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

Pathway.Name	Avg.Num.Perturbations
Nephrin/Neph1 signaling in the kidney podocyte	132
EGFR-dependent Endothelin signaling events	114
Angiopoietin receptor Tie2-mediated signaling	112
PDGFR-alpha signaling pathway	85
FOXA2 and FOXA3 transcription factor networks	60
Signaling mediated by p38-alpha and p38-beta	56
Thromboxane A2 receptor signaling	55
Signaling events mediated by Stem cell factor receptor (c-Kit)	46
Arf6 signaling events	44
Endothelins	42

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
Nephrin/Neph1 signaling in the kidney podocyte	0.4552	132	4512	34	-0.63	0.012	1000	-1000	-0.055	-1000
EGFR-dependent Endothelin signaling events	0.3931	114	2399	21	-0.73	0.018	1000	-1000	-0.062	-1000
Angiopoietin receptor Tie2-mediated signaling	0.3862	112	9878	88	-1.1	0.1	1000	-1000	-0.092	-1000
PDGFR-alpha signaling pathway	0.2931	85	3749	44	-0.38	0.029	1000	-1000	-0.051	-1000
FOXA2 and FOXA3 transcription factor networks	0.2069	60	2802	46	-1.1	0.019	1000	-1000	-0.076	-1000
Signaling mediated by p38-alpha and p38-beta	0.1931	56	2507	44	-0.29	0.012	1000	-1000	-0.044	-1000
Thromboxane A2 receptor signaling	0.1897	55	5830	105	-0.73	0.088	1000	-1000	-0.062	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1586	46	3603	78	-0.42	0.099	1000	-1000	-0.068	-1000
Arf6 signaling events	0.1517	44	2761	62	-0.73	0.031	1000	-1000	-0.063	-1000
Endothelins	0.1448	42	4122	96	-0.64	0.012	1000	-1000	-0.082	-1000
Glypican 1 network	0.1345	39	1919	48	-0.43	0.03	1000	-1000	-0.048	-1000
IL4-mediated signaling events	0.1207	35	3208	91	-0.92	0.57	1000	-1000	-0.13	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.1207	35	4453	125	-0.18	0.032	1000	-1000	-0.093	-1000
BMP receptor signaling	0.1172	34	2813	81	-0.55	0.018	1000	-1000	-0.094	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1138	33	2263	68	-0.62	0.084	1000	-1000	-0.1	-1000
S1P1 pathway	0.1103	32	1157	36	-0.27	0.012	1000	-1000	-0.052	-1000
amb2 Integrin signaling	0.1034	30	2484	82	-0.47	0.012	1000	-1000	-0.072	-1000
TCGA08_retinoblastoma	0.1000	29	233	8	-0.2	0.052	1000	-1000	-0.019	-1000
Syndecan-1-mediated signaling events	0.0897	26	897	34	-0.14	0.012	1000	-1000	-0.046	-1000
Integrins in angiogenesis	0.0793	23	1989	84	-0.52	0.033	1000	-1000	-0.087	-1000
Glypican 2 network	0.0724	21	86	4	-0.1	-0.091	1000	-1000	-0.024	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0724	21	1582	74	-0.73	0.045	1000	-1000	-0.09	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0655	19	2302	120	-0.35	0.13	1000	-1000	-0.069	-1000
Noncanonical Wnt signaling pathway	0.0621	18	484	26	-0.16	0.012	1000	-1000	-0.048	-1000
Signaling events mediated by PTP1B	0.0621	18	1369	76	-0.74	0.092	1000	-1000	-0.083	-1000
Aurora C signaling	0.0621	18	132	7	-0.11	0.012	1000	-1000	-0.03	-1000
Syndecan-4-mediated signaling events	0.0621	18	1246	67	-0.42	0.072	1000	-1000	-0.09	-1000
Signaling events regulated by Ret tyrosine kinase	0.0586	17	1454	82	-0.14	0.012	1000	-1000	-0.078	-1000
Wnt signaling	0.0586	17	121	7	-0.083	0.012	1000	-1000	-0.023	-1000
Plasma membrane estrogen receptor signaling	0.0586	17	1534	86	-0.22	0.023	1000	-1000	-0.079	-1000
LPA4-mediated signaling events	0.0552	16	195	12	-0.25	0.018	1000	-1000	-0.025	-1000
Glucocorticoid receptor regulatory network	0.0552	16	1848	114	-0.72	0.2	1000	-1000	-0.067	-1000
TCR signaling in naïve CD8+ T cells	0.0552	16	1536	93	-0.56	0.26	1000	-1000	-0.079	-1000
IL6-mediated signaling events	0.0552	16	1242	75	-0.23	0.052	1000	-1000	-0.074	-1000
E-cadherin signaling events	0.0552	16	81	5	-0.064	0.012	1000	-1000	-0.047	-1000
Ephrin A reverse signaling	0.0517	15	110	7	-0.051	0	1000	-1000	-0.033	-1000
Calcium signaling in the CD4+ TCR pathway	0.0517	15	489	31	-0.2	0.013	1000	-1000	-0.071	-1000
Coregulation of Androgen receptor activity	0.0483	14	1095	76	-0.76	0.022	1000	-1000	-0.042	-1000
Signaling events mediated by the Hedgehog family	0.0483	14	769	52	-0.08	0.031	1000	-1000	-0.049	-1000
HIF-1-alpha transcription factor network	0.0483	14	1089	76	-0.2	0.046	1000	-1000	-0.11	-1000
Ceramide signaling pathway	0.0483	14	1095	76	-0.73	0.25	1000	-1000	-0.06	-1000
p75(NTR)-mediated signaling	0.0448	13	1651	125	-0.43	0.032	1000	-1000	-0.089	-1000
FoxO family signaling	0.0448	13	879	64	-0.77	0.091	1000	-1000	-0.06	-1000
IL27-mediated signaling events	0.0448	13	701	51	-1.1	0.18	1000	-1000	-0.074	-1000
Visual signal transduction: Rods	0.0448	13	697	52	-0.28	0.012	1000	-1000	-0.077	-1000
FOXM1 transcription factor network	0.0448	13	691	51	-0.2	0.028	1000	-1000	-0.17	-1000
S1P3 pathway	0.0414	12	522	42	-0.2	0.018	1000	-1000	-0.035	-1000
Presenilin action in Notch and Wnt signaling	0.0379	11	684	61	-0.25	0.12	1000	-1000	-0.062	-1000
Reelin signaling pathway	0.0379	11	631	56	-0.2	0.018	1000	-1000	-0.07	-1000
EPHB forward signaling	0.0379	11	956	85	-0.2	0.068	1000	-1000	-0.086	-1000
Nongenotropic Androgen signaling	0.0379	11	609	52	-0.078	0.019	1000	-1000	-0.064	-1000
Regulation of nuclear SMAD2/3 signaling	0.0345	10	1383	136	-0.62	0.11	1000	-1000	-0.062	-1000
ErbB4 signaling events	0.0345	10	720	69	-0.24	0.12	1000	-1000	-0.084	-1000
Osteopontin-mediated events	0.0345	10	394	38	-0.1	0.029	1000	-1000	-0.096	-1000
Regulation of Androgen receptor activity	0.0345	10	719	70	-0.87	0.027	1000	-1000	-0.062	-1000
Aurora B signaling	0.0345	10	679	67	-0.31	0.012	1000	-1000	-0.063	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0310	9	271	28	-0.2	0.018	1000	-1000	-0.027	-1000
Regulation of Telomerase	0.0310	9	932	102	-0.73	0.043	1000	-1000	-0.1	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0310	9	314	33	-0.2	0.035	1000	-1000	-0.058	-1000
E-cadherin signaling in keratinocytes	0.0310	9	400	43	-0.32	0.033	1000	-1000	-0.07	-1000
JNK signaling in the CD4+ TCR pathway	0.0276	8	145	17	-0.045	0.02	1000	-1000	-0.065	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0276	8	688	85	-0.1	0.017	1000	-1000	-0.08	-1000
Effects of Botulinum toxin	0.0276	8	212	26	-0.26	0.015	1000	-1000	-0.056	-1000
E-cadherin signaling in the nascent adherens junction	0.0276	8	659	76	-0.064	0.027	1000	-1000	-0.085	-1000
IL1-mediated signaling events	0.0241	7	443	62	-0.24	0.058	1000	-1000	-0.098	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0241	7	380	52	-0.27	0.057	1000	-1000	-0.066	-1000
Syndecan-3-mediated signaling events	0.0241	7	274	35	-0.18	0.018	1000	-1000	-0.06	-1000
IL23-mediated signaling events	0.0241	7	430	60	-0.2	0.02	1000	-1000	-0.17	-1000
Caspase cascade in apoptosis	0.0207	6	510	74	-0.41	0.041	1000	-1000	-0.035	-1000
IL12-mediated signaling events	0.0207	6	602	87	-0.15	0.038	1000	-1000	-0.12	-1000
BARD1 signaling events	0.0207	6	389	57	-0.098	0.023	1000	-1000	-0.062	-1000
Syndecan-2-mediated signaling events	0.0207	6	452	69	-0.47	0.039	1000	-1000	-0.044	-1000
Ephrin B reverse signaling	0.0207	6	301	48	-0.11	0.036	1000	-1000	-0.066	-1000
TCGA08_rtk_signaling	0.0207	6	171	26	-0.38	0.025	1000	-1000	-0.019	-1000
BCR signaling pathway	0.0207	6	666	99	-0.065	0.033	1000	-1000	-0.084	-1000
PDGFR-beta signaling pathway	0.0207	6	677	97	-0.12	0.043	1000	-1000	-0.091	-1000
Class IB PI3K non-lipid kinase events	0.0207	6	18	3	-0.008	-1000	1000	-1000	-0.014	-1000
PLK2 and PLK4 events	0.0172	5	16	3	-0.002	0.011	1000	-1000	-0.018	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0172	5	290	54	-0.19	0.025	1000	-1000	-0.087	-1000
Canonical Wnt signaling pathway	0.0172	5	263	51	-0.25	0.12	1000	-1000	-0.06	-1000
Regulation of p38-alpha and p38-beta	0.0172	5	291	54	-0.21	0.063	1000	-1000	-0.056	-1000
IGF1 pathway	0.0172	5	315	57	-0.033	0.038	1000	-1000	-0.093	-1000
Ras signaling in the CD4+ TCR pathway	0.0172	5	91	17	-0.004	0.027	1000	-1000	-0.037	-1000
Fc-epsilon receptor I signaling in mast cells	0.0138	4	394	97	-0.1	0.028	1000	-1000	-0.081	-1000
Nectin adhesion pathway	0.0138	4	268	63	-0.064	0.044	1000	-1000	-0.072	-1000
S1P5 pathway	0.0138	4	74	17	-0.044	0.025	1000	-1000	-0.036	-1000
FAS signaling pathway (CD95)	0.0138	4	215	47	-0.2	0.015	1000	-1000	-0.046	-1000
LPA receptor mediated events	0.0138	4	440	102	-0.1	0.053	1000	-1000	-0.084	-1000
Signaling events mediated by PRL	0.0138	4	168	34	-0.032	0.021	1000	-1000	-0.038	-1000
S1P4 pathway	0.0138	4	116	25	-0.044	0.027	1000	-1000	-0.047	-1000
ErbB2/ErbB3 signaling events	0.0103	3	198	65	-0.087	0.034	1000	-1000	-0.062	-1000
Cellular roles of Anthrax toxin	0.0103	3	147	39	-0.21	0.018	1000	-1000	-0.028	-1000
IFN-gamma pathway	0.0103	3	257	68	-0.28	0.069	1000	-1000	-0.097	-1000
HIF-2-alpha transcription factor network	0.0103	3	135	43	-0.25	0.095	1000	-1000	-0.079	-1000
IL2 signaling events mediated by PI3K	0.0103	3	214	58	-0.044	0.061	1000	-1000	-0.071	-1000
Class I PI3K signaling events	0.0103	3	235	73	-0.045	0.037	1000	-1000	-0.066	-1000
Arf6 trafficking events	0.0103	3	276	71	-0.34	0.04	1000	-1000	-0.077	-1000
Signaling events mediated by HDAC Class II	0.0069	2	215	75	-0.17	0.037	1000	-1000	-0.055	-1000
PLK1 signaling events	0.0069	2	207	85	-0.067	0.025	1000	-1000	-0.047	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0069	2	185	83	-0.22	0.05	1000	-1000	-0.072	-1000
IL2 signaling events mediated by STAT5	0.0069	2	53	22	-0.026	0.052	1000	-1000	-0.048	-1000
Insulin Pathway	0.0069	2	159	74	-0.05	0.033	1000	-1000	-0.085	-1000
VEGFR1 specific signals	0.0069	2	123	56	-0.009	0.045	1000	-1000	-0.084	-1000
Visual signal transduction: Cones	0.0034	1	46	38	-0.014	0.014	1000	-1000	-0.051	-1000
Hedgehog signaling events mediated by Gli proteins	0.0034	1	89	65	-0.044	0.061	1000	-1000	-0.059	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0034	1	54	37	-0.028	0.038	1000	-1000	-0.052	-1000
Signaling events mediated by HDAC Class I	0.0034	1	185	104	-0.17	0.052	1000	-1000	-0.057	-1000
Signaling mediated by p38-gamma and p38-delta	0.0034	1	25	15	0	0.026	1000	-1000	-0.031	-1000
Retinoic acid receptors-mediated signaling	0.0034	1	80	58	-0.076	0.033	1000	-1000	-0.071	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0034	1	52	45	-0.017	0.067	1000	-1000	-0.082	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	10	23	-0.002	0.044	1000	-1000	-0.055	-1000
Canonical NF-kappaB pathway	0.0000	0	9	39	-0.009	0.076	1000	-1000	-0.077	-1000
Circadian rhythm pathway	0.0000	0	14	22	-0.013	0.044	1000	-1000	-0.056	-1000
a4b1 and a4b7 Integrin signaling	0.0000	0	0	5	0.012	0.018	1000	-1000	-0.016	-1000
Aurora A signaling	0.0000	0	39	60	-0.068	0.036	1000	-1000	-0.048	-1000
Arf6 downstream pathway	0.0000	0	0	43	-0.027	0.028	1000	-1000	-0.043	-1000
EPO signaling pathway	0.0000	0	53	55	-0.032	0.074	1000	-1000	-0.094	-1000
Insulin-mediated glucose transport	0.0000	0	10	32	-0.12	0.07	1000	-1000	-0.054	-1000
mTOR signaling pathway	0.0000	0	45	53	-0.006	0.033	1000	-1000	-0.059	-1000
Class I PI3K signaling events mediated by Akt	0.0000	0	10	68	-0.12	0.047	1000	-1000	-0.052	-1000
Signaling events mediated by HDAC Class III	0.0000	0	22	40	-0.019	0.021	1000	-1000	-0.037	-1000
TRAIL signaling pathway	0.0000	0	10	48	-0.003	0.043	1000	-1000	-0.059	-1000
ceramide signaling pathway	0.0000	0	14	49	-0.012	0.048	1000	-1000	-0.042	-1000
TCGA08_p53	0.0000	0	0	7	-0.13	0.084	1000	-1000	-0.013	-1000
Paxillin-dependent events mediated by a4b1	0.0000	0	4	36	-0.036	0.038	1000	-1000	-0.069	-1000
Atypical NF-kappaB pathway	0.0000	0	29	31	-0.003	0.044	1000	-1000	-0.043	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	3	27	-0.001	0.032	1000	-1000	-0.052	-1000
Rapid glucocorticoid signaling	0.0000	0	15	20	-0.002	0.012	1000	-1000	-0.034	-1000
p38 MAPK signaling pathway	0.0000	0	26	44	-0.059	0.034	1000	-1000	-0.06	-1000
Arf1 pathway	0.0000	0	0	54	-0.005	0.03	1000	-1000	-0.047	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.018	1000	-1000	-0.056	-1000
Total	NA	1831	110477	7203	-32	-990	131000	-131000	-8.4	-131000

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.48	0.36	0.72	192	-10000	0	192
KIRREL	-0.12	0.24	-10000	0	-0.87	27	27
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.48	0.36	-10000	0	-0.72	192	192
PLCG1	0.012	0	-10000	0	-10000	0	0
ARRB2	0.01	0.022	-10000	0	-10000	0	0
WASL	0.012	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.52	0.38	-10000	0	-0.7	214	214
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.39	0.31	-10000	0	-0.54	214	214
FYN	-0.49	0.36	-10000	0	-0.67	214	214
mol:Ca2+	-0.51	0.37	-10000	0	-0.69	214	214
mol:DAG	-0.52	0.38	-10000	0	-0.7	214	214
NPHS2	-0.36	0.4	-10000	0	-0.87	109	109
mol:IP3	-0.52	0.38	-10000	0	-0.7	214	214
regulation of endocytosis	-0.46	0.34	-10000	0	-0.62	214	214
Nephrin/NEPH1/podocin/Cholesterol	-0.52	0.38	-10000	0	-0.71	214	214
establishment of cell polarity	-0.48	0.36	-10000	0	-0.72	192	192
Nephrin/NEPH1/podocin/NCK1-2	-0.48	0.36	-10000	0	-0.66	214	214
Nephrin/NEPH1/beta Arrestin2	-0.47	0.36	-10000	0	-0.64	214	214
NPHS1	-0.55	0.4	-10000	0	-0.85	183	183
Nephrin/NEPH1/podocin	-0.49	0.37	-10000	0	-0.67	214	214
TJP1	0.012	0	-10000	0	-10000	0	0
NCK1	0.012	0	-10000	0	-10000	0	0
NCK2	0.012	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.52	0.38	-10000	0	-0.7	214	214
CD2AP	0.012	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.52	0.38	-10000	0	-0.7	214	214
GRB2	0.012	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.63	0.41	-10000	0	-0.77	237	237
cytoskeleton organization	-0.51	0.39	-10000	0	-0.7	214	214
Nephrin/NEPH1	-0.37	0.28	-10000	0	-0.55	192	192
Nephrin/NEPH1/ZO-1	-0.4	0.3	-10000	0	-0.6	192	192

×

EGFR-dependent Endothelin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.011	0.016	-9999	-10000	0	0
EGFR	0.012	0	-9999	-10000	0	0
EGF/EGFR	-0.43	0.17	-9999	-0.48	265	265
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.41	0.14	-9999	-0.46	262	262
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.036	0.19	-9999	-0.81	17	17
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.73	0.24	-9999	-0.81	262	262
EGF/EGFR dimer/SHC	-0.49	0.16	-9999	-0.54	262	262
mol:GDP	-0.41	0.13	-9999	-0.45	262	262
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.007	0.068	-9999	-0.81	2	2
GRB2/SOS1	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.38	0.12	-9999	-0.42	262	262
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	-0.38	0.12	-9999	-0.42	262	262
FRAP1	-0.39	0.14	-9999	-0.44	262	262
EGF/EGFR dimer	-0.56	0.19	-9999	-0.62	262	262
SOS1	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.024	0.16	-9999	-0.62	19	19

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.65	0.56	-10000	0	-1.1	187	187
NCK1/PAK1/Dok-R	-0.29	0.22	-10000	0	-0.45	187	187
NCK1/Dok-R	-0.86	0.72	-10000	0	-1.4	187	187
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.1	0.12	0.25	113	-10000	0	113
RELA	0.012	0	-10000	0	-10000	0	0
SHC1	0.01	0.002	-10000	0	-10000	0	0
Rac/GDP	0.009	0	-10000	0	-10000	0	0
F2	0.074	0.15	0.26	88	-0.27	19	107
TNIP2	0.012	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.79	0.61	-10000	0	-1.2	187	187
FN1	-0.001	0.057	-10000	0	-0.25	14	14
PLD2	-0.91	0.77	-10000	0	-1.4	187	187
PTPN11	0.012	0	-10000	0	-10000	0	0
GRB14	-0.05	0.22	-10000	0	-0.81	22	22
ELK1	-0.75	0.64	-10000	0	-1.2	187	187
GRB7	0.012	0	-10000	0	-10000	0	0
PAK1	0.012	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.85	0.66	-10000	0	-1.3	187	187
CDKN1A	-0.42	0.37	-10000	0	-0.69	185	185
ITGA5	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.86	0.72	-10000	0	-1.4	187	187
CRK	0.012	0	-10000	0	-10000	0	0
mol:NO	-0.44	0.4	-10000	0	-0.73	187	187
PLG	-1.1	0.73	-10000	0	-1.6	187	187
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.6	0.52	-10000	0	-0.98	187	187
GRB2	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.01	0.002	-10000	0	-10000	0	0
ANGPT2	-0.34	0.37	-10000	0	-0.7	126	126
BMX	-0.91	0.77	-10000	0	-1.4	187	187
ANGPT1	-0.58	0.7	-10000	0	-1.4	115	115
tube development	-0.49	0.43	-10000	0	-0.8	187	187
ANGPT4	0.004	0.031	-10000	0	-10000	0	0
response to hypoxia	-0.043	0.035	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.98	0.81	-10000	0	-1.5	187	187
alpha5/beta1 Integrin	0.018	0	-10000	0	-10000	0	0
FGF2	-0.007	0.13	-10000	0	-0.81	7	7
STAT5A (dimer)	-0.58	0.5	-10000	0	-0.94	185	185
mol:L-citrulline	-0.44	0.4	-10000	0	-0.73	187	187
AGTR1	-0.29	0.4	-10000	0	-0.81	105	105
MAPK14	-0.89	0.74	-10000	0	-1.4	187	187
Tie2/SHP2	-0.8	0.63	-10000	0	-1.3	177	177
TEK	-0.88	0.73	-10000	0	-1.5	177	177
RPS6KB1	-0.61	0.53	-10000	0	-0.99	187	187
Angiotensin II/AT1	-0.22	0.31	-10000	0	-0.63	105	105
Tie2/Ang1/GRB2	-0.96	0.82	-10000	0	-1.5	187	187
MAPK3	-0.78	0.67	-10000	0	-1.3	187	187
MAPK1	-0.78	0.67	-10000	0	-1.3	187	187
Tie2/Ang1/GRB7	-0.96	0.82	-10000	0	-1.5	187	187
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	-0.91	0.78	-10000	0	-1.5	187	187
PI3K	-0.79	0.67	-10000	0	-1.3	187	187
FES	-0.88	0.74	-10000	0	-1.4	187	187
Crk/Dok-R	-0.86	0.72	-10000	0	-1.4	187	187
Tie2/Ang1/ABIN2	-0.96	0.82	-10000	0	-1.5	187	187
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.55	0.48	-10000	0	-0.91	187	187
STAT5A	0.012	0	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.61	0.53	-10000	0	-0.99	187	187
Tie2/Ang2	-0.75	0.64	-10000	0	-1.2	187	187
Tie2/Ang1	-1.1	0.92	-10000	0	-1.7	187	187
FOXO1	-0.56	0.49	-10000	0	-0.92	187	187
ELF1	-0.046	0.054	-10000	0	-10000	0	0
ELF2	-0.93	0.79	-10000	0	-1.5	187	187
mol:Choline	-0.83	0.7	-10000	0	-1.3	187	187
cell migration	-0.16	0.12	-10000	0	-0.25	185	185
FYN	-0.58	0.5	-10000	0	-0.94	187	187
DOK2	-0.008	0.081	-10000	0	-0.28	20	20
negative regulation of cell cycle	-0.37	0.34	-10000	0	-0.62	185	185
ETS1	-0.082	0.12	-10000	0	-10000	0	0
PXN	-0.48	0.42	-10000	0	-0.79	187	187
ITGB1	0.012	0	-10000	0	-10000	0	0
NOS3	-0.52	0.46	-10000	0	-0.86	187	187
RAC1	0.012	0	-10000	0	-10000	0	0
TNF	-0.1	0.15	-10000	0	-0.62	9	9
MAPKKK cascade	-0.83	0.7	-10000	0	-1.3	187	187
RASA1	0.012	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.96	0.82	-10000	0	-1.5	187	187
NCK1	0.012	0	-10000	0	-10000	0	0
vasculogenesis	-0.38	0.36	-10000	0	-0.65	187	187
mol:Phosphatidic acid	-0.83	0.7	-10000	0	-1.3	187	187
mol:Angiotensin II	0	0.002	-10000	0	-10000	0	0
mol:NADP	-0.44	0.4	-10000	0	-0.73	187	187
Rac1/GTP	-0.59	0.44	-10000	0	-0.91	187	187
MMP2	-0.91	0.77	-10000	0	-1.4	187	187

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.38	0.42	-9999	-0.82	137	137
PDGF/PDGFRA/CRKL	-0.28	0.32	-9999	-0.62	137	137
positive regulation of JUN kinase activity	-0.22	0.24	-9999	-0.47	137	137
CRKL	0.012	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.29	0.32	-9999	-0.62	137	137
AP1	-0.35	0.48	-9999	-1.4	41	41
mol:IP3	-0.29	0.33	-9999	-0.64	137	137
PLCG1	-0.29	0.33	-9999	-0.64	137	137
PDGF/PDGFRA/alphaV Integrin	-0.28	0.32	-9999	-0.62	137	137
RAPGEF1	0.012	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
mol:Ca2+	-0.29	0.33	-9999	-0.63	137	137
CAV3	0.002	0.005	-9999	-10000	0	0
CAV1	0.012	0	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.21	0.25	-9999	-0.48	137	137
PDGF/PDGFRA/Shf	-0.28	0.32	-9999	-0.62	137	137
FOS	-0.33	0.48	-9999	-0.7	145	145
JUN	-0.024	0.025	-9999	-10000	0	0
oligodendrocyte development	-0.28	0.32	-9999	-0.62	137	137
GRB2	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
mol:DAG	-0.29	0.33	-9999	-0.64	137	137
PDGF/PDGFRA	-0.38	0.42	-9999	-0.82	137	137
actin cytoskeleton reorganization	-0.28	0.32	-9999	-0.61	137	137
SRF	0.029	0.011	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
PI3K	-0.25	0.26	-9999	-0.53	137	137
PDGF/PDGFRA/Crk/C3G	-0.25	0.26	-9999	-0.53	137	137
JAK1	-0.28	0.32	-9999	-0.61	137	137
ELK1/SRF	-0.21	0.26	-9999	-0.47	137	137
SHB	0.012	0	-9999	-10000	0	0
SHF	0.012	0	-9999	-10000	0	0
CSNK2A1	0.024	0.025	-9999	-10000	0	0
GO:0007205	-0.29	0.33	-9999	-0.64	137	137
SOS1	0.012	0	-9999	-10000	0	0
Ras protein signal transduction	-0.22	0.24	-9999	-0.47	137	137
PDGF/PDGFRA/SHB	-0.28	0.32	-9999	-0.62	137	137
PDGF/PDGFRA/Caveolin-1	-0.28	0.32	-9999	-0.62	137	137
ITGAV	0.009	0.048	-9999	-0.81	1	1
ELK1	-0.26	0.3	-9999	-0.57	137	137
PIK3CA	0.012	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.28	0.32	-9999	-0.62	137	137
JAK-STAT cascade	-0.28	0.32	-9999	-0.61	137	137
cell proliferation	-0.28	0.32	-9999	-0.61	137	137

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.39	0.38	-9999	-1	57	57
PCK1	-0.95	0.72	-9999	-1.6	149	149
HNF4A	-0.45	0.48	-9999	-1.3	55	55
KCNJ11	-0.42	0.4	-9999	-1.1	56	56
AKT1	-0.2	0.14	-9999	-0.43	32	32
response to starvation	-0.005	0.015	-9999	-10000	0	0
DLK1	-0.44	0.43	-9999	-1.1	61	61
NKX2-1	-0.091	0.15	-9999	-0.46	4	4
ACADM	-0.39	0.38	-9999	-1	58	58
TAT	-0.41	0.25	-9999	-0.73	74	74
CEBPB	-0.029	0.059	-9999	-0.32	8	8
CEBPA	-0.059	0.11	-9999	-0.32	36	36
TTR	-0.71	0.41	-9999	-0.92	176	176
PKLR	-0.5	0.56	-9999	-1.4	73	73
APOA1	-0.45	0.45	-9999	-1.2	59	59
CPT1C	-0.41	0.41	-9999	-1.1	62	62
ALAS1	-0.17	0.15	-9999	-10000	0	0
TFRC	-0.53	0.32	-9999	-0.86	104	104
FOXF1	0.005	0.07	-9999	-0.81	2	2
NF1	0.019	0	-9999	-10000	0	0
HNF1A (dimer)	-0.035	0.11	-9999	-0.85	4	4
CPT1A	-0.39	0.38	-9999	-1	57	57
HMGCS1	-0.39	0.38	-9999	-1	59	59
NR3C1	0.008	0.039	-9999	-10000	0	0
CPT1B	-0.39	0.38	-9999	-1	57	57
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.013	0.006	-9999	-10000	0	0
GCK	-0.39	0.38	-9999	-1	59	59
CREB1	-0.059	0.068	-9999	-10000	0	0
IGFBP1	-0.25	0.38	-9999	-1.4	25	25
PDX1	-0.21	0.2	-9999	-0.87	8	8
UCP2	-0.4	0.38	-9999	-1	58	58
ALDOB	-1.1	0.45	-9999	-1.2	265	265
AFP	-0.49	0.38	-9999	-0.98	75	75
BDH1	-0.39	0.38	-9999	-1.1	51	51
HADH	-0.41	0.4	-9999	-1.1	55	55
F2	-0.46	0.44	-9999	-1.2	59	59
HNF1A	-0.035	0.11	-9999	-0.85	4	4
G6PC	-0.96	0.66	-9999	-1.5	176	176
SLC2A2	-0.41	0.56	-9999	-1.7	41	41
INS	0	0.049	-9999	-10000	0	0
FOXA1	-0.23	0.12	-9999	-0.37	66	66
FOXA3	-0.48	0.3	-9999	-0.57	217	217
FOXA2	-0.49	0.45	-9999	-1.1	78	78
ABCC8	-0.42	0.4	-9999	-1.1	58	58
ALB	-1.1	0.4	-9999	-1.2	264	264

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.29	0.57	-9999	-1.3	72	72
MKNK1	0.012	0	-9999	-10000	0	0
MAPK14	-0.067	0.16	-9999	-0.44	12	12
ATF2/c-Jun	-0.037	0.13	-9999	-0.43	10	10
MAPK11	-0.067	0.16	-9999	-0.32	82	82
MITF	-0.076	0.2	-9999	-0.38	84	84
MAPKAPK5	-0.073	0.2	-9999	-0.38	82	82
KRT8	-0.076	0.2	-9999	-0.38	82	82
MAPKAPK3	0.012	0	-9999	-10000	0	0
MAPKAPK2	0.012	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.1	0.25	-9999	-0.48	82	82
CEBPB	-0.077	0.2	-9999	-0.38	82	82
SLC9A1	-0.073	0.2	-9999	-0.38	82	82
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.066	0.19	-9999	-0.36	82	82
p38alpha-beta/MNK1	-0.075	0.2	-9999	-0.38	82	82
JUN	-0.037	0.13	-9999	-0.42	10	10
PPARGC1A	-0.087	0.21	-9999	-0.39	88	88
USF1	-0.073	0.2	-9999	-0.38	82	82
RAB5/GDP/GDI1	-0.077	0.13	-9999	-0.47	10	10
NOS2	-0.13	0.38	-9999	-1.4	20	20
DDIT3	-0.074	0.2	-9999	-0.38	82	82
RAB5A	0.012	0	-9999	-10000	0	0
HSPB1	-0.057	0.16	-9999	-0.5	11	11
p38alpha-beta/HBP1	-0.075	0.2	-9999	-0.38	82	82
CREB1	-0.077	0.21	-9999	-0.4	82	82
RAB5/GDP	0.009	0	-9999	-10000	0	0
EIF4E	-0.061	0.18	-9999	-0.62	10	10
RPS6KA4	-0.073	0.2	-9999	-0.38	82	82
PLA2G4A	-0.087	0.24	-9999	-0.72	23	23
GDI1	-0.073	0.2	-9999	-0.38	82	82
TP53	-0.097	0.24	-9999	-0.47	82	82
RPS6KA5	-0.081	0.22	-9999	-0.39	84	84
ESR1	-0.11	0.26	-9999	-0.45	89	89
HBP1	0.012	0	-9999	-10000	0	0
MEF2C	-0.073	0.2	-9999	-0.38	82	82
MEF2A	-0.073	0.2	-9999	-0.38	82	82
EIF4EBP1	-0.078	0.21	-9999	-0.4	82	82
KRT19	-0.13	0.27	-9999	-0.45	98	98
ELK4	-0.073	0.2	-9999	-0.38	82	82
ATF6	-0.073	0.2	-9999	-0.38	82	82
ATF1	-0.077	0.21	-9999	-0.4	82	82
p38alpha-beta/MAPKAPK2	-0.075	0.2	-9999	-0.38	82	82
p38alpha-beta/MAPKAPK3	-0.075	0.2	-9999	-0.38	82	82

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.005	0.059	-10000	0	-10000	0	0
GNB1/GNG2	-0.11	0.089	-10000	0	-0.19	84	84
AKT1	-0.095	0.12	-10000	0	-0.2	70	70
EGF	-0.73	0.24	-10000	0	-0.81	262	262
mol:TXA2	-0.001	0.001	-10000	0	-10000	0	0
FGR	0.012	0.093	-10000	0	-0.37	11	11
mol:Ca2+	-0.16	0.17	-10000	0	-0.3	161	161
LYN	0.016	0.085	-10000	0	-0.34	11	11
RhoA/GTP	-0.072	0.059	-10000	0	-10000	0	0
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.18	0.19	-10000	0	-0.34	161	161
GNG2	0.012	0	-10000	0	-10000	0	0
ARRB2	0.01	0.022	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.033	0.12	-10000	0	-0.5	6	6
G beta5/gamma2	-0.14	0.12	-10000	0	-0.26	83	83
PRKCH	-0.19	0.2	-10000	0	-0.35	161	161
DNM1	-0.11	0.13	-10000	0	-0.25	132	132
TXA2/TP beta/beta Arrestin3	-0.027	0.035	-10000	0	-10000	0	0
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
PTGDR	0.012	0.001	-10000	0	-10000	0	0
G12 family/GTP	-0.18	0.14	-10000	0	-0.3	161	161
ADRBK1	0.012	0	-10000	0	-10000	0	0
ADRBK2	0.012	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0.004	0.007	-10000	0	-10000	0	0
mol:GDP	0.088	0.12	0.4	13	-10000	0	13
mol:NADP	-0.016	0.15	-10000	0	-0.81	10	10
RAB11A	0.012	0	-10000	0	-10000	0	0
PRKG1	-0.21	0.37	-10000	0	-0.81	79	79
mol:IP3	-0.2	0.21	-10000	0	-0.38	161	161
cell morphogenesis	0.004	0.007	-10000	0	-10000	0	0
PLCB2	-0.28	0.28	-10000	0	-0.52	161	161
mol:cGMP	-0.001	0.001	-10000	0	-10000	0	0
BLK	0.008	0.086	-10000	0	-0.34	12	12
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.006	0.095	-10000	0	-0.37	11	11
RHOA	0.012	0	-10000	0	-10000	0	0
PTGIR	0.006	0.068	-10000	0	-0.81	2	2
PRKCB1	-0.2	0.21	-10000	0	-0.38	161	161
GNAQ	0.012	0	-10000	0	-10000	0	0
mol:L-citrulline	-0.016	0.15	-10000	0	-0.81	10	10
TXA2/TXA2-R family	-0.28	0.28	-10000	0	-0.53	161	161
LCK	0.013	0.098	-10000	0	-0.39	12	12
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.023	0.098	-10000	0	-0.43	15	15
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.03	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.023	0.097	-10000	0	-0.42	15	15
MAPK14	-0.11	0.13	-10000	0	-0.23	74	74
TGM2/GTP	-0.23	0.23	-10000	0	-0.44	119	119
MAPK11	-0.11	0.13	-10000	0	-0.23	116	116
ARHGEF1	-0.086	0.1	-10000	0	-0.19	13	13
GNAI2	0.012	0	-10000	0	-10000	0	0
JNK cascade	-0.2	0.21	-10000	0	-0.39	161	161
RAB11/GDP	0.013	0.002	-10000	0	-10000	0	0
ICAM1	-0.14	0.16	-10000	0	-0.28	161	161
cAMP biosynthetic process	-0.19	0.2	-10000	0	-0.36	161	161
Gq family/GTP/EBP50	-0.051	0.12	-10000	0	-0.24	80	80
actin cytoskeleton reorganization	0.004	0.007	-10000	0	-10000	0	0
SRC	0.016	0.085	-10000	0	-0.34	11	11
GNB5	0.012	0	-10000	0	-10000	0	0
GNB1	0.012	0	-10000	0	-10000	0	0
EGF/EGFR	-0.099	0.078	-10000	0	-0.34	16	16
VCAM1	-0.15	0.17	-10000	0	-0.3	161	161
TP beta/Gq family/GDP/G beta5/gamma2	-0.033	0.12	-10000	0	-0.5	6	6
platelet activation	-0.15	0.18	-10000	0	-0.3	161	161
PGI2/IP	-0.001	0.053	-10000	0	-0.63	2	2
PRKACA	0.016	0.033	-10000	0	-0.38	2	2
Gq family/GDP/G beta5/gamma2	-0.029	0.11	-10000	0	-0.46	6	6
TXA2/TP beta/beta Arrestin2	-0.033	0.041	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.004	0.12	-10000	0	-0.48	16	16
mol:DAG	-0.23	0.23	-10000	0	-0.43	161	161
EGFR	0.012	0	-10000	0	-10000	0	0
TXA2/TP alpha	-0.26	0.26	-10000	0	-0.48	161	161
Gq family/GTP	-0.083	0.13	-10000	0	-0.29	80	80
YES1	0.016	0.085	-10000	0	-0.34	12	12
GNAI2/GTP	-0.021	0.088	-10000	0	-0.39	15	15
PGD2/DP	0.004	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.012	0	-10000	0	-10000	0	0
FYN	0.016	0.085	-10000	0	-0.38	4	4
mol:NO	-0.016	0.15	-10000	0	-0.81	10	10
GNA15	-0.003	0.062	-10000	0	-10000	0	0
PGK/cGMP	-0.16	0.27	-10000	0	-0.57	85	85
RhoA/GDP	0.013	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.012	0.11	-10000	0	-0.43	15	15
NOS3	-0.016	0.15	-10000	0	-0.81	10	10
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	-0.18	0.2	-10000	0	-0.35	161	161
PRKCB	-0.19	0.2	-10000	0	-0.36	161	161
PRKCE	-0.19	0.2	-10000	0	-0.36	161	161
PRKCD	-0.2	0.21	-10000	0	-0.38	161	161
PRKCG	-0.22	0.22	-10000	0	-0.41	161	161
muscle contraction	-0.26	0.27	-10000	0	-0.49	161	161
PRKCZ	-0.18	0.19	-10000	0	-0.34	161	161
ARR3	0.003	0.005	-10000	0	-10000	0	0
TXA2/TP beta	-0.014	0.1	-10000	0	-0.44	15	15
PRKCQ	-0.2	0.2	-10000	0	-0.37	162	162
MAPKKK cascade	-0.24	0.25	-10000	0	-0.45	161	161
SELE	-0.23	0.23	-10000	0	-0.43	161	161
TP beta/GNAI2/GDP/G beta/gamma	0.018	0.1	-10000	0	-0.42	15	15
ROCK1	0.012	0	-10000	0	-10000	0	0
GNA14	-0.2	0.36	-10000	0	-0.81	76	76
chemotaxis	-0.33	0.33	-10000	0	-0.61	161	161
GNA12	0.012	0	-10000	0	-10000	0	0
GNA13	0.011	0.016	-10000	0	-0.25	1	1
GNA11	-0.005	0.12	-10000	0	-0.81	6	6
Rac1/GTP	0.003	0.005	-10000	0	-10000	0	0

×

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

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
MAP4K1	-0.088	0.2	-10000	0	-0.41	74	74
CRKL	-0.077	0.21	-10000	0	-0.43	72	72
HRAS	-0.056	0.18	-10000	0	-0.56	9	9
mol:PIP3	-0.084	0.19	-10000	0	-0.4	75	75
SPRED1	0.012	0	-10000	0	-10000	0	0
SPRED2	0.012	0	-10000	0	-10000	0	0
GAB1	-0.088	0.22	-10000	0	-0.45	75	75
FOXO3	-0.064	0.19	-10000	0	-0.38	72	72
AKT1	-0.076	0.2	-10000	0	-0.42	75	75
BAD	-0.064	0.19	-10000	0	-0.38	72	72
megakaryocyte differentiation	-0.14	0.27	-10000	0	-0.5	97	97
GSK3B	-0.064	0.19	-10000	0	-0.38	72	72
RAF1	-0.037	0.15	-10000	0	-0.43	9	9
SHC1	0.012	0	-10000	0	-10000	0	0
STAT3	-0.088	0.22	-10000	0	-0.45	75	75
STAT1	-0.21	0.47	-10000	0	-1	72	72
HRAS/SPRED1	-0.038	0.15	-10000	0	-0.43	9	9
cell proliferation	-0.093	0.22	-10000	0	-0.45	78	78
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
TEC	0.012	0	-10000	0	-10000	0	0
RPS6KB1	-0.087	0.22	-10000	0	-0.45	75	75
HRAS/SPRED2	-0.038	0.15	-10000	0	-0.43	9	9
LYN/TEC/p62DOK	-0.11	0.19	-10000	0	-0.42	72	72
MAPK3	-0.014	0.12	-10000	0	-0.29	9	9
STAP1	-0.42	0.3	-10000	0	-0.54	227	227
GRAP2	0.006	0.041	-10000	0	-10000	0	0
JAK2	-0.21	0.38	-10000	0	-0.87	72	72
STAT1 (dimer)	-0.2	0.46	-10000	0	-1	72	72
mol:Gleevec	0.002	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.2	-10000	0	-0.45	76	76
actin filament polymerization	-0.088	0.22	-10000	0	-0.44	75	75
LYN	0.012	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.42	0.34	-10000	0	-0.86	78	78
PIK3R1	0.012	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.057	0.19	-10000	0	-0.38	72	72
PI3K	-0.072	0.21	-10000	0	-0.42	72	72
PTEN	0.012	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.27	0.58	-10000	0	-1.3	72	72
MAPK8	-0.096	0.23	-10000	0	-0.46	78	78
STAT3 (dimer)	-0.086	0.22	-10000	0	-0.44	75	75
positive regulation of transcription	-0.008	0.097	-10000	0	-0.24	6	6
mol:GDP	-0.1	0.17	-10000	0	-0.52	17	17
PIK3C2B	-0.088	0.22	-10000	0	-0.45	75	75
CBL/CRKL	-0.065	0.2	-10000	0	-0.4	72	72
FER	-0.088	0.22	-10000	0	-0.45	75	75
SH2B3	-0.088	0.22	-10000	0	-0.45	75	75
PDPK1	-0.071	0.18	-10000	0	-0.38	72	72
SNAI2	-0.15	0.28	-10000	0	-0.51	100	100
positive regulation of cell proliferation	-0.15	0.35	-10000	0	-0.76	72	72
KITLG	-0.016	0.15	-10000	0	-0.84	9	9
cell motility	-0.15	0.35	-10000	0	-0.76	72	72
PTPN6	0.015	0.011	-10000	0	-10000	0	0
EPOR	-0.026	0.14	-10000	0	-10000	0	0
STAT5A (dimer)	-0.12	0.3	-10000	0	-0.63	72	72
SOCS1	-0.003	0.11	-10000	0	-0.81	5	5
cell migration	0.099	0.22	0.46	75	-10000	0	75
SOS1	0.012	0	-10000	0	-10000	0	0
EPO	0.005	0.024	-10000	0	-0.25	2	2
VAV1	-0.035	0.11	-10000	0	-0.81	1	1
GRB10	-0.088	0.22	-10000	0	-0.45	75	75
PTPN11	0.014	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.1	0.23	-10000	0	-0.48	75	75
GO:0007205	0.003	0.011	-10000	0	-10000	0	0
MAP2K1	-0.02	0.12	-10000	0	-0.33	9	9
CBL	0.012	0	-10000	0	-10000	0	0
KIT	-0.3	0.6	-10000	0	-1.3	72	72
MAP2K2	-0.02	0.12	-10000	0	-0.33	9	9
SHC/Grb2/SOS1	-0.11	0.19	-10000	0	-0.42	72	72
STAT5A	-0.12	0.31	-10000	0	-0.65	72	72
GRB2	0.012	0	-10000	0	-10000	0	0
response to radiation	-0.15	0.27	-10000	0	-0.5	100	100
SHC/GRAP2	0.014	0.027	-10000	0	-10000	0	0
PTPRO	-0.14	0.28	-10000	0	-0.51	97	97
SH2B2	-0.091	0.22	-10000	0	-0.45	75	75
DOK1	0.01	0.022	-10000	0	-0.25	2	2
MATK	-0.1	0.22	-10000	0	-0.47	75	75
CREBBP	0.027	0.016	-10000	0	-10000	0	0
BCL2	-0.024	0.13	-10000	0	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0	0	-9999	-10000	0	0
ARNO/beta Arrestin1-2	-0.01	0.032	-9999	-0.41	1	1
EGFR	0.012	0	-9999	-10000	0	0
EPHA2	0.011	0.016	-9999	-10000	0	0
USP6	0.001	0.053	-9999	-10000	0	0
IQSEC1	0.012	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.56	0.19	-9999	-0.62	262	262
ARRB2	-0.001	0.036	-9999	-0.21	1	1
mol:GTP	0.014	0.011	-9999	-10000	0	0
ARRB1	0.009	0.048	-9999	-0.81	1	1
FBXO8	0.012	0	-9999	-10000	0	0
TSHR	0.008	0.022	-9999	-0.25	2	2
EGF	-0.73	0.24	-9999	-0.81	262	262
somatostatin receptor activity	0	0	-9999	-0.001	133	133
ARAP2	0.012	0	-9999	-10000	0	0
mol:GDP	-0.14	0.12	-9999	-0.28	100	100
mol:PI-3-4-5-P3	0	0	-9999	-0.001	131	131
ITGA2B	-0.002	0.071	-9999	-0.81	1	1
ARF6	0.012	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.008	-9999	-10000	0	0
ADAP1	0.012	0	-9999	-10000	0	0
KIF13B	0.012	0	-9999	-10000	0	0
HGF/MET	-0.073	0.22	-9999	-0.65	34	34
PXN	0.012	0	-9999	-10000	0	0
ARF6/GTP	-0.19	0.13	-9999	-0.32	133	133
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.49	0.16	-9999	-0.54	262	262
ADRB2	0.001	0.053	-9999	-10000	0	0
receptor agonist activity	0	0	-9999	0	133	133
actin filament binding	0	0	-9999	-0.001	133	133
SRC	0.011	0.016	-9999	-10000	0	0
ITGB3	-0.036	0.18	-9999	-0.81	15	15
GNAQ	0.012	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	-0.001	0	-9999	-0.001	131	131
ARF6/GDP	-0.036	0.056	-9999	-10000	0	0
ARF6/GDP/GULP/ACAP1	-0.12	0.11	-9999	-0.4	14	14
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.005	0.12	-9999	-0.49	16	16
ACAP1	-0.032	0.099	-9999	-10000	0	0
ACAP2	0.012	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.009	0.046	-9999	-0.24	1	1
EFNA1	0.012	0	-9999	-10000	0	0
HGF	-0.084	0.26	-9999	-0.81	34	34
CYTH3	0.01	0	-9999	-10000	0	0
CYTH2	0.006	0.002	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	88	88
endosomal lumen acidification	0	0	-9999	-0.001	133	133
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.011	0.016	-9999	-10000	0	0
GNAQ/ARNO	0.007	0.007	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	113	113
MET	-0.013	0.077	-9999	-10000	0	0
GNA14	-0.2	0.36	-9999	-0.81	76	76
GNA15	-0.003	0.062	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	132	132
GNA11	-0.005	0.12	-9999	-0.81	6	6
LHCGR	-0.021	0.078	-9999	-0.25	29	29
AGTR1	-0.29	0.4	-9999	-0.81	105	105
desensitization of G-protein coupled receptor protein signaling pathway	-0.009	0.046	-9999	-0.23	1	1
IPCEF1/ARNO	-0.38	0.13	-9999	-0.43	262	262
alphaIIb/beta3 Integrin	-0.028	0.15	-9999	-0.62	16	16

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.019	0.2	-10000	0	-0.57	22	22
PTK2B	0.012	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.35	0.5	-10000	0	-1	101	101
EDN1	0.008	0.12	-10000	0	-0.62	4	4
EDN3	0.005	0.031	-10000	0	-0.25	4	4
EDN2	-0.036	0.19	-10000	0	-0.72	19	19
HRAS/GDP	-0.15	0.25	-10000	0	-0.55	61	61
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.15	0.25	-10000	0	-0.5	77	77
ADCY4	-0.042	0.22	-10000	0	-0.59	30	30
ADCY5	-0.047	0.2	-10000	0	-0.52	35	35
ADCY6	-0.016	0.16	-10000	0	-0.5	20	20
ADCY7	-0.021	0.16	-10000	0	-0.5	20	20
ADCY1	-0.24	0.29	-10000	0	-0.51	137	137
ADCY2	-0.086	0.17	-10000	0	-0.56	21	21
ADCY3	-0.016	0.16	-10000	0	-0.5	20	20
ADCY8	-0.025	0.16	-10000	0	-0.5	20	20
ADCY9	-0.016	0.16	-10000	0	-0.5	20	20
arachidonic acid secretion	-0.2	0.31	-10000	0	-0.59	93	93
ETB receptor/Endothelin-1/Gq/GTP	-0.094	0.19	-10000	0	-0.37	82	82
GNAO1	-0.044	0.2	-10000	0	-0.74	22	22
HRAS	0.011	0.016	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.015	0.21	0.34	38	-0.54	22	60
ETA receptor/Endothelin-1/Gs/GTP	-0.017	0.2	0.32	37	-0.51	23	60
mol:GTP	-0.004	0.008	-10000	0	-10000	0	0
COL3A1	-0.037	0.25	-10000	0	-0.71	24	24
EDNRB	0.002	0.096	-10000	0	-0.81	4	4
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.092	0.3	-10000	0	-0.77	40	40
CYSLTR1	-0.02	0.21	-10000	0	-0.62	19	19
SLC9A1	-0.015	0.11	0.19	15	-0.3	19	34
mol:GDP	-0.17	0.27	-10000	0	-0.58	67	67
SLC9A3	-0.64	0.4	-10000	0	-0.78	232	232
RAF1	-0.18	0.28	-10000	0	-0.58	74	74
JUN	-0.18	0.3	-10000	0	-0.71	46	46
JAK2	-0.019	0.2	-10000	0	-0.57	22	22
mol:IP3	-0.17	0.26	-10000	0	-0.52	83	83
ETA receptor/Endothelin-1	-0.025	0.26	0.42	38	-0.65	23	61
PLCB1	-0.16	0.33	-10000	0	-0.81	60	60
PLCB2	-0.021	0.085	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.033	0.17	-10000	0	-0.63	18	18
FOS	-0.2	0.37	-10000	0	-0.84	60	60
Gai/GDP	-0.046	0.22	-10000	0	-0.85	19	19
CRK	0.012	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.16	0.29	-10000	0	-0.66	54	54
BCAR1	0.012	0.001	-10000	0	-10000	0	0
PRKCB1	-0.17	0.25	-10000	0	-0.51	83	83
GNAQ	0.009	0.008	-10000	0	-10000	0	0
GNAZ	0.012	0	-10000	0	-10000	0	0
GNAL	0.009	0.048	-10000	0	-0.81	1	1
Gs family/GDP	-0.18	0.22	-10000	0	-0.52	66	66
ETA receptor/Endothelin-1/Gq/GTP	-0.13	0.27	-10000	0	-0.51	75	75
MAPK14	-0.12	0.19	-10000	0	-0.48	35	35
TRPC6	-0.38	0.55	-10000	0	-1.1	100	100
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.2	-10000	0	-0.4	76	76
ETB receptor/Endothelin-2	-0.028	0.16	-10000	0	-0.62	20	20
ETB receptor/Endothelin-3	0.004	0.078	-10000	0	-0.63	4	4
ETB receptor/Endothelin-1	0.006	0.12	-10000	0	-0.66	6	6
MAPK3	-0.2	0.36	-10000	0	-0.78	65	65
MAPK1	-0.2	0.36	-10000	0	-0.78	65	65
Rac1/GDP	-0.15	0.25	-10000	0	-0.55	61	61
cAMP biosynthetic process	-0.14	0.21	-10000	0	-0.54	42	42
MAPK8	-0.23	0.38	-10000	0	-0.68	93	93
SRC	0.011	0.016	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.005	0.099	-10000	0	-0.3	18	18
p130Cas/CRK/Src/PYK2	-0.23	0.32	-10000	0	-0.63	90	90
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.15	0.25	-10000	0	-0.54	65	65
COL1A2	-0.01	0.18	-10000	0	-0.56	11	11
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.064	0.22	-10000	0	-0.67	31	31
mol:DAG	-0.17	0.26	-10000	0	-0.53	81	81
MAP2K2	-0.18	0.3	-10000	0	-0.66	68	68
MAP2K1	-0.18	0.3	-10000	0	-0.66	68	68
EDNRA	-0.035	0.22	-10000	0	-0.77	19	19
positive regulation of muscle contraction	-0.011	0.18	-10000	0	-0.53	19	19
Gq family/GDP	-0.22	0.29	-10000	0	-0.64	81	81
HRAS/GTP	-0.18	0.27	-10000	0	-0.54	81	81
PRKCH	-0.16	0.26	-10000	0	-0.54	71	71
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCA	-0.16	0.26	-10000	0	-0.55	67	67
PRKCB	-0.16	0.26	-10000	0	-0.56	66	66
PRKCE	-0.16	0.25	-10000	0	-0.53	71	71
PRKCD	-0.16	0.26	-10000	0	-0.54	71	71
PRKCG	-0.2	0.27	-10000	0	-0.56	81	81
regulation of vascular smooth muscle contraction	-0.24	0.43	-10000	0	-0.99	60	60
PRKCQ	-0.18	0.27	-10000	0	-0.54	81	81
PLA2G4A	-0.23	0.35	-10000	0	-0.66	93	93
GNA14	-0.21	0.36	-10000	0	-0.82	76	76
GNA15	-0.007	0.062	-10000	0	-10000	0	0
GNA12	0.012	0	-10000	0	-10000	0	0
GNA11	-0.008	0.12	-10000	0	-0.81	6	6
Rac1/GTP	-0.015	0.21	0.34	38	-0.54	22	60
MMP1	-0.16	0.43	-10000	0	-1.1	48	48

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.014	0.083	-9999	-0.54	7	7
fibroblast growth factor receptor signaling pathway	-0.014	0.083	-9999	-0.54	7	7
LAMA1	-0.02	0.14	-9999	-0.81	8	8
PRNP	0.012	0	-9999	-10000	0	0
GPC1/SLIT2	-0.1	0.25	-9999	-0.62	52	52
SMAD2	0.03	0.013	-9999	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.013	-9999	-10000	0	0
GPC1/Laminin alpha1	-0.007	0.11	-9999	-0.64	8	8
TDGF1	-0.43	0.41	-9999	-0.81	155	155
CRIPTO/GPC1	-0.33	0.32	-9999	-0.62	155	155
APP/GPC1	0.016	0.018	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	-0.28	0.28	-9999	-0.54	155	155
FLT1	0.004	0.083	-9999	-0.81	3	3
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.012	-9999	-10000	0	0
SERPINC1	-0.006	0.11	-9999	-0.6	8	8
FYN	-0.28	0.28	-9999	-0.54	155	155
FGR	-0.28	0.28	-9999	-0.55	155	155
positive regulation of MAPKKK cascade	-0.27	0.29	-9999	-0.53	155	155
SLIT2	-0.14	0.32	-9999	-0.81	52	52
GPC1/NRG	0.003	0.091	-9999	-0.59	6	6
NRG1	-0.006	0.11	-9999	-0.56	9	9
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.008	0.057	-9999	-0.54	3	3
LYN	-0.28	0.28	-9999	-0.54	155	155
mol:Spermine	0.009	0.018	-9999	-10000	0	0
cell growth	-0.014	0.083	-9999	-0.54	7	7
BMP signaling pathway	-0.01	0.027	-9999	-10000	0	0
SRC	-0.28	0.28	-9999	-0.54	155	155
TGFBR1	0.012	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.011	0.063	-9999	-0.25	18	18
GPC1	0.01	0.027	-9999	-10000	0	0
TGFBR1 (dimer)	0.012	0	-9999	-10000	0	0
VEGFA	0.01	0.027	-9999	-0.25	3	3
BLK	-0.29	0.28	-9999	-0.55	155	155
HCK	-0.29	0.28	-9999	-0.55	155	155
FGF2	-0.008	0.13	-9999	-0.81	7	7
FGFR1	0.012	0	-9999	-10000	0	0
VEGFR1 homodimer	0.004	0.083	-9999	-0.81	3	3
TGFBR2	0.012	0	-9999	-10000	0	0
cell death	0.016	0.018	-9999	-10000	0	0
ATIII/GPC1	0.002	0.087	-9999	-0.62	5	5
PLA2G2A/GPC1	0	0.047	-9999	-0.32	1	1
LCK	-0.28	0.28	-9999	-0.54	156	156
neuron differentiation	0.003	0.091	-9999	-0.59	6	6
PrPc/Cu2+	0.009	0	-9999	-10000	0	0
APP	0.012	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.012	0	-9999	-10000	0	0

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.51	0.45	-10000	0	-1.2	67	67
STAT6 (cleaved dimer)	-0.54	0.43	-10000	0	-1	105	105
IGHG1	-0.18	0.15	-10000	0	-0.38	15	15
IGHG3	-0.5	0.43	-10000	0	-0.98	102	102
AKT1	-0.22	0.2	-10000	0	-0.64	10	10
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.16	-10000	0	-0.72	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.24	0.21	-10000	0	-0.57	28	28
THY1	-0.68	0.64	-10000	0	-1.5	97	97
MYB	-0.052	0.11	-10000	0	-10000	0	0
HMGA1	0.004	0.046	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.24	-10000	0	-0.59	63	63
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.24	0.2	-10000	0	-0.54	27	27
SP1	0.019	0.004	-10000	0	-10000	0	0
INPP5D	0.006	0.041	-10000	0	-10000	0	0
SOCS5	0.026	0.012	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.51	0.44	-10000	0	-1	97	97
SOCS1	-0.34	0.3	-10000	0	-0.75	60	60
SOCS3	-0.24	0.22	-10000	0	-0.82	8	8
FCER2	-0.39	0.32	-10000	0	-0.82	60	60
PARP14	0.012	0.003	-10000	0	-10000	0	0
CCL17	-0.53	0.45	-10000	0	-1.1	74	74
GRB2	0.012	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.17	-10000	0	-0.58	6	6
T cell proliferation	-0.5	0.46	-10000	0	-1.1	71	71
IL4R/JAK1	-0.51	0.45	-10000	0	-1.1	70	70
EGR2	-0.56	0.54	-10000	0	-1.3	73	73
JAK2	-0.014	0.026	-10000	0	-10000	0	0
JAK3	-0.022	0.095	-10000	0	-0.25	42	42
PIK3R1	0.012	0	-10000	0	-10000	0	0
JAK1	0.004	0.01	-10000	0	-10000	0	0
COL1A2	-0.16	0.14	-10000	0	-10000	0	0
CCL26	-0.51	0.45	-10000	0	-1.2	68	68
IL4R	-0.54	0.48	-10000	0	-1.2	70	70
PTPN6	0.026	0.011	-10000	0	-10000	0	0
IL13RA2	-0.92	0.68	-10000	0	-1.5	166	166
IL13RA1	-0.014	0.026	-10000	0	-10000	0	0
IRF4	-0.1	0.12	-10000	0	-0.53	2	2
ARG1	-0.14	0.13	-10000	0	-10000	0	0
CBL	-0.27	0.23	-10000	0	-0.57	51	51
GTF3A	0.018	0.007	-10000	0	-10000	0	0
PIK3CA	0.012	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.02	0.037	-10000	0	-10000	0	0
IRF4/BCL6	-0.091	0.1	-10000	0	-0.5	1	1
CD40LG	0.008	0.053	-10000	0	-0.28	7	7
MAPK14	-0.27	0.23	-10000	0	-0.6	37	37
mitosis	-0.22	0.2	-10000	0	-0.6	10	10
STAT6	-0.58	0.53	-10000	0	-1.2	100	100
SPI1	-0.029	0.099	-10000	0	-10000	0	0
RPS6KB1	-0.2	0.19	-10000	0	-0.6	8	8
STAT6 (dimer)	-0.58	0.53	-10000	0	-1.2	100	100
STAT6 (dimer)/PARP14	-0.54	0.49	-10000	0	-1.1	101	101
mast cell activation	0.013	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.23	0.2	-10000	0	-0.64	12	12
FRAP1	-0.22	0.2	-10000	0	-0.64	10	10
LTA	-0.52	0.45	-10000	0	-1.2	69	69
FES	0.009	0.048	-10000	0	-0.81	1	1
T-helper 1 cell differentiation	0.57	0.51	1.1	100	-10000	0	100
CCL11	-0.63	0.57	-10000	0	-1.3	96	96
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.23	0.2	-10000	0	-0.58	15	15
IL2RG	0.011	0.058	-10000	0	-0.36	5	5
IL10	-0.52	0.45	-10000	0	-1.2	68	68
IRS1	-0.002	0.11	-10000	0	-0.81	5	5
IRS2	0.01	0.022	-10000	0	-0.25	2	2
IL4	-0.12	0.1	-10000	0	-10000	0	0
IL5	-0.52	0.45	-10000	0	-1.1	70	70
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.42	0.34	-10000	0	-0.85	75	75
COL1A1	-0.18	0.16	-10000	0	-0.56	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.51	0.47	-10000	0	-1.2	65	65
IL2R gamma/JAK3	-0.009	0.081	-10000	0	-0.38	5	5
TFF3	-0.71	0.65	-10000	0	-1.4	113	113
ALOX15	-0.51	0.45	-10000	0	-1.2	65	65
MYBL1	-0.004	0.064	-10000	0	-0.25	18	18
T-helper 2 cell differentiation	-0.42	0.35	-10000	0	-0.82	89	89
SHC1	0.012	0	-10000	0	-10000	0	0
CEBPB	0.006	0.046	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.2	-10000	0	-0.52	26	26
mol:PI-3-4-5-P3	-0.22	0.2	-10000	0	-0.64	10	10
PI3K	-0.23	0.21	-10000	0	-0.68	10	10
DOK2	-0.008	0.081	-10000	0	-0.28	20	20
ETS1	0.026	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.16	-10000	0	-0.56	6	6
ITGB3	-0.55	0.5	-10000	0	-1.2	75	75
PIGR	-0.56	0.49	-10000	0	-1.2	83	83
IGHE	0.04	0.041	-10000	0	-10000	0	0
MAPKKK cascade	-0.17	0.16	-10000	0	-0.55	6	6
BCL6	0.012	0.002	-10000	0	-10000	0	0
OPRM1	-0.52	0.45	-10000	0	-1.2	68	68
RETNLB	-0.52	0.45	-10000	0	-1.1	71	71
SELP	-0.59	0.58	-10000	0	-1.4	77	77
AICDA	-0.52	0.44	-10000	0	-1.1	71	71

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.02	0.15	-9999	-0.66	15	15
AKT1	-0.06	0.28	-9999	-0.61	59	59
PTK2B	-0.14	0.34	-9999	-0.77	60	60
VEGFR2 homodimer/Frs2	-0.16	0.38	-9999	-0.9	59	59
CAV1	0.012	0	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.14	0.36	-9999	-0.84	59	59
endothelial cell proliferation	-0.045	0.27	-9999	-0.57	59	59
mol:Ca2+	-0.11	0.33	-9999	-0.76	59	59
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.12	0.34	-9999	-0.8	59	59
RP11-342D11.1	-0.12	0.33	-9999	-0.76	59	59
CDH5	0.012	0	-9999	-10000	0	0
VEGFA homodimer	0.032	0.013	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
SHC2	-0.005	0.077	-9999	-0.29	17	17
HRAS/GDP	-0.13	0.26	-9999	-0.65	59	59
SH2D2A	-0.012	0.076	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.13	0.26	-9999	-0.63	59	59
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.15	0.36	-9999	-0.85	59	59
VEGFR1 homodimer	0.004	0.083	-9999	-0.81	3	3
SHC/GRB2/SOS1	-0.15	0.29	-9999	-0.73	59	59
GRB10	-0.11	0.33	-9999	-0.76	59	59
PTPN11	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
PAK1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.16	0.31	-9999	-0.77	59	59
HRAS	0.011	0.016	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.056	0.18	-9999	-0.39	60	60
HIF1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.16	0.32	-9999	-0.79	59	59
mol:GTP	0	0	-9999	-10000	0	0
FLT4	-0.005	0.12	-9999	-0.81	6	6
Nck/Pak	0.018	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.14	0.36	-9999	-0.84	59	59
mol:GDP	-0.14	0.28	-9999	-0.7	59	59
mol:NADP	-0.055	0.25	-9999	-0.53	61	61
eNOS/Hsp90	-0.045	0.23	-9999	-0.5	59	59
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	-0.12	0.33	-9999	-0.77	59	59
HIF1A/ARNT	0.018	0	-9999	-10000	0	0
SHB	0.012	0	-9999	-10000	0	0
VEGFA	0.011	0.027	-9999	-0.25	3	3
VEGFC	0.01	0.022	-9999	-10000	0	0
FAK1/Vinculin	-0.12	0.33	-9999	-0.75	60	60
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.16	0.36	-9999	-0.82	60	60
PTPN6	0.012	0	-9999	-10000	0	0
EPAS1	-0.063	0.17	-9999	-0.4	59	59
mol:L-citrulline	-0.055	0.25	-9999	-0.53	61	61
ITGAV	0.009	0.048	-9999	-0.81	1	1
PIK3CA	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.12	0.34	-9999	-0.8	59	59
VEGFR2 homodimer/VEGFA homodimer	-0.13	0.36	-9999	-0.84	59	59
VEGFR2/3 heterodimer	-0.17	0.4	-9999	-0.92	61	61
VEGFB	0.012	0	-9999	-10000	0	0
MAPK11	-0.12	0.34	-9999	-0.78	59	59
VEGFR2 homodimer	-0.18	0.42	-9999	-1	59	59
FLT1	0.004	0.083	-9999	-0.81	3	3
NEDD4	0.014	0.001	-9999	-10000	0	0
MAPK3	-0.096	0.3	-9999	-0.69	59	59
MAPK1	-0.096	0.3	-9999	-0.69	59	59
VEGFA145/NRP2	0.014	0.044	-9999	-0.62	1	1
VEGFR1/2 heterodimer	-0.16	0.39	-9999	-0.93	59	59
KDR	-0.18	0.42	-9999	-1	59	59
VEGFA165/NRP1/VEGFR2 homodimer	-0.12	0.33	-9999	-0.77	59	59
SRC	0.011	0.016	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.098	0.31	-9999	-0.71	59	59
PI3K	-0.096	0.34	-9999	-0.75	59	59
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.14	0.36	-9999	-0.84	59	59
FES	-0.12	0.34	-9999	-0.79	59	59
GAB1	-0.16	0.31	-9999	-0.78	59	59
VEGFR2 homodimer/VEGFA homodimer/Src	-0.14	0.36	-9999	-0.84	59	59
CTNNB1	0.012	0	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
ARNT	0.012	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.045	0.23	-9999	-0.5	59	59
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.14	0.36	-9999	-0.84	59	59
PI3K/GAB1	-0.062	0.29	-9999	-0.63	59	59
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.16	0.31	-9999	-0.77	59	59
PRKACA	0.012	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.15	0.37	-9999	-0.86	61	61
HSP90AA1	0.012	0	-9999	-10000	0	0
CDC42	-0.12	0.34	-9999	-0.79	59	59
actin cytoskeleton reorganization	-0.18	0.33	-9999	-0.84	59	59
PTK2	-0.14	0.36	-9999	-0.82	60	60
EDG1	-0.12	0.33	-9999	-0.76	59	59
mol:DAG	-0.12	0.33	-9999	-0.77	59	59
CaM/Ca2+	-0.14	0.28	-9999	-0.71	59	59
MAP2K3	-0.11	0.33	-9999	-0.75	59	59
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.12	0.34	-9999	-0.8	59	59
PLCG1	-0.12	0.34	-9999	-0.79	59	59
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.13	0.34	-9999	-0.8	59	59
IQGAP1	0.012	0	-9999	-10000	0	0
YES1	0.012	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.14	0.36	-9999	-0.84	59	59
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.14	0.36	-9999	-0.84	59	59
cell migration	-0.073	0.29	-9999	-0.62	59	59
mol:PI-3-4-5-P3	-0.083	0.3	-9999	-0.68	59	59
FYN	0.012	0	-9999	-10000	0	0
VEGFB/NRP1	-0.11	0.31	-9999	-0.72	59	59
mol:NO	-0.055	0.25	-9999	-0.53	61	61
PXN	0.012	0	-9999	-10000	0	0
HRAS/GTP	-0.13	0.26	-9999	-0.65	59	59
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.12	0.34	-9999	-0.8	59	59
VHL	0.012	0	-9999	-10000	0	0
ITGB3	-0.036	0.18	-9999	-0.81	15	15
NOS3	-0.07	0.29	-9999	-0.61	61	61
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.15	0.36	-9999	-0.85	60	60
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	-0.1	0.31	-9999	-0.72	59	59
PRKCB	-0.1	0.31	-9999	-0.72	59	59
VCL	0.012	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.12	0.33	-9999	-0.77	59	59
VEGFR1/2 heterodimer/VEGFA homodimer	-0.14	0.37	-9999	-0.86	59	59
VEGFA165/NRP2	0.014	0.044	-9999	-0.62	1	1
MAPKKK cascade	-0.076	0.29	-9999	-0.65	59	59
NRP2	0.008	0.053	-9999	-0.44	3	3
VEGFC homodimer	0.01	0.022	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
ROCK1	0.012	0	-9999	-10000	0	0
FAK1/Paxillin	-0.12	0.33	-9999	-0.75	60	60
MAP3K13	-0.12	0.34	-9999	-0.79	59	59
PDPK1	-0.062	0.27	-9999	-0.59	59	59

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.55	0.37	-9999	-0.69	231	231
SMAD6-7/SMURF1	-0.002	0.032	-9999	-0.54	1	1
NOG	0.005	0.057	-9999	-0.36	5	5
SMAD9	-0.079	0.13	-9999	-0.58	13	13
SMAD4	0.012	0	-9999	-10000	0	0
SMAD5	-0.22	0.18	-9999	-0.49	19	19
BMP7/USAG1	-0.33	0.37	-9999	-0.71	129	129
SMAD5/SKI	-0.2	0.17	-9999	-0.46	19	19
SMAD1	-0.018	0.044	-9999	-10000	0	0
BMP2	0.012	0	-9999	-10000	0	0
SMAD1/SMAD1/SMAD4	-0.01	0.024	-9999	-10000	0	0
BMPR1A	0.009	0.048	-9999	-0.81	1	1
BMPR1B	-0.52	0.39	-9999	-0.81	186	186
BMPR1A-1B/BAMBI	-0.35	0.26	-9999	-0.54	188	188
AHSG	-0.003	0.045	-9999	-0.25	9	9
CER1	0.003	0.016	-9999	-0.25	1	1
BMP2-4/CER1	0	0.007	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.16	0.15	-9999	-0.54	14	14
BMP2-4 (homodimer)	0.018	0	-9999	-10000	0	0
RGMB	0.012	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.32	0.25	-9999	-0.5	192	192
RGMA	-0.064	0.24	-9999	-0.81	27	27
SMURF1	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.18	0.15	-9999	-0.47	16	16
BMP2-4/USAG1	-0.13	0.21	-9999	-0.54	60	60
SMAD6/SMURF1/SMAD5	-0.2	0.17	-9999	-0.46	19	19
SOSTDC1	-0.2	0.33	-9999	-0.57	104	104
BMP7/BMPR2/BMPR1A-1B	-0.46	0.31	-9999	-0.6	225	225
SKI	0.012	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.01	0.14	-9999	-0.81	8	8
HFE2	0.006	0.027	-9999	-10000	0	0
ZFYVE16	0.012	0	-9999	-10000	0	0
MAP3K7	0.012	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.034	0.13	-9999	-0.54	18	18
SMAD5/SMAD5/SMAD4	-0.2	0.17	-9999	-0.46	19	19
MAPK1	0.012	0	-9999	-10000	0	0
TAK1/TAB family	-0.15	0.11	-9999	-0.42	14	14
BMP7 (homodimer)	-0.24	0.38	-9999	-0.8	91	91
NUP214	0.012	0	-9999	-10000	0	0
BMP6/FETUA	-0.01	0.11	-9999	-0.64	8	8
SMAD1/SKI	-0.011	0.042	-9999	-10000	0	0
SMAD6	0.009	0.048	-9999	-0.81	1	1
CTDSP2	0.012	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.004	0.021	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.33	0.4	-9999	-0.81	120	120
BMPR2 (homodimer)	0.012	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.4	0.3	-9999	-0.62	187	187
CHRDL1	-0.33	0.4	-9999	-0.81	120	120
ENDOFIN/SMAD1	-0.011	0.042	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.019	0.029	-9999	-0.46	1	1
SMAD6/SMURF1	0.012	0	-9999	-10000	0	0
BAMBI	0.009	0.048	-9999	-0.81	1	1
SMURF2	0.012	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.22	0.26	-9999	-0.54	120	120
BMP2-4/GREM1	-0.22	0.26	-9999	-0.54	119	119
SMAD7	0.012	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.067	0.12	-9999	-0.56	12	12
SMAD1/SMAD6	-0.011	0.042	-9999	-10000	0	0
TAK1/SMAD6	0.018	0	-9999	-10000	0	0
BMP7	-0.24	0.38	-9999	-0.8	91	91
BMP6	-0.01	0.14	-9999	-0.81	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.14	0.13	-9999	-0.44	14	14
PPM1A	0.012	0	-9999	-10000	0	0
SMAD1/SMURF2	-0.011	0.042	-9999	-10000	0	0
SMAD7/SMURF1	0.018	0	-9999	-10000	0	0
CTDSPL	0.012	0	-9999	-10000	0	0
PPP1CA	0.012	0	-9999	-10000	0	0
XIAP	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
PPP1R15A	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.3	0.29	-9999	-0.73	72	72
CHRD	-0.04	0.2	-9999	-0.81	18	18
BMPR2	0.012	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.18	0.16	-9999	-0.51	16	16
BMP4	0.012	0	-9999	-10000	0	0
FST	-0.2	0.35	-9999	-0.81	70	70
BMP2-4/NOG	-0.004	0.034	-9999	-0.54	1	1
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.44	0.29	-9999	-0.56	225	225

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.002	0.065	-10000	0	-0.35	7	7
NFATC2	-0.042	0.24	-10000	0	-0.72	26	26
NFATC3	-0.023	0.11	-10000	0	-0.31	20	20
CD40LG	-0.19	0.45	-10000	0	-1	57	57
ITCH	0.037	0.05	-10000	0	-10000	0	0
CBLB	0.037	0.05	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.16	0.24	-10000	0	-0.79	17	17
JUNB	0.012	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.008	0.053	-10000	0	-0.34	7	7
T cell anergy	0.009	0.083	-10000	0	-0.44	7	7
TLE4	-0.007	0.17	-10000	0	-0.52	26	26
Jun/NFAT1-c-4/p21SNFT	-0.15	0.39	-10000	0	-0.94	48	48
AP-1/NFAT1-c-4	-0.24	0.56	-10000	0	-1.2	57	57
IKZF1	-0.018	0.18	-10000	0	-0.52	26	26
T-helper 2 cell differentiation	-0.5	0.32	-10000	0	-0.65	224	224
AP-1/NFAT1	-0.12	0.24	-10000	0	-0.59	53	53
CALM1	0.021	0.032	-10000	0	-10000	0	0
EGR2	-0.16	0.54	-10000	0	-1.2	45	45
EGR3	-0.22	0.61	-10000	0	-1.6	45	45
NFAT1/FOXP3	-0.03	0.18	-10000	0	-0.51	30	30
EGR1	-0.053	0.22	-10000	0	-0.81	23	23
JUN	0.009	0.018	-10000	0	-10000	0	0
EGR4	0.005	0.028	-10000	0	-0.25	3	3
mol:Ca2+	0.009	0.034	-10000	0	-10000	0	0
GBP3	-0.009	0.18	-10000	0	-0.53	27	27
FOSL1	0	0.068	-10000	0	-0.81	1	1
NFAT1-c-4/MAF/IRF4	-0.14	0.38	-10000	0	-0.92	48	48
DGKA	-0.011	0.18	-10000	0	-0.56	15	15
CREM	0.012	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.16	0.39	-10000	0	-0.96	48	48
CTLA4	-0.031	0.18	-10000	0	-0.53	15	15
NFAT1-c-4 (dimer)/EGR1	-0.17	0.47	-10000	0	-1.1	52	52
NFAT1-c-4 (dimer)/EGR4	-0.14	0.4	-10000	0	-0.97	48	48
FOS	-0.11	0.29	-10000	0	-0.83	41	41
IFNG	-0.095	0.18	-10000	0	-0.64	15	15
T cell activation	-0.095	0.27	-10000	0	-0.75	29	29
MAF	0.012	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	0.084	0.3	0.72	48	-10000	0	48
TNF	-0.14	0.41	-10000	0	-0.96	48	48
FASLG	-0.2	0.57	-10000	0	-1.4	48	48
TBX21	-0.004	0.069	-10000	0	-0.26	19	19
BATF3	0.011	0.016	-10000	0	-0.25	1	1
PRKCQ	-0.017	0.16	-10000	0	-0.81	11	11
PTPN1	-0.007	0.17	-10000	0	-0.58	12	12
NFAT1-c-4/ICER1	-0.16	0.39	-10000	0	-0.96	48	48
GATA3	-0.62	0.34	-10000	0	-0.81	224	224
T-helper 1 cell differentiation	-0.062	0.2	-10000	0	-0.62	16	16
IL2RA	-0.16	0.23	-10000	0	-0.69	22	22
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.007	0.17	-10000	0	-0.52	26	26
E2F1	-0.053	0.12	-10000	0	-10000	0	0
PPARG	0.011	0.016	-10000	0	-10000	0	0
SLC3A2	-0.007	0.17	-10000	0	-0.52	26	26
IRF4	-0.012	0.077	-10000	0	-0.25	27	27
PTGS2	-0.28	0.56	-10000	0	-1.1	84	84
CSF2	-0.2	0.45	-10000	0	-1	57	57
JunB/Fra1/NFAT1-c-4	-0.14	0.38	-10000	0	-0.93	48	48
IL4	-0.52	0.34	-10000	0	-0.67	224	224
IL5	-0.2	0.45	-10000	0	-1	57	57
IL2	-0.097	0.28	-10000	0	-0.78	28	28
IL3	-0.042	0.056	-10000	0	-10000	0	0
RNF128	0.022	0.14	-10000	0	-0.87	7	7
NFATC1	-0.084	0.3	-10000	0	-0.72	48	48
CDK4	0.036	0.2	0.59	3	-10000	0	3
PTPRK	-0.007	0.17	-10000	0	-0.57	14	14
IL8	-0.2	0.45	-10000	0	-1	57	57
POU2F1	0.012	0.001	-10000	0	-10000	0	0

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	-0.12	0.26	-9999	-0.63	59	59
PDGFRB	-0.024	0.16	-9999	-0.82	12	12
SPHK1	-0.061	0.054	-9999	-10000	0	0
mol:S1P	-0.06	0.058	-9999	-10000	0	0
S1P1/S1P/Gi	-0.14	0.25	-9999	-0.48	81	81
GNAO1	-0.047	0.21	-9999	-0.74	22	22
PDGFB-D/PDGFRB/PLCgamma1	-0.12	0.24	-9999	-0.59	42	42
PLCG1	-0.12	0.23	-9999	-0.52	55	55
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.024	0.16	-9999	-0.82	12	12
GNAI2	0.01	0.006	-9999	-10000	0	0
GNAI3	0.009	0.006	-9999	-10000	0	0
GNAI1	0.004	0.068	-9999	-0.81	2	2
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.1	0.22	-9999	-0.55	59	59
S1P1/S1P	-0.14	0.19	-9999	-0.5	59	59
negative regulation of cAMP metabolic process	-0.13	0.24	-9999	-0.46	81	81
MAPK3	-0.17	0.31	-9999	-0.64	77	77
calcium-dependent phospholipase C activity	-0.002	0.004	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
RhoA/GDP	0.009	0	-9999	-10000	0	0
KDR	-0.16	0.33	-9999	-0.81	59	59
PLCB2	-0.12	0.18	-9999	-0.44	59	59
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.12	0.16	-9999	-0.42	59	59
receptor internalization	-0.13	0.18	-9999	-0.46	59	59
PTGS2	-0.27	0.49	-9999	-1.1	76	76
Rac1/GTP	-0.12	0.16	-9999	-0.42	59	59
RHOA	0.012	0	-9999	-10000	0	0
VEGFA	0.008	0.027	-9999	-0.25	3	3
negative regulation of T cell proliferation	-0.13	0.24	-9999	-0.46	81	81
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.009	0.006	-9999	-10000	0	0
MAPK1	-0.17	0.31	-9999	-0.65	76	76
S1P1/S1P/PDGFB-D/PDGFRB	-0.14	0.23	-9999	-0.53	65	65
ABCC1	0.011	0.003	-9999	-10000	0	0

×

amb2 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.044	0.084	-9999	-0.42	3	3
alphaM/beta2 Integrin/GPIbA	-0.043	0.089	-9999	-0.55	2	2
alphaM/beta2 Integrin/proMMP-9	-0.096	0.12	-9999	-0.4	24	24
PLAUR	0.001	0.053	-9999	-10000	0	0
HMGB1	0.005	0.02	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.041	0.078	-9999	-0.34	1	1
AGER	-0.038	0.1	-9999	-0.27	46	46
RAP1A	0.012	0	-9999	-10000	0	0
SELPLG	-0.016	0.082	-9999	-10000	0	0
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.083	0.1	-9999	-0.38	5	5
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.099	0.15	-9999	-0.27	115	115
CYR61	-0.036	0.19	-9999	-0.81	17	17
TLN1	0.012	0	-9999	-10000	0	0
Rap1/GTP	-0.16	0.14	-9999	-0.45	31	31
RHOA	0.012	0	-9999	-10000	0	0
P-selectin oligomer	-0.095	0.28	-9999	-0.81	38	38
MYH2	-0.22	0.21	-9999	-0.46	80	80
MST1R	-0.022	0.1	-9999	-0.81	2	2
leukocyte activation during inflammatory response	-0.064	0.12	-9999	-0.49	16	16
APOB	-0.044	0.19	-9999	-0.81	15	15
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.008	0.053	-9999	-0.81	1	1
JAM3	0.004	0.083	-9999	-0.81	3	3
GP1BA	0.008	0.051	-9999	-0.53	2	2
alphaM/beta2 Integrin/CTGF	-0.056	0.12	-9999	-0.53	9	9
alphaM/beta2 Integrin	-0.19	0.17	-9999	-0.36	102	102
JAM3 homodimer	0.004	0.083	-9999	-0.81	3	3
ICAM2	0.012	0	-9999	-10000	0	0
ICAM1	0.012	0	-9999	-10000	0	0
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.19	0.17	-9999	-0.36	102	102
cell adhesion	-0.043	0.088	-9999	-0.55	2	2
NFKB1	-0.079	0.18	-9999	-0.52	16	16
THY1	-0.19	0.35	-9999	-0.81	70	70
RhoA/GDP	0.009	0	-9999	-10000	0	0
Lipoprotein(a)	-0.037	0.12	-9999	-0.55	15	15
alphaM/beta2 Integrin/LRP/tPA	-0.1	0.18	-9999	-0.52	41	41
IL6	-0.17	0.38	-9999	-0.97	51	51
ITGB2	-0.038	0.097	-9999	-0.25	47	47
elevation of cytosolic calcium ion concentration	-0.059	0.12	-9999	-0.52	12	12
alphaM/beta2 Integrin/JAM2/JAM3	-0.052	0.11	-9999	-0.51	11	11
JAM2	-0.01	0.14	-9999	-0.81	8	8
alphaM/beta2 Integrin/ICAM1	-0.048	0.082	-9999	-0.45	4	4
alphaM/beta2 Integrin/uPA/Plg	-0.32	0.27	-9999	-0.55	162	162
RhoA/GTP	-0.24	0.22	-9999	-0.44	103	103
positive regulation of phagocytosis	-0.15	0.13	-9999	-0.41	35	35
Ron/MSP	-0.015	0.091	-9999	-0.5	5	5
alphaM/beta2 Integrin/uPAR/uPA	-0.059	0.13	-9999	-0.53	12	12
alphaM/beta2 Integrin/uPAR	-0.047	0.09	-9999	-0.37	7	7
PLAU	-0.022	0.16	-9999	-0.81	12	12
PLAT	-0.1	0.29	-9999	-0.81	41	41
actin filament polymerization	-0.22	0.2	-9999	-0.44	80	80
MST1	-0.002	0.073	-9999	-0.29	14	14
alphaM/beta2 Integrin/lipoprotein(a)	-0.065	0.12	-9999	-0.49	16	16
TNF	-0.076	0.2	-9999	-0.75	7	7
RAP1B	0.012	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.064	0.13	-9999	-0.56	13	13
fibrinolysis	-0.32	0.27	-9999	-0.54	162	162
HCK	-0.014	0.089	-9999	-0.27	27	27
dendritic cell antigen processing and presentation	-0.19	0.17	-9999	-0.36	102	102
VTN	-0.13	0.3	-9999	-0.81	46	46
alphaM/beta2 Integrin/CYR61	-0.073	0.15	-9999	-0.57	18	18
LPA	0.001	0.031	-9999	-10000	0	0
LRP1	0.012	0	-9999	-10000	0	0
cell migration	-0.07	0.12	-9999	-0.37	24	24
FN1	-0.001	0.057	-9999	-0.25	14	14
alphaM/beta2 Integrin/Thy1	-0.17	0.23	-9999	-0.56	71	71
MPO	-0.001	0.057	-9999	-10000	0	0
KNG1	-0.47	0.4	-9999	-0.81	169	169
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.22	0.21	-9999	-0.49	62	62
ELA2	0	0	-9999	-10000	0	0
PLG	-0.43	0.41	-9999	-0.81	154	154
CTGF	-0.01	0.14	-9999	-0.81	8	8
alphaM/beta2 Integrin/Hck	-0.055	0.11	-9999	-0.39	21	21
ITGAM	-0.024	0.082	-9999	-0.3	1	1
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.11	0.18	-9999	-0.45	56	56
HP	-0.023	0.088	-9999	-0.25	37	37
leukocyte adhesion	-0.18	0.23	-9999	-0.53	73	73
SELP	-0.096	0.28	-9999	-0.81	38	38

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.012	0.027	-10000	0	-10000	0	0
CDKN2C	0.029	0.018	-10000	0	-10000	0	0
CDKN2A	-0.2	0.11	-10000	0	-0.26	231	231
CCND2	0.041	0.028	0.15	2	-10000	0	2
RB1	-0.044	0.033	-10000	0	-10000	0	0
CDK4	0.052	0.029	-10000	0	-10000	0	0
CDK6	0.048	0.028	-10000	0	-10000	0	0
G1/S progression	0.044	0.033	-10000	0	-10000	0	0

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.01	0.022	-9999	-0.25	2	2
CCL5	-0.02	0.087	-9999	-10000	0	0
SDCBP	0.012	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.094	0.16	-9999	-0.39	56	56
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.083	0.16	-9999	-0.46	22	22
Syndecan-1/Syntenin	-0.083	0.16	-9999	-0.42	29	29
MAPK3	-0.063	0.15	-9999	-0.53	8	8
HGF/MET	-0.072	0.22	-9999	-0.65	34	34
TGFB1/TGF beta receptor Type II	0.01	0.022	-9999	-0.25	2	2
BSG	0.012	0	-9999	-10000	0	0
keratinocyte migration	-0.082	0.16	-9999	-0.45	22	22
Syndecan-1/RANTES	-0.097	0.16	-9999	-0.45	26	26
Syndecan-1/CD147	-0.074	0.15	-9999	-0.44	22	22
Syndecan-1/Syntenin/PIP2	-0.081	0.15	-9999	-0.41	29	29
LAMA5	0.012	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.093	0.14	-9999	-0.4	29	29
MMP7	-0.037	0.14	-9999	-0.34	41	41
HGF	-0.084	0.26	-9999	-0.81	34	34
Syndecan-1/CASK	-0.091	0.16	-9999	-0.37	56	56
Syndecan-1/HGF/MET	-0.14	0.22	-9999	-0.52	55	55
regulation of cell adhesion	-0.055	0.14	-9999	-0.51	8	8
HPSE	-0.037	0.19	-9999	-0.81	17	17
positive regulation of cell migration	-0.094	0.16	-9999	-0.39	56	56
SDC1	-0.095	0.17	-9999	-0.39	56	56
Syndecan-1/Collagen	-0.094	0.16	-9999	-0.39	56	56
PPIB	0.012	0	-9999	-10000	0	0
MET	-0.012	0.077	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
MMP9	-0.099	0.15	-9999	-0.27	115	115
MAPK1	-0.063	0.15	-9999	-0.53	8	8
homophilic cell adhesion	-0.094	0.16	-9999	-0.38	56	56
MMP1	-0.13	0.3	-9999	-0.72	58	58

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.11	0.26	-9999	-0.62	59	59
alphaV beta3 Integrin	-0.045	0.15	-9999	-0.56	22	22
PTK2	-0.15	0.27	-9999	-0.65	41	41
IGF1R	0.012	0	-9999	-10000	0	0
PI4KB	0.012	0	-9999	-10000	0	0
MFGE8	0.009	0.048	-9999	-0.81	1	1
SRC	0.011	0.016	-9999	-10000	0	0
CDKN1B	-0.11	0.22	-9999	-0.61	46	46
VEGFA	0.01	0.027	-9999	-0.25	3	3
ILK	-0.11	0.22	-9999	-0.61	46	46
ROCK1	0.012	0	-9999	-10000	0	0
AKT1	-0.08	0.22	-9999	-0.56	46	46
PTK2B	-0.094	0.22	-9999	-0.48	72	72
alphaV/beta3 Integrin/JAM-A	-0.087	0.22	-9999	-0.48	67	67
CBL	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.38	0.28	-9999	-0.56	195	195
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.005	0.12	-9999	-0.49	15	15
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.098	0.21	-9999	-0.65	23	23
alphaV/beta3 Integrin/Syndecan-1	-0.032	0.13	-9999	-0.57	15	15
PI4KA	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.06	0.16	-9999	-0.48	33	33
PI4 Kinase	0.018	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.042	0.15	-9999	-0.59	18	18
RPS6KB1	-0.012	0.17	-9999	-0.73	6	6
TLN1	0.012	0	-9999	-10000	0	0
MAPK3	-0.05	0.2	-9999	-0.64	22	22
GPR124	0.009	0.048	-9999	-0.81	1	1
MAPK1	-0.05	0.2	-9999	-0.64	22	22
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.059	0.18	-9999	-0.61	27	27
cell adhesion	-0.3	0.23	-9999	-0.44	195	195
ANGPTL3	-0.52	0.39	-9999	-0.81	188	188
VEGFR2 homodimer/VEGFA homodimer/Src	-0.11	0.22	-9999	-0.54	59	59
IGF-1R heterotetramer	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
TGFBR2	0.012	0	-9999	-10000	0	0
ITGB3	-0.036	0.18	-9999	-0.81	15	15
IGF1	-0.016	0.15	-9999	-0.81	10	10
RAC1	0.012	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.034	0.13	-9999	-0.56	16	16
apoptosis	0.009	0.048	-9999	-0.81	1	1
CD47	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.032	0.13	-9999	-0.57	15	15
VCL	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.12	0.25	-9999	-0.6	59	59
CSF1	0.005	0.071	-9999	-0.81	2	2
PIK3C2A	-0.11	0.22	-9999	-0.61	46	46
PI4 Kinase/Pyk2	-0.17	0.24	-9999	-0.73	24	24
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.24	-9999	-0.51	72	72
FAK1/Vinculin	-0.11	0.21	-9999	-0.51	36	36
alphaV beta3/Integrin/ppsTEM5	-0.034	0.13	-9999	-0.57	16	16
RHOA	0.012	0	-9999	-10000	0	0
VTN	-0.13	0.3	-9999	-0.81	46	46
BCAR1	0.012	0	-9999	-10000	0	0
FGF2	-0.008	0.13	-9999	-0.81	7	7
F11R	0.006	0.099	-9999	-0.62	7	7
alphaV/beta3 Integrin/Lactadherin	-0.034	0.13	-9999	-0.57	16	16
alphaV/beta3 Integrin/TGFBR2	-0.032	0.13	-9999	-0.57	15	15
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.025	0.054	-9999	-0.49	3	3
HSP90AA1	0.012	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.007	0.13	-9999	-0.53	15	15
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.001	0.057	-9999	-0.25	14	14
alphaV/beta3 Integrin/Pyk2	-0.094	0.22	-9999	-0.48	72	72
SDC1	0.011	0.016	-9999	-10000	0	0
VAV3	0.029	0.058	-9999	-0.46	4	4
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
FAK1/Paxillin	-0.11	0.21	-9999	-0.51	36	36
cell migration	-0.09	0.2	-9999	-0.45	36	36
ITGAV	0.009	0.048	-9999	-0.81	1	1
PI3K	-0.1	0.18	-9999	-0.6	7	7
SPP1	-0.005	0.1	-9999	-0.81	4	4
KDR	-0.16	0.33	-9999	-0.81	59	59
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.009	0.048	-9999	-0.81	1	1
COL4A3	-0.03	0.18	-9999	-0.81	15	15
angiogenesis	-0.067	0.22	-9999	-0.63	23	23
Rac1/GTP	0.033	0.054	-9999	-0.42	4	4
EDIL3	-0.13	0.31	-9999	-0.81	50	50
cell proliferation	-0.032	0.13	-9999	-0.57	15	15

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.044	0.11	-9999	-10000	0	0
GPC2	-0.1	0.13	-9999	-10000	0	0
GPC2/Midkine	-0.091	0.12	-9999	-0.32	43	43
neuron projection morphogenesis	-0.091	0.12	-9999	-0.32	43	43

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.004	0.1	-10000	0	-0.33	27	27
epithelial cell differentiation	-0.043	0.13	-10000	0	-0.46	27	27
CYFIP2	0.007	0.068	-10000	0	-0.81	2	2
ENAH	0.03	0.095	-10000	0	-10000	0	0
EGFR	0.012	0	-10000	0	-10000	0	0
EPHA2	0.011	0.016	-10000	0	-10000	0	0
MYO6	-0.009	0.14	-10000	0	-0.44	27	27
CTNNB1	0.012	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.045	-10000	0	-0.54	2	2
AQP5	-0.093	0.21	-10000	0	-0.63	29	29
CTNND1	0.012	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.008	0.14	-10000	0	-0.43	27	27
regulation of calcium-dependent cell-cell adhesion	-0.047	0.2	-10000	0	-0.48	46	46
EGF	-0.73	0.24	-10000	0	-0.81	262	262
NCKAP1	0.012	0	-10000	0	-10000	0	0
AQP3	-0.26	0.31	-10000	0	-0.63	113	113
cortical microtubule organization	-0.043	0.13	-10000	0	-0.46	27	27
GO:0000145	-0.008	0.13	-10000	0	-0.41	27	27
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.043	0.14	-10000	0	-0.46	27	27
MLLT4	0.012	0	-10000	0	-10000	0	0
ARF6/GDP	-0.034	0.1	-10000	0	-10000	0	0
ARF6	0.012	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.031	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.004	0.13	-10000	0	-10000	0	0
PVRL2	0.012	0	-10000	0	-10000	0	0
ZYX	-0.009	0.14	-10000	0	-0.44	27	27
ARF6/GTP	0	0.005	-10000	0	-10000	0	0
CDH1	-0.064	0.24	-10000	0	-0.81	27	27
EGFR/EGFR/EGF/EGF	-0.42	0.17	-10000	0	-0.46	267	267
RhoA/GDP	-0.04	0.12	-10000	0	-0.43	27	27
actin cytoskeleton organization	-0.002	0.13	-10000	0	-0.41	27	27
IGF-1R heterotetramer	0.012	0	-10000	0	-10000	0	0
GIT1	0.012	0	-10000	0	-10000	0	0
IGF1R	0.012	0	-10000	0	-10000	0	0
IGF1	-0.016	0.15	-10000	0	-0.81	10	10
DIAPH1	-0.007	0.054	-10000	0	-0.65	2	2
Wnt receptor signaling pathway	0.043	0.13	0.46	27	-10000	0	27
RHOA	0.012	0	-10000	0	-10000	0	0
RhoA/GTP	-0.034	0.11	-10000	0	-10000	0	0
CTNNA1	0.012	0	-10000	0	-10000	0	0
VCL	-0.003	0.14	-10000	0	-0.42	27	27
EFNA1	0.012	0	-10000	0	-10000	0	0
LPP	-0.001	0.13	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.039	0.12	-10000	0	-0.42	27	27
SEC6/SEC8	-0.036	0.11	-10000	0	-10000	0	0
MGAT3	-0.048	0.2	-10000	0	-0.49	46	46
HGF/MET	-0.096	0.19	-10000	0	-0.47	56	56
HGF	-0.084	0.26	-10000	0	-0.81	34	34
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.004	0.1	-10000	0	-0.33	27	27
actin cable formation	0.045	0.092	-10000	0	-10000	0	0
KIAA1543	-0.003	0.13	-10000	0	-0.41	28	28
KIFC3	-0.009	0.14	-10000	0	-0.44	27	27
NCK1	0.012	0	-10000	0	-10000	0	0
EXOC3	0.012	0	-10000	0	-10000	0	0
ACTN1	-0.009	0.14	-10000	0	-0.44	27	27
NCK1/GIT1	0.018	0	-10000	0	-10000	0	0
mol:GDP	-0.043	0.13	-10000	0	-0.46	27	27
EXOC4	0.012	0	-10000	0	-10000	0	0
STX4	-0.009	0.14	-10000	0	-0.44	27	27
PIP5K1C	-0.009	0.14	-10000	0	-0.44	27	27
LIMA1	0.012	0	-10000	0	-10000	0	0
ABI1	0.012	0	-10000	0	-10000	0	0
ROCK1	0.022	0.11	-10000	0	-10000	0	0
adherens junction assembly	0.014	0.13	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.054	0.14	-10000	0	-0.43	36	36
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0	-10000	0	-10000	0	0
MET	-0.012	0.077	-10000	0	-10000	0	0
PLEKHA7	-0.01	0.14	-10000	0	-0.44	28	28
mol:GTP	0	0.006	-10000	0	-10000	0	0
establishment of epithelial cell apical/basal polarity	0.018	0.12	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	-0.004	0.1	-10000	0	-0.33	27	27
regulation of cell-cell adhesion	-0.002	0.13	-10000	0	-0.41	27	27
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.004	0.1	-10000	0	-0.33	27	27

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.012	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.034	0.12	-10000	0	-0.34	6	6
NT3 (dimer)/TRKC	-0.15	0.3	-10000	0	-0.66	71	71
NT3 (dimer)/TRKB	-0.31	0.32	-10000	0	-0.59	151	151
SHC/Grb2/SOS1/GAB1/PI3K	0.035	0	-10000	0	-10000	0	0
RAPGEF1	0.012	0	-10000	0	-10000	0	0
BDNF	-0.012	0.086	-10000	0	-0.28	24	24
PIK3CA	0.012	0	-10000	0	-10000	0	0
DYNLT1	0.012	0	-10000	0	-10000	0	0
NTRK1	-0.061	0.23	-10000	0	-0.81	25	25
NTRK2	-0.35	0.41	-10000	0	-0.81	129	129
NTRK3	-0.12	0.3	-10000	0	-0.81	47	47
NT-4/5 (dimer)/TRKB	-0.26	0.28	-10000	0	-0.56	135	135
neuron apoptosis	0.13	0.18	0.55	25	-10000	0	25
SHC 2-3/Grb2	-0.14	0.2	-10000	0	-0.61	25	25
SHC1	0.012	0	-10000	0	-10000	0	0
SHC2	-0.12	0.16	-10000	0	-0.54	22	22
SHC3	-0.14	0.2	-10000	0	-0.66	25	25
STAT3 (dimer)	0.018	0.024	-10000	0	-0.38	1	1
NT3 (dimer)/TRKA	-0.12	0.25	-10000	0	-0.59	57	57
RIN/GDP	-0.014	0.088	-10000	0	-0.28	3	3
GIPC1	0.012	0	-10000	0	-10000	0	0
KRAS	0.012	0	-10000	0	-10000	0	0
DNAJA3	-0.049	0.14	-10000	0	-0.37	38	38
RIN/GTP	0	0.01	-10000	0	-10000	0	0
CCND1	0.025	0.061	-10000	0	-1	1	1
MAGED1	0.012	0	-10000	0	-10000	0	0
PTPN11	0.012	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.013	0.069	-10000	0	-0.25	22	22
SHC/GRB2/SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.078	0.18	-10000	0	-0.56	33	33
TRKA/NEDD4-2	-0.04	0.18	-10000	0	-0.62	26	26
ELMO1	0.012	0	-10000	0	-10000	0	0
RhoG/GTP/ELMO1/DOCK1	0	0	-10000	0	-10000	0	0
NGF	-0.015	0.14	-10000	0	-0.71	11	11
HRAS	0.011	0.016	-10000	0	-10000	0	0
DOCK1	0.012	0	-10000	0	-10000	0	0
GAB2	0.012	0	-10000	0	-10000	0	0
RIT2	0	0.015	-10000	0	-10000	0	0
RIT1	0.012	0	-10000	0	-10000	0	0
FRS2	0.012	0	-10000	0	-10000	0	0
DNM1	-0.11	0.13	-10000	0	-0.25	132	132
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.012	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.047	0.13	-10000	0	-0.36	38	38
mol:GDP	-0.023	0.13	-10000	0	-0.35	11	11
NGF (dimer)	-0.015	0.14	-10000	0	-0.71	11	11
RhoG/GDP	0.009	0	-10000	0	-10000	0	0
RIT1/GDP	-0.009	0.089	-10000	0	-0.28	3	3
TIAM1	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.25	0.26	-10000	0	-0.54	130	130
KIDINS220/CRKL/C3G	0.018	0	-10000	0	-10000	0	0
SHC/RasGAP	0.018	0	-10000	0	-10000	0	0
FRS2 family/SHP2	-0.001	0.012	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.032	0	-10000	0	-10000	0	0
RIT1/GTP	0.009	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.073	0.25	-10000	0	-0.81	30	30
RAP1/GDP	-0.033	0.059	-10000	0	-0.26	1	1
KIDINS220/CRKL	0.012	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.012	0.086	-10000	0	-0.28	24	24
ubiquitin-dependent protein catabolic process	-0.065	0.18	-10000	0	-0.55	34	34
Schwann cell development	-0.044	0.036	-10000	0	-10000	0	0
EHD4	0.012	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.03	0.013	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.037	0.009	-10000	0	-10000	0	0
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.29	0.28	-10000	0	-0.5	170	170
ABL1	0.012	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
Rap1/GTP	-0.084	0.092	-10000	0	-10000	0	0
STAT3	0.018	0.024	-10000	0	-0.38	1	1
axon guidance	-0.28	0.26	-10000	0	-0.47	170	170
MAPK3	-0.047	0.17	-10000	0	-0.51	33	33
MAPK1	-0.047	0.17	-10000	0	-0.51	33	33
CDC42/GDP	-0.009	0.089	-10000	0	-0.28	3	3
NTF3	-0.074	0.25	-10000	0	-0.81	30	30
NTF4	-0.013	0.069	-10000	0	-0.25	22	22
NGF (dimer)/TRKA/FAIM	-0.065	0.18	-10000	0	-0.56	33	33
PI3K	0.018	0	-10000	0	-10000	0	0
FRS3	0.01	0.027	-10000	0	-10000	0	0
FAIM	0.01	0.022	-10000	0	-10000	0	0
GAB1	0.012	0	-10000	0	-10000	0	0
RASGRF1	-0.053	0.14	-10000	0	-0.54	12	12
SOS1	0.012	0	-10000	0	-10000	0	0
MCF2L	-0.12	0.27	-10000	0	-0.58	71	71
RGS19	0.01	0.027	-10000	0	-0.25	3	3
CDC42	0.012	0	-10000	0	-10000	0	0
RAS family/GTP	0.036	0.053	-10000	0	-10000	0	0
Rac1/GDP	-0.009	0.089	-10000	0	-0.28	3	3
NGF (dimer)/TRKA/GRIT	-0.065	0.18	-10000	0	-0.56	33	33
neuron projection morphogenesis	-0.013	0.13	-10000	0	-0.54	8	8
NGF (dimer)/TRKA/NEDD4-2	-0.066	0.18	-10000	0	-0.56	34	34
MAP2K1	0.036	0	-10000	0	-10000	0	0
NGFR	-0.011	0.14	-10000	0	-0.81	8	8
NGF (dimer)/TRKA/GIPC/GAIP	-0.049	0.13	-10000	0	-0.39	33	33
RAS family/GTP/PI3K	0.029	0.005	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.001	0.009	-10000	0	-10000	0	0
NRAS	0.012	0	-10000	0	-10000	0	0
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
PRKCI	0.012	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.012	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.084	0.21	-10000	0	-0.65	33	33
RASA1	0.012	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.038	0.18	-10000	0	-0.62	25	25
SQSTM1	0.004	0.046	-10000	0	-0.25	9	9
BDNF (dimer)/TRKB/GIPC	-0.21	0.26	-10000	0	-0.5	130	130
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.057	0.15	-10000	0	-0.48	33	33
MATK	-0.019	0.085	-10000	0	-0.25	34	34
NEDD4L	0.009	0.048	-10000	0	-0.81	1	1
RAS family/GDP	-0.032	0.057	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.052	0.14	-10000	0	-0.4	38	38
Rac1/GTP	-0.053	0.089	-10000	0	-0.37	8	8
FRS2 family/SHP2/CRK family	-0.001	0.009	-10000	0	-10000	0	0

×

Noncanonical Wnt signaling pathway

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
NFATC2	-0.062	0.24	-9999	-0.81	26	26
GNB1/GNG2	-0.015	0.13	-9999	-0.44	7	7
mol:DAG	-0.007	0.12	-9999	-0.4	7	7
PLCG1	-0.007	0.12	-9999	-0.41	7	7
YES1	-0.023	0.13	-9999	-0.33	42	42
FZD3	0.012	0	-9999	-10000	0	0
FZD6	0.012	0	-9999	-10000	0	0
G protein	-0.008	0.12	-9999	-0.5	3	3
MAP3K7	-0.14	0.22	-9999	-0.41	104	104
mol:Ca2+	-0.006	0.12	-9999	-0.39	7	7
mol:IP3	-0.007	0.12	-9999	-0.4	7	7
NLK	-0.009	0.012	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
CAMK2A	-0.16	0.24	-9999	-0.44	104	104
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.032	0.14	-9999	-0.36	42	42
CSNK1A1	0.012	0	-9999	-10000	0	0
GNAS	-0.023	0.13	-9999	-0.46	7	7
GO:0007205	-0.006	0.12	-9999	-0.39	7	7
WNT6	0.01	0.016	-9999	-10000	0	0
WNT4	-0.021	0.16	-9999	-0.81	11	11
NFAT1/CK1 alpha	-0.043	0.17	-9999	-0.43	28	28
GNG2	0.012	0	-9999	-10000	0	0
WNT5A	-0.02	0.087	-9999	-0.25	35	35
WNT11	-0.083	0.26	-9999	-0.81	33	33
CDC42	-0.015	0.13	-9999	-0.43	7	7

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.022	0.16	-10000	0	-0.81	12	12
Jak2/Leptin Receptor	-0.13	0.15	-10000	0	-0.43	23	23
PTP1B/AKT1	-0.075	0.065	-10000	0	-0.31	4	4
FYN	0.012	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.092	0.072	-10000	0	-0.33	16	16
EGFR	0.001	0.004	-10000	0	-10000	0	0
EGF/EGFR	-0.44	0.13	-10000	0	-0.48	262	262
CSF1	0.005	0.071	-10000	0	-0.81	2	2
AKT1	0.012	0.001	-10000	0	-10000	0	0
INSR	0.012	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.1	0.12	-10000	0	-0.45	26	26
Insulin Receptor/Insulin	-0.05	0.049	-10000	0	-10000	0	0
HCK	-0.014	0.089	-10000	0	-0.27	27	27
CRK	0.012	0	-10000	0	-10000	0	0
TYK2	-0.08	0.069	-10000	0	-0.31	15	15
EGF	-0.74	0.24	-10000	0	-0.82	262	262
YES1	0.012	0	-10000	0	-10000	0	0
CAV1	-0.18	0.075	-10000	0	-0.34	26	26
TXN	-0.002	0.031	-10000	0	-0.26	4	4
PTP1B/IRS1/GRB2	-0.079	0.094	-10000	0	-0.46	9	9
cell migration	0.092	0.072	0.33	16	-10000	0	16
STAT3	0.012	0.001	-10000	0	-10000	0	0
PRLR	-0.24	0.38	-10000	0	-0.81	88	88
ITGA2B	-0.004	0.071	-10000	0	-0.81	1	1
CSF1R	0.001	0.066	-10000	0	-0.81	1	1
Prolactin Receptor/Prolactin	-0.19	0.29	-10000	0	-0.63	88	88
FGR	0.001	0.066	-10000	0	-0.81	1	1
PTP1B/p130 Cas	-0.081	0.069	-10000	0	-0.31	16	16
Crk/p130 Cas	-0.071	0.067	-10000	0	-0.32	2	2
DOK1	-0.075	0.082	-10000	0	-0.34	13	13
JAK2	-0.14	0.15	-10000	0	-0.36	87	87
Jak2/Leptin Receptor/Leptin	-0.09	0.096	-10000	0	-0.61	3	3
PIK3R1	0.012	0	-10000	0	-10000	0	0
PTPN1	-0.093	0.073	-10000	0	-0.34	16	16
LYN	0.012	0	-10000	0	-10000	0	0
CDH2	-0.024	0.16	-10000	0	-0.81	12	12
SRC	-0.024	0.028	-10000	0	-10000	0	0
ITGB3	-0.037	0.18	-10000	0	-0.81	15	15
CAT1/PTP1B	-0.24	0.14	-10000	0	-0.42	46	46
CAPN1	0.01	0.002	-10000	0	-10000	0	0
CSK	0.012	0	-10000	0	-10000	0	0
PI3K	-0.036	0.046	-10000	0	-10000	0	0
mol:H2O2	-0.007	0.004	-10000	0	-10000	0	0
STAT3 (dimer)	-0.081	0.092	-10000	0	-0.63	3	3
negative regulation of transcription	-0.14	0.15	-10000	0	-0.35	87	87
FCGR2A	0.002	0.051	-10000	0	-0.25	11	11
FER	0.001	0.004	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.044	0.15	-10000	0	-0.63	16	16
BLK	-0.002	0.057	-10000	0	-0.25	14	14
Insulin Receptor/Insulin/Shc	0.001	0.013	-10000	0	-10000	0	0
RHOA	0.01	0.002	-10000	0	-10000	0	0
LEPR	0.01	0.048	-10000	0	-0.81	1	1
BCAR1	0.012	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.012	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.18	0.14	-10000	0	-0.4	28	28
PRL	0.001	0.004	-10000	0	-10000	0	0
SOCS3	0.017	0.12	-10000	0	-1.4	2	2
SPRY2	0.006	0.004	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.009	0.073	-10000	0	-0.55	5	5
CSF1/CSF1R	-0.08	0.091	-10000	0	-0.5	6	6
Ras protein signal transduction	0.044	0.02	-10000	0	-10000	0	0
IRS1	-0.002	0.11	-10000	0	-0.81	5	5
INS	-0.002	0.026	-10000	0	-10000	0	0
LEP	-0.027	0.088	-10000	0	-10000	0	0
STAT5B	-0.11	0.09	-10000	0	-0.32	23	23
STAT5A	-0.11	0.09	-10000	0	-0.32	23	23
GRB2	0.012	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.1	0.11	-10000	0	-0.41	27	27
CSN2	-0.042	0.099	-10000	0	-10000	0	0
PIK3CA	0.012	0	-10000	0	-10000	0	0
LAT	-0.044	0.048	-10000	0	-10000	0	0
YBX1	0.015	0.002	-10000	0	-10000	0	0
LCK	0.004	0.073	-10000	0	-0.81	2	2
SHC1	0.012	0	-10000	0	-10000	0	0
NOX4	-0.06	0.22	-10000	0	-0.82	23	23

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.012	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.036	0.066	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.013	0.014	-9999	-10000	0	0
AURKB	-0.11	0.13	-9999	-0.25	132	132
AURKC	0.012	0.001	-9999	-10000	0	0

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.016	0.038	-9999	-10000	0	0
Syndecan-4/Syndesmos	-0.21	0.19	-9999	-0.53	20	20
positive regulation of JNK cascade	-0.24	0.21	-9999	-0.56	50	50
Syndecan-4/ADAM12	-0.22	0.19	-9999	-0.54	27	27
CCL5	-0.02	0.087	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DNM2	0.012	0	-9999	-10000	0	0
ITGA5	0.012	0	-9999	-10000	0	0
SDCBP	0.012	0	-9999	-10000	0	0
PLG	-0.42	0.4	-9999	-0.8	154	154
ADAM12	-0.017	0.083	-9999	-0.25	32	32
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.057	0.042	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.22	0.2	-9999	-0.57	28	28
Syndecan-4/CXCL12/CXCR4	-0.26	0.22	-9999	-0.6	50	50
Syndecan-4/Laminin alpha3	-0.24	0.19	-9999	-0.52	35	35
MDK	-0.044	0.11	-9999	-10000	0	0
Syndecan-4/FZD7	-0.22	0.2	-9999	-0.56	28	28
Syndecan-4/Midkine	-0.23	0.19	-9999	-0.54	28	28
FZD7	-0.016	0.15	-9999	-0.81	10	10
Syndecan-4/FGFR1/FGF	-0.21	0.17	-9999	-0.61	10	10
THBS1	-0.033	0.19	-9999	-0.81	16	16
integrin-mediated signaling pathway	-0.22	0.19	-9999	-0.54	28	28
positive regulation of MAPKKK cascade	-0.24	0.21	-9999	-0.56	50	50
Syndecan-4/TACI	-0.22	0.19	-9999	-0.54	24	24
CXCR4	-0.006	0.067	-9999	-0.25	20	20
cell adhesion	0.035	0.023	-9999	-10000	0	0
Syndecan-4/Dynamin	-0.21	0.19	-9999	-0.53	20	20
Syndecan-4/TSP1	-0.23	0.21	-9999	-0.59	32	32
Syndecan-4/GIPC	-0.21	0.19	-9999	-0.53	20	20
Syndecan-4/RANTES	-0.22	0.19	-9999	-0.54	28	28
ITGB1	0.012	0	-9999	-10000	0	0
LAMA1	-0.02	0.14	-9999	-0.81	8	8
LAMA3	-0.057	0.12	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
PRKCA	0.072	0.051	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.21	0.19	-9999	-0.53	20	20
TFPI	0.002	0.086	-9999	-0.59	5	5
F2	-0.037	0.097	-9999	-0.26	10	10
alpha5/beta1 Integrin	0.018	0	-9999	-10000	0	0
positive regulation of cell adhesion	-0.24	0.2	-9999	-0.53	46	46
ACTN1	0.012	0	-9999	-10000	0	0
TNC	-0.022	0.15	-9999	-0.81	9	9
Syndecan-4/CXCL12	-0.26	0.23	-9999	-0.59	55	55
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
CXCL12	-0.09	0.27	-9999	-0.81	36	36
TNFRSF13B	-0.009	0.063	-9999	-10000	0	0
FGF2	-0.008	0.13	-9999	-0.81	7	7
FGFR1	0.012	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.21	0.19	-9999	-0.44	76	76
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.001	0.055	-9999	-0.24	14	14
cell migration	-0.016	0.012	-9999	-10000	0	0
PRKCD	0.014	0.011	-9999	-10000	0	0
vasculogenesis	-0.22	0.2	-9999	-0.56	32	32
SDC4	-0.22	0.2	-9999	-0.46	76	76
Syndecan-4/Tenascin C	-0.22	0.2	-9999	-0.57	27	27
Syndecan-4/PI-4-5-P2/PKC alpha	-0.045	0.033	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.21	0.19	-9999	-0.53	20	20
MMP9	-0.094	0.15	-9999	-0.29	52	52
Rac1/GTP	0.035	0.023	-9999	-10000	0	0
cytoskeleton organization	-0.2	0.18	-9999	-0.51	20	20
GIPC1	0.012	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.21	0.19	-9999	-0.52	23	23

×

Signaling events regulated by Ret tyrosine kinase

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	-0.019	0.045	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.051	0.12	-9999	-0.46	6	6
JUN	-0.017	0.14	-9999	-0.54	8	8
HRAS	0.011	0.016	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.055	0.19	-9999	-0.52	41	41
RAP1A	0.012	0	-9999	-10000	0	0
FRS2	0.012	0	-9999	-10000	0	0
RAP1A/GDP	0.009	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.056	0.2	-9999	-0.52	41	41
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.029	0.14	-9999	-0.5	24	24
RHOA	0.012	0	-9999	-10000	0	0
RAP1A/GTP	-0.068	0.16	-9999	-0.46	41	41
GRB7	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	-0.055	0.19	-9999	-0.52	41	41
MAPKKK cascade	-0.061	0.15	-9999	-0.42	41	41
BCAR1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.037	0.17	-9999	-0.54	27	27
lamellipodium assembly	-0.046	0.11	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/SHC	-0.055	0.19	-9999	-0.52	41	41
PIK3CA	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.029	0.14	-9999	-0.5	24	24
RET9/GFRalpha1/GDNF/Shank3	-0.029	0.14	-9999	-0.5	24	24
MAPK3	-0.034	0.17	-9999	-0.44	41	41
DOK1	0.01	0.022	-9999	-0.25	2	2
DOK6	-0.12	0.3	-9999	-0.81	45	45
PXN	0.012	0	-9999	-10000	0	0
neurite development	-0.049	0.18	-9999	-0.62	8	8
DOK5	0.002	0.086	-9999	-0.59	5	5
GFRA1	-0.062	0.23	-9999	-0.81	24	24
MAPK8	-0.025	0.15	-9999	-0.36	44	44
HRAS/GTP	-0.071	0.17	-9999	-0.48	41	41
tube development	-0.035	0.13	-9999	-0.47	24	24
MAPK1	-0.034	0.17	-9999	-0.44	41	41
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.007	0.099	-9999	-0.34	24	24
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
PDLIM7	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.14	0.25	-9999	-0.52	79	79
SHC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.055	0.19	-9999	-0.52	41	41
RET51/GFRalpha1/GDNF/Dok5	-0.061	0.2	-9999	-0.52	44	44
PRKCA	0.012	0	-9999	-10000	0	0
HRAS/GDP	0.009	0.01	-9999	-10000	0	0
CREB1	-0.015	0.12	-9999	-0.38	24	24
PIK3R1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.007	0.099	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/Grb7	-0.055	0.19	-9999	-0.52	41	41
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.043	0.2	-9999	-0.81	19	19
DOK4	0.012	0	-9999	-10000	0	0
JNK cascade	-0.016	0.14	-9999	-0.53	8	8
RET9/GFRalpha1/GDNF/FRS2	-0.029	0.14	-9999	-0.5	24	24
SHANK3	0.012	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.007	0.1	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.025	0.13	-9999	-0.35	41	41
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.026	0.14	-9999	-0.35	41	41
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.027	0.14	-9999	-0.36	41	41
PI3K	-0.026	0.19	-9999	-0.52	27	27
SOS1	0.012	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.041	0.13	-9999	-0.47	24	24
GRB10	0.012	0	-9999	-10000	0	0
activation of MAPKK activity	-0.018	0.12	-9999	-0.34	24	24
RET51/GFRalpha1/GDNF/FRS2	-0.055	0.19	-9999	-0.52	41	41
GAB1	0.012	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
IRS2	0.01	0.022	-9999	-0.25	2	2
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.027	0.14	-9999	-0.36	41	41
RET51/GFRalpha1/GDNF/PKC alpha	-0.055	0.19	-9999	-0.52	41	41
GRB2	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GDNF	0.003	0.005	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.064	0.21	-9999	-0.54	44	44
Rac1/GTP	-0.055	0.13	-9999	-0.41	24	24
RET9/GFRalpha1/GDNF	-0.049	0.15	-9999	-0.55	24	24
GFRalpha1/GDNF	-0.046	0.18	-9999	-0.63	24	24

×

Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.032	0.14	-9999	-0.36	42	42
FZD6	0.012	0	-9999	-10000	0	0
WNT6	0.01	0.016	-9999	-10000	0	0
WNT4	-0.021	0.16	-9999	-0.81	11	11
FZD3	0.012	0	-9999	-10000	0	0
WNT5A	-0.02	0.087	-9999	-0.25	35	35
WNT11	-0.083	0.26	-9999	-0.81	33	33

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.027	0.11	-10000	0	-0.46	17	17
ER alpha/Gai/GDP/Gbeta gamma	-0.013	0.17	-10000	0	-0.45	32	32
AKT1	-0.018	0.2	-10000	0	-0.83	17	17
PIK3CA	0.012	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.02	0.21	-10000	0	-0.84	17	17
mol:Ca2+	-0.21	0.3	-10000	0	-0.54	118	118
IGF1R	0.012	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.047	0.15	-10000	0	-0.55	25	25
SHC1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.016	0.19	0.79	17	-10000	0	17
RhoA/GTP	-0.024	0.096	-10000	0	-0.41	17	17
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.047	0.15	-10000	0	-0.59	17	17
regulation of stress fiber formation	-0.015	0.1	0.32	25	-10000	0	25
E2/ERA-ERB (dimer)	-0.032	0.13	-10000	0	-0.55	17	17
KRAS	0.012	0	-10000	0	-10000	0	0
G13/GTP	-0.015	0.12	-10000	0	-0.5	17	17
pseudopodium formation	0.015	0.1	-10000	0	-0.32	25	25
E2/ER alpha (dimer)/PELP1	-0.032	0.13	-10000	0	-0.55	17	17
GRB2	0.012	0	-10000	0	-10000	0	0
GNG2	0.012	0	-10000	0	-10000	0	0
GNAO1	-0.044	0.2	-10000	0	-0.74	22	22
HRAS	0.011	0.016	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.008	0.17	-10000	0	-0.62	18	18
E2/ER beta (dimer)	0.009	0	-10000	0	-10000	0	0
mol:GDP	-0.032	0.13	-10000	0	-0.55	17	17
mol:NADP	-0.008	0.17	-10000	0	-0.62	18	18
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	-0.22	0.32	-10000	0	-0.57	118	118
IGF-1R heterotetramer	0.012	0	-10000	0	-10000	0	0
PLCB1	-0.22	0.33	-10000	0	-0.59	118	118
PLCB2	-0.14	0.27	-10000	0	-0.57	76	76
IGF1	-0.016	0.15	-10000	0	-0.81	10	10
mol:L-citrulline	-0.008	0.17	-10000	0	-0.62	18	18
RHOA	0.012	0	-10000	0	-10000	0	0
Gai/GDP	-0.052	0.18	-10000	0	-0.73	19	19
JNK cascade	0.009	0	-10000	0	-10000	0	0
BCAR1	0.012	0	-10000	0	-10000	0	0
ESR2	0.012	0	-10000	0	-10000	0	0
GNAQ	0.012	0	-10000	0	-10000	0	0
ESR1	-0.036	0.19	-10000	0	-0.81	17	17
Gq family/GDP/Gbeta gamma	-0.065	0.17	-10000	0	-0.62	6	6
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.014	0.086	-10000	0	-0.32	17	17
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.047	0.15	-10000	0	-0.59	17	17
GNAZ	0.012	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)	-0.028	0.15	-10000	0	-0.63	17	17
STRN	-0.01	0.14	-10000	0	-0.81	8	8
GNAL	0.009	0.048	-10000	0	-0.81	1	1
PELP1	0.012	0	-10000	0	-10000	0	0
MAPK11	0.018	0	-10000	0	-10000	0	0
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
HBEGF	-0.024	0.16	-10000	0	-0.49	19	19
cAMP biosynthetic process	-0.028	0.11	-10000	0	-0.44	18	18
SRC	-0.005	0.16	-10000	0	-0.52	17	17
PI3K	0.018	0	-10000	0	-10000	0	0
GNB1	0.012	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.028	0.11	-10000	0	-0.48	17	17
SOS1	0.012	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.047	0.13	-10000	0	-0.49	18	18
Gs family/GTP	-0.028	0.11	-10000	0	-0.45	18	18
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.023	0.008	-10000	0	-10000	0	0
vasodilation	-0.006	0.16	-10000	0	-0.59	18	18
mol:DAG	-0.22	0.32	-10000	0	-0.57	118	118
Gs family/GDP/Gbeta gamma	-0.027	0.11	-10000	0	-0.44	18	18
MSN	0.015	0.11	-10000	0	-0.36	8	8
Gq family/GTP	-0.15	0.29	-10000	0	-0.59	80	80
mol:PI-3-4-5-P3	-0.018	0.2	-10000	0	-0.81	17	17
NRAS	0.012	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.006	0.16	0.59	18	-10000	0	18
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
RhoA/GDP	-0.03	0.12	-10000	0	-0.51	17	17
NOS3	-0.01	0.19	-10000	0	-0.66	18	18
GNA11	-0.005	0.12	-10000	0	-0.81	6	6
MAPKKK cascade	-0.007	0.18	-10000	0	-0.58	25	25
E2/ER alpha (dimer)/PELP1/Src	-0.05	0.16	-10000	0	-0.62	17	17
ruffle organization	0.015	0.1	-10000	0	-0.32	25	25
ROCK2	0.007	0.12	-10000	0	-0.38	25	25
GNA14	-0.2	0.36	-10000	0	-0.81	76	76
GNA15	-0.003	0.062	-10000	0	-10000	0	0
GNA13	0.011	0.016	-10000	0	-0.25	1	1
MMP9	-0.044	0.16	-10000	0	-0.49	25	25
MMP2	0.001	0.15	-10000	0	-0.48	18	18

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.013	0.13	-9999	-0.55	16	16
ADCY5	-0.019	0.14	-9999	-0.55	19	19
ADCY6	0.018	0	-9999	-10000	0	0
ADCY7	0.013	0.028	-9999	-10000	0	0
ADCY1	-0.25	0.28	-9999	-0.55	138	138
ADCY2	-0.072	0.078	-9999	-0.55	1	1
ADCY3	0.018	0	-9999	-10000	0	0
ADCY8	0.009	0.03	-9999	-10000	0	0
PRKCE	0.011	0	-9999	-10000	0	0
ADCY9	0.018	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.077	0.09	-9999	-0.31	21	21

×

Glucocorticoid receptor regulatory network

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
PCK2	0.006	0.034	-10000	0	-10000	0	0
SMARCC2	0.014	0	-10000	0	-10000	0	0
SMARCC1	0.014	0	-10000	0	-10000	0	0
TBX21	-0.034	0.095	-10000	0	-0.37	6	6
SUMO2	0.01	0.006	-10000	0	-10000	0	0
STAT1 (dimer)	0.017	0.027	-10000	0	-10000	0	0
FKBP4	0.012	0	-10000	0	-10000	0	0
FKBP5	-0.008	0.13	-10000	0	-0.81	7	7
GR alpha/HSP90/FKBP51/HSP90	0.066	0.11	0.31	2	-0.48	7	9
PRL	-0.031	0.083	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.11	0.25	0.47	23	-0.47	26	49
RELA	-0.1	0.1	-10000	0	-10000	0	0
FGG	0.12	0.15	0.48	6	-10000	0	6
GR beta/TIF2	0.012	0.22	0.34	2	-0.58	31	33
IFNG	-0.17	0.18	-10000	0	-0.56	17	17
apoptosis	-0.055	0.2	0.5	4	-0.59	11	15
CREB1	0.009	0.037	-10000	0	-0.35	3	3
histone acetylation	-0.013	0.071	-10000	0	-0.34	3	3
BGLAP	-0.018	0.07	-10000	0	-10000	0	0
GR/PKAc	0.079	0.061	0.32	1	-10000	0	1
NF kappa B1 p50/RelA	-0.18	0.19	-10000	0	-0.46	47	47
SMARCD1	0.014	0	-10000	0	-10000	0	0
MDM2	0.064	0.057	0.24	6	-10000	0	6
GATA3	-0.62	0.35	-10000	0	-0.81	224	224
AKT1	0	0.001	-10000	0	-10000	0	0
CSF2	-0.032	0.063	-10000	0	-10000	0	0
GSK3B	0.01	0.006	-10000	0	-10000	0	0
NR1I3	-0.008	0.2	0.52	3	-0.83	4	7
CSN2	0.12	0.11	0.4	4	-10000	0	4
BRG1/BAF155/BAF170/BAF60A	0.04	0	-10000	0	-10000	0	0
NFATC1	0.014	0.004	-10000	0	-10000	0	0
POU2F1	0.013	0.003	-10000	0	-10000	0	0
CDKN1A	0.026	0.037	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.002	0.007	-10000	0	-10000	0	0
SFN	-0.12	0.16	-10000	0	-0.81	5	5
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.01	0.14	-10000	0	-0.49	11	11
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.049	0.29	0.5	3	-0.9	23	26
JUN	-0.12	0.17	-10000	0	-0.5	25	25
IL4	-0.034	0.077	-10000	0	-0.42	1	1
CDK5R1	0.006	0.035	-10000	0	-0.25	5	5
PRKACA	0.012	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.071	0.23	0.28	5	-0.59	31	36
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.071	0.1	0.33	1	-0.44	7	8
cortisol/GR alpha (monomer)	0.2	0.18	0.52	30	-10000	0	30
NCOA2	-0.076	0.25	-10000	0	-0.81	31	31
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.13	0.29	-10000	0	-0.83	41	41
AP-1/NFAT1-c-4	-0.23	0.28	-10000	0	-0.73	46	46
AFP	-0.21	0.44	-10000	0	-1.4	31	31
SUV420H1	0.012	0	-10000	0	-10000	0	0
IRF1	0.12	0.09	0.42	3	-10000	0	3
TP53	0.031	0.017	-10000	0	-10000	0	0
PPP5C	0.012	0	-10000	0	-10000	0	0
KRT17	-0.24	0.33	-10000	0	-1	28	28
KRT14	-0.09	0.11	-10000	0	-10000	0	0
TBP	0.021	0	-10000	0	-10000	0	0
CREBBP	0.026	0.031	-10000	0	-10000	0	0
HDAC1	0.011	0.003	-10000	0	-10000	0	0
HDAC2	0.012	0.002	-10000	0	-10000	0	0
AP-1	-0.23	0.29	-10000	0	-0.73	46	46
MAPK14	0.01	0.006	-10000	0	-10000	0	0
MAPK10	0.01	0.006	-10000	0	-10000	0	0
MAPK11	0.01	0.006	-10000	0	-10000	0	0
KRT5	-0.18	0.19	-10000	0	-0.55	27	27
interleukin-1 receptor activity	-0.001	0.002	-10000	0	-10000	0	0
NCOA1	0.015	0.001	-10000	0	-10000	0	0
STAT1	0.017	0.027	-10000	0	-10000	0	0
CGA	-0.05	0.15	-10000	0	-1.3	3	3
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.04	0.07	0.31	3	-10000	0	3
MAPK3	0.01	0.006	-10000	0	-10000	0	0
MAPK1	0.01	0.006	-10000	0	-10000	0	0
ICAM1	-0.19	0.18	-10000	0	-0.5	42	42
NFKB1	-0.1	0.1	-10000	0	-10000	0	0
MAPK8	-0.1	0.15	-10000	0	-0.52	14	14
MAPK9	0.01	0.006	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.063	0.2	0.5	4	-0.62	11	15
BAX	0.027	0.032	-10000	0	-10000	0	0
POMC	-0.22	0.3	-10000	0	-0.72	41	41
EP300	0.026	0.031	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.19	0.16	0.48	24	-10000	0	24
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.045	0.22	1	-10000	0	1
SGK1	0.073	0.041	-10000	0	-10000	0	0
IL13	-0.51	0.28	-10000	0	-0.79	112	112
IL6	-0.36	0.5	-10000	0	-1.4	53	53
PRKACG	0.002	0.016	-10000	0	-10000	0	0
IL5	-0.42	0.22	-10000	0	-0.61	136	136
IL2	-0.16	0.17	-10000	0	-0.65	6	6
CDK5	0.01	0.005	-10000	0	-10000	0	0
PRKACB	0.012	0	-10000	0	-10000	0	0
HSP90AA1	0.012	0	-10000	0	-10000	0	0
IL8	-0.21	0.2	-10000	0	-0.52	49	49
CDK5R1/CDK5	0.011	0.024	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	-0.11	0.14	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.18	0.15	0.48	17	-10000	0	17
SMARCA4	0.014	0	-10000	0	-10000	0	0
chromatin remodeling	0.13	0.091	0.37	7	-10000	0	7
NF kappa B1 p50/RelA/Cbp	-0.11	0.16	-10000	0	-0.39	5	5
JUN (dimer)	-0.12	0.17	-10000	0	-0.5	25	25
YWHAH	0.012	0	-10000	0	-10000	0	0
VIPR1	-0.056	0.22	-10000	0	-1.1	11	11
NR3C1	0.11	0.1	0.43	7	-10000	0	7
NR4A1	-0.27	0.4	-10000	0	-0.8	102	102
TIF2/SUV420H1	-0.05	0.2	-10000	0	-0.62	31	31
MAPKKK cascade	-0.055	0.2	0.5	4	-0.59	11	15
cortisol/GR alpha (dimer)/Src-1	0.19	0.16	0.51	17	-10000	0	17
PBX1	-0.004	0.12	-10000	0	-0.81	6	6
POU1F1	0.007	0.007	-10000	0	-10000	0	0
SELE	-0.72	0.63	-10000	0	-1.3	161	161
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.13	0.092	0.37	7	-10000	0	7
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.18	0.15	0.48	17	-10000	0	17
mol:cortisol	0.095	0.1	0.27	36	-10000	0	36
MMP1	-0.26	0.5	-10000	0	-1.4	48	48

×

TCR signaling in naïve CD8+ T cells

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.024	0.08	-10000	0	-0.39	7	7
FYN	0.023	0.12	-10000	0	-0.49	7	7
LAT/GRAP2/SLP76	-0.003	0.12	-10000	0	-0.48	9	9
IKBKB	0.012	0	-10000	0	-10000	0	0
AKT1	0.011	0.11	-10000	0	-0.37	11	11
B2M	0.013	0.003	-10000	0	-10000	0	0
IKBKG	-0.012	0.03	-10000	0	-10000	0	0
MAP3K8	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	-0.085	0.057	-10000	0	-0.12	199	199
integrin-mediated signaling pathway	-0.001	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.003	0.14	-10000	0	-0.52	11	11
TRPV6	-0.56	0.38	-10000	0	-0.82	201	201
CD28	0	0.07	-10000	0	-0.3	12	12
SHC1	0.017	0.12	-10000	0	-0.46	8	8
receptor internalization	0.011	0.11	-10000	0	-0.42	10	10
PRF1	0.02	0.1	-10000	0	-0.52	5	5
KRAS	0.012	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
COT/AKT1	0.018	0.089	-10000	0	-0.31	8	8
LAT	-0.005	0.13	-10000	0	-0.46	13	13
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.024	0.094	-10000	0	-0.26	41	41
CD3E	-0.026	0.1	-10000	0	-0.82	1	1
CD3G	0	0.058	-10000	0	-0.26	10	10
RASGRP2	0	0.015	-10000	0	-10000	0	0
RASGRP1	0.013	0.11	-10000	0	-0.36	13	13
HLA-A	0.011	0.028	-10000	0	-0.26	3	3
RASSF5	0.01	0.022	-10000	0	-0.25	2	2
RAP1A/GTP/RAPL	-0.001	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.027	0.041	-10000	0	-0.099	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.024	0.051	-10000	0	-0.23	4	4
PRKCA	0.01	0.077	-10000	0	-0.26	6	6
GRAP2	0.006	0.041	-10000	0	-10000	0	0
mol:IP3	0.14	0.18	0.26	183	-0.37	11	194
EntrezGene:6957	0.001	0.002	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0.01	0.092	-10000	0	-0.34	11	11
ORAI1	0.26	0.17	0.38	199	-10000	0	199
CSK	0.015	0.12	-10000	0	-0.47	8	8
B7 family/CD28	-0.039	0.11	-10000	0	-0.52	10	10
CHUK	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.01	0.13	-10000	0	-0.47	11	11
PTPN6	0.019	0.11	-10000	0	-0.48	7	7
VAV1	-0.001	0.15	-10000	0	-0.5	13	13
Monovalent TCR/CD3	-0.005	0.084	-10000	0	-0.28	17	17
CBL	0.012	0	-10000	0	-10000	0	0
LCK	0.019	0.12	-10000	0	-0.53	7	7
PAG1	0.015	0.12	-10000	0	-0.46	9	9
RAP1A	0.012	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.015	0.12	-10000	0	-0.47	10	10
CD80	0.001	0.054	-10000	0	-0.26	12	12
CD86	-0.017	0.084	-10000	0	-10000	0	0
PDK1/CARD11/BCL10/MALT1	-0.03	0.061	-10000	0	-0.26	8	8
HRAS	0.011	0.016	-10000	0	-10000	0	0
GO:0035030	0.015	0.12	-10000	0	-0.45	10	10
CD8A	-0.006	0.07	-10000	0	-0.26	6	6
CD8B	-0.007	0.082	-10000	0	-0.81	1	1
PTPRC	0.006	0.058	-10000	0	-0.37	5	5
PDK1/PKC theta	0.009	0.13	-10000	0	-0.45	11	11
CSK/PAG1	0.019	0.12	-10000	0	-0.47	7	7
SOS1	0.012	0	-10000	0	-10000	0	0
peptide-MHC class I	0.018	0.02	-10000	0	-10000	0	0
GRAP2/SLP76	0.011	0.13	-10000	0	-0.53	8	8
STIM1	0.14	0.09	-10000	0	-10000	0	0
RAS family/GTP	0.031	0.051	-10000	0	-0.15	1	1
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.01	0.12	-10000	0	-0.43	10	10
mol:DAG	0.034	0.12	-10000	0	-0.34	11	11
RAP1A/GDP	0.013	0.018	-10000	0	-10000	0	0
PLCG1	0.012	0	-10000	0	-10000	0	0
CD247	0.001	0.056	-10000	0	-0.26	13	13
cytotoxic T cell degranulation	0.02	0.099	-10000	0	-0.51	5	5
RAP1A/GTP	-0.001	0.004	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.007	0.12	-10000	0	-0.44	11	11
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.12	0.21	0.28	163	-0.49	11	174
NRAS	0.012	0	-10000	0	-10000	0	0
ZAP70	-0.042	0.11	-10000	0	-10000	0	0
GRB2/SOS1	0.018	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.013	0.14	-10000	0	-0.51	11	11
MALT1	0.012	0	-10000	0	-10000	0	0
TRAF6	0.012	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.005	0.089	-10000	0	-0.34	15	15
CARD11	-0.059	0.12	-10000	0	-0.25	78	78
PRKCB	0.009	0.079	-10000	0	-0.27	7	7
PRKCE	0.01	0.077	-10000	0	-0.26	6	6
PRKCQ	0	0.14	-10000	0	-0.51	11	11
LCP2	0.008	0.035	-10000	0	-10000	0	0
BCL10	0.012	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.013	0.095	-10000	0	-0.32	11	11
IKK complex	0.031	0.042	-10000	0	-10000	0	0
RAS family/GDP	-0.002	0.005	-10000	0	-10000	0	0
MAP3K14	0.022	0.072	-10000	0	-0.25	4	4
PDPK1	0.014	0.1	-10000	0	-0.35	11	11
TCR/CD3/MHC I/CD8/Fyn	0.01	0.12	-10000	0	-0.49	9	9

×

IL6-mediated signaling events

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
BCL2L1	-0.053	0.19	-9999	-0.61	8	8
CRP	-0.062	0.2	-9999	-0.62	10	10
cell cycle arrest	-0.068	0.21	-9999	-0.63	14	14
TIMP1	-0.068	0.19	-9999	-0.55	13	13
IL6ST	-0.12	0.3	-9999	-0.81	47	47
Rac1/GDP	-0.087	0.21	-9999	-0.58	23	23
AP1	-0.056	0.17	-9999	-0.48	28	28
GAB2	0.013	0.003	-9999	-10000	0	0
TNFSF11	-0.064	0.2	-9999	-0.62	10	10
HSP90B1	0.013	0.047	-9999	-10000	0	0
GAB1	0.013	0.001	-9999	-10000	0	0
MAPK14	-0.07	0.2	-9999	-0.74	13	13
AKT1	0.047	0.013	-9999	-10000	0	0
FOXO1	0.052	0.013	-9999	-10000	0	0
MAP2K6	-0.081	0.21	-9999	-0.62	19	19
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.069	0.2	-9999	-0.59	18	18
MITF	-0.087	0.21	-9999	-0.55	27	27
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.012	0	-9999	-10000	0	0
A2M	0.007	0.15	-9999	-1.4	3	3
CEBPB	0.008	0.047	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.015	0.081	-9999	-10000	0	0
STAT3	-0.075	0.22	-9999	-0.68	14	14
STAT1	-0.011	0.02	-9999	-10000	0	0
CEBPD	-0.053	0.19	-9999	-0.58	11	11
PIK3CA	0.014	0	-9999	-10000	0	0
PI3K	0.021	0.001	-9999	-10000	0	0
JUN	0.012	0.001	-9999	-10000	0	0
PIAS3/MITF	-0.074	0.2	-9999	-0.65	16	16
MAPK11	-0.07	0.2	-9999	-0.74	13	13
STAT3 (dimer)/FOXO1	-0.023	0.19	-9999	-0.54	10	10
GRB2/SOS1/GAB family	-0.098	0.17	-9999	-0.69	11	11
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.099	0.22	-9999	-0.44	57	57
GRB2	0.013	0.001	-9999	-10000	0	0
JAK2	0.012	0	-9999	-10000	0	0
LBP	-0.23	0.42	-9999	-0.96	67	67
PIK3R1	0.013	0	-9999	-10000	0	0
JAK1	0.014	0.003	-9999	-10000	0	0
MYC	-0.056	0.19	-9999	-0.58	11	11
FGG	-0.067	0.2	-9999	-0.6	12	12
macrophage differentiation	-0.068	0.21	-9999	-0.63	14	14
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.15	0.25	-9999	-0.5	90	90
JUNB	-0.051	0.18	-9999	-0.58	9	9
FOS	-0.1	0.29	-9999	-0.81	41	41
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.097	0.22	-9999	-0.45	54	54
STAT1/PIAS1	-0.081	0.2	-9999	-0.46	37	37
GRB2/SOS1/GAB family/SHP2/PI3K	0.033	0.019	-9999	-10000	0	0
STAT3 (dimer)	-0.071	0.21	-9999	-0.66	14	14
PRKCD	-0.053	0.19	-9999	-0.58	14	14
IL6R	0.011	0.048	-9999	-0.81	1	1
SOCS3	-0.066	0.21	-9999	-0.8	12	12
gp130 (dimer)/JAK1/JAK1/LMO4	-0.063	0.21	-9999	-0.54	47	47
Rac1/GTP	-0.087	0.21	-9999	-0.6	21	21
HCK	-0.015	0.089	-9999	-0.27	27	27
MAPKKK cascade	0.005	0.062	-9999	-10000	0	0
bone resorption	-0.061	0.19	-9999	-0.58	11	11
IRF1	-0.053	0.19	-9999	-0.58	11	11
mol:GDP	-0.1	0.22	-9999	-0.52	36	36
SOS1	0.012	0.003	-9999	-10000	0	0
VAV1	-0.1	0.22	-9999	-0.53	36	36
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.082	0.21	-9999	-0.78	13	13
PTPN11	-0.01	0.016	-9999	-10000	0	0
IL6/IL6RA	-0.099	0.24	-9999	-0.62	52	52
gp130 (dimer)/TYK2/TYK2/LMO4	-0.068	0.21	-9999	-0.54	47	47
gp130 (dimer)/JAK2/JAK2/LMO4	-0.068	0.21	-9999	-0.54	47	47
IL6	-0.14	0.31	-9999	-0.81	51	51
PIAS3	0.012	0	-9999	-10000	0	0
PTPRE	0.008	0.008	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
RAC1	0.013	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.11	0.22	-9999	-0.39	90	90
LMO4	0.014	0.017	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.12	0.18	-9999	-0.72	12	12
MCL1	0.052	0.013	-9999	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.05	0.16	-9999	-0.54	27	27
E-cadherin/beta catenin	-0.041	0.19	-9999	-0.62	27	27
CTNNB1	0.012	0	-9999	-10000	0	0
JUP	0.012	0	-9999	-10000	0	0
CDH1	-0.064	0.24	-9999	-0.81	27	27

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.046	0.15	-9999	-0.55	22	22
EFNA5	-0.051	0.22	-9999	-0.81	22	22
FYN	-0.026	0.14	-9999	-0.5	22	22
neuron projection morphogenesis	-0.046	0.15	-9999	-0.55	22	22
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.047	0.15	-9999	-0.56	22	22
EPHA5	-0.006	0.047	-9999	-10000	0	0

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.013	0.024	-9999	-10000	0	0
NFATC2	-0.038	0.16	-9999	-0.55	26	26
NFATC3	0.013	0.024	-9999	-10000	0	0
CD40LG	-0.11	0.26	-9999	-0.62	39	39
PTGS2	-0.2	0.4	-9999	-0.83	73	73
JUNB	0.012	0	-9999	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.003	0.009	-9999	-10000	0	0
CaM/Ca2+	-0.003	0.009	-9999	-10000	0	0
CALM1	0.011	0.007	-9999	-10000	0	0
JUN	0.011	0.007	-9999	-10000	0	0
mol:Ca2+	-0.004	0.01	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.001	0.003	-9999	-10000	0	0
FOSL1	0	0.068	-9999	-0.81	1	1
CREM	0.012	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.067	0.13	-9999	-0.46	18	18
FOS	-0.11	0.29	-9999	-0.82	41	41
IFNG	-0.11	0.27	-9999	-0.64	39	39
AP-1/NFAT1-c-4	-0.13	0.31	-9999	-0.74	41	41
FASLG	-0.11	0.27	-9999	-0.63	39	39
NFAT1-c-4/ICER1	-0.04	0.14	-9999	-0.45	26	26
IL2RA	-0.11	0.26	-9999	-0.62	40	40
FKBP12/FK506	0.009	0	-9999	-10000	0	0
CSF2	-0.11	0.26	-9999	-0.62	39	39
JunB/Fra1/NFAT1-c-4	-0.052	0.13	-9999	-0.43	27	27
IL4	-0.11	0.26	-9999	-0.62	39	39
IL2	-0.007	0.03	-9999	-10000	0	0
IL3	-0.015	0.022	-9999	-10000	0	0
FKBP1A	0.012	0	-9999	-10000	0	0
BATF3	0.011	0.016	-9999	-0.25	1	1
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.012	0.001	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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
NRIP1	0.012	0.003	-9999	-10000	0	0
SVIL	0.012	0.003	-9999	-10000	0	0
ZNF318	0.014	0.01	-9999	-10000	0	0
JMJD2C	-0.002	0.016	-9999	-0.054	24	24
T-DHT/AR/Ubc9	-0.068	0.12	-9999	-0.58	12	12
CARM1	0.012	0	-9999	-10000	0	0
PRDX1	0.012	0.001	-9999	-10000	0	0
PELP1	0.012	0.001	-9999	-10000	0	0
CTNNB1	0.012	0.003	-9999	-10000	0	0
AKT1	0.013	0.003	-9999	-10000	0	0
PTK2B	0.012	0.003	-9999	-10000	0	0
MED1	0.013	0.003	-9999	-10000	0	0
MAK	0.004	0.05	-9999	-0.25	10	10
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.003	0.083	-9999	-0.81	3	3
GSN	0.012	0.003	-9999	-10000	0	0
NCOA2	-0.076	0.25	-9999	-0.81	31	31
NCOA6	0.012	0.003	-9999	-10000	0	0
DNA-PK	0.004	0.016	-9999	-10000	0	0
NCOA4	0.012	0	-9999	-10000	0	0
PIAS3	0.012	0.003	-9999	-10000	0	0
cell proliferation	-0.034	0.031	-9999	-10000	0	0
XRCC5	0.013	0.002	-9999	-10000	0	0
UBE3A	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.11	0.18	-9999	-0.59	31	31
FHL2	-0.034	0.081	-9999	-1.1	1	1
RANBP9	0.012	0.003	-9999	-10000	0	0
JMJD1A	-0.094	0.076	-9999	-0.15	195	195
CDK6	0.012	0	-9999	-10000	0	0
TGFB1I1	0.001	0.096	-9999	-0.81	4	4
T-DHT/AR/CyclinD1	-0.071	0.12	-9999	-0.58	13	13
XRCC6	0.013	0.002	-9999	-10000	0	0
T-DHT/AR	-0.13	0.14	-9999	-0.61	12	12
CTDSP1	0.012	0.001	-9999	-10000	0	0
CTDSP2	0.013	0.007	-9999	-10000	0	0
BRCA1	0.009	0.028	-9999	-10000	0	0
TCF4	0.007	0.068	-9999	-0.81	2	2
CDKN2A	-0.2	0.11	-9999	-0.25	217	217
SRF	0.02	0.009	-9999	-10000	0	0
NKX3-1	-0.16	0.12	-9999	-10000	0	0
KLK3	0.003	0.063	-9999	-10000	0	0
TMF1	0.009	0.048	-9999	-0.81	1	1
HNRNPA1	0.013	0.004	-9999	-10000	0	0
AOF2	-0.001	0.004	-9999	-10000	0	0
APPL1	0.022	0.006	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.068	0.12	-9999	-0.58	12	12
AR	-0.069	0.16	-9999	-0.83	12	12
UBA3	0.012	0.001	-9999	-10000	0	0
PATZ1	0.013	0.004	-9999	-10000	0	0
PAWR	0.012	0.001	-9999	-10000	0	0
PRKDC	0.013	0.002	-9999	-10000	0	0
PA2G4	0.013	0.004	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.062	0.11	-9999	-0.54	12	12
RPS6KA3	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.068	0.12	-9999	-0.58	12	12
LATS2	0.013	0.003	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.06	0.11	-9999	-0.54	12	12
Cyclin D3/CDK11 p58	0.007	0.018	-9999	-10000	0	0
VAV3	0.009	0.048	-9999	-0.81	1	1
KLK2	-0.074	0.077	-9999	-0.47	1	1
CASP8	0.012	0.001	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.11	0.21	-9999	-0.62	38	38
TMPRSS2	-0.76	0.54	-9999	-1.1	195	195
CCND1	0.009	0.048	-9999	-0.81	1	1
PIAS1	0.012	0.003	-9999	-10000	0	0
mol:T-DHT	-0.049	0.038	-9999	-0.076	191	191
CDC2L1	0	0	-9999	-10000	0	0
PIAS4	0.011	0.008	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.068	0.12	-9999	-0.58	12	12
CMTM2	-0.007	0.069	-9999	-0.25	21	21
SNURF	-0.043	0.2	-9999	-0.81	19	19
ZMIZ1	-0.031	0.034	-9999	-10000	0	0
CCND3	0.01	0.027	-9999	-10000	0	0
TGIF1	0.013	0.004	-9999	-10000	0	0
FKBP4	0.012	0.003	-9999	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.014	0.14	-10000	0	-0.72	3	3
IHH	-0.039	0.22	-10000	0	-0.78	22	22
SHH Np/Cholesterol/GAS1	-0.025	0.15	-10000	0	-0.5	25	25
LRPAP1	0.012	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.025	0.15	0.5	25	-10000	0	25
SMO/beta Arrestin2	0.014	0.14	-10000	0	-0.48	21	21
SMO	0.01	0.15	-10000	0	-0.51	21	21
AKT1	0.028	0.069	-10000	0	-10000	0	0
ARRB2	0.01	0.022	-10000	0	-10000	0	0
BOC	0.012	0	-10000	0	-10000	0	0
ADRBK1	0.012	0	-10000	0	-10000	0	0
heart looping	0.01	0.15	-10000	0	-0.5	21	21
STIL	0.014	0.12	-10000	0	-0.43	9	9
DHH N/PTCH2	-0.033	0.16	-10000	0	-0.62	20	20
DHH N/PTCH1	-0.028	0.18	-10000	0	-0.47	40	40
PIK3CA	0.012	0	-10000	0	-10000	0	0
DHH	-0.045	0.21	-10000	0	-0.81	20	20
PTHLH	0.009	0.16	-10000	0	-0.74	3	3
determination of left/right symmetry	0.01	0.15	-10000	0	-0.5	21	21
PIK3R1	0.012	0	-10000	0	-10000	0	0
skeletal system development	0.009	0.15	-10000	0	-0.74	3	3
IHH N/Hhip	-0.076	0.23	-10000	0	-0.63	43	43
DHH N/Hhip	-0.08	0.25	-10000	0	-0.69	39	39
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.01	0.15	-10000	0	-0.5	21	21
pancreas development	-0.059	0.23	-10000	0	-0.81	24	24
HHAT	0.012	0	-10000	0	-10000	0	0
PI3K	0.018	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.05	0.22	-10000	0	-0.81	22	22
somite specification	0.01	0.15	-10000	0	-0.5	21	21
SHH Np/Cholesterol/PTCH1	0.009	0.12	-10000	0	-0.39	24	24
SHH Np/Cholesterol/PTCH2	0.01	0.06	-10000	0	-0.5	3	3
SHH Np/Cholesterol/Megalin	-0.032	0.16	-10000	0	-0.52	28	28
SHH	0.011	0.07	-10000	0	-0.62	3	3
catabolic process	0.004	0.14	-10000	0	-0.48	21	21
SMO/Vitamin D3	0.011	0.14	-10000	0	-0.43	23	23
SHH Np/Cholesterol/Hhip	-0.031	0.15	-10000	0	-0.5	27	27
LRP2	-0.062	0.24	-10000	0	-0.81	26	26
receptor-mediated endocytosis	-0.012	0.18	-10000	0	-0.6	14	14
SHH Np/Cholesterol/BOC	0.015	0.055	-10000	0	-0.5	3	3
SHH Np/Cholesterol/CDO	0.013	0.057	-10000	0	-0.5	3	3
mesenchymal cell differentiation	0.031	0.15	0.49	27	-10000	0	27
mol:Vitamin D3	0.012	0.12	-10000	0	-0.4	24	24
IHH N/PTCH2	-0.023	0.15	-10000	0	-0.56	20	20
CDON	0.009	0.031	-10000	0	-0.25	4	4
IHH N/PTCH1	0.005	0.14	-10000	0	-0.49	21	21
Megalin/LRPAP1	-0.039	0.18	-10000	0	-0.62	26	26
PTCH2	0.003	0.048	-10000	0	-10000	0	0
SHH Np/Cholesterol	-0.008	0.053	-10000	0	-0.5	3	3
PTCH1	0.004	0.14	-10000	0	-0.48	21	21
HHIP	-0.059	0.23	-10000	0	-0.81	24	24

×

HIF-1-alpha transcription factor network

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
PKM2	-0.067	0.36	-9999	-1	15	15
HDAC7	0.014	0.002	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.078	0.23	-9999	-0.7	12	12
SMAD4	0.014	0	-9999	-10000	0	0
ID2	-0.067	0.36	-9999	-1	15	15
AP1	-0.07	0.22	-9999	-0.62	41	41
ABCG2	-0.071	0.37	-9999	-1	17	17
HIF1A	0	0.07	-9999	-10000	0	0
TFF3	-0.2	0.48	-9999	-1	49	49
GATA2	-0.16	0.34	-9999	-0.81	63	63
AKT1	0.005	0.073	-9999	-10000	0	0
response to hypoxia	-0.011	0.078	-9999	-10000	0	0
MCL1	-0.067	0.36	-9999	-1	15	15
NDRG1	-0.067	0.36	-9999	-1	15	15
SERPINE1	-0.1	0.42	-9999	-1	27	27
FECH	-0.067	0.36	-9999	-1	15	15
FURIN	-0.067	0.36	-9999	-0.98	16	16
NCOA2	-0.074	0.25	-9999	-0.81	31	31
EP300	0.028	0.098	-9999	-10000	0	0
HMOX1	-0.08	0.38	-9999	-1	16	16
BHLHE40	-0.067	0.36	-9999	-1	15	15
BHLHE41	-0.079	0.37	-9999	-0.98	18	18
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.008	0.05	-9999	-10000	0	0
ENG	0.046	0.089	-9999	-10000	0	0
JUN	0.013	0.002	-9999	-10000	0	0
RORA	-0.068	0.36	-9999	-1	15	15
ABCB1	-0.093	0.28	-9999	-1.3	14	14
TFRC	-0.067	0.36	-9999	-1	15	15
CXCR4	-0.074	0.37	-9999	-0.95	19	19
TF	-0.075	0.37	-9999	-0.99	18	18
CITED2	-0.067	0.36	-9999	-1	15	15
HIF1A/ARNT	-0.13	0.37	-9999	-1	20	20
LDHA	-0.016	0.033	-9999	-10000	0	0
ETS1	-0.067	0.36	-9999	-1	15	15
PGK1	-0.067	0.36	-9999	-1	15	15
NOS2	-0.098	0.42	-9999	-1.1	24	24
ITGB2	-0.085	0.37	-9999	-0.98	17	17
ALDOA	-0.067	0.36	-9999	-1	15	15
Cbp/p300/CITED2	-0.054	0.35	-9999	-1	12	12
FOS	-0.1	0.29	-9999	-0.81	41	41
HK2	-0.12	0.38	-9999	-0.99	21	21
SP1	0.017	0.021	-9999	-10000	0	0
GCK	0.019	0.16	-9999	-0.49	2	2
HK1	-0.067	0.36	-9999	-1	15	15
NPM1	-0.067	0.36	-9999	-1	15	15
EGLN1	-0.067	0.36	-9999	-1	15	15
CREB1	0.02	0	-9999	-10000	0	0
PGM1	-0.067	0.36	-9999	-1	15	15
SMAD3	0.014	0	-9999	-10000	0	0
EDN1	-0.085	0.3	-9999	-0.84	24	24
IGFBP1	-0.11	0.41	-9999	-1	24	24
VEGFA	0.007	0.27	-9999	-0.71	4	4
HIF1A/JAB1	-0.008	0.025	-9999	-10000	0	0
CP	-0.14	0.44	-9999	-1	34	34
CXCL12	-0.12	0.46	-9999	-1	37	37
COPS5	0.013	0.001	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.067	0.36	-9999	-1	15	15
EGLN3	-0.07	0.37	-9999	-0.98	16	16
CA9	-0.14	0.39	-9999	-0.99	21	21
TERT	-0.09	0.37	-9999	-1	17	17
ENO1	-0.067	0.36	-9999	-1	15	15
PFKL	-0.067	0.36	-9999	-0.96	17	17
NCOA1	0.013	0.001	-9999	-10000	0	0
ADM	-0.068	0.36	-9999	-0.96	17	17
ARNT	0	0.07	-9999	-10000	0	0
HNF4A	-0.055	0.23	-9999	-0.81	25	25
ADFP	-0.076	0.36	-9999	-0.97	17	17
SLC2A1	0.006	0.28	-9999	-0.7	6	6
LEP	-0.084	0.37	-9999	-0.99	17	17
HIF1A/ARNT/Cbp/p300	-0.068	0.26	-9999	-0.72	13	13
EPO	-0.035	0.27	-9999	-0.75	9	9
CREBBP	0.028	0.098	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/HDAC7	-0.08	0.23	-9999	-0.72	11	11
PFKFB3	-0.067	0.36	-9999	-0.96	17	17
NT5E	-0.068	0.37	-9999	-1	15	15

×

Ceramide 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
SPHK2	0.014	0.034	-10000	0	-10000	0	0
MAP4K4	0.036	0.034	-10000	0	-10000	0	0
BAG4	0.009	0.048	-10000	0	-0.81	1	1
PKC zeta/ceramide	-0.1	0.036	-10000	0	-10000	0	0
NFKBIA	0.012	0	-10000	0	-10000	0	0
BIRC3	0	0.055	-10000	0	-10000	0	0
BAX	-0.045	0.018	-10000	0	-0.13	2	2
RIPK1	0.012	0	-10000	0	-10000	0	0
AKT1	0.037	0.007	-10000	0	-10000	0	0
BAD	-0.1	0.035	-10000	0	-10000	0	0
SMPD1	0.022	0.031	-10000	0	-0.24	3	3
RB1	-0.1	0.035	-10000	0	-10000	0	0
FADD/Caspase 8	0.045	0.032	-10000	0	-10000	0	0
MAP2K4	-0.088	0.034	-10000	0	-10000	0	0
NSMAF	0.012	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.088	0.034	-10000	0	-10000	0	0
EGF	-0.73	0.24	-10000	0	-0.81	262	262
mol:ceramide	-0.11	0.038	-10000	0	-0.13	249	249
MADD	0.012	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.014	0.034	-10000	0	-10000	0	0
ASAH1	0.012	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.099	0.035	-10000	0	-10000	0	0
cell proliferation	-0.07	0.075	-10000	0	-0.44	10	10
BID	-0.005	0.027	-10000	0	-10000	0	0
MAP3K1	-0.1	0.035	-10000	0	-10000	0	0
EIF2A	-0.077	0.032	-10000	0	-10000	0	0
TRADD	0.012	0	-10000	0	-10000	0	0
CRADD	0.012	0	-10000	0	-10000	0	0
MAPK3	-0.073	0.032	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.073	0.032	-10000	0	-10000	0	0
Cathepsin D/ceramide	-0.1	0.038	-10000	0	-0.23	3	3
FADD	0.036	0.034	-10000	0	-10000	0	0
KSR1	-0.1	0.036	-10000	0	-0.23	1	1
MAPK8	-0.087	0.05	-10000	0	-0.37	5	5
PRKRA	-0.1	0.035	-10000	0	-10000	0	0
PDGFA	0.002	0.051	-10000	0	-0.25	11	11
TRAF2	0.012	0	-10000	0	-10000	0	0
IGF1	-0.016	0.15	-10000	0	-0.81	10	10
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.037	-10000	0	-0.13	249	249
CTSD	0.01	0.027	-10000	0	-0.25	3	3
regulation of nitric oxide biosynthetic process	0.018	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.074	0.082	-10000	0	-0.47	10	10
PRKCD	0.012	0	-10000	0	-10000	0	0
PRKCZ	0.012	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.014	0.034	-10000	0	-10000	0	0
RelA/NF kappa B1	0.018	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.012	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.031	0.036	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.067	-10000	0	-0.54	4	4
mol:Sphingosine-1-phosphate	0.014	0.034	-10000	0	-10000	0	0
MAP2K1	-0.078	0.033	-10000	0	-10000	0	0
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
CYCS	-0.066	0.024	-10000	0	-10000	0	0
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
NFKB1	0.012	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.016	0.038	-10000	0	-0.62	1	1
EIF2AK2	-0.088	0.034	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.011	0.06	-10000	0	-0.54	3	3
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.036	0.022	-10000	0	-10000	0	0
MAP2K2	-0.078	0.033	-10000	0	-10000	0	0
SMPD3	0.024	0.032	-10000	0	-0.24	3	3
TNF	-0.009	0.1	-10000	0	-0.81	3	3
PKC zeta/PAR4	0.018	0	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.25	0.087	0.28	262	-10000	0	262
NF kappa B1/RelA/I kappa B alpha	0	0	-10000	0	-10000	0	0
AIFM1	-0.066	0.024	-10000	0	-10000	0	0
BCL2	0.012	0	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.018	0	-9999	-10000	0	0
Necdin/E2F1	-0.077	0.18	-9999	-0.64	22	22
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.028	0.12	-9999	-0.49	16	16
NGF (dimer)/p75(NTR)/BEX1	-0.071	0.19	-9999	-0.57	35	35
NT-4/5 (dimer)/p75(NTR)	-0.017	0.12	-9999	-0.64	8	8
IKBKB	0.012	0	-9999	-10000	0	0
AKT1	0.007	0.12	-9999	-0.48	16	16
IKBKG	0.012	0	-9999	-10000	0	0
BDNF	-0.012	0.086	-9999	-0.28	24	24
MGDIs/NGR/p75(NTR)/LINGO1	-0.027	0.12	-9999	-0.58	11	11
FURIN	0.012	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.027	0.11	-9999	-0.63	8	8
LINGO1	0	0.097	-9999	-0.81	4	4
Sortilin/TRAF6/NRIF	-0.003	0.033	-9999	-10000	0	0
proBDNF (dimer)	-0.012	0.086	-9999	-0.28	24	24
NTRK1	-0.061	0.23	-9999	-0.81	25	25
RTN4R	0.003	0.049	-9999	-0.25	10	10
neuron apoptosis	0.004	0.12	-9999	-0.57	8	8
IRAK1	0.012	0	-9999	-10000	0	0
SHC1	-0.008	0.14	-9999	-0.57	16	16
ARHGDIA	0.012	0	-9999	-10000	0	0
RhoA/GTP	0.009	0	-9999	-10000	0	0
Gamma Secretase	-0.003	0.038	-9999	-0.46	2	2
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.001	0.13	-9999	-0.52	16	16
MAGEH1	0.011	0.016	-9999	-0.25	1	1
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.039	0.2	-9999	-0.57	33	33
Mammalian IAPs/DIABLO	0.026	0.027	-9999	-10000	0	0
proNGF (dimer)	-0.015	0.14	-9999	-0.71	11	11
MAGED1	0.012	0	-9999	-10000	0	0
APP	0.012	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.013	0.069	-9999	-0.25	22	22
ZNF274	0.012	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	0	0.12	-9999	-0.49	16	16
NGF	-0.015	0.14	-9999	-0.71	11	11
cell cycle arrest	-0.014	0.12	-9999	-0.47	16	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.013	0.09	-9999	-0.35	16	16
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.025	0.095	-9999	-0.56	8	8
NCSTN	0.012	0	-9999	-10000	0	0
mol:GTP	-0.032	0.13	-9999	-0.56	16	16
PSENEN	0.012	0	-9999	-10000	0	0
mol:ceramide	0	0.13	-9999	-0.51	16	16
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.02	0.075	-9999	-0.54	1	1
p75(NTR)/beta APP	0	0.1	-9999	-0.62	8	8
BEX1	-0.048	0.21	-9999	-0.81	20	20
mol:GDP	-0.018	0.14	-9999	-0.56	17	17
NGF (dimer)	-0.29	0.28	-9999	-0.53	159	159
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.005	0.11	-9999	-0.53	11	11
PIK3R1	0.012	0	-9999	-10000	0	0
RAC1/GTP	-0.029	0.12	-9999	-0.5	16	16
MYD88	0.012	0	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.033	0.13	-9999	-0.57	16	16
RHOB	0.012	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.029	0.078	-9999	-10000	0	0
NT3 (dimer)	-0.073	0.25	-9999	-0.81	30	30
TP53	0.018	0.097	-9999	-0.51	8	8
PRDM4	-0.001	0.13	-9999	-0.52	16	16
BDNF (dimer)	-0.3	0.26	-9999	-0.53	158	158
PIK3CA	0.012	0	-9999	-10000	0	0
SORT1	0.012	0	-9999	-10000	0	0
activation of caspase activity	-0.028	0.11	-9999	-0.48	16	16
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0	0.13	-9999	-0.52	16	16
RHOC	0.012	0	-9999	-10000	0	0
XIAP	0.012	0	-9999	-10000	0	0
MAPK10	0.027	0.12	-9999	-0.49	8	8
DIABLO	0.012	0	-9999	-10000	0	0
SMPD2	-0.001	0.13	-9999	-0.52	16	16
APH1B	0.007	0.068	-9999	-0.81	2	2
APH1A	0.012	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.033	0.13	-9999	-0.57	16	16
PSEN1	0.012	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.018	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.066	0.22	-9999	-0.65	36	36
MAPK8	0.021	0.12	-9999	-0.49	8	8
MAPK9	0.027	0.12	-9999	-0.49	8	8
APAF1	0.012	0	-9999	-10000	0	0
NTF3	-0.074	0.25	-9999	-0.81	30	30
NTF4	-0.013	0.069	-9999	-0.25	22	22
NDN	-0.05	0.22	-9999	-0.81	22	22
RAC1/GDP	0.009	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.026	0.11	-9999	-0.45	16	16
p75 CTF/Sortilin/TRAF6/NRIF	0.032	0	-9999	-10000	0	0
RhoA-B-C/GTP	-0.032	0.13	-9999	-0.56	16	16
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.022	0.094	-9999	-0.54	8	8
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.005	0.11	-9999	-0.58	8	8
PRKACB	0.012	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	0.002	0.06	-9999	-0.62	1	1
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0	0.055	-9999	-10000	0	0
BIRC2	0.012	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.031	0.16	-9999	-0.57	16	16
BAD	0.031	0.11	-9999	-0.48	8	8
RIPK2	0.012	0	-9999	-10000	0	0
NGFR	-0.011	0.14	-9999	-0.81	8	8
CYCS	0.006	0.12	-9999	-0.48	16	16
ADAM17	0.012	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0	0.13	-9999	-0.52	16	16
BCL2L11	0.031	0.11	-9999	-0.48	8	8
BDNF (dimer)/p75(NTR)	-0.015	0.13	-9999	-0.72	8	8
PI3K	0	0.13	-9999	-0.52	16	16
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0	0.13	-9999	-0.52	16	16
NDNL2	0.012	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
PRKCI	0.012	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.021	0.16	-9999	-0.63	17	17
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0	0.13	-9999	-0.52	16	16
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
PRKCZ	0.012	0	-9999	-10000	0	0
PLG	-0.43	0.41	-9999	-0.81	154	154
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.005	0.14	-9999	-0.52	16	16
SQSTM1	0.004	0.046	-9999	-0.25	9	9
NGFRAP1	0.012	0	-9999	-10000	0	0
CASP3	0.032	0.11	-9999	-0.44	8	8
E2F1	-0.059	0.12	-9999	-0.25	78	78
CASP9	0.012	0	-9999	-10000	0	0
IKK complex	-0.053	0.14	-9999	-0.54	12	12
NGF (dimer)/TRKA	-0.059	0.21	-9999	-0.64	33	33
MMP7	-0.037	0.14	-9999	-0.34	41	41
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.028	0.12	-9999	-0.49	16	16
MMP3	-0.013	0.062	-9999	-0.25	18	18
APAF-1/Caspase 9	-0.022	0.085	-9999	-0.66	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.77	0.68	-9999	-1.3	171	171
PLK1	0.045	0.11	-9999	-10000	0	0
CDKN1B	-0.012	0.11	-9999	-10000	0	0
FOXO3	0.066	0.08	-9999	-10000	0	0
KAT2B	0.019	0.011	-9999	-10000	0	0
FOXO1/SIRT1	-0.22	0.19	-9999	-0.38	171	171
CAT	0.069	0.073	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
AKT1	-0.009	0.028	-9999	-10000	0	0
FOXO1	-0.23	0.22	-9999	-0.42	171	171
MAPK10	0.024	0.012	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.072	0.043	-9999	-10000	0	0
response to oxidative stress	-0.025	0.031	-9999	-10000	0	0
FOXO3A/SIRT1	0.047	0.075	-9999	-10000	0	0
XPO1	0.013	0	-9999	-10000	0	0
EP300	-0.019	0.028	-9999	-10000	0	0
BCL2L11	0.03	0.016	-9999	-10000	0	0
FOXO1/SKP2	-0.2	0.21	-9999	-0.38	171	171
mol:GDP	-0.025	0.031	-9999	-10000	0	0
RAN	0.014	0	-9999	-10000	0	0
GADD45A	0.091	0.043	-9999	-10000	0	0
YWHAQ	0.012	0	-9999	-10000	0	0
FOXO1/14-3-3 family	-0.016	0.065	-9999	-10000	0	0
MST1	0.005	0.074	-9999	-0.29	14	14
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.016	0.056	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
MAPK8	0.016	0.067	-9999	-0.48	5	5
MAPK9	0.024	0.012	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
SIRT1	0.012	0.008	-9999	-10000	0	0
SOD2	-0.01	0.12	-9999	-10000	0	0
RBL2	0.079	0.059	-9999	-10000	0	0
RAL/GDP	0.01	0.017	-9999	-10000	0	0
CHUK	0.019	0.011	-9999	-10000	0	0
Ran/GTP	0.013	0.001	-9999	-10000	0	0
CSNK1G2	0.012	0	-9999	-10000	0	0
RAL/GTP	0.015	0.018	-9999	-10000	0	0
CSNK1G1	0.012	0	-9999	-10000	0	0
FASLG	0.014	0.065	-9999	-10000	0	0
SKP2	0.012	0	-9999	-10000	0	0
USP7	0.014	0	-9999	-10000	0	0
IKBKB	0.019	0.011	-9999	-10000	0	0
CCNB1	0.069	0.075	-9999	-10000	0	0
FOXO1-3a-4/beta catenin	0.001	0.12	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.2	0.2	-9999	-0.38	171	171
CSNK1A1	0.012	0	-9999	-10000	0	0
SGK1	0.019	0.011	-9999	-10000	0	0
CSNK1G3	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.003	-9999	-10000	0	0
ZFAND5	0.074	0.038	-9999	-10000	0	0
SFN	-0.12	0.16	-9999	-0.81	5	5
CDK2	-0.038	0.043	-9999	-10000	0	0
FOXO3A/14-3-3	0.025	0.054	-9999	-10000	0	0
CREBBP	-0.038	0.043	-9999	-10000	0	0
FBXO32	0.067	0.079	-9999	-10000	0	0
BCL6	0.079	0.059	-9999	-10000	0	0
RALB	0.014	0	-9999	-10000	0	0
RALA	0.014	0	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.012	0.022	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.026	0.14	0.41	9	-10000	0	9
IL27/IL27R/JAK1	0.038	0.25	-10000	0	-0.59	12	12
TBX21	-0.007	0.19	-10000	0	-0.53	10	10
IL12B	0.005	0.023	-10000	0	-10000	0	0
IL12A	0.009	0.004	-10000	0	-10000	0	0
IL6ST	-0.12	0.31	-10000	0	-0.81	47	47
IL27RA/JAK1	0.025	0.027	-10000	0	-10000	0	0
IL27	0.001	0.05	-10000	0	-0.26	10	10
TYK2	0.013	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.055	0.14	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.026	0.14	0.41	9	-10000	0	9
T cell proliferation during immune response	0.026	0.14	0.41	9	-10000	0	9
MAPKKK cascade	-0.026	0.14	-10000	0	-0.41	9	9
STAT3	0.012	0	-10000	0	-10000	0	0
STAT2	0.012	0	-10000	0	-10000	0	0
STAT1	0.012	0.027	-10000	0	-10000	0	0
IL12RB1	-0.011	0.075	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.055	0.21	-10000	0	-0.49	28	28
IL27/IL27R/JAK2/TYK2	-0.027	0.14	-10000	0	-0.42	9	9
positive regulation of T cell mediated cytotoxicity	-0.026	0.14	-10000	0	-0.41	9	9
STAT1 (dimer)	0.18	0.35	0.5	84	-0.64	10	94
JAK2	0.013	0.004	-10000	0	-10000	0	0
JAK1	0.015	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	-0.019	0.13	-10000	0	-0.43	4	4
T cell proliferation	-0.1	0.23	-10000	0	-0.5	54	54
IL12/IL12R/TYK2/JAK2	0.015	0.043	-10000	0	-10000	0	0
IL17A	-0.055	0.14	-10000	0	-10000	0	0
mast cell activation	0.026	0.14	0.41	9	-10000	0	9
IFNG	-0.001	0.026	-10000	0	-0.086	2	2
T cell differentiation	-0.003	0.005	-10000	0	-0.019	2	2
STAT3 (dimer)	-0.019	0.13	-10000	0	-0.42	5	5
STAT5A (dimer)	-0.019	0.13	-10000	0	-0.43	4	4
STAT4 (dimer)	-0.027	0.14	-10000	0	-0.48	6	6
STAT4	-0.004	0.064	-10000	0	-0.25	18	18
T cell activation	-0.01	0.006	-10000	0	-10000	0	0
IL27R/JAK2/TYK2	-0.057	0.18	-10000	0	-0.51	6	6
GATA3	-1.1	0.59	-10000	0	-1.4	224	224
IL18	0.008	0.021	-10000	0	-10000	0	0
positive regulation of mast cell cytokine production	-0.019	0.13	-10000	0	-0.4	6	6
IL27/EBI3	-0.01	0.086	-10000	0	-0.36	8	8
IL27RA	0.012	0.024	-10000	0	-10000	0	0
IL6	-0.14	0.31	-10000	0	-0.81	51	51
STAT5A	0.012	0	-10000	0	-10000	0	0
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	-0.002	0.02	-10000	0	-10000	0	0
IL1B	-0.003	0.091	-10000	0	-0.63	6	6
EBI3	-0.022	0.1	-10000	0	-0.27	38	38
TNF	-0.005	0.075	-10000	0	-0.63	3	3

×

Visual signal transduction: Rods

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
mol:K +	0.012	0	-9999	-10000	0	0
GNAT1/GTP	0	0.018	-9999	-10000	0	0
Metarhodopsin II/Arrestin	-0.002	0.018	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.014	0.08	-9999	-0.55	6	6
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0	0.026	-9999	-0.25	3	3
GRK1	0.002	0.016	-9999	-10000	0	0
CNG Channel	-0.17	0.22	-9999	-0.45	108	108
mol:Na +	-0.16	0.21	-9999	-0.44	102	102
mol:ADP	0.002	0.016	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.014	0.076	-9999	-0.56	5	5
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.17	0.22	-9999	-0.46	102	102
CNGB1	0	0.046	-9999	-10000	0	0
RDH5	-0.042	0.11	-9999	-0.25	59	59
SAG	0.001	0.003	-9999	-10000	0	0
mol:Ca2+	-0.14	0.22	-9999	-0.47	34	34
Na + (4 Units)	-0.15	0.2	-9999	-0.46	34	34
RGS9	-0.009	0.11	-9999	-0.81	4	4
GNB1/GNGT1	-0.02	0.07	-9999	-10000	0	0
GNAT1/GDP	-0.013	0.067	-9999	-0.49	5	5
GUCY2D	-0.018	0.082	-9999	-0.25	31	31
GNGT1	-0.044	0.1	-9999	-10000	0	0
GUCY2F	0.001	0.003	-9999	-10000	0	0
GNB5	0.012	0	-9999	-10000	0	0
mol:GMP (4 units)	0.002	0.086	-9999	-0.47	8	8
mol:11-cis-retinal	-0.042	0.11	-9999	-0.25	59	59
mol:cGMP	0.004	0.045	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
Rhodopsin	-0.025	0.076	-9999	-0.32	2	2
SLC24A1	0.012	0	-9999	-10000	0	0
CNGA1	-0.28	0.39	-9999	-0.81	102	102
Metarhodopsin II	0.003	0.021	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	0.003	0.048	-9999	-10000	0	0
RGS9BP	0.008	0.051	-9999	-0.53	2	2
Metarhodopsin II/Transducin	-0.005	0.037	-9999	-10000	0	0
GCAP Family/Ca ++	0.011	0.025	-9999	-10000	0	0
PDE6A/B	0.005	0.063	-9999	-0.63	2	2
mol:Pi	-0.014	0.076	-9999	-0.56	5	5
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.012	0.055	-9999	-10000	0	0
PDE6B	0.004	0.073	-9999	-0.48	5	5
PDE6A	0.002	0.043	-9999	-10000	0	0
PDE6G	-0.007	0.12	-9999	-0.81	6	6
RHO	0.001	0.034	-9999	-10000	0	0
PDE6	-0.027	0.1	-9999	-0.49	12	12
GUCA1A	-0.002	0.043	-9999	-10000	0	0
GC2/GCAP Family	0.011	0.025	-9999	-10000	0	0
GUCA1C	0.006	0.016	-9999	-0.25	1	1
GUCA1B	0.01	0.022	-9999	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.001	0.39	-9999	-0.91	12	12
PLK1	-0.011	0.14	-9999	-10000	0	0
BIRC5	-0.029	0.16	-9999	-10000	0	0
HSPA1B	0.001	0.39	-9999	-0.91	12	12
MAP2K1	0.027	0.036	-9999	-10000	0	0
BRCA2	-0.001	0.39	-9999	-0.91	15	15
FOXM1	-0.016	0.43	-9999	-0.99	21	21
XRCC1	0.001	0.39	-9999	-0.91	12	12
FOXM1B/p19	-0.079	0.34	-9999	-0.86	21	21
Cyclin D1/CDK4	0.004	0.37	-9999	-0.87	12	12
CDC2	-0.006	0.4	-9999	-0.88	21	21
TGFA	0.01	0.37	-9999	-0.85	13	13
SKP2	0.001	0.39	-9999	-0.92	11	11
CCNE1	0.002	0.061	-9999	-0.27	14	14
CKS1B	0.001	0.39	-9999	-0.91	12	12
RB1	-0.08	0.13	-9999	-0.48	3	3
FOXM1C/SP1	-0.014	0.4	-9999	-0.94	20	20
AURKB	-0.063	0.16	-9999	-10000	0	0
CENPF	-0.012	0.41	-9999	-0.95	17	17
CDK4	0.018	0.014	-9999	-10000	0	0
MYC	0.009	0.36	-9999	-0.83	14	14
CHEK2	0.022	0.053	-9999	-0.3	2	2
ONECUT1	-0.001	0.38	-9999	-0.88	15	15
CDKN2A	-0.2	0.1	-9999	-0.26	116	116
LAMA4	-0.004	0.39	-9999	-0.92	12	12
FOXM1B/HNF6	-0.012	0.41	-9999	-0.98	16	16
FOS	-0.11	0.55	-9999	-1.2	45	45
SP1	0.013	0.002	-9999	-10000	0	0
CDC25B	0	0.39	-9999	-0.93	12	12
response to radiation	0.012	0.033	-9999	-10000	0	0
CENPB	0.001	0.39	-9999	-0.91	12	12
CENPA	-0.026	0.42	-9999	-0.96	16	16
NEK2	-0.021	0.42	-9999	-0.94	19	19
HIST1H2BA	-0.005	0.39	-9999	-0.92	12	12
CCNA2	-0.024	0.099	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
CCNB1/CDK1	-0.013	0.41	-9999	-0.98	16	16
CCNB2	-0.019	0.42	-9999	-0.94	19	19
CCNB1	-0.004	0.4	-9999	-0.93	14	14
ETV5	0.001	0.39	-9999	-0.92	11	11
ESR1	-0.045	0.47	-9999	-1.1	27	27
CCND1	0.006	0.38	-9999	-0.87	14	14
GSK3A	0.028	0.029	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	0.01	0.091	-9999	-10000	0	0
CDK2	0.015	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.013	0.04	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.17	0.27	-9999	-0.88	21	21
GAS1	-0.06	0.49	-9999	-1.1	32	32
MMP2	-0.002	0.39	-9999	-0.94	13	13
RB1/FOXM1C	0.004	0.39	-9999	-0.9	17	17
CREBBP	0.012	0	-9999	-10000	0	0

×

S1P3 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
PDGFRB	-0.022	0.16	-9999	-0.81	12	12
mol:S1P	0.001	0.002	-9999	-10000	0	0
S1P1/S1P/Gi	0.009	0.081	-9999	-0.28	21	21
GNAO1	-0.043	0.2	-9999	-0.73	22	22
S1P/S1P3/G12/G13	-0.044	0.18	-9999	-0.5	39	39
AKT1	-0.021	0.16	-9999	-0.71	12	12
AKT3	0.001	0.12	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	-0.022	0.16	-9999	-0.81	12	12
GNAI2	0.014	0.002	-9999	-10000	0	0
GNAI3	0.014	0.002	-9999	-10000	0	0
GNAI1	0.008	0.068	-9999	-0.81	2	2
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.097	0.28	-9999	-0.81	39	39
S1PR2	0.012	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.037	0.18	-9999	-0.39	52	52
MAPK3	-0.029	0.18	-9999	-0.76	8	8
MAPK1	-0.029	0.18	-9999	-0.82	7	7
JAK2	-0.03	0.18	-9999	-0.71	9	9
CXCR4	-0.037	0.18	-9999	-0.77	8	8
FLT1	0.006	0.083	-9999	-0.81	3	3
RhoA/GDP	0.009	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
SRC	-0.029	0.18	-9999	-0.82	7	7
S1P/S1P3/Gi	-0.038	0.19	-9999	-0.39	52	52
RAC1	0.012	0	-9999	-10000	0	0
RhoA/GTP	-0.029	0.17	-9999	-0.8	7	7
VEGFA	0.012	0.027	-9999	-0.25	3	3
S1P/S1P2/Gi	0.012	0.093	-9999	-0.32	19	19
VEGFR1 homodimer/VEGFA homodimer	0.017	0.068	-9999	-0.62	3	3
RHOA	0.012	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.12	0.24	-9999	-0.44	94	94
GNAQ	0.012	0	-9999	-10000	0	0
GNAZ	0.014	0.002	-9999	-10000	0	0
G12/G13	0.018	0.01	-9999	-10000	0	0
GNA14	-0.2	0.36	-9999	-0.81	76	76
GNA15	-0.003	0.062	-9999	-10000	0	0
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.011	0.016	-9999	-0.25	1	1
GNA11	-0.005	0.12	-9999	-0.81	6	6
Rac1/GTP	-0.029	0.17	-9999	-0.8	7	7

×

Presenilin action in Notch and Wnt 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.035	0.12	-10000	0	-0.45	21	21
HDAC1	0.009	0.003	-10000	0	-10000	0	0
AES	0.011	0.001	-10000	0	-10000	0	0
FBXW11	0.012	0	-10000	0	-10000	0	0
DTX1	-0.008	0.13	-10000	0	-0.81	7	7
LRP6/FZD1	0.013	0.031	-10000	0	-10000	0	0
TLE1	0.012	0.001	-10000	0	-10000	0	0
AP1	-0.16	0.26	-10000	0	-0.43	119	119
NCSTN	0.012	0	-10000	0	-10000	0	0
ADAM10	0.012	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.05	0.045	-10000	0	-10000	0	0
NICD/RBPSUH	0	0.009	-10000	0	-10000	0	0
WIF1	0.002	0.038	-10000	0	-0.25	6	6
NOTCH1	-0.001	0.008	-10000	0	-10000	0	0
PSENEN	0.012	0	-10000	0	-10000	0	0
KREMEN2	-0.022	0.088	-10000	0	-10000	0	0
DKK1	0.005	0.038	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.089	0.092	-10000	0	-10000	0	0
APH1B	0.007	0.068	-10000	0	-0.81	2	2
APH1A	0.012	0	-10000	0	-10000	0	0
AXIN1	-0.019	0.038	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.016	0.044	-10000	0	-0.34	4	4
PSEN1	0.012	0	-10000	0	-10000	0	0
FOS	-0.1	0.29	-10000	0	-0.81	41	41
JUN	0.012	0	-10000	0	-10000	0	0
MAP3K7	0.011	0.002	-10000	0	-10000	0	0
CTNNB1	0.087	0.099	0.24	76	-10000	0	76
MAPK3	0.012	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.022	0.069	-10000	0	-0.54	3	3
HNF1A	0	0.096	-10000	0	-0.81	4	4
CTBP1	0.011	0.001	-10000	0	-10000	0	0
MYC	0.02	0.042	-10000	0	-10000	0	0
NKD1	-0.25	0.38	-10000	0	-0.81	92	92
FZD1	0.004	0.046	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.011	0.07	-10000	0	-0.45	7	7
apoptosis	-0.16	0.26	-10000	0	-0.43	119	119
Delta 1/NOTCHprecursor	-0.034	0.12	-10000	0	-0.45	21	21
DLL1	-0.053	0.22	-10000	0	-0.69	27	27
PPARD	0.026	0.01	-10000	0	-10000	0	0
Gamma Secretase	0.031	0.042	-10000	0	-0.46	2	2
APC	-0.019	0.038	-10000	0	-10000	0	0
DVL1	0.002	0.008	-10000	0	-10000	0	0
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.018	0.045	-10000	0	-10000	0	0
LRP6	0.012	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.001	-10000	0	-10000	0	0
NLK	0.012	0.004	-10000	0	-10000	0	0
CCND1	0.021	0.085	-10000	0	-1.4	1	1
WNT1	-0.017	0.081	-10000	0	-0.25	30	30
Axin1/APC/beta catenin	0.072	0.048	-10000	0	-10000	0	0
DKK2	0.001	0.086	-10000	0	-0.81	3	3
NOTCH1 precursor/DVL1	0.003	0.01	-10000	0	-10000	0	0
GSK3B	0.012	0	-10000	0	-10000	0	0
FRAT1	0.011	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.012	0.069	-10000	0	-0.45	7	7
PPP2R5D	0.12	0.17	0.36	92	-10000	0	92
MAPK1	0.012	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.007	0.05	-10000	0	-10000	0	0
RBPJ	0.012	0	-10000	0	-10000	0	0
CREBBP	0.015	0.003	-10000	0	-10000	0	0

×

Reelin signaling 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
CDK5R1/CDK5	0.015	0.023	-9999	-10000	0	0
VLDLR	0.012	0	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
LRPAP1	0.012	0	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
ITGA3	-0.003	0.062	-9999	-0.25	17	17
RELN/VLDLR/Fyn	-0.063	0.13	-9999	-0.54	18	18
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.008	0.06	-9999	-0.46	5	5
AKT1	-0.012	0.086	-9999	-0.32	18	18
MAP2K7	0.012	0	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0
DAB1	-0.003	0.045	-9999	-0.25	9	9
RELN/LRP8/DAB1	-0.051	0.13	-9999	-0.51	18	18
LRPAP1/LRP8	0.016	0.021	-9999	-10000	0	0
RELN/LRP8/DAB1/Fyn	-0.057	0.12	-9999	-0.48	18	18
DAB1/alpha3/beta1 Integrin	-0.051	0.1	-9999	-0.43	18	18
long-term memory	-0.16	0.23	-9999	-0.5	88	88
DAB1/LIS1	-0.05	0.11	-9999	-0.45	18	18
DAB1/CRLK/C3G	-0.046	0.1	-9999	-0.43	18	18
PIK3CA	0.012	0	-9999	-10000	0	0
DAB1/NCK2	-0.05	0.11	-9999	-0.45	18	18
ARHGEF2	0.012	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.2	0.36	-9999	-0.81	74	74
CDK5R1	0.008	0.035	-9999	-0.25	5	5
RELN	-0.1	0.21	-9999	-0.81	18	18
PIK3R1	0.012	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.065	0.13	-9999	-0.55	18	18
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.18	0.24	-9999	-0.52	88	88
MAPK8	-0.002	0.11	-9999	-0.81	5	5
RELN/VLDLR/DAB1	-0.049	0.13	-9999	-0.51	18	18
ITGB1	0.012	0	-9999	-10000	0	0
MAP1B	-0.034	0.12	-9999	-0.47	18	18
RELN/LRP8	-0.065	0.13	-9999	-0.55	18	18
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.057	0.12	-9999	-0.48	18	18
PI3K	0.018	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.008	0.042	-9999	-10000	0	0
RAP1A	-0.01	0.11	-9999	-0.49	2	2
PAFAH1B1	0.012	0	-9999	-10000	0	0
MAPK8IP1	0.012	0	-9999	-10000	0	0
CRLK/C3G	0.018	0	-9999	-10000	0	0
GRIN2B	0.003	0.031	-9999	-10000	0	0
NCK2	0.012	0	-9999	-10000	0	0
neuron differentiation	0.002	0.07	-9999	-0.28	1	1
neuron adhesion	-0.003	0.11	-9999	-0.46	2	2
LRP8	0.009	0.031	-9999	-0.25	4	4
GSK3B	-0.004	0.082	-9999	-0.36	1	1
RELN/VLDLR/DAB1/Fyn	-0.056	0.12	-9999	-0.48	18	18
MAP3K11	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.02	0.091	-9999	-0.34	18	18
CDK5	0.012	0	-9999	-10000	0	0
MAPT	-0.001	0.091	-9999	-0.65	5	5
neuron migration	0.005	0.11	-9999	-0.4	18	18
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.002	0.071	-9999	-0.29	1	1
RELN/VLDLR	-0.035	0.13	-9999	-0.5	18	18

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.044	0.14	-10000	0	-0.55	22	22
cell-cell adhesion	0.033	0.098	0.46	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	-0.027	0.096	-10000	0	-0.46	13	13
ITSN1	0.012	0	-10000	0	-10000	0	0
PIK3CA	0.012	0	-10000	0	-10000	0	0
SHC1	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	-0.14	0.24	-10000	0	-0.55	74	74
Ephrin B1/EPHB1	-0.019	0.091	-10000	0	-0.55	8	8
HRAS/GDP	-0.028	0.09	-10000	0	-0.42	8	8
Ephrin B/EPHB1/GRB7	-0.041	0.12	-10000	0	-0.47	21	21
Endophilin/SYNJ1	0.005	0.099	-10000	0	-0.43	13	13
KRAS	0.012	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.042	0.12	-10000	0	-0.47	21	21
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
GRB7	0.012	0	-10000	0	-10000	0	0
PAK1	0.011	0.1	-10000	0	-0.43	13	13
HRAS	0.011	0.016	-10000	0	-10000	0	0
RRAS	0.005	0.1	-10000	0	-0.44	13	13
DNM1	-0.11	0.13	-10000	0	-0.25	132	132
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.01	0.13	-10000	0	-0.45	21	21
lamellipodium assembly	-0.033	0.098	-10000	0	-0.46	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.007	0.087	-10000	0	-0.33	9	9
PIK3R1	0.012	0	-10000	0	-10000	0	0
EPHB2	0.009	0.031	-10000	0	-10000	0	0
EPHB3	-0.2	0.36	-10000	0	-0.81	74	74
EPHB1	-0.018	0.14	-10000	0	-0.53	16	16
EPHB4	0.012	0	-10000	0	-10000	0	0
mol:GDP	0.042	0.13	-10000	0	-0.44	8	8
Ephrin B/EPHB2	-0.028	0.098	-10000	0	-0.46	13	13
Ephrin B/EPHB3	-0.15	0.23	-10000	0	-0.5	82	82
JNK cascade	0.018	0.083	-10000	0	-0.45	8	8
Ephrin B/EPHB1	-0.043	0.12	-10000	0	-0.48	21	21
RAP1/GDP	0.018	0.12	-10000	0	-0.44	1	1
EFNB2	0.012	0	-10000	0	-10000	0	0
EFNB3	-0.042	0.18	-10000	0	-0.81	13	13
EFNB1	0.012	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.004	0.089	-10000	0	-0.5	8	8
RAP1B	0.012	0	-10000	0	-10000	0	0
RAP1A	0.012	0	-10000	0	-10000	0	0
CDC42/GTP	-0.035	0.11	-10000	0	-0.49	2	2
Rap1/GTP	-0.032	0.098	-10000	0	-0.46	2	2
axon guidance	-0.043	0.14	-10000	0	-0.54	22	22
MAPK3	0.021	0.078	-10000	0	-0.34	1	1
MAPK1	0.021	0.078	-10000	0	-0.34	1	1
Rac1/GDP	0.048	0.12	-10000	0	-0.4	8	8
actin cytoskeleton reorganization	-0.021	0.069	-10000	0	-0.37	1	1
CDC42/GDP	0.048	0.12	-10000	0	-0.4	8	8
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.051	0.22	-10000	0	-0.81	22	22
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.012	0.077	-10000	0	-0.33	13	13
CDC42	0.012	0	-10000	0	-10000	0	0
RAS family/GTP	-0.032	0.096	-10000	0	-0.45	2	2
PTK2	0.004	0.018	-10000	0	-10000	0	0
MAP4K4	0.018	0.084	-10000	0	-0.46	8	8
SRC	0.011	0.016	-10000	0	-10000	0	0
KALRN	0.012	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0.018	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.031	0.099	-10000	0	-10000	0	0
MAP2K1	0.014	0.082	-10000	0	-0.34	2	2
WASL	0.012	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.012	0.089	-10000	0	-0.49	8	8
cell migration	0.029	0.094	-10000	0	-0.34	4	4
NRAS	0.012	0	-10000	0	-10000	0	0
SYNJ1	0.005	0.1	-10000	0	-0.44	13	13
PXN	0.012	0	-10000	0	-10000	0	0
TF	0.003	0.1	-10000	0	-0.41	15	15
HRAS/GTP	-0.036	0.1	-10000	0	-0.4	21	21
Ephrin B1/EPHB1-2	0.004	0.089	-10000	0	-0.5	8	8
cell adhesion mediated by integrin	0.068	0.13	0.53	13	-10000	0	13
RAC1	0.012	0	-10000	0	-10000	0	0
mol:GTP	-0.039	0.11	-10000	0	-0.43	21	21
RAC1-CDC42/GTP	-0.13	0.2	-10000	0	-0.63	18	18
RASA1	0.012	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.018	0.12	-10000	0	-0.44	1	1
ruffle organization	0.015	0.12	-10000	0	-0.46	2	2
NCK1	0.012	0	-10000	0	-10000	0	0
receptor internalization	-0.04	0.11	-10000	0	-0.44	13	13
Ephrin B/EPHB2/KALRN	-0.027	0.096	-10000	0	-0.46	13	13
ROCK1	-0.11	0.23	-10000	0	-0.49	74	74
RAS family/GDP	-0.02	0.066	-10000	0	-0.38	1	1
Rac1/GTP	-0.035	0.1	-10000	0	-0.49	2	2
Ephrin B/EPHB1/Src/Paxillin	0.001	0.097	-10000	0	-0.33	21	21

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	0	0.1	-10000	0	-0.5	12	12
regulation of S phase of mitotic cell cycle	0.012	0.074	-10000	0	-0.34	12	12
GNAO1	-0.045	0.2	-10000	0	-0.74	22	22
HRAS	0.011	0.016	-10000	0	-10000	0	0
SHBG/T-DHT	-0.005	0.056	-10000	0	-0.55	3	3
PELP1	0.012	0.001	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
MAP2K1	0.008	0.1	-10000	0	-0.42	12	12
T-DHT/AR	-0.02	0.13	-10000	0	-0.63	12	12
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.008	41	41
GNAI2	0.012	0	-10000	0	-10000	0	0
GNAI3	0.012	0	-10000	0	-10000	0	0
GNAI1	0.007	0.068	-10000	0	-0.81	2	2
mol:GDP	-0.026	0.12	-10000	0	-0.61	12	12
cell proliferation	-0.013	0.17	-10000	0	-0.45	12	12
PIK3CA	0.012	0	-10000	0	-10000	0	0
FOS	-0.078	0.32	-10000	0	-0.85	41	41
mol:Ca2+	-0.009	0.022	-10000	0	-0.074	23	23
MAPK3	-0.001	0.13	-10000	0	-0.59	3	3
MAPK1	-0.001	0.085	-10000	0	-0.31	2	2
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	0	0.002	-10000	0	-0.005	41	41
cAMP biosynthetic process	0.002	0.057	-10000	0	-0.52	3	3
GNG2	0.012	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	-10000	0	-0.005	41	41
HRAS/GTP	-0.025	0.095	-10000	0	-0.47	12	12
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.011	0.016	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.005	41	41
PI3K	0.002	0.006	-10000	0	-10000	0	0
apoptosis	0.019	0.16	0.4	42	-10000	0	42
T-DHT/AR/PELP1	-0.023	0.11	-10000	0	-0.55	12	12
HRAS/GDP	-0.024	0.12	-10000	0	-0.58	12	12
CREB1	-0.022	0.17	-10000	0	-0.42	42	42
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.025	0.17	-10000	0	-0.81	12	12
GNB1	0.012	0	-10000	0	-10000	0	0
RAF1	0.005	0.1	-10000	0	-0.45	12	12
RAC1-CDC42/GDP	-0.02	0.11	-10000	0	-0.55	12	12
T-DHT/AR/PELP1/Src	-0.002	0.11	-10000	0	-0.51	12	12
MAP2K2	0.008	0.1	-10000	0	-0.42	12	12
T-DHT/AR/PELP1/Src/PI3K	0.012	0.074	-10000	0	-0.34	12	12
GNAZ	0.012	0	-10000	0	-10000	0	0
SHBG	0.004	0.083	-10000	0	-0.81	3	3
Gi family/GNB1/GNG2/GDP	0.007	0.11	-10000	0	-0.39	19	19
mol:T-DHT	0	0.001	0.001	2	-0.003	37	39
RAC1	0.012	0	-10000	0	-10000	0	0
GNRH1	-0.026	0.072	-10000	0	-10000	0	0
Gi family/GTP	-0.006	0.085	-10000	0	-0.26	21	21
CDC42	0.012	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.01	0.009	-10000	0	-10000	0	0
HSPA8	0.01	0.048	-10000	0	-0.8	1	1
SMAD3/SMAD4/ER alpha	-0.032	0.13	-10000	0	-0.56	17	17
AKT1	0.015	0.003	-10000	0	-10000	0	0
GSC	0.015	0.045	-10000	0	-10000	0	0
NKX2-5	-0.012	0.061	-10000	0	-10000	0	0
muscle cell differentiation	0	0.026	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1	0.065	0.037	-10000	0	-10000	0	0
SMAD4	0.021	0.021	-10000	0	-10000	0	0
CBFB	0.012	0	-10000	0	-10000	0	0
SAP18	0.013	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.004	0.02	-10000	0	-10000	0	0
SMAD3/SMAD4/VDR	0	0.04	-10000	0	-0.45	2	2
MYC	0.002	0.043	-10000	0	-0.26	7	7
CDKN2B	0.039	0.03	-10000	0	-10000	0	0
AP1	-0.009	0.16	-10000	0	-0.41	36	36
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.063	0.01	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.046	0.024	-10000	0	-10000	0	0
SP3	0.015	0	-10000	0	-10000	0	0
CREB1	0.012	0	-10000	0	-10000	0	0
FOXH1	-0.031	0.1	-10000	0	-0.25	51	51
SMAD3/SMAD4/GR	0	0.016	-10000	0	-10000	0	0
GATA3	-0.62	0.34	-10000	0	-0.8	224	224
SKI/SIN3/HDAC complex/NCoR1	0.046	0.008	-10000	0	-10000	0	0
MEF2C/TIF2	-0.022	0.18	-10000	0	-0.53	24	24
endothelial cell migration	0.11	0.38	1.4	23	-10000	0	23
MAX	0.015	0.014	-10000	0	-10000	0	0
RBBP7	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.013	0.001	-10000	0	-10000	0	0
RUNX2	0.01	0.027	-10000	0	-0.25	3	3
RUNX3	-0.021	0.088	-10000	0	-10000	0	0
RUNX1	0.002	0.051	-10000	0	-0.25	11	11
CTBP1	0.012	0	-10000	0	-10000	0	0
NR3C1	0.015	0.014	-10000	0	-10000	0	0
VDR	0.007	0.068	-10000	0	-0.81	2	2
CDKN1A	0.056	0.039	-10000	0	-10000	0	0
KAT2B	0.011	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	0.01	0.06	-10000	0	-10000	0	0
DCP1A	0.012	0	-10000	0	-10000	0	0
SKI	0.013	0.001	-10000	0	-10000	0	0
SERPINE1	-0.11	0.39	-10000	0	-1.4	23	23
SMAD3/SMAD4/ATF2	0.001	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.034	0.14	-10000	0	-0.57	18	18
SAP30	0.012	0.016	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.005	0.017	-10000	0	-10000	0	0
JUN	-0.005	0.16	-10000	0	-0.41	30	30
SMAD3/SMAD4/IRF7	0	0.022	-10000	0	-10000	0	0
TFE3	0.015	0.015	-10000	0	-10000	0	0
COL1A2	0.006	0.064	-10000	0	-10000	0	0
mesenchymal cell differentiation	0	0.02	-10000	0	-10000	0	0
DLX1	-0.001	0.055	-10000	0	-10000	0	0
TCF3	0.012	0	-10000	0	-10000	0	0
FOS	-0.097	0.28	-10000	0	-0.8	41	41
SMAD3/SMAD4/Max	0	0.016	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.001	0.007	-10000	0	-10000	0	0
ZBTB17	0.01	0.002	-10000	0	-10000	0	0
LAMC1	0.047	0.027	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.001	0.017	-10000	0	-10000	0	0
IRF7	0.011	0.023	-10000	0	-10000	0	0
ESR1	-0.037	0.19	-10000	0	-0.81	17	17
HNF4A	-0.059	0.23	-10000	0	-0.81	25	25
MEF2C	0.023	0.06	-10000	0	-10000	0	0
SMAD2-3/SMAD4	0.022	0.031	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.006	0.013	-10000	0	-10000	0	0
IGHV3OR16-13	-0.002	0.008	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.012	0	-10000	0	-10000	0	0
CREBBP	0.011	0.006	-10000	0	-10000	0	0
SKIL	0.012	0	-10000	0	-10000	0	0
HDAC1	0.013	0.001	-10000	0	-10000	0	0
HDAC2	0.013	0.001	-10000	0	-10000	0	0
SNIP1	0.013	0.002	-10000	0	-10000	0	0
GCN5L2	-0.002	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.045	0.032	-10000	0	-10000	0	0
MSG1/HSC70	0.015	0.041	-10000	0	-0.61	1	1
SMAD2	0.019	0.004	-10000	0	-10000	0	0
SMAD3	0.018	0.022	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.041	0.022	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.014	0.013	-10000	0	-10000	0	0
NCOR1	0.013	0.001	-10000	0	-10000	0	0
NCOA2	-0.076	0.25	-10000	0	-0.81	31	31
NCOA1	0.012	0	-10000	0	-10000	0	0
MYOD/E2A	0.007	0.022	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.07	0.036	-10000	0	-10000	0	0
IFNB1	0.032	0.037	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	0.031	0.063	-10000	0	-10000	0	0
CITED1	0.009	0.027	-10000	0	-0.25	3	3
SMAD2-3/SMAD4/ARC105	0.048	0.029	-10000	0	-10000	0	0
RBL1	0.012	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.054	0.027	-10000	0	-10000	0	0
RUNX1-3/PEBPB2	-0.02	0.049	-10000	0	-10000	0	0
SMAD7	0.036	0.13	-10000	0	-10000	0	0
MYC/MIZ-1	-0.004	0.027	-10000	0	-10000	0	0
SMAD3/SMAD4	-0.03	0.12	-10000	0	-0.42	23	23
IL10	-0.37	0.22	-10000	0	-0.48	224	224
PIASy/HDAC complex	0.014	0.008	-10000	0	-10000	0	0
PIAS3	0.011	0.003	-10000	0	-10000	0	0
CDK2	0.011	0.004	-10000	0	-10000	0	0
IL5	-0.37	0.22	-10000	0	-0.48	224	224
CDK4	0.011	0.004	-10000	0	-10000	0	0
PIAS4	0.014	0.008	-10000	0	-10000	0	0
ATF3	-0.04	0.2	-10000	0	-0.78	19	19
SMAD3/SMAD4/SP1	0.049	0.035	-10000	0	-10000	0	0
FOXG1	-0.006	0.047	-10000	0	-10000	0	0
FOXO3	0.025	0.004	-10000	0	-10000	0	0
FOXO1	0.025	0.004	-10000	0	-10000	0	0
FOXO4	0.025	0.004	-10000	0	-10000	0	0
heart looping	0.023	0.06	-10000	0	-10000	0	0
CEBPB	0.005	0.046	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.004	0.036	-10000	0	-10000	0	0
MYOD1	-0.003	0.033	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.048	0.16	-10000	0	-0.56	25	25
SMAD3/SMAD4/GATA3	-0.42	0.23	-10000	0	-0.55	224	224
SnoN/SIN3/HDAC complex/NCoR1	0.012	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.022	0.054	-10000	0	-10000	0	0
SMAD3/SMAD4/SP1-3	0.059	0.035	-10000	0	-10000	0	0
MED15	0.012	0	-10000	0	-10000	0	0
SP1	0.02	0.011	-10000	0	-10000	0	0
SIN3B	0.013	0.001	-10000	0	-10000	0	0
SIN3A	0.013	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.008	0.065	-10000	0	-10000	0	0
ITGB5	0.062	0.026	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.045	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.023	0.11	-10000	0	-0.56	12	12
AR	-0.025	0.17	-10000	0	-0.81	12	12
negative regulation of cell growth	0.031	0.065	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	0.001	0.027	-10000	0	-10000	0	0
E2F5	0.012	0	-10000	0	-10000	0	0
E2F4	0.012	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.021	0.051	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4	0.052	0.023	-10000	0	-10000	0	0
TFDP1	0.012	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.005	0.16	-10000	0	-0.42	30	30
SMAD3/SMAD4/RUNX2	0	0.02	-10000	0	-10000	0	0
TGIF2	0.012	0	-10000	0	-10000	0	0
TGIF1	0.012	0	-10000	0	-10000	0	0
ATF2	0.012	0	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.1	-10000	0	-0.62	3	3
epithelial cell differentiation	-0.15	0.18	-10000	0	-0.44	71	71
ITCH	0.047	0.021	-10000	0	-10000	0	0
WWP1	-0.098	0.083	-10000	0	-10000	0	0
FYN	0.012	0	-10000	0	-10000	0	0
EGFR	0.012	0	-10000	0	-10000	0	0
PRL	0.002	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.037	0.076	-10000	0	-0.48	2	2
PTPRZ1	-0.012	0.11	-10000	0	-0.56	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.067	0.065	-10000	0	-0.46	5	5
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.086	0.093	-10000	0	-0.54	5	5
ADAM17	0.047	0.021	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.13	0.11	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.11	-10000	0	-0.68	3	3
NCOR1	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.087	-10000	0	-0.51	5	5
GRIN2B	-0.066	0.084	-10000	0	-0.48	5	5
ErbB4/ErbB2/betacellulin	-0.1	0.15	-10000	0	-0.56	22	22
STAT1	0.01	0.027	-10000	0	-10000	0	0
HBEGF	0.004	0.083	-10000	0	-0.81	3	3
PRLR	-0.24	0.38	-10000	0	-0.81	88	88
E4ICDs/ETO2	-0.11	0.09	-10000	0	-10000	0	0
axon guidance	-0.039	0.052	-10000	0	-10000	0	0
NEDD4	0.047	0.021	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.18	0.29	-10000	0	-0.63	88	88
CBFA2T3	0.011	0.016	-10000	0	-10000	0	0
ErbB4/ErbB2/HBEGF	-0.068	0.081	-10000	0	-0.54	3	3
MAPK3	-0.044	0.078	-10000	0	-0.43	5	5
STAT1 (dimer)	-0.11	0.091	-10000	0	-10000	0	0
MAPK1	-0.044	0.078	-10000	0	-0.43	5	5
JAK2	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.073	0.087	-10000	0	-0.51	5	5
NRG1	0.028	0.09	-10000	0	-0.62	5	5
NRG3	-0.008	0.098	-10000	0	-0.81	3	3
NRG2	0.006	0.07	-10000	0	-0.81	2	2
NRG4	-0.005	0.11	-10000	0	-0.81	5	5
heart development	-0.039	0.052	-10000	0	-10000	0	0
neural crest cell migration	-0.072	0.086	-10000	0	-0.5	5	5
ERBB2	0.042	0.013	-10000	0	-10000	0	0
WWOX/E4ICDs	-0.11	0.09	-10000	0	-10000	0	0
SHC1	0.012	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.1	0.11	-10000	0	-0.63	5	5
apoptosis	0.12	0.083	0.51	3	-10000	0	3
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.11	0.098	-10000	0	-0.59	2	2
ErbB4/ErbB2/epiregulin	-0.11	0.091	-10000	0	-10000	0	0
ErbB4/ErbB4/betacellulin/betacellulin	-0.15	0.17	-10000	0	-0.64	22	22
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.23	0.23	-10000	0	-0.55	90	90
MDM2	-0.11	0.091	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.059	0.073	-10000	0	-0.51	5	5
STAT5A	-0.03	0.049	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.073	0.087	-10000	0	-0.51	5	5
DLG4	0.012	0	-10000	0	-10000	0	0
GRB2/SHC	0.018	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	-0.11	0.068	-10000	0	-10000	0	0
STAT5A (dimer)	-0.16	0.2	-10000	0	-0.47	71	71
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.03	0.048	-10000	0	-10000	0	0
LRIG1	0.011	0.016	-10000	0	-10000	0	0
EREG	-0.098	0.13	-10000	0	-0.25	120	120
BTC	-0.05	0.22	-10000	0	-0.81	22	22
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.04	0.053	-10000	0	-10000	0	0
ERBB4	-0.13	0.11	-10000	0	-10000	0	0
STAT5B	0.012	0	-10000	0	-10000	0	0
YAP1	-0.036	0.023	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.073	0.093	-10000	0	-0.59	5	5
glial cell differentiation	0.11	0.068	-10000	0	-10000	0	0
WWOX	0.012	0	-10000	0	-10000	0	0
cell proliferation	-0.063	0.12	-10000	0	-0.42	23	23

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.009	0.14	-9999	-0.49	18	18
NF kappa B1 p50/RelA/I kappa B alpha	0.029	0.13	-9999	-0.7	3	3
alphaV/beta3 Integrin/Osteopontin/Src	-0.015	0.083	-9999	-0.61	5	5
AP1	-0.032	0.23	-9999	-0.73	16	16
ILK	0.004	0.14	-9999	-0.52	18	18
bone resorption	0.009	0.15	-9999	-0.68	6	6
PTK2B	0.012	0	-9999	-10000	0	0
PYK2/p130Cas	-0.034	0.12	-9999	-0.47	19	19
ITGAV	0.013	0.049	-9999	-0.81	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.008	0.11	-9999	-0.62	8	8
alphaV/beta3 Integrin/Osteopontin	-0.042	0.15	-9999	-0.58	18	18
MAP3K1	0.003	0.14	-9999	-0.52	18	18
JUN	0.013	0.001	-9999	-10000	0	0
MAPK3	0.011	0.14	-9999	-0.49	18	18
MAPK1	0.011	0.14	-9999	-0.49	18	18
Rac1/GDP	0.009	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	0.004	0.16	-9999	-0.52	21	21
ITGB3	-0.032	0.18	-9999	-0.8	15	15
NFKBIA	0.018	0.14	-9999	-0.48	18	18
FOS	-0.1	0.29	-9999	-0.81	41	41
CD44	-0.001	0.057	-9999	-0.25	14	14
CHUK	0.012	0	-9999	-10000	0	0
PLAU	-0.013	0.27	-9999	-1.1	14	14
NF kappa B1 p50/RelA	-0.037	0.11	-9999	-0.7	3	3
BCAR1	0.012	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.037	0.15	-9999	-0.65	15	15
mol:GDP	0	0	-9999	-10000	0	0
SYK	0	0.15	-9999	-0.52	19	19
VAV3	0.007	0.14	-9999	-0.48	20	20
MAP3K14	0.003	0.15	-9999	-0.53	18	18
ROCK2	-0.01	0.14	-9999	-0.81	8	8
SPP1	-0.002	0.1	-9999	-0.7	5	5
RAC1	0.012	0	-9999	-10000	0	0
Rac1/GTP	0.011	0.13	-9999	-0.57	5	5
MMP2	-0.016	0.19	-9999	-0.63	12	12

×

Regulation of Androgen receptor activity

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
HDAC1	0.021	0.001	-9999	-10000	0	0
SMARCC1	0.011	0.008	-9999	-10000	0	0
REL	-0.003	0.11	-9999	-0.81	5	5
HDAC7	-0.093	0.13	-9999	-0.67	5	5
JUN	0.012	0.003	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
KAT2B	0.012	0	-9999	-10000	0	0
KAT5	0.012	0	-9999	-10000	0	0
MAPK14	0.002	0.016	-9999	-10000	0	0
FOXO1	0.012	0	-9999	-10000	0	0
T-DHT/AR	-0.1	0.14	-9999	-0.72	5	5
MAP2K6	0.003	0.008	-9999	-10000	0	0
BRM/BAF57	0.018	0.005	-9999	-10000	0	0
MAP2K4	0.003	0.008	-9999	-10000	0	0
SMARCA2	0.012	0.002	-9999	-10000	0	0
PDE9A	-0.19	0.2	-9999	-0.61	40	40
NCOA2	-0.076	0.25	-9999	-0.81	31	31
CEBPA	-0.027	0.1	-9999	-0.27	41	41
EHMT2	0.012	0.003	-9999	-10000	0	0
cell proliferation	-0.16	0.19	-9999	-0.51	43	43
NR0B1	-0.046	0.1	-9999	-0.25	59	59
EGR1	-0.053	0.22	-9999	-0.81	23	23
RXRs/9cRA	0.017	0.01	-9999	-10000	0	0
AR/RACK1/Src	-0.033	0.082	-9999	-0.58	5	5
AR/GR	-0.01	0.089	-9999	-0.5	5	5
GNB2L1	0.012	0.001	-9999	-10000	0	0
PKN1	0.012	0	-9999	-10000	0	0
RCHY1	0.012	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.001	-9999	-10000	0	0
MAPK8	-0.009	0.087	-9999	-0.65	5	5
T-DHT/AR/TIF2/CARM1	-0.072	0.2	-9999	-0.6	31	31
SRC	-0.016	0.075	-9999	-0.52	5	5
NR3C1	0.012	0	-9999	-10000	0	0
KLK3	-0.1	0.21	-9999	-0.54	20	20
APPBP2	0.003	0.008	-9999	-10000	0	0
TRIM24	0.012	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.03	0.091	-9999	-0.61	5	5
TMPRSS2	-0.87	0.56	-9999	-1.2	195	195
RXRG	0.003	0.016	-9999	-0.25	1	1
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.012	0	-9999	-10000	0	0
RXRB	0.012	0	-9999	-10000	0	0
CARM1	0.012	0.001	-9999	-10000	0	0
NR2C2	0.004	0.083	-9999	-0.81	3	3
KLK2	-0.052	0.15	-9999	-0.58	11	11
AR	-0.018	0.097	-9999	-0.39	15	15
SENP1	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
MDM2	0.013	0.004	-9999	-10000	0	0
SRY	0.001	0.004	-9999	-10000	0	0
GATA2	-0.17	0.34	-9999	-0.81	63	63
MYST2	0.012	0	-9999	-10000	0	0
HOXB13	-0.071	0.12	-9999	-0.27	12	12
T-DHT/AR/RACK1/Src	-0.023	0.09	-9999	-0.59	5	5
positive regulation of transcription	-0.17	0.34	-9999	-0.81	63	63
DNAJA1	0.003	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.001	-9999	-10000	0	0
NCOA1	0.019	0.004	-9999	-10000	0	0
SPDEF	-0.011	0.074	-9999	-10000	0	0
T-DHT/AR/TIF2	-0.022	0.12	-9999	-0.55	8	8
T-DHT/AR/Hsp90	-0.03	0.091	-9999	-0.61	5	5
GSK3B	0.009	0.003	-9999	-10000	0	0
NR2C1	0.012	0.001	-9999	-10000	0	0
mol:T-DHT	-0.023	0.08	-9999	-0.56	5	5
SIRT1	0.012	0	-9999	-10000	0	0
ZMIZ2	0.013	0.004	-9999	-10000	0	0
POU2F1	-0.039	0.048	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.06	0.1	-9999	-0.66	5	5
CREBBP	0.012	0	-9999	-10000	0	0
SMARCE1	0.012	0.002	-9999	-10000	0	0

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.023	0.078	-9999	-10000	0	0
STMN1	-0.057	0.089	-9999	-10000	0	0
Aurora B/RasGAP/Survivin	-0.081	0.12	-9999	-10000	0	0
Chromosomal passenger complex/Cul3 protein complex	-0.042	0.1	-9999	-0.32	24	24
BIRC5	-0.07	0.12	-9999	-10000	0	0
DES	-0.31	0.3	-9999	-0.62	134	134
Aurora C/Aurora B/INCENP	-0.036	0.065	-9999	-10000	0	0
Aurora B/TACC1	-0.05	0.078	-9999	-0.66	1	1
Aurora B/PP2A	-0.062	0.086	-9999	-0.31	1	1
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.009	0.027	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.003	-9999	-10000	0	0
NDC80	-0.073	0.12	-9999	-0.32	29	29
Cul3 protein complex	-0.045	0.15	-9999	-0.54	24	24
KIF2C	-0.028	0.068	-9999	-0.19	26	26
PEBP1	0.009	0.005	-9999	-10000	0	0
KIF20A	-0.067	0.12	-9999	-0.25	86	86
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.061	0.085	-9999	-10000	0	0
SEPT1	0.003	0.049	-9999	-0.25	10	10
SMC2	0.012	0	-9999	-10000	0	0
SMC4	0.012	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.025	0.059	-9999	-10000	0	0
PSMA3	0.012	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.002	-9999	-10000	0	0
H3F3B	-0.033	0.057	-9999	-10000	0	0
AURKB	-0.1	0.14	-9999	-0.25	132	132
AURKC	0.012	0.001	-9999	-10000	0	0
CDCA8	-0.007	0.066	-9999	-0.27	1	1
cytokinesis	-0.092	0.096	-9999	-0.34	7	7
Aurora B/Septin1	-0.067	0.11	-9999	-0.35	1	1
AURKA	0.008	0.035	-9999	-0.26	5	5
INCENP	0.009	0.006	-9999	-10000	0	0
KLHL13	-0.053	0.22	-9999	-0.81	23	23
BUB1	-0.065	0.12	-9999	-10000	0	0
hSgo1/Aurora B/Survivin	-0.08	0.12	-9999	-0.35	20	20
EVI5	0.012	0.002	-9999	-10000	0	0
RhoA/GTP	-0.054	0.076	-9999	-0.34	1	1
SGOL1	-0.006	0.067	-9999	-10000	0	0
CENPA	-0.051	0.093	-9999	-0.23	19	19
NCAPG	-0.041	0.11	-9999	-0.25	58	58
Aurora B/HC8 Proteasome	-0.061	0.085	-9999	-10000	0	0
NCAPD2	0.012	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.061	0.085	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
NCAPH	-0.023	0.091	-9999	-0.25	39	39
NPM1	-0.04	0.056	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
KLHL9	0.009	0.048	-9999	-0.81	1	1
mitotic prometaphase	-0.002	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.061	0.085	-9999	-10000	0	0
PPP1CC	0.012	0	-9999	-10000	0	0
Centraspindlin	-0.061	0.084	-9999	-0.38	1	1
RhoA/GDP	0.009	0	-9999	-10000	0	0
NSUN2	-0.04	0.056	-9999	-10000	0	0
MYLK	-0.054	0.11	-9999	-0.5	13	13
KIF23	0.009	0.022	-9999	-0.26	2	2
VIM	-0.058	0.09	-9999	-0.32	1	1
RACGAP1	0.011	0.003	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
NCL	-0.04	0.056	-9999	-10000	0	0
Chromosomal passenger complex	-0.054	0.11	-9999	-0.28	19	19
Chromosomal passenger complex/EVI5	-0.054	0.13	-9999	-10000	0	0
TACC1	0.009	0.048	-9999	-0.81	1	1
PPP2R5D	0.011	0.016	-9999	-10000	0	0
CUL3	0.012	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.012	0	-9999	-10000	0	0
SPHK1	-0.12	0.13	-9999	-10000	0	0
GNAI2	0.012	0	-9999	-10000	0	0
mol:S1P	-0.027	0.049	-9999	-10000	0	0
GNAO1	-0.044	0.2	-9999	-0.74	22	22
mol:Sphinganine-1-P	-0.069	0.09	-9999	-10000	0	0
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.002	0.034	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0.01	-9999	-10000	0	0
S1PR3	-0.098	0.28	-9999	-0.81	39	39
S1PR2	0.012	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.032	0.032	-9999	-10000	0	0
S1PR5	-0.002	0.091	-9999	-0.81	3	3
S1PR4	0.007	0.038	-9999	-0.25	6	6
GNAI1	0.007	0.068	-9999	-0.81	2	2
S1P/S1P5/G12	-0.013	0.064	-9999	-0.52	3	3
S1P/S1P3/Gq	-0.13	0.23	-9999	-0.42	94	94
S1P/S1P4/Gi	-0.006	0.093	-9999	-0.33	19	19
GNAQ	0.012	0	-9999	-10000	0	0
GNAZ	0.012	0	-9999	-10000	0	0
GNA14	-0.2	0.36	-9999	-0.81	76	76
GNA15	-0.003	0.062	-9999	-10000	0	0
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.011	0.016	-9999	-0.25	1	1
GNA11	-0.005	0.12	-9999	-0.81	6	6
ABCC1	0.012	0	-9999	-10000	0	0

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.19	0.13	-9999	-0.54	1	1
RAD9A	0.01	0.027	-9999	-10000	0	0
AP1	-0.074	0.22	-9999	-0.62	41	41
IFNAR2	0.011	0.005	-9999	-10000	0	0
AKT1	-0.004	0.073	-9999	-0.29	17	17
ER alpha/Oestrogen	-0.029	0.15	-9999	-0.63	17	17
NFX1/SIN3/HDAC complex	0.037	0.016	-9999	-10000	0	0
EGF	-0.73	0.24	-9999	-0.81	262	262
SMG5	0.012	0	-9999	-10000	0	0
SMG6	0.012	0	-9999	-10000	0	0
SP3/HDAC2	0.017	0.007	-9999	-10000	0	0
TERT/c-Abl	-0.17	0.12	-9999	-0.5	1	1
SAP18	0.012	0.001	-9999	-10000	0	0
MRN complex	-0.002	0.032	-9999	-0.54	1	1
WT1	-0.44	0.41	-9999	-0.81	158	158
WRN	0.012	0	-9999	-10000	0	0
SP1	0.012	0.005	-9999	-10000	0	0
SP3	0.012	0.002	-9999	-10000	0	0
TERF2IP	0.012	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.14	0.11	-9999	-10000	0	0
Mad/Max	0.016	0.007	-9999	-10000	0	0
TERT	-0.19	0.13	-9999	-0.55	1	1
CCND1	-0.17	0.13	-9999	-1.2	1	1
MAX	0.012	0.002	-9999	-10000	0	0
RBBP7	0.012	0.001	-9999	-10000	0	0
RBBP4	0.012	0.001	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0.001	-9999	-10000	0	0
Telomerase/911	0.003	0.021	-9999	-10000	0	0
CDKN1B	0.023	0.036	-9999	-10000	0	0
RAD1	0.012	0	-9999	-10000	0	0
XRCC5	0.012	0	-9999	-10000	0	0
XRCC6	0.012	0	-9999	-10000	0	0
SAP30	0.011	0.016	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.012	0.002	-9999	-10000	0	0
JUN	0.012	0.002	-9999	-10000	0	0
E6	0	0.002	-9999	-10000	0	0
HPV-16 E6/E6AP	0.009	0.004	-9999	-10000	0	0
FOS	-0.1	0.29	-9999	-0.81	41	41
IFN-gamma/IRF1	-0.004	0.04	-9999	-10000	0	0
PARP2	0.012	0	-9999	-10000	0	0
BLM	0.001	0.053	-9999	-10000	0	0
Telomerase	-0.023	0.031	-9999	-10000	0	0
IRF1	0.017	0.002	-9999	-10000	0	0
ESR1	-0.036	0.19	-9999	-0.81	17	17
KU/TER	0.018	0	-9999	-10000	0	0
ATM/TRF2	0.019	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.043	0.015	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.041	0.018	-9999	-10000	0	0
HDAC1	0.012	0.001	-9999	-10000	0	0
HDAC2	0.011	0.005	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.02	0.015	-9999	-10000	0	0
ABL1	0.012	0	-9999	-10000	0	0
MXD1	0.012	0.002	-9999	-10000	0	0
MRE11A	0.012	0	-9999	-10000	0	0
HUS1	0.012	0	-9999	-10000	0	0
RPS6KB1	0.012	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.13	0.12	-9999	-0.55	1	1
NR2F2	0.013	0.004	-9999	-10000	0	0
MAPK3	0.011	0.019	-9999	-10000	0	0
MAPK1	0.011	0.019	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.011	0.022	-9999	-0.25	2	2
NFKB1	0.012	0	-9999	-10000	0	0
HNRNPC	0.012	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	0.012	0	-9999	-10000	0	0
EGFR	0.012	0.001	-9999	-10000	0	0
mol:Oestrogen	0	0.001	-9999	-10000	0	0
EGF/EGFR	-0.56	0.19	-9999	-0.62	262	262
MYC	0.004	0.044	-9999	-0.25	8	8
IL2	0.001	0.027	-9999	-10000	0	0
KU	0.018	0	-9999	-10000	0	0
RAD50	0.009	0.048	-9999	-0.81	1	1
HSP90AA1	0.012	0	-9999	-10000	0	0
TGFB1	0.011	0.022	-9999	-0.25	2	2
TRF2/BLM	-0.006	0.028	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.16	0.12	-9999	-10000	0	0
SP1/HDAC2	0.018	0.008	-9999	-10000	0	0
PINX1	0.012	0	-9999	-10000	0	0
Telomerase/EST1A	-0.14	0.11	-9999	-10000	0	0
Smad3/Myc	0.02	0.029	-9999	-10000	0	0
911 complex	-0.001	0.012	-9999	-10000	0	0
IFNG	-0.005	0.064	-9999	-0.25	19	19
Telomerase/PinX1	-0.14	0.11	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	-0.02	0.043	-9999	-10000	0	0
SIN3B	0.012	0.001	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
Telomerase/EST1B	-0.14	0.11	-9999	-10000	0	0
response to DNA damage stimulus	0.003	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	-0.002	0.026	-9999	-0.45	1	1
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.14	0.11	-9999	-10000	0	0
E2F1	-0.06	0.12	-9999	-0.26	78	78
ZNFX1	0.012	0.001	-9999	-10000	0	0
PIF1	-0.012	0.076	-9999	-10000	0	0
NCL	0.012	0	-9999	-10000	0	0
DKC1	0.012	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.09	0.27	-9999	-0.81	35	35
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.01	0.022	-9999	-0.25	2	2
TCEB1	0.012	0	-9999	-10000	0	0
HIF1A/p53	0.029	0.007	-9999	-10000	0	0
HIF1A	0.022	0.008	-9999	-10000	0	0
COPS5	0.012	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.007	-9999	-10000	0	0
FIH (dimer)	0.012	0	-9999	-10000	0	0
CDKN2A	-0.2	0.11	-9999	-0.25	232	232
ARNT/IPAS	-0.061	0.21	-9999	-0.62	35	35
HIF1AN	0.012	0	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
HIF1A/ARNT	0.029	0.007	-9999	-10000	0	0
CUL2	0.012	0	-9999	-10000	0	0
OS9	0.012	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.01	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.029	0.007	-9999	-10000	0	0
PHD1-3/OS9	0.027	0.024	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0	0.006	-9999	-10000	0	0
VHL	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
HIF1A/JAB1	0.029	0.007	-9999	-10000	0	0
EGLN3	0.003	0.049	-9999	-0.25	10	10
EGLN2	0.012	0	-9999	-10000	0	0
EGLN1	0.012	0	-9999	-10000	0	0
TP53	0.012	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.035	0.007	-9999	-10000	0	0
ARNT	0.012	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.012	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.061	0.046	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.028	0.059	-9999	-10000	0	0
adherens junction organization	-0.001	0.11	-9999	-0.44	5	5
mol:GTP	0	0	-9999	-10000	0	0
Rac1/GDP	0.033	0.058	-9999	-10000	0	0
FMN1	-0.029	0.17	-9999	-0.5	24	24
mol:IP3	0.02	0.06	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.003	0.1	-9999	-0.32	27	27
CTNNB1	0.013	0.004	-9999	-10000	0	0
AKT1	0.023	0.069	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.044	0.17	-9999	-0.56	27	27
CTNND1	0.013	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0.01	0.097	-9999	-10000	0	0
VASP	0.01	0.098	-9999	-10000	0	0
ZYX	0.01	0.098	-9999	-10000	0	0
JUB	0.01	0.098	-9999	-10000	0	0
EGFR(dimer)	0.009	0.098	-9999	-10000	0	0
E-cadherin/beta catenin-gamma catenin	-0.049	0.15	-9999	-0.52	27	27
mol:PI-3-4-5-P3	-0.019	0.06	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
PI3K	0.016	0.073	-9999	-10000	0	0
FYN	-0.26	0.16	-9999	-0.49	17	17
mol:Ca2+	0.02	0.059	-9999	-10000	0	0
JUP	0.013	0.004	-9999	-10000	0	0
PIK3R1	0.013	0.001	-9999	-10000	0	0
mol:DAG	0.02	0.06	-9999	-10000	0	0
CDH1	-0.065	0.24	-9999	-0.81	27	27
RhoA/GDP	0.033	0.058	-9999	-10000	0	0
establishment of polarity of embryonic epithelium	0.01	0.097	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
EGFR	0.012	0	-9999	-10000	0	0
CASR	-0.32	0.2	-9999	-0.43	222	222
RhoA/GTP	-0.014	0.043	-9999	-10000	0	0
AKT2	0.023	0.069	-9999	-10000	0	0
actin cable formation	-0.021	0.16	-9999	-0.48	24	24
apoptosis	-0.022	0.067	-9999	-10000	0	0
CTNNA1	0.013	0.001	-9999	-10000	0	0
mol:GDP	0.027	0.061	-9999	-10000	0	0
PIP5K1A	0.01	0.098	-9999	-10000	0	0
PLCG1	0.02	0.061	-9999	-10000	0	0
Rac1/GTP	-0.025	0.078	-9999	-10000	0	0
homophilic cell adhesion	0.001	0.001	-9999	-10000	0	0

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.029	0.096	-9999	-0.38	7	7
MAP4K1	-0.044	0.11	-9999	-0.25	61	61
MAP3K8	0.012	0	-9999	-10000	0	0
PRKCB	0.009	0.048	-9999	-0.81	1	1
DBNL	0.012	0	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
MAP3K1	0.011	0.052	-9999	-10000	0	0
JUN	0.016	0.087	-9999	-0.57	6	6
MAP3K7	0.011	0.052	-9999	-10000	0	0
GRAP2	0.006	0.041	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
MAP2K4	0.02	0.05	-9999	-10000	0	0
LAT	-0.045	0.11	-9999	-0.25	62	62
LCP2	0.008	0.035	-9999	-10000	0	0
MAPK8	0.009	0.092	-9999	-0.61	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.004	0.055	-9999	-10000	0	0
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.044	0.075	-9999	-0.43	2	2

×

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

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
MET/RANBP9	0.002	0.051	-9999	-10000	0	0
CRKL	-0.003	0.098	-9999	-0.32	7	7
mol:PIP3	-0.018	0.005	-9999	-10000	0	0
AKT1	0.002	0.004	-9999	-10000	0	0
PTK2B	0.012	0	-9999	-10000	0	0
RAPGEF1	0.004	0.094	-9999	-10000	0	0
RANBP10	0.012	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.074	0.18	-9999	-0.56	34	34
MAP3K5	0.001	0.088	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.041	0.18	-9999	-0.51	34	34
AP1	-0.069	0.2	-9999	-0.56	41	41
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
apoptosis	-0.093	0.26	-9999	-0.74	41	41
STAT3 (dimer)	-0.008	0.12	-9999	-0.32	34	34
GAB1/CRKL/SHP2/PI3K	-0.028	0.073	-9999	-10000	0	0
INPP5D	0.006	0.041	-9999	-10000	0	0
CBL/CRK	0.004	0.094	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.012	0	-9999	-10000	0	0
PTEN	0.012	0	-9999	-10000	0	0
ELK1	-0.011	0.032	-9999	-10000	0	0
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.024	0.063	-9999	-0.24	7	7
PAK1	0.008	0.004	-9999	-10000	0	0
HGF/MET/RANBP10	-0.074	0.18	-9999	-0.56	34	34
HRAS	-0.022	0.14	-9999	-0.41	34	34
DOCK1	0.004	0.094	-9999	-10000	0	0
GAB1	-0.011	0.1	-9999	-0.34	7	7
CRK	-0.003	0.098	-9999	-0.32	7	7
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.072	0.18	-9999	-0.57	34	34
JUN	0.012	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.025	0.093	-9999	-0.27	34	34
PIK3R1	0.012	0	-9999	-10000	0	0
cell morphogenesis	0.017	0.12	-9999	-10000	0	0
GRB2/SHC	-0.007	0.084	-9999	-0.29	7	7
FOS	-0.1	0.29	-9999	-0.81	41	41
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.011	0.032	-9999	-10000	0	0
HGF/MET/MUC20	-0.076	0.18	-9999	-0.57	34	34
cell migration	-0.008	0.082	-9999	-0.28	7	7
GRB2	0.012	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
MET/RANBP10	0.002	0.051	-9999	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.12	-9999	-0.34	34	34
MET/MUC20	-0.007	0.052	-9999	-10000	0	0
RAP1B	0.011	0.089	-9999	-10000	0	0
RAP1A	0.011	0.089	-9999	-10000	0	0
HGF/MET/RANBP9	-0.074	0.18	-9999	-0.56	34	34
RAF1	-0.014	0.14	-9999	-0.45	7	7
STAT3	-0.008	0.12	-9999	-0.32	34	34
cell proliferation	-0.011	0.16	-9999	-0.43	34	34
RPS6KB1	-0.002	0.035	-9999	-10000	0	0
MAPK3	-0.015	0.029	-9999	-10000	0	0
MAPK1	-0.015	0.029	-9999	-10000	0	0
RANBP9	0.012	0	-9999	-10000	0	0
MAPK8	0.011	0.1	-9999	-0.52	5	5
SRC	-0.007	0.12	-9999	-0.38	7	7
PI3K	-0.007	0.084	-9999	-10000	0	0
MET/Glomulin	-0.003	0.045	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
MAP2K1	-0.006	0.13	-9999	-0.41	7	7
MET	-0.012	0.077	-9999	-10000	0	0
MAP4K1	-0.006	0.092	-9999	-10000	0	0
PTK2	0.012	0	-9999	-10000	0	0
MAP2K2	-0.006	0.13	-9999	-0.41	7	7
BAD	0.008	0.004	-9999	-10000	0	0
MAP2K4	0.008	0.082	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.031	0.078	-9999	-10000	0	0
INPPL1	0.012	0	-9999	-10000	0	0
PXN	0.012	0	-9999	-10000	0	0
SH3KBP1	0.012	0	-9999	-10000	0	0
HGS	-0.016	0.087	-9999	-0.31	7	7
PLCgamma1/PKC	0.009	0	-9999	-10000	0	0
HGF	-0.084	0.26	-9999	-0.81	34	34
RASA1	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
PTPRJ	0.012	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.009	0.094	-9999	-0.32	7	7
PDPK1	-0.007	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.077	0.18	-9999	-0.56	34	34

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	0.007	0.023	-9999	-10000	0	0
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.006	0.037	-9999	-10000	0	0
STXBP1	0.012	0	-9999	-10000	0	0
ACh/CHRNA1	-0.099	0.076	-9999	-0.22	2	2
RAB3GAP2/RIMS1/UNC13B	-0.006	0.026	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.006	0.056	-9999	-0.25	14	14
mol:ACh	-0.008	0.024	-9999	-0.15	1	1
RAB3GAP2	0.012	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.012	0.024	-9999	-10000	0	0
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.099	0.076	-9999	-0.22	2	2
UNC13B	0.012	0	-9999	-10000	0	0
CHRNA1	-0.16	0.13	-9999	-10000	0	0
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.19	0.28	-9999	-0.58	96	96
SNAP25	-0.028	0.051	-9999	-0.38	1	1
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.26	0.39	-9999	-0.81	96	96
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.015	0.019	-9999	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	-0.012	0.024	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.017	0.18	-9999	-0.57	27	27
KLHL20	-0.016	0.051	-9999	-0.35	1	1
CYFIP2	0.007	0.068	-9999	-0.81	2	2
Rac1/GDP	0.02	0.12	-9999	-0.37	1	1
ENAH	-0.017	0.18	-9999	-0.57	27	27
AP1M1	0.012	0	-9999	-10000	0	0
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
CDC42/GTP	-0.027	0.083	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.012	0.036	-9999	-0.22	1	1
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.15	-9999	-0.49	27	27
RAPGEF1	0.001	0.15	-9999	-0.48	27	27
CTNND1	0.012	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.055	0.17	-9999	-0.59	27	27
CRK	-0.008	0.17	-9999	-0.52	27	27
E-cadherin/gamma catenin/alpha catenin	-0.05	0.16	-9999	-0.54	27	27
alphaE/beta7 Integrin	0.018	0	-9999	-10000	0	0
IQGAP1	0.012	0	-9999	-10000	0	0
NCKAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0.001	-9999	-10000	0	0
DLG1	-0.017	0.18	-9999	-0.57	27	27
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.019	0.06	-9999	-10000	0	0
MLLT4	0.012	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.022	0.017	-9999	-10000	0	0
PI3K	-0.025	0.077	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.041	0.19	-9999	-0.62	27	27
TIAM1	0.012	0	-9999	-10000	0	0
E-cadherin(dimer)/Ca2+	-0.016	0.14	-9999	-0.46	27	27
AKT1	-0.014	0.043	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
CDH1	-0.064	0.24	-9999	-0.81	27	27
RhoA/GDP	0.019	0.12	-9999	-0.36	1	1
actin cytoskeleton organization	0.027	0.05	-9999	-0.24	1	1
CDC42/GDP	0.019	0.12	-9999	-0.36	1	1
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.01	0.1	-9999	-0.34	27	27
ITGB7	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.016	0.15	-9999	-0.49	27	27
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.024	0.14	-9999	-0.47	27	27
mol:GDP	0.011	0.14	-9999	-0.41	27	27
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.012	0	-9999	-10000	0	0
p120 catenin/RhoA/GDP	-0.033	0.1	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0.018	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
CDC42	0.012	0	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.023	0.037	-9999	-0.29	1	1
NME1	0.008	0.035	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.017	0.18	-9999	-0.57	27	27
regulation of cell-cell adhesion	-0.023	0.073	-9999	-10000	0	0
WASF2	-0.006	0.019	-9999	-10000	0	0
Rap1/GTP	-0.031	0.095	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.043	0.13	-9999	-0.46	27	27
CCND1	0.026	0.045	-9999	-0.38	1	1
VAV2	-0.002	0.16	-9999	-0.5	27	27
RAP1/GDP	0.016	0.11	-9999	-10000	0	0
adherens junction assembly	-0.015	0.17	-9999	-0.55	27	27
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.012	0	-9999	-10000	0	0
PIP5K1C	0.012	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.002	0.14	-9999	-0.44	27	27
E-cadherin/beta catenin	-0.046	0.14	-9999	-0.5	27	27
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.017	0.18	-9999	-0.57	27	27
PIK3CA	0.012	0	-9999	-10000	0	0
Rac1/GTP	-0.025	0.083	-9999	-0.65	1	1
E-cadherin/beta catenin/alpha catenin	-0.05	0.16	-9999	-0.54	27	27
ITGAE	0.012	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.056	0.18	-9999	-0.6	27	27

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.011	0.004	-9999	-10000	0	0
PRKCZ	0.012	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.005	0.033	-9999	-10000	0	0
IRAK/TOLLIP	0.025	0.003	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
IKBKG	0.012	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.2	0.29	-9999	-0.63	90	90
IL1A	-0.013	0.076	-9999	-10000	0	0
IL1B	0.007	0.093	-9999	-0.62	6	6
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.012	-9999	-10000	0	0
IL1R2	-0.24	0.38	-9999	-0.81	90	90
IL1R1	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.032	0.033	-9999	-10000	0	0
TOLLIP	0.012	0	-9999	-10000	0	0
TICAM2	0.009	0.048	-9999	-0.81	1	1
MAP3K3	0.012	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.058	0.006	-9999	-10000	0	0
JUN	0.032	0.056	-9999	-0.39	5	5
MAP3K7	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.031	0.069	-9999	-0.44	6	6
IL1 alpha/IL1R1/IL1RAP/MYD88	0.019	0.038	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.008	0.025	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	0.019	0.075	-9999	-0.49	6	6
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	0.027	0.059	-9999	-0.42	5	5
IRAK1	0.019	0.004	-9999	-10000	0	0
IL1RN/IL1R1	0.002	0.082	-9999	-0.62	4	4
IRAK4	0.012	0	-9999	-10000	0	0
PRKCI	0.012	0	-9999	-10000	0	0
TRAF6	0.012	0	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.031	0.042	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.019	0.075	-9999	-0.49	6	6
IL1 beta/IL1R2	-0.16	0.27	-9999	-0.55	94	94
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.056	-9999	-10000	0	0
IRAK3	0.011	0.016	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.029	0.083	-9999	-0.51	6	6
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.027	0.025	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.011	0.035	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.004	0.046	-9999	-0.25	9	9
MYD88	0.012	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.032	0.003	-9999	-10000	0	0
IL1RAP	0.011	0.016	-9999	-0.25	1	1
UBE2N	0.012	0	-9999	-10000	0	0
IRAK/TRAF6	-0.009	0.063	-9999	-0.72	1	1
CASP1	0.01	0.022	-9999	-10000	0	0
IL1RN/IL1R2	-0.2	0.31	-9999	-0.64	91	91
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.026	0.071	-9999	-0.46	6	6
TMEM189-UBE2V1	0.003	0.005	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.033	0.019	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
IL1RN	-0.01	0.11	-9999	-0.39	16	16
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.029	0.003	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.001	0.02	-9999	-10000	0	0
VDR	0.007	0.068	-9999	-0.81	2	2
FAM120B	0.012	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.047	0.039	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.052	0.056	-9999	-0.39	3	3
MED1	0.012	0	-9999	-10000	0	0
mol:9cRA	0.005	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.02	0.072	-9999	-0.33	12	12
RXRs/NUR77	-0.14	0.25	-9999	-0.49	99	99
RXRs/PPAR	0.037	0.013	-9999	-10000	0	0
NCOR2	0.012	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.005	0.053	-9999	-0.63	2	2
RARs/VDR/DNA/Vit D3	-0.004	0.039	-9999	-0.46	2	2
RARA	0.012	0	-9999	-10000	0	0
NCOA1	0.012	0	-9999	-10000	0	0
VDR/VDR/DNA	0.007	0.068	-9999	-0.81	2	2
RARs/RARs/DNA/9cRA	0.024	0.01	-9999	-10000	0	0
RARG	0.011	0.016	-9999	-0.25	1	1
RPS6KB1	0.002	0.014	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.02	0.072	-9999	-0.33	12	12
THRA	0.012	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.005	0.053	-9999	-0.63	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	0.034	0.024	-9999	-10000	0	0
NR1H4	0	0.097	-9999	-0.7	5	5
RXRs/LXRs/DNA	0.054	0.029	-9999	-10000	0	0
NR1H2	0.017	0.006	-9999	-10000	0	0
NR1H3	0.018	0.007	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.032	0.044	-9999	-0.46	2	2
NR4A1	-0.27	0.39	-9999	-0.81	99	99
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.027	0.046	-9999	-0.34	4	4
RXRG	0.008	0.018	-9999	-10000	0	0
RXR alpha/CCPG	0.021	0.006	-9999	-10000	0	0
RXRA	0.017	0.006	-9999	-10000	0	0
RXRB	0.017	0.007	-9999	-10000	0	0
THRB	-0.022	0.16	-9999	-0.81	12	12
PPARG	0.011	0.016	-9999	-10000	0	0
PPARD	0.012	0	-9999	-10000	0	0
TNF	0.043	0.13	-9999	-1.2	3	3
mol:Oxysterols	0.005	0.007	-9999	-10000	0	0
cholesterol transport	0.052	0.056	-9999	-0.38	3	3
PPARA	0.012	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.012	0	-9999	-10000	0	0
RXRs/NUR77/BCL2	-0.096	0.17	-9999	-0.34	99	99
SREBF1	0.056	0.054	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	0.034	0.024	-9999	-10000	0	0
ABCA1	0.057	0.052	-9999	-10000	0	0
RARs/THRs	-0.019	0.091	-9999	-0.46	12	12
RXRs/FXR	0.03	0.064	-9999	-0.49	4	4
BCL2	0.012	0	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.012	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.098	0.18	-9999	-0.42	65	65
Syndecan-3/Neurocan	-0.009	0.028	-9999	-10000	0	0
POMC	-0.005	0.12	-9999	-0.81	6	6
EGFR	0.012	0	-9999	-10000	0	0
Syndecan-3/EGFR	-0.002	0.011	-9999	-10000	0	0
AGRP	0.008	0.016	-9999	-10000	0	0
NCSTN	0.012	0	-9999	-10000	0	0
PSENEN	0.012	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.007	0.068	-9999	-0.81	2	2
APH1A	0.012	0	-9999	-10000	0	0
NCAN	-0.012	0.073	-9999	-0.25	24	24
long-term memory	-0.001	0.009	-9999	-10000	0	0
Syndecan-3/IL8	-0.014	0.041	-9999	-0.46	1	1
PSEN1	0.012	0	-9999	-10000	0	0
Src/Cortactin	0.018	0.01	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
limb bud formation	-0.002	0.013	-9999	-10000	0	0
MC4R	0	0.026	-9999	-0.25	3	3
SRC	0.011	0.016	-9999	-10000	0	0
PTN	-0.18	0.34	-9999	-0.81	65	65
FGFR/FGF/Syndecan-3	-0.002	0.013	-9999	-10000	0	0
neuron projection morphogenesis	-0.1	0.17	-9999	-0.41	65	65
Syndecan-3/AgRP	-0.002	0.013	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	-0.003	0.014	-9999	-10000	0	0
Fyn/Cortactin	0.018	0	-9999	-10000	0	0
SDC3	-0.002	0.013	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.014	0.041	-9999	-0.45	1	1
IL8	-0.021	0.096	-9999	-0.27	34	34
Syndecan-3/Fyn/Cortactin	-0.001	0.01	-9999	-10000	0	0
Syndecan-3/CASK	-0.002	0.012	-9999	-10000	0	0
alpha-MSH/MC4R	-0.004	0.093	-9999	-0.63	6	6
Gamma Secretase	-0.003	0.038	-9999	-0.46	2	2

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.063	0.31	-10000	0	-1.2	7	7
IL23A	-0.06	0.31	-10000	0	-1.1	8	8
NF kappa B1 p50/RelA/I kappa B alpha	-0.13	0.22	-10000	0	-0.87	12	12
positive regulation of T cell mediated cytotoxicity	-0.065	0.31	-10000	0	-0.98	12	12
ITGA3	-0.058	0.29	-10000	0	-0.93	10	10
IL17F	-0.023	0.22	-10000	0	-0.71	3	3
IL12B	0.009	0.037	-10000	0	-0.31	1	1
STAT1 (dimer)	-0.063	0.29	-10000	0	-0.94	12	12
CD4	-0.055	0.29	-10000	0	-1	4	4
IL23	-0.07	0.3	-10000	0	-1.1	8	8
IL23R	0.004	0.089	-10000	0	-10000	0	0
IL1B	-0.069	0.33	-10000	0	-1.2	11	11
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.054	0.28	-10000	0	-0.93	8	8
TYK2	0.014	0.018	-10000	0	-10000	0	0
STAT4	-0.004	0.064	-10000	0	-0.25	18	18
STAT3	0.012	0.001	-10000	0	-10000	0	0
IL18RAP	-0.009	0.072	-10000	0	-10000	0	0
IL12RB1	-0.009	0.082	-10000	0	-0.28	16	16
PIK3CA	0.012	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.002	0.06	-10000	0	-10000	0	0
IL23R/JAK2	0.011	0.1	-10000	0	-10000	0	0
positive regulation of chronic inflammatory response	-0.065	0.31	-10000	0	-0.98	12	12
natural killer cell activation	0	0.008	0.035	2	-10000	0	2
JAK2	0.02	0.023	-10000	0	-10000	0	0
PIK3R1	0.012	0.001	-10000	0	-10000	0	0
NFKB1	0.012	0.003	-10000	0	-10000	0	0
RELA	0.012	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.067	0.29	-10000	0	-1	8	8
ALOX12B	-0.058	0.29	-10000	0	-0.91	9	9
CXCL1	-0.1	0.34	-10000	0	-1.1	16	16
T cell proliferation	-0.065	0.31	-10000	0	-0.98	12	12
NFKBIA	0.012	0.003	-10000	0	-10000	0	0
IL17A	-0.002	0.19	-10000	0	-0.56	2	2
PI3K	-0.12	0.23	-10000	0	-0.9	12	12
IFNG	0.001	0.025	-10000	0	-10000	0	0
STAT3 (dimer)	-0.13	0.21	-10000	0	-0.87	11	11
IL18R1	0.009	0.048	-10000	0	-0.81	1	1
IL23/IL23R/JAK2/TYK2/SOCS3	-0.021	0.2	-10000	0	-0.78	2	2
IL18/IL18R	0.007	0.055	-10000	0	-0.54	1	1
macrophage activation	-0.01	0.013	-10000	0	-0.043	8	8
TNF	-0.066	0.32	-10000	0	-1.1	10	10
STAT3/STAT4	-0.13	0.24	-10000	0	-0.92	12	12
STAT4 (dimer)	-0.068	0.3	-10000	0	-0.96	12	12
IL18	0.008	0.031	-10000	0	-0.25	4	4
IL19	-0.059	0.28	-10000	0	-0.98	5	5
STAT5A (dimer)	-0.062	0.29	-10000	0	-0.94	12	12
STAT1	0.01	0.027	-10000	0	-10000	0	0
SOCS3	0.004	0.073	-10000	0	-0.48	5	5
CXCL9	-0.067	0.32	-10000	0	-1	13	13
MPO	-0.057	0.29	-10000	0	-0.98	5	5
positive regulation of humoral immune response	-0.065	0.31	-10000	0	-0.98	12	12
IL23/IL23R/JAK2/TYK2	-0.068	0.31	-10000	0	-1	12	12
IL6	-0.2	0.52	-10000	0	-1.2	55	55
STAT5A	0.012	0	-10000	0	-10000	0	0
IL2	0.002	0.027	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0	0.008	0.035	2	-10000	0	2
CD3E	-0.067	0.3	-10000	0	-1.1	6	6
keratinocyte proliferation	-0.065	0.31	-10000	0	-0.98	12	12
NOS2	-0.11	0.4	-10000	0	-1.2	27	27

×

Caspase cascade in apoptosis

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
TOP1	0.023	0.039	-10000	0	-0.39	1	1
ACTA1	0.016	0.047	-10000	0	-0.51	1	1
NUMA1	0.023	0.039	-10000	0	-0.39	1	1
SPTAN1	0.017	0.047	-10000	0	-0.5	1	1
LIMK1	0.016	0.049	-10000	0	-0.5	1	1
BIRC3	0	0.055	-10000	0	-10000	0	0
BIRC2	0.012	0	-10000	0	-10000	0	0
BAX	0.01	0.022	-10000	0	-0.25	2	2
CASP10	0.014	0.058	-10000	0	-0.54	1	1
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0	-10000	0	-10000	0	0
PTK2	0.023	0.039	-10000	0	-0.39	1	1
DIABLO	0.012	0	-10000	0	-10000	0	0
apoptotic nuclear changes	0.017	0.046	-10000	0	-0.5	1	1
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.012	0	-10000	0	-10000	0	0
GSN	0.017	0.047	-10000	0	-0.5	1	1
MADD	0.012	0	-10000	0	-10000	0	0
TFAP2A	-0.41	0.24	-10000	0	-0.53	229	229
BID	0.016	0.03	-10000	0	-0.27	1	1
MAP3K1	0.013	0.019	-10000	0	-10000	0	0
TRADD	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.018	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.017	0.047	-10000	0	-0.5	1	1
CASP9	0.012	0	-10000	0	-10000	0	0
DNA repair	-0.009	0.018	-10000	0	-10000	0	0
neuron apoptosis	0.024	0.007	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.024	0.045	-10000	0	-0.48	1	1
APAF1	0.012	0	-10000	0	-10000	0	0
CASP6	0.03	0.026	-10000	0	-10000	0	0
TRAF2	0.012	0	-10000	0	-10000	0	0
ICAD/CAD	0.023	0.045	-10000	0	-0.48	1	1
CASP7	-0.006	0.026	-10000	0	-10000	0	0
KRT18	0.016	0.015	-10000	0	-10000	0	0
apoptosis	0.027	0.044	-10000	0	-0.43	1	1
DFFA	0.017	0.047	-10000	0	-0.5	1	1
DFFB	0.017	0.047	-10000	0	-0.5	1	1
PARP1	0.009	0.018	-10000	0	-10000	0	0
actin filament polymerization	-0.022	0.046	0.46	1	-10000	0	1
TNF	-0.009	0.1	-10000	0	-0.81	3	3
CYCS	0.016	0.024	-10000	0	-0.19	1	1
SATB1	0.034	0.037	-10000	0	-0.42	1	1
SLK	0.017	0.047	-10000	0	-0.5	1	1
p15 BID/BAX	0.02	0.028	-10000	0	-0.23	1	1
CASP2	0.036	0.035	-10000	0	-10000	0	0
JNK cascade	-0.013	0.019	-10000	0	-10000	0	0
CASP3	0.011	0.049	-10000	0	-0.54	1	1
LMNB2	0.039	0.026	-10000	0	-10000	0	0
RIPK1	0.012	0	-10000	0	-10000	0	0
CASP4	0.012	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	0.026	0.027	-10000	0	-10000	0	0
negative regulation of DNA binding	-0.41	0.23	-10000	0	-0.52	229	229
stress fiber formation	0.017	0.046	-10000	0	-0.5	1	1
GZMB	0.005	0.068	-10000	0	-0.37	6	6
CASP1	0.015	0.01	-10000	0	-10000	0	0
LMNB1	0.038	0.027	-10000	0	-10000	0	0
APP	0.024	0.007	-10000	0	-10000	0	0
TNFRSF1A	0.012	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.011	0	-10000	0	-10000	0	0
VIM	0.022	0.043	-10000	0	-0.42	1	1
LMNA	0.039	0.026	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.03	0.037	-10000	0	-10000	0	0
LRDD	-0.001	0.057	-10000	0	-10000	0	0
SREBF1	0.017	0.047	-10000	0	-0.5	1	1
APAF-1/Caspase 9	0	0.011	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	0.023	0.038	-10000	0	-0.38	1	1
CFL2	0.022	0.047	-10000	0	-0.47	1	1
GAS2	0.007	0.089	-10000	0	-0.51	7	7
positive regulation of apoptosis	0.041	0.027	-10000	0	-10000	0	0
PRF1	0.006	0.041	-10000	0	-0.25	7	7

×

IL12-mediated signaling events

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
IL12/IL12R/TYK2/JAK2/SOCS1	-0.009	0.096	-10000	0	-0.39	6	6
TBX21	-0.005	0.24	-10000	0	-0.78	11	11
B2M	0.013	0.003	-10000	0	-10000	0	0
TYK2	0.017	0.016	-10000	0	-10000	0	0
IL12RB1	-0.006	0.084	-10000	0	-0.28	18	18
GADD45B	0.018	0.21	-10000	0	-0.74	5	5
IL12RB2	-0.12	0.15	-10000	0	-0.52	7	7
GADD45G	0.015	0.22	-10000	0	-0.85	6	6
natural killer cell activation	0.007	0.018	-10000	0	-10000	0	0
RELB	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL18	0.012	0.032	-10000	0	-0.25	4	4
IL2RA	-0.009	0.072	-10000	0	-10000	0	0
IFNG	-0.01	0.065	-10000	0	-0.25	19	19
STAT3 (dimer)	0.013	0.21	-10000	0	-0.57	16	16
HLA-DRB5	-0.002	0.083	-10000	0	-0.82	2	2
FASLG	-0.005	0.24	-10000	0	-0.77	12	12
NF kappa B2 p52/RelB	-0.083	0.18	-10000	0	-0.64	17	17
CD4	0	0.053	-10000	0	-10000	0	0
SOCS1	-0.003	0.11	-10000	0	-0.81	5	5
EntrezGene:6955	-0.002	0.01	-10000	0	-10000	0	0
CD3D	-0.026	0.094	-10000	0	-0.26	41	41
CD3E	-0.027	0.1	-10000	0	-0.82	1	1
CD3G	-0.001	0.059	-10000	0	-0.26	12	12
IL12Rbeta2/JAK2	-0.064	0.11	-10000	0	-0.64	3	3
CCL3	-0.015	0.26	-10000	0	-0.9	10	10
CCL4	-0.007	0.25	-10000	0	-0.78	12	12
HLA-A	0.01	0.028	-10000	0	-0.26	3	3
IL18/IL18R	0.038	0.068	-10000	0	-0.52	1	1
NOS2	-0.044	0.38	-10000	0	-1.1	25	25
IL12/IL12R/TYK2/JAK2/SPHK2	-0.003	0.083	-10000	0	-0.41	2	2
IL1R1	0.002	0.23	-10000	0	-0.74	10	10
IL4	-0.003	0.019	-10000	0	-10000	0	0
JAK2	0.017	0.016	-10000	0	-10000	0	0
EntrezGene:6957	-0.001	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	0	0.12	-10000	0	-0.43	13	13
RAB7A	0.037	0.19	-10000	0	-0.6	4	4
lysosomal transport	0.038	0.18	-10000	0	-0.56	5	5
FOS	-0.15	0.48	-10000	0	-1.2	44	44
STAT4 (dimer)	0.02	0.22	-10000	0	-0.64	11	11
STAT5A (dimer)	-0.09	0.19	-10000	0	-0.67	18	18
GZMA	-0.002	0.24	-10000	0	-0.77	12	12
GZMB	-0.005	0.24	-10000	0	-0.81	12	12
HLX	0.011	0.016	-10000	0	-0.25	1	1
LCK	-0.006	0.25	-10000	0	-0.72	18	18
TCR/CD3/MHC II/CD4	-0.021	0.12	-10000	0	-0.39	10	10
IL2/IL2R	-0.002	0.073	-10000	0	-0.48	2	2
MAPK14	0.026	0.21	-10000	0	-0.64	8	8
CCR5	0.006	0.22	-10000	0	-0.64	10	10
IL1B	0	0.12	-10000	0	-0.83	6	6
STAT6	0.018	0.086	-10000	0	-0.24	1	1
STAT4	-0.004	0.064	-10000	0	-0.25	18	18
STAT3	0.012	0	-10000	0	-10000	0	0
STAT1	0.01	0.027	-10000	0	-10000	0	0
NFKB1	0.012	0	-10000	0	-10000	0	0
NFKB2	0.012	0	-10000	0	-10000	0	0
IL12B	0.013	0.029	-10000	0	-0.3	1	1
CD8A	-0.006	0.072	-10000	0	-0.27	15	15
CD8B	-0.007	0.082	-10000	0	-0.81	1	1
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.009	0.095	0.39	6	-10000	0	6
IL2RB	-0.015	0.081	-10000	0	-0.25	30	30
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.21	-10000	0	-0.6	11	11
IL2RG	0.006	0.057	-10000	0	-0.36	5	5
IL12	0.024	0.033	-10000	0	-10000	0	0
STAT5A	0.012	0	-10000	0	-10000	0	0
CD247	0	0.057	-10000	0	-0.26	13	13
IL2	0.001	0.027	-10000	0	-10000	0	0
SPHK2	0.012	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.016	0.016	-10000	0	-10000	0	0
IL12/IL12R/TYK2/JAK2	-0.007	0.26	-10000	0	-0.7	20	20
MAP2K3	0.022	0.21	-10000	0	-0.58	12	12
RIPK2	0.012	0	-10000	0	-10000	0	0
MAP2K6	0.022	0.21	-10000	0	-0.62	9	9
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.007	0.053	-10000	0	-0.82	1	1
IL18RAP	-0.005	0.073	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	0.008	0.063	-10000	0	-10000	0	0
EOMES	-0.003	0.058	-10000	0	-10000	0	0
STAT1 (dimer)	0.012	0.21	-10000	0	-0.65	10	10
T cell proliferation	0.034	0.19	-10000	0	-0.48	13	13
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.013	0.049	-10000	0	-0.8	1	1
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.065	0.15	-10000	0	-0.58	7	7
ATF2	0.034	0.2	-10000	0	-0.63	6	6

×

BARD1 signaling events

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
BARD1/CSTF1	-0.009	0.13	-10000	0	-0.62	12	12
ATM	0.012	0	-10000	0	-10000	0	0
UBE2D3	0.012	0	-10000	0	-10000	0	0
PRKDC	0.012	0	-10000	0	-10000	0	0
ATR	0.012	0	-10000	0	-10000	0	0
UBE2L3	0.012	0	-10000	0	-10000	0	0
FANCD2	0.023	0.01	-10000	0	-10000	0	0
protein ubiquitination	-0.024	0.092	-10000	0	-0.45	12	12
XRCC5	0.012	0	-10000	0	-10000	0	0
XRCC6	0.012	0	-10000	0	-10000	0	0
M/R/N Complex	-0.002	0.032	-10000	0	-0.54	1	1
MRE11A	0.012	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.02	0.037	-10000	0	-10000	0	0
FANCF	0.012	0	-10000	0	-10000	0	0
BRCA1	0.01	0.027	-10000	0	-10000	0	0
CCNE1	-0.001	0.057	-10000	0	-10000	0	0
CDK2/Cyclin E1	0.01	0.038	-10000	0	-10000	0	0
FANCG	0.012	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.01	0.13	-10000	0	-0.62	12	12
FANCE	0.012	0	-10000	0	-10000	0	0
FANCC	0.012	0	-10000	0	-10000	0	0
NBN	0.012	0	-10000	0	-10000	0	0
FANCA	-0.098	0.13	-10000	0	-0.25	120	120
DNA repair	0.018	0.099	-10000	0	-10000	0	0
BRCA1/BARD1/ubiquitin	-0.01	0.13	-10000	0	-0.62	12	12
BARD1/DNA-PK	0.01	0.1	-10000	0	-0.49	12	12
FANCL	0.012	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.009	0.13	0.62	12	-10000	0	12
BRCA1/BARD1/CTIP/M/R/N Complex	0.02	0.075	-10000	0	-0.32	13	13
BRCA1/BACH1/BARD1/TopBP1	-0.024	0.11	-10000	0	-0.54	12	12
BRCA1/BARD1/P53	0.009	0.1	-10000	0	-0.49	12	12
BARD1/CSTF1/BRCA1	-0.024	0.11	-10000	0	-0.54	12	12
BRCA1/BACH1	0.01	0.027	-10000	0	-10000	0	0
BARD1	-0.022	0.16	-10000	0	-0.81	12	12
PCNA	0.012	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.024	0.11	-10000	0	-0.54	12	12
BRCA1/BARD1/UbcH7	-0.024	0.11	-10000	0	-0.54	12	12
BRCA1/BARD1/RAD51/PCNA	0	0.11	-10000	0	-0.49	12	12
BARD1/DNA-PK/P53	-0.019	0.091	-10000	0	-0.46	12	12
BRCA1/BARD1/Ubiquitin	-0.01	0.13	-10000	0	-0.62	12	12
BRCA1/BARD1/CTIP	0.006	0.11	-10000	0	-0.49	13	13
FA complex	0.003	0.042	-10000	0	-10000	0	0
BARD1/EWS	-0.009	0.13	-10000	0	-0.62	12	12
RBBP8	0.019	0.038	-10000	0	-0.62	1	1
TP53	0.012	0	-10000	0	-10000	0	0
TOPBP1	0.012	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.021	0.097	0.49	12	-10000	0	12
BRCA1/BARD1	-0.024	0.093	-10000	0	-0.46	12	12
CSTF1	0.012	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.018	0.13	-10000	0	-0.63	12	12
CDK2	0.012	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.006	0.067	-10000	0	-10000	0	0
RAD50	0.009	0.048	-10000	0	-0.81	1	1
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.01	0.13	-10000	0	-0.62	12	12
EWSR1	0.012	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.015	0.032	-9999	-10000	0	0
EPHB2	0.009	0.031	-9999	-10000	0	0
Syndecan-2/TACI	0.005	0.035	-9999	-10000	0	0
LAMA1	-0.02	0.14	-9999	-0.81	8	8
Syndecan-2/alpha2 ITGB1	-0.007	0.085	-9999	-0.46	6	6
HRAS	0.011	0.016	-9999	-10000	0	0
Syndecan-2/CASK	0	0.005	-9999	-10000	0	0
ITGA5	0.012	0	-9999	-10000	0	0
BAX	0.026	0.07	-9999	-0.48	5	5
EPB41	0.012	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0.005	-9999	-10000	0	0
LAMA3	-0.057	0.12	-9999	-10000	0	0
EZR	0.012	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.01	0.022	-9999	-0.25	2	2
Syndecan-2/MMP2	0.02	0.036	-9999	-0.54	1	1
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.005	0.091	-9999	-0.62	6	6
dendrite morphogenesis	0.02	0.018	-9999	-10000	0	0
Syndecan-2/GM-CSF	0.009	0.017	-9999	-10000	0	0
determination of left/right symmetry	0.018	0.008	-9999	-10000	0	0
Syndecan-2/PKC delta	0.022	0.006	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
MAPK3	0.024	0.013	-9999	-10000	0	0
MAPK1	0.024	0.013	-9999	-10000	0	0
Syndecan-2/RACK1	0.027	0.009	-9999	-10000	0	0
NF1	0.012	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.018	0.008	-9999	-10000	0	0
ITGA2	-0.005	0.12	-9999	-0.81	6	6
MAPK8	0.021	0.075	-9999	-0.53	5	5
Syndecan-2/alpha2/beta1 Integrin	0.007	0.11	-9999	-0.46	14	14
Syndecan-2/Kininogen	-0.32	0.27	-9999	-0.54	169	169
ITGB1	0.012	0	-9999	-10000	0	0
SRC	0.033	0.014	-9999	-10000	0	0
Syndecan-2/CASK/Protein 4.1	0.021	0.006	-9999	-10000	0	0
extracellular matrix organization	0.021	0.014	-9999	-10000	0	0
actin cytoskeleton reorganization	0.015	0.032	-9999	-10000	0	0
Syndecan-2/Caveolin-2/Ras	0.028	0.014	-9999	-10000	0	0
Syndecan-2/Laminin alpha3	-0.016	0.064	-9999	-10000	0	0
Syndecan-2/RasGAP	0	0.007	-9999	-10000	0	0
alpha5/beta1 Integrin	0.018	0	-9999	-10000	0	0
PRKCD	0.012	0	-9999	-10000	0	0
Syndecan-2 dimer	0.02	0.018	-9999	-10000	0	0
GO:0007205	0.003	0.005	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.039	0.014	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
SDCBP	0.012	0	-9999	-10000	0	0
TNFRSF13B	-0.009	0.063	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.005	0.091	-9999	-0.62	6	6
Syndecan-2/Synbindin	0.022	0.006	-9999	-10000	0	0
TGFB1	0.01	0.022	-9999	-0.25	2	2
CASP3	0.029	0.01	-9999	-10000	0	0
FN1	-0.001	0.057	-9999	-0.25	14	14
Syndecan-2/IL8	0.004	0.057	-9999	-0.54	1	1
SDC2	0.018	0.008	-9999	-10000	0	0
KNG1	-0.47	0.4	-9999	-0.81	169	169
Syndecan-2/Neurofibromin	0.022	0.006	-9999	-10000	0	0
TRAPPC4	0.012	0	-9999	-10000	0	0
CSF2	0.004	0.022	-9999	-0.25	2	2
Syndecan-2/TGFB1	0.021	0.014	-9999	-10000	0	0
Syndecan-2/Syntenin/PI-4-5-P2	0.021	0.006	-9999	-10000	0	0
Syndecan-2/Ezrin	0.029	0.006	-9999	-10000	0	0
PRKACA	0.03	0.006	-9999	-10000	0	0
angiogenesis	0.004	0.057	-9999	-0.54	1	1
MMP2	0.008	0.053	-9999	-0.81	1	1
IL8	-0.021	0.096	-9999	-0.27	34	34
calcineurin-NFAT signaling pathway	0.005	0.035	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.012	0	-10000	0	-10000	0	0
EPHB2	0.009	0.031	-10000	0	-10000	0	0
EFNB1	-0.06	0.089	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.048	0.086	-10000	0	-0.5	8	8
Ephrin B2/EPHB1-2	0.004	0.088	-10000	0	-0.49	8	8
neuron projection morphogenesis	-0.047	0.082	-10000	0	-0.48	8	8
Ephrin B1/EPHB1-2/Tiam1	-0.036	0.11	-10000	0	-0.54	8	8
DNM1	-0.11	0.13	-10000	0	-0.25	132	132
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.019	0.042	-10000	0	-0.68	1	1
YES1	0.003	0.054	-10000	0	-0.91	1	1
Ephrin B1/EPHB1-2/NCK2	-0.036	0.11	-10000	0	-0.54	8	8
PI3K	0.02	0.042	-10000	0	-0.69	1	1
mol:GDP	-0.036	0.1	-10000	0	-0.53	8	8
ITGA2B	-0.002	0.071	-10000	0	-0.81	1	1
endothelial cell proliferation	0.002	0.005	-10000	0	-10000	0	0
FYN	0.003	0.054	-10000	0	-0.91	1	1
MAP3K7	0.005	0.044	-10000	0	-0.73	1	1
FGR	0.002	0.055	-10000	0	-0.9	1	1
TIAM1	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.012	0	-10000	0	-10000	0	0
RGS3	0.012	0	-10000	0	-10000	0	0
cell adhesion	0	0.12	-10000	0	-0.46	12	12
LYN	0.003	0.054	-10000	0	-0.91	1	1
Ephrin B1/EPHB1-2/Src Family Kinases	0.001	0.051	-10000	0	-0.86	1	1
Ephrin B1/EPHB1-2	0	0.047	-10000	0	-0.79	1	1
SRC	0.003	0.054	-10000	0	-0.9	1	1
ITGB3	-0.036	0.18	-10000	0	-0.81	15	15
EPHB1	-0.018	0.14	-10000	0	-0.53	16	16
EPHB4	0.012	0	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.002	0.006	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.028	0.15	-10000	0	-0.62	16	16
BLK	0.001	0.054	-10000	0	-0.91	1	1
HCK	-0.001	0.056	-10000	0	-0.91	1	1
regulation of stress fiber formation	0.036	0.1	0.53	8	-10000	0	8
MAPK8	0.017	0.085	-10000	0	-0.57	5	5
Ephrin B1/EPHB1-2/RGS3	-0.036	0.11	-10000	0	-0.54	8	8
endothelial cell migration	0.008	0.039	-10000	0	-0.63	1	1
NCK2	0.012	0	-10000	0	-10000	0	0
PTPN13	0.005	0.054	-10000	0	-0.91	1	1
regulation of focal adhesion formation	0.036	0.1	0.53	8	-10000	0	8
chemotaxis	0.036	0.1	0.53	8	-10000	0	8
PIK3CA	0.012	0	-10000	0	-10000	0	0
Rac1/GTP	-0.048	0.085	-10000	0	-0.49	8	8
angiogenesis	0	0.046	-10000	0	-0.78	1	1
LCK	0.002	0.056	-10000	0	-0.9	1	1

×

TCGA08_rtk_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
PDGFRA	-0.38	0.41	-9999	-0.81	137	137
HRAS	0.011	0.016	-9999	-10000	0	0
EGFR	0.012	0	-9999	-10000	0	0
AKT	0.019	0.034	-9999	-0.44	1	1
FOXO3	0.012	0	-9999	-10000	0	0
AKT1	0.012	0	-9999	-10000	0	0
FOXO1	0.012	0	-9999	-10000	0	0
AKT3	0.009	0.048	-9999	-0.81	1	1
FOXO4	0.012	0	-9999	-10000	0	0
MET	-0.012	0.077	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
PIK3CB	0.011	0.016	-9999	-10000	0	0
NRAS	0.012	0	-9999	-10000	0	0
PIK3CG	0.001	0.096	-9999	-0.81	4	4
PIK3R3	0.012	0	-9999	-10000	0	0
PIK3R2	0.012	0	-9999	-10000	0	0
NF1	0.012	0	-9999	-10000	0	0
RAS	-0.072	0.1	-9999	-0.24	12	12
ERBB2	0.012	0	-9999	-10000	0	0
proliferation/survival/translation	-0.026	0.015	-9999	-10000	0	0
PI3K	-0.057	0.096	-9999	-0.22	16	16
PIK3R1	0.012	0	-9999	-10000	0	0
KRAS	0.012	0	-9999	-10000	0	0
FOXO	0.025	0.025	-9999	-10000	0	0
AKT2	0.012	0	-9999	-10000	0	0
PTEN	0.012	0	-9999	-10000	0	0

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.012	0.072	-10000	0	-0.36	5	5
IKBKB	0.005	0.056	-10000	0	-0.26	1	1
AKT1	0.003	0.058	-10000	0	-0.23	3	3
IKBKG	0.007	0.058	-10000	0	-0.28	1	1
CALM1	-0.01	0.11	-10000	0	-0.48	9	9
PIK3CA	0.012	0	-10000	0	-10000	0	0
MAP3K1	0.005	0.087	-10000	0	-0.47	5	5
MAP3K7	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	-0.018	0.12	0.24	10	-0.52	9	19
DOK1	0.01	0.022	-10000	0	-0.25	2	2
AP-1	-0.01	0.091	0.19	6	-0.25	11	17
LYN	0.012	0	-10000	0	-10000	0	0
BLNK	-0.016	0.15	-10000	0	-0.81	10	10
SHC1	0.012	0	-10000	0	-10000	0	0
BCR complex	-0.019	0.097	-10000	0	-0.56	5	5
CD22	-0.046	0.093	-10000	0	-0.56	5	5
CAMK2G	-0.002	0.1	-10000	0	-0.49	7	7
CSNK2A1	0.012	0	-10000	0	-10000	0	0
INPP5D	0.006	0.041	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.03	0.094	-10000	0	-0.42	14	14
GO:0007205	-0.018	0.12	0.24	10	-0.53	9	19
SYK	0.009	0.048	-10000	0	-0.81	1	1
ELK1	-0.011	0.11	-10000	0	-0.49	9	9
NFATC1	0.003	0.081	-10000	0	-0.45	5	5
B-cell antigen/BCR complex	-0.019	0.097	-10000	0	-0.56	5	5
PAG1/CSK	0.018	0	-10000	0	-10000	0	0
NFKBIB	0.011	0.023	0.084	7	-10000	0	7
HRAS	-0.004	0.11	-10000	0	-0.48	9	9
NFKBIA	0.011	0.023	0.084	7	-10000	0	7
NF-kappa-B/RelA/I kappa B beta	0.015	0.02	-10000	0	-10000	0	0
RasGAP/Csk	-0.047	0.08	-10000	0	-0.46	5	5
mol:GDP	-0.017	0.11	0.23	10	-0.51	9	19
PTEN	0.012	0	-10000	0	-10000	0	0
CD79B	0.003	0.085	-10000	0	-0.67	4	4
NF-kappa-B/RelA/I kappa B alpha	0.015	0.02	-10000	0	-10000	0	0
GRB2	0.012	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.004	0.11	-10000	0	-0.54	5	5
PIK3R1	0.012	0	-10000	0	-10000	0	0
mol:IP3	-0.019	0.12	0.24	10	-0.54	9	19
CSK	0.012	0	-10000	0	-10000	0	0
FOS	-0.065	0.19	-10000	0	-0.47	45	45
CHUK	0.007	0.058	-10000	0	-0.28	1	1
IBTK	0.012	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.043	0.085	-10000	0	-0.47	6	6
PTPN6	-0.021	0.097	-10000	0	-0.57	4	4
RELA	0.012	0	-10000	0	-10000	0	0
BCL2A1	0.002	0.028	-10000	0	-0.14	1	1
VAV2	-0.032	0.089	-10000	0	-0.58	5	5
ubiquitin-dependent protein catabolic process	0.015	0.022	0.087	7	-10000	0	7
BTK	-0.02	0.047	-10000	0	-10000	0	0
CD19	-0.036	0.092	-10000	0	-0.53	6	6
MAP4K1	-0.044	0.11	-10000	0	-0.25	61	61
CD72	-0.015	0.081	-10000	0	-10000	0	0
PAG1	0.012	0	-10000	0	-10000	0	0
MAPK14	0.012	0.077	-10000	0	-0.42	4	4
SH3BP5	-0.027	0.18	-10000	0	-0.81	14	14
PIK3AP1	-0.009	0.12	0.27	9	-0.53	10	19
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.023	0.14	-10000	0	-0.7	9	9
RAF1	0.003	0.1	-10000	0	-0.45	9	9
RasGAP/p62DOK/SHIP	-0.045	0.077	-10000	0	-0.43	6	6
CD79A	-0.033	0.11	-10000	0	-0.26	47	47
re-entry into mitotic cell cycle	-0.01	0.09	0.19	6	-0.24	14	20
RASA1	0.012	0	-10000	0	-10000	0	0
MAPK3	0.017	0.086	-10000	0	-0.41	6	6
MAPK1	0.017	0.086	-10000	0	-0.41	6	6
CD72/SHP1	-0.023	0.11	-10000	0	-0.54	4	4
NFKB1	0.012	0	-10000	0	-10000	0	0
MAPK8	0.005	0.094	-10000	0	-0.41	9	9
actin cytoskeleton organization	0	0.088	-10000	0	-0.49	5	5
NF-kappa-B/RelA	0.033	0.04	0.17	7	-10000	0	7
Calcineurin	-0.02	0.077	-10000	0	-0.46	6	6
PI3K	-0.037	0.077	-10000	0	-0.44	5	5
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.02	0.12	0.27	9	-0.57	9	18
SOS1	0.012	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.024	0.12	-10000	0	-0.7	5	5
DAPP1	-0.026	0.11	-10000	0	-0.79	5	5
cytokine secretion	0.004	0.077	-10000	0	-0.42	5	5
mol:DAG	-0.019	0.12	0.24	10	-0.54	9	19
PLCG2	-0.032	0.18	-10000	0	-0.74	17	17
MAP2K1	0.01	0.093	-10000	0	-0.46	6	6
B-cell antigen/BCR complex/FcgammaRIIB	-0.063	0.1	-10000	0	-0.54	5	5
mol:PI-3-4-5-P3	-0.03	0.058	-10000	0	-0.31	5	5
ETS1	0.004	0.094	-10000	0	-0.46	6	6
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.033	0.11	-10000	0	-0.49	14	14
B-cell antigen/BCR complex/LYN	-0.029	0.082	-10000	0	-0.58	5	5
MALT1	0.012	0	-10000	0	-10000	0	0
TRAF6	0.012	0	-10000	0	-10000	0	0
RAC1	-0.001	0.093	-10000	0	-0.52	5	5
B-cell antigen/BCR complex/LYN/SYK	-0.039	0.09	-10000	0	-0.56	4	4
CARD11	-0.041	0.12	-10000	0	-0.46	11	11
FCGR2B	-0.063	0.13	-10000	0	-0.81	1	1
PPP3CA	0.012	0	-10000	0	-10000	0	0
BCL10	0.012	0	-10000	0	-10000	0	0
IKK complex	0.011	0.027	-10000	0	-10000	0	0
PTPRC	0.006	0.057	-10000	0	-0.36	5	5
PDPK1	0	0.052	-10000	0	-0.23	1	1
PPP3CB	0.012	0	-10000	0	-10000	0	0
PPP3CC	0.012	0	-10000	0	-10000	0	0
POU2F2	0.014	0.017	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.05	0.12	-9999	-0.57	12	12
PDGFB-D/PDGFRB/SLAP	-0.023	0.13	-9999	-0.63	12	12
PDGFB-D/PDGFRB/APS/CBL	-0.023	0.11	-9999	-0.53	12	12
AKT1	0.037	0.081	-9999	-10000	0	0
mol:PI-4-5-P2	0	0.001	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	-0.039	0.13	-9999	-0.61	12	12
PIK3CA	0.012	0	-9999	-10000	0	0
FGR	-0.02	0.11	-9999	-0.52	13	13
mol:Ca2+	-0.006	0.13	-9999	-0.62	12	12
MYC	0.011	0.094	-9999	-0.38	12	12
SHC1	0.012	0	-9999	-10000	0	0
HRAS/GDP	0.013	0.094	-9999	-0.44	12	12
LRP1/PDGFRB/PDGFB	-0.022	0.11	-9999	-0.53	13	13
GRB10	0.012	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
GO:0007205	-0.007	0.13	-9999	-0.64	12	12
PTEN	0.012	0	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
GRB7	0.012	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHP2	-0.016	0.13	-9999	-0.62	12	12
PDGFB-D/PDGFRB/GRB10	-0.016	0.13	-9999	-0.62	12	12
cell cycle arrest	-0.023	0.13	-9999	-0.63	12	12
HRAS	0.011	0.016	-9999	-10000	0	0
HIF1A	0.043	0.073	-9999	-10000	0	0
GAB1	-0.011	0.13	-9999	-0.6	12	12
mol:GTP	0	0	-9999	-10000	0	0
DNM2	-0.011	0.12	-9999	-0.56	12	12
PDGFB-D/PDGFRB	-0.019	0.11	-9999	-0.54	12	12
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.016	0.13	-9999	-0.62	12	12
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.048	0.11	-9999	-0.56	12	12
positive regulation of MAPKKK cascade	-0.016	0.12	-9999	-0.62	12	12
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	-0.007	0.13	-9999	-0.64	12	12
E5	0	0.001	-9999	-10000	0	0
CSK	0.012	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.016	0.13	-9999	-0.62	12	12
SHB	0.012	0	-9999	-10000	0	0
BLK	-0.02	0.1	-9999	-0.51	12	12
PTPN2	0.012	0.002	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.016	0.13	-9999	-0.62	12	12
BCAR1	0.012	0	-9999	-10000	0	0
VAV2	-0.01	0.13	-9999	-0.58	12	12
CBL	0.012	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	-0.016	0.13	-9999	-0.62	12	12
LCK	-0.021	0.11	-9999	-0.52	14	14
PDGFRB	-0.022	0.16	-9999	-0.81	12	12
ACP1	0.012	0	-9999	-10000	0	0
HCK	-0.025	0.11	-9999	-0.53	13	13
ABL1	-0.006	0.12	-9999	-0.55	12	12
PDGFB-D/PDGFRB/CBL	-0.011	0.14	-9999	-0.65	12	12
PTPN1	0.012	0.002	-9999	-10000	0	0
SNX15	0.012	0	-9999	-10000	0	0
STAT3	0.012	0	-9999	-10000	0	0
STAT1	0.01	0.027	-9999	-10000	0	0
cell proliferation	0.012	0.088	-9999	-0.35	12	12
SLA	0.002	0.051	-9999	-10000	0	0
actin cytoskeleton reorganization	0.026	0.092	-9999	-0.42	12	12
SRC	-0.016	0.1	-9999	-0.51	12	12
PI3K	-0.016	0.077	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.02	0.11	-9999	-0.53	12	12
SH2B2	0.006	0.041	-9999	-0.25	7	7
PLCgamma1/SPHK1	-0.041	0.14	-9999	-0.64	12	12
LYN	-0.015	0.1	-9999	-0.51	12	12
LRP1	0.012	0	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
STAT5B	0.012	0	-9999	-10000	0	0
STAT5A	0.012	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.016	0.087	-9999	-0.43	12	12
SPHK1	-0.12	0.13	-9999	-0.26	4	4
EDG1	-0.001	0.002	-9999	-10000	0	0
mol:DAG	-0.007	0.13	-9999	-0.64	12	12
PLCG1	-0.007	0.14	-9999	-0.66	12	12
NHERF/PDGFRB	-0.02	0.11	-9999	-0.53	12	12
YES1	-0.016	0.1	-9999	-0.51	12	12
cell migration	-0.021	0.11	-9999	-0.53	12	12
SHC/Grb2/SOS1	-0.016	0.087	-9999	-0.43	12	12
SLC9A3R2	0.012	0	-9999	-10000	0	0
SLC9A3R1	0.012	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	0.009	0.1	-9999	-0.48	12	12
FYN	-0.015	0.1	-9999	-0.51	12	12
DOK1	0.008	0.1	-9999	-0.49	12	12
HRAS/GTP	0.009	0.01	-9999	-10000	0	0
PDGFB	0.009	0.048	-9999	-0.81	1	1
RAC1	0.002	0.12	-9999	-0.52	12	12
PRKCD	0.008	0.1	-9999	-0.49	12	12
FER	0.008	0.1	-9999	-0.49	12	12
MAPKKK cascade	-0.017	0.084	-9999	-0.42	12	12
RASA1	0.008	0.1	-9999	-0.49	12	12
NCK1	0.012	0	-9999	-10000	0	0
NCK2	0.012	0	-9999	-10000	0	0
p62DOK/Csk	0.015	0.097	-9999	-0.45	12	12
PDGFB-D/PDGFRB/SHB	-0.016	0.13	-9999	-0.62	12	12
chemotaxis	-0.006	0.11	-9999	-0.54	12	12
STAT1-3-5/STAT1-3-5	-0.018	0.082	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.021	0.13	-9999	-0.63	12	12
PTPRJ	0.012	0	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	0.008	0.12	0.81	6	-10000	0	6
PI3K Class IB/PDE3B	-0.008	0.12	-10000	0	-0.81	6	6
PDE3B	-0.008	0.12	-10000	0	-0.81	6	6

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.002	0.061	-9999	-0.25	16	16
PLK4	0.011	0.016	-9999	-10000	0	0
regulation of centriole replication	0.011	0.042	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.012	0	-9999	-10000	0	0
VLDLR	0.012	0	-9999	-10000	0	0
LRPAP1	0.012	0	-9999	-10000	0	0
NUDC	0.012	0	-9999	-10000	0	0
RELN/LRP8	-0.065	0.13	-9999	-0.55	18	18
CaM/Ca2+	0.009	0	-9999	-10000	0	0
KATNA1	0.012	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.035	0.13	-9999	-0.49	18	18
IQGAP1/CaM	0.018	0	-9999	-10000	0	0
DAB1	-0.003	0.045	-9999	-0.25	9	9
IQGAP1	0.012	0	-9999	-10000	0	0
PLA2G7	-0.19	0.11	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
DYNLT1	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.016	0.021	-9999	-10000	0	0
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.012	0	-9999	-10000	0	0
CDK5R1	0.008	0.035	-9999	-0.25	5	5
LIS1/Poliovirus Protein 3A	0.016	0	-9999	-10000	0	0
CDK5R2	-0.048	0.11	-9999	-0.25	63	63
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.068	0.14	-9999	-0.55	18	18
YWHAE	0.012	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.018	0.11	-9999	-0.45	3	3
MAP1B	0	0.006	-9999	-10000	0	0
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.019	0.12	-9999	-0.43	18	18
RELN	-0.1	0.21	-9999	-0.81	18	18
PAFAH/LIS1	-0.086	0.062	-9999	-10000	0	0
LIS1/CLIP170	0.025	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.026	0.074	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.012	0.091	-9999	-0.33	19	19
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.026	0.11	-9999	-0.41	18	18
LIS1/IQGAP1	0.025	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.021	0	-9999	-10000	0	0
PAFAH1B3	0.01	0.022	-9999	-10000	0	0
PAFAH1B2	0.009	0.048	-9999	-0.81	1	1
MAP1B/LIS1/Dynein heavy chain	0.024	0.003	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.012	0.1	-9999	-0.43	3	3
LRP8	0.009	0.031	-9999	-0.25	4	4
NDEL1/Katanin 60	-0.018	0.11	-9999	-0.45	3	3
P39/CDK5	-0.043	0.12	-9999	-0.44	18	18
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.025	0	-9999	-10000	0	0
CDK5	-0.025	0.12	-9999	-0.46	18	18
PPP2R5D	0.011	0.016	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.012	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.032	0.12	-9999	-0.47	18	18
RELN/VLDLR	-0.035	0.13	-9999	-0.5	18	18
CDC42	0	0	-9999	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.001	0.007	-10000	0	-10000	0	0
AES	0.008	0.005	-10000	0	-10000	0	0
FBXW11	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.013	0.031	-10000	0	-10000	0	0
SMAD4	0.012	0	-10000	0	-10000	0	0
DKK2	0.001	0.086	-10000	0	-0.81	3	3
TLE1	0.008	0.005	-10000	0	-10000	0	0
MACF1	0.013	0	-10000	0	-10000	0	0
CTNNB1	0.053	0.054	-10000	0	-10000	0	0
WIF1	0.002	0.038	-10000	0	-0.25	6	6
beta catenin/RanBP3	0	0.035	0.35	1	-10000	0	1
KREMEN2	-0.023	0.088	-10000	0	-10000	0	0
DKK1	0.005	0.038	-10000	0	-10000	0	0
beta catenin/beta TrCP1	0.057	0.051	-10000	0	-10000	0	0
FZD1	0.005	0.046	-10000	0	-10000	0	0
AXIN2	0.022	0.027	-10000	0	-10000	0	0
AXIN1	0.013	0.001	-10000	0	-10000	0	0
RAN	0.012	0	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.004	0.012	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.025	0.098	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.048	0.073	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.048	0.042	-10000	0	-10000	0	0
HNF1A	-0.003	0.096	-10000	0	-0.81	4	4
CTBP1	0.002	0.007	-10000	0	-10000	0	0
MYC	0.017	0.049	-10000	0	-10000	0	0
RANBP3	0.012	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.022	0.069	-10000	0	-0.54	3	3
NKD1	-0.25	0.38	-10000	0	-0.81	92	92
TCF4	-0.004	0.068	-10000	0	-0.81	2	2
TCF3	0.008	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.012	0.037	-10000	0	-10000	0	0
Ran/GTP	0.009	0	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	-0.023	0.088	0.44	1	-10000	0	1
LEF1	-0.077	0.24	-10000	0	-0.81	28	28
DVL1	0.026	0.012	-10000	0	-10000	0	0
CSNK2A1	0.012	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.037	0.098	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.018	0.045	-10000	0	-10000	0	0
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.001	0.007	-10000	0	-10000	0	0
NLK	0.013	0.001	-10000	0	-10000	0	0
CCND1	0.018	0.091	-10000	0	-1.5	1	1
WNT1	-0.016	0.08	-10000	0	-0.25	30	30
GSK3A	0.013	0.001	-10000	0	-10000	0	0
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.012	0	-10000	0	-10000	0	0
PPP2R5D	0.12	0.16	0.36	92	-10000	0	92
APC	0.021	0.043	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.006	0.03	-10000	0	-10000	0	0
CREBBP	0.008	0.005	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.012	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.024	0.002	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.012	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	0.012	0	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
MAP3K12	0.01	0.022	-9999	-10000	0	0
FGR	0.001	0.066	-9999	-0.81	1	1
p38 alpha/TAB1	-0.002	0.017	-9999	-10000	0	0
PRKG1	-0.21	0.37	-9999	-0.81	79	79
DUSP8	0.012	0	-9999	-10000	0	0
PGK/cGMP/p38 alpha	-0.11	0.17	-9999	-0.39	79	79
apoptosis	-0.002	0.016	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.012	0	-9999	-10000	0	0
DUSP1	0.007	0.068	-9999	-0.81	2	2
PAK1	0.012	0	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.032	0	-9999	-10000	0	0
TRAF6	0.012	0	-9999	-10000	0	0
RAC1	0.012	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	0.012	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.049	0.037	-9999	-0.35	1	1
BLK	-0.002	0.057	-9999	-0.25	14	14
HCK	-0.014	0.089	-9999	-0.27	27	27
MAP2K3	0.012	0	-9999	-10000	0	0
DUSP16	0.012	0	-9999	-10000	0	0
DUSP10	0.004	0.046	-9999	-10000	0	0
TRAF6/MEKK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.047	0.029	-9999	-0.24	1	1
positive regulation of innate immune response	0.058	0.041	-9999	-0.38	1	1
LCK	0.004	0.073	-9999	-0.81	2	2
p38alpha-beta/MKP7	0.063	0.039	-9999	-0.36	1	1
p38alpha-beta/MKP5	0.059	0.044	-9999	-0.36	1	1
PGK/cGMP	-0.16	0.28	-9999	-0.63	79	79
PAK2	0.012	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.06	0.052	-9999	-0.35	3	3
CDC42	0.012	0	-9999	-10000	0	0
RALB	0.012	0	-9999	-10000	0	0
RALA	0.012	0	-9999	-10000	0	0
PAK3	0.01	0.005	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.012	0	-9999	-10000	0	0
PTK2	0.012	0	-9999	-10000	0	0
CRKL	0.003	0.097	-9999	-0.41	15	15
GRB2/SOS1/SHC	0	0	-9999	-10000	0	0
HRAS	0.011	0.016	-9999	-10000	0	0
IRS1/Crk	0.003	0.097	-9999	-0.41	15	15
IGF-1R heterotetramer/IGF1/PTP1B	-0.019	0.093	-9999	-0.51	10	10
AKT1	0.022	0.084	-9999	-10000	0	0
BAD	0.028	0.08	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.003	0.097	-9999	-0.41	15	15
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.002	0.097	-9999	-0.41	15	15
RAF1	0.033	0.077	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.01	0.093	-9999	-0.39	15	15
YWHAZ	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.006	0.1	-9999	-0.45	15	15
PIK3CA	0.012	0	-9999	-10000	0	0
RPS6KB1	0.022	0.084	-9999	-10000	0	0
GNB2L1	0.012	0	-9999	-10000	0	0
positive regulation of MAPKKK cascade	0.028	0.067	-9999	-10000	0	0
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0.018	0	-9999	-10000	0	0
HRAS/GTP	-0.018	0.076	-9999	-0.36	10	10
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.02	0.081	-9999	-0.4	10	10
IGF-1R heterotetramer	0.008	0.022	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	0.003	0.097	-9999	-0.41	15	15
Crk/p130 Cas/Paxillin	0.016	0.089	-9999	-0.39	10	10
IGF1R	0.008	0.022	-9999	-10000	0	0
IGF1	-0.017	0.15	-9999	-0.82	10	10
IRS2/Crk	0.009	0.093	-9999	-0.38	15	15
PI3K	0.01	0.093	-9999	-0.38	15	15
apoptosis	-0.033	0.071	-9999	-10000	0	0
HRAS/GDP	0.009	0.01	-9999	-10000	0	0
PRKCD	0.018	0.099	-9999	-0.49	10	10
RAF1/14-3-3 E	0.038	0.069	-9999	-10000	0	0
BAD/14-3-3	0.034	0.075	-9999	-10000	0	0
PRKCZ	0.022	0.084	-9999	-0.36	10	10
Crk/p130 Cas/Paxillin/FAK1	-0.015	0.063	-9999	-10000	0	0
PTPN1	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.011	0.1	-9999	-0.52	10	10
BCAR1	0.012	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.016	0.081	-9999	-0.44	10	10
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
IRS1/NCK2	0.003	0.097	-9999	-0.41	15	15
GRB10	0.012	0	-9999	-10000	0	0
PTPN11	0.003	0.097	-9999	-0.41	15	15
IRS1	-0.006	0.1	-9999	-0.45	15	15
IRS2	0.002	0.097	-9999	-0.41	15	15
IGF-1R heterotetramer/IGF1	-0.008	0.12	-9999	-0.64	10	10
GRB2	0.012	0	-9999	-10000	0	0
PDPK1	0.016	0.088	-9999	-0.38	10	10
YWHAE	0.012	0	-9999	-10000	0	0
PRKD1	0.018	0.099	-9999	-0.49	10	10
SHC1	0.012	0	-9999	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.004	0.16	-9999	-0.38	41	41
MAP3K8	0.011	0.004	-9999	-10000	0	0
FOS	0.012	0.096	-9999	-0.6	2	2
PRKCA	0.012	0.005	-9999	-10000	0	0
PTPN7	0.006	0.058	-9999	-0.82	1	1
HRAS	0.011	0.016	-9999	-10000	0	0
PRKCB	0.009	0.049	-9999	-0.82	1	1
NRAS	0.012	0.001	-9999	-10000	0	0
RAS family/GTP	0.022	0.012	-9999	-10000	0	0
MAPK3	0.017	0.056	-9999	-0.55	1	1
MAP2K1	0.027	0.051	-9999	-0.61	1	1
ELK1	0.01	0.009	-9999	-10000	0	0
BRAF	0.022	0.041	-9999	-0.57	1	1
mol:GTP	-0.001	0.002	-9999	-0.006	41	41
MAPK1	0.017	0.056	-9999	-0.55	1	1
RAF1	0.022	0.041	-9999	-0.57	1	1
KRAS	0.012	0.001	-9999	-10000	0	0

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.012	0	-9999	-10000	0	0
LAT2	-0.022	0.083	-9999	-0.29	2	2
AP1	-0.083	0.14	-9999	-0.4	41	41
mol:PIP3	-0.039	0.13	-9999	-0.38	17	17
IKBKB	-0.009	0.075	-9999	-0.28	1	1
AKT1	-0.006	0.088	-9999	-10000	0	0
IKBKG	-0.009	0.075	-9999	-0.28	1	1
MS4A2	-0.072	0.12	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.012	0.001	-9999	-10000	0	0
MAP3K1	-0.003	0.086	-9999	-0.45	1	1
mol:Ca2+	-0.029	0.1	-9999	-0.29	17	17
LYN	0.011	0.004	-9999	-10000	0	0
CBLB	-0.009	0.064	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
RasGAP/p62DOK	0.019	0.044	-9999	-0.5	2	2
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.006	0.041	-9999	-10000	0	0
PLD2	-0.034	0.099	-9999	-0.44	8	8
PTPN13	0	0.069	-9999	-0.63	1	1
PTPN11	0.012	0.003	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	0.016	0.071	-9999	-10000	0	0
SYK	0.008	0.049	-9999	-0.82	1	1
GRB2	0.012	0	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.068	0.1	-9999	-0.4	8	8
LAT	-0.033	0.085	-9999	-0.32	3	3
PAK2	-0.01	0.092	-9999	-0.51	1	1
NFATC2	-0.083	0.2	-9999	-0.71	26	26
HRAS	-0.019	0.097	-9999	-0.56	1	1
GAB2	0.012	0	-9999	-10000	0	0
PLA2G1B	0.028	0.011	-9999	-10000	0	0
Fc epsilon R1	-0.078	0.11	-9999	-0.52	10	10
Antigen/IgE/Fc epsilon R1	-0.07	0.1	-9999	-0.47	10	10
mol:GDP	-0.028	0.1	-9999	-0.46	2	2
JUN	0.012	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.012	0.001	-9999	-10000	0	0
FOS	-0.1	0.29	-9999	-0.81	41	41
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.017	0.067	-9999	-0.27	1	1
CHUK	-0.009	0.075	-9999	-0.28	1	1
KLRG1	-0.013	0.065	-9999	-10000	0	0
VAV1	-0.029	0.096	-9999	-0.69	1	1
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.009	0.064	-9999	-10000	0	0
negative regulation of mast cell degranulation	-0.008	0.065	-9999	-10000	0	0
BTK	-0.022	0.083	-9999	-0.29	1	1
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.039	0.1	-9999	-0.4	9	9
GAB2/PI3K/SHP2	-0.042	0.075	-9999	-10000	0	0
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.016	0.07	-9999	-0.28	9	9
RAF1	0.017	0.013	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.092	0.12	-9999	-0.51	10	10
FCER1G	-0.036	0.1	-9999	-0.26	53	53
FCER1A	-0.016	0.14	-9999	-0.63	12	12
Antigen/IgE/Fc epsilon R1/Fyn	-0.061	0.093	-9999	-0.44	10	10
MAPK3	0.027	0.011	-9999	-10000	0	0
MAPK1	0.027	0.011	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
MAPK8	0.003	0.087	-9999	-0.61	5	5
DUSP1	0.007	0.068	-9999	-0.81	2	2
NF-kappa-B/RelA	-0.018	0.034	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.006	0.061	-9999	-10000	0	0
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.043	0.08	-9999	-0.6	1	1
FER	-0.009	0.064	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
ITK	-0.01	0.023	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
PLCG1	-0.023	0.11	-9999	-0.47	2	2
cytokine secretion	-0.014	0.025	-9999	-10000	0	0
SPHK1	-0.066	0.092	-9999	-0.33	5	5
PTK2	-0.006	0.062	-9999	-10000	0	0
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.061	0.1	-9999	-0.41	9	9
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.025	0.12	-9999	-0.38	8	8
MAP2K2	0.023	0.011	-9999	-10000	0	0
MAP2K1	0.023	0.011	-9999	-10000	0	0
MAP2K7	0.012	0	-9999	-10000	0	0
KLRG1/SHP2	-0.031	0.05	-9999	-10000	0	0
MAP2K4	0.018	0.007	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.1	0.13	-9999	-0.42	24	24
mol:Choline	-0.034	0.098	-9999	-0.43	8	8
SHC/Grb2/SOS1	-0.022	0.045	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
DOK1	0.01	0.022	-9999	-0.25	2	2
PXN	0.001	0.059	-9999	-10000	0	0
HCLS1	-0.011	0.067	-9999	-10000	0	0
PRKCB	-0.022	0.096	-9999	-0.35	2	2
FCGR2B	-0.063	0.13	-9999	-0.81	1	1
IGHE	-0.001	0.004	-9999	-10000	0	0
KLRG1/SHIP	-0.008	0.066	-9999	-10000	0	0
LCP2	0.008	0.035	-9999	-10000	0	0
PLA2G4A	-0.033	0.13	-9999	-0.5	15	15
RASA1	0.012	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.034	0.098	-9999	-0.43	8	8
IKK complex	0.004	0.061	-9999	-0.2	1	1
WIPF1	0.011	0.016	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	-0.022	0.16	-9999	-0.81	12	12
alphaV beta3 Integrin	-0.02	0.15	-9999	-0.66	15	15
PTK2	-0.021	0.1	-9999	-0.72	5	5
positive regulation of JNK cascade	-0.008	0.048	-9999	-0.36	5	5
CDC42/GDP	0.043	0.075	-9999	-0.5	5	5
Rac1/GDP	0.044	0.075	-9999	-0.49	5	5
RAP1B	0.012	0	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
CTNNB1	0.012	0	-9999	-10000	0	0
CDC42/GTP	-0.01	0.06	-9999	-0.45	5	5
nectin-3/I-afadin	0.007	0.083	-9999	-0.62	5	5
RAPGEF1	0.037	0.086	-9999	-0.58	5	5
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.031	0.099	-9999	-0.68	5	5
PDGFB-D/PDGFRB	-0.022	0.16	-9999	-0.81	12	12
TLN1	0.026	0.034	-9999	-10000	0	0
Rap1/GTP	-0.008	0.052	-9999	-0.39	5	5
IQGAP1	0.012	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.024	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.007	0.083	-9999	-0.62	5	5
PVR	0.011	0.016	-9999	-10000	0	0
Necl-5(dimer)	0.011	0.016	-9999	-10000	0	0
mol:GDP	0.04	0.093	-9999	-0.64	5	5
MLLT4	0.012	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
PI3K	-0.027	0.11	-9999	-0.46	17	17
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.017	0.015	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.008	0.05	-9999	-0.38	5	5
PVRL1	0.01	0.022	-9999	-0.25	2	2
PVRL3	-0.002	0.11	-9999	-0.81	5	5
PVRL2	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
CDH1	-0.064	0.24	-9999	-0.81	27	27
CLDN1	-0.038	0.1	-9999	-10000	0	0
JAM-A/CLDN1	-0.002	0.085	-9999	-0.51	5	5
SRC	-0.017	0.1	-9999	-0.78	5	5
ITGB3	-0.036	0.18	-9999	-0.81	15	15
nectin-1(dimer)/I-afadin/I-afadin	0.017	0.015	-9999	-10000	0	0
FARP2	0.035	0.091	-9999	-0.62	5	5
RAC1	0.012	0	-9999	-10000	0	0
CTNNA1	0.012	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.01	0.07	-9999	-0.54	5	5
nectin-1/I-afadin	0.017	0.015	-9999	-10000	0	0
nectin-2/I-afadin	0.018	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.01	0.074	-9999	-0.56	5	5
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.012	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.008	0.048	-9999	-0.36	5	5
alphaV/beta3 Integrin/Talin	0.011	0.12	-9999	-0.5	15	15
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.018	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.018	0	-9999	-10000	0	0
PIP5K1C	0.02	0.036	-9999	-10000	0	0
VAV2	0.034	0.092	-9999	-0.63	5	5
RAP1/GDP	-0.009	0.061	-9999	-0.46	5	5
ITGAV	0.009	0.048	-9999	-0.81	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.009	0.07	-9999	-0.54	5	5
nectin-3(dimer)/I-afadin/I-afadin	0.007	0.083	-9999	-0.62	5	5
Rac1/GTP	-0.01	0.062	-9999	-0.47	5	5
PTPRM	0.013	0.04	-9999	-0.29	5	5
E-cadherin/beta catenin/alpha catenin	-0.041	0.13	-9999	-0.44	27	27
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.012	0	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.025	0.078	-9999	-10000	0	0
GNAI2	0.012	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.008	0.058	-9999	-0.55	3	3
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	-0.044	0.2	-9999	-0.74	22	22
RhoA/GTP	0.007	0.089	-9999	-10000	0	0
negative regulation of cAMP metabolic process	0.001	0.097	-9999	-0.32	22	22
GNAZ	0.012	0	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
GNA12	0.012	0	-9999	-10000	0	0
S1PR5	-0.002	0.091	-9999	-0.81	3	3
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	0.001	0.098	-9999	-0.33	22	22
RhoA/GDP	0.009	0	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
GNAI1	0.007	0.068	-9999	-0.81	2	2

×

FAS signaling pathway (CD95)

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
SPTAN1	0.004	0.016	-9999	-10000	0	0
RFC1	0.004	0.016	-9999	-10000	0	0
PRKDC	0.004	0.016	-9999	-10000	0	0
RIPK1	0.014	0.004	-9999	-10000	0	0
CASP7	-0.005	0.034	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.006	0.035	-9999	-10000	0	0
MAP2K4	-0.002	0.11	-9999	-0.31	1	1
mol:ceramide	0.006	0.072	-9999	-10000	0	0
GSN	0.004	0.016	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	0.008	0.047	-9999	-10000	0	0
FAS	0.011	0.005	-9999	-10000	0	0
BID	0.006	0.023	-9999	-10000	0	0
MAP3K1	0.01	0.069	-9999	-10000	0	0
MAP3K7	0.01	0.005	-9999	-10000	0	0
RB1	0.004	0.016	-9999	-10000	0	0
CFLAR	0.014	0.004	-9999	-10000	0	0
HGF/MET	-0.076	0.18	-9999	-0.56	35	35
ARHGDIB	0.004	0.016	-9999	-10000	0	0
FADD	0.011	0.005	-9999	-10000	0	0
actin filament polymerization	-0.004	0.016	-9999	-10000	0	0
NFKB1	-0.038	0.076	-9999	-10000	0	0
MAPK8	-0.035	0.2	-9999	-0.44	53	53
DFFA	0.004	0.016	-9999	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.016	-9999	-10000	0	0
FAS/FADD/MET	0.006	0.043	-9999	-10000	0	0
CFLAR/RIP1	0.014	0.007	-9999	-10000	0	0
FAIM3	-0.005	0.068	-9999	-0.25	20	20
FAF1	0.011	0.006	-9999	-10000	0	0
PARP1	0.004	0.016	-9999	-10000	0	0
DFFB	0.004	0.016	-9999	-10000	0	0
CHUK	-0.032	0.066	-9999	-10000	0	0
FASLG	-0.008	0.068	-9999	-0.26	20	20
FAS/FADD	0.015	0.01	-9999	-10000	0	0
HGF	-0.084	0.26	-9999	-0.81	34	34
LMNA	0.004	0.016	-9999	-10000	0	0
CASP6	0.004	0.016	-9999	-10000	0	0
CASP10	0.011	0.005	-9999	-10000	0	0
CASP3	0.004	0.017	-9999	-10000	0	0
PTPN13	0.009	0.048	-9999	-0.81	1	1
CASP8	0.009	0.033	-9999	-10000	0	0
IL6	-0.2	0.51	-9999	-1.3	51	51
MET	-0.012	0.077	-9999	-10000	0	0
ICAD/CAD	0.004	0.016	-9999	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	0.006	0.073	-9999	-10000	0	0
activation of caspase activity by cytochrome c	0.006	0.023	-9999	-10000	0	0
PAK2	0.004	0.016	-9999	-10000	0	0
BCL2	0.013	0.001	-9999	-10000	0	0

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.003	0.033	-9999	-0.48	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.045	-9999	-10000	0	0
AP1	-0.065	0.16	-9999	-0.44	41	41
mol:PIP3	-0.004	0.028	-9999	-10000	0	0
AKT1	0.053	0.027	-9999	-10000	0	0
PTK2B	0.017	0.03	-9999	-0.25	1	1
RHOA	0.028	0.014	-9999	-10000	0	0
PIK3CB	0.011	0.016	-9999	-10000	0	0
mol:Ca2+	-0.005	0.067	-9999	-0.31	1	1
MAGI3	0.012	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
apoptosis	0.019	0.035	-9999	-0.34	2	2
HRAS/GDP	0.009	0.01	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.022	0.06	-9999	-0.43	4	4
NF kappa B1 p50/RelA	-0.019	0.039	-9999	-10000	0	0
endothelial cell migration	0.02	0.066	-9999	-0.7	2	2
ADCY4	0.003	0.11	-9999	-0.64	3	3
ADCY5	0.001	0.1	-9999	-0.62	2	2
ADCY6	0.017	0.084	-9999	-0.55	1	1
ADCY7	0.015	0.085	-9999	-0.55	1	1
ADCY1	-0.1	0.18	-9999	-0.66	17	17
ADCY2	-0.016	0.092	-9999	-0.34	15	15
ADCY3	0.017	0.084	-9999	-0.55	1	1
ADCY8	0.014	0.085	-9999	-0.44	2	2
ADCY9	0.017	0.084	-9999	-0.55	1	1
GSK3B	0.023	0.028	-9999	-10000	0	0
arachidonic acid secretion	0.018	0.093	-9999	-0.5	1	1
GNG2	0.012	0	-9999	-10000	0	0
TRIP6	0.023	0.012	-9999	-10000	0	0
GNAO1	-0.016	0.14	-9999	-0.53	21	21
HRAS	0.011	0.016	-9999	-10000	0	0
NFKBIA	0.015	0.055	-9999	-10000	0	0
GAB1	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.001	0.003	-9999	-10000	0	0
JUN	0.012	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.001	0.01	-9999	-10000	0	0
TIAM1	0	0.003	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
mol:IP3	-0.005	0.068	-9999	-0.32	1	1
PLCB3	0.025	0.011	-9999	-10000	0	0
FOS	-0.1	0.29	-9999	-0.81	41	41
positive regulation of mitosis	0.018	0.093	-9999	-0.5	1	1
LPA/LPA1-2-3	-0.005	0.038	-9999	-0.49	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.012	0	-9999	-10000	0	0
stress fiber formation	0.027	0.031	-9999	-0.32	1	1
GNAZ	0.022	0.04	-9999	-0.42	2	2
EGFR/PI3K-beta/Gab1	-0.004	0.029	-9999	-10000	0	0
positive regulation of dendritic cell cytokine production	-0.005	0.037	-9999	-0.49	1	1
LPA/LPA2/MAGI-3	-0.001	0.01	-9999	-10000	0	0
ARHGEF1	0.032	0.035	-9999	-0.45	1	1
GNAI2	0.022	0.04	-9999	-0.42	2	2
GNAI3	0.022	0.04	-9999	-0.42	2	2
GNAI1	0.018	0.061	-9999	-0.48	4	4
LPA/LPA3	-0.003	0.021	-9999	-10000	0	0
LPA/LPA2	-0.001	0.013	-9999	-10000	0	0
LPA/LPA1	-0.004	0.044	-9999	-0.49	2	2
HB-EGF/EGFR	-0.044	0.1	-9999	-0.56	6	6
HBEGF	-0.061	0.12	-9999	-0.64	6	6
mol:DAG	-0.005	0.068	-9999	-0.32	1	1
cAMP biosynthetic process	-0.018	0.12	-9999	-0.45	20	20
NFKB1	0.012	0	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
LYN	0.015	0.055	-9999	-10000	0	0
GNAQ	0.017	0.018	-9999	-10000	0	0
LPAR2	0.011	0.016	-9999	-0.25	1	1
LPAR3	0.001	0.031	-9999	-0.25	4	4
LPAR1	0.013	0.05	-9999	-0.8	1	1
IL8	-0.025	0.12	-9999	-0.43	7	7
PTK2	0.027	0.039	-9999	-0.46	1	1
Rac1/GDP	0.009	0	-9999	-10000	0	0
CASP3	0.019	0.035	-9999	-0.34	2	2
EGFR	0.012	0	-9999	-10000	0	0
PLCG1	-0.023	0.078	-9999	-0.36	2	2
PLD2	0.027	0.039	-9999	-0.46	1	1
G12/G13	-0.004	0.034	-9999	-0.48	1	1
PI3K-beta	-0.002	0.025	-9999	-10000	0	0
cell migration	0.01	0.021	-9999	-10000	0	0
SLC9A3R2	0.012	0	-9999	-10000	0	0
PXN	0.027	0.032	-9999	-0.33	1	1
HRAS/GTP	0.018	0.095	-9999	-0.52	1	1
RAC1	0.012	0	-9999	-10000	0	0
MMP9	-0.099	0.15	-9999	-0.27	115	115
PRKCE	0.012	0	-9999	-10000	0	0
PRKCD	0.002	0.065	-9999	-10000	0	0
Gi(beta/gamma)	0.02	0.084	-9999	-0.51	1	1
mol:LPA	0.003	0.015	-9999	-0.22	1	1
TRIP6/p130 Cas/FAK1/Paxillin	0.009	0.037	-9999	-0.41	1	1
MAPKKK cascade	0.018	0.093	-9999	-0.5	1	1
contractile ring contraction involved in cytokinesis	0.028	0.014	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.1	0.2	-9999	-0.42	76	76
GNA15	0.011	0.036	-9999	-0.29	1	1
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.011	0.016	-9999	-0.25	1	1
MAPT	0.022	0.062	-9999	-0.45	4	4
GNA11	0.008	0.066	-9999	-0.43	6	6
Rac1/GTP	0.025	0	-9999	-10000	0	0
MMP2	0.02	0.066	-9999	-0.71	2	2

×

Signaling events mediated by PRL

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
CCNE1	-0.001	0.057	-9999	-10000	0	0
mol:Halofuginone	0.005	0.001	-9999	-10000	0	0
ITGA1	-0.005	0.12	-9999	-0.81	6	6
CDKN1A	0.013	0.057	-9999	-10000	0	0
PRL-3/alpha Tubulin	0.018	0	-9999	-10000	0	0
mol:Ca2+	-0.032	0.12	-9999	-0.64	9	9
AGT	-0.032	0.16	-9999	-0.81	9	9
CCNA2	-0.017	0.13	-9999	-0.45	23	23
TUBA1B	0.012	0	-9999	-10000	0	0
EGR1	-0.028	0.17	-9999	-0.62	23	23
CDK2/Cyclin E1	0.02	0.055	-9999	-10000	0	0
MAPK3	0.021	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.018	0	-9999	-10000	0	0
MAPK1	0.021	0	-9999	-10000	0	0
PTP4A1	-0.007	0.14	-9999	-0.48	23	23
PTP4A3	0.012	0	-9999	-10000	0	0
PTP4A2	0.012	0	-9999	-10000	0	0
ITGB1	0.021	0	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
RAC1	0.015	0.057	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.018	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.001	0.13	-9999	-0.45	23	23
RABGGTA	0.012	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	0.015	0.057	-9999	-10000	0	0
RHOA	0.015	0.057	-9999	-10000	0	0
cell motility	0.018	0.061	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.001	0.13	-9999	-0.44	23	23
PRL-3/alpha1 Integrin	0.005	0.091	-9999	-0.62	6	6
ROCK1	0.018	0.062	-9999	-10000	0	0
RABGGTB	0.012	0	-9999	-10000	0	0
CDK2	0.012	0	-9999	-10000	0	0
mitosis	-0.007	0.14	-9999	-0.48	23	23
ATF5	0.011	0.016	-9999	-10000	0	0

×

S1P4 pathway

Figure S90. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S90. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.044	0.2	-9999	-0.74	22	22
CDC42/GTP	0.01	0.084	-9999	-10000	0	0
PLCG1	0.012	0.087	-9999	-0.3	19	19
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.012	0	-9999	-10000	0	0
GNAI3	0.012	0	-9999	-10000	0	0
G12/G13	0.018	0.01	-9999	-10000	0	0
cell migration	-0.022	0.073	-9999	-10000	0	0
S1PR5	-0.002	0.091	-9999	-0.81	3	3
S1PR4	0.007	0.038	-9999	-0.25	6	6
MAPK3	0.012	0.087	-9999	-0.3	19	19
MAPK1	0.012	0.087	-9999	-10000	0	0
S1P/S1P5/Gi	0.001	0.098	-9999	-0.33	22	22
GNAI1	0.007	0.068	-9999	-0.81	2	2
CDC42/GDP	0.009	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.008	0.058	-9999	-0.55	3	3
RHOA	0.027	0.019	-9999	-10000	0	0
S1P/S1P4/Gi	0.004	0.092	-9999	-0.33	19	19
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.012	0	-9999	-10000	0	0
S1P/S1P4/G12/G13	0.021	0.02	-9999	-10000	0	0
GNA12	0.012	0	-9999	-10000	0	0
GNA13	0.011	0.016	-9999	-0.25	1	1
CDC42	0.012	0	-9999	-10000	0	0

×

ErbB2/ErbB3 signaling events

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
USP8	0.019	0.003	-9999	-10000	0	0
RAS family/GTP	0.001	0.054	-9999	-0.37	1	1
NFATC4	0.023	0.066	-9999	-0.31	10	10
ERBB2IP	0.012	0.001	-9999	-10000	0	0
HSP90 (dimer)	0.012	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.004	0.068	-9999	-0.39	8	8
JUN	0.003	0.052	-9999	-0.24	1	1
HRAS	0.011	0.016	-9999	-10000	0	0
DOCK7	0.001	0.066	-9999	-0.37	8	8
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.008	0.08	-9999	-0.47	8	8
AKT1	0.011	0.002	-9999	-10000	0	0
BAD	0.019	0.001	-9999	-10000	0	0
MAPK10	0.018	0.038	-9999	-10000	0	0
mol:GTP	-0.002	0.001	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.002	0.074	-9999	-0.42	8	8
RAF1	0.007	0.057	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 2	-0.009	0.066	-9999	-0.5	5	5
STAT3	0	0.006	-9999	-10000	0	0
cell migration	0.034	0.043	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-9999	-10000	0	0
cell proliferation	-0.08	0.14	-9999	-0.46	2	2
FOS	-0.087	0.19	-9999	-0.53	41	41
NRAS	0.012	0.001	-9999	-10000	0	0
mol:Ca2+	-0.004	0.068	-9999	-0.39	8	8
MAPK3	-0.054	0.1	-9999	-10000	0	0
MAPK1	-0.054	0.1	-9999	-0.39	1	1
JAK2	0	0.066	-9999	-0.37	8	8
NF2	-0.001	0.007	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.013	0.063	-9999	-0.35	8	8
NRG1	-0.006	0.11	-9999	-0.56	9	9
GRB2/SOS1	0.017	0.001	-9999	-10000	0	0
MAPK8	-0.003	0.077	-9999	-0.34	13	13
MAPK9	0.018	0.038	-9999	-10000	0	0
ERBB2	0	0	-9999	-10000	0	0
ERBB3	0.003	0.083	-9999	-0.81	3	3
SHC1	0.011	0.001	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
apoptosis	0	0.005	-9999	-10000	0	0
STAT3 (dimer)	0.019	0.007	-9999	-10000	0	0
RNF41	0.024	0.004	-9999	-10000	0	0
FRAP1	0.009	0.001	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.008	0.043	-9999	-10000	0	0
ErbB2/ErbB2/HSP90 (dimer)	0	0	-9999	-10000	0	0
CHRNA1	-0.086	0.11	-9999	-10000	0	0
myelination	0.027	0.062	-9999	-0.3	10	10
PPP3CB	0.001	0.062	-9999	-0.34	8	8
KRAS	0.012	0.001	-9999	-10000	0	0
RAC1-CDC42/GDP	0.026	0.055	-9999	-10000	0	0
NRG2	0.006	0.07	-9999	-0.81	2	2
mol:GDP	0.013	0.062	-9999	-0.35	8	8
SOS1	0.012	0.001	-9999	-10000	0	0
MAP2K2	0.007	0.058	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
mol:cAMP	0	0.001	-9999	-10000	0	0
PTPN11	0	0.066	-9999	-0.37	8	8
MAP2K1	-0.048	0.1	-9999	-0.42	2	2
heart morphogenesis	-0.004	0.068	-9999	-0.39	8	8
RAS family/GDP	0.004	0.056	-9999	-0.38	1	1
GRB2	0.012	0.001	-9999	-10000	0	0
PRKACA	-0.001	0.004	-9999	-10000	0	0
CHRNE	0.009	0.015	-9999	-0.12	1	1
HSP90AA1	0.012	0	-9999	-10000	0	0
activation of caspase activity	-0.011	0.002	-9999	-10000	0	0
nervous system development	-0.004	0.068	-9999	-0.39	8	8
CDC42	0.012	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.012	0	-9999	-10000	0	0
ANTXR2	0.012	0	-9999	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0	-9999	-10000	0	0
monocyte activation	-0.001	0.065	-9999	-0.44	5	5
MAP2K2	0	0	-9999	-10000	0	0
MAP2K1	0	0	-9999	-10000	0	0
MAP2K7	0	0	-9999	-10000	0	0
MAP2K6	0	0	-9999	-10000	0	0
CYAA	0.014	0	-9999	-10000	0	0
MAP2K4	0	0	-9999	-10000	0	0
IL1B	0.006	0.069	-9999	-0.47	6	6
Channel	0.016	0	-9999	-10000	0	0
NLRP1	-0.001	0.009	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
negative regulation of phagocytosis	0	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
regulation of endothelial cell proliferation	0	0	-9999	-10000	0	0
MAPK3	0	0	-9999	-10000	0	0
MAPK1	0	0	-9999	-10000	0	0
PGR	-0.21	0.24	-9999	-0.48	128	128
PA/Cellular Receptors	0	0	-9999	-10000	0	0
apoptosis	0	0	-9999	-10000	0	0
LOC728358	0	0	-9999	-10000	0	0
Lethal toxin (unfolded)	0.015	0	-9999	-10000	0	0
macrophage activation	0.018	0	-9999	-10000	0	0
TNF	-0.009	0.1	-9999	-0.81	3	3
VCAM1	-0.001	0.065	-9999	-0.44	5	5
platelet activation	0	0	-9999	-10000	0	0
MAPKKK cascade	-0.015	0	-9999	-10000	0	0
IL18	0.014	0.015	-9999	-10000	0	0
negative regulation of macrophage activation	0	0	-9999	-10000	0	0
LEF	0	0	-9999	-10000	0	0
CASP1	0	0.005	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
necrosis	0	0	-9999	-10000	0	0
intracellular pH reduction	0	0	-9999	-10000	0	0
PAGA	0	0	-9999	-10000	0	0
Edema toxin (unfolded)	0.016	0	-9999	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-9999	-10000	0	0

×

IFN-gamma pathway

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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.03	0.027	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.056	0.026	-9999	-10000	0	0
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.055	0.076	-9999	-10000	0	0
CaM/Ca2+	-0.004	0.014	-9999	-10000	0	0
RAP1A	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.036	0.029	-9999	-10000	0	0
AKT1	0.045	0.023	-9999	-10000	0	0
MAP2K1	0.043	0.025	-9999	-10000	0	0
MAP3K11	0.035	0.026	-9999	-10000	0	0
IFNGR1	0.013	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.19	0.24	-9999	-0.51	102	102
Rap1/GTP	-0.002	0.006	-9999	-10000	0	0
CRKL/C3G	0.018	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.03	0.029	-9999	-10000	0	0
CEBPB	0.069	0.026	-9999	-10000	0	0
STAT3	0.012	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.014	0.16	-9999	-1.2	5	5
STAT1	0.035	0.029	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.007	0.064	-9999	-0.25	19	19
PIK3CA	0.012	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.041	0.028	-9999	-10000	0	0
CEBPB/PTGES2/Cbp/p300	0	0.003	-9999	-10000	0	0
mol:Ca2+	0.027	0.026	-9999	-10000	0	0
MAPK3	0.052	0.023	-9999	-10000	0	0
STAT1 (dimer)	-0.064	0.11	-9999	-10000	0	0
MAPK1	0.052	0.023	-9999	-10000	0	0
JAK2	0.013	0.002	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
JAK1	0.013	0.002	-9999	-10000	0	0
CAMK2D	0.012	0	-9999	-10000	0	0
DAPK1	0.065	0.021	-9999	-10000	0	0
SMAD7	0.004	0.063	-9999	-10000	0	0
CBL/CRKL/C3G	0.043	0.024	-9999	-10000	0	0
PI3K	-0.003	0.012	-9999	-10000	0	0
IFNG	-0.007	0.064	-9999	-0.25	19	19
apoptosis	0.042	0.023	-9999	-10000	0	0
CAMK2G	0.012	0	-9999	-10000	0	0
STAT3 (dimer)	0.012	0	-9999	-10000	0	0
CAMK2A	-0.28	0.39	-9999	-0.81	102	102
CAMK2B	-0.058	0.14	-9999	-0.81	3	3
FRAP1	0.043	0.022	-9999	-10000	0	0
PRKCD	0.046	0.024	-9999	-10000	0	0
RAP1B	0.012	0	-9999	-10000	0	0
negative regulation of cell growth	-0.055	0.076	-9999	-10000	0	0
PTPN2	0.012	0	-9999	-10000	0	0
EP300	0.013	0.001	-9999	-10000	0	0
IRF1	0.058	0.049	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.039	0.033	-9999	-10000	0	0
SOCS1	-0.024	0.19	-9999	-1.4	5	5
mol:GDP	-0.003	0.01	-9999	-10000	0	0
CASP1	0.003	0.065	-9999	-0.22	2	2
PTGES2	0.012	0	-9999	-10000	0	0
IRF9	0.053	0.011	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.003	0.012	-9999	-10000	0	0
RAP1/GDP	-0.002	0.006	-9999	-10000	0	0
CBL	0.034	0.025	-9999	-10000	0	0
MAP3K1	0.036	0.026	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
PIAS4	0.012	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.055	0.076	-9999	-10000	0	0
PTPN11	0.028	0.027	-9999	-10000	0	0
CREBBP	0.013	0.001	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0

×

HIF-2-alpha transcription factor network

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
MMP14	-0.013	0.045	-10000	0	-10000	0	0
oxygen homeostasis	0.006	0.014	-10000	0	-10000	0	0
TCEB2	0.01	0.022	-10000	0	-0.25	2	2
TCEB1	0.012	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.008	0.039	-10000	0	-0.47	1	1
EPO	0.093	0.17	-10000	0	-0.73	1	1
FIH (dimer)	0.019	0.012	-10000	0	-10000	0	0
APEX1	0.018	0.014	-10000	0	-10000	0	0
SERPINE1	0.054	0.28	-10000	0	-0.76	23	23
FLT1	-0.042	0.15	-10000	0	-1.4	3	3
ADORA2A	0.09	0.18	-10000	0	-0.84	1	1
germ cell development	0.063	0.21	-10000	0	-0.63	4	4
SLC11A2	0.092	0.18	-10000	0	-0.88	1	1
BHLHE40	0.092	0.18	-10000	0	-0.88	1	1
HIF1AN	0.019	0.012	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.011	0.073	-10000	0	-0.62	1	1
ETS1	0.008	0.041	-10000	0	-10000	0	0
CITED2	-0.003	0.01	-10000	0	-10000	0	0
KDR	-0.25	0.49	-10000	0	-1.2	59	59
PGK1	0.092	0.18	-10000	0	-0.88	1	1
SIRT1	0.013	0	-10000	0	-10000	0	0
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	0.095	0.21	-10000	0	-0.64	6	6
EPAS1	0.06	0.091	-10000	0	-0.55	1	1
SP1	0.018	0.005	-10000	0	-10000	0	0
ABCG2	0.088	0.2	-10000	0	-0.97	3	3
EFNA1	0.092	0.18	-10000	0	-0.88	1	1
FXN	0.09	0.18	-10000	0	-0.84	1	1
POU5F1	0.062	0.21	-10000	0	-0.66	4	4
neuron apoptosis	-0.093	0.2	0.62	6	-10000	0	6
EP300	0.012	0	-10000	0	-10000	0	0
EGLN3	0.01	0.051	-10000	0	-0.26	7	7
EGLN2	0.019	0.013	-10000	0	-10000	0	0
EGLN1	0.019	0.012	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.01	-10000	0	-10000	0	0
VHL	0.012	0	-10000	0	-10000	0	0
ARNT	0.018	0.014	-10000	0	-10000	0	0
SLC2A1	0.087	0.18	-10000	0	-0.84	1	1
TWIST1	0.082	0.2	-10000	0	-0.72	5	5
ELK1	0.02	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.01	0.072	-10000	0	-0.62	1	1
VEGFA	0.091	0.19	-10000	0	-0.88	1	1
CREBBP	0.012	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.037	0.055	-10000	0	-10000	0	0
UGCG	0.015	0.057	-10000	0	-0.63	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	0.043	0.057	-10000	0	-0.33	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	0.018	0.056	-10000	0	-0.63	2	2
mol:DAG	0.001	0.002	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.007	0.036	-10000	0	-0.44	1	1
FRAP1	0.058	0.063	-10000	0	-0.51	1	1
FOXO3	0.061	0.061	-10000	0	-0.51	1	1
AKT1	0.057	0.064	-10000	0	-0.56	1	1
GAB2	0.013	0.001	-10000	0	-10000	0	0
SMPD1	0.019	0.017	-10000	0	-10000	0	0
SGMS1	0.019	0.017	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.004	-10000	0	-10000	0	0
CALM1	0.012	0	-10000	0	-10000	0	0
cell proliferation	0.036	0.043	-10000	0	-0.31	2	2
EIF3A	0.012	0	-10000	0	-10000	0	0
PI3K	0.023	0.004	-10000	0	-10000	0	0
RPS6KB1	0.007	0.036	-10000	0	-10000	0	0
mol:sphingomyelin	0.001	0.002	-10000	0	-10000	0	0
natural killer cell activation	0.001	0.001	-10000	0	-10000	0	0
JAK3	-0.023	0.094	-10000	0	-0.25	42	42
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
JAK1	0.015	0.001	-10000	0	-10000	0	0
NFKB1	0.012	0	-10000	0	-10000	0	0
MYC	0.058	0.065	-10000	0	-0.46	1	1
MYB	-0.044	0.11	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.05	0.065	-10000	0	-0.64	1	1
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.021	0.033	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.05	0.063	-10000	0	-0.62	1	1
Rac1/GDP	0.026	0.005	-10000	0	-10000	0	0
T cell proliferation	0.054	0.06	-10000	0	-0.57	1	1
SHC1	0.013	0.001	-10000	0	-10000	0	0
RAC1	0.012	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.013	-10000	0	-0.025	70	70
PRKCZ	0.055	0.062	-10000	0	-0.6	1	1
NF kappa B1 p50/RelA	0.001	0.041	-10000	0	-0.44	1	1
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.031	0.059	-10000	0	-0.52	1	1
HSP90AA1	0.012	0	-10000	0	-10000	0	0
RELA	0.012	0	-10000	0	-10000	0	0
IL2RA	-0.008	0.072	-10000	0	-10000	0	0
IL2RB	-0.013	0.081	-10000	0	-0.26	3	3
TERT	-0.036	0.092	-10000	0	-10000	0	0
E2F1	-0.03	0.08	-10000	0	-0.22	2	2
SOS1	0.013	0.001	-10000	0	-10000	0	0
RPS6	0.012	0	-10000	0	-10000	0	0
mol:cAMP	0.001	0.006	0.012	70	-10000	0	70
PTPN11	0.013	0.001	-10000	0	-10000	0	0
IL2RG	0.009	0.057	-10000	0	-0.36	5	5
actin cytoskeleton organization	0.054	0.06	-10000	0	-0.57	1	1
GRB2	0.013	0.001	-10000	0	-10000	0	0
IL2	0.004	0.027	-10000	0	-10000	0	0
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
Rac1/GTP	0.032	0.007	-10000	0	-10000	0	0
LCK	0.007	0.073	-10000	0	-0.81	2	2
BCL2	0.061	0.055	-10000	0	-0.4	1	1

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.007	0.049	-9999	-10000	0	0
DAPP1	0.028	0.064	-9999	-0.79	1	1
Src family/SYK family/BLNK-LAT/BTK-ITK	0.01	0.099	-9999	-0.56	4	4
mol:DAG	0.014	0.071	-9999	-0.28	3	3
HRAS	0.012	0.016	-9999	-10000	0	0
RAP1A	0.012	0.004	-9999	-10000	0	0
ARF5/GDP	0.03	0.037	-9999	-0.32	2	2
PLCG2	-0.032	0.18	-9999	-0.74	17	17
PLCG1	0.012	0	-9999	-10000	0	0
ARF5	0.012	0	-9999	-10000	0	0
mol:GTP	-0.007	0.053	-9999	-0.41	5	5
ARF1/GTP	-0.007	0.051	-9999	-0.39	5	5
RHOA	0.012	0	-9999	-10000	0	0
YES1	0.012	0	-9999	-10000	0	0
RAP1A/GTP	-0.007	0.052	-9999	-0.4	5	5
ADAP1	-0.007	0.05	-9999	-0.38	5	5
ARAP3	-0.007	0.053	-9999	-0.41	5	5
INPPL1	0.012	0	-9999	-10000	0	0
PREX1	0.007	0.068	-9999	-0.81	2	2
ARHGEF6	0.012	0	-9999	-10000	0	0
ARHGEF7	0.012	0	-9999	-10000	0	0
ARF1	0.012	0	-9999	-10000	0	0
NRAS	0.013	0.004	-9999	-10000	0	0
FYN	0.012	0	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
FGR	0.001	0.066	-9999	-0.81	1	1
mol:Ca2+	0.016	0.039	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.012	0	-9999	-10000	0	0
ZAP70	-0.042	0.11	-9999	-10000	0	0
mol:IP3	0.019	0.051	-9999	-10000	0	0
LYN	0.012	0	-9999	-10000	0	0
ARF1/GDP	0.03	0.037	-9999	-0.32	2	2
RhoA/GDP	-0.003	0.051	-9999	-0.45	1	1
PDK1/Src/Hsp90	0	0.007	-9999	-10000	0	0
BLNK	-0.016	0.15	-9999	-0.81	10	10
actin cytoskeleton reorganization	0.043	0.066	-9999	-0.48	2	2
SRC	0.011	0.016	-9999	-10000	0	0
PLEKHA2	0.024	0.023	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
PTEN	0.001	0.006	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
ARF6/GTP	-0.007	0.049	-9999	-10000	0	0
RhoA/GTP	-0.007	0.05	-9999	-0.38	5	5
Src family/SYK family/BLNK-LAT	0.002	0.091	-9999	-0.5	3	3
BLK	-0.002	0.057	-9999	-0.25	14	14
PDPK1	0.012	0	-9999	-10000	0	0
CYTH1	-0.007	0.05	-9999	-0.38	5	5
HCK	-0.014	0.089	-9999	-0.27	27	27
CYTH3	-0.007	0.05	-9999	-0.38	5	5
CYTH2	-0.007	0.05	-9999	-0.38	5	5
KRAS	0.013	0.004	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.037	0.03	-9999	-10000	0	0
SGK1	-0.004	0.027	-9999	-10000	0	0
INPP5D	0.006	0.041	-9999	-10000	0	0
mol:GDP	0.024	0.038	-9999	-0.34	2	2
SOS1	0.012	0	-9999	-10000	0	0
SYK	0.009	0.048	-9999	-0.81	1	1
ARF6/GDP	-0.007	0.05	-9999	-0.45	1	1
mol:PI-3-4-5-P3	-0.007	0.053	-9999	-0.4	5	5
ARAP3/RAP1A/GTP	-0.007	0.053	-9999	-0.41	5	5
VAV1	-0.035	0.11	-9999	-0.81	1	1
mol:PI-3-4-P2	0.017	0.028	-9999	-10000	0	0
RAS family/GTP/PI3K Class I	0.022	0.057	-9999	-0.41	5	5
PLEKHA1	0.024	0.023	-9999	-10000	0	0
Rac1/GDP	0.03	0.037	-9999	-0.32	2	2
LAT	-0.045	0.11	-9999	-0.25	62	62
Rac1/GTP	0.024	0.052	-9999	-0.69	1	1
ITK	-0.01	0.051	-9999	-0.38	5	5
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.013	0.093	-9999	-0.38	4	4
LCK	0.004	0.073	-9999	-0.81	2	2
BTK	-0.024	0.057	-9999	-0.38	5	5

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.003	0.075	-10000	0	-0.44	6	6
CLTC	0.029	0.011	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.025	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	0.021	0.017	-10000	0	-10000	0	0
EXOC4	0.012	0	-10000	0	-10000	0	0
CD59	0.026	0.007	-10000	0	-10000	0	0
CPE	0.016	0.033	-10000	0	-0.55	1	1
CTNNB1	0.012	0	-10000	0	-10000	0	0
membrane fusion	0.025	0	-10000	0	-10000	0	0
CTNND1	0.027	0.016	-10000	0	-10000	0	0
DNM2	0.012	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.03	0.005	-10000	0	-10000	0	0
TSHR	0.015	0.013	-10000	0	-10000	0	0
INS	0.01	0.008	-10000	0	-10000	0	0
BIN1	0.008	0.053	-10000	0	-0.81	1	1
mol:Choline	0.025	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.019	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.012	0	-10000	0	-10000	0	0
mol:Ca2+	0.02	0.017	-10000	0	-10000	0	0
JUP	0.026	0.007	-10000	0	-10000	0	0
ASAP2/amphiphysin II	0.018	0.054	-10000	0	-0.5	3	3
ARF6/GTP	0.009	0	-10000	0	-10000	0	0
CDH1	-0.002	0.087	-10000	0	-0.27	27	27
clathrin-independent pinocytosis	0.009	0	-10000	0	-10000	0	0
MAPK8IP3	-0.009	0.072	-10000	0	-10000	0	0
positive regulation of endocytosis	0.009	0	-10000	0	-10000	0	0
EXOC2	0.012	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.04	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.012	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.055	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.017	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.01	0.035	-10000	0	-10000	0	0
ACAP1	0.02	0.009	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.021	0.008	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.033	0.01	-10000	0	-10000	0	0
JIP4/KLC1	0.024	0	-10000	0	-10000	0	0
EXOC1	0.012	0	-10000	0	-10000	0	0
exocyst	0.04	0	-10000	0	-10000	0	0
RALA/GTP	0.009	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0.009	0	-10000	0	-10000	0	0
CTNNA1	0.027	0.016	-10000	0	-10000	0	0
NME1	0.015	0.019	-10000	0	-10000	0	0
clathrin coat assembly	0.029	0.011	-10000	0	-10000	0	0
IL2RA	0.02	0.021	-10000	0	-10000	0	0
VAMP3	0.018	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.004	0.035	-10000	0	-0.4	2	2
EXOC6	0.012	0	-10000	0	-10000	0	0
PLD1	0.021	0	-10000	0	-10000	0	0
PLD2	0.021	0	-10000	0	-10000	0	0
EXOC5	0.012	0	-10000	0	-10000	0	0
PIP5K1C	0.03	0.005	-10000	0	-10000	0	0
SDC1	0.026	0.009	-10000	0	-10000	0	0
ARF6/GDP	0.015	0.019	-10000	0	-10000	0	0
EXOC7	0.012	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.019	0.057	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.025	0	-10000	0	-10000	0	0
endocytosis	0.006	0.051	0.49	3	-10000	0	3
SCAMP2	0.012	0	-10000	0	-10000	0	0
ADRB2	0.029	0.025	-10000	0	-10000	0	0
EXOC3	0.012	0	-10000	0	-10000	0	0
ASAP2	0.007	0.068	-10000	0	-0.81	2	2
Dynamin 2/GDP	0.021	0.017	-10000	0	-10000	0	0
KLC1	0.012	0	-10000	0	-10000	0	0
AVPR2	-0.34	0.19	-10000	0	-0.44	231	231
RALA	0.012	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.05	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.032	0	-10000	0	-10000	0	0
HDAC3	0.012	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.024	-10000	0	-0.41	1	1
GATA1/HDAC4	-0.003	0.064	-10000	0	-0.63	1	1
GATA1/HDAC5	0	0.052	-10000	0	-10000	0	0
GATA2/HDAC5	-0.12	0.26	-10000	0	-0.62	63	63
HDAC5/BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC9	0.012	0	-10000	0	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	0.016	0.038	-10000	0	-0.62	1	1
HDAC5/YWHAB	0.018	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.02	0	-10000	0	-10000	0	0
GATA2	-0.17	0.34	-10000	0	-0.81	63	63
HDAC4/RFXANK	0.016	0.038	-10000	0	-0.62	1	1
BCOR	0.012	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.012	0	-10000	0	-10000	0	0
HDAC5	0.012	0	-10000	0	-10000	0	0
GNB1/GNG2	0.018	0	-10000	0	-10000	0	0
Histones	0.037	0.018	-10000	0	-10000	0	0
ADRBK1	0.012	0	-10000	0	-10000	0	0
HDAC4	0.009	0.048	-10000	0	-0.81	1	1
XPO1	0.012	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.018	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.016	0.038	-10000	0	-0.62	1	1
HDAC7	0.012	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.018	0	-10000	0	-10000	0	0
TUBA1B	0.012	0	-10000	0	-10000	0	0
HDAC6	0.012	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.018	0	-10000	0	-10000	0	0
CAMK4	-0.005	0.12	-10000	0	-0.81	6	6
Tubulin/HDAC6	0	0	-10000	0	-10000	0	0
SUMO1	0.012	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.012	0	-10000	0	-10000	0	0
GATA1	-0.016	0.078	-10000	0	-0.25	28	28
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.012	0	-10000	0	-10000	0	0
NR3C1	0.012	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.027	0.028	-10000	0	-0.45	1	1
SRF	0.012	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.016	0.038	-10000	0	-0.62	1	1
Tubulin	0.018	0	-10000	0	-10000	0	0
HDAC4/14-3-3 E	0.016	0.038	-10000	0	-0.62	1	1
GNB1	0.012	0	-10000	0	-10000	0	0
RANGAP1	0.012	0	-10000	0	-10000	0	0
BCL6/BCoR	0.018	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	-0.002	0.032	-10000	0	-0.54	1	1
HDAC4/SRF	-0.013	0.083	-10000	0	-0.54	7	7
HDAC4/ER alpha	-0.021	0.16	-10000	0	-0.62	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.037	0.017	-10000	0	-10000	0	0
cell motility	0	0	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.012	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.018	0	-10000	0	-10000	0	0
BCL6	0.012	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.009	0.048	-10000	0	-0.81	1	1
Hsp90/HDAC6	0.018	0	-10000	0	-10000	0	0
ESR1	-0.036	0.19	-10000	0	-0.81	17	17
HDAC6/HDAC11	0.018	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	0.012	0	-10000	0	-10000	0	0
RAN	0.012	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.002	0.027	-10000	0	-0.46	1	1
GNG2	0.012	0	-10000	0	-10000	0	0
NCOR2	0.012	0	-10000	0	-10000	0	0
TUBB2A	0.012	0	-10000	0	-10000	0	0
HDAC11	0.012	0	-10000	0	-10000	0	0
HSP90AA1	0.012	0	-10000	0	-10000	0	0
RANBP2	0.012	0	-10000	0	-10000	0	0
ANKRA2	0.012	0	-10000	0	-10000	0	0
RFXANK	0.012	0	-10000	0	-10000	0	0
nuclear import	-0.026	0.027	0.44	1	-10000	0	1

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.003	0.023	-9999	-10000	0	0
BUB1B	0.008	0.036	-9999	-0.16	1	1
PLK1	0.009	0.017	-9999	-10000	0	0
PLK1S1	0.01	0.009	-9999	-10000	0	0
KIF2A	0.016	0.015	-9999	-10000	0	0
regulation of mitotic centrosome separation	0.009	0.017	-9999	-10000	0	0
GOLGA2	0.012	0	-9999	-10000	0	0
Hec1/SPC24	-0.008	0.08	-9999	-0.24	21	21
WEE1	0.016	0.015	-9999	-10000	0	0
cytokinesis	-0.015	0.072	-9999	-0.23	8	8
PP2A-alpha B56	0.008	0.041	-9999	-10000	0	0
AURKA	0.01	0.014	-9999	-10000	0	0
PICH/PLK1	0.018	0.044	-9999	-10000	0	0
CENPE	0.007	0.043	-9999	-10000	0	0
RhoA/GTP	0.009	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.016	0.015	-9999	-10000	0	0
PPP2CA	0.012	0	-9999	-10000	0	0
FZR1	0.012	0	-9999	-10000	0	0
TPX2	-0.003	0.033	-9999	-10000	0	0
PAK1	0.012	0	-9999	-10000	0	0
SPC24	-0.029	0.095	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
CLSPN	0.003	0.028	-9999	-10000	0	0
GORASP1	0.012	0	-9999	-10000	0	0
metaphase	-0.001	0.002	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NLP	0.005	0.009	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0.001	-9999	-10000	0	0
STAG2	0.012	0	-9999	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.009	-9999	-10000	0	0
spindle elongation	0.009	0.017	-9999	-10000	0	0
ODF2	0.012	0.001	-9999	-10000	0	0
BUB1	-0.021	0.036	-9999	-10000	0	0
TPT1	0.01	0.009	-9999	-10000	0	0
CDC25C	-0.008	0.042	-9999	-10000	0	0
CDC25B	0.011	0.022	-9999	-10000	0	0
SGOL1	0.003	0.023	-9999	-10000	0	0
RHOA	0.012	0	-9999	-10000	0	0
CCNB1/CDK1	0.003	0.015	-9999	-10000	0	0
CDC14B	0.011	0	-9999	-10000	0	0
CDC20	-0.017	0.083	-9999	-0.25	32	32
PLK1/PBIP1	-0.008	0.031	-9999	-10000	0	0
mitosis	0	0.002	-9999	-10000	0	0
FBXO5	0.015	0.012	-9999	-10000	0	0
CDC2	0.001	0.001	-9999	-10000	0	0
NDC80	-0.014	0.08	-9999	-0.25	29	29
metaphase plate congression	0.009	0.012	-9999	-10000	0	0
ERCC6L	-0.005	0.035	-9999	-10000	0	0
NLP/gamma Tubulin	0.008	0.01	-9999	-10000	0	0
microtubule cytoskeleton organization	0.01	0.009	-9999	-10000	0	0
G2/M transition DNA damage checkpoint	0	0	-9999	-10000	0	0
PPP1R12A	0.012	0	-9999	-10000	0	0
interphase	0	0	-9999	-10000	0	0
PLK1/PRC1-2	-0.015	0.071	-9999	-0.26	5	5
GRASP65/GM130/RAB1/GTP/PLK1	0.004	0.009	-9999	-10000	0	0
RAB1A	0.012	0	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
Aurora A/BORA	0.014	0.012	-9999	-10000	0	0
mitotic prometaphase	-0.001	0.001	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.02	-9999	-10000	0	0
microtubule-based process	-0.022	0.07	-9999	-0.17	5	5
Golgi organization	0.009	0.017	-9999	-10000	0	0
Cohesin/SA2	-0.003	0.007	-9999	-10000	0	0
PPP1CB/MYPT1	0.018	0.002	-9999	-10000	0	0
KIF20A	-0.067	0.12	-9999	-0.25	86	86
APC/C/CDC20	0.001	0.051	-9999	-10000	0	0
PPP2R1A	0.012	0	-9999	-10000	0	0
chromosome segregation	-0.008	0.031	-9999	-10000	0	0
PRC1	0.008	0.035	-9999	-0.25	5	5
ECT2	0.016	0.015	-9999	-10000	0	0
C13orf34	0.014	0.013	-9999	-10000	0	0
NUDC	0.009	0.012	-9999	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	0.008	0.036	-9999	-0.15	1	1
spindle assembly	0.01	0.014	-9999	-10000	0	0
spindle stabilization	0.01	0.009	-9999	-10000	0	0
APC/C/HCDH1	0.017	0	-9999	-10000	0	0
MKLP2/PLK1	-0.023	0.07	-9999	-0.17	5	5
CCNB1	0.012	0.016	-9999	-0.26	1	1
PPP1CB	0.012	0	-9999	-10000	0	0
BTRC	0.012	0	-9999	-10000	0	0
ROCK2	0.003	0.085	-9999	-0.5	8	8
TUBG1	0.01	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.001	0.012	-9999	-10000	0	0
MLF1IP	0.001	0.041	-9999	-10000	0	0
INCENP	0.012	0.001	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.012	0	-10000	0	-10000	0	0
NFATC1	0.045	0.013	-10000	0	-10000	0	0
NFATC2	-0.01	0.074	-10000	0	-0.26	10	10
NFATC3	0.015	0.011	-10000	0	-10000	0	0
YWHAE	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.008	0.061	-10000	0	-0.56	1	1
Exportin 1/Ran/NUP214	0.017	0.012	-10000	0	-10000	0	0
mol:DAG	-0.002	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.02	0.074	-10000	0	-0.43	7	7
BCL2/BAX	0.017	0.015	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0.003	0.011	-10000	0	-10000	0	0
CaM/Ca2+	0.003	0.011	-10000	0	-10000	0	0
BAX	0.01	0.022	-10000	0	-0.25	2	2
MAPK14	0.008	0.006	-10000	0	-10000	0	0
BAD	0.012	0	-10000	0	-10000	0	0
CABIN1/MEF2D	0.012	0.059	-10000	0	-0.53	1	1
Calcineurin A alpha-beta B1/BCL2	0.012	0	-10000	0	-10000	0	0
FKBP8	0.012	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	-0.012	0.058	0.52	1	-10000	0	1
KPNB1	0.012	0	-10000	0	-10000	0	0
KPNA2	0.012	0	-10000	0	-10000	0	0
XPO1	0.012	0.001	-10000	0	-10000	0	0
SFN	-0.12	0.16	-10000	0	-0.81	5	5
MAP3K8	0.008	0.006	-10000	0	-10000	0	0
NFAT4/CK1 alpha	0	0	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.084	0.19	-10000	0	-0.5	9	9
CABIN1	0.008	0.062	-10000	0	-0.56	1	1
CALM1	0.008	0.006	-10000	0	-10000	0	0
RAN	0.012	0.001	-10000	0	-10000	0	0
MAP3K1	0.012	0	-10000	0	-10000	0	0
CAMK4	-0.005	0.12	-10000	0	-0.81	6	6
mol:Ca2+	-0.006	0.01	-10000	0	-10000	0	0
MAPK3	0.012	0	-10000	0	-10000	0	0
YWHAH	0.012	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.01	0.038	-10000	0	-0.62	1	1
YWHAB	0.012	0	-10000	0	-10000	0	0
MAPK8	-0.006	0.11	-10000	0	-0.81	5	5
MAPK9	0.012	0	-10000	0	-10000	0	0
YWHAG	0.012	0	-10000	0	-10000	0	0
FKBP1A	0.012	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.04	0.041	-10000	0	-10000	0	0
PRKCH	0.009	0.048	-10000	0	-0.81	1	1
CABIN1/Cbp/p300	0.009	0.015	-10000	0	-10000	0	0
CASP3	0.007	0.016	-10000	0	-0.25	1	1
PIM1	0.01	0.022	-10000	0	-0.25	2	2
Calcineurin A alpha-beta B1/FKBP12/FK506	0.006	0.004	-10000	0	-10000	0	0
apoptosis	-0.001	0.006	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.007	0.041	-10000	0	-10000	0	0
PRKCB	0.009	0.048	-10000	0	-0.81	1	1
PRKCE	0.012	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.022	0.008	-10000	0	-10000	0	0
BAD/BCL-XL	0.018	0	-10000	0	-10000	0	0
PRKCD	0.012	0	-10000	0	-10000	0	0
NUP214	0.012	0.001	-10000	0	-10000	0	0
PRKCZ	0.008	0.006	-10000	0	-10000	0	0
PRKCA	0.012	0	-10000	0	-10000	0	0
PRKCG	-0.066	0.12	-10000	0	-10000	0	0
PRKCQ	-0.019	0.16	-10000	0	-0.81	11	11
FKBP38/BCL2	0.018	0	-10000	0	-10000	0	0
EP300	0.007	0.008	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.012	0	-10000	0	-10000	0	0
NFATc/JNK1	0.031	0.064	-10000	0	-0.4	5	5
CaM/Ca2+/FKBP38	0.012	0.009	-10000	0	-10000	0	0
FKBP12/FK506	0.009	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.013	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0	0.08	-10000	0	-0.55	6	6
NFATc/ERK1	0.05	0.013	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.018	0.073	-10000	0	-0.43	7	7
NR4A1	-0.22	0.37	-10000	0	-0.73	99	99
GSK3B	0.008	0.006	-10000	0	-10000	0	0
positive T cell selection	0.015	0.011	-10000	0	-10000	0	0
NFAT1/CK1 alpha	-0.027	0.047	-10000	0	-0.3	2	2
RCH1/ KPNB1	0.018	0	-10000	0	-10000	0	0
YWHAQ	0.012	0	-10000	0	-10000	0	0
PRKACA	0.008	0.006	-10000	0	-10000	0	0
AKAP5	0.009	0.048	-10000	0	-0.81	1	1
MEF2D	0.007	0.008	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.012	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.028	-10000	0	-10000	0	0
CREBBP	0.007	0.008	-10000	0	-10000	0	0
BCL2	0.012	0	-10000	0	-10000	0	0

×

IL2 signaling events mediated by STAT5

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
GAB2	0.013	0.001	-9999	-10000	0	0
ELF1	0.009	0.039	-9999	-10000	0	0
CCNA2	-0.026	0.094	-9999	-10000	0	0
PIK3CA	0.013	0.001	-9999	-10000	0	0
JAK3	-0.026	0.094	-9999	-0.25	42	42
PIK3R1	0.013	0.001	-9999	-10000	0	0
JAK1	0.013	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.048	0.063	-9999	-0.64	1	1
SHC1	0.013	0.001	-9999	-10000	0	0
SP1	0.002	0.047	-9999	-10000	0	0
IL2RA	0.009	0.07	-9999	-10000	0	0
IL2RB	-0.015	0.081	-9999	-0.26	2	2
SOS1	0.013	0.001	-9999	-10000	0	0
IL2RG	0.006	0.057	-9999	-0.36	5	5
G1/S transition of mitotic cell cycle	0.008	0.061	-9999	-10000	0	0
PTPN11	0.013	0.001	-9999	-10000	0	0
CCND2	-0.002	0.084	-9999	-10000	0	0
LCK	0.004	0.073	-9999	-0.81	2	2
GRB2	0.013	0.001	-9999	-10000	0	0
IL2	0.002	0.027	-9999	-10000	0	0
CDK6	0.012	0	-9999	-10000	0	0
CCND3	0.052	0.06	-9999	-0.53	1	1

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.057	-9999	-0.43	5	5
TC10/GTP	-0.002	0.011	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.01	0.066	-9999	-0.51	5	5
HRAS	0.011	0.016	-9999	-10000	0	0
APS homodimer	0.006	0.041	-9999	-0.25	7	7
GRB14	-0.05	0.22	-9999	-0.81	22	22
FOXO3	-0.006	0.019	-9999	-10000	0	0
AKT1	0.007	0.13	-9999	-0.75	2	2
INSR	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insulin	0.033	0.01	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0	-9999	-10000	0	0
SORBS1	0.012	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
PTPN1	0.031	0.01	-9999	-10000	0	0
CAV1	0.016	0.066	-9999	-0.47	5	5
CBL/APS/CAP/Crk-II/C3G	-0.002	0.013	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.01	0.066	-9999	-0.51	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.058	-9999	-0.44	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.03	0.042	-9999	-10000	0	0
RPS6KB1	0.015	0.12	-9999	-0.66	2	2
PARD6A	0.012	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	-0.001	0.01	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.032	0.11	-9999	-0.69	2	2
HRAS/GTP	-0.009	0.053	-9999	-0.48	1	1
Insulin Receptor	0.014	0.001	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.009	0.062	-9999	-0.47	5	5
PRKCI	-0.009	0.029	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.039	0.13	-9999	-0.45	25	25
SHC1	0.012	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0	0.007	-9999	-10000	0	0
PI3K	-0.008	0.059	-9999	-0.45	5	5
NCK2	0.012	0	-9999	-10000	0	0
RHOQ	0.012	0	-9999	-10000	0	0
mol:H2O2	0	0.001	-9999	-10000	0	0
HRAS/GDP	0.009	0.01	-9999	-10000	0	0
AKT2	0.007	0.13	-9999	-0.75	2	2
PRKCZ	-0.009	0.029	-9999	-10000	0	0
SH2B2	0.006	0.041	-9999	-0.25	7	7
SHC/SHIP	0.02	0.067	-9999	-0.46	5	5
F2RL2	-0.034	0.17	-9999	-0.81	11	11
TRIP10	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.01	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.007	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	0.029	0.02	-9999	-10000	0	0
TC10/GDP	0.009	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.009	-9999	-10000	0	0
INPP5D	0.013	0.071	-9999	-0.5	5	5
SOS1	0.012	0	-9999	-10000	0	0
SGK1	-0.003	0.008	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0	-9999	-10000	0	0
IRS1	-0.002	0.11	-9999	-0.81	5	5
p62DOK/RasGAP	0	0.007	-9999	-10000	0	0
INS	0.001	0.025	-9999	-10000	0	0
mol:PI-3-4-P2	0.013	0.07	-9999	-0.49	5	5
GRB2	0.012	0	-9999	-10000	0	0
EIF4EBP1	0.012	0.12	-9999	-0.7	2	2
PTPRA	0.014	0.001	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.012	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.025	0.047	-9999	-0.33	5	5
Insulin Receptor/Insulin/IRS1	-0.01	0.067	-9999	-0.51	5	5
Insulin Receptor/Insulin/IRS3	-0.002	0.015	-9999	-10000	0	0
Par3/Par6	-0.023	0.09	-9999	-0.47	11	11

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.021	0.095	-9999	-0.9	3	3
VEGFR1 homodimer/NRP1	0.012	0.094	-9999	-0.91	3	3
mol:DAG	0.026	0.089	-9999	-0.83	3	3
VEGFR1 homodimer/NRP1/VEGFR 121	0.017	0.09	-9999	-0.85	3	3
CaM/Ca2+	0.031	0.085	-9999	-0.79	3	3
HIF1A	0.016	0.041	-9999	-0.38	3	3
GAB1	0.012	0	-9999	-10000	0	0
AKT1	0.045	0.079	-9999	-0.72	3	3
PLCG1	0.026	0.09	-9999	-0.84	3	3
NOS3	0.035	0.11	-9999	-0.71	3	3
CBL	0.012	0	-9999	-10000	0	0
mol:NO	0.035	0.1	-9999	-0.67	3	3
FLT1	0.018	0.1	-9999	-1	3	3
PGF	0.008	0.035	-9999	-10000	0	0
VEGFR1 homodimer/NRP2/VEGFR121	0.023	0.095	-9999	-0.75	4	4
CALM1	0.012	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
eNOS/Hsp90	0.041	0.1	-9999	-0.64	3	3
endothelial cell proliferation	0.039	0.087	-9999	-0.78	3	3
mol:Ca2+	0.026	0.088	-9999	-0.82	3	3
MAPK3	0.037	0.079	-9999	-0.72	3	3
MAPK1	0.037	0.079	-9999	-0.72	3	3
PIK3R1	0.012	0	-9999	-10000	0	0
PLGF homodimer	0.008	0.035	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	0.012	0	-9999	-10000	0	0
VEGFA homodimer	0.01	0.027	-9999	-0.25	3	3
VEGFR1 homodimer/VEGFA homodimer	0.019	0.096	-9999	-0.9	3	3
platelet activating factor biosynthetic process	0.043	0.077	-9999	-0.7	3	3
PI3K	0.031	0.086	-9999	-0.8	3	3
PRKCA	0.032	0.083	-9999	-0.77	3	3
PRKCB	0.03	0.088	-9999	-0.69	4	4
VEGFR1 homodimer/PLGF homodimer	0.018	0.096	-9999	-0.9	3	3
VEGFA	0.01	0.027	-9999	-0.25	3	3
VEGFB	0.012	0	-9999	-10000	0	0
mol:IP3	0.026	0.089	-9999	-0.83	3	3
RASA1	0.028	0.088	-9999	-0.84	3	3
NRP2	0.008	0.053	-9999	-0.44	3	3
VEGFR1 homodimer	0.018	0.1	-9999	-1	3	3
VEGFB homodimer	0.012	0	-9999	-10000	0	0
NCK1	0.012	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.041	0.1	-9999	-0.64	3	3
PTPN11	0.012	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.009	0.08	-9999	-0.78	3	3
mol:L-citrulline	0.035	0.1	-9999	-0.67	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.032	0.086	-9999	-0.8	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.026	0.09	-9999	-0.84	3	3
CD2AP	0.012	0	-9999	-10000	0	0
PI3K/GAB1	-0.009	0.076	-9999	-0.75	3	3
PDPK1	0.036	0.08	-9999	-0.74	3	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.026	0.09	-9999	-0.84	3	3
mol:NADP	0.035	0.1	-9999	-0.67	3	3
HSP90AA1	0.012	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.009	0.08	-9999	-0.79	3	3
VEGFR1 homodimer/NRP2	0.018	0.1	-9999	-0.81	4	4

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.007	0.036	-9999	-0.47	1	1
RGS9BP	0.008	0.051	-9999	-0.53	2	2
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.002	0.016	-9999	-10000	0	0
mol:Na +	-0.006	0.028	-9999	-10000	0	0
mol:ADP	0.006	0.019	-9999	-10000	0	0
GNAT2	0.01	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.014	0.076	-9999	-0.56	5	5
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0	0	-9999	-10000	0	0
GRK7	0.004	0.022	-9999	-10000	0	0
CNGB3	-0.006	0.049	-9999	-10000	0	0
Cone Metarhodopsin II/X-Arrestin	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.001	0.027	-9999	-10000	0	0
Cone PDE6	-0.012	0.066	-9999	-0.49	5	5
Cone Metarhodopsin II	0.005	0.014	-9999	-10000	0	0
Na + (4 Units)	-0.005	0.026	-9999	-10000	0	0
GNAT2/GDP	-0.012	0.065	-9999	-0.48	5	5
GNB5	0.012	0	-9999	-10000	0	0
mol:GMP (4 units)	0.01	0.006	-9999	-10000	0	0
Cone Transducin	0.014	0.043	-9999	-0.5	1	1
SLC24A2	-0.001	0.021	-9999	-10000	0	0
GNB3/GNGT2	0.007	0.055	-9999	-0.47	2	2
GNB3	0	0.055	-9999	-0.25	13	13
GNAT2/GTP	0.007	0.004	-9999	-10000	0	0
CNGA3	0.002	0.022	-9999	-0.25	2	2
ARR3	0.003	0.005	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.006	0.028	-9999	-10000	0	0
mol:Pi	-0.014	0.076	-9999	-0.56	5	5
Cone CNG Channel	-0.004	0.02	-9999	-10000	0	0
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.001	0.021	-9999	-10000	0	0
RGS9	-0.009	0.11	-9999	-0.81	4	4
PDE6C	0.004	0.006	-9999	-10000	0	0
GNGT2	0.008	0.051	-9999	-0.81	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.002	0.005	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.012	0	-9999	-10000	0	0
HDAC2	0.012	0	-9999	-10000	0	0
GNB1/GNG2	0.021	0.048	-9999	-0.54	2	2
forebrain development	0.034	0.072	-9999	-0.41	5	5
GNAO1	-0.044	0.2	-9999	-0.73	22	22
SMO/beta Arrestin2	0.014	0.056	-9999	-0.62	2	2
SMO	0.007	0.07	-9999	-0.81	2	2
ARRB2	0.011	0.022	-9999	-10000	0	0
GLI3/SPOP	0.045	0.024	-9999	-10000	0	0
mol:GTP	0.001	0.001	-9999	-10000	0	0
GSK3B	0.012	0	-9999	-10000	0	0
GNAI2	0.013	0.001	-9999	-10000	0	0
SIN3/HDAC complex	0.016	0.017	-9999	-10000	0	0
GNAI1	0.007	0.068	-9999	-0.81	2	2
XPO1	0.015	0.003	-9999	-10000	0	0
GLI1/Su(fu)	-0.01	0.044	-9999	-10000	0	0
SAP30	0.011	0.016	-9999	-10000	0	0
mol:GDP	0.007	0.07	-9999	-0.81	2	2
MIM/GLI2A	0.013	0.049	-9999	-0.81	1	1
IFT88	0.012	0	-9999	-10000	0	0
GNAI3	0.013	0.001	-9999	-10000	0	0
GLI2	0.032	0.052	-9999	-10000	0	0
GLI3	0.04	0.025	-9999	-10000	0	0
CSNK1D	0.012	0	-9999	-10000	0	0
CSNK1E	0.012	0	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
embryonic digit morphogenesis	0.012	0	-9999	-10000	0	0
GNG2	0.012	0	-9999	-10000	0	0
Gi family/GTP	0.007	0.096	-9999	-0.32	21	21
SIN3B	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
GLI3/Su(fu)	0.058	0.016	-9999	-10000	0	0
GLI2/Su(fu)	0.045	0.05	-9999	-10000	0	0
FOXA2	-0.011	0.062	-9999	-0.82	1	1
neural tube patterning	0.034	0.072	-9999	-0.41	5	5
SPOP	0.012	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.029	0.024	-9999	-10000	0	0
GNB1	0.012	0	-9999	-10000	0	0
CSNK1G2	0.012	0	-9999	-10000	0	0
CSNK1G3	0.012	0	-9999	-10000	0	0
MTSS1	0.013	0.049	-9999	-0.81	1	1
embryonic limb morphogenesis	0.034	0.072	-9999	-0.41	5	5
SUFU	0.025	0.027	-9999	-10000	0	0
LGALS3	0.007	0.055	-9999	-0.81	1	1
catabolic process	0.061	0.042	-9999	-10000	0	0
GLI3A/CBP	0.013	0.053	-9999	-0.38	5	5
KIF3A	0.012	0	-9999	-10000	0	0
GLI1	0.034	0.073	-9999	-0.41	5	5
RAB23	0.012	0	-9999	-10000	0	0
CSNK1A1	0.012	0	-9999	-10000	0	0
IFT172	0.012	0	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
Su(fu)/Galectin3	0.026	0.043	-9999	-0.42	2	2
GNAZ	0.013	0.001	-9999	-10000	0	0
RBBP4	0.012	0	-9999	-10000	0	0
CSNK1G1	0.012	0	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GLI2/SPOP	0.036	0.049	-9999	-10000	0	0
STK36	0.014	0.003	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.018	0.081	-9999	-10000	0	0
PTCH1	0.04	0.067	-9999	-10000	0	0
MIM/GLI1	0.04	0.08	-9999	-10000	0	0
CREBBP	0.013	0.053	-9999	-0.38	5	5
Su(fu)/SIN3/HDAC complex	0.045	0.008	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

Figure S106. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S106. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.029	0	-9999	-10000	0	0
CRKL	0.012	0	-9999	-10000	0	0
Rac1/GDP	0.009	0	-9999	-10000	0	0
DOCK1	0.012	0	-9999	-10000	0	0
ITGA4	0.012	0	-9999	-10000	0	0
alpha4/beta7 Integrin/MAdCAM1	0.012	0.046	-9999	-10000	0	0
EPO	0.007	0.022	-9999	-0.25	2	2
alpha4/beta7 Integrin	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.018	0	-9999	-10000	0	0
EPO/EPOR (dimer)	0.014	0.015	-9999	-10000	0	0
lamellipodium assembly	0.002	0.006	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
JAK2	0.03	0.008	-9999	-10000	0	0
PXN	0.012	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
MADCAM1	-0.028	0.093	-9999	-0.25	42	42
cell adhesion	-0.014	0.035	-9999	-10000	0	0
CRKL/CBL	0.018	0	-9999	-10000	0	0
ITGB1	0.012	0	-9999	-10000	0	0
SRC	0.019	0.053	-9999	-0.49	2	2
ITGB7	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.011	0.053	-9999	-0.54	2	2
p130Cas/Crk/Dock1	0.038	0.046	-9999	-0.41	2	2
VCAM1	-0.01	0.093	-9999	-0.81	2	2
RHOA	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.032	0	-9999	-10000	0	0
BCAR1	0.026	0.05	-9999	-0.45	2	2
EPOR	0.012	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
Rac1/GTP	0.002	0.006	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.009	0.052	-9999	-0.5	3	3
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.035	0.05	-9999	-0.41	3	3
SUMO1	0.012	0	-9999	-10000	0	0
ZFPM1	0.01	0.027	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.02	0	-9999	-10000	0	0
FKBP3	0.012	0	-9999	-10000	0	0
Histones	0.037	0.029	-9999	-10000	0	0
YY1/LSF	0.029	0	-9999	-10000	0	0
SMG5	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.023	0.044	-9999	-0.36	3	3
I kappa B alpha/HDAC1	0.024	0.032	-9999	-10000	0	0
SAP18	0.012	0	-9999	-10000	0	0
RELA	0.028	0.04	-9999	-0.32	3	3
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.012	0	-9999	-10000	0	0
HDAC3/TR2	0.024	0.032	-9999	-10000	0	0
NuRD/MBD3 Complex	0.045	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.031	0.036	-9999	-0.28	3	3
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.17	0.34	-9999	-0.81	63	63
GATA1	-0.016	0.078	-9999	-0.25	28	28
Mad/Max	0.018	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.047	0.02	-9999	-10000	0	0
RBBP7	0.012	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.012	0	-9999	-10000	0	0
MAX	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
NFKBIA	0.02	0.035	-9999	-10000	0	0
KAT2B	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.04	0.004	-9999	-10000	0	0
SIN3 complex	0.031	0.008	-9999	-10000	0	0
SMURF1	0.012	0	-9999	-10000	0	0
CHD3	0.012	0	-9999	-10000	0	0
SAP30	0.011	0.016	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.012	0	-9999	-10000	0	0
YY1/HDAC3	0.035	0.029	-9999	-10000	0	0
YY1/HDAC2	0.029	0	-9999	-10000	0	0
YY1/HDAC1	0.029	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.045	0	-9999	-10000	0	0
PPARG	0.026	0.053	-9999	-0.44	3	3
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
TNFRSF1A	0.012	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.024	0.032	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.048	0	-9999	-10000	0	0
HDAC1	0.012	0	-9999	-10000	0	0
HDAC3	0.02	0.035	-9999	-0.28	3	3
HDAC2	0.012	0	-9999	-10000	0	0
YY1	0.028	0	-9999	-10000	0	0
HDAC8	0.012	0	-9999	-10000	0	0
SMAD7	0.012	0	-9999	-10000	0	0
NCOR2	0.012	0	-9999	-10000	0	0
MXD1	0.012	0	-9999	-10000	0	0
STAT3	0.024	0	-9999	-10000	0	0
NFKB1	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.035	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.034	0.007	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.024	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.035	-9999	-10000	0	0
histone deacetylation	0.044	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.033	0.03	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GATAD2B	0.012	0	-9999	-10000	0	0
GATAD2A	0.012	0	-9999	-10000	0	0
GATA2/HDAC3	-0.088	0.22	-9999	-0.49	63	63
GATA1/HDAC1	0	0.052	-9999	-10000	0	0
GATA1/HDAC3	0.007	0.049	-9999	-10000	0	0
CHD4	0.012	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.003	0.074	-9999	-0.62	3	3
SIN3/HDAC complex/Mad/Max	0.044	0.004	-9999	-10000	0	0
NuRD Complex	0.052	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.021	-9999	-10000	0	0
SIN3B	0.012	0	-9999	-10000	0	0
MTA2	0.012	0	-9999	-10000	0	0
SIN3A	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
SUMO1/HDAC1	0.028	0	-9999	-10000	0	0
HDAC complex	0.032	0	-9999	-10000	0	0
GATA1/Fog1	-0.002	0.056	-9999	-0.32	1	1
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.009	0.1	-9999	-0.81	3	3
negative regulation of cell growth	0.044	0.004	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.045	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.03	0.052	-9999	-0.43	3	3
SIN3/HDAC complex/NCoR1	0.042	0.003	-9999	-10000	0	0
TFCP2	0.012	0	-9999	-10000	0	0
NR2C1	0.012	0	-9999	-10000	0	0
MBD3	0.012	0	-9999	-10000	0	0
MBD2	0.012	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	0.02	0.058	-9999	-0.54	3	3
SNTA1	0.002	0.086	-9999	-0.59	5	5
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.021	0.057	-9999	-0.54	3	3
MAPK12	0.026	0.017	-9999	-10000	0	0
CCND1	0.018	0.029	-9999	-0.45	1	1
p38 gamma/SNTA1	0.025	0.053	-9999	-0.46	3	3
MAP2K3	0.012	0	-9999	-10000	0	0
PKN1	0.012	0	-9999	-10000	0	0
G2/M transition checkpoint	0.026	0.017	-9999	-10000	0	0
MAP2K6	0.022	0	-9999	-10000	0	0
MAPT	0.019	0.061	-9999	-0.36	7	7
MAPK13	0.015	0.065	-9999	-0.62	3	3
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.016	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	0.012	0	-10000	0	-10000	0	0
HDAC3	0.012	0	-10000	0	-10000	0	0
VDR	0.007	0.068	-10000	0	-0.81	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.012	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.033	0.023	-10000	0	-10000	0	0
KAT2B	0.012	0	-10000	0	-10000	0	0
MAPK14	0.012	0	-10000	0	-10000	0	0
AKT1	0.013	0.03	0.2	1	-10000	0	1
RAR alpha/9cRA/Cyclin H	-0.009	0.042	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.03	0.023	-10000	0	-10000	0	0
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.007	0.095	-10000	0	-0.7	5	5
NCOR2	0.012	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.005	0.053	-10000	0	-0.63	2	2
RXRs/RARs/NRIP1/9cRA	0.027	0.051	-10000	0	-10000	0	0
NCOA2	-0.076	0.25	-10000	0	-0.81	31	31
NCOA3	0.012	0	-10000	0	-10000	0	0
NCOA1	0.012	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.007	0.068	-10000	0	-0.81	2	2
RARG	0.012	0.016	-10000	0	-0.25	1	1
RAR gamma1/9cRA	0.017	0.009	-10000	0	-10000	0	0
MAPK3	0.013	0	-10000	0	-10000	0	0
MAPK1	0.012	0	-10000	0	-10000	0	0
MAPK8	-0.001	0.11	-10000	0	-0.81	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.019	0.052	-10000	0	-0.45	2	2
RARA	-0.002	0.06	-10000	0	-0.37	5	5
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.001	0.1	-10000	0	-0.32	15	15
PRKCA	0.015	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.022	0.051	-10000	0	-10000	0	0
RXRG	-0.012	0.052	-10000	0	-10000	0	0
RXRA	0.008	0.056	-10000	0	-0.34	5	5
RXRB	-0.007	0.051	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.005	0.053	-10000	0	-0.63	2	2
RBP1	0.009	0.048	-10000	0	-0.81	1	1
CRBP1/9-cic-RA	0.007	0.037	-10000	0	-0.63	1	1
RARB	0.015	0	-10000	0	-10000	0	0
PRKCG	-0.063	0.12	-10000	0	-10000	0	0
MNAT1	0.012	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.021	0.055	-10000	0	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.026	0.049	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.043	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.022	0.051	-10000	0	-10000	0	0
positive regulation of DNA binding	-0.009	0.039	-10000	0	-10000	0	0
NRIP1	0.023	0.047	-10000	0	-10000	0	0
RXRs/RARs	0.016	0.051	-10000	0	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.008	0.049	-10000	0	-10000	0	0
PRKACA	0.012	0	-10000	0	-10000	0	0
CDK7	0.012	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.006	0.031	-10000	0	-10000	0	0
CCNH	0.012	0	-10000	0	-10000	0	0
CREBBP	0.012	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0.004	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.009	0.048	-9999	-0.81	1	1
Caspase 8 (4 units)	-0.004	0.02	-9999	-10000	0	0
NEF	-0.001	0.023	-9999	-10000	0	0
NFKBIA	0.013	0.012	-9999	-10000	0	0
BIRC3	0.03	0.055	-9999	-10000	0	0
CYCS	0.04	0.033	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
CD247	-0.001	0.072	-9999	-0.32	13	13
MAP2K7	0.043	0.027	-9999	-10000	0	0
protein ubiquitination	0.059	0.03	-9999	-10000	0	0
CRADD	0.012	0	-9999	-10000	0	0
DAXX	0.012	0	-9999	-10000	0	0
FAS	0.012	0	-9999	-10000	0	0
BID	0.035	0.034	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.005	0.025	-9999	-10000	0	0
TRADD	0.012	0	-9999	-10000	0	0
MAP3K5	0.012	0	-9999	-10000	0	0
CFLAR	0.012	0	-9999	-10000	0	0
FADD	0.012	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.005	0.025	-9999	-10000	0	0
MAPK8	0.04	0.064	-9999	-0.4	5	5
APAF1	0.012	0	-9999	-10000	0	0
TRAF1	0.011	0.016	-9999	-10000	0	0
TRAF2	0.012	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.029	0.036	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.052	0.033	-9999	-10000	0	0
CHUK	0.06	0.031	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.017	0.064	-9999	-0.32	10	10
TNF	-0.009	0.1	-9999	-0.81	3	3
FASLG	0.002	0.088	-9999	-0.38	10	10
NFKB1	0.013	0.012	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.067	-9999	-0.54	4	4
CASP6	-0.001	0.01	-9999	-10000	0	0
CASP7	0.067	0.048	-9999	-10000	0	0
RELA	0.013	0.012	-9999	-10000	0	0
CASP2	0.012	0	-9999	-10000	0	0
CASP3	0.067	0.048	-9999	-10000	0	0
TNFRSF1A	0.012	0	-9999	-10000	0	0
TNFR1A/BAG4	0.016	0.038	-9999	-0.62	1	1
CASP8	0.012	0	-9999	-10000	0	0
CASP9	0.012	0	-9999	-10000	0	0
MAP3K14	0.057	0.033	-9999	-10000	0	0
APAF-1/Caspase 9	-0.007	0.029	-9999	-10000	0	0
BCL2	0.045	0.06	-9999	-0.36	5	5

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.012	0	-9999	-10000	0	0
SMAD2	0.013	0	-9999	-10000	0	0
SMAD3	0.039	0	-9999	-10000	0	0
SMAD3/SMAD4	0.044	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.037	0	-9999	-10000	0	0
PPM1A	0.012	0	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
SMAD2/SMAD4	0.019	0	-9999	-10000	0	0
MAP3K1	0.012	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.007	0.083	-9999	-0.62	5	5
MAPK3	0.012	0	-9999	-10000	0	0
MAPK1	0.012	0	-9999	-10000	0	0
NUP214	0.012	0	-9999	-10000	0	0
CTDSP1	0.012	0	-9999	-10000	0	0
CTDSP2	0.012	0	-9999	-10000	0	0
CTDSPL	0.012	0	-9999	-10000	0	0
KPNB1	0.012	0	-9999	-10000	0	0
TGFBRAP1	-0.002	0.11	-9999	-0.81	5	5
UBE2I	0.012	0	-9999	-10000	0	0
NUP153	0.012	0	-9999	-10000	0	0
KPNA2	0.012	0	-9999	-10000	0	0
PIAS4	0.012	0	-9999	-10000	0	0

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.076	0.012	-9999	-10000	0	0
ERC1	0.012	0	-9999	-10000	0	0
RIP2/NOD2	0.007	0.043	-9999	-10000	0	0
NFKBIA	0.043	0	-9999	-10000	0	0
BIRC2	0.012	0	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
RIPK2	0.012	0	-9999	-10000	0	0
IKBKG	-0.002	0.006	-9999	-10000	0	0
IKK complex/A20	-0.007	0.041	-9999	-0.39	3	3
NEMO/A20/RIP2	0.012	0	-9999	-10000	0	0
XPO1	0.012	0	-9999	-10000	0	0
NEMO/ATM	0.044	0.016	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	0	0.001	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.004	0.064	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
MALT1	0.012	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.018	0	-9999	-10000	0	0
ATM	0.012	0	-9999	-10000	0	0
TNF/TNFR1A	0.003	0.074	-9999	-0.62	3	3
TRAF6	0.012	0	-9999	-10000	0	0
PRKCA	0.012	0	-9999	-10000	0	0
CHUK	0.012	0	-9999	-10000	0	0
UBE2D3	0.012	0	-9999	-10000	0	0
TNF	-0.009	0.1	-9999	-0.81	3	3
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.012	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.043	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
TNFRSF1A	0.012	0	-9999	-10000	0	0
IKK complex	0.049	0.016	-9999	-10000	0	0
CYLD	0.012	0	-9999	-10000	0	0
IKK complex/PKC alpha	0	0.001	-9999	-10000	0	0

×

Circadian rhythm pathway

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
chromatin modification	0.043	0.018	-9999	-10000	0	0
CLOCK	-0.002	0.12	-9999	-0.81	6	6
TIMELESS/CRY2	0.038	0.019	-9999	-10000	0	0
DEC1/BMAL1	0.013	0.004	-9999	-10000	0	0
ATR	0.012	0	-9999	-10000	0	0
NR1D1	0.036	0.028	-9999	-10000	0	0
ARNTL	0.015	0.001	-9999	-10000	0	0
TIMELESS	0.037	0.021	-9999	-10000	0	0
NPAS2	0.012	0.048	-9999	-0.81	1	1
CRY2	0.012	0	-9999	-10000	0	0
mol:CO	-0.013	0.005	-9999	-10000	0	0
CHEK1	0.012	0	-9999	-10000	0	0
mol:HEME	0.013	0.005	-9999	-10000	0	0
PER1	0.012	0	-9999	-10000	0	0
BMAL/CLOCK/NPAS2	0.027	0.088	-9999	-0.53	7	7
BMAL1/CLOCK	0.038	0.067	-9999	-10000	0	0
S phase of mitotic cell cycle	0.043	0.018	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.044	0.018	-9999	-10000	0	0
mol:NADPH	0.013	0.005	-9999	-10000	0	0
PER1/TIMELESS	0.038	0.019	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	0.003	0.005	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
ITGB1	0.012	-9999	-9999
ITGB7	0.012	-9999	-9999
ITGA4	0.012	-9999	-9999
alpha4/beta7 Integrin	0.018	-9999	-9999
alpha4/beta1 Integrin	0.018	-9999	-9999

×

Aurora A signaling

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
Aurora A/GADD45A	0.026	0.012	-9999	-10000	0	0
BIRC5	-0.068	0.12	-9999	-10000	0	0
NFKBIA	0.029	0.013	-9999	-10000	0	0
CPEB1	-0.021	0.12	-9999	-0.33	28	28
AKT1	0.029	0.013	-9999	-10000	0	0
NDEL1	0.012	0	-9999	-10000	0	0
Aurora A/BRCA1	0.01	0.021	-9999	-10000	0	0
NDEL1/TACC3	0.013	0.025	-9999	-10000	0	0
GADD45A	0.012	0	-9999	-10000	0	0
GSK3B	0.013	0.004	-9999	-10000	0	0
PAK1/Aurora A	0.026	0.012	-9999	-10000	0	0
MDM2	0.012	0	-9999	-10000	0	0
JUB	0.012	0	-9999	-10000	0	0
TPX2	-0.018	0.074	-9999	-10000	0	0
TP53	0.028	0.009	-9999	-10000	0	0
DLG7	0.019	0.013	-9999	-10000	0	0
AURKAIP1	0.012	0	-9999	-10000	0	0
ARHGEF7	0.012	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.029	0.023	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0.006	0.021	-9999	-10000	0	0
AURKA	0.024	0.017	-9999	-10000	0	0
AURKB	-0.032	0.036	-9999	-10000	0	0
CDC25B	0.028	0.015	-9999	-10000	0	0
G2/M transition checkpoint	0.008	0.016	-9999	-10000	0	0
mRNA polyadenylation	-0.01	0.065	-9999	-0.48	4	4
Aurora A/CPEB	-0.006	0.067	-9999	-0.49	4	4
Aurora A/TACC1/TRAP/chTOG	0.036	0.031	-9999	-0.45	1	1
BRCA1	0.01	0.027	-9999	-10000	0	0
centrosome duplication	0.026	0.012	-9999	-10000	0	0
regulation of centrosome cycle	0.007	0.024	-9999	-10000	0	0
spindle assembly	0.016	0.035	-9999	-0.45	1	1
TDRD7	0.012	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.023	0.044	-9999	-10000	0	0
CENPA	-0.015	0.039	-9999	-10000	0	0
Aurora A/PP2A	0.025	0.015	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.034	0.011	-9999	-10000	0	0
negative regulation of DNA binding	0.028	0.009	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.018	0	-9999	-10000	0	0
RASA1	0.012	0	-9999	-10000	0	0
Ajuba/Aurora A	0.012	0.016	-9999	-10000	0	0
mitotic prometaphase	0.011	0.012	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.024	0.017	-9999	-10000	0	0
TACC1	0.009	0.048	-9999	-0.81	1	1
TACC3	0.008	0.035	-9999	-10000	0	0
Aurora A/Antizyme1	0.032	0.011	-9999	-10000	0	0
Aurora A/RasGAP	0.026	0.012	-9999	-10000	0	0
OAZ1	0.012	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.004	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.018	0.074	-9999	-10000	0	0
PPP2R5D	0.011	0.016	-9999	-10000	0	0
Aurora A/TPX2	0.004	0.055	-9999	-10000	0	0
PAK1	0.012	0	-9999	-10000	0	0
CKAP5	0.012	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	Mean.of.Down.Perturbations
PLAUR	0.029	0.05	-9999	-9999
regulation of axonogenesis	-0.025	0.012	-9999	-9999
myoblast fusion	-0.013	0.028	-9999	-9999
mol:GTP	-0.003	0.017	-9999	-9999
regulation of calcium-dependent cell-cell adhesion	-0.027	0.025	-9999	-9999
ARF1/GTP	-0.002	0.01	-9999	-9999
mol:GM1	0.008	0.014	-9999	-9999
mol:Choline	0.025	0.012	-9999	-9999
lamellipodium assembly	-0.004	0.024	-9999	-9999
MAPK3	0.022	0.026	-9999	-9999
ARF6/GTP/NME1/Tiam1	0.028	0.026	-9999	-9999
ARF1	0.012	0	-9999	-9999
ARF6/GDP	0.013	0.028	-9999	-9999
ARF1/GDP	0.021	0.025	-9999	-9999
ARF6	0.01	0.01	-9999	-9999
RAB11A	0.012	0	-9999	-9999
TIAM1	0.014	0.002	-9999	-9999
fibronectin binding	0	0	-9999	-9999
MAPK1	0.022	0.026	-9999	-9999
actin filament bundle formation	-0.02	0.025	-9999	-9999
KALRN	-0.003	0.019	-9999	-9999
RAB11FIP3/RAB11A	0.018	0	-9999	-9999
RhoA/GDP	0.02	0.025	-9999	-9999
NME1	0.009	0.035	-9999	-9999
Rac1/GDP	0.02	0.025	-9999	-9999
substrate adhesion-dependent cell spreading	-0.003	0.017	-9999	-9999
cortical actin cytoskeleton organization	-0.004	0.025	-9999	-9999
RAC1	0.012	0	-9999	-9999
liver development	-0.003	0.017	-9999	-9999
ARF6/GTP	-0.003	0.017	-9999	-9999
RhoA/GTP	-0.002	0.01	-9999	-9999
mol:GDP	-0.004	0.025	-9999	-9999
ARF6/GTP/RAB11FIP3/RAB11A	-0.001	0.007	-9999	-9999
RHOA	0.012	0	-9999	-9999
PLD1	0.017	0.014	-9999	-9999
RAB11FIP3	0.012	0	-9999	-9999
tube morphogenesis	-0.004	0.024	-9999	-9999
ruffle organization	0.025	0.012	-9999	-9999
regulation of epithelial cell migration	-0.003	0.017	-9999	-9999
PLD2	0.017	0.014	-9999	-9999
PIP5K1A	0.025	0.012	-9999	-9999
mol:Phosphatidic acid	0.025	0.012	-9999	-9999
Rac1/GTP	-0.004	0.025	-9999	-9999

×

EPO signaling 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
BCL2L1	0.074	0.01	-9999	-10000	0	0
CRKL	0.045	0.009	-9999	-10000	0	0
mol:DAG	0.05	0.008	-9999	-10000	0	0
HRAS	0.063	0.01	-9999	-10000	0	0
MAPK8	0.025	0.07	-9999	-0.5	5	5
RAP1A	0.045	0.009	-9999	-10000	0	0
GAB1	0.045	0.009	-9999	-10000	0	0
MAPK14	0.034	0.01	-9999	-10000	0	0
EPO	0.01	0.022	-9999	-0.25	2	2
PLCG1	0.051	0.008	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.015	0.001	-9999	-10000	0	0
RAPGEF1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.022	0.052	-9999	-0.56	2	2
GAB1/SHC/GRB2/SOS1	0	0.003	-9999	-10000	0	0
EPO/EPOR (dimer)	0.021	0.015	-9999	-10000	0	0
IRS2	0.044	0.013	-9999	-10000	0	0
STAT1	0.059	0.014	-9999	-10000	0	0
STAT5B	0.056	0.008	-9999	-10000	0	0
cell proliferation	0.031	0.066	-9999	-0.46	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.001	0.006	-9999	-10000	0	0
TEC	0.045	0.009	-9999	-10000	0	0
SOCS3	0.004	0.073	-9999	-0.48	5	5
STAT1 (dimer)	0.059	0.014	-9999	-10000	0	0
JAK2	0.015	0.001	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.052	0.01	-9999	-10000	0	0
EPO/EPOR	0.021	0.015	-9999	-10000	0	0
LYN	0.014	0	-9999	-10000	0	0
TEC/VAV2	0.052	0.009	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.015	0.001	-9999	-10000	0	0
SHC1	0.012	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	0.034	0.012	-9999	-10000	0	0
mol:IP3	0.05	0.008	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.051	0.02	-9999	-10000	0	0
SH2B3	0.015	0.001	-9999	-10000	0	0
NFKB1	0.034	0.01	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.003	0.024	-9999	-0.28	2	2
PTPN6	0.039	0.009	-9999	-10000	0	0
TEC/VAV2/GRB2	0.056	0.008	-9999	-10000	0	0
EPOR	0.015	0.001	-9999	-10000	0	0
INPP5D	0.006	0.041	-9999	-10000	0	0
mol:GDP	0	0.003	-9999	-10000	0	0
SOS1	0.012	0	-9999	-10000	0	0
PLCG2	-0.032	0.18	-9999	-0.74	17	17
CRKL/CBL/C3G	0.056	0.008	-9999	-10000	0	0
VAV2	0.045	0.009	-9999	-10000	0	0
CBL	0.045	0.009	-9999	-10000	0	0
SHC/Grb2/SOS1	0	0.003	-9999	-10000	0	0
STAT5A	0.056	0.008	-9999	-10000	0	0
GRB2	0.012	0	-9999	-10000	0	0
STAT5 (dimer)	0.074	0.009	-9999	-10000	0	0
LYN/PLCgamma2	-0.015	0.14	-9999	-0.62	15	15
PTPN11	0.012	0	-9999	-10000	0	0
BTK	0.019	0.049	-9999	-10000	0	0
BCL2	0.074	0.01	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.003	0.036	-9999	-10000	0	0
CaM/Ca2+	0.009	0	-9999	-10000	0	0
AKT1	0.012	0	-9999	-10000	0	0
AKT2	0.012	0	-9999	-10000	0	0
STXBP4	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
mol:glucose	0.068	0.06	-9999	-0.27	1	1
YWHAZ	0.012	0	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
YWHAQ	0.012	0	-9999	-10000	0	0
TBC1D4	0.021	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
SNARE/Synip	0	0	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
ASIP	-0.1	0.13	-9999	-10000	0	0
PRKCI	0.012	0	-9999	-10000	0	0
AS160/CaM/Ca2+	0.009	0	-9999	-10000	0	0
RHOQ	0.012	0	-9999	-10000	0	0
GYS1	0.029	0	-9999	-10000	0	0
PRKCZ	0.012	0	-9999	-10000	0	0
TRIP10	0.012	0	-9999	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
AS160/14-3-3	0.009	0.048	-9999	-10000	0	0
VAMP2	0.012	0	-9999	-10000	0	0
SLC2A4	0.07	0.062	-9999	-0.3	1	1
STX4	0.012	0	-9999	-10000	0	0
GSK3B	0.024	0	-9999	-10000	0	0
SFN	-0.12	0.16	-9999	-0.81	5	5
LNPEP	0.004	0.083	-9999	-0.81	3	3
YWHAE	0.012	0	-9999	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.012	0	-10000	0	-10000	0	0
mol:PIP3	-0.006	0.045	-10000	0	-0.34	5	5
FRAP1	0.013	0.008	-10000	0	-10000	0	0
AKT1	0.021	0.04	-10000	0	-10000	0	0
INSR	0.012	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	-0.001	0.013	-10000	0	-10000	0	0
mol:GTP	-0.004	0.027	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.008	-10000	0	-10000	0	0
TSC2	0.012	0	-10000	0	-10000	0	0
RHEB/GDP	-0.003	0.023	-10000	0	-10000	0	0
TSC1	0.012	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.008	0.056	-10000	0	-0.41	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.01	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.012	0	-10000	0	-10000	0	0
RPS6KB1	0.023	0.021	-10000	0	-10000	0	0
MAP3K5	0.01	0	-10000	0	-10000	0	0
PIK3R1	0.012	0	-10000	0	-10000	0	0
apoptosis	0.01	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	5	5
EIF4B	0.028	0.019	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.014	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0.003	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.016	0.051	-10000	0	-0.37	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.028	0.013	-10000	0	-10000	0	0
FKBP1A	0.012	0	-10000	0	-10000	0	0
RHEB/GTP	-0.003	0.023	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.002	5	5
FKBP12/Rapamycin	0.009	0.001	-10000	0	-10000	0	0
PDPK1	-0.005	0.04	-10000	0	-0.31	5	5
EIF4E	0.012	0	-10000	0	-10000	0	0
ASK1/PP5C	0.02	0.006	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.016	0	-10000	0	-10000	0	0
TSC1/TSC2	0.033	0.034	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.002	5	-10000	0	5
RPS6	0.012	0	-10000	0	-10000	0	0
PPP5C	0.012	0	-10000	0	-10000	0	0
EIF4G1	0.012	0	-10000	0	-10000	0	0
IRS1	0	0.059	-10000	0	-0.45	5	5
INS	-0.002	0.026	-10000	0	-10000	0	0
PTEN	0.012	0	-10000	0	-10000	0	0
PDK2	-0.005	0.04	-10000	0	-0.31	5	5
EIF4EBP1	0.009	0.019	-10000	0	-10000	0	0
PIK3CA	0.012	0	-10000	0	-10000	0	0
PPP2R5D	0.019	0.01	-10000	0	-10000	0	0
peptide biosynthetic process	0.015	0.013	-10000	0	-10000	0	0
RHEB	0.012	0	-10000	0	-10000	0	0
EIF4A1	0.012	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.015	0.013	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.015	0.016	-10000	0	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.021	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	0.031	0	-9999	-10000	0	0
CDKN1B	0.035	0.003	-9999	-10000	0	0
CDKN1A	0.033	0.014	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.012	0	-9999	-10000	0	0
FOXO3	0.035	0.003	-9999	-10000	0	0
AKT1	0	0.001	-9999	-10000	0	0
BAD	0.012	0	-9999	-10000	0	0
AKT3	0.014	0.027	-9999	-0.44	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.035	0.003	-9999	-10000	0	0
AKT1/ASK1	0.033	0.003	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.012	0	-9999	-10000	0	0
RAF1	0.012	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
TSC1	0.035	0.003	-9999	-10000	0	0
YWHAZ	0.012	0	-9999	-10000	0	0
AKT1/RAF1	0.035	0.003	-9999	-10000	0	0
EP300	0.012	0	-9999	-10000	0	0
mol:GDP	0.029	0.003	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.035	0.003	-9999	-10000	0	0
YWHAQ	0.012	0	-9999	-10000	0	0
TBC1D4	0.022	0	-9999	-10000	0	0
MAP3K5	0.012	0	-9999	-10000	0	0
MAPKAP1	0.012	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.019	0.031	-9999	-10000	0	0
YWHAH	0.012	0	-9999	-10000	0	0
AKT1S1	0.035	0.003	-9999	-10000	0	0
CASP9	0.035	0.003	-9999	-10000	0	0
YWHAB	0.012	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.04	0.003	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0.007	-9999	-10000	0	0
YWHAE	0.012	0	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
AKT2/p21CIP1	-0.001	0.008	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.017	0.001	-9999	-10000	0	0
CHUK	0.035	0.003	-9999	-10000	0	0
BAD/BCL-XL	0.047	0.002	-9999	-10000	0	0
mTORC2	0.016	0	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.031	0.035	-9999	-10000	0	0
PDPK1	0.012	0	-9999	-10000	0	0
MDM2	0.035	0.003	-9999	-10000	0	0
MAPKKK cascade	-0.034	0.003	-9999	-10000	0	0
MDM2/Cbp/p300	0.046	0.002	-9999	-10000	0	0
TSC1/TSC2	0.04	0.003	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.044	0.002	-9999	-10000	0	0
glucose import	0.023	0.045	-9999	-0.48	2	2
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.029	0.002	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.023	0.045	-9999	-0.49	2	2
GSK3A	0.035	0.003	-9999	-10000	0	0
FOXO1	0.035	0.003	-9999	-10000	0	0
GSK3B	0.035	0.003	-9999	-10000	0	0
SFN	-0.12	0.16	-9999	-0.81	5	5
G1/S transition of mitotic cell cycle	0.04	0.003	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.013	0.045	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
KPNA1	0.012	0	-9999	-10000	0	0
HSP90AA1	0.012	0	-9999	-10000	0	0
YWHAG	0.012	0	-9999	-10000	0	0
RHEB	0.012	0	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0	-9999	-10000	0	0
HDAC4	0.009	0.048	-9999	-0.81	1	1
induction of apoptosis	0	0	-9999	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.019	0.003	-9999	-10000	0	0
CDKN1A	-0.002	0.021	-9999	-10000	0	0
KAT2B	0.012	0	-9999	-10000	0	0
BAX	0.01	0.022	-9999	-0.25	2	2
FOXO3	0	0	-9999	-10000	0	0
FOXO1	0.012	0	-9999	-10000	0	0
FOXO4	0.021	0	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
XRCC6	0.012	0	-9999	-10000	0	0
TAT	0.002	0.046	-9999	-10000	0	0
mol:Lysophosphatidic acid	0	0	-9999	-10000	0	0
MYOD1	0.009	0.023	-9999	-10000	0	0
PPARGC1A	-0.01	0.14	-9999	-0.81	8	8
FHL2	0.009	0.048	-9999	-0.81	1	1
response to nutrient levels	0	0	-9999	-10000	0	0
KU70/SIRT1	0.001	0.007	-9999	-10000	0	0
HIST2H4A	0.019	0.003	-9999	-10000	0	0
SIRT1/FOXO3a	0.001	0.005	-9999	-10000	0	0
SIRT1	0.001	0.008	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
SIRT1/MEF2D/HDAC4	-0.001	0.032	-9999	-0.54	1	1
SIRT1/Histone H1b	0.001	0.007	-9999	-10000	0	0
apoptosis	0	0.012	-9999	-10000	0	0
SIRT1/PGC1A	-0.014	0.09	-9999	-0.55	8	8
p53/SIRT1	0.002	0.019	-9999	-10000	0	0
SIRT1/FOXO4	0.001	0.007	-9999	-10000	0	0
FOXO1/FHL2/SIRT1	-0.001	0.03	-9999	-0.5	1	1
HIST1H1E	0.021	0.002	-9999	-10000	0	0
SIRT1/p300	0.001	0.007	-9999	-10000	0	0
muscle cell differentiation	0.001	0.017	-9999	-10000	0	0
TP53	0.001	0.008	-9999	-10000	0	0
KU70/SIRT1/BAX	0	0.012	-9999	-10000	0	0
CREBBP	0.012	0	-9999	-10000	0	0
MEF2D	0.012	0	-9999	-10000	0	0
HIV-1 Tat/SIRT1	-0.004	0.029	-9999	-10000	0	0
ACSS2	0.018	0.011	-9999	-10000	0	0
SIRT1/PCAF/MYOD	-0.001	0.017	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.01	0.027	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0.016	0.021	-9999	-10000	0	0
MAP2K4	0.043	0.009	-9999	-10000	0	0
IKBKB	0.012	0	-9999	-10000	0	0
TNFRSF10B	0.01	0.027	-9999	-10000	0	0
TNFRSF10A	0.012	0	-9999	-10000	0	0
SMPD1	0.017	0.012	-9999	-10000	0	0
IKBKG	0.012	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.011	0.016	-9999	-0.25	1	1
TRAIL/TRAILR2	0.015	0.025	-9999	-10000	0	0
TRAIL/TRAILR3	0.006	0.056	-9999	-0.62	1	1
TRAIL/TRAILR1	0.016	0.018	-9999	-10000	0	0
TRAIL/TRAILR4	0.016	0.021	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP	0.022	0.013	-9999	-10000	0	0
IKK complex	0	0.002	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0.009	0	-9999	-10000	0	0
MAPK3	0.019	0.018	-9999	-10000	0	0
MAP3K1	0.038	0.009	-9999	-10000	0	0
TRAILR4 (trimer)	0.011	0.016	-9999	-0.25	1	1
TRADD	0.012	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.034	0.009	-9999	-10000	0	0
CFLAR	0.012	0	-9999	-10000	0	0
MAPK1	0.019	0.018	-9999	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.001	0.009	-9999	-10000	0	0
mol:ceramide	0.017	0.012	-9999	-10000	0	0
FADD	0.012	0	-9999	-10000	0	0
MAPK8	0.04	0.061	-9999	-0.42	5	5
TRAF2	0.012	0	-9999	-10000	0	0
TRAILR3 (trimer)	-0.003	0.074	-9999	-0.81	1	1
CHUK	0.012	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.001	0.012	-9999	-10000	0	0
DAP3	0.012	0	-9999	-10000	0	0
CASP10	-0.001	0.011	-9999	-10000	0	0
JNK cascade	0.016	0.021	-9999	-10000	0	0
TRAIL (trimer)	0.01	0.027	-9999	-10000	0	0
TNFRSF10C	-0.003	0.074	-9999	-0.81	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.001	0.009	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.003	0.017	-9999	-10000	0	0
cell death	0.017	0.012	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.033	0.012	-9999	-10000	0	0
TRAILR2 (trimer)	0.01	0.027	-9999	-10000	0	0
CASP8	0.001	0.006	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.012	-9999	-10000	0	0

×

ceramide signaling 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
MAP4K4	0.041	0.033	-9999	-10000	0	0
BAG4	0.009	0.048	-9999	-0.81	1	1
BAD	0.028	0.014	-9999	-10000	0	0
NFKBIA	0.012	0	-9999	-10000	0	0
BIRC3	0	0.055	-9999	-10000	0	0
BAX	0.028	0.016	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.013	0.01	-9999	-10000	0	0
IKBKB	0.047	0.031	-9999	-10000	0	0
MAP2K2	0.039	0.017	-9999	-10000	0	0
MAP2K1	0.039	0.017	-9999	-10000	0	0
SMPD1	0.019	0.01	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.048	0.032	-9999	-10000	0	0
MAP2K4	0.034	0.014	-9999	-10000	0	0
protein ubiquitination	0.048	0.032	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.043	0.019	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
RAF1	0.034	0.017	-9999	-10000	0	0
CRADD	0.013	0	-9999	-10000	0	0
mol:ceramide	0.023	0.014	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.013	0	-9999	-10000	0	0
MAP3K1	0.029	0.014	-9999	-10000	0	0
TRADD	0.013	0	-9999	-10000	0	0
RELA/p50	0.012	0	-9999	-10000	0	0
MAPK3	0.041	0.017	-9999	-10000	0	0
MAPK1	0.041	0.017	-9999	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.018	0	-9999	-10000	0	0
FADD	0.041	0.033	-9999	-10000	0	0
KSR1	0.029	0.016	-9999	-10000	0	0
MAPK8	0.032	0.058	-9999	-0.39	5	5
TRAF2	0.012	0	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.047	0.031	-9999	-10000	0	0
TNF R/SODD	0.016	0.038	-9999	-0.62	1	1
TNF	-0.009	0.1	-9999	-0.81	3	3
CYCS	0.029	0.014	-9999	-10000	0	0
IKBKG	0.047	0.031	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.036	0.034	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
RIPK1	0.012	0	-9999	-10000	0	0
AIFM1	0.029	0.014	-9999	-10000	0	0
TNF/TNF R/SODD	-0.012	0.068	-9999	-0.54	4	4
TNFRSF1A	0.012	0	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.027	0.01	-9999	-10000	0	0
NSMAF	0.041	0.033	-9999	-10000	0	0
response to hydrogen peroxide	0	0	-9999	-10000	0	0
BCL2	0.012	0	-9999	-10000	0	0

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
CDKN2A	-0.13	0.072	-9999	-9999
TP53	-0.045	0.023	-9999	-9999
Senescence	-0.045	0.022	-9999	-9999
Apoptosis	-0.045	0.022	-9999	-9999
Activated_Oncogenes	0	0	-9999	-9999
MDM2	0.084	0.042	-9999	-9999
MDM4	0.012	0	-9999	-9999

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.012	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.012	0	-9999	-10000	0	0
ITGA4	0.012	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
alpha4/beta7 Integrin	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0	0	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.031	0	-9999	-10000	0	0
lamellipodium assembly	0	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
ARF6	0.012	0	-9999	-10000	0	0
TLN1	0.012	0	-9999	-10000	0	0
PXN	0.021	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
cell adhesion	0.036	0	-9999	-10000	0	0
CRKL/CBL	0.018	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.031	0	-9999	-10000	0	0
ITGB1	0.012	0	-9999	-10000	0	0
ITGB7	0.012	0	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.026	0.05	-9999	-0.46	2	2
p130Cas/Crk/Dock1	0	0	-9999	-10000	0	0
VCAM1	-0.01	0.093	-9999	-0.81	2	2
alpha4/beta1 Integrin/Paxillin/Talin	0.038	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.038	0	-9999	-10000	0	0
BCAR1	0.012	0	-9999	-10000	0	0
mol:GDP	-0.036	0	-9999	-10000	0	0
CBL	0.012	0	-9999	-10000	0	0
PRKACA	0.012	0	-9999	-10000	0	0
GIT1	0.012	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.038	0	-9999	-10000	0	0
Rac1/GTP	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.017	0.015	-9999	-10000	0	0
FBXW11	0.012	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.015	0.074	-9999	-0.54	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.041	0.028	-9999	-10000	0	0
NFKBIA	0.023	0.032	-9999	-0.27	3	3
MAPK14	0.012	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.025	0	-9999	-10000	0	0
ARRB2	0.015	0.01	-9999	-10000	0	0
REL	-0.003	0.11	-9999	-0.81	5	5
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.024	0.012	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.025	0	-9999	-10000	0	0
PIK3CA	0.012	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.019	0	-9999	-10000	0	0
PIK3R1	0.012	0	-9999	-10000	0	0
NFKB1	0.021	0	-9999	-10000	0	0
RELA	0.012	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.03	0.031	-9999	-0.26	3	3
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.044	0.028	-9999	-10000	0	0
SRC	0.011	0.016	-9999	-10000	0	0
PI3K	0.018	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.03	0.031	-9999	-0.27	3	3
IKBKB	0.012	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-10000	0	0
SYK	0.009	0.048	-9999	-0.81	1	1
I kappa B alpha/PIK3R1	0.029	0.03	-9999	-10000	0	0
cell death	0.042	0.027	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.015	0.074	-9999	-0.54	5	5
LCK	0.004	0.073	-9999	-0.81	2	2
BCL3	0.01	0.022	-9999	-0.25	2	2

×

Sumoylation by RanBP2 regulates transcriptional repression

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
HDAC1	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.001	0.022	-9999	-0.38	1	1
MDM2/SUMO1	0.028	0	-9999	-10000	0	0
HDAC4	0.009	0.048	-9999	-0.81	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.012	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.026	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.012	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.012	0	-9999	-10000	0	0
SUMO1/HDAC4	0.027	0.028	-9999	-0.45	1	1
SUMO1/HDAC1	0.028	0	-9999	-10000	0	0
RANGAP1	0.012	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.032	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.02	0	-9999	-10000	0	0
Ran/GTP	0.025	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.012	0	-9999	-10000	0	0
UBE2I	0.012	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.031	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.012	0	-9999	-10000	0	0
PIAS1	0.012	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.002	0.028	-10000	0	-0.47	1	1
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	0.001	0.025	-10000	0	-10000	0	0
GNB1/GNG2	0	0	-10000	0	-10000	0	0
GNB1	0.012	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	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	0.006	0.03	-10000	0	-0.51	1	1
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	0.007	0.12	1	-10000	0	1
GNAL	0.009	0.048	-10000	0	-0.81	1	1
GNG2	0.012	0	-10000	0	-10000	0	0
CRH	0	0.037	-10000	0	-0.25	6	6
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0	0.06	-10000	0	-0.45	5	5
MAPK11	0.008	0	-10000	0	-10000	0	0

×

p38 MAPK 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.013	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0.012	0	-9999	-10000	0	0
MAP2K3	0.026	0.028	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.034	0.029	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.005	0.071	-9999	-0.53	4	4
TXN	0.006	0.014	-9999	-10000	0	0
CALM1	0.012	0	-9999	-10000	0	0
GADD45A	0.012	0	-9999	-10000	0	0
GADD45B	0.009	0.048	-9999	-0.81	1	1
MAP3K1	0.012	0	-9999	-10000	0	0
MAP3K6	0.012	0	-9999	-10000	0	0
MAP3K7	0.012	0	-9999	-10000	0	0
MAP3K4	0.012	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.018	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.024	0	-9999	-10000	0	0
TRAF2	0.012	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.003	0.012	-9999	-10000	0	0
TRAF6	0.008	0	-9999	-10000	0	0
RAC1	0.012	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.059	0.14	-9999	-0.81	3	3
CCM2	0.012	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.036	0.076	-9999	-0.55	3	3
MAPK11	0.012	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.012	0.075	-9999	-0.5	3	3
OSM/MEKK3	0.018	0	-9999	-10000	0	0
TAOK1	0.002	0.08	-9999	-0.44	9	9
TAOK2	0.016	0	-9999	-10000	0	0
TAOK3	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.012	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.012	0	-9999	-10000	0	0
MAP3K10	0.012	0	-9999	-10000	0	0
MAP3K3	0.012	0	-9999	-10000	0	0
TRX/ASK1	0.014	0.011	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.005	0.048	-9999	-0.46	3	3

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
coatomer protein complex	0	0	-9999	-9999
EntrezGene:79658	0	0	-9999	-9999
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.019	0	-9999	-9999
AP2	0.018	0	-9999	-9999
mol:DAG	0	0	-9999	-9999
Arfaptin 2/Rac/GTP	0	0	-9999	-9999
CLTB	0.012	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ER cargo protein	0.024	0	-9999	-9999
CD4	0.001	0.053	-9999	-9999
CLTA	0.012	0	-9999	-9999
mol:GTP	0.001	0	-9999	-9999
ARFGAP1	0.011	0	-9999	-9999
mol:PI-4-5-P2	0	0	-9999	-9999
ARF1/GTP	0	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.025	0	-9999	-9999
mol:Choline	0	0	-9999	-9999
mol:GDP	0	0	-9999	-9999
ARF1	0.012	0	-9999	-9999
DDEF1	0	0	-9999	-9999
ARF1/GDP	0	0	-9999	-9999
AP2M1	0.012	0	-9999	-9999
EntrezGene:1313	0	0	-9999	-9999
actin filament polymerization	0.016	0	-9999	-9999
Rac/GTP	0.01	0	-9999	-9999
ARF1/GTP/GGA3/ARF-GAP1	0.023	0	-9999	-9999
ARFIP2	0.011	0	-9999	-9999
COPA	0.012	0	-9999	-9999
RAC1	0.012	0	-9999	-9999
ARF1/GTP/coatomer protein complex	0.024	0	-9999	-9999
ARF1/GTP/ARHGAP10	0	0	-9999	-9999
GGA3	0.012	0	-9999	-9999
ARF1/GTP/Membrin	0	0	-9999	-9999
AP2A1	0.012	0	-9999	-9999
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.026	0	-9999	-9999
ARF1/GDP/Membrin	0.017	0	-9999	-9999
Arfaptin 2/Rac/GDP	0	0	-9999	-9999
CYTH2	0.012	0	-9999	-9999
ARF1/GTP/GGA3	0	0	-9999	-9999
mol:ATP	0	0	-9999	-9999
Rac/GDP	0.009	0	-9999	-9999
mol:Brefeldin A	0	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.03	0.014	-9999	-9999
PLD2	0	0	-9999	-9999
ARF-GAP1/v-SNARE	0.011	0	-9999	-9999
PIP5K1A	0	0	-9999	-9999
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-9999
mol:Phosphatic acid	0	0	-9999	-9999
mol:Phosphatidic acid	0	0	-9999	-9999
KDEL Receptor/Ligand/ARF-GAP1	0.011	0	-9999	-9999
GOSR2	0	0	-9999	-9999
USO1	0	0	-9999	-9999
GBF1	0	0	-9999	-9999
ARF1/GTP/Arfaptin 2	0	0	-9999	-9999
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.005	0.024	-9999	-9999

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.018	0.01	-9999	-9999
FBXW11	0.012	0	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.012	0	-9999	-9999
CHUK	0.012	0	-9999	-9999
NF kappa B2 p100/RelB	0	0.005	-9999	-9999
NFKB1	0.012	0	-9999	-9999
MAP3K14	0.011	0.016	-9999	-9999
NF kappa B1 p50/RelB	0.018	0	-9999	-9999
RELB	0.012	0	-9999	-9999
NFKB2	0.012	0	-9999	-9999
NF kappa B2 p52/RelB	0	0	-9999	-9999
regulation of B cell activation	0	0	-9999	-9999

pid_entity	TCGA.Y8.A8S1	TCGA.Y8.A8S0	TCGA.Y8.A8RZ	TCGA.Y8.A8RY
109_MAP3K5	-0.0062	0.051	0.051	0.051
47_PPARGC1A	0.012	0.012	0.012	0.012
105_BMP4	0.012	0.012	0.012	0.012
105_BMP6	0.012	0.012	0.012	0.012
105_BMP7	0.012	0.012	-0.81	0.012
105_BMP2	0.012	0.012	0.012	0.012
131_RELN/VLDLR	0.032	-0.1	0.032	0.032
30_TGFB1/TGF beta receptor Type II	0.012	0.012	0.012	0.012
84_STAT5B	-0.051	-0.17	-0.15	-0.17
84_STAT5A	-0.051	-0.17	-0.15	-0.17