PARADIGM pathway analysis of mRNASeq expression data - Bladder Urothelial Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	80
Glypican 2 network	59
Aurora B signaling	56
Signaling events regulated by Ret tyrosine kinase	55
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	47
Signaling events mediated by the Hedgehog family	44
IL4-mediated signaling events	39
Nongenotropic Androgen signaling	39
Signaling events mediated by Stem cell factor receptor (c-Kit)	38
Reelin signaling pathway	37

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
FOXM1 transcription factor network	0.3320	80	4087	51	-0.79	0.015	1000	-1000	-0.14	-1000
Glypican 2 network	0.2448	59	238	4	-0.12	-0.098	1000	-1000	-0.019	-1000
Aurora B signaling	0.2324	56	3809	67	-0.5	0.015	1000	-1000	-0.055	-1000
Signaling events regulated by Ret tyrosine kinase	0.2282	55	4513	82	-0.29	0.015	1000	-1000	-0.066	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1950	47	3216	68	-0.68	0.34	1000	-1000	-0.087	-1000
Signaling events mediated by the Hedgehog family	0.1826	44	2323	52	-0.19	0.18	1000	-1000	-0.034	-1000
IL4-mediated signaling events	0.1618	39	3573	91	-0.8	0.55	1000	-1000	-0.11	-1000
Nongenotropic Androgen signaling	0.1618	39	2055	52	-0.25	0.14	1000	-1000	-0.049	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.1577	38	2976	78	-0.28	0.094	1000	-1000	-0.049	-1000
Reelin signaling pathway	0.1535	37	2097	56	-0.22	0.038	1000	-1000	-0.065	-1000
Endothelins	0.1494	36	3467	96	-0.33	0.065	1000	-1000	-0.059	-1000
IGF1 pathway	0.1494	36	2104	57	-0.25	0.048	1000	-1000	-0.081	-1000
Signaling mediated by p38-alpha and p38-beta	0.1452	35	1564	44	-0.23	0.015	1000	-1000	-0.052	-1000
TCGA08_p53	0.1411	34	242	7	-0.16	0.076	1000	-1000	-0.021	-1000
TCGA08_retinoblastoma	0.1411	34	273	8	-0.24	0.063	1000	-1000	-0.012	-1000
Ephrin A reverse signaling	0.1286	31	221	7	-0.084	0	1000	-1000	-0.03	-1000
Thromboxane A2 receptor signaling	0.1286	31	3270	105	-0.18	0.036	1000	-1000	-0.051	-1000
p75(NTR)-mediated signaling	0.1286	31	3930	125	-0.16	0.044	1000	-1000	-0.077	-1000
Fc-epsilon receptor I signaling in mast cells	0.1286	31	3018	97	-0.19	0.039	1000	-1000	-0.067	-1000
PLK1 signaling events	0.1245	30	2608	85	-0.34	0.05	1000	-1000	-0.035	-1000
IL23-mediated signaling events	0.1162	28	1709	60	-0.61	0.015	1000	-1000	-0.12	-1000
HIF-1-alpha transcription factor network	0.1120	27	2069	76	-0.32	0.032	1000	-1000	-0.054	-1000
Plasma membrane estrogen receptor signaling	0.1120	27	2369	86	-0.25	0.11	1000	-1000	-0.065	-1000
Calcium signaling in the CD4+ TCR pathway	0.1079	26	815	31	-0.29	0.015	1000	-1000	-0.07	-1000
Glypican 1 network	0.1037	25	1217	48	-0.26	0.034	1000	-1000	-0.037	-1000
PDGFR-alpha signaling pathway	0.1037	25	1119	44	-0.34	0.032	1000	-1000	-0.056	-1000
Integrins in angiogenesis	0.1037	25	2172	84	-0.26	0.029	1000	-1000	-0.08	-1000
Rapid glucocorticoid signaling	0.1037	25	517	20	-0.22	0.034	1000	-1000	-0.021	-1000
Ras signaling in the CD4+ TCR pathway	0.1037	25	429	17	-0.16	0.02	1000	-1000	-0.026	-1000
Syndecan-1-mediated signaling events	0.0996	24	822	34	-0.27	0.015	1000	-1000	-0.044	-1000
BMP receptor signaling	0.0996	24	1989	81	-0.31	0.049	1000	-1000	-0.074	-1000
amb2 Integrin signaling	0.0996	24	2034	82	-0.34	0.015	1000	-1000	-0.066	-1000
Glucocorticoid receptor regulatory network	0.0996	24	2815	114	-0.6	0.27	1000	-1000	-0.064	-1000
TCR signaling in naïve CD8+ T cells	0.0954	23	2178	93	-0.13	0.067	1000	-1000	-0.064	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0954	23	2805	120	-0.33	0.19	1000	-1000	-0.064	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0913	22	1148	52	-0.31	0.029	1000	-1000	-0.043	-1000
LPA receptor mediated events	0.0913	22	2332	102	-0.22	0.036	1000	-1000	-0.067	-1000
IL6-mediated signaling events	0.0913	22	1666	75	-0.25	0.068	1000	-1000	-0.06	-1000
Visual signal transduction: Cones	0.0871	21	828	38	-0.12	0.017	1000	-1000	-0.05	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0830	20	1124	54	-0.18	0.03	1000	-1000	-0.077	-1000
S1P5 pathway	0.0830	20	353	17	-0.15	0.11	1000	-1000	-0.023	-1000
S1P1 pathway	0.0830	20	745	36	-0.28	0.015	1000	-1000	-0.05	-1000
BCR signaling pathway	0.0830	20	2002	99	-0.19	0.034	1000	-1000	-0.069	-1000
LPA4-mediated signaling events	0.0747	18	223	12	-0.17	0.022	1000	-1000	-0.012	-1000
JNK signaling in the CD4+ TCR pathway	0.0747	18	306	17	-0.16	0.017	1000	-1000	-0.024	-1000
S1P3 pathway	0.0747	18	778	42	-0.15	0.03	1000	-1000	-0.025	-1000
S1P4 pathway	0.0747	18	462	25	-0.15	0.029	1000	-1000	-0.042	-1000
Coregulation of Androgen receptor activity	0.0705	17	1332	76	-0.24	0.031	1000	-1000	-0.038	-1000
IL12-mediated signaling events	0.0705	17	1555	87	-0.41	0.029	1000	-1000	-0.098	-1000
Aurora A signaling	0.0705	17	1022	60	-0.34	0.022	1000	-1000	-0.042	-1000
Aurora C signaling	0.0705	17	119	7	-0.2	0	1000	-1000	-0.029	-1000
Class IB PI3K non-lipid kinase events	0.0705	17	51	3	-0.027	-1000	1000	-1000	-0.014	-1000
Arf6 signaling events	0.0622	15	975	62	-0.25	0.028	1000	-1000	-0.054	-1000
FAS signaling pathway (CD95)	0.0622	15	723	47	-0.57	0.019	1000	-1000	-0.037	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0622	15	1326	88	-0.25	0.054	1000	-1000	-0.092	-1000
Osteopontin-mediated events	0.0581	14	547	38	-0.18	0.015	1000	-1000	-0.086	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0539	13	448	34	-0.043	0.015	1000	-1000	-0.049	-1000
Syndecan-2-mediated signaling events	0.0539	13	939	69	-0.086	0.036	1000	-1000	-0.037	-1000
Presenilin action in Notch and Wnt signaling	0.0539	13	841	61	-0.17	0.041	1000	-1000	-0.058	-1000
Canonical Wnt signaling pathway	0.0539	13	677	51	-0.17	0.081	1000	-1000	-0.038	-1000
Wnt signaling	0.0539	13	97	7	-0.055	0.015	1000	-1000	-0.02	-1000
Visual signal transduction: Rods	0.0539	13	683	52	-0.2	0.015	1000	-1000	-0.073	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0498	12	339	28	-0.15	0.029	1000	-1000	-0.024	-1000
Syndecan-4-mediated signaling events	0.0498	12	845	67	-0.18	0.022	1000	-1000	-0.077	-1000
ErbB2/ErbB3 signaling events	0.0456	11	727	65	-0.25	0.025	1000	-1000	-0.06	-1000
Effects of Botulinum toxin	0.0456	11	292	26	-0.075	0.015	1000	-1000	-0.056	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0456	11	375	33	-0.28	0.043	1000	-1000	-0.042	-1000
Noncanonical Wnt signaling pathway	0.0415	10	281	26	-0.091	0.015	1000	-1000	-0.047	-1000
Regulation of Androgen receptor activity	0.0415	10	736	70	-0.25	0.03	1000	-1000	-0.055	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0373	9	835	85	-0.22	0.022	1000	-1000	-0.059	-1000
IL2 signaling events mediated by STAT5	0.0373	9	204	22	-0.12	0.064	1000	-1000	-0.022	-1000
EGFR-dependent Endothelin signaling events	0.0373	9	198	21	-0.06	0.022	1000	-1000	-0.053	-1000
Caspase cascade in apoptosis	0.0332	8	650	74	-0.041	0.044	1000	-1000	-0.029	-1000
ErbB4 signaling events	0.0332	8	563	69	-0.25	0.036	1000	-1000	-0.077	-1000
Hedgehog signaling events mediated by Gli proteins	0.0332	8	581	65	-0.15	0.063	1000	-1000	-0.046	-1000
FOXA2 and FOXA3 transcription factor networks	0.0332	8	396	46	-0.2	0.11	1000	-1000	-0.036	-1000
Nectin adhesion pathway	0.0332	8	546	63	-0.043	0.03	1000	-1000	-0.057	-1000
IL27-mediated signaling events	0.0332	8	444	51	-0.25	0.02	1000	-1000	-0.071	-1000
Regulation of nuclear SMAD2/3 signaling	0.0290	7	1022	136	-0.18	0.066	1000	-1000	-0.056	-1000
IL1-mediated signaling events	0.0290	7	478	62	-0.1	0.072	1000	-1000	-0.087	-1000
IL2 signaling events mediated by PI3K	0.0290	7	411	58	-0.18	0.052	1000	-1000	-0.061	-1000
Insulin Pathway	0.0290	7	518	74	-0.26	0.04	1000	-1000	-0.072	-1000
Cellular roles of Anthrax toxin	0.0249	6	268	39	-0.096	0.018	1000	-1000	-0.027	-1000
Signaling events mediated by PTP1B	0.0249	6	531	76	-0.12	0.037	1000	-1000	-0.061	-1000
Signaling events mediated by HDAC Class III	0.0249	6	250	40	-0.22	0.025	1000	-1000	-0.038	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0249	6	523	83	-0.27	0.04	1000	-1000	-0.065	-1000
Syndecan-3-mediated signaling events	0.0249	6	242	35	-0.13	0.044	1000	-1000	-0.043	-1000
Regulation of p38-alpha and p38-beta	0.0249	6	355	54	-0.15	0.039	1000	-1000	-0.041	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0249	6	450	74	-0.25	0.074	1000	-1000	-0.076	-1000
BARD1 signaling events	0.0207	5	289	57	-0.15	0.045	1000	-1000	-0.054	-1000
a4b1 and a4b7 Integrin signaling	0.0207	5	29	5	-0.002	0.01	1000	-1000	-0.015	-1000
EPO signaling pathway	0.0207	5	295	55	-0.042	0.051	1000	-1000	-0.07	-1000
Class I PI3K signaling events mediated by Akt	0.0207	5	390	68	-0.21	0.058	1000	-1000	-0.046	-1000
Ephrin B reverse signaling	0.0207	5	283	48	-0.042	0.016	1000	-1000	-0.06	-1000
Regulation of Telomerase	0.0207	5	555	102	-0.17	0.036	1000	-1000	-0.087	-1000
Signaling events mediated by PRL	0.0207	5	185	34	-0.1	0.025	1000	-1000	-0.026	-1000
E-cadherin signaling events	0.0207	5	25	5	-0.013	0.015	1000	-1000	-0.035	-1000
IFN-gamma pathway	0.0166	4	330	68	-0.18	0.055	1000	-1000	-0.071	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0166	4	181	37	-0.033	0.037	1000	-1000	-0.046	-1000
Signaling mediated by p38-gamma and p38-delta	0.0166	4	67	15	0	0.032	1000	-1000	-0.019	-1000
EPHB forward signaling	0.0166	4	363	85	-0.038	0.044	1000	-1000	-0.079	-1000
Arf6 trafficking events	0.0166	4	287	71	-0.42	0.048	1000	-1000	-0.065	-1000
PDGFR-beta signaling pathway	0.0166	4	390	97	-0.06	0.058	1000	-1000	-0.068	-1000
PLK2 and PLK4 events	0.0124	3	10	3	0.005	0.018	1000	-1000	-0.007	-1000
Ceramide signaling pathway	0.0124	3	240	76	-0.25	0.043	1000	-1000	-0.04	-1000
TRAIL signaling pathway	0.0124	3	186	48	-0.02	0.047	1000	-1000	-0.061	-1000
Retinoic acid receptors-mediated signaling	0.0124	3	189	58	-0.081	0.034	1000	-1000	-0.065	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0124	3	157	45	-0.033	0.066	1000	-1000	-0.074	-1000
TCGA08_rtk_signaling	0.0124	3	90	26	-0.074	0.045	1000	-1000	-0.016	-1000
E-cadherin signaling in the nascent adherens junction	0.0124	3	232	76	-0.017	0.056	1000	-1000	-0.07	-1000
Signaling events mediated by HDAC Class II	0.0083	2	177	75	-0.081	0.037	1000	-1000	-0.046	-1000
Paxillin-dependent events mediated by a4b1	0.0083	2	84	36	-0.034	0.036	1000	-1000	-0.058	-1000
Class I PI3K signaling events	0.0083	2	172	73	-0.06	0.037	1000	-1000	-0.055	-1000
E-cadherin signaling in keratinocytes	0.0083	2	97	43	-0.044	0.047	1000	-1000	-0.05	-1000
p38 MAPK signaling pathway	0.0083	2	109	44	-0.04	0.044	1000	-1000	-0.054	-1000
Canonical NF-kappaB pathway	0.0041	1	72	39	-0.03	0.088	1000	-1000	-0.072	-1000
Circadian rhythm pathway	0.0041	1	22	22	-0.015	0.05	1000	-1000	-0.034	-1000
Insulin-mediated glucose transport	0.0041	1	46	32	-0.14	0.039	1000	-1000	-0.052	-1000
ceramide signaling pathway	0.0041	1	72	49	-0.024	0.049	1000	-1000	-0.037	-1000
HIF-2-alpha transcription factor network	0.0041	1	58	43	-0.16	0.16	1000	-1000	-0.058	-1000
FoxO family signaling	0.0041	1	105	64	-0.071	0.095	1000	-1000	-0.049	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0041	1	213	125	-0.039	0.096	1000	-1000	-0.076	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	10	23	0	0.052	1000	-1000	-0.044	-1000
Arf6 downstream pathway	0.0000	0	6	43	-0.037	0.038	1000	-1000	-0.035	-1000
mTOR signaling pathway	0.0000	0	50	53	-0.006	0.04	1000	-1000	-0.052	-1000
Signaling events mediated by HDAC Class I	0.0000	0	65	104	-0.01	0.064	1000	-1000	-0.057	-1000
Atypical NF-kappaB pathway	0.0000	0	22	31	0	0.053	1000	-1000	-0.028	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	14	27	0	0.037	1000	-1000	-0.038	-1000
VEGFR1 specific signals	0.0000	0	50	56	-0.05	0.07	1000	-1000	-0.057	-1000
Arf1 pathway	0.0000	0	6	54	-0.003	0.038	1000	-1000	-0.041	-1000
Alternative NF-kappaB pathway	0.0000	0	0	13	0	0.044	1000	-1000	-0.028	-1000
Total	NA	1983	117228	7203	-24	-990	131000	-131000	-6.9	-131000

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.62	0.49	-9999	-1.1	106	106
PLK1	-0.12	0.16	-9999	-10000	0	0
BIRC5	-0.23	0.18	-9999	-1.5	1	1
HSPA1B	-0.62	0.49	-9999	-1.1	108	108
MAP2K1	-0.008	0.03	-9999	-10000	0	0
BRCA2	-0.63	0.5	-9999	-1.1	108	108
FOXM1	-0.79	0.67	-9999	-1.3	124	124
XRCC1	-0.62	0.49	-9999	-1.1	102	102
FOXM1B/p19	-0.72	0.49	-9999	-1.1	130	130
Cyclin D1/CDK4	-0.57	0.45	-9999	-0.96	105	105
CDC2	-0.66	0.52	-9999	-1.1	124	124
TGFA	-0.54	0.43	-9999	-0.92	104	104
SKP2	-0.62	0.49	-9999	-1.1	104	104
CCNE1	-0.065	0.18	-9999	-0.48	36	36
CKS1B	-0.62	0.49	-9999	-1.1	107	107
RB1	-0.24	0.14	-9999	-0.43	3	3
FOXM1C/SP1	-0.71	0.58	-9999	-1.2	123	123
AURKB	-0.14	0.17	-9999	-10000	0	0
CENPF	-0.7	0.52	-9999	-1.1	120	120
CDK4	0.005	0.012	-9999	-10000	0	0
MYC	-0.55	0.44	-9999	-0.93	110	110
CHEK2	-0.008	0.03	-9999	-10000	0	0
ONECUT1	-0.6	0.47	-9999	-1	113	113
CDKN2A	-0.22	0.24	-9999	-0.47	119	119
LAMA4	-0.62	0.49	-9999	-1.1	106	106
FOXM1B/HNF6	-0.7	0.57	-9999	-1.2	114	114
FOS	-0.75	0.6	-9999	-1.3	120	120
SP1	0.015	0.001	-9999	-10000	0	0
CDC25B	-0.62	0.49	-9999	-1.1	107	107
response to radiation	-0.024	0.028	-9999	-10000	0	0
CENPB	-0.62	0.49	-9999	-1.1	107	107
CENPA	-0.7	0.52	-9999	-1.1	125	125
NEK2	-0.7	0.52	-9999	-1.1	121	121
HIST1H2BA	-0.63	0.49	-9999	-1.1	107	107
CCNA2	-0.13	0.22	-9999	-0.49	68	68
EP300	0.015	0	-9999	-10000	0	0
CCNB1/CDK1	-0.74	0.59	-9999	-1.2	118	118
CCNB2	-0.7	0.53	-9999	-1.1	123	123
CCNB1	-0.68	0.54	-9999	-1.1	118	118
ETV5	-0.62	0.49	-9999	-1.1	108	108
ESR1	-0.7	0.55	-9999	-1.1	122	122
CCND1	-0.58	0.46	-9999	-0.98	109	109
GSK3A	0.001	0.024	-9999	-10000	0	0
Cyclin A-E1/CDK1-2	-0.12	0.18	-9999	-0.34	86	86
CDK2	0.008	0.008	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.03	0.033	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.7	0.48	-9999	-1.1	128	128
GAS1	-0.75	0.55	-9999	-1.2	132	132
MMP2	-0.64	0.52	-9999	-1.1	108	108
RB1/FOXM1C	-0.61	0.49	-9999	-1	113	113
CREBBP	0.015	0	-9999	-10000	0	0

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.016	0.12	-9999	-0.47	15	15
GPC2	-0.12	0.22	-9999	-0.47	69	69
GPC2/Midkine	-0.098	0.18	-9999	-0.35	77	77
neuron projection morphogenesis	-0.098	0.18	-9999	-0.35	77	77

×

Aurora B 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.14	0.14	-9999	-0.3	71	71
STMN1	-0.15	0.2	-9999	-0.35	115	115
Aurora B/RasGAP/Survivin	-0.3	0.22	-9999	-0.49	117	117
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.15	-9999	-0.32	86	86
BIRC5	-0.35	0.22	-9999	-0.48	177	177
DES	-0.5	0.36	-9999	-0.75	158	158
Aurora C/Aurora B/INCENP	-0.1	0.14	-9999	-0.43	4	4
Aurora B/TACC1	-0.11	0.15	-9999	-0.27	107	107
Aurora B/PP2A	-0.13	0.17	-9999	-0.32	107	107
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.017	0.04	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.003	0.004	-9999	-10000	0	0
NDC80	-0.23	0.27	-9999	-0.48	124	124
Cul3 protein complex	-0.08	0.16	-9999	-0.37	52	52
KIF2C	-0.11	0.087	-9999	-0.19	109	109
PEBP1	0.006	0.006	-9999	-10000	0	0
KIF20A	-0.35	0.22	-9999	-0.48	177	177
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.13	0.17	-9999	-0.32	107	107
SEPT1	0.011	0.044	-9999	-0.47	2	2
SMC2	0.013	0.031	-9999	-0.47	1	1
SMC4	0.015	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.046	0.057	-9999	-10000	0	0
PSMA3	0.015	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.003	-9999	-10000	0	0
H3F3B	-0.059	0.089	-9999	-10000	0	0
AURKB	-0.2	0.25	-9999	-0.48	107	107
AURKC	-0.001	0.087	-9999	-0.47	8	8
CDCA8	-0.14	0.23	-9999	-0.48	73	73
cytokinesis	-0.24	0.16	-9999	-0.4	101	101
Aurora B/Septin1	-0.21	0.17	-9999	-0.38	90	90
AURKA	-0.14	0.23	-9999	-0.48	77	77
INCENP	0.004	0.033	-9999	-0.49	1	1
KLHL13	-0.096	0.23	-9999	-0.58	45	45
BUB1	-0.084	0.2	-9999	-0.48	48	48
hSgo1/Aurora B/Survivin	-0.39	0.27	-9999	-0.56	154	154
EVI5	0.014	0.002	-9999	-10000	0	0
RhoA/GTP	-0.24	0.19	-9999	-0.42	115	115
SGOL1	-0.21	0.24	-9999	-0.47	112	112
CENPA	-0.15	0.13	-9999	-0.27	109	109
NCAPG	-0.2	0.24	-9999	-0.47	107	107
Aurora B/HC8 Proteasome	-0.13	0.17	-9999	-0.32	107	107
NCAPD2	0.013	0.031	-9999	-0.47	1	1
Aurora B/PP1-gamma	-0.13	0.17	-9999	-0.32	107	107
RHOA	0.015	0	-9999	-10000	0	0
NCAPH	-0.29	0.24	-9999	-0.47	150	150
NPM1	-0.056	0.07	-9999	-10000	0	0
RASA1	0.015	0	-9999	-10000	0	0
KLHL9	-0.012	0.12	-9999	-0.58	11	11
mitotic prometaphase	-0.009	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.13	0.17	-9999	-0.32	107	107
PPP1CC	0.015	0	-9999	-10000	0	0
Centraspindlin	-0.27	0.21	-9999	-0.45	125	125
RhoA/GDP	0.011	0	-9999	-10000	0	0
NSUN2	-0.056	0.07	-9999	-10000	0	0
MYLK	-0.17	0.19	-9999	-0.42	76	76
KIF23	-0.24	0.25	-9999	-0.48	123	123
VIM	-0.13	0.18	-9999	-0.33	108	108
RACGAP1	0.007	0.045	-9999	-0.48	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.056	0.07	-9999	-10000	0	0
Chromosomal passenger complex	-0.18	0.15	-9999	-0.32	111	111
Chromosomal passenger complex/EVI5	-0.3	0.27	-9999	-0.54	119	119
TACC1	0.012	0.038	-9999	-0.58	1	1
PPP2R5D	0.015	0	-9999	-10000	0	0
CUL3	0.015	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.045	0.044	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.14	0.13	-9999	-0.39	17	17
JUN	-0.1	0.14	-9999	-0.42	12	12
HRAS	0.015	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.16	0.18	-9999	-0.33	125	125
RAP1A	0.015	0	-9999	-10000	0	0
FRS2	0.007	0.062	-9999	-0.47	4	4
RAP1A/GDP	0.011	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.16	0.18	-9999	-0.32	125	125
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.16	0.18	-9999	-0.32	124	124
RHOA	0.015	0	-9999	-10000	0	0
RAP1A/GTP	-0.15	0.15	-9999	-0.3	66	66
GRB7	-0.006	0.1	-9999	-0.49	10	10
RET51/GFRalpha1/GDNF	-0.16	0.18	-9999	-0.32	125	125
MAPKKK cascade	-0.14	0.14	-9999	-0.47	7	7
BCAR1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.16	0.18	-9999	-0.33	125	125
lamellipodium assembly	-0.14	0.13	-9999	-0.26	124	124
RET51/GFRalpha1/GDNF/SHC	-0.16	0.18	-9999	-0.33	125	125
PIK3CA	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.16	0.18	-9999	-0.33	124	124
RET9/GFRalpha1/GDNF/Shank3	-0.16	0.18	-9999	-0.32	124	124
MAPK3	-0.12	0.16	-9999	-0.49	7	7
DOK1	0.013	0.031	-9999	-0.47	1	1
DOK6	-0.21	0.29	-9999	-0.58	91	91
PXN	0.015	0	-9999	-10000	0	0
neurite development	-0.15	0.18	-9999	-0.38	64	64
DOK5	-0.037	0.17	-9999	-0.57	21	21
GFRA1	-0.29	0.3	-9999	-0.58	124	124
MAPK8	-0.11	0.14	-9999	-0.38	10	10
HRAS/GTP	-0.16	0.16	-9999	-0.31	125	125
tube development	-0.14	0.16	-9999	-0.3	124	124
MAPK1	-0.12	0.16	-9999	-0.49	7	7
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.12	0.14	-9999	-0.26	124	124
Rac1/GDP	0.011	0	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
PDLIM7	0.015	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.26	0.25	-9999	-0.42	154	154
SHC1	0.013	0.031	-9999	-0.47	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.16	0.18	-9999	-0.32	125	125
RET51/GFRalpha1/GDNF/Dok5	-0.19	0.22	-9999	-0.36	129	129
PRKCA	0.015	0	-9999	-10000	0	0
HRAS/GDP	0.011	0	-9999	-10000	0	0
CREB1	-0.13	0.17	-9999	-0.29	124	124
PIK3R1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.12	0.14	-9999	-0.26	124	124
RET51/GFRalpha1/GDNF/Grb7	-0.17	0.2	-9999	-0.34	126	126
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.007	0.11	-9999	-0.52	10	10
DOK4	0.015	0	-9999	-10000	0	0
JNK cascade	-0.099	0.14	-9999	-0.41	12	12
RET9/GFRalpha1/GDNF/FRS2	-0.16	0.18	-9999	-0.33	125	125
SHANK3	0.015	0	-9999	-10000	0	0
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.12	0.14	-9999	-0.26	124	124
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.12	0.15	-9999	-0.26	125	125
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.12	0.15	-9999	-0.26	125	125
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.12	0.16	-9999	-0.26	125	125
PI3K	-0.17	0.23	-9999	-0.38	124	124
SOS1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.14	0.17	-9999	-0.3	124	124
GRB10	0.012	0.038	-9999	-0.58	1	1
activation of MAPKK activity	-0.11	0.14	-9999	-0.39	8	8
RET51/GFRalpha1/GDNF/FRS2	-0.16	0.18	-9999	-0.33	126	126
GAB1	0.015	0	-9999	-10000	0	0
IRS1	0.002	0.084	-9999	-0.58	5	5
IRS2	-0.01	0.12	-9999	-0.58	10	10
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.12	0.16	-9999	-0.26	125	125
RET51/GFRalpha1/GDNF/PKC alpha	-0.16	0.18	-9999	-0.32	125	125
GRB2	0.015	0	-9999	-10000	0	0
PRKACA	0.015	0	-9999	-10000	0	0
GDNF	0.002	0.054	-9999	-0.47	3	3
RAC1	0.015	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.16	0.19	-9999	-0.34	126	126
Rac1/GTP	-0.16	0.15	-9999	-0.3	124	124
RET9/GFRalpha1/GDNF	-0.19	0.19	-9999	-0.36	124	124
GFRalpha1/GDNF	-0.21	0.22	-9999	-0.43	124	124

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.001	0.1	-10000	0	-0.61	6	6
NFATC2	-0.11	0.28	-10000	0	-0.66	41	41
NFATC3	-0.085	0.13	-10000	0	-0.31	19	19
CD40LG	-0.53	0.56	-10000	0	-1.1	105	105
ITCH	0.024	0.087	-10000	0	-0.38	1	1
CBLB	0.025	0.084	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.38	0.46	-10000	0	-1.1	53	53
JUNB	0.007	0.066	-10000	0	-0.58	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.03	0.085	-10000	0	-0.28	24	24
T cell anergy	-0.014	0.14	-10000	0	-0.39	24	24
TLE4	-0.07	0.25	-10000	0	-0.63	31	31
Jun/NFAT1-c-4/p21SNFT	-0.44	0.55	-10000	0	-1	97	97
AP-1/NFAT1-c-4	-0.62	0.71	-10000	0	-1.3	105	105
IKZF1	-0.063	0.24	-10000	0	-0.64	24	24
T-helper 2 cell differentiation	-0.23	0.36	-10000	0	-0.95	38	38
AP-1/NFAT1	-0.2	0.26	-10000	0	-0.51	82	82
CALM1	0.012	0.055	-10000	0	-10000	0	0
EGR2	-0.48	0.73	-10000	0	-1.6	61	61
EGR3	-0.68	0.84	-10000	0	-1.6	108	108
NFAT1/FOXP3	-0.081	0.23	-10000	0	-0.53	39	39
EGR1	-0.13	0.26	-10000	0	-0.58	60	60
JUN	-0.006	0.094	-10000	0	-0.58	6	6
EGR4	-0.017	0.13	-10000	0	-0.54	13	13
mol:Ca2+	-0.003	0.059	-10000	0	-10000	0	0
GBP3	-0.061	0.22	-10000	0	-0.58	26	26
FOSL1	-0.029	0.16	-10000	0	-0.58	18	18
NFAT1-c-4/MAF/IRF4	-0.44	0.56	-10000	0	-0.99	105	105
DGKA	-0.053	0.21	-10000	0	-0.55	24	24
CREM	0.014	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.47	0.54	-10000	0	-0.99	109	109
CTLA4	-0.07	0.24	-10000	0	-0.67	23	23
NFAT1-c-4 (dimer)/EGR1	-0.49	0.63	-10000	0	-1.1	109	109
NFAT1-c-4 (dimer)/EGR4	-0.44	0.57	-10000	0	-0.99	110	110
FOS	-0.18	0.28	-10000	0	-0.59	74	74
IFNG	-0.23	0.31	-10000	0	-0.81	38	38
T cell activation	-0.24	0.32	-10000	0	-0.71	55	55
MAF	-0.002	0.099	-10000	0	-0.58	7	7
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.34	0.5	0.83	100	-10000	0	100
TNF	-0.42	0.53	-10000	0	-0.96	103	103
FASLG	-0.65	0.81	-10000	0	-1.4	115	115
TBX21	-0.013	0.12	-10000	0	-0.58	10	10
BATF3	0.008	0.062	-10000	0	-0.54	3	3
PRKCQ	-0.039	0.17	-10000	0	-0.57	22	22
PTPN1	-0.053	0.21	-10000	0	-0.54	26	26
NFAT1-c-4/ICER1	-0.44	0.54	-10000	0	-0.97	109	109
GATA3	-0.032	0.16	-10000	0	-0.58	19	19
T-helper 1 cell differentiation	-0.21	0.31	-10000	0	-0.79	38	38
IL2RA	-0.37	0.44	-10000	0	-0.94	69	69
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.053	0.21	-10000	0	-0.52	31	31
E2F1	-0.095	0.21	-10000	0	-0.46	58	58
PPARG	-0.038	0.17	-10000	0	-0.57	22	22
SLC3A2	-0.053	0.21	-10000	0	-0.55	24	24
IRF4	-0.036	0.16	-10000	0	-0.57	21	21
PTGS2	-0.55	0.57	-10000	0	-1.1	107	107
CSF2	-0.54	0.54	-10000	0	-1	113	113
JunB/Fra1/NFAT1-c-4	-0.43	0.56	-10000	0	-0.98	107	107
IL4	-0.25	0.38	-10000	0	-1	38	38
IL5	-0.51	0.53	-10000	0	-1	104	104
IL2	-0.25	0.33	-10000	0	-0.73	53	53
IL3	-0.079	0.063	-10000	0	-10000	0	0
RNF128	-0.019	0.21	-10000	0	-0.64	25	25
NFATC1	-0.34	0.51	-10000	0	-0.84	99	99
CDK4	0.17	0.27	0.62	30	-10000	0	30
PTPRK	-0.053	0.21	-10000	0	-0.54	26	26
IL8	-0.53	0.56	-10000	0	-1.1	106	106
POU2F1	0.015	0.002	-10000	0	-10000	0	0

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.061	0.24	-10000	0	-0.64	29	29
IHH	-0.068	0.18	-10000	0	-0.49	37	37
SHH Np/Cholesterol/GAS1	-0.18	0.2	-10000	0	-0.36	127	127
LRPAP1	0.013	0.031	-10000	0	-0.47	1	1
dorsoventral neural tube patterning	0.18	0.2	0.35	127	-10000	0	127
SMO/beta Arrestin2	-0.051	0.17	-10000	0	-0.46	24	24
SMO	-0.062	0.18	-10000	0	-0.5	24	24
AKT1	-0.005	0.082	-10000	0	-0.3	2	2
ARRB2	0.015	0	-10000	0	-10000	0	0
BOC	-0.037	0.17	-10000	0	-0.58	21	21
ADRBK1	0.015	0	-10000	0	-10000	0	0
heart looping	-0.061	0.18	-10000	0	-0.49	24	24
STIL	-0.16	0.21	-10000	0	-0.45	59	59
DHH N/PTCH2	-0.023	0.13	-10000	0	-0.42	24	24
DHH N/PTCH1	-0.039	0.15	-10000	0	-0.41	22	22
PIK3CA	0.015	0	-10000	0	-10000	0	0
DHH	-0.014	0.12	-10000	0	-0.58	11	11
PTHLH	-0.11	0.36	-10000	0	-1	29	29
determination of left/right symmetry	-0.061	0.18	-10000	0	-0.49	24	24
PIK3R1	0.015	0	-10000	0	-10000	0	0
skeletal system development	-0.11	0.36	-10000	0	-1	29	29
IHH N/Hhip	-0.15	0.23	-10000	0	-0.43	88	88
DHH N/Hhip	-0.11	0.21	-10000	0	-0.43	70	70
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.061	0.18	-10000	0	-0.49	24	24
pancreas development	-0.14	0.26	-10000	0	-0.57	62	62
HHAT	0.015	0	-10000	0	-10000	0	0
PI3K	0.022	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.12	0.25	-10000	0	-0.57	56	56
somite specification	-0.061	0.18	-10000	0	-0.49	24	24
SHH Np/Cholesterol/PTCH1	-0.13	0.19	-10000	0	-0.44	39	39
SHH Np/Cholesterol/PTCH2	-0.12	0.18	-10000	0	-0.33	96	96
SHH Np/Cholesterol/Megalin	-0.15	0.2	-10000	0	-0.35	114	114
SHH	-0.14	0.21	-10000	0	-0.42	88	88
catabolic process	-0.035	0.15	-10000	0	-0.37	33	33
SMO/Vitamin D3	-0.12	0.2	-10000	0	-0.44	42	42
SHH Np/Cholesterol/Hhip	-0.19	0.22	-10000	0	-0.38	125	125
LRP2	-0.084	0.19	-10000	0	-0.47	48	48
receptor-mediated endocytosis	-0.16	0.2	-10000	0	-0.44	61	61
SHH Np/Cholesterol/BOC	-0.13	0.19	-10000	0	-0.35	99	99
SHH Np/Cholesterol/CDO	-0.15	0.19	-10000	0	-0.34	114	114
mesenchymal cell differentiation	0.18	0.22	0.38	125	-10000	0	125
mol:Vitamin D3	-0.12	0.19	-10000	0	-0.44	39	39
IHH N/PTCH2	-0.052	0.15	-10000	0	-0.32	50	50
CDON	-0.069	0.21	-10000	0	-0.58	34	34
IHH N/PTCH1	-0.035	0.16	-10000	0	-0.37	33	33
Megalin/LRPAP1	-0.05	0.14	-10000	0	-0.33	49	49
PTCH2	-0.017	0.13	-10000	0	-0.58	13	13
SHH Np/Cholesterol	-0.12	0.16	-10000	0	-0.32	88	88
PTCH1	-0.035	0.15	-10000	0	-0.37	33	33
HHIP	-0.14	0.26	-10000	0	-0.57	62	62

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.55	-10000	0	-1.2	70	70
STAT6 (cleaved dimer)	-0.55	0.54	-10000	0	-1.1	91	91
IGHG1	-0.15	0.18	-10000	0	-0.36	42	42
IGHG3	-0.47	0.53	-10000	0	-1.1	79	79
AKT1	-0.21	0.3	-10000	0	-0.7	35	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.16	0.27	-10000	0	-0.71	24	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.22	0.31	-10000	0	-0.66	41	41
THY1	-0.48	0.55	-10000	0	-1.2	70	70
MYB	-0.046	0.16	-10000	0	-0.48	30	30
HMGA1	0.013	0.031	-10000	0	-0.47	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.38	-10000	0	-0.75	69	69
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.22	0.31	-10000	0	-0.65	46	46
SP1	0.023	0.005	-10000	0	-10000	0	0
INPP5D	0	0.092	-10000	0	-0.58	6	6
SOCS5	0.028	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.51	0.54	-10000	0	-1.2	77	77
SOCS1	-0.29	0.35	-10000	0	-0.73	67	67
SOCS3	-0.3	0.45	-10000	0	-1.2	33	33
FCER2	-0.72	0.74	-10000	0	-1.4	112	112
PARP14	0.01	0.013	-10000	0	-10000	0	0
CCL17	-0.5	0.55	-10000	0	-1.2	73	73
GRB2	0.015	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.17	0.24	-10000	0	-0.6	24	24
T cell proliferation	-0.49	0.58	-10000	0	-1.2	74	74
IL4R/JAK1	-0.48	0.56	-10000	0	-1.2	70	70
EGR2	-0.65	0.71	-10000	0	-1.4	91	91
JAK2	-0.008	0.051	-10000	0	-0.61	1	1
JAK3	0.013	0.046	-10000	0	-0.48	2	2
PIK3R1	0.015	0	-10000	0	-10000	0	0
JAK1	0.008	0.015	-10000	0	-10000	0	0
COL1A2	-0.18	0.35	-10000	0	-1.6	11	11
CCL26	-0.5	0.57	-10000	0	-1.2	72	72
IL4R	-0.52	0.6	-10000	0	-1.3	70	70
PTPN6	0.026	0.013	-10000	0	-10000	0	0
IL13RA2	-0.5	0.57	-10000	0	-1.2	74	74
IL13RA1	-0.006	0.032	-10000	0	-10000	0	0
IRF4	-0.25	0.5	-10000	0	-1.3	37	37
ARG1	-0.11	0.18	-10000	0	-0.63	10	10
CBL	-0.28	0.36	-10000	0	-0.72	65	65
GTF3A	0.023	0.004	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.01	0.055	-10000	0	-0.45	1	1
IRF4/BCL6	-0.2	0.45	-10000	0	-1.2	35	35
CD40LG	-0.058	0.19	-10000	0	-0.58	29	29
MAPK14	-0.29	0.4	-10000	0	-0.82	59	59
mitosis	-0.2	0.28	-10000	0	-0.66	35	35
STAT6	-0.57	0.69	-10000	0	-1.4	79	79
SPI1	0.003	0.086	-10000	0	-0.53	6	6
RPS6KB1	-0.19	0.28	-10000	0	-0.67	28	28
STAT6 (dimer)	-0.57	0.69	-10000	0	-1.4	79	79
STAT6 (dimer)/PARP14	-0.56	0.63	-10000	0	-1.2	89	89
mast cell activation	0.011	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.32	-10000	0	-0.74	34	34
FRAP1	-0.21	0.3	-10000	0	-0.7	35	35
LTA	-0.5	0.58	-10000	0	-1.2	72	72
FES	0.012	0.038	-10000	0	-0.58	1	1
T-helper 1 cell differentiation	0.55	0.65	1.3	79	-10000	0	79
CCL11	-0.51	0.6	-10000	0	-1.3	73	73
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.21	0.31	-10000	0	-0.7	35	35
IL2RG	-0.006	0.11	-10000	0	-0.53	10	10
IL10	-0.51	0.6	-10000	0	-1.3	73	73
IRS1	0.002	0.084	-10000	0	-0.58	5	5
IRS2	-0.01	0.12	-10000	0	-0.58	10	10
IL4	-0.1	0.13	-10000	0	-10000	0	0
IL5	-0.49	0.55	-10000	0	-1.2	70	70
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.41	-10000	0	-0.86	72	72
COL1A1	-0.15	0.25	-10000	0	-1.7	3	3
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.49	0.58	-10000	0	-1.3	65	65
IL2R gamma/JAK3	-0.001	0.095	-10000	0	-0.44	10	10
TFF3	-0.66	0.7	-10000	0	-1.4	96	96
ALOX15	-0.52	0.56	-10000	0	-1.2	72	72
MYBL1	0.009	0.054	-10000	0	-0.47	3	3
T-helper 2 cell differentiation	-0.41	0.46	-10000	0	-0.95	76	76
SHC1	0.013	0.031	-10000	0	-0.47	1	1
CEBPB	0.016	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.21	0.3	-10000	0	-0.63	45	45
mol:PI-3-4-5-P3	-0.21	0.3	-10000	0	-0.71	35	35
PI3K	-0.22	0.32	-10000	0	-0.76	35	35
DOK2	-0.004	0.1	-10000	0	-0.56	8	8
ETS1	0.026	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.16	0.23	-10000	0	-0.56	24	24
ITGB3	-0.53	0.62	-10000	0	-1.3	75	75
PIGR	-0.8	0.73	-10000	0	-1.4	126	126
IGHE	0.035	0.045	-10000	0	-10000	0	0
MAPKKK cascade	-0.15	0.23	-10000	0	-0.55	24	24
BCL6	0.02	0.009	-10000	0	-10000	0	0
OPRM1	-0.49	0.55	-10000	0	-1.2	70	70
RETNLB	-0.49	0.56	-10000	0	-1.2	70	70
SELP	-0.61	0.69	-10000	0	-1.4	86	86
AICDA	-0.47	0.53	-10000	0	-1.1	73	73

×

Nongenotropic Androgen signaling

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
PTK2	0.013	0.001	-10000	0	-10000	0	0
GNB1/GNG2	-0.09	0.16	-10000	0	-0.32	82	82
regulation of S phase of mitotic cell cycle	-0.063	0.13	-10000	0	-0.25	81	81
GNAO1	-0.15	0.27	-10000	0	-0.58	68	68
HRAS	0.014	0.002	-10000	0	-10000	0	0
SHBG/T-DHT	0.003	0.005	-10000	0	-10000	0	0
PELP1	0.014	0.002	-10000	0	-10000	0	0
AKT1	0.013	0.001	-10000	0	-10000	0	0
MAP2K1	-0.081	0.15	-10000	0	-0.36	32	32
T-DHT/AR	-0.14	0.21	-10000	0	-0.43	81	81
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	74	74
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.58	1	1
mol:GDP	-0.15	0.21	-10000	0	-0.45	81	81
cell proliferation	-0.15	0.24	-10000	0	-0.45	75	75
PIK3CA	0.015	0	-10000	0	-10000	0	0
FOS	-0.25	0.4	-10000	0	-0.84	74	74
mol:Ca2+	-0.043	0.043	-10000	0	-0.085	105	105
MAPK3	-0.12	0.19	-10000	0	-0.49	32	32
MAPK1	-0.068	0.12	-10000	0	-0.27	31	31
PIK3R1	0.015	0	-10000	0	-10000	0	0
mol:IP3	-0.001	0.002	-10000	0	-0.004	74	74
cAMP biosynthetic process	0.036	0.037	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.58	1	1
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	74	74
HRAS/GTP	-0.1	0.14	-10000	0	-0.29	81	81
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.014	0.002	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	74	74
PI3K	0.006	0.009	-10000	0	-10000	0	0
apoptosis	0.14	0.23	0.45	74	-10000	0	74
T-DHT/AR/PELP1	-0.12	0.17	-10000	0	-0.36	81	81
HRAS/GDP	-0.14	0.2	-10000	0	-0.42	81	81
CREB1	-0.15	0.24	-10000	0	-0.49	74	74
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.19	0.28	-10000	0	-0.58	81	81
GNB1	0.015	0	-10000	0	-10000	0	0
RAF1	-0.083	0.15	-10000	0	-0.35	32	32
RAC1-CDC42/GDP	-0.13	0.19	-10000	0	-0.4	81	81
T-DHT/AR/PELP1/Src	-0.093	0.16	-10000	0	-0.32	81	81
MAP2K2	-0.081	0.15	-10000	0	-0.36	32	32
T-DHT/AR/PELP1/Src/PI3K	-0.064	0.13	-10000	0	-0.25	81	81
GNAZ	-0.11	0.24	-10000	0	-0.58	52	52
SHBG	0.014	0.002	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.14	0.24	-10000	0	-0.49	68	68
mol:T-DHT	0	0.001	-10000	0	-0.003	43	43
RAC1	0.015	0	-10000	0	-10000	0	0
GNRH1	0.012	0.001	-10000	0	-10000	0	0
Gi family/GTP	-0.15	0.2	-10000	0	-0.42	73	73
CDC42	0.015	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.062	0.2	-10000	0	-0.4	57	57
CRKL	-0.066	0.2	-10000	0	-0.41	56	56
HRAS	-0.067	0.21	-10000	0	-0.39	63	63
mol:PIP3	-0.075	0.18	-10000	0	-0.4	56	56
SPRED1	0.015	0	-10000	0	-10000	0	0
SPRED2	0.015	0	-10000	0	-10000	0	0
GAB1	-0.076	0.2	-10000	0	-0.43	57	57
FOXO3	-0.052	0.18	-10000	0	-0.37	56	56
AKT1	-0.065	0.19	-10000	0	-0.4	56	56
BAD	-0.052	0.18	-10000	0	-0.37	56	56
megakaryocyte differentiation	-0.081	0.2	-10000	0	-0.42	61	61
GSK3B	-0.052	0.18	-10000	0	-0.37	56	56
RAF1	-0.044	0.18	-10000	0	-0.38	28	28
SHC1	0.013	0.031	-10000	0	-0.47	1	1
STAT3	-0.076	0.2	-10000	0	-0.43	57	57
STAT1	-0.21	0.48	-10000	0	-1	61	61
HRAS/SPRED1	-0.046	0.17	-10000	0	-0.38	28	28
cell proliferation	-0.078	0.21	-10000	0	-0.44	57	57
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
TEC	0.015	0	-10000	0	-10000	0	0
RPS6KB1	-0.075	0.2	-10000	0	-0.43	58	58
HRAS/SPRED2	-0.046	0.17	-10000	0	-0.38	28	28
LYN/TEC/p62DOK	-0.098	0.17	-10000	0	-0.4	56	56
MAPK3	-0.016	0.13	-10000	0	-0.27	22	22
STAP1	-0.096	0.22	-10000	0	-0.46	57	57
GRAP2	-0.057	0.19	-10000	0	-0.58	29	29
JAK2	-0.21	0.38	-10000	0	-0.84	61	61
STAT1 (dimer)	-0.2	0.46	-10000	0	-0.98	61	61
mol:Gleevec	0.002	0.008	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.11	0.18	-10000	0	-0.42	58	58
actin filament polymerization	-0.077	0.2	-10000	0	-0.42	58	58
LYN	0.015	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.12	0.29	-10000	0	-0.62	58	58
PIK3R1	0.015	0.001	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.045	0.18	-10000	0	-0.36	56	56
PI3K	-0.058	0.2	-10000	0	-0.4	56	56
PTEN	0.015	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.26	0.57	-10000	0	-1.3	58	58
MAPK8	-0.08	0.21	-10000	0	-0.45	57	57
STAT3 (dimer)	-0.074	0.2	-10000	0	-0.42	57	57
positive regulation of transcription	-0.009	0.11	-10000	0	-0.22	22	22
mol:GDP	-0.12	0.19	-10000	0	-0.41	65	65
PIK3C2B	-0.076	0.2	-10000	0	-0.43	57	57
CBL/CRKL	-0.054	0.19	-10000	0	-0.38	56	56
FER	-0.077	0.21	-10000	0	-0.44	56	56
SH2B3	-0.076	0.2	-10000	0	-0.43	57	57
PDPK1	-0.062	0.17	-10000	0	-0.36	56	56
SNAI2	-0.079	0.21	-10000	0	-0.43	58	58
positive regulation of cell proliferation	-0.14	0.35	-10000	0	-0.72	61	61
KITLG	0.013	0.04	-10000	0	-0.58	1	1
cell motility	-0.14	0.35	-10000	0	-0.72	61	61
PTPN6	0.018	0.011	-10000	0	-10000	0	0
EPOR	-0.029	0.15	-10000	0	-0.52	1	1
STAT5A (dimer)	-0.11	0.29	-10000	0	-0.6	61	61
SOCS1	0.013	0.031	-10000	0	-0.47	1	1
cell migration	0.094	0.21	0.42	68	-10000	0	68
SOS1	0.015	0	-10000	0	-10000	0	0
EPO	-0.034	0.14	-10000	0	-0.48	22	22
VAV1	-0.019	0.14	-10000	0	-0.57	14	14
GRB10	-0.077	0.21	-10000	0	-0.44	57	57
PTPN11	0.017	0.008	-10000	0	-10000	0	0
SCF/KIT	-0.089	0.21	-10000	0	-0.44	62	62
GO:0007205	0.003	0.011	-10000	0	-10000	0	0
MAP2K1	-0.023	0.14	-10000	0	-0.3	22	22
CBL	0.015	0	-10000	0	-10000	0	0
KIT	-0.28	0.6	-10000	0	-1.4	56	56
MAP2K2	-0.023	0.14	-10000	0	-0.3	22	22
SHC/Grb2/SOS1	-0.098	0.17	-10000	0	-0.4	56	56
STAT5A	-0.12	0.3	-10000	0	-0.61	61	61
GRB2	0.015	0	-10000	0	-10000	0	0
response to radiation	-0.077	0.2	-10000	0	-0.43	58	58
SHC/GRAP2	-0.032	0.14	-10000	0	-0.41	30	30
PTPRO	-0.083	0.21	-10000	0	-0.43	61	61
SH2B2	-0.079	0.21	-10000	0	-0.43	58	58
DOK1	0.013	0.031	-10000	0	-0.47	1	1
MATK	-0.097	0.22	-10000	0	-0.43	68	68
CREBBP	0.032	0.02	-10000	0	-10000	0	0
BCL2	-0.074	0.33	-10000	0	-1.5	11	11

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.001	0.087	-9999	-0.33	16	16
VLDLR	-0.005	0.11	-9999	-0.58	8	8
CRKL	0.011	0.044	-9999	-0.47	2	2
LRPAP1	0.013	0.031	-9999	-0.47	1	1
FYN	0.01	0.054	-9999	-0.58	2	2
ITGA3	0.009	0.054	-9999	-0.47	3	3
RELN/VLDLR/Fyn	-0.13	0.17	-9999	-0.35	87	87
MAPK8IP1/MKK7/MAP3K11/JNK1	0.038	0.044	-9999	-10000	0	0
AKT1	-0.09	0.16	-9999	-0.27	97	97
MAP2K7	0.015	0	-9999	-10000	0	0
RAPGEF1	0.015	0	-9999	-10000	0	0
DAB1	-0.075	0.2	-9999	-0.54	37	37
RELN/LRP8/DAB1	-0.18	0.22	-9999	-0.37	125	125
LRPAP1/LRP8	-0.043	0.14	-9999	-0.33	45	45
RELN/LRP8/DAB1/Fyn	-0.17	0.21	-9999	-0.38	97	97
DAB1/alpha3/beta1 Integrin	-0.17	0.19	-9999	-0.51	41	41
long-term memory	-0.22	0.26	-9999	-0.6	56	56
DAB1/LIS1	-0.17	0.2	-9999	-0.53	40	40
DAB1/CRLK/C3G	-0.17	0.19	-9999	-0.51	41	41
PIK3CA	0.015	0	-9999	-10000	0	0
DAB1/NCK2	-0.17	0.2	-9999	-0.53	40	40
ARHGEF2	0.015	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.1	0.23	-9999	-0.57	48	48
CDK5R1	-0.018	0.12	-9999	-0.47	16	16
RELN	-0.18	0.28	-9999	-0.57	80	80
PIK3R1	0.015	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.16	0.2	-9999	-0.37	107	107
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.27	-9999	-0.44	116	116
MAPK8	0.007	0.066	-9999	-0.58	3	3
RELN/VLDLR/DAB1	-0.15	0.2	-9999	-0.36	108	108
ITGB1	0.015	0	-9999	-10000	0	0
MAP1B	-0.19	0.23	-9999	-0.4	112	112
RELN/LRP8	-0.16	0.2	-9999	-0.37	106	106
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.17	0.22	-9999	-0.38	97	97
PI3K	0.022	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.018	0.039	-9999	-0.33	3	3
RAP1A	-0.13	0.2	-9999	-0.47	41	41
PAFAH1B1	0.015	0	-9999	-10000	0	0
MAPK8IP1	0.01	0.049	-9999	-0.52	2	2
CRLK/C3G	0.019	0.032	-9999	-0.33	2	2
GRIN2B	-0.008	0.081	-9999	-0.47	7	7
NCK2	0.015	0	-9999	-10000	0	0
neuron differentiation	-0.073	0.14	-9999	-0.32	32	32
neuron adhesion	-0.11	0.2	-9999	-0.44	41	41
LRP8	-0.074	0.19	-9999	-0.47	44	44
GSK3B	-0.078	0.15	-9999	-0.42	17	17
RELN/VLDLR/DAB1/Fyn	-0.13	0.19	-9999	-0.34	99	99
MAP3K11	0.015	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.1	0.17	-9999	-0.29	97	97
CDK5	0.015	0	-9999	-10000	0	0
MAPT	-0.027	0.16	-9999	-0.52	23	23
neuron migration	-0.13	0.21	-9999	-0.46	42	42
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.074	0.14	-9999	-0.32	32	32
RELN/VLDLR	-0.14	0.21	-9999	-0.38	84	84

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.013	0.18	-10000	0	-0.5	17	17
PTK2B	0.012	0.038	-10000	0	-0.58	1	1
mol:Ca2+	-0.001	0.2	-10000	0	-0.62	14	14
EDN1	0.041	0.1	-10000	0	-0.41	7	7
EDN3	-0.005	0.068	-10000	0	-0.47	5	5
EDN2	-0.056	0.18	-10000	0	-0.53	31	31
HRAS/GDP	-0.065	0.24	-10000	0	-0.52	37	37
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.022	0.19	-10000	0	-0.44	26	26
ADCY4	-0.12	0.23	-10000	0	-0.56	32	32
ADCY5	-0.27	0.31	-10000	0	-0.63	89	89
ADCY6	-0.12	0.23	-10000	0	-0.55	33	33
ADCY7	-0.12	0.23	-10000	0	-0.55	33	33
ADCY1	-0.13	0.24	-10000	0	-0.58	34	34
ADCY2	-0.23	0.3	-10000	0	-0.64	66	66
ADCY3	-0.12	0.23	-10000	0	-0.56	32	32
ADCY8	-0.13	0.23	-10000	0	-0.55	35	35
ADCY9	-0.12	0.23	-10000	0	-0.57	33	33
arachidonic acid secretion	-0.12	0.28	-10000	0	-0.5	66	66
ETB receptor/Endothelin-1/Gq/GTP	-0.046	0.2	-10000	0	-0.47	31	31
GNAO1	-0.15	0.27	-10000	0	-0.58	68	68
HRAS	0.012	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	0.065	0.21	0.24	89	-0.46	17	106
ETA receptor/Endothelin-1/Gs/GTP	-0.089	0.29	0.22	60	-0.59	33	93
mol:GTP	0	0.005	-10000	0	-10000	0	0
COL3A1	0.01	0.2	-10000	0	-0.55	16	16
EDNRB	-0.051	0.19	-10000	0	-0.58	27	27
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	0.008	0.19	-10000	0	-0.48	19	19
CYSLTR1	-0.003	0.22	-10000	0	-0.64	18	18
SLC9A1	0.008	0.11	-10000	0	-0.31	9	9
mol:GDP	-0.078	0.25	-10000	0	-0.53	43	43
SLC9A3	-0.021	0.23	-10000	0	-0.56	30	30
RAF1	-0.13	0.28	-10000	0	-0.55	54	54
JUN	-0.016	0.26	-10000	0	-0.84	16	16
JAK2	0.012	0.19	-10000	0	-0.5	18	18
mol:IP3	-0.048	0.22	-10000	0	-0.54	29	29
ETA receptor/Endothelin-1	0.064	0.26	0.27	85	-0.49	29	114
PLCB1	-0.005	0.099	-10000	0	-0.58	7	7
PLCB2	0.009	0.039	-10000	0	-0.58	1	1
ETA receptor/Endothelin-3	-0.021	0.17	-10000	0	-0.44	32	32
FOS	-0.27	0.48	-10000	0	-0.94	78	78
Gai/GDP	-0.23	0.39	-10000	0	-0.83	68	68
CRK	0.015	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.058	0.26	-10000	0	-0.56	39	39
BCAR1	0.015	0.001	-10000	0	-10000	0	0
PRKCB1	-0.05	0.21	-10000	0	-0.52	29	29
GNAQ	0.013	0.008	-10000	0	-10000	0	0
GNAZ	-0.11	0.24	-10000	0	-0.58	52	52
GNAL	-0.22	0.29	-10000	0	-0.58	96	96
Gs family/GDP	-0.2	0.25	-10000	0	-0.53	76	76
ETA receptor/Endothelin-1/Gq/GTP	-0.023	0.2	-10000	0	-0.49	25	25
MAPK14	-0.03	0.17	-10000	0	-0.49	22	22
TRPC6	-0.003	0.21	-10000	0	-0.65	14	14
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.58	1	1
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.038	0.18	-10000	0	-0.47	27	27
ETB receptor/Endothelin-2	-0.077	0.19	-10000	0	-0.43	52	52
ETB receptor/Endothelin-3	-0.042	0.14	-10000	0	-0.41	32	32
ETB receptor/Endothelin-1	-0.008	0.17	-10000	0	-0.39	34	34
MAPK3	-0.23	0.42	-10000	0	-0.79	81	81
MAPK1	-0.23	0.42	-10000	0	-0.79	81	81
Rac1/GDP	-0.064	0.23	-10000	0	-0.53	36	36
cAMP biosynthetic process	-0.21	0.28	-10000	0	-0.52	94	94
MAPK8	-0.02	0.25	-10000	0	-0.71	19	19
SRC	0.015	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.1	0.21	-10000	0	-0.43	55	55
p130Cas/CRK/Src/PYK2	-0.055	0.24	-10000	0	-0.56	32	32
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.064	0.23	-10000	0	-0.52	37	37
COL1A2	-0.03	0.3	-10000	0	-0.89	19	19
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.062	0.2	-10000	0	-0.41	58	58
mol:DAG	-0.048	0.22	-10000	0	-0.54	29	29
MAP2K2	-0.17	0.33	-10000	0	-0.59	84	84
MAP2K1	-0.17	0.33	-10000	0	-0.59	84	84
EDNRA	-0.013	0.23	-10000	0	-0.62	27	27
positive regulation of muscle contraction	0.02	0.16	-10000	0	-0.44	15	15
Gq family/GDP	-0.13	0.21	-10000	0	-0.53	42	42
HRAS/GTP	-0.097	0.25	-10000	0	-0.53	44	44
PRKCH	-0.041	0.21	-10000	0	-0.52	29	29
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCA	-0.041	0.21	-10000	0	-0.53	28	28
PRKCB	-0.13	0.26	-10000	0	-0.5	65	65
PRKCE	-0.04	0.21	-10000	0	-0.53	27	27
PRKCD	-0.042	0.21	-10000	0	-0.52	29	29
PRKCG	-0.053	0.21	-10000	0	-0.53	29	29
regulation of vascular smooth muscle contraction	-0.33	0.56	-10000	0	-1.1	78	78
PRKCQ	-0.069	0.23	-10000	0	-0.52	39	39
PLA2G4A	-0.13	0.31	-10000	0	-0.55	66	66
GNA14	-0.08	0.22	-10000	0	-0.58	38	38
GNA15	0.009	0.054	-10000	0	-0.58	2	2
GNA12	0.015	0	-10000	0	-10000	0	0
GNA11	0.011	0.039	-10000	0	-0.58	1	1
Rac1/GTP	0.065	0.21	0.24	88	-0.46	17	105
MMP1	-0.18	0.21	-10000	0	-0.36	127	127

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.015	0	-10000	0	-10000	0	0
PTK2	0.015	0	-10000	0	-10000	0	0
CRKL	-0.12	0.16	-10000	0	-0.29	106	106
GRB2/SOS1/SHC	-0.001	0.017	-10000	0	-0.27	1	1
HRAS	0.015	0	-10000	0	-10000	0	0
IRS1/Crk	-0.11	0.16	-10000	0	-0.29	106	106
IGF-1R heterotetramer/IGF1/PTP1B	-0.15	0.17	-10000	0	-0.33	106	106
AKT1	-0.075	0.14	-10000	0	-0.46	4	4
BAD	-0.063	0.13	-10000	0	-0.43	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.11	0.16	-10000	0	-0.29	106	106
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.11	0.16	-10000	0	-0.29	106	106
RAF1	-0.055	0.13	-10000	0	-0.4	4	4
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.099	0.16	-10000	0	-0.27	106	106
YWHAZ	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.13	0.18	-10000	0	-0.32	109	109
PIK3CA	0.015	0	-10000	0	-10000	0	0
RPS6KB1	-0.075	0.14	-10000	0	-0.46	4	4
GNB2L1	0.015	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.051	0.12	-10000	0	-0.35	4	4
PXN	0.015	0	-10000	0	-10000	0	0
PIK3R1	0.015	0	-10000	0	-10000	0	0
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
HRAS/GTP	-0.1	0.12	-10000	0	-0.46	5	5
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.086	0.15	-10000	0	-0.43	5	5
IGF-1R heterotetramer	-0.024	0.069	-10000	0	-0.66	2	2
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.11	0.16	-10000	0	-0.29	106	106
Crk/p130 Cas/Paxillin	-0.088	0.15	-10000	0	-0.5	4	4
IGF1R	-0.024	0.069	-10000	0	-0.66	2	2
IGF1	-0.25	0.3	-10000	0	-0.59	106	106
IRS2/Crk	-0.11	0.18	-10000	0	-0.53	14	14
PI3K	-0.099	0.16	-10000	0	-0.27	106	106
apoptosis	0.048	0.12	0.36	4	-10000	0	4
HRAS/GDP	0.011	0	-10000	0	-10000	0	0
PRKCD	-0.14	0.21	-10000	0	-0.37	106	106
RAF1/14-3-3 E	-0.042	0.12	-10000	0	-0.36	5	5
BAD/14-3-3	-0.051	0.13	-10000	0	-0.39	4	4
PRKCZ	-0.076	0.14	-10000	0	-0.47	5	5
Crk/p130 Cas/Paxillin/FAK1	-0.08	0.093	-10000	0	-0.39	4	4
PTPN1	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.16	0.22	-10000	0	-0.4	106	106
BCAR1	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.12	0.15	-10000	0	-0.28	106	106
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.015	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.11	0.16	-10000	0	-0.29	106	106
GRB10	0.012	0.038	-10000	0	-0.58	1	1
PTPN11	-0.11	0.16	-10000	0	-0.29	106	106
IRS1	-0.13	0.17	-10000	0	-0.32	109	109
IRS2	-0.13	0.18	-10000	0	-0.32	107	107
IGF-1R heterotetramer/IGF1	-0.18	0.23	-10000	0	-0.44	106	106
GRB2	0.015	0	-10000	0	-10000	0	0
PDPK1	-0.087	0.15	-10000	0	-0.49	4	4
YWHAE	0.012	0.038	-10000	0	-0.58	1	1
PRKD1	-0.15	0.23	-10000	0	-0.4	107	107
SHC1	0.013	0.031	-10000	0	-0.47	1	1

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	-0.23	0.49	-9999	-1.1	54	54
MKNK1	0.015	0	-9999	-10000	0	0
MAPK14	-0.052	0.14	-9999	-0.39	10	10
ATF2/c-Jun	-0.036	0.18	-9999	-0.85	7	7
MAPK11	-0.052	0.14	-9999	-0.39	10	10
MITF	-0.079	0.21	-9999	-0.39	60	60
MAPKAPK5	-0.053	0.17	-9999	-0.35	57	57
KRT8	-0.066	0.21	-9999	-0.4	59	59
MAPKAPK3	0.015	0	-9999	-10000	0	0
MAPKAPK2	0.015	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.079	0.21	-9999	-0.44	57	57
CEBPB	-0.052	0.17	-9999	-0.35	57	57
SLC9A1	-0.052	0.17	-9999	-0.35	57	57
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.047	0.18	-9999	-0.53	10	10
p38alpha-beta/MNK1	-0.05	0.17	-9999	-0.5	10	10
JUN	-0.035	0.18	-9999	-0.84	7	7
PPARGC1A	-0.21	0.26	-9999	-0.4	134	134
USF1	-0.052	0.17	-9999	-0.35	57	57
RAB5/GDP/GDI1	-0.063	0.11	-9999	-0.35	10	10
NOS2	-0.082	0.24	-9999	-0.88	10	10
DDIT3	-0.053	0.17	-9999	-0.35	57	57
RAB5A	0.015	0	-9999	-10000	0	0
HSPB1	-0.035	0.15	-9999	-0.42	10	10
p38alpha-beta/HBP1	-0.05	0.17	-9999	-0.5	10	10
CREB1	-0.056	0.19	-9999	-0.38	57	57
RAB5/GDP	0.011	0	-9999	-10000	0	0
EIF4E	-0.037	0.15	-9999	-0.44	10	10
RPS6KA4	-0.052	0.17	-9999	-0.35	57	57
PLA2G4A	-0.055	0.18	-9999	-0.54	15	15
GDI1	-0.052	0.17	-9999	-0.35	57	57
TP53	-0.07	0.21	-9999	-0.44	57	57
RPS6KA5	-0.061	0.19	-9999	-0.37	58	58
ESR1	-0.12	0.24	-9999	-0.4	86	86
HBP1	0.015	0	-9999	-10000	0	0
MEF2C	-0.061	0.19	-9999	-0.37	60	60
MEF2A	-0.052	0.17	-9999	-0.35	57	57
EIF4EBP1	-0.057	0.19	-9999	-0.38	57	57
KRT19	-0.074	0.21	-9999	-0.41	59	59
ELK4	-0.052	0.17	-9999	-0.35	57	57
ATF6	-0.052	0.17	-9999	-0.35	57	57
ATF1	-0.056	0.19	-9999	-0.38	57	57
p38alpha-beta/MAPKAPK2	-0.05	0.17	-9999	-0.5	10	10
p38alpha-beta/MAPKAPK3	-0.05	0.17	-9999	-0.5	10	10

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.16	0.18	-10000	0	-0.34	119	119
TP53	-0.039	0.056	-10000	0	-10000	0	0
Senescence	-0.039	0.055	-10000	0	-10000	0	0
Apoptosis	-0.039	0.055	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.076	0.11	0.18	116	-0.31	7	123
MDM4	0.015	0	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	-0.033	0.15	-10000	0	-0.51	22	22
CDKN2C	0.038	0.04	-10000	0	-0.42	1	1
CDKN2A	-0.24	0.25	-10000	0	-0.49	119	119
CCND2	0.048	0.081	0.22	23	-0.14	8	31
RB1	-0.046	0.087	0.16	1	-0.23	23	24
CDK4	0.063	0.081	0.23	24	-10000	0	24
CDK6	0.053	0.089	0.25	22	-0.18	6	28
G1/S progression	0.046	0.086	0.23	23	-0.16	1	24

×

Ephrin A reverse signaling

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
MAPKKK cascade	-0.065	0.14	-9999	-0.36	44	44
EFNA5	-0.002	0.099	-9999	-0.58	7	7
FYN	-0.041	0.14	-9999	-0.32	44	44
neuron projection morphogenesis	-0.065	0.14	-9999	-0.36	44	44
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.061	0.14	-9999	-0.36	44	44
EPHA5	-0.084	0.21	-9999	-0.57	38	38

×

Thromboxane A2 receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.013	0.12	-10000	0	-0.53	12	12
GNB1/GNG2	-0.073	0.088	-10000	0	-0.18	91	91
AKT1	-0.034	0.13	-10000	0	-0.2	42	42
EGF	-0.017	0.12	-10000	0	-0.47	15	15
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.034	0.058	-10000	0	-0.37	1	1
mol:Ca2+	-0.073	0.18	-10000	0	-0.3	89	89
LYN	0.035	0.056	-10000	0	-0.37	1	1
RhoA/GTP	-0.047	0.058	-10000	0	-0.13	31	31
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.084	0.2	-10000	0	-0.34	90	90
GNG2	0.012	0.038	-10000	0	-0.58	1	1
ARRB2	0.015	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.012	0.073	-10000	0	-0.34	3	3
G beta5/gamma2	-0.094	0.12	-10000	0	-0.24	91	91
PRKCH	-0.085	0.2	-10000	0	-0.34	89	89
DNM1	0.002	0.084	-10000	0	-0.58	5	5
TXA2/TP beta/beta Arrestin3	-0.007	0.035	-10000	0	-0.24	5	5
mol:GTP	0	0.002	-10000	0	-10000	0	0
PTGDR	-0.016	0.13	-10000	0	-0.58	12	12
G12 family/GTP	-0.12	0.14	-10000	0	-0.3	89	89
ADRBK1	0.015	0	-10000	0	-10000	0	0
ADRBK2	0.01	0.049	-10000	0	-0.52	2	2
RhoA/GTP/ROCK1	0.01	0.01	-10000	0	-10000	0	0
mol:GDP	0.031	0.12	0.28	11	-10000	0	11
mol:NADP	0.013	0.031	-10000	0	-0.47	1	1
RAB11A	0.015	0	-10000	0	-10000	0	0
PRKG1	-0.099	0.23	-10000	0	-0.58	46	46
mol:IP3	-0.098	0.22	-10000	0	-0.37	89	89
cell morphogenesis	0.009	0.01	-10000	0	-10000	0	0
PLCB2	-0.14	0.29	-10000	0	-0.5	89	89
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.003	0.1	-10000	0	-0.4	3	3
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.025	0.082	-10000	0	-0.4	4	4
RHOA	0.015	0	-10000	0	-10000	0	0
PTGIR	0.015	0	-10000	0	-10000	0	0
PRKCB1	-0.098	0.22	-10000	0	-0.37	89	89
GNAQ	0.015	0	-10000	0	-10000	0	0
mol:L-citrulline	0.013	0.031	-10000	0	-0.47	1	1
TXA2/TXA2-R family	-0.15	0.3	-10000	0	-0.53	89	89
LCK	0.032	0.062	-10000	0	-0.37	1	1
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.011	0.047	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.032	0.022	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.011	0.046	-10000	0	-10000	0	0
MAPK14	-0.044	0.14	-10000	0	-0.22	89	89
TGM2/GTP	-0.12	0.25	-10000	0	-0.42	89	89
MAPK11	-0.044	0.14	-10000	0	-0.22	89	89
ARHGEF1	-0.034	0.11	-10000	0	-0.17	89	89
GNAI2	0.015	0	-10000	0	-10000	0	0
JNK cascade	-0.1	0.23	-10000	0	-0.39	89	89
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	-0.067	0.17	-10000	0	-0.28	91	91
cAMP biosynthetic process	-0.095	0.21	-10000	0	-0.35	89	89
Gq family/GTP/EBP50	-0.008	0.086	-10000	0	-0.26	6	6
actin cytoskeleton reorganization	0.009	0.01	-10000	0	-10000	0	0
SRC	0.035	0.056	-10000	0	-0.37	1	1
GNB5	0.015	0	-10000	0	-10000	0	0
GNB1	0.015	0	-10000	0	-10000	0	0
EGF/EGFR	0.033	0.074	-10000	0	-0.23	4	4
VCAM1	-0.076	0.18	-10000	0	-0.3	89	89
TP beta/Gq family/GDP/G beta5/gamma2	0.012	0.073	-10000	0	-0.34	3	3
platelet activation	-0.06	0.19	-10000	0	-0.3	89	89
PGI2/IP	0.007	0.005	-10000	0	-10000	0	0
PRKACA	0.008	0.065	-10000	0	-0.28	12	12
Gq family/GDP/G beta5/gamma2	0.009	0.073	-10000	0	-0.31	3	3
TXA2/TP beta/beta Arrestin2	-0.012	0.076	-10000	0	-0.54	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	0.015	0.063	-10000	0	-0.25	13	13
mol:DAG	-0.11	0.24	-10000	0	-0.41	89	89
EGFR	-0.01	0.11	-10000	0	-0.52	11	11
TXA2/TP alpha	-0.14	0.28	-10000	0	-0.48	89	89
Gq family/GTP	-0.038	0.088	-10000	0	-0.23	41	41
YES1	0.035	0.056	-10000	0	-0.37	1	1
GNAI2/GTP	-0.012	0.051	-10000	0	-0.44	1	1
PGD2/DP	-0.015	0.094	-10000	0	-0.43	12	12
SLC9A3R1	-0.001	0.087	-10000	0	-0.47	8	8
FYN	0.033	0.061	-10000	0	-0.37	1	1
mol:NO	0.013	0.031	-10000	0	-0.47	1	1
GNA15	0.01	0.054	-10000	0	-0.58	2	2
PGK/cGMP	-0.064	0.14	-10000	0	-0.35	47	47
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.023	0.084	-10000	0	-0.52	1	1
NOS3	0.013	0.031	-10000	0	-0.47	1	1
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCA	-0.085	0.2	-10000	0	-0.34	89	89
PRKCB	-0.14	0.24	-10000	0	-0.42	91	91
PRKCE	-0.082	0.2	-10000	0	-0.34	89	89
PRKCD	-0.099	0.22	-10000	0	-0.38	89	89
PRKCG	-0.1	0.22	-10000	0	-0.38	89	89
muscle contraction	-0.14	0.28	-10000	0	-0.49	89	89
PRKCZ	-0.084	0.2	-10000	0	-0.34	89	89
ARR3	0.003	0.006	-10000	0	-10000	0	0
TXA2/TP beta	0.006	0.066	-10000	0	-0.49	1	1
PRKCQ	-0.098	0.22	-10000	0	-0.36	89	89
MAPKKK cascade	-0.13	0.26	-10000	0	-0.46	89	89
SELE	-0.12	0.23	-10000	0	-0.41	91	91
TP beta/GNAI2/GDP/G beta/gamma	0.036	0.059	-10000	0	-10000	0	0
ROCK1	0.015	0	-10000	0	-10000	0	0
GNA14	-0.079	0.22	-10000	0	-0.58	38	38
chemotaxis	-0.18	0.34	-10000	0	-0.62	89	89
GNA12	0.015	0	-10000	0	-10000	0	0
GNA13	0.015	0	-10000	0	-10000	0	0
GNA11	0.012	0.038	-10000	0	-0.58	1	1
Rac1/GTP	0.007	0.006	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.022	0	-10000	0	-10000	0	0
Necdin/E2F1	-0.12	0.21	-10000	0	-0.39	82	82
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.079	0.19	-10000	0	-0.54	19	19
NGF (dimer)/p75(NTR)/BEX1	-0.16	0.23	-10000	0	-0.43	90	90
NT-4/5 (dimer)/p75(NTR)	-0.12	0.23	-10000	0	-0.45	74	74
IKBKB	0.015	0	-10000	0	-10000	0	0
AKT1	-0.075	0.19	-10000	0	-0.33	74	74
IKBKG	0.015	0	-10000	0	-10000	0	0
BDNF	-0.088	0.22	-10000	0	-0.58	42	42
MGDIs/NGR/p75(NTR)/LINGO1	-0.14	0.18	-10000	0	-0.38	63	63
FURIN	0.013	0.031	-10000	0	-0.47	1	1
proBDNF (dimer)/p75(NTR)/Sortilin	-0.14	0.21	-10000	0	-0.4	88	88
LINGO1	-0.008	0.1	-10000	0	-0.47	11	11
Sortilin/TRAF6/NRIF	0	0	-10000	0	-10000	0	0
proBDNF (dimer)	-0.088	0.22	-10000	0	-0.58	42	42
NTRK1	0.007	0.054	-10000	0	-0.47	3	3
RTN4R	-0.052	0.17	-10000	0	-0.47	33	33
neuron apoptosis	-0.12	0.22	-10000	0	-0.52	35	35
IRAK1	0.015	0	-10000	0	-10000	0	0
SHC1	-0.11	0.22	-10000	0	-0.4	77	77
ARHGDIA	0.015	0	-10000	0	-10000	0	0
RhoA/GTP	0.011	0	-10000	0	-10000	0	0
Gamma Secretase	0.044	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.089	0.2	-10000	0	-0.36	74	74
MAGEH1	0.015	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.13	0.24	-10000	0	-0.42	89	89
Mammalian IAPs/DIABLO	0.013	0.091	-10000	0	-0.32	15	15
proNGF (dimer)	-0.059	0.2	-10000	0	-0.58	30	30
MAGED1	0.015	0	-10000	0	-10000	0	0
APP	0.015	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.04	0.17	-10000	0	-0.58	22	22
ZNF274	0.015	0	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.084	0.19	-10000	0	-0.34	74	74
NGF	-0.059	0.2	-10000	0	-0.58	30	30
cell cycle arrest	-0.089	0.17	-10000	0	-0.5	18	18
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.062	0.16	-10000	0	-0.51	14	14
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.12	0.19	-10000	0	-0.38	74	74
NCSTN	0.015	0	-10000	0	-10000	0	0
mol:GTP	-0.13	0.2	-10000	0	-0.4	78	78
PSENEN	0.015	0	-10000	0	-10000	0	0
mol:ceramide	-0.089	0.2	-10000	0	-0.36	74	74
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.041	0.14	-10000	0	-0.42	15	15
p75(NTR)/beta APP	-0.088	0.19	-10000	0	-0.41	61	61
BEX1	-0.042	0.17	-10000	0	-0.56	23	23
mol:GDP	-0.12	0.21	-10000	0	-0.41	77	77
NGF (dimer)	-0.081	0.16	-10000	0	-0.35	42	42
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.096	0.18	-10000	0	-0.34	63	63
PIK3R1	0.015	0	-10000	0	-10000	0	0
RAC1/GTP	-0.093	0.19	-10000	0	-0.35	77	77
MYD88	0.015	0	-10000	0	-10000	0	0
CHUK	0.015	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.13	0.2	-10000	0	-0.4	78	78
RHOB	0.015	0	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
MAGE-G1/E2F1	-0.062	0.15	-10000	0	-0.33	58	58
NT3 (dimer)	-0.096	0.23	-10000	0	-0.57	45	45
TP53	-0.08	0.18	-10000	0	-0.55	15	15
PRDM4	-0.089	0.2	-10000	0	-0.36	74	74
BDNF (dimer)	-0.16	0.21	-10000	0	-0.41	77	77
PIK3CA	0.015	0	-10000	0	-10000	0	0
SORT1	0.015	0	-10000	0	-10000	0	0
activation of caspase activity	-0.11	0.17	-10000	0	-0.59	15	15
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.089	0.2	-10000	0	-0.36	74	74
RHOC	0.015	0	-10000	0	-10000	0	0
XIAP	0.013	0.031	-10000	0	-0.47	1	1
MAPK10	-0.11	0.22	-10000	0	-0.52	35	35
DIABLO	0.015	0	-10000	0	-10000	0	0
SMPD2	-0.089	0.2	-10000	0	-0.36	74	74
APH1B	0.015	0	-10000	0	-10000	0	0
APH1A	0.015	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.13	0.2	-10000	0	-0.4	77	77
PSEN1	0.015	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.022	0	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.16	0.24	-10000	0	-0.46	94	94
MAPK8	-0.087	0.21	-10000	0	-0.52	27	27
MAPK9	-0.084	0.21	-10000	0	-0.52	27	27
APAF1	0.015	0	-10000	0	-10000	0	0
NTF3	-0.096	0.23	-10000	0	-0.57	45	45
NTF4	-0.04	0.17	-10000	0	-0.58	22	22
NDN	-0.066	0.2	-10000	0	-0.58	33	33
RAC1/GDP	0.011	0	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.098	0.16	-10000	0	-0.54	14	14
p75 CTF/Sortilin/TRAF6/NRIF	0.038	0	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.13	0.2	-10000	0	-0.4	78	78
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.092	0.19	-10000	0	-0.58	15	15
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.11	0.2	-10000	0	-0.36	85	85
PRKACB	0.012	0.038	-10000	0	-0.58	1	1
proBDNF (dimer)/p75 ECD	-0.054	0.17	-10000	0	-0.42	42	42
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.14	-10000	0	-0.56	16	16
BIRC2	0.011	0.044	-10000	0	-0.47	2	2
neuron projection morphogenesis	-0.12	0.21	0.2	8	-0.41	70	78
BAD	-0.088	0.21	-10000	0	-0.5	32	32
RIPK2	0.015	0	-10000	0	-10000	0	0
NGFR	-0.13	0.26	-10000	0	-0.57	61	61
CYCS	-0.076	0.19	-10000	0	-0.34	74	74
ADAM17	0.015	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.089	0.2	-10000	0	-0.36	74	74
BCL2L11	-0.088	0.21	-10000	0	-0.5	32	32
BDNF (dimer)/p75(NTR)	-0.16	0.25	-10000	0	-0.47	88	88
PI3K	-0.089	0.2	-10000	0	-0.36	74	74
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.089	0.2	-10000	0	-0.36	74	74
NDNL2	0.015	0	-10000	0	-10000	0	0
YWHAE	0.012	0.038	-10000	0	-0.58	1	1
PRKCI	0.015	0	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.14	0.24	-10000	0	-0.48	77	77
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.089	0.2	-10000	0	-0.36	74	74
TRAF6	0.015	0	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.58	1	1
PLG	0.003	0.006	-10000	0	-10000	0	0
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.14	0.25	-10000	0	-0.4	97	97
SQSTM1	0.015	0	-10000	0	-10000	0	0
NGFRAP1	0.012	0.038	-10000	0	-0.58	1	1
CASP3	-0.079	0.2	-10000	0	-0.45	32	32
E2F1	-0.1	0.21	-10000	0	-0.47	58	58
CASP9	0.015	0	-10000	0	-10000	0	0
IKK complex	-0.076	0.14	-10000	0	-0.49	15	15
NGF (dimer)/TRKA	-0.038	0.15	-10000	0	-0.41	33	33
MMP7	-0.11	0.22	-10000	0	-0.5	57	57
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.076	0.19	-10000	0	-0.58	14	14
MMP3	-0.11	0.23	-10000	0	-0.53	54	54
APAF-1/Caspase 9	-0.088	0.13	-10000	0	-0.43	21	21

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.012	0.038	-9999	-0.58	1	1
LAT2	-0.095	0.19	-9999	-0.43	44	44
AP1	-0.19	0.22	-9999	-0.52	59	59
mol:PIP3	-0.11	0.24	-9999	-0.5	46	46
IKBKB	-0.072	0.15	-9999	-0.29	58	58
AKT1	-0.072	0.18	-9999	-0.43	34	34
IKBKG	-0.072	0.15	-9999	-0.29	58	58
MS4A2	-0.14	0.26	-9999	-0.58	61	61
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.001	-9999	-10000	0	0
MAP3K1	-0.067	0.19	-9999	-0.4	42	42
mol:Ca2+	-0.077	0.18	-9999	-0.37	46	46
LYN	0.013	0.006	-9999	-10000	0	0
CBLB	-0.092	0.19	-9999	-0.36	66	66
SHC1	0.013	0.031	-9999	-0.47	1	1
RasGAP/p62DOK	-0.066	0.16	-9999	-0.32	66	66
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0	0.092	-9999	-0.58	6	6
PLD2	-0.12	0.21	-9999	-0.5	40	40
PTPN13	-0.092	0.2	-9999	-0.48	36	36
PTPN11	0.011	0.009	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.043	0.16	-9999	-0.34	32	32
SYK	0.008	0.056	-9999	-0.6	2	2
GRB2	0.014	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.16	0.21	-9999	-0.52	46	46
LAT	-0.093	0.19	-9999	-0.44	39	39
PAK2	-0.084	0.21	-9999	-0.46	42	42
NFATC2	-0.16	0.26	-9999	-0.69	40	40
HRAS	-0.1	0.22	-9999	-0.5	43	43
GAB2	0.015	0	-9999	-10000	0	0
PLA2G1B	0.039	0.023	-9999	-10000	0	0
Fc epsilon R1	-0.18	0.24	-9999	-0.44	98	98
Antigen/IgE/Fc epsilon R1	-0.16	0.22	-9999	-0.4	98	98
mol:GDP	-0.11	0.24	-9999	-0.53	44	44
JUN	0	0.092	-9999	-0.58	6	6
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.001	-9999	-10000	0	0
FOS	-0.17	0.27	-9999	-0.58	74	74
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.11	0.2	-9999	-0.38	66	66
CHUK	-0.072	0.15	-9999	-0.29	58	58
KLRG1	-0.09	0.18	-9999	-0.42	41	41
VAV1	-0.11	0.21	-9999	-0.38	74	74
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.092	0.19	-9999	-0.36	66	66
negative regulation of mast cell degranulation	-0.083	0.18	-9999	-0.42	39	39
BTK	-0.12	0.25	-9999	-0.57	42	42
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.15	0.27	-9999	-0.49	71	71
GAB2/PI3K/SHP2	-0.12	0.17	-9999	-0.48	34	34
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.11	0.21	-9999	-0.51	40	40
RAF1	0.028	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.18	0.24	-9999	-0.48	72	72
FCER1G	-0.005	0.11	-9999	-0.5	11	11
FCER1A	-0.14	0.26	-9999	-0.59	60	60
Antigen/IgE/Fc epsilon R1/Fyn	-0.15	0.21	-9999	-0.38	94	94
MAPK3	0.038	0.023	-9999	-10000	0	0
MAPK1	0.038	0.023	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
MAPK8	-0.012	0.09	-9999	-0.59	3	3
DUSP1	-0.15	0.26	-9999	-0.58	66	66
NF-kappa-B/RelA	-0.059	0.071	-9999	-0.22	7	7
actin cytoskeleton reorganization	-0.095	0.2	-9999	-0.48	33	33
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.12	0.18	-9999	-0.46	41	41
FER	-0.093	0.19	-9999	-0.46	38	38
RELA	0.015	0	-9999	-10000	0	0
ITK	-0.075	0.16	-9999	-0.51	25	25
SOS1	0.015	0	-9999	-10000	0	0
PLCG1	-0.11	0.24	-9999	-0.54	42	42
cytokine secretion	-0.043	0.051	-9999	-10000	0	0
SPHK1	-0.12	0.2	-9999	-0.45	48	48
PTK2	-0.099	0.2	-9999	-0.51	32	32
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.16	0.22	-9999	-0.45	72	72
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.1	0.23	-9999	-0.49	46	46
MAP2K2	0.034	0.024	-9999	-10000	0	0
MAP2K1	0.034	0.024	-9999	-10000	0	0
MAP2K7	0.015	0	-9999	-10000	0	0
KLRG1/SHP2	-0.1	0.15	-9999	-0.4	36	36
MAP2K4	0.018	0.012	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.18	0.24	-9999	-0.43	99	99
mol:Choline	-0.12	0.21	-9999	-0.49	40	40
SHC/Grb2/SOS1	-0.11	0.16	-9999	-0.44	33	33
FYN	0.01	0.054	-9999	-0.58	2	2
DOK1	0.013	0.031	-9999	-0.47	1	1
PXN	-0.085	0.19	-9999	-0.47	32	32
HCLS1	-0.092	0.19	-9999	-0.45	38	38
PRKCB	-0.12	0.21	-9999	-0.4	66	66
FCGR2B	-0.029	0.15	-9999	-0.57	18	18
IGHE	-0.003	0.007	-9999	-10000	0	0
KLRG1/SHIP	-0.085	0.19	-9999	-0.43	39	39
LCP2	0.012	0.038	-9999	-0.58	1	1
PLA2G4A	-0.11	0.21	-9999	-0.38	72	72
RASA1	0.015	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.12	0.21	-9999	-0.49	40	40
IKK complex	-0.039	0.12	-9999	-0.22	46	46
WIPF1	0	0.092	-9999	-0.58	6	6

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.05	0.061	0.11	112	-10000	0	112
BUB1B	-0.072	0.1	-10000	0	-0.2	83	83
PLK1	-0.019	0.047	-10000	0	-0.096	49	49
PLK1S1	-0.004	0.025	-10000	0	-0.093	1	1
KIF2A	-0.008	0.043	-10000	0	-0.17	1	1
regulation of mitotic centrosome separation	-0.019	0.047	-10000	0	-0.096	49	49
GOLGA2	0.015	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.16	0.22	-10000	0	-0.38	106	106
WEE1	-0.016	0.05	-10000	0	-10000	0	0
cytokinesis	-0.13	0.1	-10000	0	-0.23	74	74
PP2A-alpha B56	0.019	0.031	-10000	0	-10000	0	0
AURKA	-0.017	0.042	-10000	0	-0.13	1	1
PICH/PLK1	-0.11	0.18	-10000	0	-0.35	66	66
CENPE	-0.068	0.13	-10000	0	-0.3	56	56
RhoA/GTP	0.011	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.042	-10000	0	-0.17	1	1
PPP2CA	0.015	0	-10000	0	-10000	0	0
FZR1	0.015	0	-10000	0	-10000	0	0
TPX2	-0.033	0.044	-10000	0	-0.14	1	1
PAK1	0.011	0.039	-10000	0	-0.59	1	1
SPC24	-0.14	0.23	-10000	0	-0.47	76	76
FBXW11	0.015	0	-10000	0	-10000	0	0
CLSPN	-0.032	0.049	-10000	0	-0.11	25	25
GORASP1	0.015	0	-10000	0	-10000	0	0
metaphase	-0.002	0.004	-10000	0	-0.01	47	47
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.01	0.025	-10000	0	-0.05	49	49
G2 phase of mitotic cell cycle	-0.002	0.003	-10000	0	-0.008	6	6
STAG2	0.015	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.011	-10000	0	-10000	0	0
spindle elongation	-0.019	0.047	-10000	0	-0.096	49	49
ODF2	0.012	0.003	-10000	0	-10000	0	0
BUB1	-0.012	0.027	-10000	0	-10000	0	0
TPT1	-0.004	0.025	-10000	0	-10000	0	0
CDC25C	-0.046	0.051	-10000	0	-10000	0	0
CDC25B	0.001	0.076	-10000	0	-0.48	6	6
SGOL1	-0.05	0.061	-10000	0	-0.11	112	112
RHOA	0.015	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.072	0.1	-10000	0	-0.24	29	29
CDC14B	0.01	0.029	-10000	0	-0.44	1	1
CDC20	-0.28	0.24	-10000	0	-0.47	143	143
PLK1/PBIP1	-0.03	0.056	-10000	0	-0.26	10	10
mitosis	-0.003	0.009	0.018	16	-0.017	62	78
FBXO5	-0.012	0.046	-10000	0	-0.26	2	2
CDC2	-0.003	0.005	-10000	0	-0.011	37	37
NDC80	-0.15	0.23	-10000	0	-0.47	81	81
metaphase plate congression	-0.008	0.03	-10000	0	-10000	0	0
ERCC6L	-0.11	0.15	-10000	0	-0.4	38	38
NLP/gamma Tubulin	-0.006	0.026	-10000	0	-0.091	2	2
microtubule cytoskeleton organization	-0.004	0.025	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	-0.001	0.002	-10000	0	-10000	0	0
PPP1R12A	0.014	0.001	-10000	0	-10000	0	0
interphase	-0.001	0.002	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.23	0.19	-10000	0	-0.32	178	178
GRASP65/GM130/RAB1/GTP/PLK1	-0.009	0.025	-10000	0	-10000	0	0
RAB1A	0.015	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.013	0.046	-10000	0	-0.2	2	2
mitotic prometaphase	-0.002	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.014	0.047	-10000	0	-0.29	1	1
microtubule-based process	-0.2	0.14	-10000	0	-0.28	177	177
Golgi organization	-0.019	0.047	-10000	0	-0.096	49	49
Cohesin/SA2	-0.023	0.032	-10000	0	-0.16	1	1
PPP1CB/MYPT1	0.013	0.01	-10000	0	-10000	0	0
KIF20A	-0.34	0.22	-10000	0	-0.47	177	177
APC/C/CDC20	-0.16	0.16	-10000	0	-0.29	143	143
PPP2R1A	0.015	0	-10000	0	-10000	0	0
chromosome segregation	-0.03	0.056	-10000	0	-0.25	10	10
PRC1	-0.086	0.2	-10000	0	-0.47	50	50
ECT2	-0.038	0.11	-10000	0	-0.31	29	29
C13orf34	-0.011	0.043	-10000	0	-0.21	2	2
NUDC	-0.008	0.03	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.071	0.1	-10000	0	-0.2	83	83
spindle assembly	-0.012	0.038	-10000	0	-0.11	3	3
spindle stabilization	-0.004	0.025	-10000	0	-0.093	1	1
APC/C/HCDH1	0.018	0.024	-10000	0	-0.36	1	1
MKLP2/PLK1	-0.2	0.14	-10000	0	-0.28	177	177
CCNB1	-0.16	0.23	-10000	0	-0.47	88	88
PPP1CB	0.014	0.001	-10000	0	-10000	0	0
BTRC	0.015	0	-10000	0	-10000	0	0
ROCK2	-0.009	0.069	-10000	0	-0.43	5	5
TUBG1	-0.004	0.025	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.072	0.096	-10000	0	-0.24	29	29
MLF1IP	-0.005	0.068	-10000	0	-0.35	9	9
INCENP	0.012	0.031	-10000	0	-0.47	1	1

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.34	0.54	-9999	-1.3	45	45
IL23A	-0.29	0.46	-9999	-1.1	40	40
NF kappa B1 p50/RelA/I kappa B alpha	-0.32	0.4	-9999	-1	47	47
positive regulation of T cell mediated cytotoxicity	-0.32	0.5	-9999	-1.1	49	49
ITGA3	-0.27	0.44	-9999	-1	40	40
IL17F	-0.18	0.31	-9999	-0.67	42	42
IL12B	-0.008	0.08	-9999	-0.47	6	6
STAT1 (dimer)	-0.3	0.47	-9999	-1.1	47	47
CD4	-0.28	0.44	-9999	-1	44	44
IL23	-0.29	0.43	-9999	-1.1	38	38
IL23R	-0.03	0.088	-9999	-10000	0	0
IL1B	-0.31	0.49	-9999	-1.1	46	46
T-helper cell lineage commitment	0	0	-9999	-10000	0	0
IL24	-0.3	0.44	-9999	-1	46	46
TYK2	0.008	0.02	-9999	-10000	0	0
STAT4	-0.012	0.12	-9999	-0.58	11	11
STAT3	0.015	0	-9999	-10000	0	0
IL18RAP	-0.019	0.13	-9999	-0.57	13	13
IL12RB1	-0.027	0.13	-9999	-0.51	16	16
PIK3CA	0.015	0	-9999	-10000	0	0
IL12Rbeta1/TYK2	-0.018	0.097	-9999	-0.36	16	16
IL23R/JAK2	-0.036	0.11	-9999	-0.47	1	1
positive regulation of chronic inflammatory response	-0.32	0.5	-9999	-1.1	49	49
natural killer cell activation	0.003	0.008	-9999	-10000	0	0
JAK2	0.011	0.047	-9999	-0.61	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
NFKB1	0.013	0.004	-9999	-10000	0	0
RELA	0.013	0.004	-9999	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.27	0.41	-9999	-1	40	40
ALOX12B	-0.28	0.44	-9999	-1	45	45
CXCL1	-0.34	0.53	-9999	-1.2	49	49
T cell proliferation	-0.32	0.5	-9999	-1.1	49	49
NFKBIA	0.013	0.004	-9999	-10000	0	0
IL17A	-0.12	0.25	-9999	-0.54	33	33
PI3K	-0.32	0.41	-9999	-1	49	49
IFNG	-0.016	0.032	-9999	-0.092	3	3
STAT3 (dimer)	-0.31	0.38	-9999	-0.99	46	46
IL18R1	0.008	0.054	-9999	-0.57	2	2
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.31	-9999	-0.73	37	37
IL18/IL18R	0	0.11	-9999	-0.38	17	17
macrophage activation	-0.017	0.017	-9999	-0.043	39	39
TNF	-0.29	0.46	-9999	-1	46	46
STAT3/STAT4	-0.34	0.42	-9999	-1	50	50
STAT4 (dimer)	-0.31	0.49	-9999	-1.1	49	49
IL18	0.003	0.075	-9999	-0.57	4	4
IL19	-0.28	0.43	-9999	-1	42	42
STAT5A (dimer)	-0.3	0.48	-9999	-1.1	47	47
STAT1	0.011	0.044	-9999	-0.47	2	2
SOCS3	-0.042	0.17	-9999	-0.58	23	23
CXCL9	-0.32	0.46	-9999	-1.1	46	46
MPO	-0.27	0.43	-9999	-1	43	43
positive regulation of humoral immune response	-0.32	0.5	-9999	-1.1	49	49
IL23/IL23R/JAK2/TYK2	-0.33	0.54	-9999	-1.2	49	49
IL6	-0.61	0.69	-9999	-1.3	114	114
STAT5A	0.012	0.038	-9999	-0.58	1	1
IL2	0.005	0.012	-9999	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.003	0.008	-9999	-10000	0	0
CD3E	-0.32	0.52	-9999	-1.2	46	46
keratinocyte proliferation	-0.32	0.5	-9999	-1.1	49	49
NOS2	-0.29	0.46	-9999	-1.1	43	43

×

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.18	0.42	-9999	-0.91	35	35
HDAC7	0.017	0.001	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.11	0.35	-9999	-0.74	29	29
SMAD4	0.016	0	-9999	-10000	0	0
ID2	-0.18	0.42	-9999	-0.92	36	36
AP1	-0.12	0.22	-9999	-0.44	74	74
ABCG2	-0.18	0.43	-9999	-0.92	37	37
HIF1A	-0.014	0.082	-9999	-0.62	1	1
TFF3	-0.26	0.48	-9999	-1	49	49
GATA2	-0.008	0.11	-9999	-0.52	11	11
AKT1	-0.013	0.085	-9999	-10000	0	0
response to hypoxia	-0.035	0.091	-9999	-0.23	8	8
MCL1	-0.18	0.42	-9999	-0.92	34	34
NDRG1	-0.18	0.42	-9999	-0.93	35	35
SERPINE1	-0.18	0.42	-9999	-0.91	38	38
FECH	-0.18	0.42	-9999	-0.89	38	38
FURIN	-0.18	0.42	-9999	-0.91	35	35
NCOA2	-0.017	0.13	-9999	-0.58	13	13
EP300	-0.004	0.12	-9999	-0.32	12	12
HMOX1	-0.18	0.42	-9999	-0.92	35	35
BHLHE40	-0.18	0.42	-9999	-0.92	36	36
BHLHE41	-0.19	0.43	-9999	-0.92	39	39
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.002	0.077	-9999	-0.39	1	1
ENG	0.032	0.095	-9999	-0.35	1	1
JUN	0.001	0.092	-9999	-0.58	6	6
RORA	-0.18	0.42	-9999	-0.91	36	36
ABCB1	-0.18	0.4	-9999	-1.2	29	29
TFRC	-0.18	0.42	-9999	-0.93	35	35
CXCR4	-0.18	0.42	-9999	-0.92	36	36
TF	-0.21	0.44	-9999	-0.94	41	41
CITED2	-0.18	0.42	-9999	-0.91	35	35
HIF1A/ARNT	-0.17	0.5	-9999	-0.98	42	42
LDHA	-0.023	0.043	-9999	-10000	0	0
ETS1	-0.18	0.42	-9999	-0.88	39	39
PGK1	-0.18	0.42	-9999	-0.91	35	35
NOS2	-0.2	0.44	-9999	-0.96	39	39
ITGB2	-0.19	0.43	-9999	-0.93	35	35
ALDOA	-0.18	0.42	-9999	-0.9	36	36
Cbp/p300/CITED2	-0.16	0.44	-9999	-0.98	31	31
FOS	-0.17	0.27	-9999	-0.58	74	74
HK2	-0.18	0.42	-9999	-0.92	34	34
SP1	0.017	0.028	-9999	-10000	0	0
GCK	-0.068	0.36	-9999	-1.5	13	13
HK1	-0.18	0.42	-9999	-0.91	35	35
NPM1	-0.18	0.42	-9999	-0.91	35	35
EGLN1	-0.18	0.42	-9999	-0.91	35	35
CREB1	0.024	0	-9999	-10000	0	0
PGM1	-0.18	0.42	-9999	-0.91	35	35
SMAD3	0.016	0	-9999	-10000	0	0
EDN1	-0.049	0.21	-9999	-0.75	6	6
IGFBP1	-0.2	0.42	-9999	-0.89	40	40
VEGFA	-0.072	0.32	-9999	-0.7	16	16
HIF1A/JAB1	-0.006	0.045	-9999	-0.45	1	1
CP	-0.27	0.48	-9999	-0.99	50	50
CXCL12	-0.27	0.5	-9999	-0.97	62	62
COPS5	0.015	0.005	-9999	-10000	0	0
SMAD3/SMAD4	0.006	0.011	-9999	-10000	0	0
BNIP3	-0.18	0.42	-9999	-0.92	35	35
EGLN3	-0.18	0.42	-9999	-0.93	34	34
CA9	-0.32	0.48	-9999	-0.98	56	56
TERT	-0.25	0.46	-9999	-0.99	45	45
ENO1	-0.18	0.42	-9999	-0.92	34	34
PFKL	-0.18	0.42	-9999	-0.9	36	36
NCOA1	0.015	0.002	-9999	-10000	0	0
ADM	-0.18	0.42	-9999	-0.92	35	35
ARNT	-0.013	0.072	-9999	-10000	0	0
HNF4A	-0.042	0.15	-9999	-0.48	26	26
ADFP	-0.19	0.41	-9999	-0.88	42	42
SLC2A1	-0.073	0.32	-9999	-0.7	17	17
LEP	-0.22	0.45	-9999	-0.95	46	46
HIF1A/ARNT/Cbp/p300	-0.12	0.36	-9999	-0.76	30	30
EPO	-0.086	0.29	-9999	-0.8	7	7
CREBBP	-0.004	0.12	-9999	-0.32	12	12
HIF1A/ARNT/Cbp/p300/HDAC7	-0.099	0.35	-9999	-0.74	27	27
PFKFB3	-0.18	0.42	-9999	-0.91	36	36
NT5E	-0.2	0.45	-9999	-0.94	43	43

×

Plasma membrane estrogen 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
GNB1/GNG2	-0.019	0.12	-10000	0	-0.3	39	39
ER alpha/Gai/GDP/Gbeta gamma	-0.17	0.33	-10000	0	-0.66	59	59
AKT1	-0.12	0.34	-10000	0	-0.9	39	39
PIK3CA	0.015	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.13	0.35	-10000	0	-0.93	39	39
mol:Ca2+	-0.049	0.19	-10000	0	-0.43	40	40
IGF1R	0.01	0.054	-10000	0	-0.58	2	2
E2/ER alpha (dimer)/Striatin	-0.057	0.13	-10000	0	-0.35	39	39
SHC1	0.013	0.031	-10000	0	-0.47	1	1
apoptosis	0.11	0.32	0.85	39	-10000	0	39
RhoA/GTP	-0.04	0.093	-10000	0	-0.46	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.16	0.25	-10000	0	-0.54	59	59
regulation of stress fiber formation	-0.012	0.099	0.38	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.058	0.13	-10000	0	-0.35	40	40
KRAS	0.013	0.031	-10000	0	-0.47	1	1
G13/GTP	-0.036	0.12	-10000	0	-0.32	39	39
pseudopodium formation	0.012	0.099	-10000	0	-0.38	2	2
E2/ER alpha (dimer)/PELP1	-0.057	0.13	-10000	0	-0.35	39	39
GRB2	0.015	0	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.58	1	1
GNAO1	-0.15	0.27	-10000	0	-0.58	68	68
HRAS	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.11	0.28	-10000	0	-0.7	39	39
E2/ER beta (dimer)	0.01	0.022	-10000	0	-0.34	1	1
mol:GDP	-0.065	0.15	-10000	0	-0.4	39	39
mol:NADP	-0.11	0.28	-10000	0	-0.7	39	39
PIK3R1	0.015	0	-10000	0	-10000	0	0
mol:IP3	-0.052	0.2	-10000	0	-0.45	40	40
IGF-1R heterotetramer	0.01	0.054	-10000	0	-0.58	2	2
PLCB1	-0.06	0.2	-10000	0	-0.47	40	40
PLCB2	-0.053	0.19	-10000	0	-0.45	40	40
IGF1	-0.25	0.29	-10000	0	-0.58	106	106
mol:L-citrulline	-0.11	0.28	-10000	0	-0.7	39	39
RHOA	0.015	0	-10000	0	-10000	0	0
Gai/GDP	-0.23	0.4	-10000	0	-0.85	68	68
JNK cascade	0.009	0.022	-10000	0	-0.34	1	1
BCAR1	0.015	0	-10000	0	-10000	0	0
ESR2	0.013	0.031	-10000	0	-0.47	1	1
GNAQ	0.015	0	-10000	0	-10000	0	0
ESR1	-0.081	0.22	-10000	0	-0.58	39	39
Gq family/GDP/Gbeta gamma	-0.006	0.11	-10000	0	-0.48	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.024	0.12	-10000	0	-0.3	27	27
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.16	0.25	-10000	0	-0.54	60	60
GNAZ	-0.11	0.24	-10000	0	-0.58	52	52
E2/ER alpha (dimer)	-0.06	0.16	-10000	0	-0.42	39	39
STRN	0.015	0	-10000	0	-10000	0	0
GNAL	-0.22	0.29	-10000	0	-0.58	96	96
PELP1	0.015	0	-10000	0	-10000	0	0
MAPK11	0.02	0.019	-10000	0	-0.28	1	1
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.58	1	1
HBEGF	-0.18	0.28	-10000	0	-0.6	61	61
cAMP biosynthetic process	-0.16	0.18	-10000	0	-0.34	113	113
SRC	-0.15	0.31	-10000	0	-0.61	59	59
PI3K	0.022	0	-10000	0	-10000	0	0
GNB1	0.015	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.057	0.13	-10000	0	-0.35	39	39
SOS1	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.21	0.24	-10000	0	-0.49	88	88
Gs family/GTP	-0.16	0.19	-10000	0	-0.34	113	113
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.027	0.017	-10000	0	-0.24	1	1
vasodilation	-0.1	0.26	-10000	0	-0.65	39	39
mol:DAG	-0.052	0.2	-10000	0	-0.45	40	40
Gs family/GDP/Gbeta gamma	-0.14	0.18	-10000	0	-0.45	40	40
MSN	0.011	0.1	-10000	0	-0.41	2	2
Gq family/GTP	-0.064	0.19	-10000	0	-0.47	40	40
mol:PI-3-4-5-P3	-0.12	0.34	-10000	0	-0.88	39	39
NRAS	0.015	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.1	0.26	0.65	39	-10000	0	39
GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
RhoA/GDP	-0.061	0.14	-10000	0	-0.37	39	39
NOS3	-0.12	0.3	-10000	0	-0.75	39	39
GNA11	0.012	0.038	-10000	0	-0.58	1	1
MAPKKK cascade	-0.098	0.28	-10000	0	-0.7	39	39
E2/ER alpha (dimer)/PELP1/Src	-0.17	0.26	-10000	0	-0.58	59	59
ruffle organization	0.012	0.099	-10000	0	-0.38	2	2
ROCK2	0.002	0.11	-10000	0	-0.46	2	2
GNA14	-0.079	0.22	-10000	0	-0.58	38	38
GNA15	0.01	0.054	-10000	0	-0.58	2	2
GNA13	0.015	0	-10000	0	-10000	0	0
MMP9	-0.2	0.28	-10000	0	-0.61	59	59
MMP2	-0.16	0.3	-10000	0	-0.64	54	54

×

Calcium signaling in the CD4+ TCR 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
NFATC1	-0.012	0.089	-9999	-0.38	12	12
NFATC2	-0.058	0.14	-9999	-0.38	40	40
NFATC3	0.007	0.028	-9999	-10000	0	0
CD40LG	-0.26	0.34	-9999	-0.72	65	65
PTGS2	-0.29	0.36	-9999	-0.7	84	84
JUNB	0.007	0.066	-9999	-0.58	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.005	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.005	0.011	-9999	-10000	0	0
CALM1	0.011	0.008	-9999	-10000	0	0
JUN	-0.004	0.094	-9999	-0.59	6	6
mol:Ca2+	-0.008	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.003	0.004	-9999	-10000	0	0
FOSL1	-0.029	0.16	-9999	-0.58	18	18
CREM	0.015	0	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.12	0.17	-9999	-0.46	37	37
FOS	-0.17	0.28	-9999	-0.59	74	74
IFNG	-0.26	0.33	-9999	-0.68	68	68
AP-1/NFAT1-c-4	-0.28	0.38	-9999	-0.72	80	80
FASLG	-0.25	0.33	-9999	-0.7	62	62
NFAT1-c-4/ICER1	-0.08	0.15	-9999	-0.4	34	34
IL2RA	-0.25	0.34	-9999	-0.73	61	61
FKBP12/FK506	0.011	0	-9999	-10000	0	0
CSF2	-0.26	0.33	-9999	-0.67	75	75
JunB/Fra1/NFAT1-c-4	-0.1	0.17	-9999	-0.44	36	36
IL4	-0.24	0.3	-9999	-0.66	57	57
IL2	-0.008	0.019	-9999	-10000	0	0
IL3	-0.024	0.023	-9999	-10000	0	0
FKBP1A	0.015	0	-9999	-10000	0	0
BATF3	0.008	0.062	-9999	-0.54	3	3
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.015	0.002	-9999	-10000	0	0

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.19	0.26	-9999	-0.5	89	89
fibroblast growth factor receptor signaling pathway	-0.18	0.26	-9999	-0.5	89	89
LAMA1	-0.086	0.2	-9999	-0.49	48	48
PRNP	0.002	0.084	-9999	-0.58	5	5
GPC1/SLIT2	-0.18	0.22	-9999	-0.42	110	110
SMAD2	0.034	0.031	-9999	-0.3	2	2
GPC1/PrPc/Cu2+	-0.007	0.05	-9999	-0.35	5	5
GPC1/Laminin alpha1	-0.051	0.15	-9999	-0.34	48	48
TDGF1	0.006	0.032	-9999	-0.47	1	1
CRIPTO/GPC1	0.016	0.023	-9999	-0.33	1	1
APP/GPC1	0.022	0	-9999	-10000	0	0
mol:NO	0	0	-9999	-10000	0	0
YES1	0.025	0.019	-9999	-0.27	1	1
FLT1	0.015	0	-9999	-10000	0	0
GPC1/TGFB/TGFBR1/TGFBR2	-0.003	0.031	-9999	-0.34	2	2
SERPINC1	-0.012	0.11	-9999	-0.47	12	12
FYN	0.022	0.039	-9999	-0.32	3	3
FGR	0.024	0.031	-9999	-0.31	2	2
positive regulation of MAPKKK cascade	0.021	0.071	-9999	-0.38	1	1
SLIT2	-0.26	0.29	-9999	-0.58	110	110
GPC1/NRG	-0.08	0.18	-9999	-0.39	59	59
NRG1	-0.12	0.24	-9999	-0.55	59	59
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0	0	-9999	-10000	0	0
LYN	0.025	0.019	-9999	-0.27	1	1
mol:Spermine	0.013	0	-9999	-10000	0	0
cell growth	-0.18	0.26	-9999	-0.5	89	89
BMP signaling pathway	-0.015	0	-9999	-10000	0	0
SRC	0.025	0.019	-9999	-0.27	1	1
TGFBR1	0.015	0	-9999	-10000	0	0
mol:Cu2+	0	0	-9999	-10000	0	0
PLA2G2A	-0.26	0.29	-9999	-0.58	110	110
GPC1	0.015	0	-9999	-10000	0	0
TGFBR1 (dimer)	0.015	0	-9999	-10000	0	0
VEGFA	0.015	0	-9999	-10000	0	0
BLK	-0.022	0.12	-9999	-0.33	32	32
HCK	0.011	0.073	-9999	-0.32	11	11
FGF2	-0.17	0.28	-9999	-0.58	77	77
FGFR1	-0.12	0.25	-9999	-0.58	55	55
VEGFR1 homodimer	0.015	0	-9999	-10000	0	0
TGFBR2	0.01	0.054	-9999	-0.58	2	2
cell death	0.022	0	-9999	-10000	0	0
ATIII/GPC1	0.003	0.076	-9999	-0.33	12	12
PLA2G2A/GPC1	-0.18	0.22	-9999	-0.41	110	110
LCK	0.021	0.043	-9999	-0.31	4	4
neuron differentiation	-0.08	0.18	-9999	-0.39	59	59
PrPc/Cu2+	0.002	0.062	-9999	-0.42	5	5
APP	0.015	0	-9999	-10000	0	0
TGFBR2 (dimer)	0.01	0.054	-9999	-0.58	2	2

×

PDGFR-alpha signaling pathway

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
PDGFRA	-0.084	0.22	-9999	-0.6	36	36
PDGF/PDGFRA/CRKL	-0.05	0.16	-9999	-0.43	37	37
positive regulation of JUN kinase activity	-0.042	0.11	-9999	-0.3	36	36
CRKL	0.011	0.044	-9999	-0.47	2	2
PDGF/PDGFRA/Caveolin-3	-0.056	0.16	-9999	-0.43	36	36
AP1	-0.34	0.47	-9999	-1	74	74
mol:IP3	-0.057	0.17	-9999	-0.44	36	36
PLCG1	-0.057	0.17	-9999	-0.45	36	36
PDGF/PDGFRA/alphaV Integrin	-0.049	0.16	-9999	-0.43	36	36
RAPGEF1	0.015	0	-9999	-10000	0	0
CRK	0.015	0	-9999	-10000	0	0
mol:Ca2+	-0.056	0.16	-9999	-0.44	36	36
CAV3	0.004	0.007	-9999	-10000	0	0
CAV1	-0.01	0.12	-9999	-0.58	10	10
SHC/Grb2/SOS1	-0.017	0.12	-9999	-0.3	36	36
PDGF/PDGFRA/Shf	-0.054	0.17	-9999	-0.44	38	38
FOS	-0.3	0.48	-9999	-1	74	74
JUN	-0.032	0.079	-9999	-0.49	6	6
oligodendrocyte development	-0.049	0.16	-9999	-0.43	36	36
GRB2	0.015	0	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
mol:DAG	-0.057	0.17	-9999	-0.44	36	36
PDGF/PDGFRA	-0.084	0.22	-9999	-0.6	36	36
actin cytoskeleton reorganization	-0.048	0.16	-9999	-0.42	36	36
SRF	0.032	0.012	-9999	-10000	0	0
SHC1	0.013	0.031	-9999	-0.47	1	1
PI3K	-0.049	0.12	-9999	-0.35	36	36
PDGF/PDGFRA/Crk/C3G	-0.049	0.12	-9999	-0.35	36	36
JAK1	-0.045	0.16	-9999	-0.42	36	36
ELK1/SRF	-0.016	0.13	-9999	-0.32	36	36
SHB	0.015	0	-9999	-10000	0	0
SHF	0.005	0.076	-9999	-0.58	4	4
CSNK2A1	0.021	0.028	-9999	-10000	0	0
GO:0007205	-0.061	0.18	-9999	-0.47	36	36
SOS1	0.015	0	-9999	-10000	0	0
Ras protein signal transduction	-0.042	0.11	-9999	-0.3	36	36
PDGF/PDGFRA/SHB	-0.048	0.16	-9999	-0.42	36	36
PDGF/PDGFRA/Caveolin-1	-0.065	0.18	-9999	-0.46	42	42
ITGAV	0.012	0.038	-9999	-0.58	1	1
ELK1	-0.055	0.16	-9999	-0.42	36	36
PIK3CA	0.015	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.048	0.16	-9999	-0.42	36	36
JAK-STAT cascade	-0.045	0.16	-9999	-0.42	36	36
cell proliferation	-0.054	0.17	-9999	-0.44	38	38

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.02	0.028	-9999	-0.42	1	1
alphaV beta3 Integrin	-0.14	0.21	-9999	-0.42	82	82
PTK2	-0.094	0.23	-9999	-0.55	36	36
IGF1R	0.01	0.054	-9999	-0.58	2	2
PI4KB	0.015	0	-9999	-10000	0	0
MFGE8	0.015	0	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
CDKN1B	-0.16	0.28	-9999	-0.74	40	40
VEGFA	0.015	0	-9999	-10000	0	0
ILK	-0.16	0.28	-9999	-0.74	40	40
ROCK1	0.015	0	-9999	-10000	0	0
AKT1	-0.12	0.27	-9999	-0.69	40	40
PTK2B	0.01	0.1	-9999	-0.3	23	23
alphaV/beta3 Integrin/JAM-A	-0.14	0.26	-9999	-0.65	38	38
CBL	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.033	0.11	-9999	-0.36	22	22
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.12	0.18	-9999	-0.32	109	109
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.016	0.13	-9999	-0.45	11	11
alphaV/beta3 Integrin/Syndecan-1	-0.037	0.11	-9999	-0.36	25	25
PI4KA	0.015	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.25	0.27	-9999	-0.61	75	75
PI4 Kinase	0.022	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.14	0.15	-9999	-0.29	121	121
RPS6KB1	-0.2	0.28	-9999	-0.57	75	75
TLN1	0.015	0	-9999	-10000	0	0
MAPK3	-0.26	0.4	-9999	-0.78	82	82
GPR124	-0.039	0.17	-9999	-0.58	22	22
MAPK1	-0.26	0.4	-9999	-0.78	82	82
PXN	0.015	0	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.13	0.2	-9999	-0.39	80	80
cell adhesion	-0.031	0.099	-9999	-0.34	22	22
ANGPTL3	0.011	0.007	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Src	-0.001	0.022	-9999	-0.34	1	1
IGF-1R heterotetramer	0.01	0.054	-9999	-0.58	2	2
Rac1/GDP	0.011	0	-9999	-10000	0	0
TGFBR2	0.01	0.054	-9999	-0.58	2	2
ITGB3	-0.039	0.17	-9999	-0.58	22	22
IGF1	-0.25	0.29	-9999	-0.58	106	106
RAC1	0.015	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.063	0.17	-9999	-0.45	34	34
apoptosis	0.012	0.038	-9999	-0.57	1	1
CD47	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.033	0.11	-9999	-0.36	22	22
VCL	0.012	0.038	-9999	-0.58	1	1
alphaV/beta3 Integrin/Del1	-0.071	0.18	-9999	-0.46	37	37
CSF1	-0.005	0.11	-9999	-0.58	8	8
PIK3C2A	-0.16	0.28	-9999	-0.74	40	40
PI4 Kinase/Pyk2	-0.14	0.21	-9999	-0.55	39	39
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.004	0.11	-9999	-0.33	22	22
FAK1/Vinculin	-0.066	0.18	-9999	-0.42	37	37
alphaV beta3/Integrin/ppsTEM5	-0.064	0.17	-9999	-0.45	34	34
RHOA	0.015	0	-9999	-10000	0	0
VTN	-0.086	0.22	-9999	-0.57	41	41
BCAR1	0.015	0	-9999	-10000	0	0
FGF2	-0.17	0.28	-9999	-0.58	77	77
F11R	-0.12	0.2	-9999	-0.42	77	77
alphaV/beta3 Integrin/Lactadherin	-0.033	0.11	-9999	-0.36	22	22
alphaV/beta3 Integrin/TGFBR2	-0.036	0.11	-9999	-0.37	23	23
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.025	0.065	-9999	-0.31	9	9
HSP90AA1	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.004	0.1	-9999	-0.33	22	22
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.029	0.14	-9999	-0.51	20	20
alphaV/beta3 Integrin/Pyk2	0.011	0.11	-9999	-0.31	23	23
SDC1	0.007	0.066	-9999	-0.58	3	3
VAV3	0.024	0.075	-9999	-0.28	11	11
PTPN11	0.015	0	-9999	-10000	0	0
IRS1	0.002	0.084	-9999	-0.58	5	5
FAK1/Paxillin	-0.065	0.18	-9999	-0.42	36	36
cell migration	-0.051	0.17	-9999	-0.41	25	25
ITGAV	0.012	0.038	-9999	-0.58	1	1
PI3K	-0.15	0.22	-9999	-0.59	38	38
SPP1	-0.19	0.24	-9999	-0.47	100	100
KDR	0.012	0.038	-9999	-0.58	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.012	0.038	-9999	-0.58	1	1
COL4A3	-0.15	0.26	-9999	-0.57	68	68
angiogenesis	-0.26	0.39	-9999	-0.76	83	83
Rac1/GTP	0.029	0.069	-9999	-10000	0	0
EDIL3	-0.052	0.19	-9999	-0.58	27	27
cell proliferation	-0.036	0.11	-9999	-0.37	23	23

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.1	0.16	-10000	0	-0.3	96	96
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.087	0.16	-10000	0	-0.34	64	64
GNB1/GNG2	-0.001	0.023	-10000	0	-0.35	1	1
GNB1	0.015	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0	-10000	0	-10000	0	0
Gs family/GTP	-0.13	0.17	-10000	0	-0.33	96	96
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	0.034	0.042	0.085	96	-10000	0	96
GNAL	-0.22	0.29	-10000	0	-0.58	96	96
GNG2	0.012	0.038	-10000	0	-0.58	1	1
CRH	-0.12	0.22	-10000	0	-0.48	64	64
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.041	-10000	0	-0.36	3	3
MAPK11	0.01	0	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.12	0.22	-9999	-0.56	30	30
MAP3K8	0.004	0.066	-9999	-0.58	3	3
FOS	-0.09	0.17	-9999	-0.45	28	28
PRKCA	0.011	0.007	-9999	-10000	0	0
PTPN7	-0.002	0.085	-9999	-0.53	6	6
HRAS	0.014	0.002	-9999	-10000	0	0
PRKCB	-0.16	0.27	-9999	-0.58	69	69
NRAS	0.014	0.002	-9999	-10000	0	0
RAS family/GTP	0.02	0.023	-9999	-0.26	1	1
MAPK3	-0.047	0.12	-9999	-0.5	5	5
MAP2K1	-0.11	0.22	-9999	-0.44	69	69
ELK1	0.009	0.01	-9999	-10000	0	0
BRAF	-0.11	0.2	-9999	-0.43	69	69
mol:GTP	-0.001	0.003	-9999	-0.005	74	74
MAPK1	-0.047	0.12	-9999	-0.5	5	5
RAF1	-0.11	0.2	-9999	-0.43	69	69
KRAS	0.012	0.032	-9999	-0.48	1	1

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.015	0	-9999	-10000	0	0
CCL5	-0.017	0.13	-9999	-0.54	14	14
SDCBP	0.015	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.11	0.13	-9999	-0.32	36	36
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.098	0.12	-9999	-0.37	15	15
Syndecan-1/Syntenin	-0.098	0.12	-9999	-0.37	15	15
MAPK3	-0.074	0.11	-9999	-0.37	9	9
HGF/MET	-0.083	0.18	-9999	-0.41	59	59
TGFB1/TGF beta receptor Type II	0.015	0	-9999	-10000	0	0
BSG	0.015	0	-9999	-10000	0	0
keratinocyte migration	-0.097	0.12	-9999	-0.36	15	15
Syndecan-1/RANTES	-0.11	0.14	-9999	-0.43	23	23
Syndecan-1/CD147	-0.086	0.12	-9999	-0.36	14	14
Syndecan-1/Syntenin/PIP2	-0.094	0.12	-9999	-0.36	15	15
LAMA5	0.015	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.1	0.099	-9999	-0.35	15	15
MMP7	-0.11	0.22	-9999	-0.5	57	57
HGF	-0.13	0.25	-9999	-0.57	59	59
Syndecan-1/CASK	-0.11	0.12	-9999	-0.31	36	36
Syndecan-1/HGF/MET	-0.16	0.17	-9999	-0.44	46	46
regulation of cell adhesion	-0.064	0.11	-9999	-0.39	6	6
HPSE	-0.037	0.15	-9999	-0.48	25	25
positive regulation of cell migration	-0.11	0.13	-9999	-0.32	36	36
SDC1	-0.11	0.13	-9999	-0.33	36	36
Syndecan-1/Collagen	-0.11	0.13	-9999	-0.32	36	36
PPIB	0.015	0	-9999	-10000	0	0
MET	0.015	0	-9999	-10000	0	0
PRKACA	0.015	0	-9999	-10000	0	0
MMP9	-0.13	0.22	-9999	-0.48	70	70
MAPK1	-0.074	0.11	-9999	-0.37	9	9
homophilic cell adhesion	-0.11	0.12	-9999	-0.32	36	36
MMP1	-0.27	0.24	-9999	-0.47	140	140

×

BMP receptor signaling

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
BMP7/BMPR2/BMPR1A-1B/FS	-0.15	0.22	-9999	-0.57	29	29
SMAD6-7/SMURF1	-0.004	0.036	-9999	-0.32	3	3
NOG	-0.026	0.13	-9999	-0.47	19	19
SMAD9	-0.14	0.25	-9999	-0.57	58	58
SMAD4	0.015	0	-9999	-10000	0	0
SMAD5	-0.038	0.11	-9999	-0.34	9	9
BMP7/USAG1	-0.28	0.26	-9999	-0.48	145	145
SMAD5/SKI	-0.028	0.1	-9999	-0.36	5	5
SMAD1	0.042	0.022	-9999	-10000	0	0
BMP2	-0.057	0.19	-9999	-0.58	29	29
SMAD1/SMAD1/SMAD4	-0.002	0.021	-9999	-10000	0	0
BMPR1A	0.015	0	-9999	-10000	0	0
BMPR1B	-0.077	0.19	-9999	-0.48	44	44
BMPR1A-1B/BAMBI	-0.08	0.16	-9999	-0.45	23	23
AHSG	-0.029	0.12	-9999	-0.47	17	17
CER1	0.004	0.006	-9999	-10000	0	0
BMP2-4/CER1	-0.055	0.13	-9999	-0.35	38	38
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.069	0.15	-9999	-0.37	23	23
BMP2-4 (homodimer)	-0.046	0.16	-9999	-0.41	38	38
RGMB	0.015	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	-0.016	0.11	-9999	-0.31	5	5
RGMA	-0.16	0.27	-9999	-0.58	69	69
SMURF1	0.015	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.069	0.14	-9999	-0.35	26	26
BMP2-4/USAG1	-0.17	0.21	-9999	-0.39	106	106
SMAD6/SMURF1/SMAD5	-0.028	0.1	-9999	-0.36	5	5
SOSTDC1	-0.2	0.28	-9999	-0.57	85	85
BMP7/BMPR2/BMPR1A-1B	-0.13	0.2	-9999	-0.36	90	90
SKI	0.015	0	-9999	-10000	0	0
BMP6 (homodimer)	0.01	0.049	-9999	-0.52	2	2
HFE2	0.006	0.007	-9999	-10000	0	0
ZFYVE16	0.015	0	-9999	-10000	0	0
MAP3K7	0.015	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.086	0.17	-9999	-0.38	55	55
SMAD5/SMAD5/SMAD4	-0.028	0.1	-9999	-0.36	5	5
MAPK1	0.015	0	-9999	-10000	0	0
TAK1/TAB family	-0.072	0.096	-9999	-0.37	12	12
BMP7 (homodimer)	-0.2	0.28	-9999	-0.58	86	86
NUP214	0.015	0	-9999	-10000	0	0
BMP6/FETUA	-0.013	0.094	-9999	-0.33	19	19
SMAD1/SKI	0.049	0.02	-9999	-10000	0	0
SMAD6	0.01	0.049	-9999	-0.52	2	2
CTDSP2	0.015	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.073	0.15	-9999	-0.35	50	50
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.15	0.25	-9999	-0.53	74	74
BMPR2 (homodimer)	0.015	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.044	0.14	-9999	-0.34	44	44
CHRDL1	-0.31	0.29	-9999	-0.58	132	132
ENDOFIN/SMAD1	0.049	0.02	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.002	0.026	-9999	-10000	0	0
SMAD6/SMURF1	0.015	0	-9999	-10000	0	0
BAMBI	-0.038	0.17	-9999	-0.56	22	22
SMURF2	0.015	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.24	0.21	-9999	-0.39	150	150
BMP2-4/GREM1	-0.15	0.17	-9999	-0.33	109	109
SMAD7	0.012	0.038	-9999	-0.58	1	1
SMAD8A/SMAD8A/SMAD4	-0.13	0.24	-9999	-0.53	58	58
SMAD1/SMAD6	0.049	0.02	-9999	-10000	0	0
TAK1/SMAD6	0.022	0	-9999	-10000	0	0
BMP7	-0.2	0.28	-9999	-0.58	86	86
BMP6	0.01	0.049	-9999	-0.52	2	2
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.062	0.13	-9999	-0.33	26	26
PPM1A	0.015	0	-9999	-10000	0	0
SMAD1/SMURF2	0.049	0.02	-9999	-10000	0	0
SMAD7/SMURF1	0.02	0.028	-9999	-0.42	1	1
CTDSPL	0.015	0	-9999	-10000	0	0
PPP1CA	0.015	0	-9999	-10000	0	0
XIAP	0.013	0.031	-9999	-0.47	1	1
CTDSP1	0.015	0	-9999	-10000	0	0
PPP1R15A	0.015	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.1	0.18	-9999	-0.45	34	34
CHRD	-0.041	0.17	-9999	-0.57	23	23
BMPR2	0.015	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.085	0.15	-9999	-0.39	26	26
BMP4	-0.007	0.11	-9999	-0.55	9	9
FST	-0.041	0.17	-9999	-0.55	24	24
BMP2-4/NOG	-0.075	0.16	-9999	-0.37	49	49
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.12	0.19	-9999	-0.52	21	21

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.08	0.16	-9999	-0.42	39	39
alphaM/beta2 Integrin/GPIbA	-0.057	0.12	-9999	-0.41	22	22
alphaM/beta2 Integrin/proMMP-9	-0.13	0.18	-9999	-0.35	80	80
PLAUR	0.015	0	-9999	-10000	0	0
HMGB1	-0.004	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.049	0.11	-9999	-0.39	22	22
AGER	-0.012	0.067	-9999	-0.5	4	4
RAP1A	0.015	0	-9999	-10000	0	0
SELPLG	0.003	0.079	-9999	-0.54	5	5
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.11	0.13	-9999	-0.47	18	18
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.13	0.22	-9999	-0.48	70	70
CYR61	-0.16	0.27	-9999	-0.58	70	70
TLN1	0.015	0	-9999	-10000	0	0
Rap1/GTP	-0.056	0.13	-9999	-0.47	16	16
RHOA	0.015	0	-9999	-10000	0	0
P-selectin oligomer	-0.1	0.24	-9999	-0.58	48	48
MYH2	-0.054	0.15	-9999	-0.42	21	21
MST1R	-0.015	0.12	-9999	-0.54	13	13
leukocyte activation during inflammatory response	-0.12	0.17	-9999	-0.36	70	70
APOB	-0.081	0.21	-9999	-0.57	38	38
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.037	0.17	-9999	-0.58	21	21
JAM3	-0.017	0.13	-9999	-0.58	13	13
GP1BA	0.001	0.079	-9999	-0.49	6	6
alphaM/beta2 Integrin/CTGF	-0.12	0.2	-9999	-0.44	58	58
alphaM/beta2 Integrin	-0.052	0.16	-9999	-0.52	18	18
JAM3 homodimer	-0.017	0.13	-9999	-0.58	13	13
ICAM2	0.012	0.038	-9999	-0.58	1	1
ICAM1	0.005	0.069	-9999	-0.47	5	5
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.052	0.16	-9999	-0.52	18	18
cell adhesion	-0.057	0.12	-9999	-0.41	22	22
NFKB1	-0.14	0.21	-9999	-0.59	16	16
THY1	0.011	0.044	-9999	-0.47	2	2
RhoA/GDP	0.011	0	-9999	-10000	0	0
Lipoprotein(a)	-0.09	0.17	-9999	-0.38	60	60
alphaM/beta2 Integrin/LRP/tPA	-0.058	0.14	-9999	-0.43	26	26
IL6	-0.34	0.42	-9999	-0.78	111	111
ITGB2	-0.028	0.11	-9999	-0.52	11	11
elevation of cytosolic calcium ion concentration	-0.073	0.13	-9999	-0.4	17	17
alphaM/beta2 Integrin/JAM2/JAM3	-0.13	0.21	-9999	-0.42	71	71
JAM2	-0.13	0.25	-9999	-0.58	58	58
alphaM/beta2 Integrin/ICAM1	-0.058	0.13	-9999	-0.37	26	26
alphaM/beta2 Integrin/uPA/Plg	-0.078	0.13	-9999	-0.35	30	30
RhoA/GTP	-0.043	0.15	-9999	-0.44	19	19
positive regulation of phagocytosis	-0.067	0.16	-9999	-0.5	21	21
Ron/MSP	-0.01	0.11	-9999	-0.38	19	19
alphaM/beta2 Integrin/uPAR/uPA	-0.073	0.13	-9999	-0.4	17	17
alphaM/beta2 Integrin/uPAR	-0.049	0.11	-9999	-0.44	16	16
PLAU	-0.054	0.17	-9999	-0.47	34	34
PLAT	-0.016	0.13	-9999	-0.56	13	13
actin filament polymerization	-0.052	0.14	-9999	-0.4	21	21
MST1	0	0.085	-9999	-0.49	7	7
alphaM/beta2 Integrin/lipoprotein(a)	-0.12	0.17	-9999	-0.37	70	70
TNF	-0.13	0.2	-9999	-0.54	16	16
RAP1B	0.015	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.088	0.14	-9999	-0.34	50	50
fibrinolysis	-0.077	0.13	-9999	-0.35	30	30
HCK	-0.009	0.11	-9999	-0.55	10	10
dendritic cell antigen processing and presentation	-0.052	0.16	-9999	-0.52	18	18
VTN	-0.086	0.22	-9999	-0.57	41	41
alphaM/beta2 Integrin/CYR61	-0.15	0.23	-9999	-0.46	77	77
LPA	-0.055	0.18	-9999	-0.56	27	27
LRP1	0.01	0.054	-9999	-0.58	2	2
cell migration	-0.13	0.2	-9999	-0.44	48	48
FN1	-0.029	0.14	-9999	-0.51	20	20
alphaM/beta2 Integrin/Thy1	-0.051	0.12	-9999	-0.38	24	24
MPO	0.01	0.032	-9999	-0.47	1	1
KNG1	0	0	-9999	-10000	0	0
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.032	0.14	-9999	-0.42	18	18
ELA2	0	0	-9999	-10000	0	0
PLG	0.003	0.006	-9999	-10000	0	0
CTGF	-0.096	0.23	-9999	-0.58	45	45
alphaM/beta2 Integrin/Hck	-0.062	0.15	-9999	-0.47	25	25
ITGAM	-0.039	0.14	-9999	-0.59	14	14
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.11	0.18	-9999	-0.39	61	61
HP	-0.039	0.15	-9999	-0.48	25	25
leukocyte adhesion	-0.16	0.2	-9999	-0.48	58	58
SELP	-0.1	0.24	-9999	-0.58	48	48

×

Glucocorticoid receptor regulatory network

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
PCK2	0.013	0.057	-10000	0	-10000	0	0
SMARCC2	0.015	0.013	-10000	0	-10000	0	0
SMARCC1	0.015	0.014	-10000	0	-10000	0	0
TBX21	-0.074	0.19	-10000	0	-0.81	12	12
SUMO2	0.011	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.02	0.044	-10000	0	-0.46	2	2
FKBP4	0.015	0	-10000	0	-10000	0	0
FKBP5	-0.015	0.13	-10000	0	-0.58	12	12
GR alpha/HSP90/FKBP51/HSP90	0.079	0.12	0.28	11	-0.3	1	12
PRL	-0.065	0.12	-10000	0	-0.5	1	1
cortisol/GR alpha (dimer)/TIF2	0.22	0.22	0.47	70	-0.41	2	72
RELA	-0.096	0.12	-10000	0	-0.29	15	15
FGG	0.17	0.2	0.43	36	-0.47	3	39
GR beta/TIF2	0.083	0.14	0.27	22	-0.37	13	35
IFNG	-0.3	0.24	-10000	0	-0.64	51	51
apoptosis	-0.07	0.18	0.41	3	-0.54	8	11
CREB1	0.012	0.031	-10000	0	-10000	0	0
histone acetylation	-0.01	0.13	0.5	1	-0.37	11	12
BGLAP	-0.044	0.1	-10000	0	-0.43	3	3
GR/PKAc	0.1	0.085	0.28	7	-10000	0	7
NF kappa B1 p50/RelA	-0.18	0.23	-10000	0	-0.45	82	82
SMARCD1	0.015	0.014	-10000	0	-10000	0	0
MDM2	0.089	0.083	0.23	22	-0.24	1	23
GATA3	-0.026	0.16	-10000	0	-0.57	19	19
AKT1	0.001	0.006	-10000	0	-10000	0	0
CSF2	-0.077	0.12	-10000	0	-0.5	1	1
GSK3B	0.011	0.007	-10000	0	-10000	0	0
NR1I3	-0.027	0.18	0.46	1	-0.49	5	6
CSN2	0.16	0.14	0.36	32	-10000	0	32
BRG1/BAF155/BAF170/BAF60A	0.039	0.046	-10000	0	-0.31	1	1
NFATC1	-0.014	0.13	-10000	0	-0.58	12	12
POU2F1	0.016	0.011	-10000	0	-10000	0	0
CDKN1A	0.034	0.098	-10000	0	-1.4	1	1
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.039	0.15	-10000	0	-0.48	26	26
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.071	0.12	0.27	9	-10000	0	9
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.17	0.39	0.44	1	-0.84	60	61
JUN	-0.16	0.16	-10000	0	-0.46	32	32
IL4	-0.088	0.15	-10000	0	-0.57	10	10
CDK5R1	-0.019	0.12	-10000	0	-0.48	16	16
PRKACA	0.015	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.23	0.28	-10000	0	-0.53	87	87
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.089	0.11	0.27	10	-10000	0	10
cortisol/GR alpha (monomer)	0.27	0.23	0.54	73	-10000	0	73
NCOA2	-0.017	0.13	-10000	0	-0.58	13	13
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.22	0.28	-10000	0	-0.63	74	74
AP-1/NFAT1-c-4	-0.38	0.32	-10000	0	-0.69	102	102
AFP	-0.13	0.14	-10000	0	-0.55	5	5
SUV420H1	0.015	0	-10000	0	-10000	0	0
IRF1	0.16	0.12	0.39	12	-10000	0	12
TP53	0.037	0.035	-10000	0	-0.5	1	1
PPP5C	0.015	0	-10000	0	-10000	0	0
KRT17	-0.35	0.39	-10000	0	-0.8	71	71
KRT14	-0.22	0.23	-10000	0	-0.5	62	62
TBP	0.024	0.013	-10000	0	-10000	0	0
CREBBP	0.069	0.08	0.31	3	-10000	0	3
HDAC1	0.013	0.008	-10000	0	-10000	0	0
HDAC2	0.018	0.012	-10000	0	-10000	0	0
AP-1	-0.39	0.32	-10000	0	-0.69	103	103
MAPK14	0.011	0.007	-10000	0	-10000	0	0
MAPK10	-0.046	0.17	-10000	0	-0.58	23	23
MAPK11	0.011	0.007	-10000	0	-10000	0	0
KRT5	-0.54	0.54	-10000	0	-1.1	94	94
interleukin-1 receptor activity	0.004	0.012	-10000	0	-10000	0	0
NCOA1	0.018	0.003	-10000	0	-10000	0	0
STAT1	0.02	0.044	-10000	0	-0.46	2	2
CGA	-0.073	0.13	-10000	0	-0.46	7	7
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.12	0.14	0.32	43	-0.5	1	44
MAPK3	0.011	0.007	-10000	0	-10000	0	0
MAPK1	0.011	0.007	-10000	0	-10000	0	0
ICAM1	-0.24	0.24	-10000	0	-0.54	68	68
NFKB1	-0.096	0.12	-10000	0	-0.29	14	14
MAPK8	-0.13	0.14	-10000	0	-0.38	31	31
MAPK9	0.011	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.08	0.18	0.44	2	-0.57	8	10
BAX	0.039	0.032	-10000	0	-10000	0	0
POMC	-0.31	0.33	-10000	0	-0.75	45	45
EP300	0.069	0.08	0.31	3	-10000	0	3
cortisol/GR alpha (dimer)/p53	0.26	0.2	0.48	73	-10000	0	73
proteasomal ubiquitin-dependent protein catabolic process	0.062	0.066	0.22	3	-0.2	1	4
SGK1	0.094	0.26	-10000	0	-1.3	7	7
IL13	-0.23	0.22	-10000	0	-0.61	41	41
IL6	-0.6	0.6	-10000	0	-1.2	114	114
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.21	0.19	-10000	0	-0.64	19	19
IL2	-0.27	0.21	-10000	0	-0.58	51	51
CDK5	0.013	0.003	-10000	0	-10000	0	0
PRKACB	0.012	0.038	-10000	0	-0.58	1	1
HSP90AA1	0.015	0	-10000	0	-10000	0	0
IL8	-0.36	0.45	-10000	0	-1	57	57
CDK5R1/CDK5	-0.007	0.087	-10000	0	-0.33	16	16
NF kappa B1 p50/RelA/PKAc	-0.11	0.18	-10000	0	-0.37	35	35
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.24	0.18	0.45	73	-10000	0	73
SMARCA4	0.015	0.013	-10000	0	-10000	0	0
chromatin remodeling	0.16	0.14	0.34	40	-0.38	3	43
NF kappa B1 p50/RelA/Cbp	-0.072	0.24	0.39	1	-0.44	31	32
JUN (dimer)	-0.16	0.16	-10000	0	-0.46	32	32
YWHAH	0.015	0	-10000	0	-10000	0	0
VIPR1	-0.08	0.21	-10000	0	-0.7	19	19
NR3C1	0.15	0.14	0.37	36	-0.52	1	37
NR4A1	-0.31	0.3	-10000	0	-0.58	132	132
TIF2/SUV420H1	-0.002	0.099	-10000	0	-0.42	13	13
MAPKKK cascade	-0.07	0.18	0.41	3	-0.54	8	11
cortisol/GR alpha (dimer)/Src-1	0.25	0.2	0.47	73	-10000	0	73
PBX1	-0.018	0.14	-10000	0	-0.57	14	14
POU1F1	0.004	0.034	-10000	0	-0.47	1	1
SELE	-0.53	0.58	-10000	0	-1.2	98	98
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.14	0.34	38	-0.38	3	41
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.24	0.18	0.45	73	-10000	0	73
mol:cortisol	0.14	0.13	0.3	71	-10000	0	71
MMP1	-0.24	0.16	-10000	0	-0.43	62	62

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.085	0.2	-10000	0	-0.54	33	33
FYN	-0.065	0.31	-10000	0	-0.72	38	38
LAT/GRAP2/SLP76	-0.094	0.24	-10000	0	-0.6	38	38
IKBKB	0.015	0	-10000	0	-10000	0	0
AKT1	-0.023	0.2	-10000	0	-0.46	35	35
B2M	0.015	0.005	-10000	0	-10000	0	0
IKBKG	-0.021	0.043	-10000	0	-0.14	15	15
MAP3K8	0.007	0.066	-10000	0	-0.58	3	3
mol:Ca2+	-0.023	0.037	-10000	0	-0.1	30	30
integrin-mediated signaling pathway	-0.003	0.032	-10000	0	-0.35	2	2
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.059	0.29	-10000	0	-0.7	36	36
TRPV6	-0.12	0.23	-10000	0	-0.55	52	52
CD28	-0.012	0.12	-10000	0	-0.57	11	11
SHC1	-0.058	0.28	-10000	0	-0.65	39	39
receptor internalization	-0.066	0.29	-10000	0	-0.69	37	37
PRF1	-0.059	0.29	-10000	0	-0.86	20	20
KRAS	0.013	0.031	-10000	0	-0.47	1	1
GRB2	0.015	0	-10000	0	-10000	0	0
COT/AKT1	-0.009	0.16	-10000	0	-0.36	35	35
LAT	-0.057	0.28	-10000	0	-0.69	35	35
EntrezGene:6955	0	0.004	-10000	0	-10000	0	0
CD3D	-0.048	0.18	-10000	0	-0.58	26	26
CD3E	-0.047	0.18	-10000	0	-0.59	25	25
CD3G	-0.042	0.18	-10000	0	-0.58	23	23
RASGRP2	-0.047	0.085	-10000	0	-0.17	73	73
RASGRP1	-0.019	0.2	-10000	0	-0.46	36	36
HLA-A	0.014	0.006	-10000	0	-10000	0	0
RASSF5	0.01	0.054	-10000	0	-0.58	2	2
RAP1A/GTP/RAPL	-0.003	0.032	-10000	0	-0.35	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.005	0.068	-10000	0	-0.13	36	36
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.039	0.076	-10000	0	-0.22	28	28
PRKCA	-0.037	0.11	-10000	0	-0.27	35	35
GRAP2	-0.057	0.19	-10000	0	-0.58	29	29
mol:IP3	-0.034	0.2	0.22	47	-0.45	35	82
EntrezGene:6957	0	0.004	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.064	0.27	-10000	0	-0.67	33	33
ORAI1	0.067	0.13	0.3	52	-0.34	1	53
CSK	-0.06	0.29	-10000	0	-0.7	35	35
B7 family/CD28	-0.13	0.25	-10000	0	-0.63	40	40
CHUK	0.015	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.081	0.33	-10000	0	-0.77	39	39
PTPN6	-0.063	0.29	-10000	0	-0.67	38	38
VAV1	-0.068	0.3	-10000	0	-0.69	40	40
Monovalent TCR/CD3	-0.067	0.24	-10000	0	-0.53	42	42
CBL	0.015	0	-10000	0	-10000	0	0
LCK	-0.07	0.31	-10000	0	-0.73	38	38
PAG1	-0.06	0.29	-10000	0	-0.7	35	35
RAP1A	0.015	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.081	0.33	-10000	0	-0.75	39	39
CD80	-0.047	0.16	-10000	0	-0.47	30	30
CD86	0.01	0.054	-10000	0	-0.58	2	2
PDK1/CARD11/BCL10/MALT1	-0.047	0.093	-10000	0	-0.26	31	31
HRAS	0.015	0	-10000	0	-10000	0	0
GO:0035030	-0.055	0.23	-10000	0	-0.53	38	38
CD8A	-0.039	0.17	-10000	0	-0.58	22	22
CD8B	-0.028	0.15	-10000	0	-0.57	18	18
PTPRC	-0.061	0.2	-10000	0	-0.58	31	31
PDK1/PKC theta	-0.034	0.25	-10000	0	-0.57	37	37
CSK/PAG1	-0.052	0.28	-10000	0	-0.7	33	33
SOS1	0.015	0	-10000	0	-10000	0	0
peptide-MHC class I	0.021	0.011	-10000	0	-10000	0	0
GRAP2/SLP76	-0.11	0.28	-10000	0	-0.7	39	39
STIM1	0.036	0.063	-10000	0	-10000	0	0
RAS family/GTP	0.024	0.084	-10000	0	-0.17	26	26
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.074	0.32	-10000	0	-0.75	37	37
mol:DAG	-0.054	0.16	-10000	0	-0.41	35	35
RAP1A/GDP	0.004	0.029	-10000	0	-10000	0	0
PLCG1	0.015	0	-10000	0	-10000	0	0
CD247	0.008	0.063	-10000	0	-0.55	3	3
cytotoxic T cell degranulation	-0.055	0.27	-10000	0	-0.8	20	20
RAP1A/GTP	-0.02	0.028	-10000	0	-0.07	6	6
mol:PI-3-4-5-P3	-0.038	0.24	-10000	0	-0.56	36	36
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.057	0.26	0.24	40	-0.6	35	75
NRAS	0.015	0	-10000	0	-10000	0	0
ZAP70	-0.01	0.12	-10000	0	-0.58	10	10
GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.093	0.23	-10000	0	-0.61	35	35
MALT1	0.015	0	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.046	0.19	-10000	0	-0.53	30	30
CARD11	-0.004	0.1	-10000	0	-0.55	8	8
PRKCB	-0.084	0.15	-10000	0	-0.35	48	48
PRKCE	-0.037	0.11	-10000	0	-0.27	35	35
PRKCQ	-0.054	0.28	-10000	0	-0.66	37	37
LCP2	0.012	0.038	-10000	0	-0.58	1	1
BCL10	0.015	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.014	0.17	-10000	0	-0.39	35	35
IKK complex	0.015	0.068	-10000	0	-0.12	28	28
RAS family/GDP	-0.005	0.011	-10000	0	-10000	0	0
MAP3K14	0.005	0.13	-10000	0	-0.28	32	32
PDPK1	-0.017	0.19	-10000	0	-0.44	35	35
TCR/CD3/MHC I/CD8/Fyn	-0.094	0.36	-10000	0	-0.88	36	36

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0.044	-10000	0	-0.47	2	2
RAS family/GTP/Tiam1	-0.089	0.12	-10000	0	-0.28	28	28
NT3 (dimer)/TRKC	-0.27	0.27	-10000	0	-0.48	138	138
NT3 (dimer)/TRKB	-0.29	0.29	-10000	0	-0.5	138	138
SHC/Grb2/SOS1/GAB1/PI3K	0.041	0.009	-10000	0	-10000	0	0
RAPGEF1	0.015	0	-10000	0	-10000	0	0
BDNF	-0.088	0.22	-10000	0	-0.58	42	42
PIK3CA	0.015	0	-10000	0	-10000	0	0
DYNLT1	0.015	0	-10000	0	-10000	0	0
NTRK1	0.007	0.054	-10000	0	-0.47	3	3
NTRK2	-0.23	0.29	-10000	0	-0.57	99	99
NTRK3	-0.28	0.3	-10000	0	-0.58	120	120
NT-4/5 (dimer)/TRKB	-0.25	0.27	-10000	0	-0.46	132	132
neuron apoptosis	0.19	0.25	0.52	72	-10000	0	72
SHC 2-3/Grb2	-0.21	0.28	-10000	0	-0.58	72	72
SHC1	0.013	0.031	-10000	0	-0.47	1	1
SHC2	-0.21	0.28	-10000	0	-0.64	59	59
SHC3	-0.22	0.27	-10000	0	-0.6	68	68
STAT3 (dimer)	0.014	0.051	-10000	0	-0.34	3	3
NT3 (dimer)/TRKA	-0.15	0.2	-10000	0	-0.38	96	96
RIN/GDP	-0.07	0.1	-10000	0	-0.24	20	20
GIPC1	0.015	0	-10000	0	-10000	0	0
KRAS	0.013	0.031	-10000	0	-0.47	1	1
DNAJA3	-0.11	0.17	-10000	0	-0.37	58	58
RIN/GTP	0	0.022	-10000	0	-0.34	1	1
CCND1	0.014	0.11	-10000	0	-0.5	9	9
MAGED1	0.015	0	-10000	0	-10000	0	0
PTPN11	0.015	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.04	0.17	-10000	0	-0.58	22	22
SHC/GRB2/SOS1	-0.001	0.017	-10000	0	-0.27	1	1
GRB2	0.015	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.07	0.15	-10000	0	-0.36	47	47
TRKA/NEDD4-2	0.016	0.039	-10000	0	-0.33	3	3
ELMO1	0.01	0.054	-10000	0	-0.58	2	2
RhoG/GTP/ELMO1/DOCK1	-0.004	0.049	-10000	0	-0.52	2	2
NGF	-0.059	0.2	-10000	0	-0.58	30	30
HRAS	0.015	0	-10000	0	-10000	0	0
DOCK1	0.012	0.038	-10000	0	-0.58	1	1
GAB2	0.015	0	-10000	0	-10000	0	0
RIT2	-0.001	0.031	-10000	0	-0.47	1	1
RIT1	0.015	0	-10000	0	-10000	0	0
FRS2	0.007	0.062	-10000	0	-0.47	4	4
DNM1	0.002	0.084	-10000	0	-0.58	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.11	0.17	-10000	0	-0.36	60	60
mol:GDP	-0.1	0.15	-10000	0	-0.34	30	30
NGF (dimer)	-0.059	0.2	-10000	0	-0.58	30	30
RhoG/GDP	0.007	0.04	-10000	0	-0.42	2	2
RIT1/GDP	-0.064	0.1	-10000	0	-0.24	20	20
TIAM1	0.012	0.038	-10000	0	-0.58	1	1
PIK3R1	0.015	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.2	0.22	-10000	0	-0.41	117	117
KIDINS220/CRKL/C3G	0.019	0.032	-10000	0	-0.33	2	2
SHC/RasGAP	0.02	0.022	-10000	0	-0.33	1	1
FRS2 family/SHP2	-0.004	0.034	-10000	0	-0.27	4	4
SHC/GRB2/SOS1/GAB1	0.037	0.017	-10000	0	-10000	0	0
RIT1/GTP	0.011	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.096	0.23	-10000	0	-0.57	45	45
RAP1/GDP	-0.07	0.069	-10000	0	-0.22	9	9
KIDINS220/CRKL	0.011	0.044	-10000	0	-0.47	2	2
BDNF (dimer)	-0.088	0.22	-10000	0	-0.58	42	42
ubiquitin-dependent protein catabolic process	-0.046	0.12	-10000	0	-0.34	33	33
Schwann cell development	-0.055	0.037	-10000	0	-10000	0	0
EHD4	0.015	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.034	0.035	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.042	0.018	-10000	0	-10000	0	0
RAP1B	0.015	0	-10000	0	-10000	0	0
RAP1A	0.015	0	-10000	0	-10000	0	0
CDC42/GTP	-0.33	0.28	-10000	0	-0.62	102	102
ABL1	0.015	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
Rap1/GTP	-0.065	0.074	-10000	0	-10000	0	0
STAT3	0.014	0.051	-10000	0	-0.34	3	3
axon guidance	-0.32	0.26	-10000	0	-0.59	102	102
MAPK3	-0.033	0.14	-10000	0	-0.33	41	41
MAPK1	-0.033	0.14	-10000	0	-0.33	41	41
CDC42/GDP	-0.064	0.1	-10000	0	-0.24	20	20
NTF3	-0.096	0.23	-10000	0	-0.57	45	45
NTF4	-0.04	0.17	-10000	0	-0.58	22	22
NGF (dimer)/TRKA/FAIM	-0.047	0.12	-10000	0	-0.34	33	33
PI3K	0.022	0	-10000	0	-10000	0	0
FRS3	0.015	0	-10000	0	-10000	0	0
FAIM	0.015	0	-10000	0	-10000	0	0
GAB1	0.015	0	-10000	0	-10000	0	0
RASGRF1	-0.14	0.17	-10000	0	-0.38	61	61
SOS1	0.015	0	-10000	0	-10000	0	0
MCF2L	-0.24	0.26	-10000	0	-0.43	139	139
RGS19	0.015	0	-10000	0	-10000	0	0
CDC42	0.015	0	-10000	0	-10000	0	0
RAS family/GTP	0.006	0.072	-10000	0	-10000	0	0
Rac1/GDP	-0.064	0.1	-10000	0	-0.24	20	20
NGF (dimer)/TRKA/GRIT	-0.047	0.12	-10000	0	-0.35	33	33
neuron projection morphogenesis	-0.077	0.18	-10000	0	-0.52	15	15
NGF (dimer)/TRKA/NEDD4-2	-0.047	0.12	-10000	0	-0.34	33	33
MAP2K1	0.042	0.016	-10000	0	-10000	0	0
NGFR	-0.13	0.26	-10000	0	-0.57	61	61
NGF (dimer)/TRKA/GIPC/GAIP	-0.002	0.11	-10000	0	-0.27	32	32
RAS family/GTP/PI3K	0.034	0.009	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0.04	0.032	-10000	0	-10000	0	0
NRAS	0.015	0	-10000	0	-10000	0	0
GRB2/SOS1	0.022	0	-10000	0	-10000	0	0
PRKCI	0.015	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.58	1	1
MAPKKK cascade	-0.12	0.24	-10000	0	-0.74	30	30
RASA1	0.015	0	-10000	0	-10000	0	0
TRKA/c-Abl	0.016	0.039	-10000	0	-0.33	3	3
SQSTM1	0.015	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.16	0.22	-10000	0	-0.37	112	112
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.002	0.11	-10000	0	-0.29	30	30
MATK	-0.026	0.15	-10000	0	-0.56	17	17
NEDD4L	0.015	0	-10000	0	-10000	0	0
RAS family/GDP	-0.066	0.065	-10000	0	-0.22	4	4
NGF (dimer)/TRKA	-0.12	0.18	-10000	0	-0.37	75	75
Rac1/GTP	-0.12	0.11	-10000	0	-0.29	52	52
FRS2 family/SHP2/CRK family	0.038	0.039	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	0.019	0.028	-9999	-10000	0	0
VDR	0.01	0.049	-9999	-0.52	2	2
FAM120B	0.015	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	-0.019	0.13	-9999	-0.42	4	4
RXRs/LXRs/DNA/Oxysterols	0	0.12	-9999	-0.39	4	4
MED1	0.015	0	-9999	-10000	0	0
mol:9cRA	0.006	0.007	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	0.003	0.11	-9999	-0.51	4	4
RXRs/NUR77	-0.23	0.23	-9999	-0.37	162	162
RXRs/PPAR	-0.06	0.15	-9999	-0.39	12	12
NCOR2	0.015	0	-9999	-10000	0	0
VDR/VDR/Vit D3	0.008	0.036	-9999	-0.38	2	2
RARs/VDR/DNA/Vit D3	0.006	0.092	-9999	-0.29	21	21
RARA	0.015	0	-9999	-10000	0	0
NCOA1	0.015	0	-9999	-10000	0	0
VDR/VDR/DNA	0.01	0.049	-9999	-0.52	2	2
RARs/RARs/DNA/9cRA	0.002	0.09	-9999	-0.29	20	20
RARG	0.015	0	-9999	-10000	0	0
RPS6KB1	0.029	0.044	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	0.003	0.11	-9999	-0.51	4	4
THRA	0.015	0	-9999	-10000	0	0
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	0.008	0.036	-9999	-0.38	2	2
RXRs/PPAR/9cRA/PGJ2/DNA	-0.054	0.16	-9999	-0.3	67	67
NR1H4	-0.13	0.24	-9999	-0.55	59	59
RXRs/LXRs/DNA	-0.024	0.15	-9999	-0.4	4	4
NR1H2	0.021	0.005	-9999	-10000	0	0
NR1H3	0.021	0.005	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.049	0.15	-9999	-0.29	68	68
NR4A1	-0.31	0.3	-9999	-0.58	131	131
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.091	0.16	-9999	-0.26	99	99
RXRG	-0.15	0.26	-9999	-0.57	67	67
RXR alpha/CCPG	0.024	0.029	-9999	-0.41	1	1
RXRA	0.018	0.038	-9999	-0.57	1	1
RXRB	0.021	0.005	-9999	-10000	0	0
THRB	-0.017	0.13	-9999	-0.58	13	13
PPARG	-0.038	0.17	-9999	-0.57	22	22
PPARD	0.015	0	-9999	-10000	0	0
TNF	0.003	0.12	-9999	-0.46	4	4
mol:Oxysterols	0.006	0.006	-9999	-10000	0	0
cholesterol transport	0	0.12	-9999	-0.39	4	4
PPARA	0.01	0.054	-9999	-0.58	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	-0.034	0.16	-9999	-0.58	20	20
RXRs/NUR77/BCL2	-0.21	0.21	-9999	-0.33	164	164
SREBF1	0.009	0.11	-9999	-0.47	1	1
RXRs/RXRs/DNA/9cRA	-0.053	0.16	-9999	-0.3	67	67
ABCA1	0.01	0.11	-9999	-0.47	1	1
RARs/THRs	0	0.12	-9999	-0.58	4	4
RXRs/FXR	-0.13	0.21	-9999	-0.35	99	99
BCL2	-0.012	0.12	-9999	-0.58	11	11

×

LPA receptor mediated events

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
GNB1/GNG2	-0.035	0.1	-9999	-0.39	12	12
NF kappa B1 p50/RelA/I kappa B alpha	0.006	0.11	-9999	-0.35	6	6
AP1	-0.14	0.21	-9999	-0.51	40	40
mol:PIP3	-0.06	0.12	-9999	-0.44	16	16
AKT1	0.036	0.086	-9999	-0.38	4	4
PTK2B	-0.005	0.1	-9999	-0.28	20	20
RHOA	0.018	0.049	-9999	-0.25	1	1
PIK3CB	0.014	0	-9999	-10000	0	0
mol:Ca2+	-0.006	0.1	-9999	-0.37	5	5
MAGI3	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
apoptosis	-0.035	0.15	-9999	-0.32	45	45
HRAS/GDP	0.011	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.015	0.12	-9999	-0.29	31	31
NF kappa B1 p50/RelA	-0.052	0.12	-9999	-0.43	12	12
endothelial cell migration	-0.044	0.22	-9999	-0.62	28	28
ADCY4	-0.095	0.2	-9999	-0.42	49	49
ADCY5	-0.22	0.29	-9999	-0.55	88	88
ADCY6	-0.094	0.2	-9999	-0.42	49	49
ADCY7	-0.094	0.2	-9999	-0.42	49	49
ADCY1	-0.097	0.2	-9999	-0.42	53	53
ADCY2	-0.18	0.27	-9999	-0.52	82	82
ADCY3	-0.094	0.2	-9999	-0.42	49	49
ADCY8	-0.098	0.2	-9999	-0.43	49	49
ADCY9	-0.098	0.21	-9999	-0.44	50	50
GSK3B	0.004	0.095	-9999	-0.31	11	11
arachidonic acid secretion	-0.095	0.2	-9999	-0.43	50	50
GNG2	0.012	0.038	-9999	-0.58	1	1
TRIP6	0.022	0.024	-9999	-10000	0	0
GNAO1	-0.12	0.21	-9999	-0.38	85	85
HRAS	0.015	0	-9999	-10000	0	0
NFKBIA	-0.003	0.12	-9999	-0.36	11	11
GAB1	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.06	-9999	-0.92	1	1
JUN	0	0.092	-9999	-0.58	6	6
LPA/LPA2/NHERF2	-0.009	0.039	-9999	-0.3	3	3
TIAM1	-0.002	0.071	-9999	-1.1	1	1
PIK3R1	0.014	0	-9999	-10000	0	0
mol:IP3	-0.007	0.1	-9999	-0.37	5	5
PLCB3	0.021	0.04	-9999	-0.27	3	3
FOS	-0.17	0.27	-9999	-0.58	74	74
positive regulation of mitosis	-0.095	0.2	-9999	-0.43	50	50
LPA/LPA1-2-3	-0.068	0.14	-9999	-0.38	32	32
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.015	0	-9999	-10000	0	0
stress fiber formation	-0.006	0.12	-9999	-0.38	12	12
GNAZ	-0.091	0.19	-9999	-0.37	74	74
EGFR/PI3K-beta/Gab1	-0.062	0.13	-9999	-0.46	16	16
positive regulation of dendritic cell cytokine production	-0.067	0.14	-9999	-0.38	32	32
LPA/LPA2/MAGI-3	-0.009	0.039	-9999	-0.3	3	3
ARHGEF1	0.007	0.11	-9999	-0.37	11	11
GNAI2	-0.011	0.12	-9999	-0.33	28	28
GNAI3	-0.011	0.12	-9999	-0.33	28	28
GNAI1	-0.012	0.13	-9999	-0.33	29	29
LPA/LPA3	-0.051	0.13	-9999	-0.42	25	25
LPA/LPA2	-0.013	0.049	-9999	-0.37	3	3
LPA/LPA1	-0.046	0.14	-9999	-0.4	28	28
HB-EGF/EGFR	-0.087	0.17	-9999	-0.31	81	81
HBEGF	-0.093	0.18	-9999	-0.35	76	76
mol:DAG	-0.007	0.1	-9999	-0.37	5	5
cAMP biosynthetic process	-0.14	0.24	-9999	-0.44	79	79
NFKB1	0.015	0	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	-0.003	0.12	-9999	-0.32	22	22
GNAQ	-0.014	0.099	-9999	-0.3	23	23
LPAR2	0.008	0.054	-9999	-0.47	3	3
LPAR3	-0.045	0.18	-9999	-0.56	25	25
LPAR1	-0.023	0.14	-9999	-0.63	11	11
IL8	-0.12	0.23	-9999	-0.5	53	53
PTK2	-0.028	0.15	-9999	-0.36	31	31
Rac1/GDP	0.011	0	-9999	-10000	0	0
CASP3	-0.035	0.15	-9999	-0.32	45	45
EGFR	-0.01	0.11	-9999	-0.52	11	11
PLCG1	-0.027	0.12	-9999	-0.32	26	26
PLD2	-0.028	0.15	-9999	-0.36	31	31
G12/G13	-0.034	0.1	-9999	-0.4	11	11
PI3K-beta	-0.025	0.076	-9999	-0.44	4	4
cell migration	-0.016	0.052	-9999	-0.21	4	4
SLC9A3R2	0.015	0	-9999	-10000	0	0
PXN	-0.006	0.12	-9999	-0.39	12	12
HRAS/GTP	-0.098	0.21	-9999	-0.44	50	50
RAC1	0.015	0	-9999	-10000	0	0
MMP9	-0.13	0.22	-9999	-0.48	70	70
PRKCE	0.015	0	-9999	-10000	0	0
PRKCD	0.002	0.1	-9999	-0.35	5	5
Gi(beta/gamma)	-0.09	0.2	-9999	-0.41	50	50
mol:LPA	-0.01	0.051	-9999	-0.19	17	17
TRIP6/p130 Cas/FAK1/Paxillin	-0.047	0.12	-9999	-0.48	10	10
MAPKKK cascade	-0.095	0.2	-9999	-0.43	50	50
contractile ring contraction involved in cytokinesis	0.018	0.049	-9999	-0.25	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.065	0.16	-9999	-0.33	58	58
GNA15	-0.016	0.1	-9999	-0.3	25	25
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
MAPT	-0.016	0.13	-9999	-0.29	31	31
GNA11	-0.015	0.11	-9999	-0.31	23	23
Rac1/GTP	0.025	0.065	-9999	-0.98	1	1
MMP2	-0.045	0.22	-9999	-0.63	28	28

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.047	0.23	-10000	0	-0.62	15	15
CRP	-0.053	0.23	-10000	0	-0.66	14	14
cell cycle arrest	-0.062	0.26	-10000	0	-0.66	26	26
TIMP1	-0.04	0.21	-10000	0	-0.58	10	10
IL6ST	-0.059	0.2	-10000	0	-0.58	32	32
Rac1/GDP	-0.12	0.26	-10000	0	-0.55	49	49
AP1	-0.053	0.17	-10000	0	-0.47	10	10
GAB2	0.018	0.007	-10000	0	-10000	0	0
TNFSF11	-0.057	0.25	-10000	0	-0.78	11	11
HSP90B1	0.024	0.047	-10000	0	-10000	0	0
GAB1	0.017	0.004	-10000	0	-10000	0	0
MAPK14	-0.16	0.3	-10000	0	-0.73	41	41
AKT1	0.062	0.015	-10000	0	-10000	0	0
FOXO1	0.067	0.013	-10000	0	-10000	0	0
MAP2K6	-0.15	0.28	-10000	0	-0.6	48	48
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	-0.089	0.26	-10000	0	-0.56	40	40
MITF	-0.15	0.28	-10000	0	-0.57	52	52
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.015	0	-10000	0	-10000	0	0
A2M	-0.095	0.4	-10000	0	-1.4	20	20
CEBPB	0.023	0.003	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.012	0.096	-10000	0	-10000	0	0
STAT3	-0.065	0.28	-10000	0	-0.69	28	28
STAT1	-0.006	0.018	-10000	0	-10000	0	0
CEBPD	-0.049	0.24	-10000	0	-0.77	9	9
PIK3CA	0.017	0	-10000	0	-10000	0	0
PI3K	0.025	0.002	-10000	0	-10000	0	0
JUN	0	0.092	-10000	0	-0.58	6	6
PIAS3/MITF	-0.13	0.26	-10000	0	-0.57	46	46
MAPK11	-0.16	0.3	-10000	0	-0.73	41	41
STAT3 (dimer)/FOXO1	-0.018	0.24	-10000	0	-0.58	16	16
GRB2/SOS1/GAB family	-0.13	0.2	0.21	3	-0.57	31	34
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.15	0.26	-10000	0	-0.48	63	63
GRB2	0.017	0.004	-10000	0	-10000	0	0
JAK2	0.012	0.038	-10000	0	-0.58	1	1
LBP	-0.057	0.21	-10000	0	-0.63	7	7
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
MYC	-0.073	0.3	-10000	0	-0.98	16	16
FGG	-0.066	0.24	-10000	0	-0.73	10	10
macrophage differentiation	-0.062	0.26	-10000	0	-0.66	26	26
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.18	0.23	-10000	0	-0.47	59	59
JUNB	-0.051	0.24	-10000	0	-0.76	10	10
FOS	-0.17	0.27	-10000	0	-0.58	74	74
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.14	0.27	-10000	0	-0.5	59	59
STAT1/PIAS1	-0.1	0.23	-10000	0	-0.55	34	34
GRB2/SOS1/GAB family/SHP2/PI3K	0.05	0.017	-10000	0	-10000	0	0
STAT3 (dimer)	-0.061	0.27	-10000	0	-0.69	26	26
PRKCD	-0.06	0.25	-10000	0	-0.56	34	34
IL6R	-0.023	0.15	-10000	0	-0.58	16	16
SOCS3	-0.2	0.4	-10000	0	-1	39	39
gp130 (dimer)/JAK1/JAK1/LMO4	-0.008	0.14	-10000	0	-0.35	32	32
Rac1/GTP	-0.12	0.26	-10000	0	-0.55	49	49
HCK	-0.008	0.11	-10000	0	-0.55	10	10
MAPKKK cascade	0.024	0.074	-10000	0	-10000	0	0
bone resorption	-0.053	0.24	-10000	0	-0.67	15	15
IRF1	-0.047	0.23	-10000	0	-0.62	15	15
mol:GDP	-0.14	0.27	-10000	0	-0.58	50	50
SOS1	0.017	0.007	-10000	0	-10000	0	0
VAV1	-0.14	0.28	-10000	0	-0.59	50	50
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.18	0.34	-10000	0	-0.78	42	42
PTPN11	-0.005	0.017	-10000	0	-10000	0	0
IL6/IL6RA	-0.19	0.26	-10000	0	-0.46	111	111
gp130 (dimer)/TYK2/TYK2/LMO4	-0.014	0.13	-10000	0	-0.35	32	32
gp130 (dimer)/JAK2/JAK2/LMO4	-0.015	0.14	-10000	0	-0.36	32	32
IL6	-0.25	0.3	-10000	0	-0.58	109	109
PIAS3	0.015	0	-10000	0	-10000	0	0
PTPRE	0.003	0.048	-10000	0	-0.51	2	2
PIAS1	0.015	0	-10000	0	-10000	0	0
RAC1	0.015	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.16	0.25	-10000	0	-0.45	66	66
LMO4	0.019	0.01	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.13	0.22	-10000	0	-0.66	29	29
MCL1	0.068	0.014	-10000	0	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.016	0.051	-9999	-0.28	7	7
RGS9BP	-0.017	0.13	-9999	-0.56	13	13
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.001	0.004	-9999	-10000	0	0
mol:Na +	-0.11	0.16	-9999	-0.32	79	79
mol:ADP	0.01	0.023	-9999	-0.34	1	1
GNAT2	0.008	0.044	-9999	-0.47	2	2
RGS9-1/Gbeta5/R9AP	-0.095	0.16	-9999	-0.36	64	64
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.004	0.032	-9999	-0.28	3	3
GRK7	0.01	0.032	-9999	-0.47	1	1
CNGB3	-0.11	0.21	-9999	-0.47	61	61
Cone Metarhodopsin II/X-Arrestin	0.002	0.004	-9999	-10000	0	0
mol:Ca2+	-0.096	0.17	-9999	-0.3	87	87
Cone PDE6	-0.082	0.14	-9999	-0.31	62	62
Cone Metarhodopsin II	0.007	0.018	-9999	-0.26	1	1
Na + (4 Units)	-0.095	0.16	-9999	-0.3	87	87
GNAT2/GDP	-0.082	0.14	-9999	-0.3	62	62
GNB5	0.015	0	-9999	-10000	0	0
mol:GMP (4 units)	0.008	0.03	-9999	-0.25	3	3
Cone Transducin	0.017	0.055	-9999	-0.3	7	7
SLC24A2	-0.018	0.11	-9999	-0.47	14	14
GNB3/GNGT2	0.013	0.062	-9999	-0.42	5	5
GNB3	0.01	0.054	-9999	-0.58	2	2
GNAT2/GTP	0.006	0.032	-9999	-0.34	2	2
CNGA3	-0.052	0.18	-9999	-0.58	25	25
ARR3	0.003	0.006	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.1	0.16	-9999	-0.33	79	79
mol:Pi	-0.095	0.16	-9999	-0.36	64	64
Cone CNG Channel	-0.087	0.13	-9999	-0.34	25	25
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.018	0.11	-9999	-0.47	14	14
RGS9	-0.12	0.25	-9999	-0.58	54	54
PDE6C	0.002	0.005	-9999	-10000	0	0
GNGT2	0.007	0.066	-9999	-0.58	3	3
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.001	0.031	-9999	-0.47	1	1

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.015	0	-9999	-10000	0	0
VLDLR	-0.005	0.11	-9999	-0.58	8	8
LRPAP1	0.013	0.031	-9999	-0.47	1	1
NUDC	0.015	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.2	-9999	-0.37	106	106
CaM/Ca2+	0.011	0	-9999	-10000	0	0
KATNA1	0.015	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.12	0.19	-9999	-0.36	79	79
IQGAP1/CaM	0.022	0	-9999	-10000	0	0
DAB1	-0.075	0.2	-9999	-0.54	37	37
IQGAP1	0.015	0	-9999	-10000	0	0
PLA2G7	-0.064	0.18	-9999	-0.47	39	39
CALM1	0.015	0	-9999	-10000	0	0
DYNLT1	0.015	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.043	0.14	-9999	-0.33	45	45
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.015	0	-9999	-10000	0	0
CDK5R1	-0.018	0.12	-9999	-0.47	16	16
LIS1/Poliovirus Protein 3A	0.019	0	-9999	-10000	0	0
CDK5R2	-0.018	0.11	-9999	-0.47	14	14
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.17	0.21	-9999	-0.39	108	108
YWHAE	0.012	0.038	-9999	-0.58	1	1
NDEL1/14-3-3 E	-0.085	0.17	-9999	-0.43	23	23
MAP1B	-0.024	0.083	-9999	-0.31	19	19
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.11	0.19	-9999	-0.51	25	25
RELN	-0.18	0.28	-9999	-0.57	80	80
PAFAH/LIS1	-0.018	0.11	-9999	-0.27	39	39
LIS1/CLIP170	0.03	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.085	0.11	-9999	-0.35	19	19
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.18	-9999	-0.34	54	54
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.097	0.18	-9999	-0.46	24	24
LIS1/IQGAP1	0.03	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.025	0	-9999	-10000	0	0
PAFAH1B3	-0.018	0.12	-9999	-0.47	16	16
PAFAH1B2	0.015	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	0.012	0.058	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.074	0.16	-9999	-0.43	20	20
LRP8	-0.074	0.19	-9999	-0.47	44	44
NDEL1/Katanin 60	-0.084	0.17	-9999	-0.43	23	23
P39/CDK5	-0.11	0.18	-9999	-0.49	24	24
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.03	0	-9999	-10000	0	0
CDK5	-0.11	0.18	-9999	-0.33	79	79
PPP2R5D	0.015	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.026	0	-9999	-10000	0	0
CSNK2A1	0.015	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.12	0.19	-9999	-0.33	97	97
RELN/VLDLR	-0.14	0.21	-9999	-0.38	84	84
CDC42	0	0	-9999	-10000	0	0

×

S1P5 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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.11	0.16	0.42	36	-10000	0	36
GNAI2	0.015	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.012	0.059	-10000	0	-0.29	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.15	0.27	-10000	0	-0.58	68	68
RhoA/GTP	-0.084	0.18	-10000	0	-0.43	36	36
negative regulation of cAMP metabolic process	-0.099	0.19	-10000	0	-0.36	70	70
GNAZ	-0.11	0.24	-10000	0	-0.58	52	52
GNAI3	0.015	0	-10000	0	-10000	0	0
GNA12	0.015	0	-10000	0	-10000	0	0
S1PR5	-0.006	0.1	-10000	0	-0.49	10	10
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.1	0.2	-10000	0	-0.36	70	70
RhoA/GDP	0.011	0	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.58	1	1

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.016	0.03	-9999	-0.42	1	1
PDGFRB	0.001	0.076	-9999	-0.58	4	4
SPHK1	-0.032	0.074	-9999	-1.1	1	1
mol:S1P	-0.038	0.075	-9999	-0.66	2	2
S1P1/S1P/Gi	-0.17	0.26	-9999	-0.46	85	85
GNAO1	-0.16	0.27	-9999	-0.58	68	68
PDGFB-D/PDGFRB/PLCgamma1	-0.14	0.23	-9999	-0.48	55	55
PLCG1	-0.15	0.24	-9999	-0.51	54	54
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.001	0.076	-9999	-0.58	4	4
GNAI2	0.012	0.007	-9999	-10000	0	0
GNAI3	0.012	0.006	-9999	-10000	0	0
GNAI1	0.009	0.039	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
EDG1	0.015	0.027	-9999	-0.35	1	1
S1P1/S1P	-0.04	0.075	-9999	-0.46	3	3
negative regulation of cAMP metabolic process	-0.16	0.25	-9999	-0.45	85	85
MAPK3	-0.2	0.3	-9999	-0.56	84	84
calcium-dependent phospholipase C activity	-0.003	0.004	-9999	-10000	0	0
Rac1/GDP	0.011	0	-9999	-10000	0	0
RhoA/GDP	0.011	0	-9999	-10000	0	0
KDR	0.011	0.038	-9999	-0.58	1	1
PLCB2	-0.011	0.083	-9999	-0.38	4	4
RAC1	0.015	0	-9999	-10000	0	0
RhoA/GTP	-0.032	0.062	-9999	-0.38	3	3
receptor internalization	-0.038	0.07	-9999	-0.43	3	3
PTGS2	-0.28	0.46	-9999	-1.1	55	55
Rac1/GTP	-0.032	0.062	-9999	-0.38	3	3
RHOA	0.015	0	-9999	-10000	0	0
VEGFA	0.014	0.004	-9999	-10000	0	0
negative regulation of T cell proliferation	-0.16	0.25	-9999	-0.45	85	85
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.12	0.24	-9999	-0.58	52	52
MAPK1	-0.2	0.3	-9999	-0.56	84	84
S1P1/S1P/PDGFB-D/PDGFRB	-0.027	0.11	-9999	-0.51	5	5
ABCC1	0.009	0.045	-9999	-0.48	2	2

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.054	0.16	-10000	0	-0.4	30	30
IKBKB	-0.007	0.072	-10000	0	-0.27	2	2
AKT1	-0.05	0.12	-10000	0	-0.24	50	50
IKBKG	-0.005	0.075	-10000	0	-0.29	2	2
CALM1	-0.04	0.12	-10000	0	-0.38	16	16
PIK3CA	0.015	0	-10000	0	-10000	0	0
MAP3K1	-0.093	0.23	-10000	0	-0.54	41	41
MAP3K7	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	-0.05	0.13	-10000	0	-0.36	21	21
DOK1	0.013	0.031	-10000	0	-0.47	1	1
AP-1	-0.052	0.11	-10000	0	-0.23	34	34
LYN	0.015	0	-10000	0	-10000	0	0
BLNK	-0.002	0.099	-10000	0	-0.58	7	7
SHC1	0.013	0.031	-10000	0	-0.47	1	1
BCR complex	-0.096	0.22	-10000	0	-0.46	59	59
CD22	-0.18	0.3	-10000	0	-0.69	51	51
CAMK2G	-0.029	0.11	-10000	0	-0.35	16	16
CSNK2A1	0.015	0	-10000	0	-10000	0	0
INPP5D	0	0.092	-10000	0	-0.58	6	6
SHC/GRB2/SOS1	-0.074	0.14	-10000	0	-0.48	13	13
GO:0007205	-0.051	0.13	-10000	0	-0.37	21	21
SYK	0.01	0.054	-10000	0	-0.58	2	2
ELK1	-0.041	0.12	-10000	0	-0.38	16	16
NFATC1	-0.11	0.23	-10000	0	-0.51	47	47
B-cell antigen/BCR complex	-0.096	0.22	-10000	0	-0.46	59	59
PAG1/CSK	0.022	0	-10000	0	-10000	0	0
NFKBIB	0.009	0.028	-10000	0	-10000	0	0
HRAS	-0.036	0.12	-10000	0	-0.33	21	21
NFKBIA	0.009	0.027	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.015	0.023	-10000	0	-10000	0	0
RasGAP/Csk	-0.096	0.19	-10000	0	-0.39	59	59
mol:GDP	-0.048	0.12	-10000	0	-0.38	17	17
PTEN	0.015	0	-10000	0	-10000	0	0
CD79B	-0.018	0.13	-10000	0	-0.55	14	14
NF-kappa-B/RelA/I kappa B alpha	0.015	0.023	-10000	0	-10000	0	0
GRB2	0.015	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.12	0.24	-10000	0	-0.5	57	57
PIK3R1	0.015	0	-10000	0	-10000	0	0
mol:IP3	-0.052	0.13	-10000	0	-0.37	21	21
CSK	0.015	0	-10000	0	-10000	0	0
FOS	-0.12	0.18	-10000	0	-0.33	84	84
CHUK	-0.005	0.075	-10000	0	-0.29	2	2
IBTK	0.015	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.051	0.1	-10000	0	-0.44	8	8
PTPN6	-0.14	0.3	-10000	0	-0.64	51	51
RELA	0.015	0	-10000	0	-10000	0	0
BCL2A1	0.012	0.031	-10000	0	-0.098	13	13
VAV2	-0.18	0.27	-10000	0	-0.65	47	47
ubiquitin-dependent protein catabolic process	0.013	0.027	-10000	0	-10000	0	0
BTK	-0.05	0.25	0.35	5	-1.2	11	16
CD19	-0.19	0.29	-10000	0	-0.61	58	58
MAP4K1	-0.002	0.097	-10000	0	-0.56	7	7
CD72	-0.001	0.087	-10000	0	-0.47	8	8
PAG1	0.015	0	-10000	0	-10000	0	0
MAPK14	-0.069	0.2	-10000	0	-0.44	41	41
SH3BP5	0.012	0.038	-10000	0	-0.58	1	1
PIK3AP1	-0.048	0.15	-10000	0	-0.42	22	22
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.067	0.2	-10000	0	-0.42	51	51
RAF1	-0.027	0.12	-10000	0	-0.4	9	9
RasGAP/p62DOK/SHIP	-0.1	0.2	-10000	0	-0.59	24	24
CD79A	-0.12	0.24	-10000	0	-0.56	55	55
re-entry into mitotic cell cycle	-0.051	0.1	-10000	0	-0.23	34	34
RASA1	0.015	0	-10000	0	-10000	0	0
MAPK3	-0.007	0.1	-10000	0	-0.4	5	5
MAPK1	-0.007	0.1	-10000	0	-0.4	5	5
CD72/SHP1	-0.13	0.28	-10000	0	-0.61	49	49
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	-0.072	0.2	-10000	0	-0.44	42	42
actin cytoskeleton organization	-0.12	0.24	-10000	0	-0.54	46	46
NF-kappa-B/RelA	0.034	0.044	-10000	0	-10000	0	0
Calcineurin	-0.043	0.09	-10000	0	-0.44	5	5
PI3K	-0.16	0.21	-10000	0	-0.49	59	59
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.051	0.14	-10000	0	-0.4	21	21
SOS1	0.015	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.11	0.27	-10000	0	-0.77	29	29
DAPP1	-0.14	0.28	-10000	0	-0.85	28	28
cytokine secretion	-0.096	0.21	-10000	0	-0.46	47	47
mol:DAG	-0.052	0.13	-10000	0	-0.37	21	21
PLCG2	0.013	0.031	-10000	0	-0.47	1	1
MAP2K1	-0.017	0.11	-10000	0	-0.45	5	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.12	0.22	-10000	0	-0.46	62	62
mol:PI-3-4-5-P3	-0.11	0.14	-10000	0	-0.34	59	59
ETS1	-0.019	0.1	-10000	0	-0.33	13	13
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.08	0.17	-10000	0	-0.56	13	13
B-cell antigen/BCR complex/LYN	-0.13	0.26	-10000	0	-0.53	56	56
MALT1	0.015	0	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
RAC1	-0.13	0.26	-10000	0	-0.59	46	46
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.27	-10000	0	-0.63	49	49
CARD11	-0.05	0.14	-10000	0	-0.4	21	21
FCGR2B	-0.029	0.15	-10000	0	-0.57	18	18
PPP3CA	0.015	0	-10000	0	-10000	0	0
BCL10	0.015	0	-10000	0	-10000	0	0
IKK complex	0.005	0.037	-10000	0	-0.097	1	1
PTPRC	-0.061	0.2	-10000	0	-0.57	31	31
PDPK1	-0.051	0.12	-10000	0	-0.23	50	50
PPP3CB	0.015	0	-10000	0	-10000	0	0
PPP3CC	0.015	0	-10000	0	-10000	0	0
POU2F2	0.015	0.023	-10000	0	-0.096	5	5

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.02	0.024	-9999	-0.36	1	1
ADCY5	-0.17	0.19	-9999	-0.36	121	121
ADCY6	0.022	0	-9999	-10000	0	0
ADCY7	0.022	0	-9999	-10000	0	0
ADCY1	0.014	0.049	-9999	-0.29	6	6
ADCY2	-0.12	0.18	-9999	-0.36	87	87
ADCY3	0.022	0	-9999	-10000	0	0
ADCY8	0.013	0.019	-9999	-0.28	1	1
PRKCE	0.013	0	-9999	-10000	0	0
ADCY9	0.017	0.042	-9999	-0.36	3	3
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.06	0.093	-9999	-0.26	4	4

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.015	0.14	-9999	-0.34	32	32
MAP4K1	-0.002	0.097	-9999	-0.56	7	7
MAP3K8	0.007	0.066	-9999	-0.58	3	3
PRKCB	-0.16	0.27	-9999	-0.58	69	69
DBNL	0.015	0	-9999	-10000	0	0
CRKL	0.011	0.044	-9999	-0.47	2	2
MAP3K1	0.01	0.11	-9999	-0.57	3	3
JUN	-0.15	0.29	-9999	-0.58	72	72
MAP3K7	0.01	0.11	-9999	-0.57	3	3
GRAP2	-0.057	0.19	-9999	-0.58	29	29
CRK	0.015	0	-9999	-10000	0	0
MAP2K4	0.017	0.11	-9999	-0.48	5	5
LAT	0.013	0.031	-9999	-0.47	1	1
LCP2	0.012	0.038	-9999	-0.58	1	1
MAPK8	-0.16	0.3	-9999	-0.61	72	72
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.001	0.12	-9999	-0.6	3	3
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.006	0.13	-9999	-0.58	4	4

×

S1P3 pathway

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
PDGFRB	0.005	0.076	-9999	-0.58	4	4
mol:S1P	0.001	0.005	-9999	-10000	0	0
S1P1/S1P/Gi	-0.094	0.19	-9999	-0.32	88	88
GNAO1	-0.15	0.27	-9999	-0.58	68	68
S1P/S1P3/G12/G13	0.022	0.052	-9999	-0.3	6	6
AKT1	-0.028	0.13	-9999	-0.84	4	4
AKT3	-0.063	0.27	-9999	-1.3	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.005	0.076	-9999	-0.58	4	4
GNAI2	0.016	0.004	-9999	-10000	0	0
GNAI3	0.016	0.004	-9999	-10000	0	0
GNAI1	0.013	0.038	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.001	0.09	-9999	-0.56	6	6
S1PR2	0.015	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.099	0.21	-9999	-0.5	42	42
MAPK3	-0.086	0.2	-9999	-0.47	42	42
MAPK1	-0.086	0.2	-9999	-0.47	42	42
JAK2	-0.086	0.21	-9999	-0.48	43	43
CXCR4	-0.09	0.21	-9999	-0.47	44	44
FLT1	0.017	0.003	-9999	-10000	0	0
RhoA/GDP	0.011	0	-9999	-10000	0	0
Rac1/GDP	0.011	0	-9999	-10000	0	0
SRC	-0.086	0.2	-9999	-0.47	42	42
S1P/S1P3/Gi	-0.1	0.22	-9999	-0.5	42	42
RAC1	0.015	0	-9999	-10000	0	0
RhoA/GTP	-0.085	0.2	-9999	-0.46	42	42
VEGFA	0.017	0.003	-9999	-10000	0	0
S1P/S1P2/Gi	-0.09	0.19	-9999	-0.36	69	69
VEGFR1 homodimer/VEGFA homodimer	0.03	0.009	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.02	0.12	-9999	-0.26	45	45
GNAQ	0.015	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	52	52
G12/G13	0.022	0	-9999	-10000	0	0
GNA14	-0.079	0.22	-9999	-0.58	38	38
GNA15	0.01	0.054	-9999	-0.58	2	2
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
GNA11	0.012	0.038	-9999	-0.58	1	1
Rac1/GTP	-0.085	0.2	-9999	-0.46	42	42

×

S1P4 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
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.15	0.27	-9999	-0.58	68	68
CDC42/GTP	-0.081	0.17	-9999	-0.43	34	34
PLCG1	-0.083	0.18	-9999	-0.44	34	34
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
G12/G13	0.022	0	-9999	-10000	0	0
cell migration	-0.1	0.15	-9999	-0.42	34	34
S1PR5	-0.006	0.1	-9999	-0.49	10	10
S1PR4	0.004	0.076	-9999	-0.52	5	5
MAPK3	-0.083	0.18	-9999	-0.44	34	34
MAPK1	-0.083	0.18	-9999	-0.44	34	34
S1P/S1P5/Gi	-0.1	0.2	-9999	-0.36	70	70
GNAI1	0.012	0.038	-9999	-0.58	1	1
CDC42/GDP	0.011	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.012	0.059	-9999	-0.29	10	10
RHOA	0.029	0.04	-9999	-0.29	2	2
S1P/S1P4/Gi	-0.097	0.19	-9999	-0.36	69	69
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	52	52
S1P/S1P4/G12/G13	0.022	0.043	-9999	-0.27	5	5
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.011	0.016	-9999	-10000	0	0
SVIL	0.006	0.055	-9999	-0.58	2	2
ZNF318	0.024	0.037	-9999	-10000	0	0
JMJD2C	-0.003	0.026	-9999	-0.069	29	29
T-DHT/AR/Ubc9	-0.12	0.19	-9999	-0.38	81	81
CARM1	0.014	0.002	-9999	-10000	0	0
PRDX1	0.015	0.002	-9999	-10000	0	0
PELP1	0.016	0.006	-9999	-10000	0	0
CTNNB1	0.012	0.011	-9999	-10000	0	0
AKT1	0.017	0.01	-9999	-10000	0	0
PTK2B	0.01	0.039	-9999	-0.58	1	1
MED1	0.018	0.011	-9999	-10000	0	0
MAK	0.01	0.089	-9999	-0.46	7	7
response to oxidative stress	0.001	0.003	-9999	-10000	0	0
HIP1	0.009	0.04	-9999	-0.58	1	1
GSN	0.001	0.077	-9999	-0.58	4	4
NCOA2	-0.018	0.13	-9999	-0.58	13	13
NCOA6	0.009	0.034	-9999	-0.47	1	1
DNA-PK	0.013	0.042	-9999	-10000	0	0
NCOA4	0.014	0.002	-9999	-10000	0	0
PIAS3	0.012	0.011	-9999	-10000	0	0
cell proliferation	-0.019	0.054	-9999	-10000	0	0
XRCC5	0.017	0.008	-9999	-10000	0	0
UBE3A	0.01	0.022	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.15	0.24	-9999	-0.44	86	86
FHL2	-0.028	0.15	-9999	-1.1	3	3
RANBP9	0.011	0.014	-9999	-10000	0	0
JMJD1A	-0.016	0.059	-9999	-0.12	57	57
CDK6	-0.005	0.11	-9999	-0.58	8	8
TGFB1I1	-0.004	0.094	-9999	-0.58	6	6
T-DHT/AR/CyclinD1	-0.13	0.2	-9999	-0.4	86	86
XRCC6	0.017	0.008	-9999	-10000	0	0
T-DHT/AR	-0.13	0.22	-9999	-0.4	84	84
CTDSP1	0.014	0.004	-9999	-10000	0	0
CTDSP2	0.021	0.024	-9999	-10000	0	0
BRCA1	0.009	0.036	-9999	-0.5	1	1
TCF4	0.012	0.068	-9999	-0.58	3	3
CDKN2A	-0.22	0.25	-9999	-0.47	119	119
SRF	0.025	0.018	-9999	-10000	0	0
NKX3-1	-0.082	0.16	-9999	-0.56	7	7
KLK3	-0.07	0.33	-9999	-1.5	12	12
TMF1	0.014	0.003	-9999	-10000	0	0
HNRNPA1	0.018	0.013	-9999	-10000	0	0
AOF2	-0.004	0.016	-9999	-0.071	12	12
APPL1	0.031	0.022	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.12	0.19	-9999	-0.38	81	81
AR	-0.2	0.29	-9999	-0.6	81	81
UBA3	0.014	0.004	-9999	-10000	0	0
PATZ1	0.018	0.013	-9999	-10000	0	0
PAWR	0.011	0.038	-9999	-0.58	1	1
PRKDC	0.017	0.008	-9999	-10000	0	0
PA2G4	0.019	0.016	-9999	-10000	0	0
UBE2I	0.015	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.11	0.18	-9999	-0.35	81	81
RPS6KA3	0.011	0.016	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.12	0.19	-9999	-0.38	81	81
LATS2	0.016	0.04	-9999	-0.58	1	1
T-DHT/AR/PRX1	-0.1	0.18	-9999	-0.35	81	81
Cyclin D3/CDK11 p58	0.011	0.003	-9999	-10000	0	0
VAV3	-0.003	0.089	-9999	-0.51	7	7
KLK2	-0.091	0.12	-9999	-0.44	13	13
CASP8	0.016	0.005	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.12	0.19	-9999	-0.36	88	88
TMPRSS2	-0.24	0.44	-9999	-1.1	52	52
CCND1	-0.006	0.1	-9999	-0.51	9	9
PIAS1	0.01	0.022	-9999	-10000	0	0
mol:T-DHT	-0.01	0.028	-9999	-0.073	26	26
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.006	0.035	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.13	0.2	-9999	-0.4	85	85
CMTM2	0.011	0.045	-9999	-0.47	2	2
SNURF	-0.037	0.16	-9999	-0.58	20	20
ZMIZ1	0.008	0.024	-9999	-10000	0	0
CCND3	0.015	0.001	-9999	-10000	0	0
TGIF1	0.018	0.013	-9999	-10000	0	0
FKBP4	0.011	0.014	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.012	0.12	-10000	0	-0.34	13	13
TBX21	-0.12	0.45	-10000	0	-1.2	27	27
B2M	0.015	0.008	-10000	0	-10000	0	0
TYK2	0.016	0.021	-10000	0	-10000	0	0
IL12RB1	-0.018	0.14	-10000	0	-0.52	16	16
GADD45B	-0.073	0.36	-10000	0	-0.97	23	23
IL12RB2	-0.082	0.2	-10000	0	-0.49	47	47
GADD45G	-0.076	0.36	-10000	0	-0.92	26	26
natural killer cell activation	0.001	0.025	-10000	0	-10000	0	0
RELB	0.015	0	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
IL18	0.008	0.078	-10000	0	-0.59	4	4
IL2RA	-0.048	0.17	-10000	0	-0.52	28	28
IFNG	-0.075	0.18	-10000	0	-0.47	43	43
STAT3 (dimer)	-0.071	0.33	-10000	0	-0.71	38	38
HLA-DRB5	-0.028	0.14	-10000	0	-0.54	17	17
FASLG	-0.15	0.48	-10000	0	-1.1	37	37
NF kappa B2 p52/RelB	-0.18	0.35	-10000	0	-0.88	39	39
CD4	0.006	0.054	-10000	0	-0.58	2	2
SOCS1	0.013	0.031	-10000	0	-0.47	1	1
EntrezGene:6955	-0.007	0.016	-10000	0	-10000	0	0
CD3D	-0.052	0.18	-10000	0	-0.57	26	26
CD3E	-0.05	0.18	-10000	0	-0.58	25	25
CD3G	-0.046	0.17	-10000	0	-0.58	23	23
IL12Rbeta2/JAK2	-0.048	0.15	-10000	0	-0.35	48	48
CCL3	-0.13	0.46	-10000	0	-1.1	34	34
CCL4	-0.16	0.51	-10000	0	-1.3	33	33
HLA-A	0.015	0.008	-10000	0	-10000	0	0
IL18/IL18R	0.029	0.13	-10000	0	-0.39	17	17
NOS2	-0.1	0.39	-10000	0	-1	25	25
IL12/IL12R/TYK2/JAK2/SPHK2	-0.012	0.12	-10000	0	-0.33	13	13
IL1R1	-0.1	0.4	-10000	0	-1	29	29
IL4	0.001	0.024	-10000	0	-10000	0	0
JAK2	0.014	0.044	-10000	0	-0.58	1	1
EntrezGene:6957	-0.006	0.015	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.11	0.34	-10000	0	-0.77	40	40
RAB7A	-0.031	0.3	-10000	0	-0.72	23	23
lysosomal transport	-0.026	0.28	-10000	0	-0.66	26	26
FOS	-0.41	0.65	-10000	0	-1.2	88	88
STAT4 (dimer)	-0.067	0.37	-10000	0	-0.81	35	35
STAT5A (dimer)	-0.2	0.36	-10000	0	-0.87	43	43
GZMA	-0.15	0.5	-10000	0	-1.2	34	34
GZMB	-0.13	0.45	-10000	0	-1.2	27	27
HLX	0.015	0	-10000	0	-10000	0	0
LCK	-0.12	0.45	-10000	0	-0.98	39	39
TCR/CD3/MHC II/CD4	-0.12	0.28	-10000	0	-0.63	39	39
IL2/IL2R	-0.02	0.14	-10000	0	-0.39	20	20
MAPK14	-0.059	0.36	-10000	0	-0.84	29	29
CCR5	-0.097	0.41	-10000	0	-1.1	26	26
IL1B	-0.04	0.17	-10000	0	-0.53	25	25
STAT6	-0.017	0.17	-10000	0	-0.42	15	15
STAT4	-0.012	0.12	-10000	0	-0.58	11	11
STAT3	0.015	0	-10000	0	-10000	0	0
STAT1	0.011	0.044	-10000	0	-0.47	2	2
NFKB1	0.015	0	-10000	0	-10000	0	0
NFKB2	0.015	0	-10000	0	-10000	0	0
IL12B	-0.001	0.078	-10000	0	-0.46	6	6
CD8A	-0.039	0.17	-10000	0	-0.58	22	22
CD8B	-0.028	0.15	-10000	0	-0.56	18	18
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.011	0.12	0.34	13	-10000	0	13
IL2RB	0.007	0.066	-10000	0	-0.58	3	3
proteasomal ubiquitin-dependent protein catabolic process	-0.055	0.34	-10000	0	-0.73	35	35
IL2RG	-0.008	0.11	-10000	0	-0.52	10	10
IL12	0.007	0.078	-10000	0	-0.32	10	10
STAT5A	0.012	0.038	-10000	0	-0.58	1	1
CD247	0.004	0.063	-10000	0	-0.55	3	3
IL2	0.004	0.007	-10000	0	-10000	0	0
SPHK2	0.013	0.031	-10000	0	-0.47	1	1
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.007	0.067	-10000	0	-0.48	4	4
IL12/IL12R/TYK2/JAK2	-0.14	0.51	-10000	0	-1.1	39	39
MAP2K3	-0.063	0.35	-10000	0	-0.84	29	29
RIPK2	0.015	0	-10000	0	-10000	0	0
MAP2K6	-0.067	0.36	-10000	0	-0.86	29	29
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.008	0.11	-10000	0	-0.58	8	8
IL18RAP	-0.014	0.14	-10000	0	-0.58	13	13
IL12Rbeta1/TYK2	-0.005	0.1	-10000	0	-0.37	16	16
EOMES	-0.06	0.3	-10000	0	-1.4	11	11
STAT1 (dimer)	-0.076	0.33	-10000	0	-0.73	34	34
T cell proliferation	-0.038	0.28	-10000	0	-0.62	30	30
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.013	0.056	-10000	0	-0.59	2	2
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.13	0.24	-10000	0	-0.65	33	33
ATF2	-0.044	0.33	-10000	0	-0.78	28	28

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	-0.016	0.071	-9999	-10000	0	0
BIRC5	-0.34	0.22	-9999	-0.47	177	177
NFKBIA	-0.015	0.072	-9999	-10000	0	0
CPEB1	-0.28	0.29	-9999	-0.58	117	117
AKT1	-0.015	0.072	-9999	-10000	0	0
NDEL1	0.015	0	-9999	-10000	0	0
Aurora A/BRCA1	-0.022	0.063	-9999	-0.37	1	1
NDEL1/TACC3	-0.031	0.089	-9999	-0.34	9	9
GADD45A	0.015	0	-9999	-10000	0	0
GSK3B	0.016	0.003	-9999	-10000	0	0
PAK1/Aurora A	-0.018	0.076	-9999	-0.47	1	1
MDM2	0.001	0.082	-9999	-0.47	7	7
JUB	0.011	0.044	-9999	-0.47	2	2
TPX2	-0.17	0.18	-9999	-0.33	135	135
TP53	-0.001	0.05	-9999	-10000	0	0
DLG7	-0.026	0.071	-9999	-10000	0	0
AURKAIP1	0.013	0.031	-9999	-0.47	1	1
ARHGEF7	0.015	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.024	0.099	-9999	-0.36	9	9
G2/M transition of mitotic cell cycle	-0.022	0.063	-9999	-0.36	1	1
AURKA	-0.03	0.088	-9999	-10000	0	0
AURKB	-0.042	0.046	-9999	-10000	0	0
CDC25B	-0.009	0.066	-9999	-0.21	6	6
G2/M transition checkpoint	-0.023	0.064	-9999	-0.3	2	2
mRNA polyadenylation	-0.18	0.19	-9999	-0.36	117	117
Aurora A/CPEB	-0.18	0.19	-9999	-0.37	117	117
Aurora A/TACC1/TRAP/chTOG	0.004	0.065	-9999	-0.4	1	1
BRCA1	0.013	0.031	-9999	-0.47	1	1
centrosome duplication	-0.018	0.076	-9999	-0.47	1	1
regulation of centrosome cycle	-0.031	0.088	-9999	-0.33	9	9
spindle assembly	-0.008	0.06	-9999	-0.39	1	1
TDRD7	0.015	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.18	0.12	-9999	-0.32	75	75
CENPA	-0.036	0.051	-9999	-10000	0	0
Aurora A/PP2A	-0.016	0.071	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.003	0.054	-9999	-10000	0	0
negative regulation of DNA binding	-0.001	0.05	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.022	0	-9999	-10000	0	0
RASA1	0.015	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.023	0.065	-9999	-0.3	2	2
mitotic prometaphase	0.01	0.013	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.03	0.088	-9999	-10000	0	0
TACC1	0.012	0.038	-9999	-0.58	1	1
TACC3	-0.022	0.13	-9999	-0.47	18	18
Aurora A/Antizyme1	-0.006	0.065	-9999	-10000	0	0
Aurora A/RasGAP	-0.016	0.071	-9999	-10000	0	0
OAZ1	0.015	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.016	0.003	-9999	-10000	0	0
GIT1	0.015	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	-0.001	0.022	-9999	-0.34	1	1
Importin alpha/Importin beta/TPX2	-0.17	0.18	-9999	-0.33	135	135
PPP2R5D	0.015	0	-9999	-10000	0	0
Aurora A/TPX2	-0.15	0.17	-9999	-0.36	74	74
PAK1	0.012	0.038	-9999	-0.58	1	1
CKAP5	0.015	0	-9999	-10000	0	0

×

Aurora C 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0.031	-9999	-0.47	1	1
Aurora C/Aurora B/INCENP	-0.1	0.14	-9999	-0.49	3	3
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.032	0.034	-9999	-10000	0	0
AURKB	-0.2	0.24	-9999	-0.47	107	107
AURKC	-0.001	0.087	-9999	-0.47	8	8

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	0.027	0.15	0.57	17	-10000	0	17
PI3K Class IB/PDE3B	-0.027	0.15	-10000	0	-0.58	17	17
PDE3B	-0.027	0.15	-10000	0	-0.58	17	17

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.005	0.048	-9999	-0.35	4	4
ARNO/beta Arrestin1-2	-0.021	0.07	-9999	-10000	0	0
EGFR	-0.01	0.11	-9999	-0.52	11	11
EPHA2	0.01	0.054	-9999	-0.58	2	2
USP6	0.015	0	-9999	-10000	0	0
IQSEC1	0.013	0.031	-9999	-0.47	1	1
EGFR/EGFR/EGF/EGF	-0.019	0.11	-9999	-0.34	26	26
ARRB2	0.011	0.016	-9999	-10000	0	0
mol:GTP	0.014	0.036	-9999	-0.21	4	4
ARRB1	0.012	0.038	-9999	-0.58	1	1
FBXO8	0.015	0	-9999	-10000	0	0
TSHR	0.001	0.069	-9999	-0.47	5	5
EGF	-0.017	0.12	-9999	-0.47	15	15
somatostatin receptor activity	0	0	-9999	-0.001	40	40
ARAP2	0.012	0.038	-9999	-0.58	1	1
mol:GDP	-0.072	0.12	-9999	-0.25	48	48
mol:PI-3-4-5-P3	0	0	-9999	-0.001	28	28
ITGA2B	-0.02	0.12	-9999	-0.47	17	17
ARF6	0.015	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.028	0.052	-9999	-0.31	2	2
ADAP1	0.005	0.076	-9999	-0.58	4	4
KIF13B	0.015	0	-9999	-10000	0	0
HGF/MET	-0.083	0.18	-9999	-0.41	59	59
PXN	0.015	0	-9999	-10000	0	0
ARF6/GTP	-0.065	0.12	-9999	-0.27	39	39
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.016	0.096	-9999	-0.28	27	27
ADRB2	-0.03	0.16	-9999	-0.58	18	18
receptor agonist activity	0	0	-9999	0	47	47
actin filament binding	0	0	-9999	-0.001	40	40
SRC	0.015	0	-9999	-10000	0	0
ITGB3	-0.039	0.17	-9999	-0.58	22	22
GNAQ	0.015	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	35	35
ARF6/GDP	0.006	0.098	-9999	-0.38	11	11
ARF6/GDP/GULP/ACAP1	-0.12	0.16	-9999	-0.42	41	41
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.012	0.12	-9999	-0.33	22	22
ACAP1	-0.016	0.13	-9999	-0.55	13	13
ACAP2	0.015	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0.003	0.024	-9999	-0.24	2	2
EFNA1	0.003	0.076	-9999	-0.47	6	6
HGF	-0.13	0.25	-9999	-0.57	59	59
CYTH3	0.012	0	-9999	-10000	0	0
CYTH2	0.01	0.002	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	30	30
endosomal lumen acidification	0	0	-9999	0	35	35
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.064	0.2	-9999	-0.58	32	32
GNAQ/ARNO	0.016	0.008	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	3	3
MET	0.015	0	-9999	-10000	0	0
GNA14	-0.079	0.22	-9999	-0.58	38	38
GNA15	0.01	0.054	-9999	-0.58	2	2
GIT1	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	35	35
GNA11	0.012	0.038	-9999	-0.58	1	1
LHCGR	0	0.044	-9999	-0.47	2	2
AGTR1	-0.25	0.29	-9999	-0.58	108	108
desensitization of G-protein coupled receptor protein signaling pathway	0.003	0.023	-9999	-0.24	2	2
IPCEF1/ARNO	-0.003	0.074	-9999	-10000	0	0
alphaIIb/beta3 Integrin	-0.042	0.15	-9999	-0.4	37	37

×

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0.012	0.052	0.24	12	-10000	0	12
RFC1	0.012	0.052	0.24	12	-10000	0	12
PRKDC	0.012	0.052	0.24	12	-10000	0	12
RIPK1	0.019	0.005	-10000	0	-10000	0	0
CASP7	-0.031	0.042	0.25	1	-10000	0	1
FASLG/FAS/FADD/FAF1	-0.04	0.088	0.21	3	-0.31	16	19
MAP2K4	-0.09	0.17	-10000	0	-0.44	16	16
mol:ceramide	-0.058	0.14	-10000	0	-0.4	20	20
GSN	0.006	0.069	0.24	12	-0.34	4	16
FASLG/FAS/FADD/FAF1/Caspase 8	-0.037	0.11	0.21	1	-0.37	15	16
FAS	-0.001	0.076	-10000	0	-0.59	4	4
BID	0	0.028	0.3	1	-0.29	1	2
MAP3K1	-0.039	0.1	0.21	1	-0.26	12	13
MAP3K7	0.009	0.007	-10000	0	-10000	0	0
RB1	0.012	0.052	0.24	12	-10000	0	12
CFLAR	0.019	0.005	-10000	0	-10000	0	0
HGF/MET	-0.091	0.16	-10000	0	-0.35	63	63
ARHGDIB	0.012	0.052	0.24	12	-10000	0	12
FADD	0.001	0.064	-10000	0	-0.49	4	4
actin filament polymerization	-0.006	0.069	0.34	4	-0.24	12	16
NFKB1	-0.096	0.1	-10000	0	-0.27	14	14
MAPK8	-0.16	0.25	-10000	0	-0.43	109	109
DFFA	0.012	0.052	0.24	12	-10000	0	12
DNA fragmentation during apoptosis	0.012	0.052	0.24	12	-10000	0	12
FAS/FADD/MET	0.005	0.063	-10000	0	-0.34	6	6
CFLAR/RIP1	0.012	0.011	-10000	0	-10000	0	0
FAIM3	0.013	0.05	-10000	0	-0.52	2	2
FAF1	0.009	0.008	-10000	0	-10000	0	0
PARP1	0.012	0.052	0.24	12	-10000	0	12
DFFB	0.012	0.052	0.24	12	-10000	0	12
CHUK	-0.083	0.091	-10000	0	-0.27	1	1
FASLG	-0.037	0.16	-10000	0	-0.57	19	19
FAS/FADD	-0.001	0.073	-10000	0	-0.39	8	8
HGF	-0.13	0.25	-10000	0	-0.57	59	59
LMNA	0.011	0.048	0.22	11	-10000	0	11
CASP6	0.012	0.052	0.24	12	-10000	0	12
CASP10	0.009	0.008	-10000	0	-10000	0	0
CASP3	0.014	0.061	0.28	12	-10000	0	12
PTPN13	0	0.092	-10000	0	-0.58	6	6
CASP8	0.002	0.028	0.4	1	-10000	0	1
IL6	-0.57	0.67	-10000	0	-1.3	109	109
MET	0.015	0	-10000	0	-10000	0	0
ICAD/CAD	0.011	0.049	0.23	11	-10000	0	11
FASLG/FAS/FADD/FAF1/Caspase 10	-0.059	0.14	-10000	0	-0.4	20	20
activation of caspase activity by cytochrome c	0	0.028	0.3	1	-0.29	1	2
PAK2	0.012	0.051	0.24	12	-10000	0	12
BCL2	-0.011	0.12	-10000	0	-0.58	11	11

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	0.036	0.25	-10000	0	-0.83	18	18
NCK1/PAK1/Dok-R	-0.035	0.11	-10000	0	-0.41	18	18
NCK1/Dok-R	0	0.29	-10000	0	-1	18	18
PIK3CA	0.014	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.001	0.058	0.24	13	-10000	0	13
RELA	0.015	0	-10000	0	-10000	0	0
SHC1	0.014	0.031	-10000	0	-0.47	1	1
Rac/GDP	0.011	0	-10000	0	-10000	0	0
F2	-0.025	0.14	0.26	12	-0.5	16	28
TNIP2	0.015	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.068	0.24	-10000	0	-0.93	18	18
FN1	-0.029	0.14	-10000	0	-0.51	20	20
PLD2	0.003	0.29	-10000	0	-1	18	18
PTPN11	0.015	0	-10000	0	-10000	0	0
GRB14	-0.052	0.17	-10000	0	-0.47	33	33
ELK1	0.018	0.27	-10000	0	-0.93	18	18
GRB7	-0.006	0.1	-10000	0	-0.49	10	10
PAK1	0.012	0.038	-10000	0	-0.58	1	1
Tie2/Ang1/alpha5/beta1 Integrin	-0.09	0.28	-10000	0	-1.1	18	18
CDKN1A	0.031	0.19	-10000	0	-0.59	17	17
ITGA5	-0.002	0.099	-10000	0	-0.58	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	0	0.29	-10000	0	-1	18	18
CRK	0.015	0	-10000	0	-10000	0	0
mol:NO	0.051	0.2	-10000	0	-0.62	18	18
PLG	-0.003	0.29	-10000	0	-1	18	18
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	0.018	0.24	-10000	0	-0.82	18	18
GRB2	0.015	0	-10000	0	-10000	0	0
PIK3R1	0.016	0.001	-10000	0	-10000	0	0
ANGPT2	-0.044	0.19	-10000	0	-0.63	13	13
BMX	-0.087	0.34	-10000	0	-1.2	18	18
ANGPT1	-0.024	0.31	-10000	0	-1.3	13	13
tube development	0.023	0.2	-10000	0	-0.64	17	17
ANGPT4	0.002	0.062	-10000	0	-0.47	4	4
response to hypoxia	0.001	0.019	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.031	0.3	-10000	0	-1.1	18	18
alpha5/beta1 Integrin	0.009	0.073	-10000	0	-0.42	7	7
FGF2	-0.18	0.28	-10000	0	-0.58	77	77
STAT5A (dimer)	0.025	0.23	-10000	0	-0.72	17	17
mol:L-citrulline	0.051	0.2	-10000	0	-0.62	18	18
AGTR1	-0.25	0.29	-10000	0	-0.57	108	108
MAPK14	0.001	0.3	-10000	0	-1	18	18
Tie2/SHP2	-0.032	0.16	-10000	0	-1.1	5	5
TEK	0.018	0.19	-10000	0	-1.2	5	5
RPS6KB1	0.033	0.24	-10000	0	-0.81	18	18
Angiotensin II/AT1	-0.18	0.22	-10000	0	-0.42	108	108
Tie2/Ang1/GRB2	-0.001	0.3	-10000	0	-1.1	18	18
MAPK3	0.013	0.27	-10000	0	-0.95	18	18
MAPK1	0.013	0.27	-10000	0	-0.95	18	18
Tie2/Ang1/GRB7	-0.011	0.3	-10000	0	-1.1	18	18
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	0	0.29	-10000	0	-1	18	18
PI3K	0.018	0.28	-10000	0	-0.95	18	18
FES	0	0.29	-10000	0	-1	18	18
Crk/Dok-R	0	0.29	-10000	0	-1	18	18
Tie2/Ang1/ABIN2	-0.001	0.3	-10000	0	-1.1	18	18
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	0.041	0.23	-10000	0	-0.75	18	18
STAT5A	0.013	0.038	-10000	0	-0.58	1	1
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	0.033	0.24	-10000	0	-0.81	18	18
Tie2/Ang2	0.007	0.25	-10000	0	-0.86	16	16
Tie2/Ang1	-0.006	0.31	-10000	0	-1.1	18	18
FOXO1	0.049	0.23	-10000	0	-0.74	18	18
ELF1	0.023	0.015	-10000	0	-10000	0	0
ELF2	0.001	0.29	-10000	0	-1	18	18
mol:Choline	0.006	0.28	-10000	0	-0.98	18	18
cell migration	-0.023	0.064	-10000	0	-0.23	18	18
FYN	0.018	0.23	-10000	0	-0.73	17	17
DOK2	-0.004	0.1	-10000	0	-0.56	8	8
negative regulation of cell cycle	0.033	0.18	-10000	0	-0.54	17	17
ETS1	0.013	0.055	-10000	0	-0.22	12	12
PXN	0.046	0.21	-10000	0	-0.67	18	18
ITGB1	0.015	0	-10000	0	-10000	0	0
NOS3	0.047	0.22	-10000	0	-0.7	18	18
RAC1	0.015	0	-10000	0	-10000	0	0
TNF	-0.01	0.12	-10000	0	-0.46	13	13
MAPKKK cascade	0.006	0.28	-10000	0	-0.98	18	18
RASA1	0.015	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0	0.3	-10000	0	-1.1	18	18
NCK1	0.015	0	-10000	0	-10000	0	0
vasculogenesis	0.054	0.18	-10000	0	-0.56	18	18
mol:Phosphatidic acid	0.006	0.28	-10000	0	-0.98	18	18
mol:Angiotensin II	0.001	0.001	-10000	0	-10000	0	0
mol:NADP	0.051	0.2	-10000	0	-0.62	18	18
Rac1/GTP	-0.057	0.2	-10000	0	-0.75	18	18
MMP2	-0.023	0.31	-10000	0	-1.1	18	18

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.08	0.14	-9999	-0.56	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.045	0.13	-9999	-0.51	2	2
alphaV/beta3 Integrin/Osteopontin/Src	-0.13	0.16	-9999	-0.32	101	101
AP1	-0.16	0.24	-9999	-0.58	32	32
ILK	-0.093	0.15	-9999	-0.59	2	2
bone resorption	-0.069	0.14	-9999	-0.46	10	10
PTK2B	0.012	0.038	-9999	-0.58	1	1
PYK2/p130Cas	-0.1	0.11	-9999	-0.54	2	2
ITGAV	0.015	0.039	-9999	-0.58	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.005	0.1	-9999	-0.41	15	15
alphaV/beta3 Integrin/Osteopontin	-0.14	0.14	-9999	-0.32	46	46
MAP3K1	-0.095	0.15	-9999	-0.36	10	10
JUN	0	0.093	-9999	-0.58	6	6
MAPK3	-0.08	0.15	-9999	-0.57	2	2
MAPK1	-0.08	0.15	-9999	-0.57	2	2
Rac1/GDP	0.011	0	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
MAPK8	-0.083	0.14	-9999	-0.49	4	4
ITGB3	-0.036	0.17	-9999	-0.57	22	22
NFKBIA	-0.064	0.14	-9999	-0.56	2	2
FOS	-0.17	0.27	-9999	-0.58	74	74
CD44	-0.009	0.12	-9999	-0.57	10	10
CHUK	0.015	0	-9999	-10000	0	0
PLAU	-0.08	0.17	-9999	-0.79	1	1
NF kappa B1 p50/RelA	-0.086	0.096	-9999	-0.5	2	2
BCAR1	0.015	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.034	0.12	-9999	-0.42	22	22
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.097	0.15	-9999	-0.31	24	24
VAV3	-0.089	0.15	-9999	-0.43	8	8
MAP3K14	-0.094	0.15	-9999	-0.42	5	5
ROCK2	0.002	0.084	-9999	-0.58	5	5
SPP1	-0.18	0.24	-9999	-0.47	100	100
RAC1	0.015	0	-9999	-10000	0	0
Rac1/GTP	-0.075	0.14	-9999	-0.46	5	5
MMP2	-0.15	0.23	-9999	-0.6	29	29

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.033	0.13	0.41	26	-10000	0	26
KIRREL	-0.037	0.17	-10000	0	-0.59	20	20
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.033	0.13	-10000	0	-0.41	26	26
PLCG1	0.015	0	-10000	0	-10000	0	0
ARRB2	0.015	0	-10000	0	-10000	0	0
WASL	0.015	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.042	0.11	-10000	0	-0.34	20	20
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.001	0.093	-10000	0	-0.29	20	20
FYN	-0.023	0.11	-10000	0	-0.33	21	21
mol:Ca2+	-0.042	0.11	-10000	0	-0.34	20	20
mol:DAG	-0.042	0.11	-10000	0	-0.34	20	20
NPHS2	-0.022	0.11	-10000	0	-0.48	12	12
mol:IP3	-0.042	0.11	-10000	0	-0.34	20	20
regulation of endocytosis	-0.013	0.1	-10000	0	-0.31	20	20
Nephrin/NEPH1/podocin/Cholesterol	-0.043	0.11	-10000	0	-0.35	20	20
establishment of cell polarity	-0.033	0.13	-10000	0	-0.41	26	26
Nephrin/NEPH1/podocin/NCK1-2	-0.031	0.099	-10000	0	-0.46	4	4
Nephrin/NEPH1/beta Arrestin2	-0.012	0.11	-10000	0	-0.31	20	20
NPHS1	-0.011	0.075	-10000	0	-0.46	6	6
Nephrin/NEPH1/podocin	-0.023	0.11	-10000	0	-0.34	21	21
TJP1	0.015	0	-10000	0	-10000	0	0
NCK1	0.015	0	-10000	0	-10000	0	0
NCK2	0.015	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.042	0.11	-10000	0	-0.34	20	20
CD2AP	0.015	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.042	0.11	-10000	0	-0.34	20	20
GRB2	0.015	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.017	0.11	-10000	0	-0.31	20	20
cytoskeleton organization	0	0.11	-10000	0	-0.33	20	20
Nephrin/NEPH1	-0.021	0.095	-10000	0	-0.29	26	26
Nephrin/NEPH1/ZO-1	-0.035	0.1	-10000	0	-0.34	20	20

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.014	0.12	-9999	-0.32	29	29
EPHB2	-0.014	0.11	-9999	-0.47	14	14
Syndecan-2/TACI	-0.025	0.13	-9999	-0.34	33	33
LAMA1	-0.086	0.2	-9999	-0.49	48	48
Syndecan-2/alpha2 ITGB1	-0.021	0.13	-9999	-0.31	26	26
HRAS	0.015	0	-9999	-10000	0	0
Syndecan-2/CASK	0.001	0.074	-9999	-0.35	10	10
ITGA5	-0.002	0.099	-9999	-0.58	7	7
BAX	0.026	0.076	-9999	-10000	0	0
EPB41	0.015	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.013	0.062	-9999	-0.31	10	10
LAMA3	-0.074	0.2	-9999	-0.52	40	40
EZR	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.012	0.038	-9999	-0.58	1	1
Syndecan-2/MMP2	-0.019	0.14	-9999	-0.41	26	26
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	0.018	0.039	-9999	-0.33	3	3
dendrite morphogenesis	-0.005	0.098	-9999	-0.3	24	24
Syndecan-2/GM-CSF	-0.044	0.13	-9999	-0.28	55	55
determination of left/right symmetry	0.004	0.087	-9999	-0.41	10	10
Syndecan-2/PKC delta	0.012	0.074	-9999	-0.34	10	10
GNB2L1	0.015	0	-9999	-10000	0	0
MAPK3	-0.029	0.12	-9999	-0.31	10	10
MAPK1	-0.029	0.12	-9999	-0.31	10	10
Syndecan-2/RACK1	0.02	0.064	-9999	-0.29	10	10
NF1	0.015	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.004	0.087	-9999	-0.41	10	10
ITGA2	0.009	0.054	-9999	-0.47	3	3
MAPK8	0.018	0.085	-9999	-0.34	13	13
Syndecan-2/alpha2/beta1 Integrin	-0.027	0.13	-9999	-0.32	19	19
Syndecan-2/Kininogen	0.001	0.074	-9999	-0.35	10	10
ITGB1	0.015	0	-9999	-10000	0	0
SRC	0.028	0.061	-9999	-0.26	10	10
Syndecan-2/CASK/Protein 4.1	0.011	0.067	-9999	-0.31	10	10
extracellular matrix organization	0.012	0.074	-9999	-0.34	10	10
actin cytoskeleton reorganization	-0.014	0.12	-9999	-0.32	29	29
Syndecan-2/Caveolin-2/Ras	0.02	0.071	-9999	-0.3	11	11
Syndecan-2/Laminin alpha3	-0.042	0.15	-9999	-0.33	47	47
Syndecan-2/RasGAP	-0.011	0.053	-9999	-0.27	10	10
alpha5/beta1 Integrin	0.009	0.073	-9999	-0.42	7	7
PRKCD	0.015	0	-9999	-10000	0	0
Syndecan-2 dimer	-0.005	0.099	-9999	-0.3	24	24
GO:0007205	0.004	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.036	0.06	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
SDCBP	0.015	0	-9999	-10000	0	0
TNFRSF13B	-0.044	0.17	-9999	-0.56	23	23
RASA1	0.015	0	-9999	-10000	0	0
alpha2/beta1 Integrin	0.018	0.039	-9999	-0.33	3	3
Syndecan-2/Synbindin	0.012	0.074	-9999	-0.34	10	10
TGFB1	0.015	0	-9999	-10000	0	0
CASP3	0.022	0.068	-9999	-0.3	10	10
FN1	-0.029	0.14	-9999	-0.51	20	20
Syndecan-2/IL8	-0.044	0.16	-9999	-0.37	44	44
SDC2	0.004	0.087	-9999	-0.41	10	10
KNG1	0	0	-9999	-10000	0	0
Syndecan-2/Neurofibromin	0.012	0.074	-9999	-0.34	10	10
TRAPPC4	0.015	0	-9999	-10000	0	0
CSF2	-0.078	0.19	-9999	-0.47	45	45
Syndecan-2/TGFB1	0.012	0.074	-9999	-0.34	10	10
Syndecan-2/Syntenin/PI-4-5-P2	0.011	0.067	-9999	-0.31	10	10
Syndecan-2/Ezrin	0.021	0.068	-9999	-0.3	10	10
PRKACA	0.022	0.068	-9999	-0.3	10	10
angiogenesis	-0.044	0.16	-9999	-0.36	44	44
MMP2	-0.037	0.17	-9999	-0.58	21	21
IL8	-0.076	0.21	-9999	-0.57	37	37
calcineurin-NFAT signaling pathway	-0.025	0.12	-9999	-0.34	33	33

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.005	0.035	-10000	0	-10000	0	0
HDAC1	0.013	0.01	-10000	0	-10000	0	0
AES	0.014	0.003	-10000	0	-10000	0	0
FBXW11	0.015	0	-10000	0	-10000	0	0
DTX1	-0.009	0.11	-10000	0	-0.55	10	10
LRP6/FZD1	0.022	0	-10000	0	-10000	0	0
TLE1	0.009	0.054	-10000	0	-0.58	2	2
AP1	-0.085	0.17	-10000	0	-0.31	80	80
NCSTN	0.015	0	-10000	0	-10000	0	0
ADAM10	0.015	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.031	0.07	-10000	0	-10000	0	0
NICD/RBPSUH	0.003	0.011	-10000	0	-10000	0	0
WIF1	-0.14	0.25	-10000	0	-0.57	63	63
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0.015	0	-10000	0	-10000	0	0
KREMEN2	-0.17	0.24	-10000	0	-0.47	91	91
DKK1	-0.07	0.2	-10000	0	-0.55	36	36
beta catenin/beta TrCP1	0.028	0.04	-10000	0	-10000	0	0
APH1B	0.015	0	-10000	0	-10000	0	0
APH1A	0.015	0	-10000	0	-10000	0	0
AXIN1	0.005	0.013	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.027	0.048	0.29	1	-10000	0	1
PSEN1	0.015	0	-10000	0	-10000	0	0
FOS	-0.17	0.27	-10000	0	-0.58	74	74
JUN	0	0.092	-10000	0	-0.58	6	6
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
CTNNB1	0.02	0.042	-10000	0	-10000	0	0
MAPK3	0.015	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.16	0.18	-10000	0	-0.32	123	123
HNF1A	0.006	0.063	-10000	0	-0.48	4	4
CTBP1	0.012	0.031	-10000	0	-0.47	1	1
MYC	-0.04	0.31	-10000	0	-1.4	11	11
NKD1	-0.014	0.12	-10000	0	-0.55	12	12
FZD1	0.015	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.008	0.053	-10000	0	-10000	0	0
apoptosis	-0.084	0.17	-10000	0	-0.31	80	80
Delta 1/NOTCHprecursor	-0.002	0.037	-10000	0	-10000	0	0
DLL1	0.003	0.079	-10000	0	-0.54	5	5
PPARD	0.022	0.024	-10000	0	-10000	0	0
Gamma Secretase	0.041	0.012	-10000	0	-10000	0	0
APC	0.005	0.013	-10000	0	-10000	0	0
DVL1	-0.007	0.023	-10000	0	-10000	0	0
CSNK2A1	0.015	0.002	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.005	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.15	0.18	-10000	0	-0.32	112	112
LRP6	0.015	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.002	-10000	0	-10000	0	0
NLK	0.017	0.011	-10000	0	-10000	0	0
CCND1	-0.002	0.17	-10000	0	-1.5	3	3
WNT1	0.009	0.032	-10000	0	-0.47	1	1
Axin1/APC/beta catenin	0.039	0.031	-10000	0	-10000	0	0
DKK2	-0.1	0.21	-10000	0	-0.48	57	57
NOTCH1 precursor/DVL1	0	0.006	-10000	0	-10000	0	0
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.014	0.002	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.011	0.051	-10000	0	-10000	0	0
PPP2R5D	0.008	0.06	0.26	12	-10000	0	12
MAPK1	0.015	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.058	0.15	-10000	0	-0.31	57	57
RBPJ	0.015	0	-10000	0	-10000	0	0
CREBBP	0.018	0.005	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.03	-10000	0	-10000	0	0
AES	0.018	0.023	-10000	0	-10000	0	0
FBXW11	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.018	0.009	-10000	0	-10000	0	0
SMAD4	0.015	0	-10000	0	-10000	0	0
DKK2	-0.1	0.21	-10000	0	-0.48	57	57
TLE1	0.013	0.059	-10000	0	-0.58	2	2
MACF1	0.015	0	-10000	0	-10000	0	0
CTNNB1	0.046	0.081	0.27	5	-10000	0	5
WIF1	-0.14	0.25	-10000	0	-0.57	63	63
beta catenin/RanBP3	0.034	0.13	0.38	27	-10000	0	27
KREMEN2	-0.17	0.24	-10000	0	-0.47	91	91
DKK1	-0.07	0.2	-10000	0	-0.55	36	36
beta catenin/beta TrCP1	0.053	0.076	0.26	5	-10000	0	5
FZD1	0.015	0.001	-10000	0	-10000	0	0
AXIN2	-0.081	0.36	-10000	0	-1.4	15	15
AXIN1	0.015	0.001	-10000	0	-10000	0	0
RAN	0.015	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.017	0.035	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.081	0.06	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.015	0.044	0.23	5	-10000	0	5
Axin1/APC/GSK3/beta catenin/Macf1	0.063	0.033	-10000	0	-10000	0	0
HNF1A	0.009	0.068	-10000	0	-0.48	4	4
CTBP1	0.01	0.04	-10000	0	-0.45	1	1
MYC	-0.063	0.32	-10000	0	-1.5	11	11
RANBP3	0.015	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.16	0.18	-10000	0	-0.32	123	123
NKD1	-0.014	0.12	-10000	0	-0.55	12	12
TCF4	0.009	0.069	-10000	0	-0.56	3	3
TCF3	0.018	0.024	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.009	0.023	-10000	0	-10000	0	0
Ran/GTP	0.011	0.002	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.049	0.15	0.47	26	-10000	0	26
LEF1	0.008	0.067	-10000	0	-0.47	4	4
DVL1	0.061	0.041	-10000	0	-10000	0	0
CSNK2A1	0.015	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.083	-10000	0	-0.35	1	1
DKK1/LRP6/Kremen 2	-0.15	0.18	-10000	0	-0.32	112	112
LRP6	0.015	0.001	-10000	0	-10000	0	0
CSNK1A1	0.013	0.03	-10000	0	-10000	0	0
NLK	0.014	0.005	-10000	0	-10000	0	0
CCND1	-0.026	0.19	-10000	0	-1.3	4	4
WNT1	0.01	0.032	-10000	0	-0.47	1	1
GSK3A	0.015	0.001	-10000	0	-10000	0	0
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.014	0	-10000	0	-10000	0	0
PPP2R5D	0.045	0.066	0.31	12	-10000	0	12
APC	0.042	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.078	0.095	0.24	57	-10000	0	57
CREBBP	0.018	0.024	-10000	0	-10000	0	0

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.035	0.14	-9999	-0.56	7	7
FZD6	0.015	0	-9999	-10000	0	0
WNT6	-0.055	0.18	-9999	-0.5	32	32
WNT4	-0.029	0.15	-9999	-0.57	18	18
FZD3	0.012	0.038	-9999	-0.58	1	1
WNT5A	-0.01	0.11	-9999	-0.52	11	11
WNT11	-0.046	0.17	-9999	-0.51	28	28

×

Visual signal transduction: Rods

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
mol:K +	0.015	0	-9999	-10000	0	0
GNAT1/GTP	0.006	0.023	-9999	-0.34	1	1
Metarhodopsin II/Arrestin	0.002	0.004	-9999	-10000	0	0
PDE6G/GNAT1/GTP	-0.006	0.051	-9999	-0.28	8	8
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.008	0.032	-9999	-0.47	1	1
GRK1	0.001	0.004	-9999	-10000	0	0
CNG Channel	-0.13	0.14	-9999	-0.44	27	27
mol:Na +	-0.14	0.14	-9999	-0.44	28	28
mol:ADP	0.001	0.004	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.095	0.16	-9999	-0.36	64	64
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.15	0.15	-9999	-0.46	28	28
CNGB1	-0.2	0.24	-9999	-0.47	105	105
RDH5	0.012	0.038	-9999	-0.58	1	1
SAG	0	0	-9999	-10000	0	0
mol:Ca2+	-0.12	0.16	-9999	-0.43	28	28
Na + (4 Units)	-0.13	0.13	-9999	-0.42	28	28
RGS9	-0.12	0.25	-9999	-0.58	54	54
GNB1/GNGT1	0.003	0.076	-9999	-0.33	12	12
GNAT1/GDP	-0.081	0.14	-9999	-0.3	62	62
GUCY2D	-0.036	0.14	-9999	-0.47	24	24
GNGT1	-0.011	0.11	-9999	-0.47	12	12
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.015	0	-9999	-10000	0	0
mol:GMP (4 units)	0.009	0.078	-9999	-0.29	8	8
mol:11-cis-retinal	0.012	0.038	-9999	-0.58	1	1
mol:cGMP	-0.014	0.094	-9999	-0.38	2	2
GNB1	0.015	0	-9999	-10000	0	0
Rhodopsin	0.012	0.029	-9999	-0.42	1	1
SLC24A1	0.015	0	-9999	-10000	0	0
CNGA1	-0.054	0.18	-9999	-0.52	31	31
Metarhodopsin II	0.003	0.005	-9999	-10000	0	0
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.016	0.1	-9999	-0.41	2	2
RGS9BP	-0.017	0.13	-9999	-0.56	13	13
Metarhodopsin II/Transducin	0.012	0.03	-9999	-10000	0	0
GCAP Family/Ca ++	0.003	0.062	-9999	-0.26	13	13
PDE6A/B	0.001	0.089	-9999	-0.39	12	12
mol:Pi	-0.095	0.16	-9999	-0.36	64	64
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.01	0.06	-9999	-0.24	13	13
PDE6B	-0.005	0.11	-9999	-0.58	8	8
PDE6A	0.005	0.062	-9999	-0.47	4	4
PDE6G	0	0.082	-9999	-0.47	7	7
RHO	0.004	0.006	-9999	-10000	0	0
PDE6	-0.091	0.14	-9999	-0.59	7	7
GUCA1A	-0.011	0.1	-9999	-0.47	11	11
GC2/GCAP Family	0.004	0.062	-9999	-0.33	1	1
GUCA1C	-0.001	0.031	-9999	-0.47	1	1
GUCA1B	0.012	0.038	-9999	-0.58	1	1

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.013	0.031	-9999	-0.47	1	1
SPHK1	-0.05	0.17	-9999	-0.48	32	32
GNAI2	0.015	0	-9999	-10000	0	0
mol:S1P	0.004	0.054	-9999	-0.29	1	1
GNAO1	-0.15	0.27	-9999	-0.58	68	68
mol:Sphinganine-1-P	-0.023	0.12	-9999	-0.33	33	33
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.029	0.038	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
G12/G13	0.022	0	-9999	-10000	0	0
S1PR3	0	0.09	-9999	-0.56	6	6
S1PR2	0.015	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.015	0.038	-9999	-0.25	1	1
S1PR5	-0.006	0.1	-9999	-0.49	10	10
S1PR4	0.004	0.076	-9999	-0.52	5	5
GNAI1	0.012	0.038	-9999	-0.58	1	1
S1P/S1P5/G12	0.009	0.069	-9999	-0.31	4	4
S1P/S1P3/Gq	-0.02	0.12	-9999	-0.35	9	9
S1P/S1P4/Gi	-0.095	0.19	-9999	-0.34	73	73
GNAQ	0.015	0	-9999	-10000	0	0
GNAZ	-0.11	0.24	-9999	-0.58	52	52
GNA14	-0.079	0.22	-9999	-0.58	38	38
GNA15	0.01	0.054	-9999	-0.58	2	2
GNA12	0.015	0	-9999	-10000	0	0
GNA13	0.015	0	-9999	-10000	0	0
GNA11	0.012	0.038	-9999	-0.58	1	1
ABCC1	0.011	0.044	-9999	-0.47	2	2

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0	0.1	-9999	-0.52	7	7
Syndecan-4/Syndesmos	-0.023	0.12	-9999	-0.51	6	6
positive regulation of JNK cascade	-0.1	0.17	-9999	-0.53	15	15
Syndecan-4/ADAM12	-0.048	0.14	-9999	-0.49	10	10
CCL5	-0.017	0.13	-9999	-0.54	14	14
Rac1/GDP	0.011	0	-9999	-10000	0	0
DNM2	0.015	0	-9999	-10000	0	0
ITGA5	-0.002	0.099	-9999	-0.58	7	7
SDCBP	0.015	0	-9999	-10000	0	0
PLG	0.003	0.009	-9999	-10000	0	0
ADAM12	-0.04	0.15	-9999	-0.47	27	27
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.036	0.049	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.071	0.16	-9999	-0.54	13	13
Syndecan-4/CXCL12/CXCR4	-0.11	0.18	-9999	-0.57	15	15
Syndecan-4/Laminin alpha3	-0.066	0.15	-9999	-0.48	9	9
MDK	-0.016	0.12	-9999	-0.47	15	15
Syndecan-4/FZD7	-0.035	0.13	-9999	-0.51	6	6
Syndecan-4/Midkine	-0.037	0.13	-9999	-0.55	6	6
FZD7	-0.01	0.12	-9999	-0.58	10	10
Syndecan-4/FGFR1/FGF	-0.18	0.22	-9999	-0.56	49	49
THBS1	-0.005	0.11	-9999	-0.58	8	8
integrin-mediated signaling pathway	-0.047	0.15	-9999	-0.54	12	12
positive regulation of MAPKKK cascade	-0.1	0.17	-9999	-0.53	15	15
Syndecan-4/TACI	-0.052	0.14	-9999	-0.47	9	9
CXCR4	0.007	0.066	-9999	-0.58	3	3
cell adhesion	0.009	0.098	-9999	-0.48	7	7
Syndecan-4/Dynamin	-0.023	0.12	-9999	-0.51	6	6
Syndecan-4/TSP1	-0.032	0.13	-9999	-0.55	7	7
Syndecan-4/GIPC	-0.023	0.12	-9999	-0.51	6	6
Syndecan-4/RANTES	-0.038	0.14	-9999	-0.6	8	8
ITGB1	0.015	0	-9999	-10000	0	0
LAMA1	-0.086	0.2	-9999	-0.49	48	48
LAMA3	-0.074	0.2	-9999	-0.52	40	40
RAC1	0.015	0	-9999	-10000	0	0
PRKCA	0.022	0.031	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.023	0.12	-9999	-0.51	6	6
TFPI	0.005	0.076	-9999	-0.58	4	4
F2	-0.028	0.12	-9999	-0.48	17	17
alpha5/beta1 Integrin	0.009	0.073	-9999	-0.42	7	7
positive regulation of cell adhesion	-0.1	0.18	-9999	-0.52	18	18
ACTN1	0.015	0	-9999	-10000	0	0
TNC	-0.04	0.17	-9999	-0.56	23	23
Syndecan-4/CXCL12	-0.11	0.18	-9999	-0.55	16	16
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
CXCL12	-0.17	0.27	-9999	-0.58	74	74
TNFRSF13B	-0.044	0.17	-9999	-0.56	23	23
FGF2	-0.17	0.28	-9999	-0.58	77	77
FGFR1	-0.12	0.25	-9999	-0.58	55	55
Syndecan-4/PI-4-5-P2	-0.032	0.12	-9999	-0.52	6	6
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.028	0.14	-9999	-0.51	20	20
cell migration	-0.014	0.022	-9999	-10000	0	0
PRKCD	0.016	0.006	-9999	-10000	0	0
vasculogenesis	-0.031	0.12	-9999	-0.53	7	7
SDC4	-0.033	0.12	-9999	-0.55	6	6
Syndecan-4/Tenascin C	-0.049	0.16	-9999	-0.56	12	12
Syndecan-4/PI-4-5-P2/PKC alpha	-0.028	0.039	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.023	0.12	-9999	-0.51	6	6
MMP9	-0.13	0.22	-9999	-0.48	70	70
Rac1/GTP	0.009	0.1	-9999	-0.5	7	7
cytoskeleton organization	-0.022	0.11	-9999	-0.49	6	6
GIPC1	0.015	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.027	0.13	-9999	-0.59	7	7

×

ErbB2/ErbB3 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
USP8	0.02	0.005	-9999	-10000	0	0
RAS family/GTP	-0.025	0.12	-9999	-0.42	6	6
NFATC4	-0.026	0.11	-9999	-0.38	5	5
ERBB2IP	0.015	0.003	-9999	-10000	0	0
HSP90 (dimer)	0.015	0	-9999	-10000	0	0
mammary gland morphogenesis	-0.048	0.13	-9999	-0.46	4	4
JUN	0.002	0.082	-9999	-0.34	1	1
HRAS	0.014	0.001	-9999	-10000	0	0
DOCK7	-0.039	0.12	-9999	-0.43	4	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.068	0.14	-9999	-0.32	48	48
AKT1	0.012	0.003	-9999	-10000	0	0
BAD	0.021	0.003	-9999	-10000	0	0
MAPK10	-0.02	0.095	-9999	-0.28	8	8
mol:GTP	-0.001	0.002	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.049	0.14	-9999	-0.5	4	4
RAF1	-0.016	0.12	-9999	-0.42	6	6
ErbB2/ErbB3/neuregulin 2	-0.16	0.18	-9999	-0.34	110	110
STAT3	0.003	0.005	-9999	-10000	0	0
cell migration	-0.007	0.089	-9999	-0.25	8	8
mol:PI-3-4-5-P3	-0.001	0.002	-9999	-10000	0	0
cell proliferation	-0.086	0.23	-9999	-0.5	33	33
FOS	-0.12	0.27	-9999	-0.51	74	74
NRAS	0.014	0.001	-9999	-10000	0	0
mol:Ca2+	-0.048	0.13	-9999	-0.46	4	4
MAPK3	-0.054	0.18	-9999	-0.56	10	10
MAPK1	-0.054	0.18	-9999	-0.56	10	10
JAK2	-0.04	0.12	-9999	-0.43	4	4
NF2	-0.001	0.004	-9999	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.042	0.13	-9999	-0.29	48	48
NRG1	-0.12	0.24	-9999	-0.55	59	59
GRB2/SOS1	0.022	0.002	-9999	-10000	0	0
MAPK8	-0.036	0.12	-9999	-0.29	20	20
MAPK9	0	0.073	-9999	-0.21	3	3
ERBB2	-0.01	0.058	-9999	-0.35	7	7
ERBB3	-0.001	0.09	-9999	-0.56	6	6
SHC1	0.012	0.031	-9999	-0.47	1	1
RAC1	0.015	0	-9999	-10000	0	0
apoptosis	0.005	0.012	-9999	-10000	0	0
STAT3 (dimer)	0.02	0.006	-9999	-10000	0	0
RNF41	0.025	0.008	-9999	-10000	0	0
FRAP1	0.01	0.003	-9999	-10000	0	0
RAC1-CDC42/GTP	-0.045	0.076	-9999	-0.3	4	4
ErbB2/ErbB2/HSP90 (dimer)	-0.008	0.047	-9999	-0.28	7	7
CHRNA1	-0.051	0.17	-9999	-0.39	24	24
myelination	-0.018	0.11	-9999	-0.36	5	5
PPP3CB	-0.036	0.12	-9999	-0.4	4	4
KRAS	0.012	0.031	-9999	-0.47	1	1
RAC1-CDC42/GDP	-0.02	0.12	-9999	-0.44	4	4
NRG2	-0.25	0.29	-9999	-0.58	106	106
mol:GDP	-0.042	0.13	-9999	-0.29	48	48
SOS1	0.014	0.001	-9999	-10000	0	0
MAP2K2	-0.012	0.12	-9999	-0.45	5	5
SRC	0.015	0	-9999	-10000	0	0
mol:cAMP	-0.001	0.002	-9999	-10000	0	0
PTPN11	-0.035	0.12	-9999	-0.43	4	4
MAP2K1	-0.069	0.19	-9999	-0.48	19	19
heart morphogenesis	-0.048	0.13	-9999	-0.46	4	4
RAS family/GDP	-0.025	0.12	-9999	-0.49	4	4
GRB2	0.014	0.001	-9999	-10000	0	0
PRKACA	-0.004	0.007	-9999	-10000	0	0
CHRNE	0.013	0.024	-9999	-0.22	1	1
HSP90AA1	0.015	0	-9999	-10000	0	0
activation of caspase activity	-0.012	0.003	-9999	-10000	0	0
nervous system development	-0.048	0.13	-9999	-0.46	4	4
CDC42	0.015	0	-9999	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0.01	0.032	-9999	-0.34	2	2
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.002	0.089	-9999	-0.41	11	11
STXBP1	-0.007	0.11	-9999	-0.58	9	9
ACh/CHRNA1	-0.049	0.12	-9999	-0.3	44	44
RAB3GAP2/RIMS1/UNC13B	-0.015	0.071	-9999	-0.34	11	11
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	-0.018	0.12	-9999	-0.57	11	11
mol:ACh	-0.002	0.037	-9999	-0.12	18	18
RAB3GAP2	0.015	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.032	0.085	-9999	-0.4	6	6
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.049	0.12	-9999	-0.3	44	44
UNC13B	0.015	0	-9999	-10000	0	0
CHRNA1	-0.075	0.19	-9999	-0.47	44	44
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.03	0.12	-9999	-0.38	25	25
SNAP25	-0.018	0.082	-9999	-0.25	25	25
VAMP2	0.007	0	-9999	-10000	0	0
SYT1	-0.045	0.18	-9999	-0.56	25	25
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.004	0.076	-9999	-0.34	11	11
STX1A/SNAP25 fragment 1/VAMP2	-0.032	0.085	-9999	-0.4	6	6

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	-0.28	0.3	-9999	-0.58	119	119
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.013	0.031	-9999	-0.47	1	1
TCEB1	0.015	0	-9999	-10000	0	0
HIF1A/p53	0.034	0.016	-9999	-10000	0	0
HIF1A	0.026	0.017	-9999	-10000	0	0
COPS5	0.015	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.043	0.016	-9999	-10000	0	0
FIH (dimer)	0.015	0	-9999	-10000	0	0
CDKN2A	-0.23	0.25	-9999	-0.48	119	119
ARNT/IPAS	-0.19	0.22	-9999	-0.42	119	119
HIF1AN	0.015	0	-9999	-10000	0	0
GNB2L1	0.015	0	-9999	-10000	0	0
HIF1A/ARNT	0.034	0.016	-9999	-10000	0	0
CUL2	0.015	0	-9999	-10000	0	0
OS9	0.015	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.001	0.017	-9999	-0.27	1	1
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.034	0.016	-9999	-10000	0	0
PHD1-3/OS9	0.031	0.049	-9999	-0.31	5	5
HIF1A/RACK1/Elongin B/Elongin C	-0.002	0.013	-9999	-10000	0	0
VHL	0.015	0	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
HIF1A/JAB1	0.034	0.016	-9999	-10000	0	0
EGLN3	0.002	0.084	-9999	-0.58	5	5
EGLN2	0.015	0	-9999	-10000	0	0
EGLN1	0.015	0	-9999	-10000	0	0
TP53	0.015	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.042	0.009	-9999	-10000	0	0
ARNT	0.015	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.015	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.082	0.12	-9999	-0.27	6	6

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.084	0.22	-9999	-0.58	40	40
GNB1/GNG2	-0.017	0.13	-9999	-0.5	7	7
mol:DAG	-0.007	0.12	-9999	-0.45	7	7
PLCG1	-0.007	0.12	-9999	-0.49	6	6
YES1	-0.024	0.13	-9999	-0.52	7	7
FZD3	0.012	0.038	-9999	-0.58	1	1
FZD6	0.015	0	-9999	-10000	0	0
G protein	-0.007	0.12	-9999	-0.47	7	7
MAP3K7	-0.077	0.16	-9999	-0.37	32	32
mol:Ca2+	-0.006	0.12	-9999	-0.43	7	7
mol:IP3	-0.007	0.12	-9999	-0.45	7	7
NLK	-0.003	0.008	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
CAMK2A	-0.091	0.18	-9999	-0.41	32	32
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.035	0.14	-9999	-0.56	7	7
CSNK1A1	0.015	0	-9999	-10000	0	0
GNAS	-0.024	0.13	-9999	-0.52	7	7
GO:0007205	-0.006	0.12	-9999	-0.46	6	6
WNT6	-0.055	0.18	-9999	-0.5	32	32
WNT4	-0.029	0.15	-9999	-0.57	18	18
NFAT1/CK1 alpha	-0.049	0.15	-9999	-0.48	11	11
GNG2	0.012	0.038	-9999	-0.58	1	1
WNT5A	-0.01	0.11	-9999	-0.52	11	11
WNT11	-0.046	0.17	-9999	-0.51	28	28
CDC42	-0.015	0.13	-9999	-0.49	7	7

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.025	0.002	-9999	-10000	0	0
SMARCC1	0.011	0.012	-9999	-10000	0	0
REL	0.011	0.048	-9999	-0.51	2	2
HDAC7	-0.025	0.14	-9999	-0.34	19	19
JUN	-0.001	0.092	-9999	-0.58	6	6
EP300	0.015	0.001	-9999	-10000	0	0
KAT2B	0.015	0.001	-9999	-10000	0	0
KAT5	0.015	0.001	-9999	-10000	0	0
MAPK14	0.013	0.055	-9999	-0.39	4	4
FOXO1	0.015	0.001	-9999	-10000	0	0
T-DHT/AR	-0.034	0.15	-9999	-0.37	19	19
MAP2K6	0.003	0.072	-9999	-0.55	4	4
BRM/BAF57	0.02	0.008	-9999	-10000	0	0
MAP2K4	0.012	0.008	-9999	-10000	0	0
SMARCA2	0.014	0.004	-9999	-10000	0	0
PDE9A	-0.18	0.43	-9999	-1.3	33	33
NCOA2	-0.018	0.13	-9999	-0.58	13	13
CEBPA	0.004	0.073	-9999	-0.49	5	5
EHMT2	0.013	0.004	-9999	-10000	0	0
cell proliferation	-0.015	0.16	-9999	-0.44	10	10
NR0B1	-0.033	0.13	-9999	-0.47	19	19
EGR1	-0.13	0.26	-9999	-0.58	60	60
RXRs/9cRA	-0.074	0.15	-9999	-0.32	67	67
AR/RACK1/Src	-0.023	0.093	-9999	-0.39	5	5
AR/GR	-0.074	0.16	-9999	-0.32	51	51
GNB2L1	0.015	0.001	-9999	-10000	0	0
PKN1	0.012	0.038	-9999	-0.58	1	1
RCHY1	0.015	0	-9999	-10000	0	0
epidermal growth factor receptor activity	-0.001	0.002	-9999	-10000	0	0
MAPK8	0.014	0.051	-9999	-0.42	3	3
T-DHT/AR/TIF2/CARM1	-0.024	0.12	-9999	-0.41	11	11
SRC	0.021	0.061	-9999	-0.28	6	6
NR3C1	0	0.092	-9999	-0.58	6	6
KLK3	-0.14	0.29	-9999	-1.1	16	16
APPBP2	0.012	0.008	-9999	-10000	0	0
TRIM24	0.009	0.045	-9999	-0.48	2	2
T-DHT/AR/TIP60	-0.015	0.098	-9999	-0.4	5	5
TMPRSS2	-0.25	0.48	-9999	-1.2	49	49
RXRG	-0.16	0.26	-9999	-0.58	67	67
mol:9cRA	0	0.002	-9999	-10000	0	0
RXRA	0.012	0.038	-9999	-0.58	1	1
RXRB	0.015	0.001	-9999	-10000	0	0
CARM1	0.015	0.002	-9999	-10000	0	0
NR2C2	0.01	0.049	-9999	-0.52	2	2
KLK2	-0.033	0.14	-9999	-0.45	8	8
AR	-0.08	0.17	-9999	-0.3	81	81
SENP1	0.014	0.001	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
MDM2	0.002	0.083	-9999	-0.47	7	7
SRY	0	0.062	-9999	-0.47	4	4
GATA2	-0.01	0.11	-9999	-0.52	11	11
MYST2	0.015	0.001	-9999	-10000	0	0
HOXB13	-0.08	0.21	-9999	-0.56	39	39
T-DHT/AR/RACK1/Src	-0.009	0.097	-9999	-0.39	5	5
positive regulation of transcription	-0.01	0.11	-9999	-0.52	11	11
DNAJA1	0.012	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.02	-9999	-10000	0	0
NCOA1	0.019	0.006	-9999	-10000	0	0
SPDEF	-0.099	0.22	-9999	-0.54	49	49
T-DHT/AR/TIF2	0	0.093	-9999	-0.33	8	8
T-DHT/AR/Hsp90	-0.016	0.098	-9999	-0.38	6	6
GSK3B	0.013	0.005	-9999	-10000	0	0
NR2C1	0.015	0.002	-9999	-10000	0	0
mol:T-DHT	0.013	0.066	-9999	-0.31	6	6
SIRT1	0.015	0.001	-9999	-10000	0	0
ZMIZ2	0.017	0.008	-9999	-10000	0	0
POU2F1	0.013	0.047	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.054	0.11	-9999	-0.34	15	15
CREBBP	0.015	0.001	-9999	-10000	0	0
SMARCE1	0.014	0.004	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.022	0	-9999	-10000	0	0
CRKL	-0.012	0.1	-9999	-0.35	2	2
mol:PIP3	-0.02	0.006	-9999	-10000	0	0
AKT1	0.003	0.005	-9999	-10000	0	0
PTK2B	0.012	0.038	-9999	-0.58	1	1
RAPGEF1	-0.003	0.098	-9999	-0.4	1	1
RANBP10	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.083	0.14	-9999	-0.34	59	59
MAP3K5	0.002	0.1	-9999	-0.38	3	3
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.044	0.14	-9999	-0.31	53	53
AP1	-0.11	0.2	-9999	-0.39	74	74
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.013	0.031	-9999	-0.47	1	1
apoptosis	-0.22	0.36	-9999	-0.75	74	74
STAT3 (dimer)	-0.018	0.12	-9999	-0.49	1	1
GAB1/CRKL/SHP2/PI3K	-0.037	0.069	-9999	-0.37	1	1
INPP5D	0	0.092	-9999	-0.58	6	6
CBL/CRK	-0.001	0.095	-9999	-10000	0	0
PTPN11	0.015	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.015	0	-9999	-10000	0	0
PTEN	0.015	0	-9999	-10000	0	0
ELK1	-0.003	0.009	-9999	-10000	0	0
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.032	0.058	-9999	-10000	0	0
PAK1	0.009	0.02	-9999	-0.29	1	1
HGF/MET/RANBP10	-0.083	0.14	-9999	-0.34	59	59
HRAS	-0.032	0.14	-9999	-10000	0	0
DOCK1	-0.005	0.1	-9999	-0.4	1	1
GAB1	-0.019	0.1	-9999	-0.3	1	1
CRK	-0.01	0.099	-9999	-0.27	1	1
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.1	0.2	-9999	-0.47	53	53
JUN	0	0.092	-9999	-0.58	6	6
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.033	0.091	-9999	-0.2	53	53
PIK3R1	0.015	0	-9999	-10000	0	0
cell morphogenesis	0.008	0.13	-9999	-0.41	2	2
GRB2/SHC	-0.013	0.082	-9999	-0.21	1	1
FOS	-0.17	0.27	-9999	-0.58	74	74
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.003	0.009	-9999	-10000	0	0
HGF/MET/MUC20	-0.085	0.15	-9999	-0.35	59	59
cell migration	-0.013	0.081	-9999	-0.21	1	1
GRB2	0.015	0	-9999	-10000	0	0
CBL	0.015	0	-9999	-10000	0	0
MET/RANBP10	0.022	0	-9999	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.025	0.12	-9999	-0.51	1	1
MET/MUC20	0.011	0	-9999	-10000	0	0
RAP1B	0.005	0.094	-9999	-0.37	1	1
RAP1A	0.005	0.094	-9999	-0.37	1	1
HGF/MET/RANBP9	-0.083	0.14	-9999	-0.34	59	59
RAF1	-0.023	0.13	-9999	-10000	0	0
STAT3	-0.018	0.12	-9999	-0.5	1	1
cell proliferation	-0.027	0.16	-9999	-0.33	53	53
RPS6KB1	-0.003	0.035	-9999	-10000	0	0
MAPK3	-0.008	0.007	-9999	-10000	0	0
MAPK1	-0.008	0.007	-9999	-10000	0	0
RANBP9	0.015	0	-9999	-10000	0	0
MAPK8	0.018	0.1	-9999	-0.4	3	3
SRC	-0.015	0.11	-9999	-0.47	1	1
PI3K	-0.012	0.081	-9999	-10000	0	0
MET/Glomulin	0.014	0	-9999	-10000	0	0
SOS1	0.015	0	-9999	-10000	0	0
MAP2K1	-0.013	0.12	-9999	-10000	0	0
MET	0.015	0	-9999	-10000	0	0
MAP4K1	-0.007	0.11	-9999	-0.41	3	3
PTK2	0.015	0	-9999	-10000	0	0
MAP2K2	-0.013	0.12	-9999	-10000	0	0
BAD	0.01	0.005	-9999	-10000	0	0
MAP2K4	0.011	0.096	-9999	-0.34	3	3
SHP2/GRB2/SOS1/GAB1	-0.037	0.068	-9999	-10000	0	0
INPPL1	0.015	0	-9999	-10000	0	0
PXN	0.015	0	-9999	-10000	0	0
SH3KBP1	0.015	0	-9999	-10000	0	0
HGS	-0.022	0.084	-9999	-10000	0	0
PLCgamma1/PKC	0.011	0	-9999	-10000	0	0
HGF	-0.13	0.25	-9999	-0.57	59	59
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
PTPRJ	0.015	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.015	0.091	-9999	-10000	0	0
PDPK1	-0.008	0.005	-9999	-10000	0	0
HGF/MET/SHIP	-0.091	0.16	-9999	-0.35	62	62

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.016	0	-9999	-10000	0	0
ELF1	-0.009	0.095	-9999	-0.34	14	14
CCNA2	-0.12	0.22	-9999	-0.47	68	68
PIK3CA	0.016	0	-9999	-10000	0	0
JAK3	0.012	0.044	-9999	-0.47	2	2
PIK3R1	0.016	0	-9999	-10000	0	0
JAK1	0.016	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.058	0.094	-9999	-0.46	4	4
SHC1	0.014	0.031	-9999	-0.47	1	1
SP1	-0.005	0.098	-9999	-0.34	19	19
IL2RA	-0.036	0.21	-9999	-0.58	28	28
IL2RB	0.008	0.066	-9999	-0.58	3	3
SOS1	0.016	0	-9999	-10000	0	0
IL2RG	-0.007	0.11	-9999	-0.52	10	10
G1/S transition of mitotic cell cycle	-0.061	0.24	-9999	-0.74	23	23
PTPN11	0.016	0	-9999	-10000	0	0
CCND2	-0.032	0.23	-9999	-0.81	19	19
LCK	0.009	0.062	-9999	-0.54	3	3
GRB2	0.016	0	-9999	-10000	0	0
IL2	0.005	0.007	-9999	-10000	0	0
CDK6	-0.005	0.11	-9999	-0.58	8	8
CCND3	0.064	0.084	-9999	-0.5	2	2

×

EGFR-dependent Endothelin 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
HRAS	0.015	0	-9999	-10000	0	0
EGFR	-0.01	0.11	-9999	-0.52	11	11
EGF/EGFR	-0.06	0.11	-9999	-0.29	33	33
EGF/EGFR dimer/SHC/GRB2/SOS1	0.013	0.087	-9999	-0.31	6	6
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.052	0.19	-9999	-0.58	27	27
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.017	0.12	-9999	-0.47	15	15
EGF/EGFR dimer/SHC	-0.031	0.092	-9999	-0.29	26	26
mol:GDP	-0.025	0.073	-9999	-0.3	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	0.002	0.079	-9999	-0.49	6	6
GRB2/SOS1	0.022	0	-9999	-10000	0	0
HRAS/GTP	-0.022	0.066	-9999	-0.41	1	1
SHC1	0.013	0.031	-9999	-0.47	1	1
HRAS/GDP	-0.023	0.067	-9999	-0.42	1	1
FRAP1	0.011	0.082	-9999	-0.29	6	6
EGF/EGFR dimer	-0.019	0.11	-9999	-0.34	26	26
SOS1	0.015	0	-9999	-10000	0	0
GRB2	0.015	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.036	0.15	-9999	-0.4	33	33

×

Caspase cascade in apoptosis

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
TOP1	0.006	0.11	-10000	0	-0.32	18	18
ACTA1	-0.01	0.14	-10000	0	-0.4	19	19
NUMA1	0.006	0.11	-10000	0	-0.32	18	18
SPTAN1	-0.006	0.13	-10000	0	-0.41	18	18
LIMK1	-0.006	0.13	-10000	0	-0.41	18	18
BIRC3	-0.024	0.14	-10000	0	-0.56	16	16
BIRC2	0.011	0.044	-10000	0	-0.47	2	2
BAX	0.015	0	-10000	0	-10000	0	0
CASP10	-0.023	0.15	-10000	0	-0.39	32	32
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.013	0.031	-10000	0	-0.47	1	1
PTK2	0.006	0.11	-10000	0	-0.32	18	18
DIABLO	0.015	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.005	0.13	-10000	0	-0.4	18	18
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.015	0	-10000	0	-10000	0	0
GSN	-0.011	0.14	-10000	0	-0.4	22	22
MADD	0.015	0	-10000	0	-10000	0	0
TFAP2A	0.022	0.026	-10000	0	-10000	0	0
BID	-0.001	0.076	-10000	0	-0.23	20	20
MAP3K1	0.007	0.051	-10000	0	-0.2	3	3
TRADD	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.022	0.002	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.006	0.13	-10000	0	-0.41	18	18
CASP9	0.015	0	-10000	0	-10000	0	0
DNA repair	-0.009	0.05	0.16	1	-0.19	10	11
neuron apoptosis	0.025	0.016	-10000	0	-10000	0	0
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.004	0.13	-10000	0	-0.38	18	18
APAF1	0.015	0	-10000	0	-10000	0	0
CASP6	0.024	0.067	-10000	0	-0.36	2	2
TRAF2	0.015	0	-10000	0	-10000	0	0
ICAD/CAD	0.003	0.13	-10000	0	-0.39	18	18
CASP7	0.009	0.074	0.29	14	-10000	0	14
KRT18	0.014	0.047	-10000	0	-0.63	1	1
apoptosis	0.01	0.12	-10000	0	-0.37	16	16
DFFA	-0.006	0.13	-10000	0	-0.41	18	18
DFFB	-0.006	0.13	-10000	0	-0.41	18	18
PARP1	0.009	0.05	0.19	10	-0.16	1	11
actin filament polymerization	-0.002	0.12	0.37	18	-10000	0	18
TNF	-0.01	0.11	-10000	0	-0.47	12	12
CYCS	0.003	0.059	-10000	0	-0.19	11	11
SATB1	0.018	0.088	-10000	0	-0.36	3	3
SLK	-0.006	0.13	-10000	0	-0.41	18	18
p15 BID/BAX	0.007	0.068	-10000	0	-0.3	3	3
CASP2	0.039	0.051	-10000	0	-10000	0	0
JNK cascade	-0.007	0.05	0.2	3	-10000	0	3
CASP3	-0.014	0.14	-10000	0	-0.44	18	18
LMNB2	0.041	0.041	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
CASP4	0.013	0.031	-10000	0	-0.47	1	1
Mammalian IAPs/DIABLO	0.01	0.091	-10000	0	-0.32	15	15
negative regulation of DNA binding	0.022	0.026	-10000	0	-10000	0	0
stress fiber formation	-0.005	0.13	-10000	0	-0.4	18	18
GZMB	-0.039	0.17	-10000	0	-0.46	32	32
CASP1	0.008	0.063	-10000	0	-0.35	7	7
LMNB1	0.04	0.041	-10000	0	-10000	0	0
APP	0.026	0.017	-10000	0	-10000	0	0
TNFRSF1A	0.015	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.013	0	-10000	0	-10000	0	0
VIM	0.005	0.12	-10000	0	-0.37	16	16
LMNA	0.041	0.041	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.033	0.054	-10000	0	-10000	0	0
LRDD	0.015	0	-10000	0	-10000	0	0
SREBF1	-0.007	0.13	-10000	0	-0.41	18	18
APAF-1/Caspase 9	0.004	0.045	0.32	1	-10000	0	1
nuclear fragmentation during apoptosis	0.006	0.11	-10000	0	-0.32	18	18
CFL2	0.002	0.13	-10000	0	-0.38	18	18
GAS2	-0.041	0.16	-10000	0	-0.36	39	39
positive regulation of apoptosis	0.044	0.041	-10000	0	-10000	0	0
PRF1	-0.014	0.12	-10000	0	-0.51	13	13

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.02	0.071	-9999	-0.37	1	1
epithelial cell differentiation	-0.042	0.093	-9999	-0.44	4	4
ITCH	0.016	0.033	-9999	-0.47	1	1
WWP1	0.032	0.031	-9999	-10000	0	0
FYN	0.01	0.054	-9999	-0.58	2	2
EGFR	-0.01	0.11	-9999	-0.52	11	11
PRL	-0.003	0.061	-9999	-0.47	4	4
neuron projection morphogenesis	0.002	0.12	-9999	-10000	0	0
PTPRZ1	-0.16	0.26	-9999	-0.54	76	76
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.057	0.1	-9999	-10000	0	0
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.044	0.14	-9999	-0.36	11	11
ADAM17	0.018	0.008	-9999	-10000	0	0
ErbB4/ErbB4	0.03	0.038	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.005	0.055	-9999	-10000	0	0
NCOR1	0.015	0	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.036	0.14	-9999	-0.48	2	2
GRIN2B	-0.037	0.14	-9999	-0.47	5	5
ErbB4/ErbB2/betacellulin	-0.003	0.11	-9999	-0.39	2	2
STAT1	0.011	0.044	-9999	-0.47	2	2
HBEGF	-0.005	0.11	-9999	-0.58	8	8
PRLR	-0.047	0.17	-9999	-0.51	28	28
E4ICDs/ETO2	0.018	0.073	-9999	-10000	0	0
axon guidance	0.029	0.1	-9999	-10000	0	0
NEDD4	0.018	0.008	-9999	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.035	0.13	-9999	-0.36	32	32
CBFA2T3	-0.007	0.11	-9999	-0.58	9	9
ErbB4/ErbB2/HBEGF	0.024	0.079	-9999	-0.51	1	1
MAPK3	-0.006	0.12	-9999	-10000	0	0
STAT1 (dimer)	0.029	0.04	-9999	-10000	0	0
MAPK1	-0.006	0.12	-9999	-10000	0	0
JAK2	0.012	0.038	-9999	-0.58	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.04	0.14	-9999	-0.39	1	1
NRG1	-0.077	0.18	-9999	-0.4	59	59
NRG3	-0.007	0.081	-9999	-0.47	7	7
NRG2	-0.25	0.29	-9999	-0.58	106	106
NRG4	-0.042	0.17	-9999	-0.58	23	23
heart development	0.029	0.1	-9999	-10000	0	0
neural crest cell migration	-0.04	0.14	-9999	-0.38	1	1
ERBB2	0.017	0.06	-9999	-0.33	7	7
WWOX/E4ICDs	0.03	0.038	-9999	-10000	0	0
SHC1	0.013	0.031	-9999	-0.47	1	1
ErbB4/EGFR/neuregulin 4	-0.008	0.12	-9999	-0.49	5	5
apoptosis	0.013	0.045	-9999	-10000	0	0
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.13	0.18	-9999	-0.42	8	8
ErbB4/ErbB2/epiregulin	-0.044	0.14	-9999	-0.48	3	3
ErbB4/ErbB4/betacellulin/betacellulin	-0.01	0.12	-9999	-0.46	2	2
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.04	0.093	-9999	-0.45	3	3
MDM2	0.027	0.058	-9999	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.062	0.13	-9999	-0.33	9	9
STAT5A	0.036	0.1	-9999	-0.4	1	1
ErbB4/EGFR/neuregulin 1 beta	-0.046	0.15	-9999	-0.53	4	4
DLG4	0.015	0	-9999	-10000	0	0
GRB2/SHC	0.02	0.022	-9999	-0.33	1	1
E4ICDs/TAB2/NCoR1	-0.005	0.018	-9999	-10000	0	0
STAT5A (dimer)	-0.044	0.099	-9999	-0.48	4	4
MAP3K7IP2	0	0	-9999	-10000	0	0
STAT5B (dimer)	0.034	0.093	-9999	-10000	0	0
LRIG1	-0.022	0.14	-9999	-0.58	15	15
EREG	-0.13	0.24	-9999	-0.52	66	66
BTC	-0.052	0.19	-9999	-0.58	27	27
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.029	0.1	-9999	-10000	0	0
ERBB4	0.03	0.038	-9999	-10000	0	0
STAT5B	0.015	0	-9999	-10000	0	0
YAP1	-0.001	0.013	-9999	-10000	0	0
GRB2	0.015	0	-9999	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.003	0.11	-9999	-0.53	3	3
glial cell differentiation	0.005	0.018	-9999	-10000	0	0
WWOX	0.012	0.038	-9999	-0.58	1	1
cell proliferation	-0.056	0.16	-9999	-0.49	6	6

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.015	0	-10000	0	-10000	0	0
HDAC2	0.015	0.001	-10000	0	-10000	0	0
GNB1/GNG2	0.008	0.082	-10000	0	-0.34	12	12
forebrain development	-0.083	0.24	-10000	0	-0.58	36	36
GNAO1	-0.15	0.27	-10000	0	-0.58	68	68
SMO/beta Arrestin2	0.002	0.092	-10000	0	-0.42	11	11
SMO	-0.013	0.12	-10000	0	-0.58	11	11
ARRB2	0.014	0.005	-10000	0	-10000	0	0
GLI3/SPOP	0.05	0.059	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.015	0	-10000	0	-10000	0	0
GNAI2	0.015	0.002	-10000	0	-10000	0	0
SIN3/HDAC complex	0.038	0.002	-10000	0	-10000	0	0
GNAI1	0.012	0.038	-10000	0	-0.58	1	1
XPO1	0.015	0.006	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.088	0.19	-10000	0	-0.63	17	17
SAP30	0.015	0.001	-10000	0	-10000	0	0
mol:GDP	-0.013	0.12	-10000	0	-0.58	11	11
MIM/GLI2A	0.016	0.008	-10000	0	-10000	0	0
IFT88	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0.001	-10000	0	-10000	0	0
GLI2	0.021	0.074	-10000	0	-10000	0	0
GLI3	0.044	0.062	0.2	9	-0.24	8	17
CSNK1D	0.015	0	-10000	0	-10000	0	0
CSNK1E	0.015	0	-10000	0	-10000	0	0
SAP18	0.015	0	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.015	0	-10000	0	-10000	0	0
GNG2	0.012	0.038	-10000	0	-0.58	1	1
Gi family/GTP	-0.11	0.22	-10000	0	-0.38	74	74
SIN3B	0.015	0.001	-10000	0	-10000	0	0
SIN3A	0.015	0	-10000	0	-10000	0	0
GLI3/Su(fu)	0.063	0.043	-10000	0	-10000	0	0
GLI2/Su(fu)	0.027	0.084	-10000	0	-10000	0	0
FOXA2	-0.052	0.11	-10000	0	-10000	0	0
neural tube patterning	-0.083	0.24	-10000	0	-0.58	36	36
SPOP	0.015	0	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.024	0.045	-10000	0	-10000	0	0
GNB1	0.015	0	-10000	0	-10000	0	0
CSNK1G2	0.015	0	-10000	0	-10000	0	0
CSNK1G3	0.015	0	-10000	0	-10000	0	0
MTSS1	0.016	0.008	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.083	0.24	-10000	0	-0.58	36	36
SUFU	0.019	0.05	-10000	0	-10000	0	0
LGALS3	0.012	0.038	-10000	0	-0.58	1	1
catabolic process	0.056	0.078	-10000	0	-0.31	4	4
GLI3A/CBP	-0.029	0.13	-10000	0	-0.34	35	35
KIF3A	0.015	0	-10000	0	-10000	0	0
GLI1	-0.086	0.25	-10000	0	-0.59	36	36
RAB23	0.012	0.038	-10000	0	-0.58	1	1
CSNK1A1	0.015	0	-10000	0	-10000	0	0
IFT172	0.015	0	-10000	0	-10000	0	0
RBBP7	0.015	0.001	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.023	0.05	-10000	0	-0.3	1	1
GNAZ	-0.11	0.24	-10000	0	-0.58	52	52
RBBP4	0.015	0	-10000	0	-10000	0	0
CSNK1G1	0.015	0	-10000	0	-10000	0	0
PIAS1	0.015	0	-10000	0	-10000	0	0
PRKACA	0.015	0	-10000	0	-10000	0	0
GLI2/SPOP	0.027	0.069	-10000	0	-10000	0	0
STK36	0.015	0.006	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.088	0.19	-10000	0	-0.46	37	37
PTCH1	-0.065	0.21	-10000	0	-0.63	19	19
MIM/GLI1	-0.086	0.24	-10000	0	-0.63	29	29
CREBBP	-0.029	0.13	-10000	0	-0.34	35	35
Su(fu)/SIN3/HDAC complex	0.053	0.014	-10000	0	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.002	0.22	-10000	0	-0.78	5	5
PCK1	-0.007	0.16	-10000	0	-0.64	3	3
HNF4A	-0.024	0.27	-10000	0	-0.9	7	7
KCNJ11	-0.031	0.32	-10000	0	-0.9	18	18
AKT1	0.021	0.11	-10000	0	-10000	0	0
response to starvation	-0.002	0.017	-10000	0	-10000	0	0
DLK1	-0.055	0.35	-10000	0	-0.98	22	22
NKX2-1	0.11	0.23	0.66	10	-0.58	1	11
ACADM	-0.001	0.23	-10000	0	-0.83	6	6
TAT	-0.004	0.16	-10000	0	-0.7	4	4
CEBPB	0.013	0.008	-10000	0	-10000	0	0
CEBPA	0.003	0.074	-10000	0	-0.5	5	5
TTR	-0.079	0.22	-10000	0	-0.68	9	9
PKLR	-0.013	0.24	-10000	0	-0.84	5	5
APOA1	-0.002	0.26	-10000	0	-1.1	3	3
CPT1C	-0.002	0.23	-10000	0	-0.78	5	5
ALAS1	0.04	0.13	-10000	0	-10000	0	0
TFRC	0.008	0.17	-10000	0	-0.68	1	1
FOXF1	-0.2	0.29	-10000	0	-0.57	89	89
NF1	0.023	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.02	0.075	-10000	0	-0.5	4	4
CPT1A	-0.001	0.23	-10000	0	-0.91	5	5
HMGCS1	0.002	0.22	-10000	0	-0.84	4	4
NR3C1	0.004	0.096	-10000	0	-0.57	6	6
CPT1B	-0.002	0.24	-10000	0	-0.91	5	5
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	-0.012	0.038	-10000	0	-10000	0	0
GCK	-0.04	0.32	-10000	0	-0.98	16	16
CREB1	0.014	0.019	-10000	0	-10000	0	0
IGFBP1	0.008	0.15	-10000	0	-0.56	3	3
PDX1	-0.057	0.19	-10000	0	-0.68	2	2
UCP2	0.001	0.22	-10000	0	-0.75	6	6
ALDOB	-0.003	0.25	-10000	0	-0.77	9	9
AFP	-0.065	0.14	-10000	0	-0.45	11	11
BDH1	0.002	0.22	-10000	0	-0.84	4	4
HADH	0.01	0.24	-10000	0	-0.78	6	6
F2	-0.004	0.26	-10000	0	-0.95	4	4
HNF1A	-0.02	0.075	-10000	0	-0.5	4	4
G6PC	-0.015	0.1	-10000	0	-0.5	1	1
SLC2A2	-0.003	0.17	-10000	0	-0.59	3	3
INS	-0.008	0.024	-10000	0	-10000	0	0
FOXA1	-0.064	0.21	-10000	0	-0.58	33	33
FOXA3	-0.085	0.21	-10000	0	-0.48	50	50
FOXA2	0.002	0.28	-10000	0	-0.86	7	7
ABCC8	0	0.24	-10000	0	-0.81	6	6
ALB	-0.07	0.15	-10000	0	-0.45	14	14

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.005	0.076	-9999	-0.58	4	4
alphaV beta3 Integrin	-0.019	0.13	-9999	-0.43	22	22
PTK2	-0.041	0.12	-9999	-0.44	16	16
positive regulation of JNK cascade	-0.021	0.076	-9999	-0.3	16	16
CDC42/GDP	0.028	0.12	-9999	-0.41	16	16
Rac1/GDP	0.03	0.12	-9999	-0.4	16	16
RAP1B	0.015	0	-9999	-10000	0	0
RAP1A	0.015	0	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
CDC42/GTP	-0.026	0.093	-9999	-0.37	16	16
nectin-3/I-afadin	-0.01	0.11	-9999	-0.4	18	18
RAPGEF1	0.021	0.13	-9999	-0.46	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.012	0.15	-9999	-0.52	16	16
PDGFB-D/PDGFRB	0.005	0.076	-9999	-0.58	4	4
TLN1	0.017	0.067	-9999	-0.33	4	4
Rap1/GTP	-0.022	0.08	-9999	-0.32	16	16
IQGAP1	0.015	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.029	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.01	0.11	-9999	-0.4	18	18
PVR	0.015	0	-9999	-10000	0	0
Necl-5(dimer)	0.015	0	-9999	-10000	0	0
mol:GDP	0.022	0.14	-9999	-0.5	16	16
MLLT4	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	0.015	0.091	-9999	-0.28	20	20
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.022	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.024	0.083	-9999	-0.31	18	18
PVRL1	0.015	0	-9999	-10000	0	0
PVRL3	-0.029	0.15	-9999	-0.57	18	18
PVRL2	0.015	0	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
CDH1	-0.005	0.11	-9999	-0.58	8	8
CLDN1	-0.02	0.13	-9999	-0.54	15	15
JAM-A/CLDN1	-0.006	0.12	-9999	-0.32	25	25
SRC	-0.043	0.15	-9999	-0.59	16	16
ITGB3	-0.039	0.17	-9999	-0.58	22	22
nectin-1(dimer)/I-afadin/I-afadin	0.022	0	-9999	-10000	0	0
FARP2	0.017	0.14	-9999	-0.5	16	16
RAC1	0.015	0	-9999	-10000	0	0
CTNNA1	0.015	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.025	0.089	-9999	-0.34	18	18
nectin-1/I-afadin	0.022	0	-9999	-10000	0	0
nectin-2/I-afadin	0.022	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	-0.025	0.089	-9999	-0.34	18	18
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.015	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.021	0.076	-9999	-0.3	16	16
alphaV/beta3 Integrin/Talin	0.004	0.12	-9999	-0.44	9	9
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.022	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.022	0	-9999	-10000	0	0
PIP5K1C	0.008	0.072	-9999	-0.36	4	4
VAV2	0.012	0.15	-9999	-0.5	18	18
RAP1/GDP	-0.026	0.094	-9999	-0.37	16	16
ITGAV	0.012	0.038	-9999	-0.58	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.025	0.089	-9999	-0.34	18	18
nectin-3(dimer)/I-afadin/I-afadin	-0.01	0.11	-9999	-0.4	18	18
Rac1/GTP	-0.03	0.1	-9999	-0.38	18	18
PTPRM	-0.002	0.079	-9999	-0.25	20	20
E-cadherin/beta catenin/alpha catenin	-0.009	0.047	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.019	0.005	-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	0.02	0.12	0.46	5	-10000	0	5
IL27/IL27R/JAK1	-0.055	0.15	-10000	0	-0.66	3	3
TBX21	-0.031	0.19	-10000	0	-0.53	15	15
IL12B	-0.004	0.076	-10000	0	-0.48	6	6
IL12A	0.006	0.045	-10000	0	-0.34	4	4
IL6ST	-0.066	0.2	-10000	0	-0.58	32	32
IL27RA/JAK1	0.017	0.032	-10000	0	-10000	0	0
IL27	-0.016	0.11	-10000	0	-0.48	13	13
TYK2	0.014	0.007	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.12	0.15	-10000	0	-10000	0	0
T-helper 2 cell differentiation	0.02	0.12	0.46	5	-10000	0	5
T cell proliferation during immune response	0.02	0.12	0.46	5	-10000	0	5
MAPKKK cascade	-0.02	0.12	-10000	0	-0.46	5	5
STAT3	0.015	0	-10000	0	-10000	0	0
STAT2	0.015	0	-10000	0	-10000	0	0
STAT1	0.011	0.044	-10000	0	-0.47	2	2
IL12RB1	-0.02	0.13	-10000	0	-0.5	16	16
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.061	0.22	-10000	0	-0.54	18	18
IL27/IL27R/JAK2/TYK2	-0.02	0.12	-10000	0	-0.47	5	5
positive regulation of T cell mediated cytotoxicity	-0.02	0.12	-10000	0	-0.46	5	5
STAT1 (dimer)	-0.066	0.21	0.5	10	-0.63	9	19
JAK2	0.011	0.039	-10000	0	-0.58	1	1
JAK1	0.015	0.003	-10000	0	-10000	0	0
STAT2 (dimer)	-0.012	0.12	-10000	0	-0.46	4	4
T cell proliferation	-0.15	0.19	-10000	0	-0.51	23	23
IL12/IL12R/TYK2/JAK2	0.006	0.075	-10000	0	-10000	0	0
IL17A	-0.12	0.15	-10000	0	-10000	0	0
mast cell activation	0.02	0.12	0.46	5	-10000	0	5
IFNG	-0.005	0.032	-10000	0	-0.087	5	5
T cell differentiation	-0.005	0.006	-10000	0	-0.018	21	21
STAT3 (dimer)	-0.012	0.12	-10000	0	-0.46	4	4
STAT5A (dimer)	-0.013	0.12	-10000	0	-0.46	4	4
STAT4 (dimer)	-0.026	0.13	-10000	0	-0.48	6	6
STAT4	-0.012	0.12	-10000	0	-0.58	11	11
T cell activation	-0.01	0.007	0.046	2	-10000	0	2
IL27R/JAK2/TYK2	-0.025	0.12	-10000	0	-0.59	1	1
GATA3	-0.09	0.38	-10000	0	-1.4	19	19
IL18	0.005	0.056	-10000	0	-0.43	4	4
positive regulation of mast cell cytokine production	-0.012	0.11	-10000	0	-0.45	4	4
IL27/EBI3	-0.013	0.11	-10000	0	-0.37	18	18
IL27RA	0.007	0.032	-10000	0	-10000	0	0
IL6	-0.25	0.3	-10000	0	-0.57	109	109
STAT5A	0.012	0.038	-10000	0	-0.58	1	1
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.003	0.018	-10000	0	-10000	0	0
IL1B	-0.028	0.12	-10000	0	-0.38	25	25
EBI3	-0.002	0.085	-10000	0	-0.49	7	7
TNF	-0.005	0.076	-10000	0	-0.34	12	12

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0.006	-10000	0	-10000	0	0
HSPA8	0.014	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.062	0.15	0.22	3	-0.38	40	43
AKT1	0.015	0.013	-10000	0	-10000	0	0
GSC	-0.001	0.075	-10000	0	-10000	0	0
NKX2-5	-0.074	0.18	-10000	0	-0.47	41	41
muscle cell differentiation	0.045	0.083	0.4	6	-10000	0	6
SMAD2-3/SMAD4/SP1	0.046	0.089	-10000	0	-0.37	3	3
SMAD4	0.011	0.049	-10000	0	-0.25	1	1
CBFB	0.015	0	-10000	0	-10000	0	0
SAP18	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.005	0.044	-10000	0	-0.27	5	5
SMAD3/SMAD4/VDR	-0.002	0.043	-10000	0	-0.48	1	1
MYC	-0.012	0.13	-10000	0	-0.58	11	11
CDKN2B	-0.009	0.24	-10000	0	-1.4	6	6
AP1	-0.047	0.2	-10000	0	-0.59	13	13
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.066	0.021	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.026	0.071	-10000	0	-0.32	4	4
SP3	0.018	0	-10000	0	-10000	0	0
CREB1	0.015	0	-10000	0	-10000	0	0
FOXH1	-0.086	0.2	-10000	0	-0.47	51	51
SMAD3/SMAD4/GR	-0.019	0.081	-10000	0	-0.47	6	6
GATA3	-0.035	0.16	-10000	0	-0.58	19	19
SKI/SIN3/HDAC complex/NCoR1	0.052	0.008	-10000	0	-10000	0	0
MEF2C/TIF2	-0.057	0.2	-10000	0	-0.57	19	19
endothelial cell migration	-0.004	0.13	1.4	2	-10000	0	2
MAX	0.013	0.004	-10000	0	-10000	0	0
RBBP7	0.015	0.001	-10000	0	-10000	0	0
RBBP4	0.015	0.001	-10000	0	-10000	0	0
RUNX2	0.004	0.073	-10000	0	-0.49	5	5
RUNX3	-0.005	0.11	-10000	0	-0.58	8	8
RUNX1	0.015	0	-10000	0	-10000	0	0
CTBP1	0.013	0.031	-10000	0	-0.47	1	1
NR3C1	-0.002	0.093	-10000	0	-0.58	6	6
VDR	0.01	0.049	-10000	0	-0.52	2	2
CDKN1A	0.053	0.12	-10000	0	-1.4	1	1
KAT2B	0.015	0.002	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.028	0.14	-10000	0	-0.36	18	18
DCP1A	0.015	0	-10000	0	-10000	0	0
SKI	0.015	0.001	-10000	0	-10000	0	0
SERPINE1	0.002	0.14	-10000	0	-1.4	2	2
SMAD3/SMAD4/ATF2	-0.006	0.044	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	-0.077	0.16	-10000	0	-0.39	46	46
SAP30	0.015	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.012	0.024	-10000	0	-10000	0	0
JUN	-0.047	0.19	-10000	0	-0.58	13	13
SMAD3/SMAD4/IRF7	-0.019	0.077	-10000	0	-0.36	5	5
TFE3	0.022	0.013	-10000	0	-10000	0	0
COL1A2	-0.023	0.23	-10000	0	-0.96	12	12
mesenchymal cell differentiation	0.014	0.059	0.31	4	-10000	0	4
DLX1	-0.044	0.16	-10000	0	-0.47	28	28
TCF3	0.015	0	-10000	0	-10000	0	0
FOS	-0.16	0.28	-10000	0	-0.58	74	74
SMAD3/SMAD4/Max	-0.009	0.041	-10000	0	-0.27	1	1
Cbp/p300/SNIP1	0.009	0.016	-10000	0	-10000	0	0
ZBTB17	0.016	0.011	-10000	0	-10000	0	0
LAMC1	0.044	0.066	-10000	0	-0.63	1	1
TGIF2/HDAC complex/SMAD3/SMAD4	-0.006	0.044	-10000	0	-0.26	1	1
IRF7	-0.004	0.097	-10000	0	-0.49	9	9
ESR1	-0.08	0.22	-10000	0	-0.57	39	39
HNF4A	-0.041	0.15	-10000	0	-0.47	26	26
MEF2C	-0.052	0.18	-10000	0	-0.59	11	11
SMAD2-3/SMAD4	-0.001	0.055	-10000	0	-0.29	2	2
Cbp/p300/Src-1	0.01	0.019	-10000	0	-10000	0	0
IGHV3OR16-13	-0.003	0.016	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.015	0	-10000	0	-10000	0	0
CREBBP	0.015	0.004	-10000	0	-10000	0	0
SKIL	0.013	0.031	-10000	0	-0.47	1	1
HDAC1	0.015	0.001	-10000	0	-10000	0	0
HDAC2	0.015	0.001	-10000	0	-10000	0	0
SNIP1	0.015	0.001	-10000	0	-10000	0	0
GCN5L2	0.001	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.033	0.065	-10000	0	-0.33	1	1
MSG1/HSC70	0.012	0.05	-10000	0	-0.33	5	5
SMAD2	0.018	0.017	-10000	0	-10000	0	0
SMAD3	0.01	0.046	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.035	0.046	-10000	0	-0.25	1	1
SMAD2/SMAD2/SMAD4	0.012	0.022	-10000	0	-10000	0	0
NCOR1	0.015	0.001	-10000	0	-10000	0	0
NCOA2	-0.017	0.13	-10000	0	-0.58	13	13
NCOA1	0.015	0	-10000	0	-10000	0	0
MYOD/E2A	0.011	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.061	0.083	-10000	0	-0.38	2	2
IFNB1	0.014	0.096	-10000	0	-0.45	5	5
SMAD3/SMAD4/MEF2C	-0.051	0.18	-10000	0	-0.54	14	14
CITED1	0.004	0.069	-10000	0	-0.47	5	5
SMAD2-3/SMAD4/ARC105	0.035	0.061	-10000	0	-0.28	1	1
RBL1	0.013	0.031	-10000	0	-0.47	1	1
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.042	0.098	-10000	0	-0.49	6	6
RUNX1-3/PEBPB2	-0.011	0.062	-10000	0	-0.34	8	8
SMAD7	0.001	0.17	-10000	0	-0.56	9	9
MYC/MIZ-1	-0.01	0.095	-10000	0	-0.42	11	11
SMAD3/SMAD4	0.008	0.059	0.23	1	-0.42	2	3
IL10	-0.016	0.19	-10000	0	-0.6	17	17
PIASy/HDAC complex	0.013	0.005	-10000	0	-10000	0	0
PIAS3	0.015	0.002	-10000	0	-10000	0	0
CDK2	0.015	0.004	-10000	0	-10000	0	0
IL5	-0.006	0.13	-10000	0	-0.49	6	6
CDK4	0.016	0.004	-10000	0	-10000	0	0
PIAS4	0.013	0.005	-10000	0	-10000	0	0
ATF3	-0.098	0.23	-10000	0	-0.58	46	46
SMAD3/SMAD4/SP1	0.031	0.086	-10000	0	-0.38	4	4
FOXG1	-0.071	0.17	-10000	0	-0.48	37	37
FOXO3	0.026	0.018	-10000	0	-10000	0	0
FOXO1	0.026	0.018	-10000	0	-10000	0	0
FOXO4	0.024	0.029	-10000	0	-0.32	1	1
heart looping	-0.052	0.17	-10000	0	-0.58	11	11
CEBPB	0.015	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.039	0.099	-10000	0	-0.32	13	13
MYOD1	0	0	-10000	0	-10000	0	0
SMAD3/SMAD4/HNF4	-0.036	0.097	-10000	0	-0.33	9	9
SMAD3/SMAD4/GATA3	-0.047	0.13	-10000	0	-0.38	24	24
SnoN/SIN3/HDAC complex/NCoR1	0.013	0.031	-10000	0	-0.47	1	1
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.022	0.084	-10000	0	-0.37	6	6
SMAD3/SMAD4/SP1-3	0.043	0.079	-10000	0	-0.36	2	2
MED15	0.015	0	-10000	0	-10000	0	0
SP1	0.019	0.031	-10000	0	-10000	0	0
SIN3B	0.015	0.001	-10000	0	-10000	0	0
SIN3A	0.015	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.06	0.16	-10000	0	-0.46	14	14
ITGB5	0.055	0.066	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.13	0.18	-10000	0	-0.37	82	82
AR	-0.18	0.28	-10000	0	-0.58	81	81
negative regulation of cell growth	0.006	0.092	-10000	0	-0.31	2	2
SMAD3/SMAD4/MYOD	-0.008	0.046	-10000	0	-0.27	2	2
E2F5	0.01	0.049	-10000	0	-0.52	2	2
E2F4	0.015	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.003	0.12	-10000	0	-0.36	7	7
SMAD2-3/SMAD4/FOXO1-3a-4	0.044	0.074	-10000	0	-0.34	6	6
TFDP1	0.015	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.046	0.2	-10000	0	-0.59	13	13
SMAD3/SMAD4/RUNX2	-0.012	0.061	-10000	0	-0.31	4	4
TGIF2	0.015	0	-10000	0	-10000	0	0
TGIF1	0.015	0	-10000	0	-10000	0	0
ATF2	0.015	0	-10000	0	-10000	0	0

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.017	0.005	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.58	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.015	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.02	0.052	-10000	0	-0.29	2	2
IRAK/TOLLIP	0.033	0.004	-10000	0	-10000	0	0
IKBKB	0.015	0	-10000	0	-10000	0	0
IKBKG	0.015	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.1	0.19	-10000	0	-0.38	74	74
IL1A	-0.089	0.21	-10000	0	-0.52	47	47
IL1B	-0.028	0.14	-10000	0	-0.39	31	31
IRAK/TRAF6/p62/Atypical PKCs	-0.001	0.016	-10000	0	-10000	0	0
IL1R2	-0.052	0.17	-10000	0	-0.49	32	32
IL1R1	0.012	0.038	-10000	0	-0.58	1	1
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.025	0.062	0.21	2	-0.41	1	3
TOLLIP	0.015	0	-10000	0	-10000	0	0
TICAM2	0.012	0.038	-10000	0	-0.58	1	1
MAP3K3	0.015	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.01	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.072	0.007	-10000	0	-10000	0	0
JUN	0.035	0.063	-10000	0	-10000	0	0
MAP3K7	0.015	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.004	0.12	-10000	0	-0.49	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.031	0.14	-10000	0	-0.34	23	23
PIK3R1	0.015	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.021	0.13	-10000	0	-0.49	3	3
IL1 beta fragment/IL1R1/IL1RAP	-0.014	0.13	-10000	0	-0.35	20	20
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	0.036	0.048	-10000	0	-10000	0	0
IRAK1	0.026	0.005	-10000	0	-10000	0	0
IL1RN/IL1R1	0.002	0.09	-10000	0	-0.37	12	12
IRAK4	0.015	0	-10000	0	-10000	0	0
PRKCI	0.015	0	-10000	0	-10000	0	0
TRAF6	0.015	0	-10000	0	-10000	0	0
PI3K	0.022	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.017	0.073	-10000	0	-0.38	2	2
CHUK	0.015	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.014	0.13	-10000	0	-0.35	20	20
IL1 beta/IL1R2	-0.056	0.16	-10000	0	-0.33	57	57
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.034	0.086	-10000	0	-0.44	4	4
IRAK3	0.005	0.076	-10000	0	-0.58	4	4
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.002	0.12	-10000	0	-0.49	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.093	-10000	0	-0.51	1	1
IL1 alpha/IL1R1/IL1RAP	-0.069	0.14	-10000	0	-0.31	53	53
RELA	0.015	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.015	0	-10000	0	-10000	0	0
MYD88	0.015	0	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.041	0.004	-10000	0	-10000	0	0
IL1RAP	-0.001	0.087	-10000	0	-0.47	8	8
UBE2N	0.015	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.031	0.078	-10000	0	-0.46	2	2
CASP1	-0.002	0.099	-10000	0	-0.58	7	7
IL1RN/IL1R2	-0.044	0.14	-10000	0	-0.35	42	42
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.004	0.12	-10000	0	-0.52	4	4
TMEM189-UBE2V1	0.008	0.007	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.014	0.077	-10000	0	-0.52	1	1
PIK3CA	0.015	0	-10000	0	-10000	0	0
IL1RN	-0.01	0.11	-10000	0	-0.49	12	12
TRAF6/TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
MAP2K6	0.032	0.037	-10000	0	-0.26	3	3

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.053	0.072	-10000	0	-0.43	3	3
UGCG	-0.014	0.16	-10000	0	-0.65	13	13
AKT1/mTOR/p70S6K/Hsp90/TERT	0.025	0.12	-10000	0	-0.37	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.011	0.15	-10000	0	-0.64	13	13
mol:DAG	0	0.003	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.039	0.12	-10000	0	-0.38	22	22
FRAP1	0.039	0.17	-10000	0	-0.45	22	22
FOXO3	0.051	0.14	-10000	0	-0.41	16	16
AKT1	0.044	0.15	-10000	0	-0.44	16	16
GAB2	0.015	0.004	-10000	0	-10000	0	0
SMPD1	0.022	0.028	-10000	0	-10000	0	0
SGMS1	0.022	0.028	-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	0.023	0.007	-10000	0	-10000	0	0
CALM1	0.015	0	-10000	0	-10000	0	0
cell proliferation	0.015	0.12	-10000	0	-0.31	23	23
EIF3A	0.015	0	-10000	0	-10000	0	0
PI3K	0.027	0.008	-10000	0	-10000	0	0
RPS6KB1	0.018	0.035	-10000	0	-10000	0	0
mol:sphingomyelin	0	0.003	-10000	0	-10000	0	0
natural killer cell activation	0	0.003	-10000	0	-0.015	1	1
JAK3	0.013	0.044	-10000	0	-0.47	2	2
PIK3R1	0.017	0.004	-10000	0	-10000	0	0
JAK1	0.017	0.004	-10000	0	-10000	0	0
NFKB1	0.015	0	-10000	0	-10000	0	0
MYC	0.025	0.24	-10000	0	-0.96	12	12
MYB	-0.012	0.13	-10000	0	-1.3	1	1
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.046	0.12	-10000	0	-0.57	4	4
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.033	0.033	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.047	0.12	-10000	0	-0.5	5	5
Rac1/GDP	0.03	0.009	-10000	0	-10000	0	0
T cell proliferation	0.052	0.11	-10000	0	-0.51	4	4
SHC1	0.013	0.032	-10000	0	-0.47	1	1
RAC1	0.015	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.002	0.012	-10000	0	-0.029	30	30
PRKCZ	0.052	0.11	-10000	0	-0.53	4	4
NF kappa B1 p50/RelA	-0.032	0.12	-10000	0	-0.41	16	16
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.046	0.077	-10000	0	-0.46	4	4
HSP90AA1	0.015	0	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
IL2RA	-0.048	0.17	-10000	0	-0.52	28	28
IL2RB	0.01	0.066	-10000	0	-0.58	3	3
TERT	-0.18	0.24	-10000	0	-0.47	97	97
E2F1	-0.003	0.077	-10000	0	-0.49	1	1
SOS1	0.015	0.004	-10000	0	-10000	0	0
RPS6	0.015	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.006	0.014	28	-10000	0	28
PTPN11	0.015	0.004	-10000	0	-10000	0	0
IL2RG	-0.005	0.11	-10000	0	-0.52	10	10
actin cytoskeleton organization	0.052	0.11	-10000	0	-0.51	4	4
GRB2	0.015	0.004	-10000	0	-10000	0	0
IL2	0.007	0.008	-10000	0	-10000	0	0
PIK3CA	0.017	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.037	0.013	-10000	0	-10000	0	0
LCK	0.01	0.062	-10000	0	-0.54	3	3
BCL2	0.025	0.23	-10000	0	-0.82	14	14

×

Insulin 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
CBL/APS/CAP	-0.13	0.14	-9999	-0.55	3	3
TC10/GTP	-0.12	0.12	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.007	0.046	-9999	-0.32	5	5
HRAS	0.015	0	-9999	-10000	0	0
APS homodimer	0.009	0.054	-9999	-0.47	3	3
GRB14	-0.052	0.17	-9999	-0.47	33	33
FOXO3	-0.02	0.098	-9999	-0.58	7	7
AKT1	0.02	0.083	-9999	-10000	0	0
INSR	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0.04	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.012	0.038	-9999	-0.58	1	1
SORBS1	-0.26	0.3	-9999	-0.58	111	111
CRK	0.015	0	-9999	-10000	0	0
PTPN1	0.038	0	-9999	-10000	0	0
CAV1	0.01	0.089	-9999	-0.34	13	13
CBL/APS/CAP/Crk-II/C3G	-0.11	0.16	-9999	-0.28	111	111
Insulin Receptor/Insulin/IRS1/NCK2	-0.007	0.046	-9999	-0.32	5	5
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.039	-9999	-0.27	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.038	0.035	-9999	-10000	0	0
RPS6KB1	0.028	0.079	-9999	-10000	0	0
PARD6A	0.012	0.038	-9999	-0.58	1	1
CBL	0.015	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.009	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.023	0.054	-9999	-10000	0	0
HRAS/GTP	-0.011	0.048	-9999	-10000	0	0
Insulin Receptor	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.007	0.044	-9999	-0.29	5	5
PRKCI	-0.008	0.033	-9999	-0.47	1	1
Insulin Receptor/Insulin/GRB14/PDK1	-0.03	0.069	-9999	-10000	0	0
SHC1	0.013	0.031	-9999	-0.47	1	1
negative regulation of MAPKKK cascade	0	0.007	-9999	-10000	0	0
PI3K	-0.006	0.039	-9999	-0.28	5	5
NCK2	0.015	0	-9999	-10000	0	0
RHOQ	0.015	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0.011	0	-9999	-10000	0	0
AKT2	0.02	0.083	-9999	-10000	0	0
PRKCZ	-0.01	0.045	-9999	-0.48	2	2
SH2B2	0.009	0.054	-9999	-0.47	3	3
SHC/SHIP	0.023	0.067	-9999	-0.27	11	11
F2RL2	-0.024	0.14	-9999	-0.53	17	17
TRIP10	0.012	0.038	-9999	-0.58	1	1
Insulin Receptor/Insulin/Shc	-0.001	0.016	-9999	-0.25	1	1
TC10/GTP/CIP4/Exocyst	-0.001	0.023	-9999	-0.35	1	1
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.014	-9999	-10000	0	0
RAPGEF1	0.015	0	-9999	-10000	0	0
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.12	0.17	-9999	-0.31	111	111
TC10/GDP	0.011	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.002	0.026	-9999	-0.28	2	2
INPP5D	0.015	0.068	-9999	-0.3	11	11
SOS1	0.015	0	-9999	-10000	0	0
SGK1	-0.027	0.15	-9999	-0.89	7	7
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.015	0	-9999	-10000	0	0
IRS1	0.002	0.084	-9999	-0.58	5	5
p62DOK/RasGAP	0	0.007	-9999	-10000	0	0
INS	0.003	0	-9999	-10000	0	0
mol:PI-3-4-P2	0.015	0.068	-9999	-0.3	11	11
GRB2	0.015	0	-9999	-10000	0	0
EIF4EBP1	0.02	0.09	-9999	-0.36	2	2
PTPRA	0.016	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
TC10/GTP/CIP4	-0.001	0.023	-9999	-0.35	1	1
PDPK1	0.015	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.031	0.041	-9999	-0.24	5	5
Insulin Receptor/Insulin/IRS1	-0.007	0.047	-9999	-0.33	5	5
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.021	0.071	-9999	-0.29	12	12

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.015	0	-10000	0	-10000	0	0
ANTXR2	-0.01	0.12	-10000	0	-0.58	10	10
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.015	-10000	0	-0.075	10	10
monocyte activation	-0.002	0.083	-10000	0	-0.42	9	9
MAP2K2	-0.001	0.005	-10000	0	-10000	0	0
MAP2K1	-0.003	0.012	-10000	0	-10000	0	0
MAP2K7	-0.003	0.012	-10000	0	-10000	0	0
MAP2K6	-0.007	0.039	-10000	0	-0.29	4	4
CYAA	0.003	0.064	-10000	0	-0.3	10	10
MAP2K4	-0.003	0.012	-10000	0	-10000	0	0
IL1B	-0.017	0.094	-10000	0	-0.27	26	26
Channel	0.005	0.068	-10000	0	-0.32	10	10
NLRP1	-0.008	0.041	-10000	0	-0.31	4	4
CALM1	0.015	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.003	0.016	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.015	0.075	10	-10000	0	10
MAPK3	-0.003	0.012	-10000	0	-10000	0	0
MAPK1	-0.003	0.012	-10000	0	-10000	0	0
PGR	-0.096	0.14	-10000	0	-0.32	73	73
PA/Cellular Receptors	-0.015	0.071	-10000	0	-0.35	10	10
apoptosis	-0.003	0.015	-10000	0	-0.075	10	10
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.005	0.064	-10000	0	-0.3	10	10
macrophage activation	0.018	0.014	-10000	0	-10000	0	0
TNF	-0.01	0.11	-10000	0	-0.47	12	12
VCAM1	-0.002	0.084	-10000	0	-0.42	9	9
platelet activation	-0.003	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.014	0.018	-10000	0	-10000	0	0
IL18	0.006	0.054	-10000	0	-0.32	5	5
negative regulation of macrophage activation	-0.003	0.015	-10000	0	-0.075	10	10
LEF	-0.003	0.015	-10000	0	-0.075	10	10
CASP1	-0.008	0.034	-10000	0	-0.18	6	6
mol:cAMP	-0.003	0.017	-10000	0	-10000	0	0
necrosis	-0.003	0.015	-10000	0	-0.075	10	10
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.005	0.064	-10000	0	-0.3	10	10
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.005	0.076	-10000	0	-0.58	4	4
Jak2/Leptin Receptor	-0.001	0.085	0.2	9	-0.42	3	12
PTP1B/AKT1	0.028	0.045	-10000	0	-0.24	2	2
FYN	0.01	0.054	-10000	0	-0.58	2	2
p210 bcr-abl/PTP1B	0.022	0.05	-10000	0	-0.25	3	3
EGFR	-0.009	0.11	-10000	0	-0.52	11	11
EGF/EGFR	-0.024	0.069	-10000	0	-0.28	9	9
CSF1	-0.005	0.11	-10000	0	-0.58	8	8
AKT1	0.015	0.001	-10000	0	-10000	0	0
INSR	0.015	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	0.003	0.09	-10000	0	-0.25	14	14
Insulin Receptor/Insulin	-0.003	0.024	-10000	0	-10000	0	0
HCK	-0.009	0.11	-10000	0	-0.55	10	10
CRK	0.015	0	-10000	0	-10000	0	0
TYK2	0.029	0.047	-10000	0	-0.25	2	2
EGF	-0.016	0.12	-10000	0	-0.47	15	15
YES1	0.015	0	-10000	0	-10000	0	0
CAV1	0.025	0.063	-10000	0	-0.26	3	3
TXN	0.013	0.032	-10000	0	-0.47	1	1
PTP1B/IRS1/GRB2	0.03	0.064	-10000	0	-0.3	4	4
cell migration	-0.022	0.05	0.25	3	-10000	0	3
STAT3	0.015	0.001	-10000	0	-10000	0	0
PRLR	-0.045	0.17	-10000	0	-0.51	28	28
ITGA2B	-0.02	0.12	-10000	0	-0.47	17	17
CSF1R	-0.021	0.14	-10000	0	-0.56	15	15
Prolactin Receptor/Prolactin	-0.042	0.13	-10000	0	-0.36	32	32
FGR	0.012	0.038	-10000	0	-0.58	1	1
PTP1B/p130 Cas	0.029	0.046	-10000	0	-0.25	2	2
Crk/p130 Cas	0.037	0.045	-10000	0	-10000	0	0
DOK1	0.032	0.058	-10000	0	-0.27	4	4
JAK2	0.013	0.07	-10000	0	-0.32	4	4
Jak2/Leptin Receptor/Leptin	-0.07	0.14	-10000	0	-0.44	24	24
PIK3R1	0.015	0	-10000	0	-10000	0	0
PTPN1	0.022	0.05	-10000	0	-0.25	3	3
LYN	0.015	0	-10000	0	-10000	0	0
CDH2	-0.036	0.15	-10000	0	-0.48	25	25
SRC	0.028	0.021	-10000	0	-10000	0	0
ITGB3	-0.04	0.17	-10000	0	-0.58	22	22
CAT1/PTP1B	-0.004	0.11	-10000	0	-0.38	6	6
CAPN1	0.015	0.002	-10000	0	-10000	0	0
CSK	0.015	0	-10000	0	-10000	0	0
PI3K	-0.001	0.02	-10000	0	-10000	0	0
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.068	0.15	-10000	0	-0.48	23	23
negative regulation of transcription	0.016	0.071	-10000	0	-0.32	4	4
FCGR2A	-0.006	0.1	-10000	0	-0.48	10	10
FER	0.012	0.039	-10000	0	-0.58	1	1
alphaIIb/beta3 Integrin	-0.048	0.15	-10000	0	-0.4	37	37
BLK	-0.06	0.19	-10000	0	-0.55	31	31
Insulin Receptor/Insulin/Shc	0.019	0.02	-10000	0	-0.28	1	1
RHOA	0.015	0.002	-10000	0	-10000	0	0
LEPR	0.003	0.084	-10000	0	-0.57	5	5
BCAR1	0.015	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.015	0	-10000	0	-10000	0	0
mol:NADPH	0.001	0.002	-10000	0	-10000	0	0
TRPV6	-0.028	0.13	-10000	0	-0.4	10	10
PRL	-0.001	0.062	-10000	0	-0.47	4	4
SOCS3	-0.12	0.41	-10000	0	-1.4	23	23
SPRY2	0.002	0.085	-10000	0	-0.58	5	5
Insulin Receptor/Insulin/IRS1	0.012	0.054	-10000	0	-0.36	5	5
CSF1/CSF1R	0.008	0.11	-10000	0	-0.32	15	15
Ras protein signal transduction	0.009	0.017	-10000	0	-10000	0	0
IRS1	0.002	0.084	-10000	0	-0.58	5	5
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.068	0.2	-10000	0	-0.55	34	34
STAT5B	0.024	0.051	-10000	0	-0.24	3	3
STAT5A	0.023	0.052	-10000	0	-0.24	3	3
GRB2	0.015	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.023	0.066	-10000	0	-0.31	6	6
CSN2	-0.013	0.046	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
LAT	0.023	0.037	-10000	0	-0.39	1	1
YBX1	0.022	0.031	-10000	0	-0.45	1	1
LCK	0.008	0.062	-10000	0	-0.54	3	3
SHC1	0.013	0.031	-10000	0	-0.47	1	1
NOX4	-0.013	0.11	-10000	0	-0.47	14	14

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.015	0	-10000	0	-10000	0	0
HDAC4	0.015	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.004	0.093	0.33	18	-10000	0	18
CDKN1A	-0.003	0.049	-10000	0	-0.77	1	1
KAT2B	0.015	0	-10000	0	-10000	0	0
BAX	0.015	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.015	0	-10000	0	-10000	0	0
FOXO4	0.025	0.009	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.015	0	-10000	0	-10000	0	0
TAT	-0.002	0.076	-10000	0	-0.47	6	6
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	0.013	0	-10000	0	-10000	0	0
PPARGC1A	-0.22	0.29	-10000	0	-0.58	96	96
FHL2	0.007	0.066	-10000	0	-0.58	3	3
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.01	-10000	0	-10000	0	0
HIST2H4A	-0.004	0.093	-10000	0	-0.33	18	18
SIRT1/FOXO3a	0.001	0.009	-10000	0	-10000	0	0
SIRT1	0.001	0.013	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.009	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.008	0.029	-10000	0	-10000	0	0
apoptosis	-0.001	0.009	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.14	0.17	-10000	0	-0.36	96	96
p53/SIRT1	0.002	0.026	0.4	1	-10000	0	1
SIRT1/FOXO4	0	0.012	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.003	0.036	-10000	0	-0.32	3	3
HIST1H1E	0.011	0.043	-10000	0	-10000	0	0
SIRT1/p300	0.001	0.01	-10000	0	-10000	0	0
muscle cell differentiation	-0.001	0.009	-10000	0	-10000	0	0
TP53	0.001	0.013	0.2	1	-10000	0	1
KU70/SIRT1/BAX	0.001	0.009	-10000	0	-10000	0	0
CREBBP	0.015	0	-10000	0	-10000	0	0
MEF2D	0.015	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.008	0.052	-10000	0	-0.33	6	6
ACSS2	0.021	0.024	-10000	0	-0.33	1	1
SIRT1/PCAF/MYOD	0.001	0.009	-10000	0	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.013	0.031	-10000	0	-0.47	1	1
NFATC1	0.033	0.079	-10000	0	-0.3	9	9
NFATC2	-0.025	0.08	-10000	0	-0.2	28	28
NFATC3	0.011	0.031	-10000	0	-0.42	1	1
YWHAE	0.012	0.038	-10000	0	-0.58	1	1
Calcineurin A alpha-beta B1/CABIN1	-0.043	0.14	-10000	0	-0.44	17	17
Exportin 1/Ran/NUP214	0.014	0.015	-10000	0	-10000	0	0
mol:DAG	-0.003	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.07	0.13	-10000	0	-0.42	21	21
BCL2/BAX	0.002	0.091	-10000	0	-0.42	11	11
CaM/Ca2+/Calcineurin A alpha-beta B1	0.002	0.01	-10000	0	-10000	0	0
CaM/Ca2+	0.002	0.01	-10000	0	-10000	0	0
BAX	0.015	0	-10000	0	-10000	0	0
MAPK14	0.007	0.008	-10000	0	-10000	0	0
BAD	0.015	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.037	0.14	-10000	0	-0.42	17	17
Calcineurin A alpha-beta B1/BCL2	-0.012	0.12	-10000	0	-0.58	11	11
FKBP8	0.015	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.037	0.13	0.42	17	-10000	0	17
KPNB1	0.015	0	-10000	0	-10000	0	0
KPNA2	0.011	0.044	-10000	0	-0.47	2	2
XPO1	0.014	0.001	-10000	0	-10000	0	0
SFN	-0.039	0.15	-10000	0	-0.48	26	26
MAP3K8	0	0.066	-10000	0	-0.58	3	3
NFAT4/CK1 alpha	-0.001	0.016	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.13	0.18	-10000	0	-0.39	28	28
CABIN1	-0.043	0.14	-10000	0	-0.45	17	17
CALM1	0.01	0.006	-10000	0	-10000	0	0
RAN	0.014	0.001	-10000	0	-10000	0	0
MAP3K1	0.015	0	-10000	0	-10000	0	0
CAMK4	-0.01	0.12	-10000	0	-0.57	10	10
mol:Ca2+	-0.009	0.009	-10000	0	-10000	0	0
MAPK3	0.015	0	-10000	0	-10000	0	0
YWHAH	0.015	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.006	0.039	-10000	0	-0.33	3	3
YWHAB	0.015	0	-10000	0	-10000	0	0
MAPK8	0	0.065	-10000	0	-0.58	3	3
MAPK9	0.015	0	-10000	0	-10000	0	0
YWHAG	0.015	0	-10000	0	-10000	0	0
FKBP1A	0.015	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	0.025	0.082	-10000	0	-0.35	2	2
PRKCH	0.015	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0.009	0.014	-10000	0	-10000	0	0
CASP3	0.007	0.008	-10000	0	-10000	0	0
PIM1	0.015	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.005	0.005	-10000	0	-10000	0	0
apoptosis	-0.006	0.027	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.037	-10000	0	-0.27	1	1
PRKCB	-0.16	0.27	-10000	0	-0.58	69	69
PRKCE	0.015	0	-10000	0	-10000	0	0
JNK2/NFAT4	0.023	0.027	-10000	0	-0.37	1	1
BAD/BCL-XL	0.02	0.022	-10000	0	-0.33	1	1
PRKCD	0.015	0	-10000	0	-10000	0	0
NUP214	0.014	0.001	-10000	0	-10000	0	0
PRKCZ	0.005	0.039	-10000	0	-0.58	1	1
PRKCA	0.015	0	-10000	0	-10000	0	0
PRKCG	-0.007	0.081	-10000	0	-0.47	7	7
PRKCQ	-0.039	0.17	-10000	0	-0.57	22	22
FKBP38/BCL2	0.002	0.091	-10000	0	-0.42	11	11
EP300	0.009	0.006	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.015	0	-10000	0	-10000	0	0
NFATc/JNK1	0.013	0.082	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	0.01	0.011	-10000	0	-10000	0	0
FKBP12/FK506	0.011	0	-10000	0	-10000	0	0
CSNK1A1	0.01	0.011	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.005	0.074	-10000	0	-0.36	10	10
NFATc/ERK1	0.04	0.075	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.068	0.12	-10000	0	-0.41	21	21
NR4A1	-0.27	0.31	-10000	0	-0.55	131	131
GSK3B	0.007	0.008	-10000	0	-10000	0	0
positive T cell selection	0.011	0.031	-10000	0	-0.42	1	1
NFAT1/CK1 alpha	-0.035	0.053	-10000	0	-0.3	3	3
RCH1/ KPNB1	0.019	0.032	-10000	0	-0.33	2	2
YWHAQ	0.015	0	-10000	0	-10000	0	0
PRKACA	0.007	0.008	-10000	0	-10000	0	0
AKAP5	0.009	0.054	-10000	0	-0.47	3	3
MEF2D	0.009	0.006	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.015	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.016	0.077	-10000	0	-10000	0	0
CREBBP	0.009	0.006	-10000	0	-10000	0	0
BCL2	-0.012	0.12	-10000	0	-0.58	11	11

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.013	0.031	-9999	-0.47	1	1
Syndecan-3/Src/Cortactin	-0.062	0.11	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.009	0.043	-9999	-10000	0	0
POMC	-0.014	0.12	-9999	-0.52	13	13
EGFR	-0.01	0.11	-9999	-0.52	11	11
Syndecan-3/EGFR	-0.011	0.052	-9999	-0.28	5	5
AGRP	0.008	0.007	-9999	-10000	0	0
NCSTN	0.015	0	-9999	-10000	0	0
PSENEN	0.015	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.015	0	-9999	-10000	0	0
APH1A	0.015	0	-9999	-10000	0	0
NCAN	-0.012	0.096	-9999	-0.47	10	10
long-term memory	-0.003	0.027	-9999	-0.26	2	2
Syndecan-3/IL8	-0.043	0.1	-9999	-0.28	36	36
PSEN1	0.015	0	-9999	-10000	0	0
Src/Cortactin	0.02	0.022	-9999	-0.33	1	1
FYN	0.01	0.054	-9999	-0.58	2	2
limb bud formation	0	0	-9999	-10000	0	0
MC4R	-0.002	0.062	-9999	-0.47	4	4
SRC	0.015	0	-9999	-10000	0	0
PTN	-0.13	0.25	-9999	-0.56	61	61
FGFR/FGF/Syndecan-3	0	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.066	0.1	-9999	-0.39	1	1
Syndecan-3/AgRP	0	0	-9999	-10000	0	0
Syndecan-3/AgRP/MC4R	0.004	0.031	-9999	-10000	0	0
Fyn/Cortactin	0.017	0.045	-9999	-0.39	3	3
SDC3	0	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.043	0.1	-9999	-0.28	36	36
IL8	-0.076	0.21	-9999	-0.57	37	37
Syndecan-3/Fyn/Cortactin	0.033	0.031	-9999	-0.27	2	2
Syndecan-3/CASK	0	0	-9999	-10000	0	0
alpha-MSH/MC4R	-0.012	0.098	-9999	-0.36	17	17
Gamma Secretase	0.044	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.015	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.005	0.073	-9999	-0.55	4	4
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.015	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	0.023	0.024	-9999	-0.22	1	1
response to UV	0	0	-9999	-10000	0	0
YES1	0.015	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	0.015	0	-9999	-10000	0	0
FYN	0.01	0.054	-9999	-0.58	2	2
MAP3K12	0.012	0.038	-9999	-0.58	1	1
FGR	0.012	0.038	-9999	-0.58	1	1
p38 alpha/TAB1	-0.02	0.045	-9999	-0.23	5	5
PRKG1	-0.099	0.23	-9999	-0.58	46	46
DUSP8	-0.025	0.15	-9999	-0.58	16	16
PGK/cGMP/p38 alpha	-0.063	0.11	-9999	-0.27	48	48
apoptosis	-0.019	0.043	-9999	-0.22	5	5
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.015	0	-9999	-10000	0	0
DUSP1	-0.15	0.26	-9999	-0.58	66	66
PAK1	0.012	0.038	-9999	-0.58	1	1
SRC	0.015	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.037	0.017	-9999	-10000	0	0
TRAF6	0.015	0	-9999	-10000	0	0
RAC1	0.015	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0.031	-9999	-0.47	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.025	0.09	-9999	-0.28	6	6
BLK	-0.06	0.19	-9999	-0.55	31	31
HCK	-0.009	0.11	-9999	-0.55	10	10
MAP2K3	0.015	0	-9999	-10000	0	0
DUSP16	0.015	0	-9999	-10000	0	0
DUSP10	0.009	0.054	-9999	-0.47	3	3
TRAF6/MEKK3	0.019	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.03	0.073	-9999	-0.24	6	6
positive regulation of innate immune response	0.032	0.099	-9999	-0.31	6	6
LCK	0.008	0.062	-9999	-0.54	3	3
p38alpha-beta/MKP7	0.039	0.095	-9999	-0.29	6	6
p38alpha-beta/MKP5	0.036	0.099	-9999	-0.29	7	7
PGK/cGMP	-0.073	0.17	-9999	-0.42	46	46
PAK2	0.015	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.034	0.17	-9999	-0.4	26	26
CDC42	0.015	0	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
PAK3	-0.008	0.087	-9999	-0.47	8	8

×

Stabilization and expansion of the E-cadherin adherens junction

Figure S89. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S89. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	0.025	0.05	-10000	0	-0.25	8	8
epithelial cell differentiation	-0.009	0.051	-10000	0	-0.28	8	8
CYFIP2	-0.005	0.11	-10000	0	-0.58	8	8
ENAH	0.059	0.054	-10000	0	-0.33	1	1
EGFR	-0.01	0.11	-10000	0	-0.52	11	11
EPHA2	0.01	0.054	-10000	0	-0.58	2	2
MYO6	0.032	0.055	-10000	0	-0.26	8	8
CTNNB1	0.015	0	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.062	-10000	0	-0.34	8	8
AQP5	-0.011	0.045	-10000	0	-0.33	1	1
CTNND1	0.015	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.031	0.054	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.016	0.087	-10000	0	-0.35	5	5
EGF	-0.017	0.12	-10000	0	-0.47	15	15
NCKAP1	0.015	0	-10000	0	-10000	0	0
AQP3	-0.1	0.2	-10000	0	-0.49	49	49
cortical microtubule organization	-0.009	0.051	-10000	0	-0.28	8	8
GO:0000145	0.03	0.052	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.024	0.058	-10000	0	-0.29	8	8
MLLT4	0.015	0	-10000	0	-10000	0	0
ARF6/GDP	-0.012	0.052	-10000	0	-0.46	1	1
ARF6	0.015	0	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.029	0.052	-10000	0	-0.31	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	0.043	0.055	-10000	0	-10000	0	0
PVRL2	0.015	0	-10000	0	-10000	0	0
ZYX	0.03	0.058	-10000	0	-0.27	9	9
ARF6/GTP	-0.007	0.041	-10000	0	-10000	0	0
CDH1	-0.005	0.11	-10000	0	-0.58	8	8
EGFR/EGFR/EGF/EGF	-0.03	0.085	-10000	0	-0.5	3	3
RhoA/GDP	-0.009	0.047	-10000	0	-0.26	8	8
actin cytoskeleton organization	0.037	0.056	-10000	0	-10000	0	0
IGF-1R heterotetramer	0.01	0.054	-10000	0	-0.58	2	2
GIT1	0.015	0	-10000	0	-10000	0	0
IGF1R	0.01	0.054	-10000	0	-0.58	2	2
IGF1	-0.25	0.29	-10000	0	-0.58	106	106
DIAPH1	-0.018	0.1	-10000	0	-0.59	8	8
Wnt receptor signaling pathway	0.009	0.051	0.28	8	-10000	0	8
RHOA	0.015	0	-10000	0	-10000	0	0
RhoA/GTP	-0.013	0.052	-10000	0	-0.46	1	1
CTNNA1	0.015	0	-10000	0	-10000	0	0
VCL	0.037	0.058	-10000	0	-10000	0	0
EFNA1	0.003	0.076	-10000	0	-0.47	6	6
LPP	0.039	0.053	-10000	0	-10000	0	0
Ephrin A1/EPHA2	-0.015	0.063	-10000	0	-0.54	1	1
SEC6/SEC8	-0.007	0.04	-10000	0	-10000	0	0
MGAT3	0.016	0.088	-10000	0	-0.36	5	5
HGF/MET	-0.069	0.11	-10000	0	-0.47	1	1
HGF	-0.13	0.25	-10000	0	-0.57	59	59
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.025	0.051	-10000	0	-0.25	8	8
actin cable formation	0.074	0.054	-10000	0	-0.26	1	1
KIAA1543	0.031	0.092	-10000	0	-0.53	5	5
KIFC3	0.032	0.055	-10000	0	-0.26	8	8
NCK1	0.015	0	-10000	0	-10000	0	0
EXOC3	0.015	0	-10000	0	-10000	0	0
ACTN1	0.032	0.055	-10000	0	-0.26	8	8
NCK1/GIT1	0.022	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.051	-10000	0	-0.28	8	8
EXOC4	0.015	0	-10000	0	-10000	0	0
STX4	0.032	0.055	-10000	0	-0.26	8	8
PIP5K1C	0.032	0.055	-10000	0	-10000	0	0
LIMA1	0.015	0	-10000	0	-10000	0	0
ABI1	0.015	0	-10000	0	-10000	0	0
ROCK1	0.054	0.061	-10000	0	-0.4	1	1
adherens junction assembly	0.047	0.092	-10000	0	-0.51	5	5
IGF-1R heterotetramer/IGF1	-0.12	0.13	-10000	0	-0.54	2	2
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.022	0	-10000	0	-10000	0	0
MET	0.015	0	-10000	0	-10000	0	0
PLEKHA7	0.031	0.064	-10000	0	-0.3	8	8
mol:GTP	-0.008	0.045	-10000	0	-0.3	2	2
establishment of epithelial cell apical/basal polarity	0.059	0.05	-10000	0	-10000	0	0
cortical actin cytoskeleton stabilization	0.025	0.05	-10000	0	-0.25	8	8
regulation of cell-cell adhesion	0.037	0.056	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.025	0.051	-10000	0	-0.25	8	8

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.011	0.068	-10000	0	-0.42	6	6
ATM	0.015	0	-10000	0	-10000	0	0
UBE2D3	0.015	0	-10000	0	-10000	0	0
PRKDC	0.015	0	-10000	0	-10000	0	0
ATR	0.015	0	-10000	0	-10000	0	0
UBE2L3	0.015	0	-10000	0	-10000	0	0
FANCD2	0.027	0.017	-10000	0	-10000	0	0
protein ubiquitination	-0.039	0.084	-10000	0	-10000	0	0
XRCC5	0.015	0	-10000	0	-10000	0	0
XRCC6	0.015	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.015	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.045	0.031	-10000	0	-10000	0	0
FANCF	0.013	0.031	-10000	0	-0.47	1	1
BRCA1	0.013	0.031	-10000	0	-0.47	1	1
CCNE1	-0.058	0.17	-10000	0	-0.47	36	36
CDK2/Cyclin E1	-0.03	0.12	-10000	0	-0.33	36	36
FANCG	0.015	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.009	0.071	-10000	0	-0.4	7	7
FANCE	0.015	0	-10000	0	-10000	0	0
FANCC	0.013	0.031	-10000	0	-0.47	1	1
NBN	0.015	0	-10000	0	-10000	0	0
FANCA	-0.014	0.11	-10000	0	-0.47	14	14
DNA repair	-0.014	0.12	-10000	0	-0.4	1	1
BRCA1/BARD1/ubiquitin	0.009	0.071	-10000	0	-0.4	7	7
BARD1/DNA-PK	0.029	0.054	-10000	0	-0.31	6	6
FANCL	0.013	0.031	-10000	0	-0.47	1	1
mRNA polyadenylation	-0.011	0.068	0.41	6	-10000	0	6
BRCA1/BARD1/CTIP/M/R/N Complex	0.038	0.044	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.01	0.056	-10000	0	-0.33	7	7
BRCA1/BARD1/P53	0.028	0.056	-10000	0	-0.31	6	6
BARD1/CSTF1/BRCA1	-0.01	0.056	-10000	0	-0.33	7	7
BRCA1/BACH1	0.013	0.031	-10000	0	-0.47	1	1
BARD1	0	0.092	-10000	0	-0.58	6	6
PCNA	0.013	0.031	-10000	0	-0.47	1	1
BRCA1/BARD1/UbcH5C	-0.01	0.056	-10000	0	-0.33	7	7
BRCA1/BARD1/UbcH7	-0.01	0.056	-10000	0	-0.33	7	7
BRCA1/BARD1/RAD51/PCNA	-0.062	0.14	-10000	0	-0.35	6	6
BARD1/DNA-PK/P53	0.036	0.05	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	0.009	0.071	-10000	0	-0.4	7	7
BRCA1/BARD1/CTIP	0.027	0.056	-10000	0	-0.31	6	6
FA complex	0.036	0.037	-10000	0	-10000	0	0
BARD1/EWS	0.011	0.068	-10000	0	-0.42	6	6
RBBP8	0.025	0	-10000	0	-10000	0	0
TP53	0.015	0	-10000	0	-10000	0	0
TOPBP1	0.015	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.009	0.049	0.3	6	-10000	0	6
BRCA1/BARD1	-0.003	0.1	-10000	0	-10000	0	0
CSTF1	0.015	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0	0.068	-10000	0	-0.42	6	6
CDK2	0.015	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.15	0.23	-10000	0	-0.47	80	80
RAD50	0.015	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.009	0.071	-10000	0	-0.4	7	7
EWSR1	0.015	0	-10000	0	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.015	0	-9999	-10000	0	0
ITGB7	0.005	0.076	-9999	-0.58	4	4
ITGA4	-0.002	0.097	-9999	-0.56	7	7
alpha4/beta7 Integrin	0.002	0.09	-9999	-0.41	11	11
alpha4/beta1 Integrin	0.01	0.071	-9999	-0.4	7	7

×

EPO signaling pathway

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
BCL2L1	0.056	0.094	-9999	-0.41	3	3
CRKL	0.023	0.077	-9999	-0.28	1	1
mol:DAG	0.035	0.064	-9999	-10000	0	0
HRAS	0.05	0.066	-9999	-10000	0	0
MAPK8	0.007	0.092	-9999	-0.4	3	3
RAP1A	0.025	0.074	-9999	-10000	0	0
GAB1	0.025	0.074	-9999	-10000	0	0
MAPK14	0.011	0.081	-9999	-0.26	1	1
EPO	-0.029	0.14	-9999	-0.46	22	22
PLCG1	0.036	0.065	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.004	0.076	-9999	-0.47	6	6
RAPGEF1	0.015	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.036	0.15	-9999	-0.32	47	47
GAB1/SHC/GRB2/SOS1	-0.017	0.044	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.014	0.11	-9999	-0.32	28	28
IRS2	0.012	0.097	-9999	-0.36	3	3
STAT1	0.04	0.082	-9999	-0.36	3	3
STAT5B	0.039	0.074	-9999	-0.32	3	3
cell proliferation	0.016	0.086	-9999	-0.41	2	2
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.021	0.058	-9999	-0.42	2	2
TEC	0.025	0.074	-9999	-0.28	1	1
SOCS3	-0.042	0.17	-9999	-0.58	23	23
STAT1 (dimer)	0.04	0.081	-9999	-0.36	3	3
JAK2	0.013	0.038	-9999	-0.57	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	0.03	0.083	-9999	-0.28	4	4
EPO/EPOR	-0.014	0.11	-9999	-0.32	28	28
LYN	0.016	0.004	-9999	-10000	0	0
TEC/VAV2	0.032	0.077	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.004	0.075	-9999	-0.47	6	6
SHC1	0.013	0.031	-9999	-0.47	1	1
EPO/EPOR (dimer)/LYN	0.007	0.093	-9999	-0.25	28	28
mol:IP3	0.035	0.064	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.019	0.1	-9999	-0.41	4	4
SH2B3	0.015	0.006	-9999	-10000	0	0
NFKB1	0.011	0.081	-9999	-0.26	3	3
EPO/EPOR (dimer)/JAK2/SOCS3	-0.035	0.081	-9999	-0.26	23	23
PTPN6	0.017	0.077	-9999	-0.28	4	4
TEC/VAV2/GRB2	0.038	0.075	-9999	-10000	0	0
EPOR	0.004	0.076	-9999	-0.47	6	6
INPP5D	0	0.092	-9999	-0.58	6	6
mol:GDP	-0.017	0.045	-9999	-10000	0	0
SOS1	0.015	0	-9999	-10000	0	0
PLCG2	0.013	0.031	-9999	-0.47	1	1
CRKL/CBL/C3G	0.038	0.073	-9999	-10000	0	0
VAV2	0.022	0.079	-9999	-0.28	1	1
CBL	0.025	0.074	-9999	-0.27	3	3
SHC/Grb2/SOS1	-0.019	0.049	-9999	-10000	0	0
STAT5A	0.037	0.077	-9999	-0.31	4	4
GRB2	0.015	0	-9999	-10000	0	0
STAT5 (dimer)	0.051	0.1	-9999	-0.45	3	3
LYN/PLCgamma2	0.021	0.023	-9999	-0.33	1	1
PTPN11	0.015	0	-9999	-10000	0	0
BTK	0.01	0.099	-9999	-0.32	6	6
BCL2	0.03	0.21	-9999	-0.9	11	11

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.024	0.023	-9999	-0.33	1	1
BAD/BCL-XL/YWHAZ	0.036	0.017	-9999	-10000	0	0
CDKN1B	0.041	0	-9999	-10000	0	0
CDKN1A	0.04	0.02	-9999	-10000	0	0
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.015	0	-9999	-10000	0	0
FOXO3	0.041	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.015	0	-9999	-10000	0	0
AKT3	0.006	0.07	-9999	-0.35	9	9
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.04	0.015	-9999	-10000	0	0
AKT1/ASK1	0.039	0	-9999	-10000	0	0
BAD/YWHAZ	0	0	-9999	-10000	0	0
RICTOR	0.015	0	-9999	-10000	0	0
RAF1	0.013	0.031	-9999	-0.47	1	1
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.041	0	-9999	-10000	0	0
YWHAZ	0.015	0	-9999	-10000	0	0
AKT1/RAF1	0.041	0.015	-9999	-10000	0	0
EP300	0.015	0	-9999	-10000	0	0
mol:GDP	0.034	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.041	0	-9999	-10000	0	0
YWHAQ	0.015	0	-9999	-10000	0	0
TBC1D4	0.027	0	-9999	-10000	0	0
MAP3K5	0.015	0	-9999	-10000	0	0
MAPKAP1	0.015	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.041	0.027	-9999	-10000	0	0
YWHAH	0.015	0	-9999	-10000	0	0
AKT1S1	0.041	0	-9999	-10000	0	0
CASP9	0.041	0	-9999	-10000	0	0
YWHAB	0.015	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.048	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.012	0.038	-9999	-0.58	1	1
SRC	0.015	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.001	0.016	-9999	-10000	0	0
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.021	0	-9999	-10000	0	0
CHUK	0.041	0	-9999	-10000	0	0
BAD/BCL-XL	0.055	0.015	-9999	-10000	0	0
mTORC2	0.019	0	-9999	-10000	0	0
AKT2	0.019	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.058	0.03	-9999	-10000	0	0
PDPK1	0.015	0	-9999	-10000	0	0
MDM2	0.034	0.04	-9999	-10000	0	0
MAPKKK cascade	-0.04	0.015	-9999	-10000	0	0
MDM2/Cbp/p300	0.049	0.038	-9999	-10000	0	0
TSC1/TSC2	0.048	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.046	0.036	-9999	-10000	0	0
glucose import	-0.21	0.15	-9999	-0.3	176	176
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.035	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	-0.21	0.15	-9999	-0.31	176	176
GSK3A	0.041	0	-9999	-10000	0	0
FOXO1	0.041	0	-9999	-10000	0	0
GSK3B	0.041	0	-9999	-10000	0	0
SFN	-0.039	0.15	-9999	-0.48	26	26
G1/S transition of mitotic cell cycle	0.048	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.042	0.04	-9999	-10000	0	0
PRKACA	0.015	0	-9999	-10000	0	0
KPNA1	0.015	0	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
YWHAG	0.015	0	-9999	-10000	0	0
RHEB	0.015	0	-9999	-10000	0	0
CREBBP	0.015	0	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.015	0	-10000	0	-10000	0	0
EPHB2	-0.013	0.11	-10000	0	-0.47	14	14
EFNB1	0.016	0.063	-10000	0	-0.42	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.026	0.095	-10000	0	-0.52	3	3
Ephrin B2/EPHB1-2	-0.007	0.099	-10000	0	-0.27	29	29
neuron projection morphogenesis	-0.031	0.087	-10000	0	-0.49	3	3
Ephrin B1/EPHB1-2/Tiam1	0.003	0.11	-10000	0	-0.56	3	3
DNM1	0.002	0.085	-10000	0	-0.58	5	5
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.01	0.1	-10000	0	-0.62	6	6
YES1	-0.019	0.14	-10000	0	-0.87	6	6
Ephrin B1/EPHB1-2/NCK2	0.004	0.11	-10000	0	-0.58	2	2
PI3K	0.011	0.1	-10000	0	-0.63	6	6
mol:GDP	0.002	0.11	-10000	0	-0.55	3	3
ITGA2B	-0.02	0.12	-10000	0	-0.47	17	17
endothelial cell proliferation	0.004	0.008	-10000	0	-10000	0	0
FYN	-0.02	0.14	-10000	0	-0.9	6	6
MAP3K7	-0.014	0.1	-10000	0	-0.66	6	6
FGR	-0.02	0.14	-10000	0	-0.89	6	6
TIAM1	0.012	0.038	-10000	0	-0.58	1	1
PIK3R1	0.015	0	-10000	0	-10000	0	0
RGS3	0.015	0	-10000	0	-10000	0	0
cell adhesion	-0.017	0.14	-10000	0	-0.49	10	10
LYN	-0.019	0.14	-10000	0	-0.87	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.02	0.13	-10000	0	-0.81	6	6
Ephrin B1/EPHB1-2	-0.018	0.11	-10000	0	-0.72	6	6
SRC	-0.019	0.14	-10000	0	-0.86	6	6
ITGB3	-0.039	0.17	-10000	0	-0.58	22	22
EPHB1	-0.022	0.14	-10000	0	-0.57	15	15
EPHB4	0.015	0	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.006	0.009	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.042	0.15	-10000	0	-0.4	37	37
BLK	-0.037	0.14	-10000	0	-0.86	6	6
HCK	-0.024	0.14	-10000	0	-0.89	6	6
regulation of stress fiber formation	-0.003	0.11	0.57	2	-10000	0	2
MAPK8	0.014	0.11	-10000	0	-0.62	7	7
Ephrin B1/EPHB1-2/RGS3	0.004	0.11	-10000	0	-0.58	2	2
endothelial cell migration	-0.009	0.088	-10000	0	-0.56	6	6
NCK2	0.015	0	-10000	0	-10000	0	0
PTPN13	-0.011	0.11	-10000	0	-0.69	6	6
regulation of focal adhesion formation	-0.003	0.11	0.57	2	-10000	0	2
chemotaxis	-0.003	0.11	0.57	2	-10000	0	2
PIK3CA	0.015	0	-10000	0	-10000	0	0
Rac1/GTP	-0.032	0.089	-10000	0	-0.51	3	3
angiogenesis	-0.018	0.11	-10000	0	-0.71	6	6
LCK	-0.021	0.14	-10000	0	-0.86	6	6

×

Regulation of Telomerase

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.1	0.17	-9999	-0.49	3	3
RAD9A	0.007	0.062	-9999	-0.47	4	4
AP1	-0.13	0.22	-9999	-0.45	74	74
IFNAR2	0.01	0.009	-9999	-10000	0	0
AKT1	-0.024	0.087	-9999	-0.24	15	15
ER alpha/Oestrogen	-0.063	0.16	-9999	-0.43	39	39
NFX1/SIN3/HDAC complex	0.032	0.027	-9999	-10000	0	0
EGF	-0.019	0.12	-9999	-0.48	15	15
SMG5	0.015	0	-9999	-10000	0	0
SMG6	0.015	0	-9999	-10000	0	0
SP3/HDAC2	0.015	0.013	-9999	-10000	0	0
TERT/c-Abl	-0.1	0.14	-9999	-0.46	3	3
SAP18	0.014	0.001	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.067	0.17	-9999	-0.48	36	36
WRN	0.015	0	-9999	-10000	0	0
SP1	0.011	0.009	-9999	-10000	0	0
SP3	0.013	0.004	-9999	-10000	0	0
TERF2IP	0.015	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.097	0.12	-9999	-10000	0	0
Mad/Max	0.013	0.026	-9999	-0.34	1	1
TERT	-0.1	0.17	-9999	-0.5	3	3
CCND1	-0.096	0.2	-9999	-1	4	4
MAX	0.013	0.004	-9999	-10000	0	0
RBBP7	0.014	0.002	-9999	-10000	0	0
RBBP4	0.014	0.001	-9999	-10000	0	0
TERF2	0.014	0	-9999	-10000	0	0
PTGES3	0.015	0	-9999	-10000	0	0
SIN3A	0.014	0.001	-9999	-10000	0	0
Telomerase/911	0.026	0.035	-9999	-10000	0	0
CDKN1B	-0.015	0.11	-9999	-10000	0	0
RAD1	0.015	0	-9999	-10000	0	0
XRCC5	0.015	0	-9999	-10000	0	0
XRCC6	0.015	0	-9999	-10000	0	0
SAP30	0.014	0.002	-9999	-10000	0	0
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.013	0.003	-9999	-10000	0	0
JUN	-0.001	0.092	-9999	-0.58	6	6
E6	-0.002	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0.008	0.007	-9999	-10000	0	0
FOS	-0.17	0.27	-9999	-0.58	74	74
IFN-gamma/IRF1	-0.04	0.13	-9999	-0.32	43	43
PARP2	0.015	0	-9999	-10000	0	0
BLM	0.001	0.082	-9999	-0.47	7	7
Telomerase	-0.004	0.054	-9999	-0.41	1	1
IRF1	0.018	0.004	-9999	-10000	0	0
ESR1	-0.082	0.22	-9999	-0.58	39	39
KU/TER	0.022	0	-9999	-10000	0	0
ATM/TRF2	0.023	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.036	0.03	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.036	0.03	-9999	-10000	0	0
HDAC1	0.014	0.001	-9999	-10000	0	0
HDAC2	0.01	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.027	0.004	-9999	-10000	0	0
ABL1	0.015	0	-9999	-10000	0	0
MXD1	0.011	0.032	-9999	-0.48	1	1
MRE11A	0.015	0	-9999	-10000	0	0
HUS1	0.015	0	-9999	-10000	0	0
RPS6KB1	0.015	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.1	0.14	-9999	-0.48	1	1
NR2F2	0.016	0.039	-9999	-0.58	1	1
MAPK3	0.012	0.01	-9999	-10000	0	0
MAPK1	0.012	0.01	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.016	0.002	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
HNRNPC	0.015	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	0.015	0	-9999	-10000	0	0
EGFR	-0.011	0.11	-9999	-0.52	11	11
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.025	0.11	-9999	-0.35	26	26
MYC	-0.017	0.12	-9999	-0.58	11	11
IL2	0	0.012	-9999	-10000	0	0
KU	0.022	0	-9999	-10000	0	0
RAD50	0.015	0	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
TGFB1	0.016	0.002	-9999	-10000	0	0
TRF2/BLM	-0.009	0.051	-9999	-0.3	7	7
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.079	0.16	-9999	-0.46	2	2
SP1/HDAC2	0.017	0.015	-9999	-10000	0	0
PINX1	0.015	0	-9999	-10000	0	0
Telomerase/EST1A	-0.097	0.12	-9999	-10000	0	0
Smad3/Myc	0.014	0.079	-9999	-0.34	11	11
911 complex	-0.004	0.034	-9999	-10000	0	0
IFNG	-0.071	0.18	-9999	-0.47	43	43
Telomerase/PinX1	-0.097	0.12	-9999	-10000	0	0
Telomerase/AKT1/mTOR/p70S6K	-0.005	0.058	-9999	-10000	0	0
SIN3B	0.014	0.002	-9999	-10000	0	0
YWHAE	0.012	0.038	-9999	-0.58	1	1
Telomerase/EST1B	-0.097	0.12	-9999	-10000	0	0
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.097	0.12	-9999	-10000	0	0
E2F1	-0.11	0.21	-9999	-0.48	58	58
ZNFX1	0.014	0.001	-9999	-10000	0	0
PIF1	-0.016	0.12	-9999	-0.48	15	15
NCL	0.015	0	-9999	-10000	0	0
DKC1	0.015	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Signaling events mediated by PRL

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
CCNE1	-0.058	0.17	-9999	-0.47	36	36
mol:Halofuginone	0.005	0.001	-9999	-10000	0	0
ITGA1	0.015	0	-9999	-10000	0	0
CDKN1A	-0.003	0.079	-9999	-0.68	1	1
PRL-3/alpha Tubulin	0.022	0	-9999	-10000	0	0
mol:Ca2+	-0.055	0.14	-9999	-0.43	31	31
AGT	-0.061	0.2	-9999	-0.57	31	31
CCNA2	-0.1	0.17	-9999	-0.51	16	16
TUBA1B	0.015	0	-9999	-10000	0	0
EGR1	-0.081	0.19	-9999	-0.41	60	60
CDK2/Cyclin E1	-0.023	0.12	-9999	-0.38	9	9
MAPK3	0.025	0	-9999	-10000	0	0
PRL-2 /Rab GGTase beta	0.022	0	-9999	-10000	0	0
MAPK1	0.025	0	-9999	-10000	0	0
PTP4A1	-0.043	0.15	-9999	-10000	0	0
PTP4A3	0.015	0	-9999	-10000	0	0
PTP4A2	0.015	0	-9999	-10000	0	0
ITGB1	0.025	0	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
RAC1	-0.001	0.067	-9999	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0.022	0	-9999	-10000	0	0
PRL-1/ATF-5	-0.034	0.14	-9999	-10000	0	0
RABGGTA	0.015	0	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
RHOC	-0.001	0.067	-9999	-10000	0	0
RHOA	-0.001	0.067	-9999	-10000	0	0
cell motility	0.002	0.072	-9999	-10000	0	0
PRL-1/alpha Tubulin	-0.033	0.14	-9999	-10000	0	0
PRL-3/alpha1 Integrin	0.022	0	-9999	-10000	0	0
ROCK1	0.002	0.072	-9999	-10000	0	0
RABGGTB	0.015	0	-9999	-10000	0	0
CDK2	0.015	0	-9999	-10000	0	0
mitosis	-0.043	0.14	-9999	-10000	0	0
ATF5	0.013	0.031	-9999	-0.47	1	1

×

E-cadherin signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.013	0.072	-9999	-0.39	8	8
E-cadherin/beta catenin	0.007	0.078	-9999	-0.42	8	8
CTNNB1	0.015	0	-9999	-10000	0	0
JUP	0.012	0.038	-9999	-0.58	1	1
CDH1	-0.005	0.11	-9999	-0.58	8	8

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.003	0.085	-9999	-0.26	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
CRKL	0.011	0.044	-9999	-0.47	2	2
STAT1 (dimer)/Cbp/p300	0.04	0.081	-9999	-0.33	2	2
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.005	0.023	-9999	-0.34	1	1
antigen processing and presentation of peptide antigen via MHC class I	-0.032	0.064	-9999	-0.32	5	5
CaM/Ca2+	-0.028	0.06	-9999	-10000	0	0
RAP1A	0.015	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.011	0.087	-9999	-0.39	2	2
AKT1	0.026	0.073	-9999	-10000	0	0
MAP2K1	0.022	0.077	-9999	-10000	0	0
MAP3K11	0.011	0.08	-9999	-10000	0	0
IFNGR1	0.014	0.006	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.19	-9999	-0.41	77	77
Rap1/GTP	-0.02	0.044	-9999	-0.29	1	1
CRKL/C3G	0.019	0.032	-9999	-0.33	2	2
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0	0.093	-9999	-0.27	1	1
CEBPB	0.055	0.083	-9999	-0.37	3	3
STAT3	0.015	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.01	0.087	-9999	-0.39	1	1
STAT1	0.011	0.086	-9999	-0.39	2	2
CALM1	0.015	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.072	0.18	-9999	-0.46	43	43
PIK3CA	0.015	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.019	0.083	-9999	-0.36	2	2
CEBPB/PTGES2/Cbp/p300	-0.007	0.027	-9999	-10000	0	0
mol:Ca2+	0.001	0.083	-9999	-0.26	1	1
MAPK3	0.037	0.069	-9999	-10000	0	0
STAT1 (dimer)	-0.041	0.089	-9999	-0.45	5	5
MAPK1	0.037	0.069	-9999	-10000	0	0
JAK2	0.012	0.038	-9999	-0.57	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
JAK1	0.014	0.006	-9999	-10000	0	0
CAMK2D	0.015	0	-9999	-10000	0	0
DAPK1	0.052	0.094	-9999	-0.62	3	3
SMAD7	0.019	0.061	-9999	-0.35	1	1
CBL/CRKL/C3G	0.023	0.078	-9999	-0.35	1	1
PI3K	-0.026	0.056	-9999	-10000	0	0
IFNG	-0.072	0.18	-9999	-0.46	43	43
apoptosis	0.033	0.072	-9999	-0.44	3	3
CAMK2G	0.015	0	-9999	-10000	0	0
STAT3 (dimer)	0.015	0	-9999	-10000	0	0
CAMK2A	-0.18	0.28	-9999	-0.58	77	77
CAMK2B	-0.04	0.15	-9999	-0.47	27	27
FRAP1	0.025	0.069	-9999	-10000	0	0
PRKCD	0.027	0.074	-9999	-10000	0	0
RAP1B	0.015	0	-9999	-10000	0	0
negative regulation of cell growth	-0.032	0.064	-9999	-0.32	5	5
PTPN2	0.015	0	-9999	-10000	0	0
EP300	0.015	0	-9999	-10000	0	0
IRF1	0.052	0.071	-9999	-10000	0	0
STAT1 (dimer)/PIASy	0.015	0.082	-9999	-0.36	2	2
SOCS1	0.005	0.021	-9999	-10000	0	0
mol:GDP	-0.025	0.054	-9999	-0.34	1	1
CASP1	0.014	0.076	-9999	-0.29	8	8
PTGES2	0.015	0	-9999	-10000	0	0
IRF9	0.053	0.033	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.026	0.055	-9999	-10000	0	0
RAP1/GDP	-0.02	0.044	-9999	-0.29	1	1
CBL	0.011	0.08	-9999	-10000	0	0
MAP3K1	0.012	0.08	-9999	-10000	0	0
PIAS1	0.015	0	-9999	-10000	0	0
PIAS4	0.014	0	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.032	0.064	-9999	-0.32	5	5
PTPN11	0.002	0.083	-9999	-0.26	1	1
CREBBP	0.015	0	-9999	-10000	0	0
RAPGEF1	0.015	0	-9999	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.018	0.078	-9999	-0.35	10	10
CRKL	0.011	0.044	-9999	-0.47	2	2
Rac1/GDP	0.011	0	-9999	-10000	0	0
DOCK1	0.012	0.038	-9999	-0.58	1	1
ITGA4	-0.002	0.097	-9999	-0.56	7	7
alpha4/beta7 Integrin/MAdCAM1	0.013	0.091	-9999	-0.36	10	10
EPO	-0.033	0.14	-9999	-0.47	22	22
alpha4/beta7 Integrin	0.002	0.09	-9999	-0.41	11	11
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0.01	0.071	-9999	-0.4	7	7
EPO/EPOR (dimer)	-0.021	0.11	-9999	-0.33	28	28
lamellipodium assembly	0.001	0.011	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	0.022	0	-9999	-10000	0	0
ARF6	0.015	0	-9999	-10000	0	0
JAK2	0.008	0.078	-9999	-0.32	7	7
PXN	0.015	0	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
MADCAM1	-0.003	0.087	-9999	-0.47	8	8
cell adhesion	-0.021	0.082	-9999	-0.36	10	10
CRKL/CBL	0.019	0.032	-9999	-0.33	2	2
ITGB1	0.015	0	-9999	-10000	0	0
SRC	0.015	0.097	-9999	-0.38	12	12
ITGB7	0.005	0.076	-9999	-0.58	4	4
RAC1	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.022	0.099	-9999	-0.42	13	13
p130Cas/Crk/Dock1	0.037	0.087	-9999	-0.52	3	3
VCAM1	-0.007	0.11	-9999	-0.58	9	9
RHOA	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.028	0.056	-9999	-0.31	6	6
BCAR1	0.024	0.092	-9999	-0.57	3	3
EPOR	0.003	0.076	-9999	-0.47	6	6
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.015	0	-9999	-10000	0	0
GIT1	0.015	0	-9999	-10000	0	0
Rac1/GTP	0.001	0.011	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.033	0	-9999	-10000	0	0
SNTA1	0.015	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.008	0.083	-9999	-0.27	20	20
MAPK12	0.026	0.048	-9999	-0.27	6	6
CCND1	0.015	0.054	-9999	-0.42	3	3
p38 gamma/SNTA1	0.032	0.045	-9999	-0.27	4	4
MAP2K3	0.015	0	-9999	-10000	0	0
PKN1	0.012	0.038	-9999	-0.58	1	1
G2/M transition checkpoint	0.026	0.048	-9999	-0.27	6	6
MAP2K6	0.02	0.049	-9999	-0.32	5	5
MAPT	0.002	0.099	-9999	-0.31	21	21
MAPK13	0.025	0	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.018	0.024	-9999	-0.35	1	1

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.026	0.086	-10000	0	-0.3	21	21
cell-cell adhesion	0.03	0.069	-10000	0	-10000	0	0
Ephrin B/EPHB2/RasGAP	0.017	0.082	-10000	0	-10000	0	0
ITSN1	0.015	0	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
SHC1	0.013	0.031	-10000	0	-0.47	1	1
Ephrin B1/EPHB3	-0.014	0.062	-10000	0	-0.28	12	12
Ephrin B1/EPHB1	-0.022	0.084	-10000	0	-0.35	15	15
HRAS/GDP	-0.018	0.063	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	0.001	0.11	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.016	0.077	-10000	0	-10000	0	0
KRAS	0.013	0.031	-10000	0	-0.47	1	1
Ephrin B/EPHB1/Src	0.012	0.095	-10000	0	-0.28	20	20
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.015	0	-10000	0	-10000	0	0
GRB7	-0.006	0.1	-10000	0	-0.49	10	10
PAK1	0.02	0.085	-10000	0	-10000	0	0
HRAS	0.015	0	-10000	0	-10000	0	0
RRAS	0.015	0.08	-10000	0	-10000	0	0
DNM1	0.002	0.084	-10000	0	-0.58	5	5
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.011	0.09	-10000	0	-10000	0	0
lamellipodium assembly	-0.03	0.069	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.02	0.076	-10000	0	-0.24	14	14
PIK3R1	0.015	0	-10000	0	-10000	0	0
EPHB2	-0.014	0.11	-10000	0	-0.47	14	14
EPHB3	-0.01	0.11	-10000	0	-0.48	12	12
EPHB1	-0.022	0.14	-10000	0	-0.57	15	15
EPHB4	0.015	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.079	-10000	0	-10000	0	0
Ephrin B/EPHB2	0.008	0.082	-10000	0	-0.29	6	6
Ephrin B/EPHB3	0.01	0.084	-10000	0	-0.32	7	7
JNK cascade	0.009	0.093	-10000	0	-0.28	14	14
Ephrin B/EPHB1	0.003	0.095	-10000	0	-0.29	20	20
RAP1/GDP	-0.011	0.059	-10000	0	-10000	0	0
EFNB2	0.015	0	-10000	0	-10000	0	0
EFNB3	-0.008	0.11	-10000	0	-0.54	10	10
EFNB1	0.015	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.008	0.1	-10000	0	-0.28	29	29
RAP1B	0.015	0	-10000	0	-10000	0	0
RAP1A	0.015	0	-10000	0	-10000	0	0
CDC42/GTP	-0.029	0.07	-10000	0	-10000	0	0
Rap1/GTP	-0.029	0.068	-10000	0	-10000	0	0
axon guidance	-0.026	0.086	-10000	0	-0.3	21	21
MAPK3	0.035	0.069	-10000	0	-10000	0	0
MAPK1	0.035	0.069	-10000	0	-10000	0	0
Rac1/GDP	0.032	0.075	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.021	0.049	-10000	0	-10000	0	0
CDC42/GDP	0.032	0.075	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.002	0.099	-10000	0	-0.58	7	7
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	0.025	0.056	-10000	0	-10000	0	0
CDC42	0.015	0	-10000	0	-10000	0	0
RAS family/GTP	-0.029	0.066	-10000	0	-10000	0	0
PTK2	0.009	0.024	-10000	0	-10000	0	0
MAP4K4	0.009	0.094	-10000	0	-0.28	14	14
SRC	0.015	0	-10000	0	-10000	0	0
KALRN	0.008	0.062	-10000	0	-0.54	3	3
Intersectin/N-WASP	0.022	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.044	0.084	-10000	0	-0.36	1	1
MAP2K1	0.028	0.072	-10000	0	-10000	0	0
WASL	0.015	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.001	0.1	-10000	0	-0.31	14	14
cell migration	0.033	0.082	-10000	0	-10000	0	0
NRAS	0.015	0	-10000	0	-10000	0	0
SYNJ1	0.016	0.078	-10000	0	-10000	0	0
PXN	0.015	0	-10000	0	-10000	0	0
TF	-0.011	0.12	-10000	0	-0.42	5	5
HRAS/GTP	-0.033	0.075	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2	-0.008	0.1	-10000	0	-0.28	29	29
cell adhesion mediated by integrin	0.011	0.062	0.31	6	-10000	0	6
RAC1	0.015	0	-10000	0	-10000	0	0
mol:GTP	-0.036	0.082	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.038	0.083	-10000	0	-0.38	5	5
RASA1	0.015	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.011	0.059	-10000	0	-10000	0	0
ruffle organization	0.028	0.093	-10000	0	-10000	0	0
NCK1	0.015	0	-10000	0	-10000	0	0
receptor internalization	0.018	0.084	-10000	0	-10000	0	0
Ephrin B/EPHB2/KALRN	0.013	0.087	-10000	0	-10000	0	0
ROCK1	0.015	0.06	-10000	0	-0.25	12	12
RAS family/GDP	-0.02	0.046	-10000	0	-10000	0	0
Rac1/GTP	-0.031	0.072	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src/Paxillin	0.015	0.08	-10000	0	-0.24	20	20

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.42	0.26	-10000	0	-0.58	176	176
CLTC	0.035	0.009	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.03	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	0.026	0.017	-10000	0	-10000	0	0
EXOC4	0.015	0	-10000	0	-10000	0	0
CD59	0.032	0.006	-10000	0	-10000	0	0
CPE	0.012	0.057	-10000	0	-0.34	6	6
CTNNB1	0.015	0	-10000	0	-10000	0	0
membrane fusion	0.029	0	-10000	0	-10000	0	0
CTNND1	0.034	0.016	-10000	0	-10000	0	0
DNM2	0.015	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.036	0.004	-10000	0	-10000	0	0
TSHR	0.012	0.042	-10000	0	-0.28	5	5
INS	0.013	0.002	-10000	0	-10000	0	0
BIN1	-0.059	0.2	-10000	0	-0.58	30	30
mol:Choline	0.029	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.019	-10000	0	-0.28	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	0.026	0.017	-10000	0	-10000	0	0
JUP	0.031	0.016	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.014	0.11	-10000	0	-0.31	30	30
ARF6/GTP	0.011	0	-10000	0	-10000	0	0
CDH1	0.024	0.042	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0.011	0	-10000	0	-10000	0	0
MAPK8IP3	0.008	0.058	-10000	0	-0.51	3	3
positive regulation of endocytosis	0.011	0	-10000	0	-10000	0	0
EXOC2	0.015	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.048	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.015	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.005	0.024	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.021	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.004	0.034	-10000	0	-0.3	3	3
ACAP1	0.023	0.027	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.064	0.11	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.04	0.011	-10000	0	-10000	0	0
JIP4/KLC1	0.029	0	-10000	0	-10000	0	0
EXOC1	0.015	0	-10000	0	-10000	0	0
exocyst	0.048	0	-10000	0	-10000	0	0
RALA/GTP	0.011	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0.011	0	-10000	0	-10000	0	0
CTNNA1	0.034	0.016	-10000	0	-10000	0	0
NME1	0.02	0.019	-10000	0	-0.28	1	1
clathrin coat assembly	0.035	0.009	-10000	0	-10000	0	0
IL2RA	0.011	0.06	-10000	0	-10000	0	0
VAMP3	0.021	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.18	0.11	-10000	0	-0.36	1	1
EXOC6	0.015	0	-10000	0	-10000	0	0
PLD1	0.025	0	-10000	0	-10000	0	0
PLD2	0.025	0	-10000	0	-10000	0	0
EXOC5	0.015	0	-10000	0	-10000	0	0
PIP5K1C	0.036	0.004	-10000	0	-10000	0	0
SDC1	0.029	0.026	-10000	0	-10000	0	0
ARF6/GDP	0.019	0.019	-10000	0	-0.28	1	1
EXOC7	0.015	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.005	0.025	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.029	0	-10000	0	-10000	0	0
endocytosis	0.039	0.1	0.31	30	-10000	0	30
SCAMP2	0.015	0	-10000	0	-10000	0	0
ADRB2	0.019	0.08	-10000	0	-10000	0	0
EXOC3	0.015	0	-10000	0	-10000	0	0
ASAP2	0.015	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.027	0.017	-10000	0	-10000	0	0
KLC1	0.015	0	-10000	0	-10000	0	0
AVPR2	0.01	0.092	-10000	0	-10000	0	0
RALA	0.015	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.004	0.021	-10000	0	-10000	0	0

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.023	0.088	-9999	-0.53	4	4
PDGFB-D/PDGFRB/SLAP	0.004	0.093	-9999	-0.46	9	9
PDGFB-D/PDGFRB/APS/CBL	0.016	0.058	-9999	-0.31	7	7
AKT1	0.054	0.051	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.005	0.1	-9999	-0.57	4	4
PIK3CA	0.015	0	-9999	-10000	0	0
FGR	-0.007	0.06	-9999	-0.4	5	5
mol:Ca2+	0.019	0.082	-9999	-0.57	4	4
MYC	0.006	0.19	-9999	-0.76	13	13
SHC1	0.013	0.031	-9999	-0.47	1	1
HRAS/GDP	0.035	0.041	-9999	-0.27	4	4
LRP1/PDGFRB/PDGFB	0.015	0.062	-9999	-0.33	7	7
GRB10	0.012	0.038	-9999	-0.58	1	1
PTPN11	0.015	0	-9999	-10000	0	0
GO:0007205	0.019	0.083	-9999	-0.58	4	4
PTEN	0.015	0	-9999	-10000	0	0
GRB2	0.015	0	-9999	-10000	0	0
GRB7	-0.006	0.1	-9999	-0.49	10	10
PDGFB-D/PDGFRB/SHP2	0.014	0.056	-9999	-0.41	4	4
PDGFB-D/PDGFRB/GRB10	0.012	0.062	-9999	-0.42	5	5
cell cycle arrest	0.004	0.093	-9999	-0.46	9	9
HRAS	0.015	0	-9999	-10000	0	0
HIF1A	0.058	0.049	-9999	-10000	0	0
GAB1	0.016	0.089	-9999	-0.55	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.019	0.085	-9999	-0.5	4	4
PDGFB-D/PDGFRB	0.003	0.049	-9999	-0.36	4	4
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.014	0.056	-9999	-0.41	4	4
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.026	0.081	-9999	-0.49	4	4
positive regulation of MAPKKK cascade	0.014	0.056	-9999	-0.41	4	4
PIK3R1	0.015	0	-9999	-10000	0	0
mol:IP3	0.019	0.084	-9999	-0.58	4	4
E5	0	0.001	-9999	-10000	0	0
CSK	0.014	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.001	0.092	-9999	-0.37	14	14
SHB	0.015	0	-9999	-10000	0	0
BLK	-0.06	0.17	-9999	-0.54	26	26
PTPN2	0.014	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.014	0.056	-9999	-0.41	4	4
BCAR1	0.015	0	-9999	-10000	0	0
VAV2	0.015	0.1	-9999	-0.47	6	6
CBL	0.015	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.014	0.056	-9999	-0.41	4	4
LCK	-0.009	0.068	-9999	-0.42	6	6
PDGFRB	0.005	0.076	-9999	-0.58	4	4
ACP1	0.015	0	-9999	-10000	0	0
HCK	-0.021	0.12	-9999	-0.56	10	10
ABL1	0.016	0.078	-9999	-0.48	4	4
PDGFB-D/PDGFRB/CBL	0.014	0.096	-9999	-0.62	4	4
PTPN1	0.014	0.003	-9999	-10000	0	0
SNX15	0.015	0	-9999	-10000	0	0
STAT3	0.015	0	-9999	-10000	0	0
STAT1	0.011	0.044	-9999	-0.47	2	2
cell proliferation	0.011	0.17	-9999	-0.67	13	13
SLA	0	0.092	-9999	-0.58	6	6
actin cytoskeleton reorganization	0.049	0.041	-9999	-10000	0	0
SRC	-0.004	0.05	-9999	-0.37	4	4
PI3K	-0.009	0.041	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	0.006	0.08	-9999	-0.3	15	15
SH2B2	0.009	0.054	-9999	-0.47	3	3
PLCgamma1/SPHK1	0.005	0.11	-9999	-0.59	4	4
LYN	-0.004	0.05	-9999	-0.37	4	4
LRP1	0.01	0.054	-9999	-0.58	2	2
SOS1	0.015	0	-9999	-10000	0	0
STAT5B	0.015	0	-9999	-10000	0	0
STAT5A	0.012	0.038	-9999	-0.58	1	1
NCK1-2/p130 Cas	0.001	0.038	-9999	-10000	0	0
SPHK1	-0.05	0.17	-9999	-0.47	32	32
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.019	0.084	-9999	-0.58	4	4
PLCG1	0.019	0.086	-9999	-0.6	4	4
NHERF/PDGFRB	0.01	0.071	-9999	-0.29	12	12
YES1	-0.004	0.05	-9999	-0.37	4	4
cell migration	-0.01	0.066	-9999	-0.29	12	12
SHC/Grb2/SOS1	0.001	0.04	-9999	-10000	0	0
SLC9A3R2	0.015	0	-9999	-10000	0	0
SLC9A3R1	-0.001	0.087	-9999	-0.47	8	8
NHERF1-2/PDGFRB/PTEN	0.022	0.065	-9999	-0.3	4	4
FYN	-0.008	0.065	-9999	-0.4	6	6
DOK1	0.028	0.048	-9999	-0.31	4	4
HRAS/GTP	0.011	0	-9999	-10000	0	0
PDGFB	0.013	0.031	-9999	-0.47	1	1
RAC1	0.019	0.12	-9999	-0.43	15	15
PRKCD	0.03	0.045	-9999	-0.31	4	4
FER	0.029	0.05	-9999	-0.31	5	5
MAPKKK cascade	-0.005	0.035	-9999	-10000	0	0
RASA1	0.03	0.045	-9999	-0.31	4	4
NCK1	0.015	0	-9999	-10000	0	0
NCK2	0.015	0	-9999	-10000	0	0
p62DOK/Csk	0.037	0.044	-9999	-0.28	4	4
PDGFB-D/PDGFRB/SHB	0.014	0.056	-9999	-0.41	4	4
chemotaxis	0.016	0.076	-9999	-0.47	4	4
STAT1-3-5/STAT1-3-5	-0.007	0.039	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0.003	0.056	-9999	-0.43	4	4
PTPRJ	0.015	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.015	0	-9999	-10000	0	0
PLK4	0.005	0.069	-9999	-0.47	5	5
regulation of centriole replication	0.018	0.05	-9999	-0.33	5	5

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.024	0.023	-10000	0	-0.33	1	1
MAP4K4	0.035	0.058	-10000	0	-10000	0	0
BAG4	0.015	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.004	0.026	-10000	0	-0.32	1	1
NFKBIA	0.015	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.14	-10000	0	-0.56	16	16
BAX	0.002	0.009	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
AKT1	0.021	0.006	-10000	0	-10000	0	0
BAD	-0.004	0.017	-10000	0	-10000	0	0
SMPD1	0.024	0.029	-10000	0	-10000	0	0
RB1	-0.004	0.017	-10000	0	-10000	0	0
FADD/Caspase 8	0.043	0.064	-10000	0	-10000	0	0
MAP2K4	0.004	0.016	-10000	0	-10000	0	0
NSMAF	0.015	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.003	0.024	-10000	0	-0.29	1	1
EGF	-0.017	0.12	-10000	0	-0.47	15	15
mol:ceramide	-0.014	0.018	0.13	1	-10000	0	1
MADD	0.015	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.025	0	-10000	0	-10000	0	0
ASAH1	0.015	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.004	0.017	-10000	0	-10000	0	0
cell proliferation	-0.088	0.13	-10000	0	-0.28	6	6
BID	0.028	0.041	-10000	0	-10000	0	0
MAP3K1	-0.004	0.017	-10000	0	-10000	0	0
EIF2A	0.012	0.015	-10000	0	-10000	0	0
TRADD	0.015	0	-10000	0	-10000	0	0
CRADD	0.015	0	-10000	0	-10000	0	0
MAPK3	0.015	0.023	-10000	0	-0.26	1	1
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.015	0.023	-10000	0	-0.26	1	1
Cathepsin D/ceramide	-0.003	0.017	-10000	0	-10000	0	0
FADD	0.031	0.068	-10000	0	-0.29	2	2
KSR1	-0.004	0.017	-10000	0	-10000	0	0
MAPK8	0.006	0.035	-10000	0	-0.23	4	4
PRKRA	-0.004	0.017	-10000	0	-10000	0	0
PDGFA	0.015	0	-10000	0	-10000	0	0
TRAF2	0.015	0	-10000	0	-10000	0	0
IGF1	-0.25	0.29	-10000	0	-0.58	106	106
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.014	0.018	0.13	1	-10000	0	1
CTSD	0.015	0	-10000	0	-10000	0	0
regulation of nitric oxide biosynthetic process	0.022	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.093	0.14	-10000	0	-0.3	6	6
PRKCD	0.015	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.58	1	1
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.025	0	-10000	0	-10000	0	0
RelA/NF kappa B1	0.022	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.012	0.038	-10000	0	-0.58	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.028	0.061	-10000	0	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.058	-10000	0	-0.27	12	12
mol:Sphingosine-1-phosphate	0.024	0.023	-10000	0	-0.33	1	1
MAP2K1	0.011	0.023	-10000	0	-0.27	1	1
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
CYCS	0.007	0.035	0.16	11	-10000	0	11
TNFRSF1A	0.015	0	-10000	0	-10000	0	0
NFKB1	0.015	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0.022	0	-10000	0	-10000	0	0
EIF2AK2	0.004	0.016	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.013	0.058	-10000	0	-0.27	12	12
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.038	0.037	-10000	0	-10000	0	0
MAP2K2	0.011	0.023	-10000	0	-0.27	1	1
SMPD3	0.026	0.033	-10000	0	-10000	0	0
TNF	-0.01	0.11	-10000	0	-0.47	12	12
PKC zeta/PAR4	0.018	0.04	-10000	0	-0.42	2	2
mol:PHOSPHOCHOLINE	-0.003	0.034	-10000	0	-10000	0	0
NF kappa B1/RelA/I kappa B alpha	0.041	0.029	-10000	0	-0.28	2	2
AIFM1	0.007	0.035	0.16	11	-10000	0	11
BCL2	-0.012	0.12	-10000	0	-0.58	11	11

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	-0.012	0.11	-10000	0	-0.47	13	13
positive regulation of NF-kappaB transcription factor activity	-0.002	0.091	-10000	0	-0.34	16	16
MAP2K4	0.044	0.03	-10000	0	-10000	0	0
IKBKB	0.015	0	-10000	0	-10000	0	0
TNFRSF10B	0.015	0	-10000	0	-10000	0	0
TNFRSF10A	0.012	0.038	-10000	0	-0.58	1	1
SMPD1	0.014	0.033	-10000	0	-10000	0	0
IKBKG	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.007	0.066	-10000	0	-0.58	3	3
TRAIL/TRAILR2	0.003	0.079	-10000	0	-0.33	13	13
TRAIL/TRAILR3	-0.005	0.096	-10000	0	-0.34	18	18
TRAIL/TRAILR1	0.001	0.083	-10000	0	-0.33	14	14
TRAIL/TRAILR4	-0.002	0.092	-10000	0	-0.34	16	16
TRAIL/TRAILR1/DAP3/GTP	0.013	0.064	-10000	0	-0.25	14	14
IKK complex	-0.005	0.019	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.011	0	-10000	0	-10000	0	0
MAPK3	0.006	0.08	-10000	0	-0.33	13	13
MAP3K1	0.038	0.032	-10000	0	-10000	0	0
TRAILR4 (trimer)	0.007	0.066	-10000	0	-0.58	3	3
TRADD	0.015	0	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.012	0.038	-10000	0	-0.58	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.031	0.039	-10000	0	-10000	0	0
CFLAR	0.015	0	-10000	0	-10000	0	0
MAPK1	0.006	0.08	-10000	0	-0.33	13	13
TRAIL/TRAILR1/FADD/TRADD/RIP	0.025	0.068	-10000	0	-10000	0	0
mol:ceramide	0.014	0.032	-10000	0	-10000	0	0
FADD	0.007	0.062	-10000	0	-0.47	4	4
MAPK8	0.047	0.044	-10000	0	-10000	0	0
TRAF2	0.015	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.003	0.079	-10000	0	-0.54	5	5
CHUK	0.015	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.02	0.071	-10000	0	-0.34	1	1
DAP3	0.015	0	-10000	0	-10000	0	0
CASP10	-0.01	0.058	0.27	3	-10000	0	3
JNK cascade	-0.002	0.091	-10000	0	-0.34	16	16
TRAIL (trimer)	-0.012	0.11	-10000	0	-0.47	13	13
TNFRSF10C	0.003	0.079	-10000	0	-0.54	5	5
TRAIL/TRAILR1/DAP3/GTP/FADD	0.016	0.068	-10000	0	-0.29	1	1
TRAIL/TRAILR2/FADD	-0.019	0.068	-10000	0	-10000	0	0
cell death	0.014	0.032	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.032	0.035	-10000	0	-10000	0	0
TRAILR2 (trimer)	0.015	0	-10000	0	-10000	0	0
CASP8	0.004	0.02	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.026	0.065	-10000	0	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.015	0	-10000	0	-10000	0	0
HDAC3	0.015	0	-10000	0	-10000	0	0
VDR	0.01	0.049	-10000	0	-0.52	2	2
Cbp/p300/PCAF	0	0	-10000	0	-10000	0	0
EP300	0.015	0	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.032	0.06	-10000	0	-0.26	1	1
KAT2B	0.015	0	-10000	0	-10000	0	0
MAPK14	0.015	0	-10000	0	-10000	0	0
AKT1	0.012	0.086	0.22	8	-0.26	18	26
RAR alpha/9cRA/Cyclin H	-0.004	0.024	-10000	0	-10000	0	0
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.027	0.069	-10000	0	-0.29	1	1
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.017	0.057	-10000	0	-0.47	3	3
NCOR2	0.015	0	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.008	0.036	-10000	0	-0.38	2	2
RXRs/RARs/NRIP1/9cRA	0.014	0.085	-10000	0	-0.36	1	1
NCOA2	-0.017	0.13	-10000	0	-0.58	13	13
NCOA3	0.015	0	-10000	0	-10000	0	0
NCOA1	0.015	0	-10000	0	-10000	0	0
VDR/VDR/DNA	0.01	0.049	-10000	0	-0.52	2	2
RARG	0.016	0	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.021	0	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
MAPK1	0.015	0	-10000	0	-10000	0	0
MAPK8	0.009	0.066	-10000	0	-0.58	3	3
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.02	0.046	-10000	0	-0.35	1	1
RARA	0.024	0.036	-10000	0	-0.24	3	3
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.013	0.097	-10000	0	-0.49	3	3
PRKCA	0.019	0	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.001	0.086	-10000	0	-0.38	1	1
RXRG	-0.081	0.17	-10000	0	-0.34	67	67
RXRA	0.032	0.037	-10000	0	-0.25	1	1
RXRB	0.024	0.03	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.008	0.036	-10000	0	-0.38	2	2
RBP1	-0.012	0.12	-10000	0	-0.57	11	11
CRBP1/9-cic-RA	-0.009	0.089	-10000	0	-0.42	11	11
RARB	-0.032	0.16	-10000	0	-0.58	20	20
PRKCG	-0.003	0.081	-10000	0	-0.47	7	7
MNAT1	0.015	0	-10000	0	-10000	0	0
RAR alpha/RXRs	0.012	0.088	-10000	0	-0.38	1	1
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.018	0.08	-10000	0	-0.33	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.062	-10000	0	-0.34	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.001	0.086	-10000	0	-0.38	1	1
positive regulation of DNA binding	-0.004	0.023	-10000	0	-10000	0	0
NRIP1	0.004	0.081	-10000	0	-10000	0	0
RXRs/RARs	-0.006	0.087	-10000	0	-0.32	4	4
RXRs/RXRs/DNA/9cRA	-0.014	0.05	-10000	0	-10000	0	0
PRKACA	0.015	0	-10000	0	-10000	0	0
CDK7	0.015	0	-10000	0	-10000	0	0
TFIIH	0	0	-10000	0	-10000	0	0
RAR alpha/9cRA	-0.002	0.015	-10000	0	-10000	0	0
CCNH	0.015	0	-10000	0	-10000	0	0
CREBBP	0.015	0	-10000	0	-10000	0	0
RAR gamma2/9cRA	0	0	-10000	0	-10000	0	0

×

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

Figure 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
BAG4	0.015	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.017	0.061	-9999	-0.36	2	2
NEF	-0.009	0.051	-9999	-10000	0	0
NFKBIA	0.011	0.027	-9999	-10000	0	0
BIRC3	0.009	0.16	-9999	-0.57	16	16
CYCS	0.031	0.083	-9999	-0.37	2	2
RIPK1	0.015	0	-9999	-10000	0	0
CD247	-0.001	0.077	-9999	-0.54	3	3
MAP2K7	0.038	0.065	-9999	-0.31	1	1
protein ubiquitination	0.065	0.04	-9999	-10000	0	0
CRADD	0.015	0	-9999	-10000	0	0
DAXX	0.015	0	-9999	-10000	0	0
FAS	0.005	0.076	-9999	-0.58	4	4
BID	0.023	0.087	-9999	-0.4	2	2
NF-kappa-B/RelA/I kappa B alpha	-0.018	0.067	-9999	-10000	0	0
TRADD	0.015	0	-9999	-10000	0	0
MAP3K5	0.015	0	-9999	-10000	0	0
CFLAR	0.015	0	-9999	-10000	0	0
FADD	0.007	0.062	-9999	-0.47	4	4
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.018	0.067	-9999	-10000	0	0
MAPK8	0.041	0.069	-9999	-10000	0	0
APAF1	0.015	0	-9999	-10000	0	0
TRAF1	0.015	0	-9999	-10000	0	0
TRAF2	0.015	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.016	0.09	-9999	-0.29	16	16
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.055	0.046	-9999	-10000	0	0
CHUK	0.066	0.042	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.034	0.052	-9999	-10000	0	0
TCRz/NEF	-0.028	0.09	-9999	-0.33	18	18
TNF	-0.01	0.11	-9999	-0.47	12	12
FASLG	-0.024	0.18	-9999	-0.57	22	22
NFKB1	0.011	0.027	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.013	0.058	-9999	-0.27	12	12
CASP6	-0.01	0.039	-9999	-10000	0	0
CASP7	0.043	0.15	-9999	-0.52	14	14
RELA	0.011	0.027	-9999	-10000	0	0
CASP2	0.015	0	-9999	-10000	0	0
CASP3	0.043	0.15	-9999	-0.52	14	14
TNFRSF1A	0.015	0	-9999	-10000	0	0
TNFR1A/BAG4	0.022	0	-9999	-10000	0	0
CASP8	0.015	0	-9999	-10000	0	0
CASP9	0.015	0	-9999	-10000	0	0
MAP3K14	0.061	0.044	-9999	-10000	0	0
APAF-1/Caspase 9	-0.033	0.095	-9999	-0.37	14	14
BCL2	0.034	0.088	-9999	-0.4	1	1

×

TCGA08_rtk_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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.074	0.21	-9999	-0.58	36	36
HRAS	0.015	0	-9999	-10000	0	0
EGFR	-0.01	0.11	-9999	-0.52	11	11
AKT	0.028	0.061	-9999	-0.26	9	9
FOXO3	0.015	0	-9999	-10000	0	0
AKT1	0.015	0	-9999	-10000	0	0
FOXO1	0.015	0	-9999	-10000	0	0
AKT3	-0.007	0.11	-9999	-0.58	9	9
FOXO4	0.013	0.031	-9999	-0.47	1	1
MET	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
NRAS	0.015	0	-9999	-10000	0	0
PIK3CG	-0.004	0.1	-9999	-0.55	8	8
PIK3R3	0.015	0	-9999	-10000	0	0
PIK3R2	0.015	0	-9999	-10000	0	0
NF1	0.015	0	-9999	-10000	0	0
RAS	-0.002	0.069	-9999	-0.27	3	3
ERBB2	0.001	0.082	-9999	-0.47	7	7
proliferation/survival/translation	-0.034	0.027	-9999	-10000	0	0
PI3K	0.008	0.067	-9999	-0.22	5	5
PIK3R1	0.015	0	-9999	-10000	0	0
KRAS	0.013	0.031	-9999	-0.47	1	1
FOXO	0.045	0.027	-9999	-10000	0	0
AKT2	0.015	0	-9999	-10000	0	0
PTEN	0.015	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.029	0.091	-9999	-0.45	8	8
KLHL20	-0.011	0.037	-9999	-0.21	2	2
CYFIP2	-0.005	0.11	-9999	-0.58	8	8
Rac1/GDP	0.056	0.059	-9999	-10000	0	0
ENAH	0.03	0.09	-9999	-0.45	8	8
AP1M1	0.015	0	-9999	-10000	0	0
RAP1B	0.015	0	-9999	-10000	0	0
RAP1A	0.015	0	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
CDC42/GTP	-0.006	0.032	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.028	-9999	-0.14	2	2
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.02	0.08	-9999	-0.33	11	11
RAPGEF1	0.045	0.079	-9999	-0.38	8	8
CTNND1	0.015	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.016	0.085	-9999	-0.48	8	8
CRK	0.038	0.085	-9999	-0.42	8	8
E-cadherin/gamma catenin/alpha catenin	-0.013	0.072	-9999	-0.39	8	8
alphaE/beta7 Integrin	0.015	0.056	-9999	-0.42	4	4
IQGAP1	0.015	0	-9999	-10000	0	0
NCKAP1	0.015	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0.028	0.005	-9999	-10000	0	0
DLG1	0.03	0.09	-9999	-0.45	8	8
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.023	-9999	-10000	0	0
MLLT4	0.015	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.026	0.028	-9999	-0.31	1	1
PI3K	-0.005	0.029	-9999	-10000	0	0
ARF6	0.015	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	0.006	0.089	-9999	-0.46	8	8
TIAM1	0.012	0.038	-9999	-0.58	1	1
E-cadherin(dimer)/Ca2+	0.024	0.058	-9999	-0.29	8	8
AKT1	-0.003	0.017	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
CDH1	-0.005	0.11	-9999	-0.58	8	8
RhoA/GDP	0.055	0.059	-9999	-10000	0	0
actin cytoskeleton organization	0.04	0.042	-9999	-0.15	2	2
CDC42/GDP	0.055	0.059	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.017	0.059	-9999	-0.29	8	8
ITGB7	0.005	0.076	-9999	-0.58	4	4
RAC1	0.015	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.026	0.062	-9999	-0.3	8	8
E-cadherin/Ca2+/beta catenin/alpha catenin	0.015	0.058	-9999	-0.3	8	8
mol:GDP	0.051	0.067	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0.001	0.004	-9999	-10000	0	0
JUP	0.012	0.038	-9999	-0.58	1	1
p120 catenin/RhoA/GDP	-0.009	0.047	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0.001	0.004	-9999	-10000	0	0
PIP5K1C/AP1M1	0.022	0	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0
CTNNA1	0.015	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.028	0.048	-9999	-0.19	9	9
NME1	0.013	0.031	-9999	-0.47	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	0.03	0.09	-9999	-0.45	8	8
regulation of cell-cell adhesion	-0.005	0.029	-9999	-10000	0	0
WASF2	-0.005	0.015	-9999	-10000	0	0
Rap1/GTP	-0.007	0.037	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.025	0.083	-9999	-0.34	11	11
CCND1	0.032	0.058	-9999	-0.23	9	9
VAV2	0.037	0.11	-9999	-0.46	10	10
RAP1/GDP	0.053	0.052	-9999	-10000	0	0
adherens junction assembly	0.03	0.087	-9999	-0.44	8	8
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.015	0	-9999	-10000	0	0
PIP5K1C	0.015	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.034	0.08	-9999	-0.56	2	2
E-cadherin/beta catenin	-0.013	0.068	-9999	-0.38	8	8
mol:GTP	0	0	-9999	-10000	0	0
SRC	0.029	0.09	-9999	-0.45	8	8
PIK3CA	0.015	0	-9999	-10000	0	0
Rac1/GTP	-0.017	0.059	-9999	-0.34	2	2
E-cadherin/beta catenin/alpha catenin	0.017	0.067	-9999	-0.34	8	8
ITGAE	0.015	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.087	-9999	-0.49	8	8

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.037	0.022	-10000	0	-0.31	1	1
HDAC3	0.015	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-10000	0	-10000	0	0
GATA1/HDAC4	0.018	0.005	-10000	0	-10000	0	0
GATA1/HDAC5	0.018	0.005	-10000	0	-10000	0	0
GATA2/HDAC5	0.004	0.082	-10000	0	-0.37	11	11
HDAC5/BCL6/BCoR	0	0	-10000	0	-10000	0	0
HDAC9	-0.025	0.15	-10000	0	-0.58	16	16
Glucocorticoid receptor/Hsp90/HDAC6	-0.009	0.054	-10000	0	-0.34	6	6
HDAC4/ANKRA2	0.022	0	-10000	0	-10000	0	0
HDAC5/YWHAB	0.022	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-10000	0	-10000	0	0
GATA2	-0.01	0.11	-10000	0	-0.52	11	11
HDAC4/RFXANK	0.02	0.022	-10000	0	-0.33	1	1
BCOR	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.015	0	-10000	0	-10000	0	0
HDAC5	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	0.02	0.028	-10000	0	-0.42	1	1
Histones	0.027	0.063	-10000	0	-0.24	1	1
ADRBK1	0.015	0	-10000	0	-10000	0	0
HDAC4	0.015	0	-10000	0	-10000	0	0
XPO1	0.015	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.022	0	-10000	0	-10000	0	0
HDAC4/Ubc9	0.022	0	-10000	0	-10000	0	0
HDAC7	0.015	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.02	0.028	-10000	0	-0.42	1	1
TUBA1B	0.015	0	-10000	0	-10000	0	0
HDAC6	0.015	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.02	0.022	-10000	0	-0.33	1	1
CAMK4	-0.01	0.12	-10000	0	-0.57	10	10
Tubulin/HDAC6	-0.001	0.022	-10000	0	-0.34	1	1
SUMO1	0.015	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0	-10000	0	-10000	0	0
GATA1	0.01	0.007	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.012	0.038	-10000	0	-0.58	1	1
NR3C1	0	0.092	-10000	0	-0.58	6	6
SUMO1/HDAC4	0.034	0	-10000	0	-10000	0	0
SRF	0.015	0	-10000	0	-10000	0	0
HDAC4/YWHAB	0.022	0	-10000	0	-10000	0	0
Tubulin	0.02	0.028	-10000	0	-0.42	1	1
HDAC4/14-3-3 E	0.02	0.028	-10000	0	-0.42	1	1
GNB1	0.015	0	-10000	0	-10000	0	0
RANGAP1	0.015	0	-10000	0	-10000	0	0
BCL6/BCoR	0.022	0	-10000	0	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-10000	0	-10000	0	0
HDAC4/SRF	-0.014	0.067	-10000	0	-0.34	9	9
HDAC4/ER alpha	-0.049	0.16	-10000	0	-0.42	39	39
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.027	0.063	-10000	0	-0.24	1	1
cell motility	-0.001	0.022	-10000	0	-0.34	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.015	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0.022	0	-10000	0	-10000	0	0
BCL6	0.015	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.015	0	-10000	0	-10000	0	0
Hsp90/HDAC6	0.022	0	-10000	0	-10000	0	0
ESR1	-0.081	0.22	-10000	0	-0.58	39	39
HDAC6/HDAC11	0.019	0.036	-10000	0	-0.37	2	2
Ran/GTP/Exportin 1	0.037	0	-10000	0	-10000	0	0
NPC	0.009	0	-10000	0	-10000	0	0
MEF2C	0.002	0.084	-10000	0	-0.58	5	5
RAN	0.015	0	-10000	0	-10000	0	0
HDAC4/MEF2C	0.037	0.046	-10000	0	-0.28	5	5
GNG2	0.012	0.038	-10000	0	-0.58	1	1
NCOR2	0.015	0	-10000	0	-10000	0	0
TUBB2A	0.012	0.038	-10000	0	-0.58	1	1
HDAC11	0.01	0.049	-10000	0	-0.52	2	2
HSP90AA1	0.015	0	-10000	0	-10000	0	0
RANBP2	0.015	0	-10000	0	-10000	0	0
ANKRA2	0.015	0	-10000	0	-10000	0	0
RFXANK	0.013	0.031	-10000	0	-0.47	1	1
nuclear import	-0.031	0.022	0.32	1	-10000	0	1

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.011	0.044	-10000	0	-0.47	2	2
Rac1/GDP	0.002	0.009	-10000	0	-10000	0	0
DOCK1	0.012	0.038	-10000	0	-0.58	1	1
ITGA4	-0.002	0.097	-10000	0	-0.56	7	7
RAC1	0.015	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.002	0.09	-10000	0	-0.41	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.01	0.056	-10000	0	-0.33	7	7
alpha4/beta7 Integrin/Paxillin	0.022	0.07	-10000	0	-0.31	10	10
lamellipodium assembly	0	0.02	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
PI3K	0.022	0	-10000	0	-10000	0	0
ARF6	0.015	0	-10000	0	-10000	0	0
TLN1	0.015	0	-10000	0	-10000	0	0
PXN	0.025	0	-10000	0	-10000	0	0
PIK3R1	0.015	0	-10000	0	-10000	0	0
ARF6/GTP	-0.007	0.041	-10000	0	-10000	0	0
cell adhesion	0.034	0.052	-10000	0	-10000	0	0
CRKL/CBL	0.019	0.032	-10000	0	-0.33	2	2
alpha4/beta1 Integrin/Paxillin	0.028	0.056	-10000	0	-0.31	6	6
ITGB1	0.015	0	-10000	0	-10000	0	0
ITGB7	0.005	0.076	-10000	0	-0.58	4	4
ARF6/GDP	0.002	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.024	0.093	-10000	0	-0.36	12	12
p130Cas/Crk/Dock1	-0.001	0.022	-10000	0	-0.34	1	1
VCAM1	-0.007	0.11	-10000	0	-0.58	9	9
alpha4/beta1 Integrin/Paxillin/Talin	0.036	0.053	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.036	0.053	-10000	0	-0.28	6	6
BCAR1	0.015	0	-10000	0	-10000	0	0
mol:GDP	-0.034	0.052	0.28	6	-10000	0	6
CBL	0.015	0	-10000	0	-10000	0	0
PRKACA	0.015	0	-10000	0	-10000	0	0
GIT1	0.015	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.036	0.053	-10000	0	-10000	0	0
Rac1/GTP	0	0.022	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.01	-9999	-10000	0	0
DAPP1	0.014	0.086	-9999	-0.37	3	3
Src family/SYK family/BLNK-LAT/BTK-ITK	0.009	0.14	-9999	-0.45	14	14
mol:DAG	0.032	0.081	-9999	-0.22	9	9
HRAS	0.016	0.001	-9999	-10000	0	0
RAP1A	0.015	0.001	-9999	-10000	0	0
ARF5/GDP	0.037	0.048	-9999	-10000	0	0
PLCG2	0.013	0.031	-9999	-0.47	1	1
PLCG1	0.015	0	-9999	-10000	0	0
ARF5	0.015	0	-9999	-10000	0	0
mol:GTP	-0.001	0.012	-9999	-10000	0	0
ARF1/GTP	-0.001	0.009	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
YES1	0.015	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.011	-9999	-10000	0	0
ADAP1	-0.005	0.035	-9999	-10000	0	0
ARAP3	-0.001	0.011	-9999	-10000	0	0
INPPL1	0.015	0	-9999	-10000	0	0
PREX1	0.015	0	-9999	-10000	0	0
ARHGEF6	0.01	0.054	-9999	-0.58	2	2
ARHGEF7	0.015	0	-9999	-10000	0	0
ARF1	0.015	0	-9999	-10000	0	0
NRAS	0.016	0.001	-9999	-10000	0	0
FYN	0.01	0.054	-9999	-0.58	2	2
ARF6	0.015	0	-9999	-10000	0	0
FGR	0.012	0.038	-9999	-0.58	1	1
mol:Ca2+	0.028	0.047	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.012	0.038	-9999	-0.58	1	1
ZAP70	-0.01	0.12	-9999	-0.58	10	10
mol:IP3	0.032	0.062	-9999	-0.21	1	1
LYN	0.015	0	-9999	-10000	0	0
ARF1/GDP	0.037	0.048	-9999	-10000	0	0
RhoA/GDP	-0.002	0.011	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	-0.002	0.099	-9999	-0.58	7	7
actin cytoskeleton reorganization	0.06	0.045	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
PLEKHA2	0.023	0.059	-9999	-0.34	6	6
RAC1	0.015	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.01	-9999	-10000	0	0
RhoA/GTP	-0.001	0.01	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	0.009	0.12	-9999	-0.42	9	9
BLK	-0.06	0.19	-9999	-0.55	31	31
PDPK1	0.015	0	-9999	-10000	0	0
CYTH1	-0.001	0.011	-9999	-10000	0	0
HCK	-0.009	0.11	-9999	-0.55	10	10
CYTH3	-0.001	0.011	-9999	-10000	0	0
CYTH2	-0.001	0.011	-9999	-10000	0	0
KRAS	0.014	0.031	-9999	-0.47	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0.034	0.084	-9999	-0.45	7	7
SGK1	-0.015	0.082	-9999	-0.49	7	7
INPP5D	0	0.092	-9999	-0.58	6	6
mol:GDP	0.03	0.051	-9999	-10000	0	0
SOS1	0.015	0	-9999	-10000	0	0
SYK	0.01	0.054	-9999	-0.58	2	2
ARF6/GDP	-0.002	0.011	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.012	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.001	0.012	-9999	-10000	0	0
VAV1	-0.019	0.14	-9999	-0.57	14	14
mol:PI-3-4-P2	0.014	0.069	-9999	-0.42	6	6
RAS family/GTP/PI3K Class I	0.034	0.014	-9999	-10000	0	0
PLEKHA1	0.023	0.059	-9999	-0.34	6	6
Rac1/GDP	0.037	0.048	-9999	-10000	0	0
LAT	0.013	0.031	-9999	-0.47	1	1
Rac1/GTP	0.031	0.061	-9999	-0.27	3	3
ITK	-0.028	0.08	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	0.033	0.1	-9999	-0.31	9	9
LCK	0.008	0.062	-9999	-0.54	3	3
BTK	-0.013	0.056	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.049	0.039	-10000	0	-0.38	1	1
adherens junction organization	0.037	0.066	-10000	0	-0.29	8	8
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.044	0.066	-10000	0	-0.36	2	2
FMN1	0.029	0.075	-10000	0	-0.58	1	1
mol:IP3	0.04	0.039	-10000	0	-0.39	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.031	0.064	-10000	0	-0.3	8	8
CTNNB1	0.015	0.002	-10000	0	-10000	0	0
AKT1	0.047	0.044	-10000	0	-0.42	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.033	0.086	-10000	0	-0.42	8	8
CTNND1	0.016	0.001	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.038	0.06	-10000	0	-0.57	1	1
VASP	0.038	0.062	-10000	0	-0.58	1	1
ZYX	0.037	0.064	-10000	0	-0.42	2	2
JUB	0.037	0.069	-10000	0	-0.52	2	2
EGFR(dimer)	0.026	0.086	-10000	0	-0.29	12	12
E-cadherin/beta catenin-gamma catenin	-0.012	0.068	-10000	0	-0.37	8	8
mol:PI-3-4-5-P3	-0.006	0.039	-10000	0	-0.45	1	1
PIK3CA	0.016	0.001	-10000	0	-10000	0	0
PI3K	0.039	0.047	-10000	0	-0.46	1	1
FYN	0.046	0.052	-10000	0	-0.3	3	3
mol:Ca2+	0.04	0.038	-10000	0	-0.38	1	1
JUP	0.012	0.038	-10000	0	-0.57	1	1
PIK3R1	0.016	0.001	-10000	0	-10000	0	0
mol:DAG	0.04	0.039	-10000	0	-0.39	1	1
CDH1	-0.005	0.11	-10000	0	-0.58	8	8
RhoA/GDP	0.044	0.066	-10000	0	-0.36	2	2
establishment of polarity of embryonic epithelium	0.038	0.06	-10000	0	-0.57	1	1
SRC	0.015	0	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
EGFR	-0.01	0.11	-10000	0	-0.52	11	11
CASR	0.04	0.049	-10000	0	-0.36	1	1
RhoA/GTP	-0.004	0.028	-10000	0	-0.34	1	1
AKT2	0.047	0.044	-10000	0	-0.42	1	1
actin cable formation	0.036	0.073	-10000	0	-0.56	1	1
apoptosis	-0.044	0.043	0.41	1	-10000	0	1
CTNNA1	0.016	0.001	-10000	0	-10000	0	0
mol:GDP	0.037	0.069	-10000	0	-0.4	2	2
PIP5K1A	0.038	0.062	-10000	0	-0.58	1	1
PLCG1	0.041	0.04	-10000	0	-0.4	1	1
Rac1/GTP	-0.017	0.067	-10000	0	-0.5	2	2
homophilic cell adhesion	0.001	0.001	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.015	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0.015	0	-9999	-10000	0	0
MAP2K3	0.039	0.02	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.044	0.034	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	0.002	0.084	-9999	-0.58	5	5
TXN	0.009	0.012	-9999	-0.17	1	1
CALM1	0.015	0	-9999	-10000	0	0
GADD45A	0.015	0	-9999	-10000	0	0
GADD45B	0	0.092	-9999	-0.58	6	6
MAP3K1	0.015	0	-9999	-10000	0	0
MAP3K6	0.015	0	-9999	-10000	0	0
MAP3K7	0.015	0	-9999	-10000	0	0
MAP3K4	0.015	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	0.022	0	-9999	-10000	0	0
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0.027	0.017	-9999	-0.24	1	1
TRAF2	0.015	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0.01	-9999	-10000	0	0
TRAF6	0.01	0	-9999	-10000	0	0
RAC1	0.015	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.04	0.15	-9999	-0.47	27	27
CCM2	0.013	0.031	-9999	-0.47	1	1
CaM/Ca2+/CAMKIIB	-0.031	0.087	-9999	-0.28	27	27
MAPK11	0.015	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.002	0.085	-9999	-0.24	27	27
OSM/MEKK3	0.02	0.022	-9999	-0.33	1	1
TAOK1	0.018	0.024	-9999	-0.35	1	1
TAOK2	0.019	0	-9999	-10000	0	0
TAOK3	0.019	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.015	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.015	0	-9999	-10000	0	0
MAP3K10	0.013	0.031	-9999	-0.47	1	1
MAP3K3	0.015	0	-9999	-10000	0	0
TRX/ASK1	0.017	0.01	-9999	-10000	0	0
GADD45/MTK1/MTK1	0.02	0.067	-9999	-0.29	11	11

×

Canonical NF-kappaB 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	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.018	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.088	0.024	-9999	-10000	0	0
ERC1	0.015	0	-9999	-10000	0	0
RIP2/NOD2	-0.01	0.1	-9999	-0.33	22	22
NFKBIA	0.051	0	-9999	-10000	0	0
BIRC2	0.011	0.044	-9999	-0.47	2	2
IKBKB	0.015	0	-9999	-10000	0	0
RIPK2	0.015	0	-9999	-10000	0	0
IKBKG	-0.006	0.02	-9999	-10000	0	0
IKK complex/A20	-0.012	0.044	-9999	-10000	0	0
NEMO/A20/RIP2	0.015	0	-9999	-10000	0	0
XPO1	0.015	0	-9999	-10000	0	0
NEMO/ATM	0.047	0.033	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.003	0.012	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.03	0.14	-9999	-0.48	22	22
NFKB1	0.018	0	-9999	-10000	0	0
RELA	0.018	0	-9999	-10000	0	0
MALT1	0.015	0	-9999	-10000	0	0
cIAP1/UbcH5C	0.019	0.032	-9999	-0.33	2	2
ATM	0.015	0	-9999	-10000	0	0
TNF/TNFR1A	0.004	0.076	-9999	-0.33	12	12
TRAF6	0.015	0	-9999	-10000	0	0
PRKCA	0.015	0	-9999	-10000	0	0
CHUK	0.015	0	-9999	-10000	0	0
UBE2D3	0.015	0	-9999	-10000	0	0
TNF	-0.01	0.11	-9999	-0.47	12	12
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.015	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.051	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.018	0	-9999	-10000	0	0
TNFRSF1A	0.015	0	-9999	-10000	0	0
IKK complex	0.054	0.032	-9999	-10000	0	0
CYLD	0.015	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.003	0.012	-9999	-10000	0	0

×

Circadian rhythm 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
chromatin modification	0.05	0.036	-9999	-10000	0	0
CLOCK	0.018	0.002	-9999	-10000	0	0
TIMELESS/CRY2	0.047	0.025	-9999	-10000	0	0
DEC1/BMAL1	0.01	0.044	-9999	-0.32	4	4
ATR	0.015	0	-9999	-10000	0	0
NR1D1	0.047	0.015	-9999	-10000	0	0
ARNTL	0.018	0.002	-9999	-10000	0	0
TIMELESS	0.046	0.028	-9999	-10000	0	0
NPAS2	0.016	0.038	-9999	-0.57	1	1
CRY2	0.015	0	-9999	-10000	0	0
mol:CO	-0.015	0.006	-9999	-10000	0	0
CHEK1	0.009	0.054	-9999	-0.47	3	3
mol:HEME	0.015	0.006	-9999	-10000	0	0
PER1	-0.007	0.11	-9999	-0.58	9	9
BMAL/CLOCK/NPAS2	0.047	0.025	-9999	-0.33	1	1
BMAL1/CLOCK	0.05	0.036	-9999	-10000	0	0
S phase of mitotic cell cycle	0.05	0.036	-9999	-10000	0	0
TIMELESS/CHEK1/ATR	0.05	0.036	-9999	-10000	0	0
mol:NADPH	0.015	0.006	-9999	-10000	0	0
PER1/TIMELESS	0.035	0.069	-9999	-10000	0	0
PER1-2 / CRY1-2	0	0	-9999	-10000	0	0
DEC1	-0.006	0.061	-9999	-0.47	4	4

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.13	0.084	-10000	0	-0.35	3	3
CaM/Ca2+	0.011	0	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
AKT2	0.015	0	-10000	0	-10000	0	0
STXBP4	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.13	0.11	0.21	1	-0.36	4	5
YWHAZ	0.015	0	-10000	0	-10000	0	0
CALM1	0.015	0	-10000	0	-10000	0	0
YWHAQ	0.015	0	-10000	0	-10000	0	0
TBC1D4	0.025	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.015	0	-10000	0	-10000	0	0
YWHAB	0.015	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.015	0	-10000	0	-10000	0	0
ASIP	0.003	0.054	-10000	0	-0.47	3	3
PRKCI	0.015	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.011	0	-10000	0	-10000	0	0
RHOQ	0.015	0	-10000	0	-10000	0	0
GYS1	0.035	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.038	-10000	0	-0.58	1	1
TRIP10	0.012	0.038	-10000	0	-0.58	1	1
TC10/GTP/CIP4/Exocyst	-0.001	0.023	-10000	0	-0.35	1	1
AS160/14-3-3	0.039	0.043	-10000	0	-0.3	1	1
VAMP2	0.015	0	-10000	0	-10000	0	0
SLC2A4	-0.14	0.12	-10000	0	-0.4	4	4
STX4	0.015	0	-10000	0	-10000	0	0
GSK3B	0.029	0	-10000	0	-10000	0	0
SFN	-0.039	0.15	-10000	0	-0.48	26	26
LNPEP	0.015	0	-10000	0	-10000	0	0
YWHAE	0.012	0.038	-10000	0	-0.58	1	1

×

ceramide 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
MAP4K4	0.037	0.074	-10000	0	-10000	0	0
BAG4	0.015	0	-10000	0	-10000	0	0
BAD	0.03	0.025	-10000	0	-10000	0	0
NFKBIA	0.015	0	-10000	0	-10000	0	0
BIRC3	-0.024	0.14	-10000	0	-0.56	16	16
BAX	0.03	0.025	-10000	0	-10000	0	0
EnzymeConsortium:3.1.4.12	0.013	0.019	-10000	0	-10000	0	0
IKBKB	0.044	0.071	-10000	0	-10000	0	0
MAP2K2	0.043	0.026	-10000	0	-10000	0	0
MAP2K1	0.043	0.026	-10000	0	-10000	0	0
SMPD1	0.019	0.019	-10000	0	-10000	0	0
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.041	0.079	-10000	0	-10000	0	0
MAP2K4	0.038	0.024	-10000	0	-10000	0	0
protein ubiquitination	0.045	0.072	-10000	0	-10000	0	0
EnzymeConsortium:2.7.1.37	0.049	0.025	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.038	0.027	-10000	0	-10000	0	0
CRADD	0.015	0	-10000	0	-10000	0	0
mol:ceramide	0.023	0.026	-10000	0	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-10000	0	-10000	0	0
MADD	0.015	0	-10000	0	-10000	0	0
MAP3K1	0.031	0.025	-10000	0	-10000	0	0
TRADD	0.015	0	-10000	0	-10000	0	0
RELA/p50	0.015	0	-10000	0	-10000	0	0
MAPK3	0.046	0.025	-10000	0	-10000	0	0
MAPK1	0.046	0.025	-10000	0	-10000	0	0
p50/RELA/I-kappa-B-alpha	0.022	0	-10000	0	-10000	0	0
FADD	0.033	0.081	-10000	0	-10000	0	0
KSR1	0.031	0.025	-10000	0	-10000	0	0
MAPK8	0.04	0.038	-10000	0	-0.23	3	3
TRAF2	0.015	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
CHUK	0.044	0.071	-10000	0	-10000	0	0
TNF R/SODD	0.022	0	-10000	0	-10000	0	0
TNF	-0.009	0.11	-10000	0	-0.47	12	12
CYCS	0.036	0.032	0.14	9	-10000	0	9
IKBKG	0.044	0.071	-10000	0	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.03	0.077	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
AIFM1	0.036	0.032	0.14	9	-10000	0	9
TNF/TNF R/SODD	-0.011	0.058	-10000	0	-0.26	12	12
TNFRSF1A	0.015	0	-10000	0	-10000	0	0
response to heat	0	0	-10000	0	-10000	0	0
CASP8	0.03	0.021	-10000	0	-10000	0	0
NSMAF	0.037	0.072	-10000	0	-10000	0	0
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
BCL2	-0.012	0.12	-10000	0	-0.58	11	11

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	0.007	0.023	-10000	0	-10000	0	0
oxygen homeostasis	0.011	0.016	-10000	0	-10000	0	0
TCEB2	0.013	0.031	-10000	0	-0.47	1	1
TCEB1	0.015	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	0	0.036	-10000	0	-10000	0	0
EPO	0.12	0.2	-10000	0	-0.77	1	1
FIH (dimer)	0.026	0.015	-10000	0	-10000	0	0
APEX1	0.025	0.016	-10000	0	-10000	0	0
SERPINE1	0.14	0.2	-10000	0	-0.62	4	4
FLT1	0.009	0.023	-10000	0	-10000	0	0
ADORA2A	0.14	0.18	-10000	0	-0.58	2	2
germ cell development	0.11	0.24	-10000	0	-0.64	2	2
SLC11A2	0.14	0.19	-10000	0	-0.58	2	2
BHLHE40	0.14	0.2	-10000	0	-0.7	3	3
HIF1AN	0.026	0.015	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.011	0.06	-10000	0	-10000	0	0
ETS1	0.032	0.002	-10000	0	-10000	0	0
CITED2	0.007	0.017	-10000	0	-10000	0	0
KDR	0.005	0.086	-10000	0	-1.3	1	1
PGK1	0.14	0.19	-10000	0	-0.58	2	2
SIRT1	0.015	0.002	-10000	0	-10000	0	0
response to hypoxia	-0.001	0.004	-10000	0	-10000	0	0
HIF2A/ARNT	0.16	0.21	-10000	0	-0.67	2	2
EPAS1	0.089	0.098	-10000	0	-0.29	1	1
SP1	0.023	0.003	-10000	0	-10000	0	0
ABCG2	0.14	0.21	-10000	0	-0.72	2	2
EFNA1	0.14	0.19	-10000	0	-0.58	2	2
FXN	0.14	0.18	-10000	0	-0.58	2	2
POU5F1	0.11	0.24	-10000	0	-0.67	2	2
neuron apoptosis	-0.16	0.2	0.66	2	-10000	0	2
EP300	0.015	0	-10000	0	-10000	0	0
EGLN3	0.013	0.086	-10000	0	-0.57	5	5
EGLN2	0.026	0.015	-10000	0	-10000	0	0
EGLN1	0.026	0.015	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.017	-10000	0	-0.27	1	1
VHL	0.015	0	-10000	0	-10000	0	0
ARNT	0.025	0.016	-10000	0	-10000	0	0
SLC2A1	0.14	0.18	-10000	0	-0.58	2	2
TWIST1	0.079	0.29	-10000	0	-0.63	17	17
ELK1	0.024	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.008	0.054	-10000	0	-10000	0	0
VEGFA	0.14	0.19	-10000	0	-0.58	2	2
CREBBP	0.015	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.029	0.057	-9999	-10000	0	0
PLK1	-0.048	0.2	-9999	-0.55	5	5
CDKN1B	0.075	0.097	-9999	-10000	0	0
FOXO3	-0.01	0.17	-9999	-0.47	5	5
KAT2B	0.013	0.017	-9999	-10000	0	0
FOXO1/SIRT1	0.024	0.038	-9999	-10000	0	0
CAT	0	0.16	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
AKT1	0.016	0.017	-9999	-10000	0	0
FOXO1	0.035	0.035	-9999	-10000	0	0
MAPK10	0.008	0.098	-9999	-0.29	23	23
mol:GTP	0.002	0	-9999	-10000	0	0
FOXO4	0.087	0.069	-9999	-10000	0	0
response to oxidative stress	-0.001	0.022	-9999	-10000	0	0
FOXO3A/SIRT1	-0.05	0.11	-9999	-0.42	2	2
XPO1	0.016	0	-9999	-10000	0	0
EP300	0.016	0.004	-9999	-10000	0	0
BCL2L11	0.022	0.033	-9999	-10000	0	0
FOXO1/SKP2	0.033	0.048	-9999	-10000	0	0
mol:GDP	-0.001	0.022	-9999	-10000	0	0
RAN	0.017	0	-9999	-10000	0	0
GADD45A	0.067	0.086	-9999	-10000	0	0
YWHAQ	0.015	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.073	0.035	-9999	-10000	0	0
MST1	-0.001	0.087	-9999	-0.49	7	7
CSNK1D	0.015	0	-9999	-10000	0	0
CSNK1E	0.015	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.052	0.046	-9999	-0.33	1	1
YWHAB	0.015	0	-9999	-10000	0	0
MAPK8	0.036	0.037	-9999	-0.29	3	3
MAPK9	0.039	0.009	-9999	-10000	0	0
YWHAG	0.015	0	-9999	-10000	0	0
YWHAE	0.012	0.038	-9999	-0.58	1	1
YWHAZ	0.015	0	-9999	-10000	0	0
SIRT1	0.013	0.017	-9999	-10000	0	0
SOD2	0.079	0.11	-9999	-10000	0	0
RBL2	0.033	0.12	-9999	-10000	0	0
RAL/GDP	0.024	0.018	-9999	-10000	0	0
CHUK	0.014	0.017	-9999	-10000	0	0
Ran/GTP	0.016	0	-9999	-10000	0	0
CSNK1G2	0.015	0	-9999	-10000	0	0
RAL/GTP	0.034	0.015	-9999	-10000	0	0
CSNK1G1	0.015	0	-9999	-10000	0	0
FASLG	-0.071	0.36	-9999	-1.4	15	15
SKP2	0.005	0.069	-9999	-0.47	5	5
USP7	0.017	0	-9999	-10000	0	0
IKBKB	0.014	0.017	-9999	-10000	0	0
CCNB1	-0.046	0.2	-9999	-0.55	4	4
FOXO1-3a-4/beta catenin	0.095	0.11	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.033	0.047	-9999	-10000	0	0
CSNK1A1	0.015	0	-9999	-10000	0	0
SGK1	-0.004	0.1	-9999	-0.58	7	7
CSNK1G3	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.028	0.001	-9999	-10000	0	0
ZFAND5	0.09	0.061	-9999	-10000	0	0
SFN	-0.039	0.15	-9999	-0.48	26	26
CDK2	0.015	0.007	-9999	-10000	0	0
FOXO3A/14-3-3	0.041	0.061	-9999	-0.36	1	1
CREBBP	0.015	0.007	-9999	-10000	0	0
FBXO32	0	0.16	-9999	-10000	0	0
BCL6	0.033	0.12	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
YWHAH	0.015	0	-9999	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	-0.019	0.13	-9999	-0.43	22	22
AKT1	0.094	0.045	-9999	-0.52	1	1
PTK2B	0.03	0.11	-9999	-0.59	3	3
VEGFR2 homodimer/Frs2	0.033	0.061	-9999	-0.71	1	1
CAV1	-0.01	0.12	-9999	-0.58	10	10
CALM1	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.043	0.057	-9999	-0.65	1	1
endothelial cell proliferation	0.052	0.1	-9999	-0.59	1	1
mol:Ca2+	0.059	0.046	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.055	0.044	-9999	-0.61	1	1
RP11-342D11.1	0.049	0.046	-9999	-0.59	1	1
CDH5	0.012	0.038	-9999	-0.58	1	1
VEGFA homodimer	0.038	0.017	-9999	-10000	0	0
SHC1	0.013	0.031	-9999	-0.47	1	1
SHC2	-0.019	0.14	-9999	-0.57	14	14
HRAS/GDP	-0.003	0.035	-9999	-0.5	1	1
SH2D2A	0.009	0.054	-9999	-0.47	3	3
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.003	0.032	-9999	-0.48	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.044	0.055	-9999	-0.65	1	1
VEGFR1 homodimer	0.015	0	-9999	-10000	0	0
SHC/GRB2/SOS1	-0.004	0.039	-9999	-0.55	1	1
GRB10	0.058	0.059	-9999	-0.59	2	2
PTPN11	0.015	0	-9999	-10000	0	0
GRB2	0.015	0	-9999	-10000	0	0
PAK1	0.012	0.038	-9999	-0.58	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.004	0.056	-9999	-0.86	1	1
HRAS	0.015	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	0.033	0.083	-9999	-0.43	3	3
HIF1A	0.013	0.031	-9999	-0.47	1	1
FRS2	0.007	0.062	-9999	-0.47	4	4
oxygen and reactive oxygen species metabolic process	-0.003	0.039	-9999	-0.6	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.015	0	-9999	-10000	0	0
Nck/Pak	0.02	0.028	-9999	-0.42	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.045	0.056	-9999	-0.65	1	1
mol:GDP	-0.004	0.038	-9999	-0.53	1	1
mol:NADP	0.084	0.036	-9999	-0.41	1	1
eNOS/Hsp90	0.087	0.034	-9999	-0.38	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
mol:IP3	0.06	0.046	-9999	-0.59	1	1
HIF1A/ARNT	0.02	0.022	-9999	-0.33	1	1
SHB	0.015	0	-9999	-10000	0	0
VEGFA	0.017	0.005	-9999	-10000	0	0
VEGFC	0.01	0.054	-9999	-0.58	2	2
FAK1/Vinculin	0.054	0.098	-9999	-0.61	2	2
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.024	0.12	-9999	-0.63	3	3
PTPN6	0.015	0	-9999	-10000	0	0
EPAS1	0.024	0.024	-9999	-0.34	1	1
mol:L-citrulline	0.084	0.036	-9999	-0.41	1	1
ITGAV	0.012	0.038	-9999	-0.58	1	1
PIK3CA	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.051	0.055	-9999	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer	0.053	0.05	-9999	-0.64	1	1
VEGFR2/3 heterodimer	0.038	0.048	-9999	-0.71	1	1
VEGFB	0.015	0	-9999	-10000	0	0
MAPK11	0.063	0.048	-9999	-0.61	1	1
VEGFR2 homodimer	0.037	0.055	-9999	-0.8	1	1
FLT1	0.015	0	-9999	-10000	0	0
NEDD4	0.017	0.005	-9999	-10000	0	0
MAPK3	0.029	0.076	-9999	-0.49	2	2
MAPK1	0.029	0.076	-9999	-0.49	2	2
VEGFA145/NRP2	0.004	0.092	-9999	-0.42	11	11
VEGFR1/2 heterodimer	0.038	0.048	-9999	-0.71	1	1
KDR	0.037	0.055	-9999	-0.8	1	1
VEGFA165/NRP1/VEGFR2 homodimer	0.044	0.083	-9999	-0.56	2	2
SRC	0.015	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.033	0.073	-9999	-0.65	1	1
PI3K	0.083	0.049	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.048	0.046	-9999	-0.65	1	1
FES	0.059	0.051	-9999	-0.6	1	1
GAB1	-0.003	0.041	-9999	-0.61	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	0.048	0.046	-9999	-0.65	1	1
CTNNB1	0.015	0	-9999	-10000	0	0
SOS1	0.015	0	-9999	-10000	0	0
ARNT	0.015	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.076	0.063	-9999	-0.38	1	1
VEGFR2 homodimer/VEGFA homodimer/Yes	0.048	0.046	-9999	-0.65	1	1
PI3K/GAB1	0.096	0.046	-9999	-0.53	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.007	0.047	-9999	-0.58	1	1
PRKACA	0.015	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.041	0.055	-9999	-0.65	1	1
HSP90AA1	0.015	0	-9999	-10000	0	0
CDC42	0.06	0.047	-9999	-0.6	1	1
actin cytoskeleton reorganization	0.044	0.054	-9999	-0.64	1	1
PTK2	0.049	0.1	-9999	-0.67	2	2
EDG1	0.049	0.046	-9999	-0.59	1	1
mol:DAG	0.06	0.046	-9999	-0.59	1	1
CaM/Ca2+	-0.003	0.037	-9999	-0.54	1	1
MAP2K3	0.064	0.05	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.059	0.061	-9999	-0.61	2	2
PLCG1	0.06	0.047	-9999	-0.6	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.055	0.044	-9999	-0.61	1	1
IQGAP1	0.015	0	-9999	-10000	0	0
YES1	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.048	0.046	-9999	-0.65	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.048	0.046	-9999	-0.65	1	1
cell migration	0.078	0.089	-9999	-0.74	1	1
mol:PI-3-4-5-P3	0.081	0.046	-9999	-0.54	1	1
FYN	0.01	0.054	-9999	-0.58	2	2
VEGFB/NRP1	0.056	0.044	-9999	-0.56	1	1
mol:NO	0.084	0.036	-9999	-0.41	1	1
PXN	0.015	0	-9999	-10000	0	0
HRAS/GTP	-0.003	0.035	-9999	-0.5	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.059	0.061	-9999	-0.6	2	2
VHL	0.015	0	-9999	-10000	0	0
ITGB3	-0.039	0.17	-9999	-0.58	22	22
NOS3	0.086	0.039	-9999	-0.46	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	0.028	0.091	-9999	-0.65	1	1
RAC1	0.015	0	-9999	-10000	0	0
PRKCA	0.066	0.044	-9999	-0.55	1	1
PRKCB	-0.024	0.15	-9999	-0.68	2	2
VCL	0.012	0.038	-9999	-0.58	1	1
VEGFA165/NRP1	0.05	0.046	-9999	-0.59	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	0.048	0.046	-9999	-0.65	1	1
VEGFA165/NRP2	0.004	0.092	-9999	-0.42	11	11
MAPKKK cascade	0.08	0.054	-9999	-0.49	2	2
NRP2	-0.012	0.12	-9999	-0.58	11	11
VEGFC homodimer	0.01	0.054	-9999	-0.58	2	2
NCK1	0.015	0	-9999	-10000	0	0
ROCK1	0.015	0	-9999	-10000	0	0
FAK1/Paxillin	0.055	0.097	-9999	-0.61	2	2
MAP3K13	0.058	0.052	-9999	-0.6	1	1
PDPK1	0.086	0.042	-9999	-0.48	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.015	0	-9999	-10000	0	0
SMAD2	0.015	0	-9999	-10000	0	0
SMAD3	0.046	0	-9999	-10000	0	0
SMAD3/SMAD4	0.052	0.005	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0.042	0.021	-9999	-10000	0	0
PPM1A	0.015	0	-9999	-10000	0	0
CALM1	0.015	0	-9999	-10000	0	0
SMAD2/SMAD4	0.023	0	-9999	-10000	0	0
MAP3K1	0.015	0	-9999	-10000	0	0
TRAP-1/SMAD4	0.015	0.056	-9999	-0.42	4	4
MAPK3	0.015	0	-9999	-10000	0	0
MAPK1	0.015	0	-9999	-10000	0	0
NUP214	0.015	0	-9999	-10000	0	0
CTDSP1	0.015	0	-9999	-10000	0	0
CTDSP2	0.015	0	-9999	-10000	0	0
CTDSPL	0.015	0	-9999	-10000	0	0
KPNB1	0.015	0	-9999	-10000	0	0
TGFBRAP1	0.005	0.076	-9999	-0.58	4	4
UBE2I	0.015	0	-9999	-10000	0	0
NUP153	0.015	0	-9999	-10000	0	0
KPNA2	0.011	0.044	-9999	-0.47	2	2
PIAS4	0.015	0	-9999	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.048	0.005	-10000	0	-10000	0	0
regulation of axonogenesis	-0.033	0.003	-10000	0	-10000	0	0
myoblast fusion	-0.022	0.013	-10000	0	-10000	0	0
mol:GTP	0	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.037	0.03	0.32	1	-10000	0	1
ARF1/GTP	0	0.001	-10000	0	-10000	0	0
mol:GM1	0.012	0.004	-10000	0	-10000	0	0
mol:Choline	0.032	0.003	-10000	0	-10000	0	0
lamellipodium assembly	0	0.014	-10000	0	-10000	0	0
MAPK3	0.033	0.003	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.038	0.03	-10000	0	-0.33	1	1
ARF1	0.015	0	-10000	0	-10000	0	0
ARF6/GDP	0.022	0.013	-10000	0	-10000	0	0
ARF1/GDP	0.03	0.012	-10000	0	-10000	0	0
ARF6	0.014	0.002	-10000	0	-10000	0	0
RAB11A	0.015	0	-10000	0	-10000	0	0
TIAM1	0.014	0.038	-10000	0	-0.58	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.033	0.003	-10000	0	-10000	0	0
actin filament bundle formation	-0.029	0.012	-10000	0	-10000	0	0
KALRN	-0.003	0.032	-10000	0	-0.32	2	2
RAB11FIP3/RAB11A	0.022	0	-10000	0	-10000	0	0
RhoA/GDP	0.029	0.012	-10000	0	-10000	0	0
NME1	0.015	0.031	-10000	0	-0.47	1	1
Rac1/GDP	0.029	0.012	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0	0.003	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	0	0.014	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
liver development	0	0.003	-10000	0	-10000	0	0
ARF6/GTP	0	0.003	-10000	0	-10000	0	0
RhoA/GTP	0	0.001	-10000	0	-10000	0	0
mol:GDP	0	0.013	-10000	0	-10000	0	0
ARF6/GTP/RAB11FIP3/RAB11A	0	0.001	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
PLD1	0.024	0.004	-10000	0	-10000	0	0
RAB11FIP3	0.015	0	-10000	0	-10000	0	0
tube morphogenesis	0	0.014	-10000	0	-10000	0	0
ruffle organization	0.033	0.003	-10000	0	-10000	0	0
regulation of epithelial cell migration	0	0.003	-10000	0	-10000	0	0
PLD2	0.024	0.004	-10000	0	-10000	0	0
PIP5K1A	0.033	0.003	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.032	0.003	-10000	0	-10000	0	0
Rac1/GTP	0	0.014	-10000	0	-10000	0	0

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.015	0	-10000	0	-10000	0	0
mol:PIP3	-0.006	0.041	-10000	0	-0.29	5	5
FRAP1	0.016	0.008	-10000	0	-10000	0	0
AKT1	0.026	0.037	-10000	0	-0.23	5	5
INSR	0.015	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.004	0.024	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.006	-10000	0	-10000	0	0
TSC2	0.015	0	-10000	0	-10000	0	0
RHEB/GDP	-0.003	0.02	-10000	0	-10000	0	0
TSC1	0.015	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.011	0.053	-10000	0	-0.35	5	5
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.007	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.015	0	-10000	0	-10000	0	0
RPS6KB1	0.029	0.02	-10000	0	-10000	0	0
MAP3K5	0.012	0	-10000	0	-10000	0	0
PIK3R1	0.015	0	-10000	0	-10000	0	0
apoptosis	0.012	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.001	5	5
EIF4B	0.034	0.018	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.002	0.011	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.021	0.049	-10000	0	-0.31	5	5
mTOR/RHEB/GTP/Raptor/GBL	0.033	0.013	-10000	0	-10000	0	0
FKBP1A	0.015	0	-10000	0	-10000	0	0
RHEB/GTP	-0.003	0.02	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.001	5	5
FKBP12/Rapamycin	0.011	0.002	-10000	0	-10000	0	0
PDPK1	-0.005	0.037	-10000	0	-0.26	5	5
EIF4E	0.015	0	-10000	0	-10000	0	0
ASK1/PP5C	0.024	0.005	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.019	0	-10000	0	-10000	0	0
TSC1/TSC2	0.04	0.032	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.001	5	-10000	0	5
RPS6	0.015	0	-10000	0	-10000	0	0
PPP5C	0.015	0	-10000	0	-10000	0	0
EIF4G1	0.015	0	-10000	0	-10000	0	0
IRS1	0.002	0.056	-10000	0	-0.38	5	5
INS	0	0	-10000	0	-10000	0	0
PTEN	0.014	0	-10000	0	-10000	0	0
PDK2	-0.005	0.037	-10000	0	-0.26	5	5
EIF4EBP1	0.013	0.008	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
PPP2R5D	0.023	0.007	-10000	0	-10000	0	0
peptide biosynthetic process	0.019	0	-10000	0	-10000	0	0
RHEB	0.015	0	-10000	0	-10000	0	0
EIF4A1	0.015	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.019	0	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.02	0.007	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.008	0.033	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.046	0.031	-9999	-10000	0	0
SUMO1	0.015	0	-9999	-10000	0	0
ZFPM1	0.015	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.024	0	-9999	-10000	0	0
FKBP3	0.015	0	-9999	-10000	0	0
Histones	0.045	0.025	-9999	-10000	0	0
YY1/LSF	0.035	0	-9999	-10000	0	0
SMG5	0.015	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	0.03	0.036	-9999	-10000	0	0
I kappa B alpha/HDAC1	0.03	0.028	-9999	-10000	0	0
SAP18	0.015	0	-9999	-10000	0	0
RELA	0.036	0.03	-9999	-10000	0	0
HDAC1/Smad7	-0.001	0.022	-9999	-0.34	1	1
RANGAP1	0.015	0	-9999	-10000	0	0
HDAC3/TR2	0.03	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0.053	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.04	0.027	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.01	0.11	-9999	-0.52	11	11
GATA1	0.01	0.007	-9999	-10000	0	0
Mad/Max	0.02	0.022	-9999	-0.33	1	1
NuRD/MBD3 Complex/GATA1/Fog1	0.064	0.003	-9999	-10000	0	0
RBBP7	0.015	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
RBBP4	0.015	0	-9999	-10000	0	0
MAX	0.015	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.015	0	-9999	-10000	0	0
NFKBIA	0.025	0.031	-9999	-10000	0	0
KAT2B	0.015	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	0.049	0	-9999	-10000	0	0
SIN3 complex	0.038	0	-9999	-10000	0	0
SMURF1	0.015	0	-9999	-10000	0	0
CHD3	0.015	0	-9999	-10000	0	0
SAP30	0.015	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.015	0	-9999	-10000	0	0
YY1/HDAC3	0.043	0.026	-9999	-10000	0	0
YY1/HDAC2	0.035	0	-9999	-10000	0	0
YY1/HDAC1	0.035	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.053	0	-9999	-10000	0	0
PPARG	0.007	0.1	-9999	-0.32	20	20
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.015	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
TNFRSF1A	0.015	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.03	0.028	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.022	-9999	-0.34	1	1
CREBBP	0.015	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.057	0	-9999	-10000	0	0
HDAC1	0.015	0	-9999	-10000	0	0
HDAC3	0.025	0.031	-9999	-10000	0	0
HDAC2	0.015	0	-9999	-10000	0	0
YY1	0.034	0	-9999	-10000	0	0
HDAC8	0.015	0	-9999	-10000	0	0
SMAD7	0.012	0.038	-9999	-0.58	1	1
NCOR2	0.015	0	-9999	-10000	0	0
MXD1	0.013	0.031	-9999	-0.47	1	1
STAT3	0.029	0	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.015	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0.042	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	0.042	0	-9999	-10000	0	0
EP300	0.015	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.029	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.025	0.031	-9999	-10000	0	0
histone deacetylation	0.053	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.04	0.026	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.015	0	-9999	-10000	0	0
GATAD2B	0.015	0	-9999	-10000	0	0
GATAD2A	0.015	0	-9999	-10000	0	0
GATA2/HDAC3	0.017	0.068	-9999	-0.3	5	5
GATA1/HDAC1	0.018	0.005	-9999	-10000	0	0
GATA1/HDAC3	0.019	0.031	-9999	-10000	0	0
CHD4	0.015	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	0.004	0.076	-9999	-0.33	12	12
SIN3/HDAC complex/Mad/Max	0.053	0.006	-9999	-10000	0	0
NuRD Complex	0.062	0	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.015	-9999	-10000	0	0
SIN3B	0.015	0	-9999	-10000	0	0
MTA2	0.015	0	-9999	-10000	0	0
SIN3A	0.015	0	-9999	-10000	0	0
XPO1	0.015	0	-9999	-10000	0	0
SUMO1/HDAC1	0.034	0	-9999	-10000	0	0
HDAC complex	0.038	0	-9999	-10000	0	0
GATA1/Fog1	0.018	0.005	-9999	-10000	0	0
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	-0.01	0.11	-9999	-0.47	12	12
negative regulation of cell growth	0.053	0.005	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.053	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	0.04	0.033	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.051	0	-9999	-10000	0	0
TFCP2	0.015	0	-9999	-10000	0	0
NR2C1	0.015	0	-9999	-10000	0	0
MBD3	0.015	0	-9999	-10000	0	0
MBD2	0.015	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.02	0.028	-9999	-0.42	1	1
FBXW11	0.015	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.027	0.031	-9999	-0.31	2	2
NF kappa B1 p50/RelA/I kappa B alpha	0.05	0.028	-9999	-10000	0	0
NFKBIA	0.028	0.032	-9999	-0.21	4	4
MAPK14	0.015	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0.03	0	-9999	-10000	0	0
ARRB2	0.019	0	-9999	-10000	0	0
REL	0.01	0.049	-9999	-0.52	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.028	0.024	-9999	-0.34	1	1
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.03	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.023	0	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
NFKB1	0.025	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.036	0.032	-9999	-0.21	2	2
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.053	0.028	-9999	-10000	0	0
SRC	0.015	0	-9999	-10000	0	0
PI3K	0.022	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.036	0.032	-9999	-0.21	2	2
IKBKB	0.015	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
SYK	0.01	0.054	-9999	-0.58	2	2
I kappa B alpha/PIK3R1	0.035	0.03	-9999	-10000	0	0
cell death	0.051	0.027	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	0.027	0.031	-9999	-0.31	2	2
LCK	0.008	0.062	-9999	-0.54	3	3
BCL3	0.012	0.038	-9999	-0.58	1	1

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
MDM2/SUMO1	0.027	0.041	-9999	-0.21	7	7
HDAC4	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
SUMO1	0.015	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.019	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.032	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.015	0	-9999	-10000	0	0
SUMO1/HDAC4	0.034	0	-9999	-10000	0	0
SUMO1/HDAC1	0.034	0	-9999	-10000	0	0
RANGAP1	0.015	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	0.03	0.045	-9999	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.024	0	-9999	-10000	0	0
Ran/GTP	0.03	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.001	0.082	-9999	-0.47	7	7
UBE2I	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.037	0	-9999	-10000	0	0
NPC	0.009	0	-9999	-10000	0	0
PIAS2	0.015	0	-9999	-10000	0	0
PIAS1	0.015	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.035	0.019	-9999	-10000	0	0
VEGFR1 homodimer/NRP1	0.024	0.018	-9999	-10000	0	0
mol:DAG	0.036	0.045	-9999	-10000	0	0
VEGFR1 homodimer/NRP1/VEGFR 121	0.032	0.017	-9999	-10000	0	0
CaM/Ca2+	0.042	0.042	-9999	-10000	0	0
HIF1A	0.022	0.031	-9999	-0.46	1	1
GAB1	0.015	0	-9999	-10000	0	0
AKT1	0.059	0.035	-9999	-10000	0	0
PLCG1	0.037	0.045	-9999	-10000	0	0
NOS3	0.065	0.034	-9999	-10000	0	0
CBL	0.015	0	-9999	-10000	0	0
mol:NO	0.064	0.034	-9999	-10000	0	0
FLT1	0.033	0.022	-9999	-10000	0	0
PGF	0.003	0.076	-9999	-0.47	6	6
VEGFR1 homodimer/NRP2/VEGFR121	0.027	0.073	-9999	-10000	0	0
CALM1	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
eNOS/Hsp90	0.07	0.033	-9999	-10000	0	0
endothelial cell proliferation	-0.019	0.12	-9999	-0.37	2	2
mol:Ca2+	0.036	0.045	-9999	-10000	0	0
MAPK3	0.049	0.04	-9999	-10000	0	0
MAPK1	0.049	0.04	-9999	-10000	0	0
PIK3R1	0.015	0	-9999	-10000	0	0
PLGF homodimer	0.003	0.076	-9999	-0.47	6	6
PRKACA	0.015	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.01	0.12	-9999	-0.58	10	10
VEGFA homodimer	0.015	0	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.035	0.019	-9999	-10000	0	0
platelet activating factor biosynthetic process	0.056	0.038	-9999	-10000	0	0
PI3K	0.043	0.042	-9999	-10000	0	0
PRKCA	0.043	0.042	-9999	-10000	0	0
PRKCB	-0.05	0.15	-9999	-0.51	2	2
VEGFR1 homodimer/PLGF homodimer	0.028	0.05	-9999	-10000	0	0
VEGFA	0.015	0	-9999	-10000	0	0
VEGFB	0.015	0	-9999	-10000	0	0
mol:IP3	0.036	0.045	-9999	-10000	0	0
RASA1	0.043	0.017	-9999	-10000	0	0
NRP2	-0.012	0.12	-9999	-0.58	11	11
VEGFR1 homodimer	0.033	0.022	-9999	-10000	0	0
VEGFB homodimer	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.058	0.069	-9999	-0.4	1	1
PTPN11	0.015	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.006	0.034	-9999	-10000	0	0
mol:L-citrulline	0.064	0.034	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.05	0.016	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.042	0.017	-9999	-10000	0	0
CD2AP	0.015	0	-9999	-10000	0	0
PI3K/GAB1	-0.005	0.031	-9999	-10000	0	0
PDPK1	0.049	0.04	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.042	0.017	-9999	-10000	0	0
mol:NADP	0.064	0.034	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.001	0.012	-9999	-10000	0	0
VEGFR1 homodimer/NRP2	0.018	0.08	-9999	-0.34	11	11

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	0	0	-9999	-10000	0	0
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.023	0	-9999	-10000	0	0
AP2	0.022	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.015	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.029	0	-9999	-10000	0	0
CD4	0.01	0.054	-9999	-0.58	2	2
CLTA	0.015	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.03	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.015	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	0	0	-9999	-10000	0	0
AP2M1	0.015	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.019	0	-9999	-10000	0	0
Rac/GTP	0.012	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.028	0	-9999	-10000	0	0
ARFIP2	0.013	0	-9999	-10000	0	0
COPA	0.015	0	-9999	-10000	0	0
RAC1	0.015	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.029	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.015	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.015	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.031	0	-9999	-10000	0	0
ARF1/GDP/Membrin	0.021	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.015	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0.011	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.038	0.022	-9999	-0.21	2	2
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.013	0	-9999	-10000	0	0
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.013	0	-9999	-10000	0	0
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.003	0.031	-9999	-0.34	2	2

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
IKK alpha homodimer	0.022	-9999	-9999
FBXW11	0.015	-9999	-9999
proteasomal ubiquitin-dependent protein catabolic process	0	-9999	-9999
beta TrCP1/SCF ubiquitin ligase complex	0.015	-9999	-9999
CHUK	0.015	-9999	-9999
NF kappa B2 p100/RelB	0.044	-9999	-9999
NFKB1	0.015	-9999	-9999
MAP3K14	0.015	-9999	-9999
NF kappa B1 p50/RelB	0.022	-9999	-9999
RELB	0.015	-9999	-9999
NFKB2	0.015	-9999	-9999
NF kappa B2 p52/RelB	0	-9999	-9999
regulation of B cell activation	0	-9999	-9999

pid_entity	TCGA.UY.A78O	TCGA.UY.A78N	TCGA.UY.A78L	TCGA.UY.A78K
109_MAP3K5	0.061	0.061	0.061	0.061
47_PPARGC1A	-0.58	-0.58	0.015	-0.58
105_BMP4	0.015	0.015	0.015	0.015
105_BMP6	0.015	0.015	0.015	0.015
105_BMP7	0.015	0.015	0.015	-0.58
105_BMP2	0.015	-0.58	-0.58	-0.58
131_RELN/VLDLR	-0.31	-0.31	0.038	0.038
30_TGFB1/TGF beta receptor Type II	0.017	0.014	0.014	0.014
84_STAT5B	0.048	0.015	0.017	-0.016
84_STAT5A	0.048	0.015	0.017	-0.016