081	-10000	0	-0.67	1	1
E-cadherin(dimer)/Ca2+	0.061	0.017	-10000	0	-10000	0	0
AKT1	0.018	0.021	-10000	0	-10000	0	0
PIK3R1	0.027	0.005	-10000	0	-10000	0	0
CDH1	0.026	0.006	-10000	0	-10000	0	0
RhoA/GDP	0.046	0.067	0.44	7	-10000	0	7
actin cytoskeleton organization	0.012	0.041	0.19	3	-10000	0	3
CDC42/GDP	0.046	0.075	0.48	9	-10000	0	9
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.023	0.008	-10000	0	-10000	0	0
ITGB7	0.004	0.11	-10000	0	-0.65	12	12
RAC1	0.026	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.066	0.019	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	0.046	0.012	-10000	0	-10000	0	0
mol:GDP	0.036	0.081	0.54	8	-10000	0	8
CDC42/GTP/IQGAP1	0.036	0.008	-10000	0	-10000	0	0
JUP	0.026	0.007	-10000	0	-10000	0	0
p120 catenin/RhoA/GDP	0.046	0.043	0.26	1	-10000	0	1
RAC1/GTP/IQGAP1	0.035	0.009	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.037	0.012	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
CDC42	0.027	0.005	-10000	0	-10000	0	0
CTNNA1	0.027	0.006	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.012	0.037	0.2	5	-10000	0	5
NME1	0.026	0.007	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.029	0.033	-10000	0	-10000	0	0
regulation of cell-cell adhesion	0.025	0.011	-10000	0	-10000	0	0
WASF2	0.007	0.022	-10000	0	-10000	0	0
Rap1/GTP	0.042	0.027	0.24	2	-10000	0	2
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.064	0.072	-10000	0	-0.38	11	11
CCND1	0.012	0.04	0.19	4	-10000	0	4
VAV2	0.006	0.14	-10000	0	-0.53	27	27
RAP1/GDP	0.048	0.039	0.3	5	-10000	0	5
adherens junction assembly	0.029	0.032	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.027	0.004	-10000	0	-10000	0	0
PIP5K1C	0.025	0.008	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.053	0.067	-10000	0	-0.37	11	11
E-cadherin/beta catenin	0.015	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	0.03	0.029	-10000	0	-10000	0	0
PIK3CA	0.023	0.054	-10000	0	-0.67	3	3
Rac1/GTP	-0.006	0.076	-10000	0	-0.32	1	1
E-cadherin/beta catenin/alpha catenin	0.053	0.014	-10000	0	-10000	0	0
ITGAE	0.026	0.007	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.033	0.034	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.003	0.14	-10000	0	-0.66	20	20
CLTC	0.029	0.022	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.019	0.015	-10000	0	-10000	0	0
Dynamin 2/GTP	0.027	0.01	-10000	0	-10000	0	0
EXOC4	0.026	0.006	-10000	0	-10000	0	0
CD59	0.022	0.011	-10000	0	-10000	0	0
CPE	0.011	0.05	-10000	0	-0.44	6	6
CTNNB1	0.027	0.003	-10000	0	-10000	0	0
membrane fusion	0.02	0.013	-10000	0	-10000	0	0
CTNND1	0.022	0.037	0.36	3	-10000	0	3
DNM2	0.025	0.008	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.023	0.031	0.24	1	-10000	0	1
TSHR	0.015	0.029	-10000	0	-0.44	2	2
INS	0.007	0.073	-10000	0	-0.48	10	10
BIN1	0.027	0.005	-10000	0	-10000	0	0
mol:Choline	0.02	0.013	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.016	0.005	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.027	0.005	-10000	0	-10000	0	0
mol:Ca2+	0.027	0.01	-10000	0	-10000	0	0
JUP	0.021	0.01	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.05	0.023	-10000	0	-0.4	1	1
ARF6/GTP	0.02	0.004	-10000	0	-10000	0	0
CDH1	0.021	0.011	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.02	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.026	0.009	-10000	0	-10000	0	0
positive regulation of endocytosis	0.02	0.003	-10000	0	-10000	0	0
EXOC2	0.027	0.004	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.033	0.014	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.026	0.007	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.047	0.025	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.016	0.004	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.035	0.01	-10000	0	-10000	0	0
ACAP1	0.024	0.014	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.017	0.01	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.029	0.024	-10000	0	-10000	0	0
JIP4/KLC1	0.049	0.014	-10000	0	-10000	0	0
EXOC1	0.027	0.004	-10000	0	-10000	0	0
exocyst	0.033	0.014	-10000	0	-10000	0	0
RALA/GTP	0.02	0.004	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.035	0.01	-10000	0	-10000	0	0
receptor recycling	0.02	0.003	-10000	0	-10000	0	0
CTNNA1	0.02	0.029	0.36	1	-10000	0	1
NME1	0.016	0.005	-10000	0	-10000	0	0
clathrin coat assembly	0.032	0.036	0.34	3	-10000	0	3
IL2RA	0.008	0.055	-10000	0	-10000	0	0
VAMP3	0.016	0.004	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.024	0.071	-10000	0	-0.32	19	19
EXOC6	0.027	0.005	-10000	0	-10000	0	0
PLD1	0.018	0.005	-10000	0	-10000	0	0
PLD2	0.018	0.006	-10000	0	-10000	0	0
EXOC5	0.027	0.005	-10000	0	-10000	0	0
PIP5K1C	0.021	0.012	-10000	0	-10000	0	0
SDC1	0.021	0.012	-10000	0	-10000	0	0
ARF6/GDP	0.025	0.007	-10000	0	-10000	0	0
EXOC7	0.026	0.007	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.049	0.026	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.02	0.013	-10000	0	-10000	0	0
endocytosis	-0.048	0.023	0.4	1	-10000	0	1
SCAMP2	0.027	0.004	-10000	0	-10000	0	0
ADRB2	0.03	0.084	0.43	9	-10000	0	9
EXOC3	0.026	0.007	-10000	0	-10000	0	0
ASAP2	0.025	0.032	-10000	0	-0.67	1	1
Dynamin 2/GDP	0.03	0.011	-10000	0	-10000	0	0
KLC1	0.027	0.005	-10000	0	-10000	0	0
AVPR2	0.029	0.082	0.46	7	-10000	0	7
RALA	0.026	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.046	0.026	-10000	0	-10000	0	0

×

PLK2 and PLK4 events

Figure S124. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S124. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
PLK2	0.025	0.018	-9999	-9999
PLK4	0.027	0.004	-9999	-9999
regulation of centriole replication	0.016	0.011	-9999	-9999

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.004	0.042	-10000	0	-10000	0	0
regulation of axonogenesis	-0.011	0.021	0.27	2	-10000	0	2
myoblast fusion	-0.01	0.028	-10000	0	-10000	0	0
mol:GTP	0.008	0.019	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.024	0.063	0.41	1	-10000	0	1
ARF1/GTP	0.03	0.014	-10000	0	-10000	0	0
mol:GM1	0.004	0.012	-10000	0	-10000	0	0
mol:Choline	0.008	0.014	-10000	0	-10000	0	0
lamellipodium assembly	0.015	0.027	-10000	0	-10000	0	0
MAPK3	0.008	0.027	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.024	0.064	-10000	0	-0.42	1	1
ARF1	0.025	0.008	-10000	0	-10000	0	0
ARF6/GDP	0.01	0.028	-10000	0	-10000	0	0
ARF1/GDP	0.02	0.03	-10000	0	-10000	0	0
ARF6	0.03	0.009	-10000	0	-10000	0	0
RAB11A	0.027	0.004	-10000	0	-10000	0	0
TIAM1	-0.061	0.082	-10000	0	-0.67	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.025	-10000	0	-10000	0	0
actin filament bundle formation	-0.023	0.03	-10000	0	-10000	0	0
KALRN	0.009	0.021	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	0.038	0.011	-10000	0	-10000	0	0
RhoA/GDP	0.023	0.03	-10000	0	-10000	0	0
NME1	0.026	0.007	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.027	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.008	0.019	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0.015	0.027	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
liver development	0.008	0.019	-10000	0	-10000	0	0
ARF6/GTP	0.009	0.019	-10000	0	-10000	0	0
RhoA/GTP	0.031	0.012	-10000	0	-10000	0	0
mol:GDP	0.008	0.021	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0.045	0.016	-10000	0	-10000	0	0
RHOA	0.027	0.003	-10000	0	-10000	0	0
PLD1	0.012	0.018	-10000	0	-10000	0	0
RAB11FIP3	0.026	0.007	-10000	0	-10000	0	0
tube morphogenesis	0.015	0.027	-10000	0	-10000	0	0
ruffle organization	0.011	0.021	-10000	0	-0.27	2	2
regulation of epithelial cell migration	0.008	0.019	-10000	0	-10000	0	0
PLD2	0.012	0.017	-10000	0	-10000	0	0
PIP5K1A	0.011	0.021	-10000	0	-0.27	2	2
mol:Phosphatidic acid	0.008	0.014	-10000	0	-10000	0	0
Rac1/GTP	0.015	0.027	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.024	0.045	-9999	-0.67	2	2
Aurora C/Aurora B/INCENP	0.046	0.041	-9999	-0.45	2	2
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.009	0.014	-9999	-10000	0	0
AURKB	-0.007	0.063	-9999	-10000	0	0
AURKC	0.02	0.03	-9999	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.02	0.076	-9999	-0.67	1	1
GPC2	0.016	0.038	-9999	-10000	0	0
GPC2/Midkine	-0.004	0.061	-9999	-0.3	1	1
neuron projection morphogenesis	-0.004	0.061	-9999	-0.3	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.027	0.005	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0.001	0.014	-9999	-10000	0	0
MDM2/SUMO1	0.015	0.054	-9999	-0.22	1	1
HDAC4	0.027	0.005	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0.001	0.013	-9999	-10000	0	0
SUMO1	0.027	0.005	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.007	0.035	-9999	-0.24	9	9
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.012	0.008	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.027	0.005	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.027	0.005	-9999	-10000	0	0
SUMO1/HDAC4	0.014	0.058	-9999	-0.29	1	1
SUMO1/HDAC1	0.014	0.057	-9999	-0.27	2	2
RANGAP1	0.02	0.012	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.066	0.018	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.013	0.009	-9999	-10000	0	0
Ran/GTP	0.006	0.048	-9999	-0.23	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.027	0.005	-9999	-10000	0	0
UBE2I	0.026	0.007	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.006	0.046	-9999	-10000	0	0
NPC	0.016	0.003	-9999	-10000	0	0
PIAS2	0.027	0.004	-9999	-10000	0	0
PIAS1	0.027	0.004	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

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	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
E-cadherin/beta catenin-gamma catenin	0.051	0.016	-9999	-9999
E-cadherin/beta catenin	0.039	0.009	-9999	-9999
CTNNB1	0.027	0.003	-9999	-9999
JUP	0.026	0.007	-9999	-9999
CDH1	0.026	0.006	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.011	0.017	-10000	0	-10000	0	0
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.025	0.034	0.2	2	-0.17	2	4
AP2	0.038	0.011	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.036	0.011	-10000	0	-10000	0	0
CLTB	0.026	0.006	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.021	0.009	-10000	0	-10000	0	0
CD4	0.021	0.03	-10000	0	-10000	0	0
CLTA	0.025	0.007	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ARFGAP1	0.009	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.006	0.024	-10000	0	-0.37	2	2
ARF1/GTP	0.028	0.02	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.015	0.007	-10000	0	-10000	0	0
mol:Choline	0.006	0.024	-10000	0	-0.37	2	2
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.026	0.009	-10000	0	-10000	0	0
DDEF1	0.007	0.028	-10000	0	-0.37	2	2
ARF1/GDP	0.005	0.017	-10000	0	-10000	0	0
AP2M1	0.027	0.003	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	0.014	0.006	-10000	0	-10000	0	0
Rac/GTP	0.021	0.007	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.036	0.015	-10000	0	-10000	0	0
ARFIP2	0.022	0.013	-10000	0	-10000	0	0
COPA	0.025	0.007	-10000	0	-10000	0	0
RAC1	0.026	0.006	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.014	0.033	-10000	0	-0.48	1	1
ARF1/GTP/ARHGAP10	0.018	0.007	-10000	0	-10000	0	0
GGA3	0.026	0.007	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.024	0.022	-10000	0	-0.28	1	1
AP2A1	0.025	0.008	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.019	0.009	-10000	0	-10000	0	0
ARF1/GDP/Membrin	0.026	0.024	-10000	0	-0.25	2	2
Arfaptin 2/Rac/GDP	0.034	0.011	-10000	0	-10000	0	0
CYTH2	0.028	0.01	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.033	0.014	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.02	0.004	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.025	0.025	-10000	0	-10000	0	0
PLD2	0.006	0.024	-10000	0	-0.37	2	2
ARF-GAP1/v-SNARE	0.009	0.002	-10000	0	-10000	0	0
PIP5K1A	0.006	0.024	-10000	0	-0.37	2	2
ARF1/GTP/Membrin/GBF1/p115	0.023	0.02	-10000	0	-0.19	2	2
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.006	0.024	-10000	0	-0.37	2	2
KDEL Receptor/Ligand/ARF-GAP1	0.009	0.002	-10000	0	-10000	0	0
GOSR2	0.014	0.013	-10000	0	-10000	0	0
USO1	0.014	0.013	-10000	0	-10000	0	0
GBF1	0.013	0.024	-10000	0	-0.3	2	2
ARF1/GTP/Arfaptin 2	0.035	0.014	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.052	0.017	-10000	0	-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
IKK alpha homodimer	0.038	0.011	-9999	-9999
FBXW11	0.026	0.006	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.026	0.006	-9999	-9999
CHUK	0.027	0.004	-9999	-9999
NF kappa B2 p100/RelB	0.072	0.027	-9999	-9999
NFKB1	0.027	0.004	-9999	-9999
MAP3K14	0.026	0.007	-9999	-9999
NF kappa B1 p50/RelB	0.038	0.011	-9999	-9999
RELB	0.026	0.007	-9999	-9999
NFKB2	0.027	0.004	-9999	-9999
NF kappa B2 p52/RelB	0.034	0.01	-9999	-9999
regulation of B cell activation	0.034	0.01	-9999	-9999

pid_entity	TCGA.QD.A8IV	TCGA.MK.A84Z	TCGA.MK.A4N9	TCGA.MK.A4N7
109_MAP3K5	-0.065	0.053	-0.2	0.025
47_PPARGC1A	0.028	0	-0.67	-0.67
105_BMP4	0.028	0.028	0.028	-0.13
105_BMP6	0.028	0.028	0.028	0.028
105_BMP7	0.028	0.028	0.028	0.028
105_BMP2	0.028	0.028	0.028	0.028
131_RELN/VLDLR	0.064	-0.22	-0.4	-0.4
30_TGFB1/TGF beta receptor Type II	0.027	0.027	0.027	0.027
84_STAT5B	0.04	0.053	0.04	-0.05
84_STAT5A	0.04	0.053	0.04	-0.05