PARADIGM pathway analysis of mRNASeq expression data - Skin Cutaneous Melanoma (Metastatic)

Pathway.Name	Avg.Num.Perturbations
BCR signaling pathway	138
IL4-mediated signaling events	135
TCR signaling in naïve CD8+ T cells	104
IL23-mediated signaling events	102
Nephrin/Neph1 signaling in the kidney podocyte	91
IL12-mediated signaling events	80
Caspase cascade in apoptosis	74
FAS signaling pathway (CD95)	66
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	62
E-cadherin signaling events	62

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
BCR signaling pathway	0.3760	138	13731	99	-0.76	0.026	1000	-1000	-0.056	-1000
IL4-mediated signaling events	0.3678	135	12285	91	-1.3	1	1000	-1000	-0.12	-1000
TCR signaling in naïve CD8+ T cells	0.2834	104	9697	93	-0.59	0.028	1000	-1000	-0.042	-1000
IL23-mediated signaling events	0.2779	102	6145	60	-0.74	0.019	1000	-1000	-0.064	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.2480	91	3110	34	-0.21	0.019	1000	-1000	-0.01	-1000
IL12-mediated signaling events	0.2180	80	7038	87	-0.68	0.11	1000	-1000	-0.087	-1000
Caspase cascade in apoptosis	0.2016	74	5507	74	-0.21	0.14	1000	-1000	-0.015	-1000
FAS signaling pathway (CD95)	0.1798	66	3130	47	-0.16	0.12	1000	-1000	-0.032	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1689	62	4273	68	-0.62	0.12	1000	-1000	-0.043	-1000
E-cadherin signaling events	0.1689	62	314	5	-0.13	0.019	1000	-1000	-0.005	-1000
Calcium signaling in the CD4+ TCR pathway	0.1580	58	1807	31	-0.43	0.019	1000	-1000	-0.036	-1000
Ras signaling in the CD4+ TCR pathway	0.1526	56	956	17	-0.17	0.037	1000	-1000	-0.016	-1000
JNK signaling in the CD4+ TCR pathway	0.1499	55	941	17	-0.2	0.019	1000	-1000	-0.021	-1000
S1P4 pathway	0.1444	53	1329	25	-0.16	0.028	1000	-1000	-0.011	-1000
IL27-mediated signaling events	0.1417	52	2665	51	-0.26	0.17	1000	-1000	-0.047	-1000
Signaling events regulated by Ret tyrosine kinase	0.1335	49	4057	82	-0.13	0.019	1000	-1000	-0.053	-1000
Glypican 1 network	0.1308	48	2317	48	-0.3	0.069	1000	-1000	-0.017	-1000
Wnt signaling	0.1308	48	342	7	-0.082	0.007	1000	-1000	-0.008	-1000
Glucocorticoid receptor regulatory network	0.1253	46	5259	114	-0.52	0.31	1000	-1000	-0.045	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.1226	45	3395	74	-0.13	0.05	1000	-1000	-0.047	-1000
a4b1 and a4b7 Integrin signaling	0.1199	44	222	5	-0.076	-0.019	1000	-1000	-0.002	-1000
amb2 Integrin signaling	0.1199	44	3630	82	-0.27	0.026	1000	-1000	-0.031	-1000
Endothelins	0.1172	43	4160	96	-0.18	0.02	1000	-1000	-0.049	-1000
E-cadherin signaling in the nascent adherens junction	0.1144	42	3224	76	-0.13	0.028	1000	-1000	-0.051	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.1117	41	1846	45	-0.28	0.046	1000	-1000	-0.052	-1000
TCGA08_retinoblastoma	0.1117	41	333	8	-0.11	0.03	1000	-1000	-0.004	-1000
Thromboxane A2 receptor signaling	0.1090	40	4262	105	-0.12	0.041	1000	-1000	-0.038	-1000
Syndecan-4-mediated signaling events	0.1090	40	2692	67	-0.26	0.025	1000	-1000	-0.018	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1090	40	3539	88	-0.22	0.03	1000	-1000	-0.054	-1000
Syndecan-1-mediated signaling events	0.1063	39	1331	34	-0.15	0.019	1000	-1000	-0.016	-1000
LPA receptor mediated events	0.1063	39	3994	102	-0.13	0.025	1000	-1000	-0.053	-1000
IL2 signaling events mediated by PI3K	0.1035	38	2221	58	-0.19	0.046	1000	-1000	-0.024	-1000
IL2 signaling events mediated by STAT5	0.1035	38	844	22	-0.2	0.02	1000	-1000	-0.022	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.1008	37	1390	37	-0.29	0.041	1000	-1000	-0.015	-1000
Regulation of p38-alpha and p38-beta	0.0981	36	1976	54	-0.34	0.049	1000	-1000	-0.038	-1000
Class I PI3K signaling events	0.0926	34	2552	73	-0.45	0.048	1000	-1000	-0.024	-1000
Fc-epsilon receptor I signaling in mast cells	0.0872	32	3163	97	-0.14	0.033	1000	-1000	-0.05	-1000
HIF-1-alpha transcription factor network	0.0845	31	2392	76	-0.11	0.084	1000	-1000	-0.056	-1000
Ephrin A reverse signaling	0.0817	30	213	7	-0.071	0.008	1000	-1000	-0.004	-1000
Visual signal transduction: Cones	0.0763	28	1088	38	-0.21	0.017	1000	-1000	-0.007	-1000
TRAIL signaling pathway	0.0763	28	1377	48	-0.057	0.022	1000	-1000	-0.023	-1000
Visual signal transduction: Rods	0.0763	28	1468	52	-0.21	0.019	1000	-1000	-0.043	-1000
TCGA08_p53	0.0736	27	190	7	-0.072	0.051	1000	-1000	-0.003	-1000
ceramide signaling pathway	0.0708	26	1317	49	-0.18	0.028	1000	-1000	-0.017	-1000
Atypical NF-kappaB pathway	0.0708	26	810	31	-0.2	0.033	1000	-1000	-0.014	-1000
FOXA2 and FOXA3 transcription factor networks	0.0681	25	1158	46	-0.5	0.027	1000	-1000	-0.023	-1000
Noncanonical Wnt signaling pathway	0.0654	24	628	26	-0.082	0.019	1000	-1000	-0.021	-1000
BMP receptor signaling	0.0654	24	1984	81	-0.23	0.059	1000	-1000	-0.057	-1000
IFN-gamma pathway	0.0654	24	1654	68	-0.18	0.028	1000	-1000	-0.055	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0654	24	1290	52	-0.19	0.031	1000	-1000	-0.025	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0627	23	663	28	-0.16	0.049	1000	-1000	-0.014	-1000
Aurora C signaling	0.0599	22	156	7	-0.098	0.017	1000	-1000	-0.008	-1000
Signaling events mediated by PTP1B	0.0545	20	1575	76	-0.34	0.032	1000	-1000	-0.033	-1000
Paxillin-dependent events mediated by a4b1	0.0545	20	734	36	-0.077	0.059	1000	-1000	-0.027	-1000
Integrins in angiogenesis	0.0545	20	1700	84	-0.2	0.043	1000	-1000	-0.05	-1000
Osteopontin-mediated events	0.0518	19	735	38	-0.049	0.035	1000	-1000	-0.025	-1000
Syndecan-2-mediated signaling events	0.0518	19	1374	69	-0.26	0.046	1000	-1000	-0.005	-1000
Arf6 signaling events	0.0518	19	1218	62	-0.18	0.045	1000	-1000	-0.017	-1000
p75(NTR)-mediated signaling	0.0518	19	2420	125	-0.18	0.054	1000	-1000	-0.052	-1000
IL6-mediated signaling events	0.0518	19	1458	75	-0.19	0.068	1000	-1000	-0.034	-1000
Effects of Botulinum toxin	0.0463	17	448	26	-0.066	0.025	1000	-1000	-0.012	-1000
EGFR-dependent Endothelin signaling events	0.0463	17	362	21	-0.031	0.028	1000	-1000	-0.034	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0463	17	1360	78	-0.15	0.055	1000	-1000	-0.042	-1000
Signaling events mediated by the Hedgehog family	0.0436	16	839	52	-0.28	0.043	1000	-1000	-0.013	-1000
Cellular roles of Anthrax toxin	0.0436	16	629	39	-0.15	0.019	1000	-1000	-0.01	-1000
Nectin adhesion pathway	0.0409	15	954	63	-0.24	0.046	1000	-1000	-0.047	-1000
Ceramide signaling pathway	0.0409	15	1195	76	-0.18	0.042	1000	-1000	-0.015	-1000
EPHB forward signaling	0.0409	15	1301	85	-0.059	0.041	1000	-1000	-0.055	-1000
S1P5 pathway	0.0381	14	253	17	-0.093	0.019	1000	-1000	-0.005	-1000
Plasma membrane estrogen receptor signaling	0.0381	14	1286	86	-0.093	0.048	1000	-1000	-0.05	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0354	13	1112	85	-0.075	0.042	1000	-1000	-0.043	-1000
Ephrin B reverse signaling	0.0354	13	647	48	-0.12	0.021	1000	-1000	-0.032	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0354	13	1114	83	-0.16	0.084	1000	-1000	-0.02	-1000
Nongenotropic Androgen signaling	0.0354	13	684	52	-0.093	0.037	1000	-1000	-0.034	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0354	13	1603	120	-0.12	0.078	1000	-1000	-0.044	-1000
E-cadherin signaling in keratinocytes	0.0354	13	572	43	-0.13	0.022	1000	-1000	-0.022	-1000
LPA4-mediated signaling events	0.0327	12	154	12	-0.056	0.02	1000	-1000	-0.01	-1000
EPO signaling pathway	0.0327	12	707	55	-0.079	0.029	1000	-1000	-0.052	-1000
Reelin signaling pathway	0.0327	12	705	56	-0.11	0.052	1000	-1000	-0.045	-1000
IL1-mediated signaling events	0.0327	12	755	62	-0.069	0.07	1000	-1000	-0.05	-1000
Coregulation of Androgen receptor activity	0.0300	11	849	76	-0.11	0.038	1000	-1000	-0.019	-1000
Syndecan-3-mediated signaling events	0.0300	11	412	35	-0.055	0.054	1000	-1000	-0.025	-1000
Glypican 2 network	0.0300	11	47	4	0.004	0.01	1000	-1000	-0.005	-1000
S1P3 pathway	0.0300	11	495	42	-0.091	0.037	1000	-1000	-0.013	-1000
ErbB4 signaling events	0.0272	10	702	69	-0.12	0.053	1000	-1000	-0.052	-1000
Presenilin action in Notch and Wnt signaling	0.0272	10	619	61	-0.11	0.055	1000	-1000	-0.024	-1000
S1P1 pathway	0.0272	10	392	36	-0.094	0.021	1000	-1000	-0.034	-1000
Canonical Wnt signaling pathway	0.0272	10	540	51	-0.078	0.071	1000	-1000	-0.027	-1000
ErbB2/ErbB3 signaling events	0.0245	9	630	65	-0.024	0.042	1000	-1000	-0.041	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0245	9	495	54	-0.13	0.033	1000	-1000	-0.057	-1000
PDGFR-beta signaling pathway	0.0245	9	951	97	-0.34	0.061	1000	-1000	-0.046	-1000
Regulation of Androgen receptor activity	0.0245	9	665	70	-0.14	0.056	1000	-1000	-0.027	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0218	8	269	33	-0.11	0.055	1000	-1000	-0.015	-1000
Rapid glucocorticoid signaling	0.0218	8	170	20	-0.02	0.02	1000	-1000	-0.007	-1000
Regulation of nuclear SMAD2/3 signaling	0.0191	7	1055	136	-0.11	0.082	1000	-1000	-0.026	-1000
Signaling events mediated by HDAC Class I	0.0191	7	748	104	-0.095	0.063	1000	-1000	-0.021	-1000
Regulation of Telomerase	0.0191	7	714	102	-0.17	0.069	1000	-1000	-0.068	-1000
Hedgehog signaling events mediated by Gli proteins	0.0163	6	403	65	-0.093	0.085	1000	-1000	-0.043	-1000
Signaling mediated by p38-gamma and p38-delta	0.0163	6	103	15	-0.03	0.027	1000	-1000	-0.012	-1000
Signaling mediated by p38-alpha and p38-beta	0.0163	6	278	44	-0.039	0.028	1000	-1000	-0.015	-1000
Insulin Pathway	0.0163	6	459	74	-0.061	0.048	1000	-1000	-0.052	-1000
Signaling events mediated by PRL	0.0163	6	215	34	-0.089	0.049	1000	-1000	-0.01	-1000
Class IB PI3K non-lipid kinase events	0.0163	6	18	3	-0.01	0.01	1000	-1000	-0.005	-1000
Aurora B signaling	0.0163	6	444	67	-0.15	0.057	1000	-1000	-0.031	-1000
Canonical NF-kappaB pathway	0.0136	5	232	39	-0.095	0.085	1000	-1000	-0.047	-1000
Signaling events mediated by HDAC Class III	0.0136	5	201	40	-0.094	0.035	1000	-1000	-0.006	-1000
TCGA08_rtk_signaling	0.0136	5	151	26	-0.055	0.05	1000	-1000	-0.005	-1000
FOXM1 transcription factor network	0.0136	5	274	51	-0.12	0.29	1000	-1000	-0.088	-1000
Retinoic acid receptors-mediated signaling	0.0109	4	233	58	-0.05	0.057	1000	-1000	-0.044	-1000
Insulin-mediated glucose transport	0.0082	3	118	32	-0.035	0.049	1000	-1000	-0.02	-1000
PDGFR-alpha signaling pathway	0.0082	3	174	44	-0.013	0.041	1000	-1000	-0.021	-1000
FoxO family signaling	0.0082	3	201	64	-0.43	0.18	1000	-1000	-0.023	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0082	3	421	125	-0.12	0.083	1000	-1000	-0.054	-1000
p38 MAPK signaling pathway	0.0082	3	152	44	-0.046	0.042	1000	-1000	-0.043	-1000
Signaling events mediated by HDAC Class II	0.0054	2	175	75	-0.063	0.055	1000	-1000	-0.024	-1000
Arf6 downstream pathway	0.0054	2	93	43	-0.031	0.036	1000	-1000	-0.016	-1000
IGF1 pathway	0.0054	2	118	57	-0.046	0.054	1000	-1000	-0.052	-1000
Aurora A signaling	0.0027	1	103	60	-0.023	0.052	1000	-1000	-0.01	-1000
Class I PI3K signaling events mediated by Akt	0.0027	1	83	68	-0.044	0.059	1000	-1000	-0.018	-1000
HIF-2-alpha transcription factor network	0.0027	1	77	43	-0.16	0.16	1000	-1000	-0.049	-1000
Arf6 trafficking events	0.0027	1	114	71	-0.028	0.049	1000	-1000	-0.033	-1000
VEGFR1 specific signals	0.0027	1	110	56	-0.052	0.065	1000	-1000	-0.031	-1000
Arf1 pathway	0.0027	1	105	54	-0.034	0.034	1000	-1000	-0.011	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	0	23	0.015	0.056	1000	-1000	-0.015	-1000
BARD1 signaling events	0.0000	0	5	57	-0.047	0.08	1000	-1000	-0.017	-1000
PLK2 and PLK4 events	0.0000	0	2	3	0.017	0.025	1000	-1000	0	-1000
Circadian rhythm pathway	0.0000	0	12	22	-0.016	0.06	1000	-1000	-0.015	-1000
PLK1 signaling events	0.0000	0	45	85	-0.013	0.05	1000	-1000	-0.025	-1000
mTOR signaling pathway	0.0000	0	18	53	-0.005	0.041	1000	-1000	-0.039	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	9	27	-0.001	0.046	1000	-1000	-0.029	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.056	1000	-1000	-0.006	-1000
Total	NA	3169	188858	7203	-22	7.6	131000	-131000	-4	-131000

BCR signaling pathway

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
JUN	-0.32	0.28	-9999	-0.52	227	227
IKBKB	-0.14	0.14	-9999	-0.25	197	197
AKT1	-0.18	0.15	-9999	-0.28	246	246
IKBKG	-0.14	0.15	-9999	-0.27	178	178
CALM1	-0.37	0.37	-9999	-0.62	219	219
PIK3CA	0.018	0.014	-9999	-0.24	1	1
MAP3K1	-0.49	0.4	-9999	-0.76	241	241
MAP3K7	0.019	0	-9999	-10000	0	0
mol:Ca2+	-0.41	0.4	-9999	-0.68	219	219
DOK1	0.019	0	-9999	-10000	0	0
AP-1	-0.16	0.15	-9999	-0.27	225	225
LYN	-0.004	0.11	-9999	-0.54	15	15
BLNK	-0.19	0.27	-9999	-0.54	140	140
SHC1	0.019	0	-9999	-10000	0	0
BCR complex	-0.39	0.33	-9999	-0.62	236	236
CD22	-0.62	0.51	-9999	-0.98	230	230
CAMK2G	-0.33	0.33	-9999	-0.59	201	201
CSNK2A1	0.019	0	-9999	-10000	0	0
INPP5D	-0.075	0.21	-9999	-0.54	62	62
SHC/GRB2/SOS1	-0.38	0.34	-9999	-0.65	203	203
GO:0007205	-0.42	0.42	-9999	-0.7	219	219
SYK	-0.052	0.19	-9999	-0.54	47	47
ELK1	-0.38	0.38	-9999	-0.64	219	219
NFATC1	-0.43	0.36	-9999	-0.68	237	237
B-cell antigen/BCR complex	-0.39	0.33	-9999	-0.62	236	236
PAG1/CSK	0.026	0.03	-9999	-0.38	2	2
NFKBIB	-0.032	0.046	-9999	-0.082	57	57
HRAS	-0.37	0.36	-9999	-0.62	219	219
NFKBIA	-0.031	0.046	-9999	-0.08	57	57
NF-kappa-B/RelA/I kappa B beta	-0.017	0.037	-9999	-10000	0	0
RasGAP/Csk	-0.28	0.27	-9999	-0.47	237	237
mol:GDP	-0.39	0.38	-9999	-0.65	219	219
PTEN	0.017	0.029	-9999	-0.54	1	1
CD79B	-0.27	0.28	-9999	-0.54	192	192
NF-kappa-B/RelA/I kappa B alpha	-0.016	0.037	-9999	-10000	0	0
GRB2	0.019	0	-9999	-10000	0	0
PI3K/BCAP/CD19	-0.45	0.36	-9999	-0.7	237	237
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	-0.43	0.43	-9999	-0.72	219	219
CSK	0.019	0	-9999	-10000	0	0
FOS	-0.34	0.34	-9999	-0.57	222	222
CHUK	-0.14	0.15	-9999	-0.29	141	141
IBTK	0.019	0	-9999	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.34	0.34	-9999	-0.6	205	205
PTPN6	-0.62	0.52	-9999	-0.98	230	230
RELA	0.019	0	-9999	-10000	0	0
BCL2A1	-0.012	0.036	-9999	-0.1	24	24
VAV2	-0.66	0.52	-9999	-1	237	237
ubiquitin-dependent protein catabolic process	-0.025	0.045	-9999	-0.076	19	19
BTK	-0.17	0.41	-9999	-1	65	65
CD19	-0.66	0.52	-9999	-1	238	238
MAP4K1	-0.081	0.21	-9999	-0.54	66	66
CD72	-0.14	0.25	-9999	-0.54	105	105
PAG1	0.016	0.041	-9999	-0.54	2	2
MAPK14	-0.38	0.32	-9999	-0.61	239	239
SH3BP5	0.019	0	-9999	-10000	0	0
PIK3AP1	-0.46	0.47	-9999	-0.76	225	225
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.59	0.64	-9999	-1	219	219
RAF1	-0.33	0.33	-9999	-0.57	219	219
RasGAP/p62DOK/SHIP	-0.31	0.31	-9999	-0.52	237	237
CD79A	-0.31	0.27	-9999	-0.54	215	215
re-entry into mitotic cell cycle	-0.16	0.15	-9999	-0.27	225	225
RASA1	0.017	0.029	-9999	-0.54	1	1
MAPK3	-0.26	0.26	-9999	-0.47	201	201
MAPK1	-0.26	0.26	-9999	-0.47	201	201
CD72/SHP1	-0.6	0.52	-9999	-0.96	230	230
NFKB1	0.019	0	-9999	-10000	0	0
MAPK8	-0.38	0.32	-9999	-0.6	241	241
actin cytoskeleton organization	-0.5	0.4	-9999	-0.78	237	237
NF-kappa-B/RelA	-0.026	0.072	-9999	-10000	0	0
Calcineurin	-0.29	0.3	-9999	-0.52	201	201
PI3K	-0.46	0.32	-9999	-0.67	246	246
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.49	0.5	-9999	-0.81	223	223
SOS1	0.019	0	-9999	-10000	0	0
Bam32/HPK1	-0.63	0.53	-9999	-1	227	227
DAPP1	-0.76	0.65	-9999	-1.2	227	227
cytokine secretion	-0.39	0.32	-9999	-0.61	237	237
mol:DAG	-0.43	0.43	-9999	-0.72	219	219
PLCG2	-0.03	0.16	-9999	-0.54	32	32
MAP2K1	-0.3	0.3	-9999	-0.53	201	201
B-cell antigen/BCR complex/FcgammaRIIB	-0.34	0.3	-9999	-0.55	237	237
mol:PI-3-4-5-P3	-0.3	0.2	-9999	-0.43	246	246
ETS1	-0.29	0.29	-9999	-0.52	201	201
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.42	0.41	-9999	-0.68	238	238
B-cell antigen/BCR complex/LYN	-0.57	0.48	-9999	-0.88	237	237
MALT1	0.018	0.029	-9999	-0.54	1	1
TRAF6	0.019	0	-9999	-10000	0	0
RAC1	-0.56	0.45	-9999	-0.87	237	237
B-cell antigen/BCR complex/LYN/SYK	-0.59	0.51	-9999	-0.95	229	229
CARD11	-0.44	0.44	-9999	-0.73	224	224
FCGR2B	-0.005	0.11	-9999	-0.52	16	16
PPP3CA	0.019	0	-9999	-10000	0	0
BCL10	0.018	0.014	-9999	-0.24	1	1
IKK complex	-0.044	0.056	-9999	-0.096	130	130
PTPRC	-0.18	0.27	-9999	-0.54	131	131
PDPK1	-0.18	0.15	-9999	-0.28	246	246
PPP3CB	0.019	0	-9999	-10000	0	0
PPP3CC	0.019	0	-9999	-10000	0	0
POU2F2	-0.02	0.047	-9999	-0.11	62	62

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.89	0.59	-10000	0	-1.3	221	221
STAT6 (cleaved dimer)	-0.99	0.6	-10000	0	-1.3	265	265
IGHG1	-0.25	0.16	-10000	0	-0.36	147	147
IGHG3	-0.87	0.56	-10000	0	-1.2	242	242
AKT1	-0.54	0.45	-10000	0	-0.98	152	152
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.58	0.61	-10000	0	-1.3	130	130
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.61	0.54	-10000	0	-1	179	179
THY1	-0.9	0.59	-10000	0	-1.3	231	231
MYB	-0.01	0.12	-10000	0	-0.54	19	19
HMGA1	0.016	0.041	-10000	0	-0.54	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.66	0.54	-10000	0	-0.96	229	229
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.64	0.59	-10000	0	-1.1	171	171
SP1	0.022	0.013	-10000	0	-10000	0	0
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
SOCS5	0.034	0.015	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.95	0.64	-10000	0	-1.3	245	245
SOCS1	-0.55	0.35	-10000	0	-0.79	224	224
SOCS3	-0.51	0.4	-10000	0	-0.97	127	127
FCER2	-1.3	0.69	-10000	0	-1.6	294	294
PARP14	0.007	0.051	-10000	0	-0.54	3	3
CCL17	-0.92	0.62	-10000	0	-1.3	230	230
GRB2	0.019	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.48	0.44	-10000	0	-0.98	129	129
T cell proliferation	-0.94	0.64	-10000	0	-1.3	237	237
IL4R/JAK1	-0.9	0.59	-10000	0	-1.3	225	225
EGR2	-1	0.61	-10000	0	-1.3	257	257
JAK2	-0.036	0.076	-10000	0	-0.53	7	7
JAK3	-0.013	0.14	-10000	0	-0.51	25	25
PIK3R1	0.019	0	-10000	0	-10000	0	0
JAK1	0.005	0.013	-10000	0	-10000	0	0
COL1A2	-0.26	0.19	-10000	0	-0.58	42	42
CCL26	-0.9	0.59	-10000	0	-1.3	229	229
IL4R	-0.96	0.64	-10000	0	-1.4	221	221
PTPN6	-0.1	0.24	-10000	0	-0.52	92	92
IL13RA2	-0.95	0.6	-10000	0	-1.3	237	237
IL13RA1	-0.026	0.03	-10000	0	-10000	0	0
IRF4	-0.7	0.61	-10000	0	-1.2	202	202
ARG1	-0.22	0.21	-10000	0	-0.73	35	35
CBL	-0.61	0.49	-10000	0	-0.89	229	229
GTF3A	0.02	0.015	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
IL13RA1/JAK2	-0.041	0.065	-10000	0	-0.39	7	7
IRF4/BCL6	-0.61	0.56	-10000	0	-1.1	202	202
CD40LG	-0.28	0.28	-10000	0	-0.54	195	195
MAPK14	-0.61	0.49	-10000	0	-0.92	210	210
mitosis	-0.49	0.41	-10000	0	-0.9	151	151
STAT6	-1.1	0.81	-10000	0	-1.6	241	241
SPI1	-0.023	0.15	-10000	0	-0.54	28	28
RPS6KB1	-0.47	0.39	-10000	0	-0.89	137	137
STAT6 (dimer)	-1.1	0.81	-10000	0	-1.6	241	241
STAT6 (dimer)/PARP14	-1.1	0.7	-10000	0	-1.4	261	261
mast cell activation	0.018	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.62	0.59	-10000	0	-1.2	161	161
FRAP1	-0.54	0.46	-10000	0	-0.98	152	152
LTA	-1.1	0.73	-10000	0	-1.6	230	230
FES	0.007	0.081	-10000	0	-0.54	8	8
T-helper 1 cell differentiation	1	0.72	1.5	241	-10000	0	241
CCL11	-0.9	0.56	-10000	0	-1.3	237	237
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.61	0.57	-10000	0	-1.1	163	163
IL2RG	-0.14	0.25	-10000	0	-0.52	112	112
IL10	-0.92	0.61	-10000	0	-1.3	222	222
IRS1	-0.002	0.071	-10000	0	-0.24	29	29
IRS2	0.019	0	-10000	0	-10000	0	0
IL4	-0.17	0.11	-10000	0	-10000	0	0
IL5	-0.9	0.59	-10000	0	-1.3	225	225
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.66	0.41	-10000	0	-0.92	234	234
COL1A1	-0.29	0.21	-10000	0	-0.59	69	69
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.93	0.63	-10000	0	-1.4	217	217
IL2R gamma/JAK3	-0.12	0.23	-10000	0	-0.44	112	112
TFF3	-0.97	0.65	-10000	0	-1.4	228	228
ALOX15	-0.9	0.6	-10000	0	-1.3	220	220
MYBL1	0.016	0.041	-10000	0	-0.54	2	2
T-helper 2 cell differentiation	-0.83	0.58	-10000	0	-1.2	242	242
SHC1	0.019	0	-10000	0	-10000	0	0
CEBPB	0.02	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.59	0.54	-10000	0	-1	171	171
mol:PI-3-4-5-P3	-0.54	0.46	-10000	0	-0.98	152	152
PI3K	-0.6	0.53	-10000	0	-1.1	152	152
DOK2	-0.037	0.17	-10000	0	-0.54	37	37
ETS1	0.037	0.013	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.44	0.4	-10000	0	-0.91	127	127
ITGB3	-0.92	0.6	-10000	0	-1.3	230	230
PIGR	-0.99	0.66	-10000	0	-1.4	228	228
IGHE	0.057	0.039	0.28	2	-10000	0	2
MAPKKK cascade	-0.43	0.39	-10000	0	-0.88	127	127
BCL6	0.024	0.008	-10000	0	-10000	0	0
OPRM1	-0.9	0.59	-10000	0	-1.3	221	221
RETNLB	-0.9	0.59	-10000	0	-1.3	225	225
SELP	-1	0.7	-10000	0	-1.5	229	229
AICDA	-1.1	0.67	-10000	0	-1.5	266	266

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.27	0.4	-10000	0	-0.71	161	161
FYN	-0.44	0.59	-10000	0	-1.1	163	163
LAT/GRAP2/SLP76	-0.33	0.38	-10000	0	-0.74	164	164
IKBKB	0.019	0	-10000	0	-10000	0	0
AKT1	-0.2	0.31	-10000	0	-0.54	163	163
B2M	0.004	0.082	-10000	0	-0.55	8	8
IKBKG	-0.044	0.1	-10000	0	-0.16	154	154
MAP3K8	-0.003	0.11	-10000	0	-0.52	15	15
mol:Ca2+	-0.019	0.022	-10000	0	-0.077	11	11
integrin-mediated signaling pathway	-0.02	0.12	-10000	0	-0.32	48	48
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.35	0.5	-10000	0	-0.89	163	163
TRPV6	-0.011	0.055	-10000	0	-0.26	17	17
CD28	-0.071	0.2	-10000	0	-0.54	58	58
SHC1	-0.4	0.55	-10000	0	-1	161	161
receptor internalization	-0.48	0.64	-10000	0	-1.2	163	163
PRF1	-0.51	0.69	-10000	0	-1.3	149	149
KRAS	0.018	0.014	-10000	0	-0.24	1	1
GRB2	0.019	0	-10000	0	-10000	0	0
COT/AKT1	-0.15	0.25	-10000	0	-0.42	160	160
LAT	-0.42	0.56	-10000	0	-1	162	162
EntrezGene:6955	-0.002	0.005	-10000	0	-10000	0	0
CD3D	-0.22	0.28	-10000	0	-0.55	155	155
CD3E	-0.19	0.28	-10000	0	-0.55	137	137
CD3G	-0.18	0.27	-10000	0	-0.54	126	126
RASGRP2	-0.089	0.1	-10000	0	-0.19	186	186
RASGRP1	-0.22	0.34	-10000	0	-0.58	165	165
HLA-A	0.012	0.042	-10000	0	-0.55	2	2
RASSF5	-0.054	0.19	-10000	0	-0.54	48	48
RAP1A/GTP/RAPL	-0.02	0.12	-10000	0	-0.32	48	48
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.042	0.095	-10000	0	-0.14	163	163
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.13	0.14	-10000	0	-0.29	157	157
PRKCA	-0.13	0.16	-10000	0	-0.31	159	159
GRAP2	-0.046	0.18	-10000	0	-0.54	43	43
mol:IP3	-0.23	0.27	0.15	7	-0.52	163	170
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.59	0.78	-10000	0	-1.4	157	157
ORAI1	0.017	0.041	-10000	0	-0.38	1	1
CSK	-0.42	0.57	-10000	0	-1	161	161
B7 family/CD28	-0.45	0.61	-10000	0	-1.1	161	161
CHUK	0.019	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.54	0.71	-10000	0	-1.3	161	161
PTPN6	-0.46	0.61	-10000	0	-1.1	159	159
VAV1	-0.42	0.57	-10000	0	-1	161	161
Monovalent TCR/CD3	-0.45	0.59	-10000	0	-1	169	169
CBL	0.019	0	-10000	0	-10000	0	0
LCK	-0.51	0.67	-10000	0	-1.2	162	162
PAG1	-0.42	0.57	-10000	0	-1	161	161
RAP1A	0.019	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.55	0.72	-10000	0	-1.3	161	161
CD80	-0.099	0.23	-10000	0	-0.54	76	76
CD86	-0.053	0.19	-10000	0	-0.54	46	46
PDK1/CARD11/BCL10/MALT1	-0.16	0.18	-10000	0	-0.35	160	160
HRAS	0.019	0	-10000	0	-10000	0	0
GO:0035030	-0.32	0.44	-10000	0	-0.81	161	161
CD8A	-0.19	0.27	-10000	0	-0.55	134	134
CD8B	-0.19	0.28	-10000	0	-0.55	137	137
PTPRC	-0.18	0.27	-10000	0	-0.54	131	131
PDK1/PKC theta	-0.26	0.4	-10000	0	-0.7	163	163
CSK/PAG1	-0.4	0.55	-10000	0	-1	160	160
SOS1	0.019	0	-10000	0	-10000	0	0
peptide-MHC class I	0.009	0.069	-10000	0	-0.4	10	10
GRAP2/SLP76	-0.37	0.51	-10000	0	-0.92	163	163
STIM1	0.01	0.019	-10000	0	-10000	0	0
RAS family/GTP	-0.045	0.13	-10000	0	-0.19	153	153
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.58	0.76	-10000	0	-1.4	163	163
mol:DAG	-0.21	0.23	-10000	0	-0.46	163	163
RAP1A/GDP	-0.016	0.042	-10000	0	-0.064	134	134
PLCG1	0.019	0	-10000	0	-10000	0	0
CD247	-0.18	0.27	-10000	0	-0.54	128	128
cytotoxic T cell degranulation	-0.46	0.63	-10000	0	-1.2	149	149
RAP1A/GTP	-0.035	0.033	-10000	0	-0.067	186	186
mol:PI-3-4-5-P3	-0.26	0.38	-10000	0	-0.67	163	163
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.32	0.37	0.17	7	-0.72	163	170
NRAS	0.019	0	-10000	0	-10000	0	0
ZAP70	-0.17	0.26	-10000	0	-0.54	126	126
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.32	0.37	-10000	0	-0.72	164	164
MALT1	0.017	0.029	-10000	0	-0.54	1	1
TRAF6	0.019	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.25	0.35	-10000	0	-0.66	149	149
CARD11	-0.14	0.25	-10000	0	-0.54	108	108
PRKCB	-0.17	0.21	-10000	0	-0.38	166	166
PRKCE	-0.13	0.16	-10000	0	-0.31	158	158
PRKCQ	-0.33	0.47	-10000	0	-0.84	163	163
LCP2	-0.016	0.14	-10000	0	-0.54	23	23
BCL10	0.018	0.014	-10000	0	-0.24	1	1
regulation of survival gene product expression	-0.16	0.26	-10000	0	-0.45	163	163
IKK complex	-0.021	0.09	-10000	0	-0.12	153	153
RAS family/GDP	-0.015	0.016	-10000	0	-10000	0	0
MAP3K14	-0.099	0.19	-10000	0	-0.31	157	157
PDPK1	-0.18	0.3	-10000	0	-0.51	163	163
TCR/CD3/MHC I/CD8/Fyn	-0.57	0.74	-10000	0	-1.4	158	158

×

IL23-mediated signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.48	0.67	-9999	-1.2	150	150
IL23A	-0.52	0.71	-9999	-1.3	151	151
NF kappa B1 p50/RelA/I kappa B alpha	-0.6	0.65	-9999	-1.3	154	154
positive regulation of T cell mediated cytotoxicity	-0.62	0.85	-9999	-1.5	155	155
ITGA3	-0.5	0.68	-9999	-1.2	152	152
IL17F	-0.29	0.43	-9999	-0.75	153	153
IL12B	-0.009	0.1	-9999	-0.57	9	9
STAT1 (dimer)	-0.58	0.79	-9999	-1.4	155	155
CD4	-0.5	0.69	-9999	-1.3	151	151
IL23	-0.5	0.68	-9999	-1.3	151	151
IL23R	-0.041	0.11	-9999	-10000	0	0
IL1B	-0.54	0.74	-9999	-1.4	150	150
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.6	0.74	-9999	-1.3	182	182
TYK2	0.008	0.029	-9999	-10000	0	0
STAT4	-0.12	0.24	-9999	-0.54	92	92
STAT3	0.019	0	-9999	-10000	0	0
IL18RAP	-0.17	0.26	-9999	-0.54	119	119
IL12RB1	-0.14	0.26	-9999	-0.57	97	97
PIK3CA	0.018	0.014	-9999	-0.24	1	1
IL12Rbeta1/TYK2	-0.097	0.2	-9999	-0.43	97	97
IL23R/JAK2	-0.047	0.15	-9999	-10000	0	0
positive regulation of chronic inflammatory response	-0.62	0.85	-9999	-1.5	155	155
natural killer cell activation	0.005	0.01	-9999	-10000	0	0
JAK2	0	0.085	-9999	-0.53	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
NFKB1	0.017	0.005	-9999	-10000	0	0
RELA	0.017	0.005	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.46	0.63	-9999	-1.2	152	152
ALOX12B	-0.48	0.67	-9999	-1.2	152	152
CXCL1	-0.51	0.67	-9999	-1.2	154	154
T cell proliferation	-0.62	0.85	-9999	-1.5	155	155
NFKBIA	0.017	0.005	-9999	-10000	0	0
IL17A	-0.2	0.35	-9999	-0.58	140	140
PI3K	-0.54	0.74	-9999	-1.3	154	154
IFNG	-0.05	0.07	-9999	-0.12	175	175
STAT3 (dimer)	-0.57	0.62	-9999	-1.2	154	154
IL18R1	-0.073	0.2	-9999	-0.54	58	58
IL23/IL23R/JAK2/TYK2/SOCS3	-0.28	0.44	-9999	-0.76	142	142
IL18/IL18R	-0.23	0.33	-9999	-0.58	151	151
macrophage activation	-0.023	0.02	-9999	-0.045	153	153
TNF	-0.57	0.77	-9999	-1.4	153	153
STAT3/STAT4	-0.57	0.77	-9999	-1.4	157	157
STAT4 (dimer)	-0.62	0.82	-9999	-1.5	159	159
IL18	-0.14	0.25	-9999	-0.54	99	99
IL19	-0.49	0.66	-9999	-1.2	146	146
STAT5A (dimer)	-0.58	0.79	-9999	-1.4	155	155
STAT1	0.016	0.041	-9999	-0.54	2	2
SOCS3	0.014	0.05	-9999	-0.54	3	3
CXCL9	-0.65	0.81	-9999	-1.5	173	173
MPO	-0.51	0.7	-9999	-1.3	158	158
positive regulation of humoral immune response	-0.62	0.85	-9999	-1.5	155	155
IL23/IL23R/JAK2/TYK2	-0.74	1.1	-9999	-1.8	155	155
IL6	-0.5	0.69	-9999	-1.3	145	145
STAT5A	0.017	0.029	-9999	-0.54	1	1
IL2	0.002	0.021	-9999	-0.24	1	1
positive regulation of tyrosine phosphorylation of STAT protein	0.005	0.01	-9999	-10000	0	0
CD3E	-0.6	0.8	-9999	-1.5	156	156
keratinocyte proliferation	-0.62	0.85	-9999	-1.5	155	155
NOS2	-0.48	0.67	-9999	-1.2	151	151

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.14	0.2	0.39	148	-10000	0	148
KIRREL	-0.004	0.047	-10000	0	-0.54	2	2
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.15	0.2	-10000	0	-0.39	148	148
PLCG1	0.019	0	-10000	0	-10000	0	0
ARRB2	0.019	0	-10000	0	-10000	0	0
WASL	0.019	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.095	0.15	-10000	0	-0.28	149	149
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.084	0.14	-10000	0	-0.26	148	148
FYN	-0.095	0.14	-10000	0	-0.27	148	148
mol:Ca2+	-0.094	0.15	-10000	0	-0.27	148	148
mol:DAG	-0.094	0.15	-10000	0	-0.28	148	148
NPHS2	-0.019	0.026	-10000	0	-10000	0	0
mol:IP3	-0.094	0.15	-10000	0	-0.28	148	148
regulation of endocytosis	-0.079	0.14	-10000	0	-0.24	148	148
Nephrin/NEPH1/podocin/Cholesterol	-0.1	0.15	-10000	0	-0.28	148	148
establishment of cell polarity	-0.14	0.2	-10000	0	-0.39	148	148
Nephrin/NEPH1/podocin/NCK1-2	-0.076	0.14	-10000	0	-0.24	148	148
Nephrin/NEPH1/beta Arrestin2	-0.079	0.14	-10000	0	-0.25	148	148
NPHS1	-0.21	0.27	-10000	0	-0.54	146	146
Nephrin/NEPH1/podocin	-0.096	0.14	-10000	0	-0.27	148	148
TJP1	0.019	0	-10000	0	-10000	0	0
NCK1	0.019	0	-10000	0	-10000	0	0
NCK2	0.019	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.095	0.15	-10000	0	-0.28	148	148
CD2AP	0.017	0.029	-10000	0	-0.54	1	1
Nephrin/NEPH1/podocin/GRB2	-0.095	0.15	-10000	0	-0.28	148	148
GRB2	0.019	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.098	0.14	-10000	0	-0.26	148	148
cytoskeleton organization	-0.1	0.17	-10000	0	-0.31	148	148
Nephrin/NEPH1	-0.1	0.14	-10000	0	-0.27	148	148
Nephrin/NEPH1/ZO-1	-0.1	0.16	-10000	0	-0.3	148	148

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.12	0.27	-10000	0	-0.48	107	107
TBX21	-0.47	0.81	-10000	0	-1.5	133	133
B2M	0.008	0.081	-10000	0	-0.54	8	8
TYK2	0.014	0.03	-10000	0	-10000	0	0
IL12RB1	-0.13	0.27	-10000	0	-0.57	97	97
GADD45B	-0.36	0.67	-10000	0	-1.2	126	126
IL12RB2	-0.058	0.13	-10000	0	-0.27	95	95
GADD45G	-0.4	0.71	-10000	0	-1.3	136	136
natural killer cell activation	-0.001	0.029	-10000	0	-10000	0	0
RELB	0.019	0	-10000	0	-10000	0	0
RELA	0.019	0	-10000	0	-10000	0	0
IL18	-0.13	0.25	-10000	0	-0.55	99	99
IL2RA	-0.12	0.24	-10000	0	-0.54	93	93
IFNG	-0.18	0.26	-10000	0	-0.54	129	129
STAT3 (dimer)	-0.29	0.57	-10000	0	-1	134	134
HLA-DRB5	-0.014	0.13	-10000	0	-0.5	24	24
FASLG	-0.5	0.83	-10000	0	-1.5	137	137
NF kappa B2 p52/RelB	-0.51	0.68	-10000	0	-1.4	134	134
CD4	-0.034	0.16	-10000	0	-0.54	35	35
SOCS1	-0.01	0.12	-10000	0	-0.54	19	19
EntrezGene:6955	0.002	0.003	-10000	0	-10000	0	0
CD3D	-0.21	0.28	-10000	0	-0.54	155	155
CD3E	-0.19	0.27	-10000	0	-0.54	137	137
CD3G	-0.17	0.26	-10000	0	-0.54	126	126
IL12Rbeta2/JAK2	-0.034	0.11	-10000	0	-0.29	35	35
CCL3	-0.41	0.74	-10000	0	-1.4	126	126
CCL4	-0.45	0.79	-10000	0	-1.5	129	129
HLA-A	0.017	0.041	-10000	0	-0.54	2	2
IL18/IL18R	-0.19	0.36	-10000	0	-0.58	151	151
NOS2	-0.42	0.75	-10000	0	-1.4	129	129
IL12/IL12R/TYK2/JAK2/SPHK2	-0.098	0.24	-10000	0	-0.43	104	104
IL1R1	-0.4	0.72	-10000	0	-1.3	129	129
IL4	0.004	0.032	-10000	0	-0.27	1	1
JAK2	0.004	0.081	-10000	0	-0.53	7	7
EntrezGene:6957	0.002	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.6	0.83	-10000	0	-1.5	156	156
RAB7A	-0.24	0.52	-10000	0	-0.92	126	126
lysosomal transport	-0.22	0.48	-10000	0	-0.85	126	126
FOS	-0.38	0.64	-10000	0	-1.2	131	131
STAT4 (dimer)	-0.38	0.7	-10000	0	-1.2	139	139
STAT5A (dimer)	-0.56	0.69	-10000	0	-1.3	153	153
GZMA	-0.48	0.82	-10000	0	-1.6	129	129
GZMB	-0.5	0.82	-10000	0	-1.5	141	141
HLX	0.017	0.019	-10000	0	-0.24	2	2
LCK	-0.55	0.9	-10000	0	-1.6	145	145
TCR/CD3/MHC II/CD4	-0.46	0.66	-10000	0	-1.2	147	147
IL2/IL2R	-0.18	0.32	-10000	0	-0.56	138	138
MAPK14	-0.37	0.7	-10000	0	-1.2	136	136
CCR5	-0.4	0.72	-10000	0	-1.3	130	130
IL1B	-0.045	0.17	-10000	0	-0.5	43	43
STAT6	-0.042	0.16	-10000	0	-0.25	113	113
STAT4	-0.12	0.24	-10000	0	-0.54	92	92
STAT3	0.019	0	-10000	0	-10000	0	0
STAT1	0.016	0.041	-10000	0	-0.54	2	2
NFKB1	0.019	0	-10000	0	-10000	0	0
NFKB2	0.019	0	-10000	0	-10000	0	0
IL12B	-0.001	0.094	-10000	0	-0.56	9	9
CD8A	-0.18	0.27	-10000	0	-0.54	134	134
CD8B	-0.19	0.27	-10000	0	-0.54	137	137
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.11	0.26	0.48	107	-10000	0	107
IL2RB	-0.083	0.22	-10000	0	-0.54	67	67
proteasomal ubiquitin-dependent protein catabolic process	-0.31	0.6	-10000	0	-1	139	139
IL2RG	-0.15	0.26	-10000	0	-0.54	112	112
IL12	-0.01	0.13	-10000	0	-0.42	29	29
STAT5A	0.017	0.029	-10000	0	-0.54	1	1
CD247	-0.17	0.27	-10000	0	-0.54	128	128
IL2	0.005	0.016	-10000	0	-0.24	1	1
SPHK2	0.019	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.019	0.14	-10000	0	-0.55	21	21
IL12/IL12R/TYK2/JAK2	-0.68	1.2	-10000	0	-2.1	134	134
MAP2K3	-0.39	0.72	-10000	0	-1.3	135	135
RIPK2	0.019	0	-10000	0	-10000	0	0
MAP2K6	-0.4	0.72	-10000	0	-1.3	135	135
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.1	0.23	-10000	0	-0.54	81	81
IL18RAP	-0.16	0.27	-10000	0	-0.54	119	119
IL12Rbeta1/TYK2	-0.088	0.21	-10000	0	-0.43	97	97
EOMES	-0.15	0.41	-10000	0	-1.4	33	33
STAT1 (dimer)	-0.38	0.58	-10000	0	-0.99	162	162
T cell proliferation	-0.22	0.46	-10000	0	-0.79	138	138
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.067	0.21	-10000	0	-0.55	58	58
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.42	-10000	0	-0.86	141	141
ATF2	-0.31	0.61	-10000	0	-1.1	134	134

×

Caspase cascade in apoptosis

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
TOP1	-0.12	0.26	0.19	1	-0.49	115	116
ACTA1	-0.16	0.31	0.2	41	-0.59	115	156
NUMA1	-0.12	0.26	0.19	1	-0.49	115	116
SPTAN1	-0.16	0.31	0.2	7	-0.58	115	122
LIMK1	-0.16	0.31	0.2	41	-0.58	115	156
BIRC3	-0.18	0.26	-10000	0	-0.54	128	128
BIRC2	0.013	0.052	-10000	0	-0.46	4	4
BAX	0.019	0	-10000	0	-10000	0	0
CASP10	-0.18	0.29	-10000	0	-0.54	137	137
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.019	0	-10000	0	-10000	0	0
PTK2	-0.12	0.26	-10000	0	-0.49	115	115
DIABLO	0.019	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.15	0.3	0.2	7	-0.57	115	122
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.018	0.014	-10000	0	-0.24	1	1
GSN	-0.16	0.31	0.2	41	-0.59	115	156
MADD	0.019	0	-10000	0	-10000	0	0
TFAP2A	-0.16	0.34	-10000	0	-0.79	81	81
BID	-0.091	0.16	-10000	0	-0.29	137	137
MAP3K1	-0.036	0.1	-10000	0	-0.21	37	37
TRADD	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.029	0.001	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.18	0.35	0.2	38	-0.65	117	155
CASP9	0.019	0	-10000	0	-10000	0	0
DNA repair	-0.019	0.08	0.15	31	-0.18	43	74
neuron apoptosis	-0.003	0.091	-10000	0	-0.65	5	5
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.14	0.3	0.22	1	-0.56	115	116
APAF1	0.019	0	-10000	0	-10000	0	0
CASP6	-0.084	0.19	-10000	0	-0.41	76	76
TRAF2	0.019	0	-10000	0	-10000	0	0
ICAD/CAD	-0.14	0.3	0.23	1	-0.56	115	116
CASP7	0.11	0.15	0.31	128	-10000	0	128
KRT18	-0.096	0.25	-10000	0	-0.69	49	49
apoptosis	-0.1	0.25	0.22	41	-0.45	115	156
DFFA	-0.16	0.31	0.2	41	-0.58	115	156
DFFB	-0.16	0.31	0.2	41	-0.58	115	156
PARP1	0.019	0.081	0.18	43	-0.15	31	74
actin filament polymerization	0.14	0.29	0.53	115	-0.19	41	156
TNF	-0.095	0.22	-10000	0	-0.54	75	75
CYCS	-0.063	0.11	-10000	0	-0.2	137	137
SATB1	-0.091	0.21	-10000	0	-0.44	80	80
SLK	-0.16	0.31	0.2	41	-0.58	115	156
p15 BID/BAX	-0.073	0.14	-10000	0	-0.25	137	137
CASP2	-0.053	0.14	-10000	0	-0.34	53	53
JNK cascade	0.036	0.1	0.21	37	-10000	0	37
CASP3	-0.17	0.33	0.2	41	-0.62	115	156
LMNB2	-0.053	0.15	-10000	0	-0.32	64	64
RIPK1	0.019	0	-10000	0	-10000	0	0
CASP4	0.013	0.058	-10000	0	-0.54	4	4
Mammalian IAPs/DIABLO	-0.069	0.16	-10000	0	-0.29	128	128
negative regulation of DNA binding	-0.16	0.34	-10000	0	-0.78	81	81
stress fiber formation	-0.15	0.3	0.19	41	-0.57	115	156
GZMB	-0.21	0.32	-10000	0	-0.6	137	137
CASP1	-0.003	0.099	-10000	0	-0.37	22	22
LMNB1	-0.053	0.15	-10000	0	-0.29	84	84
APP	-0.003	0.092	-10000	0	-0.66	5	5
TNFRSF1A	0.019	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0.03	-10000	0	-0.39	2	2
VIM	-0.1	0.25	0.21	41	-0.44	115	156
LMNA	-0.054	0.15	-10000	0	-0.33	62	62
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.064	0.15	-10000	0	-0.37	53	53
LRDD	0.017	0.029	-10000	0	-0.54	1	1
SREBF1	-0.16	0.31	0.2	41	-0.58	115	156
APAF-1/Caspase 9	0.029	0.073	0.42	3	-10000	0	3
nuclear fragmentation during apoptosis	-0.12	0.26	0.19	1	-0.48	115	116
CFL2	-0.14	0.3	0.2	7	-0.55	115	122
GAS2	-0.17	0.32	0.2	30	-0.59	121	151
positive regulation of apoptosis	-0.048	0.15	-10000	0	-0.32	62	62
PRF1	-0.15	0.26	-10000	0	-0.54	110	110

×

FAS signaling pathway (CD95)

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
SPTAN1	0.066	0.086	0.19	117	-10000	0	117
RFC1	0.066	0.086	0.19	117	-10000	0	117
PRKDC	0.066	0.086	0.19	117	-10000	0	117
RIPK1	0.019	0.002	-10000	0	-10000	0	0
CASP7	0.064	0.11	0.25	57	-0.26	1	58
FASLG/FAS/FADD/FAF1	-0.006	0.15	0.22	60	-0.28	64	124
MAP2K4	-0.018	0.16	-10000	0	-0.41	20	20
mol:ceramide	-0.073	0.19	-10000	0	-0.33	120	120
GSN	0.066	0.086	0.19	116	-10000	0	116
FASLG/FAS/FADD/FAF1/Caspase 8	-0.04	0.17	-10000	0	-0.32	66	66
FAS	0.007	0.081	-10000	0	-0.54	8	8
BID	0.1	0.13	0.3	117	-10000	0	117
MAP3K1	0.034	0.11	0.21	55	-0.25	14	69
MAP3K7	0.019	0.002	-10000	0	-10000	0	0
RB1	0.065	0.088	0.19	117	-0.31	1	118
CFLAR	0.019	0.002	-10000	0	-10000	0	0
HGF/MET	-0.004	0.11	-10000	0	-0.34	31	31
ARHGDIB	0.034	0.13	0.19	107	-0.31	26	133
FADD	0.018	0.014	-10000	0	-0.24	1	1
actin filament polymerization	-0.066	0.085	-10000	0	-0.19	116	116
NFKB1	-0.015	0.065	-10000	0	-0.27	8	8
MAPK8	-0.012	0.16	-10000	0	-0.44	23	23
DFFA	0.066	0.086	0.19	117	-10000	0	117
DNA fragmentation during apoptosis	0.066	0.086	0.19	117	-10000	0	117
FAS/FADD/MET	0.004	0.1	-10000	0	-0.33	29	29
CFLAR/RIP1	0.027	0.005	-10000	0	-10000	0	0
FAIM3	-0.16	0.26	-10000	0	-0.54	119	119
FAF1	0.019	0.005	-10000	0	-10000	0	0
PARP1	0.066	0.086	0.19	117	-10000	0	117
DFFB	0.066	0.086	0.19	117	-10000	0	117
CHUK	-0.006	0.06	-10000	0	-0.24	8	8
FASLG	-0.16	0.26	-10000	0	-0.54	120	120
FAS/FADD	0.019	0.061	-10000	0	-0.38	8	8
HGF	0	0.085	-10000	0	-0.34	19	19
LMNA	0.066	0.077	-10000	0	-10000	0	0
CASP6	0.066	0.086	0.19	117	-10000	0	117
CASP10	0.009	0.076	-10000	0	-0.54	7	7
CASP3	0.07	0.1	0.22	117	-10000	0	117
PTPN13	0.011	0.062	-10000	0	-0.41	7	7
CASP8	0.12	0.18	0.38	117	-10000	0	117
IL6	-0.044	0.27	-10000	0	-1.3	14	14
MET	-0.024	0.14	-10000	0	-0.43	35	35
ICAD/CAD	0.067	0.078	0.18	112	-10000	0	112
FASLG/FAS/FADD/FAF1/Caspase 10	-0.074	0.19	-10000	0	-0.33	120	120
activation of caspase activity by cytochrome c	0.1	0.13	0.3	117	-10000	0	117
PAK2	0.066	0.086	0.19	117	-10000	0	117
BCL2	0.019	0	-10000	0	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.089	0.23	-10000	0	-0.59	62	62
NFATC2	-0.16	0.39	-10000	0	-0.68	109	109
NFATC3	-0.006	0.065	-10000	0	-0.22	5	5
CD40LG	-0.51	0.55	-10000	0	-1	180	180
ITCH	0.004	0.066	-10000	0	-10000	0	0
CBLB	0.003	0.067	-10000	0	-0.35	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.5	0.7	-10000	0	-1.3	141	141
JUNB	0.017	0.019	-10000	0	-0.24	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.01	0.079	-10000	0	-0.28	2	2
T cell anergy	-0.04	0.099	-10000	0	-0.31	8	8
TLE4	-0.13	0.35	-10000	0	-0.73	70	70
Jun/NFAT1-c-4/p21SNFT	-0.28	0.46	-10000	0	-0.86	108	108
AP-1/NFAT1-c-4	-0.44	0.59	-10000	0	-1.1	142	142
IKZF1	-0.22	0.46	-10000	0	-0.9	106	106
T-helper 2 cell differentiation	-0.24	0.42	-10000	0	-0.9	96	96
AP-1/NFAT1	-0.15	0.29	-10000	0	-0.52	106	106
CALM1	0.001	0.046	-10000	0	-10000	0	0
EGR2	-0.14	0.33	-10000	0	-0.8	40	40
EGR3	-0.17	0.39	-10000	0	-1.1	33	33
NFAT1/FOXP3	-0.19	0.41	-10000	0	-0.76	110	110
EGR1	-0.005	0.074	-10000	0	-0.25	31	31
JUN	-0.031	0.087	-10000	0	-0.28	37	37
EGR4	0	0.062	-10000	0	-0.25	21	21
mol:Ca2+	-0.019	0.048	-10000	0	-0.17	2	2
GBP3	-0.14	0.36	-10000	0	-0.76	77	77
FOSL1	-0.014	0.12	-10000	0	-0.45	26	26
NFAT1-c-4/MAF/IRF4	-0.21	0.42	-10000	0	-0.87	79	79
DGKA	-0.12	0.34	-10000	0	-0.74	64	64
CREM	0.018	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.21	0.43	-10000	0	-0.9	74	74
CTLA4	-0.21	0.43	-10000	0	-0.83	106	106
NFAT1-c-4 (dimer)/EGR1	-0.23	0.44	-10000	0	-0.88	87	87
NFAT1-c-4 (dimer)/EGR4	-0.22	0.44	-10000	0	-0.9	83	83
FOS	-0.013	0.055	-10000	0	-0.28	12	12
IFNG	-0.62	0.76	-10000	0	-1.4	178	178
T cell activation	-0.14	0.27	-10000	0	-0.75	32	32
MAF	0.019	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.12	0.31	1.1	18	-10000	0	18
TNF	-0.27	0.48	-10000	0	-0.99	99	99
FASLG	-0.57	0.85	-10000	0	-1.7	126	126
TBX21	-0.16	0.25	-10000	0	-0.56	104	104
BATF3	0.007	0.081	-10000	0	-0.54	8	8
PRKCQ	-0.17	0.27	-10000	0	-0.56	116	116
PTPN1	-0.1	0.3	-10000	0	-0.66	62	62
NFAT1-c-4/ICER1	-0.21	0.42	-10000	0	-0.88	75	75
GATA3	-0.1	0.23	-10000	0	-0.54	80	80
T-helper 1 cell differentiation	-0.59	0.72	-10000	0	-1.3	179	179
IL2RA	-0.45	0.64	-10000	0	-1.2	144	144
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.1	0.3	-10000	0	-0.66	62	62
E2F1	0.026	0.006	-10000	0	-10000	0	0
PPARG	0.011	0.064	-10000	0	-0.54	5	5
SLC3A2	-0.1	0.3	-10000	0	-0.65	64	64
IRF4	-0.033	0.16	-10000	0	-0.54	34	34
PTGS2	-0.4	0.49	-10000	0	-0.94	143	143
CSF2	-0.39	0.48	-10000	0	-0.92	142	142
JunB/Fra1/NFAT1-c-4	-0.2	0.41	-10000	0	-0.91	67	67
IL4	-0.26	0.45	-10000	0	-0.96	95	95
IL5	-0.39	0.48	-10000	0	-0.92	142	142
IL2	-0.14	0.27	-10000	0	-0.76	32	32
IL3	-0.067	0.06	-10000	0	-10000	0	0
RNF128	-0.05	0.14	-10000	0	-0.48	2	2
NFATC1	-0.12	0.31	-10000	0	-1.1	18	18
CDK4	0.1	0.21	0.66	13	-10000	0	13
PTPRK	-0.11	0.3	-10000	0	-0.63	69	69
IL8	-0.41	0.48	-10000	0	-0.94	144	144
POU2F1	0.019	0	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.064	0.16	-9999	-0.32	101	101
E-cadherin/beta catenin	-0.085	0.18	-9999	-0.38	101	101
CTNNB1	0.019	0	-9999	-10000	0	0
JUP	0.011	0.045	-9999	-0.24	11	11
CDH1	-0.13	0.25	-9999	-0.54	101	101

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.027	0.072	-9999	-0.4	9	9
NFATC2	-0.042	0.1	-9999	-0.37	25	25
NFATC3	-0.017	0.042	-9999	-10000	0	0
CD40LG	-0.43	0.44	-9999	-0.75	222	222
PTGS2	-0.32	0.37	-9999	-0.65	183	183
JUNB	0.017	0.019	-9999	-0.24	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.027	-9999	-10000	0	0
CaM/Ca2+	-0.012	0.026	-9999	-10000	0	0
CALM1	0.005	0.016	-9999	-10000	0	0
JUN	-0.022	0.082	-9999	-0.26	37	37
mol:Ca2+	-0.017	0.016	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.004	0.01	-9999	-10000	0	0
FOSL1	-0.014	0.12	-9999	-0.45	26	26
CREM	0.019	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.16	0.22	-9999	-0.41	125	125
FOS	-0.004	0.051	-9999	-0.26	12	12
IFNG	-0.39	0.43	-9999	-0.76	191	191
AP-1/NFAT1-c-4	-0.38	0.46	-9999	-0.79	180	180
FASLG	-0.38	0.44	-9999	-0.77	179	179
NFAT1-c-4/ICER1	-0.082	0.15	-9999	-0.43	31	31
IL2RA	-0.36	0.42	-9999	-0.74	179	179
FKBP12/FK506	0.014	0	-9999	-10000	0	0
CSF2	-0.31	0.36	-9999	-0.64	177	177
JunB/Fra1/NFAT1-c-4	-0.087	0.16	-9999	-0.4	45	45
IL4	-0.31	0.36	-9999	-0.64	176	176
IL2	-0.013	0.021	-9999	-10000	0	0
IL3	-0.029	0.026	-9999	-10000	0	0
FKBP1A	0.019	0	-9999	-10000	0	0
BATF3	0.007	0.081	-9999	-0.54	8	8
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.019	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.15	0.33	-9999	-0.66	98	98
MAP3K8	-0.003	0.11	-9999	-0.52	15	15
FOS	-0.17	0.34	-9999	-0.69	99	99
PRKCA	0.014	0.044	-9999	-0.29	7	7
PTPN7	-0.12	0.24	-9999	-0.54	96	96
HRAS	0.019	0	-9999	-10000	0	0
PRKCB	-0.15	0.26	-9999	-0.54	110	110
NRAS	0.019	0	-9999	-10000	0	0
RAS family/GTP	0.037	0.008	-9999	-10000	0	0
MAPK3	-0.17	0.33	-9999	-0.7	96	96
MAP2K1	-0.093	0.22	-9999	-0.42	110	110
ELK1	0.02	0.002	-9999	-10000	0	0
BRAF	-0.095	0.21	-9999	-0.41	110	110
mol:GTP	0	0	-9999	-0.003	8	8
MAPK1	-0.17	0.33	-9999	-0.7	96	96
RAF1	-0.094	0.2	-9999	-0.4	110	110
KRAS	0.018	0.014	-9999	-0.24	1	1

×

JNK 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
LAT/GRAP2/SLP76/HPK1	-0.1	0.27	-9999	-0.49	101	101
MAP4K1	-0.081	0.21	-9999	-0.54	66	66
MAP3K8	-0.003	0.11	-9999	-0.52	15	15
PRKCB	-0.15	0.26	-9999	-0.54	110	110
DBNL	0.019	0	-9999	-10000	0	0
CRKL	0.018	0.014	-9999	-0.24	1	1
MAP3K1	-0.073	0.24	-9999	-0.6	53	53
JUN	-0.2	0.35	-9999	-0.71	110	110
MAP3K7	-0.073	0.24	-9999	-0.6	53	53
GRAP2	-0.046	0.18	-9999	-0.54	43	43
CRK	0.019	0	-9999	-10000	0	0
MAP2K4	-0.07	0.25	-9999	-0.59	57	57
LAT	-0.049	0.18	-9999	-0.54	45	45
LCP2	-0.016	0.14	-9999	-0.54	23	23
MAPK8	-0.2	0.37	-9999	-0.75	110	110
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.084	0.26	-9999	-0.64	53	53
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.086	0.26	-9999	-0.46	101	101

×

S1P4 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.093	0.13	-9999	-0.25	155	155
CDC42/GTP	-0.088	0.14	-9999	-0.27	121	121
PLCG1	-0.092	0.14	-9999	-0.28	121	121
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.019	0	-9999	-10000	0	0
GNAI3	0.019	0	-9999	-10000	0	0
G12/G13	0.028	0	-9999	-10000	0	0
cell migration	-0.087	0.14	-9999	-0.26	121	121
S1PR5	0.008	0.052	-9999	-0.24	15	15
S1PR4	-0.16	0.26	-9999	-0.54	121	121
MAPK3	-0.092	0.14	-9999	-0.28	121	121
MAPK1	-0.092	0.14	-9999	-0.28	121	121
S1P/S1P5/Gi	-0.017	0.065	-9999	-0.24	5	5
GNAI1	0.004	0.06	-9999	-0.24	20	20
CDC42/GDP	0.014	0	-9999	-10000	0	0
S1P/S1P5/G12	0.019	0.03	-9999	-10000	0	0
RHOA	-0.063	0.14	-9999	-0.26	121	121
S1P/S1P4/Gi	-0.1	0.15	-9999	-0.3	121	121
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.015	0.093	-9999	-0.26	45	45
S1P/S1P4/G12/G13	-0.07	0.15	-9999	-0.29	121	121
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.016	0.041	-10000	0	-0.54	2	2
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.17	0.31	0.63	81	-10000	0	81
IL27/IL27R/JAK1	-0.17	0.35	-10000	0	-0.96	42	42
TBX21	-0.22	0.32	-10000	0	-0.66	115	115
IL12B	-0.004	0.085	-10000	0	-0.54	9	9
IL12A	-0.014	0.092	-10000	0	-0.38	21	21
IL6ST	-0.001	0.082	-10000	0	-0.55	8	8
IL27RA/JAK1	-0.07	0.3	-10000	0	-1.3	20	20
IL27	-0.053	0.18	-10000	0	-0.55	40	40
TYK2	0.011	0.013	-10000	0	-10000	0	0
T-helper cell lineage commitment	0.003	0.07	-10000	0	-0.67	1	1
T-helper 2 cell differentiation	0.17	0.31	0.63	81	-10000	0	81
T cell proliferation during immune response	0.17	0.31	0.63	81	-10000	0	81
MAPKKK cascade	-0.17	0.31	-10000	0	-0.63	81	81
STAT3	0.019	0	-10000	0	-10000	0	0
STAT2	0.019	0	-10000	0	-10000	0	0
STAT1	0.015	0.041	-10000	0	-0.54	2	2
IL12RB1	-0.13	0.24	-10000	0	-0.54	97	97
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.2	0.27	-10000	0	-0.57	98	98
IL27/IL27R/JAK2/TYK2	-0.17	0.32	-10000	0	-0.64	81	81
positive regulation of T cell mediated cytotoxicity	-0.17	0.31	-10000	0	-0.63	81	81
STAT1 (dimer)	-0.26	0.37	-10000	0	-0.86	79	79
JAK2	0.006	0.073	-10000	0	-0.5	7	7
JAK1	0.018	0.002	-10000	0	-10000	0	0
STAT2 (dimer)	-0.15	0.3	-10000	0	-0.6	81	81
T cell proliferation	-0.17	0.3	-10000	0	-0.61	84	84
IL12/IL12R/TYK2/JAK2	-0.17	0.28	-10000	0	-0.6	80	80
IL17A	0.003	0.07	-10000	0	-0.67	1	1
mast cell activation	0.17	0.31	0.63	81	-10000	0	81
IFNG	-0.046	0.067	-10000	0	-0.12	145	145
T cell differentiation	-0.01	0.011	0.012	1	-0.023	139	140
STAT3 (dimer)	-0.15	0.3	-10000	0	-0.6	81	81
STAT5A (dimer)	-0.15	0.3	-10000	0	-0.6	82	82
STAT4 (dimer)	-0.22	0.36	-10000	0	-0.66	114	114
STAT4	-0.12	0.24	-10000	0	-0.54	92	92
T cell activation	-0.003	0.032	0.13	20	-10000	0	20
IL27R/JAK2/TYK2	-0.08	0.3	-10000	0	-1.2	23	23
GATA3	-0.26	0.57	-10000	0	-1.3	80	80
IL18	-0.097	0.18	-10000	0	-0.39	99	99
positive regulation of mast cell cytokine production	-0.15	0.28	-10000	0	-0.58	81	81
IL27/EBI3	-0.12	0.23	-10000	0	-0.48	99	99
IL27RA	-0.083	0.32	-10000	0	-1.4	20	20
IL6	-0.008	0.11	-10000	0	-0.54	14	14
STAT5A	0.017	0.029	-10000	0	-0.54	1	1
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0.031	0.12	0.5	20	-10000	0	20
IL1B	-0.03	0.12	-10000	0	-0.34	43	43
EBI3	-0.11	0.23	-10000	0	-0.55	82	82
TNF	-0.071	0.16	-10000	0	-0.39	75	75

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.048	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.069	0.11	-9999	-0.3	15	15
JUN	-0.039	0.12	-9999	-0.31	14	14
HRAS	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.064	0.15	-9999	-0.29	106	106
RAP1A	0.019	0	-9999	-10000	0	0
FRS2	0.017	0.024	-9999	-0.24	3	3
RAP1A/GDP	0.014	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.063	0.15	-9999	-0.29	105	105
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.071	0.15	-9999	-0.29	103	103
RHOA	0.019	0	-9999	-10000	0	0
RAP1A/GTP	-0.052	0.13	-9999	-0.25	102	102
GRB7	-0.004	0.068	-9999	-0.24	27	27
RET51/GFRalpha1/GDNF	-0.063	0.15	-9999	-0.29	105	105
MAPKKK cascade	-0.073	0.11	-9999	-0.37	4	4
BCAR1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.081	0.15	-9999	-0.3	106	106
lamellipodium assembly	-0.07	0.1	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/SHC	-0.063	0.15	-9999	-0.29	105	105
PIK3CA	0.018	0.014	-9999	-0.24	1	1
RET9/GFRalpha1/GDNF/SHC	-0.071	0.15	-9999	-0.29	103	103
RET9/GFRalpha1/GDNF/Shank3	-0.072	0.15	-9999	-0.29	103	103
MAPK3	-0.046	0.12	-9999	-0.23	102	102
DOK1	0.019	0	-9999	-10000	0	0
DOK6	-0.011	0.1	-9999	-0.3	34	34
PXN	0.019	0	-9999	-10000	0	0
neurite development	-0.036	0.12	-9999	-0.32	12	12
DOK5	-0.05	0.12	-9999	-0.26	92	92
GFRA1	-0.13	0.24	-9999	-0.52	101	101
MAPK8	-0.036	0.12	-9999	-0.33	4	4
HRAS/GTP	-0.062	0.14	-9999	-0.28	102	102
tube development	-0.06	0.14	-9999	-0.27	103	103
MAPK1	-0.046	0.12	-9999	-0.23	102	102
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.051	0.12	-9999	-0.24	101	101
Rac1/GDP	0.014	0	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
PDLIM7	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.065	0.15	-9999	-0.28	104	104
SHC1	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.063	0.15	-9999	-0.29	105	105
RET51/GFRalpha1/GDNF/Dok5	-0.098	0.16	-9999	-0.3	120	120
PRKCA	0.013	0.044	-9999	-0.29	7	7
HRAS/GDP	0.014	0	-9999	-10000	0	0
CREB1	-0.052	0.14	-9999	-0.27	101	101
PIK3R1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.05	0.12	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/Grb7	-0.075	0.15	-9999	-0.29	110	110
mol:GDP	0	0	-9999	-10000	0	0
RET	0.014	0.04	-9999	-0.3	5	5
DOK4	0.019	0	-9999	-10000	0	0
JNK cascade	-0.038	0.11	-9999	-0.3	14	14
RET9/GFRalpha1/GDNF/FRS2	-0.072	0.15	-9999	-0.29	103	103
SHANK3	0.017	0.019	-9999	-0.24	2	2
RASA1	0.017	0.029	-9999	-0.54	1	1
NCK1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.051	0.12	-9999	-0.24	101	101
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.046	0.12	-9999	-0.23	102	102
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.046	0.12	-9999	-0.23	103	103
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.045	0.12	-9999	-0.23	102	102
PI3K	-0.062	0.18	-9999	-0.34	101	101
SOS1	0.019	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.058	0.14	-9999	-0.27	103	103
GRB10	0.017	0.019	-9999	-0.24	2	2
activation of MAPKK activity	-0.046	0.12	-9999	-0.33	11	11
RET51/GFRalpha1/GDNF/FRS2	-0.064	0.15	-9999	-0.28	106	106
GAB1	0.019	0	-9999	-10000	0	0
IRS1	-0.002	0.071	-9999	-0.24	29	29
IRS2	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.045	0.12	-9999	-0.23	102	102
RET51/GFRalpha1/GDNF/PKC alpha	-0.066	0.15	-9999	-0.29	108	108
GRB2	0.019	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GDNF	-0.022	0.11	-9999	-0.3	43	43
RAC1	0.019	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.073	0.15	-9999	-0.3	108	108
Rac1/GTP	-0.081	0.12	-9999	-0.28	101	101
RET9/GFRalpha1/GDNF	-0.091	0.16	-9999	-0.33	103	103
GFRalpha1/GDNF	-0.11	0.18	-9999	-0.39	103	103

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.038	0.1	-10000	0	-0.28	27	27
fibroblast growth factor receptor signaling pathway	-0.038	0.1	-10000	0	-0.28	27	27
LAMA1	-0.2	0.1	-10000	0	-0.24	302	302
PRNP	0.017	0.029	-10000	0	-0.54	1	1
GPC1/SLIT2	-0.052	0.11	-10000	0	-0.33	22	22
SMAD2	-0.007	0.062	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.025	0.072	-10000	0	-0.32	1	1
GPC1/Laminin alpha1	-0.17	0.1	-10000	0	-0.31	104	104
TDGF1	-0.088	0.21	-10000	0	-0.54	64	64
CRIPTO/GPC1	-0.11	0.16	-10000	0	-0.42	64	64
APP/GPC1	-0.035	0.09	-10000	0	-0.38	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.081	0.14	-10000	0	-0.35	64	64
FLT1	0.018	0.014	-10000	0	-0.24	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.013	0.073	-10000	0	-10000	0	0
SERPINC1	0.006	0.047	-10000	0	-0.24	12	12
FYN	-0.081	0.14	-10000	0	-0.35	64	64
FGR	-0.11	0.17	-10000	0	-0.37	95	95
positive regulation of MAPKKK cascade	-0.3	0.29	-10000	0	-0.51	198	198
SLIT2	-0.012	0.095	-10000	0	-0.28	39	39
GPC1/NRG	-0.044	0.1	-10000	0	-0.33	16	16
NRG1	-0.001	0.074	-10000	0	-0.29	20	20
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.021	0.083	-10000	0	-0.25	12	12
LYN	-0.095	0.15	-10000	0	-0.36	77	77
mol:Spermine	-0.045	0.083	-10000	0	-10000	0	0
cell growth	-0.038	0.1	-10000	0	-0.28	27	27
BMP signaling pathway	0.069	0.12	0.24	122	-10000	0	122
SRC	-0.081	0.14	-10000	0	-0.35	64	64
TGFBR1	0.019	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.061	0.16	-10000	0	-0.32	85	85
GPC1	-0.069	0.12	-10000	0	-0.24	122	122
TGFBR1 (dimer)	0.019	0	-10000	0	-10000	0	0
VEGFA	0.004	0.061	-10000	0	-0.24	21	21
BLK	-0.3	0.21	-10000	0	-0.42	256	256
HCK	-0.11	0.16	-10000	0	-0.36	91	91
FGF2	-0.004	0.08	-10000	0	-0.26	30	30
FGFR1	-0.003	0.073	-10000	0	-0.24	31	31
VEGFR1 homodimer	0.018	0.014	-10000	0	-0.24	1	1
TGFBR2	0.019	0	-10000	0	-10000	0	0
cell death	-0.035	0.09	-10000	0	-0.38	3	3
ATIII/GPC1	-0.04	0.092	-10000	0	-0.31	7	7
PLA2G2A/GPC1	-0.086	0.14	-10000	0	-0.37	44	44
LCK	-0.21	0.22	-10000	0	-0.41	180	180
neuron differentiation	-0.044	0.1	-10000	0	-0.33	16	16
PrPc/Cu2+	0.013	0.021	-10000	0	-0.39	1	1
APP	0.014	0.05	-10000	0	-0.54	3	3
TGFBR2 (dimer)	0.019	0	-10000	0	-10000	0	0

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.049	0.11	-9999	-0.33	31	31
FZD6	-0.01	0.12	-9999	-0.54	19	19
WNT6	0.007	0.052	-9999	-0.24	15	15
WNT4	-0.082	0.13	-9999	-0.24	140	140
FZD3	0.019	0	-9999	-10000	0	0
WNT5A	-0.001	0.092	-9999	-0.37	19	19
WNT11	-0.066	0.12	-9999	-0.24	118	118

×

Glucocorticoid receptor regulatory 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
PCK2	0.069	0.11	0.34	10	-10000	0	10
SMARCC2	0.021	0	-10000	0	-10000	0	0
SMARCC1	0.021	0	-10000	0	-10000	0	0
TBX21	-0.28	0.41	-10000	0	-0.83	121	121
SUMO2	0.021	0.009	-10000	0	-10000	0	0
STAT1 (dimer)	-0.012	0.12	-10000	0	-0.33	39	39
FKBP4	0.018	0.014	-10000	0	-0.24	1	1
FKBP5	-0.021	0.14	-10000	0	-0.54	26	26
GR alpha/HSP90/FKBP51/HSP90	0.1	0.14	0.3	84	-0.27	8	92
PRL	-0.11	0.17	-10000	0	-0.55	19	19
cortisol/GR alpha (dimer)/TIF2	0.27	0.29	0.56	152	-0.35	1	153
RELA	-0.006	0.066	-10000	0	-0.22	5	5
FGG	0.2	0.23	0.5	102	-0.47	1	103
GR beta/TIF2	0.14	0.14	0.32	107	-10000	0	107
IFNG	-0.52	0.6	-10000	0	-1.2	145	145
apoptosis	0.086	0.16	0.49	37	-10000	0	37
CREB1	0.019	0.016	-10000	0	-10000	0	0
histone acetylation	-0.079	0.17	-10000	0	-0.35	77	77
BGLAP	-0.091	0.17	-10000	0	-0.44	37	37
GR/PKAc	0.13	0.11	0.3	83	-10000	0	83
NF kappa B1 p50/RelA	-0.006	0.12	-10000	0	-0.32	17	17
SMARCD1	0.021	0	-10000	0	-10000	0	0
MDM2	0.1	0.11	0.24	118	-10000	0	118
GATA3	-0.1	0.23	-10000	0	-0.54	80	80
AKT1	0.01	0.001	-10000	0	-10000	0	0
CSF2	-0.1	0.18	-10000	0	-0.55	20	20
GSK3B	0.021	0.009	-10000	0	-10000	0	0
NR1I3	0.096	0.14	0.48	34	-10000	0	34
CSN2	0.16	0.18	0.4	95	-0.32	1	96
BRG1/BAF155/BAF170/BAF60A	0.058	0.001	-10000	0	-10000	0	0
NFATC1	0.007	0.086	-10000	0	-0.54	9	9
POU2F1	0.013	0.027	-10000	0	-10000	0	0
CDKN1A	0.033	0.032	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.002	0.009	-10000	0	-10000	0	0
SFN	-0.035	0.11	-10000	0	-0.24	74	74
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.084	0.14	0.3	62	-0.3	9	71
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.083	0.15	0.45	36	-10000	0	36
JUN	-0.2	0.22	-10000	0	-0.45	123	123
IL4	-0.12	0.19	-10000	0	-0.5	42	42
CDK5R1	0.018	0.029	-10000	0	-0.54	1	1
PRKACA	0.019	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.096	0.17	0.22	19	-0.39	60	79
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.13	0.3	81	-0.24	5	86
cortisol/GR alpha (monomer)	0.31	0.36	0.68	152	-0.42	1	153
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.036	0.075	-10000	0	-0.29	12	12
AP-1/NFAT1-c-4	-0.27	0.31	-10000	0	-0.62	130	130
AFP	-0.14	0.15	-10000	0	-0.59	1	1
SUV420H1	0.019	0	-10000	0	-10000	0	0
IRF1	0.061	0.34	0.46	59	-0.76	43	102
TP53	0.043	0.013	-10000	0	-10000	0	0
PPP5C	0.019	0	-10000	0	-10000	0	0
KRT17	-0.27	0.3	-10000	0	-0.68	98	98
KRT14	-0.18	0.19	-10000	0	-0.55	40	40
TBP	0.03	0.007	-10000	0	-10000	0	0
CREBBP	0.044	0.044	-10000	0	-10000	0	0
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.017	0.005	-10000	0	-10000	0	0
AP-1	-0.28	0.32	-10000	0	-0.62	130	130
MAPK14	0.021	0.008	-10000	0	-10000	0	0
MAPK10	-0.031	0.1	-10000	0	-0.24	71	71
MAPK11	0.021	0.009	-10000	0	-10000	0	0
KRT5	-0.33	0.42	-10000	0	-0.86	111	111
interleukin-1 receptor activity	-0.002	0.005	-10000	0	-10000	0	0
NCOA1	0.023	0.002	-10000	0	-10000	0	0
STAT1	-0.012	0.12	-10000	0	-0.33	39	39
CGA	-0.11	0.17	-10000	0	-0.47	35	35
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.15	0.14	0.35	86	-10000	0	86
MAPK3	0.021	0.009	-10000	0	-10000	0	0
MAPK1	0.021	0.008	-10000	0	-10000	0	0
ICAM1	-0.15	0.26	-10000	0	-0.59	70	70
NFKB1	-0.006	0.066	-10000	0	-0.21	7	7
MAPK8	-0.17	0.21	-10000	0	-0.42	119	119
MAPK9	0.021	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.082	0.16	0.49	37	-10000	0	37
BAX	0.034	0.019	-10000	0	-10000	0	0
POMC	-0.27	0.53	-10000	0	-1.4	53	53
EP300	0.044	0.044	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.28	0.29	0.58	151	-10000	0	151
proteasomal ubiquitin-dependent protein catabolic process	0.07	0.085	0.2	80	-10000	0	80
SGK1	0.1	0.064	-10000	0	-10000	0	0
IL13	-0.29	0.36	-10000	0	-0.88	76	76
IL6	-0.17	0.3	-10000	0	-0.78	48	48
PRKACG	0.002	0.02	-10000	0	-0.24	2	2
IL5	-0.26	0.31	-10000	0	-0.78	73	73
IL2	-0.25	0.29	-10000	0	-0.69	76	76
CDK5	0.02	0.004	-10000	0	-10000	0	0
PRKACB	0.018	0.014	-10000	0	-0.24	1	1
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
IL8	-0.18	0.27	-10000	0	-0.61	77	77
CDK5R1/CDK5	0.029	0.024	-10000	0	-0.38	1	1
NF kappa B1 p50/RelA/PKAc	0.021	0.09	-10000	0	-0.28	5	5
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.26	0.27	0.54	151	-10000	0	151
SMARCA4	0.021	0	-10000	0	-10000	0	0
chromatin remodeling	0.19	0.17	0.4	112	-10000	0	112
NF kappa B1 p50/RelA/Cbp	0.046	0.11	0.32	1	-0.31	2	3
JUN (dimer)	-0.19	0.22	-10000	0	-0.45	123	123
YWHAH	0.019	0	-10000	0	-10000	0	0
VIPR1	-0.25	0.39	-10000	0	-0.79	116	116
NR3C1	0.19	0.23	0.45	128	-10000	0	128
NR4A1	-0.029	0.15	-10000	0	-0.41	46	46
TIF2/SUV420H1	0.028	0.009	-10000	0	-10000	0	0
MAPKKK cascade	0.086	0.16	0.49	37	-10000	0	37
cortisol/GR alpha (dimer)/Src-1	0.27	0.29	0.57	152	-0.35	1	153
PBX1	-0.006	0.081	-10000	0	-0.28	26	26
POU1F1	-0.002	0.028	-10000	0	-10000	0	0
SELE	-0.23	0.41	-10000	0	-0.95	74	74
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.19	0.17	0.4	112	-10000	0	112
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.26	0.27	0.54	151	-10000	0	151
mol:cortisol	0.18	0.23	0.41	146	-0.24	1	147
MMP1	-0.17	0.34	-10000	0	-0.86	52	52

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.037	0.12	-10000	0	-0.23	101	101
epithelial cell differentiation	-0.042	0.14	-10000	0	-0.26	101	101
CYFIP2	-0.01	0.12	-10000	0	-0.54	19	19
ENAH	0.005	0.095	-10000	0	-0.31	2	2
EGFR	-0.007	0.087	-10000	0	-0.27	33	33
EPHA2	0.013	0.058	-10000	0	-0.54	4	4
MYO6	-0.039	0.13	-10000	0	-0.24	101	101
CTNNB1	0.019	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.02	0.079	-10000	0	-0.32	19	19
AQP5	-0.043	0.12	-10000	0	-0.32	15	15
CTNND1	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.037	0.12	-10000	0	-0.24	101	101
regulation of calcium-dependent cell-cell adhesion	-0.046	0.13	-10000	0	-0.24	110	110
EGF	-0.031	0.15	-10000	0	-0.42	41	41
NCKAP1	0.019	0	-10000	0	-10000	0	0
AQP3	-0.085	0.2	-10000	0	-0.52	49	49
cortical microtubule organization	-0.042	0.14	-10000	0	-0.26	101	101
GO:0000145	-0.037	0.12	-10000	0	-0.23	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.04	0.14	-10000	0	-0.26	101	101
MLLT4	0.001	0.066	-10000	0	-0.24	25	25
ARF6/GDP	-0.055	0.089	-10000	0	-0.43	2	2
ARF6	0.019	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.034	-10000	0	-0.28	4	4
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.024	0.12	-10000	0	-0.29	2	2
PVRL2	0.019	0	-10000	0	-10000	0	0
ZYX	-0.038	0.13	-10000	0	-0.25	101	101
ARF6/GTP	0.05	0.032	-10000	0	-0.25	4	4
CDH1	-0.13	0.25	-10000	0	-0.54	101	101
EGFR/EGFR/EGF/EGF	-0.092	0.13	-10000	0	-0.27	119	119
RhoA/GDP	-0.036	0.13	-10000	0	-0.24	101	101
actin cytoskeleton organization	-0.032	0.12	-10000	0	-0.23	101	101
IGF-1R heterotetramer	0.016	0.027	-10000	0	-0.24	4	4
GIT1	0.019	0	-10000	0	-10000	0	0
IGF1R	0.016	0.027	-10000	0	-0.24	4	4
IGF1	0.008	0.066	-10000	0	-0.36	10	10
DIAPH1	-0.026	0.14	-10000	0	-0.63	19	19
Wnt receptor signaling pathway	0.042	0.14	0.26	101	-10000	0	101
RHOA	0.019	0	-10000	0	-10000	0	0
RhoA/GTP	-0.055	0.09	-10000	0	-0.43	2	2
CTNNA1	0.019	0	-10000	0	-10000	0	0
VCL	-0.033	0.13	-10000	0	-0.24	101	101
EFNA1	0.019	0	-10000	0	-10000	0	0
LPP	-0.03	0.12	-10000	0	-0.23	102	102
Ephrin A1/EPHA2	-0.066	0.11	-10000	0	-0.23	103	103
SEC6/SEC8	-0.061	0.094	-10000	0	-0.3	7	7
MGAT3	-0.046	0.13	-10000	0	-0.25	110	110
HGF/MET	-0.088	0.14	-10000	0	-0.27	115	115
HGF	0	0.085	-10000	0	-0.34	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.038	0.12	-10000	0	-0.23	101	101
actin cable formation	0.021	0.097	-10000	0	-0.22	10	10
KIAA1543	-0.059	0.14	-10000	0	-0.32	34	34
KIFC3	-0.038	0.13	-10000	0	-0.24	101	101
NCK1	0.019	0	-10000	0	-10000	0	0
EXOC3	0.018	0.014	-10000	0	-0.24	1	1
ACTN1	-0.038	0.13	-10000	0	-0.24	102	102
NCK1/GIT1	0.028	0	-10000	0	-10000	0	0
mol:GDP	-0.042	0.14	-10000	0	-0.26	101	101
EXOC4	0.019	0	-10000	0	-10000	0	0
STX4	-0.038	0.13	-10000	0	-0.24	101	101
PIP5K1C	-0.038	0.13	-10000	0	-0.24	101	101
LIMA1	0.019	0	-10000	0	-10000	0	0
ABI1	0.019	0	-10000	0	-10000	0	0
ROCK1	-0.003	0.11	-10000	0	-0.37	2	2
adherens junction assembly	-0.039	0.14	-10000	0	-0.36	19	19
IGF-1R heterotetramer/IGF1	-0.068	0.11	-10000	0	-0.36	5	5
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0.045	-10000	0	-10000	0	0
MET	-0.024	0.14	-10000	0	-0.43	35	35
PLEKHA7	-0.048	0.14	-10000	0	-0.25	112	112
mol:GTP	0.043	0.034	-10000	0	-0.28	4	4
establishment of epithelial cell apical/basal polarity	-0.015	0.12	-10000	0	-0.29	7	7
cortical actin cytoskeleton stabilization	-0.037	0.12	-10000	0	-0.23	101	101
regulation of cell-cell adhesion	-0.032	0.12	-10000	0	-0.23	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.038	0.12	-10000	0	-0.23	101	101

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.017	0.019	-9999	-0.24	2	2
ITGB7	-0.063	0.2	-9999	-0.54	54	54
ITGA4	-0.043	0.18	-9999	-0.54	41	41
alpha4/beta7 Integrin	-0.076	0.2	-9999	-0.42	84	84
alpha4/beta1 Integrin	-0.019	0.13	-9999	-0.38	41	41

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.048	0.17	-9999	-0.42	53	53
alphaM/beta2 Integrin/GPIbA	-0.2	0.25	-9999	-0.4	202	202
alphaM/beta2 Integrin/proMMP-9	-0.086	0.23	-9999	-0.47	86	86
PLAUR	0.013	0.044	-9999	-0.29	7	7
HMGB1	0.011	0.021	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.027	0.16	-9999	-0.44	44	44
AGER	0.009	0.031	-9999	-0.24	3	3
RAP1A	0.019	0	-9999	-10000	0	0
SELPLG	-0.036	0.16	-9999	-0.54	36	36
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.038	0.2	-9999	-0.47	48	48
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
CYR61	0.011	0.054	-9999	-0.31	9	9
TLN1	0.019	0	-9999	-10000	0	0
Rap1/GTP	-0.11	0.19	-9999	-0.48	60	60
RHOA	0.019	0	-9999	-10000	0	0
P-selectin oligomer	-0.17	0.26	-9999	-0.54	123	123
MYH2	-0.12	0.22	-9999	-0.44	81	81
MST1R	-0.014	0.13	-9999	-0.48	24	24
leukocyte activation during inflammatory response	-0.04	0.14	-9999	-0.4	44	44
APOB	-0.013	0.071	-9999	-0.24	31	31
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.019	0.097	-9999	-0.26	50	50
JAM3	-0.007	0.078	-9999	-0.24	36	36
GP1BA	-0.27	0.28	-9999	-0.54	191	191
alphaM/beta2 Integrin/CTGF	-0.034	0.16	-9999	-0.43	46	46
alphaM/beta2 Integrin	-0.12	0.24	-9999	-0.52	70	70
JAM3 homodimer	-0.007	0.078	-9999	-0.24	36	36
ICAM2	-0.019	0.14	-9999	-0.54	25	25
ICAM1	0.008	0.076	-9999	-0.54	7	7
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.12	0.24	-9999	-0.51	70	70
cell adhesion	-0.2	0.25	-9999	-0.4	202	202
NFKB1	-0.066	0.25	-9999	-0.46	87	87
THY1	0.015	0.043	-9999	-0.44	3	3
RhoA/GDP	0.014	0	-9999	-10000	0	0
Lipoprotein(a)	-0.006	0.039	-9999	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	-0.019	0.15	-9999	-0.39	46	46
IL6	-0.07	0.26	-9999	-0.67	45	45
ITGB2	-0.057	0.19	-9999	-0.57	44	44
elevation of cytosolic calcium ion concentration	-0.02	0.16	-9999	-0.4	46	46
alphaM/beta2 Integrin/JAM2/JAM3	-0.027	0.16	-9999	-0.42	45	45
JAM2	0.015	0.043	-9999	-0.44	3	3
alphaM/beta2 Integrin/ICAM1	-0.026	0.18	-9999	-0.38	63	63
alphaM/beta2 Integrin/uPA/Plg	-0.027	0.15	-9999	-0.41	44	44
RhoA/GTP	-0.13	0.23	-9999	-0.38	123	123
positive regulation of phagocytosis	-0.099	0.25	-9999	-0.58	62	62
Ron/MSP	0.002	0.096	-9999	-0.38	21	21
alphaM/beta2 Integrin/uPAR/uPA	-0.019	0.16	-9999	-0.4	46	46
alphaM/beta2 Integrin/uPAR	-0.03	0.17	-9999	-0.45	44	44
PLAU	0.012	0.048	-9999	-0.28	9	9
PLAT	0.012	0.051	-9999	-0.33	7	7
actin filament polymerization	-0.11	0.21	-9999	-0.42	81	81
MST1	0.016	0.035	-9999	-0.34	3	3
alphaM/beta2 Integrin/lipoprotein(a)	-0.038	0.15	-9999	-0.4	44	44
TNF	-0.14	0.38	-9999	-0.83	79	79
RAP1B	0.019	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.031	0.17	-9999	-0.45	44	44
fibrinolysis	-0.028	0.15	-9999	-0.41	44	44
HCK	-0.028	0.16	-9999	-0.54	31	31
dendritic cell antigen processing and presentation	-0.12	0.24	-9999	-0.51	70	70
VTN	-0.058	0.19	-9999	-0.5	54	54
alphaM/beta2 Integrin/CYR61	-0.031	0.16	-9999	-0.44	46	46
LPA	0	0	-9999	-10000	0	0
LRP1	0.014	0.036	-9999	-0.24	7	7
cell migration	-0.09	0.22	-9999	-0.43	89	89
FN1	0	0.1	-9999	-0.52	13	13
alphaM/beta2 Integrin/Thy1	-0.029	0.16	-9999	-0.44	46	46
MPO	-0.033	0.16	-9999	-0.53	34	34
KNG1	-0.004	0.049	-9999	-0.24	14	14
RAP1/GDP	0.026	0	-9999	-10000	0	0
ROCK1	-0.11	0.22	-9999	-0.45	74	74
ELA2	0	0	-9999	-10000	0	0
PLG	0	0	-9999	-10000	0	0
CTGF	0.007	0.059	-9999	-0.26	16	16
alphaM/beta2 Integrin/Hck	-0.052	0.23	-9999	-0.62	46	46
ITGAM	-0.006	0.099	-9999	-0.56	11	11
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.14	0.29	-9999	-0.45	139	139
HP	-0.12	0.23	-9999	-0.5	94	94
leukocyte adhesion	-0.035	0.19	-9999	-0.51	38	38
SELP	-0.17	0.26	-9999	-0.54	123	123

×

Endothelins

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
AKT1	-0.026	0.18	0.29	21	-0.42	33	54
PTK2B	0.008	0.076	-10000	0	-0.54	7	7
mol:Ca2+	-0.031	0.18	-10000	0	-0.5	13	13
EDN1	-0.017	0.13	0.24	21	-0.33	24	45
EDN3	-0.063	0.15	-10000	0	-0.31	86	86
EDN2	0	0	-10000	0	-10000	0	0
HRAS/GDP	-0.07	0.22	-10000	0	-0.46	61	61
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.04	0.18	0.21	13	-0.43	44	57
ADCY4	-0.038	0.16	-10000	0	-0.34	50	50
ADCY5	-0.096	0.19	-10000	0	-0.33	110	110
ADCY6	-0.036	0.15	-10000	0	-0.34	47	47
ADCY7	-0.036	0.15	-10000	0	-0.34	48	48
ADCY1	-0.078	0.18	-10000	0	-0.33	89	89
ADCY2	-0.089	0.16	-10000	0	-0.34	76	76
ADCY3	-0.035	0.15	-10000	0	-0.34	46	46
ADCY8	-0.05	0.16	-10000	0	-0.34	54	54
ADCY9	-0.035	0.15	-10000	0	-0.34	46	46
arachidonic acid secretion	-0.037	0.18	-10000	0	-0.4	46	46
ETB receptor/Endothelin-1/Gq/GTP	-0.039	0.14	-10000	0	-0.3	68	68
GNAO1	-0.093	0.13	-10000	0	-0.25	155	155
HRAS	0.019	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.005	0.18	0.37	23	-0.38	33	56
ETA receptor/Endothelin-1/Gs/GTP	-0.026	0.18	0.33	23	-0.36	47	70
mol:GTP	0.001	0.004	-10000	0	-10000	0	0
COL3A1	-0.046	0.2	0.29	21	-0.4	54	75
EDNRB	-0.024	0.094	-10000	0	-0.25	50	50
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.065	0.25	0.29	21	-0.61	48	69
CYSLTR1	-0.073	0.27	0.29	20	-0.6	60	80
SLC9A1	-0.006	0.1	0.21	20	-0.23	27	47
mol:GDP	-0.085	0.23	0.23	6	-0.49	65	71
SLC9A3	-0.18	0.3	-10000	0	-0.59	103	103
RAF1	-0.067	0.21	-10000	0	-0.47	54	54
JUN	-0.035	0.19	-10000	0	-0.52	12	12
JAK2	-0.032	0.19	0.29	20	-0.42	37	57
mol:IP3	-0.054	0.2	-10000	0	-0.42	59	59
ETA receptor/Endothelin-1	-0.029	0.23	0.44	23	-0.46	38	61
PLCB1	-0.002	0.11	-10000	0	-0.54	14	14
PLCB2	0.001	0.099	-10000	0	-0.54	12	12
ETA receptor/Endothelin-3	-0.055	0.14	-10000	0	-0.3	60	60
FOS	-0.031	0.17	-10000	0	-0.5	16	16
Gai/GDP	-0.034	0.091	-10000	0	-0.62	2	2
CRK	0.019	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.07	0.23	0.27	12	-0.49	58	70
BCAR1	0.019	0.001	-10000	0	-10000	0	0
PRKCB1	-0.05	0.19	-10000	0	-0.4	59	59
GNAQ	0.02	0.005	-10000	0	-10000	0	0
GNAZ	-0.015	0.093	-10000	0	-0.26	45	45
GNAL	-0.02	0.1	-10000	0	-0.28	49	49
Gs family/GDP	-0.094	0.21	-10000	0	-0.46	63	63
ETA receptor/Endothelin-1/Gq/GTP	-0.041	0.17	0.23	15	-0.39	48	63
MAPK14	-0.028	0.15	-10000	0	-0.4	31	31
TRPC6	-0.033	0.19	-10000	0	-0.52	13	13
GNAI2	0.019	0	-10000	0	-10000	0	0
GNAI3	0.019	0	-10000	0	-10000	0	0
GNAI1	0.004	0.06	-10000	0	-0.24	20	20
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.037	0.16	-10000	0	-0.35	50	50
ETB receptor/Endothelin-2	-0.014	0.064	-10000	0	-0.25	5	5
ETB receptor/Endothelin-3	-0.058	0.12	-10000	0	-0.27	49	49
ETB receptor/Endothelin-1	-0.026	0.12	-10000	0	-0.31	24	24
MAPK3	-0.044	0.2	-10000	0	-0.48	33	33
MAPK1	-0.044	0.2	-10000	0	-0.48	33	33
Rac1/GDP	-0.071	0.22	-10000	0	-0.47	59	59
cAMP biosynthetic process	-0.091	0.18	0.22	3	-0.37	72	75
MAPK8	-0.039	0.19	-10000	0	-0.44	41	41
SRC	0.019	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.027	0.079	-10000	0	-0.26	11	11
p130Cas/CRK/Src/PYK2	-0.074	0.23	-10000	0	-0.49	59	59
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.071	0.22	-10000	0	-0.46	61	61
COL1A2	-0.057	0.2	-10000	0	-0.5	29	29
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.012	0.088	-10000	0	-0.25	14	14
mol:DAG	-0.054	0.2	-10000	0	-0.42	59	59
MAP2K2	-0.052	0.2	-10000	0	-0.46	44	44
MAP2K1	-0.052	0.2	-10000	0	-0.47	42	42
EDNRA	-0.023	0.13	0.24	21	-0.31	29	50
positive regulation of muscle contraction	-0.014	0.15	0.25	21	-0.37	29	50
Gq family/GDP	-0.12	0.22	-10000	0	-0.52	67	67
HRAS/GTP	-0.082	0.22	-10000	0	-0.45	69	69
PRKCH	-0.044	0.19	-10000	0	-0.42	52	52
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCA	-0.045	0.19	-10000	0	-0.42	52	52
PRKCB	-0.12	0.26	-10000	0	-0.49	92	92
PRKCE	-0.041	0.19	-10000	0	-0.42	49	49
PRKCD	-0.043	0.19	-10000	0	-0.41	51	51
PRKCG	-0.046	0.19	-10000	0	-0.42	52	52
regulation of vascular smooth muscle contraction	-0.04	0.2	-10000	0	-0.61	15	15
PRKCQ	-0.13	0.26	-10000	0	-0.45	107	107
PLA2G4A	-0.041	0.2	-10000	0	-0.43	46	46
GNA14	-0.083	0.22	-10000	0	-0.53	69	69
GNA15	0.003	0.095	-10000	0	-0.54	11	11
GNA12	0.019	0	-10000	0	-10000	0	0
GNA11	0.02	0.004	-10000	0	-10000	0	0
Rac1/GTP	-0.005	0.18	0.38	23	-0.38	33	56
MMP1	-0.058	0.26	0.29	2	-0.66	43	45

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.09	0.22	-9999	-0.44	101	101
KLHL20	-0.002	0.089	-9999	-0.22	8	8
CYFIP2	-0.01	0.12	-9999	-0.54	19	19
Rac1/GDP	-0.021	0.14	-9999	-0.25	99	99
ENAH	-0.09	0.22	-9999	-0.44	101	101
AP1M1	0.019	0	-9999	-10000	0	0
RAP1B	0.019	0	-9999	-10000	0	0
RAP1A	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
CDC42/GTP	-0.048	0.079	-9999	-0.24	7	7
ABI1/Sra1/Nap1	-0.032	0.046	-9999	-0.17	15	15
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.088	0.19	-9999	-0.32	134	134
RAPGEF1	-0.064	0.19	-9999	-0.38	101	101
CTNND1	0.019	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.098	0.23	-9999	-0.46	101	101
CRK	-0.077	0.21	-9999	-0.41	101	101
E-cadherin/gamma catenin/alpha catenin	-0.064	0.16	-9999	-0.32	101	101
alphaE/beta7 Integrin	-0.032	0.14	-9999	-0.38	54	54
IQGAP1	0.019	0	-9999	-10000	0	0
NCKAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.027	0.035	-9999	-10000	0	0
DLG1	-0.089	0.22	-9999	-0.44	101	101
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.057	-9999	-0.17	8	8
MLLT4	0.001	0.066	-9999	-0.24	25	25
ARF6/GTP/NME1/Tiam1	0.017	0.077	-9999	-0.29	22	22
PI3K	-0.044	0.072	-9999	-0.22	8	8
ARF6	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.09	0.19	-9999	-0.39	101	101
TIAM1	-0.014	0.13	-9999	-0.54	22	22
E-cadherin(dimer)/Ca2+	-0.04	0.14	-9999	-0.26	101	101
AKT1	-0.025	0.042	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
CDH1	-0.13	0.25	-9999	-0.54	101	101
RhoA/GDP	-0.021	0.14	-9999	-0.25	99	99
actin cytoskeleton organization	0.001	0.068	-9999	-0.16	7	7
CDC42/GDP	-0.021	0.14	-9999	-0.25	99	99
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.048	0.12	-9999	-0.25	101	101
ITGB7	-0.063	0.2	-9999	-0.54	54	54
RAC1	0.019	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.042	0.15	-9999	-0.28	101	101
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.05	0.14	-9999	-0.27	101	101
mol:GDP	-0.038	0.16	-9999	-0.29	101	101
CDC42/GTP/IQGAP1	0.026	0	-9999	-10000	0	0
JUP	0.011	0.045	-9999	-0.24	11	11
p120 catenin/RhoA/GDP	-0.022	0.14	-9999	-0.25	99	99
RAC1/GTP/IQGAP1	0.026	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.028	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0
CTNNA1	0.019	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.004	0.05	-9999	-0.12	6	6
NME1	0.019	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.089	0.22	-9999	-0.44	101	101
regulation of cell-cell adhesion	-0.043	0.07	-9999	-0.21	7	7
WASF2	-0.016	0.025	-9999	-0.11	2	2
Rap1/GTP	-0.015	0.12	-9999	-0.28	7	7
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.077	0.18	-9999	-0.3	134	134
CCND1	0.003	0.06	-9999	-0.15	6	6
VAV2	-0.073	0.22	-9999	-0.41	102	102
RAP1/GDP	-0.019	0.12	-9999	-0.28	7	7
adherens junction assembly	-0.086	0.21	-9999	-0.43	101	101
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.019	0	-9999	-10000	0	0
PIP5K1C	0.019	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.069	0.18	-9999	-0.29	134	134
E-cadherin/beta catenin	-0.086	0.17	-9999	-0.36	101	101
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.089	0.22	-9999	-0.44	101	101
PIK3CA	0.018	0.014	-9999	-0.24	1	1
Rac1/GTP	-0.066	0.095	-9999	-0.35	8	8
E-cadherin/beta catenin/alpha catenin	-0.059	0.16	-9999	-0.32	101	101
ITGAE	0.019	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.1	0.23	-9999	-0.48	101	101

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.017	0.029	-9999	-0.54	1	1
Caspase 8 (4 units)	-0.037	0.13	-9999	-0.44	11	11
NEF	-0.029	0.054	-9999	-0.19	19	19
NFKBIA	-0.017	0.054	-9999	-10000	0	0
BIRC3	-0.16	0.29	-9999	-0.56	128	128
CYCS	-0.049	0.14	-9999	-0.44	11	11
RIPK1	0.019	0	-9999	-10000	0	0
CD247	-0.23	0.33	-9999	-0.67	128	128
MAP2K7	-0.042	0.14	-9999	-0.38	15	15
protein ubiquitination	-0.011	0.12	-9999	-0.39	11	11
CRADD	0.018	0.014	-9999	-0.24	1	1
DAXX	0.019	0	-9999	-10000	0	0
FAS	0.007	0.081	-9999	-0.54	8	8
BID	-0.058	0.15	-9999	-0.25	121	121
NF-kappa-B/RelA/I kappa B alpha	-0.059	0.15	-9999	-0.27	128	128
TRADD	0.019	0	-9999	-10000	0	0
MAP3K5	0.016	0.041	-9999	-0.54	2	2
CFLAR	0.019	0	-9999	-10000	0	0
FADD	0.018	0.014	-9999	-0.24	1	1
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.06	0.15	-9999	-0.27	128	128
MAPK8	-0.033	0.13	-9999	-0.36	15	15
APAF1	0.019	0	-9999	-10000	0	0
TRAF1	-0.001	0.098	-9999	-0.46	15	15
TRAF2	0.019	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.069	0.15	-9999	-0.27	121	121
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.034	0.15	-9999	-0.33	58	58
CHUK	-0.014	0.13	-9999	-0.43	11	11
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.046	0.056	-9999	-0.26	12	12
TCRz/NEF	-0.21	0.31	-9999	-0.57	147	147
TNF	-0.095	0.22	-9999	-0.54	75	75
FASLG	-0.28	0.4	-9999	-0.74	147	147
NFKB1	-0.017	0.054	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.035	0.14	-9999	-0.32	76	76
CASP6	-0.01	0.11	-9999	-0.4	11	11
CASP7	-0.15	0.3	-9999	-0.55	128	128
RELA	-0.017	0.054	-9999	-10000	0	0
CASP2	0.019	0	-9999	-10000	0	0
CASP3	-0.15	0.3	-9999	-0.55	128	128
TNFRSF1A	0.019	0	-9999	-10000	0	0
TNFR1A/BAG4	0.027	0.021	-9999	-0.38	1	1
CASP8	0.016	0.041	-9999	-0.54	2	2
CASP9	0.019	0	-9999	-10000	0	0
MAP3K14	-0.024	0.14	-9999	-0.31	48	48
APAF-1/Caspase 9	-0.16	0.2	-9999	-0.43	128	128
BCL2	-0.023	0.12	-9999	-0.36	10	10

×

TCGA08_retinoblastoma

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
CDKN2B	-0.008	0.088	-10000	0	-0.28	31	31
CDKN2C	0.029	0.012	-10000	0	-10000	0	0
CDKN2A	-0.11	0.14	-10000	0	-0.25	172	172
CCND2	0.022	0.065	0.18	23	-0.13	14	37
RB1	-0.026	0.063	-10000	0	-0.18	23	23
CDK4	0.03	0.063	0.19	23	-10000	0	23
CDK6	0.028	0.066	0.2	23	-0.16	1	24
G1/S progression	0.026	0.063	0.18	23	-10000	0	23

×

Thromboxane A2 receptor 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
TGM2	0.014	0.04	-10000	0	-0.3	5	5
GNB1/GNG2	-0.057	0.085	-10000	0	-0.2	93	93
AKT1	-0.011	0.12	-10000	0	-0.2	92	92
EGF	-0.031	0.15	-10000	0	-0.42	41	41
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.013	0.097	-10000	0	-0.25	38	38
mol:Ca2+	-0.04	0.17	-10000	0	-0.31	94	94
LYN	0.027	0.08	-10000	0	-0.29	16	16
RhoA/GTP	-0.035	0.055	-10000	0	-0.13	93	93
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.064	0.21	-10000	0	-0.38	104	104
GNG2	0.01	0.071	-10000	0	-0.54	6	6
ARRB2	0.019	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.001	0.11	-10000	0	-0.48	12	12
G beta5/gamma2	-0.073	0.11	-10000	0	-0.26	93	93
PRKCH	-0.046	0.18	-10000	0	-0.34	95	95
DNM1	-0.009	0.081	-10000	0	-0.24	39	39
TXA2/TP beta/beta Arrestin3	-0.006	0.024	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	0.002	0.095	-10000	0	-0.54	11	11
G12 family/GTP	-0.087	0.13	-10000	0	-0.31	94	94
ADRBK1	0.019	0	-10000	0	-10000	0	0
ADRBK2	0.014	0.05	-10000	0	-0.54	3	3
RhoA/GTP/ROCK1	0.025	0.001	-10000	0	-10000	0	0
mol:GDP	0.012	0.12	0.37	12	-10000	0	12
mol:NADP	0.014	0.042	-10000	0	-0.29	6	6
RAB11A	0.019	0	-10000	0	-10000	0	0
PRKG1	-0.088	0.13	-10000	0	-0.24	148	148
mol:IP3	-0.058	0.2	-10000	0	-0.39	94	94
cell morphogenesis	0.025	0.001	-10000	0	-10000	0	0
PLCB2	-0.091	0.27	-10000	0	-0.53	94	94
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.12	0.13	-10000	0	-0.24	113	113
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.017	0.095	-10000	0	-0.27	28	28
RHOA	0.019	0	-10000	0	-10000	0	0
PTGIR	0.014	0.05	-10000	0	-0.54	3	3
PRKCB1	-0.055	0.2	-10000	0	-0.37	94	94
GNAQ	0.019	0	-10000	0	-10000	0	0
mol:L-citrulline	0.014	0.042	-10000	0	-0.29	6	6
TXA2/TXA2-R family	-0.097	0.28	-10000	0	-0.55	94	94
LCK	-0.058	0.14	-10000	0	-0.23	135	135
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.024	0.05	-10000	0	-0.26	2	2
TXA2-R family/G12 family/GDP/G beta/gamma	0.034	0.029	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.033	0.051	-10000	0	-0.26	2	2
MAPK14	-0.029	0.14	-10000	0	-0.25	95	95
TGM2/GTP	-0.082	0.22	-10000	0	-0.44	94	94
MAPK11	-0.029	0.14	-10000	0	-0.24	101	101
ARHGEF1	-0.014	0.1	-10000	0	-0.18	93	93
GNAI2	0.019	0	-10000	0	-10000	0	0
JNK cascade	-0.061	0.21	-10000	0	-0.4	94	94
RAB11/GDP	0.019	0.002	-10000	0	-10000	0	0
ICAM1	-0.036	0.16	-10000	0	-0.29	93	93
cAMP biosynthetic process	-0.059	0.19	-10000	0	-0.37	94	94
Gq family/GTP/EBP50	-0.012	0.095	-10000	0	-0.33	11	11
actin cytoskeleton reorganization	0.025	0.001	-10000	0	-10000	0	0
SRC	0.037	0.05	-10000	0	-0.25	2	2
GNB5	0.017	0.029	-10000	0	-0.54	1	1
GNB1	0.019	0	-10000	0	-10000	0	0
EGF/EGFR	-0.11	0.15	-10000	0	-0.28	127	127
VCAM1	-0.059	0.2	-10000	0	-0.38	93	93
TP beta/Gq family/GDP/G beta5/gamma2	0.001	0.11	-10000	0	-0.48	12	12
platelet activation	-0.034	0.18	-10000	0	-0.32	94	94
PGI2/IP	0.011	0.037	-10000	0	-0.39	3	3
PRKACA	0.015	0.055	-10000	0	-0.26	14	14
Gq family/GDP/G beta5/gamma2	0	0.11	-10000	0	-0.46	12	12
TXA2/TP beta/beta Arrestin2	-0.011	0.031	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.018	0.056	-10000	0	-0.25	15	15
mol:DAG	-0.064	0.22	-10000	0	-0.42	94	94
EGFR	-0.007	0.087	-10000	0	-0.27	33	33
TXA2/TP alpha	-0.089	0.26	-10000	0	-0.51	94	94
Gq family/GTP	-0.045	0.097	-10000	0	-0.24	72	72
YES1	0.037	0.05	-10000	0	-0.25	2	2
GNAI2/GTP	-0.01	0.044	-10000	0	-0.24	5	5
PGD2/DP	0.002	0.069	-10000	0	-0.39	11	11
SLC9A3R1	0.019	0	-10000	0	-10000	0	0
FYN	0.037	0.05	-10000	0	-0.25	2	2
mol:NO	0.014	0.042	-10000	0	-0.29	6	6
GNA15	0.002	0.095	-10000	0	-0.54	11	11
PGK/cGMP	-0.038	0.078	-10000	0	-0.32	3	3
RhoA/GDP	0.019	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.039	0.066	-10000	0	-0.37	2	2
NOS3	0.014	0.042	-10000	0	-0.3	6	6
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCA	-0.047	0.18	-10000	0	-0.34	94	94
PRKCB	-0.087	0.23	-10000	0	-0.44	94	94
PRKCE	-0.039	0.18	-10000	0	-0.34	94	94
PRKCD	-0.054	0.2	-10000	0	-0.38	94	94
PRKCG	-0.057	0.2	-10000	0	-0.38	94	94
muscle contraction	-0.092	0.26	-10000	0	-0.52	94	94
PRKCZ	-0.048	0.19	-10000	0	-0.35	93	93
ARR3	0.004	0.008	-10000	0	-10000	0	0
TXA2/TP beta	0.032	0.06	-10000	0	-0.24	9	9
PRKCQ	-0.09	0.23	-10000	0	-0.44	95	95
MAPKKK cascade	-0.089	0.25	-10000	0	-0.5	94	94
SELE	-0.056	0.19	-10000	0	-0.36	93	93
TP beta/GNAI2/GDP/G beta/gamma	0.041	0.064	-10000	0	-0.32	3	3
ROCK1	0.019	0	-10000	0	-10000	0	0
GNA14	-0.084	0.22	-10000	0	-0.53	69	69
chemotaxis	-0.12	0.32	-10000	0	-0.64	93	93
GNA12	0.019	0	-10000	0	-10000	0	0
GNA13	0.019	0	-10000	0	-10000	0	0
GNA11	0.019	0	-10000	0	-10000	0	0
Rac1/GTP	0.014	0.002	-10000	0	-10000	0	0

×

Syndecan-4-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.003	0.11	-9999	-0.56	12	12
Syndecan-4/Syndesmos	-0.055	0.21	-9999	-0.49	65	65
positive regulation of JNK cascade	-0.07	0.22	-9999	-0.5	68	68
Syndecan-4/ADAM12	-0.063	0.21	-9999	-0.49	65	65
CCL5	-0.15	0.26	-9999	-0.54	110	110
Rac1/GDP	0.014	0	-9999	-10000	0	0
DNM2	0.019	0	-9999	-10000	0	0
ITGA5	0.015	0.031	-9999	-0.24	5	5
SDCBP	0.019	0	-9999	-10000	0	0
PLG	0	0.006	-9999	-10000	0	0
ADAM12	-0.001	0.07	-9999	-0.24	28	28
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.019	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.005	0.01	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.2	-9999	-0.56	66	66
Syndecan-4/CXCL12/CXCR4	-0.074	0.24	-9999	-0.54	68	68
Syndecan-4/Laminin alpha3	-0.064	0.21	-9999	-0.5	66	66
MDK	0.004	0.07	-9999	-0.3	17	17
Syndecan-4/FZD7	-0.056	0.21	-9999	-0.5	65	65
Syndecan-4/Midkine	-0.061	0.21	-9999	-0.5	65	65
FZD7	0.015	0.037	-9999	-0.32	4	4
Syndecan-4/FGFR1/FGF	-0.064	0.2	-9999	-0.46	65	65
THBS1	-0.006	0.077	-9999	-0.24	34	34
integrin-mediated signaling pathway	-0.061	0.21	-9999	-0.49	67	67
positive regulation of MAPKKK cascade	-0.07	0.22	-9999	-0.5	68	68
Syndecan-4/TACI	-0.19	0.25	-9999	-0.61	73	73
CXCR4	-0.024	0.15	-9999	-0.54	28	28
cell adhesion	0.019	0.059	-9999	-0.27	13	13
Syndecan-4/Dynamin	-0.055	0.21	-9999	-0.49	65	65
Syndecan-4/TSP1	-0.065	0.21	-9999	-0.49	66	66
Syndecan-4/GIPC	-0.055	0.21	-9999	-0.49	65	65
Syndecan-4/RANTES	-0.13	0.26	-9999	-0.63	67	67
ITGB1	0.017	0.019	-9999	-0.24	2	2
LAMA1	-0.2	0.1	-9999	-0.24	302	302
LAMA3	0	0.1	-9999	-0.52	13	13
RAC1	0.019	0	-9999	-10000	0	0
PRKCA	0.018	0.053	-9999	-0.27	6	6
Syndecan-4/alpha-Actinin	-0.056	0.21	-9999	-0.49	65	65
TFPI	0.014	0.04	-9999	-0.3	5	5
F2	-0.01	0.052	-9999	-0.25	16	16
alpha5/beta1 Integrin	0.025	0.029	-9999	-0.31	2	2
positive regulation of cell adhesion	-0.14	0.2	-9999	-0.52	75	75
ACTN1	0.017	0.029	-9999	-0.54	1	1
TNC	-0.001	0.1	-9999	-0.48	15	15
Syndecan-4/CXCL12	-0.067	0.22	-9999	-0.5	66	66
FGF6	0	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CXCL12	-0.005	0.11	-9999	-0.54	16	16
TNFRSF13B	-0.26	0.28	-9999	-0.54	180	180
FGF2	-0.004	0.08	-9999	-0.26	30	30
FGFR1	-0.003	0.073	-9999	-0.24	31	31
Syndecan-4/PI-4-5-P2	-0.066	0.2	-9999	-0.49	65	65
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.001	0.096	-9999	-0.5	13	13
cell migration	0.002	0.006	-9999	-10000	0	0
PRKCD	0.02	0.005	-9999	-10000	0	0
vasculogenesis	-0.062	0.2	-9999	-0.47	66	66
SDC4	-0.069	0.22	-9999	-0.52	65	65
Syndecan-4/Tenascin C	-0.064	0.22	-9999	-0.51	67	67
Syndecan-4/PI-4-5-P2/PKC alpha	-0.004	0.008	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.055	0.21	-9999	-0.49	65	65
MMP9	-0.081	0.21	-9999	-0.52	68	68
Rac1/GTP	0.019	0.06	-9999	-0.28	13	13
cytoskeleton organization	-0.052	0.2	-9999	-0.47	65	65
GIPC1	0.019	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.057	0.21	-9999	-0.49	65	65

×

Angiopoietin receptor Tie2-mediated signaling

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
AKT1	-0.083	0.36	-10000	0	-0.84	63	63
NCK1/PAK1/Dok-R	-0.087	0.16	-10000	0	-0.42	64	64
NCK1/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
mol:beta2-estradiol	0.03	0.089	0.22	62	-10000	0	62
RELA	0.019	0	-10000	0	-10000	0	0
SHC1	0.019	0.002	-10000	0	-10000	0	0
Rac/GDP	0.014	0	-10000	0	-10000	0	0
F2	0.022	0.11	0.24	43	-0.26	15	58
TNIP2	0.019	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.12	0.4	-10000	0	-0.99	63	63
FN1	0	0.1	-10000	0	-0.52	13	13
PLD2	-0.15	0.44	-10000	0	-1.1	63	63
PTPN11	0.019	0	-10000	0	-10000	0	0
GRB14	-0.027	0.096	-10000	0	-0.24	59	59
ELK1	-0.12	0.4	-10000	0	-0.97	63	63
GRB7	-0.004	0.068	-10000	0	-0.24	27	27
PAK1	0.018	0.014	-10000	0	-0.24	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.14	0.42	-10000	0	-1	63	63
CDKN1A	-0.02	0.23	-10000	0	-0.5	61	61
ITGA5	0.015	0.031	-10000	0	-0.24	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
CRK	0.019	0	-10000	0	-10000	0	0
mol:NO	-0.046	0.28	-10000	0	-0.63	63	63
PLG	-0.16	0.44	-10000	0	-1.1	63	63
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.081	0.35	-10000	0	-0.83	63	63
GRB2	0.019	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.002	-10000	0	-10000	0	0
ANGPT2	-0.035	0.18	-10000	0	-0.4	60	60
BMX	-0.2	0.45	-10000	0	-1.1	63	63
ANGPT1	-0.22	0.52	-10000	0	-1.3	63	63
tube development	-0.034	0.25	-10000	0	-0.55	63	63
ANGPT4	0.001	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.01	0.028	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.18	0.45	-10000	0	-1.1	63	63
alpha5/beta1 Integrin	0.025	0.029	-10000	0	-0.31	2	2
FGF2	-0.005	0.08	-10000	0	-0.26	30	30
STAT5A (dimer)	-0.035	0.28	-10000	0	-0.62	62	62
mol:L-citrulline	-0.046	0.28	-10000	0	-0.63	63	63
AGTR1	0.001	0.003	-10000	0	-10000	0	0
MAPK14	-0.13	0.41	-10000	0	-1	63	63
Tie2/SHP2	-0.004	0.14	-10000	0	-1.2	2	2
TEK	-0.012	0.16	-10000	0	-1.4	2	2
RPS6KB1	-0.077	0.34	-10000	0	-0.81	63	63
Angiotensin II/AT1	0.004	0.005	-10000	0	-10000	0	0
Tie2/Ang1/GRB2	-0.16	0.45	-10000	0	-1.1	63	63
MAPK3	-0.13	0.4	-10000	0	-1	63	63
MAPK1	-0.13	0.4	-10000	0	-1	63	63
Tie2/Ang1/GRB7	-0.16	0.45	-10000	0	-1.1	63	63
NFKB1	0.019	0	-10000	0	-10000	0	0
MAPK8	-0.15	0.44	-10000	0	-1.1	63	63
PI3K	-0.11	0.4	-10000	0	-0.96	63	63
FES	-0.13	0.42	-10000	0	-1	63	63
Crk/Dok-R	-0.16	0.44	-10000	0	-1.1	63	63
Tie2/Ang1/ABIN2	-0.16	0.45	-10000	0	-1.1	63	63
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.069	0.32	-10000	0	-0.75	63	63
STAT5A	0.018	0.029	-10000	0	-0.54	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.077	0.34	-10000	0	-0.81	63	63
Tie2/Ang2	-0.062	0.31	-10000	0	-0.71	63	63
Tie2/Ang1	-0.17	0.47	-10000	0	-1.2	63	63
FOXO1	-0.067	0.32	-10000	0	-0.76	63	63
ELF1	0.027	0.011	-10000	0	-10000	0	0
ELF2	-0.15	0.43	-10000	0	-1.1	63	63
mol:Choline	-0.14	0.42	-10000	0	-1	63	63
cell migration	-0.049	0.088	-10000	0	-0.23	64	64
FYN	-0.043	0.28	-10000	0	-0.62	63	63
DOK2	-0.037	0.17	-10000	0	-0.54	37	37
negative regulation of cell cycle	-0.014	0.22	-10000	0	-0.46	61	61
ETS1	-0.012	0.087	-10000	0	-0.22	40	40
PXN	-0.051	0.29	-10000	0	-0.67	63	63
ITGB1	0.017	0.019	-10000	0	-0.24	2	2
NOS3	-0.059	0.31	-10000	0	-0.71	63	63
RAC1	0.019	0	-10000	0	-10000	0	0
TNF	-0.13	0.25	-10000	0	-0.46	115	115
MAPKKK cascade	-0.14	0.42	-10000	0	-1	63	63
RASA1	0.017	0.029	-10000	0	-0.54	1	1
Tie2/Ang1/Shc	-0.15	0.45	-10000	0	-1.1	63	63
NCK1	0.019	0	-10000	0	-10000	0	0
vasculogenesis	-0.035	0.25	-10000	0	-0.56	63	63
mol:Phosphatidic acid	-0.14	0.42	-10000	0	-1	63	63
mol:Angiotensin II	0.001	0.003	-10000	0	-10000	0	0
mol:NADP	-0.046	0.28	-10000	0	-0.63	63	63
Rac1/GTP	-0.14	0.28	-10000	0	-0.76	63	63
MMP2	-0.17	0.44	-10000	0	-1.1	63	63

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0.041	-9999	-0.54	2	2
CCL5	-0.15	0.26	-9999	-0.54	110	110
SDCBP	0.019	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.06	0.17	-9999	-0.32	89	89
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.049	0.17	-9999	-0.51	29	29
Syndecan-1/Syntenin	-0.048	0.17	-9999	-0.5	29	29
MAPK3	-0.031	0.15	-9999	-0.44	29	29
HGF/MET	-0.016	0.12	-9999	-0.4	27	27
TGFB1/TGF beta receptor Type II	0.016	0.041	-9999	-0.54	2	2
BSG	0.018	0.014	-9999	-0.24	1	1
keratinocyte migration	-0.048	0.17	-9999	-0.5	29	29
Syndecan-1/RANTES	-0.13	0.23	-9999	-0.4	122	122
Syndecan-1/CD147	-0.038	0.16	-9999	-0.48	29	29
Syndecan-1/Syntenin/PIP2	-0.047	0.16	-9999	-0.48	29	29
LAMA5	0.017	0.029	-9999	-0.54	1	1
positive regulation of cell-cell adhesion	-0.047	0.16	-9999	-0.47	29	29
MMP7	-0.016	0.11	-9999	-0.33	35	35
HGF	0	0.085	-9999	-0.34	19	19
Syndecan-1/CASK	-0.059	0.16	-9999	-0.31	89	89
Syndecan-1/HGF/MET	-0.066	0.19	-9999	-0.49	45	45
regulation of cell adhesion	-0.024	0.15	-9999	-0.46	25	25
HPSE	0.019	0	-9999	-10000	0	0
positive regulation of cell migration	-0.06	0.17	-9999	-0.32	89	89
SDC1	-0.061	0.18	-9999	-0.32	89	89
Syndecan-1/Collagen	-0.06	0.17	-9999	-0.32	89	89
PPIB	0.019	0	-9999	-10000	0	0
MET	-0.024	0.14	-9999	-0.43	35	35
PRKACA	0.019	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
MAPK1	-0.031	0.15	-9999	-0.47	26	26
homophilic cell adhesion	-0.059	0.17	-9999	-0.32	89	89
MMP1	-0.058	0.16	-9999	-0.35	76	76

×

LPA receptor mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.034	0.14	-9999	-0.31	66	66
NF kappa B1 p50/RelA/I kappa B alpha	-0.001	0.092	-9999	-0.3	11	11
AP1	-0.082	0.11	-9999	-0.28	71	71
mol:PIP3	-0.068	0.096	-9999	-0.24	70	70
AKT1	0.012	0.1	-9999	-0.32	11	11
PTK2B	-0.035	0.12	-9999	-0.26	70	70
RHOA	0.01	0.045	-9999	-0.29	1	1
PIK3CB	0.019	0.001	-9999	-10000	0	0
mol:Ca2+	-0.008	0.077	-9999	-0.33	7	7
MAGI3	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
apoptosis	-0.061	0.13	-9999	-0.29	73	73
HRAS/GDP	0.014	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.071	0.12	-9999	-0.3	64	64
NF kappa B1 p50/RelA	-0.062	0.11	-9999	-0.31	44	44
endothelial cell migration	-0.066	0.16	-9999	-0.3	107	107
ADCY4	-0.086	0.18	-9999	-0.44	69	69
ADCY5	-0.13	0.22	-9999	-0.46	91	91
ADCY6	-0.084	0.18	-9999	-0.43	69	69
ADCY7	-0.085	0.18	-9999	-0.44	68	68
ADCY1	-0.12	0.2	-9999	-0.44	86	86
ADCY2	-0.11	0.18	-9999	-0.44	75	75
ADCY3	-0.084	0.18	-9999	-0.43	68	68
ADCY8	-0.093	0.18	-9999	-0.42	72	72
ADCY9	-0.084	0.18	-9999	-0.43	68	68
GSK3B	-0.026	0.12	-9999	-0.27	49	49
arachidonic acid secretion	-0.077	0.17	-9999	-0.4	69	69
GNG2	0.01	0.07	-9999	-0.54	6	6
TRIP6	0.025	0.022	-9999	-10000	0	0
GNAO1	-0.11	0.16	-9999	-0.38	77	77
HRAS	0.019	0	-9999	-10000	0	0
NFKBIA	-0.018	0.099	-9999	-0.32	16	16
GAB1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.023	0.23	-9999	-0.94	22	22
JUN	-0.008	0.079	-9999	-0.24	37	37
LPA/LPA2/NHERF2	0.018	0.038	-9999	-0.32	3	3
TIAM1	-0.06	0.27	-9999	-1.1	22	22
PIK3R1	0.019	0.001	-9999	-10000	0	0
mol:IP3	-0.008	0.079	-9999	-0.34	7	7
PLCB3	0.022	0.033	-9999	-0.28	3	3
FOS	0.01	0.047	-9999	-0.24	12	12
positive regulation of mitosis	-0.077	0.17	-9999	-0.4	69	69
LPA/LPA1-2-3	-0.063	0.14	-9999	-0.3	75	75
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.019	0	-9999	-10000	0	0
stress fiber formation	-0.035	0.12	-9999	-0.27	67	67
GNAZ	-0.066	0.15	-9999	-0.34	70	70
EGFR/PI3K-beta/Gab1	-0.07	0.1	-9999	-0.25	70	70
positive regulation of dendritic cell cytokine production	-0.064	0.14	-9999	-0.3	75	75
LPA/LPA2/MAGI-3	0.019	0.037	-9999	-0.32	3	3
ARHGEF1	-0.025	0.12	-9999	-0.26	65	65
GNAI2	-0.047	0.14	-9999	-0.32	65	65
GNAI3	-0.047	0.14	-9999	-0.32	65	65
GNAI1	-0.055	0.14	-9999	-0.33	69	69
LPA/LPA3	-0.033	0.076	-9999	-0.16	85	85
LPA/LPA2	0.006	0.042	-9999	-0.39	3	3
LPA/LPA1	-0.068	0.16	-9999	-0.29	108	108
HB-EGF/EGFR	-0.046	0.14	-9999	-0.32	68	68
HBEGF	-0.049	0.16	-9999	-0.38	65	65
mol:DAG	-0.008	0.079	-9999	-0.34	7	7
cAMP biosynthetic process	-0.11	0.18	-9999	-0.44	74	74
NFKB1	0.019	0	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
GNB1	0.019	0.001	-9999	-10000	0	0
LYN	-0.036	0.15	-9999	-0.44	28	28
GNAQ	-0.007	0.056	-9999	-0.25	4	4
LPAR2	0.014	0.05	-9999	-0.54	3	3
LPAR3	-0.044	0.11	-9999	-0.24	85	85
LPAR1	-0.085	0.21	-9999	-0.52	66	66
IL8	-0.094	0.17	-9999	-0.36	64	64
PTK2	-0.056	0.13	-9999	-0.28	75	75
Rac1/GDP	0.014	0	-9999	-10000	0	0
CASP3	-0.062	0.13	-9999	-0.29	73	73
EGFR	-0.008	0.087	-9999	-0.27	33	33
PLCG1	-0.025	0.087	-9999	-0.25	27	27
PLD2	-0.056	0.13	-9999	-0.28	75	75
G12/G13	-0.028	0.13	-9999	-0.29	65	65
PI3K-beta	-0.042	0.086	-9999	-0.37	11	11
cell migration	-0.006	0.091	-9999	-0.27	23	23
SLC9A3R2	0.018	0.014	-9999	-0.24	1	1
PXN	-0.036	0.12	-9999	-0.27	67	67
HRAS/GTP	-0.079	0.17	-9999	-0.41	69	69
RAC1	0.019	0	-9999	-10000	0	0
MMP9	-0.082	0.21	-9999	-0.52	68	68
PRKCE	0.019	0	-9999	-10000	0	0
PRKCD	-0.001	0.075	-9999	-0.34	6	6
Gi(beta/gamma)	-0.077	0.17	-9999	-0.4	69	69
mol:LPA	-0.008	0.035	-9999	-0.18	2	2
TRIP6/p130 Cas/FAK1/Paxillin	-0.029	0.14	-9999	-0.31	44	44
MAPKKK cascade	-0.077	0.17	-9999	-0.4	69	69
contractile ring contraction involved in cytokinesis	0.01	0.045	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.064	0.14	-9999	-0.32	69	69
GNA15	-0.017	0.083	-9999	-0.35	13	13
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
MAPT	-0.073	0.13	-9999	-0.3	64	64
GNA11	-0.007	0.056	-9999	-0.25	4	4
Rac1/GTP	-0.025	0.25	-9999	-1	22	22
MMP2	-0.066	0.16	-9999	-0.3	107	107

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.15	0.32	-10000	0	-0.72	71	71
UGCG	-0.011	0.082	-10000	0	-0.78	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.061	0.21	-10000	0	-0.38	97	97
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.011	0.081	-10000	0	-0.76	2	2
mol:DAG	-0.011	0.079	-10000	0	-1.1	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.16	0.22	-10000	0	-0.47	112	112
FRAP1	-0.12	0.31	-10000	0	-0.55	112	112
FOXO3	-0.12	0.3	-10000	0	-0.55	112	112
AKT1	-0.14	0.33	-10000	0	-0.6	112	112
GAB2	0.016	0.031	-10000	0	-0.24	5	5
SMPD1	-0.007	0.058	-10000	0	-10000	0	0
SGMS1	-0.012	0.096	-10000	0	-1	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.023	0.008	-10000	0	-10000	0	0
CALM1	0.019	0	-10000	0	-10000	0	0
cell proliferation	-0.032	0.14	-10000	0	-0.32	19	19
EIF3A	0.019	0	-10000	0	-10000	0	0
PI3K	0.034	0.01	-10000	0	-10000	0	0
RPS6KB1	0.005	0.063	-10000	0	-0.25	13	13
mol:sphingomyelin	-0.011	0.079	-10000	0	-1.1	2	2
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.016	0.14	-10000	0	-0.54	25	25
PIK3R1	0.022	0.002	-10000	0	-10000	0	0
JAK1	0.022	0.002	-10000	0	-10000	0	0
NFKB1	0.019	0	-10000	0	-10000	0	0
MYC	-0.099	0.27	-10000	0	-0.52	94	94
MYB	-0.031	0.29	-10000	0	-1.3	19	19
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.17	0.36	-10000	0	-0.66	121	121
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.024	0.061	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.16	0.35	-10000	0	-0.64	121	121
Rac1/GDP	0.034	0.007	-10000	0	-10000	0	0
T cell proliferation	-0.15	0.32	-10000	0	-0.58	121	121
SHC1	0.02	0.001	-10000	0	-10000	0	0
RAC1	0.019	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.003	0.016	-10000	0	-0.066	19	19
PRKCZ	-0.16	0.34	-10000	0	-0.61	121	121
NF kappa B1 p50/RelA	-0.086	0.27	-10000	0	-0.47	112	112
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.17	0.35	-10000	0	-0.65	112	112
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
RELA	0.019	0	-10000	0	-10000	0	0
IL2RA	-0.12	0.24	-10000	0	-0.54	93	93
IL2RB	-0.08	0.22	-10000	0	-0.54	67	67
TERT	0.001	0.072	-10000	0	-0.27	22	22
E2F1	0.007	0.11	-10000	0	-0.45	19	19
SOS1	0.02	0.001	-10000	0	-10000	0	0
RPS6	0.019	0	-10000	0	-10000	0	0
mol:cAMP	-0.002	0.008	0.031	19	-10000	0	19
PTPN11	0.02	0.001	-10000	0	-10000	0	0
IL2RG	-0.15	0.26	-10000	0	-0.54	112	112
actin cytoskeleton organization	-0.15	0.32	-10000	0	-0.58	121	121
GRB2	0.02	0.001	-10000	0	-10000	0	0
IL2	0.008	0.016	-10000	0	-0.24	1	1
PIK3CA	0.021	0.014	-10000	0	-0.24	1	1
Rac1/GTP	0.046	0.013	-10000	0	-10000	0	0
LCK	-0.19	0.27	-10000	0	-0.54	142	142
BCL2	-0.075	0.24	-10000	0	-0.44	95	95

×

IL2 signaling events mediated by STAT5

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
GAB2	0.016	0.031	-9999	-0.24	5	5
ELF1	-0.063	0.16	-9999	-0.34	93	93
CCNA2	0.017	0.029	-9999	-0.54	1	1
PIK3CA	0.019	0.014	-9999	-0.24	1	1
JAK3	-0.018	0.14	-9999	-0.54	25	25
PIK3R1	0.019	0	-9999	-10000	0	0
JAK1	0.02	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.18	0.37	-9999	-0.68	121	121
SHC1	0.02	0	-9999	-10000	0	0
SP1	0.003	0.094	-9999	-0.34	26	26
IL2RA	-0.17	0.36	-9999	-0.78	93	93
IL2RB	-0.082	0.22	-9999	-0.54	67	67
SOS1	0.019	0	-9999	-10000	0	0
IL2RG	-0.15	0.26	-9999	-0.54	112	112
G1/S transition of mitotic cell cycle	-0.032	0.24	-9999	-0.81	30	30
PTPN11	0.02	0	-9999	-10000	0	0
CCND2	-0.022	0.21	-9999	-0.76	27	27
LCK	-0.2	0.27	-9999	-0.54	142	142
GRB2	0.019	0	-9999	-10000	0	0
IL2	0.005	0.016	-9999	-0.24	1	1
CDK6	0.014	0.052	-9999	-0.46	4	4
CCND3	-0.14	0.31	-9999	-0.61	96	96

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.053	0.17	-9999	-0.35	84	84
CRKL	0.018	0.014	-9999	-0.24	1	1
Rac1/GDP	0.014	0	-9999	-10000	0	0
DOCK1	0.019	0	-9999	-10000	0	0
ITGA4	-0.043	0.18	-9999	-0.54	41	41
alpha4/beta7 Integrin/MAdCAM1	-0.21	0.22	-9999	-0.36	237	237
EPO	0.011	0.021	-9999	-0.24	2	2
alpha4/beta7 Integrin	-0.076	0.2	-9999	-0.42	84	84
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.13	-9999	-0.38	41	41
EPO/EPOR (dimer)	0.022	0.017	-9999	-10000	0	0
lamellipodium assembly	0.041	0.01	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PI3K	0.028	0.009	-9999	-10000	0	0
ARF6	0.019	0	-9999	-10000	0	0
JAK2	-0.002	0.12	-9999	-0.31	41	41
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
MADCAM1	-0.29	0.27	-9999	-0.54	204	204
cell adhesion	-0.21	0.22	-9999	-0.35	237	237
CRKL/CBL	0.028	0.009	-9999	-10000	0	0
ITGB1	0.017	0.019	-9999	-0.24	2	2
SRC	-0.051	0.18	-9999	-0.38	76	76
ITGB7	-0.063	0.2	-9999	-0.54	54	54
RAC1	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.059	0.2	-9999	-0.43	76	76
p130Cas/Crk/Dock1	-0.018	0.16	-9999	-0.47	28	28
VCAM1	-0.077	0.21	-9999	-0.54	63	63
RHOA	0.019	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.011	0.1	-9999	-0.28	41	41
BCAR1	-0.041	0.17	-9999	-0.35	76	76
EPOR	0.018	0.014	-9999	-0.24	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
GIT1	0.019	0	-9999	-10000	0	0
Rac1/GTP	0.041	0.01	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.026	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.019	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.008	0.076	-9999	-0.54	7	7
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.019	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.021	0.025	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.019	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.019	0	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
MAP3K12	0.019	0	-9999	-10000	0	0
FGR	-0.036	0.16	-9999	-0.54	36	36
p38 alpha/TAB1	-0.13	0.15	-9999	-0.3	122	122
PRKG1	-0.088	0.13	-9999	-0.24	148	148
DUSP8	-0.026	0.1	-9999	-0.24	63	63
PGK/cGMP/p38 alpha	-0.16	0.16	-9999	-0.35	119	119
apoptosis	-0.12	0.14	-9999	-0.28	122	122
RAL/GTP	0.026	0	-9999	-10000	0	0
LYN	-0.004	0.11	-9999	-0.54	15	15
DUSP1	0.014	0.036	-9999	-0.24	7	7
PAK1	0.018	0.014	-9999	-0.24	1	1
SRC	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.049	0	-9999	-10000	0	0
TRAF6	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.019	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.026	0	-9999	-10000	0	0
MAPK11	-0.16	0.21	-9999	-0.39	122	122
BLK	-0.34	0.26	-9999	-0.54	236	236
HCK	-0.028	0.16	-9999	-0.54	31	31
MAP2K3	0.019	0	-9999	-10000	0	0
DUSP16	0.019	0	-9999	-10000	0	0
DUSP10	0.013	0.058	-9999	-0.54	4	4
TRAF6/MEKK3	0.024	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	-0.12	0.18	-9999	-0.32	122	122
positive regulation of innate immune response	-0.17	0.23	-9999	-0.42	124	124
LCK	-0.2	0.27	-9999	-0.54	142	142
p38alpha-beta/MKP7	-0.16	0.22	-9999	-0.4	121	121
p38alpha-beta/MKP5	-0.16	0.22	-9999	-0.4	124	124
PGK/cGMP	-0.057	0.087	-9999	-0.16	148	148
PAK2	0.019	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.16	0.22	-9999	-0.4	122	122
CDC42	0.019	0	-9999	-10000	0	0
RALB	0.019	0	-9999	-10000	0	0
RALA	0.019	0	-9999	-10000	0	0
PAK3	-0.014	0.081	-9999	-0.24	40	40

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0.042	0.014	0.25	1	-10000	0	1
DAPP1	-0.34	0.43	-10000	0	-0.75	154	154
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.42	0.46	-10000	0	-0.86	167	167
mol:DAG	-0.13	0.16	-10000	0	-0.31	145	145
HRAS	0.02	0.001	-10000	0	-10000	0	0
RAP1A	0.02	0.001	-10000	0	-10000	0	0
ARF5/GDP	-0.005	0.12	-10000	0	-0.36	22	22
PLCG2	-0.03	0.16	-10000	0	-0.54	32	32
PLCG1	0.019	0	-10000	0	-10000	0	0
ARF5	0.019	0	-10000	0	-10000	0	0
mol:GTP	0.026	0.013	0.23	1	-10000	0	1
ARF1/GTP	0.04	0.013	0.24	1	-10000	0	1
RHOA	0.019	0	-10000	0	-10000	0	0
YES1	0.019	0	-10000	0	-10000	0	0
RAP1A/GTP	0.031	0.013	0.23	1	-10000	0	1
ADAP1	0.023	0.049	-10000	0	-0.24	12	12
ARAP3	0.026	0.013	0.23	1	-10000	0	1
INPPL1	0.019	0	-10000	0	-10000	0	0
PREX1	0.016	0.041	-10000	0	-0.54	2	2
ARHGEF6	-0.005	0.11	-10000	0	-0.54	16	16
ARHGEF7	0.019	0	-10000	0	-10000	0	0
ARF1	0.019	0	-10000	0	-10000	0	0
NRAS	0.02	0.001	-10000	0	-10000	0	0
FYN	0.019	0	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
FGR	-0.036	0.16	-10000	0	-0.54	36	36
mol:Ca2+	-0.053	0.081	-10000	0	-0.15	87	87
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	-0.014	0.13	-10000	0	-0.54	22	22
ZAP70	-0.17	0.26	-10000	0	-0.54	126	126
mol:IP3	-0.079	0.11	-10000	0	-0.21	137	137
LYN	-0.004	0.11	-10000	0	-0.54	15	15
ARF1/GDP	-0.005	0.12	-10000	0	-0.36	22	22
RhoA/GDP	0.029	0.062	-10000	0	-0.34	2	2
PDK1/Src/Hsp90	0.037	0.019	-10000	0	-0.32	1	1
BLNK	-0.19	0.27	-10000	0	-0.54	140	140
actin cytoskeleton reorganization	0.02	0.099	-10000	0	-0.48	3	3
SRC	0.019	0	-10000	0	-10000	0	0
PLEKHA2	-0.03	0.14	-10000	0	-0.33	62	62
RAC1	0.019	0	-10000	0	-10000	0	0
PTEN	0.013	0.028	-10000	0	-0.51	1	1
HSP90AA1	0.017	0.029	-10000	0	-0.54	1	1
ARF6/GTP	0.042	0.013	0.25	1	-10000	0	1
RhoA/GTP	0.037	0.012	0.23	1	-10000	0	1
Src family/SYK family/BLNK-LAT	-0.45	0.54	-10000	0	-0.94	167	167
BLK	-0.34	0.26	-10000	0	-0.54	236	236
PDPK1	0.019	0	-10000	0	-10000	0	0
CYTH1	0.032	0.012	0.23	1	-10000	0	1
HCK	-0.028	0.16	-10000	0	-0.54	31	31
CYTH3	0.032	0.014	0.23	1	-10000	0	1
CYTH2	0.032	0.012	0.23	1	-10000	0	1
KRAS	0.019	0.014	-10000	0	-0.24	1	1
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.048	0.015	-10000	0	-10000	0	0
SGK1	0.043	0.016	-10000	0	-10000	0	0
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
mol:GDP	-0.016	0.12	-10000	0	-0.31	34	34
SOS1	0.019	0	-10000	0	-10000	0	0
SYK	-0.052	0.19	-10000	0	-0.54	47	47
ARF6/GDP	0.027	0.061	-10000	0	-0.34	2	2
mol:PI-3-4-5-P3	0	0.016	0.28	1	-10000	0	1
ARAP3/RAP1A/GTP	0.031	0.013	0.23	1	-10000	0	1
VAV1	-0.09	0.22	-10000	0	-0.54	72	72
mol:PI-3-4-P2	-0.043	0.15	-10000	0	-0.38	62	62
RAS family/GTP/PI3K Class I	0.04	0.012	0.19	1	-10000	0	1
PLEKHA1	-0.028	0.13	-10000	0	-0.32	62	62
Rac1/GDP	-0.005	0.12	-10000	0	-0.36	22	22
LAT	-0.049	0.18	-10000	0	-0.54	45	45
Rac1/GTP	-0.027	0.16	-10000	0	-0.44	35	35
ITK	-0.047	0.12	-10000	0	-0.24	105	105
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.19	0.24	-10000	0	-0.47	145	145
LCK	-0.2	0.27	-10000	0	-0.54	142	142
BTK	-0.016	0.1	-10000	0	-0.24	64	64

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.019	0	-9999	-10000	0	0
LAT2	-0.063	0.24	-9999	-0.54	60	60
AP1	-0.087	0.28	-9999	-0.6	77	77
mol:PIP3	-0.082	0.27	-9999	-0.58	75	75
IKBKB	-0.04	0.15	-9999	-0.3	73	73
AKT1	0.026	0.078	-9999	-0.26	7	7
IKBKG	-0.04	0.15	-9999	-0.3	72	72
MS4A2	0.009	0.04	-9999	-0.25	8	8
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
MAP3K1	-0.057	0.23	-9999	-0.51	69	69
mol:Ca2+	-0.05	0.2	-9999	-0.41	75	75
LYN	-0.005	0.11	-9999	-0.55	15	15
CBLB	-0.028	0.17	-9999	-0.44	41	41
SHC1	0.019	0	-9999	-10000	0	0
RasGAP/p62DOK	0.033	0.025	-9999	-0.29	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	-0.075	0.21	-9999	-0.54	62	62
PLD2	0.006	0.084	-9999	-0.25	31	31
PTPN13	-0.022	0.17	-9999	-0.5	30	30
PTPN11	0.016	0.011	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.021	0.11	-9999	-0.29	27	27
SYK	-0.054	0.19	-9999	-0.55	47	47
GRB2	0.019	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.14	0.25	-9999	-0.6	73	73
LAT	-0.061	0.22	-9999	-0.47	66	66
PAK2	-0.076	0.27	-9999	-0.59	69	69
NFATC2	-0.03	0.14	-9999	-0.56	23	23
HRAS	-0.094	0.3	-9999	-0.66	70	70
GAB2	0.015	0.031	-9999	-0.24	5	5
PLA2G1B	0.03	0.015	-9999	-10000	0	0
Fc epsilon R1	-0.007	0.11	-9999	-0.32	34	34
Antigen/IgE/Fc epsilon R1	-0.006	0.097	-9999	-0.29	34	34
mol:GDP	-0.12	0.32	-9999	-0.68	81	81
JUN	-0.008	0.079	-9999	-0.24	37	37
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.019	0.001	-9999	-10000	0	0
FOS	0.01	0.047	-9999	-0.24	12	12
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.036	0.18	-9999	-0.39	57	57
CHUK	-0.04	0.15	-9999	-0.3	72	72
KLRG1	-0.033	0.17	-9999	-0.38	56	56
VAV1	-0.077	0.25	-9999	-0.52	74	74
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.028	0.17	-9999	-0.44	41	41
negative regulation of mast cell degranulation	-0.065	0.23	-9999	-0.5	70	70
BTK	-0.13	0.35	-9999	-0.78	75	75
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.039	0.18	-9999	-0.41	50	50
GAB2/PI3K/SHP2	-0.024	0.065	-9999	-0.25	14	14
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.046	0.21	-9999	-0.45	61	61
RAF1	0.018	0.018	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.047	0.19	-9999	-0.39	75	75
FCER1G	-0.029	0.16	-9999	-0.54	31	31
FCER1A	0.004	0.06	-9999	-0.26	16	16
Antigen/IgE/Fc epsilon R1/Fyn	0.006	0.091	-9999	-0.26	34	34
MAPK3	0.029	0.016	-9999	-10000	0	0
MAPK1	0.029	0.016	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
MAPK8	0.01	0.072	-9999	-10000	0	0
DUSP1	0.014	0.036	-9999	-0.24	7	7
NF-kappa-B/RelA	-0.043	0.07	-9999	-0.2	38	38
actin cytoskeleton reorganization	-0.026	0.17	-9999	-0.5	33	33
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.067	0.26	-9999	-0.57	68	68
FER	-0.028	0.17	-9999	-0.44	41	41
RELA	0.019	0	-9999	-10000	0	0
ITK	-0.12	0.22	-9999	-0.46	106	106
SOS1	0.019	0	-9999	-10000	0	0
PLCG1	-0.11	0.32	-9999	-0.7	72	72
cytokine secretion	-0.032	0.051	-9999	-0.16	1	1
SPHK1	-0.031	0.17	-9999	-0.45	42	42
PTK2	-0.028	0.18	-9999	-0.53	32	32
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.13	0.26	-9999	-0.62	71	71
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.065	0.25	-9999	-0.55	69	69
MAP2K2	0.024	0.016	-9999	-10000	0	0
MAP2K1	0.024	0.016	-9999	-10000	0	0
MAP2K7	0.019	0	-9999	-10000	0	0
KLRG1/SHP2	-0.028	0.16	-9999	-0.42	40	40
MAP2K4	0.025	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.006	0.13	-9999	-0.33	42	42
mol:Choline	0.006	0.083	-9999	-0.25	31	31
SHC/Grb2/SOS1	-0.007	0.16	-9999	-0.43	38	38
FYN	0.019	0	-9999	-10000	0	0
DOK1	0.019	0	-9999	-10000	0	0
PXN	-0.018	0.16	-9999	-0.52	27	27
HCLS1	-0.073	0.25	-9999	-0.55	65	65
PRKCB	-0.073	0.2	-9999	-0.41	83	83
FCGR2B	-0.005	0.11	-9999	-0.52	16	16
IGHE	-0.001	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.067	0.24	-9999	-0.51	70	70
LCP2	-0.016	0.14	-9999	-0.54	23	23
PLA2G4A	-0.032	0.17	-9999	-0.44	45	45
RASA1	0.017	0.029	-9999	-0.54	1	1
mol:Phosphatidic acid	0.006	0.083	-9999	-0.25	31	31
IKK complex	-0.015	0.11	-9999	-0.22	65	65
WIPF1	0.011	0.064	-9999	-0.54	5	5

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.001	0.38	-9999	-0.79	43	43
HDAC7	0.021	0.004	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	0	0.36	-9999	-0.76	29	29
SMAD4	0.02	0	-9999	-10000	0	0
ID2	-0.001	0.38	-9999	-0.79	43	43
AP1	0.007	0.069	-9999	-0.3	7	7
ABCG2	-0.021	0.41	-9999	-0.84	47	47
HIF1A	0.026	0.074	-9999	-10000	0	0
TFF3	-0.059	0.43	-9999	-0.82	62	62
GATA2	0.016	0.036	-9999	-0.24	7	7
AKT1	0.018	0.092	-9999	-0.22	5	5
response to hypoxia	-0.001	0.094	-9999	-0.2	22	22
MCL1	-0.001	0.38	-9999	-0.79	43	43
NDRG1	-0.003	0.38	-9999	-0.8	43	43
SERPINE1	-0.01	0.39	-9999	-0.8	45	45
FECH	-0.001	0.38	-9999	-0.79	43	43
FURIN	-0.001	0.38	-9999	-0.79	43	43
NCOA2	0.02	0.014	-9999	-0.24	1	1
EP300	0.025	0.15	-9999	-0.28	39	39
HMOX1	-0.003	0.38	-9999	-0.79	43	43
BHLHE40	-0.002	0.38	-9999	-0.79	43	43
BHLHE41	-0.006	0.39	-9999	-0.81	44	44
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.084	0.11	-9999	-10000	0	0
ENG	0.074	0.093	-9999	-10000	0	0
JUN	-0.007	0.079	-9999	-0.24	37	37
RORA	-0.003	0.38	-9999	-0.78	44	44
ABCB1	-0.11	0.34	-9999	-1.3	29	29
TFRC	-0.001	0.38	-9999	-0.79	43	43
CXCR4	-0.021	0.41	-9999	-0.84	50	50
TF	-0.081	0.42	-9999	-0.84	56	56
CITED2	-0.001	0.38	-9999	-0.79	43	43
HIF1A/ARNT	-0.006	0.45	-9999	-0.89	42	42
LDHA	-0.017	0.077	-9999	-1.3	1	1
ETS1	-0.001	0.38	-9999	-0.79	43	43
PGK1	-0.001	0.38	-9999	-0.79	43	43
NOS2	-0.011	0.38	-9999	-0.8	44	44
ITGB2	-0.033	0.43	-9999	-0.87	52	52
ALDOA	-0.001	0.38	-9999	-0.79	43	43
Cbp/p300/CITED2	-0.015	0.42	-9999	-0.87	42	42
FOS	0.011	0.047	-9999	-0.24	12	12
HK2	-0.001	0.38	-9999	-0.79	43	43
SP1	0.025	0.022	-9999	-10000	0	0
GCK	-0.089	0.48	-9999	-1.3	43	43
HK1	-0.001	0.38	-9999	-0.79	43	43
NPM1	-0.001	0.38	-9999	-0.79	43	43
EGLN1	-0.001	0.38	-9999	-0.79	43	43
CREB1	0.028	0.001	-9999	-10000	0	0
PGM1	-0.001	0.38	-9999	-0.79	43	43
SMAD3	0.02	0	-9999	-10000	0	0
EDN1	0.022	0.21	-9999	-0.63	14	14
IGFBP1	-0.012	0.38	-9999	-0.8	43	43
VEGFA	0.021	0.33	-9999	-0.65	30	30
HIF1A/JAB1	0.033	0.05	-9999	-10000	0	0
CP	-0.11	0.46	-9999	-0.86	68	68
CXCL12	-0.013	0.4	-9999	-0.82	49	49
COPS5	0.02	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0.031	0.001	-9999	-10000	0	0
BNIP3	-0.002	0.38	-9999	-0.79	43	43
EGLN3	-0.004	0.38	-9999	-0.79	44	44
CA9	-0.034	0.39	-9999	-0.82	46	46
TERT	-0.011	0.39	-9999	-0.79	46	46
ENO1	-0.001	0.38	-9999	-0.79	43	43
PFKL	-0.001	0.38	-9999	-0.79	43	43
NCOA1	0.019	0.001	-9999	-10000	0	0
ADM	-0.042	0.39	-9999	-0.8	49	49
ARNT	0.026	0.074	-9999	-10000	0	0
HNF4A	-0.024	0.083	-9999	-0.25	34	34
ADFP	-0.012	0.38	-9999	-0.79	44	44
SLC2A1	0.027	0.32	-9999	-0.65	28	28
LEP	-0.034	0.38	-9999	-0.81	43	43
HIF1A/ARNT/Cbp/p300	-0.01	0.37	-9999	-0.75	35	35
EPO	0.056	0.26	-9999	-0.55	5	5
CREBBP	0.025	0.15	-9999	-0.3	32	32
HIF1A/ARNT/Cbp/p300/HDAC7	0.017	0.37	-9999	-0.76	29	29
PFKFB3	-0.001	0.38	-9999	-0.79	43	43
NT5E	-0.028	0.38	-9999	-0.8	47	47

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.034	0.1	-9999	-0.33	26	26
EFNA5	0.008	0.076	-9999	-0.54	7	7
FYN	-0.024	0.092	-9999	-0.3	26	26
neuron projection morphogenesis	-0.034	0.1	-9999	-0.33	26	26
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.034	0.1	-9999	-0.33	26	26
EPHA5	-0.071	0.15	-9999	-0.3	102	102

×

Visual signal transduction: Cones

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.033	0.12	-9999	-0.27	78	78
RGS9BP	0.017	0.019	-9999	-0.24	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
mol:Na +	0.001	0.023	-9999	-10000	0	0
mol:ADP	0.007	0.011	-9999	-0.16	1	1
GNAT2	0.017	0.015	-9999	-0.24	1	1
RGS9-1/Gbeta5/R9AP	-0.11	0.18	-9999	-0.32	150	150
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.013	0.021	-9999	-10000	0	0
GRK7	0.01	0.016	-9999	-0.24	1	1
CNGB3	0	0.042	-9999	-0.24	10	10
Cone Metarhodopsin II/X-Arrestin	0.003	0.006	-9999	-10000	0	0
mol:Ca2+	-0.001	0.02	-9999	-10000	0	0
Cone PDE6	-0.091	0.15	-9999	-0.27	150	150
Cone Metarhodopsin II	0.007	0.009	-9999	-0.12	1	1
Na + (4 Units)	0.001	0.021	-9999	-10000	0	0
GNAT2/GDP	-0.084	0.15	-9999	-0.26	150	150
GNB5	0.017	0.029	-9999	-0.54	1	1
mol:GMP (4 units)	0.008	0.017	-9999	-10000	0	0
Cone Transducin	-0.035	0.13	-9999	-0.29	78	78
SLC24A2	0	0	-9999	-10000	0	0
GNB3/GNGT2	-0.06	0.17	-9999	-0.38	78	78
GNB3	0.013	0.054	-9999	-0.42	5	5
GNAT2/GTP	0.012	0.01	-9999	-0.16	1	1
CNGA3	0	0	-9999	-10000	0	0
ARR3	0.004	0.008	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	0.001	0.023	-9999	-10000	0	0
mol:Pi	-0.11	0.18	-9999	-0.32	150	150
Cone CNG Channel	0.01	0.024	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	0	0	-9999	-10000	0	0
RGS9	-0.21	0.27	-9999	-0.54	150	150
PDE6C	0	0	-9999	-10000	0	0
GNGT2	-0.095	0.22	-9999	-0.54	75	75
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.033	-9999	-0.24	6	6

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.036	0.16	-10000	0	-0.54	36	36
positive regulation of NF-kappaB transcription factor activity	-0.027	0.13	-10000	0	-0.3	62	62
MAP2K4	0.009	0.1	-10000	0	-0.36	15	15
IKBKB	0.019	0	-10000	0	-10000	0	0
TNFRSF10B	0.008	0.076	-10000	0	-0.54	7	7
TNFRSF10A	-0.046	0.18	-10000	0	-0.54	43	43
SMPD1	-0.002	0.073	-10000	0	-0.21	41	41
IKBKG	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	-0.003	0.075	-10000	0	-0.26	29	29
TRAIL/TRAILR2	-0.02	0.14	-10000	0	-0.4	41	41
TRAIL/TRAILR3	-0.038	0.16	-10000	0	-0.41	55	55
TRAIL/TRAILR1	-0.057	0.19	-10000	0	-0.46	64	64
TRAIL/TRAILR4	-0.027	0.13	-10000	0	-0.3	62	62
TRAIL/TRAILR1/DAP3/GTP	-0.032	0.16	-10000	0	-0.36	64	64
IKK complex	0.022	0.064	-10000	0	-10000	0	0
RIPK1	0.019	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0	-10000	0	-10000	0	0
MAPK3	-0.014	0.12	-10000	0	-0.38	36	36
MAP3K1	0.002	0.11	-10000	0	-0.29	39	39
TRAILR4 (trimer)	-0.003	0.075	-10000	0	-0.26	29	29
TRADD	0.019	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	-0.046	0.18	-10000	0	-0.54	43	43
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.014	0.13	-10000	0	-0.29	64	64
CFLAR	0.019	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.12	-10000	0	-0.38	36	36
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.01	0.15	-10000	0	-0.32	64	64
mol:ceramide	-0.002	0.072	-10000	0	-0.2	41	41
FADD	0.018	0.014	-10000	0	-0.24	1	1
MAPK8	0.015	0.1	-10000	0	-0.34	15	15
TRAF2	0.019	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.018	0.14	-10000	0	-0.54	24	24
CHUK	0.019	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.036	0.17	-10000	0	-0.39	64	64
DAP3	0.019	0	-10000	0	-10000	0	0
CASP10	-0.033	0.17	0.26	1	-0.44	42	43
JNK cascade	-0.027	0.13	-10000	0	-0.3	62	62
TRAIL (trimer)	-0.036	0.16	-10000	0	-0.54	36	36
TNFRSF10C	-0.018	0.14	-10000	0	-0.54	24	24
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.021	0.15	-10000	0	-0.33	64	64
TRAIL/TRAILR2/FADD	-0.003	0.12	-10000	0	-0.33	41	41
cell death	-0.002	0.072	-10000	0	-0.2	41	41
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.012	0.091	-10000	0	-0.24	41	41
TRAILR2 (trimer)	0.008	0.076	-10000	0	-0.54	7	7
CASP8	0.005	0.075	-10000	0	-0.88	2	2
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.019	0.1	-10000	0	-0.27	41	41

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.019	0	-9999	-10000	0	0
GNAT1/GTP	0	0	-9999	-10000	0	0
Metarhodopsin II/Arrestin	0	0	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.041	0.12	-9999	-0.33	57	57
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0	-9999	-10000	0	0
GRK1	0	0	-9999	-10000	0	0
CNG Channel	-0.085	0.15	-9999	-0.32	95	95
mol:Na +	-0.008	0.06	-9999	-0.27	10	10
mol:ADP	0	0	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.11	0.18	-9999	-0.32	150	150
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	0.005	0.066	-9999	-0.28	10	10
CNGB1	0.01	0.009	-9999	-10000	0	0
RDH5	0.008	0.066	-9999	-0.36	10	10
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.062	-9999	-0.26	10	10
Na + (4 Units)	-0.019	0.048	-9999	-0.25	10	10
RGS9	-0.21	0.27	-9999	-0.54	150	150
GNB1/GNGT1	-0.016	0.069	-9999	-10000	0	0
GNAT1/GDP	-0.092	0.15	-9999	-0.27	150	150
GUCY2D	0.009	0.041	-9999	-0.24	9	9
GNGT1	-0.044	0.1	-9999	-0.24	75	75
GUCY2F	0	0	-9999	-10000	0	0
GNB5	0.017	0.029	-9999	-0.54	1	1
mol:GMP (4 units)	-0.068	0.18	-9999	-0.36	91	91
mol:11-cis-retinal	0.008	0.066	-9999	-0.36	10	10
mol:cGMP	0.001	0.062	-9999	-0.3	6	6
GNB1	0.019	0	-9999	-10000	0	0
Rhodopsin	0.007	0.047	-9999	-0.39	4	4
SLC24A1	0.019	0	-9999	-10000	0	0
CNGA1	0.006	0.068	-9999	-0.43	8	8
Metarhodopsin II	0	0	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.002	0.066	-9999	-0.32	6	6
RGS9BP	0.017	0.019	-9999	-0.24	2	2
Metarhodopsin II/Transducin	-0.008	0.036	-9999	-10000	0	0
GCAP Family/Ca ++	-0.004	0.061	-9999	-0.32	5	5
PDE6A/B	-0.046	0.15	-9999	-0.36	69	69
mol:Pi	-0.11	0.18	-9999	-0.32	150	150
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.009	0.052	-9999	-10000	0	0
PDE6B	-0.074	0.21	-9999	-0.54	61	61
PDE6A	0.011	0.039	-9999	-0.24	8	8
PDE6G	-0.068	0.2	-9999	-0.54	57	57
RHO	0	0	-9999	-10000	0	0
PDE6	-0.16	0.24	-9999	-0.36	186	186
GUCA1A	-0.027	0.095	-9999	-0.24	58	58
GC2/GCAP Family	-0.004	0.061	-9999	-0.32	5	5
GUCA1C	0	0	-9999	-10000	0	0
GUCA1B	0.011	0.064	-9999	-0.54	5	5

×

TCGA08_p53

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
CDKN2A	-0.072	0.093	-10000	0	-0.17	172	172
TP53	-0.027	0.033	-10000	0	-0.15	4	4
Senescence	-0.028	0.032	-10000	0	-0.14	4	4
Apoptosis	-0.028	0.032	-10000	0	-0.14	4	4
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.051	0.06	0.25	4	-0.17	2	6
MDM4	0.019	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.083	0.19	-9999	-0.43	53	53
BAG4	0.017	0.029	-9999	-0.54	1	1
BAD	-0.012	0.063	-9999	-0.13	53	53
NFKBIA	0.019	0	-9999	-10000	0	0
BIRC3	-0.18	0.26	-9999	-0.54	128	128
BAX	-0.012	0.063	-9999	-0.13	53	53
EnzymeConsortium:3.1.4.12	-0.017	0.046	-9999	-0.1	53	53
IKBKB	-0.072	0.18	-9999	-0.4	53	53
MAP2K2	0.001	0.062	-9999	-10000	0	0
MAP2K1	0.001	0.062	-9999	-10000	0	0
SMPD1	-0.011	0.046	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	-0.073	0.18	-9999	-0.41	56	56
MAP2K4	-0.004	0.061	-9999	-10000	0	0
protein ubiquitination	-0.072	0.18	-9999	-0.41	53	53
EnzymeConsortium:2.7.1.37	0.005	0.066	-9999	-10000	0	0
response to UV	0	0.001	-9999	-0.002	53	53
RAF1	-0.005	0.063	-9999	-10000	0	0
CRADD	0.018	0.014	-9999	-0.24	1	1
mol:ceramide	-0.02	0.065	-9999	-0.14	53	53
I-kappa-B-alpha/RELA/p50/ubiquitin	0.026	0	-9999	-10000	0	0
MADD	0.019	0	-9999	-10000	0	0
MAP3K1	-0.012	0.063	-9999	-10000	0	0
TRADD	0.019	0	-9999	-10000	0	0
RELA/p50	0.019	0	-9999	-10000	0	0
MAPK3	0.005	0.061	-9999	-10000	0	0
MAPK1	0.005	0.061	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.028	0	-9999	-10000	0	0
FADD	-0.083	0.19	-9999	-0.43	54	54
KSR1	-0.012	0.064	-9999	-0.13	53	53
MAPK8	0.003	0.058	-9999	-10000	0	0
TRAF2	0.019	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	-0.072	0.18	-9999	-0.4	53	53
TNF R/SODD	0.027	0.021	-9999	-0.38	1	1
TNF	-0.095	0.22	-9999	-0.54	75	75
CYCS	-0.01	0.061	-9999	-0.12	53	53
IKBKG	-0.072	0.18	-9999	-0.4	53	53
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.094	0.19	-9999	-0.34	128	128
RELA	0.019	0	-9999	-10000	0	0
RIPK1	0.019	0.001	-9999	-10000	0	0
AIFM1	-0.01	0.061	-9999	-0.12	53	53
TNF/TNF R/SODD	-0.035	0.14	-9999	-0.32	76	76
TNFRSF1A	0.019	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	-0.001	0.075	-9999	-0.78	2	2
NSMAF	-0.081	0.18	-9999	-0.42	53	53
response to hydrogen peroxide	0	0.001	-9999	-0.002	53	53
BCL2	0.019	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.026	0.03	-9999	-0.38	2	2
FBXW11	0.019	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.033	0.001	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.065	0.18	-9999	-0.46	47	47
NFKBIA	-0.1	0.2	-9999	-0.31	142	142
MAPK14	0.019	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.033	0	-9999	-10000	0	0
ARRB2	0.02	0	-9999	-10000	0	0
REL	0.019	0.001	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.026	-9999	-0.32	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.033	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
NF kappa B1 p50 dimer	0.025	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
NFKB1	0.026	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.08	0.16	-9999	-0.27	142	142
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.059	0.17	-9999	-0.45	47	47
SRC	0.019	0	-9999	-10000	0	0
PI3K	0.028	0.009	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.08	0.16	-9999	-0.27	142	142
IKBKB	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
SYK	-0.052	0.19	-9999	-0.54	47	47
I kappa B alpha/PIK3R1	-0.086	0.19	-9999	-0.5	47	47
cell death	-0.056	0.17	-9999	-0.43	47	47
NF kappa B1 p105/c-Rel	0.033	0.001	-9999	-10000	0	0
LCK	-0.2	0.27	-9999	-0.54	142	142
BCL3	0.016	0.041	-9999	-0.54	2	2

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.15	0.3	-9999	-0.79	35	35
PCK1	-0.11	0.19	-9999	-0.52	23	23
HNF4A	-0.17	0.32	-9999	-0.92	30	30
KCNJ11	-0.2	0.38	-9999	-0.92	53	53
AKT1	-0.088	0.16	-9999	-0.38	26	26
response to starvation	-0.001	0.011	-9999	-10000	0	0
DLK1	-0.2	0.37	-9999	-0.9	53	53
NKX2-1	-0.075	0.17	-9999	-0.47	2	2
ACADM	-0.15	0.3	-9999	-0.76	39	39
TAT	-0.08	0.16	-9999	-0.6	4	4
CEBPB	0.017	0.009	-9999	-10000	0	0
CEBPA	-0.029	0.16	-9999	-0.54	31	31
TTR	-0.13	0.28	-9999	-0.78	38	38
PKLR	-0.5	0.53	-9999	-0.94	205	205
APOA1	-0.19	0.35	-9999	-1	28	28
CPT1C	-0.17	0.34	-9999	-0.89	39	39
ALAS1	-0.052	0.16	-9999	-0.59	1	1
TFRC	-0.1	0.21	-9999	-0.71	7	7
FOXF1	-0.021	0.14	-9999	-0.51	28	28
NF1	0.027	0.003	-9999	-10000	0	0
HNF1A (dimer)	0.019	0	-9999	-10000	0	0
CPT1A	-0.15	0.3	-9999	-0.78	37	37
HMGCS1	-0.15	0.3	-9999	-0.78	37	37
NR3C1	0.019	0	-9999	-10000	0	0
CPT1B	-0.16	0.31	-9999	-0.78	43	43
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.019	0	-9999	-10000	0	0
GCK	-0.22	0.41	-9999	-0.96	65	65
CREB1	0.009	0.029	-9999	-10000	0	0
IGFBP1	-0.062	0.14	-9999	-10000	0	0
PDX1	-0.064	0.16	-9999	-10000	0	0
UCP2	-0.22	0.41	-9999	-0.98	62	62
ALDOB	-0.16	0.32	-9999	-0.84	36	36
AFP	-0.012	0.071	-9999	-10000	0	0
BDH1	-0.16	0.31	-9999	-0.84	34	34
HADH	-0.16	0.32	-9999	-0.83	36	36
F2	-0.19	0.35	-9999	-1	27	27
HNF1A	0.019	0	-9999	-10000	0	0
G6PC	-0.014	0.096	-9999	-0.47	1	1
SLC2A2	-0.09	0.19	-9999	-0.54	3	3
INS	-0.008	0.003	-9999	-10000	0	0
FOXA1	0.006	0.057	-9999	-0.27	12	12
FOXA3	-0.026	0.13	-9999	-0.39	33	33
FOXA2	-0.2	0.37	-9999	-0.83	53	53
ABCC8	-0.17	0.32	-9999	-0.82	37	37
ALB	-0.014	0.086	-9999	-10000	0	0

×

Noncanonical Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.019	0.14	-9999	-0.49	27	27
GNB1/GNG2	-0.031	0.12	-9999	-0.38	22	22
mol:DAG	-0.024	0.11	-9999	-0.38	17	17
PLCG1	-0.025	0.11	-9999	-0.39	17	17
YES1	-0.039	0.1	-9999	-0.36	19	19
FZD3	0.019	0	-9999	-10000	0	0
FZD6	-0.01	0.12	-9999	-0.54	19	19
G protein	-0.023	0.11	-9999	-0.36	22	22
MAP3K7	-0.023	0.1	-9999	-0.35	17	17
mol:Ca2+	-0.023	0.1	-9999	-0.34	22	22
mol:IP3	-0.024	0.11	-9999	-0.38	17	17
NLK	0.012	0.01	-9999	-10000	0	0
GNB1	0.019	0	-9999	-10000	0	0
CAMK2A	-0.031	0.11	-9999	-0.38	17	17
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.049	0.11	-9999	-0.33	31	31
CSNK1A1	0.019	0	-9999	-10000	0	0
GNAS	-0.039	0.1	-9999	-0.36	19	19
GO:0007205	-0.024	0.1	-9999	-0.37	17	17
WNT6	0.007	0.052	-9999	-0.24	15	15
WNT4	-0.082	0.13	-9999	-0.24	140	140
NFAT1/CK1 alpha	-0.029	0.13	-9999	-0.36	29	29
GNG2	0.01	0.07	-9999	-0.54	6	6
WNT5A	-0.001	0.092	-9999	-0.37	19	19
WNT11	-0.066	0.12	-9999	-0.24	118	118
CDC42	-0.03	0.1	-9999	-0.34	18	18

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.11	0.13	-9999	-0.33	60	60
SMAD6-7/SMURF1	0.035	0.022	-9999	-10000	0	0
NOG	-0.15	0.25	-9999	-0.53	112	112
SMAD9	-0.006	0.087	-9999	-0.47	10	10
SMAD4	0.019	0	-9999	-10000	0	0
SMAD5	-0.016	0.063	-9999	-0.3	2	2
BMP7/USAG1	-0.22	0.21	-9999	-0.42	168	168
SMAD5/SKI	-0.007	0.062	-9999	-0.28	2	2
SMAD1	0.036	0.014	-9999	-10000	0	0
BMP2	-0.003	0.089	-9999	-0.32	24	24
SMAD1/SMAD1/SMAD4	-0.001	0.006	-9999	-10000	0	0
BMPR1A	0.018	0.014	-9999	-0.24	1	1
BMPR1B	-0.14	0.13	-9999	-0.24	215	215
BMPR1A-1B/BAMBI	-0.06	0.09	-9999	-0.39	8	8
AHSG	-0.01	0.064	-9999	-0.24	25	25
CER1	0.002	0.03	-9999	-0.24	5	5
BMP2-4/CER1	0.005	0.079	-9999	-0.32	16	16
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.009	0.071	-9999	-0.29	8	8
BMP2-4 (homodimer)	0.002	0.09	-9999	-0.39	15	15
RGMB	0.002	0.064	-9999	-0.24	23	23
BMP6/BMPR2/BMPR1A-1B	-0.038	0.072	-9999	-0.22	3	3
RGMA	-0.006	0.082	-9999	-0.26	32	32
SMURF1	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.025	0.075	-9999	-0.3	13	13
BMP2-4/USAG1	-0.14	0.18	-9999	-0.33	158	158
SMAD6/SMURF1/SMAD5	-0.007	0.062	-9999	-0.28	2	2
SOSTDC1	-0.23	0.26	-9999	-0.48	182	182
BMP7/BMPR2/BMPR1A-1B	-0.092	0.11	-9999	-0.25	78	78
SKI	0.019	0	-9999	-10000	0	0
BMP6 (homodimer)	0.015	0.033	-9999	-0.24	6	6
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.019	0	-9999	-10000	0	0
MAP3K7	0.019	0	-9999	-10000	0	0
BMP2-4/CHRD	0.006	0.085	-9999	-0.32	16	16
SMAD5/SMAD5/SMAD4	-0.007	0.062	-9999	-0.28	2	2
MAPK1	0.019	0	-9999	-10000	0	0
TAK1/TAB family	-0.024	0.052	-9999	-0.28	8	8
BMP7 (homodimer)	-0.09	0.16	-9999	-0.29	128	128
NUP214	0.019	0	-9999	-10000	0	0
BMP6/FETUA	0.005	0.05	-9999	-0.31	1	1
SMAD1/SKI	0.046	0.013	-9999	-10000	0	0
SMAD6	0.013	0.039	-9999	-0.24	8	8
CTDSP2	0.019	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.002	0.085	-9999	-0.33	16	16
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.02	0.13	-9999	-0.37	37	37
BMPR2 (homodimer)	0.019	0	-9999	-10000	0	0
GADD34/PP1CA	0.038	0.008	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.078	0.089	-9999	-10000	0	0
CHRDL1	-0.062	0.18	-9999	-0.39	72	72
ENDOFIN/SMAD1	0.046	0.013	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.059	0.02	-9999	-10000	0	0
SMAD6/SMURF1	0.019	0	-9999	-10000	0	0
BAMBI	0.007	0.081	-9999	-0.54	8	8
SMURF2	0.019	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.033	0.14	-9999	-0.36	48	48
BMP2-4/GREM1	-0.008	0.11	-9999	-0.32	35	35
SMAD7	0.019	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	0.005	0.082	-9999	-0.44	10	10
SMAD1/SMAD6	0.046	0.013	-9999	-10000	0	0
TAK1/SMAD6	0.028	0	-9999	-10000	0	0
BMP7	-0.091	0.16	-9999	-0.29	128	128
BMP6	0.015	0.033	-9999	-0.24	6	6
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.013	0.067	-9999	-0.26	13	13
PPM1A	0.019	0	-9999	-10000	0	0
SMAD1/SMURF2	0.046	0.013	-9999	-10000	0	0
SMAD7/SMURF1	0.028	0	-9999	-10000	0	0
CTDSPL	0.019	0	-9999	-10000	0	0
PPP1CA	0.019	0	-9999	-10000	0	0
XIAP	0.019	0	-9999	-10000	0	0
CTDSP1	0.019	0	-9999	-10000	0	0
PPP1R15A	0.018	0.014	-9999	-0.24	1	1
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.049	0.1	-9999	-0.32	28	28
CHRD	0.002	0.064	-9999	-0.24	23	23
BMPR2	0.019	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.029	0.078	-9999	-0.32	13	13
BMP4	0.004	0.085	-9999	-0.44	12	12
FST	-0.045	0.15	-9999	-0.36	61	61
BMP2-4/NOG	-0.093	0.17	-9999	-0.33	121	121
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.078	0.1	-9999	-0.33	21	21

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.06	0.15	-9999	-0.25	126	126
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.018	0.014	-9999	-0.24	1	1
STAT1 (dimer)/Cbp/p300	-0.052	0.17	-9999	-0.37	40	40
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.006	0.06	-9999	-0.35	6	6
antigen processing and presentation of peptide antigen via MHC class I	-0.045	0.077	-9999	-0.28	20	20
CaM/Ca2+	-0.051	0.14	-9999	-0.23	126	126
RAP1A	0.019	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.058	0.14	-9999	-0.33	27	27
AKT1	-0.039	0.12	-9999	-0.29	16	16
MAP2K1	-0.044	0.13	-9999	-0.3	16	16
MAP3K11	-0.055	0.13	-9999	-0.28	27	27
IFNGR1	0.008	0.017	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.024	0.1	-9999	-0.42	6	6
Rap1/GTP	-0.059	0.082	-9999	-0.35	3	3
CRKL/C3G	0.028	0.009	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.057	0.15	-9999	-0.26	132	132
CEBPB	0.001	0.12	-9999	-0.36	3	3
STAT3	0.019	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.11	0.31	-9999	-1.2	22	22
STAT1	-0.06	0.14	-9999	-0.33	27	27
CALM1	0.019	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.18	0.26	-9999	-0.54	129	129
PIK3CA	0.018	0.014	-9999	-0.24	1	1
STAT1 (dimer)/PIAS1	-0.048	0.14	-9999	-0.33	21	21
CEBPB/PTGES2/Cbp/p300	-0.036	0.051	-9999	-10000	0	0
mol:Ca2+	-0.061	0.14	-9999	-0.25	126	126
MAPK3	-0.019	0.12	-9999	-0.37	3	3
STAT1 (dimer)	-0.058	0.11	-9999	-0.4	20	20
MAPK1	-0.019	0.12	-9999	-0.37	3	3
JAK2	-0.001	0.074	-9999	-0.51	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
JAK1	0.008	0.017	-9999	-10000	0	0
CAMK2D	0.019	0	-9999	-10000	0	0
DAPK1	0.018	0.09	-9999	-10000	0	0
SMAD7	0.012	0.064	-9999	-0.16	10	10
CBL/CRKL/C3G	-0.036	0.13	-9999	-0.29	16	16
PI3K	-0.048	0.13	-9999	-0.31	16	16
IFNG	-0.18	0.26	-9999	-0.54	129	129
apoptosis	0.006	0.082	-9999	-0.24	1	1
CAMK2G	0.019	0	-9999	-10000	0	0
STAT3 (dimer)	0.019	0	-9999	-10000	0	0
CAMK2A	-0.018	0.1	-9999	-0.28	46	46
CAMK2B	-0.011	0.1	-9999	-0.33	31	31
FRAP1	-0.038	0.12	-9999	-0.27	16	16
PRKCD	-0.038	0.12	-9999	-0.29	16	16
RAP1B	0.019	0	-9999	-10000	0	0
negative regulation of cell growth	-0.045	0.077	-9999	-0.28	20	20
PTPN2	0.019	0	-9999	-10000	0	0
EP300	0.019	0.002	-9999	-10000	0	0
IRF1	-0.077	0.23	-9999	-0.56	54	54
STAT1 (dimer)/PIASy	-0.048	0.14	-9999	-0.36	18	18
SOCS1	-0.048	0.32	-9999	-1.4	19	19
mol:GDP	-0.036	0.12	-9999	-0.28	16	16
CASP1	0.003	0.092	-9999	-0.31	20	20
PTGES2	0.019	0	-9999	-10000	0	0
IRF9	0.026	0.052	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.078	0.1	-9999	-0.3	16	16
RAP1/GDP	-0.06	0.082	-9999	-0.35	3	3
CBL	-0.057	0.13	-9999	-0.23	126	126
MAP3K1	-0.055	0.13	-9999	-0.28	27	27
PIAS1	0.019	0	-9999	-10000	0	0
PIAS4	0.019	0.002	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.045	0.077	-9999	-0.28	20	20
PTPN11	-0.067	0.14	-9999	-0.25	126	126
CREBBP	0.019	0.002	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.014	0.099	-10000	0	-1.3	2	2
VDR	0.016	0.041	-10000	0	-0.54	2	2
FAM120B	0.019	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.048	0.17	-10000	0	-0.46	20	20
RXRs/LXRs/DNA/Oxysterols	-0.06	0.21	-10000	0	-0.42	75	75
MED1	0.019	0	-10000	0	-10000	0	0
mol:9cRA	-0.003	0.022	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.017	0.065	-10000	0	-0.24	15	15
RXRs/NUR77	-0.031	0.15	-10000	0	-0.29	82	82
RXRs/PPAR	-0.025	0.12	-10000	0	-0.23	87	87
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.012	0.03	-10000	0	-0.39	2	2
RARs/VDR/DNA/Vit D3	0.031	0.063	-10000	0	-0.26	16	16
RARA	0.019	0	-10000	0	-10000	0	0
NCOA1	0.019	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.016	0.041	-10000	0	-0.54	2	2
RARs/RARs/DNA/9cRA	0.02	0.061	-10000	0	-0.28	14	14
RARG	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.052	-10000	0	-0.41	2	2
RARs/THRs/DNA/SMRT	0.017	0.065	-10000	0	-0.24	15	15
THRA	0.019	0	-10000	0	-10000	0	0
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.012	0.03	-10000	0	-0.39	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.044	0.15	0.3	1	-0.3	82	83
NR1H4	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA	-0.026	0.16	-10000	0	-0.27	84	84
NR1H2	0.017	0.019	-10000	0	-10000	0	0
NR1H3	0.013	0.047	-10000	0	-0.55	2	2
RXRs/VDR/DNA/Vit D3	-0.03	0.14	-10000	0	-0.27	84	84
NR4A1	0.016	0.035	-10000	0	-0.34	3	3
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.033	0.11	-10000	0	-0.21	82	82
RXRG	-0.11	0.23	-10000	0	-0.54	82	82
RXR alpha/CCPG	0.026	0.014	-10000	0	-10000	0	0
RXRA	0.016	0.019	-10000	0	-10000	0	0
RXRB	0.016	0.022	-10000	0	-10000	0	0
THRB	-0.026	0.1	-10000	0	-0.26	60	60
PPARG	0.011	0.064	-10000	0	-0.54	5	5
PPARD	0.017	0.019	-10000	0	-0.24	2	2
TNF	-0.19	0.46	-10000	0	-1.1	75	75
mol:Oxysterols	-0.002	0.02	-10000	0	-10000	0	0
cholesterol transport	-0.06	0.21	-10000	0	-0.42	75	75
PPARA	0.019	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	-0.003	0.11	-10000	0	-0.52	15	15
RXRs/NUR77/BCL2	-0.027	0.12	-10000	0	-0.24	82	82
SREBF1	-0.046	0.19	-10000	0	-0.53	20	20
RXRs/RXRs/DNA/9cRA	-0.044	0.15	0.3	1	-0.3	82	83
ABCA1	-0.046	0.19	-10000	0	-0.53	20	20
RARs/THRs	0.021	0.08	-10000	0	-0.28	15	15
RXRs/FXR	-0.04	0.14	-10000	0	-0.3	82	82
BCL2	0.019	0	-10000	0	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.019	0	-9999	-10000	0	0
SPHK1	0.011	0.058	-9999	-0.36	8	8
GNAI2	0.019	0	-9999	-10000	0	0
mol:S1P	0.022	0.034	-9999	-0.28	4	4
GNAO1	-0.093	0.13	-9999	-0.25	155	155
mol:Sphinganine-1-P	0.02	0.042	-9999	-0.38	3	3
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.049	0.026	-9999	-0.18	4	4
GNAI3	0.019	0	-9999	-10000	0	0
G12/G13	0.028	0	-9999	-10000	0	0
S1PR3	0.014	0.052	-9999	-0.46	4	4
S1PR2	0.019	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.014	0.028	-9999	-0.24	4	4
S1PR5	0.008	0.052	-9999	-0.24	15	15
S1PR4	-0.16	0.26	-9999	-0.54	121	121
GNAI1	0.004	0.06	-9999	-0.24	20	20
S1P/S1P5/G12	0.033	0.037	-9999	-0.2	4	4
S1P/S1P3/Gq	-0.017	0.13	-9999	-0.27	73	73
S1P/S1P4/Gi	-0.095	0.15	-9999	-0.29	122	122
GNAQ	0.019	0	-9999	-10000	0	0
GNAZ	-0.015	0.093	-9999	-0.26	45	45
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
GNA11	0.019	0	-9999	-10000	0	0
ABCC1	0.017	0.029	-9999	-0.54	1	1

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.019	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.032	0.13	-9999	-0.29	78	78
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.002	0.043	-9999	-10000	0	0
AURKB	0.017	0.029	-9999	-0.54	1	1
AURKC	-0.098	0.23	-9999	-0.54	77	77

×

Signaling events mediated by PTP1B

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
PDGFRB	0.015	0.031	-10000	0	-0.24	5	5
Jak2/Leptin Receptor	-0.002	0.076	0.21	1	-0.46	6	7
PTP1B/AKT1	0.021	0.043	-10000	0	-0.23	3	3
FYN	0.019	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	0.012	0.046	-10000	0	-0.26	3	3
EGFR	-0.008	0.087	-10000	0	-0.27	33	33
EGF/EGFR	-0.005	0.098	-10000	0	-0.29	32	32
CSF1	0.01	0.07	-10000	0	-0.54	6	6
AKT1	0.019	0	-10000	0	-10000	0	0
INSR	0.019	0.014	-10000	0	-0.24	1	1
PTP1B/N-cadherin	-0.02	0.1	-10000	0	-0.27	42	42
Insulin Receptor/Insulin	0.028	0.034	-10000	0	-10000	0	0
HCK	-0.028	0.16	-10000	0	-0.54	31	31
CRK	0.019	0	-10000	0	-10000	0	0
TYK2	0.019	0.044	-10000	0	-0.24	3	3
EGF	-0.031	0.15	-10000	0	-0.43	41	41
YES1	0.019	0	-10000	0	-10000	0	0
CAV1	0.018	0.06	-10000	0	-0.22	5	5
TXN	0.018	0.002	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	0.023	0.056	-10000	0	-0.23	3	3
cell migration	-0.012	0.046	0.26	3	-10000	0	3
STAT3	0.019	0.001	-10000	0	-10000	0	0
PRLR	-0.048	0.11	-10000	0	-0.24	92	92
ITGA2B	-0.005	0.073	-10000	0	-0.24	31	31
CSF1R	-0.013	0.13	-10000	0	-0.54	21	21
Prolactin Receptor/Prolactin	-0.046	0.096	-10000	0	-0.3	16	16
FGR	-0.036	0.16	-10000	0	-0.54	36	36
PTP1B/p130 Cas	0.021	0.045	-10000	0	-0.24	3	3
Crk/p130 Cas	0.032	0.044	-10000	0	-0.23	3	3
DOK1	0.026	0.041	-10000	0	-0.21	2	2
JAK2	-0.009	0.078	-10000	0	-0.48	6	6
Jak2/Leptin Receptor/Leptin	0.002	0.071	-10000	0	-0.34	8	8
PIK3R1	0.019	0	-10000	0	-10000	0	0
PTPN1	0.012	0.047	-10000	0	-0.26	3	3
LYN	-0.004	0.11	-10000	0	-0.54	15	15
CDH2	-0.063	0.18	-10000	0	-0.41	69	69
SRC	0.027	0.02	-10000	0	-10000	0	0
ITGB3	-0.033	0.14	-10000	0	-0.36	50	50
CAT1/PTP1B	-0.17	0.23	-10000	0	-0.42	131	131
CAPN1	0.019	0.001	-10000	0	-10000	0	0
CSK	0.019	0	-10000	0	-10000	0	0
PI3K	0.012	0.025	-10000	0	-10000	0	0
mol:H2O2	0	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	0.011	0.072	-10000	0	-0.34	7	7
negative regulation of transcription	-0.009	0.078	-10000	0	-0.48	6	6
FCGR2A	0.013	0.058	-10000	0	-0.54	4	4
FER	0.018	0.002	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.025	0.11	-10000	0	-0.37	25	25
BLK	-0.34	0.26	-10000	0	-0.54	236	236
Insulin Receptor/Insulin/Shc	0.026	0.008	-10000	0	-10000	0	0
RHOA	0.019	0.001	-10000	0	-10000	0	0
LEPR	0.018	0.001	-10000	0	-10000	0	0
BCAR1	0.019	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.019	0	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	-0.29	0.32	-10000	0	-0.61	142	142
PRL	-0.023	0.083	-10000	0	-0.24	45	45
SOCS3	0.006	0.13	-10000	0	-1.4	3	3
SPRY2	0.017	0.02	-10000	0	-0.24	2	2
Insulin Receptor/Insulin/IRS1	0.014	0.042	-10000	0	-10000	0	0
CSF1/CSF1R	0.012	0.098	-10000	0	-0.31	25	25
Ras protein signal transduction	0.011	0.015	-10000	0	-10000	0	0
IRS1	-0.002	0.071	-10000	0	-0.24	29	29
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.035	0.1	-10000	0	-0.24	70	70
STAT5B	0.008	0.052	-10000	0	-0.27	4	4
STAT5A	0.007	0.053	-10000	0	-0.27	4	4
GRB2	0.019	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.019	0.048	-10000	0	-0.24	3	3
CSN2	-0.02	0.036	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
LAT	-0.038	0.18	-10000	0	-0.5	45	45
YBX1	0.029	0.001	-10000	0	-10000	0	0
LCK	-0.2	0.27	-10000	0	-0.54	142	142
SHC1	0.019	0	-10000	0	-10000	0	0
NOX4	-0.04	0.12	-10000	0	-0.26	78	78

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.018	0.014	-10000	0	-0.24	1	1
Rac1/GDP	0.015	0.014	-10000	0	-10000	0	0
DOCK1	0.019	0	-10000	0	-10000	0	0
ITGA4	-0.043	0.18	-10000	0	-0.54	41	41
RAC1	0.019	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.076	0.2	-10000	0	-0.42	84	84
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.002	0.11	-10000	0	-0.32	41	41
alpha4/beta7 Integrin/Paxillin	-0.039	0.16	-10000	0	-0.32	84	84
lamellipodium assembly	0.057	0.007	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
PI3K	0.028	0.009	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
TLN1	0.019	0	-10000	0	-10000	0	0
PXN	0.026	0	-10000	0	-10000	0	0
PIK3R1	0.019	0	-10000	0	-10000	0	0
ARF6/GTP	0.017	0.088	-10000	0	-0.23	41	41
cell adhesion	0.017	0.096	-10000	0	-0.25	41	41
CRKL/CBL	0.028	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.006	0.1	-10000	0	-0.28	41	41
ITGB1	0.017	0.019	-10000	0	-0.24	2	2
ITGB7	-0.063	0.2	-10000	0	-0.54	54	54
ARF6/GDP	0.015	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.033	0.18	-10000	0	-0.36	76	76
p130Cas/Crk/Dock1	0.038	0	-10000	0	-10000	0	0
VCAM1	-0.077	0.21	-10000	0	-0.54	63	63
alpha4/beta1 Integrin/Paxillin/Talin	0.018	0.098	-10000	0	-0.26	41	41
alpha4/beta1 Integrin/Paxillin/GIT1	0.018	0.098	-10000	0	-0.26	41	41
BCAR1	0.019	0	-10000	0	-10000	0	0
mol:GDP	-0.017	0.096	0.25	41	-10000	0	41
CBL	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0	-10000	0	-10000	0	0
GIT1	0.019	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.018	0.098	-10000	0	-0.26	41	41
Rac1/GTP	0.059	0.007	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.049	-9999	-0.31	1	1
alphaV beta3 Integrin	-0.006	0.1	-9999	-0.29	32	32
PTK2	-0.063	0.15	-9999	-0.4	36	36
IGF1R	0.016	0.027	-9999	-0.24	4	4
PI4KB	0.019	0	-9999	-10000	0	0
MFGE8	0.004	0.06	-9999	-0.24	20	20
SRC	0.019	0	-9999	-10000	0	0
CDKN1B	-0.05	0.18	-9999	-0.48	48	48
VEGFA	0.004	0.061	-9999	-0.24	21	21
ILK	-0.05	0.18	-9999	-0.48	48	48
ROCK1	0.019	0	-9999	-10000	0	0
AKT1	-0.04	0.17	-9999	-0.45	48	48
PTK2B	0.001	0.088	-9999	-0.26	26	26
alphaV/beta3 Integrin/JAM-A	-0.032	0.14	-9999	-0.3	69	69
CBL	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.006	0.086	-9999	-0.32	20	20
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.03	0.056	-9999	-0.27	5	5
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.007	0.1	-9999	-0.32	12	12
alphaV/beta3 Integrin/Syndecan-1	-0.001	0.1	-9999	-0.34	26	26
PI4KA	0.018	0.014	-9999	-0.24	1	1
IGF-1R heterotetramer/IGF1/IRS1	-0.042	0.089	-9999	-0.28	32	32
PI4 Kinase	0.028	0.009	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
alphaV/beta3 Integrin/Osteopontin	-0.03	0.14	-9999	-0.35	53	53
RPS6KB1	0.002	0.1	-9999	-0.41	8	8
TLN1	0.019	0	-9999	-10000	0	0
MAPK3	-0.024	0.14	-9999	-0.47	25	25
GPR124	0.016	0.027	-9999	-0.24	4	4
MAPK1	-0.024	0.14	-9999	-0.48	24	24
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.13	0.19	-9999	-0.35	151	151
cell adhesion	0.004	0.088	-9999	-0.32	19	19
ANGPTL3	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.027	0.042	-9999	-0.25	1	1
IGF-1R heterotetramer	0.016	0.027	-9999	-0.24	4	4
Rac1/GDP	0.014	0	-9999	-10000	0	0
TGFBR2	0.019	0	-9999	-10000	0	0
ITGB3	-0.032	0.14	-9999	-0.36	50	50
IGF1	0.008	0.066	-9999	-0.36	10	10
RAC1	0.019	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	0.005	0.089	-9999	-0.32	20	20
apoptosis	0.018	0.014	-9999	-0.24	1	1
CD47	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	0.007	0.088	-9999	-0.31	20	20
VCL	0.019	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.036	0.11	-9999	-0.29	41	41
CSF1	0.01	0.07	-9999	-0.54	6	6
PIK3C2A	-0.05	0.18	-9999	-0.48	48	48
PI4 Kinase/Pyk2	-0.059	0.1	-9999	-0.37	17	17
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.009	0.089	-9999	-0.26	26	26
FAK1/Vinculin	-0.043	0.13	-9999	-0.33	32	32
alphaV beta3/Integrin/ppsTEM5	0.005	0.09	-9999	-0.32	20	20
RHOA	0.019	0	-9999	-10000	0	0
VTN	-0.058	0.19	-9999	-0.5	54	54
BCAR1	0.019	0	-9999	-10000	0	0
FGF2	-0.004	0.08	-9999	-0.26	30	30
F11R	0.004	0.078	-9999	-0.42	8	8
alphaV/beta3 Integrin/Lactadherin	-0.001	0.095	-9999	-0.32	23	23
alphaV/beta3 Integrin/TGFBR2	0.007	0.088	-9999	-0.31	20	20
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.043	0.042	-9999	-0.28	6	6
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
alphaV/beta3 Integrin/Talin	0.008	0.08	-9999	-0.28	20	20
mol:GDP	0	0	-9999	-10000	0	0
FN1	0	0.1	-9999	-0.52	13	13
alphaV/beta3 Integrin/Pyk2	0.008	0.091	-9999	-0.26	26	26
SDC1	0.005	0.08	-9999	-0.43	11	11
VAV3	0.032	0.054	-9999	-0.29	8	8
PTPN11	0.019	0	-9999	-10000	0	0
IRS1	-0.002	0.071	-9999	-0.24	29	29
FAK1/Paxillin	-0.043	0.13	-9999	-0.34	27	27
cell migration	-0.033	0.12	-9999	-0.32	23	23
ITGAV	0.018	0.014	-9999	-0.24	1	1
PI3K	-0.019	0.13	-9999	-0.41	15	15
SPP1	-0.04	0.17	-9999	-0.52	40	40
KDR	0.014	0.036	-9999	-0.24	7	7
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.018	0.014	-9999	-0.24	1	1
COL4A3	-0.2	0.27	-9999	-0.54	144	144
angiogenesis	-0.032	0.16	-9999	-0.46	31	31
Rac1/GTP	0.039	0.05	-9999	-0.26	8	8
EDIL3	-0.056	0.12	-9999	-0.24	104	104
cell proliferation	0.006	0.087	-9999	-0.31	20	20

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.005	0.12	-9999	-0.42	11	11
NF kappa B1 p50/RelA/I kappa B alpha	0.032	0.12	-9999	-0.39	10	10
alphaV/beta3 Integrin/Osteopontin/Src	-0.007	0.12	-9999	-0.37	38	38
AP1	0.008	0.14	-9999	-0.44	9	9
ILK	-0.009	0.13	-9999	-0.44	11	11
bone resorption	-0.017	0.16	-9999	-0.44	25	25
PTK2B	0.008	0.076	-9999	-0.54	7	7
PYK2/p130Cas	-0.026	0.17	-9999	-0.43	32	32
ITGAV	0.022	0.014	-9999	-0.24	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.027	0.021	-9999	-0.38	1	1
alphaV/beta3 Integrin/Osteopontin	-0.013	0.14	-9999	-0.34	53	53
MAP3K1	-0.009	0.13	-9999	-0.3	51	51
JUN	-0.008	0.08	-9999	-0.25	37	37
MAPK3	0.004	0.12	-9999	-0.43	11	11
MAPK1	0.004	0.12	-9999	-0.43	11	11
Rac1/GDP	0.014	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
MAPK8	-0.002	0.12	-9999	-0.27	51	51
ITGB3	-0.028	0.14	-9999	-0.35	50	50
NFKBIA	0.015	0.12	-9999	-0.44	10	10
FOS	0.01	0.047	-9999	-0.25	12	12
CD44	0.017	0.029	-9999	-0.54	1	1
CHUK	0.019	0	-9999	-10000	0	0
PLAU	0.02	0.13	-9999	-0.84	2	2
NF kappa B1 p50/RelA	0.035	0.11	-9999	-0.4	9	9
BCAR1	0.019	0	-9999	-10000	0	0
RELA	0.019	0	-9999	-10000	0	0
alphaV beta3 Integrin	0	0.1	-9999	-0.37	20	20
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.049	0.17	-9999	-0.33	86	86
VAV3	-0.044	0.17	-9999	-0.36	55	55
MAP3K14	-0.006	0.13	-9999	-0.3	51	51
ROCK2	0.019	0	-9999	-10000	0	0
SPP1	-0.036	0.17	-9999	-0.51	40	40
RAC1	0.019	0	-9999	-10000	0	0
Rac1/GTP	-0.032	0.16	-9999	-0.45	25	25
MMP2	-0.005	0.14	-9999	-0.38	15	15

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.077	-9999	-0.34	15	15
EPHB2	-0.005	0.11	-9999	-0.54	16	16
Syndecan-2/TACI	-0.15	0.17	-9999	-0.32	183	183
LAMA1	-0.2	0.1	-9999	-0.24	302	302
Syndecan-2/alpha2 ITGB1	0.031	0.076	-9999	-0.28	17	17
HRAS	0.019	0	-9999	-10000	0	0
Syndecan-2/CASK	0.01	0.04	-9999	-0.32	4	4
ITGA5	0.015	0.031	-9999	-0.24	5	5
BAX	0.037	0.037	-9999	-10000	0	0
EPB41	0.017	0.029	-9999	-0.54	1	1
positive regulation of cell-cell adhesion	0.022	0.037	-9999	-0.28	4	4
LAMA3	0	0.1	-9999	-0.52	13	13
EZR	0.011	0.064	-9999	-0.54	5	5
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.019	0	-9999	-10000	0	0
Syndecan-2/MMP2	0.003	0.068	-9999	-0.3	8	8
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.022	0.04	-9999	-0.21	9	9
dendrite morphogenesis	0.009	0.081	-9999	-0.32	20	20
Syndecan-2/GM-CSF	0.018	0.046	-9999	-0.32	5	5
determination of left/right symmetry	0.015	0.049	-9999	-0.23	12	12
Syndecan-2/PKC delta	0.024	0.041	-9999	-0.31	4	4
GNB2L1	0.019	0	-9999	-10000	0	0
MAPK3	0.025	0.041	-9999	-0.28	5	5
MAPK1	0.025	0.041	-9999	-0.28	5	5
Syndecan-2/RACK1	0.033	0.036	-9999	-0.26	4	4
NF1	0.019	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.015	0.049	-9999	-0.23	12	12
ITGA2	0.012	0.048	-9999	-0.28	9	9
MAPK8	0.03	0.041	-9999	-0.31	4	4
Syndecan-2/alpha2/beta1 Integrin	-0.067	0.062	-9999	-0.26	14	14
Syndecan-2/Kininogen	0.009	0.048	-9999	-0.32	4	4
ITGB1	0.017	0.019	-9999	-0.24	2	2
SRC	0.035	0.034	-9999	-0.24	4	4
Syndecan-2/CASK/Protein 4.1	0.021	0.041	-9999	-0.29	5	5
extracellular matrix organization	0.022	0.048	-9999	-0.31	6	6
actin cytoskeleton reorganization	0.013	0.077	-9999	-0.34	15	15
Syndecan-2/Caveolin-2/Ras	0.035	0.038	-9999	-0.28	4	4
Syndecan-2/Laminin alpha3	0.013	0.08	-9999	-0.36	14	14
Syndecan-2/RasGAP	0.041	0.038	-9999	-0.24	5	5
alpha5/beta1 Integrin	0.025	0.029	-9999	-0.31	2	2
PRKCD	0.019	0	-9999	-10000	0	0
Syndecan-2 dimer	0.009	0.081	-9999	-0.32	20	20
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.046	0.037	-9999	-0.23	5	5
RHOA	0.019	0	-9999	-10000	0	0
SDCBP	0.019	0	-9999	-10000	0	0
TNFRSF13B	-0.26	0.28	-9999	-0.54	180	180
RASA1	0.017	0.029	-9999	-0.54	1	1
alpha2/beta1 Integrin	0.022	0.04	-9999	-0.21	9	9
Syndecan-2/Synbindin	0.024	0.041	-9999	-0.31	4	4
TGFB1	0.016	0.041	-9999	-0.54	2	2
CASP3	0.03	0.037	-9999	-0.28	4	4
FN1	0	0.1	-9999	-0.52	13	13
Syndecan-2/IL8	-0.015	0.078	-9999	-0.3	9	9
SDC2	0.015	0.049	-9999	-0.23	12	12
KNG1	-0.004	0.049	-9999	-0.24	14	14
Syndecan-2/Neurofibromin	0.024	0.041	-9999	-0.31	4	4
TRAPPC4	0.019	0	-9999	-10000	0	0
CSF2	0.01	0.033	-9999	-0.39	2	2
Syndecan-2/TGFB1	0.022	0.048	-9999	-0.32	6	6
Syndecan-2/Syntenin/PI-4-5-P2	0.022	0.037	-9999	-0.28	4	4
Syndecan-2/Ezrin	0.03	0.053	-9999	-0.28	9	9
PRKACA	0.03	0.037	-9999	-0.28	4	4
angiogenesis	-0.015	0.078	-9999	-0.3	9	9
MMP2	-0.019	0.097	-9999	-0.26	50	50
IL8	-0.05	0.12	-9999	-0.25	93	93
calcineurin-NFAT signaling pathway	-0.15	0.17	-9999	-0.32	183	183

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.013	0.065	-9999	-0.32	13	13
ARNO/beta Arrestin1-2	0.032	0.027	-9999	-10000	0	0
EGFR	-0.007	0.087	-9999	-0.27	33	33
EPHA2	0.013	0.058	-9999	-0.54	4	4
USP6	0.019	0	-9999	-10000	0	0
IQSEC1	0.019	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.026	0.12	-9999	-0.38	31	31
ARRB2	0.01	0	-9999	-10000	0	0
mol:GTP	-0.021	0.066	-9999	-0.21	19	19
ARRB1	0.019	0	-9999	-10000	0	0
FBXO8	0.019	0	-9999	-10000	0	0
TSHR	-0.03	0.16	-9999	-0.53	32	32
EGF	-0.031	0.15	-9999	-0.42	41	41
somatostatin receptor activity	0	0	-9999	-0.001	33	33
ARAP2	0.007	0.081	-9999	-0.54	8	8
mol:GDP	-0.001	0.07	-9999	-0.24	18	18
mol:PI-3-4-5-P3	0	0	-9999	-0.001	23	23
ITGA2B	-0.004	0.073	-9999	-0.24	31	31
ARF6	0.019	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.045	0.034	-9999	-0.28	4	4
ADAP1	-0.001	0.1	-9999	-0.54	13	13
KIF13B	0.019	0	-9999	-10000	0	0
HGF/MET	-0.016	0.12	-9999	-0.4	27	27
PXN	0.019	0	-9999	-10000	0	0
ARF6/GTP	-0.018	0.1	-9999	-0.25	32	32
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.008	0.11	-9999	-0.32	31	31
ADRB2	0.013	0.058	-9999	-0.54	4	4
receptor agonist activity	0	0	-9999	0	34	34
actin filament binding	0	0	-9999	0	33	33
SRC	0.019	0	-9999	-10000	0	0
ITGB3	-0.032	0.14	-9999	-0.36	50	50
GNAQ	0.019	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	27	27
ARF6/GDP	-0.066	0.18	-9999	-0.3	128	128
ARF6/GDP/GULP/ACAP1	-0.077	0.18	-9999	-0.31	106	106
alphaIIb/beta3 Integrin/paxillin/GIT1	0.007	0.089	-9999	-0.27	25	25
ACAP1	-0.18	0.26	-9999	-0.54	128	128
ACAP2	0.019	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0	0	-9999	-10000	0	0
EFNA1	0.019	0	-9999	-10000	0	0
HGF	0	0.085	-9999	-0.34	19	19
CYTH3	0.012	0.009	-9999	-0.16	1	1
CYTH2	0.014	0.002	-9999	-10000	0	0
NCK1	0.019	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	43	43
endosomal lumen acidification	0	0	-9999	0	33	33
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.007	0.12	-9999	-0.54	17	17
GNAQ/ARNO	0.024	0.004	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	8	8
MET	-0.024	0.14	-9999	-0.43	35	35
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GIT1	0.019	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	27	27
GNA11	0.019	0	-9999	-10000	0	0
LHCGR	0	0	-9999	-10000	0	0
AGTR1	0	0	-9999	-10000	0	0
desensitization of G-protein coupled receptor protein signaling pathway	0	0	-9999	-10000	0	0
IPCEF1/ARNO	-0.001	0.08	-9999	-0.34	2	2
alphaIIb/beta3 Integrin	-0.024	0.11	-9999	-0.36	25	25

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.024	0.043	-9999	-0.38	4	4
Necdin/E2F1	0.016	0.07	-9999	-0.38	11	11
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.005	0.086	-9999	-0.3	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.025	0.1	-9999	-0.29	29	29
NT-4/5 (dimer)/p75(NTR)	-0.017	0.074	-9999	-0.39	4	4
IKBKB	0.019	0	-9999	-10000	0	0
AKT1	0.013	0.063	-9999	-0.25	4	4
IKBKG	0.019	0	-9999	-10000	0	0
BDNF	-0.12	0.24	-9999	-0.54	88	88
MGDIs/NGR/p75(NTR)/LINGO1	-0.029	0.1	-9999	-0.28	30	30
FURIN	0.019	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.077	0.16	-9999	-0.34	93	93
LINGO1	-0.026	0.1	-9999	-0.25	61	61
Sortilin/TRAF6/NRIF	-0.004	0.029	-9999	-10000	0	0
proBDNF (dimer)	-0.12	0.24	-9999	-0.54	88	88
NTRK1	-0.001	0.1	-9999	-0.5	14	14
RTN4R	-0.007	0.089	-9999	-0.28	32	32
neuron apoptosis	-0.031	0.13	-9999	-0.37	11	11
IRAK1	0.019	0	-9999	-10000	0	0
SHC1	-0.003	0.075	-9999	-0.27	14	14
ARHGDIA	0.019	0	-9999	-10000	0	0
RhoA/GTP	0.014	0	-9999	-10000	0	0
Gamma Secretase	0.054	0.028	-9999	-0.26	3	3
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.011	0.078	-9999	-0.24	18	18
MAGEH1	0.019	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	0.002	0.095	-9999	-0.27	29	29
Mammalian IAPs/DIABLO	-0.069	0.16	-9999	-0.29	128	128
proNGF (dimer)	0.002	0.062	-9999	-0.24	22	22
MAGED1	0.019	0	-9999	-10000	0	0
APP	0.014	0.05	-9999	-0.54	3	3
NT-4/5 (dimer)	0	0	-9999	-10000	0	0
ZNF274	0.019	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	0.01	0.065	-9999	-0.22	14	14
NGF	0.002	0.063	-9999	-0.24	22	22
cell cycle arrest	0.004	0.071	-9999	-0.22	18	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.021	0.052	-9999	-0.23	5	5
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.001	0.063	-9999	-0.32	4	4
NCSTN	0.019	0	-9999	-10000	0	0
mol:GTP	0.002	0.077	-9999	-0.27	14	14
PSENEN	0.019	0	-9999	-10000	0	0
mol:ceramide	0.002	0.076	-9999	-0.25	19	19
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.03	0.047	-9999	-0.28	1	1
p75(NTR)/beta APP	-0.007	0.084	-9999	-0.4	7	7
BEX1	-0.029	0.099	-9999	-0.24	64	64
mol:GDP	-0.015	0.073	-9999	-0.28	14	14
NGF (dimer)	0.008	0.071	-9999	-0.3	11	11
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.014	0.097	-9999	-0.25	30	30
PIK3R1	0.019	0	-9999	-10000	0	0
RAC1/GTP	0.003	0.065	-9999	-0.23	14	14
MYD88	0.017	0.029	-9999	-0.54	1	1
CHUK	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	0.002	0.078	-9999	-0.27	14	14
RHOB	0.017	0.019	-9999	-0.24	2	2
RHOA	0.019	0	-9999	-10000	0	0
MAGE-G1/E2F1	0.028	0	-9999	-10000	0	0
NT3 (dimer)	-0.004	0.068	-9999	-0.24	27	27
TP53	-0.044	0.13	-9999	-0.25	93	93
PRDM4	0.002	0.074	-9999	-0.24	18	18
BDNF (dimer)	-0.12	0.15	-9999	-0.32	114	114
PIK3CA	0.018	0.014	-9999	-0.24	1	1
SORT1	0.013	0.058	-9999	-0.54	4	4
activation of caspase activity	0.002	0.083	-9999	-0.3	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.011	0.078	-9999	-0.24	18	18
RHOC	0.019	0	-9999	-10000	0	0
XIAP	0.019	0	-9999	-10000	0	0
MAPK10	-0.029	0.11	-9999	-0.37	7	7
DIABLO	0.019	0	-9999	-10000	0	0
SMPD2	0.002	0.076	-9999	-0.25	19	19
APH1B	0.014	0.05	-9999	-0.54	3	3
APH1A	0.019	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.002	0.084	-9999	-0.28	18	18
PSEN1	0.019	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.028	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.019	0.091	-9999	-0.34	12	12
MAPK8	-0.014	0.11	-9999	-0.37	7	7
MAPK9	-0.014	0.11	-9999	-0.37	7	7
APAF1	0.019	0	-9999	-10000	0	0
NTF3	-0.004	0.068	-9999	-0.24	27	27
NTF4	0	0	-9999	-10000	0	0
NDN	0.002	0.095	-9999	-0.54	11	11
RAC1/GDP	0.014	0	-9999	-10000	0	0
RhoA-B-C/GDP	0.021	0.061	-9999	-0.23	4	4
p75 CTF/Sortilin/TRAF6/NRIF	0.045	0.034	-9999	-0.28	4	4
RhoA-B-C/GTP	0.001	0.077	-9999	-0.27	14	14
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.045	0.14	-9999	-0.28	93	93
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.058	0.15	-9999	-0.3	93	93
PRKACB	0.018	0.014	-9999	-0.24	1	1
proBDNF (dimer)/p75 ECD	-0.071	0.18	-9999	-0.38	88	88
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.18	0.26	-9999	-0.54	128	128
BIRC2	0.014	0.052	-9999	-0.46	4	4
neuron projection morphogenesis	-0.014	0.07	-9999	-0.27	7	7
BAD	-0.014	0.11	-9999	-0.37	7	7
RIPK2	0.019	0	-9999	-10000	0	0
NGFR	-0.027	0.11	-9999	-0.26	59	59
CYCS	0.01	0.069	-9999	-0.26	8	8
ADAM17	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.015	0.072	-9999	-0.24	14	14
BCL2L11	-0.014	0.11	-9999	-0.37	7	7
BDNF (dimer)/p75(NTR)	-0.1	0.18	-9999	-0.4	90	90
PI3K	0.015	0.072	-9999	-0.23	14	14
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.011	0.078	-9999	-0.24	18	18
NDNL2	0.019	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
PRKCI	0.019	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.014	0.09	-9999	-0.33	14	14
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.011	0.078	-9999	-0.24	18	18
TRAF6	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
PRKCZ	0.016	0.041	-9999	-0.54	2	2
PLG	0	0	-9999	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.06	0.14	-9999	-0.27	93	93
SQSTM1	0.019	0	-9999	-10000	0	0
NGFRAP1	-0.013	0.086	-9999	-0.24	44	44
CASP3	-0.01	0.1	-9999	-0.34	7	7
E2F1	0.019	0	-9999	-10000	0	0
CASP9	0.019	0	-9999	-10000	0	0
IKK complex	-0.011	0.047	-9999	-0.32	2	2
NGF (dimer)/TRKA	0.002	0.083	-9999	-0.38	12	12
MMP7	-0.016	0.11	-9999	-0.33	35	35
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.021	0.074	-9999	-0.26	8	8
MMP3	-0.1	0.13	-9999	-0.24	162	162
APAF-1/Caspase 9	-0.079	0.1	-9999	-0.31	28	28

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.044	0.27	-10000	0	-0.69	25	25
CRP	-0.052	0.27	-10000	0	-0.72	24	24
cell cycle arrest	-0.065	0.3	-10000	0	-0.68	48	48
TIMP1	-0.022	0.22	-10000	0	-0.55	20	20
IL6ST	0.008	0.082	-10000	0	-0.54	8	8
Rac1/GDP	-0.03	0.19	-10000	0	-0.42	51	51
AP1	0.032	0.088	-10000	0	-0.31	1	1
GAB2	0.016	0.031	-10000	0	-0.24	5	5
TNFSF11	-0.18	0.49	-10000	0	-1.1	79	79
HSP90B1	0.029	0.055	-10000	0	-10000	0	0
GAB1	0.019	0.001	-10000	0	-10000	0	0
MAPK14	0.031	0.12	-10000	0	-0.66	5	5
AKT1	0.063	0.017	-10000	0	-10000	0	0
FOXO1	0.068	0.016	-10000	0	-10000	0	0
MAP2K6	0.02	0.12	-10000	0	-0.4	14	14
mol:GTP	0	0.003	-10000	0	-10000	0	0
MAP2K4	-0.032	0.22	-10000	0	-0.48	51	51
MITF	0.007	0.13	-10000	0	-0.33	28	28
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.019	0	-10000	0	-10000	0	0
A2M	0.019	0.031	-10000	0	-10000	0	0
CEBPB	0.025	0.008	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.028	0.064	-10000	0	-10000	0	0
STAT3	-0.068	0.31	-10000	0	-0.71	48	48
STAT1	0.003	0.071	-10000	0	-0.92	2	2
CEBPD	-0.047	0.28	-10000	0	-0.73	25	25
PIK3CA	0.02	0.014	-10000	0	-0.24	1	1
PI3K	0.031	0.009	-10000	0	-10000	0	0
JUN	-0.008	0.079	-10000	0	-0.24	37	37
PIAS3/MITF	0.015	0.12	-10000	0	-0.33	22	22
MAPK11	0.031	0.12	-10000	0	-0.66	5	5
STAT3 (dimer)/FOXO1	0.008	0.24	-10000	0	-0.55	24	24
GRB2/SOS1/GAB family	0.023	0.12	-10000	0	-0.48	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0	0.14	-10000	0	-0.34	42	42
GRB2	0.019	0.001	-10000	0	-10000	0	0
JAK2	0.009	0.072	-10000	0	-0.5	7	7
LBP	-0.19	0.44	-10000	0	-0.91	87	87
PIK3R1	0.02	0	-10000	0	-10000	0	0
JAK1	0.02	0.006	-10000	0	-10000	0	0
MYC	-0.044	0.27	-10000	0	-0.7	25	25
FGG	-0.057	0.27	-10000	0	-0.72	25	25
macrophage differentiation	-0.065	0.3	-10000	0	-0.68	48	48
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.026	0.11	-10000	0	-0.32	30	30
JUNB	-0.043	0.26	-10000	0	-0.69	22	22
FOS	0.01	0.047	-10000	0	-0.24	12	12
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.013	0.12	-10000	0	-0.37	21	21
STAT1/PIAS1	0.01	0.13	-10000	0	-0.35	21	21
GRB2/SOS1/GAB family/SHP2/PI3K	0.052	0.018	-10000	0	-10000	0	0
STAT3 (dimer)	-0.067	0.31	-10000	0	-0.71	48	48
PRKCD	-0.036	0.25	-10000	0	-0.54	51	51
IL6R	0.012	0.067	-10000	0	-0.56	5	5
SOCS3	0.035	0.14	-10000	0	-1.2	3	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.032	0.062	-10000	0	-0.32	9	9
Rac1/GTP	-0.035	0.2	-10000	0	-0.44	53	53
HCK	-0.029	0.16	-10000	0	-0.54	31	31
MAPKKK cascade	0.04	0.054	-10000	0	-10000	0	0
bone resorption	-0.16	0.45	-10000	0	-0.98	79	79
IRF1	-0.11	0.41	-10000	0	-1.1	47	47
mol:GDP	-0.039	0.19	-10000	0	-0.4	58	58
SOS1	0.019	0.002	-10000	0	-10000	0	0
VAV1	-0.04	0.19	-10000	0	-0.41	58	58
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.031	0.12	-10000	0	-0.54	8	8
PTPN11	0.016	0.022	-10000	0	-10000	0	0
IL6/IL6RA	0.005	0.1	-10000	0	-0.42	18	18
gp130 (dimer)/TYK2/TYK2/LMO4	0.031	0.058	-10000	0	-0.32	9	9
gp130 (dimer)/JAK2/JAK2/LMO4	0.025	0.083	-10000	0	-0.4	12	12
IL6	-0.007	0.11	-10000	0	-0.43	22	22
PIAS3	0.019	0	-10000	0	-10000	0	0
PTPRE	0.008	0.07	-10000	0	-0.52	6	6
PIAS1	0.019	0	-10000	0	-10000	0	0
RAC1	0.019	0.002	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.012	0.094	0.2	1	-0.29	27	28
LMO4	0.018	0.032	-10000	0	-0.55	1	1
STAT3 (dimer)/PIAS3	-0.058	0.3	-10000	0	-0.7	39	39
MCL1	0.068	0.016	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.004	0.039	-9999	-0.16	19	19
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.013	0.038	-9999	-0.39	1	1
STXBP1	0.019	0	-9999	-10000	0	0
ACh/CHRNA1	-0.047	0.13	-9999	-0.31	64	64
RAB3GAP2/RIMS1/UNC13B	0.025	0.032	-9999	-0.32	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	0	0.046	-9999	-0.24	12	12
mol:ACh	-0.007	0.024	-9999	-0.077	6	6
RAB3GAP2	0.019	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	0.012	0.043	-9999	-0.27	1	1
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.047	0.13	-9999	-0.31	64	64
UNC13B	0.017	0.029	-9999	-0.54	1	1
CHRNA1	-0.066	0.19	-9999	-0.46	64	64
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.016	0.064	-9999	-0.16	52	52
SNAP25	-0.024	0.049	-9999	-0.099	110	110
VAMP2	0.008	0	-9999	-10000	0	0
SYT1	-0.021	0.098	-9999	-0.26	52	52
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.016	0.033	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.012	0.043	-9999	-0.27	1	1

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.019	0	-9999	-10000	0	0
EGFR	-0.007	0.087	-9999	-0.27	33	33
EGF/EGFR	-0.009	0.096	-9999	-0.24	47	47
EGF/EGFR dimer/SHC/GRB2/SOS1	0.015	0.093	-9999	-0.26	31	31
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.006	0.057	-9999	-0.24	18	18
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.031	0.15	-9999	-0.42	41	41
EGF/EGFR dimer/SHC	-0.008	0.11	-9999	-0.32	31	31
mol:GDP	0.011	0.091	-9999	-0.26	31	31
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.012	0.055	-9999	-0.39	6	6
GRB2/SOS1	0.028	0	-9999	-10000	0	0
HRAS/GTP	-0.026	0.066	-9999	-0.24	28	28
SHC1	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.013	0.084	-9999	-0.24	28	28
FRAP1	0	0.082	-9999	-0.24	31	31
EGF/EGFR dimer	-0.026	0.12	-9999	-0.38	31	31
SOS1	0.019	0	-9999	-10000	0	0
GRB2	0.019	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	0.015	0.059	-9999	-0.34	6	6

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.003	0.13	-10000	0	-0.37	15	15
CRKL	0.04	0.11	-10000	0	-0.36	8	8
HRAS	-0.005	0.15	-10000	0	-0.38	37	37
mol:PIP3	0.025	0.1	0.35	1	-0.35	8	9
SPRED1	0.016	0.041	-10000	0	-0.54	2	2
SPRED2	0.019	0	-10000	0	-10000	0	0
GAB1	0.035	0.12	0.22	1	-0.39	8	9
FOXO3	0.046	0.1	0.26	1	-0.36	6	7
AKT1	0.04	0.11	0.26	1	-0.39	6	7
BAD	0.046	0.1	0.26	1	-0.36	6	7
megakaryocyte differentiation	0.007	0.13	-10000	0	-0.32	26	26
GSK3B	0.046	0.1	0.26	1	-0.36	6	7
RAF1	0.005	0.13	-10000	0	-0.32	29	29
SHC1	0.019	0	-10000	0	-10000	0	0
STAT3	0.035	0.12	-10000	0	-0.39	8	8
STAT1	0.021	0.2	-10000	0	-0.87	10	10
HRAS/SPRED1	0.005	0.13	-10000	0	-0.31	38	38
cell proliferation	0.035	0.12	0.22	1	-0.38	8	9
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
TEC	0.005	0.086	-10000	0	-0.54	9	9
RPS6KB1	0.039	0.12	0.24	1	-0.38	8	9
HRAS/SPRED2	0.006	0.13	-10000	0	-0.3	37	37
LYN/TEC/p62DOK	0.035	0.12	-10000	0	-0.38	13	13
MAPK3	0.018	0.098	0.19	13	-0.24	20	33
STAP1	-0.15	0.16	-10000	0	-0.28	192	192
GRAP2	-0.046	0.18	-10000	0	-0.54	43	43
JAK2	0.022	0.18	-10000	0	-0.76	10	10
STAT1 (dimer)	0.022	0.19	-10000	0	-0.85	10	10
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.016	0.14	-10000	0	-0.37	26	26
actin filament polymerization	0.03	0.12	-10000	0	-0.32	13	13
LYN	-0.004	0.11	-10000	0	-0.54	15	15
STAP1/STAT5A (dimer)	-0.13	0.18	-10000	0	-0.44	50	50
PIK3R1	0.019	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	0.055	0.1	-10000	0	-0.35	6	6
PI3K	0.053	0.11	0.24	1	-0.39	6	7
PTEN	0.017	0.029	-10000	0	-0.54	1	1
SCF/KIT/EPO/EPOR	-0.014	0.2	-10000	0	-1.2	7	7
MAPK8	0.035	0.12	-10000	0	-0.39	8	8
STAT3 (dimer)	0.035	0.12	-10000	0	-0.38	8	8
positive regulation of transcription	0.02	0.084	0.17	13	-0.2	20	33
mol:GDP	-0.02	0.16	-10000	0	-0.39	42	42
PIK3C2B	0.036	0.12	-10000	0	-0.39	8	8
CBL/CRKL	0.048	0.11	-10000	0	-0.34	8	8
FER	0.035	0.12	-10000	0	-0.39	8	8
SH2B3	0.035	0.12	-10000	0	-0.39	8	8
PDPK1	0.031	0.1	0.34	1	-0.32	8	9
SNAI2	0.032	0.12	-10000	0	-0.39	9	9
positive regulation of cell proliferation	0.032	0.16	-10000	0	-0.63	10	10
KITLG	0.018	0.037	-10000	0	-0.35	3	3
cell motility	0.032	0.16	-10000	0	-0.63	10	10
PTPN6	-0.12	0.24	-10000	0	-0.53	92	92
EPOR	0.039	0.074	-10000	0	-10000	0	0
STAT5A (dimer)	0.035	0.14	-10000	0	-0.52	10	10
SOCS1	-0.01	0.12	-10000	0	-0.54	19	19
cell migration	-0.001	0.13	0.31	24	-10000	0	24
SOS1	0.019	0	-10000	0	-10000	0	0
EPO	0.013	0.021	-10000	0	-0.24	2	2
VAV1	-0.09	0.22	-10000	0	-0.54	72	72
GRB10	0.035	0.12	-10000	0	-0.39	8	8
PTPN11	0.017	0.005	-10000	0	-10000	0	0
SCF/KIT	0.031	0.12	0.22	59	-0.38	10	69
GO:0007205	0	0.006	-10000	0	-10000	0	0
MAP2K1	0.014	0.1	-10000	0	-0.26	24	24
CBL	0.019	0	-10000	0	-10000	0	0
KIT	-0.022	0.22	-10000	0	-1.3	7	7
MAP2K2	0.014	0.1	-10000	0	-0.26	26	26
SHC/Grb2/SOS1	0.052	0.11	-10000	0	-0.35	8	8
STAT5A	0.035	0.14	-10000	0	-0.54	10	10
GRB2	0.019	0	-10000	0	-10000	0	0
response to radiation	0.033	0.12	-10000	0	-0.38	9	9
SHC/GRAP2	-0.02	0.13	-10000	0	-0.38	43	43
PTPRO	0.006	0.13	-10000	0	-0.32	26	26
SH2B2	0.03	0.12	-10000	0	-0.33	13	13
DOK1	0.019	0	-10000	0	-10000	0	0
MATK	0.001	0.13	-10000	0	-0.31	24	24
CREBBP	0.035	0.027	-10000	0	-10000	0	0
BCL2	0.04	0.071	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.027	0.12	-10000	0	-0.49	13	13
IHH	0.014	0.052	-10000	0	-0.24	10	10
SHH Np/Cholesterol/GAS1	0.017	0.035	-10000	0	-0.3	4	4
LRPAP1	0.019	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	-0.017	0.035	0.29	4	-10000	0	4
SMO/beta Arrestin2	0.039	0.094	-10000	0	-0.5	4	4
SMO	0.031	0.097	-10000	0	-0.53	4	4
AKT1	0.043	0.049	-10000	0	-10000	0	0
ARRB2	0.019	0	-10000	0	-10000	0	0
BOC	0.015	0.031	-10000	0	-0.24	5	5
ADRBK1	0.019	0	-10000	0	-10000	0	0
heart looping	0.031	0.096	-10000	0	-0.52	4	4
STIL	0.034	0.065	-10000	0	-0.36	4	4
DHH N/PTCH2	0.002	0.084	-10000	0	-0.38	12	12
DHH N/PTCH1	0.019	0.1	-10000	0	-0.32	18	18
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
DHH	-0.011	0.11	-10000	0	-0.36	29	29
PTHLH	0.02	0.16	-10000	0	-0.69	13	13
determination of left/right symmetry	0.031	0.096	-10000	0	-0.52	4	4
PIK3R1	0.019	0	-10000	0	-10000	0	0
skeletal system development	0.021	0.16	-10000	0	-0.68	13	13
IHH N/Hhip	0.011	0.028	-10000	0	-0.18	1	1
DHH N/Hhip	-0.007	0.078	-10000	0	-0.39	11	11
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.031	0.096	-10000	0	-0.52	4	4
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.017	0.032	-10000	0	-0.39	2	2
PI3K	0.028	0.009	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.013	0.054	-10000	0	-0.42	5	5
somite specification	0.031	0.096	-10000	0	-0.52	4	4
SHH Np/Cholesterol/PTCH1	0.03	0.069	-10000	0	-0.38	4	4
SHH Np/Cholesterol/PTCH2	0.017	0.03	-10000	0	-0.3	2	2
SHH Np/Cholesterol/Megalin	-0.15	0.16	-10000	0	-0.3	195	195
SHH	0.011	0.023	-10000	0	-0.28	2	2
catabolic process	0.029	0.085	-10000	0	-0.36	9	9
SMO/Vitamin D3	0.035	0.081	-10000	0	-0.52	3	3
SHH Np/Cholesterol/Hhip	0.008	0.017	-10000	0	-0.3	1	1
LRP2	-0.28	0.28	-10000	0	-0.54	195	195
receptor-mediated endocytosis	-0.084	0.15	-10000	0	-0.41	21	21
SHH Np/Cholesterol/BOC	0.019	0.023	-10000	0	-0.29	1	1
SHH Np/Cholesterol/CDO	0.02	0.018	-10000	0	-0.29	1	1
mesenchymal cell differentiation	-0.007	0.017	0.3	1	-10000	0	1
mol:Vitamin D3	0.034	0.071	-10000	0	-0.38	4	4
IHH N/PTCH2	0.021	0.046	-10000	0	-0.2	9	9
CDON	0.019	0	-10000	0	-10000	0	0
IHH N/PTCH1	0.032	0.087	-10000	0	-0.36	9	9
Megalin/LRPAP1	-0.19	0.2	-10000	0	-0.38	195	195
PTCH2	0.012	0.046	-10000	0	-0.28	8	8
SHH Np/Cholesterol	0.011	0.018	-10000	0	-0.3	1	1
PTCH1	0.029	0.085	-10000	0	-0.36	9	9
HHIP	0	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.005	0.058	-10000	0	-0.24	19	19
ANTXR2	0.013	0.049	-10000	0	-0.34	6	6
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.009	-10000	0	-0.065	3	3
monocyte activation	-0.15	0.29	-10000	0	-0.56	105	105
MAP2K2	0.015	0.005	-10000	0	-10000	0	0
MAP2K1	0.01	0.009	-10000	0	-10000	0	0
MAP2K7	0.01	0.009	-10000	0	-10000	0	0
MAP2K6	0.004	0.041	-10000	0	-0.28	7	7
CYAA	0.006	0.036	-10000	0	-0.26	3	3
MAP2K4	0.01	0.009	-10000	0	-10000	0	0
IL1B	-0.038	0.12	-10000	0	-0.28	64	64
Channel	0.014	0.041	-10000	0	-0.27	3	3
NLRP1	-0.023	0.094	-10000	0	-0.29	41	41
CALM1	0.019	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0.014	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.009	0.065	3	-10000	0	3
MAPK3	0.01	0.009	-10000	0	-10000	0	0
MAPK1	0.01	0.009	-10000	0	-10000	0	0
PGR	0.008	0.016	-10000	0	-0.12	4	4
PA/Cellular Receptors	0.014	0.045	-10000	0	-0.15	24	24
apoptosis	-0.002	0.009	-10000	0	-0.065	3	3
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.014	0.037	-10000	0	-0.26	3	3
macrophage activation	0.016	0.009	-10000	0	-10000	0	0
TNF	-0.095	0.22	-10000	0	-0.54	75	75
VCAM1	-0.15	0.29	-10000	0	-0.57	105	105
platelet activation	0.014	0.012	-10000	0	-10000	0	0
MAPKKK cascade	-0.012	0.014	-10000	0	-10000	0	0
IL18	-0.085	0.18	-10000	0	-0.34	103	103
negative regulation of macrophage activation	-0.002	0.009	-10000	0	-0.065	3	3
LEF	-0.002	0.009	-10000	0	-0.065	3	3
CASP1	-0.018	0.081	-10000	0	-0.2	46	46
mol:cAMP	0.014	0.012	-10000	0	-10000	0	0
necrosis	-0.002	0.009	-10000	0	-0.065	3	3
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.014	0.038	-10000	0	-0.26	3	3
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.031	-9999	-0.24	5	5
alphaV beta3 Integrin	-0.009	0.1	-9999	-0.38	20	20
PTK2	0.018	0.079	-9999	-0.36	8	8
positive regulation of JNK cascade	-0.011	0.043	-9999	-0.28	8	8
CDC42/GDP	0.044	0.076	-9999	-0.37	8	8
Rac1/GDP	0.046	0.076	-9999	-0.37	8	8
RAP1B	0.019	0	-9999	-10000	0	0
RAP1A	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.054	-9999	-0.34	8	8
nectin-3/I-afadin	-0.004	0.084	-9999	-0.37	10	10
RAPGEF1	0.034	0.08	-9999	-0.4	9	9
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.028	0.088	-9999	-0.45	9	9
PDGFB-D/PDGFRB	0.015	0.031	-9999	-0.24	5	5
TLN1	0.021	0.036	-9999	-10000	0	0
Rap1/GTP	-0.01	0.045	-9999	-0.29	8	8
IQGAP1	0.019	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.027	0.035	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.084	-9999	-0.37	10	10
PVR	0.017	0.029	-9999	-0.54	1	1
Necl-5(dimer)	0.017	0.029	-9999	-0.54	1	1
mol:GDP	0.039	0.088	-9999	-0.43	9	9
MLLT4	0.001	0.066	-9999	-0.24	25	25
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PI3K	0.03	0.066	-9999	-0.24	11	11
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.014	0.049	-9999	-0.31	1	1
positive regulation of lamellipodium assembly	-0.013	0.05	-9999	-0.28	11	11
PVRL1	0.017	0.024	-9999	-0.24	3	3
PVRL3	-0.009	0.1	-9999	-0.32	30	30
PVRL2	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
CDH1	-0.13	0.25	-9999	-0.54	101	101
CLDN1	-0.24	0.28	-9999	-0.54	173	173
JAM-A/CLDN1	-0.14	0.18	-9999	-0.31	179	179
SRC	0.021	0.095	-9999	-0.5	9	9
ITGB3	-0.032	0.14	-9999	-0.36	50	50
nectin-1(dimer)/I-afadin/I-afadin	0.014	0.049	-9999	-0.31	1	1
FARP2	0.035	0.085	-9999	-0.45	8	8
RAC1	0.019	0	-9999	-10000	0	0
CTNNA1	0.019	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.01	0.076	-9999	-0.32	11	11
nectin-1/I-afadin	0.014	0.049	-9999	-0.31	1	1
nectin-2/I-afadin	0.016	0.045	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.026	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.01	0.074	-9999	-0.3	11	11
CDC42/GTP/IQGAP1/filamentous actin	0.026	0	-9999	-10000	0	0
F11R	0.01	0.07	-9999	-0.54	6	6
positive regulation of filopodium formation	-0.011	0.043	-9999	-0.28	8	8
alphaV/beta3 Integrin/Talin	0.016	0.075	-9999	-0.23	19	19
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.016	0.045	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.016	0.045	-9999	-10000	0	0
PIP5K1C	0.015	0.039	-9999	-0.17	8	8
VAV2	0.03	0.096	-9999	-0.45	11	11
RAP1/GDP	0.045	0.07	-9999	-0.34	8	8
ITGAV	0.018	0.014	-9999	-0.24	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.011	0.072	-9999	-0.3	10	10
nectin-3(dimer)/I-afadin/I-afadin	-0.004	0.084	-9999	-0.37	10	10
Rac1/GTP	-0.013	0.061	-9999	-0.33	11	11
PTPRM	0.007	0.043	-9999	-0.2	8	8
E-cadherin/beta catenin/alpha catenin	-0.034	0.14	-9999	-0.25	101	101
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.019	0	-9999	-10000	0	0

×

Ceramide signaling 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
SPHK2	0.015	0.064	-10000	0	-0.38	9	9
MAP4K4	-0.082	0.19	-10000	0	-0.48	53	53
BAG4	0.017	0.029	-10000	0	-0.54	1	1
PKC zeta/ceramide	0	0.038	0.14	8	-0.29	2	10
NFKBIA	0.019	0	-10000	0	-10000	0	0
BIRC3	-0.18	0.26	-10000	0	-0.54	128	128
BAX	0.005	0.017	-10000	0	-10000	0	0
RIPK1	0.019	0	-10000	0	-10000	0	0
AKT1	0.019	0.007	-10000	0	-10000	0	0
BAD	-0.004	0.032	0.15	9	-10000	0	9
SMPD1	-0.032	0.099	-10000	0	-0.22	75	75
RB1	-0.004	0.035	0.15	9	-0.29	1	10
FADD/Caspase 8	-0.069	0.19	-10000	0	-0.46	56	56
MAP2K4	0.004	0.03	0.15	8	-10000	0	8
NSMAF	0.019	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.004	0.03	0.15	8	-10000	0	8
EGF	-0.031	0.15	-10000	0	-0.42	41	41
mol:ceramide	-0.012	0.034	0.15	9	-10000	0	9
MADD	0.019	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.015	0.064	-10000	0	-0.38	9	9
ASAH1	0.019	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.004	0.035	0.15	9	-0.29	1	10
cell proliferation	0.025	0.034	-10000	0	-0.23	3	3
BID	-0.047	0.13	-10000	0	-0.31	49	49
MAP3K1	-0.004	0.032	0.15	9	-10000	0	9
EIF2A	0.01	0.029	-10000	0	-10000	0	0
TRADD	0.019	0	-10000	0	-10000	0	0
CRADD	0.018	0.014	-10000	0	-0.24	1	1
MAPK3	0.015	0.028	0.15	8	-10000	0	8
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.028	0.15	8	-10000	0	8
Cathepsin D/ceramide	0	0.034	0.14	9	-0.12	4	13
FADD	-0.082	0.19	-10000	0	-0.48	54	54
KSR1	-0.004	0.032	0.15	9	-10000	0	9
MAPK8	0.01	0.034	0.15	8	-0.22	2	10
PRKRA	-0.004	0.032	0.15	9	-10000	0	9
PDGFA	0.004	0.088	-10000	0	-0.48	11	11
TRAF2	0.019	0	-10000	0	-10000	0	0
IGF1	0.008	0.066	-10000	0	-0.36	10	10
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.012	0.034	0.15	9	-10000	0	9
CTSD	0.016	0.027	-10000	0	-0.24	4	4
regulation of nitric oxide biosynthetic process	0.028	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.031	0.04	-10000	0	-0.24	3	3
PRKCD	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.015	0.064	-10000	0	-0.38	9	9
RelA/NF kappa B1	0.028	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.004	0.11	-10000	0	-0.54	15	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.094	0.2	-10000	0	-0.52	53	53
TNFR1A/BAG4/TNF-alpha	-0.035	0.14	-10000	0	-0.32	76	76
mol:Sphingosine-1-phosphate	0.015	0.064	-10000	0	-0.38	9	9
MAP2K1	0.01	0.029	0.15	8	-10000	0	8
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.019	0	-10000	0	-10000	0	0
CYCS	0.001	0.023	0.11	8	-10000	0	8
TNFRSF1A	0.019	0	-10000	0	-10000	0	0
NFKB1	0.019	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.027	0.021	-10000	0	-0.38	1	1
EIF2AK2	0.004	0.03	0.15	8	-10000	0	8
TNF-alpha/TNFR1A/FAN	-0.034	0.14	-10000	0	-0.32	75	75
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.03	0.12	-10000	0	-0.26	55	55
MAP2K2	0.01	0.029	0.15	8	-10000	0	8
SMPD3	-0.04	0.12	-10000	0	-0.25	75	75
TNF	-0.095	0.22	-10000	0	-0.54	75	75
PKC zeta/PAR4	0.009	0.086	-10000	0	-0.38	17	17
mol:PHOSPHOCHOLINE	-0.001	0.066	0.19	30	-10000	0	30
NF kappa B1/RelA/I kappa B alpha	0.042	0.066	-10000	0	-0.26	17	17
AIFM1	0.001	0.023	0.11	8	-10000	0	8
BCL2	0.019	0	-10000	0	-10000	0	0

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.004	0.085	-10000	0	-0.32	23	23
cell-cell adhesion	0.032	0.076	0.32	8	-10000	0	8
Ephrin B/EPHB2/RasGAP	0.014	0.1	-10000	0	-0.26	40	40
ITSN1	0.019	0	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
SHC1	0.019	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.009	0.049	-10000	0	-0.26	2	2
Ephrin B1/EPHB1	0.006	0.066	-10000	0	-0.3	11	11
HRAS/GDP	-0.024	0.073	-10000	0	-0.26	25	25
Ephrin B/EPHB1/GRB7	0.004	0.1	-10000	0	-0.28	33	33
Endophilin/SYNJ1	0.003	0.091	-10000	0	-0.24	39	39
KRAS	0.018	0.014	-10000	0	-0.24	1	1
Ephrin B/EPHB1/Src	0.016	0.098	-10000	0	-0.27	32	32
endothelial cell migration	0.037	0.022	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
GRB7	-0.004	0.068	-10000	0	-0.24	27	27
PAK1	0.008	0.098	-10000	0	-0.26	39	39
HRAS	0.019	0	-10000	0	-10000	0	0
RRAS	0.003	0.092	-10000	0	-0.25	39	39
DNM1	-0.009	0.081	-10000	0	-0.24	39	39
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.005	0.089	-10000	0	-0.26	32	32
lamellipodium assembly	-0.032	0.076	-10000	0	-0.32	8	8
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.018	0.074	-10000	0	-0.24	9	9
PIK3R1	0.019	0	-10000	0	-10000	0	0
EPHB2	-0.005	0.11	-10000	0	-0.54	16	16
EPHB3	-0.001	0.069	-10000	0	-0.24	27	27
EPHB1	-0.005	0.094	-10000	0	-0.33	25	25
EPHB4	0.018	0.014	-10000	0	-0.24	1	1
mol:GDP	0.012	0.092	-10000	0	-0.27	25	25
Ephrin B/EPHB2	0.004	0.1	-10000	0	-0.26	42	42
Ephrin B/EPHB3	0.008	0.088	-10000	0	-0.27	27	27
JNK cascade	0.013	0.085	-10000	0	-0.27	25	25
Ephrin B/EPHB1	0.005	0.097	-10000	0	-0.27	34	34
RAP1/GDP	0.029	0.086	-10000	0	-0.3	4	4
EFNB2	0.012	0.041	-10000	0	-0.24	9	9
EFNB3	-0.016	0.14	-10000	0	-0.54	23	23
EFNB1	0.009	0.051	-10000	0	-0.24	14	14
Ephrin B2/EPHB1-2	0.006	0.091	-10000	0	-0.31	23	23
RAP1B	0.019	0	-10000	0	-10000	0	0
RAP1A	0.019	0	-10000	0	-10000	0	0
CDC42/GTP	-0.037	0.088	-10000	0	-0.4	6	6
Rap1/GTP	-0.031	0.075	-10000	0	-0.35	6	6
axon guidance	0.003	0.085	-10000	0	-0.32	23	23
MAPK3	0.029	0.067	-10000	0	-0.28	2	2
MAPK1	0.029	0.067	-10000	0	-0.32	1	1
Rac1/GDP	0.022	0.088	-10000	0	-0.25	24	24
actin cytoskeleton reorganization	-0.026	0.064	-10000	0	-0.3	6	6
CDC42/GDP	0.022	0.088	-10000	0	-0.25	24	24
PI3K	0.041	0.023	-10000	0	-10000	0	0
EFNA5	0.008	0.076	-10000	0	-0.54	7	7
Ephrin B2/EPHB4	0.022	0.024	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.01	0.087	-10000	0	-0.23	39	39
CDC42	0.019	0	-10000	0	-10000	0	0
RAS family/GTP	-0.031	0.073	-10000	0	-0.34	6	6
PTK2	0.008	0.022	-10000	0	-10000	0	0
MAP4K4	0.013	0.086	-10000	0	-0.28	25	25
SRC	0.019	0	-10000	0	-10000	0	0
KALRN	0.014	0.045	-10000	0	-0.39	4	4
Intersectin/N-WASP	0.028	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.032	0.097	-10000	0	-0.32	8	8
MAP2K1	0.024	0.07	-10000	0	-0.3	2	2
WASL	0.019	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.016	0.095	-10000	0	-0.3	25	25
cell migration	0.026	0.082	-10000	0	-0.35	2	2
NRAS	0.019	0	-10000	0	-10000	0	0
SYNJ1	0.003	0.092	-10000	0	-0.25	39	39
PXN	0.019	0	-10000	0	-10000	0	0
TF	-0.059	0.14	-10000	0	-0.27	97	97
HRAS/GTP	0.005	0.1	-10000	0	-0.35	8	8
Ephrin B1/EPHB1-2	0.005	0.094	-10000	0	-0.31	25	25
cell adhesion mediated by integrin	0.022	0.072	0.26	26	-10000	0	26
RAC1	0.019	0	-10000	0	-10000	0	0
mol:GTP	0.006	0.11	-10000	0	-0.26	47	47
RAC1-CDC42/GTP	-0.035	0.077	-10000	0	-0.34	8	8
RASA1	0.017	0.029	-10000	0	-0.54	1	1
RAC1-CDC42/GDP	0.029	0.086	-10000	0	-0.3	4	4
ruffle organization	0.018	0.097	-10000	0	-0.35	6	6
NCK1	0.019	0	-10000	0	-10000	0	0
receptor internalization	-0.003	0.094	-10000	0	-0.24	40	40
Ephrin B/EPHB2/KALRN	0.013	0.11	-10000	0	-0.28	39	39
ROCK1	0.014	0.043	-10000	0	-0.22	2	2
RAS family/GDP	-0.026	0.064	-10000	0	-0.29	6	6
Rac1/GTP	-0.034	0.08	-10000	0	-0.34	8	8
Ephrin B/EPHB1/Src/Paxillin	0.012	0.082	-10000	0	-0.24	32	32

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.007	0.059	0.22	4	-10000	0	4
GNAI2	0.019	0	-10000	0	-10000	0	0
S1P/S1P5/G12	0.019	0.03	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.093	0.13	-10000	0	-0.25	155	155
RhoA/GTP	-0.007	0.06	-10000	0	-0.23	4	4
negative regulation of cAMP metabolic process	-0.017	0.065	-10000	0	-0.24	5	5
GNAZ	-0.015	0.093	-10000	0	-0.26	45	45
GNAI3	0.019	0	-10000	0	-10000	0	0
GNA12	0.019	0	-10000	0	-10000	0	0
S1PR5	0.008	0.052	-10000	0	-0.24	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.017	0.065	-10000	0	-0.24	5	5
RhoA/GDP	0.014	0	-10000	0	-10000	0	0
RHOA	0.019	0	-10000	0	-10000	0	0
GNAI1	0.004	0.06	-10000	0	-0.24	20	20

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.023	0.081	-10000	0	-0.28	24	24
ER alpha/Gai/GDP/Gbeta gamma	-0.007	0.09	-10000	0	-0.37	12	12
AKT1	0.023	0.12	-10000	0	-0.79	7	7
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.019	0.12	-10000	0	-0.81	7	7
mol:Ca2+	-0.052	0.19	-10000	0	-0.4	73	73
IGF1R	0.016	0.027	-10000	0	-0.24	4	4
E2/ER alpha (dimer)/Striatin	0.019	0.048	-10000	0	-0.32	7	7
SHC1	0.019	0	-10000	0	-10000	0	0
apoptosis	-0.023	0.11	0.76	7	-10000	0	7
RhoA/GTP	-0.004	0.031	-10000	0	-0.22	7	7
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.01	0.073	-10000	0	-0.41	9	9
regulation of stress fiber formation	-0.047	0.031	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	0.007	0.078	-10000	0	-0.32	19	19
KRAS	0.018	0.014	-10000	0	-0.24	1	1
G13/GTP	0.018	0.044	-10000	0	-0.29	7	7
pseudopodium formation	0.047	0.031	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	0.019	0.048	-10000	0	-0.32	7	7
GRB2	0.019	0	-10000	0	-10000	0	0
GNG2	0.01	0.07	-10000	0	-0.54	6	6
GNAO1	-0.093	0.13	-10000	0	-0.25	155	155
HRAS	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.014	0.094	-10000	0	-0.5	8	8
E2/ER beta (dimer)	0	0.073	-10000	0	-0.36	14	14
mol:GDP	-0.017	0.071	-10000	0	-0.32	19	19
mol:NADP	0.014	0.094	-10000	0	-0.5	8	8
PIK3R1	0.019	0	-10000	0	-10000	0	0
mol:IP3	-0.055	0.2	-10000	0	-0.42	73	73
IGF-1R heterotetramer	0.016	0.027	-10000	0	-0.24	4	4
PLCB1	-0.055	0.19	-10000	0	-0.42	69	69
PLCB2	-0.054	0.2	-10000	0	-0.42	71	71
IGF1	0.008	0.066	-10000	0	-0.36	10	10
mol:L-citrulline	0.014	0.094	-10000	0	-0.5	8	8
RHOA	0.019	0	-10000	0	-10000	0	0
Gai/GDP	-0.022	0.081	-10000	0	-0.5	2	2
JNK cascade	0	0.073	-10000	0	-0.36	14	14
BCAR1	0.019	0	-10000	0	-10000	0	0
ESR2	-0.001	0.1	-10000	0	-0.5	14	14
GNAQ	0.019	0	-10000	0	-10000	0	0
ESR1	0.008	0.076	-10000	0	-0.54	7	7
Gq family/GDP/Gbeta gamma	-0.012	0.14	-10000	0	-0.57	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.034	0.042	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.01	0.073	-10000	0	-0.41	9	9
GNAZ	-0.015	0.093	-10000	0	-0.26	45	45
E2/ER alpha (dimer)	0.006	0.055	-10000	0	-0.39	7	7
STRN	0.019	0	-10000	0	-10000	0	0
GNAL	-0.02	0.1	-10000	0	-0.28	49	49
PELP1	0.019	0	-10000	0	-10000	0	0
MAPK11	0.01	0.062	-10000	0	-0.32	12	12
GNAI2	0.019	0	-10000	0	-10000	0	0
GNAI3	0.019	0	-10000	0	-10000	0	0
GNAI1	0.004	0.06	-10000	0	-0.24	20	20
HBEGF	-0.023	0.1	-10000	0	-0.36	13	13
cAMP biosynthetic process	-0.01	0.08	-10000	0	-0.27	25	25
SRC	0.001	0.086	-10000	0	-0.39	9	9
PI3K	0.028	0.009	-10000	0	-10000	0	0
GNB1	0.019	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.027	0.08	-10000	0	-0.28	19	19
SOS1	0.019	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.013	0.063	-10000	0	-0.35	9	9
Gs family/GTP	-0.006	0.083	-10000	0	-0.27	25	25
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.007	-10000	0	-10000	0	0
vasodilation	0.014	0.091	-10000	0	-0.48	8	8
mol:DAG	-0.055	0.2	-10000	0	-0.42	73	73
Gs family/GDP/Gbeta gamma	-0.025	0.073	-10000	0	-0.29	19	19
MSN	0.048	0.033	-10000	0	-10000	0	0
Gq family/GTP	-0.054	0.19	-10000	0	-0.43	67	67
mol:PI-3-4-5-P3	0.02	0.11	-10000	0	-0.78	7	7
NRAS	0.019	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.014	0.091	0.48	8	-10000	0	8
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
RhoA/GDP	0.025	0.076	-10000	0	-0.3	19	19
NOS3	0.013	0.098	-10000	0	-0.53	8	8
GNA11	0.019	0	-10000	0	-10000	0	0
MAPKKK cascade	0.032	0.094	-10000	0	-0.59	7	7
E2/ER alpha (dimer)/PELP1/Src	0.015	0.088	-10000	0	-0.43	9	9
ruffle organization	0.047	0.031	-10000	0	-10000	0	0
ROCK2	0.045	0.035	-10000	0	-10000	0	0
GNA14	-0.084	0.22	-10000	0	-0.53	69	69
GNA15	0.002	0.095	-10000	0	-0.54	11	11
GNA13	0.019	0	-10000	0	-10000	0	0
MMP9	-0.04	0.14	-10000	0	-0.33	45	45
MMP2	-0.008	0.09	-10000	0	-0.37	9	9

×

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

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
MET/RANBP9	-0.003	0.1	-10000	0	-0.38	22	22
CRKL	0.017	0.079	-10000	0	-0.26	23	23
mol:PIP3	-0.019	0.028	0.51	1	-10000	0	1
AKT1	0.001	0.019	0.36	1	-10000	0	1
PTK2B	0.008	0.076	-10000	0	-0.54	7	7
RAPGEF1	0.024	0.076	-10000	0	-0.32	4	4
RANBP10	0.019	0	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
HGF/MET/SHIP2	0.001	0.1	-10000	0	-0.33	27	27
MAP3K5	-0.013	0.14	-10000	0	-0.37	28	28
HGF/MET/CIN85/CBL/ENDOPHILINS	0.014	0.095	-10000	0	-0.3	27	27
AP1	-0.004	0.066	-10000	0	-0.26	11	11
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.019	0	-10000	0	-10000	0	0
apoptosis	0.003	0.056	-10000	0	-10000	0	0
STAT3 (dimer)	0.016	0.091	-10000	0	-0.47	4	4
GAB1/CRKL/SHP2/PI3K	0.041	0.075	-10000	0	-0.33	3	3
INPP5D	-0.075	0.21	-10000	0	-0.54	62	62
CBL/CRK	0.028	0.077	-10000	0	-0.32	4	4
PTPN11	0.019	0	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.019	0	-10000	0	-10000	0	0
PTEN	0.017	0.029	-10000	0	-0.54	1	1
ELK1	-0.017	0.049	-10000	0	-0.2	22	22
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.019	0.051	-10000	0	-0.24	3	3
PAK1	0.008	0.019	0.34	1	-10000	0	1
HGF/MET/RANBP10	0.001	0.1	-10000	0	-0.33	27	27
HRAS	-0.005	0.16	-10000	0	-0.61	22	22
DOCK1	0.024	0.076	-10000	0	-0.32	4	4
GAB1	0.011	0.083	-10000	0	-0.28	23	23
CRK	0.018	0.079	-10000	0	-0.26	23	23
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.16	-10000	0	-0.55	27	27
JUN	-0.008	0.079	-10000	0	-0.24	37	37
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.008	0.075	-10000	0	-0.26	27	27
PIK3R1	0.019	0	-10000	0	-10000	0	0
cell morphogenesis	0.042	0.092	-10000	0	-0.43	4	4
GRB2/SHC	0.015	0.07	-10000	0	-0.23	22	22
FOS	0.01	0.047	-10000	0	-0.24	12	12
GLMN	-0.003	0.027	-10000	0	-0.26	4	4
cell motility	-0.017	0.049	-10000	0	-0.2	22	22
HGF/MET/MUC20	-0.012	0.1	-10000	0	-0.34	27	27
cell migration	0.015	0.069	-10000	0	-0.23	22	22
GRB2	0.019	0	-10000	0	-10000	0	0
CBL	0.019	0	-10000	0	-10000	0	0
MET/RANBP10	-0.003	0.1	-10000	0	-0.38	22	22
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.011	0.092	-10000	0	-0.26	33	33
MET/MUC20	-0.017	0.1	-10000	0	-0.31	35	35
RAP1B	0.03	0.072	-10000	0	-0.32	3	3
RAP1A	0.03	0.072	-10000	0	-0.32	3	3
HGF/MET/RANBP9	0.001	0.1	-10000	0	-0.33	27	27
RAF1	0.003	0.15	-10000	0	-0.57	22	22
STAT3	0.016	0.092	-10000	0	-0.48	4	4
cell proliferation	0.019	0.12	-10000	0	-0.37	27	27
RPS6KB1	0.006	0.034	-10000	0	-0.19	2	2
MAPK3	-0.023	0.045	-10000	0	-0.19	2	2
MAPK1	-0.023	0.045	-10000	0	-10000	0	0
RANBP9	0.019	0	-10000	0	-10000	0	0
MAPK8	0.018	0.11	-10000	0	-0.33	14	14
SRC	0.017	0.086	-10000	0	-0.44	4	4
PI3K	0.015	0.07	-10000	0	-0.23	22	22
MET/Glomulin	-0.012	0.092	-10000	0	-0.26	38	38
SOS1	0.019	0	-10000	0	-10000	0	0
MAP2K1	0.011	0.14	-10000	0	-0.52	22	22
MET	-0.024	0.14	-10000	0	-0.43	35	35
MAP4K1	-0.02	0.14	-10000	0	-0.38	27	27
PTK2	0.019	0	-10000	0	-10000	0	0
MAP2K2	0.011	0.14	-10000	0	-0.52	22	22
BAD	0.008	0.018	0.34	1	-10000	0	1
MAP2K4	-0.004	0.13	-10000	0	-0.36	22	22
SHP2/GRB2/SOS1/GAB1	-0.025	0.083	-10000	0	-0.34	22	22
INPPL1	0.019	0	-10000	0	-10000	0	0
PXN	0.019	0	-10000	0	-10000	0	0
SH3KBP1	0.019	0	-10000	0	-10000	0	0
HGS	0	0.07	-10000	0	-0.23	27	27
PLCgamma1/PKC	0.014	0	-10000	0	-10000	0	0
HGF	0	0.085	-10000	0	-0.34	19	19
RASA1	0.017	0.029	-10000	0	-0.54	1	1
NCK1	0.019	0	-10000	0	-10000	0	0
PTPRJ	0.019	0	-10000	0	-10000	0	0
NCK/PLCgamma1	0.017	0.071	-10000	0	-0.23	22	22
PDPK1	-0.008	0.022	0.4	1	-10000	0	1
HGF/MET/SHIP	-0.058	0.17	-10000	0	-0.37	78	78

×

Ephrin B reverse 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
EFNB2	0.012	0.041	-10000	0	-0.24	9	9
EPHB2	-0.006	0.12	-10000	0	-0.54	16	16
EFNB1	-0.001	0.069	-10000	0	-0.31	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.004	0.12	-10000	0	-0.3	41	41
Ephrin B2/EPHB1-2	0.005	0.093	-10000	0	-0.32	23	23
neuron projection morphogenesis	-0.025	0.11	-10000	0	-0.29	41	41
Ephrin B1/EPHB1-2/Tiam1	-0.012	0.13	-10000	0	-0.33	41	41
DNM1	-0.01	0.082	-10000	0	-0.25	39	39
cell-cell signaling	-0.001	0.003	-10000	0	-10000	0	0
MAP2K4	0.002	0.077	-10000	0	-0.7	4	4
YES1	-0.002	0.1	-10000	0	-0.94	4	4
Ephrin B1/EPHB1-2/NCK2	0.006	0.1	-10000	0	-0.31	23	23
PI3K	0.011	0.079	-10000	0	-0.7	4	4
mol:GDP	-0.013	0.13	-10000	0	-0.32	41	41
ITGA2B	-0.004	0.073	-10000	0	-0.24	31	31
endothelial cell proliferation	0.021	0.024	-10000	0	-10000	0	0
FYN	-0.002	0.1	-10000	0	-0.94	4	4
MAP3K7	-0.005	0.081	-10000	0	-0.74	4	4
FGR	-0.019	0.12	-10000	0	-0.95	4	4
TIAM1	-0.014	0.13	-10000	0	-0.54	22	22
PIK3R1	0.019	0	-10000	0	-10000	0	0
RGS3	0.019	0	-10000	0	-10000	0	0
cell adhesion	-0.01	0.12	-10000	0	-0.55	8	8
LYN	-0.009	0.11	-10000	0	-0.94	4	4
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.093	-10000	0	-0.88	4	4
Ephrin B1/EPHB1-2	-0.019	0.085	-10000	0	-0.8	4	4
SRC	-0.002	0.099	-10000	0	-0.92	4	4
ITGB3	-0.032	0.14	-10000	0	-0.36	50	50
EPHB1	-0.006	0.094	-10000	0	-0.33	25	25
EPHB4	0.018	0.014	-10000	0	-0.24	1	1
RAC1	0.019	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.021	0.025	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.024	0.11	-10000	0	-0.36	25	25
BLK	-0.12	0.12	-10000	0	-0.99	4	4
HCK	-0.021	0.11	-10000	0	-0.96	4	4
regulation of stress fiber formation	-0.005	0.1	0.31	23	-10000	0	23
MAPK8	0.009	0.073	-10000	0	-0.66	4	4
Ephrin B1/EPHB1-2/RGS3	0.006	0.1	-10000	0	-0.31	23	23
endothelial cell migration	-0.002	0.073	-10000	0	-0.63	4	4
NCK2	0.019	0	-10000	0	-10000	0	0
PTPN13	0.018	0.077	-10000	0	-0.49	7	7
regulation of focal adhesion formation	-0.005	0.1	0.31	23	-10000	0	23
chemotaxis	-0.005	0.1	0.31	23	-10000	0	23
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
Rac1/GTP	-0.009	0.12	-10000	0	-0.29	41	41
angiogenesis	-0.019	0.085	-10000	0	-0.8	4	4
LCK	-0.069	0.14	-10000	0	-0.99	4	4

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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	0.018	0.014	-10000	0	-0.24	1	1
NFATC1	0.056	0.055	-10000	0	-0.27	9	9
NFATC2	0.032	0.047	-10000	0	-0.25	2	2
NFATC3	0.027	0.03	-10000	0	-0.38	2	2
YWHAE	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.099	0.2	-10000	0	-0.44	81	81
Exportin 1/Ran/NUP214	0.039	0.001	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.1	0.22	-10000	0	-0.44	99	99
BCL2/BAX	0.028	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.016	0.002	-10000	0	-10000	0	0
CaM/Ca2+	0.016	0.002	-10000	0	-10000	0	0
BAX	0.019	0	-10000	0	-10000	0	0
MAPK14	0.019	0.001	-10000	0	-10000	0	0
BAD	0.019	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.085	0.19	-10000	0	-0.42	81	81
Calcineurin A alpha-beta B1/BCL2	0.019	0	-10000	0	-10000	0	0
FKBP8	0.019	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.084	0.19	0.41	81	-10000	0	81
KPNB1	0.019	0	-10000	0	-10000	0	0
KPNA2	0.019	0	-10000	0	-10000	0	0
XPO1	0.019	0	-10000	0	-10000	0	0
SFN	-0.035	0.11	-10000	0	-0.24	74	74
MAP3K8	-0.003	0.11	-10000	0	-0.52	15	15
NFAT4/CK1 alpha	0.041	0.019	-10000	0	-0.21	2	2
MEF2D/NFAT1/Cbp/p300	0.069	0.049	-10000	0	-0.24	1	1
CABIN1	-0.1	0.2	-10000	0	-0.45	81	81
CALM1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.019	0	-10000	0	-10000	0	0
MAP3K1	0.019	0	-10000	0	-10000	0	0
CAMK4	-0.063	0.2	-10000	0	-0.54	54	54
mol:Ca2+	0.001	0.001	-10000	0	-10000	0	0
MAPK3	0.019	0	-10000	0	-10000	0	0
YWHAH	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.042	0.16	-10000	0	-0.38	63	63
YWHAB	0.019	0	-10000	0	-10000	0	0
MAPK8	0.019	0.001	-10000	0	-10000	0	0
MAPK9	0.019	0	-10000	0	-10000	0	0
YWHAG	0.019	0	-10000	0	-10000	0	0
FKBP1A	0.019	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.074	0.055	-10000	0	-0.27	2	2
PRKCH	0.016	0.041	-10000	0	-0.54	2	2
CABIN1/Cbp/p300	0.029	0.002	-10000	0	-10000	0	0
CASP3	0.019	0.001	-10000	0	-10000	0	0
PIM1	0.019	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.013	0.001	-10000	0	-10000	0	0
apoptosis	0	0.005	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.036	0.027	-10000	0	-10000	0	0
PRKCB	-0.15	0.26	-10000	0	-0.54	110	110
PRKCE	0.019	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.035	0.028	-10000	0	-0.34	2	2
BAD/BCL-XL	0.028	0.009	-10000	0	-10000	0	0
PRKCD	0.019	0	-10000	0	-10000	0	0
NUP214	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
PRKCA	0.013	0.044	-10000	0	-0.29	7	7
PRKCG	0.01	0.025	-10000	0	-0.24	3	3
PRKCQ	-0.16	0.26	-10000	0	-0.54	116	116
FKBP38/BCL2	0.028	0	-10000	0	-10000	0	0
EP300	0.02	0.001	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.019	0	-10000	0	-10000	0	0
NFATc/JNK1	0.065	0.053	-10000	0	-0.27	1	1
CaM/Ca2+/FKBP38	0.027	0.002	-10000	0	-10000	0	0
FKBP12/FK506	0.014	0	-10000	0	-10000	0	0
CSNK1A1	0.024	0.002	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.025	0.12	-10000	0	-0.32	54	54
NFATc/ERK1	0.064	0.053	-10000	0	-0.27	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.1	0.22	-10000	0	-0.44	99	99
NR4A1	0.062	0.051	-10000	0	-0.49	1	1
GSK3B	0.019	0.001	-10000	0	-10000	0	0
positive T cell selection	0.027	0.03	-10000	0	-0.38	2	2
NFAT1/CK1 alpha	0.031	0.039	-10000	0	-0.22	2	2
RCH1/ KPNB1	0.028	0	-10000	0	-10000	0	0
YWHAQ	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0.001	-10000	0	-10000	0	0
AKAP5	-0.077	0.21	-10000	0	-0.54	63	63
MEF2D	0.02	0.001	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.019	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.065	0.053	-10000	0	-0.27	1	1
CREBBP	0.02	0.001	-10000	0	-10000	0	0
BCL2	0.019	0	-10000	0	-10000	0	0

×

Nongenotropic Androgen 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.013	0	-9999	-10000	0	0
GNB1/GNG2	-0.024	0.076	-9999	-0.31	6	6
regulation of S phase of mitotic cell cycle	0	0.045	-9999	-10000	0	0
GNAO1	-0.093	0.13	-9999	-0.25	155	155
HRAS	0.019	0	-9999	-10000	0	0
SHBG/T-DHT	0.003	0.036	-9999	-0.13	24	24
PELP1	0.019	0	-9999	-10000	0	0
AKT1	0.013	0	-9999	-10000	0	0
MAP2K1	0.007	0.053	-9999	-10000	0	0
T-DHT/AR	-0.056	0.085	-9999	-0.16	144	144
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
mol:GTP	0	0.001	-9999	-0.004	12	12
GNAI2	0.019	0	-9999	-10000	0	0
GNAI3	0.019	0	-9999	-10000	0	0
GNAI1	0.005	0.06	-9999	-0.24	20	20
mol:GDP	-0.039	0.049	-9999	-10000	0	0
cell proliferation	0.022	0.056	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
FOS	0.03	0.055	-9999	-10000	0	0
mol:Ca2+	-0.01	0.019	-9999	-0.051	19	19
MAPK3	0.016	0.053	-9999	-10000	0	0
MAPK1	0.018	0.03	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	0	0	-9999	-0.002	12	12
cAMP biosynthetic process	0.009	0.037	-9999	-0.13	16	16
GNG2	0.01	0.07	-9999	-0.54	6	6
potassium channel inhibitor activity	0	0	-9999	-0.002	12	12
HRAS/GTP	-0.009	0.058	-9999	-10000	0	0
actin cytoskeleton reorganization	0.029	0.006	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
voltage-gated calcium channel activity	0	0	-9999	-0.002	12	12
PI3K	0.025	0.008	-9999	-10000	0	0
apoptosis	-0.028	0.046	-9999	-10000	0	0
T-DHT/AR/PELP1	-0.034	0.072	-9999	-10000	0	0
HRAS/GDP	-0.013	0.059	-9999	-10000	0	0
CREB1	0.028	0.047	-9999	-10000	0	0
RAC1-CDC42/GTP	0.037	0.006	-9999	-10000	0	0
AR	-0.086	0.13	-9999	-0.24	144	144
GNB1	0.019	0	-9999	-10000	0	0
RAF1	-0.001	0.055	-9999	-10000	0	0
RAC1-CDC42/GDP	-0.003	0.059	-9999	-10000	0	0
T-DHT/AR/PELP1/Src	-0.018	0.067	-9999	-10000	0	0
MAP2K2	0.007	0.053	-9999	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	0	0.045	-9999	-10000	0	0
GNAZ	-0.015	0.093	-9999	-0.26	45	45
SHBG	0.001	0.065	-9999	-0.24	24	24
Gi family/GNB1/GNG2/GDP	-0.018	0.076	-9999	-0.3	7	7
mol:T-DHT	0	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
GNRH1	0.005	0.055	-9999	-0.39	7	7
Gi family/GTP	-0.038	0.065	-9999	-0.19	18	18
CDC42	0.019	0	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.018	0.014	-10000	0	-0.24	1	1
RAS family/GTP/Tiam1	0.004	0.08	-10000	0	-0.23	24	24
NT3 (dimer)/TRKC	-0.019	0.12	-10000	0	-0.39	28	28
NT3 (dimer)/TRKB	-0.023	0.1	-10000	0	-0.29	28	28
SHC/Grb2/SOS1/GAB1/PI3K	0.044	0.005	-10000	0	-10000	0	0
RAPGEF1	0.019	0	-10000	0	-10000	0	0
BDNF	-0.12	0.24	-10000	0	-0.54	88	88
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
DYNLT1	0.019	0	-10000	0	-10000	0	0
NTRK1	-0.001	0.1	-10000	0	-0.5	14	14
NTRK2	-0.019	0.1	-10000	0	-0.28	47	47
NTRK3	-0.025	0.14	-10000	0	-0.49	31	31
NT-4/5 (dimer)/TRKB	-0.022	0.09	-10000	0	-0.29	21	21
neuron apoptosis	0.078	0.12	0.3	42	-10000	0	42
SHC 2-3/Grb2	-0.083	0.12	-10000	0	-0.32	42	42
SHC1	0.019	0	-10000	0	-10000	0	0
SHC2	-0.072	0.12	-10000	0	-0.32	33	33
SHC3	-0.063	0.11	-10000	0	-0.3	26	26
STAT3 (dimer)	0.024	0.029	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.014	0.1	-10000	0	-0.33	23	23
RIN/GDP	0.015	0.053	-10000	0	-0.18	1	1
GIPC1	0.019	0	-10000	0	-10000	0	0
KRAS	0.018	0.014	-10000	0	-0.24	1	1
DNAJA3	-0.003	0.072	-10000	0	-0.26	15	15
RIN/GTP	0	0	-10000	0	-10000	0	0
CCND1	0.027	0.05	-10000	0	-10000	0	0
MAGED1	0.019	0	-10000	0	-10000	0	0
PTPN11	0.019	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.038	0	-10000	0	-10000	0	0
GRB2	0.019	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.026	0.14	-10000	0	-0.36	51	51
TRKA/NEDD4-2	0.01	0.084	-10000	0	-0.39	15	15
ELMO1	-0.007	0.12	-10000	0	-0.54	17	17
RhoG/GTP/ELMO1/DOCK1	0.009	0.074	-10000	0	-0.32	17	17
NGF	0.002	0.063	-10000	0	-0.24	22	22
HRAS	0.019	0	-10000	0	-10000	0	0
DOCK1	0.019	0	-10000	0	-10000	0	0
GAB2	0.015	0.031	-10000	0	-0.24	5	5
RIT2	0	0	-10000	0	-10000	0	0
RIT1	0.019	0	-10000	0	-10000	0	0
FRS2	0.017	0.024	-10000	0	-0.24	3	3
DNM1	-0.009	0.081	-10000	0	-0.24	39	39
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.019	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.012	0.089	-10000	0	-0.26	32	32
mol:GDP	0.02	0.073	-10000	0	-0.26	1	1
NGF (dimer)	0.002	0.062	-10000	0	-0.24	22	22
RhoG/GDP	-0.005	0.085	-10000	0	-0.39	17	17
RIT1/GDP	0.023	0.055	-10000	0	-10000	0	0
TIAM1	-0.014	0.13	-10000	0	-0.54	22	22
PIK3R1	0.019	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.069	0.16	-10000	0	-0.33	92	92
KIDINS220/CRKL/C3G	0.028	0.009	-10000	0	-10000	0	0
SHC/RasGAP	0.027	0.021	-10000	0	-0.38	1	1
FRS2 family/SHP2	0.037	0.014	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.049	0	-10000	0	-10000	0	0
RIT1/GTP	0.014	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.004	0.068	-10000	0	-0.24	27	27
RAP1/GDP	-0.008	0.028	-10000	0	-10000	0	0
KIDINS220/CRKL	0.018	0.014	-10000	0	-0.24	1	1
BDNF (dimer)	-0.12	0.24	-10000	0	-0.54	88	88
ubiquitin-dependent protein catabolic process	0.013	0.079	-10000	0	-0.32	15	15
Schwann cell development	-0.023	0.026	-10000	0	-10000	0	0
EHD4	0.019	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.048	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.045	0.013	-10000	0	-10000	0	0
RAP1B	0.019	0	-10000	0	-10000	0	0
RAP1A	0.019	0	-10000	0	-10000	0	0
CDC42/GTP	-0.095	0.15	-10000	0	-0.36	52	52
ABL1	0.019	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
Rap1/GTP	0.014	0.07	-10000	0	-10000	0	0
STAT3	0.024	0.029	-10000	0	-10000	0	0
axon guidance	-0.11	0.13	-10000	0	-0.35	52	52
MAPK3	-0.02	0.13	-10000	0	-0.32	51	51
MAPK1	-0.02	0.13	-10000	0	-0.32	51	51
CDC42/GDP	0.023	0.055	-10000	0	-10000	0	0
NTF3	-0.004	0.068	-10000	0	-0.24	27	27
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.013	0.078	-10000	0	-0.32	15	15
PI3K	0.028	0.009	-10000	0	-10000	0	0
FRS3	0.019	0	-10000	0	-10000	0	0
FAIM	0.014	0.05	-10000	0	-0.54	3	3
GAB1	0.019	0	-10000	0	-10000	0	0
RASGRF1	-0.029	0.11	-10000	0	-0.28	42	42
SOS1	0.019	0	-10000	0	-10000	0	0
MCF2L	-0.055	0.11	-10000	0	-0.32	35	35
RGS19	0.019	0	-10000	0	-10000	0	0
CDC42	0.019	0	-10000	0	-10000	0	0
RAS family/GTP	0.047	0.046	-10000	0	-10000	0	0
Rac1/GDP	0.023	0.055	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	0.004	0.071	-10000	0	-0.32	12	12
neuron projection morphogenesis	0.014	0.069	-10000	0	-0.5	1	1
NGF (dimer)/TRKA/NEDD4-2	0.013	0.079	-10000	0	-0.32	15	15
MAP2K1	0.042	0	-10000	0	-10000	0	0
NGFR	-0.027	0.11	-10000	0	-0.26	59	59
NGF (dimer)/TRKA/GIPC/GAIP	0.019	0.06	-10000	0	-0.23	12	12
RAS family/GTP/PI3K	0.036	0.007	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.055	0.012	-10000	0	-10000	0	0
NRAS	0.019	0	-10000	0	-10000	0	0
GRB2/SOS1	0.028	0	-10000	0	-10000	0	0
PRKCI	0.019	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.019	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
MAPKKK cascade	-0.031	0.12	-10000	0	-0.56	15	15
RASA1	0.017	0.029	-10000	0	-0.54	1	1
TRKA/c-Abl	0.014	0.074	-10000	0	-0.38	12	12
SQSTM1	0.019	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.051	0.14	-10000	0	-0.29	92	92
NGF (dimer)/TRKA/p62/Atypical PKCs	0.035	0.067	-10000	0	-0.26	14	14
MATK	-0.049	0.18	-10000	0	-0.53	45	45
NEDD4L	0.014	0.05	-10000	0	-0.54	3	3
RAS family/GDP	-0.01	0.025	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.011	0.075	-10000	0	-0.28	15	15
Rac1/GTP	-0.04	0.074	-10000	0	-0.25	24	24
FRS2 family/SHP2/CRK family	0.055	0.014	-10000	0	-10000	0	0

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.01	0.072	-9999	-10000	0	0
adherens junction organization	-0.029	0.13	-9999	-0.31	10	10
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.007	0.085	-9999	-0.3	2	2
FMN1	-0.034	0.13	-9999	-0.34	13	13
mol:IP3	0.002	0.073	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.037	0.13	-9999	-0.24	101	101
CTNNB1	0.022	0.005	-9999	-10000	0	0
AKT1	0.001	0.086	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.069	0.19	-9999	-0.38	101	101
CTNND1	0.019	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	-0.027	0.12	-9999	-0.3	5	5
VASP	-0.028	0.12	-9999	-0.31	5	5
ZYX	-0.029	0.12	-9999	-0.31	7	7
JUB	-0.028	0.12	-9999	-0.31	6	6
EGFR(dimer)	-0.036	0.13	-9999	-0.32	22	22
E-cadherin/beta catenin-gamma catenin	-0.06	0.15	-9999	-0.3	101	101
mol:PI-3-4-5-P3	-0.005	0.09	-9999	-0.23	5	5
PIK3CA	0.019	0.014	-9999	-0.25	1	1
PI3K	-0.005	0.092	-9999	-0.24	5	5
FYN	0.014	0.063	-9999	-10000	0	0
mol:Ca2+	0.002	0.072	-9999	-10000	0	0
JUP	0.014	0.045	-9999	-0.24	11	11
PIK3R1	0.019	0.001	-9999	-10000	0	0
mol:DAG	0.002	0.073	-9999	-10000	0	0
CDH1	-0.13	0.25	-9999	-0.54	101	101
RhoA/GDP	0.007	0.085	-9999	-0.3	2	2
establishment of polarity of embryonic epithelium	-0.027	0.12	-9999	-0.3	5	5
SRC	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
EGFR	-0.007	0.087	-9999	-0.27	33	33
CASR	0.002	0.069	-9999	-10000	0	0
RhoA/GTP	0.01	0.068	-9999	-10000	0	0
AKT2	0.001	0.086	-9999	-10000	0	0
actin cable formation	-0.026	0.13	-9999	-0.37	9	9
apoptosis	0	0.082	-9999	-10000	0	0
CTNNA1	0.019	0.001	-9999	-10000	0	0
mol:GDP	-0.003	0.087	-9999	-0.33	2	2
PIP5K1A	-0.028	0.12	-9999	-0.31	5	5
PLCG1	0.001	0.074	-9999	-10000	0	0
Rac1/GTP	-0.027	0.12	-9999	-0.3	20	20
homophilic cell adhesion	0	0.002	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.016	0.036	-9999	-0.33	4	4
ADCY5	-0.056	0.14	-9999	-0.33	80	80
ADCY6	0.019	0.013	-9999	-10000	0	0
ADCY7	0.018	0.025	-9999	-0.33	2	2
ADCY1	-0.034	0.13	-9999	-0.33	58	58
ADCY2	-0.046	0.071	-9999	-10000	0	0
ADCY3	0.02	0	-9999	-10000	0	0
ADCY8	0.001	0.042	-9999	-10000	0	0
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.02	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.029	0.057	-9999	-0.19	10	10

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.029	0.12	-9999	-0.43	13	13
CRKL	-0.014	0.11	-9999	-0.36	6	6
mol:DAG	-0.002	0.12	-9999	-0.42	18	18
HRAS	0.014	0.1	-9999	-0.38	3	3
MAPK8	0.019	0.07	-9999	-0.31	15	15
RAP1A	-0.014	0.11	-9999	-0.42	4	4
GAB1	-0.014	0.11	-9999	-0.36	6	6
MAPK14	0.019	0.07	-9999	-0.31	15	15
EPO	0.007	0.026	-9999	-0.26	2	2
PLCG1	-0.003	0.12	-9999	-0.43	18	18
EPOR/TRPC2/IP3 Receptors	0.013	0.02	-9999	-0.24	1	1
RAPGEF1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.028	0.041	-9999	-0.35	3	3
GAB1/SHC/GRB2/SOS1	0.008	0.1	-9999	-0.36	4	4
EPO/EPOR (dimer)	0.016	0.029	-9999	-10000	0	0
IRS2	-0.014	0.11	-9999	-0.42	4	4
STAT1	0.006	0.13	-9999	-0.47	16	16
STAT5B	0.003	0.13	-9999	-0.45	15	15
cell proliferation	0.024	0.065	-9999	-0.28	15	15
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.079	0.14	-9999	-0.39	59	59
TEC	-0.02	0.13	-9999	-0.35	16	16
SOCS3	0.014	0.05	-9999	-0.54	3	3
STAT1 (dimer)	0.007	0.13	-9999	-0.46	16	16
JAK2	0.004	0.074	-9999	-0.51	7	7
PIK3R1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	-0.004	0.13	-9999	-0.33	9	9
EPO/EPOR	0.016	0.029	-9999	-10000	0	0
LYN	-0.002	0.11	-9999	-0.54	15	15
TEC/VAV2	-0.011	0.13	-9999	-0.43	11	11
elevation of cytosolic calcium ion concentration	0.013	0.02	-9999	-0.24	1	1
SHC1	0.019	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.025	0.081	-9999	-0.35	15	15
mol:IP3	-0.002	0.12	-9999	-0.42	18	18
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.038	0.19	-9999	-0.43	59	59
SH2B3	0.013	0.014	-9999	-10000	0	0
NFKB1	0.019	0.07	-9999	-0.31	15	15
EPO/EPOR (dimer)/JAK2/SOCS3	0.011	0.044	-9999	-0.26	7	7
PTPN6	-0.023	0.12	-9999	-0.33	9	9
TEC/VAV2/GRB2	-0.002	0.13	-9999	-0.41	11	11
EPOR	0.013	0.02	-9999	-0.24	1	1
INPP5D	-0.075	0.21	-9999	-0.54	62	62
mol:GDP	0.007	0.11	-9999	-0.37	4	4
SOS1	0.019	0	-9999	-10000	0	0
PLCG2	-0.03	0.16	-9999	-0.54	32	32
CRKL/CBL/C3G	0.006	0.11	-9999	-0.39	4	4
VAV2	-0.016	0.12	-9999	-0.37	9	9
CBL	-0.014	0.11	-9999	-0.34	7	7
SHC/Grb2/SOS1	-0.046	0.081	-9999	-0.39	4	4
STAT5A	0.002	0.13	-9999	-0.43	19	19
GRB2	0.019	0	-9999	-10000	0	0
STAT5 (dimer)	0.02	0.13	-9999	-0.43	16	16
LYN/PLCgamma2	-0.022	0.15	-9999	-0.42	42	42
PTPN11	0.019	0	-9999	-10000	0	0
BTK	-0.062	0.2	-9999	-0.45	65	65
BCL2	0.029	0.12	-9999	-0.43	13	13

×

Reelin signaling 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
CDK5R1/CDK5	0.027	0.021	-9999	-0.38	1	1
VLDLR	0.005	0.086	-9999	-0.54	9	9
CRKL	0.018	0.014	-9999	-0.24	1	1
LRPAP1	0.019	0	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
ITGA3	0.002	0.069	-9999	-0.26	23	23
RELN/VLDLR/Fyn	-0.009	0.085	-9999	-0.34	9	9
MAPK8IP1/MKK7/MAP3K11/JNK1	0.052	0.027	-9999	-0.26	1	1
AKT1	-0.002	0.068	-9999	-0.27	10	10
MAP2K7	0.019	0	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
DAB1	-0.028	0.089	-9999	-0.24	52	52
RELN/LRP8/DAB1	-0.023	0.08	-9999	-0.22	27	27
LRPAP1/LRP8	0.028	0	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.011	0.076	-9999	-0.2	27	27
DAB1/alpha3/beta1 Integrin	-0.039	0.067	-9999	-0.34	6	6
long-term memory	-0.024	0.097	-9999	-0.3	17	17
DAB1/LIS1	-0.004	0.086	-9999	-0.3	9	9
DAB1/CRLK/C3G	-0.033	0.062	-9999	-0.4	3	3
PIK3CA	0.018	0.014	-9999	-0.24	1	1
DAB1/NCK2	-0.004	0.086	-9999	-0.3	9	9
ARHGEF2	0.017	0.029	-9999	-0.54	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.002	0.07	-9999	-0.24	28	28
CDK5R1	0.017	0.029	-9999	-0.54	1	1
RELN	-0.047	0.11	-9999	-0.24	91	91
PIK3R1	0.019	0	-9999	-10000	0	0
RELN/LRP8/Fyn	0	0.066	-9999	-10000	0	0
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.012	0.087	-9999	-0.31	6	6
MAPK8	0.019	0.001	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.03	0.095	-9999	-0.26	34	34
ITGB1	0.017	0.019	-9999	-0.24	2	2
MAP1B	-0.019	0.087	-9999	-0.31	12	12
RELN/LRP8	0	0.066	-9999	-10000	0	0
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.022	0.094	-9999	-0.31	12	12
PI3K	0.028	0.009	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.015	0.05	-9999	-0.34	2	2
RAP1A	0.006	0.078	-9999	-0.37	3	3
PAFAH1B1	0.019	0	-9999	-10000	0	0
MAPK8IP1	0.012	0.041	-9999	-0.24	9	9
CRLK/C3G	0.028	0.009	-9999	-10000	0	0
GRIN2B	-0.025	0.088	-9999	-0.24	50	50
NCK2	0.019	0	-9999	-10000	0	0
neuron differentiation	0.019	0.045	-9999	-10000	0	0
neuron adhesion	0.011	0.08	-9999	-0.33	4	4
LRP8	0.019	0	-9999	-10000	0	0
GSK3B	0.005	0.065	-9999	-0.36	3	3
RELN/VLDLR/DAB1/Fyn	-0.019	0.09	-9999	-0.24	34	34
MAP3K11	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.01	0.073	-9999	-0.29	10	10
CDK5	0.019	0	-9999	-10000	0	0
MAPT	-0.11	0.12	-9999	-0.22	186	186
neuron migration	0.021	0.077	-9999	-0.35	3	3
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.019	0.046	-9999	-10000	0	0
RELN/VLDLR	0.005	0.079	-9999	-0.31	9	9

×

IL1-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
UBC13/UEV1A	0.014	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.002	0.08	-10000	0	-0.32	9	9
IRAK/TOLLIP	0.032	0	-10000	0	-10000	0	0
IKBKB	0.019	0	-10000	0	-10000	0	0
IKBKG	0.019	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.041	0.15	-10000	0	-0.34	67	67
IL1A	0.004	0.054	-10000	0	-0.24	16	16
IL1B	-0.037	0.16	-10000	0	-0.42	48	48
IRAK/TRAF6/p62/Atypical PKCs	0.055	0.021	-10000	0	-10000	0	0
IL1R2	-0.062	0.2	-10000	0	-0.54	53	53
IL1R1	0.016	0.041	-10000	0	-0.54	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.014	0.075	0.21	4	-0.28	9	13
TOLLIP	0.019	0	-10000	0	-10000	0	0
TICAM2	0.009	0.07	-10000	0	-0.54	6	6
MAP3K3	0.019	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.013	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.07	0.007	-10000	0	-10000	0	0
JUN	0.026	0.047	-10000	0	-0.31	1	1
MAP3K7	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.003	0.12	-10000	0	-0.28	49	49
IL1 alpha/IL1R1/IL1RAP/MYD88	0.028	0.055	-10000	0	-0.25	6	6
PIK3R1	0.019	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.037	0.053	-10000	0	-0.23	6	6
IL1 beta fragment/IL1R1/IL1RAP	-0.018	0.13	-10000	0	-0.32	50	50
NFKB1	0.019	0	-10000	0	-10000	0	0
MAPK8	0.032	0.036	-10000	0	-0.23	7	7
IRAK1	0.022	0	-10000	0	-10000	0	0
IL1RN/IL1R1	0.013	0.073	-10000	0	-0.38	11	11
IRAK4	0.019	0	-10000	0	-10000	0	0
PRKCI	0.019	0	-10000	0	-10000	0	0
TRAF6	0.019	0	-10000	0	-10000	0	0
PI3K	0.028	0.009	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.008	0.089	-10000	0	-0.34	10	10
CHUK	0.019	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.018	0.13	-10000	0	-0.32	50	50
IL1 beta/IL1R2	-0.069	0.19	-10000	0	-0.39	86	86
IRAK/TRAF6/TAK1/TAB1/TAB2	0.036	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.038	0.092	-10000	0	-0.45	8	8
IRAK3	0.011	0.064	-10000	0	-0.54	5	5
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.001	0.13	-10000	0	-0.3	52	52
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.03	0.04	-10000	0	-0.23	3	3
IL1 alpha/IL1R1/IL1RAP	0.017	0.057	-10000	0	-0.28	5	5
RELA	0.019	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.019	0	-10000	0	-10000	0	0
MYD88	0.017	0.029	-10000	0	-0.54	1	1
IRAK/TRAF6/MEKK3	0.043	0	-10000	0	-10000	0	0
IL1RAP	0.001	0.066	-10000	0	-0.24	25	25
UBE2N	0.019	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.038	0.093	-10000	0	-0.44	10	10
CASP1	-0.011	0.13	-10000	0	-0.54	20	20
IL1RN/IL1R2	-0.043	0.16	-10000	0	-0.39	60	60
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.006	0.13	-10000	0	-0.31	49	49
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.037	0.04	-10000	0	-0.3	3	3
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
IL1RN	0.002	0.091	-10000	0	-0.43	14	14
TRAF6/TAK1/TAB1/TAB2	0.028	0	-10000	0	-10000	0	0
MAP2K6	0.027	0.038	-10000	0	-0.25	7	7

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.019	0	-9999	-10000	0	0
SVIL	0.017	0.029	-9999	-0.54	1	1
ZNF318	0.019	0	-9999	-10000	0	0
JMJD2C	-0.005	0.027	-9999	-0.064	61	61
T-DHT/AR/Ubc9	-0.038	0.084	-9999	-0.22	19	19
CARM1	0.019	0	-9999	-10000	0	0
PRDX1	0.011	0.064	-9999	-0.54	5	5
PELP1	0.019	0	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
AKT1	0.019	0	-9999	-10000	0	0
PTK2B	0.008	0.076	-9999	-0.54	7	7
MED1	0.019	0	-9999	-10000	0	0
MAK	0.016	0.027	-9999	-0.24	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
HIP1	0.016	0.027	-9999	-0.24	4	4
GSN	0.018	0.014	-9999	-0.24	1	1
NCOA2	0.018	0.014	-9999	-0.24	1	1
NCOA6	0.019	0	-9999	-10000	0	0
DNA-PK	0.038	0	-9999	-10000	0	0
NCOA4	0.019	0	-9999	-10000	0	0
PIAS3	0.019	0	-9999	-10000	0	0
cell proliferation	-0.006	0.025	-9999	-10000	0	0
XRCC5	0.019	0	-9999	-10000	0	0
UBE3A	0.019	0	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.051	0.1	-9999	-0.27	33	33
FHL2	-0.003	0.14	-9999	-1.1	6	6
RANBP9	0.019	0	-9999	-10000	0	0
JMJD1A	0.001	0.046	-9999	-0.13	38	38
CDK6	0.014	0.052	-9999	-0.46	4	4
TGFB1I1	0.017	0.032	-9999	-0.39	2	2
T-DHT/AR/CyclinD1	-0.043	0.087	-9999	-0.22	26	26
XRCC6	0.019	0	-9999	-10000	0	0
T-DHT/AR	-0.037	0.11	-9999	-0.3	21	21
CTDSP1	0.019	0	-9999	-10000	0	0
CTDSP2	0.019	0	-9999	-10000	0	0
BRCA1	0.019	0	-9999	-10000	0	0
TCF4	0.011	0.057	-9999	-0.37	7	7
CDKN2A	-0.11	0.14	-9999	-0.25	172	172
SRF	0.026	0.017	-9999	-10000	0	0
NKX3-1	-0.055	0.24	-9999	-0.92	22	22
KLK3	0.011	0.017	-9999	-10000	0	0
TMF1	0.019	0	-9999	-10000	0	0
HNRNPA1	0.019	0	-9999	-10000	0	0
AOF2	0	0	-9999	-10000	0	0
APPL1	0.026	0	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.04	0.088	-9999	-0.23	22	22
AR	-0.091	0.13	-9999	-0.25	144	144
UBA3	0.019	0	-9999	-10000	0	0
PATZ1	0.019	0	-9999	-10000	0	0
PAWR	-0.004	0.11	-9999	-0.54	15	15
PRKDC	0.019	0	-9999	-10000	0	0
PA2G4	0.019	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.033	0.076	-9999	-0.2	20	20
RPS6KA3	0.019	0	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.038	0.084	-9999	-0.22	19	19
LATS2	0.019	0	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.037	0.081	-9999	-0.21	25	25
Cyclin D3/CDK11 p58	0.014	0	-9999	-10000	0	0
VAV3	0.008	0.064	-9999	-0.32	12	12
KLK2	-0.048	0.11	-9999	-0.31	26	26
CASP8	0.016	0.041	-9999	-0.54	2	2
T-DHT/AR/TIF2/CARM1	-0.023	0.079	-9999	-0.26	3	3
TMPRSS2	-0.049	0.22	-9999	-0.92	18	18
CCND1	0.01	0.047	-9999	-0.24	12	12
PIAS1	0.019	0	-9999	-10000	0	0
mol:T-DHT	-0.005	0.025	-9999	-0.063	45	45
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.019	0	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.041	0.089	-9999	-0.24	24	24
CMTM2	0.007	0.05	-9999	-0.24	14	14
SNURF	-0.001	0.1	-9999	-0.54	13	13
ZMIZ1	0.015	0.024	-9999	-10000	0	0
CCND3	0.019	0	-9999	-10000	0	0
TGIF1	0.019	0	-9999	-10000	0	0
FKBP4	0.018	0.014	-9999	-0.24	1	1

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.017	0.024	-9999	-0.24	3	3
Syndecan-3/Src/Cortactin	0.021	0.052	-9999	-10000	0	0
Syndecan-3/Neurocan	0.017	0.028	-9999	-10000	0	0
POMC	-0.049	0.18	-9999	-0.52	46	46
EGFR	-0.007	0.087	-9999	-0.27	33	33
Syndecan-3/EGFR	0.019	0.042	-9999	-0.26	3	3
AGRP	0.003	0.045	-9999	-0.24	11	11
NCSTN	0.019	0	-9999	-10000	0	0
PSENEN	0.019	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.014	0.05	-9999	-0.54	3	3
APH1A	0.019	0	-9999	-10000	0	0
NCAN	0.001	0.055	-9999	-0.24	17	17
long-term memory	0.04	0.014	-9999	-10000	0	0
Syndecan-3/IL8	0	0.057	-9999	-0.28	3	3
PSEN1	0.019	0	-9999	-10000	0	0
Src/Cortactin	0.027	0.016	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
limb bud formation	-0.001	0.008	-9999	-10000	0	0
MC4R	-0.031	0.095	-9999	-0.24	60	60
SRC	0.019	0	-9999	-10000	0	0
PTN	-0.046	0.11	-9999	-0.24	90	90
FGFR/FGF/Syndecan-3	-0.001	0.008	-9999	-10000	0	0
neuron projection morphogenesis	0.015	0.052	-9999	-10000	0	0
Syndecan-3/AgRP	0.014	0.027	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.008	0.048	-9999	-10000	0	0
Fyn/Cortactin	0.027	0.016	-9999	-10000	0	0
SDC3	-0.001	0.008	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	0	0.057	-9999	-0.28	3	3
IL8	-0.05	0.12	-9999	-0.25	93	93
Syndecan-3/Fyn/Cortactin	0.041	0.014	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.007	-9999	-10000	0	0
alpha-MSH/MC4R	-0.055	0.14	-9999	-0.4	44	44
Gamma Secretase	0.054	0.028	-9999	-0.26	3	3

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.004	0.07	-9999	-0.3	17	17
GPC2	0.008	0.073	-9999	-0.46	8	8
GPC2/Midkine	0.01	0.074	-9999	-0.37	11	11
neuron projection morphogenesis	0.01	0.074	-9999	-0.37	11	11

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.015	0.031	-9999	-0.24	5	5
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	-0.011	0.06	-9999	-0.24	4	4
GNAO1	-0.091	0.13	-9999	-0.24	155	155
S1P/S1P3/G12/G13	0.037	0.03	-9999	-0.29	3	3
AKT1	0.019	0.03	-9999	-10000	0	0
AKT3	0.026	0.043	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.031	-9999	-0.24	5	5
GNAI2	0.021	0	-9999	-10000	0	0
GNAI3	0.021	0	-9999	-10000	0	0
GNAI1	0.006	0.06	-9999	-0.24	20	20
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.016	0.052	-9999	-0.46	4	4
S1PR2	0.019	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.003	0.067	-9999	-0.26	6	6
MAPK3	0.004	0.063	-9999	-0.25	5	5
MAPK1	0.004	0.063	-9999	-0.29	3	3
JAK2	-0.006	0.091	-9999	-0.35	12	12
CXCR4	-0.018	0.11	-9999	-0.32	31	31
FLT1	0.022	0.014	-9999	-0.24	1	1
RhoA/GDP	0.014	0	-9999	-10000	0	0
Rac1/GDP	0.014	0	-9999	-10000	0	0
SRC	0.004	0.063	-9999	-0.29	3	3
S1P/S1P3/Gi	-0.004	0.068	-9999	-0.26	6	6
RAC1	0.019	0	-9999	-10000	0	0
RhoA/GTP	0.005	0.062	-9999	-0.24	5	5
VEGFA	0.007	0.062	-9999	-0.24	21	21
S1P/S1P2/Gi	-0.006	0.062	-9999	-0.22	4	4
VEGFR1 homodimer/VEGFA homodimer	0.027	0.046	-9999	-0.3	1	1
RHOA	0.019	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.022	0.13	-9999	-0.26	73	73
GNAQ	0.019	0	-9999	-10000	0	0
GNAZ	-0.013	0.093	-9999	-0.26	45	45
G12/G13	0.028	0	-9999	-10000	0	0
GNA14	-0.084	0.22	-9999	-0.53	69	69
GNA15	0.002	0.095	-9999	-0.54	11	11
GNA12	0.019	0	-9999	-10000	0	0
GNA13	0.019	0	-9999	-10000	0	0
GNA11	0.019	0	-9999	-10000	0	0
Rac1/GTP	0.005	0.062	-9999	-0.28	3	3

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.019	0.058	-10000	0	-10000	0	0
epithelial cell differentiation	-0.024	0.043	-10000	0	-10000	0	0
ITCH	0.026	0.014	-10000	0	-10000	0	0
WWP1	0.02	0.052	-10000	0	-10000	0	0
FYN	0.019	0	-10000	0	-10000	0	0
EGFR	-0.007	0.087	-10000	0	-0.27	33	33
PRL	-0.023	0.084	-10000	0	-0.24	45	45
neuron projection morphogenesis	0.047	0.052	-10000	0	-0.28	1	1
PTPRZ1	-0.055	0.18	-10000	0	-0.43	60	60
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.043	0.058	-10000	0	-0.32	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.016	0.061	-10000	0	-0.31	3	3
ADAM17	0.026	0.014	-10000	0	-10000	0	0
ErbB4/ErbB4	0.014	0.067	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.058	0.13	-10000	0	-0.32	48	48
NCOR1	0.019	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.025	0.058	-10000	0	-0.36	1	1
GRIN2B	0.011	0.066	-10000	0	-0.31	2	2
ErbB4/ErbB2/betacellulin	0.015	0.056	-10000	0	-10000	0	0
STAT1	0.016	0.041	-10000	0	-0.54	2	2
HBEGF	0.017	0.019	-10000	0	-0.24	2	2
PRLR	-0.048	0.11	-10000	0	-0.24	92	92
E4ICDs/ETO2	-0.007	0.1	-10000	0	-0.3	30	30
axon guidance	0.042	0.061	-10000	0	-10000	0	0
NEDD4	0.024	0.024	-10000	0	-0.24	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.045	0.097	-10000	0	-0.31	16	16
CBFA2T3	-0.028	0.15	-10000	0	-0.52	32	32
ErbB4/ErbB2/HBEGF	0.034	0.042	-10000	0	-10000	0	0
MAPK3	0.042	0.053	-10000	0	-0.3	1	1
STAT1 (dimer)	0.018	0.062	-10000	0	-0.29	2	2
MAPK1	0.042	0.053	-10000	0	-0.3	1	1
JAK2	0.009	0.072	-10000	0	-0.5	7	7
ErbB4/ErbB2/neuregulin 1 beta	0.023	0.057	-10000	0	-0.36	1	1
NRG1	0.016	0.053	-10000	0	-0.38	3	3
NRG3	-0.12	0.2	-10000	0	-0.34	142	142
NRG2	0.011	0.057	-10000	0	-0.37	7	7
NRG4	-0.002	0.094	-10000	0	-0.54	11	11
heart development	0.042	0.061	-10000	0	-10000	0	0
neural crest cell migration	0.023	0.057	-10000	0	-0.35	1	1
ERBB2	0.03	0.009	-10000	0	-10000	0	0
WWOX/E4ICDs	0.02	0.058	-10000	0	-10000	0	0
SHC1	0.019	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.006	0.089	-10000	0	-0.31	14	14
apoptosis	0.053	0.14	0.37	48	-10000	0	48
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.016	0.067	-10000	0	-0.33	3	3
ErbB4/ErbB2/epiregulin	0.02	0.054	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.002	0.071	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.008	0.087	-10000	0	-10000	0	0
MDM2	0.018	0.06	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.024	0.051	-10000	0	-0.28	3	3
STAT5A	0.046	0.058	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	0.013	0.075	-10000	0	-0.29	4	4
DLG4	0.017	0.029	-10000	0	-0.54	1	1
GRB2/SHC	0.028	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.018	0.052	-10000	0	-10000	0	0
STAT5A (dimer)	-0.012	0.058	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.048	0.054	-10000	0	-10000	0	0
LRIG1	0.017	0.029	-10000	0	-0.54	1	1
EREG	-0.01	0.072	-10000	0	-0.24	31	31
BTC	-0.021	0.083	-10000	0	-0.24	44	44
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.042	0.061	-10000	0	-10000	0	0
ERBB4	0.014	0.068	-10000	0	-10000	0	0
STAT5B	0.019	0	-10000	0	-10000	0	0
YAP1	0.015	0.022	-10000	0	-0.19	1	1
GRB2	0.019	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.023	0.07	-10000	0	-0.36	5	5
glial cell differentiation	-0.018	0.052	-10000	0	-10000	0	0
WWOX	0.019	0	-10000	0	-10000	0	0
cell proliferation	0.03	0.062	-10000	0	-0.31	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	0.038	0.027	-10000	0	-10000	0	0
HDAC1	0.013	0.029	-10000	0	-0.54	1	1
AES	0.018	0.001	-10000	0	-10000	0	0
FBXW11	0.019	0	-10000	0	-10000	0	0
DTX1	-0.11	0.23	-10000	0	-0.54	85	85
LRP6/FZD1	0.025	0.023	-10000	0	-10000	0	0
TLE1	0.016	0.029	-10000	0	-0.54	1	1
AP1	0.009	0.056	-10000	0	-0.27	8	8
NCSTN	0.019	0	-10000	0	-10000	0	0
ADAM10	0.019	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.052	0.024	-10000	0	-10000	0	0
NICD/RBPSUH	0.043	0.007	-10000	0	-10000	0	0
WIF1	-0.025	0.087	-10000	0	-0.24	49	49
NOTCH1	0.034	0.007	-10000	0	-10000	0	0
PSENEN	0.019	0	-10000	0	-10000	0	0
KREMEN2	-0.057	0.19	-10000	0	-0.54	50	50
DKK1	-0.078	0.2	-10000	0	-0.44	78	78
beta catenin/beta TrCP1	0.039	0.03	0.24	1	-10000	0	1
APH1B	0.014	0.05	-10000	0	-0.54	3	3
APH1A	0.019	0	-10000	0	-10000	0	0
AXIN1	0.008	0.016	0.26	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.027	0.024	-10000	0	-0.25	2	2
PSEN1	0.019	0	-10000	0	-10000	0	0
FOS	0.01	0.047	-10000	0	-0.24	12	12
JUN	-0.008	0.079	-10000	0	-0.24	37	37
MAP3K7	0.017	0.002	-10000	0	-10000	0	0
CTNNB1	0.029	0.033	0.25	1	-10000	0	1
MAPK3	0.019	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.13	-10000	0	-0.33	52	52
HNF1A	0.018	0.001	-10000	0	-10000	0	0
CTBP1	0.018	0.001	-10000	0	-10000	0	0
MYC	0.026	0.028	-10000	0	-10000	0	0
NKD1	-0.005	0.093	-10000	0	-0.33	24	24
FZD1	0.015	0.033	-10000	0	-0.24	6	6
NOTCH1 precursor/Deltex homolog 1	-0.024	0.12	-10000	0	-0.31	1	1
apoptosis	0.009	0.055	-10000	0	-0.27	8	8
Delta 1/NOTCHprecursor	0.04	0.028	-10000	0	-10000	0	0
DLL1	0.014	0.052	-10000	0	-0.46	4	4
PPARD	0.027	0.024	-10000	0	-0.3	1	1
Gamma Secretase	0.055	0.028	-10000	0	-0.26	3	3
APC	0.008	0.016	0.26	1	-10000	0	1
DVL1	0.029	0.023	-10000	0	-10000	0	0
CSNK2A1	0.019	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.069	0.17	-10000	0	-0.35	92	92
LRP6	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.019	0.001	-10000	0	-10000	0	0
NLK	0.016	0.004	-10000	0	-10000	0	0
CCND1	0.02	0.053	-10000	0	-10000	0	0
WNT1	-0.031	0.15	-10000	0	-0.52	32	32
Axin1/APC/beta catenin	0.05	0.025	0.3	1	-10000	0	1
DKK2	0.001	0.076	-10000	0	-0.28	22	22
NOTCH1 precursor/DVL1	0.053	0.018	-10000	0	-10000	0	0
GSK3B	0.018	0	-10000	0	-10000	0	0
FRAT1	0.016	0.029	-10000	0	-0.54	1	1
NOTCH/Deltex homolog 1	-0.026	0.12	-10000	0	-0.31	1	1
PPP2R5D	0.027	0.047	0.29	7	-10000	0	7
MAPK1	0.019	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.006	0.1	-10000	0	-0.29	34	34
RBPJ	0.019	0	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.05	-9999	-0.32	1	1
PDGFRB	0.015	0.031	-9999	-0.25	5	5
SPHK1	-0.008	0.078	-9999	-0.84	3	3
mol:S1P	0.008	0.075	-9999	-0.63	4	4
S1P1/S1P/Gi	-0.019	0.096	-9999	-0.31	15	15
GNAO1	-0.094	0.13	-9999	-0.25	155	155
PDGFB-D/PDGFRB/PLCgamma1	-0.006	0.089	-9999	-0.35	7	7
PLCG1	-0.012	0.091	-9999	-0.34	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.015	0.031	-9999	-0.24	5	5
GNAI2	0.018	0.004	-9999	-10000	0	0
GNAI3	0.018	0.003	-9999	-10000	0	0
GNAI1	0.004	0.06	-9999	-0.25	20	20
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.008	0.041	-9999	-0.27	1	1
S1P1/S1P	0.014	0.071	-9999	-0.42	5	5
negative regulation of cAMP metabolic process	-0.018	0.094	-9999	-0.3	15	15
MAPK3	-0.017	0.11	-9999	-0.4	11	11
calcium-dependent phospholipase C activity	-0.001	0.002	-9999	-10000	0	0
Rac1/GDP	0.014	0	-9999	-10000	0	0
RhoA/GDP	0.014	0	-9999	-10000	0	0
KDR	0.014	0.036	-9999	-0.24	7	7
PLCB2	0.013	0.083	-9999	-0.33	12	12
RAC1	0.019	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.049	-9999	-0.35	5	5
receptor internalization	0.014	0.066	-9999	-0.39	5	5
PTGS2	-0.024	0.15	-9999	-0.93	4	4
Rac1/GTP	-0.013	0.049	-9999	-0.35	5	5
RHOA	0.019	0	-9999	-10000	0	0
VEGFA	0.004	0.062	-9999	-0.25	21	21
negative regulation of T cell proliferation	-0.018	0.094	-9999	-0.3	15	15
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.016	0.094	-9999	-0.26	45	45
MAPK1	-0.017	0.11	-9999	-0.4	11	11
S1P1/S1P/PDGFB-D/PDGFRB	0.021	0.074	-9999	-0.4	5	5
ABCC1	0.017	0.029	-9999	-0.54	1	1

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.012	0.03	-10000	0	-0.54	1	1
AES	0.015	0.007	-10000	0	-10000	0	0
FBXW11	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.026	0.023	-10000	0	-10000	0	0
SMAD4	0.019	0	-10000	0	-10000	0	0
DKK2	0.001	0.076	-10000	0	-0.28	22	22
TLE1	0.013	0.03	-10000	0	-0.54	1	1
MACF1	0.019	0	-10000	0	-10000	0	0
CTNNB1	0.018	0.073	-10000	0	-0.27	4	4
WIF1	-0.025	0.087	-10000	0	-0.24	49	49
beta catenin/RanBP3	-0.012	0.066	0.31	4	-10000	0	4
KREMEN2	-0.057	0.19	-10000	0	-0.54	50	50
DKK1	-0.078	0.2	-10000	0	-0.44	78	78
beta catenin/beta TrCP1	0.027	0.071	-10000	0	-0.25	3	3
FZD1	0.015	0.033	-10000	0	-0.24	6	6
AXIN2	0.012	0.09	-10000	0	-1.5	1	1
AXIN1	0.019	0.001	-10000	0	-10000	0	0
RAN	0.019	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.038	0.017	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.057	0.057	-10000	0	-0.4	1	1
Axin1/APC/GSK3	0.038	0.04	0.2	1	-10000	0	1
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.084	-10000	0	-10000	0	0
HNF1A	0.014	0.007	-10000	0	-10000	0	0
CTBP1	0.014	0.007	-10000	0	-10000	0	0
MYC	0.017	0.036	-10000	0	-10000	0	0
RANBP3	0.019	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.13	-10000	0	-0.33	52	52
NKD1	-0.004	0.093	-10000	0	-0.33	24	24
TCF4	0.007	0.057	-10000	0	-0.37	7	7
TCF3	0.014	0.007	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.017	0.091	-10000	0	-0.28	30	30
Ran/GTP	0.014	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.007	0.065	0.36	4	-10000	0	4
LEF1	-0.004	0.099	-10000	0	-0.54	12	12
DVL1	0.033	0.026	-10000	0	-10000	0	0
CSNK2A1	0.019	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.071	0.059	-10000	0	-0.38	1	1
DKK1/LRP6/Kremen 2	-0.069	0.17	-10000	0	-0.35	92	92
LRP6	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.014	0.008	-10000	0	-10000	0	0
NLK	0.02	0.002	-10000	0	-10000	0	0
CCND1	0.012	0.059	-10000	0	-10000	0	0
WNT1	-0.03	0.15	-10000	0	-0.52	32	32
GSK3A	0.019	0.001	-10000	0	-10000	0	0
GSK3B	0.019	0	-10000	0	-10000	0	0
FRAT1	0.017	0.029	-10000	0	-0.54	1	1
PPP2R5D	0.029	0.047	0.27	8	-10000	0	8
APC	0.015	0.082	-10000	0	-0.25	30	30
WNT1/LRP6/FZD1	0.025	0.071	-10000	0	-0.2	26	26
CREBBP	0.014	0.007	-10000	0	-10000	0	0

×

ErbB2/ErbB3 signaling events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.021	0.003	-9999	-10000	0	0
RAS family/GTP	0.034	0.076	-9999	-0.29	10	10
NFATC4	0.018	0.068	-9999	-0.26	9	9
ERBB2IP	0.018	0.002	-9999	-10000	0	0
HSP90 (dimer)	0.017	0.029	-9999	-0.54	1	1
mammary gland morphogenesis	0.021	0.069	-9999	-0.26	17	17
JUN	0.042	0.074	-9999	-0.21	6	6
HRAS	0.019	0.001	-9999	-10000	0	0
DOCK7	0.026	0.066	-9999	-0.27	10	10
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.016	0.075	-9999	-0.3	17	17
AKT1	0.013	0.002	-9999	-10000	0	0
BAD	0.021	0.001	-9999	-10000	0	0
MAPK10	0.017	0.051	-9999	-0.18	7	7
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	0.023	0.074	-9999	-0.28	17	17
RAF1	0.036	0.085	-9999	-0.31	9	9
ErbB2/ErbB3/neuregulin 2	0.01	0.073	-9999	-0.32	16	16
STAT3	0.028	0.005	-9999	-10000	0	0
cell migration	0.032	0.045	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.007	0.25	-9999	-0.58	52	52
FOS	0.024	0.16	-9999	-0.33	52	52
NRAS	0.019	0.001	-9999	-10000	0	0
mol:Ca2+	0.021	0.069	-9999	-0.26	17	17
MAPK3	0.005	0.2	-9999	-0.45	52	52
MAPK1	0.005	0.2	-9999	-0.45	52	52
JAK2	0.022	0.072	-9999	-0.29	6	6
NF2	0.007	0.011	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.015	0.07	-9999	-0.29	17	17
NRG1	-0.001	0.074	-9999	-0.29	20	20
GRB2/SOS1	0.028	0.001	-9999	-10000	0	0
MAPK8	0.032	0.069	-9999	-0.26	17	17
MAPK9	0.033	0.038	-9999	-0.16	2	2
ERBB2	-0.001	0.002	-9999	-10000	0	0
ERBB3	-0.002	0.11	-9999	-0.54	14	14
SHC1	0.019	0.001	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
apoptosis	-0.019	0.009	-9999	-10000	0	0
STAT3 (dimer)	0.028	0.005	-9999	-10000	0	0
RNF41	0.026	0.004	-9999	-10000	0	0
FRAP1	0.01	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.009	0.038	-9999	-0.23	4	4
ErbB2/ErbB2/HSP90 (dimer)	0.013	0.018	-9999	-0.33	1	1
CHRNA1	-0.024	0.26	-9999	-0.64	52	52
myelination	0.018	0.064	-9999	-0.25	9	9
PPP3CB	0.025	0.062	-9999	-0.25	10	10
KRAS	0.018	0.014	-9999	-0.25	1	1
RAC1-CDC42/GDP	0.035	0.064	-9999	-0.24	17	17
NRG2	0.011	0.057	-9999	-0.37	7	7
mol:GDP	0.015	0.07	-9999	-0.29	17	17
SOS1	0.019	0.001	-9999	-10000	0	0
MAP2K2	0.035	0.097	-9999	-0.34	8	8
SRC	0.019	0	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0.029	0.065	-9999	-0.26	10	10
MAP2K1	0.013	0.17	-9999	-0.48	13	13
heart morphogenesis	0.021	0.069	-9999	-0.26	17	17
RAS family/GDP	0.04	0.069	-9999	-0.28	9	9
GRB2	0.019	0.001	-9999	-10000	0	0
PRKACA	0	0.004	-9999	-10000	0	0
CHRNE	0.018	0.031	-9999	-0.1	17	17
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
activation of caspase activity	-0.013	0.002	-9999	-10000	0	0
nervous system development	0.021	0.069	-9999	-0.26	17	17
CDC42	0.019	0	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.019	0	-9999	-10000	0	0
VLDLR	0.005	0.086	-9999	-0.54	9	9
LRPAP1	0.019	0	-9999	-10000	0	0
NUDC	0.019	0	-9999	-10000	0	0
RELN/LRP8	0	0.066	-9999	-10000	0	0
CaM/Ca2+	0.014	0	-9999	-10000	0	0
KATNA1	0.019	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	0.004	0.057	-9999	-10000	0	0
IQGAP1/CaM	0.028	0	-9999	-10000	0	0
DAB1	-0.028	0.089	-9999	-0.24	52	52
IQGAP1	0.019	0	-9999	-10000	0	0
PLA2G7	-0.13	0.24	-9999	-0.54	96	96
CALM1	0.019	0	-9999	-10000	0	0
DYNLT1	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.028	0	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.019	0	-9999	-10000	0	0
CDK5R1	0.017	0.029	-9999	-0.54	1	1
LIS1/Poliovirus Protein 3A	0.019	0	-9999	-10000	0	0
CDK5R2	-0.042	0.11	-9999	-0.24	83	83
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.035	0.1	-9999	-0.28	34	34
YWHAE	0.019	0	-9999	-10000	0	0
NDEL1/14-3-3 E	0.018	0.062	-9999	-0.27	1	1
MAP1B	0.006	0.017	-9999	-10000	0	0
RAC1	0.025	0	-9999	-10000	0	0
p35/CDK5	0.02	0.054	-9999	-0.34	1	1
RELN	-0.047	0.11	-9999	-0.24	91	91
PAFAH/LIS1	-0.058	0.15	-9999	-0.32	96	96
LIS1/CLIP170	0.033	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.007	0.025	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	0	0.073	-9999	-0.29	10	10
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	0.008	0.062	-9999	-0.29	1	1
LIS1/IQGAP1	0.033	0	-9999	-10000	0	0
RHOA	0.025	0	-9999	-10000	0	0
PAFAH1B1	0.026	0	-9999	-10000	0	0
PAFAH1B3	0.017	0.029	-9999	-0.54	1	1
PAFAH1B2	0.019	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.03	0.012	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	0.025	0.061	-9999	-10000	0	0
LRP8	0.019	0	-9999	-10000	0	0
NDEL1/Katanin 60	0.018	0.062	-9999	-0.27	1	1
P39/CDK5	-0.007	0.072	-9999	-10000	0	0
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.033	0	-9999	-10000	0	0
CDK5	0.011	0.052	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.029	0	-9999	-10000	0	0
CSNK2A1	0.019	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.011	0.09	-9999	-0.32	9	9
RELN/VLDLR	0.005	0.079	-9999	-0.31	9	9
CDC42	0.025	0	-9999	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.008	0.07	-9999	-0.41	3	3
PDGFB-D/PDGFRB/SLAP	-0.051	0.16	-9999	-0.39	68	68
PDGFB-D/PDGFRB/APS/CBL	0.03	0.052	-9999	-0.32	7	7
AKT1	0.054	0.019	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.011	0.07	-9999	-0.41	3	3
PIK3CA	0.018	0.014	-9999	-0.24	1	1
FGR	-0.048	0.17	-9999	-0.56	36	36
mol:Ca2+	-0.018	0.06	-9999	-0.24	2	2
MYC	-0.014	0.085	-9999	-0.38	2	2
SHC1	0.019	0	-9999	-10000	0	0
HRAS/GDP	0.04	0.021	-9999	-0.26	1	1
LRP1/PDGFRB/PDGFB	0.034	0.031	-9999	-0.25	2	2
GRB10	0.017	0.019	-9999	-0.24	2	2
PTPN11	0.019	0	-9999	-10000	0	0
GO:0007205	-0.018	0.061	-9999	-0.26	1	1
PTEN	0.017	0.029	-9999	-0.54	1	1
GRB2	0.019	0	-9999	-10000	0	0
GRB7	-0.004	0.068	-9999	-0.24	27	27
PDGFB-D/PDGFRB/SHP2	0.026	0.021	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0.025	0.025	-9999	-10000	0	0
cell cycle arrest	-0.051	0.16	-9999	-0.39	68	68
HRAS	0.019	0	-9999	-10000	0	0
HIF1A	0.057	0.018	-9999	-10000	0	0
GAB1	-0.046	0.095	-9999	-0.28	20	20
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.034	0.088	-9999	-0.33	6	6
PDGFB-D/PDGFRB	0.043	0.019	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.026	0.021	-9999	-0.15	2	2
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.025	0.075	-9999	-0.48	3	3
positive regulation of MAPKKK cascade	0.026	0.021	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	-0.018	0.061	-9999	-0.26	1	1
E5	-0.001	0.002	-9999	-10000	0	0
CSK	0.019	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.01	0.052	-9999	-0.3	1	1
SHB	0.006	0.071	-9999	-0.33	14	14
BLK	-0.34	0.26	-9999	-0.53	236	236
PTPN2	0.019	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.026	0.021	-9999	-10000	0	0
BCAR1	0.019	0	-9999	-10000	0	0
VAV2	-0.042	0.11	-9999	-0.31	25	25
CBL	0.019	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.026	0.021	-9999	-10000	0	0
LCK	-0.2	0.27	-9999	-0.53	142	142
PDGFRB	0.016	0.031	-9999	-0.25	5	5
ACP1	0.019	0	-9999	-10000	0	0
HCK	-0.031	0.16	-9999	-0.56	31	31
ABL1	-0.065	0.11	-9999	-0.31	39	39
PDGFB-D/PDGFRB/CBL	-0.054	0.1	-9999	-0.3	25	25
PTPN1	0.019	0.001	-9999	-10000	0	0
SNX15	0.019	0	-9999	-10000	0	0
STAT3	0.019	0	-9999	-10000	0	0
STAT1	0.016	0.041	-9999	-0.54	2	2
cell proliferation	-0.013	0.081	-9999	-0.34	3	3
SLA	-0.084	0.22	-9999	-0.54	68	68
actin cytoskeleton reorganization	0.048	0.038	-9999	-0.24	4	4
SRC	0.006	0.019	-9999	-10000	0	0
PI3K	-0.002	0.013	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.023	0.045	-9999	-0.24	1	1
SH2B2	0.008	0.076	-9999	-0.54	7	7
PLCgamma1/SPHK1	-0.011	0.072	-9999	-0.43	3	3
LYN	-0.013	0.11	-9999	-0.56	15	15
LRP1	0.014	0.036	-9999	-0.24	7	7
SOS1	0.019	0	-9999	-10000	0	0
STAT5B	0.019	0	-9999	-10000	0	0
STAT5A	0.017	0.029	-9999	-0.54	1	1
NCK1-2/p130 Cas	0.061	0.016	-9999	-10000	0	0
SPHK1	0.011	0.059	-9999	-0.36	8	8
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	-0.018	0.061	-9999	-0.26	1	1
PLCG1	-0.018	0.062	-9999	-0.26	1	1
NHERF/PDGFRB	0.036	0.019	-9999	-10000	0	0
YES1	0.008	0.018	-9999	-10000	0	0
cell migration	0.036	0.019	-9999	-10000	0	0
SHC/Grb2/SOS1	0.061	0.016	-9999	-10000	0	0
SLC9A3R2	0.018	0.014	-9999	-0.24	1	1
SLC9A3R1	0.019	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.046	0.025	-9999	-0.28	1	1
FYN	0.009	0.018	-9999	-10000	0	0
DOK1	0.034	0.015	-9999	-10000	0	0
HRAS/GTP	0.014	0	-9999	-10000	0	0
PDGFB	0.019	0	-9999	-10000	0	0
RAC1	-0.031	0.1	-9999	-0.4	5	5
PRKCD	0.033	0.016	-9999	-10000	0	0
FER	0.033	0.016	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.01	-9999	-10000	0	0
RASA1	0.032	0.023	-9999	-0.29	1	1
NCK1	0.019	0	-9999	-10000	0	0
NCK2	0.019	0	-9999	-10000	0	0
p62DOK/Csk	0.045	0.015	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0.016	0.056	-9999	-0.39	4	4
chemotaxis	-0.064	0.11	-9999	-0.3	39	39
STAT1-3-5/STAT1-3-5	0.033	0.035	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.011	0.021	-9999	-0.16	5	5
PTPRJ	0.019	0	-9999	-10000	0	0

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.025	0.021	-9999	-0.38	1	1
SMARCC1	0.019	0.017	-9999	-10000	0	0
REL	0.019	0.001	-9999	-10000	0	0
HDAC7	0.036	0.072	-9999	-10000	0	0
JUN	-0.008	0.079	-9999	-0.24	37	37
EP300	0.019	0	-9999	-10000	0	0
KAT2B	0.016	0.041	-9999	-0.54	2	2
KAT5	0.019	0	-9999	-10000	0	0
MAPK14	0.018	0.057	-9999	-0.38	7	7
FOXO1	0.019	0	-9999	-10000	0	0
T-DHT/AR	0.041	0.08	-9999	-0.27	2	2
MAP2K6	0.008	0.076	-9999	-0.54	7	7
BRM/BAF57	0.027	0.021	-9999	-0.38	1	1
MAP2K4	0.019	0.005	-9999	-10000	0	0
SMARCA2	0.017	0.029	-9999	-0.54	1	1
PDE9A	0.007	0.14	-9999	-1.1	3	3
NCOA2	0.018	0.014	-9999	-0.24	1	1
CEBPA	-0.028	0.16	-9999	-0.54	31	31
EHMT2	0.019	0	-9999	-10000	0	0
cell proliferation	0.056	0.078	-9999	-10000	0	0
NR0B1	0	0	-9999	-10000	0	0
EGR1	-0.003	0.073	-9999	-0.24	31	31
RXRs/9cRA	-0.036	0.14	-9999	-0.29	82	82
AR/RACK1/Src	0.027	0.062	-9999	-0.29	4	4
AR/GR	0.006	0.052	-9999	-0.24	2	2
GNB2L1	0.019	0.002	-9999	-10000	0	0
PKN1	0.017	0.029	-9999	-0.54	1	1
RCHY1	0.019	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.025	0.011	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.034	0.061	-9999	-0.29	4	4
SRC	0.031	0.046	-9999	-0.25	7	7
NR3C1	0.019	0	-9999	-10000	0	0
KLK3	-0.03	0.043	-9999	-10000	0	0
APPBP2	0.019	0.005	-9999	-10000	0	0
TRIM24	0.019	0	-9999	-10000	0	0
T-DHT/AR/TIP60	0.025	0.055	-9999	-0.28	7	7
TMPRSS2	-0.01	0.23	-9999	-1.1	15	15
RXRG	-0.1	0.23	-9999	-0.54	82	82
mol:9cRA	0	0	-9999	-10000	0	0
RXRA	0.019	0	-9999	-10000	0	0
RXRB	0.019	0	-9999	-10000	0	0
CARM1	0.018	0.002	-9999	-10000	0	0
NR2C2	0.019	0	-9999	-10000	0	0
KLK2	0.011	0.11	-9999	-0.41	2	2
AR	-0.003	0.058	-9999	-0.27	2	2
SENP1	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
MDM2	0.015	0.033	-9999	-0.24	6	6
SRY	-0.001	0.026	-9999	-0.24	4	4
GATA2	0.014	0.036	-9999	-0.24	7	7
MYST2	0.019	0	-9999	-10000	0	0
HOXB13	-0.14	0.13	-9999	-0.24	219	219
T-DHT/AR/RACK1/Src	0.029	0.057	-9999	-0.28	4	4
positive regulation of transcription	0.014	0.036	-9999	-0.24	7	7
DNAJA1	0.019	0.005	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.031	0.019	-9999	-0.22	1	1
NCOA1	0.024	0.002	-9999	-10000	0	0
SPDEF	-0.029	0.098	-9999	-0.24	63	63
T-DHT/AR/TIF2	0.041	0.04	-9999	-10000	0	0
T-DHT/AR/Hsp90	0.025	0.056	-9999	-0.28	7	7
GSK3B	0.019	0.002	-9999	-10000	0	0
NR2C1	0.019	0	-9999	-10000	0	0
mol:T-DHT	0.027	0.048	-9999	-0.28	7	7
SIRT1	0.019	0	-9999	-10000	0	0
ZMIZ2	0.019	0	-9999	-10000	0	0
POU2F1	0.026	0.027	-9999	-10000	0	0
T-DHT/AR/DAX-1	0.013	0.053	-9999	-0.28	7	7
CREBBP	0.019	0	-9999	-10000	0	0
SMARCE1	0.019	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.034	0.12	-9999	-0.29	62	62
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.017	0.029	-9999	-0.54	1	1
TCEB1	0.019	0	-9999	-10000	0	0
HIF1A/p53	0.036	0.026	-9999	-0.44	1	1
HIF1A	0.025	0.027	-9999	-0.48	1	1
COPS5	0.019	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.055	0.016	-9999	-0.26	1	1
FIH (dimer)	0.017	0.029	-9999	-0.54	1	1
CDKN2A	-0.11	0.14	-9999	-0.25	172	172
ARNT/IPAS	-0.009	0.088	-9999	-0.38	10	10
HIF1AN	0.017	0.029	-9999	-0.54	1	1
GNB2L1	0.019	0	-9999	-10000	0	0
HIF1A/ARNT	0.036	0.026	-9999	-0.44	1	1
CUL2	0.019	0	-9999	-10000	0	0
OS9	0.018	0.014	-9999	-0.24	1	1
RACK1/Elongin B/Elongin C	0.037	0.019	-9999	-0.32	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.035	0.03	-9999	-0.34	2	2
PHD1-3/OS9	0.046	0.027	-9999	-0.28	2	2
HIF1A/RACK1/Elongin B/Elongin C	0.051	0.029	-9999	-0.41	1	1
VHL	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
HIF1A/JAB1	0.036	0.026	-9999	-0.44	1	1
EGLN3	0.014	0.045	-9999	-0.39	4	4
EGLN2	0.019	0	-9999	-10000	0	0
EGLN1	0.019	0	-9999	-10000	0	0
TP53	0.019	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.047	0.014	-9999	-10000	0	0
ARNT	0.019	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.019	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.018	0.066	-9999	-0.3	5	5

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.009	0.065	-10000	0	-0.27	11	11
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0	0	-10000	0	-10000	0	0
GNB1/GNG2	0.02	0.044	-10000	0	-0.32	6	6
GNB1	0.019	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.008	0.055	-10000	0	-0.14	49	49
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	0.005	0.014	0.04	49	-10000	0	49
GNAL	-0.02	0.1	-10000	0	-0.28	49	49
GNG2	0.01	0.07	-10000	0	-0.54	6	6
CRH	0	0	-10000	0	-10000	0	0
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.01	0.001	-10000	0	-10000	0	0
MAPK11	0.01	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.021	0.008	-10000	0	-10000	0	0
HSPA8	0.018	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.055	0.072	-10000	0	-0.35	7	7
AKT1	0.019	0.013	-10000	0	-10000	0	0
GSC	-0.025	0.12	-10000	0	-10000	0	0
NKX2-5	-0.11	0.22	-10000	0	-0.49	87	87
muscle cell differentiation	-0.001	0.062	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.072	0.061	-10000	0	-10000	0	0
SMAD4	0.027	0.029	-10000	0	-10000	0	0
CBFB	0.019	0	-10000	0	-10000	0	0
SAP18	0.019	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.018	0.081	-10000	0	-0.32	16	16
SMAD3/SMAD4/VDR	0.073	0.037	-10000	0	-0.26	2	2
MYC	0.017	0.027	-10000	0	-0.25	3	3
CDKN2B	0	0.18	-10000	0	-1.4	5	5
AP1	0.037	0.091	-10000	0	-0.31	7	7
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.069	0.019	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.042	0.055	-10000	0	-0.28	5	5
SP3	0.022	0	-10000	0	-10000	0	0
CREB1	0.019	0	-10000	0	-10000	0	0
FOXH1	0.012	0.03	-10000	0	-0.25	3	3
SMAD3/SMAD4/GR	0.053	0.034	-10000	0	-10000	0	0
GATA3	-0.11	0.24	-10000	0	-0.56	80	80
SKI/SIN3/HDAC complex/NCoR1	0.053	0.012	-10000	0	-10000	0	0
MEF2C/TIF2	-0.01	0.12	-10000	0	-0.31	16	16
endothelial cell migration	-0.002	0.1	1.4	1	-10000	0	1
MAX	0.018	0.006	-10000	0	-10000	0	0
RBBP7	0.019	0.001	-10000	0	-10000	0	0
RBBP4	0.019	0.001	-10000	0	-10000	0	0
RUNX2	0.015	0.043	-10000	0	-0.44	3	3
RUNX3	-0.017	0.14	-10000	0	-0.54	24	24
RUNX1	0.014	0.05	-10000	0	-0.54	3	3
CTBP1	0.019	0	-10000	0	-10000	0	0
NR3C1	0.018	0.006	-10000	0	-10000	0	0
VDR	0.016	0.041	-10000	0	-0.54	2	2
CDKN1A	0.057	0.047	-10000	0	-10000	0	0
KAT2B	0.017	0.041	-10000	0	-0.53	2	2
SMAD2/SMAD2/SMAD4/FOXH1	0.041	0.052	-10000	0	-0.2	1	1
DCP1A	0.019	0	-10000	0	-10000	0	0
SKI	0.019	0.001	-10000	0	-10000	0	0
SERPINE1	-0.003	0.1	-10000	0	-1.4	1	1
SMAD3/SMAD4/ATF2	0.054	0.033	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.051	0.041	-10000	0	-10000	0	0
SAP30	0.019	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.044	0.02	-10000	0	-10000	0	0
JUN	0.031	0.089	-10000	0	-0.31	7	7
SMAD3/SMAD4/IRF7	0.05	0.057	-10000	0	-0.34	5	5
TFE3	0.025	0.007	-10000	0	-10000	0	0
COL1A2	-0.043	0.1	-10000	0	-10000	0	0
mesenchymal cell differentiation	-0.051	0.045	0.35	2	-10000	0	2
DLX1	-0.035	0.14	-10000	0	-0.35	54	54
TCF3	0.019	0	-10000	0	-10000	0	0
FOS	0.012	0.053	-10000	0	-0.26	12	12
SMAD3/SMAD4/Max	0.053	0.034	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.04	0.007	-10000	0	-10000	0	0
ZBTB17	0.019	0.01	-10000	0	-10000	0	0
LAMC1	0.056	0.031	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.054	0.033	-10000	0	-10000	0	0
IRF7	0.012	0.065	-10000	0	-0.54	5	5
ESR1	0.011	0.077	-10000	0	-0.54	7	7
HNF4A	-0.015	0.074	-10000	0	-0.24	34	34
MEF2C	-0.021	0.13	-10000	0	-0.33	15	15
SMAD2-3/SMAD4	0.055	0.044	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.042	0.012	-10000	0	-10000	0	0
IGHV3OR16-13	-0.002	0.019	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.019	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0
SKIL	0.019	0	-10000	0	-10000	0	0
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.019	0.001	-10000	0	-10000	0	0
SNIP1	0.018	0.002	-10000	0	-10000	0	0
GCN5L2	0.002	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.068	0.038	-10000	0	-10000	0	0
MSG1/HSC70	-0.001	0.091	-10000	0	-0.38	16	16
SMAD2	0.016	0.02	-10000	0	-10000	0	0
SMAD3	0.029	0.025	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.049	0.045	-10000	0	-0.24	5	5
SMAD2/SMAD2/SMAD4	0.015	0.029	-10000	0	-0.32	2	2
NCOR1	0.019	0.001	-10000	0	-10000	0	0
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
NCOA1	0.019	0	-10000	0	-10000	0	0
MYOD/E2A	0.019	0.023	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.082	0.059	-10000	0	-10000	0	0
IFNB1	0.035	0.051	-10000	0	-0.29	5	5
SMAD3/SMAD4/MEF2C	0.005	0.13	-10000	0	-0.4	5	5
CITED1	-0.02	0.13	-10000	0	-0.38	36	36
SMAD2-3/SMAD4/ARC105	0.065	0.04	-10000	0	-10000	0	0
RBL1	0.019	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.053	0.076	-10000	0	-0.47	5	5
RUNX1-3/PEBPB2	0.013	0.098	-10000	0	-0.34	25	25
SMAD7	0.074	0.072	-10000	0	-10000	0	0
MYC/MIZ-1	0.026	0.029	-10000	0	-10000	0	0
SMAD3/SMAD4	0.048	0.062	-10000	0	-0.39	1	1
IL10	-0.051	0.23	-10000	0	-0.57	41	41
PIASy/HDAC complex	0.017	0.006	-10000	0	-10000	0	0
PIAS3	0.02	0.003	-10000	0	-10000	0	0
CDK2	0.02	0.005	-10000	0	-10000	0	0
IL5	-0.043	0.17	-10000	0	-0.38	50	50
CDK4	0.019	0.021	-10000	0	-0.25	2	2
PIAS4	0.017	0.006	-10000	0	-10000	0	0
ATF3	0.015	0.031	-10000	0	-0.24	5	5
SMAD3/SMAD4/SP1	0.059	0.053	-10000	0	-10000	0	0
FOXG1	-0.022	0.086	-10000	0	-0.25	46	46
FOXO3	0.027	0.017	-10000	0	-10000	0	0
FOXO1	0.027	0.017	-10000	0	-10000	0	0
FOXO4	0.027	0.017	-10000	0	-10000	0	0
heart looping	-0.02	0.12	-10000	0	-0.33	15	15
CEBPB	0.019	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.017	0.1	-10000	0	-0.33	19	19
MYOD1	0.006	0.034	-10000	0	-0.24	6	6
SMAD3/SMAD4/HNF4	0.032	0.061	-10000	0	-0.23	3	3
SMAD3/SMAD4/GATA3	-0.037	0.2	-10000	0	-0.37	87	87
SnoN/SIN3/HDAC complex/NCoR1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.049	0.095	-10000	0	-0.28	25	25
SMAD3/SMAD4/SP1-3	0.077	0.048	-10000	0	-10000	0	0
MED15	0.019	0	-10000	0	-10000	0	0
SP1	0.017	0.027	-10000	0	-10000	0	0
SIN3B	0.019	0.001	-10000	0	-10000	0	0
SIN3A	0.019	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.019	0.14	-10000	0	-0.27	76	76
ITGB5	0.058	0.038	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.015	0.088	-10000	0	-0.23	3	3
AR	-0.086	0.13	-10000	0	-0.24	144	144
negative regulation of cell growth	0.058	0.04	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.045	0.041	-10000	0	-10000	0	0
E2F5	0.007	0.081	-10000	0	-0.54	8	8
E2F4	0.019	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.06	0.042	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.054	0.057	-10000	0	-0.31	5	5
TFDP1	0.019	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.05	0.097	-10000	0	-0.31	7	7
SMAD3/SMAD4/RUNX2	0.051	0.045	-10000	0	-0.35	2	2
TGIF2	0.019	0	-10000	0	-10000	0	0
TGIF1	0.019	0	-10000	0	-10000	0	0
ATF2	0.019	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.02	0.14	-9999	-0.31	75	75
Ran/GTP/Exportin 1/HDAC1	-0.001	0.012	-9999	-0.23	1	1
NF kappa B1 p50/RelA/I kappa B alpha	-0.012	0.14	-9999	-0.28	75	75
SUMO1	0.019	0	-9999	-10000	0	0
ZFPM1	0.017	0.032	-9999	-0.39	2	2
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
FKBP3	0.019	0	-9999	-10000	0	0
Histones	0.02	0.078	-9999	-0.23	1	1
YY1/LSF	0.03	0.053	-9999	-0.28	10	10
SMG5	0.019	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.017	0.11	-9999	-0.24	75	75
I kappa B alpha/HDAC1	-0.001	0.083	-9999	-0.27	1	1
SAP18	0.019	0	-9999	-10000	0	0
RELA	-0.01	0.11	-9999	-0.22	75	75
HDAC1/Smad7	0.037	0.019	-9999	-0.32	1	1
RANGAP1	0.019	0	-9999	-10000	0	0
HDAC3/TR2	0	0.082	-9999	-10000	0	0
NuRD/MBD3 Complex	0.054	0.018	-9999	-10000	0	0
NF kappa B1 p50/RelA	0	0.099	-9999	-0.2	75	75
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.014	0.036	-9999	-0.24	7	7
GATA1	0	0	-9999	-10000	0	0
Mad/Max	0.028	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.06	0.027	-9999	-0.35	1	1
RBBP7	0.019	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
RBBP4	0.019	0	-9999	-10000	0	0
MAX	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.019	0	-9999	-10000	0	0
NFKBIA	-0.011	0.09	-9999	-10000	0	0
KAT2B	0.016	0.041	-9999	-0.54	2	2
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.05	0.012	-9999	-10000	0	0
SIN3 complex	0.049	0	-9999	-10000	0	0
SMURF1	0.019	0	-9999	-10000	0	0
CHD3	0.019	0	-9999	-10000	0	0
SAP30	0.019	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.019	0	-9999	-10000	0	0
YY1/HDAC3	0.013	0.077	-9999	-0.35	1	1
YY1/HDAC2	0.037	0.019	-9999	-0.22	2	2
YY1/HDAC1	0.037	0.026	-9999	-0.25	3	3
NuRD/MBD2 Complex (MeCP1)	0.055	0.01	-9999	-10000	0	0
PPARG	-0.03	0.14	-9999	-0.3	79	79
HDAC8/hEST1B	0.038	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.019	0	-9999	-10000	0	0
TNFRSF1A	0.019	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0	0.082	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.037	0.018	-9999	-0.32	1	1
CREBBP	0.019	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.058	0.019	-9999	-10000	0	0
HDAC1	0.017	0.029	-9999	-0.54	1	1
HDAC3	-0.011	0.09	-9999	-10000	0	0
HDAC2	0.019	0	-9999	-10000	0	0
YY1	0.034	0.022	-9999	-0.27	2	2
HDAC8	0.019	0	-9999	-10000	0	0
SMAD7	0.019	0	-9999	-10000	0	0
NCOR2	0.019	0	-9999	-10000	0	0
MXD1	0.019	0	-9999	-10000	0	0
STAT3	0.031	0	-9999	-10000	0	0
NFKB1	0.019	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.019	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.039	0.052	-9999	-0.25	11	11
YY1/SAP30/HDAC1	0.046	0.024	-9999	-0.22	3	3
EP300	0.019	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.031	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.011	0.089	-9999	-10000	0	0
histone deacetylation	0.055	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.011	0.075	-9999	-10000	0	0
nuclear export	-0.038	0	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
GATAD2B	0.019	0	-9999	-10000	0	0
GATAD2A	0.019	0	-9999	-10000	0	0
GATA2/HDAC3	-0.003	0.084	-9999	-0.28	2	2
GATA1/HDAC1	0.013	0.021	-9999	-0.39	1	1
GATA1/HDAC3	-0.013	0.079	-9999	-10000	0	0
CHD4	0.019	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.056	0.16	-9999	-0.38	75	75
SIN3/HDAC complex/Mad/Max	0.055	0.01	-9999	-10000	0	0
NuRD Complex	0.063	0.019	-9999	-10000	0	0
positive regulation of chromatin silencing	0.019	0.076	-9999	-0.23	1	1
SIN3B	0.019	0	-9999	-10000	0	0
MTA2	0.019	0	-9999	-10000	0	0
SIN3A	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
SUMO1/HDAC1	0.039	0.015	-9999	-0.25	1	1
HDAC complex	0.048	0.017	-9999	-0.28	1	1
GATA1/Fog1	0.012	0.023	-9999	-0.39	1	1
FKBP25/HDAC1/HDAC2	0.037	0.019	-9999	-0.32	1	1
TNF	-0.095	0.22	-9999	-0.54	75	75
negative regulation of cell growth	0.055	0.01	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.055	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.043	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.022	0.14	-9999	-0.3	75	75
SIN3/HDAC complex/NCoR1	0.052	0.01	-9999	-10000	0	0
TFCP2	0.006	0.082	-9999	-0.5	9	9
NR2C1	0.019	0	-9999	-10000	0	0
MBD3	0.016	0.041	-9999	-0.54	2	2
MBD2	0.019	0	-9999	-10000	0	0

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	0.018	0.13	-9999	-1.2	2	2
RAD9A	0.019	0	-9999	-10000	0	0
AP1	0.006	0.069	-9999	-0.3	7	7
IFNAR2	0.02	0.004	-9999	-10000	0	0
AKT1	0.019	0.034	-9999	-0.23	3	3
ER alpha/Oestrogen	0.007	0.056	-9999	-0.39	7	7
NFX1/SIN3/HDAC complex	0.055	0.013	-9999	-10000	0	0
EGF	-0.031	0.15	-9999	-0.42	41	41
SMG5	0.019	0	-9999	-10000	0	0
SMG6	0.019	0	-9999	-10000	0	0
SP3/HDAC2	0.031	0.008	-9999	-10000	0	0
TERT/c-Abl	0.027	0.12	-9999	-1.1	2	2
SAP18	0.019	0.001	-9999	-10000	0	0
MRN complex	0.037	0.026	-9999	-0.32	2	2
WT1	0.002	0.004	-9999	-10000	0	0
WRN	0.019	0	-9999	-10000	0	0
SP1	0.021	0.006	-9999	-10000	0	0
SP3	0.02	0.002	-9999	-10000	0	0
TERF2IP	0.019	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.008	0.092	-9999	-0.94	2	2
Mad/Max	0.03	0.005	-9999	-10000	0	0
TERT	0.015	0.13	-9999	-1.3	2	2
CCND1	0.024	0.12	-9999	-0.99	2	2
MAX	0.02	0.002	-9999	-10000	0	0
RBBP7	0.019	0.001	-9999	-10000	0	0
RBBP4	0.019	0.001	-9999	-10000	0	0
TERF2	0.017	0	-9999	-10000	0	0
PTGES3	0.019	0	-9999	-10000	0	0
SIN3A	0.019	0.001	-9999	-10000	0	0
Telomerase/911	0.051	0.023	-9999	-10000	0	0
CDKN1B	-0.12	0.2	-9999	-0.34	155	155
RAD1	0.019	0	-9999	-10000	0	0
XRCC5	0.019	0	-9999	-10000	0	0
XRCC6	0.019	0	-9999	-10000	0	0
SAP30	0.019	0.001	-9999	-10000	0	0
TRF2/PARP2	0.028	0	-9999	-10000	0	0
UBE3A	0.019	0.002	-9999	-10000	0	0
JUN	-0.007	0.08	-9999	-0.24	37	37
E6	0.001	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.016	0.005	-9999	-10000	0	0
FOS	0.011	0.047	-9999	-0.24	12	12
IFN-gamma/IRF1	-0.15	0.23	-9999	-0.4	155	155
PARP2	0.019	0	-9999	-10000	0	0
BLM	0.019	0	-9999	-10000	0	0
Telomerase	0.069	0.069	-9999	-0.34	4	4
IRF1	-0.041	0.18	-9999	-0.53	43	43
ESR1	0.009	0.076	-9999	-0.54	7	7
KU/TER	0.028	0	-9999	-10000	0	0
ATM/TRF2	0.029	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.061	0.013	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.061	0.013	-9999	-10000	0	0
HDAC1	0.018	0.029	-9999	-0.54	1	1
HDAC2	0.021	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.023	0.03	-9999	-0.38	2	2
ABL1	0.019	0	-9999	-10000	0	0
MXD1	0.02	0.002	-9999	-10000	0	0
MRE11A	0.019	0	-9999	-10000	0	0
HUS1	0.019	0	-9999	-10000	0	0
RPS6KB1	0.019	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	0.044	0.12	-9999	-1	2	2
NR2F2	0.017	0.004	-9999	-10000	0	0
MAPK3	0.018	0.011	-9999	-10000	0	0
MAPK1	0.018	0.011	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.015	0.041	-9999	-0.54	2	2
NFKB1	0.019	0	-9999	-10000	0	0
HNRNPC	0.019	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.019	0	-9999	-10000	0	0
EGFR	-0.007	0.087	-9999	-0.27	33	33
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.025	0.12	-9999	-0.36	34	34
MYC	0.018	0.024	-9999	-0.25	3	3
IL2	0.007	0.017	-9999	-0.24	1	1
KU	0.028	0	-9999	-10000	0	0
RAD50	0.016	0.041	-9999	-0.54	2	2
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
TGFB1	0.015	0.041	-9999	-0.54	2	2
TRF2/BLM	0.028	0	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	0.037	0.12	-9999	-1.1	2	2
SP1/HDAC2	0.033	0.011	-9999	-10000	0	0
PINX1	0.018	0.014	-9999	-0.24	1	1
Telomerase/EST1A	-0.008	0.092	-9999	-0.94	2	2
Smad3/Myc	0.029	0.029	-9999	-0.32	2	2
911 complex	0.038	0	-9999	-10000	0	0
IFNG	-0.17	0.26	-9999	-0.53	129	129
Telomerase/PinX1	-0.008	0.092	-9999	-0.94	2	2
Telomerase/AKT1/mTOR/p70S6K	0.043	0.04	-9999	-0.29	1	1
SIN3B	0.019	0.001	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
Telomerase/EST1B	-0.008	0.092	-9999	-0.94	2	2
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0.053	0.022	-9999	-0.25	2	2
TRF2/WRN	0.028	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.008	0.092	-9999	-0.94	2	2
E2F1	0.02	0.004	-9999	-10000	0	0
ZNFX1	0.019	0.001	-9999	-10000	0	0
PIF1	0.014	0.05	-9999	-0.54	3	3
NCL	0.019	0	-9999	-10000	0	0
DKC1	0.019	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC2	0.019	0	-10000	0	-10000	0	0
GNB1/GNG2	0.024	0.073	-10000	0	-0.32	16	16
forebrain development	0.033	0.061	-10000	0	-0.38	4	4
GNAO1	-0.093	0.13	-10000	0	-0.25	155	155
SMO/beta Arrestin2	0.019	0.067	-10000	0	-0.38	10	10
SMO	0.005	0.091	-10000	0	-0.54	10	10
ARRB2	0.02	0.001	-10000	0	-10000	0	0
GLI3/SPOP	0.059	0.035	-10000	0	-10000	0	0
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
GSK3B	0.019	0	-10000	0	-10000	0	0
GNAI2	0.019	0.001	-10000	0	-10000	0	0
SIN3/HDAC complex	0.048	0.001	-10000	0	-10000	0	0
GNAI1	0.005	0.06	-10000	0	-0.24	20	20
XPO1	0.021	0.002	-10000	0	-10000	0	0
GLI1/Su(fu)	0.039	0.069	-10000	0	-0.32	9	9
SAP30	0.019	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.09	-10000	0	-0.54	10	10
MIM/GLI2A	0.014	0.05	-10000	0	-0.54	3	3
IFT88	0.017	0.029	-10000	0	-0.54	1	1
GNAI3	0.019	0.001	-10000	0	-10000	0	0
GLI2	0.048	0.018	-10000	0	-10000	0	0
GLI3	0.051	0.037	0.2	8	-0.23	3	11
CSNK1D	0.019	0	-10000	0	-10000	0	0
CSNK1E	0.019	0	-10000	0	-10000	0	0
SAP18	0.019	0	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.017	0.029	-10000	0	-0.54	1	1
GNG2	0.01	0.07	-10000	0	-0.54	6	6
Gi family/GTP	-0.017	0.082	-10000	0	-0.31	13	13
SIN3B	0.019	0	-10000	0	-10000	0	0
SIN3A	0.019	0	-10000	0	-10000	0	0
GLI3/Su(fu)	0.071	0.026	-10000	0	-10000	0	0
GLI2/Su(fu)	0.064	0.034	-10000	0	-0.27	1	1
FOXA2	-0.006	0.065	-10000	0	-0.72	3	3
neural tube patterning	0.033	0.061	-10000	0	-0.38	4	4
SPOP	0.019	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.037	0.033	-10000	0	-10000	0	0
GNB1	0.019	0	-10000	0	-10000	0	0
CSNK1G2	0.019	0	-10000	0	-10000	0	0
CSNK1G3	0.019	0	-10000	0	-10000	0	0
MTSS1	0.014	0.05	-10000	0	-0.54	3	3
embryonic limb morphogenesis	0.033	0.061	-10000	0	-0.38	4	4
SUFU	0.03	0.036	-10000	0	-0.19	10	10
LGALS3	-0.005	0.11	-10000	0	-0.54	16	16
catabolic process	0.085	0.034	-10000	0	-10000	0	0
GLI3A/CBP	0.027	0.031	-10000	0	-0.34	2	2
KIF3A	0.019	0	-10000	0	-10000	0	0
GLI1	0.033	0.062	-10000	0	-0.39	4	4
RAB23	0.019	0	-10000	0	-10000	0	0
CSNK1A1	0.019	0	-10000	0	-10000	0	0
IFT172	0.013	0.058	-10000	0	-0.54	4	4
RBBP7	0.019	0	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.023	0.071	-10000	0	-0.27	16	16
GNAZ	-0.015	0.093	-10000	0	-0.26	45	45
RBBP4	0.019	0	-10000	0	-10000	0	0
CSNK1G1	0.019	0	-10000	0	-10000	0	0
PIAS1	0.019	0	-10000	0	-10000	0	0
PRKACA	0.019	0	-10000	0	-10000	0	0
GLI2/SPOP	0.055	0.017	-10000	0	-10000	0	0
STK36	0.021	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.006	0.081	-10000	0	-0.32	12	12
PTCH1	0.037	0.099	-10000	0	-1.1	2	2
MIM/GLI1	0.041	0.064	-10000	0	-0.37	4	4
CREBBP	0.027	0.031	-10000	0	-0.34	2	2
Su(fu)/SIN3/HDAC complex	0.055	0.019	-10000	0	-0.26	1	1

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.02	0.059	-9999	-0.32	11	11
SNTA1	0.014	0.036	-9999	-0.24	7	7
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.019	0.062	-9999	-0.32	12	12
MAPK12	0.02	0.06	-9999	-0.3	12	12
CCND1	0.017	0.031	-9999	-0.19	1	1
p38 gamma/SNTA1	0.027	0.059	-9999	-0.27	12	12
MAP2K3	0.019	0	-9999	-10000	0	0
PKN1	0.017	0.029	-9999	-0.54	1	1
G2/M transition checkpoint	0.02	0.06	-9999	-0.3	12	12
MAP2K6	0.018	0.049	-9999	-0.31	8	8
MAPT	-0.03	0.072	-9999	-0.27	15	15
MAPK13	0.014	0.07	-9999	-0.38	11	11
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.019	0.019	-9999	-0.33	1	1

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.008	0.15	-9999	-0.93	4	4
MKNK1	0.019	0	-9999	-10000	0	0
MAPK14	0.008	0.067	-9999	-0.29	4	4
ATF2/c-Jun	0.006	0.097	-9999	-0.32	11	11
MAPK11	0.008	0.067	-9999	-0.28	5	5
MITF	0.006	0.11	-9999	-0.38	20	20
MAPKAPK5	0.02	0.074	-9999	-0.32	5	5
KRT8	-0.035	0.14	-9999	-0.32	60	60
MAPKAPK3	0.019	0	-9999	-10000	0	0
MAPKAPK2	0.019	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.012	0.093	-9999	-0.41	5	5
CEBPB	0.02	0.074	-9999	-0.32	5	5
SLC9A1	0.02	0.074	-9999	-0.32	5	5
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.02	0.082	-9999	-0.33	5	5
p38alpha-beta/MNK1	0.028	0.075	-9999	-0.32	5	5
JUN	0.005	0.096	-9999	-0.32	11	11
PPARGC1A	-0.039	0.11	-9999	-0.38	14	14
USF1	0.02	0.074	-9999	-0.34	4	4
RAB5/GDP/GDI1	0.021	0.05	-9999	-0.24	4	4
NOS2	0.012	0.11	-9999	-0.75	2	2
DDIT3	0.02	0.074	-9999	-0.34	4	4
RAB5A	0.019	0	-9999	-10000	0	0
HSPB1	0.025	0.059	-9999	-0.27	4	4
p38alpha-beta/HBP1	0.028	0.075	-9999	-0.32	5	5
CREB1	0.025	0.076	-9999	-0.35	4	4
RAB5/GDP	0.014	0	-9999	-10000	0	0
EIF4E	0.025	0.061	-9999	-0.28	4	4
RPS6KA4	0.02	0.074	-9999	-0.34	4	4
PLA2G4A	0.02	0.074	-9999	-0.3	10	10
GDI1	0.02	0.074	-9999	-0.34	4	4
TP53	0.017	0.086	-9999	-0.4	5	5
RPS6KA5	0.019	0.079	-9999	-0.34	6	6
ESR1	0.014	0.096	-9999	-0.39	12	12
HBP1	0.019	0	-9999	-10000	0	0
MEF2C	0.019	0.077	-9999	-0.32	6	6
MEF2A	0.02	0.074	-9999	-0.34	4	4
EIF4EBP1	0.024	0.077	-9999	-0.34	5	5
KRT19	0	0.087	-9999	-0.32	8	8
ELK4	0.02	0.074	-9999	-0.32	5	5
ATF6	0.02	0.074	-9999	-0.32	5	5
ATF1	0.025	0.076	-9999	-0.35	4	4
p38alpha-beta/MAPKAPK2	0.028	0.075	-9999	-0.32	5	5
p38alpha-beta/MAPKAPK3	0.028	0.075	-9999	-0.32	5	5

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.013	0.045	-9999	-0.24	11	11
TC10/GTP	-0.007	0.039	-9999	-0.23	11	11
Insulin Receptor/Insulin/IRS1/Shp2	0.028	0.039	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
APS homodimer	0.008	0.076	-9999	-0.54	7	7
GRB14	-0.027	0.096	-9999	-0.24	59	59
FOXO3	0.028	0.012	-9999	-10000	0	0
AKT1	0.026	0.05	-9999	-10000	0	0
INSR	0.02	0.014	-9999	-0.24	1	1
Insulin Receptor/Insulin	0.046	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.017	0.019	-9999	-0.24	2	2
SORBS1	0.012	0.059	-9999	-0.48	5	5
CRK	0.019	0	-9999	-10000	0	0
PTPN1	0.035	0.005	-9999	-10000	0	0
CAV1	0.02	0.034	-9999	-10000	0	0
CBL/APS/CAP/Crk-II/C3G	0.047	0.054	-9999	-0.26	11	11
Insulin Receptor/Insulin/IRS1/NCK2	0.028	0.039	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.024	0.032	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.023	-9999	-10000	0	0
RPS6KB1	0.031	0.047	-9999	-10000	0	0
PARD6A	0.019	0	-9999	-10000	0	0
CBL	0.019	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.004	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.011	0.024	-9999	-10000	0	0
HRAS/GTP	-0.04	0.079	-9999	-0.3	4	4
Insulin Receptor	0.02	0.014	-9999	-0.24	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.038	0.037	-9999	-10000	0	0
PRKCI	0.009	0.017	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.017	0.034	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.036	0.016	-9999	-0.27	1	1
PI3K	0.031	0.034	-9999	-10000	0	0
NCK2	0.019	0	-9999	-10000	0	0
RHOQ	0.019	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.014	0	-9999	-10000	0	0
AKT2	0.026	0.05	-9999	-10000	0	0
PRKCZ	0.006	0.042	-9999	-0.52	2	2
SH2B2	0.008	0.076	-9999	-0.54	7	7
SHC/SHIP	-0.018	0.11	-9999	-0.26	62	62
F2RL2	-0.061	0.18	-9999	-0.43	66	66
TRIP10	0.018	0.014	-9999	-0.24	1	1
Insulin Receptor/Insulin/Shc	0.027	0.006	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.025	0.008	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.048	0.006	-9999	-10000	0	0
RAPGEF1	0.019	0	-9999	-10000	0	0
RASA1	0.017	0.029	-9999	-0.54	1	1
NCK1	0.019	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.038	0.057	-9999	-0.28	11	11
TC10/GDP	0.014	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.039	0.012	-9999	-10000	0	0
INPP5D	-0.031	0.12	-9999	-0.28	62	62
SOS1	0.019	0	-9999	-10000	0	0
SGK1	0.002	0.003	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
IRS1	-0.002	0.071	-9999	-0.24	29	29
p62DOK/RasGAP	0.036	0.016	-9999	-0.27	1	1
INS	0.003	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	-0.031	0.12	-9999	-0.28	62	62
GRB2	0.019	0	-9999	-10000	0	0
EIF4EBP1	0.03	0.047	-9999	-10000	0	0
PTPRA	0.021	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
TC10/GTP/CIP4	0.025	0.008	-9999	-10000	0	0
PDPK1	0.019	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.032	0.026	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.016	0.038	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS3	0.018	0.009	-9999	-10000	0	0
Par3/Par6	0.001	0.1	-9999	-0.27	41	41

×

Signaling events mediated by PRL

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
CCNE1	0.019	0	-10000	0	-10000	0	0
mol:Halofuginone	0.005	0.013	-10000	0	-10000	0	0
ITGA1	0.009	0.051	-10000	0	-0.24	14	14
CDKN1A	0.031	0.025	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	0.026	0.025	-10000	0	-0.38	1	1
mol:Ca2+	-0.075	0.14	-10000	0	-0.32	87	87
AGT	-0.089	0.2	-10000	0	-0.43	88	88
CCNA2	0.029	0.048	-10000	0	-0.32	1	1
TUBA1B	0.019	0	-10000	0	-10000	0	0
EGR1	0.011	0.054	-10000	0	-0.32	1	1
CDK2/Cyclin E1	0.049	0.022	-10000	0	-10000	0	0
MAPK3	0.024	0.025	-10000	0	-0.38	1	1
PRL-2 /Rab GGTase beta	0.028	0	-10000	0	-10000	0	0
MAPK1	0.024	0.025	-10000	0	-0.38	1	1
PTP4A1	0.024	0.049	-10000	0	-0.35	1	1
PTP4A3	0.016	0.035	-10000	0	-0.34	3	3
PTP4A2	0.019	0	-10000	0	-10000	0	0
ITGB1	0.023	0.028	-10000	0	-0.2	5	5
SRC	0.019	0	-10000	0	-10000	0	0
RAC1	0.031	0.033	-10000	0	-0.38	1	1
Rab GGTase beta/Rab GGTase alpha	0.028	0	-10000	0	-10000	0	0
PRL-1/ATF-5	0.033	0.046	-10000	0	-0.32	1	1
RABGGTA	0.019	0	-10000	0	-10000	0	0
BCAR1	0.002	0.023	0.23	3	-10000	0	3
RHOC	0.031	0.033	-10000	0	-0.38	1	1
RHOA	0.031	0.033	-10000	0	-0.38	1	1
cell motility	0.036	0.034	-10000	0	-0.38	1	1
PRL-1/alpha Tubulin	0.033	0.046	-10000	0	-0.32	1	1
PRL-3/alpha1 Integrin	0.019	0.042	-10000	0	-0.38	1	1
ROCK1	0.036	0.034	-10000	0	-0.38	1	1
RABGGTB	0.019	0	-10000	0	-10000	0	0
CDK2	0.019	0	-10000	0	-10000	0	0
mitosis	0.024	0.049	-10000	0	-0.35	1	1
ATF5	0.019	0	-10000	0	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.01	0.07	0.54	6	-10000	0	6
PI3K Class IB/PDE3B	0.01	0.07	-10000	0	-0.54	6	6
PDE3B	0.01	0.07	-10000	0	-0.54	6	6

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.038	0.033	-9999	-0.44	1	1
STMN1	0.025	0.03	-9999	-0.38	2	2
Aurora B/RasGAP/Survivin	0.038	0.027	-9999	-0.32	2	2
Chromosomal passenger complex/Cul3 protein complex	0.019	0.054	-9999	-0.22	4	4
BIRC5	0.02	0.001	-9999	-10000	0	0
DES	-0.057	0.16	-9999	-0.56	32	32
Aurora C/Aurora B/INCENP	-0.032	0.13	-9999	-0.29	78	78
Aurora B/TACC1	0.025	0.018	-9999	-0.31	1	1
Aurora B/PP2A	0.028	0.021	-9999	-0.37	1	1
mol:GTP	0	0	-9999	-10000	0	0
CBX5	0.018	0.009	-9999	-0.15	1	1
mitotic metaphase/anaphase transition	0	0.001	-9999	-10000	0	0
NDC80	0.022	0.043	-9999	-0.38	4	4
Cul3 protein complex	-0.002	0.091	-9999	-0.34	16	16
KIF2C	0.03	0.011	-9999	-0.15	1	1
PEBP1	0.02	0.001	-9999	-10000	0	0
KIF20A	0.017	0.029	-9999	-0.54	1	1
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	0.027	0.03	-9999	-0.38	2	2
SEPT1	-0.15	0.26	-9999	-0.54	110	110
SMC2	0.017	0.029	-9999	-0.54	1	1
SMC4	0.019	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	0.041	0.038	-9999	-0.68	1	1
PSMA3	0.019	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.001	-9999	-10000	0	0
H3F3B	0.02	0.018	-9999	-0.33	1	1
AURKB	0.019	0.029	-9999	-0.54	1	1
AURKC	-0.098	0.23	-9999	-0.54	77	77
CDCA8	0.02	0.001	-9999	-10000	0	0
cytokinesis	0.047	0.035	-9999	-0.36	2	2
Aurora B/Septin1	-0.02	0.13	-9999	-0.32	3	3
AURKA	0.019	0.001	-9999	-10000	0	0
INCENP	0.02	0.001	-9999	-10000	0	0
KLHL13	-0.039	0.13	-9999	-0.29	69	69
BUB1	0.019	0.001	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	0.037	0.018	-9999	-0.28	1	1
EVI5	0.02	0.001	-9999	-10000	0	0
RhoA/GTP	0.057	0.025	-9999	-0.27	2	2
SGOL1	0.019	0	-9999	-10000	0	0
CENPA	0.033	0.037	-9999	-0.42	2	2
NCAPG	0.016	0.041	-9999	-0.54	2	2
Aurora B/HC8 Proteasome	0.028	0.021	-9999	-0.37	1	1
NCAPD2	0.019	0	-9999	-10000	0	0
Aurora B/PP1-gamma	0.027	0.03	-9999	-0.38	2	2
RHOA	0.019	0	-9999	-10000	0	0
NCAPH	0.017	0.029	-9999	-0.54	1	1
NPM1	0.026	0.029	-9999	-0.54	1	1
RASA1	0.017	0.029	-9999	-0.54	1	1
KLHL9	0.01	0.07	-9999	-0.54	6	6
mitotic prometaphase	0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.021	-9999	-0.37	1	1
PPP1CC	0.017	0.029	-9999	-0.54	1	1
Centraspindlin	0.054	0.027	-9999	-0.3	2	2
RhoA/GDP	0.014	0	-9999	-10000	0	0
NSUN2	0.026	0.029	-9999	-0.54	1	1
MYLK	0.017	0.036	-9999	-0.33	4	4
KIF23	0.019	0.029	-9999	-0.54	1	1
VIM	0.026	0.021	-9999	-0.37	1	1
RACGAP1	0.02	0.001	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	0.026	0.029	-9999	-0.54	1	1
Chromosomal passenger complex	0.042	0.022	-9999	-0.34	1	1
Chromosomal passenger complex/EVI5	0.057	0.025	-9999	-0.27	1	1
TACC1	0.019	0	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
CUL3	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.022	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.085	0.042	-9999	-10000	0	0
ERC1	0.019	0	-9999	-10000	0	0
RIP2/NOD2	0.005	0.095	-9999	-0.38	21	21
NFKBIA	0.048	0	-9999	-10000	0	0
BIRC2	0.014	0.052	-9999	-0.46	4	4
IKBKB	0.019	0	-9999	-10000	0	0
RIPK2	0.019	0	-9999	-10000	0	0
IKBKG	0.038	0.062	-9999	-0.48	1	1
IKK complex/A20	0.007	0.14	-9999	-0.41	18	18
NEMO/A20/RIP2	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
NEMO/ATM	0.046	0.06	-9999	-0.45	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
Exportin 1/RanGTP	0.026	0	-9999	-10000	0	0
IKK complex/ELKS	-0.009	0.039	-9999	-0.4	1	1
BCL10/MALT1/TRAF6	0.037	0.02	-9999	-0.32	1	1
NOD2	-0.013	0.13	-9999	-0.54	21	21
NFKB1	0.022	0	-9999	-10000	0	0
RELA	0.022	0	-9999	-10000	0	0
MALT1	0.017	0.029	-9999	-0.54	1	1
cIAP1/UbcH5C	0.024	0.038	-9999	-0.38	3	3
ATM	0.019	0	-9999	-10000	0	0
TNF/TNFR1A	-0.056	0.16	-9999	-0.38	75	75
TRAF6	0.019	0	-9999	-10000	0	0
PRKCA	0.013	0.044	-9999	-0.29	7	7
CHUK	0.019	0	-9999	-10000	0	0
UBE2D3	0.019	0	-9999	-10000	0	0
TNF	-0.095	0.22	-9999	-0.54	75	75
NF kappa B1 p50/RelA	0.052	0	-9999	-10000	0	0
BCL10	0.018	0.014	-9999	-0.24	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.048	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0	-9999	-10000	0	0
TNFRSF1A	0.019	0	-9999	-10000	0	0
IKK complex	0.055	0.059	-9999	-0.44	1	1
CYLD	0.019	0	-9999	-10000	0	0
IKK complex/PKC alpha	0.059	0.061	-9999	-0.42	1	1

×

Signaling events mediated by HDAC Class III

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
EP300	0.019	0	-10000	0	-10000	0	0
HDAC4	0.019	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.011	0.066	0.38	10	-10000	0	10
CDKN1A	0.008	0.018	-10000	0	-10000	0	0
KAT2B	0.016	0.041	-10000	0	-0.54	2	2
BAX	0.019	0	-10000	0	-10000	0	0
FOXO3	-0.007	0.001	-10000	0	-10000	0	0
FOXO1	0.019	0	-10000	0	-10000	0	0
FOXO4	0.026	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.019	0	-10000	0	-10000	0	0
TAT	0	0	-10000	0	-10000	0	0
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.015	0.041	-10000	0	-0.24	7	7
PPARGC1A	-0.094	0.15	-10000	0	-0.26	146	146
FHL2	0.01	0.07	-10000	0	-0.54	6	6
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.024	0.004	-10000	0	-10000	0	0
HIST2H4A	0.012	0.066	-10000	0	-0.38	10	10
SIRT1/FOXO3a	0.003	0.004	-10000	0	-10000	0	0
SIRT1	0.013	0.006	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.004	-10000	0	-10000	0	0
SIRT1/Histone H1b	0.028	0.005	-10000	0	-10000	0	0
apoptosis	-0.034	0.004	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.042	0.085	-10000	0	-0.32	10	10
p53/SIRT1	0.001	0.016	-10000	0	-10000	0	0
SIRT1/FOXO4	0.029	0.004	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	0.028	0.041	-10000	0	-0.29	6	6
HIST1H1E	0.026	0.002	-10000	0	-10000	0	0
SIRT1/p300	0.024	0.004	-10000	0	-10000	0	0
muscle cell differentiation	-0.023	0.035	0.38	2	-10000	0	2
TP53	0.013	0.006	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.035	0.004	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0
MEF2D	0.019	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.01	0.004	-10000	0	-10000	0	0
ACSS2	0.021	0.019	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.023	0.035	-10000	0	-0.38	2	2

×

TCGA08_rtk_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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.003	0.076	-10000	0	-0.31	18	18
HRAS	0.019	0	-10000	0	-10000	0	0
EGFR	-0.007	0.087	-10000	0	-0.27	33	33
AKT	0.039	0.026	-10000	0	-10000	0	0
FOXO3	0.019	0	-10000	0	-10000	0	0
AKT1	0.019	0	-10000	0	-10000	0	0
FOXO1	0.019	0	-10000	0	-10000	0	0
AKT3	0.019	0	-10000	0	-10000	0	0
FOXO4	0.019	0	-10000	0	-10000	0	0
MET	-0.024	0.14	-10000	0	-0.43	35	35
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
PIK3CB	0.019	0	-10000	0	-10000	0	0
NRAS	0.019	0	-10000	0	-10000	0	0
PIK3CG	-0.055	0.19	-10000	0	-0.54	49	49
PIK3R3	0.019	0	-10000	0	-10000	0	0
PIK3R2	0.019	0	-10000	0	-10000	0	0
NF1	0.019	0	-10000	0	-10000	0	0
RAS	0.009	0.049	-10000	0	-0.14	1	1
ERBB2	0.019	0	-10000	0	-10000	0	0
proliferation/survival/translation	-0.03	0.039	0.15	4	-10000	0	4
PI3K	0.008	0.063	-10000	0	-0.23	8	8
PIK3R1	0.019	0	-10000	0	-10000	0	0
KRAS	0.018	0.014	-10000	0	-0.24	1	1
FOXO	0.05	0.03	-10000	0	-10000	0	0
AKT2	0.019	0	-10000	0	-10000	0	0
PTEN	0.017	0.029	-10000	0	-0.54	1	1

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.28	0.18	-9999	-0.98	2	2
PLK1	0.09	0.036	-9999	-10000	0	0
BIRC5	0.09	0.036	-9999	-10000	0	0
HSPA1B	0.27	0.19	-9999	-0.98	2	2
MAP2K1	0.065	0.026	-9999	-10000	0	0
BRCA2	0.27	0.23	-9999	-1.1	6	6
FOXM1	0.29	0.2	-9999	-1.2	2	2
XRCC1	0.28	0.18	-9999	-0.98	2	2
FOXM1B/p19	-0.022	0.1	-9999	-1	2	2
Cyclin D1/CDK4	0.22	0.2	-9999	-0.89	2	2
CDC2	0.28	0.19	-9999	-1	2	2
TGFA	0.21	0.23	-9999	-0.78	6	6
SKP2	0.28	0.18	-9999	-0.98	2	2
CCNE1	0.028	0.006	-9999	-10000	0	0
CKS1B	0.28	0.18	-9999	-0.98	2	2
RB1	-0.004	0.081	-9999	-0.96	2	2
FOXM1C/SP1	0.27	0.18	-9999	-1.1	2	2
AURKB	0.086	0.09	-9999	-1.5	1	1
CENPF	0.28	0.19	-9999	-1.2	2	2
CDK4	0.032	0.024	-9999	-0.24	2	2
MYC	0.27	0.17	-9999	-0.85	2	2
CHEK2	0.065	0.026	-9999	-10000	0	0
ONECUT1	0.18	0.24	-9999	-0.83	3	3
CDKN2A	-0.12	0.14	-9999	-0.26	172	172
LAMA4	0.27	0.19	-9999	-0.98	2	2
FOXM1B/HNF6	0.18	0.24	-9999	-0.95	3	3
FOS	0.27	0.19	-9999	-0.98	2	2
SP1	0.021	0.002	-9999	-10000	0	0
CDC25B	0.28	0.18	-9999	-0.98	2	2
response to radiation	0.039	0.024	-9999	-10000	0	0
CENPB	0.28	0.18	-9999	-0.98	2	2
CENPA	0.28	0.2	-9999	-1.4	2	2
NEK2	0.27	0.21	-9999	-1.3	3	3
HIST1H2BA	0.27	0.18	-9999	-0.98	2	2
CCNA2	0.027	0.031	-9999	-0.55	1	1
EP300	0.019	0	-9999	-10000	0	0
CCNB1/CDK1	0.28	0.2	-9999	-1.1	2	2
CCNB2	0.27	0.22	-9999	-0.96	6	6
CCNB1	0.28	0.19	-9999	-1	2	2
ETV5	0.28	0.2	-9999	-1.1	3	3
ESR1	0.26	0.25	-9999	-1	9	9
CCND1	0.22	0.21	-9999	-0.9	2	2
GSK3A	0.057	0.024	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.079	0.035	-9999	-0.35	1	1
CDK2	0.028	0.006	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.048	0.026	-9999	-10000	0	0
FOXM1B/Cbp/p300	0.1	0.16	-9999	-1.1	2	2
GAS1	0.27	0.22	-9999	-1	5	5
MMP2	0.26	0.22	-9999	-0.99	4	4
RB1/FOXM1C	0.24	0.2	-9999	-0.93	3	3
CREBBP	0.019	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.029	-10000	0	-0.54	1	1
HDAC3	0.019	0	-10000	0	-10000	0	0
VDR	0.016	0.041	-10000	0	-0.54	2	2
Cbp/p300/PCAF	0.037	0.026	-10000	0	-0.32	2	2
EP300	0.019	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.044	0.043	-10000	0	-0.22	1	1
KAT2B	0.016	0.041	-10000	0	-0.54	2	2
MAPK14	0.019	0	-10000	0	-10000	0	0
AKT1	0.025	0.059	0.22	7	-0.24	13	20
RAR alpha/9cRA/Cyclin H	0.057	0.022	-10000	0	-0.26	1	1
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.04	0.049	-10000	0	-0.18	16	16
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.028	0.017	-10000	0	-0.18	1	1
NCOR2	0.019	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.012	0.03	-10000	0	-0.39	2	2
RXRs/RARs/NRIP1/9cRA	0.036	0.072	-10000	0	-0.58	1	1
NCOA2	0.018	0.014	-10000	0	-0.24	1	1
NCOA3	0.019	0	-10000	0	-10000	0	0
NCOA1	0.019	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.016	0.041	-10000	0	-0.54	2	2
RARG	0.02	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.026	0	-10000	0	-10000	0	0
MAPK3	0.02	0	-10000	0	-10000	0	0
MAPK1	0.019	0	-10000	0	-10000	0	0
MAPK8	0.02	0.001	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.029	0.063	-10000	0	-0.64	1	1
RARA	0.031	0.021	-10000	0	-0.23	1	1
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.04	0.049	-10000	0	-0.18	16	16
PRKCA	0.017	0.044	-10000	0	-0.28	7	7
RXRs/RARs/NRIP1/9cRA/HDAC1	0.026	0.076	-10000	0	-0.62	1	1
RXRG	-0.05	0.15	-10000	0	-0.32	83	83
RXRA	0.037	0.021	-10000	0	-0.23	1	1
RXRB	0.028	0.028	-10000	0	-0.27	2	2
VDR/Vit D3/DNA	0.012	0.03	-10000	0	-0.39	2	2
RBP1	0	0.09	-10000	0	-0.38	17	17
CRBP1/9-cic-RA	0.001	0.065	-10000	0	-0.27	17	17
RARB	0	0.11	-10000	0	-0.52	15	15
PRKCG	0.014	0.025	-10000	0	-0.24	3	3
MNAT1	0.019	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.033	0.074	-10000	0	-0.63	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.038	0.065	-10000	0	-0.31	4	4
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.043	-10000	0	-0.21	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.026	0.076	-10000	0	-0.62	1	1
positive regulation of DNA binding	-0.001	0.015	-10000	0	-0.25	1	1
NRIP1	0.027	0.072	-10000	0	-0.56	1	1
RXRs/RARs	0.019	0.077	-10000	0	-0.36	5	5
RXRs/RXRs/DNA/9cRA	0.021	0.061	-10000	0	-0.66	1	1
PRKACA	0.019	0	-10000	0	-10000	0	0
CDK7	0.019	0	-10000	0	-10000	0	0
TFIIH	0.038	0	-10000	0	-10000	0	0
RAR alpha/9cRA	0.052	0.014	-10000	0	-10000	0	0
CCNH	0.019	0	-10000	0	-10000	0	0
CREBBP	0.019	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.05	0.038	0.22	1	-0.31	2	3
CaM/Ca2+	0.014	0	-10000	0	-10000	0	0
AKT1	0.019	0	-10000	0	-10000	0	0
AKT2	0.019	0	-10000	0	-10000	0	0
STXBP4	0.019	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.048	0.046	0.23	1	-0.35	2	3
YWHAZ	0.019	0	-10000	0	-10000	0	0
CALM1	0.019	0	-10000	0	-10000	0	0
YWHAQ	0.019	0	-10000	0	-10000	0	0
TBC1D4	0.023	0.028	-10000	0	-0.38	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.019	0	-10000	0	-10000	0	0
YWHAB	0.019	0	-10000	0	-10000	0	0
SNARE/Synip	0.038	0	-10000	0	-10000	0	0
YWHAG	0.019	0	-10000	0	-10000	0	0
ASIP	-0.007	0.073	-10000	0	-0.24	31	31
PRKCI	0.019	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.014	0	-10000	0	-10000	0	0
RHOQ	0.019	0	-10000	0	-10000	0	0
GYS1	0.034	0	-10000	0	-10000	0	0
PRKCZ	0.016	0.041	-10000	0	-0.54	2	2
TRIP10	0.018	0.014	-10000	0	-0.24	1	1
TC10/GTP/CIP4/Exocyst	0.025	0.008	-10000	0	-10000	0	0
AS160/14-3-3	0.036	0.032	-10000	0	-10000	0	0
VAMP2	0.019	0	-10000	0	-10000	0	0
SLC2A4	0.049	0.048	0.23	1	-0.38	2	3
STX4	0.019	0	-10000	0	-10000	0	0
GSK3B	0.031	0	-10000	0	-10000	0	0
SFN	-0.035	0.11	-10000	0	-0.24	74	74
LNPEP	0.019	0	-10000	0	-10000	0	0
YWHAE	0.019	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.004	0.076	-9999	-0.31	18	18
PDGF/PDGFRA/CRKL	0.017	0.054	-9999	-0.37	4	4
positive regulation of JUN kinase activity	0.039	0.041	-9999	-0.26	4	4
CRKL	0.018	0.014	-9999	-0.24	1	1
PDGF/PDGFRA/Caveolin-3	0.004	0.052	-9999	-0.34	5	5
AP1	0.019	0.077	-9999	-0.44	1	1
mol:IP3	0.016	0.055	-9999	-0.38	4	4
PLCG1	0.016	0.055	-9999	-0.38	4	4
PDGF/PDGFRA/alphaV Integrin	0.017	0.054	-9999	-0.33	5	5
RAPGEF1	0.019	0	-9999	-10000	0	0
CRK	0.019	0	-9999	-10000	0	0
mol:Ca2+	0.016	0.055	-9999	-0.38	4	4
CAV3	0	0	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
SHC/Grb2/SOS1	0.041	0.042	-9999	-0.27	4	4
PDGF/PDGFRA/Shf	0.017	0.054	-9999	-0.37	4	4
FOS	0.019	0.076	-9999	-0.44	1	1
JUN	-0.013	0.054	-9999	-0.2	10	10
oligodendrocyte development	0.017	0.053	-9999	-0.33	5	5
GRB2	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
mol:DAG	0.016	0.055	-9999	-0.38	4	4
PDGF/PDGFRA	0.004	0.076	-9999	-0.31	18	18
actin cytoskeleton reorganization	0.008	0.073	-9999	-0.38	8	8
SRF	0.024	0.003	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
PI3K	0.029	0.046	-9999	-0.3	4	4
PDGF/PDGFRA/Crk/C3G	0.03	0.045	-9999	-0.3	4	4
JAK1	0.016	0.052	-9999	-0.37	4	4
ELK1/SRF	0.034	0.04	-9999	-0.27	4	4
SHB	0.006	0.071	-9999	-0.33	14	14
SHF	0.017	0.019	-9999	-0.24	2	2
CSNK2A1	0.016	0.007	-9999	-10000	0	0
GO:0007205	0.016	0.056	-9999	-0.41	4	4
SOS1	0.019	0	-9999	-10000	0	0
Ras protein signal transduction	0.039	0.041	-9999	-0.26	4	4
PDGF/PDGFRA/SHB	0.008	0.073	-9999	-0.38	8	8
PDGF/PDGFRA/Caveolin-1	0.018	0.053	-9999	-0.37	4	4
ITGAV	0.018	0.014	-9999	-0.24	1	1
ELK1	0.022	0.049	-9999	-0.34	4	4
PIK3CA	0.018	0.014	-9999	-0.24	1	1
PDGF/PDGFRA/Crk	0.018	0.053	-9999	-0.37	4	4
JAK-STAT cascade	0.016	0.052	-9999	-0.37	4	4
cell proliferation	0.017	0.054	-9999	-0.37	4	4

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.031	0.009	-9999	-10000	0	0
PLK1	0.059	0.14	-9999	-10000	0	0
CDKN1B	0.18	0.024	-9999	-10000	0	0
FOXO3	0.053	0.15	-9999	-10000	0	0
KAT2B	0.019	0.044	-9999	-0.52	2	2
FOXO1/SIRT1	0.057	0.024	-9999	-10000	0	0
CAT	0.059	0.14	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
AKT1	0.025	0.019	-9999	-10000	0	0
FOXO1	0.035	0.011	-9999	-10000	0	0
MAPK10	0.019	0.05	-9999	-10000	0	0
mol:GTP	0.003	0	-9999	-10000	0	0
FOXO4	0.1	0.03	-9999	-10000	0	0
response to oxidative stress	0.007	0.02	-9999	-10000	0	0
FOXO3A/SIRT1	0.15	0.042	-9999	-10000	0	0
XPO1	0.02	0	-9999	-10000	0	0
EP300	0.02	0	-9999	-10000	0	0
BCL2L11	0.018	0.088	-9999	-1.4	1	1
FOXO1/SKP2	0.042	0.009	-9999	-10000	0	0
mol:GDP	0.007	0.02	-9999	-10000	0	0
RAN	0.021	0	-9999	-10000	0	0
GADD45A	0.14	0.031	-9999	-10000	0	0
YWHAQ	0.019	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.074	0.023	-9999	-10000	0	0
MST1	0.019	0.041	-9999	-0.36	3	3
CSNK1D	0.019	0	-9999	-10000	0	0
CSNK1E	0.019	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.052	0.034	-9999	-10000	0	0
YWHAB	0.019	0	-9999	-10000	0	0
MAPK8	0.044	0.009	-9999	-10000	0	0
MAPK9	0.043	0.009	-9999	-10000	0	0
YWHAG	0.019	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
YWHAZ	0.019	0	-9999	-10000	0	0
SIRT1	0.036	0.034	-9999	-10000	0	0
SOD2	0.15	0.051	-9999	-10000	0	0
RBL2	0.079	0.11	-9999	-10000	0	0
RAL/GDP	0.037	0.014	-9999	-10000	0	0
CHUK	0.022	0.019	-9999	-10000	0	0
Ran/GTP	0.019	0.001	-9999	-10000	0	0
CSNK1G2	0.019	0	-9999	-10000	0	0
RAL/GTP	0.045	0.014	-9999	-10000	0	0
CSNK1G1	0.019	0	-9999	-10000	0	0
FASLG	-0.43	0.69	-9999	-1.4	120	120
SKP2	0.019	0	-9999	-10000	0	0
USP7	0.021	0	-9999	-10000	0	0
IKBKB	0.022	0.019	-9999	-10000	0	0
CCNB1	0.059	0.14	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	0.12	0.11	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.009	-9999	-10000	0	0
CSNK1A1	0.019	0	-9999	-10000	0	0
SGK1	0.022	0.019	-9999	-10000	0	0
CSNK1G3	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.034	0.001	-9999	-10000	0	0
ZFAND5	0.1	0.028	-9999	-10000	0	0
SFN	-0.035	0.11	-9999	-0.24	74	74
CDK2	0.018	0	-9999	-10000	0	0
FOXO3A/14-3-3	0.056	0.046	-9999	-10000	0	0
CREBBP	0.018	0	-9999	-10000	0	0
FBXO32	0.056	0.15	-9999	-1.2	1	1
BCL6	0.079	0.11	-9999	-10000	0	0
RALB	0.02	0	-9999	-10000	0	0
RALA	0.02	0	-9999	-10000	0	0
YWHAH	0.019	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.009	0.1	-9999	-0.38	20	20
AKT1	0.077	0.053	-9999	-10000	0	0
PTK2B	0.02	0.087	-9999	-0.33	1	1
VEGFR2 homodimer/Frs2	0.039	0.035	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
CALM1	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.044	0.046	-9999	-10000	0	0
endothelial cell proliferation	0.009	0.13	-9999	-0.36	4	4
mol:Ca2+	0.049	0.041	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.055	0.043	-9999	-10000	0	0
RP11-342D11.1	0.038	0.04	-9999	-10000	0	0
CDH5	0.018	0.014	-9999	-0.24	1	1
VEGFA homodimer	0.042	0.033	-9999	-10000	0	0
SHC1	0.019	0	-9999	-10000	0	0
SHC2	-0.063	0.12	-9999	-0.25	111	111
HRAS/GDP	-0.004	0.018	-9999	-10000	0	0
SH2D2A	-0.03	0.16	-9999	-0.54	32	32
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.02	0.12	-9999	-0.52	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.017	0.1	-9999	-0.36	4	4
VEGFR1 homodimer	0.018	0.014	-9999	-0.24	1	1
SHC/GRB2/SOS1	0.064	0.04	-9999	-10000	0	0
GRB10	0.049	0.044	-9999	-10000	0	0
PTPN11	0.019	0	-9999	-10000	0	0
GRB2	0.019	0	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.062	0.042	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.034	0.06	-9999	-10000	0	0
HIF1A	0.019	0	-9999	-10000	0	0
FRS2	0.017	0.024	-9999	-0.24	3	3
oxygen and reactive oxygen species metabolic process	0.053	0.042	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.014	0.036	-9999	-0.24	7	7
Nck/Pak	0.028	0.009	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.046	0.045	-9999	-10000	0	0
mol:GDP	-0.005	0.02	-9999	-10000	0	0
mol:NADP	0.071	0.042	-9999	-0.33	1	1
eNOS/Hsp90	0.076	0.043	-9999	-0.31	1	1
PIK3R1	0.019	0	-9999	-10000	0	0
mol:IP3	0.05	0.042	-9999	-10000	0	0
HIF1A/ARNT	0.028	0	-9999	-10000	0	0
SHB	0.006	0.071	-9999	-0.33	14	14
VEGFA	0.006	0.061	-9999	-0.24	21	21
VEGFC	0.018	0.014	-9999	-0.24	1	1
FAK1/Vinculin	0.05	0.071	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.028	0.087	-9999	-10000	0	0
PTPN6	-0.12	0.24	-9999	-0.54	92	92
EPAS1	0.029	0.022	-9999	-10000	0	0
mol:L-citrulline	0.071	0.042	-9999	-0.33	1	1
ITGAV	0.018	0.014	-9999	-0.24	1	1
PIK3CA	0.018	0.014	-9999	-0.24	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.054	0.044	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer	0.052	0.047	-9999	-10000	0	0
VEGFR2/3 heterodimer	0.038	0.04	-9999	-0.32	1	1
VEGFB	0.019	0	-9999	-10000	0	0
MAPK11	0.051	0.041	-9999	-10000	0	0
VEGFR2 homodimer	0.036	0.038	-9999	-10000	0	0
FLT1	0.018	0.014	-9999	-0.24	1	1
NEDD4	0.02	0.02	-9999	-0.24	2	2
MAPK3	0.014	0.073	-9999	-10000	0	0
MAPK1	0.014	0.073	-9999	-10000	0	0
VEGFA145/NRP2	0.019	0.046	-9999	-0.38	1	1
VEGFR1/2 heterodimer	0.04	0.035	-9999	-0.32	1	1
KDR	0.036	0.039	-9999	-10000	0	0
VEGFA165/NRP1/VEGFR2 homodimer	0.056	0.045	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.019	0.07	-9999	-10000	0	0
PI3K	0.069	0.058	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.046	0.045	-9999	-0.28	1	1
FES	0.043	0.059	-9999	-10000	0	0
GAB1	0.064	0.04	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	0.046	0.045	-9999	-10000	0	0
CTNNB1	0.019	0	-9999	-10000	0	0
SOS1	0.019	0	-9999	-10000	0	0
ARNT	0.019	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.077	0.041	-9999	-0.31	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.046	0.045	-9999	-10000	0	0
PI3K/GAB1	0.083	0.053	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.061	0.043	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.047	0.037	-9999	-0.28	1	1
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
CDC42	0.05	0.042	-9999	-10000	0	0
actin cytoskeleton reorganization	0.017	0.1	-9999	-0.35	4	4
PTK2	0.041	0.072	-9999	-10000	0	0
EDG1	0.038	0.04	-9999	-10000	0	0
mol:DAG	0.05	0.042	-9999	-10000	0	0
CaM/Ca2+	0.055	0.039	-9999	-10000	0	0
MAP2K3	0.052	0.042	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.059	0.048	-9999	-10000	0	0
PLCG1	0.05	0.042	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.048	0.056	-9999	-10000	0	0
IQGAP1	0.019	0	-9999	-10000	0	0
YES1	0.019	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.046	0.045	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.035	0.15	-9999	-0.38	12	12
cell migration	0.073	0.064	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.067	0.055	-9999	-10000	0	0
FYN	0.019	0	-9999	-10000	0	0
VEGFB/NRP1	0.047	0.039	-9999	-10000	0	0
mol:NO	0.071	0.042	-9999	-0.33	1	1
PXN	0.019	0	-9999	-10000	0	0
HRAS/GTP	-0.004	0.018	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.056	0.047	-9999	-10000	0	0
VHL	0.019	0	-9999	-10000	0	0
ITGB3	-0.032	0.14	-9999	-0.36	50	50
NOS3	0.073	0.045	-9999	-0.37	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.003	0.079	-9999	-0.28	3	3
RAC1	0.019	0	-9999	-10000	0	0
PRKCA	0.05	0.048	-9999	-0.33	1	1
PRKCB	-0.033	0.14	-9999	-0.34	16	16
VCL	0.019	0	-9999	-10000	0	0
VEGFA165/NRP1	0.043	0.042	-9999	-10000	0	0
VEGFR1/2 heterodimer/VEGFA homodimer	0.045	0.047	-9999	-0.39	1	1
VEGFA165/NRP2	0.019	0.046	-9999	-0.38	1	1
MAPKKK cascade	0.075	0.041	-9999	-10000	0	0
NRP2	0.017	0.029	-9999	-0.54	1	1
VEGFC homodimer	0.018	0.014	-9999	-0.24	1	1
NCK1	0.019	0	-9999	-10000	0	0
ROCK1	0.019	0	-9999	-10000	0	0
FAK1/Paxillin	0.05	0.071	-9999	-10000	0	0
MAP3K13	0.049	0.045	-9999	-10000	0	0
PDPK1	0.068	0.052	-9999	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.017	0.022	-9999	-0.28	2	2
TRAF2/ASK1	0.024	0.026	-9999	-0.32	2	2
ATM	0.019	0	-9999	-10000	0	0
MAP2K3	0.042	0.02	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.042	0.05	-9999	-0.44	2	2
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.046	0.18	-9999	-0.53	43	43
TXN	0.01	0	-9999	-10000	0	0
CALM1	0.019	0	-9999	-10000	0	0
GADD45A	0.017	0.024	-9999	-0.24	3	3
GADD45B	0.019	0	-9999	-10000	0	0
MAP3K1	0.019	0	-9999	-10000	0	0
MAP3K6	0.018	0.014	-9999	-0.24	1	1
MAP3K7	0.019	0	-9999	-10000	0	0
MAP3K4	0.019	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.025	0.032	-9999	-0.38	2	2
TAK1/TAB family	-0.002	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.037	0	-9999	-10000	0	0
TRAF2	0.019	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.001	0.011	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.011	0.1	-9999	-0.33	31	31
CCM2	0.019	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	0.008	0.064	-9999	-0.32	9	9
MAPK11	0.019	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.018	0.063	-9999	-0.29	11	11
OSM/MEKK3	0.028	0	-9999	-10000	0	0
TAOK1	0.02	0	-9999	-10000	0	0
TAOK2	0.02	0	-9999	-10000	0	0
TAOK3	0.02	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.019	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.016	0.041	-9999	-0.54	2	2
MAP3K10	0.019	0	-9999	-10000	0	0
MAP3K3	0.019	0	-9999	-10000	0	0
TRX/ASK1	0.02	0.025	-9999	-0.32	2	2
GADD45/MTK1/MTK1	0.008	0.099	-9999	-0.26	42	42

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.043	0.042	-9999	-0.28	6	6
HDAC3	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	0.014	0	-9999	-10000	0	0
GATA1/HDAC5	0.014	0	-9999	-10000	0	0
GATA2/HDAC5	0.025	0.025	-9999	-10000	0	0
HDAC5/BCL6/BCoR	0.038	0	-9999	-10000	0	0
HDAC9	-0.008	0.12	-9999	-0.54	18	18
Glucocorticoid receptor/Hsp90/HDAC6	0.037	0.019	-9999	-0.32	1	1
HDAC4/ANKRA2	0.027	0.021	-9999	-0.38	1	1
HDAC5/YWHAB	0.028	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.025	0	-9999	-10000	0	0
GATA2	0.014	0.036	-9999	-0.24	7	7
HDAC4/RFXANK	0.028	0	-9999	-10000	0	0
BCOR	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.019	0	-9999	-10000	0	0
HDAC5	0.019	0	-9999	-10000	0	0
GNB1/GNG2	0.021	0.052	-9999	-0.38	6	6
Histones	0.036	0.051	-9999	-10000	0	0
ADRBK1	0.019	0	-9999	-10000	0	0
HDAC4	0.019	0	-9999	-10000	0	0
XPO1	0.019	0	-9999	-10000	0	0
HDAC5/ANKRA2	0.027	0.021	-9999	-0.38	1	1
HDAC4/Ubc9	0.028	0	-9999	-10000	0	0
HDAC7	0.019	0	-9999	-10000	0	0
HDAC5/14-3-3 E	0.028	0	-9999	-10000	0	0
TUBA1B	0.019	0	-9999	-10000	0	0
HDAC6	0.019	0	-9999	-10000	0	0
HDAC5/RFXANK	0.028	0	-9999	-10000	0	0
CAMK4	-0.063	0.2	-9999	-0.54	54	54
Tubulin/HDAC6	0.038	0	-9999	-10000	0	0
SUMO1	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.019	0	-9999	-10000	0	0
GATA1	0	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.019	0	-9999	-10000	0	0
NR3C1	0.019	0	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0	-9999	-10000	0	0
SRF	0.019	0	-9999	-10000	0	0
HDAC4/YWHAB	0.028	0	-9999	-10000	0	0
Tubulin	0.028	0	-9999	-10000	0	0
HDAC4/14-3-3 E	0.028	0	-9999	-10000	0	0
GNB1	0.019	0	-9999	-10000	0	0
RANGAP1	0.019	0	-9999	-10000	0	0
BCL6/BCoR	0.028	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0.038	0	-9999	-10000	0	0
HDAC4/SRF	-0.014	0.13	-9999	-0.32	54	54
HDAC4/ER alpha	0.02	0.056	-9999	-0.38	7	7
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.036	0.05	-9999	-10000	0	0
cell motility	0.038	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.019	0	-9999	-10000	0	0
HDAC7/HDAC3	0.028	0	-9999	-10000	0	0
BCL6	0.019	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.019	0	-9999	-10000	0	0
Hsp90/HDAC6	0.027	0.021	-9999	-0.38	1	1
ESR1	0.008	0.076	-9999	-0.54	7	7
HDAC6/HDAC11	0.028	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.043	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
MEF2C	0.016	0.041	-9999	-0.54	2	2
RAN	0.019	0	-9999	-10000	0	0
HDAC4/MEF2C	0.055	0.023	-9999	-0.26	2	2
GNG2	0.01	0.07	-9999	-0.54	6	6
NCOR2	0.019	0	-9999	-10000	0	0
TUBB2A	0.019	0	-9999	-10000	0	0
HDAC11	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
RANBP2	0.019	0	-9999	-10000	0	0
ANKRA2	0.017	0.029	-9999	-0.54	1	1
RFXANK	0.019	0	-9999	-10000	0	0
nuclear import	-0.037	0	-9999	-10000	0	0

×

Arf6 downstream 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
PLAUR	0.038	0.07	-10000	0	-1.1	1	1
regulation of axonogenesis	-0.031	0.013	-10000	0	-10000	0	0
myoblast fusion	-0.025	0.035	0.41	1	-10000	0	1
mol:GTP	0.013	0.019	-10000	0	-0.23	1	1
regulation of calcium-dependent cell-cell adhesion	-0.024	0.084	0.29	23	-10000	0	23
ARF1/GTP	0.025	0.015	-10000	0	-10000	0	0
mol:GM1	0.012	0.014	-10000	0	-0.17	1	1
mol:Choline	0.03	0.012	-10000	0	-10000	0	0
lamellipodium assembly	0.029	0.037	-10000	0	-0.44	1	1
MAPK3	0.031	0.028	-10000	0	-0.33	1	1
ARF6/GTP/NME1/Tiam1	0.025	0.084	-10000	0	-0.3	23	23
ARF1	0.019	0	-10000	0	-10000	0	0
ARF6/GDP	0.025	0.035	-10000	0	-0.41	1	1
ARF1/GDP	0.034	0.033	-10000	0	-0.37	1	1
ARF6	0.018	0.011	-10000	0	-10000	0	0
RAB11A	0.019	0	-10000	0	-10000	0	0
TIAM1	-0.013	0.13	-10000	0	-0.54	22	22
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.031	0.028	-10000	0	-0.33	1	1
actin filament bundle formation	-0.029	0.03	0.37	1	-10000	0	1
KALRN	0	0.037	-10000	0	-0.3	3	3
RAB11FIP3/RAB11A	0.028	0	-10000	0	-10000	0	0
RhoA/GDP	0.029	0.031	-10000	0	-0.38	1	1
NME1	0.02	0.002	-10000	0	-10000	0	0
Rac1/GDP	0.029	0.031	-10000	0	-0.38	1	1
substrate adhesion-dependent cell spreading	0.013	0.019	-10000	0	-0.23	1	1
cortical actin cytoskeleton organization	0.029	0.038	-10000	0	-0.45	1	1
RAC1	0.019	0	-10000	0	-10000	0	0
liver development	0.013	0.019	-10000	0	-0.23	1	1
ARF6/GTP	0.013	0.019	-10000	0	-0.23	1	1
RhoA/GTP	0.025	0.015	-10000	0	-0.16	1	1
mol:GDP	0.026	0.037	-10000	0	-0.41	1	1
ARF6/GTP/RAB11FIP3/RAB11A	0.036	0.013	-10000	0	-10000	0	0
RHOA	0.019	0	-10000	0	-10000	0	0
PLD1	0.024	0.015	-10000	0	-10000	0	0
RAB11FIP3	0.019	0	-10000	0	-10000	0	0
tube morphogenesis	0.029	0.037	-10000	0	-0.44	1	1
ruffle organization	0.031	0.013	-10000	0	-10000	0	0
regulation of epithelial cell migration	0.013	0.019	-10000	0	-0.23	1	1
PLD2	0.024	0.015	-10000	0	-0.16	1	1
PIP5K1A	0.031	0.013	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0.012	-10000	0	-10000	0	0
Rac1/GTP	0.029	0.038	-10000	0	-0.45	1	1

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.019	0	-9999	-10000	0	0
PTK2	0.019	0	-9999	-10000	0	0
CRKL	0.017	0.043	-9999	-0.26	4	4
GRB2/SOS1/SHC	0.038	0	-9999	-10000	0	0
HRAS	0.019	0	-9999	-10000	0	0
IRS1/Crk	0.019	0.043	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1/PTP1B	0.027	0.041	-9999	-0.3	4	4
AKT1	0.035	0.037	-9999	-10000	0	0
BAD	0.039	0.035	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.017	0.042	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.02	0.043	-9999	-0.26	4	4
RAF1	0.047	0.033	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.034	0.043	-9999	-0.24	4	4
YWHAZ	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.013	0.047	-9999	-0.27	5	5
PIK3CA	0.018	0.014	-9999	-0.24	1	1
RPS6KB1	0.035	0.037	-9999	-10000	0	0
GNB2L1	0.019	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.038	0.03	-9999	-10000	0	0
PXN	0.019	0	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.028	0	-9999	-10000	0	0
HRAS/GTP	-0.006	0.024	-9999	-0.2	4	4
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.048	0.034	-9999	-0.22	4	4
IGF-1R heterotetramer	0.014	0.03	-9999	-0.25	4	4
IGF-1R heterotetramer/IGF1/IRS/Nck	0.024	0.045	-9999	-0.26	4	4
Crk/p130 Cas/Paxillin	0.039	0.041	-9999	-0.22	4	4
IGF1R	0.014	0.03	-9999	-0.25	4	4
IGF1	0.007	0.067	-9999	-0.36	10	10
IRS2/Crk	0.027	0.041	-9999	-0.24	4	4
PI3K	0.033	0.044	-9999	-0.24	4	4
apoptosis	-0.046	0.033	-9999	-10000	0	0
HRAS/GDP	0.014	0	-9999	-10000	0	0
PRKCD	0.036	0.044	-9999	-0.34	4	4
RAF1/14-3-3 E	0.054	0.032	-9999	-10000	0	0
BAD/14-3-3	0.048	0.034	-9999	-10000	0	0
PRKCZ	0.033	0.041	-9999	-0.23	2	2
Crk/p130 Cas/Paxillin/FAK1	-0.002	0.018	-9999	-10000	0	0
PTPN1	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.031	0.047	-9999	-0.37	4	4
BCAR1	0.019	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.038	-9999	-0.25	4	4
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.019	0	-9999	-10000	0	0
IRS1/NCK2	0.02	0.043	-9999	-0.26	4	4
GRB10	0.017	0.019	-9999	-0.24	2	2
PTPN11	0.017	0.042	-9999	-0.26	4	4
IRS1	0.009	0.046	-9999	-0.27	5	5
IRS2	0.017	0.042	-9999	-0.26	4	4
IGF-1R heterotetramer/IGF1	0.014	0.053	-9999	-0.4	4	4
GRB2	0.019	0	-9999	-10000	0	0
PDPK1	0.03	0.039	-9999	-0.22	4	4
YWHAE	0.019	0	-9999	-10000	0	0
PRKD1	0.035	0.049	-9999	-0.34	5	5
SHC1	0.019	0	-9999	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.032	0.014	-9999	-10000	0	0
BIRC5	0.019	0	-9999	-10000	0	0
NFKBIA	0.032	0.006	-9999	-10000	0	0
CPEB1	-0.023	0.15	-9999	-0.53	28	28
AKT1	0.032	0.006	-9999	-10000	0	0
NDEL1	0.019	0	-9999	-10000	0	0
Aurora A/BRCA1	0.03	0.005	-9999	-10000	0	0
NDEL1/TACC3	0.041	0.004	-9999	-10000	0	0
GADD45A	0.017	0.024	-9999	-0.24	3	3
GSK3B	0.018	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.033	0.009	-9999	-10000	0	0
MDM2	0.015	0.033	-9999	-0.24	6	6
JUB	0.018	0.014	-9999	-0.24	1	1
TPX2	0.026	0	-9999	-10000	0	0
TP53	0.033	0.014	-9999	-10000	0	0
DLG7	0.022	0.006	-9999	-10000	0	0
AURKAIP1	0.019	0	-9999	-10000	0	0
ARHGEF7	0.019	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.043	0.005	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.03	0.005	-9999	-10000	0	0
AURKA	0.028	0.008	-9999	-10000	0	0
AURKB	0.017	0.025	-9999	-0.28	2	2
CDC25B	0.033	0.006	-9999	-10000	0	0
G2/M transition checkpoint	0.029	0.008	-9999	-10000	0	0
mRNA polyadenylation	0.006	0.082	-9999	-0.28	27	27
Aurora A/CPEB	0.006	0.083	-9999	-0.29	27	27
Aurora A/TACC1/TRAP/chTOG	0.052	0.017	-9999	-0.26	1	1
BRCA1	0.019	0	-9999	-10000	0	0
centrosome duplication	0.033	0.009	-9999	-10000	0	0
regulation of centrosome cycle	0.039	0.004	-9999	-10000	0	0
spindle assembly	0.051	0.016	-9999	-0.25	1	1
TDRD7	0.017	0.029	-9999	-0.54	1	1
Aurora A/RasGAP/Survivin	0.049	0.016	-9999	-0.24	1	1
CENPA	0.021	0.027	-9999	-0.34	2	2
Aurora A/PP2A	0.033	0.005	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.038	0.008	-9999	-10000	0	0
negative regulation of DNA binding	0.033	0.014	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.028	0	-9999	-10000	0	0
RASA1	0.017	0.029	-9999	-0.54	1	1
Ajuba/Aurora A	0.03	0.008	-9999	-10000	0	0
mitotic prometaphase	0	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.028	0.008	-9999	-10000	0	0
TACC1	0.019	0	-9999	-10000	0	0
TACC3	0.019	0	-9999	-10000	0	0
Aurora A/Antizyme1	0.043	0.005	-9999	-10000	0	0
Aurora A/RasGAP	0.032	0.019	-9999	-0.32	1	1
OAZ1	0.019	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.004	-9999	-10000	0	0
GIT1	0.019	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.038	0.008	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	0.026	0	-9999	-10000	0	0
PPP2R5D	0.019	0	-9999	-10000	0	0
Aurora A/TPX2	0.039	0.005	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
CKAP5	0.019	0	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.025	0.009	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.043	0.007	-9999	-10000	0	0
CDKN1B	0.041	0.008	-9999	-10000	0	0
CDKN1A	0.04	0.013	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.019	0	-9999	-10000	0	0
FOXO3	0.041	0.008	-9999	-10000	0	0
AKT1	0.035	0.008	-9999	-10000	0	0
BAD	0.019	0	-9999	-10000	0	0
AKT3	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.041	0.008	-9999	-10000	0	0
AKT1/ASK1	0.041	0.022	-9999	-10000	0	0
BAD/YWHAZ	0.038	0	-9999	-10000	0	0
RICTOR	0.017	0.029	-9999	-0.54	1	1
RAF1	0.019	0	-9999	-10000	0	0
JNK cascade	-0.039	0.021	-9999	-10000	0	0
TSC1	0.041	0.008	-9999	-10000	0	0
YWHAZ	0.019	0	-9999	-10000	0	0
AKT1/RAF1	0.045	0.008	-9999	-10000	0	0
EP300	0.019	0	-9999	-10000	0	0
mol:GDP	0.035	0.008	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.041	0.008	-9999	-10000	0	0
YWHAQ	0.019	0	-9999	-10000	0	0
TBC1D4	0.024	0.023	-9999	-0.31	1	1
MAP3K5	0.016	0.041	-9999	-0.54	2	2
MAPKAP1	0.019	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.041	0.02	-9999	-10000	0	0
YWHAH	0.019	0	-9999	-10000	0	0
AKT1S1	0.041	0.008	-9999	-10000	0	0
CASP9	0.041	0.008	-9999	-10000	0	0
YWHAB	0.019	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.05	0.008	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0.037	0.019	-9999	-0.32	1	1
YWHAE	0.019	0	-9999	-10000	0	0
SRC	0.019	0	-9999	-10000	0	0
AKT2/p21CIP1	0.045	0.012	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.003	-9999	-10000	0	0
CHUK	0.041	0.008	-9999	-10000	0	0
BAD/BCL-XL	0.059	0.01	-9999	-10000	0	0
mTORC2	0.023	0.017	-9999	-0.3	1	1
AKT2	0.02	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.057	0.023	-9999	-10000	0	0
PDPK1	0.019	0	-9999	-10000	0	0
MDM2	0.039	0.016	-9999	-10000	0	0
MAPKKK cascade	-0.044	0.008	-9999	-10000	0	0
MDM2/Cbp/p300	0.058	0.016	-9999	-10000	0	0
TSC1/TSC2	0.046	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.016	-9999	-10000	0	0
glucose import	0.019	0.039	-9999	-0.28	1	1
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.035	0.006	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.019	0.039	-9999	-0.28	1	1
GSK3A	0.041	0.008	-9999	-10000	0	0
FOXO1	0.041	0.008	-9999	-10000	0	0
GSK3B	0.041	0.008	-9999	-10000	0	0
SFN	-0.035	0.11	-9999	-0.24	74	74
G1/S transition of mitotic cell cycle	0.046	0.007	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.042	0.029	-9999	-10000	0	0
PRKACA	0.019	0	-9999	-10000	0	0
KPNA1	0.019	0	-9999	-10000	0	0
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
YWHAG	0.019	0	-9999	-10000	0	0
RHEB	0.019	0	-9999	-10000	0	0
CREBBP	0.019	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	0.003	0.022	-10000	0	-10000	0	0
oxygen homeostasis	0.008	0.013	-10000	0	-10000	0	0
TCEB2	0.017	0.029	-10000	0	-0.54	1	1
TCEB1	0.019	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0.093	0.065	-10000	0	-10000	0	0
EPO	0.14	0.15	-10000	0	-0.48	2	2
FIH (dimer)	0.026	0.032	-10000	0	-0.53	1	1
APEX1	0.028	0.014	-10000	0	-10000	0	0
SERPINE1	0.13	0.17	-10000	0	-0.54	3	3
FLT1	0.024	0.035	-10000	0	-10000	0	0
ADORA2A	0.11	0.18	-10000	0	-0.47	14	14
germ cell development	0.13	0.15	-10000	0	-0.58	2	2
SLC11A2	0.13	0.15	-10000	0	-0.56	2	2
BHLHE40	0.13	0.16	-10000	0	-0.51	3	3
HIF1AN	0.026	0.032	-10000	0	-0.53	1	1
HIF2A/ARNT/SIRT1	0.11	0.1	-10000	0	-0.29	1	1
ETS1	0.036	0.005	-10000	0	-10000	0	0
CITED2	0.021	0.027	-10000	0	-10000	0	0
KDR	0.021	0.045	-10000	0	-10000	0	0
PGK1	0.13	0.15	-10000	0	-0.56	2	2
SIRT1	0.019	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.18	-10000	0	-0.64	2	2
EPAS1	0.078	0.078	-10000	0	-0.28	1	1
SP1	0.028	0.002	-10000	0	-10000	0	0
ABCG2	0.11	0.21	-10000	0	-0.52	23	23
EFNA1	0.13	0.15	-10000	0	-0.56	2	2
FXN	0.13	0.15	-10000	0	-0.54	2	2
POU5F1	0.13	0.16	-10000	0	-0.61	2	2
neuron apoptosis	-0.16	0.18	0.63	2	-10000	0	2
EP300	0.019	0	-10000	0	-10000	0	0
EGLN3	0.023	0.047	-10000	0	-0.38	4	4
EGLN2	0.027	0.012	-10000	0	-10000	0	0
EGLN1	0.027	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.037	0.019	-10000	0	-0.32	1	1
VHL	0.019	0	-10000	0	-10000	0	0
ARNT	0.029	0.014	-10000	0	-10000	0	0
SLC2A1	0.12	0.15	-10000	0	-0.54	2	2
TWIST1	0.075	0.18	-10000	0	-0.64	2	2
ELK1	0.028	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	0.12	0.1	-10000	0	-10000	0	0
VEGFA	0.13	0.16	-10000	0	-0.61	2	2
CREBBP	0.019	0	-10000	0	-10000	0	0

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.001	0.07	-10000	0	-0.24	28	28
CLTC	0.037	0	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.031	0	-10000	0	-10000	0	0
Dynamin 2/GTP	0.03	0	-10000	0	-10000	0	0
EXOC4	0.019	0	-10000	0	-10000	0	0
CD59	0.033	0	-10000	0	-10000	0	0
CPE	0.015	0.04	-10000	0	-0.33	3	3
CTNNB1	0.019	0	-10000	0	-10000	0	0
membrane fusion	0.03	0	-10000	0	-10000	0	0
CTNND1	0.034	0	-10000	0	-10000	0	0
DNM2	0.019	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.036	0	-10000	0	-10000	0	0
TSHR	-0.008	0.097	-10000	0	-0.33	31	31
INS	0.013	0	-10000	0	-10000	0	0
BIN1	-0.005	0.11	-10000	0	-0.54	16	16
mol:Choline	0.03	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.022	0	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.019	0	-10000	0	-10000	0	0
mol:Ca2+	0.03	0	-10000	0	-10000	0	0
JUP	0.03	0.013	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.022	0.066	-10000	0	-0.29	16	16
ARF6/GTP	0.014	0	-10000	0	-10000	0	0
CDH1	-0.028	0.098	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.014	0	-10000	0	-10000	0	0
MAPK8IP3	0.019	0	-10000	0	-10000	0	0
positive regulation of endocytosis	0.014	0	-10000	0	-10000	0	0
EXOC2	0.019	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.049	0.016	-10000	0	-0.24	1	1
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.019	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.001	0.073	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.022	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.026	0	-10000	0	-10000	0	0
ACAP1	-0.016	0.064	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.027	0	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.032	0.015	-10000	0	-10000	0	0
JIP4/KLC1	0.036	0	-10000	0	-10000	0	0
EXOC1	0.019	0	-10000	0	-10000	0	0
exocyst	0.049	0.016	-10000	0	-0.24	1	1
RALA/GTP	0.014	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.026	0	-10000	0	-10000	0	0
receptor recycling	0.014	0	-10000	0	-10000	0	0
CTNNA1	0.034	0	-10000	0	-10000	0	0
NME1	0.022	0	-10000	0	-10000	0	0
clathrin coat assembly	0.037	0	-10000	0	-10000	0	0
IL2RA	-0.023	0.096	-10000	0	-10000	0	0
VAMP3	0.022	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.006	0.02	-10000	0	-10000	0	0
EXOC6	0.017	0.029	-10000	0	-0.54	1	1
PLD1	0.026	0	-10000	0	-10000	0	0
PLD2	0.026	0	-10000	0	-10000	0	0
EXOC5	0.019	0	-10000	0	-10000	0	0
PIP5K1C	0.036	0	-10000	0	-10000	0	0
SDC1	0.028	0.031	-10000	0	-10000	0	0
ARF6/GDP	0.024	0	-10000	0	-10000	0	0
EXOC7	0.019	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.002	0.075	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.03	0	-10000	0	-10000	0	0
endocytosis	-0.021	0.066	0.29	16	-10000	0	16
SCAMP2	0.019	0	-10000	0	-10000	0	0
ADRB2	0.04	0.029	-10000	0	-10000	0	0
EXOC3	0.018	0.014	-10000	0	-0.24	1	1
ASAP2	0.019	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.032	0	-10000	0	-10000	0	0
KLC1	0.019	0	-10000	0	-10000	0	0
AVPR2	0.037	0.026	-10000	0	-10000	0	0
RALA	0.019	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.013	0.07	-10000	0	-10000	0	0

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.04	0.012	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.026	0.012	-9999	-10000	0	0
mol:DAG	0.033	0.057	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.029	0.035	-9999	-0.29	1	1
CaM/Ca2+	0.042	0.054	-9999	-10000	0	0
HIF1A	0.029	0.008	-9999	-10000	0	0
GAB1	0.019	0	-9999	-10000	0	0
AKT1	0.052	0.055	-9999	-10000	0	0
PLCG1	0.033	0.057	-9999	-10000	0	0
NOS3	0.056	0.064	-9999	-0.59	1	1
CBL	0.019	0	-9999	-10000	0	0
mol:NO	0.056	0.062	-9999	-0.57	1	1
FLT1	0.036	0.015	-9999	-10000	0	0
PGF	0.001	0.099	-9999	-0.54	12	12
VEGFR1 homodimer/NRP2/VEGFR121	0.041	0.039	-9999	-0.28	1	1
CALM1	0.019	0	-9999	-10000	0	0
PIK3CA	0.018	0.014	-9999	-0.24	1	1
eNOS/Hsp90	0.064	0.062	-9999	-0.55	1	1
endothelial cell proliferation	-0.029	0.14	-9999	-0.53	9	9
mol:Ca2+	0.033	0.057	-9999	-10000	0	0
MAPK3	0.039	0.055	-9999	-10000	0	0
MAPK1	0.039	0.055	-9999	-10000	0	0
PIK3R1	0.019	0	-9999	-10000	0	0
PLGF homodimer	0.001	0.099	-9999	-0.54	12	12
PRKACA	0.019	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.019	0	-9999	-10000	0	0
VEGFA homodimer	0.004	0.061	-9999	-0.24	21	21
VEGFR1 homodimer/VEGFA homodimer	0.032	0.039	-9999	-0.32	1	1
platelet activating factor biosynthetic process	0.044	0.053	-9999	-10000	0	0
PI3K	0.049	0.056	-9999	-10000	0	0
PRKCA	0.034	0.058	-9999	-10000	0	0
PRKCB	-0.052	0.15	-9999	-0.52	8	8
VEGFR1 homodimer/PLGF homodimer	0.029	0.064	-9999	-0.31	12	12
VEGFA	0.004	0.061	-9999	-0.24	21	21
VEGFB	0.019	0	-9999	-10000	0	0
mol:IP3	0.033	0.057	-9999	-10000	0	0
RASA1	0.043	0.02	-9999	-10000	0	0
NRP2	0.017	0.029	-9999	-0.54	1	1
VEGFR1 homodimer	0.036	0.015	-9999	-10000	0	0
VEGFB homodimer	0.019	0	-9999	-10000	0	0
NCK1	0.019	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.065	0.061	-9999	-0.55	1	1
PTPN11	0.019	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0.047	0.055	-9999	-10000	0	0
mol:L-citrulline	0.056	0.062	-9999	-0.57	1	1
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.051	0.038	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.042	0.036	-9999	-0.28	1	1
CD2AP	0.017	0.029	-9999	-0.54	1	1
PI3K/GAB1	0.056	0.054	-9999	-10000	0	0
PDPK1	0.044	0.051	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.042	0.036	-9999	-10000	0	0
mol:NADP	0.056	0.062	-9999	-0.57	1	1
HSP90AA1	0.017	0.029	-9999	-0.54	1	1
ubiquitin-dependent protein catabolic process	0.049	0.037	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.039	0.022	-9999	-0.31	1	1

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0.024	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.024	0	-9999	-10000	0	0
AP2	0.028	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0.027	0	-9999	-10000	0	0
CLTB	0.019	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.03	0	-9999	-10000	0	0
CD4	-0.034	0.16	-9999	-0.54	35	35
CLTA	0.019	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.015	0	-9999	-10000	0	0
ARF1/GTP	0.023	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.03	0	-9999	-10000	0	0
mol:Choline	0.015	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.019	0	-9999	-10000	0	0
DDEF1	0.015	0	-9999	-10000	0	0
ARF1/GDP	0.01	0	-9999	-10000	0	0
AP2M1	0.019	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.02	0	-9999	-10000	0	0
Rac/GTP	0.015	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.034	0	-9999	-10000	0	0
ARFIP2	0.017	0	-9999	-10000	0	0
COPA	0.019	0	-9999	-10000	0	0
RAC1	0.019	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.029	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0.013	0	-9999	-10000	0	0
GGA3	0.019	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0.024	0	-9999	-10000	0	0
AP2A1	0.019	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.031	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.024	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0.025	0	-9999	-10000	0	0
CYTH2	0.019	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0.026	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.014	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.019	0.069	-9999	-0.2	35	35
PLD2	0.015	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.013	0	-9999	-10000	0	0
PIP5K1A	0.015	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0.027	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0.015	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-10000	0	0
GOSR2	0.018	0	-9999	-10000	0	0
USO1	0.018	0	-9999	-10000	0	0
GBF1	0.018	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0.027	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.005	0.1	-9999	-0.32	35	35

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0.019	-9999	-9999
SMAD2	0.015	-9999	-9999
SMAD3	0.046	-9999	-9999
SMAD3/SMAD4	0.056	-9999	-9999
SMAD4/Ubc9/PIASy	0.038	-9999	-9999
SMAD2/SMAD2/SMAD4	0.053	-9999	-9999
PPM1A	0.019	-9999	-9999
CALM1	0.019	-9999	-9999
SMAD2/SMAD4	0.026	-9999	-9999
MAP3K1	0.019	-9999	-9999
TRAP-1/SMAD4	0.028	-9999	-9999
MAPK3	0.019	-9999	-9999
MAPK1	0.019	-9999	-9999
NUP214	0.019	-9999	-9999
CTDSP1	0.019	-9999	-9999
CTDSP2	0.019	-9999	-9999
CTDSPL	0.019	-9999	-9999
KPNB1	0.019	-9999	-9999
TGFBRAP1	0.019	-9999	-9999
UBE2I	0.019	-9999	-9999
NUP153	0.019	-9999	-9999
KPNA2	0.019	-9999	-9999
PIAS4	0.019	-9999	-9999

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.028	0.001	-9999	-10000	0	0
ATM	0.019	0	-9999	-10000	0	0
UBE2D3	0.019	0	-9999	-10000	0	0
PRKDC	0.019	0	-9999	-10000	0	0
ATR	0.019	0	-9999	-10000	0	0
UBE2L3	0.019	0	-9999	-10000	0	0
FANCD2	0.031	0	-9999	-10000	0	0
protein ubiquitination	0.051	0.001	-9999	-10000	0	0
XRCC5	0.019	0	-9999	-10000	0	0
XRCC6	0.019	0	-9999	-10000	0	0
M/R/N Complex	0.037	0.026	-9999	-0.32	2	2
MRE11A	0.019	0	-9999	-10000	0	0
DNA-PK	0.038	0	-9999	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.061	0	-9999	-10000	0	0
FANCF	0.019	0	-9999	-10000	0	0
BRCA1	0.019	0	-9999	-10000	0	0
CCNE1	0.019	0	-9999	-10000	0	0
CDK2/Cyclin E1	0.028	0	-9999	-10000	0	0
FANCG	0.019	0	-9999	-10000	0	0
BRCA1/BACH1/BARD1	0.028	0.001	-9999	-10000	0	0
FANCE	0.019	0	-9999	-10000	0	0
FANCC	0.019	0	-9999	-10000	0	0
NBN	0.019	0	-9999	-10000	0	0
FANCA	0.019	0	-9999	-10000	0	0
DNA repair	0.08	0	-9999	-10000	0	0
BRCA1/BARD1/ubiquitin	0.028	0.001	-9999	-10000	0	0
BARD1/DNA-PK	0.049	0.001	-9999	-10000	0	0
FANCL	0.019	0	-9999	-10000	0	0
mRNA polyadenylation	-0.028	0.001	-9999	-10000	0	0
BRCA1/BARD1/CTIP/M/R/N Complex	0.045	0.02	-9999	-0.23	1	1
BRCA1/BACH1/BARD1/TopBP1	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/P53	0.049	0.001	-9999	-10000	0	0
BARD1/CSTF1/BRCA1	0.038	0.001	-9999	-10000	0	0
BRCA1/BACH1	0.019	0	-9999	-10000	0	0
BARD1	0.019	0.001	-9999	-10000	0	0
PCNA	0.019	0	-9999	-10000	0	0
BRCA1/BARD1/UbcH5C	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/UbcH7	0.038	0.001	-9999	-10000	0	0
BRCA1/BARD1/RAD51/PCNA	0.049	0.001	-9999	-10000	0	0
BARD1/DNA-PK/P53	0.056	0.001	-9999	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.028	0.001	-9999	-10000	0	0
BRCA1/BARD1/CTIP	0.043	0.001	-9999	-10000	0	0
FA complex	0.047	0	-9999	-10000	0	0
BARD1/EWS	0.028	0.001	-9999	-10000	0	0
RBBP8	0.026	0	-9999	-10000	0	0
TP53	0.019	0	-9999	-10000	0	0
TOPBP1	0.019	0	-9999	-10000	0	0
G1/S transition of mitotic cell cycle	-0.047	0.001	-9999	-10000	0	0
BRCA1/BARD1	0.056	0.001	-9999	-10000	0	0
CSTF1	0.019	0	-9999	-10000	0	0
BARD1/EWS-Fli1	0.014	0.001	-9999	-10000	0	0
CDK2	0.019	0	-9999	-10000	0	0
UniProt:Q9BZD1	0	0	-9999	-10000	0	0
RAD51	0.019	0	-9999	-10000	0	0
RAD50	0.016	0.041	-9999	-0.54	2	2
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.028	0.001	-9999	-10000	0	0
EWSR1	0.019	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.019	0	-9999	-10000	0	0
PLK4	0.017	0.029	-9999	-0.54	1	1
regulation of centriole replication	0.025	0.021	-9999	-0.38	1	1

×

Circadian rhythm pathway

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
chromatin modification	0.059	0.009	-9999	-10000	0	0
CLOCK	0.022	0.014	-9999	-0.24	1	1
TIMELESS/CRY2	0.051	0.01	-9999	-10000	0	0
DEC1/BMAL1	0.016	0.021	-9999	-0.39	1	1
ATR	0.019	0	-9999	-10000	0	0
NR1D1	0.047	0.011	-9999	-10000	0	0
ARNTL	0.021	0.029	-9999	-0.53	1	1
TIMELESS	0.047	0.011	-9999	-10000	0	0
NPAS2	0.017	0.058	-9999	-0.53	4	4
CRY2	0.019	0	-9999	-10000	0	0
mol:CO	-0.016	0	-9999	-10000	0	0
CHEK1	0.019	0	-9999	-10000	0	0
mol:HEME	0.016	0	-9999	-10000	0	0
PER1	0.019	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.053	0.043	-9999	-0.31	5	5
BMAL1/CLOCK	0.058	0.025	-9999	-10000	0	0
S phase of mitotic cell cycle	0.059	0.009	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.06	0.01	-9999	-10000	0	0
mol:NADPH	0.016	0	-9999	-10000	0	0
PER1/TIMELESS	0.051	0.01	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0	0	-9999	-10000	0	0

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.013	0.001	-9999	-10000	0	0
BUB1B	0.027	0.016	-9999	-0.27	1	1
PLK1	0.022	0.002	-9999	-10000	0	0
PLK1S1	0.019	0.001	-9999	-10000	0	0
KIF2A	0.027	0.002	-9999	-10000	0	0
regulation of mitotic centrosome separation	0.022	0.002	-9999	-10000	0	0
GOLGA2	0.019	0	-9999	-10000	0	0
Hec1/SPC24	0.038	0.031	-9999	-0.26	4	4
WEE1	0.031	0.001	-9999	-10000	0	0
cytokinesis	0.038	0.022	-9999	-0.39	1	1
PP2A-alpha B56	0.05	0	-9999	-10000	0	0
AURKA	0.02	0.001	-9999	-10000	0	0
PICH/PLK1	0.042	0.02	-9999	-0.22	2	2
CENPE	0.022	0.042	-9999	-0.28	7	7
RhoA/GTP	0.014	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.027	0.002	-9999	-10000	0	0
PPP2CA	0.019	0	-9999	-10000	0	0
FZR1	0.019	0	-9999	-10000	0	0
TPX2	0.019	0.001	-9999	-10000	0	0
PAK1	0.018	0.014	-9999	-0.24	1	1
SPC24	0.017	0.029	-9999	-0.54	1	1
FBXW11	0.019	0	-9999	-10000	0	0
CLSPN	0.018	0.023	-9999	-0.29	2	2
GORASP1	0.019	0	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.012	0.001	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
STAG2	0.019	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.03	0	-9999	-10000	0	0
spindle elongation	0.022	0.002	-9999	-10000	0	0
ODF2	0.019	0	-9999	-10000	0	0
BUB1	0.031	0	-9999	-10000	0	0
TPT1	0.019	0.001	-9999	-10000	0	0
CDC25C	0.021	0.02	-9999	-0.36	1	1
CDC25B	0.02	0	-9999	-10000	0	0
SGOL1	0.013	0.001	-9999	-10000	0	0
RHOA	0.019	0	-9999	-10000	0	0
CCNB1/CDK1	0.033	0	-9999	-10000	0	0
CDC14B	0.013	0	-9999	-10000	0	0
CDC20	0.019	0	-9999	-10000	0	0
PLK1/PBIP1	0.02	0.033	-9999	-0.26	5	5
mitosis	0	0	-9999	-10000	0	0
FBXO5	0.026	0.001	-9999	-10000	0	0
CDC2	0.002	0	-9999	-10000	0	0
NDC80	0.014	0.05	-9999	-0.54	3	3
metaphase plate congression	0.02	0.001	-9999	-10000	0	0
ERCC6L	0.041	0.02	-9999	-0.23	2	2
NLP/gamma Tubulin	0.017	0.001	-9999	-10000	0	0
microtubule cytoskeleton organization	0.019	0.001	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-9999	-10000	0	0
PPP1R12A	0.019	0	-9999	-10000	0	0
interphase	0	0	-9999	-10000	0	0
PLK1/PRC1-2	0.041	0.016	-9999	-0.26	1	1
GRASP65/GM130/RAB1/GTP/PLK1	0.047	0.001	-9999	-10000	0	0
RAB1A	0.019	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.023	0.002	-9999	-10000	0	0
mitotic prometaphase	0	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.001	-9999	-10000	0	0
microtubule-based process	0.03	0.016	-9999	-0.28	1	1
Golgi organization	0.022	0.002	-9999	-10000	0	0
Cohesin/SA2	0.027	0.002	-9999	-10000	0	0
PPP1CB/MYPT1	0.028	0	-9999	-10000	0	0
KIF20A	0.017	0.029	-9999	-0.54	1	1
APC/C/CDC20	0.031	0.002	-9999	-10000	0	0
PPP2R1A	0.019	0	-9999	-10000	0	0
chromosome segregation	0.019	0.032	-9999	-0.25	5	5
PRC1	0.019	0	-9999	-10000	0	0
ECT2	0.027	0.002	-9999	-10000	0	0
C13orf34	0.024	0.002	-9999	-10000	0	0
NUDC	0.02	0.001	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.027	0.016	-9999	-0.27	1	1
spindle assembly	0.021	0.002	-9999	-10000	0	0
spindle stabilization	0.019	0.001	-9999	-10000	0	0
APC/C/HCDH1	0.024	0	-9999	-10000	0	0
MKLP2/PLK1	0.03	0.016	-9999	-0.28	1	1
CCNB1	0.02	0	-9999	-10000	0	0
PPP1CB	0.019	0	-9999	-10000	0	0
BTRC	0.019	0	-9999	-10000	0	0
ROCK2	0.03	0.001	-9999	-10000	0	0
TUBG1	0.019	0.001	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0	-9999	-10000	0	0
MLF1IP	0.008	0.048	-9999	-0.4	5	5
INCENP	0.019	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.019	0	-10000	0	-10000	0	0
mol:PIP3	-0.005	0.023	0.27	1	-10000	0	1
FRAP1	0.016	0.008	-10000	0	-10000	0	0
AKT1	0.023	0.024	0.23	1	-10000	0	1
INSR	0.018	0.014	-10000	0	-0.24	1	1
Insulin Receptor/Insulin	0.012	0.008	-10000	0	-10000	0	0
mol:GTP	0.036	0.02	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0	-10000	0	-10000	0	0
TSC2	0.019	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.005	-10000	0	-10000	0	0
TSC1	0.019	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.014	0.028	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.001	0.004	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.019	0	-10000	0	-10000	0	0
RPS6KB1	0.028	0.015	0.18	1	-10000	0	1
MAP3K5	0.01	0.028	-10000	0	-0.37	2	2
PIK3R1	0.019	0	-10000	0	-10000	0	0
apoptosis	0.01	0.028	-10000	0	-0.37	2	2
mol:LY294002	0	0	-10000	0	-10000	0	0
EIF4B	0.033	0.015	0.18	1	-10000	0	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.041	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.025	0.028	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.031	0.012	0.17	1	-10000	0	1
FKBP1A	0.019	0	-10000	0	-10000	0	0
RHEB/GTP	0.038	0.017	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-10000	0	0
FKBP12/Rapamycin	0.014	0.001	-10000	0	-10000	0	0
PDPK1	0.018	0.025	0.23	1	-10000	0	1
EIF4E	0.019	0	-10000	0	-10000	0	0
ASK1/PP5C	0.026	0.048	-10000	0	-0.61	2	2
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.021	0.001	-10000	0	-10000	0	0
TSC1/TSC2	0.041	0.023	0.22	1	-10000	0	1
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RPS6	0.019	0	-10000	0	-10000	0	0
PPP5C	0.019	0	-10000	0	-10000	0	0
EIF4G1	0.019	0	-10000	0	-10000	0	0
IRS1	0.002	0.029	-10000	0	-10000	0	0
INS	0	0	-10000	0	-10000	0	0
PTEN	0.017	0.029	-10000	0	-0.54	1	1
PDK2	0.017	0.026	0.23	1	-10000	0	1
EIF4EBP1	0.017	0.013	-10000	0	-10000	0	0
PIK3CA	0.018	0.014	-10000	0	-0.24	1	1
PPP2R5D	0.022	0.008	-10000	0	-10000	0	0
peptide biosynthetic process	0.02	0.007	-10000	0	-10000	0	0
RHEB	0.019	0	-10000	0	-10000	0	0
EIF4A1	0.019	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	0.003	1	-10000	0	1
EEF2	0.02	0.007	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.027	0.012	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.017	0.029	-9999	-0.54	1	1
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.038	0.015	-9999	-10000	0	0
HDAC4	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.001	0.011	-9999	-0.21	1	1
SUMO1	0.019	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.031	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.019	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.019	0	-9999	-10000	0	0
SUMO1/HDAC4	0.04	0	-9999	-10000	0	0
SUMO1/HDAC1	0.039	0.015	-9999	-0.25	1	1
RANGAP1	0.019	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.046	0.018	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.025	0	-9999	-10000	0	0
Ran/GTP	0.034	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.015	0.033	-9999	-0.24	6	6
UBE2I	0.019	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.039	0	-9999	-10000	0	0
NPC	0.011	0	-9999	-10000	0	0
PIAS2	0.019	0	-9999	-10000	0	0
PIAS1	0.019	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.028	-9999	-9999
FBXW11	0.019	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.019	-9999	-9999
CHUK	0.019	-9999	-9999
NF kappa B2 p100/RelB	0.056	-9999	-9999
NFKB1	0.019	-9999	-9999
MAP3K14	0.019	-9999	-9999
NF kappa B1 p50/RelB	0.028	-9999	-9999
RELB	0.019	-9999	-9999
NFKB2	0.019	-9999	-9999
NF kappa B2 p52/RelB	0.026	-9999	-9999
regulation of B cell activation	0.025	-9999	-9999

pid_entity	TCGA.Z2.AA3V	TCGA.Z2.AA3S	TCGA.Z2.A8RT	TCGA.YG.AA3P
109_MAP3K5	0.061	-0.017	0.061	-0.28
47_PPARGC1A	0.019	0.019	0.019	0.019
105_BMP4	0.019	0.019	0.019	0.019
105_BMP6	0.019	0.019	0.019	0.019
105_BMP7	-0.25	0.019	0.019	0.019
105_BMP2	0.019	0.019	0.019	0.019
131_RELN/VLDLR	0.049	0.049	0.049	0.049
30_TGFB1/TGF beta receptor Type II	0.018	0.018	0.018	0.018
84_STAT5B	0.043	0.041	-0.029	0.055
84_STAT5A	0.043	0.041	-0.029	0.055