PARADIGM pathway analysis of mRNASeq expression and copy number data - Uterine Corpus Endometrioid Carcinoma (Primary solid tumor)

Pathway.Name	Avg.Num.Perturbations
FOXM1 transcription factor network	222
Aurora B signaling	197
Endothelins	116
Aurora C signaling	111
PLK1 signaling events	109
Angiopoietin receptor Tie2-mediated signaling	103
Signaling events regulated by Ret tyrosine kinase	100
p75(NTR)-mediated signaling	90
Integrins in angiogenesis	82
PDGFR-alpha signaling pathway	80

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	0.4327	222	11348	51	-0.027	0.69	1000	-1000	-0.062	-1000
Aurora B signaling	0.3840	197	13251	67	-0.2	0.41	1000	-1000	-0.026	-1000
Endothelins	0.2261	116	11215	96	-0.43	0.17	1000	-1000	-0.037	-1000
Aurora C signaling	0.2164	111	779	7	0	0.26	1000	-1000	-0.007	-1000
PLK1 signaling events	0.2125	109	9327	85	-0.085	0.29	1000	-1000	-0.021	-1000
Angiopoietin receptor Tie2-mediated signaling	0.2008	103	9106	88	-0.31	0.12	1000	-1000	-0.052	-1000
Signaling events regulated by Ret tyrosine kinase	0.1949	100	8246	82	-0.13	0.023	1000	-1000	-0.041	-1000
p75(NTR)-mediated signaling	0.1754	90	11338	125	-0.15	0.077	1000	-1000	-0.041	-1000
Integrins in angiogenesis	0.1598	82	6917	84	-0.27	0.12	1000	-1000	-0.034	-1000
PDGFR-alpha signaling pathway	0.1559	80	3549	44	-0.29	0.038	1000	-1000	-0.021	-1000
Reelin signaling pathway	0.1481	76	4262	56	-0.12	0.045	1000	-1000	-0.016	-1000
Signaling events mediated by the Hedgehog family	0.1365	70	3641	52	-0.18	0.13	1000	-1000	-0.016	-1000
Syndecan-1-mediated signaling events	0.1326	68	2327	34	-0.037	0.15	1000	-1000	-0.019	-1000
Fc-epsilon receptor I signaling in mast cells	0.1326	68	6656	97	-0.1	0.023	1000	-1000	-0.034	-1000
Cellular roles of Anthrax toxin	0.1248	64	2499	39	-0.082	0.049	1000	-1000	-0.016	-1000
S1P3 pathway	0.1248	64	2714	42	-0.42	0.031	1000	-1000	-0.02	-1000
Nongenotropic Androgen signaling	0.1189	61	3182	52	-0.26	0.16	1000	-1000	-0.019	-1000
HIF-1-alpha transcription factor network	0.1111	57	4339	76	-0.2	0.079	1000	-1000	-0.024	-1000
Aurora A signaling	0.1111	57	3450	60	-0.13	0.26	1000	-1000	-0.017	-1000
Effects of Botulinum toxin	0.1111	57	1482	26	-0.1	0.14	1000	-1000	-0.012	-1000
Signaling mediated by p38-alpha and p38-beta	0.1072	55	2435	44	-0.09	0.022	1000	-1000	-0.014	-1000
TCGA08_retinoblastoma	0.1072	55	444	8	-0.051	0.15	1000	-1000	-0.008	-1000
Glypican 1 network	0.1053	54	2605	48	-0.17	0.14	1000	-1000	-0.022	-1000
IGF1 pathway	0.1053	54	3125	57	-0.075	0.04	1000	-1000	-0.02	-1000
LPA4-mediated signaling events	0.0975	50	605	12	-0.1	0	1000	-1000	-0.016	-1000
FOXA2 and FOXA3 transcription factor networks	0.0936	48	2223	46	-0.18	0.2	1000	-1000	-0.047	-1000
Thromboxane A2 receptor signaling	0.0916	47	4995	105	-0.14	0.055	1000	-1000	-0.032	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0916	47	3207	68	-0.15	0.079	1000	-1000	-0.05	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0916	47	5648	120	-0.14	0.12	1000	-1000	-0.03	-1000
Wnt signaling	0.0838	43	306	7	-0.033	0.042	1000	-1000	-0.002	-1000
Glucocorticoid receptor regulatory network	0.0819	42	4893	114	-0.2	0.25	1000	-1000	-0.039	-1000
S1P4 pathway	0.0819	42	1061	25	-0.056	0.038	1000	-1000	-0.008	-1000
Ephrin A reverse signaling	0.0799	41	287	7	-0.031	0.014	1000	-1000	-0.009	-1000
Noncanonical Wnt signaling pathway	0.0799	41	1079	26	-0.1	0.042	1000	-1000	-0.024	-1000
Ephrin B reverse signaling	0.0799	41	1993	48	-0.075	0.027	1000	-1000	-0.028	-1000
BMP receptor signaling	0.0780	40	3240	81	-0.22	0.057	1000	-1000	-0.015	-1000
amb2 Integrin signaling	0.0780	40	3331	82	-0.1	0.15	1000	-1000	-0.015	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0760	39	1350	34	-0.022	0.028	1000	-1000	-0.026	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0760	39	3076	78	-0.13	0.056	1000	-1000	-0.031	-1000
Osteopontin-mediated events	0.0741	38	1447	38	-0.09	0.099	1000	-1000	-0.015	-1000
Plasma membrane estrogen receptor signaling	0.0741	38	3346	86	-0.2	0.084	1000	-1000	-0.031	-1000
LPA receptor mediated events	0.0702	36	3768	102	-0.13	0.15	1000	-1000	-0.05	-1000
IL23-mediated signaling events	0.0702	36	2188	60	-0.01	0.29	1000	-1000	-0.043	-1000
TCGA08_p53	0.0682	35	251	7	-0.05	0.019	1000	-1000	-0.007	-1000
S1P1 pathway	0.0643	33	1203	36	-0.17	0.022	1000	-1000	-0.018	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0604	31	2706	85	-0.23	0.031	1000	-1000	-0.037	-1000
IL4-mediated signaling events	0.0604	31	2909	91	-0.28	0.064	1000	-1000	-0.088	-1000
Ras signaling in the CD4+ TCR pathway	0.0604	31	543	17	-0.1	0.022	1000	-1000	-0.01	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0585	30	1630	54	-0.094	0.05	1000	-1000	-0.028	-1000
Arf6 signaling events	0.0585	30	1884	62	-0.065	0.042	1000	-1000	-0.016	-1000
EPHB forward signaling	0.0565	29	2517	85	-0.06	0.05	1000	-1000	-0.041	-1000
S1P5 pathway	0.0546	28	483	17	-0.056	0.038	1000	-1000	-0.001	-1000
Syndecan-4-mediated signaling events	0.0546	28	1894	67	-0.18	0.15	1000	-1000	-0.025	-1000
EGFR-dependent Endothelin signaling events	0.0526	27	582	21	-0.071	0.048	1000	-1000	-0.027	-1000
Presenilin action in Notch and Wnt signaling	0.0507	26	1630	61	-0.09	0.093	1000	-1000	-0.021	-1000
FAS signaling pathway (CD95)	0.0507	26	1241	47	-0.037	0.037	1000	-1000	-0.024	-1000
IL6-mediated signaling events	0.0507	26	1994	75	-0.089	0.098	1000	-1000	-0.043	-1000
Insulin Pathway	0.0507	26	1936	74	-0.1	0.12	1000	-1000	-0.033	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0507	26	864	33	-0.11	0.14	1000	-1000	-0.027	-1000
Coregulation of Androgen receptor activity	0.0487	25	1902	76	-0.07	0.14	1000	-1000	-0.018	-1000
Visual signal transduction: Cones	0.0468	24	925	38	-0.053	0.031	1000	-1000	-0.016	-1000
Calcium signaling in the CD4+ TCR pathway	0.0468	24	774	31	-0.091	0.043	1000	-1000	-0.032	-1000
TCGA08_rtk_signaling	0.0468	24	630	26	-0.096	0.028	1000	-1000	-0.014	-1000
Syndecan-2-mediated signaling events	0.0448	23	1598	69	-0.014	0.14	1000	-1000	-0.03	-1000
Signaling events mediated by PTP1B	0.0448	23	1774	76	-0.077	0.043	1000	-1000	-0.02	-1000
TCR signaling in naïve CD8+ T cells	0.0448	23	2156	93	-0.021	0.048	1000	-1000	-0.036	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0429	22	1189	52	-0.053	0.049	1000	-1000	-0.03	-1000
IL2 signaling events mediated by STAT5	0.0429	22	502	22	-0.1	0.11	1000	-1000	-0.02	-1000
Regulation of Androgen receptor activity	0.0429	22	1567	70	-0.04	0.22	1000	-1000	-0.025	-1000
BARD1 signaling events	0.0409	21	1202	57	-0.045	0.12	1000	-1000	-0.034	-1000
Regulation of p38-alpha and p38-beta	0.0409	21	1140	54	-0.13	0.057	1000	-1000	-0.035	-1000
Visual signal transduction: Rods	0.0409	21	1124	52	-0.053	0.052	1000	-1000	-0.017	-1000
Canonical Wnt signaling pathway	0.0390	20	1060	51	-0.05	0.09	1000	-1000	-0.035	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0390	20	2563	125	-0.058	0.043	1000	-1000	-0.044	-1000
Rapid glucocorticoid signaling	0.0390	20	407	20	-0.035	0.024	1000	-1000	-0.007	-1000
mTOR signaling pathway	0.0370	19	1017	53	-0.03	0.025	1000	-1000	-0.028	-1000
Class I PI3K signaling events mediated by Akt	0.0370	19	1342	68	-0.081	0.25	1000	-1000	-0.019	-1000
Nectin adhesion pathway	0.0370	19	1231	63	-0.042	0.053	1000	-1000	-0.036	-1000
HIF-2-alpha transcription factor network	0.0370	19	835	43	-0.16	0.075	1000	-1000	-0.036	-1000
FoxO family signaling	0.0370	19	1262	64	-0.002	0.25	1000	-1000	-0.033	-1000
BCR signaling pathway	0.0370	19	1977	99	-0.05	0.061	1000	-1000	-0.054	-1000
ErbB2/ErbB3 signaling events	0.0351	18	1209	65	-0.062	0.063	1000	-1000	-0.047	-1000
IL2 signaling events mediated by PI3K	0.0351	18	1056	58	-0.035	0.14	1000	-1000	-0.031	-1000
Regulation of nuclear SMAD2/3 signaling	0.0331	17	2418	136	-0.09	0.15	1000	-1000	-0.032	-1000
IL12-mediated signaling events	0.0331	17	1500	87	-0.32	0.06	1000	-1000	-0.046	-1000
JNK signaling in the CD4+ TCR pathway	0.0331	17	295	17	-0.047	0.054	1000	-1000	-0.026	-1000
IL1-mediated signaling events	0.0331	17	1102	62	-0.044	0.069	1000	-1000	-0.033	-1000
Glypican 2 network	0.0331	17	68	4	0.022	0.04	1000	-1000	0.018	-1000
Insulin-mediated glucose transport	0.0312	16	532	32	-0.081	0.25	1000	-1000	-0.014	-1000
IFN-gamma pathway	0.0312	16	1133	68	-0.16	0.076	1000	-1000	-0.032	-1000
Retinoic acid receptors-mediated signaling	0.0312	16	974	58	-0.01	0.056	1000	-1000	-0.03	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0292	15	428	28	-0.056	0.039	1000	-1000	-0.015	-1000
Hedgehog signaling events mediated by Gli proteins	0.0292	15	1033	65	-0.081	0.051	1000	-1000	-0.03	-1000
Regulation of Telomerase	0.0292	15	1546	102	-0.22	0.095	1000	-1000	-0.03	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0273	14	1187	83	-0.046	0.25	1000	-1000	-0.015	-1000
Syndecan-3-mediated signaling events	0.0273	14	496	35	-0.052	0.079	1000	-1000	-0.016	-1000
IL27-mediated signaling events	0.0273	14	719	51	-0.042	0.038	1000	-1000	-0.021	-1000
PDGFR-beta signaling pathway	0.0273	14	1424	97	-0.028	0.049	1000	-1000	-0.035	-1000
E-cadherin signaling in keratinocytes	0.0273	14	616	43	-0.015	0.038	1000	-1000	-0.012	-1000
Caspase cascade in apoptosis	0.0253	13	1022	74	-0.025	0.16	1000	-1000	-0.026	-1000
EPO signaling pathway	0.0253	13	724	55	-0.039	0.042	1000	-1000	-0.028	-1000
Ceramide signaling pathway	0.0253	13	1056	76	-0.045	0.06	1000	-1000	-0.021	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0253	13	607	45	-0.019	0.056	1000	-1000	-0.032	-1000
Signaling events mediated by PRL	0.0253	13	453	34	-0.035	0.09	1000	-1000	-0.025	-1000
ErbB4 signaling events	0.0234	12	853	69	-0.041	0.056	1000	-1000	-0.023	-1000
ceramide signaling pathway	0.0234	12	609	49	-0.007	0.052	1000	-1000	-0.026	-1000
E-cadherin signaling in the nascent adherens junction	0.0214	11	837	76	-0.036	0.055	1000	-1000	-0.034	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0195	10	376	37	-0.032	0.065	1000	-1000	-0.015	-1000
Signaling events mediated by HDAC Class III	0.0195	10	404	40	-0.049	0.04	1000	-1000	-0.032	-1000
Signaling mediated by p38-gamma and p38-delta	0.0195	10	162	15	-0.015	0.022	1000	-1000	-0.018	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0195	10	767	74	-0.051	0.097	1000	-1000	-0.039	-1000
Class IB PI3K non-lipid kinase events	0.0195	10	30	3	-0.023	0.023	1000	-1000	-0.017	-1000
Canonical NF-kappaB pathway	0.0175	9	361	39	-0.017	0.05	1000	-1000	-0.015	-1000
Signaling events mediated by HDAC Class II	0.0156	8	609	75	-0.04	0.044	1000	-1000	-0.025	-1000
p38 MAPK signaling pathway	0.0156	8	362	44	-0.003	0.076	1000	-1000	-0.012	-1000
Arf6 trafficking events	0.0136	7	532	71	-0.15	0.04	1000	-1000	-0.03	-1000
Class I PI3K signaling events	0.0117	6	493	73	-0.028	0.043	1000	-1000	-0.019	-1000
VEGFR1 specific signals	0.0097	5	280	56	-0.049	0.046	1000	-1000	-0.023	-1000
Arf6 downstream pathway	0.0078	4	183	43	-0.036	0.041	1000	-1000	-0.022	-1000
Signaling events mediated by HDAC Class I	0.0078	4	439	104	-0.034	0.054	1000	-1000	-0.037	-1000
Paxillin-dependent events mediated by a4b1	0.0078	4	172	36	-0.039	0.041	1000	-1000	-0.032	-1000
PLK2 and PLK4 events	0.0058	3	11	3	-0.013	0.025	1000	-1000	-0.016	-1000
TRAIL signaling pathway	0.0058	3	149	48	-0.013	0.049	1000	-1000	-0.019	-1000
Arf1 pathway	0.0058	3	186	54	-0.007	0.04	1000	-1000	-0.011	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0039	2	63	23	0	0.041	1000	-1000	-0.009	-1000
a4b1 and a4b7 Integrin signaling	0.0039	2	10	5	0.022	0.033	1000	-1000	0.02	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0039	2	61	27	-0.019	0.053	1000	-1000	-0.027	-1000
E-cadherin signaling events	0.0039	2	10	5	0.019	0.038	1000	-1000	0.019	-1000
Atypical NF-kappaB pathway	0.0019	1	56	31	-0.014	0.027	1000	-1000	-0.014	-1000
Circadian rhythm pathway	0.0000	0	19	22	-0.004	0.046	1000	-1000	-0.017	-1000
Alternative NF-kappaB pathway	0.0000	0	2	13	0	0.058	1000	-1000	0	-1000
Total	NA	4304	258358	7203	-11	12	131000	-131000	-3.2	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	0.56	0.48	0.94	253	-0.86	3	256
PLK1	0.4	0.26	0.63	234	-0.58	1	235
BIRC5	0.44	0.25	0.6	288	-0.94	2	290
HSPA1B	0.56	0.48	0.94	254	-0.86	3	257
MAP2K1	0.16	0.14	0.28	245	-10000	0	245
BRCA2	0.55	0.48	0.93	254	-1	3	257
FOXM1	0.66	0.59	1.1	266	-0.93	5	271
XRCC1	0.56	0.48	0.94	252	-0.86	3	255
FOXM1B/p19	0.096	0.35	0.77	70	-0.86	8	78
Cyclin D1/CDK4	0.49	0.43	0.83	255	-0.79	3	258
CDC2	0.6	0.53	1	266	-0.84	5	271
TGFA	0.5	0.45	0.85	261	-0.75	4	265
SKP2	0.56	0.49	0.95	254	-0.86	3	257
CCNE1	0.15	0.16	0.35	187	-10000	0	187
CKS1B	0.6	0.51	1	260	-0.84	2	262
RB1	0.36	0.33	0.66	248	-0.77	1	249
FOXM1C/SP1	0.49	0.45	0.86	239	-0.9	5	244
AURKB	0.42	0.28	0.59	296	-0.72	7	303
CENPF	0.66	0.55	1.1	268	-0.82	3	271
CDK4	0.078	0.057	0.17	60	-10000	0	60
MYC	0.39	0.44	0.82	210	-0.78	6	216
CHEK2	0.16	0.14	0.3	215	-10000	0	215
ONECUT1	0.5	0.46	0.87	256	-0.78	4	260
CDKN2A	-0.027	0.19	0.26	112	-0.22	186	298
LAMA4	0.48	0.56	0.96	230	-0.9	13	243
FOXM1B/HNF6	0.5	0.47	0.89	246	-0.86	5	251
FOS	0.29	0.67	0.96	199	-1	37	236
SP1	0.021	0.022	-10000	0	-0.19	4	4
CDC25B	0.56	0.48	0.94	257	-0.86	3	260
response to radiation	0.11	0.094	0.21	204	-10000	0	204
CENPB	0.56	0.48	0.95	252	-0.86	3	255
CENPA	0.66	0.53	1	285	-0.83	3	288
NEK2	0.69	0.54	1.1	282	-0.84	2	284
HIST1H2BA	0.55	0.48	0.94	251	-0.86	3	254
CCNA2	0.13	0.15	0.37	141	-10000	0	141
EP300	0.021	0.006	-10000	0	-10000	0	0
CCNB1/CDK1	0.58	0.52	1	249	-0.92	4	253
CCNB2	0.66	0.53	1	283	-0.83	3	286
CCNB1	0.61	0.54	1	263	-0.9	3	266
ETV5	0.58	0.5	0.96	258	-1	3	261
ESR1	0.47	0.56	0.95	237	-0.92	12	249
CCND1	0.51	0.46	0.88	261	-0.8	3	264
GSK3A	0.13	0.1	0.24	193	-10000	0	193
Cyclin A-E1/CDK1-2	0.25	0.2	0.39	293	-10000	0	293
CDK2	0.052	0.038	0.15	1	-10000	0	1
G2/M transition of mitotic cell cycle	0.15	0.13	0.25	270	-10000	0	270
FOXM1B/Cbp/p300	0.23	0.37	0.7	114	-0.85	5	119
GAS1	0.04	0.68	0.99	133	-0.98	61	194
MMP2	0.52	0.53	0.94	250	-1	13	263
RB1/FOXM1C	0.47	0.45	0.84	251	-0.79	5	256
CREBBP	0.022	0.005	-10000	0	-10000	0	0

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	0.18	0.11	0.25	335	-0.22	2	337
STMN1	0.13	0.069	0.16	395	-10000	0	395
Aurora B/RasGAP/Survivin	0.3	0.16	0.38	400	-10000	0	400
Chromosomal passenger complex/Cul3 protein complex	0.13	0.1	0.21	287	-0.19	5	292
BIRC5	0.27	0.13	0.33	396	-10000	0	396
DES	-0.2	0.21	-10000	0	-0.51	66	66
Aurora C/Aurora B/INCENP	0.17	0.086	0.22	379	-10000	0	379
Aurora B/TACC1	0.099	0.13	0.21	290	-0.13	91	381
Aurora B/PP2A	0.18	0.09	0.23	387	-10000	0	387
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	0.056	0.032	0.14	21	-10000	0	21
mitotic metaphase/anaphase transition	-0.011	0.006	-10000	0	-10000	0	0
NDC80	0.14	0.094	0.18	396	-10000	0	396
Cul3 protein complex	0.001	0.091	-10000	0	-0.19	91	91
KIF2C	0.22	0.1	0.27	383	-10000	0	383
PEBP1	0.026	0.003	-10000	0	-10000	0	0
KIF20A	0.28	0.094	0.32	451	-10000	0	451
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.18	0.096	0.23	381	-0.14	5	386
SEPT1	0.021	0.016	-10000	0	-0.32	1	1
SMC2	0.022	0.015	0.32	1	-10000	0	1
SMC4	0.022	0.005	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0.16	0.16	0.25	225	-0.37	28	253
PSMA3	0.022	0.004	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.008	0.006	-10000	0	-10000	0	0
H3F3B	0.12	0.062	0.15	397	-10000	0	397
AURKB	0.26	0.13	0.32	398	-10000	0	398
AURKC	0.023	0.019	0.32	2	-10000	0	2
CDCA8	0.2	0.15	0.34	272	-10000	0	272
cytokinesis	0.2	0.12	0.27	350	-10000	0	350
Aurora B/Septin1	0.26	0.15	0.34	361	-0.26	1	362
AURKA	0.087	0.15	0.32	145	-10000	0	145
INCENP	0.035	0.008	-10000	0	-10000	0	0
KLHL13	-0.041	0.13	-10000	0	-0.32	95	95
BUB1	0.24	0.14	0.32	381	-10000	0	381
hSgo1/Aurora B/Survivin	0.41	0.2	0.49	418	-10000	0	418
EVI5	0.033	0.006	-10000	0	-10000	0	0
RhoA/GTP	0.21	0.11	0.27	336	-0.26	1	337
SGOL1	0.24	0.13	0.32	371	-10000	0	371
CENPA	0.27	0.13	0.31	427	-10000	0	427
NCAPG	0.2	0.15	0.32	307	-10000	0	307
Aurora B/HC8 Proteasome	0.18	0.089	0.23	391	-10000	0	391
NCAPD2	0.022	0.004	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.19	0.087	0.23	395	-10000	0	395
RHOA	0.022	0.005	-10000	0	-10000	0	0
NCAPH	0.24	0.13	0.32	373	-10000	0	373
NPM1	0.13	0.1	0.19	220	-0.55	5	225
RASA1	0.019	0.034	-10000	0	-0.32	5	5
KLHL9	0.021	0.016	-10000	0	-0.32	1	1
mitotic prometaphase	0.003	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.18	0.089	0.23	391	-10000	0	391
PPP1CC	0.023	0.002	-10000	0	-10000	0	0
Centraspindlin	0.23	0.12	0.3	368	-0.27	1	369
RhoA/GDP	0.016	0.003	-10000	0	-10000	0	0
NSUN2	0.14	0.082	0.28	17	-0.28	1	18
MYLK	-0.012	0.13	0.15	180	-0.14	242	422
KIF23	0.042	0.052	0.34	15	-10000	0	15
VIM	0.13	0.089	0.17	393	-0.14	5	398
RACGAP1	0.035	0.021	0.34	2	-10000	0	2
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.14	0.1	0.2	33	-0.75	3	36
Chromosomal passenger complex	0.28	0.12	0.31	439	-0.32	1	440
Chromosomal passenger complex/EVI5	0.4	0.2	0.49	401	-10000	0	401
TACC1	-0.041	0.13	-10000	0	-0.32	91	91
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
CUL3	0.023	0.003	-10000	0	-10000	0	0
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.14	0.14	-10000	0	-0.32	134	134
PTK2B	0.02	0.008	-10000	0	-10000	0	0
mol:Ca2+	-0.2	0.3	-10000	0	-0.77	93	93
EDN1	-0.054	0.084	-10000	0	-0.23	49	49
EDN3	0.086	0.15	0.32	127	-0.32	16	143
EDN2	0.059	0.099	0.32	62	-10000	0	62
HRAS/GDP	-0.2	0.21	-10000	0	-0.45	157	157
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.13	0.17	-10000	0	-0.37	135	135
ADCY4	-0.14	0.14	0.29	1	-0.32	156	157
ADCY5	-0.16	0.15	0.29	1	-0.32	183	184
ADCY6	-0.14	0.14	0.29	1	-0.31	143	144
ADCY7	-0.14	0.14	0.29	1	-0.31	144	145
ADCY1	-0.14	0.14	0.2	7	-0.32	149	156
ADCY2	-0.2	0.16	0.18	1	-0.35	241	242
ADCY3	-0.14	0.14	0.23	2	-0.31	142	144
ADCY8	-0.14	0.14	-10000	0	-0.32	150	150
ADCY9	-0.15	0.16	0.29	1	-0.35	159	160
arachidonic acid secretion	-0.25	0.27	-10000	0	-0.5	230	230
ETB receptor/Endothelin-1/Gq/GTP	-0.093	0.14	-10000	0	-0.28	155	155
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
HRAS	0.021	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.11	0.14	-10000	0	-0.3	124	124
ETA receptor/Endothelin-1/Gs/GTP	-0.13	0.15	-10000	0	-0.31	165	165
mol:GTP	-0.003	0.004	-10000	0	-10000	0	0
COL3A1	-0.14	0.15	-10000	0	-0.38	108	108
EDNRB	-0.058	0.14	-10000	0	-0.32	114	114
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.16	0.18	-10000	0	-0.43	123	123
CYSLTR1	-0.15	0.16	-10000	0	-0.39	111	111
SLC9A1	-0.086	0.092	-10000	0	-0.22	114	114
mol:GDP	-0.21	0.23	-10000	0	-0.48	160	160
SLC9A3	-0.2	0.32	-10000	0	-0.68	129	129
RAF1	-0.24	0.25	-10000	0	-0.47	217	217
JUN	-0.19	0.27	-10000	0	-0.73	83	83
JAK2	-0.14	0.14	-10000	0	-0.32	135	135
mol:IP3	-0.14	0.18	-10000	0	-0.41	120	120
ETA receptor/Endothelin-1	-0.15	0.17	-10000	0	-0.34	166	166
PLCB1	0.008	0.032	-10000	0	-0.32	3	3
PLCB2	0.008	0.021	-10000	0	-10000	0	0
ETA receptor/Endothelin-3	-0.048	0.17	0.24	61	-0.25	151	212
FOS	-0.36	0.39	-10000	0	-0.81	201	201
Gai/GDP	-0.26	0.38	-10000	0	-0.77	172	172
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:Ca ++	-0.19	0.21	-10000	0	-0.41	186	186
BCAR1	0.02	0.008	-10000	0	-10000	0	0
PRKCB1	-0.14	0.18	-10000	0	-0.4	123	123
GNAQ	0.005	0.026	-10000	0	-0.32	1	1
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
GNAL	-0.035	0.13	-10000	0	-0.32	85	85
Gs family/GDP	-0.21	0.21	-10000	0	-0.45	175	175
ETA receptor/Endothelin-1/Gq/GTP	-0.14	0.18	-10000	0	-0.36	152	152
MAPK14	-0.094	0.14	0.2	1	-0.32	100	101
TRPC6	-0.21	0.33	-10000	0	-0.83	92	92
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.016	0.045	-10000	0	-0.32	9	9
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.093	0.14	-10000	0	-0.32	101	101
ETB receptor/Endothelin-2	-0.006	0.12	0.24	41	-0.21	109	150
ETB receptor/Endothelin-3	0.015	0.16	0.24	112	-0.22	116	228
ETB receptor/Endothelin-1	-0.077	0.12	-10000	0	-0.26	127	127
MAPK3	-0.35	0.37	-10000	0	-0.76	208	208
MAPK1	-0.35	0.37	-10000	0	-0.76	208	208
Rac1/GDP	-0.2	0.21	-10000	0	-0.45	156	156
cAMP biosynthetic process	-0.22	0.2	0.28	3	-0.4	224	227
MAPK8	-0.22	0.34	-10000	0	-0.81	102	102
SRC	0.022	0.005	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.11	0.15	-10000	0	-0.3	146	146
p130Cas/CRK/Src/PYK2	-0.2	0.25	0.26	1	-0.57	124	125
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.2	0.21	-10000	0	-0.45	154	154
COL1A2	-0.17	0.18	-10000	0	-0.41	149	149
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.071	0.14	0.22	30	-0.25	152	182
mol:DAG	-0.14	0.18	-10000	0	-0.41	120	120
MAP2K2	-0.28	0.29	-10000	0	-0.58	218	218
MAP2K1	-0.28	0.29	-10000	0	-0.58	218	218
EDNRA	-0.14	0.17	-10000	0	-0.35	169	169
positive regulation of muscle contraction	-0.12	0.12	0.19	2	-0.29	114	116
Gq family/GDP	-0.17	0.21	-10000	0	-0.45	138	138
HRAS/GTP	-0.2	0.23	-10000	0	-0.47	155	155
PRKCH	-0.14	0.18	0.2	2	-0.41	116	118
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.14	0.18	-10000	0	-0.41	118	118
PRKCB	-0.15	0.19	-10000	0	-0.41	125	125
PRKCE	-0.14	0.18	-10000	0	-0.41	117	117
PRKCD	-0.14	0.18	-10000	0	-0.41	113	113
PRKCG	-0.14	0.18	-10000	0	-0.41	115	115
regulation of vascular smooth muscle contraction	-0.43	0.46	-10000	0	-0.97	200	200
PRKCQ	-0.15	0.18	0.2	2	-0.41	126	128
PLA2G4A	-0.28	0.3	-10000	0	-0.55	230	230
GNA14	-0.022	0.094	-10000	0	-0.32	43	43
GNA15	0.012	0.041	0.32	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.002	0.048	-10000	0	-0.32	9	9
Rac1/GTP	-0.11	0.14	-10000	0	-0.29	132	132
MMP1	0.17	0.17	0.36	203	-10000	0	203

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.022	0.004	-10000	0	-9999	0
Aurora C/Aurora B/INCENP	0.17	0.085	0.22	379	-9999	379
metaphase	0	0	-10000	0	-9999	0
mitosis	0	0	-10000	0	-9999	0
H3F3B	0.026	0.014	-10000	0	-9999	0
AURKB	0.26	0.13	0.32	398	-9999	398
AURKC	0.023	0.019	0.32	2	-9999	2

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.085	0.058	0.11	13	-0.12	374	387
BUB1B	0.1	0.078	0.15	328	-0.13	11	339
PLK1	0.05	0.041	0.096	159	-0.1	4	163
PLK1S1	0.029	0.027	0.13	7	-0.17	3	10
KIF2A	0.039	0.037	0.12	30	-10000	0	30
regulation of mitotic centrosome separation	0.05	0.041	0.095	159	-0.099	4	163
GOLGA2	0.022	0.005	-10000	0	-10000	0	0
Hec1/SPC24	0.16	0.12	0.27	262	-0.12	1	263
WEE1	0.038	0.073	0.17	6	-0.26	20	26
cytokinesis	0.14	0.077	0.18	300	-0.2	6	306
PP2A-alpha B56	0.15	0.11	-10000	0	-0.5	7	7
AURKA	0.06	0.061	0.14	160	-0.17	4	164
PICH/PLK1	0.11	0.11	0.22	240	-10000	0	240
CENPE	0.058	0.057	0.14	139	-0.12	1	140
RhoA/GTP	0.016	0.003	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.039	0.038	0.12	30	-10000	0	30
PPP2CA	0.022	0.003	-10000	0	-10000	0	0
FZR1	0.021	0.006	-10000	0	-10000	0	0
TPX2	0.11	0.057	0.14	395	-0.2	1	396
PAK1	0.021	0.004	-10000	0	-10000	0	0
SPC24	0.18	0.15	0.32	261	-10000	0	261
FBXW11	0.022	0.004	-10000	0	-10000	0	0
CLSPN	0.095	0.077	0.16	278	-0.21	7	285
GORASP1	0.022	0.004	-10000	0	-10000	0	0
metaphase	0	0.003	0.012	16	-0.01	3	19
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.023	0.02	0.043	158	-0.046	5	163
G2 phase of mitotic cell cycle	0.001	0.005	0.015	31	-10000	0	31
STAG2	0.023	0.002	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.006	0.082	-10000	0	-0.49	13	13
spindle elongation	0.05	0.041	0.095	159	-0.099	4	163
ODF2	0.022	0.007	-10000	0	-10000	0	0
BUB1	0.16	0.12	-10000	0	-0.54	7	7
TPT1	0.018	0.052	0.11	4	-0.18	28	32
CDC25C	0.15	0.074	0.17	442	-0.24	10	452
CDC25B	0.024	0.01	-10000	0	-10000	0	0
SGOL1	0.085	0.058	0.12	374	-0.11	13	387
RHOA	0.022	0.005	-10000	0	-10000	0	0
CCNB1/CDK1	0.063	0.072	0.22	79	-0.15	1	80
CDC14B	-0.007	0.005	-10000	0	-10000	0	0
CDC20	0.29	0.099	0.32	445	-10000	0	445
PLK1/PBIP1	0.02	0.05	0.15	59	-0.09	3	62
mitosis	-0.004	0.007	0.02	7	-0.015	104	111
FBXO5	0.032	0.035	0.12	24	-0.12	3	27
CDC2	0.003	0.004	0.012	86	-0.009	4	90
NDC80	0.031	0.053	0.32	16	-10000	0	16
metaphase plate congression	0.031	0.052	0.14	2	-0.21	16	18
ERCC6L	0.1	0.1	0.2	223	-0.15	1	224
NLP/gamma Tubulin	0.023	0.027	0.073	27	-0.1	8	35
microtubule cytoskeleton organization	0.018	0.052	0.11	4	-0.18	28	32
G2/M transition DNA damage checkpoint	-0.002	0.003	0.013	7	-10000	0	7
PPP1R12A	0.022	0.022	-10000	0	-0.32	2	2
interphase	-0.002	0.003	0.013	7	-10000	0	7
PLK1/PRC1-2	0.23	0.093	0.26	439	-10000	0	439
GRASP65/GM130/RAB1/GTP/PLK1	0.064	0.035	-10000	0	-10000	0	0
RAB1A	0.022	0.003	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.039	0.037	0.086	155	-0.085	2	157
mitotic prometaphase	0.002	0.004	0.022	17	-10000	0	17
proteasomal ubiquitin-dependent protein catabolic process	0.077	0.051	0.19	8	-0.29	3	11
microtubule-based process	0.23	0.079	0.25	451	-10000	0	451
Golgi organization	0.05	0.041	0.095	159	-0.099	4	163
Cohesin/SA2	0.053	0.032	0.12	24	-0.11	1	25
PPP1CB/MYPT1	0.033	0.018	-10000	0	-0.23	2	2
KIF20A	0.29	0.094	0.32	451	-10000	0	451
APC/C/CDC20	0.23	0.083	0.26	444	-10000	0	444
PPP2R1A	0.022	0.004	-10000	0	-10000	0	0
chromosome segregation	0.02	0.05	0.15	59	-0.089	3	62
PRC1	0.034	0.059	0.32	20	-10000	0	20
ECT2	0.064	0.085	0.24	76	-0.12	1	77
C13orf34	0.039	0.034	0.079	163	-0.076	4	167
NUDC	0.031	0.052	0.14	2	-0.21	16	18
regulation of attachment of spindle microtubules to kinetochore	0.1	0.078	0.15	340	-0.13	11	351
spindle assembly	0.035	0.032	0.077	91	-0.085	5	96
spindle stabilization	0.029	0.027	0.13	7	-0.17	3	10
APC/C/HCDH1	0.017	0.006	-10000	0	-10000	0	0
MKLP2/PLK1	0.23	0.079	0.26	451	-10000	0	451
CCNB1	0.08	0.12	0.32	95	-10000	0	95
PPP1CB	0.023	0.006	-10000	0	-10000	0	0
BTRC	0.022	0.005	-10000	0	-10000	0	0
ROCK2	0.032	0.069	0.19	3	-0.29	15	18
TUBG1	0.018	0.048	0.13	1	-0.16	26	27
G2/M transition of mitotic cell cycle	0.038	0.052	0.14	82	-0.14	1	83
MLF1IP	0.015	0.055	0.17	59	-10000	0	59
INCENP	0.023	0.005	-10000	0	-10000	0	0

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.24	0.41	0.48	1	-0.81	165	166
NCK1/PAK1/Dok-R	-0.13	0.18	-10000	0	-0.4	160	160
NCK1/Dok-R	-0.27	0.47	-10000	0	-0.91	162	162
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
mol:beta2-estradiol	0.046	0.089	0.22	99	-10000	0	99
RELA	0.023	0.003	-10000	0	-10000	0	0
SHC1	0.018	0.009	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
F2	0.081	0.13	0.29	133	-10000	0	133
TNIP2	0.022	0.005	-10000	0	-10000	0	0
NF kappa B/RelA	-0.25	0.45	-10000	0	-0.87	162	162
FN1	0.019	0.034	-10000	0	-0.32	5	5
PLD2	-0.29	0.48	-10000	0	-0.96	160	160
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GRB14	0.12	0.14	0.32	171	-0.32	1	172
ELK1	-0.27	0.43	-10000	0	-0.87	164	164
GRB7	0.021	0.032	0.32	3	-0.32	2	5
PAK1	0.022	0.004	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.26	0.47	-10000	0	-0.91	161	161
CDKN1A	-0.16	0.29	0.45	1	-0.6	120	121
ITGA5	0.022	0.015	-10000	0	-0.32	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.27	0.47	-10000	0	-0.92	163	163
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:NO	-0.17	0.31	0.41	3	-0.6	165	168
PLG	-0.31	0.48	-10000	0	-0.97	161	161
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.24	0.38	-10000	0	-0.77	165	165
GRB2	0.021	0.006	-10000	0	-10000	0	0
PIK3R1	0.018	0.031	-10000	0	-0.32	4	4
ANGPT2	-0.12	0.23	-10000	0	-0.63	52	52
BMX	-0.31	0.49	-10000	0	-0.98	163	163
ANGPT1	-0.22	0.43	-10000	0	-1.1	99	99
tube development	-0.19	0.32	0.57	1	-0.65	134	135
ANGPT4	0.007	0.034	0.32	2	-0.32	2	4
response to hypoxia	-0.02	0.03	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.25	0.53	-10000	0	-0.96	162	162
alpha5/beta1 Integrin	0.032	0.014	-10000	0	-0.22	1	1
FGF2	-0.17	0.17	-10000	0	-0.32	284	284
STAT5A (dimer)	-0.21	0.36	-10000	0	-0.75	130	130
mol:L-citrulline	-0.17	0.31	0.41	3	-0.6	165	168
AGTR1	-0.061	0.15	0.34	2	-0.32	123	125
MAPK14	-0.31	0.51	-10000	0	-1	166	166
Tie2/SHP2	-0.2	0.4	-10000	0	-0.96	103	103
TEK	-0.23	0.44	-10000	0	-1.1	101	101
RPS6KB1	-0.23	0.39	-10000	0	-0.78	165	165
Angiotensin II/AT1	-0.04	0.1	0.24	2	-0.22	123	125
Tie2/Ang1/GRB2	-0.29	0.5	-10000	0	-0.97	163	163
MAPK3	-0.27	0.44	-10000	0	-0.89	159	159
MAPK1	-0.27	0.44	-10000	0	-0.89	159	159
Tie2/Ang1/GRB7	-0.29	0.5	-10000	0	-0.97	162	162
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MAPK8	-0.3	0.48	-10000	0	-0.95	163	163
PI3K	-0.28	0.47	-10000	0	-0.92	166	166
FES	-0.31	0.51	-10000	0	-1	166	166
Crk/Dok-R	-0.27	0.47	-10000	0	-0.91	163	163
Tie2/Ang1/ABIN2	-0.3	0.5	-10000	0	-0.98	163	163
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.21	0.37	0.44	2	-0.72	166	168
STAT5A	0.022	0.006	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.22	0.4	0.52	2	-0.78	161	163
Tie2/Ang2	-0.25	0.43	-10000	0	-0.89	131	131
Tie2/Ang1	-0.31	0.52	-10000	0	-1	161	161
FOXO1	-0.21	0.37	0.45	2	-0.73	161	163
ELF1	-0.009	0.06	-10000	0	-0.13	83	83
ELF2	-0.29	0.48	-10000	0	-0.96	161	161
mol:Choline	-0.28	0.46	-10000	0	-0.92	160	160
cell migration	-0.072	0.11	-10000	0	-0.22	164	164
FYN	-0.21	0.36	0.58	1	-0.74	133	134
DOK2	0.022	0.025	0.32	3	-10000	0	3
negative regulation of cell cycle	-0.15	0.26	0.45	1	-0.55	121	122
ETS1	-0.033	0.1	-10000	0	-0.25	94	94
PXN	-0.18	0.34	0.43	5	-0.65	159	164
ITGB1	0.022	0.004	-10000	0	-10000	0	0
NOS3	-0.2	0.35	0.42	3	-0.69	165	168
RAC1	0.022	0.005	-10000	0	-10000	0	0
TNF	-0.008	0.14	0.32	41	-0.24	93	134
MAPKKK cascade	-0.28	0.46	-10000	0	-0.92	160	160
RASA1	0.019	0.034	-10000	0	-0.32	5	5
Tie2/Ang1/Shc	-0.3	0.49	-10000	0	-0.96	163	163
NCK1	0.021	0.022	-10000	0	-0.32	2	2
vasculogenesis	-0.15	0.28	0.41	3	-0.54	165	168
mol:Phosphatidic acid	-0.28	0.46	-10000	0	-0.92	160	160
mol:Angiotensin II	0	0.001	-10000	0	-10000	0	0
mol:NADP	-0.17	0.31	0.41	3	-0.6	165	168
Rac1/GTP	-0.21	0.37	-10000	0	-0.73	166	166
MMP2	-0.3	0.48	-10000	0	-0.97	160	160

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.018	0.063	-10000	0	-0.39	10	10
Crk/p130 Cas/Paxillin	-0.12	0.12	-10000	0	-0.26	187	187
JUN	-0.082	0.11	0.22	1	-0.36	30	31
HRAS	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.049	0.13	0.26	13	-0.19	213	226
RAP1A	0.023	0.001	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
RAP1A/GDP	0.017	0.001	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.048	0.13	0.25	14	-0.19	211	225
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.05	0.1	0.3	2	-0.17	210	212
RHOA	0.022	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.047	0.12	0.49	1	-0.17	212	213
GRB7	0.021	0.032	0.32	3	-0.32	2	5
RET51/GFRalpha1/GDNF	-0.048	0.13	0.26	13	-0.19	208	221
MAPKKK cascade	-0.071	0.12	0.39	1	-0.21	193	194
BCAR1	0.02	0.008	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.064	0.12	0.3	2	-0.19	229	231
lamellipodium assembly	-0.1	0.12	-10000	0	-0.24	185	185
RET51/GFRalpha1/GDNF/SHC	-0.039	0.12	0.27	7	-0.19	169	176
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
RET9/GFRalpha1/GDNF/SHC	-0.038	0.096	0.35	1	-0.17	166	167
RET9/GFRalpha1/GDNF/Shank3	-0.052	0.1	0.3	2	-0.17	212	214
MAPK3	-0.068	0.1	0.23	24	-0.28	19	43
DOK1	0.022	0.003	-10000	0	-10000	0	0
DOK6	-0.038	0.13	-10000	0	-0.32	89	89
PXN	0.022	0.003	-10000	0	-10000	0	0
neurite development	-0.08	0.11	0.27	13	-0.25	71	84
DOK5	-0.012	0.1	0.32	1	-0.32	50	51
GFRA1	-0.13	0.17	0.32	2	-0.32	221	223
MAPK8	-0.079	0.12	0.25	1	-0.37	27	28
HRAS/GTP	-0.065	0.14	0.5	1	-0.22	203	204
tube development	-0.049	0.099	0.23	6	-0.16	207	213
MAPK1	-0.067	0.1	0.23	24	-0.28	19	43
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.07	0.099	0.21	1	-0.19	208	209
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
PDLIM7	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok6	-0.066	0.15	0.25	13	-0.21	230	243
SHC1	0.019	0.009	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.051	0.13	0.26	11	-0.19	214	225
RET51/GFRalpha1/GDNF/Dok5	-0.064	0.14	0.26	12	-0.21	219	231
PRKCA	0.002	0.079	-10000	0	-0.32	29	29
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
CREB1	-0.069	0.12	0.27	2	-0.23	164	166
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.057	0.098	0.24	2	-0.19	167	169
RET51/GFRalpha1/GDNF/Grb7	-0.043	0.14	0.27	14	-0.19	208	222
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.016	0.097	0.32	19	-0.32	26	45
DOK4	0.02	0.007	-10000	0	-10000	0	0
JNK cascade	-0.081	0.11	0.22	1	-0.35	30	31
RET9/GFRalpha1/GDNF/FRS2	-0.05	0.1	0.3	2	-0.17	213	215
SHANK3	0.02	0.007	-10000	0	-10000	0	0
RASA1	0.019	0.034	-10000	0	-0.32	5	5
NCK1	0.021	0.022	-10000	0	-0.32	2	2
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.054	0.094	0.24	2	-0.19	165	167
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.074	0.12	0.3	1	-0.2	209	210
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.076	0.12	0.3	1	-0.21	206	207
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.061	0.12	0.21	8	-0.21	168	176
PI3K	-0.13	0.18	0.3	2	-0.34	184	186
SOS1	0.022	0.004	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.043	0.1	0.3	2	-0.16	207	209
GRB10	0.022	0.016	-10000	0	-0.32	1	1
activation of MAPKK activity	-0.067	0.11	0.26	1	-0.19	204	205
RET51/GFRalpha1/GDNF/FRS2	-0.049	0.13	0.25	14	-0.19	214	228
GAB1	0.019	0.03	-10000	0	-0.32	4	4
IRS1	-0.008	0.098	-10000	0	-0.32	46	46
IRS2	-0.022	0.11	-10000	0	-0.32	64	64
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.064	0.12	0.21	8	-0.22	169	177
RET51/GFRalpha1/GDNF/PKC alpha	-0.058	0.14	0.26	12	-0.2	220	232
GRB2	0.021	0.006	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GDNF	0.02	0.02	0.32	2	-10000	0	2
RAC1	0.022	0.005	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.062	0.14	0.26	13	-0.2	230	243
Rac1/GTP	-0.11	0.15	0.33	1	-0.28	184	185
RET9/GFRalpha1/GDNF	-0.063	0.11	0.3	2	-0.18	214	216
GFRalpha1/GDNF	-0.078	0.13	0.34	2	-0.22	214	216

p75(NTR)-mediated 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
Sortilin/TRAF6	0.032	0.008	-10000	0	-10000	0	0
Necdin/E2F1	-0.052	0.14	0.24	32	-0.2	208	240
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.049	0.14	0.23	1	-0.2	208	209
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.17	0.23	2	-0.26	249	251
NT-4/5 (dimer)/p75(NTR)	-0.045	0.13	0.26	10	-0.22	159	169
IKBKB	0.02	0.007	-10000	0	-10000	0	0
AKT1	-0.08	0.11	0.17	28	-0.2	182	210
IKBKG	0.023	0.003	-10000	0	-10000	0	0
BDNF	0.061	0.1	0.32	65	-10000	0	65
MGDIs/NGR/p75(NTR)/LINGO1	-0.028	0.11	0.23	7	-0.19	157	164
FURIN	0.022	0.004	-10000	0	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.01	0.13	0.23	56	-0.18	158	214
LINGO1	0.025	0.039	0.32	7	-0.32	1	8
Sortilin/TRAF6/NRIF	-0.025	0.019	-10000	0	-0.16	3	3
proBDNF (dimer)	0.06	0.1	0.32	65	-10000	0	65
NTRK1	0.02	0.048	0.32	7	-0.32	4	11
RTN4R	0.021	0.016	-10000	0	-0.32	1	1
neuron apoptosis	-0.065	0.15	0.25	1	-0.35	53	54
IRAK1	0.022	0.003	-10000	0	-10000	0	0
SHC1	-0.085	0.11	0.11	1	-0.23	167	168
ARHGDIA	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	0.016	0.003	-10000	0	-10000	0	0
Gamma Secretase	0.046	0.036	-10000	0	-0.17	3	3
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.096	0.16	0.23	1	-0.24	256	257
MAGEH1	-0.055	0.14	-10000	0	-0.32	115	115
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.14	0.17	-10000	0	-0.25	315	315
Mammalian IAPs/DIABLO	0.052	0.033	0.23	1	-0.18	8	9
proNGF (dimer)	-0.051	0.14	-10000	0	-0.32	109	109
MAGED1	0.021	0.022	-10000	0	-0.32	2	2
APP	0.022	0.004	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.026	0.053	0.32	12	-0.32	3	15
ZNF274	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP/RHOGDI	-0.064	0.12	-10000	0	-0.2	200	200
NGF	-0.051	0.14	-10000	0	-0.32	109	109
cell cycle arrest	-0.075	0.093	0.19	1	-0.27	55	56
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.081	0.13	0.19	1	-0.24	192	193
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.028	0.11	0.24	10	-0.19	158	168
NCSTN	0.019	0.009	-10000	0	-10000	0	0
mol:GTP	-0.071	0.14	0.22	1	-0.23	211	212
PSENEN	0.022	0.005	-10000	0	-10000	0	0
mol:ceramide	-0.096	0.1	0.17	1	-0.21	199	200
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.072	0.12	-10000	0	-0.32	62	62
p75(NTR)/beta APP	-0.048	0.12	0.24	1	-0.22	157	158
BEX1	-0.043	0.14	0.32	1	-0.32	98	99
mol:GDP	-0.099	0.12	0.1	1	-0.22	208	209
NGF (dimer)	-0.02	0.14	0.23	30	-0.2	149	179
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.017	0.11	0.23	7	-0.18	154	161
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
RAC1/GTP	-0.057	0.12	0.2	1	-0.19	205	206
MYD88	0.022	0.004	-10000	0	-10000	0	0
CHUK	0.022	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.071	0.14	0.23	1	-0.23	211	212
RHOB	0.021	0.016	-10000	0	-0.32	1	1
RHOA	0.022	0.005	-10000	0	-10000	0	0
MAGE-G1/E2F1	0.065	0.078	0.24	86	-10000	0	86
NT3 (dimer)	-0.002	0.091	0.32	2	-0.32	37	39
TP53	-0.048	0.083	0.23	2	-10000	0	2
PRDM4	-0.098	0.1	0.17	1	-0.21	204	205
BDNF (dimer)	0.055	0.14	0.26	105	-0.19	67	172
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
SORT1	0.023	0.002	-10000	0	-10000	0	0
activation of caspase activity	-0.052	0.13	0.21	1	-0.2	208	209
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.056	0.14	0.23	1	-0.21	205	206
RHOC	0.023	0.001	-10000	0	-10000	0	0
XIAP	0.023	0.002	-10000	0	-10000	0	0
MAPK10	-0.13	0.16	0.22	4	-0.32	165	169
DIABLO	0.022	0.003	-10000	0	-10000	0	0
SMPD2	-0.096	0.1	0.17	1	-0.21	199	200
APH1B	0.02	0.027	-10000	0	-0.32	3	3
APH1A	0.018	0.009	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.069	0.14	0.23	1	-0.23	206	207
PSEN1	0.022	0.004	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.033	0.007	-10000	0	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.063	0.13	0.24	2	-0.24	174	176
MAPK8	-0.094	0.13	0.22	4	-0.27	147	151
MAPK9	-0.096	0.13	0.22	4	-0.27	147	151
APAF1	0.023	0.002	-10000	0	-10000	0	0
NTF3	-0.002	0.091	0.32	2	-0.32	37	39
NTF4	0.026	0.053	0.32	12	-0.32	3	15
NDN	-0.13	0.17	-10000	0	-0.32	221	221
RAC1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA-B-C/GDP	-0.048	0.13	-10000	0	-0.19	202	202
p75 CTF/Sortilin/TRAF6/NRIF	0.052	0.019	-10000	0	-10000	0	0
RhoA-B-C/GTP	-0.071	0.14	0.22	1	-0.23	211	212
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.006	0.13	0.23	53	-0.17	147	200
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.001	0.13	0.23	56	-0.18	148	204
PRKACB	0.019	0.037	-10000	0	-0.32	6	6
proBDNF (dimer)/p75 ECD	0.057	0.069	0.24	65	-10000	0	65
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.017	0.045	0.32	1	-0.32	8	9
BIRC2	0.022	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.15	0.14	-10000	0	-0.29	223	223
BAD	-0.12	0.15	0.23	5	-0.3	158	163
RIPK2	0.021	0.007	-10000	0	-10000	0	0
NGFR	-0.084	0.16	0.32	1	-0.32	158	159
CYCS	-0.091	0.1	0.17	5	-0.3	52	57
ADAM17	0.022	0.005	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.053	0.13	0.23	1	-0.21	195	196
BCL2L11	-0.12	0.15	0.24	4	-0.3	159	163
BDNF (dimer)/p75(NTR)	-0.025	0.14	0.24	56	-0.22	158	214
PI3K	-0.055	0.13	0.23	1	-0.21	199	200
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.055	0.14	0.23	1	-0.21	206	207
NDNL2	0.022	0.005	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0
PRKCI	0.02	0.007	-10000	0	-10000	0	0
NGF (dimer)/p75(NTR)	-0.092	0.16	0.24	1	-0.27	208	209
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.055	0.14	0.23	1	-0.21	204	205
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCZ	0.022	0.021	0.32	1	-0.32	1	2
PLG	-0.02	0.12	0.32	5	-0.32	66	71
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	-0.089	0.13	0.14	3	-0.24	189	192
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
NGFRAP1	0.019	0.034	-10000	0	-0.32	5	5
CASP3	-0.11	0.14	0.22	5	-0.29	162	167
E2F1	0.077	0.12	0.32	93	-10000	0	93
CASP9	0.022	0.004	-10000	0	-10000	0	0
IKK complex	-0.057	0.14	-10000	0	-0.3	88	88
NGF (dimer)/TRKA	-0.02	0.1	0.23	5	-0.22	98	103
MMP7	0.029	0.13	0.32	50	-0.32	34	84
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.047	0.14	-10000	0	-0.21	201	201
MMP3	0.048	0.09	0.32	46	-0.32	2	48
APAF-1/Caspase 9	-0.095	0.082	-10000	0	-0.27	52	52

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.019	0.057	-10000	0	-0.22	26	26
alphaV beta3 Integrin	-0.12	0.14	0.23	1	-0.23	303	304
PTK2	-0.12	0.17	0.36	4	-0.37	120	124
IGF1R	0.01	0.063	-10000	0	-0.32	18	18
PI4KB	0.018	0.01	-10000	0	-10000	0	0
MFGE8	0.021	0.022	-10000	0	-0.32	2	2
SRC	0.022	0.005	-10000	0	-10000	0	0
CDKN1B	-0.12	0.19	0.18	2	-0.49	91	93
VEGFA	0.022	0.004	-10000	0	-10000	0	0
ILK	-0.11	0.17	0.18	2	-0.46	81	83
ROCK1	0.022	0.003	-10000	0	-10000	0	0
AKT1	-0.11	0.15	-10000	0	-0.43	81	81
PTK2B	-0.044	0.08	0.21	13	-0.3	11	24
alphaV/beta3 Integrin/JAM-A	-0.1	0.13	0.22	3	-0.22	246	249
CBL	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.002	0.092	0.22	3	-0.19	95	98
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.013	0.12	-10000	0	-0.22	126	126
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.052	0.1	-10000	0	-0.32	34	34
alphaV/beta3 Integrin/Syndecan-1	0.055	0.13	0.23	143	-0.17	88	231
PI4KA	0.022	0.005	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.14	0.16	-10000	0	-0.24	327	327
PI4 Kinase	0.025	0.015	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
alphaV/beta3 Integrin/Osteopontin	0.041	0.13	0.23	113	-0.18	94	207
RPS6KB1	-0.16	0.13	0.32	1	-0.33	145	146
TLN1	0.022	0.005	-10000	0	-10000	0	0
MAPK3	-0.26	0.24	-10000	0	-0.46	279	279
GPR124	-0.044	0.13	-10000	0	-0.32	95	95
MAPK1	-0.27	0.24	-10000	0	-0.46	282	282
PXN	0.022	0.003	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
alphaV/beta3 Integrin/Tumstatin	-0.026	0.12	0.23	9	-0.21	143	152
cell adhesion	-0.01	0.096	0.25	2	-0.21	91	93
ANGPTL3	0.021	0.019	0.32	2	-10000	0	2
VEGFR2 homodimer/VEGFA homodimer/Src	0.031	0.052	-10000	0	-0.19	25	25
IGF-1R heterotetramer	0.01	0.063	-10000	0	-0.32	18	18
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
TGFBR2	0.014	0.052	-10000	0	-0.32	12	12
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
IGF1	-0.045	0.14	-10000	0	-0.32	101	101
RAC1	0.022	0.005	-10000	0	-10000	0	0
regulation of cell-matrix adhesion	-0.038	0.12	0.22	1	-0.22	149	150
apoptosis	0.022	0.003	-10000	0	-10000	0	0
CD47	0.022	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/CD47	0	0.091	0.23	1	-0.19	92	93
VCL	0.021	0.006	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.064	0.14	0.23	2	-0.23	197	199
CSF1	0.016	0.048	-10000	0	-0.32	10	10
PIK3C2A	-0.11	0.16	-10000	0	-0.46	78	78
PI4 Kinase/Pyk2	-0.11	0.11	-10000	0	-0.31	77	77
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.002	0.1	0.23	1	-0.19	103	104
FAK1/Vinculin	-0.1	0.14	0.28	2	-0.32	95	97
alphaV beta3/Integrin/ppsTEM5	-0.038	0.12	0.23	1	-0.22	149	150
RHOA	0.022	0.005	-10000	0	-10000	0	0
VTN	-0.024	0.12	0.32	2	-0.32	68	70
BCAR1	0.02	0.008	-10000	0	-10000	0	0
FGF2	-0.17	0.17	-10000	0	-0.32	284	284
F11R	-0.1	0.11	-10000	0	-0.22	224	224
alphaV/beta3 Integrin/Lactadherin	-0.001	0.094	0.23	2	-0.19	94	96
alphaV/beta3 Integrin/TGFBR2	-0.004	0.1	0.23	2	-0.2	97	99
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.044	0.038	-10000	0	-0.17	10	10
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.001	0.083	0.21	2	-0.17	94	96
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.019	0.034	-10000	0	-0.32	5	5
alphaV/beta3 Integrin/Pyk2	-0.01	0.088	0.21	1	-0.18	95	96
SDC1	0.12	0.14	0.32	168	-10000	0	168
VAV3	0.03	0.097	0.18	133	-0.17	7	140
PTPN11	0.023	0.003	-10000	0	-10000	0	0
IRS1	-0.008	0.098	-10000	0	-0.32	46	46
FAK1/Paxillin	-0.1	0.14	0.37	3	-0.31	108	111
cell migration	-0.098	0.12	0.22	8	-0.3	84	92
ITGAV	0.022	0.003	-10000	0	-10000	0	0
PI3K	-0.079	0.13	-10000	0	-0.21	205	205
SPP1	0.099	0.13	0.32	129	-10000	0	129
KDR	0.004	0.077	-10000	0	-0.32	27	27
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.022	0.003	-10000	0	-10000	0	0
COL4A3	-0.018	0.13	0.32	10	-0.32	68	78
angiogenesis	-0.27	0.25	-10000	0	-0.48	273	273
Rac1/GTP	0.023	0.09	0.18	123	-10000	0	123
EDIL3	-0.081	0.16	-10000	0	-0.32	153	153
cell proliferation	-0.004	0.099	0.22	2	-0.2	97	99

PDGFR-alpha 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.082	0.15	-10000	0	-0.34	123	123
PDGF/PDGFRA/CRKL	-0.048	0.11	-10000	0	-0.23	126	126
positive regulation of JUN kinase activity	0.001	0.081	-10000	0	-0.17	83	83
CRKL	0.022	0.005	-10000	0	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.05	0.11	0.22	1	-0.23	125	126
AP1	-0.29	0.35	-10000	0	-0.77	172	172
mol:IP3	-0.081	0.096	-10000	0	-0.25	115	115
PLCG1	-0.081	0.096	-10000	0	-0.25	115	115
PDGF/PDGFRA/alphaV Integrin	-0.048	0.11	-10000	0	-0.23	126	126
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
mol:Ca2+	-0.081	0.096	-10000	0	-0.25	115	115
CAV3	0.018	0.014	0.32	1	-10000	0	1
CAV1	-0.049	0.14	-10000	0	-0.32	105	105
SHC/Grb2/SOS1	0.002	0.082	-10000	0	-0.18	83	83
PDGF/PDGFRA/Shf	-0.05	0.11	-10000	0	-0.23	127	127
FOS	-0.29	0.35	0.29	1	-0.77	171	172
JUN	-0.045	0.039	-10000	0	-0.28	6	6
oligodendrocyte development	-0.048	0.11	-10000	0	-0.23	126	126
GRB2	0.021	0.006	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:DAG	-0.081	0.096	-10000	0	-0.25	115	115
PDGF/PDGFRA	-0.082	0.15	-10000	0	-0.34	123	123
actin cytoskeleton reorganization	-0.047	0.11	-10000	0	-0.23	125	125
SRF	0.003	0.021	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
PI3K	-0.025	0.093	-10000	0	-0.2	103	103
PDGF/PDGFRA/Crk/C3G	-0.032	0.095	-10000	0	-0.19	125	125
JAK1	-0.074	0.093	-10000	0	-0.23	125	125
ELK1/SRF	-0.067	0.083	0.15	12	-0.21	107	119
SHB	0.022	0.004	-10000	0	-10000	0	0
SHF	0.02	0.027	-10000	0	-0.32	3	3
CSNK2A1	0.038	0.021	-10000	0	-10000	0	0
GO:0007205	-0.085	0.11	-10000	0	-0.28	115	115
SOS1	0.022	0.004	-10000	0	-10000	0	0
Ras protein signal transduction	0.001	0.081	-10000	0	-0.17	83	83
PDGF/PDGFRA/SHB	-0.047	0.11	-10000	0	-0.23	125	125
PDGF/PDGFRA/Caveolin-1	-0.09	0.15	-10000	0	-0.29	171	171
ITGAV	0.022	0.003	-10000	0	-10000	0	0
ELK1	-0.088	0.1	-10000	0	-0.26	114	114
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PDGF/PDGFRA/Crk	-0.047	0.11	-10000	0	-0.22	125	125
JAK-STAT cascade	-0.074	0.093	-10000	0	-0.23	125	125
cell proliferation	-0.05	0.11	-10000	0	-0.23	127	127

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.031	0.014	0.24	1	-10000	0	1
VLDLR	0.02	0.022	-10000	0	-0.32	2	2
CRKL	0.022	0.005	-10000	0	-10000	0	0
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
FYN	0.022	0.003	-10000	0	-10000	0	0
ITGA3	0.021	0.016	-10000	0	-0.32	1	1
RELN/VLDLR/Fyn	-0.036	0.11	0.23	4	-0.19	170	174
MAPK8IP1/MKK7/MAP3K11/JNK1	0.045	0.039	0.23	1	-0.17	5	6
AKT1	-0.057	0.09	0.16	4	-0.18	169	173
MAP2K7	0.021	0.006	-10000	0	-10000	0	0
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0
DAB1	0.027	0.044	0.32	11	-10000	0	11
RELN/LRP8/DAB1	-0.026	0.11	0.23	16	-0.17	174	190
LRPAP1/LRP8	0.034	0.017	0.24	3	-10000	0	3
RELN/LRP8/DAB1/Fyn	-0.018	0.11	0.23	16	-0.16	170	186
DAB1/alpha3/beta1 Integrin	-0.023	0.1	-10000	0	-0.16	157	157
long-term memory	-0.09	0.14	0.26	7	-0.21	271	278
DAB1/LIS1	-0.019	0.11	0.2	7	-0.16	165	172
DAB1/CRLK/C3G	-0.026	0.1	-10000	0	-0.16	163	163
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
DAB1/NCK2	-0.016	0.11	0.21	10	-0.17	166	176
ARHGEF2	0.018	0.01	-10000	0	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	-0.12	0.17	-10000	0	-0.32	207	207
CDK5R1	0.022	0.015	0.32	1	-10000	0	1
RELN	-0.094	0.17	0.32	5	-0.32	176	181
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
RELN/LRP8/Fyn	-0.034	0.11	0.25	6	-0.19	171	177
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.093	0.14	0.23	7	-0.21	279	286
MAPK8	0.019	0.034	-10000	0	-0.32	5	5
RELN/VLDLR/DAB1	-0.03	0.11	0.23	12	-0.17	173	185
ITGB1	0.022	0.004	-10000	0	-10000	0	0
MAP1B	-0.071	0.091	0.19	8	-0.18	178	186
RELN/LRP8	-0.035	0.11	0.26	5	-0.19	173	178
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.008	0.12	0.25	28	-0.17	167	195
PI3K	0.027	0.028	-10000	0	-0.22	5	5
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.031	0.015	-10000	0	-0.22	1	1
RAP1A	-0.062	0.085	0.29	5	-0.29	1	6
PAFAH1B1	0.021	0.006	-10000	0	-10000	0	0
MAPK8IP1	0.022	0.021	0.32	1	-0.32	1	2
CRLK/C3G	0.031	0.01	-10000	0	-10000	0	0
GRIN2B	0.029	0.053	0.32	16	-10000	0	16
NCK2	0.023	0.002	-10000	0	-10000	0	0
neuron differentiation	-0.029	0.09	0.16	5	-0.28	14	19
neuron adhesion	-0.059	0.094	0.32	8	-0.26	2	10
LRP8	0.024	0.023	0.32	3	-10000	0	3
GSK3B	-0.058	0.087	0.16	3	-0.18	164	167
RELN/VLDLR/DAB1/Fyn	-0.021	0.11	0.22	13	-0.16	170	183
MAP3K11	0.023	0.003	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.054	0.099	0.18	4	-0.19	174	178
CDK5	0.022	0.005	-10000	0	-10000	0	0
MAPT	-0.006	0.067	0.7	2	-0.28	15	17
neuron migration	-0.079	0.12	0.26	9	-0.25	156	165
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.029	0.091	0.16	5	-0.28	14	19
RELN/VLDLR	-0.025	0.11	0.23	4	-0.18	168	172

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.039	0.16	0.3	1	-0.49	37	38
IHH	0.065	0.14	0.32	98	-0.2	33	131
SHH Np/Cholesterol/GAS1	-0.069	0.092	0.14	9	-0.17	199	208
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.069	0.091	0.17	199	-0.14	9	208
SMO/beta Arrestin2	-0.028	0.16	-10000	0	-0.31	84	84
SMO	-0.041	0.16	-10000	0	-0.32	92	92
AKT1	-0.011	0.12	-10000	0	-0.44	20	20
ARRB2	0.021	0.006	-10000	0	-10000	0	0
BOC	0.002	0.08	-10000	0	-0.32	30	30
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
heart looping	-0.04	0.15	-10000	0	-0.32	92	92
STIL	-0.001	0.12	0.24	28	-0.24	27	55
DHH N/PTCH2	0	0.089	-10000	0	-0.24	61	61
DHH N/PTCH1	-0.031	0.13	-10000	0	-0.3	42	42
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
DHH	-0.005	0.092	-10000	0	-0.32	40	40
PTHLH	-0.043	0.19	0.38	1	-0.52	36	37
determination of left/right symmetry	-0.04	0.15	-10000	0	-0.32	92	92
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
skeletal system development	-0.043	0.19	0.38	1	-0.52	36	37
IHH N/Hhip	0.029	0.15	0.24	112	-0.21	94	206
DHH N/Hhip	0.023	0.09	0.24	33	-0.22	44	77
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.04	0.15	-10000	0	-0.32	92	92
pancreas development	0.04	0.083	0.32	35	-0.32	4	39
HHAT	0.017	0.027	-10000	0	-0.32	3	3
PI3K	0.027	0.028	-10000	0	-0.22	5	5
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.18	0.17	-10000	0	-0.32	299	299
somite specification	-0.04	0.15	-10000	0	-0.32	92	92
SHH Np/Cholesterol/PTCH1	-0.011	0.11	0.27	5	-0.25	28	33
SHH Np/Cholesterol/PTCH2	0.019	0.059	0.26	5	-0.18	21	26
SHH Np/Cholesterol/Megalin	0.09	0.11	0.23	168	-0.15	3	171
SHH	0.008	0.072	0.19	56	-0.22	5	61
catabolic process	-0.025	0.13	-10000	0	-0.31	36	36
SMO/Vitamin D3	0.003	0.15	0.3	23	-0.3	27	50
SHH Np/Cholesterol/Hhip	0.036	0.071	0.23	39	-0.17	8	47
LRP2	0.13	0.14	0.32	177	-10000	0	177
receptor-mediated endocytosis	0.013	0.14	0.24	37	-0.3	21	58
SHH Np/Cholesterol/BOC	0.017	0.061	0.13	53	-0.18	25	78
SHH Np/Cholesterol/CDO	0.001	0.076	0.26	5	-0.18	57	62
mesenchymal cell differentiation	-0.036	0.07	0.17	8	-0.23	39	47
mol:Vitamin D3	0.017	0.14	0.31	27	-0.25	28	55
IHH N/PTCH2	0.005	0.14	0.21	93	-0.22	111	204
CDON	-0.03	0.12	-10000	0	-0.32	76	76
IHH N/PTCH1	-0.008	0.15	-10000	0	-0.25	100	100
Megalin/LRPAP1	0.1	0.097	0.24	170	-10000	0	170
PTCH2	0.006	0.074	-10000	0	-0.32	25	25
SHH Np/Cholesterol	0.012	0.027	-10000	0	-0.16	5	5
PTCH1	-0.025	0.13	-10000	0	-0.31	36	36
HHIP	0.04	0.083	0.32	35	-0.32	4	39

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.022	0.016	-10000	0	-0.32	1	1
CCL5	0.023	0.037	0.32	5	-0.32	2	7
SDCBP	0.021	0.007	-10000	0	-10000	0	0
FGFR/FGF2/Syndecan-1	0.1	0.1	0.25	96	-0.28	2	98
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.091	0.1	0.24	71	-0.26	4	75
Syndecan-1/Syntenin	0.09	0.1	0.24	71	-0.25	5	76
MAPK3	0.075	0.094	0.22	68	-0.25	4	72
HGF/MET	-0.012	0.1	0.23	4	-0.23	89	93
TGFB1/TGF beta receptor Type II	0.022	0.016	-10000	0	-0.32	1	1
BSG	0.021	0.006	-10000	0	-10000	0	0
keratinocyte migration	0.09	0.1	0.24	71	-0.26	4	75
Syndecan-1/RANTES	0.097	0.1	0.24	78	-0.29	5	83
Syndecan-1/CD147	0.097	0.1	0.24	70	-0.26	4	74
Syndecan-1/Syntenin/PIP2	0.084	0.095	0.22	71	-0.25	4	75
LAMA5	0.021	0.006	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.082	0.093	0.22	71	-0.25	4	75
MMP7	0.029	0.13	0.32	50	-0.32	34	84
HGF	-0.037	0.13	-10000	0	-0.32	88	88
Syndecan-1/CASK	0.081	0.098	0.17	191	-0.25	6	197
Syndecan-1/HGF/MET	0.076	0.13	0.25	71	-0.28	19	90
regulation of cell adhesion	0.063	0.089	0.2	67	-0.24	3	70
HPSE	0.017	0.047	0.32	1	-0.32	9	10
positive regulation of cell migration	0.1	0.1	0.25	96	-0.28	2	98
SDC1	0.1	0.1	0.21	195	-0.28	2	197
Syndecan-1/Collagen	0.1	0.1	0.25	96	-0.28	2	98
PPIB	0.022	0.014	0.32	1	-10000	0	1
MET	0.022	0.041	0.32	4	-0.32	4	8
PRKACA	0.022	0.005	-10000	0	-10000	0	0
MMP9	0.15	0.15	0.32	213	-10000	0	213
MAPK1	0.076	0.091	0.21	68	-0.24	4	72
homophilic cell adhesion	0.1	0.11	0.25	96	-0.28	2	98
MMP1	0.14	0.15	0.32	198	-10000	0	198

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.02	0.022	-10000	0	-0.32	2	2
LAT2	-0.074	0.12	0.2	1	-0.24	139	140
AP1	-0.1	0.17	-10000	0	-0.37	87	87
mol:PIP3	-0.067	0.17	0.32	13	-0.28	134	147
IKBKB	-0.032	0.12	0.24	26	-0.22	51	77
AKT1	-0.01	0.16	0.26	89	-0.26	32	121
IKBKG	-0.043	0.11	0.27	13	-0.21	60	73
MS4A2	-0.093	0.15	-10000	0	-0.32	160	160
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.019	0.017	-10000	0	-0.32	1	1
MAP3K1	-0.045	0.14	0.24	29	-0.31	45	74
mol:Ca2+	-0.05	0.14	0.21	44	-0.22	132	176
LYN	0.02	0.013	-10000	0	-10000	0	0
CBLB	-0.075	0.12	0.2	1	-0.24	143	144
SHC1	0.019	0.009	-10000	0	-10000	0	0
RasGAP/p62DOK	-0.017	0.097	-10000	0	-0.17	136	136
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
PLD2	-0.017	0.16	0.27	90	-0.23	58	148
PTPN13	-0.091	0.16	-10000	0	-0.4	47	47
PTPN11	0.017	0.021	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.035	0.13	0.29	15	-0.27	35	50
SYK	0.022	0.018	0.32	1	-10000	0	1
GRB2	0.021	0.006	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.083	0.14	-10000	0	-0.28	138	138
LAT	-0.074	0.12	-10000	0	-0.24	136	136
PAK2	-0.049	0.15	0.25	27	-0.32	50	77
NFATC2	-0.055	0.13	-10000	0	-0.47	41	41
HRAS	-0.061	0.15	0.24	10	-0.27	134	144
GAB2	0.019	0.034	-10000	0	-0.32	5	5
PLA2G1B	-0.012	0.14	-10000	0	-0.88	12	12
Fc epsilon R1	-0.055	0.12	0.23	1	-0.2	186	187
Antigen/IgE/Fc epsilon R1	-0.047	0.11	0.22	1	-0.18	186	187
mol:GDP	-0.077	0.14	-10000	0	-0.35	51	51
JUN	0.019	0.037	-10000	0	-0.32	6	6
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
FOS	-0.09	0.16	-10000	0	-0.32	166	166
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.073	0.12	-10000	0	-0.25	143	143
CHUK	-0.041	0.11	0.3	13	-0.21	56	69
KLRG1	-0.061	0.1	0.16	1	-0.2	154	155
VAV1	-0.069	0.12	0.18	3	-0.24	130	133
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.073	0.12	0.2	1	-0.24	139	140
negative regulation of mast cell degranulation	-0.042	0.12	0.24	1	-0.27	47	48
BTK	-0.078	0.14	-10000	0	-0.38	47	47
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.074	0.12	-10000	0	-0.28	85	85
GAB2/PI3K/SHP2	-0.068	0.075	-10000	0	-0.22	60	60
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.061	0.11	-10000	0	-0.2	159	159
RAF1	-0.008	0.15	-10000	0	-0.95	12	12
Fc epsilon R1/FcgammaRIIB/SHIP	-0.036	0.12	0.23	1	-0.18	180	181
FCER1G	0.023	0.028	0.33	2	-10000	0	2
FCER1A	-0.033	0.12	-10000	0	-0.33	68	68
Antigen/IgE/Fc epsilon R1/Fyn	-0.039	0.11	0.22	1	-0.17	183	184
MAPK3	-0.013	0.14	-10000	0	-0.89	12	12
MAPK1	-0.015	0.14	-10000	0	-0.9	12	12
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MAPK8	-0.063	0.21	-10000	0	-0.59	55	55
DUSP1	-0.07	0.15	-10000	0	-0.32	137	137
NF-kappa-B/RelA	-0.03	0.066	0.13	2	-0.14	45	47
actin cytoskeleton reorganization	-0.078	0.16	-10000	0	-0.42	36	36
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.056	0.14	-10000	0	-0.26	130	130
FER	-0.074	0.12	0.2	1	-0.24	139	140
RELA	0.023	0.003	-10000	0	-10000	0	0
ITK	-0.024	0.06	-10000	0	-0.32	14	14
SOS1	0.022	0.004	-10000	0	-10000	0	0
PLCG1	-0.071	0.15	0.23	7	-0.36	49	56
cytokine secretion	-0.029	0.039	-10000	0	-10000	0	0
SPHK1	-0.073	0.12	0.2	1	-0.24	138	139
PTK2	-0.081	0.16	-10000	0	-0.43	36	36
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.083	0.14	-10000	0	-0.28	141	141
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.068	0.17	0.23	44	-0.28	138	182
MAP2K2	-0.014	0.14	-10000	0	-0.88	12	12
MAP2K1	-0.014	0.14	-10000	0	-0.89	12	12
MAP2K7	0.021	0.006	-10000	0	-10000	0	0
KLRG1/SHP2	-0.046	0.093	0.19	4	-0.22	69	73
MAP2K4	-0.092	0.32	-10000	0	-0.9	66	66
Fc epsilon R1/FcgammaRIIB	-0.043	0.12	0.23	1	-0.19	186	187
mol:Choline	-0.017	0.15	0.26	90	-0.23	58	148
SHC/Grb2/SOS1	-0.055	0.13	-10000	0	-0.24	128	128
FYN	0.022	0.003	-10000	0	-10000	0	0
DOK1	0.022	0.003	-10000	0	-10000	0	0
PXN	-0.078	0.15	0.3	1	-0.41	36	37
HCLS1	-0.073	0.12	0.2	1	-0.24	138	139
PRKCB	-0.059	0.14	0.29	11	-0.28	61	72
FCGR2B	0.019	0.022	0.32	1	-0.32	1	2
IGHE	0	0.007	-10000	0	-10000	0	0
KLRG1/SHIP	-0.042	0.12	0.25	1	-0.27	47	48
LCP2	0.023	0.014	0.32	1	-10000	0	1
PLA2G4A	-0.079	0.12	0.2	1	-0.25	143	144
RASA1	0.019	0.034	-10000	0	-0.32	5	5
mol:Phosphatidic acid	-0.017	0.15	0.26	90	-0.23	58	148
IKK complex	-0.02	0.1	0.24	30	-0.17	39	69
WIPF1	0.021	0.022	-10000	0	-0.32	2	2

Cellular roles of Anthrax toxin

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
ANTXR1	0.01	0.065	-10000	0	-0.32	19	19
ANTXR2	-0.082	0.16	-10000	0	-0.32	154	154
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.016	0.022	-10000	0	-0.048	155	155
monocyte activation	-0.008	0.12	-10000	0	-0.37	42	42
MAP2K2	-0.042	0.16	-10000	0	-0.6	40	40
MAP2K1	-0.018	0.021	0.12	1	-0.073	13	14
MAP2K7	-0.017	0.02	0.12	1	-0.073	12	13
MAP2K6	-0.009	0.034	0.071	49	-0.073	9	58
CYAA	-0.057	0.075	-10000	0	-0.17	155	155
MAP2K4	-0.017	0.02	-10000	0	-0.084	11	11
IL1B	-0.017	0.044	0.18	10	-0.14	24	34
Channel	-0.036	0.098	-10000	0	-0.18	155	155
NLRP1	-0.023	0.038	-10000	0	-0.14	32	32
CALM1	0.022	0.004	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.015	0.064	-10000	0	-0.45	9	9
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.016	0.022	0.048	155	-10000	0	155
MAPK3	-0.018	0.02	-10000	0	-0.073	12	12
MAPK1	-0.018	0.019	-10000	0	-0.073	12	12
PGR	-0.057	0.071	-10000	0	-0.17	140	140
PA/Cellular Receptors	-0.041	0.11	-10000	0	-0.2	155	155
apoptosis	-0.016	0.022	-10000	0	-0.048	155	155
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.034	0.094	-10000	0	-0.17	155	155
macrophage activation	-0.019	0.024	0.14	5	-10000	0	5
TNF	0.049	0.091	0.32	47	-0.32	2	49
VCAM1	-0.008	0.12	-10000	0	-0.37	42	42
platelet activation	-0.015	0.064	-10000	0	-0.45	9	9
MAPKKK cascade	0.014	0.029	0.087	20	-0.077	11	31
IL18	-0.018	0.029	-10000	0	-0.12	18	18
negative regulation of macrophage activation	-0.016	0.022	-10000	0	-0.048	155	155
LEF	-0.016	0.022	-10000	0	-0.048	155	155
CASP1	-0.018	0.032	-10000	0	-0.1	41	41
mol:cAMP	-0.016	0.064	-10000	0	-0.45	9	9
necrosis	-0.016	0.022	-10000	0	-0.048	155	155
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.033	0.092	-10000	0	-0.17	155	155
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.063	-10000	0	-0.32	18	18
mol:S1P	-0.01	0.013	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.092	0.12	-10000	0	-0.24	168	168
GNAO1	-0.073	0.14	-10000	0	-0.33	113	113
S1P/S1P3/G12/G13	0.003	0.052	-10000	0	-0.18	14	14
AKT1	-0.068	0.16	-10000	0	-0.67	29	29
AKT3	-0.42	0.5	-10000	0	-1	211	211
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.01	0.063	-10000	0	-0.32	18	18
GNAI2	-0.004	0.033	-10000	0	-10000	0	0
GNAI3	-0.002	0.03	-10000	0	-10000	0	0
GNAI1	-0.007	0.053	-10000	0	-0.33	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	-0.013	0.064	-10000	0	-0.33	15	15
S1PR2	0.021	0.006	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.15	0.19	-10000	0	-0.35	200	200
MAPK3	-0.14	0.18	-10000	0	-0.34	195	195
MAPK1	-0.14	0.18	-10000	0	-0.34	194	194
JAK2	-0.15	0.19	-10000	0	-0.36	200	200
CXCR4	-0.15	0.18	-10000	0	-0.34	203	203
FLT1	-0.008	0.04	-10000	0	-0.33	1	1
RhoA/GDP	0.016	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
SRC	-0.14	0.18	-10000	0	-0.34	193	193
S1P/S1P3/Gi	-0.15	0.19	-10000	0	-0.35	200	200
RAC1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.14	0.18	-10000	0	-0.32	212	212
VEGFA	-0.007	0.037	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.091	0.13	-10000	0	-0.26	162	162
VEGFR1 homodimer/VEGFA homodimer	-0.009	0.056	-10000	0	-0.14	5	5
RHOA	0.022	0.005	-10000	0	-10000	0	0
S1P/S1P3/Gq	-0.025	0.086	-10000	0	-0.24	58	58
GNAQ	0.021	0.016	-10000	0	-0.32	1	1
GNAZ	-0.018	0.077	-10000	0	-0.32	26	26
G12/G13	0.031	0.01	-10000	0	-10000	0	0
GNA14	-0.008	0.095	-10000	0	-0.32	43	43
GNA15	0.025	0.036	0.32	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.015	0.045	-10000	0	-0.32	9	9
Rac1/GTP	-0.14	0.18	-10000	0	-0.32	210	210

Nongenotropic Androgen 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
PTK2	-0.007	0.003	-10000	0	-10000	0	0
GNB1/GNG2	-0.001	0.085	-10000	0	-0.17	97	97
regulation of S phase of mitotic cell cycle	-0.02	0.07	-10000	0	-0.2	64	64
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
HRAS	0.014	0.016	-10000	0	-10000	0	0
SHBG/T-DHT	0.013	0.013	-10000	0	-0.18	2	2
PELP1	0.013	0.016	-10000	0	-10000	0	0
AKT1	-0.008	0.001	-10000	0	-10000	0	0
MAP2K1	-0.069	0.081	0.18	9	-0.25	31	40
T-DHT/AR	-0.032	0.086	-10000	0	-0.22	87	87
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.002	0.003	-10000	0	-0.006	170	170
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.016	0.045	-10000	0	-0.32	9	9
mol:GDP	-0.056	0.1	-10000	0	-0.28	83	83
cell proliferation	-0.16	0.2	0.31	1	-0.41	177	178
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
FOS	-0.26	0.34	-10000	0	-0.72	173	173
mol:Ca2+	-0.021	0.029	-10000	0	-0.061	147	147
MAPK3	-0.12	0.14	0.31	1	-0.31	161	162
MAPK1	-0.091	0.14	0.2	1	-0.34	61	62
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	-0.001	0.002	-10000	0	-0.004	168	168
cAMP biosynthetic process	0.003	0.021	-10000	0	-0.14	2	2
GNG2	0.013	0.058	0.32	1	-0.32	14	15
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	168	168
HRAS/GTP	-0.021	0.079	-10000	0	-0.17	76	76
actin cytoskeleton reorganization	0.027	0.023	-10000	0	-0.15	5	5
SRC	0.014	0.016	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	168	168
PI3K	0.024	0.024	-10000	0	-0.18	5	5
apoptosis	0.16	0.2	0.42	174	-0.26	1	175
T-DHT/AR/PELP1	-0.022	0.078	-10000	0	-0.19	85	85
HRAS/GDP	-0.046	0.11	-10000	0	-0.28	81	81
CREB1	-0.17	0.22	0.26	1	-0.45	174	175
RAC1-CDC42/GTP	0.034	0.026	-10000	0	-0.15	5	5
AR	-0.045	0.13	-10000	0	-0.32	87	87
GNB1	0.022	0.004	-10000	0	-10000	0	0
RAF1	-0.057	0.074	0.21	6	-0.23	28	34
RAC1-CDC42/GDP	-0.028	0.11	-10000	0	-0.27	76	76
T-DHT/AR/PELP1/Src	-0.013	0.076	-10000	0	-0.18	76	76
MAP2K2	-0.069	0.08	0.23	3	-0.25	30	33
T-DHT/AR/PELP1/Src/PI3K	-0.02	0.07	-10000	0	-0.2	64	64
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
SHBG	0.02	0.022	-10000	0	-0.32	2	2
Gi family/GNB1/GNG2/GDP	-0.1	0.17	-10000	0	-0.34	139	139
mol:T-DHT	-0.001	0.001	-10000	0	-0.004	25	25
RAC1	0.022	0.005	-10000	0	-10000	0	0
GNRH1	-0.009	0.019	-10000	0	-0.22	4	4
Gi family/GTP	-0.063	0.1	-10000	0	-0.24	96	96
CDC42	0.022	0.004	-10000	0	-10000	0	0

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.007	0.3	0.56	16	-0.61	47	63
HDAC7	0.022	0.005	-10000	0	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.047	0.32	0.64	18	-0.69	49	67
SMAD4	0.022	0.004	-10000	0	-10000	0	0
ID2	-0.005	0.3	0.57	14	-0.62	47	61
AP1	-0.054	0.12	-10000	0	-0.23	167	167
ABCG2	-0.082	0.34	0.58	12	-0.65	72	84
HIF1A	0.006	0.086	0.26	6	-0.2	8	14
TFF3	0.06	0.36	0.58	77	-0.68	41	118
GATA2	-0.008	0.096	-10000	0	-0.32	44	44
AKT1	-0.008	0.1	0.28	6	-0.21	38	44
response to hypoxia	-0.019	0.093	0.17	24	-0.19	64	88
MCL1	-0.026	0.27	0.6	9	-0.62	41	50
NDRG1	-0.007	0.29	0.57	13	-0.62	42	55
SERPINE1	-0.009	0.3	0.56	14	-0.63	46	60
FECH	-0.007	0.3	0.57	14	-0.62	47	61
FURIN	-0.007	0.3	0.56	13	-0.64	42	55
NCOA2	0.01	0.06	-10000	0	-0.32	16	16
EP300	-0.016	0.14	0.32	9	-0.31	65	74
HMOX1	-0.008	0.3	0.59	15	-0.61	48	63
BHLHE40	-0.005	0.3	0.55	18	-0.61	47	65
BHLHE41	-0.014	0.31	0.55	15	-0.65	47	62
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.024	0.12	0.39	6	-0.28	2	8
ENG	0.024	0.11	0.33	4	-0.26	2	6
JUN	0.018	0.038	-10000	0	-0.32	6	6
RORA	-0.016	0.31	0.57	14	-0.65	52	66
ABCB1	-0.2	0.38	0.4	2	-0.84	126	128
TFRC	-0.004	0.29	0.6	11	-0.63	40	51
CXCR4	-0.006	0.3	0.57	14	-0.64	43	57
TF	-0.004	0.31	0.59	20	-0.63	49	69
CITED2	-0.011	0.3	0.56	16	-0.63	48	64
HIF1A/ARNT	-0.015	0.36	0.83	21	-0.72	37	58
LDHA	-0.02	0.097	0.38	1	-0.55	9	10
ETS1	-0.01	0.3	0.56	15	-0.62	47	62
PGK1	-0.006	0.3	0.57	14	-0.63	45	59
NOS2	-0.005	0.3	0.58	17	-0.61	47	64
ITGB2	-0.005	0.3	0.58	16	-0.61	48	64
ALDOA	-0.005	0.3	0.57	14	-0.62	45	59
Cbp/p300/CITED2	-0.059	0.35	0.6	13	-0.74	59	72
FOS	-0.09	0.16	-10000	0	-0.32	166	166
HK2	-0.003	0.3	0.59	14	-0.63	45	59
SP1	-0.01	0.063	-10000	0	-0.14	56	56
GCK	-0.096	0.41	0.57	5	-1.1	61	66
HK1	-0.006	0.3	0.58	13	-0.63	45	58
NPM1	-0.006	0.3	0.58	13	-0.63	44	57
EGLN1	-0.023	0.28	0.59	10	-0.62	45	55
CREB1	0.025	0.003	-10000	0	-10000	0	0
PGM1	-0.006	0.3	0.58	13	-0.64	43	56
SMAD3	0.019	0.03	-10000	0	-0.32	4	4
EDN1	-0.094	0.24	-10000	0	-0.6	60	60
IGFBP1	-0.02	0.32	0.6	17	-0.65	53	70
VEGFA	-0.023	0.28	0.51	13	-0.59	54	67
HIF1A/JAB1	0.016	0.066	0.22	3	-0.18	1	4
CP	0.033	0.33	0.6	42	-0.63	45	87
CXCL12	-0.092	0.33	0.59	10	-0.66	68	78
COPS5	0.021	0.008	-10000	0	-10000	0	0
SMAD3/SMAD4	0.03	0.024	-10000	0	-0.22	4	4
BNIP3	-0.007	0.3	0.57	14	-0.62	47	61
EGLN3	-0.005	0.3	0.59	14	-0.62	46	60
CA9	0.079	0.35	0.58	74	-0.62	42	116
TERT	0.061	0.34	0.61	54	-0.61	42	96
ENO1	-0.007	0.3	0.57	14	-0.62	46	60
PFKL	-0.006	0.3	0.57	15	-0.62	46	61
NCOA1	0.022	0.016	-10000	0	-0.32	1	1
ADM	0.002	0.31	0.57	24	-0.61	47	71
ARNT	0.009	0.071	0.26	6	-10000	0	6
HNF4A	0.034	0.099	0.31	46	-0.13	24	70
ADFP	-0.037	0.28	0.5	26	-0.59	53	79
SLC2A1	-0.025	0.28	0.53	14	-0.59	54	68
LEP	-0.009	0.3	0.58	13	-0.62	46	59
HIF1A/ARNT/Cbp/p300	-0.054	0.33	0.66	19	-0.7	51	70
EPO	-0.004	0.24	0.6	5	-0.72	13	18
CREBBP	-0.018	0.14	0.3	10	-0.32	66	76
HIF1A/ARNT/Cbp/p300/HDAC7	-0.043	0.32	0.64	19	-0.69	49	68
PFKFB3	-0.007	0.3	0.56	16	-0.62	47	63
NT5E	-0.027	0.32	0.57	14	-0.64	61	75

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.006	0.063	0.2	2	-0.16	1	3
BIRC5	0.26	0.13	0.32	396	-10000	0	396
NFKBIA	-0.002	0.064	0.21	19	-10000	0	19
CPEB1	-0.13	0.17	-10000	0	-0.32	224	224
AKT1	-0.002	0.063	0.2	20	-10000	0	20
NDEL1	0.021	0.007	-10000	0	-10000	0	0
Aurora A/BRCA1	0.003	0.053	0.16	1	-0.16	1	2
NDEL1/TACC3	0.035	0.099	0.26	58	-10000	0	58
GADD45A	0.023	0.002	-10000	0	-10000	0	0
GSK3B	-0.026	0.027	-10000	0	-10000	0	0
PAK1/Aurora A	0.005	0.063	0.2	3	-0.16	1	4
MDM2	0.023	0.003	-10000	0	-10000	0	0
JUB	0	0	-10000	0	-10000	0	0
TPX2	0.13	0.083	0.17	396	-10000	0	396
TP53	0.003	0.055	-10000	0	-0.24	7	7
DLG7	-0.001	0.053	0.17	17	-10000	0	17
AURKAIP1	0.022	0.004	-10000	0	-10000	0	0
ARHGEF7	0.021	0.006	-10000	0	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.038	0.11	0.27	60	-10000	0	60
G2/M transition of mitotic cell cycle	0.003	0.053	0.15	1	-0.16	1	2
AURKA	0.007	0.074	0.22	17	-10000	0	17
AURKB	0.15	0.078	0.18	399	-10000	0	399
CDC25B	0.009	0.054	0.16	25	-0.14	2	27
G2/M transition checkpoint	-0.005	0.04	0.14	2	-0.14	3	5
mRNA polyadenylation	-0.068	0.098	-10000	0	-0.19	154	154
Aurora A/CPEB	-0.068	0.098	-10000	0	-0.19	154	154
Aurora A/TACC1/TRAP/chTOG	-0.018	0.085	-10000	0	-0.2	34	34
BRCA1	0.022	0.006	-10000	0	-10000	0	0
centrosome duplication	0.005	0.063	0.19	3	-0.16	1	4
regulation of centrosome cycle	0.034	0.097	0.25	58	-10000	0	58
spindle assembly	-0.018	0.084	-10000	0	-0.19	34	34
TDRD7	0.021	0.006	-10000	0	-10000	0	0
Aurora A/RasGAP/Survivin	0.15	0.1	0.25	179	-10000	0	179
CENPA	0.16	0.081	0.2	375	-10000	0	375
Aurora A/PP2A	0.006	0.063	0.2	3	-0.18	1	4
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.002	0.052	0.2	6	-0.18	1	7
negative regulation of DNA binding	0.003	0.056	-10000	0	-0.24	8	8
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.031	0.01	-10000	0	-10000	0	0
RASA1	0.019	0.034	-10000	0	-0.32	5	5
Ajuba/Aurora A	-0.005	0.04	0.14	2	-0.14	3	5
mitotic prometaphase	-0.024	0.03	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.073	0.22	17	-10000	0	17
TACC1	-0.041	0.13	-10000	0	-0.32	91	91
TACC3	0.075	0.12	0.32	89	-10000	0	89
Aurora A/Antizyme1	0.008	0.061	-10000	0	-10000	0	0
Aurora A/RasGAP	0.004	0.065	0.2	2	-0.2	6	8
OAZ1	0.021	0.006	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	-0.026	0.027	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
GIT1/beta-PIX/PAK1	0.041	0.015	-10000	0	-10000	0	0
Importin alpha/Importin beta/TPX2	0.13	0.083	0.17	396	-10000	0	396
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
Aurora A/TPX2	0.1	0.084	0.2	172	-10000	0	172
PAK1	0.022	0.004	-10000	0	-10000	0	0
CKAP5	0.022	0.005	-10000	0	-10000	0	0

Effects of Botulinum toxin

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
STX1A	-0.007	0.013	0.28	1	-10000	0	1
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.033	0.023	0.24	6	-10000	0	6
STXBP1	-0.001	0.084	-10000	0	-0.32	33	33
ACh/CHRNA1	0.059	0.13	0.21	191	-0.12	12	203
RAB3GAP2/RIMS1/UNC13B	0.037	0.026	0.23	5	-10000	0	5
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.024	0.033	0.32	6	-10000	0	6
mol:ACh	-0.047	0.056	0.084	17	-0.1	237	254
RAB3GAP2	0.019	0.008	-10000	0	-10000	0	0
STX1A/SNAP25/VAMP2	-0.046	0.092	0.16	3	-0.21	40	43
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.059	0.13	0.21	191	-0.12	12	203
UNC13B	0.022	0.004	-10000	0	-10000	0	0
CHRNA1	0.14	0.15	0.32	191	-10000	0	191
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	-0.068	0.1	-10000	0	-0.23	115	115
SNAP25	-0.1	0.11	-10000	0	-0.22	240	240
VAMP2	0.002	0.001	-10000	0	-10000	0	0
SYT1	-0.048	0.14	-10000	0	-0.32	105	105
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.005	0.051	0.21	1	-0.18	33	34
STX1A/SNAP25 fragment 1/VAMP2	-0.046	0.092	0.16	3	-0.21	40	43

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.09	0.29	0.37	8	-0.79	69	77
MKNK1	0.022	0.003	-10000	0	-10000	0	0
MAPK14	-0.01	0.11	-10000	0	-0.28	66	66
ATF2/c-Jun	-0.03	0.1	-10000	0	-0.35	20	20
MAPK11	-0.01	0.11	-10000	0	-0.29	61	61
MITF	-0.047	0.15	-10000	0	-0.33	95	95
MAPKAPK5	-0.025	0.12	-10000	0	-0.33	65	65
KRT8	-0.009	0.13	0.28	7	-0.33	59	66
MAPKAPK3	0.022	0.005	-10000	0	-10000	0	0
MAPKAPK2	0.019	0.008	-10000	0	-10000	0	0
p38alpha-beta/CK2	-0.017	0.15	-10000	0	-0.39	66	66
CEBPB	-0.021	0.12	0.31	1	-0.32	59	60
SLC9A1	-0.025	0.12	-10000	0	-0.33	65	65
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	-0.025	0.12	-10000	0	-0.33	62	62
p38alpha-beta/MNK1	0.002	0.13	-10000	0	-0.32	61	61
JUN	-0.031	0.1	-10000	0	-0.35	20	20
PPARGC1A	-0.077	0.17	-10000	0	-0.32	142	142
USF1	-0.021	0.12	0.34	4	-0.32	58	62
RAB5/GDP/GDI1	-0.018	0.093	-10000	0	-0.25	59	59
NOS2	-0.022	0.14	0.33	8	-0.38	52	60
DDIT3	-0.025	0.12	-10000	0	-0.33	65	65
RAB5A	0.022	0.004	-10000	0	-10000	0	0
HSPB1	-0.025	0.1	0.29	6	-0.28	59	65
p38alpha-beta/HBP1	0	0.13	-10000	0	-0.32	63	63
CREB1	-0.028	0.13	-10000	0	-0.36	65	65
RAB5/GDP	0.016	0.003	-10000	0	-10000	0	0
EIF4E	-0.044	0.099	0.18	1	-0.31	50	51
RPS6KA4	-0.026	0.12	-10000	0	-0.33	66	66
PLA2G4A	-0.045	0.11	0.25	3	-0.32	56	59
GDI1	-0.024	0.12	-10000	0	-0.33	64	64
TP53	-0.039	0.14	-10000	0	-0.41	58	58
RPS6KA5	-0.026	0.12	-10000	0	-0.32	67	67
ESR1	-0.049	0.15	-10000	0	-0.34	95	95
HBP1	0.022	0.004	-10000	0	-10000	0	0
MEF2C	-0.048	0.15	-10000	0	-0.34	95	95
MEF2A	-0.027	0.12	-10000	0	-0.32	69	69
EIF4EBP1	-0.027	0.13	-10000	0	-0.35	64	64
KRT19	-0.021	0.12	0.31	2	-0.33	61	63
ELK4	-0.022	0.12	0.33	5	-0.32	61	66
ATF6	-0.021	0.12	0.34	4	-0.32	58	62
ATF1	-0.028	0.13	-10000	0	-0.35	65	65
p38alpha-beta/MAPKAPK2	-0.006	0.12	-10000	0	-0.3	64	64
p38alpha-beta/MAPKAPK3	0.001	0.13	-10000	0	-0.32	62	62

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.015	0.035	0.33	2	-10000	0	2
CDKN2C	-0.002	0.051	-10000	0	-0.32	8	8
CDKN2A	0.15	0.15	0.33	202	-10000	0	202
CCND2	-0.048	0.067	-10000	0	-0.2	44	44
RB1	0.047	0.072	0.19	45	-10000	0	45
CDK4	-0.047	0.066	-10000	0	-0.18	41	41
CDK6	-0.051	0.077	-10000	0	-0.21	49	49
G1/S progression	-0.048	0.079	0.17	4	-0.2	49	53

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.08	0.11	-10000	0	-0.19	260	260
fibroblast growth factor receptor signaling pathway	-0.08	0.11	-10000	0	-0.19	260	260
LAMA1	0.14	0.15	0.32	209	-0.32	2	211
PRNP	-0.028	0.12	-10000	0	-0.32	75	75
GPC1/SLIT2	-0.004	0.089	-10000	0	-0.22	72	72
SMAD2	-0.021	0.032	0.17	6	-0.17	12	18
GPC1/PrPc/Cu2+	-0.003	0.076	-10000	0	-0.18	75	75
GPC1/Laminin alpha1	0.11	0.1	0.24	203	-0.22	2	205
TDGF1	0.015	0.091	0.32	16	-0.32	24	40
CRIPTO/GPC1	0.026	0.066	0.24	16	-0.22	24	40
APP/GPC1	0.033	0.007	-10000	0	-10000	0	0
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.021	0.044	0.11	16	-0.19	24	40
FLT1	0.021	0.016	-10000	0	-0.32	1	1
GPC1/TGFB/TGFBR1/TGFBR2	0.036	0.038	-10000	0	-0.19	12	12
SERPINC1	0.019	0.021	0.32	2	-10000	0	2
FYN	-0.02	0.043	0.11	16	-0.19	22	38
FGR	-0.024	0.051	0.11	16	-0.19	33	49
positive regulation of MAPKKK cascade	0.005	0.09	0.3	11	-0.27	21	32
SLIT2	-0.027	0.12	-10000	0	-0.32	72	72
GPC1/NRG	0.026	0.031	-10000	0	-0.22	7	7
NRG1	0.015	0.04	-10000	0	-0.32	7	7
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.042	0.017	-10000	0	-0.19	1	1
LYN	-0.018	0.042	0.11	16	-0.19	20	36
mol:Spermine	-0.008	0.001	-10000	0	-10000	0	0
cell growth	-0.08	0.11	-10000	0	-0.19	260	260
BMP signaling pathway	-0.022	0.003	-10000	0	-10000	0	0
SRC	-0.02	0.043	0.11	16	-0.19	23	39
TGFBR1	0.021	0.006	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.045	0.14	0.32	4	-0.32	101	105
GPC1	0.022	0.003	-10000	0	-10000	0	0
TGFBR1 (dimer)	0.021	0.006	-10000	0	-10000	0	0
VEGFA	0.022	0.004	-10000	0	-10000	0	0
BLK	-0.002	0.069	0.17	52	-0.19	18	70
HCK	-0.019	0.044	0.12	17	-0.19	22	39
FGF2	-0.17	0.17	-10000	0	-0.32	284	284
FGFR1	0.02	0.017	-10000	0	-0.32	1	1
VEGFR1 homodimer	0.021	0.016	-10000	0	-0.32	1	1
TGFBR2	0.014	0.052	-10000	0	-0.32	12	12
cell death	0.032	0.007	-10000	0	-10000	0	0
ATIII/GPC1	0.028	0.018	0.24	2	-10000	0	2
PLA2G2A/GPC1	-0.018	0.1	0.24	4	-0.22	101	105
LCK	-0.019	0.045	0.12	19	-0.19	21	40
neuron differentiation	0.026	0.031	-10000	0	-0.22	7	7
PrPc/Cu2+	-0.018	0.083	-10000	0	-0.22	75	75
APP	0.022	0.004	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.014	0.052	-10000	0	-0.32	12	12

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTK2	0.02	0.007	-10000	0	-10000	0	0
CRKL	-0.057	0.087	0.15	1	-0.22	103	104
GRB2/SOS1/SHC	0.035	0.02	-10000	0	-10000	0	0
HRAS	0.022	0.005	-10000	0	-10000	0	0
IRS1/Crk	-0.035	0.099	-10000	0	-0.22	104	104
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.1	-10000	0	-0.21	94	94
AKT1	-0.044	0.092	0.16	29	-0.21	80	109
BAD	-0.046	0.086	0.14	29	-0.2	79	108
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.055	0.087	0.15	1	-0.22	98	99
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.031	0.1	0.2	1	-0.22	108	109
RAF1	-0.034	0.1	0.27	1	-0.4	14	15
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.009	0.11	-10000	0	-0.2	104	104
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.031	0.11	-10000	0	-0.23	108	108
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
RPS6KB1	-0.045	0.088	0.16	27	-0.21	76	103
GNB2L1	0.022	0.004	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	-0.023	0.093	0.26	7	-0.33	9	16
PXN	0.022	0.003	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
HRAS/GTP	-0.019	0.083	-10000	0	-0.2	79	79
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.012	0.087	-10000	0	-0.17	78	78
IGF-1R heterotetramer	-0.009	0.078	-10000	0	-0.37	18	18
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.019	0.11	-10000	0	-0.21	108	108
Crk/p130 Cas/Paxillin	-0.013	0.1	-10000	0	-0.2	98	98
IGF1R	-0.009	0.078	-10000	0	-0.37	18	18
IGF1	-0.054	0.15	-10000	0	-0.35	100	100
IRS2/Crk	-0.074	0.099	0.15	1	-0.22	142	143
PI3K	-0.008	0.11	-10000	0	-0.21	93	93
apoptosis	0.04	0.08	0.24	30	-0.2	3	33
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
PRKCD	-0.061	0.13	-10000	0	-0.3	104	104
RAF1/14-3-3 E	-0.026	0.096	0.27	1	-0.34	16	17
BAD/14-3-3	-0.042	0.084	0.2	3	-0.26	30	33
PRKCZ	-0.042	0.092	0.16	32	-0.21	77	109
Crk/p130 Cas/Paxillin/FAK1	-0.052	0.073	-10000	0	-0.27	28	28
PTPN1	0.021	0.006	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	-0.061	0.14	-10000	0	-0.31	107	107
BCAR1	0.02	0.008	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.006	0.088	-10000	0	-0.18	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.022	0.004	-10000	0	-10000	0	0
IRS1/NCK2	-0.031	0.1	-10000	0	-0.21	108	108
GRB10	0.022	0.016	-10000	0	-0.32	1	1
PTPN11	-0.06	0.087	0.15	1	-0.21	108	109
IRS1	-0.056	0.095	0.12	4	-0.23	105	109
IRS2	-0.075	0.1	0.15	1	-0.22	147	148
IGF-1R heterotetramer/IGF1	-0.036	0.13	-10000	0	-0.27	108	108
GRB2	0.021	0.006	-10000	0	-10000	0	0
PDPK1	-0.044	0.094	0.16	28	-0.21	80	108
YWHAE	0.021	0.006	-10000	0	-10000	0	0
PRKD1	-0.07	0.14	-10000	0	-0.31	110	110
SHC1	0.019	0.009	-10000	0	-10000	0	0

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.022	0.042	-10000	0	-0.18	31	31
ADCY5	-0.045	0.068	-10000	0	-0.18	97	97
ADCY6	-0.012	0.002	-10000	0	-10000	0	0
ADCY7	-0.011	0.004	-10000	0	-10000	0	0
ADCY1	-0.015	0.034	0.1	8	-0.18	16	24
ADCY2	-0.1	0.087	-10000	0	-0.18	264	264
ADCY3	-0.013	0.011	-10000	0	-0.18	2	2
ADCY8	-0.027	0.05	-10000	0	-0.18	45	45
PRKCE	-0.008	0.001	-10000	0	-10000	0	0
ADCY9	-0.033	0.058	-10000	0	-0.18	64	64
mol:DAG	0	0	-10000	0	-10000	0	0
cAMP biosynthetic process	-0.059	0.092	0.2	21	-0.2	57	78

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.06	0.27	0.53	16	-0.65	33	49
PCK1	-0.04	0.34	0.53	20	-1.1	36	56
HNF4A	-0.062	0.37	0.72	27	-0.77	56	83
KCNJ11	-0.046	0.28	0.61	13	-0.65	34	47
AKT1	-0.008	0.18	0.46	14	-0.37	15	29
response to starvation	-0.003	0.043	0.15	2	-0.22	5	7
DLK1	-0.081	0.35	0.67	14	-0.78	61	75
NKX2-1	-0.058	0.2	0.58	7	-0.54	1	8
ACADM	-0.064	0.28	0.53	16	-0.63	39	55
TAT	-0.054	0.24	0.54	12	-0.62	25	37
CEBPB	0.023	0.012	0.18	1	-10000	0	1
CEBPA	0.022	0.032	0.26	2	-0.32	3	5
TTR	0.1	0.2	0.61	20	-0.62	7	27
PKLR	-0.018	0.29	0.6	30	-0.6	35	65
APOA1	-0.11	0.46	0.79	21	-1	65	86
CPT1C	-0.063	0.28	0.53	17	-0.65	40	57
ALAS1	-0.022	0.18	0.53	5	-0.6	2	7
TFRC	0.029	0.24	0.61	25	-0.52	5	30
FOXF1	0.004	0.053	-10000	0	-0.21	13	13
NF1	0.023	0.006	-10000	0	-10000	0	0
HNF1A (dimer)	0.059	0.087	0.35	33	-10000	0	33
CPT1A	-0.058	0.28	0.56	17	-0.65	31	48
HMGCS1	-0.054	0.28	0.55	17	-0.64	31	48
NR3C1	-0.06	0.15	-10000	0	-0.28	140	140
CPT1B	-0.058	0.28	0.56	17	-0.64	33	50
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.039	0.038	-10000	0	-10000	0	0
GCK	-0.1	0.35	0.59	16	-0.74	76	92
CREB1	0.017	0.067	0.18	1	-0.2	36	37
IGFBP1	-0.18	0.44	0.55	9	-1.1	81	90
PDX1	0.033	0.22	0.57	32	-0.57	2	34
UCP2	-0.056	0.28	0.57	19	-0.65	31	50
ALDOB	-0.045	0.28	0.62	16	-0.65	33	49
AFP	0.094	0.084	0.4	9	-10000	0	9
BDH1	-0.043	0.29	0.57	24	-0.64	32	56
HADH	-0.045	0.28	0.58	12	-0.65	32	44
F2	-0.052	0.37	0.81	24	-0.81	30	54
HNF1A	0.059	0.087	0.35	33	-10000	0	33
G6PC	0.039	0.089	0.49	3	-10000	0	3
SLC2A2	0.014	0.22	0.67	14	-10000	0	14
INS	0.006	0.069	0.21	25	-10000	0	25
FOXA1	0.2	0.16	0.32	299	-0.2	1	300
FOXA3	0.093	0.15	0.36	100	-0.23	5	105
FOXA2	-0.03	0.36	0.81	24	-0.72	38	62
ABCC8	-0.11	0.37	0.61	13	-0.77	85	98
ALB	0.095	0.093	0.38	11	-0.78	1	12

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	-0.009	0.097	-10000	0	-0.32	45	45
GNB1/GNG2	-0.054	0.074	-10000	0	-0.19	106	106
AKT1	-0.045	0.099	0.24	2	-0.24	29	31
EGF	0.032	0.058	0.32	18	-0.32	1	19
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.02	0.063	0.26	5	-0.25	4	9
mol:Ca2+	-0.077	0.14	0.28	2	-0.32	107	109
LYN	-0.017	0.054	0.26	4	-10000	0	4
RhoA/GTP	-0.033	0.059	0.12	1	-0.14	92	93
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.085	0.15	0.28	2	-0.35	107	109
GNG2	0.013	0.058	0.32	1	-0.32	14	15
ARRB2	0.021	0.006	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.057	0.19	-10000	0	-0.56	50	50
G beta5/gamma2	-0.063	0.1	-10000	0	-0.25	104	104
PRKCH	-0.089	0.16	0.28	2	-0.37	103	105
DNM1	0.02	0.027	-10000	0	-0.32	3	3
TXA2/TP beta/beta Arrestin3	0.012	0.023	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.012	0.1	-10000	0	-0.32	48	48
G12 family/GTP	-0.078	0.13	-10000	0	-0.3	112	112
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
ADRBK2	0.021	0.016	-10000	0	-0.32	1	1
RhoA/GTP/ROCK1	0.029	0.007	-10000	0	-10000	0	0
mol:GDP	0.055	0.13	0.41	35	-0.21	1	36
mol:NADP	0.022	0.021	0.32	1	-0.32	1	2
RAB11A	0.022	0.005	-10000	0	-10000	0	0
PRKG1	-0.13	0.17	-10000	0	-0.32	229	229
mol:IP3	-0.098	0.18	0.3	1	-0.4	110	111
cell morphogenesis	0.028	0.007	-10000	0	-10000	0	0
PLCB2	-0.14	0.24	-10000	0	-0.54	114	114
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.006	0.075	0.28	9	-0.2	1	10
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.017	0.056	0.23	6	-0.21	1	7
RHOA	0.022	0.005	-10000	0	-10000	0	0
PTGIR	0.022	0.016	-10000	0	-0.32	1	1
PRKCB1	-0.094	0.17	0.28	1	-0.39	106	107
GNAQ	0.021	0.016	-10000	0	-0.32	1	1
mol:L-citrulline	0.022	0.021	0.32	1	-0.32	1	2
TXA2/TXA2-R family	-0.13	0.23	-10000	0	-0.54	107	107
LCK	-0.016	0.062	0.24	7	-0.21	1	8
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.009	0.055	-10000	0	-0.16	33	33
TXA2-R family/G12 family/GDP/G beta/gamma	-0.007	0.099	-10000	0	-0.43	23	23
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.01	0.053	-10000	0	-0.16	29	29
MAPK14	-0.055	0.1	0.22	2	-0.24	93	95
TGM2/GTP	-0.11	0.2	0.36	1	-0.44	119	120
MAPK11	-0.057	0.1	0.22	2	-0.24	97	99
ARHGEF1	-0.047	0.08	0.16	2	-0.18	100	102
GNAI2	0.022	0.005	-10000	0	-10000	0	0
JNK cascade	-0.094	0.17	0.3	2	-0.39	107	109
RAB11/GDP	0.022	0.006	-10000	0	-10000	0	0
ICAM1	-0.065	0.13	0.26	4	-0.28	102	106
cAMP biosynthetic process	-0.095	0.17	0.29	1	-0.37	115	116
Gq family/GTP/EBP50	-0.016	0.079	-10000	0	-0.2	64	64
actin cytoskeleton reorganization	0.028	0.007	-10000	0	-10000	0	0
SRC	-0.017	0.057	0.24	5	-0.21	1	6
GNB5	0.022	0.005	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
EGF/EGFR	0.005	0.075	0.24	19	-0.22	6	25
VCAM1	-0.073	0.14	0.26	2	-0.32	103	105
TP beta/Gq family/GDP/G beta5/gamma2	-0.057	0.19	-10000	0	-0.56	50	50
platelet activation	-0.076	0.14	0.28	2	-0.31	101	103
PGI2/IP	0.016	0.011	-10000	0	-0.22	1	1
PRKACA	-0.005	0.054	-10000	0	-0.18	42	42
Gq family/GDP/G beta5/gamma2	-0.05	0.16	-10000	0	-0.49	50	50
TXA2/TP beta/beta Arrestin2	-0.003	0.067	-10000	0	-0.36	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.018	0.044	-10000	0	-0.17	36	36
mol:DAG	-0.11	0.2	-10000	0	-0.45	108	108
EGFR	0.013	0.054	-10000	0	-0.32	13	13
TXA2/TP alpha	-0.13	0.23	-10000	0	-0.5	116	116
Gq family/GTP	-0.028	0.087	-10000	0	-0.22	75	75
YES1	-0.016	0.058	0.25	6	-10000	0	6
GNAI2/GTP	-0.005	0.05	-10000	0	-0.16	35	35
PGD2/DP	-0.006	0.068	-10000	0	-0.22	48	48
SLC9A3R1	0.025	0.03	0.32	5	-10000	0	5
FYN	-0.019	0.058	0.26	5	-0.21	1	6
mol:NO	0.022	0.021	0.32	1	-0.32	1	2
GNA15	0.025	0.036	0.32	7	-10000	0	7
PGK/cGMP	-0.068	0.11	-10000	0	-0.18	228	228
RhoA/GDP	0.022	0.006	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	0.004	0.083	-10000	0	-0.27	14	14
NOS3	0.022	0.021	0.32	1	-0.32	1	2
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.091	0.17	0.28	2	-0.38	105	107
PRKCB	-0.094	0.17	0.27	1	-0.38	108	109
PRKCE	-0.087	0.16	0.32	2	-0.37	103	105
PRKCD	-0.094	0.17	0.28	2	-0.39	106	108
PRKCG	-0.093	0.18	0.28	1	-0.4	106	107
muscle contraction	-0.12	0.22	0.34	1	-0.5	107	108
PRKCZ	-0.085	0.15	0.28	2	-0.35	106	108
ARR3	0.02	0.014	0.32	1	-10000	0	1
TXA2/TP beta	0.005	0.057	-10000	0	-0.17	31	31
PRKCQ	-0.09	0.17	0.3	4	-0.38	107	111
MAPKKK cascade	-0.12	0.21	-10000	0	-0.48	109	109
SELE	-0.079	0.15	0.26	2	-0.35	104	106
TP beta/GNAI2/GDP/G beta/gamma	0.017	0.067	-10000	0	-0.18	36	36
ROCK1	0.022	0.003	-10000	0	-10000	0	0
GNA14	-0.008	0.095	-10000	0	-0.32	43	43
chemotaxis	-0.14	0.25	-10000	0	-0.6	106	106
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.015	0.045	-10000	0	-0.32	9	9
Rac1/GTP	0.016	0.003	-10000	0	-10000	0	0

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.064	0.11	0.39	49	-10000	0	49
NFATC2	0.006	0.18	0.41	7	-0.47	31	38
NFATC3	-0.003	0.097	-10000	0	-0.26	40	40
CD40LG	-0.11	0.31	0.45	6	-0.75	73	79
ITCH	0.02	0.034	-10000	0	-0.19	1	1
CBLB	0.021	0.035	-10000	0	-0.19	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.034	0.28	0.56	25	-0.65	40	65
JUNB	0.018	0.034	-10000	0	-0.32	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.035	0.049	0.2	37	-0.23	1	38
T cell anergy	0.018	0.069	0.24	22	-0.3	1	23
TLE4	-0.025	0.17	-10000	0	-0.52	42	42
Jun/NFAT1-c-4/p21SNFT	-0.044	0.32	0.54	6	-0.72	74	80
AP-1/NFAT1-c-4	-0.078	0.39	0.64	17	-0.85	70	87
IKZF1	-0.005	0.12	0.26	1	-0.34	27	28
T-helper 2 cell differentiation	-0.059	0.21	-10000	0	-0.76	21	21
AP-1/NFAT1	-0.031	0.18	0.36	15	-0.33	66	81
CALM1	0.03	0.026	-10000	0	-0.15	1	1
EGR2	-0.11	0.38	-10000	0	-0.95	67	67
EGR3	-0.14	0.42	-10000	0	-1.1	80	80
NFAT1/FOXP3	0.049	0.18	0.47	40	-0.33	27	67
EGR1	-0.03	0.13	-10000	0	-0.32	81	81
JUN	0.02	0.045	-10000	0	-0.32	6	6
EGR4	0.031	0.049	0.34	12	-10000	0	12
mol:Ca2+	0.009	0.023	-10000	0	-0.13	1	1
GBP3	-0.007	0.13	0.26	2	-0.37	29	31
FOSL1	0.043	0.075	0.32	34	-10000	0	34
NFAT1-c-4/MAF/IRF4	-0.063	0.33	0.54	7	-0.75	76	83
DGKA	-0.002	0.11	-10000	0	-0.35	21	21
CREM	0.02	0.012	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.063	0.33	0.49	2	-0.74	81	83
CTLA4	0.034	0.17	0.42	54	-0.29	24	78
NFAT1-c-4 (dimer)/EGR1	-0.074	0.35	0.52	4	-0.78	80	84
NFAT1-c-4 (dimer)/EGR4	-0.042	0.34	0.53	7	-0.73	80	87
FOS	-0.084	0.16	-10000	0	-0.32	161	161
IFNG	-0.027	0.2	0.42	18	-0.6	24	42
T cell activation	-0.072	0.22	0.47	4	-0.61	38	42
MAF	-0.026	0.12	-10000	0	-0.32	68	68
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.069	0.28	0.66	77	-10000	0	77
TNF	-0.074	0.32	0.46	19	-0.71	78	97
FASLG	-0.15	0.46	0.54	1	-1.1	88	89
TBX21	0.03	0.05	0.45	3	-0.32	3	6
BATF3	0.02	0.016	0.32	1	-10000	0	1
PRKCQ	0.005	0.081	0.4	1	-0.32	28	29
PTPN1	-0.005	0.12	-10000	0	-0.34	24	24
NFAT1-c-4/ICER1	-0.056	0.32	0.49	2	-0.73	80	82
GATA3	0.028	0.06	0.32	15	-0.32	4	19
T-helper 1 cell differentiation	-0.026	0.2	0.42	18	-0.59	24	42
IL2RA	-0.037	0.28	0.6	19	-0.65	41	60
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.004	0.11	-10000	0	-0.34	24	24
E2F1	0.079	0.12	0.32	93	-10000	0	93
PPARG	0.004	0.078	-10000	0	-0.32	28	28
SLC3A2	-0.004	0.11	-10000	0	-0.34	26	26
IRF4	0.021	0.061	0.32	9	-0.32	9	18
PTGS2	-0.12	0.32	0.49	8	-0.78	71	79
CSF2	-0.1	0.31	0.5	8	-0.75	71	79
JunB/Fra1/NFAT1-c-4	-0.037	0.32	0.52	8	-0.71	76	84
IL4	-0.062	0.22	-10000	0	-0.82	19	19
IL5	-0.11	0.31	0.45	6	-0.75	71	77
IL2	-0.073	0.22	0.48	4	-0.63	37	41
IL3	-0.03	0.11	-10000	0	-0.64	12	12
RNF128	0.03	0.086	0.32	37	-0.42	1	38
NFATC1	-0.069	0.28	-10000	0	-0.66	77	77
CDK4	0.073	0.21	0.54	59	-10000	0	59
PTPRK	-0.005	0.12	-10000	0	-0.36	26	26
IL8	-0.072	0.34	0.5	26	-0.76	68	94
POU2F1	0.019	0.009	-10000	0	-10000	0	0

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.022	0.005	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.052	0.079	-10000	0	-0.21	44	44
NT3 (dimer)/TRKC	-0.09	0.14	-10000	0	-0.25	219	219
NT3 (dimer)/TRKB	-0.066	0.14	0.23	5	-0.23	204	209
SHC/Grb2/SOS1/GAB1/PI3K	0.009	0.029	-10000	0	-0.18	11	11
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0
BDNF	0.061	0.1	0.32	65	-10000	0	65
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
DYNLT1	0.022	0.004	-10000	0	-10000	0	0
NTRK1	0.02	0.048	0.32	7	-0.32	4	11
NTRK2	-0.02	0.12	0.32	5	-0.32	66	71
NTRK3	-0.12	0.17	-10000	0	-0.32	215	215
NT-4/5 (dimer)/TRKB	-0.053	0.13	0.23	11	-0.21	194	205
neuron apoptosis	0.12	0.19	0.36	133	-10000	0	133
SHC 2-3/Grb2	-0.12	0.2	-10000	0	-0.4	133	133
SHC1	0.019	0.009	-10000	0	-10000	0	0
SHC2	-0.14	0.24	-10000	0	-0.47	140	140
SHC3	-0.091	0.18	-10000	0	-0.39	97	97
STAT3 (dimer)	0.024	0.006	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.035	0.11	0.23	4	-0.2	145	149
RIN/GDP	-0.04	0.098	0.22	6	-0.24	30	36
GIPC1	0.021	0.006	-10000	0	-10000	0	0
KRAS	0.022	0.004	-10000	0	-10000	0	0
DNAJA3	-0.096	0.14	0.16	1	-0.27	165	166
RIN/GTP	0.013	0.003	-10000	0	-10000	0	0
CCND1	-0.011	0.004	-10000	0	-10000	0	0
MAGED1	0.021	0.022	-10000	0	-0.32	2	2
PTPN11	0.023	0.003	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0.026	0.053	0.32	12	-0.32	3	15
SHC/GRB2/SOS1	0.035	0.02	-10000	0	-10000	0	0
GRB2	0.021	0.006	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.011	0.095	0.22	5	-0.19	103	108
TRKA/NEDD4-2	0.026	0.036	0.24	6	-0.22	5	11
ELMO1	0.02	0.03	-10000	0	-0.32	4	4
RhoG/GTP/ELMO1/DOCK1	0.025	0.032	-10000	0	-0.2	9	9
NGF	-0.051	0.14	-10000	0	-0.32	109	109
HRAS	0.022	0.005	-10000	0	-10000	0	0
DOCK1	0.018	0.037	-10000	0	-0.32	6	6
GAB2	0.019	0.034	-10000	0	-0.32	5	5
RIT2	0.017	0.004	-10000	0	-10000	0	0
RIT1	0.018	0.01	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
DNM1	0.02	0.027	-10000	0	-0.32	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.08	0.15	0.17	1	-0.26	167	168
mol:GDP	-0.063	0.14	0.27	6	-0.34	41	47
NGF (dimer)	-0.051	0.14	-10000	0	-0.32	109	109
RhoG/GDP	0.015	0.021	-10000	0	-0.22	4	4
RIT1/GDP	-0.047	0.082	0.24	2	-0.24	29	31
TIAM1	0.013	0.056	-10000	0	-0.32	14	14
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
BDNF (dimer)/TRKB	0.034	0.1	0.23	62	-0.18	65	127
KIDINS220/CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
SHC/RasGAP	0.024	0.028	-10000	0	-0.22	5	5
FRS2 family/SHP2	0.044	0.01	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	0.041	0.031	-10000	0	-0.17	3	3
RIT1/GTP	0.013	0.007	-10000	0	-10000	0	0
NT3 (dimer)	-0.002	0.091	0.32	2	-0.32	37	39
RAP1/GDP	-0.039	0.081	-10000	0	-0.2	34	34
KIDINS220/CRKL	0.022	0.005	-10000	0	-10000	0	0
BDNF (dimer)	0.06	0.1	0.32	65	-10000	0	65
ubiquitin-dependent protein catabolic process	-0.007	0.093	0.22	5	-0.19	97	102
Schwann cell development	-0.033	0.028	-10000	0	-10000	0	0
EHD4	0.022	0.005	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.052	0.019	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.002	0.059	-10000	0	-0.24	19	19
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.001	-10000	0	-10000	0	0
CDC42/GTP	-0.062	0.13	0.2	1	-0.2	195	196
ABL1	0.02	0.022	-10000	0	-0.32	2	2
SH2B family/GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
Rap1/GTP	-0.001	0.079	-10000	0	-0.28	15	15
STAT3	0.024	0.006	-10000	0	-10000	0	0
axon guidance	-0.068	0.12	-10000	0	-0.2	190	190
MAPK3	-0.02	0.1	0.17	70	-0.18	86	156
MAPK1	-0.02	0.1	0.17	70	-0.18	87	157
CDC42/GDP	-0.039	0.098	0.23	5	-0.24	31	36
NTF3	-0.002	0.091	0.32	2	-0.32	37	39
NTF4	0.026	0.053	0.32	12	-0.32	3	15
NGF (dimer)/TRKA/FAIM	-0.006	0.092	0.22	5	-0.19	94	99
PI3K	0.027	0.028	-10000	0	-0.22	5	5
FRS3	0.022	0.003	-10000	0	-10000	0	0
FAIM	0.021	0.016	-10000	0	-0.32	1	1
GAB1	0.019	0.03	-10000	0	-0.32	4	4
RASGRF1	-0.1	0.15	0.17	6	-0.28	170	176
SOS1	0.022	0.004	-10000	0	-10000	0	0
MCF2L	-0.096	0.1	-10000	0	-0.21	208	208
RGS19	0.021	0.006	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.012	0.096	-10000	0	-0.38	11	11
Rac1/GDP	-0.04	0.098	0.22	6	-0.24	34	40
NGF (dimer)/TRKA/GRIT	-0.015	0.085	0.21	5	-0.18	98	103
neuron projection morphogenesis	-0.12	0.24	-10000	0	-0.88	28	28
NGF (dimer)/TRKA/NEDD4-2	-0.007	0.093	0.22	5	-0.19	97	102
MAP2K1	0.023	0.091	0.18	112	-10000	0	112
NGFR	-0.084	0.16	0.32	1	-0.32	158	159
NGF (dimer)/TRKA/GIPC/GAIP	-0.022	0.077	-10000	0	-0.19	88	88
RAS family/GTP/PI3K	0.011	0.025	-10000	0	-0.19	7	7
FRS2 family/SHP2/GRB2/SOS1	0.06	0.022	-10000	0	-10000	0	0
NRAS	0.023	0.001	-10000	0	-10000	0	0
GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
PRKCI	0.02	0.007	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCZ	0.022	0.021	0.32	1	-0.32	1	2
MAPKKK cascade	-0.13	0.24	-10000	0	-0.56	117	117
RASA1	0.019	0.034	-10000	0	-0.32	5	5
TRKA/c-Abl	0.025	0.039	0.24	7	-0.22	6	13
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	0.045	0.1	0.23	62	-0.17	55	117
NGF (dimer)/TRKA/p62/Atypical PKCs	0.008	0.088	0.23	5	-0.17	86	91
MATK	0.016	0.045	0.32	1	-0.32	8	9
NEDD4L	0.021	0.016	-10000	0	-0.32	1	1
RAS family/GDP	-0.05	0.06	-10000	0	-0.18	43	43
NGF (dimer)/TRKA	-0.097	0.14	0.18	1	-0.28	173	174
Rac1/GTP	-0.094	0.11	-10000	0	-0.22	179	179
FRS2 family/SHP2/CRK family	0.06	0.023	-10000	0	-10000	0	0

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.024	0.12	0.21	10	-0.24	92	102
FZD6	0.02	0.017	-10000	0	-0.32	1	1
WNT6	0.017	0.1	0.32	23	-0.32	29	52
WNT4	-0.033	0.12	-10000	0	-0.32	81	81
FZD3	0.02	0.008	-10000	0	-10000	0	0
WNT5A	0.013	0.056	-10000	0	-0.32	14	14
WNT11	0.042	0.1	0.32	45	-0.32	11	56

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.068	0.082	-10000	0	-0.38	9	9
SMARCC2	0.022	0.007	-10000	0	-10000	0	0
SMARCC1	0.022	0.008	-10000	0	-10000	0	0
TBX21	0.083	0.1	0.49	5	-0.47	5	10
SUMO2	0.016	0.017	-10000	0	-10000	0	0
STAT1 (dimer)	0.025	0.014	0.32	1	-10000	0	1
FKBP4	0.022	0.004	-10000	0	-10000	0	0
FKBP5	0.016	0.048	-10000	0	-0.32	10	10
GR alpha/HSP90/FKBP51/HSP90	-0.086	0.11	0.28	3	-0.26	81	84
PRL	0.029	0.25	0.39	31	-1.1	21	52
cortisol/GR alpha (dimer)/TIF2	-0.17	0.19	0.54	4	-0.42	95	99
RELA	0.005	0.094	-10000	0	-0.2	70	70
FGG	-0.17	0.18	0.5	4	-0.42	93	97
GR beta/TIF2	-0.1	0.12	0.3	3	-0.3	86	89
IFNG	0.15	0.18	0.44	70	-0.51	3	73
apoptosis	-0.14	0.21	0.52	8	-0.53	71	79
CREB1	0.032	0.032	-10000	0	-10000	0	0
histone acetylation	0.048	0.087	0.3	3	-0.28	5	8
BGLAP	0.1	0.1	0.34	20	-0.33	1	21
GR/PKAc	-0.074	0.1	0.28	3	-0.24	74	77
NF kappa B1 p50/RelA	0.01	0.17	0.33	7	-0.33	78	85
SMARCD1	0.023	0.007	-10000	0	-10000	0	0
MDM2	-0.037	0.056	0.22	4	-0.15	5	9
GATA3	0.03	0.06	0.32	15	-0.32	4	19
AKT1	0.021	0.004	-10000	0	-10000	0	0
CSF2	0.035	0.063	0.38	1	-0.36	1	2
GSK3B	0.016	0.017	-10000	0	-10000	0	0
NR1I3	-0.093	0.2	0.52	8	-0.52	36	44
CSN2	-0.16	0.16	0.36	4	-0.37	107	111
BRG1/BAF155/BAF170/BAF60A	0.052	0.026	-10000	0	-0.16	2	2
NFATC1	0.015	0.05	-10000	0	-0.32	11	11
POU2F1	0.009	0.057	-10000	0	-0.27	19	19
CDKN1A	0.005	0.1	-10000	0	-1.1	3	3
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.007	-10000	0	-10000	0	0
SFN	0.25	0.13	0.32	380	-10000	0	380
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.061	0.15	0.31	23	-0.25	28	51
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.18	0.29	0.48	7	-0.75	89	96
JUN	0.16	0.15	0.36	129	-0.39	3	132
IL4	0.073	0.088	-10000	0	-10000	0	0
CDK5R1	0.017	0.021	0.32	1	-10000	0	1
PRKACA	0.022	0.005	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.068	0.08	-10000	0	-0.24	49	49
GR alpha/HSP90/FKBP51/HSP90/PP5C	-0.076	0.11	0.28	3	-0.25	74	77
cortisol/GR alpha (monomer)	-0.2	0.22	0.61	5	-0.47	104	109
NCOA2	0.01	0.06	-10000	0	-0.32	16	16
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.04	0.16	0.26	65	-0.31	69	134
AP-1/NFAT1-c-4	0.17	0.23	0.47	143	-0.45	5	148
AFP	0.12	0.12	0.46	6	-0.45	1	7
SUV420H1	0.022	0.004	-10000	0	-10000	0	0
IRF1	-0.092	0.11	0.36	3	-0.36	3	6
TP53	0.023	0.056	-10000	0	-0.86	2	2
PPP5C	0.022	0.004	-10000	0	-10000	0	0
KRT17	0.18	0.25	0.51	119	-0.74	7	126
KRT14	0.12	0.18	0.42	87	-1.1	2	89
TBP	0.025	0.005	-10000	0	-10000	0	0
CREBBP	-0.007	0.063	0.29	2	-0.22	3	5
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC2	0.022	0.006	-10000	0	-10000	0	0
AP-1	0.17	0.23	0.47	143	-0.45	5	148
MAPK14	0.016	0.017	-10000	0	-10000	0	0
MAPK10	-0.058	0.14	-10000	0	-0.32	112	112
MAPK11	0.014	0.027	-10000	0	-0.32	2	2
KRT5	0.23	0.25	0.5	171	-0.85	3	174
interleukin-1 receptor activity	0	0.002	-10000	0	-10000	0	0
NCOA1	0.022	0.016	-10000	0	-0.32	1	1
STAT1	0.026	0.014	0.33	1	-10000	0	1
CGA	0.097	0.11	0.43	25	-10000	0	25
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.12	0.13	0.33	2	-0.39	51	53
MAPK3	0.015	0.019	-10000	0	-10000	0	0
MAPK1	0.016	0.017	-10000	0	-10000	0	0
ICAM1	0.069	0.15	0.45	6	-0.42	8	14
NFKB1	0.003	0.095	-10000	0	-0.22	48	48
MAPK8	0.16	0.14	0.35	120	-0.33	4	124
MAPK9	0.016	0.017	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.14	0.22	0.52	8	-0.55	74	82
BAX	0.007	0.065	-10000	0	-0.46	1	1
POMC	0.051	0.23	0.47	24	-0.93	14	38
EP300	-0.007	0.063	0.29	2	-0.25	2	4
cortisol/GR alpha (dimer)/p53	-0.17	0.18	0.56	4	-0.44	77	81
proteasomal ubiquitin-dependent protein catabolic process	-0.038	0.048	0.21	4	-0.14	3	7
SGK1	-0.049	0.14	0.5	1	-0.87	6	7
IL13	0.12	0.15	0.47	4	-0.59	1	5
IL6	0.045	0.23	0.48	7	-0.83	22	29
PRKACG	0.017	0.005	-10000	0	-10000	0	0
IL5	0.099	0.14	0.42	1	-0.53	2	3
IL2	0.14	0.18	0.43	61	-0.56	2	63
CDK5	0.017	0.015	-10000	0	-10000	0	0
PRKACB	0.019	0.037	-10000	0	-0.32	6	6
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
IL8	0.11	0.19	0.43	79	-0.43	4	83
CDK5R1/CDK5	0.024	0.024	0.24	1	-10000	0	1
NF kappa B1 p50/RelA/PKAc	0.034	0.14	0.3	5	-0.28	61	66
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.15	0.18	0.51	5	-0.4	80	85
SMARCA4	0.021	0.008	-10000	0	-10000	0	0
chromatin remodeling	-0.1	0.12	0.36	3	-0.34	32	35
NF kappa B1 p50/RelA/Cbp	-0.005	0.16	0.31	5	-0.36	41	46
JUN (dimer)	0.16	0.15	0.36	129	-0.39	3	132
YWHAH	0.021	0.006	-10000	0	-10000	0	0
VIPR1	0.086	0.1	0.43	9	-0.51	4	13
NR3C1	-0.15	0.16	0.4	4	-0.38	106	110
NR4A1	-0.059	0.16	-10000	0	-0.34	117	117
TIF2/SUV420H1	0.022	0.046	-10000	0	-0.22	16	16
MAPKKK cascade	-0.14	0.21	0.52	8	-0.53	71	79
cortisol/GR alpha (dimer)/Src-1	-0.17	0.19	0.53	5	-0.43	87	92
PBX1	-0.002	0.085	-10000	0	-0.31	33	33
POU1F1	0.006	0.071	0.32	2	-0.3	23	25
SELE	-0.019	0.35	0.35	18	-0.8	77	95
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.1	0.12	0.36	3	-0.35	32	35
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.15	0.18	0.51	5	-0.4	80	85
mol:cortisol	-0.09	0.11	0.35	5	-0.24	74	79
MMP1	0.17	0.22	0.46	117	-0.51	9	126

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
CDC42/GTP	-0.046	0.1	-10000	0	-0.2	126	126
PLCG1	-0.046	0.094	-10000	0	-0.2	111	111
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
G12/G13	0.031	0.01	-10000	0	-10000	0	0
cell migration	-0.045	0.1	-10000	0	-0.2	126	126
S1PR5	0.028	0.049	0.32	12	-0.32	1	13
S1PR4	0.021	0.021	0.32	1	-0.32	1	2
MAPK3	-0.047	0.096	-10000	0	-0.2	131	131
MAPK1	-0.043	0.094	-10000	0	-0.2	122	122
S1P/S1P5/Gi	-0.039	0.1	-10000	0	-0.2	125	125
GNAI1	0.016	0.045	-10000	0	-0.32	9	9
CDC42/GDP	0.016	0.003	-10000	0	-10000	0	0
S1P/S1P5/G12	0.031	0.03	0.21	11	-0.18	1	12
RHOA	-0.012	0.032	0.17	13	-0.16	1	14
S1P/S1P4/Gi	-0.042	0.1	-10000	0	-0.2	129	129
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
S1P/S1P4/G12/G13	0.038	0.02	0.21	1	-0.17	1	2
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0

Ephrin A reverse signaling

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
MAPKKK cascade	0.004	0.067	0.21	1	-0.18	56	57
EFNA5	0.014	0.059	0.32	2	-0.32	14	16
FYN	-0.031	0.051	0.18	3	-0.17	55	58
neuron projection morphogenesis	0.004	0.067	0.21	1	-0.18	56	57
cell-cell signaling	0	0	-10000	0	-10000	0	0
Ephrin A5/EPHA5	0.004	0.067	0.21	1	-0.18	56	57
EPHA5	-0.009	0.093	-10000	0	-0.32	42	42

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.007	0.095	-10000	0	-0.32	43	43
GNB1/GNG2	-0.014	0.12	-10000	0	-0.35	29	29
mol:DAG	-0.027	0.11	0.2	12	-0.33	28	40
PLCG1	-0.028	0.11	0.2	12	-0.34	28	40
YES1	-0.033	0.11	0.18	11	-0.23	88	99
FZD3	0.02	0.008	-10000	0	-10000	0	0
FZD6	0.02	0.017	-10000	0	-0.32	1	1
G protein	-0.011	0.12	0.26	4	-0.34	28	32
MAP3K7	-0.098	0.11	0.19	5	-0.28	86	91
mol:Ca2+	-0.027	0.11	0.2	12	-0.32	28	40
mol:IP3	-0.027	0.11	0.2	12	-0.33	28	40
NLK	-0.024	0.15	-10000	0	-0.81	17	17
GNB1	0.022	0.004	-10000	0	-10000	0	0
CAMK2A	-0.1	0.12	0.21	5	-0.3	86	91
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.024	0.12	0.21	10	-0.24	92	102
CSNK1A1	0.022	0.004	-10000	0	-10000	0	0
GNAS	-0.03	0.11	0.19	12	-0.23	84	96
GO:0007205	-0.036	0.11	0.2	13	-0.32	29	42
WNT6	0.017	0.1	0.32	23	-0.32	29	52
WNT4	-0.033	0.12	-10000	0	-0.32	81	81
NFAT1/CK1 alpha	-0.028	0.12	0.27	1	-0.36	29	30
GNG2	0.013	0.058	0.32	1	-0.32	14	15
WNT5A	0.013	0.056	-10000	0	-0.32	14	14
WNT11	0.042	0.1	0.32	45	-0.32	11	56
CDC42	-0.037	0.1	0.19	5	-0.36	23	28

Ephrin B reverse 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
EFNB2	0.02	0.027	-10000	0	-0.32	3	3
EPHB2	0.024	0.02	0.32	2	-10000	0	2
EFNB1	-0.011	0.021	-10000	0	-0.22	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.073	0.26	2	-0.17	44	46
Ephrin B2/EPHB1-2	0.022	0.063	0.22	2	-0.16	48	50
neuron projection morphogenesis	0.012	0.063	0.23	1	-0.16	55	56
Ephrin B1/EPHB1-2/Tiam1	0.019	0.072	0.28	2	-0.17	57	59
DNM1	0.02	0.027	-10000	0	-0.32	3	3
cell-cell signaling	0	0.004	-10000	0	-10000	0	0
MAP2K4	-0.06	0.16	0.22	4	-0.47	63	67
YES1	-0.074	0.23	-10000	0	-0.68	64	64
Ephrin B1/EPHB1-2/NCK2	0.025	0.064	0.28	2	-0.16	46	48
PI3K	-0.032	0.17	-10000	0	-0.46	65	65
mol:GDP	0.018	0.071	0.27	2	-0.17	57	59
ITGA2B	0.021	0.035	0.32	3	-0.32	3	6
endothelial cell proliferation	0.027	0.018	-10000	0	-0.18	3	3
FYN	-0.074	0.23	-10000	0	-0.68	64	64
MAP3K7	-0.062	0.17	0.23	1	-0.5	64	65
FGR	-0.075	0.23	-10000	0	-0.68	63	63
TIAM1	0.013	0.056	-10000	0	-0.32	14	14
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
RGS3	0.021	0.006	-10000	0	-10000	0	0
cell adhesion	-0.068	0.17	0.28	1	-0.48	66	67
LYN	-0.073	0.23	-10000	0	-0.68	64	64
Ephrin B1/EPHB1-2/Src Family Kinases	-0.074	0.22	-10000	0	-0.62	66	66
Ephrin B1/EPHB1-2	-0.06	0.18	-10000	0	-0.54	60	60
SRC	-0.073	0.23	-10000	0	-0.68	64	64
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
EPHB1	-0.008	0.097	-10000	0	-0.32	45	45
EPHB4	0.022	0.004	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.027	0.019	-10000	0	-0.18	3	3
alphaIIb/beta3 Integrin	-0.016	0.1	0.24	4	-0.22	99	103
BLK	-0.071	0.23	-10000	0	-0.68	63	63
HCK	-0.071	0.23	-10000	0	-0.68	62	62
regulation of stress fiber formation	-0.024	0.063	0.16	46	-0.27	2	48
MAPK8	-0.058	0.16	0.22	2	-0.45	63	65
Ephrin B1/EPHB1-2/RGS3	0.025	0.064	0.28	2	-0.16	46	48
endothelial cell migration	-0.05	0.14	0.21	7	-0.42	60	67
NCK2	0.023	0.002	-10000	0	-10000	0	0
PTPN13	-0.021	0.13	-10000	0	-0.43	48	48
regulation of focal adhesion formation	-0.024	0.063	0.16	46	-0.27	2	48
chemotaxis	-0.023	0.063	0.16	46	-0.27	2	48
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
Rac1/GTP	0.019	0.067	0.23	2	-0.16	54	56
angiogenesis	-0.06	0.18	-10000	0	-0.54	61	61
LCK	-0.073	0.23	-10000	0	-0.68	64	64

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.031	0.11	0.24	39	-0.18	79	118
SMAD6-7/SMURF1	0.041	0.02	-10000	0	-0.19	2	2
NOG	0.055	0.095	0.32	56	-10000	0	56
SMAD9	-0.076	0.19	-10000	0	-0.49	83	83
SMAD4	0.022	0.004	-10000	0	-10000	0	0
SMAD5	-0.033	0.088	-10000	0	-0.33	20	20
BMP7/USAG1	0.048	0.11	0.25	79	-0.22	34	113
SMAD5/SKI	-0.028	0.1	-10000	0	-0.34	25	25
SMAD1	-0.001	0.064	0.24	2	-0.33	10	12
BMP2	-0.003	0.09	-10000	0	-0.32	38	38
SMAD1/SMAD1/SMAD4	0.012	0.062	-10000	0	-0.27	12	12
BMPR1A	0.022	0.005	-10000	0	-10000	0	0
BMPR1B	0.004	0.078	0.32	1	-0.32	27	28
BMPR1A-1B/BAMBI	0.025	0.071	0.23	6	-0.2	38	44
AHSG	0.023	0.036	0.32	7	-10000	0	7
CER1	0.018	0.005	-10000	0	-10000	0	0
BMP2-4/CER1	0.02	0.075	0.22	8	-0.2	47	55
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.045	0.11	-10000	0	-0.32	36	36
BMP2-4 (homodimer)	0.008	0.086	0.24	8	-0.23	52	60
RGMB	0.022	0.016	-10000	0	-0.32	1	1
BMP6/BMPR2/BMPR1A-1B	0.035	0.064	0.23	1	-0.18	37	38
RGMA	-0.047	0.14	-10000	0	-0.32	103	103
SMURF1	0.022	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.041	0.098	-10000	0	-0.3	33	33
BMP2-4/USAG1	0.027	0.1	0.23	45	-0.2	65	110
SMAD6/SMURF1/SMAD5	-0.029	0.1	-10000	0	-0.34	25	25
SOSTDC1	0.034	0.11	0.32	43	-0.32	20	63
BMP7/BMPR2/BMPR1A-1B	0.052	0.083	0.23	48	-0.18	29	77
SKI	0.022	0.004	-10000	0	-10000	0	0
BMP6 (homodimer)	0.012	0.058	-10000	0	-0.32	15	15
HFE2	0.019	0.014	0.32	1	-10000	0	1
ZFYVE16	0.022	0.005	-10000	0	-10000	0	0
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
BMP2-4/CHRD	-0.008	0.11	0.23	8	-0.21	101	109
SMAD5/SMAD5/SMAD4	-0.028	0.1	-10000	0	-0.34	25	25
MAPK1	0.022	0.005	-10000	0	-10000	0	0
TAK1/TAB family	-0.028	0.099	-10000	0	-0.29	29	29
BMP7 (homodimer)	0.043	0.12	0.32	56	-0.32	17	73
NUP214	0.021	0.006	-10000	0	-10000	0	0
BMP6/FETUA	0.024	0.051	0.24	7	-0.22	15	22
SMAD1/SKI	0.008	0.07	0.24	2	-0.32	11	13
SMAD6	0.021	0.016	-10000	0	-0.32	1	1
CTDSP2	0.023	0.001	-10000	0	-10000	0	0
BMP2-4/FETUA	0.026	0.074	0.23	14	-0.2	40	54
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	-0.063	0.15	-10000	0	-0.32	126	126
BMPR2 (homodimer)	0.023	0.003	-10000	0	-10000	0	0
GADD34/PP1CA	0.042	0.014	-10000	0	-10000	0	0
BMPR1A-1B (homodimer)	0.018	0.058	0.24	1	-0.22	26	27
CHRDL1	-0.22	0.16	-10000	0	-0.32	353	353
ENDOFIN/SMAD1	0.007	0.069	0.24	2	-0.33	9	11
SMAD6-7/SMURF1/SMAD1	0.024	0.074	-10000	0	-0.32	9	9
SMAD6/SMURF1	0.022	0.004	-10000	0	-10000	0	0
BAMBI	0.015	0.07	0.32	7	-0.32	16	23
SMURF2	0.022	0.005	-10000	0	-10000	0	0
BMP2-4/CHRDL1	-0.13	0.12	0.22	2	-0.21	350	352
BMP2-4/GREM1	-0.035	0.12	0.23	7	-0.21	157	164
SMAD7	0.021	0.016	-10000	0	-0.32	1	1
SMAD8A/SMAD8A/SMAD4	-0.069	0.19	-10000	0	-0.46	87	87
SMAD1/SMAD6	0.006	0.071	0.24	2	-0.31	13	15
TAK1/SMAD6	0.033	0.007	-10000	0	-10000	0	0
BMP7	0.043	0.12	0.32	56	-0.32	17	73
BMP6	0.012	0.058	-10000	0	-0.32	15	15
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.039	0.1	-10000	0	-0.3	37	37
PPM1A	0.022	0.004	-10000	0	-10000	0	0
SMAD1/SMURF2	0.008	0.069	0.24	2	-0.32	11	13
SMAD7/SMURF1	0.031	0.014	-10000	0	-0.22	1	1
CTDSPL	0.022	0.004	-10000	0	-10000	0	0
PPP1CA	0.022	0.004	-10000	0	-10000	0	0
XIAP	0.023	0.002	-10000	0	-10000	0	0
CTDSP1	0.022	0.003	-10000	0	-10000	0	0
PPP1R15A	0.022	0.004	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.066	0.13	-10000	0	-0.36	51	51
CHRD	-0.031	0.12	-10000	0	-0.32	77	77
BMPR2	0.023	0.003	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.048	0.1	-10000	0	-0.33	32	32
BMP4	0.015	0.077	0.32	9	-0.32	19	28
FST	-0.021	0.12	0.32	3	-0.32	65	68
BMP2-4/NOG	0.038	0.099	0.24	53	-0.18	52	105
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.057	0.082	0.23	42	-0.18	29	71

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.033	0.058	0.24	4	-0.19	20	24
alphaM/beta2 Integrin/GPIbA	0.041	0.048	0.31	5	-0.19	4	9
alphaM/beta2 Integrin/proMMP-9	0.12	0.11	0.24	202	-0.19	2	204
PLAUR	0.025	0.027	0.32	4	-10000	0	4
HMGB1	0.022	0.019	-10000	0	-10000	0	0
alphaM/beta2 Integrin/Talin	0.043	0.043	0.27	5	-0.19	3	8
AGER	0.022	0.024	-10000	0	-0.32	1	1
RAP1A	0.023	0.001	-10000	0	-10000	0	0
SELPLG	0.023	0.002	-10000	0	-10000	0	0
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.06	0.079	0.32	11	-0.19	23	34
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.15	0.15	0.32	213	-10000	0	213
CYR61	-0.011	0.1	-10000	0	-0.32	50	50
TLN1	0.022	0.005	-10000	0	-10000	0	0
Rap1/GTP	-0.004	0.1	-10000	0	-0.3	27	27
RHOA	0.022	0.005	-10000	0	-10000	0	0
P-selectin oligomer	-0.1	0.16	-10000	0	-0.32	177	177
MYH2	-0.013	0.12	0.26	10	-0.41	20	30
MST1R	0.062	0.1	0.32	69	-0.32	1	70
leukocyte activation during inflammatory response	0.049	0.053	0.22	21	-0.16	3	24
APOB	0.021	0.02	0.32	2	-10000	0	2
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.008	0.065	-10000	0	-0.32	19	19
JAM3	-0.063	0.15	-10000	0	-0.32	125	125
GP1BA	0.02	0.021	0.32	1	-0.32	1	2
alphaM/beta2 Integrin/CTGF	0.037	0.058	0.27	5	-0.18	19	24
alphaM/beta2 Integrin	-0.004	0.099	0.26	7	-0.29	24	31
JAM3 homodimer	-0.062	0.15	-10000	0	-0.32	125	125
ICAM2	0.022	0.005	-10000	0	-10000	0	0
ICAM1	0.022	0.015	0.32	1	-10000	0	1
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.003	0.1	0.26	7	-0.31	22	29
cell adhesion	0.04	0.048	0.31	5	-0.19	4	9
NFKB1	0.003	0.11	0.27	43	-0.32	19	62
THY1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.003	-10000	0	-10000	0	0
Lipoprotein(a)	0.035	0.04	0.22	22	-10000	0	22
alphaM/beta2 Integrin/LRP/tPA	0.03	0.074	0.24	4	-0.18	44	48
IL6	-0.01	0.15	0.43	12	-0.56	20	32
ITGB2	0.025	0.033	0.33	4	-10000	0	4
elevation of cytosolic calcium ion concentration	0.052	0.047	0.25	11	-0.17	2	13
alphaM/beta2 Integrin/JAM2/JAM3	-0.062	0.15	0.3	3	-0.22	212	215
JAM2	-0.091	0.16	-10000	0	-0.32	168	168
alphaM/beta2 Integrin/ICAM1	0.082	0.079	0.24	73	-0.17	2	75
alphaM/beta2 Integrin/uPA/Plg	0.028	0.086	0.27	11	-0.17	60	71
RhoA/GTP	-0.019	0.13	0.25	7	-0.38	30	37
positive regulation of phagocytosis	0.004	0.085	0.28	5	-0.24	18	23
Ron/MSP	0.063	0.075	0.24	78	-0.22	1	79
alphaM/beta2 Integrin/uPAR/uPA	0.054	0.048	0.26	11	-0.17	2	13
alphaM/beta2 Integrin/uPAR	0.045	0.046	0.26	9	-0.19	3	12
PLAU	0.023	0.02	0.32	2	-10000	0	2
PLAT	-0.011	0.097	-10000	0	-0.32	46	46
actin filament polymerization	-0.013	0.12	0.26	11	-0.4	20	31
MST1	0.027	0.04	0.32	9	-10000	0	9
alphaM/beta2 Integrin/lipoprotein(a)	0.054	0.057	0.24	21	-0.16	3	24
TNF	0.004	0.13	0.34	42	-0.33	19	61
RAP1B	0.023	0.002	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.044	0.043	0.26	7	-0.19	2	9
fibrinolysis	0.026	0.085	0.26	11	-0.17	60	71
HCK	0.022	0.015	0.32	1	-10000	0	1
dendritic cell antigen processing and presentation	-0.003	0.1	0.26	7	-0.31	22	29
VTN	-0.024	0.12	0.32	2	-0.32	68	70
alphaM/beta2 Integrin/CYR61	0.022	0.079	0.24	4	-0.2	50	54
LPA	0.033	0.061	0.32	21	-10000	0	21
LRP1	0.021	0.022	-10000	0	-0.32	2	2
cell migration	0.065	0.078	0.21	32	-0.17	14	46
FN1	0.019	0.034	-10000	0	-0.32	5	5
alphaM/beta2 Integrin/Thy1	0.043	0.043	0.27	5	-0.19	3	8
MPO	0.025	0.033	0.32	6	-10000	0	6
KNG1	0.029	0.059	0.32	19	-10000	0	19
RAP1/GDP	0.031	0.004	-10000	0	-10000	0	0
ROCK1	-0.018	0.13	0.26	9	-0.39	27	36
ELA2	0	0	-10000	0	-10000	0	0
PLG	-0.02	0.12	0.32	5	-0.32	66	71
CTGF	0.012	0.06	-10000	0	-0.32	16	16
alphaM/beta2 Integrin/Hck	0.043	0.045	0.31	5	-0.19	2	7
ITGAM	0.021	0.037	0.32	2	-0.32	3	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.028	0.11	0.28	4	-0.17	164	168
HP	0.058	0.16	0.32	101	-0.32	33	134
leukocyte adhesion	-0.055	0.14	0.28	6	-0.28	81	87
SELP	-0.1	0.16	-10000	0	-0.32	177	177

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.002	0.083	0.23	52	-0.23	6	58
KIRREL	-0.015	0.1	-10000	0	-0.33	51	51
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.002	0.083	0.23	6	-0.23	52	58
PLCG1	0.022	0.005	-10000	0	-10000	0	0
ARRB2	0.021	0.006	-10000	0	-10000	0	0
WASL	0.022	0.005	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	0.021	0.073	0.22	6	-0.18	49	55
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.008	0.067	0.19	1	-0.2	49	50
FYN	0.016	0.12	0.23	94	-0.17	50	144
mol:Ca2+	0.018	0.07	0.21	5	-0.17	49	54
mol:DAG	0.019	0.071	0.21	5	-0.18	49	54
NPHS2	-0.011	0.023	-10000	0	-10000	0	0
mol:IP3	0.019	0.071	0.21	5	-0.18	49	54
regulation of endocytosis	0.015	0.066	0.2	6	-0.16	50	56
Nephrin/NEPH1/podocin/Cholesterol	0.011	0.066	0.2	6	-0.17	50	56
establishment of cell polarity	0.002	0.083	0.23	6	-0.23	52	58
Nephrin/NEPH1/podocin/NCK1-2	0.028	0.075	-10000	0	-0.17	49	49
Nephrin/NEPH1/beta Arrestin2	0.016	0.067	0.21	6	-0.16	50	56
NPHS1	0.017	0.048	0.32	7	-10000	0	7
Nephrin/NEPH1/podocin	0.013	0.067	0.2	6	-0.17	50	56
TJP1	0.022	0.005	-10000	0	-10000	0	0
NCK1	0.021	0.022	-10000	0	-0.32	2	2
NCK2	0.023	0.002	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.02	0.072	0.22	5	-0.18	49	54
CD2AP	0.022	0.003	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	0.019	0.072	0.22	6	-0.17	49	55
GRB2	0.021	0.006	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	0.007	0.12	0.24	87	-0.18	63	150
cytoskeleton organization	-0.022	0.073	0.2	13	-0.21	46	59
Nephrin/NEPH1	0.006	0.058	0.19	6	-0.16	51	57
Nephrin/NEPH1/ZO-1	0.012	0.072	0.22	6	-0.18	51	57

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.054	0.13	-10000	0	-0.39	50	50
CRKL	-0.057	0.14	0.2	1	-0.41	52	53
HRAS	-0.042	0.12	-10000	0	-0.37	42	42
mol:PIP3	-0.023	0.15	0.27	4	-0.38	43	47
SPRED1	0.022	0.005	-10000	0	-10000	0	0
SPRED2	0.022	0.015	-10000	0	-0.32	1	1
GAB1	-0.057	0.15	-10000	0	-0.42	54	54
FOXO3	-0.039	0.14	0.31	4	-0.4	47	51
AKT1	-0.041	0.15	0.3	2	-0.42	49	51
BAD	-0.039	0.14	0.29	2	-0.39	47	49
megakaryocyte differentiation	-0.057	0.14	-10000	0	-0.41	54	54
GSK3B	-0.038	0.14	0.29	4	-0.4	47	51
RAF1	-0.024	0.12	0.24	5	-0.31	40	45
SHC1	0.019	0.009	-10000	0	-10000	0	0
STAT3	-0.055	0.14	-10000	0	-0.43	51	51
STAT1	-0.13	0.32	-10000	0	-0.81	79	79
HRAS/SPRED1	-0.017	0.12	0.22	2	-0.31	41	43
cell proliferation	-0.056	0.14	-10000	0	-0.42	52	52
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
TEC	0.023	0.014	0.32	1	-10000	0	1
RPS6KB1	-0.052	0.16	-10000	0	-0.43	62	62
HRAS/SPRED2	-0.017	0.12	0.22	1	-0.31	39	40
LYN/TEC/p62DOK	-0.023	0.15	-10000	0	-0.4	45	45
MAPK3	-0.019	0.098	0.24	7	-0.25	32	39
STAP1	-0.055	0.15	-10000	0	-0.42	53	53
GRAP2	0.009	0.063	-10000	0	-0.32	18	18
JAK2	-0.11	0.28	-10000	0	-0.72	76	76
STAT1 (dimer)	-0.12	0.32	-10000	0	-0.79	79	79
mol:Gleevec	0.002	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.023	0.15	-10000	0	-0.41	47	47
actin filament polymerization	-0.054	0.14	0.36	1	-0.42	50	51
LYN	0.021	0.007	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.089	0.22	-10000	0	-0.54	80	80
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
CBL/CRKL/GRB2	-0.036	0.14	-10000	0	-0.38	48	48
PI3K	-0.028	0.16	-10000	0	-0.42	52	52
PTEN	0.021	0.006	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.11	0.35	-10000	0	-1.1	47	47
MAPK8	-0.057	0.15	-10000	0	-0.42	53	53
STAT3 (dimer)	-0.053	0.14	0.26	1	-0.42	51	52
positive regulation of transcription	-0.014	0.084	0.21	9	-0.21	31	40
mol:GDP	-0.037	0.13	-10000	0	-0.37	43	43
PIK3C2B	-0.053	0.14	-10000	0	-0.42	49	49
CBL/CRKL	-0.047	0.14	-10000	0	-0.39	53	53
FER	-0.057	0.14	-10000	0	-0.41	55	55
SH2B3	-0.057	0.15	-10000	0	-0.42	54	54
PDPK1	-0.022	0.14	0.28	5	-0.36	42	47
SNAI2	-0.066	0.16	0.35	2	-0.43	61	63
positive regulation of cell proliferation	-0.1	0.26	-10000	0	-0.63	81	81
KITLG	-0.02	0.11	-10000	0	-0.34	52	52
cell motility	-0.1	0.26	-10000	0	-0.63	81	81
PTPN6	0.023	0.013	-10000	0	-10000	0	0
EPOR	-0.04	0.18	-10000	0	-0.8	13	13
STAT5A (dimer)	-0.087	0.22	-10000	0	-0.54	79	79
SOCS1	0.021	0.016	-10000	0	-0.32	1	1
cell migration	0.056	0.14	0.42	53	-10000	0	53
SOS1	0.022	0.004	-10000	0	-10000	0	0
EPO	0.01	0.037	0.32	1	-0.33	3	4
VAV1	0.024	0.034	0.32	5	-0.32	1	6
GRB10	-0.056	0.15	0.35	2	-0.42	52	54
PTPN11	0.023	0.011	-10000	0	-10000	0	0
SCF/KIT	-0.054	0.15	-10000	0	-0.43	54	54
GO:0007205	0.003	0.008	-10000	0	-10000	0	0
MAP2K1	-0.02	0.097	0.24	9	-0.25	37	46
CBL	0.022	0.005	-10000	0	-10000	0	0
KIT	-0.1	0.34	-10000	0	-1.1	48	48
MAP2K2	-0.019	0.095	0.24	8	-0.25	35	43
SHC/Grb2/SOS1	-0.026	0.14	-10000	0	-0.39	47	47
STAT5A	-0.09	0.23	-10000	0	-0.56	79	79
GRB2	0.021	0.006	-10000	0	-10000	0	0
response to radiation	-0.064	0.15	0.35	2	-0.42	61	63
SHC/GRAP2	0.019	0.042	-10000	0	-0.22	13	13
PTPRO	-0.058	0.15	-10000	0	-0.42	54	54
SH2B2	-0.055	0.14	0.36	1	-0.42	50	51
DOK1	0.022	0.003	-10000	0	-10000	0	0
MATK	-0.057	0.15	-10000	0	-0.43	53	53
CREBBP	0.007	0.056	-10000	0	-0.18	9	9
BCL2	-0.13	0.38	-10000	0	-1	67	67

Osteopontin-mediated events

Figure S40. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S40. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.006	0.085	0.22	3	-0.18	3	6
NF kappa B1 p50/RelA/I kappa B alpha	0.001	0.099	0.34	7	-0.28	3	10
alphaV/beta3 Integrin/Osteopontin/Src	0.084	0.089	0.24	126	-10000	0	126
AP1	-0.046	0.14	0.26	2	-0.3	54	56
ILK	-0.014	0.087	0.31	4	-0.2	2	6
bone resorption	-0.021	0.086	0.28	4	-0.29	6	10
PTK2B	0.02	0.008	-10000	0	-10000	0	0
PYK2/p130Cas	0.04	0.12	0.3	2	-0.16	64	66
ITGAV	0.023	0.006	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.023	0.048	-10000	0	-0.22	18	18
alphaV/beta3 Integrin/Osteopontin	0.044	0.13	0.23	113	-0.19	84	197
MAP3K1	-0.016	0.087	0.21	9	-0.17	80	89
JUN	0.018	0.037	-10000	0	-0.32	6	6
MAPK3	-0.019	0.078	0.24	8	-0.18	2	10
MAPK1	-0.02	0.078	0.22	9	-10000	0	9
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MAPK8	-0.022	0.078	0.21	8	-0.24	5	13
ITGB3	-0.041	0.14	0.32	2	-0.32	96	98
NFKBIA	-0.015	0.078	0.31	5	-0.21	2	7
FOS	-0.09	0.16	-10000	0	-0.32	166	166
CD44	0.015	0.048	-10000	0	-0.32	10	10
CHUK	0.022	0.005	-10000	0	-10000	0	0
PLAU	-0.024	0.1	0.51	3	-0.48	3	6
NF kappa B1 p50/RelA	0.016	0.09	0.29	7	-10000	0	7
BCAR1	0.02	0.008	-10000	0	-10000	0	0
RELA	0.023	0.003	-10000	0	-10000	0	0
alphaV beta3 Integrin	-0.014	0.1	0.24	2	-0.22	95	97
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.014	0.089	0.24	11	-0.17	78	89
VAV3	0.002	0.096	0.19	40	-0.16	62	102
MAP3K14	-0.015	0.088	0.22	10	-0.18	4	14
ROCK2	0.016	0.045	-10000	0	-0.32	9	9
SPP1	0.099	0.13	0.32	129	-10000	0	129
RAC1	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	0.003	0.091	0.18	40	-10000	0	40
MMP2	-0.07	0.11	0.29	1	-0.31	49	50

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.024	0.072	-10000	0	-0.16	61	61
ER alpha/Gai/GDP/Gbeta gamma	-0.12	0.21	-10000	0	-0.47	89	89
AKT1	-0.076	0.24	-10000	0	-0.71	61	61
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.075	0.25	-10000	0	-0.73	61	61
mol:Ca2+	-0.042	0.11	-10000	0	-0.33	54	54
IGF1R	0.01	0.063	-10000	0	-0.32	18	18
E2/ER alpha (dimer)/Striatin	0.007	0.066	-10000	0	-0.18	54	54
SHC1	0.019	0.009	-10000	0	-10000	0	0
apoptosis	0.073	0.23	0.68	61	-10000	0	61
RhoA/GTP	-0.035	0.039	-10000	0	-0.15	47	47
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.08	0.17	-10000	0	-0.42	74	74
regulation of stress fiber formation	0.03	0.055	0.24	2	-0.22	4	6
E2/ERA-ERB (dimer)	0.007	0.066	-10000	0	-0.18	53	53
KRAS	0.022	0.004	-10000	0	-10000	0	0
G13/GTP	0.008	0.059	-10000	0	-0.16	52	52
pseudopodium formation	-0.03	0.055	0.22	4	-0.24	2	6
E2/ER alpha (dimer)/PELP1	0.007	0.064	-10000	0	-0.18	50	50
GRB2	0.021	0.006	-10000	0	-10000	0	0
GNG2	0.013	0.058	0.32	1	-0.32	14	15
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
HRAS	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.088	0.19	-10000	0	-0.49	71	71
E2/ER beta (dimer)	0.017	0.003	-10000	0	-10000	0	0
mol:GDP	-0.019	0.093	-10000	0	-0.3	48	48
mol:NADP	-0.088	0.19	-10000	0	-0.49	71	71
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	-0.044	0.11	-10000	0	-0.34	54	54
IGF-1R heterotetramer	0.01	0.063	-10000	0	-0.32	18	18
PLCB1	-0.04	0.12	-10000	0	-0.35	60	60
PLCB2	-0.035	0.11	-10000	0	-0.34	55	55
IGF1	-0.045	0.14	-10000	0	-0.32	101	101
mol:L-citrulline	-0.088	0.19	-10000	0	-0.49	71	71
RHOA	0.022	0.005	-10000	0	-10000	0	0
Gai/GDP	-0.2	0.31	-10000	0	-0.62	171	171
JNK cascade	0.016	0.003	-10000	0	-10000	0	0
BCAR1	0.02	0.008	-10000	0	-10000	0	0
ESR2	0.022	0.004	-10000	0	-10000	0	0
GNAQ	0.021	0.016	-10000	0	-0.32	1	1
ESR1	-0.013	0.1	-10000	0	-0.32	53	53
Gq family/GDP/Gbeta gamma	-0.07	0.23	-10000	0	-0.66	57	57
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	-0.023	0.12	-10000	0	-0.68	11	11
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.075	0.16	-10000	0	-0.42	66	66
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
E2/ER alpha (dimer)	-0.008	0.071	-10000	0	-0.22	53	53
STRN	0.021	0.022	-10000	0	-0.32	2	2
GNAL	-0.035	0.13	-10000	0	-0.32	85	85
PELP1	0.021	0.006	-10000	0	-10000	0	0
MAPK11	-0.011	0.012	-10000	0	-0.18	2	2
GNAI2	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNAI1	0.016	0.045	-10000	0	-0.32	9	9
HBEGF	-0.086	0.19	0.3	2	-0.47	67	69
cAMP biosynthetic process	-0.021	0.083	-10000	0	-0.16	121	121
SRC	-0.11	0.19	-10000	0	-0.47	79	79
PI3K	0.027	0.028	-10000	0	-0.22	5	5
GNB1	0.022	0.004	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	0.004	0.096	-10000	0	-0.27	46	46
SOS1	0.022	0.004	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.093	0.15	-10000	0	-0.36	91	91
Gs family/GTP	-0.017	0.086	-10000	0	-0.16	121	121
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.041	0.012	-10000	0	-10000	0	0
vasodilation	-0.084	0.18	-10000	0	-0.47	71	71
mol:DAG	-0.044	0.11	-10000	0	-0.34	54	54
Gs family/GDP/Gbeta gamma	-0.035	0.1	-10000	0	-0.29	52	52
MSN	-0.032	0.058	0.23	4	-0.26	2	6
Gq family/GTP	-0.035	0.13	-10000	0	-0.36	62	62
mol:PI-3-4-5-P3	-0.071	0.24	-10000	0	-0.7	61	61
NRAS	0.023	0.001	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.084	0.18	0.47	71	-10000	0	71
GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
RhoA/GDP	-0.007	0.095	-10000	0	-0.29	47	47
NOS3	-0.092	0.2	-10000	0	-0.52	70	70
GNA11	0.015	0.045	-10000	0	-0.32	9	9
MAPKKK cascade	-0.071	0.19	-10000	0	-0.52	68	68
E2/ER alpha (dimer)/PELP1/Src	-0.085	0.18	0.25	1	-0.43	77	78
ruffle organization	-0.03	0.055	0.22	4	-0.24	2	6
ROCK2	-0.029	0.064	0.26	5	-0.28	2	7
GNA14	-0.008	0.095	-10000	0	-0.32	43	43
GNA15	0.025	0.036	0.32	7	-10000	0	7
GNA13	0.022	0.005	-10000	0	-10000	0	0
MMP9	-0.077	0.19	0.32	4	-0.46	64	68
MMP2	-0.11	0.19	0.24	1	-0.49	68	69

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.025	0.066	0.22	1	-0.2	35	36
NF kappa B1 p50/RelA/I kappa B alpha	0.01	0.09	0.31	5	-0.26	9	14
AP1	-0.023	0.12	0.21	8	-0.18	165	173
mol:PIP3	-0.024	0.057	-10000	0	-0.18	44	44
AKT1	-0.019	0.067	0.28	3	-0.27	9	12
PTK2B	-0.023	0.095	0.19	1	-0.28	38	39
RHOA	-0.005	0.056	0.21	3	-0.29	12	15
PIK3CB	0.022	0.005	-10000	0	-10000	0	0
mol:Ca2+	-0.004	0.06	0.23	10	-0.25	4	14
MAGI3	0.023	0.001	-10000	0	-10000	0	0
RELA	0.023	0.003	-10000	0	-10000	0	0
apoptosis	0.001	0.068	-10000	0	-0.2	39	39
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.029	0.09	0.22	7	-0.27	35	42
NF kappa B1 p50/RelA	0.02	0.095	0.21	11	-0.23	27	38
endothelial cell migration	-0.01	0.086	-10000	0	-0.35	27	27
ADCY4	-0.06	0.12	-10000	0	-0.32	65	65
ADCY5	-0.083	0.14	-10000	0	-0.33	81	81
ADCY6	-0.051	0.11	-10000	0	-0.3	53	53
ADCY7	-0.048	0.1	-10000	0	-0.31	46	46
ADCY1	-0.055	0.12	-10000	0	-0.32	55	55
ADCY2	-0.13	0.15	-10000	0	-0.35	125	125
ADCY3	-0.051	0.11	-10000	0	-0.3	55	55
ADCY8	-0.061	0.11	-10000	0	-0.31	52	52
ADCY9	-0.073	0.13	-10000	0	-0.32	85	85
GSK3B	-0.024	0.094	0.22	8	-0.28	37	45
arachidonic acid secretion	-0.067	0.12	-10000	0	-0.32	65	65
GNG2	0.014	0.058	0.32	1	-0.32	14	15
TRIP6	0.01	0.032	-10000	0	-0.32	4	4
GNAO1	-0.043	0.097	-10000	0	-0.21	120	120
HRAS	0.022	0.005	-10000	0	-10000	0	0
NFKBIA	-0.011	0.085	0.28	6	-0.25	20	26
GAB1	0.019	0.03	-10000	0	-0.32	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	0.001	0.18	-10000	0	-0.83	23	23
JUN	0.019	0.037	-10000	0	-0.32	6	6
LPA/LPA2/NHERF2	0.027	0.024	0.21	2	-10000	0	2
TIAM1	-0.015	0.21	-10000	0	-0.96	23	23
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	-0.004	0.06	0.23	10	-0.25	4	14
PLCB3	-0.005	0.038	0.18	16	-10000	0	16
FOS	-0.09	0.16	-10000	0	-0.32	166	166
positive regulation of mitosis	-0.067	0.12	-10000	0	-0.32	65	65
LPA/LPA1-2-3	0.043	0.088	0.22	50	-0.19	39	89
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0	-10000	0	-10000	0	0
BCAR1	0.02	0.008	-10000	0	-10000	0	0
stress fiber formation	-0.006	0.08	0.21	2	-0.28	19	21
GNAZ	-0.014	0.066	-10000	0	-0.2	50	50
EGFR/PI3K-beta/Gab1	-0.018	0.066	-10000	0	-0.19	43	43
positive regulation of dendritic cell cytokine production	0.041	0.087	0.21	50	-0.19	39	89
LPA/LPA2/MAGI-3	0.028	0.025	0.21	2	-10000	0	2
ARHGEF1	-0.018	0.048	0.18	14	-0.19	15	29
GNAI2	-0.004	0.05	-10000	0	-0.21	26	26
GNAI3	-0.005	0.051	-10000	0	-0.21	27	27
GNAI1	-0.007	0.055	-10000	0	-0.2	33	33
LPA/LPA3	0.029	0.082	0.21	59	-0.16	30	89
LPA/LPA2	0.015	0.024	0.22	2	-0.092	13	15
LPA/LPA1	0.005	0.061	-10000	0	-0.23	30	30
HB-EGF/EGFR	0.065	0.065	0.15	58	-0.19	5	63
HBEGF	0.064	0.091	0.17	216	-0.22	1	217
mol:DAG	-0.004	0.06	0.23	10	-0.25	4	14
cAMP biosynthetic process	-0.087	0.12	0.23	1	-0.28	106	107
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
SRC	0.022	0.005	-10000	0	-10000	0	0
GNB1	0.022	0.005	-10000	0	-10000	0	0
LYN	-0.003	0.087	0.27	10	-0.24	16	26
GNAQ	0.01	0.051	0.22	2	-0.19	18	20
LPAR2	0.023	0.02	0.32	2	-10000	0	2
LPAR3	0.046	0.12	0.32	59	-0.32	17	76
LPAR1	0.009	0.061	-10000	0	-0.24	25	25
IL8	0.053	0.16	0.34	81	-0.36	17	98
PTK2	-0.011	0.058	0.18	7	-0.18	33	40
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
CASP3	0.001	0.068	-10000	0	-0.2	39	39
EGFR	0.014	0.054	-10000	0	-0.32	13	13
PLCG1	0.001	0.06	0.17	6	-0.2	22	28
PLD2	-0.013	0.061	0.18	6	-0.22	16	22
G12/G13	0.03	0.055	-10000	0	-0.19	24	24
PI3K-beta	-0.002	0.064	-10000	0	-0.28	12	12
cell migration	0.002	0.065	-10000	0	-0.25	22	22
SLC9A3R2	0.022	0.005	-10000	0	-10000	0	0
PXN	-0.007	0.081	0.22	2	-0.29	19	21
HRAS/GTP	-0.068	0.12	-10000	0	-0.33	64	64
RAC1	0.022	0.005	-10000	0	-10000	0	0
MMP9	0.15	0.15	0.32	213	-10000	0	213
PRKCE	0.022	0.003	-10000	0	-10000	0	0
PRKCD	-0.01	0.068	0.27	7	-0.24	7	14
Gi(beta/gamma)	-0.051	0.11	-10000	0	-0.31	49	49
mol:LPA	-0.004	0.025	-10000	0	-0.13	16	16
TRIP6/p130 Cas/FAK1/Paxillin	0.011	0.08	-10000	0	-0.29	14	14
MAPKKK cascade	-0.067	0.12	-10000	0	-0.32	65	65
contractile ring contraction involved in cytokinesis	-0.006	0.059	0.21	3	-0.28	14	17
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	-0.004	0.075	0.22	2	-0.2	51	53
GNA15	0.013	0.053	0.17	8	-0.19	16	24
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
MAPT	-0.029	0.091	0.22	7	-0.28	34	41
GNA11	0.007	0.057	0.22	1	-0.19	26	27
Rac1/GTP	0	0.19	-10000	0	-0.88	23	23
MMP2	-0.01	0.086	-10000	0	-0.35	27	27

IL23-mediated signaling events

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
CCL2	0.23	0.32	0.76	40	-1.1	8	48
IL23A	0.26	0.32	0.83	37	-1.2	5	42
NF kappa B1 p50/RelA/I kappa B alpha	0.18	0.26	0.62	15	-1	6	21
positive regulation of T cell mediated cytotoxicity	0.26	0.34	0.84	52	-1.1	7	59
ITGA3	0.24	0.3	0.75	40	-1.1	5	45
IL17F	0.18	0.23	0.57	55	-0.64	7	62
IL12B	0.079	0.074	0.24	43	-10000	0	43
STAT1 (dimer)	0.23	0.29	0.7	42	-1	7	49
CD4	0.24	0.3	0.76	42	-1.1	4	46
IL23	0.24	0.29	0.76	31	-1.2	5	36
IL23R	0.14	0.15	0.56	19	-0.58	1	20
IL1B	0.25	0.32	0.8	44	-1.1	7	51
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.27	0.32	0.81	56	-1	5	61
TYK2	0.054	0.049	0.18	21	-10000	0	21
STAT4	0.022	0.015	-10000	0	-0.32	1	1
STAT3	0.021	0.008	-10000	0	-10000	0	0
IL18RAP	0.02	0.038	0.35	3	-0.32	3	6
IL12RB1	0.058	0.076	0.29	20	-0.34	4	24
PIK3CA	0.019	0.017	-10000	0	-0.32	1	1
IL12Rbeta1/TYK2	0.067	0.071	0.26	23	-0.25	4	27
IL23R/JAK2	0.17	0.16	0.52	33	-10000	0	33
positive regulation of chronic inflammatory response	0.26	0.34	0.84	52	-1.1	7	59
natural killer cell activation	-0.01	0.013	-10000	0	-0.05	19	19
JAK2	0.073	0.09	0.24	45	-0.32	9	54
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
NFKB1	0.027	0.019	-10000	0	-0.32	1	1
RELA	0.028	0.011	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	0.24	0.29	0.75	34	-1.1	5	39
ALOX12B	0.25	0.3	0.76	44	-1	5	49
CXCL1	0.24	0.36	0.8	53	-1	16	69
T cell proliferation	0.26	0.34	0.84	52	-1.1	7	59
NFKBIA	0.027	0.011	-10000	0	-10000	0	0
IL17A	0.18	0.22	0.53	63	-0.53	5	68
PI3K	0.18	0.27	0.64	27	-0.97	7	34
IFNG	0.033	0.055	0.18	43	-0.11	2	45
STAT3 (dimer)	0.17	0.26	0.61	17	-0.93	7	24
IL18R1	0.018	0.033	-10000	0	-0.32	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.21	0.26	0.62	67	-0.8	5	72
IL18/IL18R	0.04	0.06	0.34	8	-0.19	7	15
macrophage activation	0.018	0.027	0.054	129	-0.044	5	134
TNF	0.26	0.32	0.82	43	-1.3	5	48
STAT3/STAT4	0.21	0.27	0.64	31	-0.98	7	38
STAT4 (dimer)	0.23	0.29	0.7	41	-1	7	48
IL18	0.024	0.039	0.34	7	-10000	0	7
IL19	0.29	0.33	0.84	56	-1	5	61
STAT5A (dimer)	0.22	0.29	0.7	39	-1	7	46
STAT1	0.023	0.014	0.32	1	-10000	0	1
SOCS3	0.018	0.037	-10000	0	-0.32	6	6
CXCL9	0.25	0.33	0.79	54	-1	9	63
MPO	0.24	0.3	0.76	44	-1	5	49
positive regulation of humoral immune response	0.26	0.34	0.84	52	-1.1	7	59
IL23/IL23R/JAK2/TYK2	0.26	0.34	0.85	49	-1.1	7	56
IL6	0.22	0.36	0.76	42	-1	20	62
STAT5A	0.022	0.006	-10000	0	-10000	0	0
IL2	0.005	0.064	0.32	16	-10000	0	16
positive regulation of tyrosine phosphorylation of STAT protein	-0.01	0.013	-10000	0	-0.05	19	19
CD3E	0.23	0.32	0.78	42	-1.1	11	53
keratinocyte proliferation	0.26	0.34	0.84	52	-1.1	7	59
NOS2	0.24	0.31	0.77	43	-0.95	9	52

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	0.066	0.088	0.17	210	-10000	0	210
TP53	0.013	0.047	-10000	0	-0.12	25	25
Senescence	0.013	0.047	-10000	0	-0.14	1	1
Apoptosis	0.013	0.047	-10000	0	-0.14	1	1
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	-0.05	0.062	0.24	6	-0.19	8	14
MDM4	0.019	0.009	-10000	0	-10000	0	0

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.014	0.059	-10000	0	-0.22	26	26
PDGFRB	0.004	0.065	-10000	0	-0.32	18	18
SPHK1	-0.02	0.12	-10000	0	-0.8	11	11
mol:S1P	-0.026	0.11	-10000	0	-0.71	11	11
S1P1/S1P/Gi	-0.12	0.2	0.22	4	-0.45	100	104
GNAO1	-0.06	0.14	-10000	0	-0.32	113	113
PDGFB-D/PDGFRB/PLCgamma1	-0.098	0.18	0.27	3	-0.4	101	104
PLCG1	-0.11	0.18	0.23	6	-0.42	98	104
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.065	-10000	0	-0.32	18	18
GNAI2	0.016	0.017	-10000	0	-10000	0	0
GNAI3	0.016	0.017	-10000	0	-10000	0	0
GNAI1	0.01	0.048	-10000	0	-0.32	9	9
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.021	0.04	-10000	0	-0.18	26	26
S1P1/S1P	-0.034	0.096	0.21	2	-0.42	16	18
negative regulation of cAMP metabolic process	-0.11	0.19	0.22	4	-0.44	100	104
MAPK3	-0.14	0.23	0.26	7	-0.55	98	105
calcium-dependent phospholipase C activity	-0.002	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
RhoA/GDP	0.016	0.003	-10000	0	-10000	0	0
KDR	0	0.077	-10000	0	-0.32	27	27
PLCB2	-0.032	0.089	0.22	4	-0.38	15	19
RAC1	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.028	0.082	-10000	0	-0.36	16	16
receptor internalization	-0.033	0.088	-10000	0	-0.39	16	16
PTGS2	-0.17	0.33	0.36	1	-0.89	77	78
Rac1/GTP	-0.028	0.083	-10000	0	-0.36	16	16
RHOA	0.022	0.005	-10000	0	-10000	0	0
VEGFA	0.018	0.014	-10000	0	-10000	0	0
negative regulation of T cell proliferation	-0.11	0.19	0.22	4	-0.44	100	104
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	-0.001	0.077	-10000	0	-0.32	26	26
MAPK1	-0.14	0.24	0.26	4	-0.56	96	100
S1P1/S1P/PDGFB-D/PDGFRB	-0.031	0.11	0.25	4	-0.35	26	30
ABCC1	0.016	0.016	-10000	0	-10000	0	0

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.031	0.029	0.24	3	-0.22	4	7
CRKL	-0.032	0.13	0.32	2	-0.5	25	27
mol:PIP3	-0.01	0.12	-10000	0	-0.8	12	12
AKT1	-0.011	0.12	0.34	2	-0.71	12	14
PTK2B	0.02	0.008	-10000	0	-10000	0	0
RAPGEF1	-0.034	0.12	0.29	3	-0.48	24	27
RANBP10	0.02	0.008	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
HGF/MET/SHIP2	0.003	0.094	0.22	4	-0.19	89	93
MAP3K5	-0.026	0.13	0.26	6	-0.45	28	34
HGF/MET/CIN85/CBL/ENDOPHILINS	0.014	0.092	0.23	4	-0.18	88	92
AP1	-0.052	0.11	0.17	2	-0.2	150	152
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
apoptosis	-0.23	0.36	-10000	0	-0.71	177	177
STAT3 (dimer)	-0.024	0.087	0.2	2	-0.21	71	73
GAB1/CRKL/SHP2/PI3K	-0.007	0.13	0.27	2	-0.45	23	25
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
CBL/CRK	-0.021	0.13	0.3	3	-0.47	25	28
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0
ELK1	0.009	0.095	0.3	38	-10000	0	38
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.019	0.072	-10000	0	-0.26	25	25
PAK1	-0.012	0.12	0.35	6	-0.68	12	18
HGF/MET/RANBP10	0.001	0.092	0.22	4	-0.19	89	93
HRAS	-0.034	0.13	-10000	0	-0.53	21	21
DOCK1	-0.031	0.13	0.32	7	-0.46	27	34
GAB1	-0.029	0.13	-10000	0	-0.5	25	25
CRK	-0.03	0.13	0.29	3	-0.5	24	27
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.06	0.18	-10000	0	-0.42	93	93
JUN	0.019	0.037	-10000	0	-0.32	6	6
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.021	0.067	-10000	0	-0.16	86	86
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
cell morphogenesis	-0.027	0.13	0.28	15	-0.39	23	38
GRB2/SHC	-0.001	0.068	-10000	0	-0.22	16	16
FOS	-0.09	0.16	-10000	0	-0.32	166	166
GLMN	0.002	0.001	-10000	0	-10000	0	0
cell motility	0.009	0.095	0.3	38	-10000	0	38
HGF/MET/MUC20	-0.007	0.087	0.21	4	-0.19	89	93
cell migration	-0.001	0.067	-10000	0	-0.21	18	18
GRB2	0.021	0.006	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
MET/RANBP10	0.029	0.031	0.24	4	-0.22	4	8
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.017	0.082	0.19	1	-0.2	77	78
MET/MUC20	0.016	0.028	0.22	4	-0.22	4	8
RAP1B	-0.035	0.12	0.27	4	-0.46	23	27
RAP1A	-0.037	0.12	0.28	3	-0.46	23	26
HGF/MET/RANBP9	0.005	0.092	0.23	3	-0.2	84	87
RAF1	-0.032	0.13	-10000	0	-0.51	20	20
STAT3	-0.024	0.086	0.2	2	-0.21	70	72
cell proliferation	-0.015	0.14	0.29	15	-0.31	64	79
RPS6KB1	-0.009	0.054	-10000	0	-0.27	14	14
MAPK3	0.007	0.14	0.74	15	-10000	0	15
MAPK1	0.016	0.16	0.62	28	-10000	0	28
RANBP9	0.022	0.004	-10000	0	-10000	0	0
MAPK8	-0.021	0.13	0.31	2	-0.44	29	31
SRC	-0.026	0.075	0.22	2	-0.19	71	73
PI3K	0.001	0.075	-10000	0	-0.23	19	19
MET/Glomulin	0.016	0.031	0.22	4	-0.18	4	8
SOS1	0.022	0.004	-10000	0	-10000	0	0
MAP2K1	-0.031	0.12	-10000	0	-0.48	20	20
MET	0.022	0.041	0.32	4	-0.32	4	8
MAP4K1	-0.027	0.14	0.3	3	-0.48	27	30
PTK2	0.02	0.007	-10000	0	-10000	0	0
MAP2K2	-0.032	0.12	-10000	0	-0.47	20	20
BAD	-0.012	0.12	0.4	4	-0.68	12	16
MAP2K4	-0.026	0.12	0.27	4	-0.42	25	29
SHP2/GRB2/SOS1/GAB1	-0.011	0.12	-10000	0	-0.45	24	24
INPPL1	0.022	0.003	-10000	0	-10000	0	0
PXN	0.022	0.003	-10000	0	-10000	0	0
SH3KBP1	0.022	0.003	-10000	0	-10000	0	0
HGS	-0.027	0.058	-10000	0	-0.15	81	81
PLCgamma1/PKC	0.016	0.004	-10000	0	-10000	0	0
HGF	-0.037	0.13	-10000	0	-0.32	88	88
RASA1	0.019	0.034	-10000	0	-0.32	5	5
NCK1	0.021	0.022	-10000	0	-0.32	2	2
PTPRJ	0.023	0.014	0.32	1	-10000	0	1
NCK/PLCgamma1	-0.001	0.079	-10000	0	-0.17	82	82
PDPK1	-0.011	0.12	0.25	1	-0.74	12	13
HGF/MET/SHIP	0.004	0.094	0.22	4	-0.19	88	92

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.045	0.5	0.83	1	-1.1	38	39
STAT6 (cleaved dimer)	-0.091	0.46	-10000	0	-1.1	48	48
IGHG1	0.036	0.26	0.47	47	-1.1	3	50
IGHG3	-0.062	0.48	0.71	1	-1	48	49
AKT1	-0.002	0.3	0.57	2	-0.8	14	16
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.028	0.24	0.52	3	-0.74	10	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.002	0.32	0.53	9	-0.83	16	25
THY1	-0.054	0.5	0.77	3	-1.1	43	46
MYB	0.06	0.099	0.32	63	-10000	0	63
HMGA1	0.064	0.1	0.32	70	-10000	0	70
IL4/IL4R/JAK1/IL2R gamma/JAK3	0.012	0.35	0.61	17	-0.73	25	42
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	0.015	0.3	0.53	10	-0.9	10	20
SP1	0.024	0.013	-10000	0	-0.12	1	1
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
SOCS5	-0.003	0.044	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.072	0.48	-10000	0	-1.1	48	48
SOCS1	-0.024	0.35	0.57	1	-0.72	37	38
SOCS3	0.003	0.31	0.57	4	-0.91	14	18
FCER2	-0.04	0.44	0.72	12	-0.97	36	48
PARP14	0.023	0.009	-10000	0	-10000	0	0
CCL17	-0.048	0.51	0.82	11	-1.1	43	54
GRB2	0.021	0.006	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.036	0.26	0.49	16	-0.68	10	26
T cell proliferation	-0.083	0.48	-10000	0	-1.1	44	44
IL4R/JAK1	-0.075	0.49	-10000	0	-1.1	43	43
EGR2	-0.089	0.56	0.88	2	-1.3	49	51
JAK2	0.021	0.092	0.2	8	-0.34	8	16
JAK3	0.019	0.032	0.34	3	-0.12	1	4
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
JAK1	0.018	0.049	-10000	0	-0.31	3	3
COL1A2	0.024	0.26	0.52	1	-1	9	10
CCL26	-0.055	0.5	0.83	1	-1.1	40	41
IL4R	-0.049	0.55	0.88	8	-1.2	39	47
PTPN6	0.001	0.037	-10000	0	-10000	0	0
IL13RA2	-0.044	0.51	0.81	10	-1.1	42	52
IL13RA1	0.027	0.082	0.2	9	-10000	0	9
IRF4	0.023	0.26	0.59	4	-0.94	19	23
ARG1	0.041	0.22	0.52	2	-0.66	4	6
CBL	0.002	0.32	0.56	10	-0.68	25	35
GTF3A	0.024	0.006	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
IL13RA1/JAK2	0.044	0.12	0.26	49	-0.24	7	56
IRF4/BCL6	0.013	0.22	-10000	0	-0.9	18	18
CD40LG	0.018	0.055	0.18	2	-0.27	14	16
MAPK14	0.004	0.33	0.56	11	-0.74	22	33
mitosis	0.002	0.29	0.54	3	-0.76	13	16
STAT6	-0.042	0.59	0.95	13	-1.3	44	57
SPI1	0.025	0.024	0.32	3	-10000	0	3
RPS6KB1	0.002	0.28	0.54	2	-0.73	13	15
STAT6 (dimer)	-0.041	0.59	0.96	13	-1.3	44	57
STAT6 (dimer)/PARP14	-0.08	0.51	0.75	2	-1.2	47	49
mast cell activation	-0.005	0.022	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.008	0.3	0.53	11	-0.77	17	28
FRAP1	-0.002	0.3	0.57	2	-0.8	14	16
LTA	-0.05	0.51	0.82	6	-1.1	40	46
FES	0.021	0.016	-10000	0	-0.32	1	1
T-helper 1 cell differentiation	0.038	0.58	1.2	44	-0.95	13	57
CCL11	-0.13	0.55	0.7	1	-1.2	68	69
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.015	0.29	0.52	10	-0.84	11	21
IL2RG	0.019	0.044	0.35	5	-0.31	2	7
IL10	-0.019	0.52	0.87	20	-1.2	31	51
IRS1	-0.008	0.098	-10000	0	-0.32	46	46
IRS2	-0.022	0.11	-10000	0	-0.32	64	64
IL4	0.048	0.25	0.61	8	-1.1	7	15
IL5	-0.058	0.5	0.83	1	-1.2	38	39
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.01	0.47	0.72	38	-0.94	39	77
COL1A1	0.015	0.31	0.57	8	-1	14	22
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.084	0.49	-10000	0	-1.2	39	39
IL2R gamma/JAK3	0.035	0.045	0.34	6	-0.19	3	9
TFF3	-0.033	0.59	0.79	42	-1.2	51	93
ALOX15	-0.025	0.52	0.8	38	-1.2	36	74
MYBL1	0.021	0.007	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.06	0.46	0.69	7	-0.96	53	60
SHC1	0.019	0.009	-10000	0	-10000	0	0
CEBPB	0.022	0.008	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.005	0.3	0.51	9	-0.78	17	26
mol:PI-3-4-5-P3	-0.001	0.3	0.57	2	-0.8	14	16
PI3K	-0.006	0.31	0.58	2	-0.87	14	16
DOK2	0.022	0.025	0.32	3	-10000	0	3
ETS1	-0.008	0.049	-10000	0	-0.3	2	2
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.039	0.25	0.47	19	-0.62	10	29
ITGB3	-0.19	0.64	0.78	2	-1.3	96	98
PIGR	-0.016	0.6	0.82	56	-1.4	41	97
IGHE	-0.008	0.085	0.18	23	-0.2	13	36
MAPKKK cascade	0.039	0.24	0.47	19	-0.61	10	29
BCL6	0.019	0.018	-10000	0	-0.32	1	1
OPRM1	-0.057	0.5	0.89	2	-1.1	39	41
RETNLB	-0.055	0.5	0.93	2	-1.1	39	41
SELP	-0.28	0.73	0.86	20	-1.2	152	172
AICDA	-0.064	0.48	0.7	1	-1.1	43	44

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.1	0.2	-10000	0	-0.52	51	51
MAP3K8	0.006	0.038	-10000	0	-0.32	5	5
FOS	-0.069	0.16	-10000	0	-0.48	45	45
PRKCA	-0.013	0.079	-10000	0	-0.32	29	29
PTPN7	0.007	0.041	0.31	6	-10000	0	6
HRAS	0.021	0.006	-10000	0	-10000	0	0
PRKCB	-0.012	0.078	-10000	0	-0.32	28	28
NRAS	0.022	0.005	-10000	0	-10000	0	0
RAS family/GTP	0.018	0.035	-10000	0	-10000	0	0
MAPK3	-0.034	0.14	-10000	0	-0.68	16	16
MAP2K1	-0.063	0.15	-10000	0	-0.41	64	64
ELK1	0.003	0.028	-10000	0	-10000	0	0
BRAF	-0.04	0.12	-10000	0	-0.36	54	54
mol:GTP	-0.001	0.002	-10000	0	-0.004	172	172
MAPK1	-0.039	0.14	-10000	0	-0.6	21	21
RAF1	-0.041	0.13	-10000	0	-0.38	52	52
KRAS	0.021	0.005	-10000	0	-10000	0	0

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.022	0.004	-10000	0	-10000	0	0
VLDLR	0.02	0.022	-10000	0	-0.32	2	2
LRPAP1	0.022	0.004	-10000	0	-10000	0	0
NUDC	0.022	0.005	-10000	0	-10000	0	0
RELN/LRP8	-0.035	0.11	0.26	5	-0.19	173	178
CaM/Ca2+	0.016	0.003	-10000	0	-10000	0	0
KATNA1	0.022	0.003	-10000	0	-10000	0	0
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	-0.065	0.081	0.19	9	-0.17	163	172
IQGAP1/CaM	0.032	0.008	-10000	0	-10000	0	0
DAB1	0.027	0.044	0.32	11	-10000	0	11
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
PLA2G7	0.023	0.024	0.32	2	-0.32	1	3
CALM1	0.022	0.004	-10000	0	-10000	0	0
DYNLT1	0.022	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.034	0.017	0.24	3	-10000	0	3
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.022	0.003	-10000	0	-10000	0	0
CDK5R1	0.022	0.015	0.32	1	-10000	0	1
LIS1/Poliovirus Protein 3A	-0.011	0.004	-10000	0	-10000	0	0
CDK5R2	0.05	0.091	0.32	50	-10000	0	50
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	-0.035	0.12	0.24	12	-0.19	173	185
YWHAE	0.021	0.006	-10000	0	-10000	0	0
NDEL1/14-3-3 E	-0.051	0.088	0.29	10	-0.21	5	15
MAP1B	-0.006	0.046	-10000	0	-0.22	23	23
RAC1	0.007	0.003	-10000	0	-10000	0	0
p35/CDK5	-0.065	0.073	0.18	7	-10000	0	7
RELN	-0.094	0.17	0.32	5	-0.32	176	181
PAFAH/LIS1	0.019	0.017	0.22	2	-0.19	1	3
LIS1/CLIP170	0.019	0.007	-10000	0	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.061	0.063	0.17	1	-0.19	1	2
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.05	0.1	0.29	2	-0.18	164	166
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	-0.049	0.08	0.29	5	-0.21	3	8
LIS1/IQGAP1	0.019	0.007	-10000	0	-10000	0	0
RHOA	0.007	0.003	-10000	0	-10000	0	0
PAFAH1B1	-0.014	0.005	-10000	0	-10000	0	0
PAFAH1B3	0.027	0.038	0.32	8	-10000	0	8
PAFAH1B2	0.021	0.016	-10000	0	-0.32	1	1
MAP1B/LIS1/Dynein heavy chain	0.007	0.042	-10000	0	-0.16	21	21
NDEL1/Katanin 60/Dynein heavy chain	-0.054	0.086	0.29	10	-0.22	2	12
LRP8	0.024	0.023	0.32	3	-10000	0	3
NDEL1/Katanin 60	-0.053	0.087	0.29	10	-0.21	8	18
P39/CDK5	-0.05	0.099	0.2	39	-10000	0	39
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.019	0.007	-10000	0	-10000	0	0
CDK5	-0.065	0.075	0.18	7	-0.17	161	168
PPP2R5D	0.022	0.004	-10000	0	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.017	0.006	-10000	0	-10000	0	0
CSNK2A1	0.022	0.004	-10000	0	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.028	0.1	0.23	10	-0.17	168	178
RELN/VLDLR	-0.025	0.11	0.23	4	-0.18	168	172
CDC42	0.007	0.003	-10000	0	-10000	0	0

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.026	0.011	-10000	0	-10000	0	0
ARNO/beta Arrestin1-2	-0.006	0.11	-10000	0	-0.77	8	8
EGFR	0.013	0.054	-10000	0	-0.32	13	13
EPHA2	0.022	0.004	-10000	0	-10000	0	0
USP6	0.021	0.006	-10000	0	-10000	0	0
IQSEC1	0.021	0.016	-10000	0	-0.32	1	1
EGFR/EGFR/EGF/EGF	0.032	0.055	0.24	17	-0.22	13	30
ARRB2	0.006	0.002	-10000	0	-10000	0	0
mol:GTP	0.009	0.05	0.12	26	-0.13	26	52
ARRB1	0.022	0.016	-10000	0	-0.32	1	1
FBXO8	0.022	0.005	-10000	0	-10000	0	0
TSHR	0.029	0.059	0.32	17	-0.32	2	19
EGF	0.032	0.058	0.32	18	-0.32	1	19
somatostatin receptor activity	0	0	0.001	8	-0.001	74	82
ARAP2	0.021	0.022	-10000	0	-0.32	2	2
mol:GDP	-0.065	0.12	0.17	5	-0.29	79	84
mol:PI-3-4-5-P3	0	0	0.001	3	-0.001	46	49
ITGA2B	0.021	0.035	0.32	3	-0.32	3	6
ARF6	0.022	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.042	0.031	0.23	1	-0.18	2	3
ADAP1	0.022	0.005	-10000	0	-10000	0	0
KIF13B	0.02	0.008	-10000	0	-10000	0	0
HGF/MET	-0.012	0.1	0.23	4	-0.23	89	93
PXN	0.023	0.003	-10000	0	-10000	0	0
ARF6/GTP	-0.062	0.11	0.21	5	-0.26	75	80
EGFR/EGFR/EGF/EGF/ARFGEP100	0.041	0.052	0.23	16	-0.18	14	30
ADRB2	-0.034	0.13	-10000	0	-0.32	83	83
receptor agonist activity	0	0	0	3	0	75	78
actin filament binding	0	0	0	5	0	79	84
SRC	0.022	0.005	-10000	0	-10000	0	0
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
GNAQ	0.021	0.016	-10000	0	-0.32	1	1
EFA6/PI-4-5-P2	0	0	0.001	10	-0.001	48	58
ARF6/GDP	-0.019	0.14	0.24	9	-0.41	44	53
ARF6/GDP/GULP/ACAP1	-0.059	0.14	0.21	2	-0.32	71	73
alphaIIb/beta3 Integrin/paxillin/GIT1	0.012	0.092	0.23	4	-0.18	95	99
ACAP1	0.022	0.028	0.32	3	-0.32	1	4
ACAP2	0.02	0.017	-10000	0	-0.32	1	1
LHCGR/beta Arrestin2	0.011	0.019	-10000	0	-10000	0	0
EFNA1	0.019	0.016	0.32	1	-10000	0	1
HGF	-0.037	0.13	-10000	0	-0.32	88	88
CYTH3	-0.008	0.002	-10000	0	-10000	0	0
CYTH2	0	0.12	-10000	0	-0.98	8	8
NCK1	0.021	0.022	-10000	0	-0.32	2	2
fibronectin binding	0	0	0	8	0	65	73
endosomal lumen acidification	0	0	0	11	0	51	62
microtubule-based process	0	0	-10000	0	-10000	0	0
GULP1	-0.012	0.1	-10000	0	-0.32	51	51
GNAQ/ARNO	0.011	0.12	-10000	0	-0.92	8	8
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
PIP3-E	0	0	0	5	0	13	18
MET	0.022	0.041	0.32	4	-0.32	4	8
GNA14	-0.008	0.095	-10000	0	-0.32	43	43
GNA15	0.025	0.036	0.32	7	-10000	0	7
GIT1	0.022	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	0.001	10	-0.001	56	66
GNA11	0.015	0.045	-10000	0	-0.32	9	9
LHCGR	0.012	0.013	-10000	0	-10000	0	0
AGTR1	-0.063	0.15	0.32	2	-0.32	123	125
desensitization of G-protein coupled receptor protein signaling pathway	0.011	0.019	-10000	0	-10000	0	0
IPCEF1/ARNO	0.022	0.12	-10000	0	-0.84	8	8
alphaIIb/beta3 Integrin	-0.016	0.1	0.24	4	-0.22	99	103

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.025	0.038	0.21	3	-0.18	14	17
cell-cell adhesion	0.05	0.054	0.16	84	-10000	0	84
Ephrin B/EPHB2/RasGAP	0.034	0.074	0.23	1	-0.17	52	53
ITSN1	0.022	0.003	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
SHC1	0.019	0.009	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.031	0.038	0.21	14	-0.18	5	19
Ephrin B1/EPHB1	0.011	0.061	-10000	0	-0.18	45	45
HRAS/GDP	-0.026	0.096	-10000	0	-0.22	56	56
Ephrin B/EPHB1/GRB7	0.02	0.098	-10000	0	-0.18	83	83
Endophilin/SYNJ1	-0.028	0.053	0.17	13	-0.29	1	14
KRAS	0.022	0.004	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	0.015	0.092	-10000	0	-0.18	84	84
endothelial cell migration	0.037	0.032	-10000	0	-0.16	8	8
GRB2	0.021	0.006	-10000	0	-10000	0	0
GRB7	0.021	0.032	0.32	3	-0.32	2	5
PAK1	-0.029	0.068	0.28	5	-0.3	3	8
HRAS	0.022	0.005	-10000	0	-10000	0	0
RRAS	-0.029	0.052	0.17	11	-0.29	1	12
DNM1	0.02	0.027	-10000	0	-0.32	3	3
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.037	0.074	0.19	19	-0.29	7	26
lamellipodium assembly	-0.05	0.054	-10000	0	-0.16	84	84
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.015	0.077	-10000	0	-0.21	43	43
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
EPHB2	0.024	0.019	0.32	2	-10000	0	2
EPHB3	0.026	0.061	0.32	14	-0.32	5	19
EPHB1	-0.008	0.097	-10000	0	-0.32	45	45
EPHB4	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	-0.042	0.08	0.27	2	-0.24	48	50
Ephrin B/EPHB2	0.027	0.066	0.21	1	-0.16	48	49
Ephrin B/EPHB3	0.028	0.066	0.21	6	-0.17	37	43
JNK cascade	-0.024	0.079	0.29	20	-0.17	44	64
Ephrin B/EPHB1	0.008	0.086	-10000	0	-0.17	85	85
RAP1/GDP	-0.03	0.097	0.34	1	-0.27	27	28
EFNB2	0.02	0.027	-10000	0	-0.32	3	3
EFNB3	-0.01	0.098	-10000	0	-0.32	46	46
EFNB1	0.023	0.002	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.021	0.064	0.21	2	-0.17	48	50
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.001	-10000	0	-10000	0	0
CDC42/GTP	-0.006	0.092	-10000	0	-0.22	48	48
Rap1/GTP	-0.055	0.056	-10000	0	-0.27	8	8
axon guidance	0.024	0.038	0.21	3	-0.18	14	17
MAPK3	-0.024	0.067	0.18	4	-0.27	11	15
MAPK1	-0.023	0.062	0.17	2	-0.26	8	10
Rac1/GDP	-0.053	0.083	0.35	1	-0.27	29	30
actin cytoskeleton reorganization	-0.059	0.056	-10000	0	-0.19	48	48
CDC42/GDP	-0.05	0.087	0.23	6	-0.27	29	35
PI3K	0.041	0.033	-10000	0	-0.16	8	8
EFNA5	0.014	0.059	0.32	2	-0.32	14	16
Ephrin B2/EPHB4	0.027	0.019	-10000	0	-0.18	3	3
Ephrin B/EPHB2/Intersectin/N-WASP	-0.008	0.07	0.19	1	-0.19	48	49
CDC42	0.022	0.004	-10000	0	-10000	0	0
RAS family/GTP	-0.054	0.055	-10000	0	-0.17	86	86
PTK2	0.04	0.16	0.55	44	-10000	0	44
MAP4K4	-0.024	0.079	0.29	20	-0.17	44	64
SRC	0.022	0.005	-10000	0	-10000	0	0
KALRN	0.019	0.034	-10000	0	-0.32	5	5
Intersectin/N-WASP	0.032	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.041	0.093	0.31	17	-0.28	10	27
MAP2K1	-0.018	0.07	-10000	0	-0.2	41	41
WASL	0.022	0.005	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	0.034	0.069	0.23	1	-0.18	46	47
cell migration	-0.02	0.11	0.23	13	-0.3	19	32
NRAS	0.023	0.001	-10000	0	-10000	0	0
SYNJ1	-0.029	0.053	0.17	13	-0.29	1	14
PXN	0.022	0.003	-10000	0	-10000	0	0
TF	-0.033	0.057	0.18	10	-0.28	2	12
HRAS/GTP	0	0.081	-10000	0	-0.17	87	87
Ephrin B1/EPHB1-2	0.023	0.062	0.21	1	-0.17	45	46
cell adhesion mediated by integrin	0.016	0.056	0.17	34	-0.23	5	39
RAC1	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0.002	0.083	-10000	0	-0.17	87	87
RAC1-CDC42/GTP	-0.05	0.057	-10000	0	-0.17	76	76
RASA1	0.019	0.034	-10000	0	-0.32	5	5
RAC1-CDC42/GDP	-0.031	0.093	0.34	1	-0.26	27	28
ruffle organization	-0.041	0.087	0.32	11	-0.28	8	19
NCK1	0.021	0.022	-10000	0	-0.32	2	2
receptor internalization	-0.032	0.053	0.16	12	-0.28	2	14
Ephrin B/EPHB2/KALRN	0.034	0.075	0.23	1	-0.18	51	52
ROCK1	0.003	0.059	0.18	44	-0.17	5	49
RAS family/GDP	-0.06	0.058	-10000	0	-0.2	49	49
Rac1/GTP	-0.052	0.057	-10000	0	-0.17	84	84
Ephrin B/EPHB1/Src/Paxillin	-0.022	0.085	-10000	0	-0.2	88	88

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.038	0.099	0.27	30	-10000	0	30
GNAI2	0.022	0.005	-10000	0	-10000	0	0
S1P/S1P5/G12	0.031	0.03	0.21	11	-0.18	1	12
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
RhoA/GTP	-0.038	0.1	-10000	0	-0.28	30	30
negative regulation of cAMP metabolic process	-0.038	0.1	-10000	0	-0.2	125	125
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
GNAI3	0.023	0.002	-10000	0	-10000	0	0
GNA12	0.022	0.005	-10000	0	-10000	0	0
S1PR5	0.028	0.049	0.32	12	-0.32	1	13
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.039	0.1	-10000	0	-0.2	125	125
RhoA/GDP	0.016	0.003	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
GNAI1	0.016	0.045	-10000	0	-0.32	9	9

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.026	0.079	0.24	1	-0.41	9	10
Syndecan-4/Syndesmos	0.062	0.12	0.36	7	-0.64	3	10
positive regulation of JNK cascade	-0.026	0.14	0.39	2	-0.51	7	9
Syndecan-4/ADAM12	0.067	0.13	0.34	14	-0.59	4	18
CCL5	0.023	0.037	0.32	5	-0.32	2	7
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DNM2	0.021	0.006	-10000	0	-10000	0	0
ITGA5	0.022	0.015	-10000	0	-0.32	1	1
SDCBP	0.021	0.007	-10000	0	-10000	0	0
PLG	-0.025	0.11	0.32	5	-0.3	66	71
ADAM12	0.029	0.046	0.32	12	-10000	0	12
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0.022	0.005	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.035	0.017	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	0.13	0.16	0.35	93	-0.58	4	97
Syndecan-4/CXCL12/CXCR4	-0.026	0.14	0.41	2	-0.54	7	9
Syndecan-4/Laminin alpha3	0.059	0.13	0.36	9	-0.58	4	13
MDK	0.022	0.005	-10000	0	-10000	0	0
Syndecan-4/FZD7	0.041	0.13	0.34	7	-0.56	5	12
Syndecan-4/Midkine	0.063	0.12	0.36	7	-0.58	4	11
FZD7	-0.05	0.14	-10000	0	-0.32	108	108
Syndecan-4/FGFR1/FGF	-0.021	0.13	0.32	1	-0.52	6	7
THBS1	-0.027	0.12	-10000	0	-0.32	72	72
integrin-mediated signaling pathway	0.056	0.12	0.33	6	-0.56	4	10
positive regulation of MAPKKK cascade	-0.026	0.14	0.39	2	-0.51	7	9
Syndecan-4/TACI	0.064	0.13	0.37	17	-0.58	4	21
CXCR4	0.023	0.003	-10000	0	-10000	0	0
cell adhesion	0.007	0.041	0.18	9	-0.2	5	14
Syndecan-4/Dynamin	0.059	0.12	0.36	8	-0.55	4	12
Syndecan-4/TSP1	0.045	0.13	0.36	6	-0.58	5	11
Syndecan-4/GIPC	0.057	0.12	0.36	8	-0.59	3	11
Syndecan-4/RANTES	0.063	0.13	0.35	11	-0.58	4	15
ITGB1	0.022	0.004	-10000	0	-10000	0	0
LAMA1	0.14	0.15	0.32	209	-0.32	2	211
LAMA3	0.015	0.05	-10000	0	-0.32	11	11
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.02	0.12	0.68	10	-0.3	26	36
Syndecan-4/alpha-Actinin	0.062	0.13	0.36	9	-0.65	3	12
TFPI	-0.018	0.11	-10000	0	-0.32	60	60
F2	0.054	0.088	0.34	43	-10000	0	43
alpha5/beta1 Integrin	0.032	0.014	-10000	0	-0.22	1	1
positive regulation of cell adhesion	0.092	0.14	0.38	19	-0.56	4	23
ACTN1	0.022	0.004	-10000	0	-10000	0	0
TNC	0.013	0.056	0.32	1	-0.32	13	14
Syndecan-4/CXCL12	-0.003	0.13	0.42	2	-0.55	7	9
FGF6	0.016	0.003	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
CXCL12	-0.18	0.17	-10000	0	-0.32	298	298
TNFRSF13B	0.028	0.05	0.32	14	-10000	0	14
FGF2	-0.17	0.17	-10000	0	-0.32	284	284
FGFR1	0.02	0.017	-10000	0	-0.32	1	1
Syndecan-4/PI-4-5-P2	0.046	0.12	0.31	7	-0.59	4	11
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.015	0.038	-10000	0	-0.27	6	6
cell migration	-0.02	0.014	-10000	0	-10000	0	0
PRKCD	0.018	0.02	-10000	0	-0.13	1	1
vasculogenesis	0.044	0.13	0.36	6	-0.55	5	11
SDC4	0.057	0.12	0.33	9	-0.67	2	11
Syndecan-4/Tenascin C	0.057	0.13	0.34	6	-0.59	4	10
Syndecan-4/PI-4-5-P2/PKC alpha	-0.028	0.014	-10000	0	-10000	0	0
Syndecan-4/Syntenin	0.058	0.12	0.37	6	-0.65	3	9
MMP9	0.15	0.15	0.33	213	-10000	0	213
Rac1/GTP	0.007	0.042	0.18	9	-0.2	5	14
cytoskeleton organization	0.061	0.12	0.36	7	-0.62	3	10
GIPC1	0.021	0.006	-10000	0	-10000	0	0
Syndecan-4/TFPI	0.05	0.13	0.34	7	-0.62	4	11

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.013	0.054	-10000	0	-0.32	13	13
EGF/EGFR	-0.013	0.096	0.18	8	-0.17	128	136
EGF/EGFR dimer/SHC/GRB2/SOS1	0.048	0.052	0.23	12	-0.17	9	21
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	-0.071	0.15	-10000	0	-0.32	138	138
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.032	0.058	0.32	18	-0.32	1	19
EGF/EGFR dimer/SHC	0.037	0.05	0.23	16	-0.18	10	26
mol:GDP	0.043	0.048	0.21	12	-0.17	9	21
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.018	0.04	-10000	0	-0.32	7	7
GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
HRAS/GTP	0.028	0.037	-10000	0	-0.16	9	9
SHC1	0.019	0.009	-10000	0	-10000	0	0
HRAS/GDP	0.04	0.046	-10000	0	-0.16	9	9
FRAP1	-0.016	0.032	0.2	5	-0.16	9	14
EGF/EGFR dimer	0.032	0.055	0.24	17	-0.22	13	30
SOS1	0.022	0.004	-10000	0	-10000	0	0
GRB2	0.021	0.006	-10000	0	-10000	0	0
ETA receptor/Endothelin-1	-0.04	0.12	-10000	0	-0.23	139	139

Presenilin action in Notch and Wnt 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
Delta 1/NOTCH/NOTCH(cleaved)	-0.009	0.13	-10000	0	-0.42	38	38
HDAC1	0.022	0.006	-10000	0	-10000	0	0
AES	0.021	0.006	-10000	0	-10000	0	0
FBXW11	0.022	0.004	-10000	0	-10000	0	0
DTX1	0.019	0.034	-10000	0	-0.32	5	5
LRP6/FZD1	0.032	0.013	-10000	0	-0.22	1	1
TLE1	0.021	0.006	-10000	0	-10000	0	0
AP1	-0.051	0.11	-10000	0	-0.22	139	139
NCSTN	0.019	0.009	-10000	0	-10000	0	0
ADAM10	0.02	0.027	-10000	0	-0.32	3	3
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	-0.004	0.15	-10000	0	-0.66	21	21
NICD/RBPSUH	0.011	0.13	-10000	0	-0.41	38	38
WIF1	0.09	0.15	0.32	134	-0.32	18	152
NOTCH1	-0.01	0.1	-10000	0	-0.42	29	29
PSENEN	0.022	0.005	-10000	0	-10000	0	0
KREMEN2	0.048	0.085	0.32	44	-10000	0	44
DKK1	0.079	0.13	0.32	101	-0.32	4	105
beta catenin/beta TrCP1	0.027	0.067	-10000	0	-0.32	4	4
APH1B	0.02	0.027	-10000	0	-0.32	3	3
APH1A	0.018	0.009	-10000	0	-10000	0	0
AXIN1	-0.014	0.12	-10000	0	-0.47	23	23
CtBP/CBP/TCF1/TLE1/AES	0.009	0.05	-10000	0	-10000	0	0
PSEN1	0.022	0.004	-10000	0	-10000	0	0
FOS	-0.09	0.16	-10000	0	-0.32	166	166
JUN	0.019	0.037	-10000	0	-0.32	6	6
MAP3K7	0.022	0.004	-10000	0	-10000	0	0
CTNNB1	0.016	0.067	0.22	2	-0.32	5	7
MAPK3	0.022	0.005	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.041	0.08	0.23	40	-0.18	31	71
HNF1A	0.04	0.07	0.32	29	-10000	0	29
CTBP1	0.022	0.005	-10000	0	-10000	0	0
MYC	-0.008	0.17	-10000	0	-1.1	11	11
NKD1	0.036	0.088	0.32	34	-0.32	8	42
FZD1	0.022	0.016	-10000	0	-0.32	1	1
NOTCH1 precursor/Deltex homolog 1	0.01	0.13	-10000	0	-0.41	36	36
apoptosis	-0.05	0.11	-10000	0	-0.21	139	139
Delta 1/NOTCHprecursor	0.006	0.14	-10000	0	-0.42	38	38
DLL1	0.012	0.058	-10000	0	-0.32	15	15
PPARD	0.016	0.048	-10000	0	-1	1	1
Gamma Secretase	0.046	0.036	-10000	0	-0.17	3	3
APC	-0.013	0.12	-10000	0	-0.53	19	19
DVL1	0.013	0.033	-10000	0	-0.43	2	2
CSNK2A1	0.022	0.005	-10000	0	-10000	0	0
MAP3K7IP1	0	0.002	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	0.09	0.091	0.23	135	-0.18	4	139
LRP6	0.023	0.003	-10000	0	-10000	0	0
CSNK1A1	0.022	0.005	-10000	0	-10000	0	0
NLK	0.008	0.005	-10000	0	-10000	0	0
CCND1	0.008	0.097	-10000	0	-0.86	6	6
WNT1	0.026	0.035	0.32	7	-10000	0	7
Axin1/APC/beta catenin	0.012	0.13	0.25	1	-0.43	24	25
DKK2	-0.001	0.089	0.32	2	-0.32	35	37
NOTCH1 precursor/DVL1	-0.011	0.13	-10000	0	-0.46	36	36
GSK3B	0.022	0.004	-10000	0	-10000	0	0
FRAT1	0.021	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.006	0.12	-10000	0	-0.41	36	36
PPP2R5D	0.011	0.038	-10000	0	-0.31	2	2
MAPK1	0.022	0.005	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.093	0.095	0.23	133	-0.17	18	151
RBPJ	0.022	0.004	-10000	0	-10000	0	0
CREBBP	0.022	0.007	-10000	0	-10000	0	0

FAS signaling pathway (CD95)

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPTAN1	0	0.049	0.15	30	-0.18	13	43
RFC1	0	0.052	0.16	33	-0.18	15	48
PRKDC	0.012	0.076	0.19	61	-0.18	17	78
RIPK1	0.021	0.008	-10000	0	-10000	0	0
CASP7	-0.001	0.091	-10000	0	-0.56	12	12
FASLG/FAS/FADD/FAF1	0.015	0.048	0.16	30	-0.19	2	32
MAP2K4	0.013	0.097	0.26	11	-0.31	20	31
mol:ceramide	0.01	0.053	0.22	3	-0.22	3	6
GSN	-0.001	0.053	-10000	0	-0.19	13	13
FASLG/FAS/FADD/FAF1/Caspase 8	0.016	0.052	0.21	1	-10000	0	1
FAS	0.018	0.032	-10000	0	-0.32	4	4
BID	-0.017	0.018	0.23	2	-10000	0	2
MAP3K1	0.012	0.092	0.26	8	-0.39	13	21
MAP3K7	0.021	0.009	-10000	0	-10000	0	0
RB1	0	0.05	0.15	33	-0.18	13	46
CFLAR	0.022	0.008	-10000	0	-10000	0	0
HGF/MET	-0.018	0.11	0.23	3	-0.21	127	130
ARHGDIB	-0.001	0.058	0.16	37	-0.18	21	58
FADD	0.021	0.012	-10000	0	-10000	0	0
actin filament polymerization	0.001	0.053	0.19	13	-10000	0	13
NFKB1	-0.004	0.12	-10000	0	-0.58	17	17
MAPK8	0.006	0.12	0.3	16	-0.43	23	39
DFFA	0.002	0.056	0.24	5	-0.18	14	19
DNA fragmentation during apoptosis	0.001	0.054	0.16	35	-0.18	15	50
FAS/FADD/MET	0.037	0.04	0.23	4	-0.19	8	12
CFLAR/RIP1	0.032	0.013	-10000	0	-10000	0	0
FAIM3	0.018	0.023	-10000	0	-0.32	2	2
FAF1	0.021	0.013	-10000	0	-10000	0	0
PARP1	0	0.057	0.16	36	-0.18	19	55
DFFB	0.001	0.054	0.16	35	-0.18	15	50
CHUK	-0.01	0.11	0.38	1	-0.55	17	18
FASLG	0.021	0.041	0.32	7	-0.32	1	8
FAS/FADD	0.027	0.028	-10000	0	-0.22	4	4
HGF	-0.037	0.13	-10000	0	-0.32	88	88
LMNA	0.009	0.067	0.23	25	-10000	0	25
CASP6	0.001	0.053	0.16	36	-0.18	12	48
CASP10	0.02	0.019	-10000	0	-0.32	1	1
CASP3	0.011	0.049	0.19	35	-10000	0	35
PTPN13	-0.012	0.1	-10000	0	-0.32	51	51
CASP8	-0.017	0.021	0.29	2	-10000	0	2
IL6	-0.023	0.24	-10000	0	-0.9	30	30
MET	0.022	0.041	0.32	4	-0.32	4	8
ICAD/CAD	-0.001	0.055	0.26	6	-10000	0	6
FASLG/FAS/FADD/FAF1/Caspase 10	0.01	0.054	0.22	3	-0.22	3	6
activation of caspase activity by cytochrome c	-0.017	0.018	0.23	2	-10000	0	2
PAK2	0.015	0.083	0.2	66	-0.18	18	84
BCL2	-0.007	0.095	-10000	0	-0.32	43	43

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.079	0.19	0.61	11	-0.78	3	14
CRP	0.098	0.22	0.6	28	-0.65	5	33
cell cycle arrest	0.071	0.2	0.58	15	-0.68	8	23
TIMP1	0.068	0.18	0.55	11	-0.64	7	18
IL6ST	-0.033	0.13	-10000	0	-0.31	91	91
Rac1/GDP	0.02	0.14	0.34	11	-0.36	28	39
AP1	0.013	0.15	0.41	4	-0.57	11	15
GAB2	0.02	0.034	-10000	0	-0.32	5	5
TNFSF11	0.09	0.21	0.57	14	-0.67	5	19
HSP90B1	0.047	0.1	-10000	0	-0.8	3	3
GAB1	0.02	0.031	-10000	0	-0.32	4	4
MAPK14	-0.012	0.13	0.24	2	-0.41	29	31
AKT1	0.022	0.064	-10000	0	-0.44	4	4
FOXO1	0.021	0.061	-10000	0	-0.45	3	3
MAP2K6	-0.008	0.13	0.24	17	-0.38	31	48
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
MAP2K4	0.035	0.15	0.4	14	-0.37	24	38
MITF	-0.015	0.15	0.29	10	-0.37	45	55
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.021	0.007	-10000	0	-10000	0	0
A2M	-0.001	0.15	-10000	0	-1.1	9	9
CEBPB	0.026	0.01	-10000	0	-10000	0	0
GRB2/SOS1/GAB family/SHP2	0.019	0.11	0.29	2	-0.52	12	14
STAT3	0.066	0.21	0.58	15	-0.73	8	23
STAT1	0.024	0.072	0.39	1	-0.79	3	4
CEBPD	0.08	0.19	0.55	16	-0.71	5	21
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PI3K	0.028	0.028	-10000	0	-0.22	5	5
JUN	0.019	0.037	-10000	0	-0.32	6	6
PIAS3/MITF	-0.007	0.15	0.29	8	-0.36	43	51
MAPK11	-0.012	0.13	0.23	3	-0.41	29	32
STAT3 (dimer)/FOXO1	0.061	0.18	0.52	13	-0.56	7	20
GRB2/SOS1/GAB family	0.017	0.13	0.28	3	-0.34	29	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.016	0.12	0.25	7	-0.27	62	69
GRB2	0.022	0.006	-10000	0	-10000	0	0
JAK2	0.016	0.045	-10000	0	-0.32	9	9
LBP	0.093	0.21	0.59	31	-0.67	5	36
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
JAK1	0.023	0.029	-10000	0	-0.32	3	3
MYC	0.085	0.22	0.59	18	-0.83	11	29
FGG	0.069	0.19	0.6	14	-0.79	3	17
macrophage differentiation	0.071	0.2	0.58	15	-0.68	8	23
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.007	0.12	0.26	5	-0.22	75	80
JUNB	0.068	0.2	0.55	11	-0.84	8	19
FOS	-0.089	0.16	-10000	0	-0.32	166	166
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.003	0.14	0.32	10	-0.38	32	42
STAT1/PIAS1	0.035	0.14	0.38	11	-0.33	28	39
GRB2/SOS1/GAB family/SHP2/PI3K	0.026	0.063	-10000	0	-0.4	6	6
STAT3 (dimer)	0.069	0.21	0.58	15	-0.71	8	23
PRKCD	0.05	0.16	0.45	17	-0.46	11	28
IL6R	-0.004	0.088	-10000	0	-0.31	37	37
SOCS3	-0.027	0.16	-10000	0	-0.7	15	15
gp130 (dimer)/JAK1/JAK1/LMO4	0.015	0.098	0.22	2	-0.18	90	92
Rac1/GTP	0.026	0.14	0.35	12	-0.37	27	39
HCK	0.022	0.015	0.32	1	-10000	0	1
MAPKKK cascade	0.035	0.12	0.38	1	-0.56	12	13
bone resorption	0.091	0.2	0.55	16	-0.63	5	21
IRF1	0.067	0.19	0.58	12	-0.67	5	17
mol:GDP	0.001	0.13	0.31	12	-0.37	30	42
SOS1	0.023	0.004	-10000	0	-10000	0	0
VAV1	0.001	0.13	0.31	12	-0.37	31	43
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.034	0.17	-10000	0	-0.48	47	47
PTPN11	0.023	0.068	-10000	0	-0.64	4	4
IL6/IL6RA	0.01	0.088	0.25	6	-0.23	49	55
gp130 (dimer)/TYK2/TYK2/LMO4	0.01	0.09	0.18	1	-0.18	86	87
gp130 (dimer)/JAK2/JAK2/LMO4	0.006	0.097	-10000	0	-0.18	96	96
IL6	0.023	0.079	0.34	9	-0.32	18	27
PIAS3	0.022	0.005	-10000	0	-10000	0	0
PTPRE	-0.002	0.036	0.3	1	-0.32	1	2
PIAS1	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.023	0.005	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.022	0.12	0.25	6	-0.26	77	83
LMO4	0.03	0.017	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	0.053	0.19	0.53	9	-0.69	8	17
MCL1	0.055	0.11	0.42	1	-0.53	1	2

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.047	0.11	-10000	0	-0.18	188	188
TC10/GTP	-0.034	0.092	-10000	0	-0.16	172	172
Insulin Receptor/Insulin/IRS1/Shp2	0.031	0.069	-10000	0	-0.18	46	46
HRAS	0.022	0.005	-10000	0	-10000	0	0
APS homodimer	0.022	0.005	-10000	0	-10000	0	0
GRB14	0.12	0.14	0.32	171	-0.32	1	172
FOXO3	0.017	0.068	-10000	0	-0.56	6	6
AKT1	0.007	0.082	0.23	26	-0.28	2	28
INSR	0.023	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.043	0.03	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.022	0.016	-10000	0	-0.32	1	1
SORBS1	-0.1	0.16	-10000	0	-0.32	187	187
CRK	0.021	0.006	-10000	0	-10000	0	0
PTPN1	-0.008	0.027	-10000	0	-10000	0	0
CAV1	-0.052	0.082	0.16	4	-0.2	106	110
CBL/APS/CAP/Crk-II/C3G	-0.026	0.11	-10000	0	-0.17	176	176
Insulin Receptor/Insulin/IRS1/NCK2	0.031	0.068	-10000	0	-0.18	45	45
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.02	0.059	-10000	0	-0.17	41	41
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.01	0.09	-10000	0	-0.34	22	22
RPS6KB1	-0.001	0.074	0.21	25	-0.26	2	27
PARD6A	0.02	0.008	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.014	0.028	-10000	0	-0.57	1	1
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.006	0.066	0.16	14	-0.27	2	16
HRAS/GTP	-0.029	0.036	-10000	0	-0.16	27	27
Insulin Receptor	0.023	0.008	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.033	0.061	-10000	0	-0.17	31	31
PRKCI	0.007	0.068	-10000	0	-0.29	16	16
Insulin Receptor/Insulin/GRB14/PDK1	-0.002	0.066	0.12	1	-0.17	22	23
SHC1	0.019	0.009	-10000	0	-10000	0	0
negative regulation of MAPKKK cascade	0.033	0.041	-10000	0	-0.34	4	4
PI3K	0.027	0.063	-10000	0	-0.17	41	41
NCK2	0.023	0.002	-10000	0	-10000	0	0
RHOQ	0.022	0.003	-10000	0	-10000	0	0
mol:H2O2	-0.001	0.004	-10000	0	-10000	0	0
HRAS/GDP	0.016	0.004	-10000	0	-10000	0	0
AKT2	0.004	0.08	0.24	22	-0.28	2	24
PRKCZ	0.004	0.076	-10000	0	-0.3	22	22
SH2B2	0.022	0.005	-10000	0	-10000	0	0
SHC/SHIP	-0.021	0.043	0.15	3	-10000	0	3
F2RL2	0.005	0.08	0.32	3	-0.32	27	30
TRIP10	0.021	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin/Shc	0.032	0.02	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.028	0.009	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.047	0.032	-10000	0	-10000	0	0
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0
RASA1	0.019	0.034	-10000	0	-0.32	5	5
NCK1	0.021	0.022	-10000	0	-0.32	2	2
CBL/APS/CAP/Crk-II	-0.033	0.11	-10000	0	-0.17	181	181
TC10/GDP	0.017	0.002	-10000	0	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.042	0.029	-10000	0	-0.18	1	1
INPP5D	-0.028	0.046	0.15	3	-0.17	41	44
SOS1	0.022	0.004	-10000	0	-10000	0	0
SGK1	0.003	0.077	-10000	0	-0.7	6	6
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.023	0.003	-10000	0	-10000	0	0
IRS1	-0.008	0.098	-10000	0	-0.32	46	46
p62DOK/RasGAP	0.034	0.041	-10000	0	-0.34	4	4
INS	-0.011	0.016	-10000	0	-10000	0	0
mol:PI-3-4-P2	-0.028	0.046	0.15	3	-0.16	41	44
GRB2	0.021	0.006	-10000	0	-10000	0	0
EIF4EBP1	-0.001	0.076	0.23	25	-0.23	2	27
PTPRA	0.023	0.006	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
TC10/GTP/CIP4	0.028	0.009	-10000	0	-10000	0	0
PDPK1	0.022	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.004	0.057	-10000	0	-0.19	37	37
Insulin Receptor/Insulin/IRS1	0.019	0.063	-10000	0	-0.17	46	46
Insulin Receptor/Insulin/IRS3	0.03	0.013	-10000	0	-10000	0	0
Par3/Par6	0.034	0.052	0.21	3	-0.16	26	29

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.11	0.17	0.32	1	-0.32	199	200
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.022	0.005	-10000	0	-10000	0	0
TCEB1	0.021	0.007	-10000	0	-10000	0	0
HIF1A/p53	0.022	0.062	0.25	1	-0.27	15	16
HIF1A	0.005	0.055	-10000	0	-0.27	15	15
COPS5	0.021	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.054	0.03	-10000	0	-0.17	1	1
FIH (dimer)	0.022	0.005	-10000	0	-10000	0	0
CDKN2A	0.14	0.15	0.32	202	-10000	0	202
ARNT/IPAS	-0.053	0.11	0.24	1	-0.22	155	156
HIF1AN	0.022	0.005	-10000	0	-10000	0	0
GNB2L1	0.022	0.004	-10000	0	-10000	0	0
HIF1A/ARNT	0.009	0.051	-10000	0	-0.27	12	12
CUL2	0.022	0.005	-10000	0	-10000	0	0
OS9	0.023	0.001	-10000	0	-10000	0	0
RACK1/Elongin B/Elongin C	0.04	0.016	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	0.021	0.061	-10000	0	-0.27	16	16
PHD1-3/OS9	0.047	0.03	0.23	3	-0.18	1	4
HIF1A/RACK1/Elongin B/Elongin C	0.036	0.059	-10000	0	-0.25	13	13
VHL	0.021	0.016	-10000	0	-0.32	1	1
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
HIF1A/JAB1	0.019	0.057	-10000	0	-0.27	12	12
EGLN3	0.023	0.028	0.32	3	-0.32	1	4
EGLN2	0.022	0.004	-10000	0	-10000	0	0
EGLN1	0.019	0.009	-10000	0	-10000	0	0
TP53	0.021	0.006	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.014	0.099	-10000	0	-0.54	15	15
ARNT	0.018	0.01	-10000	0	-10000	0	0
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.021	0.006	-10000	0	-10000	0	0
HIF1A/p19ARF	0.089	0.1	0.2	182	-0.22	15	197

Coregulation of Androgen receptor activity

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
NRIP1	0.021	0.027	-10000	0	-0.32	3	3
SVIL	-0.018	0.11	-10000	0	-0.32	60	60
ZNF318	0.019	0.014	-10000	0	-10000	0	0
JMJD2C	0	0.027	0.14	8	-0.12	13	21
T-DHT/AR/Ubc9	-0.007	0.091	-10000	0	-0.19	89	89
CARM1	0.021	0.006	-10000	0	-10000	0	0
PRDX1	0.022	0.004	-10000	0	-10000	0	0
PELP1	0.019	0.01	-10000	0	-10000	0	0
CTNNB1	0.023	0.005	-10000	0	-10000	0	0
AKT1	0.02	0.01	-10000	0	-10000	0	0
PTK2B	0.02	0.008	-10000	0	-10000	0	0
MED1	0.019	0.01	-10000	0	-10000	0	0
MAK	0.04	0.08	0.32	36	-10000	0	36
response to oxidative stress	0	0.001	-10000	0	-10000	0	0
HIP1	0.021	0.03	-10000	0	-0.32	4	4
GSN	0.018	0.038	-10000	0	-0.32	6	6
NCOA2	0.01	0.06	-10000	0	-0.32	16	16
NCOA6	0.023	0.006	-10000	0	-10000	0	0
DNA-PK	0.035	0.024	-10000	0	-10000	0	0
NCOA4	0.022	0.005	-10000	0	-10000	0	0
PIAS3	0.023	0.005	-10000	0	-10000	0	0
cell proliferation	0.019	0.079	0.26	36	-0.52	2	38
XRCC5	0.021	0.01	-10000	0	-10000	0	0
UBE3A	0.023	0.007	-10000	0	-10000	0	0
T-DHT/AR/SNURF	-0.022	0.1	0.21	1	-0.19	118	119
FHL2	-0.015	0.12	-10000	0	-0.73	11	11
RANBP9	0.023	0.006	-10000	0	-10000	0	0
JMJD1A	0.007	0.04	0.15	23	-0.13	18	41
CDK6	0.017	0.043	-10000	0	-0.32	8	8
TGFB1I1	-0.07	0.15	-10000	0	-0.32	138	138
T-DHT/AR/CyclinD1	-0.006	0.09	-10000	0	-0.19	85	85
XRCC6	0.019	0.011	-10000	0	-10000	0	0
T-DHT/AR	-0.005	0.11	-10000	0	-0.2	104	104
CTDSP1	0.023	0.004	-10000	0	-10000	0	0
CTDSP2	0.02	0.012	-10000	0	-10000	0	0
BRCA1	0.022	0.007	-10000	0	-10000	0	0
TCF4	0.008	0.064	-10000	0	-0.32	18	18
CDKN2A	0.14	0.15	0.32	202	-10000	0	202
SRF	0.02	0.024	-10000	0	-0.15	7	7
NKX3-1	-0.035	0.16	-10000	0	-0.54	35	35
KLK3	-0.015	0.078	-10000	0	-10000	0	0
TMF1	0.022	0.005	-10000	0	-10000	0	0
HNRNPA1	0.02	0.01	-10000	0	-10000	0	0
AOF2	0.001	0.004	-10000	0	-10000	0	0
APPL1	-0.016	0.006	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	-0.008	0.09	-10000	0	-0.19	86	86
AR	-0.038	0.13	-10000	0	-0.32	87	87
UBA3	0.022	0.005	-10000	0	-10000	0	0
PATZ1	0.02	0.011	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
PRKDC	0.019	0.011	-10000	0	-10000	0	0
PA2G4	0.02	0.011	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.004	0.082	-10000	0	-0.18	83	83
RPS6KA3	0.023	0.016	-10000	0	-0.32	1	1
T-DHT/AR/ARA70	-0.007	0.091	-10000	0	-0.19	88	88
LATS2	0.018	0.024	-10000	0	-0.32	2	2
T-DHT/AR/PRX1	-0.006	0.082	-10000	0	-0.17	86	86
Cyclin D3/CDK11 p58	0.016	0.003	-10000	0	-10000	0	0
VAV3	0.098	0.13	0.32	126	-10000	0	126
KLK2	-0.025	0.14	0.31	8	-0.69	17	25
CASP8	0.021	0.008	-10000	0	-10000	0	0
T-DHT/AR/TIF2/CARM1	0.003	0.09	-10000	0	-0.19	79	79
TMPRSS2	-0.008	0.14	0.33	23	-0.6	15	38
CCND1	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.023	0.007	-10000	0	-10000	0	0
mol:T-DHT	0	0.017	0.048	2	-0.06	26	28
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.023	0.01	-10000	0	-10000	0	0
T-DHT/AR/CDK6	-0.009	0.094	-10000	0	-0.2	91	91
CMTM2	0.021	0.025	0.32	3	-10000	0	3
SNURF	-0.002	0.085	0.32	1	-0.32	33	34
ZMIZ1	0.016	0.037	-10000	0	-0.28	4	4
CCND3	0.022	0.004	-10000	0	-10000	0	0
TGIF1	0.02	0.011	-10000	0	-10000	0	0
FKBP4	0.023	0.006	-10000	0	-10000	0	0

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.025	0.05	0.2	2	-0.16	30	32
RGS9BP	0.031	0.053	0.32	16	-10000	0	16
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0.018	0.015	0.32	1	-10000	0	1
mol:Na +	0.014	0.047	0.21	1	-0.18	25	26
mol:ADP	-0.015	0.012	0.16	2	-10000	0	2
GNAT2	0.024	0.023	0.32	3	-10000	0	3
RGS9-1/Gbeta5/R9AP	-0.007	0.099	0.23	9	-0.19	108	117
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.027	0.015	0.21	3	-10000	0	3
GRK7	0.02	0.014	0.32	1	-10000	0	1
CNGB3	0.001	0.073	-10000	0	-0.32	25	25
Cone Metarhodopsin II/X-Arrestin	0.014	0.009	0.22	1	-10000	0	1
mol:Ca2+	-0.01	0.061	0.17	36	-0.17	24	60
Cone PDE6	0.006	0.096	0.22	8	-0.17	104	112
Cone Metarhodopsin II	0.023	0.014	0.2	2	-10000	0	2
Na + (4 Units)	0.023	0.047	0.21	1	-0.17	25	26
GNAT2/GDP	0.005	0.092	0.21	10	-0.16	104	114
GNB5	0.022	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.014	0.023	0.18	6	-10000	0	6
Cone Transducin	0.028	0.053	0.21	2	-0.17	30	32
SLC24A2	0.018	0.005	-10000	0	-10000	0	0
GNB3/GNGT2	0.016	0.062	-10000	0	-0.23	30	30
GNB3	0.003	0.079	-10000	0	-0.32	29	29
GNAT2/GTP	0.017	0.016	0.22	3	-10000	0	3
CNGA3	0.021	0.014	0.32	1	-10000	0	1
ARR3	0.02	0.014	0.32	1	-10000	0	1
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.014	0.047	0.21	1	-0.18	25	26
mol:Pi	-0.007	0.099	0.22	9	-0.19	108	117
Cone CNG Channel	0.031	0.049	0.19	1	-0.16	25	26
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.018	0.005	-10000	0	-10000	0	0
RGS9	-0.053	0.14	-10000	0	-0.32	110	110
PDE6C	0.018	0.005	-10000	0	-10000	0	0
GNGT2	0.02	0.027	-10000	0	-0.32	3	3
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.018	0.004	-10000	0	-10000	0	0

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.004	0.034	0.14	1	-0.19	9	10
NFATC2	-0.014	0.055	0.14	1	-0.19	39	40
NFATC3	0	0.024	0.14	1	-10000	0	1
CD40LG	-0.061	0.14	0.32	12	-0.36	34	46
PTGS2	-0.066	0.15	0.33	14	-0.38	56	70
JUNB	0.018	0.034	-10000	0	-0.32	5	5
CaM/Ca2+/Calcineurin A alpha-beta B1	0.013	0.018	-10000	0	-10000	0	0
CaM/Ca2+	0.013	0.018	-10000	0	-10000	0	0
CALM1	0.018	0.017	-10000	0	-10000	0	0
JUN	0.015	0.04	-10000	0	-0.32	6	6
mol:Ca2+	0	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.014	0.009	-10000	0	-10000	0	0
FOSL1	0.043	0.075	0.32	34	-10000	0	34
CREM	0.02	0.01	-10000	0	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	0.011	0.094	0.32	10	-0.25	13	23
FOS	-0.091	0.16	-10000	0	-0.32	165	165
IFNG	-0.049	0.15	0.37	24	-0.34	30	54
AP-1/NFAT1-c-4	-0.029	0.17	0.5	13	-0.35	45	58
FASLG	-0.05	0.13	0.39	12	-0.33	30	42
NFAT1-c-4/ICER1	-0.002	0.075	0.2	6	-0.19	26	32
IL2RA	-0.051	0.14	0.37	19	-0.34	28	47
FKBP12/FK506	0.017	0.003	-10000	0	-10000	0	0
CSF2	-0.056	0.13	0.34	14	-0.34	31	45
JunB/Fra1/NFAT1-c-4	0.02	0.093	0.3	10	-0.22	14	24
IL4	-0.059	0.13	0.31	12	-0.34	30	42
IL2	-0.007	0.17	-10000	0	-0.86	17	17
IL3	-0.007	0.1	-10000	0	-0.66	12	12
FKBP1A	0.022	0.004	-10000	0	-10000	0	0
BATF3	0.02	0.016	0.32	1	-10000	0	1
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.019	0.009	-10000	0	-10000	0	0

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.063	0.15	-10000	0	-0.32	127	127
HRAS	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.013	0.054	-10000	0	-0.32	13	13
AKT	-0.046	0.12	0.28	2	-0.23	127	129
FOXO3	0.022	0.003	-10000	0	-10000	0	0
AKT1	0.022	0.004	-10000	0	-10000	0	0
FOXO1	0.02	0.022	-10000	0	-0.32	2	2
AKT3	-0.096	0.16	-10000	0	-0.32	170	170
FOXO4	0.021	0.021	-10000	0	-0.32	2	2
MET	0.022	0.041	0.32	4	-0.32	4	8
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PIK3CB	0.022	0.004	-10000	0	-10000	0	0
NRAS	0.023	0.001	-10000	0	-10000	0	0
PIK3CG	0.014	0.057	0.32	2	-0.32	13	15
PIK3R3	0.023	0.014	0.32	1	-10000	0	1
PIK3R2	0.022	0.006	-10000	0	-10000	0	0
NF1	0.021	0.006	-10000	0	-10000	0	0
RAS	-0.01	0.064	0.16	9	-0.13	93	102
ERBB2	0.02	0.007	-10000	0	-10000	0	0
proliferation/survival/translation	0.009	0.09	0.24	20	-0.27	5	25
PI3K	0.001	0.067	0.18	19	-0.21	10	29
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
KRAS	0.022	0.004	-10000	0	-10000	0	0
FOXO	0.028	0.043	0.27	2	-10000	0	2
AKT2	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0

Syndecan-2-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.013	0.033	-10000	0	-0.18	14	14
EPHB2	0.024	0.019	0.32	2	-10000	0	2
Syndecan-2/TACI	0.018	0.044	0.22	13	-0.17	11	24
LAMA1	0.14	0.15	0.32	209	-0.32	2	211
Syndecan-2/alpha2 ITGB1	0.028	0.052	-10000	0	-0.18	26	26
HRAS	0.022	0.005	-10000	0	-10000	0	0
Syndecan-2/CASK	0	0.026	-10000	0	-0.18	11	11
ITGA5	0.022	0.015	-10000	0	-0.32	1	1
BAX	-0.014	0.025	-10000	0	-10000	0	0
EPB41	0.022	0.004	-10000	0	-10000	0	0
positive regulation of cell-cell adhesion	0.013	0.027	-10000	0	-0.16	11	11
LAMA3	0.015	0.05	-10000	0	-0.32	11	11
EZR	0.022	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	-0.009	0.098	-10000	0	-0.32	46	46
Syndecan-2/MMP2	0.008	0.046	-10000	0	-0.19	23	23
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.026	0.037	-10000	0	-0.22	10	10
dendrite morphogenesis	0.016	0.037	0.35	2	-0.18	11	13
Syndecan-2/GM-CSF	0.014	0.035	0.22	4	-0.18	11	15
determination of left/right symmetry	0	0.032	-10000	0	-0.21	11	11
Syndecan-2/PKC delta	0.014	0.03	-10000	0	-0.18	11	11
GNB2L1	0.022	0.004	-10000	0	-10000	0	0
MAPK3	0.001	0.06	0.18	46	-0.17	10	56
MAPK1	-0.001	0.059	0.18	43	-0.17	11	54
Syndecan-2/RACK1	0.024	0.03	-10000	0	-0.16	11	11
NF1	0.021	0.006	-10000	0	-10000	0	0
FGFR/FGF/Syndecan-2	0	0.032	-10000	0	-0.21	11	11
ITGA2	0.015	0.048	-10000	0	-0.32	10	10
MAPK8	-0.012	0.029	-10000	0	-0.18	14	14
Syndecan-2/alpha2/beta1 Integrin	0.1	0.11	0.23	188	-0.16	13	201
Syndecan-2/Kininogen	0.021	0.05	0.24	19	-0.18	8	27
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.002	0.059	0.18	44	-0.15	11	55
Syndecan-2/CASK/Protein 4.1	0.013	0.027	-10000	0	-0.16	11	11
extracellular matrix organization	0.014	0.031	-10000	0	-0.18	12	12
actin cytoskeleton reorganization	0.013	0.033	-10000	0	-0.18	14	14
Syndecan-2/Caveolin-2/Ras	0.011	0.059	-10000	0	-0.17	44	44
Syndecan-2/Laminin alpha3	0.01	0.042	-10000	0	-0.19	20	20
Syndecan-2/RasGAP	0.03	0.037	-10000	0	-0.16	16	16
alpha5/beta1 Integrin	0.032	0.014	-10000	0	-0.22	1	1
PRKCD	0.022	0.004	-10000	0	-10000	0	0
Syndecan-2 dimer	0.016	0.037	0.36	2	-0.18	11	13
GO:0007205	0.001	0	-10000	0	-10000	0	0
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.015	0.035	0.17	4	-0.15	16	20
RHOA	0.022	0.005	-10000	0	-10000	0	0
SDCBP	0.021	0.007	-10000	0	-10000	0	0
TNFRSF13B	0.028	0.05	0.32	14	-10000	0	14
RASA1	0.019	0.034	-10000	0	-0.32	5	5
alpha2/beta1 Integrin	0.026	0.037	-10000	0	-0.22	10	10
Syndecan-2/Synbindin	0.014	0.029	-10000	0	-0.18	10	10
TGFB1	0.022	0.016	-10000	0	-0.32	1	1
CASP3	0	0.06	0.18	41	-0.17	11	52
FN1	0.019	0.034	-10000	0	-0.32	5	5
Syndecan-2/IL8	0.054	0.092	0.23	94	-0.18	10	104
SDC2	0	0.032	-10000	0	-0.21	11	11
KNG1	0.029	0.059	0.32	19	-10000	0	19
Syndecan-2/Neurofibromin	0.014	0.03	-10000	0	-0.18	11	11
TRAPPC4	0.022	0.005	-10000	0	-10000	0	0
CSF2	0.022	0.027	0.32	4	-10000	0	4
Syndecan-2/TGFB1	0.014	0.031	-10000	0	-0.18	12	12
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.027	-10000	0	-0.16	11	11
Syndecan-2/Ezrin	0.025	0.031	-10000	0	-0.16	11	11
PRKACA	-0.001	0.056	0.18	36	-0.17	10	46
angiogenesis	0.054	0.091	0.23	94	-0.18	10	104
MMP2	0.008	0.065	-10000	0	-0.32	19	19
IL8	0.079	0.12	0.32	95	-10000	0	95
calcineurin-NFAT signaling pathway	0.018	0.044	0.22	13	-0.17	11	24

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.063	-10000	0	-0.32	18	18
Jak2/Leptin Receptor	-0.073	0.16	-10000	0	-0.4	73	73
PTP1B/AKT1	-0.009	0.085	0.28	1	-0.28	27	28
FYN	0.022	0.003	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.02	0.089	0.31	1	-0.3	29	30
EGFR	0.012	0.056	-10000	0	-0.32	13	13
EGF/EGFR	0.001	0.093	0.22	7	-0.3	20	27
CSF1	0.016	0.048	-10000	0	-0.32	10	10
AKT1	0.021	0.008	-10000	0	-10000	0	0
INSR	0.021	0.008	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.018	0.097	-10000	0	-0.31	34	34
Insulin Receptor/Insulin	0.003	0.084	0.25	1	-0.28	19	20
HCK	0.022	0.015	0.32	1	-10000	0	1
CRK	0.021	0.006	-10000	0	-10000	0	0
TYK2	-0.012	0.092	0.23	17	-0.28	26	43
EGF	0.03	0.059	0.32	18	-0.3	1	19
YES1	0.022	0.005	-10000	0	-10000	0	0
CAV1	-0.039	0.11	0.21	3	-0.32	40	43
TXN	0.021	0.008	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.014	0.1	-10000	0	-0.32	27	27
cell migration	0.02	0.089	0.3	29	-0.31	1	30
STAT3	0.021	0.006	-10000	0	-10000	0	0
PRLR	-0.041	0.13	-10000	0	-0.32	94	94
ITGA2B	0.021	0.035	0.32	3	-0.32	3	6
CSF1R	0.02	0.026	-10000	0	-0.32	3	3
Prolactin Receptor/Prolactin	-0.024	0.11	0.23	1	-0.23	106	107
FGR	0.014	0.052	-10000	0	-0.32	12	12
PTP1B/p130 Cas	-0.009	0.087	0.28	1	-0.28	29	30
Crk/p130 Cas	-0.002	0.089	0.28	1	-0.3	21	22
DOK1	-0.025	0.096	0.28	1	-0.33	28	29
JAK2	-0.059	0.15	0.29	1	-0.4	51	52
Jak2/Leptin Receptor/Leptin	-0.017	0.096	-10000	0	-0.32	26	26
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
PTPN1	-0.02	0.09	0.31	1	-0.3	29	30
LYN	0.021	0.007	-10000	0	-10000	0	0
CDH2	-0.007	0.095	-10000	0	-0.32	43	43
SRC	-0.004	0.11	-10000	0	-0.52	19	19
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
CAT1/PTP1B	-0.003	0.12	0.26	12	-0.38	23	35
CAPN1	0.023	0.003	-10000	0	-10000	0	0
CSK	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.008	0.081	-10000	0	-0.27	16	16
mol:H2O2	0	0.003	-10000	0	-10000	0	0
STAT3 (dimer)	-0.015	0.089	-10000	0	-0.29	26	26
negative regulation of transcription	-0.058	0.15	0.29	1	-0.4	51	52
FCGR2A	0.02	0.016	0.32	1	-10000	0	1
FER	0.022	0.006	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.017	0.1	0.24	4	-0.22	99	103
BLK	0.043	0.083	0.32	40	-10000	0	40
Insulin Receptor/Insulin/Shc	0.031	0.019	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
LEPR	-0.077	0.15	-10000	0	-0.32	149	149
BCAR1	0.02	0.008	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.021	0.006	-10000	0	-10000	0	0
mol:NADPH	0	0.002	-10000	0	-10000	0	0
TRPV6	0.014	0.11	0.25	13	-0.39	16	29
PRL	0.005	0.068	0.32	1	-0.32	20	21
SOCS3	-0.011	0.19	-10000	0	-1.1	15	15
SPRY2	0.019	0.031	-10000	0	-0.32	4	4
Insulin Receptor/Insulin/IRS1	0.017	0.068	-10000	0	-0.19	46	46
CSF1/CSF1R	-0.006	0.096	-10000	0	-0.3	28	28
Ras protein signal transduction	0.017	0.12	0.56	21	-10000	0	21
IRS1	-0.008	0.098	-10000	0	-0.32	46	46
INS	0.008	0.016	-10000	0	-10000	0	0
LEP	0.016	0.024	0.32	2	-10000	0	2
STAT5B	-0.038	0.12	0.31	1	-0.37	41	42
STAT5A	-0.037	0.12	0.31	1	-0.36	41	42
GRB2	0.021	0.006	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.014	0.093	-10000	0	-0.29	32	32
CSN2	-0.02	0.077	-10000	0	-0.45	5	5
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
LAT	0.004	0.093	-10000	0	-0.52	13	13
YBX1	0.025	0.016	-10000	0	-0.32	1	1
LCK	0.024	0.031	0.32	4	-0.32	1	5
SHC1	0.019	0.009	-10000	0	-10000	0	0
NOX4	0.018	0.043	0.32	1	-0.32	7	8

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.056	0.13	0.28	77	-0.34	17	94
FYN	0.03	0.13	0.34	21	-0.38	20	41
LAT/GRAP2/SLP76	0.031	0.12	0.35	12	-0.37	18	30
IKBKB	0.02	0.007	-10000	0	-10000	0	0
AKT1	0.018	0.11	0.33	18	-0.31	25	43
B2M	0.023	0.008	-10000	0	-10000	0	0
IKBKG	0.002	0.042	0.15	15	-0.11	11	26
MAP3K8	0.019	0.034	-10000	0	-0.32	5	5
mol:Ca2+	-0.01	0.015	0.024	42	-0.06	3	45
integrin-mediated signaling pathway	0.026	0.011	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.016	0.14	0.4	15	-0.42	27	42
TRPV6	0.011	0.18	1.2	8	-10000	0	8
CD28	0.024	0.02	0.33	2	-10000	0	2
SHC1	0.044	0.15	0.3	76	-0.38	21	97
receptor internalization	0.016	0.12	0.34	9	-0.4	27	36
PRF1	0.01	0.18	0.63	4	-0.81	15	19
KRAS	0.022	0.004	-10000	0	-10000	0	0
GRB2	0.021	0.006	-10000	0	-10000	0	0
COT/AKT1	0.025	0.098	0.33	14	-0.25	23	37
LAT	0.021	0.13	0.37	12	-0.38	24	36
EntrezGene:6955	0	0.004	0.034	3	-0.036	1	4
CD3D	0.027	0.066	0.34	14	-0.32	7	21
CD3E	0.021	0.051	0.35	4	-0.33	7	11
CD3G	0.022	0.035	0.36	3	-0.32	2	5
RASGRP2	-0.017	0.059	0.11	5	-0.15	75	80
RASGRP1	0.013	0.12	0.36	16	-0.38	19	35
HLA-A	0.024	0.016	0.32	1	-10000	0	1
RASSF5	0.019	0.008	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.026	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.025	0.073	0.16	70	-0.12	17	87
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.006	0.039	-10000	0	-0.16	22	22
PRKCA	0.002	0.072	0.23	16	-0.21	13	29
GRAP2	0.009	0.063	-10000	0	-0.32	18	18
mol:IP3	0.011	0.077	0.17	19	-0.27	19	38
EntrezGene:6957	0.001	0.004	0.036	3	-10000	0	3
TCR/CD3/MHC I/CD8	0.007	0.091	0.3	10	-0.35	17	27
ORAI1	-0.021	0.14	0.35	5	-1	8	13
CSK	0.021	0.12	0.42	8	-0.38	23	31
B7 family/CD28	0.048	0.13	0.48	11	-0.39	15	26
CHUK	0.022	0.005	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.018	0.13	0.41	8	-0.42	25	33
PTPN6	0.02	0.12	0.36	12	-0.38	23	35
VAV1	0.021	0.13	0.38	11	-0.38	24	35
Monovalent TCR/CD3	0.012	0.051	0.29	7	-0.22	11	18
CBL	0.022	0.005	-10000	0	-10000	0	0
LCK	0.028	0.14	0.34	21	-0.42	17	38
PAG1	0.024	0.12	0.37	11	-0.38	23	34
RAP1A	0.023	0.001	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	0.019	0.13	0.39	9	-0.4	25	34
CD80	0.033	0.057	0.33	18	-10000	0	18
CD86	0.024	0.021	0.34	2	-10000	0	2
PDK1/CARD11/BCL10/MALT1	0.007	0.054	0.19	2	-0.19	21	23
HRAS	0.022	0.005	-10000	0	-10000	0	0
GO:0035030	0.015	0.1	0.4	9	-0.33	16	25
CD8A	0.022	0.049	0.36	4	-0.32	6	10
CD8B	0.034	0.078	0.33	25	-0.32	6	31
PTPRC	0.015	0.045	0.33	1	-0.32	8	9
PDK1/PKC theta	0.015	0.13	0.36	19	-0.38	22	41
CSK/PAG1	0.025	0.12	0.36	14	-0.38	21	35
SOS1	0.022	0.004	-10000	0	-10000	0	0
peptide-MHC class I	0.034	0.016	0.24	1	-10000	0	1
GRAP2/SLP76	0.035	0.13	0.41	9	-0.38	24	33
STIM1	-0.007	0.064	1.2	1	-10000	0	1
RAS family/GTP	0.036	0.08	0.24	27	-0.18	10	37
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.016	0.13	0.35	9	-0.42	27	36
mol:DAG	-0.018	0.057	-10000	0	-0.24	22	22
RAP1A/GDP	0.014	0.035	0.099	31	-0.063	8	39
PLCG1	0.022	0.005	-10000	0	-10000	0	0
CD247	0.019	0.023	0.36	1	-0.32	1	2
cytotoxic T cell degranulation	0.012	0.17	0.62	4	-0.77	15	19
RAP1A/GTP	-0.007	0.023	-10000	0	-0.059	77	77
mol:PI-3-4-5-P3	0.019	0.13	0.37	16	-0.36	27	43
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.021	0.1	0.29	10	-0.35	17	27
NRAS	0.023	0.001	-10000	0	-10000	0	0
ZAP70	0.03	0.056	0.32	15	-0.32	2	17
GRB2/SOS1	0.031	0.01	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	0.016	0.099	0.62	1	-0.36	18	19
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
CD8 heterodimer	0.041	0.071	0.27	26	-0.25	11	37
CARD11	0.028	0.042	0.32	10	-10000	0	10
PRKCB	0.002	0.076	0.23	16	-0.22	20	36
PRKCE	0.006	0.07	0.23	15	-0.2	14	29
PRKCQ	0.015	0.14	0.39	16	-0.41	24	40
LCP2	0.023	0.014	0.32	1	-10000	0	1
BCL10	0.023	0.002	-10000	0	-10000	0	0
regulation of survival gene product expression	0.02	0.1	0.32	18	-0.27	25	43
IKK complex	0.013	0.062	0.2	28	-0.11	7	35
RAS family/GDP	-0.002	0.01	-10000	0	-0.041	4	4
MAP3K14	0.017	0.078	0.27	15	-0.2	21	36
PDPK1	0.018	0.11	0.33	19	-0.3	25	44
TCR/CD3/MHC I/CD8/Fyn	0.01	0.16	0.48	5	-0.49	30	35

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0	0.062	0.95	1	-10000	0	1
VDR	0.026	0.036	0.32	7	-10000	0	7
FAM120B	0.022	0.004	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.018	0.08	0.29	9	-0.34	2	11
RXRs/LXRs/DNA/Oxysterols	0.037	0.091	0.34	9	-0.53	1	10
MED1	0.021	0.006	-10000	0	-10000	0	0
mol:9cRA	0.006	0.013	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	-0.038	0.096	-10000	0	-0.2	110	110
RXRs/NUR77	-0.004	0.11	0.25	4	-0.18	112	116
RXRs/PPAR	-0.01	0.077	0.21	1	-0.2	52	53
NCOR2	0.022	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.024	0.22	7	-10000	0	7
RARs/VDR/DNA/Vit D3	0.046	0.037	0.21	6	-0.16	8	14
RARA	0.021	0.006	-10000	0	-10000	0	0
NCOA1	0.022	0.016	-10000	0	-0.32	1	1
VDR/VDR/DNA	0.026	0.036	0.32	7	-10000	0	7
RARs/RARs/DNA/9cRA	0.036	0.031	-10000	0	-0.16	9	9
RARG	0.022	0.003	-10000	0	-10000	0	0
RPS6KB1	0.005	0.071	0.56	8	-10000	0	8
RARs/THRs/DNA/SMRT	-0.037	0.095	-10000	0	-0.33	9	9
THRA	0.016	0.04	-10000	0	-0.32	7	7
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.019	0.024	0.22	7	-10000	0	7
RXRs/PPAR/9cRA/PGJ2/DNA	0.031	0.074	0.38	2	-0.17	31	33
NR1H4	0.029	0.057	0.32	18	-10000	0	18
RXRs/LXRs/DNA	0.049	0.082	0.37	1	-0.32	1	2
NR1H2	0.028	0.014	-10000	0	-10000	0	0
NR1H3	0.028	0.02	0.32	1	-10000	0	1
RXRs/VDR/DNA/Vit D3	0.036	0.07	0.24	9	-0.16	29	38
NR4A1	-0.052	0.14	-10000	0	-0.32	111	111
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.007	0.071	0.19	15	-0.2	11	26
RXRG	-0.003	0.098	0.32	4	-0.31	42	46
RXR alpha/CCPG	0.034	0.015	-10000	0	-10000	0	0
RXRA	0.026	0.014	-10000	0	-10000	0	0
RXRB	0.028	0.015	-10000	0	-10000	0	0
THRB	-0.047	0.14	-10000	0	-0.32	102	102
PPARG	0.003	0.078	-10000	0	-0.32	28	28
PPARD	0.022	0.003	-10000	0	-10000	0	0
TNF	0.036	0.12	0.43	9	-0.89	2	11
mol:Oxysterols	0.005	0.012	-10000	0	-10000	0	0
cholesterol transport	0.037	0.091	0.34	9	-0.52	1	10
PPARA	0.021	0.007	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.016	0.045	-10000	0	-0.32	9	9
RXRs/NUR77/BCL2	-0.053	0.12	0.15	2	-0.23	140	142
SREBF1	0.027	0.083	0.39	2	-0.49	1	3
RXRs/RXRs/DNA/9cRA	0.031	0.074	0.37	2	-0.17	31	33
ABCA1	0.03	0.081	0.35	2	-0.49	1	3
RARs/THRs	0.007	0.1	-10000	0	-0.18	109	109
RXRs/FXR	0.039	0.077	0.24	14	-0.18	30	44
BCL2	-0.007	0.095	-10000	0	-0.32	43	43

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.019	0.034	-10000	0	-0.32	5	5
ELF1	0.027	0.041	0.18	16	-0.31	4	20
CCNA2	0.11	0.14	0.32	141	-10000	0	141
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
JAK3	0.024	0.024	0.32	3	-10000	0	3
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
JAK1	0.021	0.026	-10000	0	-0.32	3	3
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.033	0.081	0.26	3	-0.41	5	8
SHC1	0.019	0.009	-10000	0	-10000	0	0
SP1	-0.031	0.12	-10000	0	-0.3	87	87
IL2RA	-0.003	0.065	0.32	16	-0.58	1	17
IL2RB	0.021	0.016	-10000	0	-0.32	1	1
SOS1	0.023	0.004	-10000	0	-10000	0	0
IL2RG	0.025	0.037	0.32	5	-0.32	2	7
G1/S transition of mitotic cell cycle	-0.066	0.25	0.31	5	-0.58	86	91
PTPN11	0.023	0.003	-10000	0	-10000	0	0
CCND2	-0.1	0.21	-10000	0	-0.58	80	80
LCK	0.024	0.031	0.32	4	-0.32	1	5
GRB2	0.022	0.006	-10000	0	-10000	0	0
IL2	0.028	0.054	0.32	16	-10000	0	16
CDK6	0.017	0.043	-10000	0	-0.32	8	8
CCND3	0.033	0.085	0.33	3	-0.46	2	5

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.013	0.007	-10000	0	-10000	0	0
SMARCC1	0.007	0.013	-10000	0	-10000	0	0
REL	0.02	0.011	-10000	0	-10000	0	0
HDAC7	-0.012	0.07	0.24	8	-0.26	5	13
JUN	0.019	0.037	-10000	0	-0.32	6	6
EP300	0.021	0.006	-10000	0	-10000	0	0
KAT2B	0.016	0.045	-10000	0	-0.32	9	9
KAT5	0.022	0.003	-10000	0	-10000	0	0
MAPK14	0.011	0.062	0.17	62	-10000	0	62
FOXO1	0.02	0.022	-10000	0	-0.32	2	2
T-DHT/AR	0.024	0.084	0.28	10	-0.27	5	15
MAP2K6	0.056	0.098	0.32	59	-10000	0	59
BRM/BAF57	0.026	0.04	-10000	0	-0.22	12	12
MAP2K4	0.019	0.019	-10000	0	-0.31	1	1
SMARCA2	0.014	0.054	-10000	0	-0.32	13	13
PDE9A	-0.003	0.1	-10000	0	-0.64	8	8
NCOA2	0.009	0.06	-10000	0	-0.32	16	16
CEBPA	0.019	0.031	0.32	1	-0.32	3	4
EHMT2	0.023	0.004	-10000	0	-10000	0	0
cell proliferation	0.006	0.14	0.34	23	-0.35	24	47
NR0B1	0.029	0.053	0.32	16	-10000	0	16
EGR1	-0.031	0.12	-10000	0	-0.32	81	81
RXRs/9cRA	0.017	0.06	0.22	3	-0.17	41	44
AR/RACK1/Src	0	0.077	0.24	13	-0.22	5	18
AR/GR	-0.038	0.11	0.21	4	-0.23	80	84
GNB2L1	0.022	0.007	-10000	0	-10000	0	0
PKN1	0.022	0.006	-10000	0	-10000	0	0
RCHY1	0.022	0.004	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-10000	0	-10000	0	0
MAPK8	-0.012	0.023	-10000	0	-0.22	4	4
T-DHT/AR/TIF2/CARM1	0.008	0.076	0.25	7	-0.25	10	17
SRC	-0.002	0.054	0.19	26	-0.17	2	28
NR3C1	-0.04	0.13	-10000	0	-0.32	92	92
KLK3	0.048	0.12	0.42	10	-0.51	1	11
APPBP2	0.022	0.01	-10000	0	-10000	0	0
TRIM24	0.023	0.006	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.006	0.069	0.24	11	-0.21	4	15
TMPRSS2	-0.003	0.15	0.52	1	-0.78	13	14
RXRG	-0.008	0.097	0.32	3	-0.32	42	45
mol:9cRA	0	0.001	-10000	0	-10000	0	0
RXRA	0.022	0.006	-10000	0	-10000	0	0
RXRB	0.023	0.003	-10000	0	-10000	0	0
CARM1	0.021	0.009	-10000	0	-10000	0	0
NR2C2	0.016	0.045	-10000	0	-0.32	9	9
KLK2	-0.009	0.11	0.34	7	-0.47	15	22
AR	-0.019	0.084	0.18	7	-0.21	66	73
SENP1	0.023	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
MDM2	0.02	0.013	-10000	0	-10000	0	0
SRY	-0.001	0.006	-10000	0	-0.031	18	18
GATA2	-0.008	0.096	-10000	0	-0.32	44	44
MYST2	0	0.001	-10000	0	-10000	0	0
HOXB13	0.22	0.15	0.32	328	-10000	0	328
T-DHT/AR/RACK1/Src	-0.002	0.075	0.26	9	-0.24	2	11
positive regulation of transcription	-0.008	0.096	-10000	0	-0.32	44	44
DNAJA1	0.022	0.01	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.009	0.004	-10000	0	-10000	0	0
NCOA1	0.025	0.022	-10000	0	-0.35	1	1
SPDEF	0.12	0.17	0.32	174	-0.32	19	193
T-DHT/AR/TIF2	-0.002	0.095	0.24	15	-0.32	21	36
T-DHT/AR/Hsp90	-0.006	0.069	0.24	11	-0.26	1	12
GSK3B	0.022	0.008	-10000	0	-10000	0	0
NR2C1	0.021	0.009	-10000	0	-10000	0	0
mol:T-DHT	-0.004	0.048	0.19	15	-0.18	2	17
SIRT1	0.021	0.022	-10000	0	-0.32	2	2
ZMIZ2	0.019	0.013	-10000	0	-10000	0	0
POU2F1	0.024	0.033	-10000	0	-10000	0	0
T-DHT/AR/DAX-1	-0.002	0.075	0.23	18	-0.22	3	21
CREBBP	0.022	0.005	-10000	0	-10000	0	0
SMARCE1	0.022	0.007	-10000	0	-10000	0	0

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.027	0.036	-10000	0	-0.22	10	10
ATM	0.022	0.005	-10000	0	-10000	0	0
UBE2D3	0.022	0.004	-10000	0	-10000	0	0
PRKDC	0.021	0.007	-10000	0	-10000	0	0
ATR	0.022	0.005	-10000	0	-10000	0	0
UBE2L3	0.022	0.005	-10000	0	-10000	0	0
FANCD2	0.013	0.012	0.18	2	-10000	0	2
protein ubiquitination	0.1	0.083	0.21	143	-0.17	5	148
XRCC5	0.023	0.003	-10000	0	-10000	0	0
XRCC6	0.021	0.006	-10000	0	-10000	0	0
M/R/N Complex	0.04	0.016	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
DNA-PK	0.039	0.017	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	0.01	0.1	-10000	0	-0.44	17	17
FANCF	0.021	0.022	-10000	0	-0.32	2	2
BRCA1	0.022	0.006	-10000	0	-10000	0	0
CCNE1	0.12	0.14	0.32	172	-10000	0	172
CDK2/Cyclin E1	0.097	0.098	0.24	169	-10000	0	169
FANCG	0.022	0.005	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	0.027	0.036	-10000	0	-0.22	10	10
FANCE	0.022	0.004	-10000	0	-10000	0	0
FANCC	0.021	0.006	-10000	0	-10000	0	0
NBN	0.021	0.007	-10000	0	-10000	0	0
FANCA	0.078	0.12	0.32	98	-10000	0	98
DNA repair	0.02	0.082	0.28	7	-0.34	9	16
BRCA1/BARD1/ubiquitin	0.027	0.036	-10000	0	-0.22	10	10
BARD1/DNA-PK	0.045	0.038	-10000	0	-0.18	10	10
FANCL	0.023	0.003	-10000	0	-10000	0	0
mRNA polyadenylation	-0.027	0.036	0.22	10	-10000	0	10
BRCA1/BARD1/CTIP/M/R/N Complex	0.007	0.048	-10000	0	-0.21	9	9
BRCA1/BACH1/BARD1/TopBP1	0.038	0.035	-10000	0	-0.19	10	10
BRCA1/BARD1/P53	0.046	0.037	-10000	0	-0.18	10	10
BARD1/CSTF1/BRCA1	0.037	0.035	-10000	0	-0.19	10	10
BRCA1/BACH1	0.022	0.005	-10000	0	-10000	0	0
BARD1	0.016	0.047	-10000	0	-0.32	10	10
PCNA	0.022	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	0.038	0.035	-10000	0	-0.19	10	10
BRCA1/BARD1/UbcH7	0.038	0.035	-10000	0	-0.19	10	10
BRCA1/BARD1/RAD51/PCNA	0.083	0.08	0.23	102	-0.18	4	106
BARD1/DNA-PK/P53	0.051	0.041	-10000	0	-0.17	10	10
BRCA1/BARD1/Ubiquitin	0.027	0.036	-10000	0	-0.22	10	10
BRCA1/BARD1/CTIP	0.027	0.031	-10000	0	-0.18	10	10
FA complex	0.027	0.061	0.2	7	-0.25	5	12
BARD1/EWS	0.027	0.036	-10000	0	-0.22	10	10
RBBP8	-0.014	0.004	-10000	0	-10000	0	0
TP53	0.021	0.006	-10000	0	-10000	0	0
TOPBP1	0.022	0.004	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	-0.045	0.037	0.17	10	-10000	0	10
BRCA1/BARD1	0.11	0.089	0.23	143	-0.17	5	148
CSTF1	0.022	0.005	-10000	0	-10000	0	0
BARD1/EWS-Fli1	0.012	0.033	-10000	0	-0.22	10	10
CDK2	0.022	0.004	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.095	0.13	0.32	123	-10000	0	123
RAD50	0.022	0.004	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.027	0.036	-10000	0	-0.22	10	10
EWSR1	0.022	0.006	-10000	0	-10000	0	0

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.028	0.009	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.057	0.097	0.32	59	-10000	0	59
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.02	0.017	-10000	0	-0.32	1	1
RAC1-CDC42/GTP/PAK family	-0.016	0.06	-10000	0	-0.16	70	70
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.022	0.005	-10000	0	-10000	0	0
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.022	0.005	-10000	0	-10000	0	0
FYN	0.022	0.003	-10000	0	-10000	0	0
MAP3K12	0.02	0.03	-10000	0	-0.32	4	4
FGR	0.014	0.052	-10000	0	-0.32	12	12
p38 alpha/TAB1	-0.023	0.073	-10000	0	-0.27	28	28
PRKG1	-0.13	0.17	-10000	0	-0.32	229	229
DUSP8	0.018	0.034	-10000	0	-0.32	5	5
PGK/cGMP/p38 alpha	-0.046	0.11	-10000	0	-0.28	44	44
apoptosis	-0.023	0.07	-10000	0	-0.26	28	28
RAL/GTP	0.03	0.006	-10000	0	-10000	0	0
LYN	0.021	0.007	-10000	0	-10000	0	0
DUSP1	-0.07	0.15	-10000	0	-0.32	137	137
PAK1	0.022	0.004	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.051	0.021	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0.022	0.004	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.029	0.008	-10000	0	-10000	0	0
MAPK11	0.017	0.1	0.24	13	-0.38	14	27
BLK	0.043	0.083	0.32	40	-10000	0	40
HCK	0.022	0.015	0.32	1	-10000	0	1
MAP2K3	0.021	0.006	-10000	0	-10000	0	0
DUSP16	0.022	0.003	-10000	0	-10000	0	0
DUSP10	0.019	0.008	-10000	0	-10000	0	0
TRAF6/MEKK3	0.027	0.008	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.015	0.1	0.21	15	-0.32	22	37
positive regulation of innate immune response	0.018	0.12	0.26	15	-0.45	14	29
LCK	0.024	0.031	0.32	4	-0.32	1	5
p38alpha-beta/MKP7	0.026	0.11	0.26	12	-0.43	14	26
p38alpha-beta/MKP5	0.017	0.11	0.28	8	-0.43	14	22
PGK/cGMP	-0.09	0.12	-10000	0	-0.22	229	229
PAK2	0.021	0.007	-10000	0	-10000	0	0
p38alpha-beta/MKP1	-0.001	0.13	0.26	8	-0.39	23	31
CDC42	0.022	0.004	-10000	0	-10000	0	0
RALB	0.023	0.002	-10000	0	-10000	0	0
RALA	0.022	0.004	-10000	0	-10000	0	0
PAK3	-0.03	0.12	-10000	0	-0.32	76	76

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.022	0.005	-10000	0	-10000	0	0
GNAT1/GTP	0.016	0.018	0.22	4	-10000	0	4
Metarhodopsin II/Arrestin	0.026	0.018	0.21	4	-10000	0	4
PDE6G/GNAT1/GTP	0.037	0.046	0.21	31	-0.18	1	32
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.022	0.028	0.32	4	-10000	0	4
GRK1	0.018	0.015	0.32	1	-10000	0	1
CNG Channel	0.039	0.054	0.26	4	-0.16	15	19
mol:Na +	0.041	0.046	0.24	4	-0.16	4	8
mol:ADP	0.018	0.015	0.32	1	-10000	0	1
RGS9-1/Gbeta5/R9AP	-0.007	0.099	0.23	9	-0.19	108	117
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.051	0.053	0.29	4	-0.17	4	8
CNGB1	0.03	0.055	0.32	17	-10000	0	17
RDH5	0.021	0.022	-10000	0	-0.32	2	2
SAG	0.02	0.014	0.32	1	-10000	0	1
mol:Ca2+	-0.013	0.071	0.32	16	-10000	0	16
Na + (4 Units)	0.014	0.047	0.19	3	-0.16	4	7
RGS9	-0.053	0.14	-10000	0	-0.32	110	110
GNB1/GNGT1	0.05	0.059	0.24	46	-10000	0	46
GNAT1/GDP	0.003	0.092	0.21	10	-0.16	106	116
GUCY2D	0.024	0.038	0.32	8	-10000	0	8
GNGT1	0.052	0.091	0.32	51	-10000	0	51
GUCY2F	0.019	0.003	-10000	0	-10000	0	0
GNB5	0.022	0.005	-10000	0	-10000	0	0
mol:GMP (4 units)	-0.012	0.049	0.13	35	-0.16	17	52
mol:11-cis-retinal	0.021	0.022	-10000	0	-0.32	2	2
mol:cGMP	0.039	0.04	0.22	13	-0.17	4	17
GNB1	0.022	0.004	-10000	0	-10000	0	0
Rhodopsin	0.03	0.024	0.24	3	-0.22	2	5
SLC24A1	0.022	0.005	-10000	0	-10000	0	0
CNGA1	0.031	0.051	0.32	15	-10000	0	15
Metarhodopsin II	0.023	0.017	0.2	4	-10000	0	4
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.051	0.046	0.23	19	-0.18	4	23
RGS9BP	0.031	0.053	0.32	16	-10000	0	16
Metarhodopsin II/Transducin	0.021	0.035	0.17	12	-10000	0	12
GCAP Family/Ca ++	0.04	0.035	0.21	14	-0.17	4	18
PDE6A/B	0.025	0.047	0.24	2	-0.22	16	18
mol:Pi	-0.007	0.099	0.22	9	-0.19	108	117
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.052	0.053	0.22	41	-10000	0	41
PDE6B	0.013	0.061	0.32	2	-0.32	15	17
PDE6A	0.022	0.021	0.32	1	-0.32	1	2
PDE6G	0.04	0.076	0.32	32	-0.32	1	33
RHO	0.021	0.024	0.32	3	-10000	0	3
PDE6	0.011	0.11	0.34	4	-0.17	115	119
GUCA1A	0.03	0.053	0.32	16	-10000	0	16
GC2/GCAP Family	0.052	0.037	0.22	14	-0.18	4	18
GUCA1C	0.016	0.003	-10000	0	-10000	0	0
GUCA1B	0.02	0.03	-10000	0	-0.32	4	4

Canonical Wnt signaling pathway

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
HDAC1	0.026	0.024	0.22	4	-10000	0	4
AES	0.024	0.021	0.18	4	-10000	0	4
FBXW11	0.022	0.004	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.032	0.013	-10000	0	-0.22	1	1
SMAD4	0.022	0.004	-10000	0	-10000	0	0
DKK2	-0.001	0.089	0.32	2	-0.32	35	37
TLE1	0.025	0.021	0.2	3	-10000	0	3
MACF1	0.022	0.004	-10000	0	-10000	0	0
CTNNB1	-0.006	0.083	0.34	3	-0.38	5	8
WIF1	0.089	0.15	0.32	134	-0.32	18	152
beta catenin/RanBP3	0.011	0.12	0.41	29	-0.52	1	30
KREMEN2	0.048	0.085	0.32	44	-10000	0	44
DKK1	0.079	0.13	0.32	101	-0.32	4	105
beta catenin/beta TrCP1	0.003	0.081	0.31	2	-0.36	4	6
FZD1	0.022	0.016	-10000	0	-0.32	1	1
AXIN2	-0.05	0.26	0.62	7	-1.1	25	32
AXIN1	0.022	0.005	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.001	0.11	-10000	0	-0.58	15	15
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	-0.033	0.17	0.29	2	-0.53	42	44
Axin1/APC/GSK3	-0.004	0.059	0.24	2	-0.3	6	8
Axin1/APC/GSK3/beta catenin/Macf1	0.004	0.064	0.32	2	-0.4	5	7
HNF1A	0.043	0.072	0.31	32	-10000	0	32
CTBP1	0.025	0.02	0.2	3	-10000	0	3
MYC	0.062	0.27	0.58	76	-1.1	10	86
RANBP3	0.021	0.006	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	0.042	0.08	0.23	40	-0.18	31	71
NKD1	0.036	0.088	0.32	34	-0.32	8	42
TCF4	0.014	0.064	0.19	4	-0.31	17	21
TCF3	0.024	0.022	0.2	4	-10000	0	4
WNT1/LRP6/FZD1/Axin1	0.055	0.027	0.23	5	-0.18	1	6
Ran/GTP	0.017	0.003	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.003	0.14	0.47	21	-0.42	13	34
LEF1	0.022	0.035	0.19	4	-0.3	4	8
DVL1	0	0.065	0.23	2	-0.56	4	6
CSNK2A1	0.022	0.004	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	-0.045	0.18	-10000	0	-0.55	43	43
DKK1/LRP6/Kremen 2	0.09	0.091	0.23	135	-0.18	4	139
LRP6	0.023	0.003	-10000	0	-10000	0	0
CSNK1A1	0.025	0.022	0.21	3	-10000	0	3
NLK	0.02	0.012	-10000	0	-10000	0	0
CCND1	0.001	0.11	0.6	11	-0.58	3	14
WNT1	0.024	0.036	0.32	7	-10000	0	7
GSK3A	0.022	0.004	-10000	0	-10000	0	0
GSK3B	0.022	0.004	-10000	0	-10000	0	0
FRAT1	0.021	0.006	-10000	0	-10000	0	0
PPP2R5D	0.008	0.053	0.24	6	-0.32	2	8
APC	-0.016	0.039	0.17	19	-10000	0	19
WNT1/LRP6/FZD1	-0.014	0.066	0.18	6	-0.24	4	10
CREBBP	0.025	0.02	0.19	3	-10000	0	3

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.016	0.1	0.24	2	-0.22	95	97
AKT1	-0.021	0.14	0.34	5	-0.48	31	36
PTK2B	-0.058	0.12	-10000	0	-0.48	25	25
VEGFR2 homodimer/Frs2	-0.003	0.12	-10000	0	-0.49	26	26
CAV1	-0.049	0.14	-10000	0	-0.32	105	105
CALM1	0.022	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.01	0.11	-10000	0	-0.47	25	25
endothelial cell proliferation	-0.028	0.14	0.34	11	-0.44	34	45
mol:Ca2+	-0.046	0.11	-10000	0	-0.49	25	25
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.021	0.11	-10000	0	-0.46	25	25
RP11-342D11.1	-0.042	0.11	-10000	0	-0.48	26	26
CDH5	0.016	0.037	-10000	0	-0.32	6	6
VEGFA homodimer	0.043	0.028	-10000	0	-0.18	1	1
SHC1	0.019	0.009	-10000	0	-10000	0	0
SHC2	-0.021	0.11	-10000	0	-0.32	62	62
HRAS/GDP	-0.002	0.1	-10000	0	-0.43	23	23
SH2D2A	0.028	0.053	0.32	15	-10000	0	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.002	0.13	-10000	0	-0.43	32	32
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.011	0.12	-10000	0	-0.46	25	25
VEGFR1 homodimer	0.021	0.016	-10000	0	-0.32	1	1
SHC/GRB2/SOS1	0.011	0.12	-10000	0	-0.46	24	24
GRB10	-0.046	0.11	-10000	0	-0.5	25	25
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GRB2	0.021	0.006	-10000	0	-10000	0	0
PAK1	0.022	0.004	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.027	0.12	-10000	0	-0.47	25	25
HRAS	0.022	0.005	-10000	0	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.034	0.1	-10000	0	-0.34	32	32
HIF1A	0.022	0.004	-10000	0	-10000	0	0
FRS2	0.023	0.003	-10000	0	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.019	0.11	-10000	0	-0.45	25	25
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.009	0.065	-10000	0	-0.32	19	19
Nck/Pak	0.031	0.018	-10000	0	-0.22	2	2
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.01	0.11	-10000	0	-0.48	25	25
mol:GDP	0.003	0.11	-10000	0	-0.45	24	24
mol:NADP	-0.013	0.12	0.35	5	-0.38	32	37
eNOS/Hsp90	-0.004	0.11	0.34	5	-0.36	30	35
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	-0.046	0.11	-10000	0	-0.5	25	25
HIF1A/ARNT	0.026	0.015	-10000	0	-10000	0	0
SHB	0.022	0.004	-10000	0	-10000	0	0
VEGFA	0.023	0.005	-10000	0	-10000	0	0
VEGFC	0.017	0.04	-10000	0	-0.32	7	7
FAK1/Vinculin	-0.034	0.14	-10000	0	-0.55	26	26
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.015	0.14	-10000	0	-0.5	26	26
PTPN6	0.022	0.004	-10000	0	-10000	0	0
EPAS1	0.009	0.072	-10000	0	-0.3	26	26
mol:L-citrulline	-0.013	0.12	0.35	5	-0.38	32	37
ITGAV	0.022	0.003	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.021	0.1	-10000	0	-0.43	25	25
VEGFR2 homodimer/VEGFA homodimer	-0.002	0.13	-10000	0	-0.52	26	26
VEGFR2/3 heterodimer	-0.011	0.12	-10000	0	-0.53	25	25
VEGFB	0.022	0.004	-10000	0	-10000	0	0
MAPK11	-0.042	0.12	0.3	3	-0.5	27	30
VEGFR2 homodimer	-0.039	0.12	-10000	0	-0.58	25	25
FLT1	0.021	0.016	-10000	0	-0.32	1	1
NEDD4	-0.003	0.089	-10000	0	-0.32	37	37
MAPK3	-0.041	0.12	0.3	9	-0.46	26	35
MAPK1	-0.042	0.12	0.31	8	-0.47	25	33
VEGFA145/NRP2	0.021	0.055	-10000	0	-0.22	24	24
VEGFR1/2 heterodimer	-0.004	0.12	-10000	0	-0.52	25	25
KDR	-0.039	0.12	-10000	0	-0.58	25	25
VEGFA165/NRP1/VEGFR2 homodimer	-0.009	0.13	-10000	0	-0.48	28	28
SRC	0.022	0.005	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.044	0.12	0.32	8	-0.47	27	35
PI3K	-0.02	0.13	-10000	0	-0.53	26	26
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.009	0.11	-10000	0	-0.47	25	25
FES	-0.047	0.11	-10000	0	-0.49	26	26
GAB1	-0.007	0.14	-10000	0	-0.53	27	27
VEGFR2 homodimer/VEGFA homodimer/Src	0.009	0.11	-10000	0	-0.47	25	25
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
SOS1	0.022	0.004	-10000	0	-10000	0	0
ARNT	0.018	0.01	-10000	0	-10000	0	0
eNOS/Caveolin-1	-0.019	0.13	0.36	2	-0.41	34	36
VEGFR2 homodimer/VEGFA homodimer/Yes	0.009	0.11	-10000	0	-0.47	25	25
PI3K/GAB1	-0.007	0.13	-10000	0	-0.49	27	27
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.032	0.11	-10000	0	-0.42	25	25
PRKACA	0.022	0.005	-10000	0	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.001	0.12	-10000	0	-0.49	26	26
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
CDC42	-0.047	0.11	-10000	0	-0.5	25	25
actin cytoskeleton reorganization	0.009	0.11	-10000	0	-0.46	25	25
PTK2	-0.045	0.14	0.29	3	-0.58	26	29
EDG1	-0.042	0.11	-10000	0	-0.48	26	26
mol:DAG	-0.046	0.11	-10000	0	-0.5	25	25
CaM/Ca2+	-0.045	0.1	-10000	0	-0.46	25	25
MAP2K3	-0.043	0.1	-10000	0	-0.46	24	24
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.002	0.13	-10000	0	-0.51	25	25
PLCG1	-0.047	0.11	-10000	0	-0.5	25	25
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.02	0.11	-10000	0	-0.45	25	25
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
YES1	0.022	0.005	-10000	0	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.01	0.11	-10000	0	-0.48	25	25
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.01	0.11	-10000	0	-0.48	25	25
cell migration	-0.034	0.13	0.26	1	-0.5	27	28
mol:PI-3-4-5-P3	-0.017	0.12	-10000	0	-0.49	26	26
FYN	0.022	0.003	-10000	0	-10000	0	0
VEGFB/NRP1	-0.043	0.1	-10000	0	-0.46	25	25
mol:NO	-0.013	0.12	0.35	5	-0.38	32	37
PXN	0.022	0.003	-10000	0	-10000	0	0
HRAS/GTP	-0.045	0.09	-10000	0	-0.43	23	23
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.01	0.12	-10000	0	-0.51	25	25
VHL	0.021	0.016	-10000	0	-0.32	1	1
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
NOS3	-0.016	0.13	0.36	5	-0.42	32	37
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.015	0.13	-10000	0	-0.48	26	26
RAC1	0.022	0.005	-10000	0	-10000	0	0
PRKCA	-0.051	0.11	-10000	0	-0.46	28	28
PRKCB	-0.051	0.11	-10000	0	-0.47	27	27
VCL	0.021	0.006	-10000	0	-10000	0	0
VEGFA165/NRP1	-0.017	0.12	-10000	0	-0.49	25	25
VEGFR1/2 heterodimer/VEGFA homodimer	0.009	0.11	-10000	0	-0.48	25	25
VEGFA165/NRP2	0.021	0.055	-10000	0	-0.22	24	24
MAPKKK cascade	-0.019	0.12	0.32	2	-0.45	22	24
NRP2	0.006	0.074	-10000	0	-0.32	25	25
VEGFC homodimer	0.017	0.04	-10000	0	-0.32	7	7
NCK1	0.021	0.022	-10000	0	-0.32	2	2
ROCK1	0.022	0.003	-10000	0	-10000	0	0
FAK1/Paxillin	-0.034	0.15	0.36	1	-0.54	27	28
MAP3K13	-0.045	0.11	-10000	0	-0.47	25	25
PDPK1	-0.04	0.1	0.24	1	-0.45	25	26

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0.081	0.2	1	-0.17	93	94
MAPK9	0.004	0.001	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.005	0.027	0.17	11	-10000	0	11
GNB1/GNG2	0.024	0.037	0.21	1	-0.18	14	15
GNB1	0.022	0.004	-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	0.004	0.001	-10000	0	-10000	0	0
Gs family/GTP	-0.015	0.065	-10000	0	-0.16	85	85
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	0.009	0.017	0.046	85	-10000	0	85
GNAL	-0.035	0.13	-10000	0	-0.32	85	85
GNG2	0.013	0.058	0.32	1	-0.32	14	15
CRH	0.022	0.043	0.32	10	-10000	0	10
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.002	0.025	-10000	0	-0.24	5	5
MAPK11	0.003	0.016	-10000	0	-0.24	2	2

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.022	0.003	-10000	0	-10000	0	0
mol:PIP3	-0.03	0.066	-10000	0	-0.24	43	43
FRAP1	0.008	0.052	0.27	1	-0.4	4	5
AKT1	-0.012	0.075	0.16	40	-0.21	38	78
INSR	0.021	0.006	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0.025	0.008	-10000	0	-10000	0	0
mol:GTP	-0.017	0.068	0.18	6	-0.19	34	40
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.037	-10000	0	-0.17	11	11
TSC2	0.022	0.005	-10000	0	-10000	0	0
RHEB/GDP	-0.03	0.042	-10000	0	-0.17	32	32
TSC1	0.021	0.016	-10000	0	-0.32	1	1
Insulin Receptor/IRS1	-0.01	0.088	-10000	0	-0.27	53	53
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.004	0.045	-10000	0	-0.2	10	10
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.022	0.005	-10000	0	-10000	0	0
RPS6KB1	0.004	0.078	0.25	9	-0.29	13	22
MAP3K5	0.003	0.033	0.19	7	-0.21	6	13
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
apoptosis	0.003	0.033	0.19	7	-0.21	6	13
mol:LY294002	0	0	-10000	0	-0.001	52	52
EIF4B	0.004	0.075	0.24	11	-0.26	13	24
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.02	0.068	0.24	8	-0.26	9	17
eIF4E/eIF4G1/eIF4A1	0.007	0.03	-10000	0	-0.27	3	3
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.002	0.083	-10000	0	-0.25	47	47
mTOR/RHEB/GTP/Raptor/GBL	-0.003	0.05	0.19	13	-0.14	7	20
FKBP1A	0.022	0.004	-10000	0	-10000	0	0
RHEB/GTP	0.012	0.061	-10000	0	-0.17	31	31
mol:Amino Acids	0	0	-10000	0	-0.001	52	52
FKBP12/Rapamycin	0.017	0.004	-10000	0	-10000	0	0
PDPK1	-0.022	0.075	0.15	31	-0.22	43	74
EIF4E	0.022	0.004	-10000	0	-10000	0	0
ASK1/PP5C	0.024	0.083	-10000	0	-0.54	8	8
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	-0.005	0.08	-10000	0	-0.29	27	27
TSC1/TSC2	0.01	0.077	0.23	8	-0.2	34	42
tumor necrosis factor receptor activity	0	0	0.001	52	-10000	0	52
RPS6	0.022	0.005	-10000	0	-10000	0	0
PPP5C	0.022	0.004	-10000	0	-10000	0	0
EIF4G1	0.021	0.007	-10000	0	-10000	0	0
IRS1	-0.024	0.088	-10000	0	-0.28	53	53
INS	0.016	0.004	-10000	0	-10000	0	0
PTEN	0.021	0.006	-10000	0	-10000	0	0
PDK2	-0.021	0.075	0.15	33	-0.22	41	74
EIF4EBP1	-0.019	0.22	-10000	0	-1	22	22
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PPP2R5D	0.008	0.059	0.28	7	-0.36	4	11
peptide biosynthetic process	-0.014	0.018	0.18	4	-10000	0	4
RHEB	0.022	0.005	-10000	0	-10000	0	0
EIF4A1	0.021	0.006	-10000	0	-10000	0	0
mol:Rapamycin	0	0.001	0.003	51	-0.002	1	52
EEF2	-0.014	0.018	0.18	4	-10000	0	4
eIF4E/4E-BP1	-0.008	0.2	-10000	0	-0.94	22	22

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.013	0.014	0.28	1	-10000	0	1
BAD/BCL-XL/YWHAZ	0.029	0.016	0.2	1	-10000	0	1
CDKN1B	0	0.046	-10000	0	-0.29	7	7
CDKN1A	0.005	0.047	-10000	0	-0.31	8	8
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.021	0.007	-10000	0	-10000	0	0
FOXO3	0.005	0.038	0.19	2	-0.29	6	8
AKT1	0.004	0.037	-10000	0	-0.3	7	7
BAD	0.022	0.004	-10000	0	-10000	0	0
AKT3	-0.072	0.12	-10000	0	-0.24	158	158
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.003	0.043	-10000	0	-0.29	8	8
AKT1/ASK1	0.026	0.051	0.23	2	-0.28	8	10
BAD/YWHAZ	0.039	0.017	-10000	0	-10000	0	0
RICTOR	0.021	0.022	-10000	0	-0.32	2	2
RAF1	0.022	0.004	-10000	0	-10000	0	0
JNK cascade	-0.024	0.047	0.27	8	-10000	0	8
TSC1	0.006	0.024	-10000	0	-0.28	2	2
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
AKT1/RAF1	0.029	0.051	0.24	1	-0.29	7	8
EP300	0.021	0.006	-10000	0	-10000	0	0
mol:GDP	0.007	0.041	-10000	0	-0.3	8	8
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.004	0.035	-10000	0	-0.29	6	6
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
TBC1D4	-0.005	0.011	-10000	0	-0.17	2	2
MAP3K5	0.022	0.016	-10000	0	-0.32	1	1
MAPKAP1	0.021	0.006	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.057	0.077	0.37	7	-0.21	17	24
YWHAH	0.021	0.006	-10000	0	-10000	0	0
AKT1S1	0.004	0.043	0.19	2	-0.29	8	10
CASP9	0.005	0.035	-10000	0	-0.29	5	5
YWHAB	0.022	0.005	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.02	0.064	0.27	5	-0.28	8	13
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.041	0.015	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
AKT2/p21CIP1	0.009	0.05	0.23	4	-0.28	8	12
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.003	0.048	-10000	0	-0.28	13	13
CHUK	0.006	0.039	-10000	0	-0.29	5	5
BAD/BCL-XL	0.027	0.044	0.25	1	-0.28	5	6
mTORC2	0.026	0.015	-10000	0	-0.16	2	2
AKT2	0.008	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.064	0.09	0.26	14	-0.4	7	21
PDPK1	0.022	0.005	-10000	0	-10000	0	0
MDM2	0.004	0.041	-10000	0	-0.29	7	7
MAPKKK cascade	-0.029	0.051	0.28	7	-0.24	1	8
MDM2/Cbp/p300	0.036	0.055	0.26	3	-0.27	8	11
TSC1/TSC2	0.001	0.039	0.27	3	-0.28	6	9
proteasomal ubiquitin-dependent protein catabolic process	0.034	0.053	0.26	3	-0.26	8	11
glucose import	-0.079	0.083	0.2	5	-0.16	243	248
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.004	0.037	0.17	2	-0.18	10	12
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.081	0.08	0.2	2	-0.16	243	245
GSK3A	0.004	0.043	-10000	0	-0.29	8	8
FOXO1	0.003	0.037	-10000	0	-0.29	6	6
GSK3B	0.004	0.043	-10000	0	-0.29	8	8
SFN	0.25	0.13	0.32	380	-10000	0	380
G1/S transition of mitotic cell cycle	0.009	0.058	0.24	10	-0.29	8	18
p27Kip1/14-3-3 family	0.071	0.088	0.26	9	-0.48	6	15
PRKACA	0.022	0.005	-10000	0	-10000	0	0
KPNA1	0.022	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
RHEB	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.01	0.063	-10000	0	-0.32	18	18
alphaV beta3 Integrin	-0.016	0.1	0.24	2	-0.22	95	97
PTK2	-0.026	0.099	-10000	0	-0.35	27	27
positive regulation of JNK cascade	-0.004	0.084	-10000	0	-0.29	22	22
CDC42/GDP	0	0.12	-10000	0	-0.38	29	29
Rac1/GDP	-0.002	0.12	0.31	1	-0.38	31	32
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.001	-10000	0	-10000	0	0
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.001	0.1	-10000	0	-0.36	21	21
nectin-3/I-afadin	0.02	0.055	-10000	0	-0.22	24	24
RAPGEF1	-0.01	0.11	0.31	3	-0.4	28	31
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.016	0.11	-10000	0	-0.44	30	30
PDGFB-D/PDGFRB	0.01	0.063	-10000	0	-0.32	18	18
TLN1	-0.024	0.056	-10000	0	-0.26	22	22
Rap1/GTP	-0.009	0.082	-10000	0	-0.29	30	30
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.042	0.01	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.02	0.055	-10000	0	-0.22	24	24
PVR	0.022	0.004	-10000	0	-10000	0	0
Necl-5(dimer)	0.022	0.004	-10000	0	-10000	0	0
mol:GDP	-0.014	0.14	0.32	1	-0.46	31	32
MLLT4	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PI3K	0.041	0.066	-10000	0	-0.18	33	33
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.032	0.013	0.24	1	-10000	0	1
positive regulation of lamellipodium assembly	-0.01	0.099	-10000	0	-0.3	37	37
PVRL1	0.022	0.014	0.32	1	-10000	0	1
PVRL3	0.006	0.072	-10000	0	-0.32	24	24
PVRL2	0.022	0.005	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
CDH1	0.019	0.026	0.32	1	-0.32	2	3
CLDN1	-0.042	0.13	-10000	0	-0.32	92	92
JAM-A/CLDN1	0.003	0.088	-10000	0	-0.19	81	81
SRC	-0.016	0.13	-10000	0	-0.48	32	32
ITGB3	-0.042	0.14	0.32	2	-0.32	96	98
nectin-1(dimer)/I-afadin/I-afadin	0.032	0.013	0.24	1	-10000	0	1
FARP2	-0.008	0.14	-10000	0	-0.5	15	15
RAC1	0.022	0.005	-10000	0	-10000	0	0
CTNNA1	0.022	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.032	0.05	-10000	0	-0.19	23	23
nectin-1/I-afadin	0.032	0.013	0.24	1	-10000	0	1
nectin-2/I-afadin	0.031	0.009	-10000	0	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0.029	0.008	-10000	0	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.031	0.051	-10000	0	-0.19	23	23
CDC42/GTP/IQGAP1/filamentous actin	0.029	0.007	-10000	0	-10000	0	0
F11R	0.018	0.017	-10000	0	-0.32	1	1
positive regulation of filopodium formation	-0.004	0.084	-10000	0	-0.29	22	22
alphaV/beta3 Integrin/Talin	-0.027	0.11	0.3	3	-0.3	35	38
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.031	0.009	-10000	0	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0.031	0.009	-10000	0	-10000	0	0
PIP5K1C	-0.023	0.061	-10000	0	-0.2	45	45
VAV2	-0.023	0.16	0.34	1	-0.49	37	38
RAP1/GDP	0.003	0.11	0.29	1	-0.36	28	29
ITGAV	0.022	0.003	-10000	0	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.032	0.05	-10000	0	-0.19	23	23
nectin-3(dimer)/I-afadin/I-afadin	0.02	0.055	-10000	0	-0.22	24	24
Rac1/GTP	-0.009	0.12	-10000	0	-0.38	33	33
PTPRM	-0.015	0.073	-10000	0	-0.22	49	49
E-cadherin/beta catenin/alpha catenin	0.053	0.034	-10000	0	-0.16	2	2
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0

HIF-2-alpha transcription factor network

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
MMP14	-0.005	0.089	-10000	0	-0.64	8	8
oxygen homeostasis	-0.008	0.012	-10000	0	-10000	0	0
TCEB2	0.022	0.005	-10000	0	-10000	0	0
TCEB1	0.021	0.007	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.004	0.088	0.26	2	-0.27	4	6
EPO	-0.077	0.15	0.53	1	-0.47	9	10
FIH (dimer)	-0.004	0.028	-10000	0	-10000	0	0
APEX1	-0.008	0.032	-10000	0	-10000	0	0
SERPINE1	-0.083	0.15	0.37	1	-0.41	36	37
FLT1	-0.051	0.19	-10000	0	-0.68	39	39
ADORA2A	-0.067	0.16	0.38	3	-0.39	31	34
germ cell development	-0.08	0.15	0.37	4	-0.42	34	38
SLC11A2	-0.081	0.15	0.37	1	-0.4	32	33
BHLHE40	-0.081	0.15	0.37	1	-0.4	32	33
HIF1AN	-0.004	0.028	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.038	0.1	-10000	0	-0.32	7	7
ETS1	0.019	0.035	-10000	0	-0.28	3	3
CITED2	-0.033	0.18	-10000	0	-0.86	23	23
KDR	-0.071	0.26	-10000	0	-0.9	42	42
PGK1	-0.081	0.15	-10000	0	-0.4	31	31
SIRT1	0.02	0.022	-10000	0	-0.32	2	2
response to hypoxia	0	0.001	-10000	0	-10000	0	0
HIF2A/ARNT	-0.076	0.17	-10000	0	-0.44	32	32
EPAS1	-0.032	0.066	0.21	2	-0.26	10	12
SP1	0.024	0.007	-10000	0	-10000	0	0
ABCG2	-0.16	0.22	0.37	1	-0.42	192	193
EFNA1	-0.079	0.15	0.45	1	-0.4	34	35
FXN	-0.066	0.16	0.38	3	-0.39	31	34
POU5F1	-0.082	0.16	0.4	2	-0.43	35	37
neuron apoptosis	0.075	0.17	0.44	32	-10000	0	32
EP300	0.021	0.006	-10000	0	-10000	0	0
EGLN3	-0.004	0.04	0.32	3	-0.33	1	4
EGLN2	-0.005	0.028	-10000	0	-10000	0	0
EGLN1	-0.003	0.025	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0.039	0.02	-10000	0	-0.19	1	1
VHL	0.021	0.016	-10000	0	-0.32	1	1
ARNT	-0.005	0.027	-10000	0	-10000	0	0
SLC2A1	-0.064	0.16	0.38	3	-0.39	31	34
TWIST1	-0.075	0.18	0.38	2	-0.48	36	38
ELK1	0.021	0.022	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.036	0.11	-10000	0	-0.34	3	3
VEGFA	-0.081	0.15	0.37	1	-0.4	32	33
CREBBP	0.022	0.005	-10000	0	-10000	0	0

FoxO family signaling

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
G6PC	0.005	0.048	-10000	0	-10000	0	0
PLK1	0.24	0.23	0.56	81	-0.62	1	82
CDKN1B	0.1	0.18	0.35	59	-0.39	28	87
FOXO3	0.18	0.22	0.5	80	-0.5	6	86
KAT2B	0.043	0.06	-10000	0	-0.29	8	8
FOXO1/SIRT1	0.007	0.042	-10000	0	-10000	0	0
CAT	0.16	0.2	0.55	21	-0.6	2	23
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
AKT1	0.049	0.043	-10000	0	-10000	0	0
FOXO1	0.009	0.05	0.24	1	-10000	0	1
MAPK10	0.005	0.061	0.22	10	-0.16	41	51
mol:GTP	0	0.001	-10000	0	-10000	0	0
FOXO4	0.008	0.084	0.42	2	-0.42	2	4
response to oxidative stress	0.032	0.035	0.12	4	-10000	0	4
FOXO3A/SIRT1	0.14	0.19	0.42	72	-0.41	16	88
XPO1	0.023	0.003	-10000	0	-10000	0	0
EP300	0.023	0.007	-10000	0	-10000	0	0
BCL2L11	0.056	0.09	-10000	0	-0.74	4	4
FOXO1/SKP2	0.019	0.046	-10000	0	-10000	0	0
mol:GDP	0.032	0.035	0.12	4	-10000	0	4
RAN	0.023	0.004	-10000	0	-10000	0	0
GADD45A	0.11	0.14	0.42	6	-0.6	3	9
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
FOXO1/14-3-3 family	0.041	0.15	0.24	5	-0.52	27	32
MST1	0.053	0.059	0.36	9	-10000	0	9
CSNK1D	0.022	0.005	-10000	0	-10000	0	0
CSNK1E	0.021	0.006	-10000	0	-10000	0	0
FOXO4/14-3-3 family	0.065	0.13	-10000	0	-0.43	20	20
YWHAB	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.02	0.033	0.22	8	-0.16	1	9
MAPK9	0.023	0.037	0.22	11	-10000	0	11
YWHAG	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
SIRT1	-0.002	0.03	-10000	0	-0.31	2	2
SOD2	0.12	0.16	0.44	20	-0.44	4	24
RBL2	0.082	0.27	0.52	5	-0.74	24	29
RAL/GDP	0.048	0.032	-10000	0	-10000	0	0
CHUK	0.048	0.042	-10000	0	-10000	0	0
Ran/GTP	0.018	0.004	-10000	0	-10000	0	0
CSNK1G2	0.021	0.006	-10000	0	-10000	0	0
RAL/GTP	0.05	0.027	-10000	0	-10000	0	0
CSNK1G1	0.022	0.005	-10000	0	-10000	0	0
FASLG	0.059	0.11	0.45	2	-1.1	3	5
SKP2	0.022	0.005	-10000	0	-10000	0	0
USP7	0.022	0.006	-10000	0	-10000	0	0
IKBKB	0.043	0.042	-10000	0	-10000	0	0
CCNB1	0.18	0.22	0.56	75	-0.7	1	76
FOXO1-3a-4/beta catenin	0.1	0.14	0.41	15	-0.38	2	17
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.046	-10000	0	-10000	0	0
CSNK1A1	0.022	0.004	-10000	0	-10000	0	0
SGK1	0.048	0.048	-10000	0	-0.31	2	2
CSNK1G3	0.022	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.031	0.007	-10000	0	-10000	0	0
ZFAND5	0.007	0.075	0.48	1	-10000	0	1
SFN	0.25	0.13	0.32	380	-10000	0	380
CDK2	0.02	0.009	-10000	0	-10000	0	0
FOXO3A/14-3-3	0.1	0.12	0.24	58	-0.42	13	71
CREBBP	0.019	0.01	-10000	0	-10000	0	0
FBXO32	0.098	0.4	0.56	51	-0.87	62	113
BCL6	0.14	0.18	0.49	7	-0.71	3	10
RALB	0.023	0.004	-10000	0	-10000	0	0
RALA	0.022	0.005	-10000	0	-10000	0	0
YWHAH	0.021	0.006	-10000	0	-10000	0	0

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.009	0.12	0.32	9	-0.32	30	39
IKBKB	0.02	0.087	0.27	11	-0.29	12	23
AKT1	0.015	0.097	0.26	38	-0.2	12	50
IKBKG	0.017	0.079	0.25	5	-0.29	10	15
CALM1	0.012	0.094	0.24	5	-0.34	10	15
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
MAP3K1	0.001	0.16	0.32	11	-0.43	40	51
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.014	0.097	0.22	8	-0.34	11	19
DOK1	0.022	0.003	-10000	0	-10000	0	0
AP-1	-0.007	0.086	0.26	6	-0.23	14	20
LYN	0.021	0.007	-10000	0	-10000	0	0
BLNK	0.021	0.021	0.32	1	-0.32	1	2
SHC1	0.019	0.009	-10000	0	-10000	0	0
BCR complex	0.039	0.082	0.24	47	-0.23	21	68
CD22	-0.016	0.1	0.28	4	-0.42	20	24
CAMK2G	0.016	0.098	0.26	17	-0.34	7	24
CSNK2A1	0.022	0.004	-10000	0	-10000	0	0
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
SHC/GRB2/SOS1	-0.016	0.04	0.16	1	-0.16	9	10
GO:0007205	0.014	0.098	0.22	4	-0.35	11	15
SYK	0.022	0.015	0.32	1	-10000	0	1
ELK1	0.011	0.097	0.26	3	-0.34	11	14
NFATC1	0.011	0.12	0.26	20	-0.34	25	45
B-cell antigen/BCR complex	0.039	0.082	0.24	47	-0.23	21	68
PAG1/CSK	0.029	0.016	-10000	0	-0.22	1	1
NFKBIB	0.021	0.046	0.16	8	-0.13	13	21
HRAS	0.015	0.092	0.25	10	-0.34	11	21
NFKBIA	0.021	0.045	0.15	9	-0.12	18	27
NF-kappa-B/RelA/I kappa B beta	0.024	0.04	0.15	9	-0.13	1	10
RasGAP/Csk	0.053	0.075	0.23	43	-0.17	19	62
mol:GDP	0.012	0.097	0.22	3	-0.35	11	14
PTEN	0.021	0.006	-10000	0	-10000	0	0
CD79B	0.009	0.065	-10000	0	-0.32	19	19
NF-kappa-B/RelA/I kappa B alpha	0.024	0.04	0.15	9	-0.13	1	10
GRB2	0.021	0.006	-10000	0	-10000	0	0
PI3K/BCAP/CD19	0.016	0.16	0.34	9	-0.43	34	43
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	0.016	0.094	0.22	8	-0.4	7	15
CSK	0.022	0.005	-10000	0	-10000	0	0
FOS	-0.034	0.11	0.3	4	-0.33	24	28
CHUK	0.011	0.096	0.25	6	-0.37	16	22
IBTK	0.023	0.003	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	0.03	0.091	0.28	1	-0.33	6	7
PTPN6	-0.022	0.098	0.26	4	-0.4	19	23
RELA	0.023	0.003	-10000	0	-10000	0	0
BCL2A1	0.018	0.028	0.13	4	-10000	0	4
VAV2	0.013	0.12	0.24	5	-0.39	22	27
ubiquitin-dependent protein catabolic process	0.022	0.046	0.16	8	-0.12	19	27
BTK	0.002	0.14	-10000	0	-0.94	11	11
CD19	0.003	0.087	0.24	7	-0.36	18	25
MAP4K1	0.026	0.038	0.32	8	-10000	0	8
CD72	0.024	0.024	0.32	3	-10000	0	3
PAG1	0.02	0.016	-10000	0	-0.32	1	1
MAPK14	0.004	0.14	0.29	13	-0.38	37	50
SH3BP5	-0.026	0.12	-10000	0	-0.32	72	72
PIK3AP1	0.019	0.096	0.26	9	-0.35	8	17
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	0.015	0.092	0.23	5	-0.44	9	14
RAF1	0.013	0.091	0.26	11	-0.32	11	22
RasGAP/p62DOK/SHIP	0.05	0.072	0.35	1	-0.16	22	23
CD79A	0.049	0.095	0.32	49	-0.32	4	53
re-entry into mitotic cell cycle	-0.007	0.086	0.26	6	-0.22	14	20
RASA1	0.019	0.034	-10000	0	-0.32	5	5
MAPK3	0.009	0.08	0.26	10	-0.28	8	18
MAPK1	0.008	0.078	0.25	8	-0.28	8	16
CD72/SHP1	0.011	0.13	0.28	15	-0.38	21	36
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MAPK8	0.003	0.15	0.34	12	-0.38	36	48
actin cytoskeleton organization	0.013	0.12	0.3	10	-0.35	23	33
NF-kappa-B/RelA	0.047	0.079	0.28	8	-0.21	4	12
Calcineurin	0.025	0.087	-10000	0	-0.34	6	6
PI3K	-0.018	0.086	0.19	1	-0.32	20	21
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	0.025	0.097	0.25	7	-0.32	13	20
SOS1	0.022	0.004	-10000	0	-10000	0	0
Bam32/HPK1	-0.027	0.25	0.39	1	-0.66	56	57
DAPP1	-0.05	0.27	-10000	0	-0.74	56	56
cytokine secretion	0.012	0.12	0.25	20	-0.32	24	44
mol:DAG	0.016	0.094	0.22	8	-0.4	7	15
PLCG2	0.019	0.017	-10000	0	-0.32	1	1
MAP2K1	0.01	0.083	0.24	11	-0.28	11	22
B-cell antigen/BCR complex/FcgammaRIIB	0.043	0.073	0.23	43	-0.19	17	60
mol:PI-3-4-5-P3	-0.01	0.083	0.22	12	-0.26	14	26
ETS1	0.013	0.094	0.25	19	-0.35	6	25
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.061	0.072	0.23	45	-0.17	15	60
B-cell antigen/BCR complex/LYN	0.005	0.087	0.22	1	-0.37	19	20
MALT1	0.022	0.005	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.011	0.12	0.33	5	-0.39	19	24
B-cell antigen/BCR complex/LYN/SYK	0.013	0.12	0.37	3	-0.37	21	24
CARD11	0.014	0.099	0.26	9	-0.34	11	20
FCGR2B	0.019	0.022	0.32	1	-0.32	1	2
PPP3CA	0.022	0.004	-10000	0	-10000	0	0
BCL10	0.023	0.002	-10000	0	-10000	0	0
IKK complex	0.02	0.055	0.17	28	-0.12	11	39
PTPRC	0.014	0.045	0.32	1	-0.32	8	9
PDPK1	0.003	0.082	0.23	27	-0.19	12	39
PPP3CB	0.022	0.005	-10000	0	-10000	0	0
PPP3CC	0.018	0.027	-10000	0	-0.32	3	3
POU2F2	0.018	0.03	0.15	6	-10000	0	6

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.01	0.009	-10000	0	-10000	0	0
RAS family/GTP	0.056	0.084	0.26	1	-0.23	5	6
NFATC4	-0.008	0.076	0.35	14	-0.17	2	16
ERBB2IP	0.019	0.01	-10000	0	-10000	0	0
HSP90 (dimer)	0.022	0.004	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.006	0.055	0.19	3	-0.2	6	9
JUN	0.016	0.1	0.24	14	-0.32	4	18
HRAS	0.022	0.005	-10000	0	-10000	0	0
DOCK7	-0.013	0.056	0.36	2	-0.2	2	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.022	0.047	0.21	8	-0.18	7	15
AKT1	-0.005	0.008	-10000	0	-10000	0	0
BAD	-0.011	0.006	-10000	0	-10000	0	0
MAPK10	-0.023	0.079	0.21	24	-0.18	5	29
mol:GTP	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.004	0.063	0.27	4	-0.21	6	10
RAF1	0.049	0.11	0.26	47	-0.25	5	52
ErbB2/ErbB3/neuregulin 2	0.001	0.071	0.2	12	-0.18	49	61
STAT3	-0.013	0.18	-10000	0	-0.79	25	25
cell migration	-0.015	0.085	0.23	27	-0.2	8	35
mol:PI-3-4-5-P3	0	0.002	-10000	0	-10000	0	0
cell proliferation	0.003	0.26	0.39	37	-0.54	33	70
FOS	-0.062	0.29	0.34	39	-0.42	175	214
NRAS	0.023	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.055	0.19	3	-0.2	6	9
MAPK3	0.028	0.22	0.36	38	-0.57	21	59
MAPK1	0.024	0.22	0.36	37	-0.57	23	60
JAK2	-0.014	0.054	0.26	4	-0.2	4	8
NF2	0.004	0.029	-10000	0	-0.64	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.009	0.04	0.18	5	-0.2	8	13
NRG1	0.015	0.041	-10000	0	-0.32	7	7
GRB2/SOS1	0.032	0.01	-10000	0	-10000	0	0
MAPK8	-0.005	0.067	0.29	3	-0.24	11	14
MAPK9	-0.002	0.067	0.22	27	-10000	0	27
ERBB2	-0.012	0.043	0.27	11	-10000	0	11
ERBB3	0.02	0.027	-10000	0	-0.32	3	3
SHC1	0.019	0.009	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
apoptosis	0.008	0.007	-10000	0	-10000	0	0
STAT3 (dimer)	-0.014	0.18	-10000	0	-0.76	26	26
RNF41	-0.014	0.008	-10000	0	-10000	0	0
FRAP1	-0.005	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.019	0.033	-10000	0	-0.16	7	7
ErbB2/ErbB2/HSP90 (dimer)	-0.012	0.035	0.2	11	-10000	0	11
CHRNA1	0.063	0.2	0.34	132	-0.37	15	147
myelination	0.011	0.1	0.32	37	-10000	0	37
PPP3CB	-0.013	0.05	0.25	3	-0.19	6	9
KRAS	0.023	0.005	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0.044	0.055	0.23	4	-0.2	1	5
NRG2	-0.012	0.1	0.32	1	-0.32	51	52
mol:GDP	0.009	0.04	0.18	5	-0.2	8	13
SOS1	0.023	0.004	-10000	0	-10000	0	0
MAP2K2	0.043	0.12	0.27	43	-0.28	5	48
SRC	0.022	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.018	0.054	0.32	3	-0.2	6	9
MAP2K1	0.017	0.22	0.42	7	-0.54	26	33
heart morphogenesis	-0.006	0.055	0.19	3	-0.2	6	9
RAS family/GDP	0.052	0.073	0.25	3	-0.21	5	8
GRB2	0.022	0.006	-10000	0	-10000	0	0
PRKACA	0.008	0.04	-10000	0	-0.61	2	2
CHRNE	0.008	0.03	0.1	4	-0.16	4	8
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
activation of caspase activity	0.005	0.008	-10000	0	-10000	0	0
nervous system development	-0.006	0.055	0.19	3	-0.2	6	9
CDC42	0.022	0.004	-10000	0	-10000	0	0

IL2 signaling events mediated by PI3K

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
BCL2L1	0.014	0.059	-10000	0	-10000	0	0
UGCG	-0.035	0.19	-10000	0	-0.64	42	42
AKT1/mTOR/p70S6K/Hsp90/TERT	0.054	0.15	0.28	15	-0.48	18	33
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.033	0.19	-10000	0	-0.62	43	43
mol:DAG	0.005	0.092	-10000	0	-0.79	6	6
CaM/Ca2+/Calcineurin A alpha-beta B1	0.012	0.15	0.29	2	-0.38	49	51
FRAP1	0.004	0.17	0.32	2	-0.43	51	53
FOXO3	0.014	0.14	0.34	8	-0.46	19	27
AKT1	0.015	0.15	0.3	3	-0.49	20	23
GAB2	0.015	0.036	-10000	0	-0.32	5	5
SMPD1	-0.009	0.14	-10000	0	-0.64	22	22
SGMS1	0.011	0.072	-10000	0	-0.6	6	6
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	-0.012	0.019	-10000	0	-0.19	5	5
CALM1	0.022	0.004	-10000	0	-10000	0	0
cell proliferation	0.006	0.14	0.27	2	-0.41	37	39
EIF3A	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.024	0.032	-10000	0	-0.22	5	5
RPS6KB1	0.012	0.15	-10000	0	-0.8	15	15
mol:sphingomyelin	0.005	0.092	-10000	0	-0.79	6	6
natural killer cell activation	0	0.003	-10000	0	-0.02	1	1
JAK3	0.02	0.027	0.32	3	-10000	0	3
PIK3R1	0.016	0.033	-10000	0	-0.32	4	4
JAK1	0.018	0.029	-10000	0	-0.32	3	3
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MYC	0.033	0.17	0.38	7	-0.82	11	18
MYB	0.077	0.12	0.47	8	-0.5	1	9
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.021	0.097	0.25	4	-0.41	9	13
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.031	0.14	-10000	0	-0.71	15	15
mol:PI-3-4-5-P3	0.023	0.098	0.25	4	-0.39	10	14
Rac1/GDP	0.009	0.023	-10000	0	-0.17	5	5
T cell proliferation	0.022	0.096	0.26	4	-0.39	9	13
SHC1	0.016	0.014	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	0.015	0.034	0.1	66	-10000	0	66
PRKCZ	0.02	0.097	0.26	4	-0.4	9	13
NF kappa B1 p50/RelA	0.022	0.16	0.3	2	-0.39	45	47
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.011	0.047	0.25	1	-0.52	1	2
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
RELA	0.023	0.003	-10000	0	-10000	0	0
IL2RA	0.027	0.057	0.32	16	-0.32	1	17
IL2RB	0.018	0.02	-10000	0	-0.32	1	1
TERT	0.14	0.15	0.32	201	-10000	0	201
E2F1	0.077	0.11	0.27	64	-0.66	1	65
SOS1	0.019	0.013	-10000	0	-10000	0	0
RPS6	0.022	0.005	-10000	0	-10000	0	0
mol:cAMP	-0.007	0.017	-10000	0	-0.052	65	65
PTPN11	0.018	0.014	-10000	0	-10000	0	0
IL2RG	0.021	0.039	0.32	5	-0.32	2	7
actin cytoskeleton organization	0.022	0.096	0.26	4	-0.39	9	13
GRB2	0.018	0.014	-10000	0	-10000	0	0
IL2	0.025	0.056	0.32	16	-10000	0	16
PIK3CA	0.017	0.021	-10000	0	-0.32	1	1
Rac1/GTP	0.032	0.033	-10000	0	-0.16	5	5
LCK	0.021	0.034	0.32	4	-0.32	1	5
BCL2	-0.034	0.25	-10000	0	-0.74	52	52

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.007	0.024	-10000	0	-10000	0	0
HSPA8	0.023	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0	0.09	-10000	0	-0.22	55	55
AKT1	0.023	0.006	-10000	0	-10000	0	0
GSC	0.1	0.16	0.37	46	-0.42	4	50
NKX2-5	0.047	0.1	0.32	59	-0.13	1	60
muscle cell differentiation	-0.017	0.1	0.41	8	-0.28	3	11
SMAD2-3/SMAD4/SP1	0.046	0.076	-10000	0	-0.26	5	5
SMAD4	0.011	0.044	-10000	0	-0.15	4	4
CBFB	0.02	0.008	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.024	0.051	0.22	14	-0.19	3	17
SMAD3/SMAD4/VDR	0.028	0.063	0.29	1	-10000	0	1
MYC	0.013	0.043	-10000	0	-0.32	8	8
CDKN2B	-0.01	0.1	-10000	0	-0.49	13	13
AP1	-0.034	0.1	-10000	0	-0.34	13	13
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.018	0.072	-10000	0	-0.45	7	7
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.032	0.053	0.2	4	-0.23	5	9
SP3	0.023	0.003	-10000	0	-10000	0	0
CREB1	0.023	0.003	-10000	0	-10000	0	0
FOXH1	0.082	0.12	0.33	96	-10000	0	96
SMAD3/SMAD4/GR	-0.017	0.1	-10000	0	-0.21	90	90
GATA3	0.032	0.061	0.33	15	-0.32	4	19
SKI/SIN3/HDAC complex/NCoR1	0.005	0.077	-10000	0	-0.39	13	13
MEF2C/TIF2	0.004	0.12	0.24	7	-0.32	41	48
endothelial cell migration	-0.005	0.13	0.8	11	-10000	0	11
MAX	0.022	0.005	-10000	0	-10000	0	0
RBBP7	0.023	0.003	-10000	0	-10000	0	0
RBBP4	0.021	0.022	-10000	0	-0.32	2	2
RUNX2	0.03	0.05	0.32	13	-0.32	1	14
RUNX3	0.031	0.051	0.32	15	-10000	0	15
RUNX1	0.022	0.003	-10000	0	-10000	0	0
CTBP1	0.022	0.005	-10000	0	-10000	0	0
NR3C1	-0.039	0.13	-10000	0	-0.32	91	91
VDR	0.026	0.036	0.32	7	-10000	0	7
CDKN1A	-0.008	0.094	-10000	0	-0.96	4	4
KAT2B	0.004	0.048	-10000	0	-0.32	9	9
SMAD2/SMAD2/SMAD4/FOXH1	0.097	0.12	0.28	87	-0.16	1	88
DCP1A	0.022	0.004	-10000	0	-10000	0	0
SKI	0.023	0.005	-10000	0	-10000	0	0
SERPINE1	0.005	0.13	-10000	0	-0.8	11	11
SMAD3/SMAD4/ATF2	0.022	0.06	-10000	0	-0.26	5	5
SMAD3/SMAD4/ATF3	-0.006	0.087	-10000	0	-0.21	57	57
SAP30	0.022	0.005	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.018	0.039	-10000	0	-10000	0	0
JUN	-0.043	0.095	-10000	0	-0.34	13	13
SMAD3/SMAD4/IRF7	0.028	0.069	0.3	10	-0.22	3	13
TFE3	0.023	0.011	-10000	0	-10000	0	0
COL1A2	0.015	0.077	-10000	0	-0.53	8	8
mesenchymal cell differentiation	-0.027	0.065	0.21	4	-0.29	9	13
DLX1	0.056	0.097	0.32	59	-10000	0	59
TCF3	0.021	0.006	-10000	0	-10000	0	0
FOS	-0.09	0.16	-10000	0	-0.32	164	164
SMAD3/SMAD4/Max	0.023	0.056	-10000	0	-0.22	3	3
Cbp/p300/SNIP1	0.033	0.023	-10000	0	-10000	0	0
ZBTB17	0.021	0.007	-10000	0	-10000	0	0
LAMC1	-0.007	0.043	0.22	2	-0.24	1	3
TGIF2/HDAC complex/SMAD3/SMAD4	0.023	0.055	-10000	0	-0.22	3	3
IRF7	0.028	0.044	0.35	9	-10000	0	9
ESR1	-0.013	0.1	-10000	0	-0.32	52	52
HNF4A	0.047	0.089	0.32	46	-0.32	1	47
MEF2C	0.013	0.13	0.27	17	-0.32	42	59
SMAD2-3/SMAD4	0.033	0.07	-10000	0	-0.21	5	5
Cbp/p300/Src-1	0.02	0.037	-10000	0	-0.18	1	1
IGHV3OR16-13	0.003	0.032	-10000	0	-0.34	4	4
TGIF2/HDAC complex	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.008	0.022	-10000	0	-10000	0	0
SKIL	0.02	0.007	-10000	0	-10000	0	0
HDAC1	0.023	0.004	-10000	0	-10000	0	0
HDAC2	0.023	0.003	-10000	0	-10000	0	0
SNIP1	0.023	0.004	-10000	0	-10000	0	0
GCN5L2	-0.004	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.026	0.057	-10000	0	-0.24	2	2
MSG1/HSC70	0.039	0.041	0.24	15	-0.22	3	18
SMAD2	0.026	0.033	-10000	0	-10000	0	0
SMAD3	0.004	0.043	-10000	0	-0.37	2	2
SMAD3/E2F4-5/DP1/p107/SMAD4	0.005	0.041	-10000	0	-0.2	8	8
SMAD2/SMAD2/SMAD4	-0.009	0.056	0.19	2	-0.22	19	21
NCOR1	0.021	0.007	-10000	0	-10000	0	0
NCOA2	0.01	0.06	-10000	0	-0.32	16	16
NCOA1	0.022	0.016	-10000	0	-0.32	1	1
MYOD/E2A	0.041	0.051	0.24	32	-10000	0	32
SMAD2-3/SMAD4/SP1/MIZ-1	0.065	0.068	-10000	0	-0.24	5	5
IFNB1	-0.007	0.062	0.33	11	-0.25	1	12
SMAD3/SMAD4/MEF2C	0.035	0.13	0.27	7	-0.32	42	49
CITED1	0.03	0.059	0.32	16	-0.32	3	19
SMAD2-3/SMAD4/ARC105	0.041	0.071	-10000	0	-0.24	2	2
RBL1	0.022	0.004	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.008	0.051	-10000	0	-0.31	5	5
RUNX1-3/PEBPB2	0.045	0.033	0.23	13	-10000	0	13
SMAD7	-0.036	0.12	-10000	0	-0.42	13	13
MYC/MIZ-1	0.022	0.035	-10000	0	-0.2	10	10
SMAD3/SMAD4	-0.05	0.097	-10000	0	-0.38	17	17
IL10	0.005	0.082	0.32	22	-0.25	3	25
PIASy/HDAC complex	0.024	0.009	-10000	0	-10000	0	0
PIAS3	0.011	0.019	-10000	0	-10000	0	0
CDK2	0.009	0.022	-10000	0	-10000	0	0
IL5	-0.003	0.057	0.23	3	-0.25	3	6
CDK4	0.009	0.022	-10000	0	-10000	0	0
PIAS4	0.024	0.009	-10000	0	-10000	0	0
ATF3	-0.019	0.11	-10000	0	-0.32	56	56
SMAD3/SMAD4/SP1	0.027	0.063	-10000	0	-0.26	6	6
FOXG1	0.15	0.16	0.32	228	-10000	0	228
FOXO3	-0.013	0.006	-10000	0	-10000	0	0
FOXO1	-0.014	0.015	-10000	0	-0.22	2	2
FOXO4	-0.014	0.014	-10000	0	-0.22	2	2
heart looping	0.013	0.13	0.27	17	-0.32	42	59
CEBPB	0.022	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.042	0.082	0.25	36	-0.22	3	39
MYOD1	0.042	0.082	0.32	39	-10000	0	39
SMAD3/SMAD4/HNF4	0.038	0.08	0.24	33	-0.24	4	37
SMAD3/SMAD4/GATA3	0.033	0.075	0.32	2	-0.24	6	8
SnoN/SIN3/HDAC complex/NCoR1	0.02	0.007	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.042	0.068	0.32	3	-0.21	2	5
SMAD3/SMAD4/SP1-3	0.04	0.063	-10000	0	-0.24	5	5
MED15	0.022	0.005	-10000	0	-10000	0	0
SP1	0.023	0.019	-10000	0	-0.15	3	3
SIN3B	0.022	0.006	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.11	0.14	0.37	53	-0.21	24	77
ITGB5	-0.01	0.046	-10000	0	-0.24	4	4
TGIF/SIN3/HDAC complex/CtBP	0.012	0.056	-10000	0	-0.37	6	6
SMAD3/SMAD4/AR	-0.016	0.1	-10000	0	-0.21	84	84
AR	-0.036	0.13	-10000	0	-0.32	87	87
negative regulation of cell growth	-0.004	0.073	-10000	0	-0.28	12	12
SMAD3/SMAD4/MYOD	0.033	0.078	0.26	26	-0.24	2	28
E2F5	0.021	0.007	-10000	0	-10000	0	0
E2F4	0.02	0.008	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.1	0.1	0.33	34	-10000	0	34
SMAD2-3/SMAD4/FOXO1-3a-4	0.009	0.041	-10000	0	-0.26	3	3
TFDP1	0.021	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	-0.018	0.11	-10000	0	-0.34	13	13
SMAD3/SMAD4/RUNX2	0.027	0.066	0.29	9	-0.21	4	13
TGIF2	0.022	0.005	-10000	0	-10000	0	0
TGIF1	0.022	0.005	-10000	0	-10000	0	0
ATF2	0.02	0.026	-10000	0	-0.32	3	3

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.02	0.097	0.37	15	-0.29	8	23
TBX21	-0.005	0.24	0.88	9	-1.1	7	16
B2M	0.021	0.01	-10000	0	-10000	0	0
TYK2	0.012	0.039	0.21	6	-10000	0	6
IL12RB1	0.014	0.072	0.41	9	-0.35	4	13
GADD45B	-0.005	0.21	0.78	8	-0.68	14	22
IL12RB2	0.026	0.074	0.31	26	-10000	0	26
GADD45G	-0.021	0.27	0.78	8	-0.92	23	31
natural killer cell activation	0.002	0.029	0.2	6	-10000	0	6
RELB	0.022	0.004	-10000	0	-10000	0	0
RELA	0.023	0.003	-10000	0	-10000	0	0
IL18	0.026	0.04	0.34	7	-10000	0	7
IL2RA	0.031	0.055	0.32	16	-0.32	1	17
IFNG	0.04	0.073	0.32	31	-10000	0	31
STAT3 (dimer)	-0.01	0.21	0.63	11	-0.6	19	30
HLA-DRB5	0.002	0.058	0.31	5	-0.33	8	13
FASLG	0.021	0.25	0.91	10	-0.87	10	20
NF kappa B2 p52/RelB	-0.013	0.2	0.45	1	-0.71	16	17
CD4	0.004	0.029	0.26	1	-10000	0	1
SOCS1	0.021	0.016	-10000	0	-0.32	1	1
EntrezGene:6955	-0.008	0.014	-10000	0	-10000	0	0
CD3D	0.007	0.07	0.31	14	-0.32	7	21
CD3E	0.002	0.056	0.33	4	-0.33	7	11
CD3G	0.003	0.043	0.31	3	-0.32	2	5
IL12Rbeta2/JAK2	0.027	0.079	0.26	25	-0.23	9	34
CCL3	0	0.24	0.95	9	-1	6	15
CCL4	-0.004	0.24	0.91	9	-0.92	11	20
HLA-A	0.023	0.016	0.32	1	-10000	0	1
IL18/IL18R	0.055	0.065	0.35	9	-0.2	7	16
NOS2	-0.003	0.24	0.85	10	-0.87	14	24
IL12/IL12R/TYK2/JAK2/SPHK2	0.021	0.093	0.39	13	-0.25	7	20
IL1R1	-0.014	0.26	0.85	8	-1	13	21
IL4	-0.001	0.04	-10000	0	-0.22	6	6
JAK2	0.007	0.059	0.22	5	-0.33	9	14
EntrezGene:6957	-0.007	0.012	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.02	0.13	0.37	4	-0.58	15	19
RAB7A	0.001	0.21	0.71	8	-0.64	14	22
lysosomal transport	0.003	0.2	0.68	9	-0.61	14	23
FOS	-0.32	0.55	0.69	6	-1	177	183
STAT4 (dimer)	0.016	0.21	0.7	9	-0.6	17	26
STAT5A (dimer)	0.009	0.24	0.73	12	-0.75	14	26
GZMA	-0.016	0.26	0.83	9	-1.1	15	24
GZMB	0.003	0.25	0.81	12	-1.1	8	20
HLX	0.019	0.008	-10000	0	-10000	0	0
LCK	-0.004	0.24	0.79	11	-0.81	14	25
TCR/CD3/MHC II/CD4	-0.052	0.13	0.25	4	-0.24	132	136
IL2/IL2R	0.06	0.06	0.27	29	-0.16	3	32
MAPK14	-0.007	0.23	0.76	8	-0.69	22	30
CCR5	0.002	0.22	0.82	8	-0.82	12	20
IL1B	0.01	0.05	0.22	5	-0.35	4	9
STAT6	0.019	0.11	0.51	11	-0.33	3	14
STAT4	0.022	0.015	-10000	0	-0.32	1	1
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT1	0.023	0.014	0.32	1	-10000	0	1
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
NFKB2	0.022	0.006	-10000	0	-10000	0	0
IL12B	0.012	0.043	0.24	7	-10000	0	7
CD8A	0.02	0.048	0.34	4	-0.32	6	10
CD8B	0.033	0.077	0.32	25	-0.32	6	31
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.019	0.097	0.29	8	-0.37	15	23
IL2RB	0.021	0.016	-10000	0	-0.32	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.019	0.2	0.7	9	-0.57	16	25
IL2RG	0.024	0.037	0.32	5	-0.32	2	7
IL12	0.023	0.067	0.27	15	-0.24	4	19
STAT5A	0.022	0.006	-10000	0	-10000	0	0
CD247	0.002	0.033	0.32	1	-0.33	1	2
IL2	0.028	0.054	0.32	16	-10000	0	16
SPHK2	0.022	0.004	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.015	0.065	0.28	15	-0.34	4	19
IL12/IL12R/TYK2/JAK2	-0.002	0.27	0.94	11	-0.85	15	26
MAP2K3	-0.016	0.24	0.73	9	-0.66	26	35
RIPK2	0.021	0.007	-10000	0	-10000	0	0
MAP2K6	0	0.23	0.77	8	-0.67	24	32
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.001	0.039	-10000	0	-0.33	3	3
IL18RAP	0.022	0.04	0.36	3	-0.33	3	6
IL12Rbeta1/TYK2	0.021	0.069	0.37	9	-0.27	4	13
EOMES	-0.019	0.15	-10000	0	-0.82	14	14
STAT1 (dimer)	0.018	0.22	0.7	14	-0.59	16	30
T cell proliferation	0.017	0.18	0.61	9	-0.48	18	27
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.02	0.034	-10000	0	-0.32	4	4
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.013	0.16	0.6	2	-0.56	18	20
ATF2	-0.008	0.22	0.71	8	-0.65	22	30

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	0.046	0.053	0.25	7	-0.18	17	24
MAP4K1	0.026	0.038	0.32	8	-10000	0	8
MAP3K8	0.019	0.034	-10000	0	-0.32	5	5
PRKCB	0.003	0.078	-10000	0	-0.32	28	28
DBNL	0.022	0.004	-10000	0	-10000	0	0
CRKL	0.022	0.005	-10000	0	-10000	0	0
MAP3K1	0.002	0.046	0.16	1	-0.18	16	17
JUN	-0.047	0.19	-10000	0	-0.57	54	54
MAP3K7	0	0.05	0.16	1	-0.18	16	17
GRAP2	0.009	0.063	-10000	0	-0.32	18	18
CRK	0.021	0.006	-10000	0	-10000	0	0
MAP2K4	-0.004	0.063	-10000	0	-0.24	16	16
LAT	0.022	0.005	-10000	0	-10000	0	0
LCP2	0.023	0.014	0.32	1	-10000	0	1
MAPK8	-0.043	0.2	-10000	0	-0.6	54	54
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.007	0.058	0.19	1	-0.19	31	32
LAT/GRAP2/SLP76/HPK1/HIP-55	0.054	0.052	0.25	7	-0.17	14	21

IL1-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.015	0.058	-10000	0	-0.22	28	28
PRKCZ	0.022	0.021	0.32	1	-0.32	1	2
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.022	0.004	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	0.008	0.042	-10000	0	-0.23	12	12
IRAK/TOLLIP	-0.014	0.043	-10000	0	-0.17	27	27
IKBKB	0.02	0.007	-10000	0	-10000	0	0
IKBKG	0.023	0.003	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.056	0.078	0.25	59	-0.22	4	63
IL1A	0.039	0.07	0.32	29	-10000	0	29
IL1B	-0.018	0.029	-10000	0	-0.25	7	7
IRAK/TRAF6/p62/Atypical PKCs	0.036	0.054	-10000	0	-0.17	23	23
IL1R2	0.041	0.083	0.32	35	-0.32	4	39
IL1R1	0.017	0.043	-10000	0	-0.32	8	8
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.063	0.21	2	-0.26	16	18
TOLLIP	0.022	0.005	-10000	0	-10000	0	0
TICAM2	0.017	0.043	-10000	0	-0.32	8	8
MAP3K3	0.022	0.005	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0.015	0.002	-10000	0	-10000	0	0
IKK complex/ELKS	0.009	0.059	0.26	3	-0.33	2	5
JUN	-0.013	0.064	0.16	35	-0.27	2	37
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.039	0.053	-10000	0	-0.2	16	16
IL1 alpha/IL1R1/IL1RAP/MYD88	0.056	0.055	0.23	27	-0.2	7	34
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.063	0.055	0.23	27	-0.19	7	34
IL1 beta fragment/IL1R1/IL1RAP	0.023	0.041	-10000	0	-0.19	15	15
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
MAPK8	-0.006	0.067	0.18	34	-10000	0	34
IRAK1	-0.027	0.039	-10000	0	-0.19	27	27
IL1RN/IL1R1	0.052	0.073	0.24	58	-0.2	8	66
IRAK4	0.023	0.003	-10000	0	-10000	0	0
PRKCI	0.02	0.007	-10000	0	-10000	0	0
TRAF6	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.027	0.028	-10000	0	-0.22	5	5
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.052	-10000	0	-0.28	8	8
CHUK	0.022	0.005	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.023	0.041	-10000	0	-0.19	15	15
IL1 beta/IL1R2	0.038	0.066	0.22	44	-0.22	10	54
IRAK/TRAF6/TAK1/TAB1/TAB2	0.016	0.041	-10000	0	-0.15	26	26
NF kappa B1 p50/RelA	0.028	0.048	-10000	0	-0.19	16	16
IRAK3	0.007	0.071	-10000	0	-0.32	23	23
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.039	0.054	-10000	0	-0.18	21	21
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.016	0.045	0.19	1	-0.23	7	8
IL1 alpha/IL1R1/IL1RAP	0.046	0.055	0.23	27	-0.21	7	34
RELA	0.023	0.003	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.022	0.004	-10000	0	-10000	0	0
MYD88	0.022	0.004	-10000	0	-10000	0	0
IRAK/TRAF6/MEKK3	0.026	0.053	-10000	0	-0.17	27	27
IL1RAP	0.019	0.027	-10000	0	-0.32	3	3
UBE2N	0.023	0.002	-10000	0	-10000	0	0
IRAK/TRAF6	-0.044	0.042	-10000	0	-0.28	4	4
CASP1	0.019	0.034	-10000	0	-0.32	5	5
IL1RN/IL1R2	0.069	0.09	0.25	87	-0.19	3	90
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.033	0.043	-10000	0	-0.19	15	15
TMEM189-UBE2V1	-0.001	0.077	-10000	0	-0.32	28	28
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.01	0.068	-10000	0	-0.32	12	12
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
IL1RN	0.057	0.098	0.32	60	-10000	0	60
TRAF6/TAK1/TAB1/TAB2	0.028	0.045	-10000	0	-0.16	27	27
MAP2K6	0.006	0.082	0.18	83	-10000	0	83

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	0.022	0.005	-10000	0	-9999	0
GPC2	0.037	0.067	0.32	26	-9999	26
GPC2/Midkine	0.04	0.042	0.24	21	-9999	21
neuron projection morphogenesis	0.039	0.042	0.23	21	-9999	21

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.069	0.13	-10000	0	-0.36	35	35
CaM/Ca2+	0.016	0.003	-10000	0	-10000	0	0
AKT1	0.022	0.004	-10000	0	-10000	0	0
AKT2	0.022	0.005	-10000	0	-10000	0	0
STXBP4	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.073	0.13	0.26	2	-0.37	39	41
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
TBC1D4	-0.015	0.014	-10000	0	-0.22	2	2
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.021	0.006	-10000	0	-10000	0	0
YWHAB	0.022	0.005	-10000	0	-10000	0	0
SNARE/Synip	0.04	0.016	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
ASIP	0.02	0.015	0.32	1	-10000	0	1
PRKCI	0.02	0.007	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0.016	0.003	-10000	0	-10000	0	0
RHOQ	0.022	0.003	-10000	0	-10000	0	0
GYS1	-0.002	0.018	0.24	3	-10000	0	3
PRKCZ	0.022	0.021	0.32	1	-0.32	1	2
TRIP10	0.021	0.006	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0.028	0.009	-10000	0	-10000	0	0
AS160/14-3-3	0.069	0.062	0.2	24	-0.3	4	28
VAMP2	0.021	0.007	-10000	0	-10000	0	0
SLC2A4	-0.081	0.14	0.3	1	-0.42	39	40
STX4	0.022	0.005	-10000	0	-10000	0	0
GSK3B	0.012	0.004	-10000	0	-10000	0	0
SFN	0.25	0.13	0.32	380	-10000	0	380
LNPEP	0.022	0.004	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.056	0.054	0.22	29	-0.16	12	41
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.022	0.005	-10000	0	-10000	0	0
STAT1 (dimer)/Cbp/p300	0.031	0.042	0.26	3	-10000	0	3
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.04	0.039	-10000	0	-0.19	12	12
antigen processing and presentation of peptide antigen via MHC class I	-0.037	0.053	-10000	0	-0.2	8	8
CaM/Ca2+	0.055	0.05	-10000	0	-0.16	9	9
RAP1A	0.023	0.001	-10000	0	-10000	0	0
STAT1 (dimer)/SHP2	-0.014	0.043	0.24	1	-10000	0	1
AKT1	-0.001	0.073	0.27	13	-0.25	1	14
MAP2K1	-0.016	0.042	0.22	5	-10000	0	5
MAP3K11	-0.012	0.047	0.21	6	-10000	0	6
IFNGR1	0.023	0.01	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.14	0.18	0.24	2	-0.31	209	211
Rap1/GTP	-0.029	0.025	-10000	0	-10000	0	0
CRKL/C3G	0.031	0.01	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.066	0.057	-10000	0	-0.16	12	12
CEBPB	-0.017	0.13	0.38	1	-0.52	22	23
STAT3	0.022	0.006	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.04	0.15	-10000	0	-0.69	19	19
STAT1	-0.013	0.047	0.21	7	-10000	0	7
CALM1	0.022	0.004	-10000	0	-10000	0	0
IFN-gamma (dimer)	0.033	0.076	0.32	31	-10000	0	31
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
STAT1 (dimer)/PIAS1	-0.014	0.048	0.26	4	-10000	0	4
CEBPB/PTGES2/Cbp/p300	0.005	0.083	-10000	0	-0.36	17	17
mol:Ca2+	0.052	0.053	0.2	29	-0.16	12	41
MAPK3	-0.025	0.14	-10000	0	-0.64	23	23
STAT1 (dimer)	-0.04	0.074	-10000	0	-0.3	5	5
MAPK1	-0.034	0.17	-10000	0	-0.68	30	30
JAK2	0.017	0.046	-10000	0	-0.32	9	9
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
JAK1	0.021	0.028	-10000	0	-0.32	3	3
CAMK2D	0.021	0.016	-10000	0	-0.32	1	1
DAPK1	-0.009	0.086	0.33	1	-0.37	15	16
SMAD7	-0.016	0.048	0.21	6	-0.25	1	7
CBL/CRKL/C3G	-0.016	0.049	0.26	3	-10000	0	3
PI3K	0.045	0.05	-10000	0	-0.17	11	11
IFNG	0.033	0.076	0.32	31	-10000	0	31
apoptosis	-0.006	0.074	-10000	0	-0.34	10	10
CAMK2G	0.021	0.006	-10000	0	-10000	0	0
STAT3 (dimer)	0.022	0.005	-10000	0	-10000	0	0
CAMK2A	-0.16	0.17	-10000	0	-0.32	269	269
CAMK2B	0.076	0.12	0.32	91	-10000	0	91
FRAP1	-0.002	0.068	0.22	19	-0.24	1	20
PRKCD	-0.002	0.074	0.28	13	-0.26	1	14
RAP1B	0.023	0.002	-10000	0	-10000	0	0
negative regulation of cell growth	-0.037	0.053	-10000	0	-0.2	8	8
PTPN2	0.022	0.004	-10000	0	-10000	0	0
EP300	0.021	0.006	-10000	0	-10000	0	0
IRF1	-0.014	0.046	0.27	5	-0.32	1	6
STAT1 (dimer)/PIASy	-0.015	0.048	0.26	4	-10000	0	4
SOCS1	-0.018	0.2	-10000	0	-1	19	19
mol:GDP	-0.016	0.046	0.25	3	-10000	0	3
CASP1	-0.016	0.05	0.25	4	-0.2	4	8
PTGES2	0.021	0.006	-10000	0	-10000	0	0
IRF9	0.002	0.039	0.2	2	-0.16	10	12
mol:PI-3-4-5-P3	0.032	0.042	-10000	0	-0.16	12	12
RAP1/GDP	-0.025	0.036	-10000	0	-10000	0	0
CBL	-0.012	0.046	0.21	6	-10000	0	6
MAP3K1	-0.013	0.045	0.21	6	-10000	0	6
PIAS1	0.022	0.005	-10000	0	-10000	0	0
PIAS4	0.021	0.006	-10000	0	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.037	0.053	-10000	0	-0.2	8	8
PTPN11	-0.01	0.048	0.17	19	-0.16	10	29
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0

Retinoic acid receptors-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC3	0.022	0.003	-10000	0	-10000	0	0
VDR	0.026	0.036	0.32	7	-10000	0	7
Cbp/p300/PCAF	0.038	0.032	-10000	0	-0.18	8	8
EP300	0.021	0.006	-10000	0	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.001	0.075	0.17	2	-0.31	18	20
KAT2B	0.016	0.045	-10000	0	-0.32	9	9
MAPK14	0.022	0.004	-10000	0	-10000	0	0
AKT1	0.004	0.069	0.26	4	-0.27	7	11
RAR alpha/9cRA/Cyclin H	0.016	0.094	-10000	0	-0.27	32	32
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.005	0.087	0.17	1	-0.34	21	22
CDC2	0	0.001	-10000	0	-10000	0	0
response to UV	0	0.001	-10000	0	-10000	0	0
RAR alpha/Jnk1	0.007	0.075	-10000	0	-0.28	20	20
NCOR2	0.022	0.003	-10000	0	-10000	0	0
VDR/VDR/Vit D3	0.019	0.024	0.22	7	-10000	0	7
RXRs/RARs/NRIP1/9cRA	-0.005	0.15	0.37	1	-0.46	32	33
NCOA2	0.01	0.06	-10000	0	-0.32	16	16
NCOA3	0.021	0.006	-10000	0	-10000	0	0
NCOA1	0.022	0.016	-10000	0	-0.32	1	1
VDR/VDR/DNA	0.026	0.036	0.32	7	-10000	0	7
RARG	0.022	0.005	-10000	0	-10000	0	0
RAR gamma1/9cRA	0.029	0.009	-10000	0	-10000	0	0
MAPK3	0.022	0.006	-10000	0	-10000	0	0
MAPK1	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.019	0.034	-10000	0	-0.32	5	5
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0.012	0.13	0.28	3	-0.38	31	34
RARA	0.011	0.065	0.2	6	-0.21	26	32
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	-0.009	0.085	0.17	1	-0.31	25	26
PRKCA	0.003	0.08	-10000	0	-0.32	29	29
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.005	0.15	-10000	0	-0.48	28	28
RXRG	0	0.11	0.17	64	-0.27	53	117
RXRA	0.006	0.06	0.2	6	-0.19	28	34
RXRB	0.016	0.084	0.16	62	-0.25	29	91
VDR/Vit D3/DNA	0.019	0.024	0.22	7	-10000	0	7
RBP1	0.009	0.065	-10000	0	-0.32	19	19
CRBP1/9-cic-RA	0.008	0.044	-10000	0	-0.22	19	19
RARB	0.017	0.045	-10000	0	-0.32	9	9
PRKCG	0.056	0.1	0.32	62	-0.32	4	66
MNAT1	0.022	0.004	-10000	0	-10000	0	0
RAR alpha/RXRs	-0.008	0.14	0.31	2	-0.42	34	36
RXRs/RARs/SMRT(N-CoR2)/9cRA	0	0.13	0.26	4	-0.39	31	35
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.11	0.21	8	-0.34	31	39
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.005	0.15	-10000	0	-0.48	29	29
positive regulation of DNA binding	0.007	0.084	-10000	0	-0.25	34	34
NRIP1	-0.006	0.16	-10000	0	-0.76	11	11
RXRs/RARs	-0.002	0.15	-10000	0	-0.45	33	33
RXRs/RXRs/DNA/9cRA	-0.01	0.12	0.22	4	-0.38	32	36
PRKACA	0.022	0.005	-10000	0	-10000	0	0
CDK7	0.022	0.005	-10000	0	-10000	0	0
TFIIH	0.043	0.012	-10000	0	-10000	0	0
RAR alpha/9cRA	0.031	0.074	-10000	0	-0.26	12	12
CCNH	0.022	0.005	-10000	0	-10000	0	0
CREBBP	0.022	0.005	-10000	0	-10000	0	0
RAR gamma2/9cRA	0.039	0.017	-10000	0	-10000	0	0

Sphingosine 1-phosphate (S1P) 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.022	0.004	-10000	0	-10000	0	0
SPHK1	0.022	0.014	0.32	1	-10000	0	1
GNAI2	0.022	0.005	-10000	0	-10000	0	0
mol:S1P	0.008	0.006	-10000	0	-10000	0	0
GNAO1	-0.056	0.14	-10000	0	-0.32	113	113
mol:Sphinganine-1-P	-0.013	0.016	0.22	2	-10000	0	2
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.039	0.038	-10000	0	-0.2	5	5
GNAI3	0.023	0.002	-10000	0	-10000	0	0
G12/G13	0.031	0.01	-10000	0	-10000	0	0
S1PR3	0.011	0.058	-10000	0	-0.32	15	15
S1PR2	0.021	0.006	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0	0.03	-10000	0	-0.23	5	5
S1PR5	0.028	0.049	0.32	12	-0.32	1	13
S1PR4	0.021	0.021	0.32	1	-0.32	1	2
GNAI1	0.016	0.045	-10000	0	-0.32	9	9
S1P/S1P5/G12	0.033	0.045	0.22	8	-0.22	5	13
S1P/S1P3/Gq	-0.017	0.11	-10000	0	-0.3	52	52
S1P/S1P4/Gi	-0.041	0.11	-10000	0	-0.21	112	112
GNAQ	0.021	0.016	-10000	0	-0.32	1	1
GNAZ	0.004	0.075	-10000	0	-0.32	26	26
GNA14	-0.008	0.095	-10000	0	-0.32	43	43
GNA15	0.025	0.036	0.32	7	-10000	0	7
GNA12	0.022	0.005	-10000	0	-10000	0	0
GNA13	0.022	0.005	-10000	0	-10000	0	0
GNA11	0.015	0.045	-10000	0	-0.32	9	9
ABCC1	0.022	0.005	-10000	0	-10000	0	0

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC2	0.022	0.003	-10000	0	-10000	0	0
GNB1/GNG2	0.035	0.043	0.23	1	-0.19	16	17
forebrain development	-0.079	0.19	-10000	0	-0.53	56	56
GNAO1	-0.057	0.14	-10000	0	-0.32	113	113
SMO/beta Arrestin2	0.026	0.028	-10000	0	-0.22	4	4
SMO	0.017	0.032	-10000	0	-0.32	4	4
ARRB2	0.019	0.011	-10000	0	-10000	0	0
GLI3/SPOP	-0.044	0.13	-10000	0	-0.41	16	16
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.022	0.004	-10000	0	-10000	0	0
GNAI2	0.021	0.009	-10000	0	-10000	0	0
SIN3/HDAC complex	0.051	0.021	-10000	0	-10000	0	0
GNAI1	0.015	0.045	-10000	0	-0.32	9	9
XPO1	0.02	0.012	-10000	0	-10000	0	0
GLI1/Su(fu)	-0.058	0.16	-10000	0	-0.54	34	34
SAP30	0.022	0.005	-10000	0	-10000	0	0
mol:GDP	0.017	0.032	-10000	0	-0.32	4	4
MIM/GLI2A	0.016	0.03	-10000	0	-10000	0	0
IFT88	0.022	0.005	-10000	0	-10000	0	0
GNAI3	0.022	0.006	-10000	0	-10000	0	0
GLI2	-0.036	0.095	-10000	0	-0.34	19	19
GLI3	-0.052	0.13	-10000	0	-0.43	16	16
CSNK1D	0.022	0.005	-10000	0	-10000	0	0
CSNK1E	0.021	0.006	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
embryonic digit morphogenesis	0.022	0.005	-10000	0	-10000	0	0
GNG2	0.013	0.058	0.32	1	-0.32	14	15
Gi family/GTP	-0.047	0.1	-10000	0	-0.21	120	120
SIN3B	0.022	0.006	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.034	0.11	-10000	0	-0.4	16	16
GLI2/Su(fu)	-0.03	0.1	-10000	0	-0.36	23	23
FOXA2	-0.058	0.26	-10000	0	-0.9	42	42
neural tube patterning	-0.079	0.19	-10000	0	-0.53	56	56
SPOP	0.022	0.005	-10000	0	-10000	0	0
Su(fu)/PIAS1	0.017	0.038	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
CSNK1G2	0.021	0.006	-10000	0	-10000	0	0
CSNK1G3	0.022	0.004	-10000	0	-10000	0	0
MTSS1	0.016	0.03	-10000	0	-10000	0	0
embryonic limb morphogenesis	-0.079	0.19	-10000	0	-0.53	56	56
SUFU	0.011	0.016	-10000	0	-10000	0	0
LGALS3	0.021	0.022	-10000	0	-0.32	2	2
catabolic process	-0.066	0.15	0.26	1	-0.47	21	22
GLI3A/CBP	-0.021	0.11	-10000	0	-0.3	69	69
KIF3A	0.022	0.016	-10000	0	-0.32	1	1
GLI1	-0.081	0.19	-10000	0	-0.55	56	56
RAB23	0.018	0.037	-10000	0	-0.32	6	6
CSNK1A1	0.022	0.004	-10000	0	-10000	0	0
IFT172	0.022	0.004	-10000	0	-10000	0	0
RBBP7	0.022	0.003	-10000	0	-10000	0	0
Su(fu)/Galectin3	0.015	0.042	-10000	0	-10000	0	0
GNAZ	0.003	0.075	-10000	0	-0.32	26	26
RBBP4	0.021	0.022	-10000	0	-0.32	2	2
CSNK1G1	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GLI2/SPOP	-0.027	0.1	-10000	0	-0.35	21	21
STK36	0.02	0.012	-10000	0	-10000	0	0
Gi family/GNB1/GNG2/GDP	-0.052	0.1	-10000	0	-0.34	33	33
PTCH1	-0.074	0.17	-10000	0	-0.57	32	32
MIM/GLI1	-0.072	0.2	-10000	0	-0.53	62	62
CREBBP	-0.02	0.11	-10000	0	-0.3	69	69
Su(fu)/SIN3/HDAC complex	0.002	0.084	-10000	0	-0.44	12	12

Regulation of Telomerase

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
Telomerase catalytic core complex	0.068	0.18	0.43	14	-0.57	1	15
RAD9A	0.022	0.004	-10000	0	-10000	0	0
AP1	-0.043	0.13	-10000	0	-0.22	167	167
IFNAR2	0.033	0.02	-10000	0	-0.3	1	1
AKT1	0.022	0.064	0.19	16	-0.31	3	19
ER alpha/Oestrogen	-0.001	0.072	-10000	0	-0.21	53	53
NFX1/SIN3/HDAC complex	0.022	0.062	-10000	0	-0.35	9	9
EGF	0.036	0.058	0.32	18	-0.31	1	19
SMG5	0.018	0.009	-10000	0	-10000	0	0
SMG6	0.021	0.006	-10000	0	-10000	0	0
SP3/HDAC2	0.051	0.022	-10000	0	-10000	0	0
TERT/c-Abl	0.054	0.16	0.4	8	-0.49	2	10
SAP18	0.024	0.006	-10000	0	-10000	0	0
MRN complex	0.04	0.016	-10000	0	-10000	0	0
WT1	-0.22	0.15	-10000	0	-0.31	367	367
WRN	0.02	0.007	-10000	0	-10000	0	0
SP1	0.038	0.019	-10000	0	-10000	0	0
SP3	0.028	0.007	-10000	0	-10000	0	0
TERF2IP	0.02	0.008	-10000	0	-10000	0	0
Telomerase/Nucleolin	0.034	0.14	-10000	0	-0.51	1	1
Mad/Max	0.046	0.018	-10000	0	-10000	0	0
TERT	0.068	0.18	0.44	12	-0.58	1	13
CCND1	0.065	0.17	0.48	5	-0.51	1	6
MAX	0.028	0.008	-10000	0	-10000	0	0
RBBP7	0.025	0.004	-10000	0	-10000	0	0
RBBP4	0.023	0.022	-10000	0	-0.32	2	2
TERF2	-0.015	0.014	-10000	0	-10000	0	0
PTGES3	0.023	0.003	-10000	0	-10000	0	0
SIN3A	0.024	0.006	-10000	0	-10000	0	0
Telomerase/911	0.038	0.055	0.24	5	-0.36	1	6
CDKN1B	-0.007	0.093	-10000	0	-0.43	20	20
RAD1	0.022	0.005	-10000	0	-10000	0	0
XRCC5	0.023	0.003	-10000	0	-10000	0	0
XRCC6	0.021	0.006	-10000	0	-10000	0	0
SAP30	0.024	0.006	-10000	0	-10000	0	0
TRF2/PARP2	0.028	0.013	-10000	0	-10000	0	0
UBE3A	0.027	0.008	-10000	0	-10000	0	0
JUN	0.023	0.037	-10000	0	-0.31	6	6
E6	0.005	0.005	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.028	0.014	-10000	0	-10000	0	0
FOS	-0.085	0.16	-10000	0	-0.31	166	166
IFN-gamma/IRF1	0.049	0.077	0.25	31	-0.23	20	51
PARP2	0.022	0.004	-10000	0	-10000	0	0
BLM	0.046	0.081	0.32	40	-10000	0	40
Telomerase	0.046	0.098	0.25	6	-0.45	6	12
IRF1	0.022	0.034	-10000	0	-0.14	20	20
ESR1	-0.01	0.1	-10000	0	-0.31	53	53
KU/TER	0.032	0.009	-10000	0	-10000	0	0
ATM/TRF2	0.028	0.016	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.025	0.062	-10000	0	-0.31	10	10
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.026	0.062	-10000	0	-0.33	9	9
HDAC1	0.024	0.005	-10000	0	-10000	0	0
HDAC2	0.036	0.016	-10000	0	-10000	0	0
ATM	0.015	0.019	-10000	0	-10000	0	0
SMAD3	-0.022	0.021	-10000	0	-0.23	4	4
ABL1	0.02	0.022	-10000	0	-0.32	2	2
MXD1	0.028	0.008	-10000	0	-10000	0	0
MRE11A	0.022	0.004	-10000	0	-10000	0	0
HUS1	0.022	0.004	-10000	0	-10000	0	0
RPS6KB1	0.022	0.005	-10000	0	-10000	0	0
TERT/NF kappa B1/14-3-3	0.072	0.16	0.42	6	-0.54	1	7
NR2F2	-0.015	0.067	-10000	0	-0.32	19	19
MAPK3	0.008	0.036	0.17	16	-10000	0	16
MAPK1	0.008	0.035	0.17	15	-10000	0	15
TGFB1/TGF beta receptor Type II	0.003	0.026	-10000	0	-0.32	1	1
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
HNRNPC	0.022	0.004	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.015	0.019	-10000	0	-10000	0	0
NBN	0.021	0.007	-10000	0	-10000	0	0
EGFR	0.018	0.054	-10000	0	-0.31	13	13
mol:Oestrogen	0.003	0.003	-10000	0	-10000	0	0
EGF/EGFR	0.041	0.056	0.24	17	-0.21	13	30
MYC	0.019	0.044	-10000	0	-0.31	8	8
IL2	0.044	0.056	0.34	16	-10000	0	16
KU	0.032	0.009	-10000	0	-10000	0	0
RAD50	0.022	0.004	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
TGFB1	0.003	0.026	-10000	0	-0.32	1	1
TRF2/BLM	0.041	0.05	0.22	34	-10000	0	34
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.064	0.17	0.42	5	-0.53	1	6
SP1/HDAC2	0.062	0.036	-10000	0	-10000	0	0
PINX1	0.02	0.008	-10000	0	-10000	0	0
Telomerase/EST1A	0.032	0.14	-10000	0	-0.51	1	1
Smad3/Myc	-0.004	0.036	-10000	0	-0.21	9	9
911 complex	0.042	0.014	-10000	0	-10000	0	0
IFNG	0.04	0.082	0.33	31	-0.14	20	51
Telomerase/PinX1	0.027	0.13	-10000	0	-0.51	1	1
Telomerase/AKT1/mTOR/p70S6K	0.047	0.092	0.31	6	-0.38	6	12
SIN3B	0.023	0.007	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0
Telomerase/EST1B	0.028	0.13	-10000	0	-0.45	2	2
response to DNA damage stimulus	0.004	0.019	-10000	0	-10000	0	0
MRN complex/TRF2/Rap1	0.05	0.028	-10000	0	-10000	0	0
TRF2/WRN	0.027	0.015	-10000	0	-10000	0	0
Telomerase/hnRNP C1/C2	0.034	0.14	-10000	0	-0.51	1	1
E2F1	0.091	0.12	0.33	99	-10000	0	99
ZNFX1	0.024	0.006	-10000	0	-10000	0	0
PIF1	0.095	0.13	0.32	122	-10000	0	122
NCL	0.022	0.003	-10000	0	-10000	0	0
DKC1	0.023	0.003	-10000	0	-10000	0	0
telomeric DNA binding	0	0	-10000	0	-10000	0	0

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.021	0.006	-10000	0	-10000	0	0
NFATC1	0.005	0.076	0.27	3	-0.33	8	11
NFATC2	-0.012	0.066	0.16	3	-0.22	18	21
NFATC3	0.008	0.016	-10000	0	-0.28	1	1
YWHAE	0.021	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.016	0.1	0.19	5	-0.35	25	30
Exportin 1/Ran/NUP214	0.041	0.013	-10000	0	-10000	0	0
mol:DAG	-0.001	0.002	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0	0.092	0.24	1	-0.32	19	20
BCL2/BAX	0.011	0.071	-10000	0	-0.22	42	42
CaM/Ca2+/Calcineurin A alpha-beta B1	0.009	0.016	-10000	0	-10000	0	0
CaM/Ca2+	0.009	0.016	-10000	0	-10000	0	0
BAX	0.022	0.004	-10000	0	-10000	0	0
MAPK14	0.02	0.009	-10000	0	-10000	0	0
BAD	0.022	0.004	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.005	0.094	-10000	0	-0.34	20	20
Calcineurin A alpha-beta B1/BCL2	-0.007	0.095	-10000	0	-0.32	43	43
FKBP8	0.022	0.005	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.005	0.093	0.34	20	-10000	0	20
KPNB1	0.022	0.005	-10000	0	-10000	0	0
KPNA2	0.026	0.036	0.32	7	-10000	0	7
XPO1	0.022	0.003	-10000	0	-10000	0	0
SFN	0.25	0.13	0.32	380	-10000	0	380
MAP3K8	0.011	0.037	-10000	0	-0.32	5	5
NFAT4/CK1 alpha	0.006	0.028	-10000	0	-0.15	1	1
MEF2D/NFAT1/Cbp/p300	-0.022	0.11	-10000	0	-0.23	83	83
CABIN1	-0.016	0.11	0.19	5	-0.35	25	30
CALM1	0.013	0.018	-10000	0	-10000	0	0
RAN	0.022	0.003	-10000	0	-10000	0	0
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
CAMK4	0.024	0.037	0.32	5	-0.32	2	7
mol:Ca2+	-0.002	0.005	-10000	0	-10000	0	0
MAPK3	0.022	0.005	-10000	0	-10000	0	0
YWHAH	0.021	0.006	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	0.029	0.019	-10000	0	-0.22	2	2
YWHAB	0.022	0.005	-10000	0	-10000	0	0
MAPK8	0.01	0.037	-10000	0	-0.32	5	5
MAPK9	0.022	0.004	-10000	0	-10000	0	0
YWHAG	0.022	0.004	-10000	0	-10000	0	0
FKBP1A	0.022	0.004	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.001	0.084	0.25	2	-0.36	8	10
PRKCH	0.021	0.022	-10000	0	-0.32	2	2
CABIN1/Cbp/p300	0.017	0.029	-10000	0	-10000	0	0
CASP3	0.019	0.01	-10000	0	-10000	0	0
PIM1	0.022	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.009	0.011	-10000	0	-10000	0	0
apoptosis	0.007	0.029	0.17	1	-0.23	2	3
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.065	0.06	0.22	6	-0.37	3	9
PRKCB	0.003	0.078	-10000	0	-0.32	28	28
PRKCE	0.022	0.003	-10000	0	-10000	0	0
JNK2/NFAT4	0.006	0.056	-10000	0	-0.2	3	3
BAD/BCL-XL	0.031	0.01	-10000	0	-10000	0	0
PRKCD	0.022	0.004	-10000	0	-10000	0	0
NUP214	0.021	0.006	-10000	0	-10000	0	0
PRKCZ	0.014	0.026	0.32	1	-0.32	1	2
PRKCA	0.002	0.079	-10000	0	-0.32	29	29
PRKCG	0.056	0.1	0.32	62	-0.32	4	66
PRKCQ	0.004	0.079	0.32	1	-0.32	28	29
FKBP38/BCL2	0.009	0.071	-10000	0	-0.22	43	43
EP300	0.012	0.02	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.022	0.004	-10000	0	-10000	0	0
NFATc/JNK1	0.014	0.076	0.27	3	-0.32	8	11
CaM/Ca2+/FKBP38	0.018	0.022	-10000	0	-10000	0	0
FKBP12/FK506	0.017	0.003	-10000	0	-10000	0	0
CSNK1A1	-0.015	0.008	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	0.02	0.032	0.21	5	-0.19	2	7
NFATc/ERK1	0.016	0.075	0.29	2	-0.31	8	10
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.006	0.1	0.24	2	-0.31	24	26
NR4A1	-0.046	0.17	0.22	11	-0.35	96	107
GSK3B	0.014	0.017	-10000	0	-10000	0	0
positive T cell selection	0.008	0.016	-10000	0	-0.28	1	1
NFAT1/CK1 alpha	-0.009	0.05	0.14	1	-0.19	10	11
RCH1/ KPNB1	0.034	0.026	0.24	7	-10000	0	7
YWHAQ	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.019	0.01	-10000	0	-10000	0	0
AKAP5	0.021	0.022	-10000	0	-0.32	2	2
MEF2D	0.01	0.019	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.021	0.007	-10000	0	-10000	0	0
NFATc/p38 alpha	0.014	0.074	0.29	2	-0.32	8	10
CREBBP	0.012	0.021	-10000	0	-10000	0	0
BCL2	-0.007	0.095	-10000	0	-0.32	43	43

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.022	0.004	-10000	0	-10000	0	0
Syndecan-3/Src/Cortactin	0.013	0.095	-10000	0	-0.34	10	10
Syndecan-3/Neurocan	0.016	0.062	0.27	4	-0.36	9	13
POMC	0.025	0.072	0.32	16	-0.32	10	26
EGFR	0.013	0.054	-10000	0	-0.32	13	13
Syndecan-3/EGFR	0.009	0.061	-10000	0	-0.35	11	11
AGRP	0.018	0.015	0.32	1	-10000	0	1
NCSTN	0.019	0.009	-10000	0	-10000	0	0
PSENEN	0.022	0.005	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.02	0.027	-10000	0	-0.32	3	3
APH1A	0.018	0.009	-10000	0	-10000	0	0
NCAN	0.026	0.047	0.32	12	-10000	0	12
long-term memory	0.042	0.066	-10000	0	-0.33	11	11
Syndecan-3/IL8	0.05	0.1	0.28	21	-0.35	11	32
PSEN1	0.022	0.004	-10000	0	-10000	0	0
Src/Cortactin	0.031	0.009	-10000	0	-10000	0	0
FYN	0.022	0.003	-10000	0	-10000	0	0
limb bud formation	-0.001	0.053	-10000	0	-0.39	9	9
MC4R	0.024	0.038	0.32	8	-10000	0	8
SRC	0.022	0.005	-10000	0	-10000	0	0
PTN	-0.052	0.14	-10000	0	-0.32	110	110
FGFR/FGF/Syndecan-3	-0.001	0.053	-10000	0	-0.39	9	9
neuron projection morphogenesis	-0.029	0.077	0.3	3	-0.35	8	11
Syndecan-3/AgRP	0.01	0.056	-10000	0	-0.34	11	11
Syndecan-3/AgRP/MC4R	0.04	0.07	0.26	3	-0.33	11	14
Fyn/Cortactin	0.032	0.007	-10000	0	-10000	0	0
SDC3	-0.001	0.054	-10000	0	-0.4	9	9
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	0.05	0.1	0.28	21	-0.34	11	32
IL8	0.079	0.12	0.32	95	-10000	0	95
Syndecan-3/Fyn/Cortactin	0.043	0.067	-10000	0	-0.34	11	11
Syndecan-3/CASK	-0.002	0.053	-10000	0	-0.35	11	11
alpha-MSH/MC4R	0.033	0.055	0.23	21	-0.22	10	31
Gamma Secretase	0.046	0.036	-10000	0	-0.17	3	3

IL27-mediated 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.016	0.053	-10000	0	-0.4	8	8
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.022	0.12	0.44	13	-0.38	4	17
IL27/IL27R/JAK1	0.016	0.14	0.53	5	-0.74	3	8
TBX21	-0.026	0.12	0.39	12	-0.57	3	15
IL12B	0.023	0.015	0.32	1	-10000	0	1
IL12A	-0.003	0.035	0.18	11	-0.22	4	15
IL6ST	-0.042	0.13	-10000	0	-0.32	93	93
IL27RA/JAK1	0.012	0.088	-10000	0	-1	2	2
IL27	0.024	0.048	0.34	10	-10000	0	10
TYK2	0.022	0.018	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.018	0.16	0.42	1	-1.1	9	10
T-helper 2 cell differentiation	0.022	0.12	0.44	13	-0.38	4	17
T cell proliferation during immune response	0.022	0.12	0.44	13	-0.38	4	17
MAPKKK cascade	-0.022	0.12	0.38	4	-0.44	13	17
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT2	0.022	0.003	-10000	0	-10000	0	0
STAT1	0.023	0.016	0.35	1	-10000	0	1
IL12RB1	0.024	0.048	0.33	7	-0.32	4	11
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.017	0.13	0.43	15	-0.53	3	18
IL27/IL27R/JAK2/TYK2	-0.021	0.12	0.38	4	-0.46	12	16
positive regulation of T cell mediated cytotoxicity	-0.022	0.12	0.38	4	-0.44	13	17
STAT1 (dimer)	0.009	0.16	0.66	5	-0.53	8	13
JAK2	0.016	0.047	-10000	0	-0.32	9	9
JAK1	0.021	0.027	-10000	0	-0.32	3	3
STAT2 (dimer)	-0.015	0.13	0.41	2	-0.4	16	18
T cell proliferation	-0.032	0.12	0.38	3	-0.44	16	19
IL12/IL12R/TYK2/JAK2	0.001	0.18	0.4	2	-0.71	25	27
IL17A	-0.016	0.16	0.42	1	-1.2	8	9
mast cell activation	0.022	0.12	0.44	13	-0.38	4	17
IFNG	0.005	0.042	0.14	24	-0.093	13	37
T cell differentiation	-0.002	0.006	0.015	16	-0.019	25	41
STAT3 (dimer)	-0.016	0.13	0.41	2	-0.4	18	20
STAT5A (dimer)	-0.016	0.13	0.41	2	-0.42	15	17
STAT4 (dimer)	-0.017	0.13	0.41	2	-0.41	17	19
STAT4	0.022	0.015	-10000	0	-0.32	1	1
T cell activation	-0.004	0.011	0.11	2	-0.16	1	3
IL27R/JAK2/TYK2	-0.001	0.12	-10000	0	-0.95	2	2
GATA3	0.014	0.16	0.62	17	-1.1	4	21
IL18	-0.004	0.021	0.17	7	-10000	0	7
positive regulation of mast cell cytokine production	-0.015	0.13	0.4	2	-0.4	18	20
IL27/EBI3	0.038	0.054	0.29	17	-10000	0	17
IL27RA	0	0.088	0.41	1	-1.1	2	3
IL6	0.007	0.099	0.32	9	-0.36	27	36
STAT5A	0.022	0.006	-10000	0	-10000	0	0
monocyte differentiation	0	0.002	-10000	0	-10000	0	0
IL2	-0.003	0.049	0.43	2	-10000	0	2
IL1B	-0.008	0.019	-10000	0	-0.22	4	4
EBI3	0.027	0.05	0.35	11	-10000	0	11
TNF	0.009	0.053	0.17	48	-0.22	2	50

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.008	0.089	0.25	8	-0.33	21	29
PDGFB-D/PDGFRB/SLAP	0.024	0.038	-10000	0	-0.22	11	11
PDGFB-D/PDGFRB/APS/CBL	0.036	0.04	-10000	0	-0.18	14	14
AKT1	0.005	0.094	0.3	26	-0.28	1	27
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.014	0.1	0.25	14	-0.37	22	36
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
FGR	-0.02	0.12	0.33	1	-0.5	24	25
mol:Ca2+	0.005	0.11	0.24	16	-0.38	27	43
MYC	0.027	0.15	0.35	19	-0.63	13	32
SHC1	0.019	0.009	-10000	0	-10000	0	0
HRAS/GDP	-0.011	0.047	0.16	20	-0.16	12	32
LRP1/PDGFRB/PDGFB	0.035	0.046	-10000	0	-0.19	18	18
GRB10	0.022	0.016	-10000	0	-0.32	1	1
PTPN11	0.023	0.003	-10000	0	-10000	0	0
GO:0007205	0.005	0.11	0.24	15	-0.39	27	42
PTEN	0.021	0.006	-10000	0	-10000	0	0
GRB2	0.021	0.006	-10000	0	-10000	0	0
GRB7	0.021	0.032	0.32	3	-0.32	2	5
PDGFB-D/PDGFRB/SHP2	0.025	0.046	-10000	0	-0.22	17	17
PDGFB-D/PDGFRB/GRB10	0.024	0.048	-10000	0	-0.22	18	18
cell cycle arrest	0.024	0.038	-10000	0	-0.22	11	11
HRAS	0.022	0.005	-10000	0	-10000	0	0
HIF1A	0.001	0.088	0.28	26	-0.25	1	27
GAB1	0.01	0.11	0.28	9	-0.36	24	33
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.012	0.1	0.27	24	-0.33	20	44
PDGFB-D/PDGFRB	0.036	0.04	-10000	0	-0.19	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.024	0.045	-10000	0	-0.22	16	16
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.01	0.076	0.22	2	-0.32	14	16
positive regulation of MAPKKK cascade	0.025	0.046	-10000	0	-0.22	17	17
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
mol:IP3	0.005	0.11	0.24	15	-0.39	27	42
E5	0	0.001	-10000	0	-10000	0	0
CSK	0.02	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/GRB7	0.022	0.05	0.24	2	-0.21	20	22
SHB	0.022	0.004	-10000	0	-10000	0	0
BLK	-0.019	0.14	0.41	2	-0.47	37	39
PTPN2	0.021	0.01	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0.024	0.047	-10000	0	-0.22	18	18
BCAR1	0.02	0.008	-10000	0	-10000	0	0
VAV2	0.011	0.12	0.28	11	-0.39	23	34
CBL	0.022	0.005	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0.024	0.048	0.24	1	-0.22	18	19
LCK	-0.005	0.088	0.33	1	-0.5	9	10
PDGFRB	0.011	0.064	-10000	0	-0.32	18	18
ACP1	0.022	0.005	-10000	0	-10000	0	0
HCK	0.001	0.063	0.32	1	-0.58	2	3
ABL1	0.01	0.1	0.24	18	-0.32	24	42
PDGFB-D/PDGFRB/CBL	0.007	0.12	0.28	6	-0.4	29	35
PTPN1	0.02	0.01	-10000	0	-10000	0	0
SNX15	0.023	0.003	-10000	0	-10000	0	0
STAT3	0.022	0.006	-10000	0	-10000	0	0
STAT1	0.023	0.014	0.32	1	-10000	0	1
cell proliferation	0.028	0.14	0.35	19	-0.56	13	32
SLA	0.02	0.007	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.013	0.066	0.33	7	-10000	0	7
SRC	-0.001	0.071	0.33	1	-0.82	2	3
PI3K	-0.028	0.025	-10000	0	-0.18	7	7
PDGFB-D/PDGFRB/GRB7/SHC	0.027	0.044	0.23	2	-0.18	15	17
SH2B2	0.022	0.005	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.014	0.11	0.25	14	-0.38	22	36
LYN	0	0.055	0.33	1	-0.44	2	3
LRP1	0.021	0.022	-10000	0	-0.32	2	2
SOS1	0.022	0.004	-10000	0	-10000	0	0
STAT5B	0.021	0.016	-10000	0	-0.32	1	1
STAT5A	0.022	0.006	-10000	0	-10000	0	0
NCK1-2/p130 Cas	0.049	0.047	-10000	0	-0.16	11	11
SPHK1	0.022	0.016	0.32	1	-10000	0	1
EDG1	0	0.003	-10000	0	-10000	0	0
mol:DAG	0.005	0.11	0.24	15	-0.39	27	42
PLCG1	0.004	0.12	0.24	14	-0.4	27	41
NHERF/PDGFRB	0.037	0.045	0.23	5	-0.18	15	20
YES1	-0.009	0.088	-10000	0	-0.51	11	11
cell migration	0.037	0.044	0.22	5	-0.18	15	20
SHC/Grb2/SOS1	0.043	0.043	-10000	0	-0.16	7	7
SLC9A3R2	0.022	0.005	-10000	0	-10000	0	0
SLC9A3R1	0.025	0.03	0.32	5	-10000	0	5
NHERF1-2/PDGFRB/PTEN	0.046	0.045	0.23	5	-0.16	14	19
FYN	-0.001	0.067	0.33	1	-0.54	3	4
DOK1	-0.013	0.048	0.17	24	-0.17	12	36
HRAS/GTP	0.016	0.004	-10000	0	-10000	0	0
PDGFB	0.021	0.006	-10000	0	-10000	0	0
RAC1	0.007	0.14	0.31	8	-0.46	23	31
PRKCD	-0.011	0.049	0.18	25	-0.18	10	35
FER	-0.012	0.049	0.18	24	-0.18	11	35
MAPKKK cascade	0.021	0.096	0.27	25	-10000	0	25
RASA1	-0.013	0.052	0.18	25	-0.18	16	41
NCK1	0.021	0.022	-10000	0	-0.32	2	2
NCK2	0.023	0.002	-10000	0	-10000	0	0
p62DOK/Csk	-0.017	0.044	0.16	20	-0.17	9	29
PDGFB-D/PDGFRB/SHB	0.024	0.046	-10000	0	-0.22	17	17
chemotaxis	0.01	0.099	0.24	18	-0.32	24	42
STAT1-3-5/STAT1-3-5	0.043	0.04	-10000	0	-0.16	9	9
Bovine Papilomavirus E5/PDGFRB	0.009	0.043	-10000	0	-0.22	18	18
PTPRJ	0.023	0.014	0.32	1	-10000	0	1

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.002	0.061	0.2	2	-0.22	21	23
adherens junction organization	-0.013	0.092	0.29	1	-0.36	25	26
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.007	0.062	0.21	2	-0.21	8	10
FMN1	-0.007	0.077	-10000	0	-0.31	21	21
mol:IP3	-0.003	0.042	-10000	0	-0.2	8	8
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.006	0.085	-10000	0	-0.3	27	27
CTNNB1	0.023	0.005	-10000	0	-10000	0	0
AKT1	-0.004	0.052	-10000	0	-0.22	15	15
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.011	0.12	-10000	0	-0.44	23	23
CTNND1	0.023	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.013	0.073	-10000	0	-0.3	23	23
VASP	-0.013	0.081	-10000	0	-0.29	28	28
ZYX	-0.012	0.08	-10000	0	-0.3	26	26
JUB	-0.009	0.08	-10000	0	-0.29	27	27
EGFR(dimer)	-0.003	0.094	-10000	0	-0.3	31	31
E-cadherin/beta catenin-gamma catenin	0.038	0.027	0.22	1	-0.25	2	3
mol:PI-3-4-5-P3	0.012	0.063	-10000	0	-0.21	21	21
PIK3CA	0.019	0.018	-10000	0	-0.32	1	1
PI3K	0.013	0.064	-10000	0	-0.21	21	21
FYN	-0.002	0.055	0.2	6	-0.24	8	14
mol:Ca2+	-0.003	0.041	-10000	0	-0.2	8	8
JUP	0.022	0.016	-10000	0	-0.31	1	1
PIK3R1	0.02	0.031	-10000	0	-0.32	4	4
mol:DAG	-0.003	0.042	-10000	0	-0.2	8	8
CDH1	0.02	0.026	0.32	1	-0.32	2	3
RhoA/GDP	0.008	0.063	0.21	1	-0.26	5	6
establishment of polarity of embryonic epithelium	-0.013	0.08	-10000	0	-0.29	28	28
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
EGFR	0.013	0.054	-10000	0	-0.32	13	13
CASR	-0.007	0.057	0.17	19	-0.2	7	26
RhoA/GTP	0.013	0.052	-10000	0	-0.2	5	5
AKT2	-0.005	0.052	-10000	0	-0.23	13	13
actin cable formation	-0.011	0.076	0.19	7	-0.31	19	26
apoptosis	-0.003	0.071	0.22	25	-0.24	8	33
CTNNA1	0.023	0.007	-10000	0	-10000	0	0
mol:GDP	-0.015	0.057	0.14	24	-0.23	9	33
PIP5K1A	-0.013	0.074	-10000	0	-0.3	23	23
PLCG1	-0.003	0.043	-10000	0	-0.21	8	8
Rac1/GTP	0.006	0.09	-10000	0	-0.28	30	30
homophilic cell adhesion	0	0.003	-10000	0	-10000	0	0

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	0.013	0.097	0.22	2	-0.41	16	18
ACTA1	0.017	0.074	0.22	8	-0.25	11	19
NUMA1	0.011	0.1	0.22	2	-0.41	17	19
SPTAN1	0.006	0.069	0.22	3	-0.26	11	14
LIMK1	0.008	0.076	0.28	8	-0.26	12	20
BIRC3	0.017	0.045	0.32	1	-0.32	8	9
BIRC2	0.022	0.004	-10000	0	-10000	0	0
BAX	0.022	0.004	-10000	0	-10000	0	0
CASP10	-0.005	0.05	0.11	56	-0.25	5	61
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.023	0.002	-10000	0	-10000	0	0
PTK2	0.012	0.097	0.22	2	-0.38	18	20
DIABLO	0.022	0.003	-10000	0	-10000	0	0
apoptotic nuclear changes	0.005	0.068	0.22	3	-0.26	11	14
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
GSN	0.004	0.069	0.24	2	-0.29	8	10
MADD	0.022	0.005	-10000	0	-10000	0	0
TFAP2A	0.16	0.12	0.38	38	-0.68	4	42
BID	0.005	0.03	0.14	6	-0.16	5	11
MAP3K1	-0.004	0.1	-10000	0	-0.42	24	24
TRADD	0.02	0.008	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.033	0.007	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	0.007	0.074	0.24	8	-0.26	12	20
CASP9	0.022	0.004	-10000	0	-10000	0	0
DNA repair	-0.018	0.047	0.26	4	-0.18	4	8
neuron apoptosis	0.006	0.11	-10000	0	-0.83	8	8
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.008	0.094	0.23	2	-0.37	17	19
APAF1	0.023	0.002	-10000	0	-10000	0	0
CASP6	-0.005	0.17	-10000	0	-0.89	17	17
TRAF2	0.021	0.006	-10000	0	-10000	0	0
ICAD/CAD	0.004	0.071	0.27	6	-0.34	4	10
CASP7	0	0.058	0.26	4	-0.24	8	12
KRT18	0.021	0.063	-10000	0	-0.65	2	2
apoptosis	0.007	0.12	0.41	16	-0.42	18	34
DFFA	0.007	0.072	0.26	6	-0.26	10	16
DFFB	0.006	0.07	0.22	4	-0.26	10	14
PARP1	0.018	0.047	0.18	4	-0.26	4	8
actin filament polymerization	-0.005	0.078	0.26	6	-0.3	12	18
TNF	0.049	0.091	0.32	47	-0.32	2	49
CYCS	0.009	0.045	0.17	7	-0.2	8	15
SATB1	-0.025	0.17	-10000	0	-0.85	17	17
SLK	0.01	0.083	0.31	14	-0.26	12	26
p15 BID/BAX	0.017	0.045	0.16	1	-0.17	8	9
CASP2	0.007	0.054	0.22	6	-0.3	5	11
JNK cascade	0.003	0.1	0.42	24	-10000	0	24
CASP3	0.01	0.074	0.2	10	-0.27	12	22
LMNB2	-0.017	0.16	0.24	2	-0.48	41	43
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CASP4	0.021	0.016	-10000	0	-0.32	1	1
Mammalian IAPs/DIABLO	0.052	0.033	0.23	1	-0.18	8	9
negative regulation of DNA binding	0.16	0.12	0.38	38	-0.67	4	42
stress fiber formation	0.01	0.082	0.31	14	-0.25	12	26
GZMB	0.005	0.067	0.18	56	-0.26	5	61
CASP1	0.006	0.027	-10000	0	-0.24	6	6
LMNB1	0.004	0.13	0.26	2	-0.54	18	20
APP	0.006	0.12	-10000	0	-0.85	8	8
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.008	0.001	-10000	0	-10000	0	0
VIM	0.007	0.11	0.32	14	-0.43	18	32
LMNA	0.007	0.088	0.24	1	-0.37	17	18
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.01	0.055	0.17	4	-0.26	8	12
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	0.009	0.071	0.21	7	-0.3	6	13
APAF-1/Caspase 9	0.009	0.1	-10000	0	-0.64	11	11
nuclear fragmentation during apoptosis	0.012	0.099	0.22	2	-0.4	17	19
CFL2	0.005	0.079	0.3	12	-0.27	6	18
GAS2	-0.004	0.077	0.24	1	-0.28	12	13
positive regulation of apoptosis	-0.003	0.13	0.24	3	-0.56	20	23
PRF1	0.022	0.038	0.32	4	-0.32	3	7

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.001	0.11	0.35	1	-0.47	1	2
CRKL	-0.012	0.06	0.28	2	-0.23	4	6
mol:DAG	0.006	0.056	0.21	1	-0.24	6	7
HRAS	0.008	0.09	0.26	22	-0.22	5	27
MAPK8	0	0.069	0.18	57	-0.19	7	64
RAP1A	-0.012	0.062	0.28	2	-0.23	4	6
GAB1	-0.013	0.063	0.28	2	-0.24	6	8
MAPK14	0.002	0.067	0.17	60	-0.17	3	63
EPO	0.011	0.037	0.32	1	-0.33	3	4
PLCG1	0.005	0.057	0.22	1	-0.25	6	7
EPOR/TRPC2/IP3 Receptors	0.02	0.029	0.32	3	-10000	0	3
RAPGEF1	0.021	0.006	-10000	0	-10000	0	0
EPO/EPOR (dimer)/SOCS3	0.033	0.043	0.22	4	-0.2	8	12
GAB1/SHC/GRB2/SOS1	0.02	0.054	0.26	1	-0.22	5	6
EPO/EPOR (dimer)	0.026	0.036	0.23	4	-0.23	3	7
IRS2	-0.029	0.077	0.28	2	-0.24	14	16
STAT1	0	0.078	0.22	1	-0.28	10	11
STAT5B	0.002	0.069	0.22	1	-0.26	9	10
cell proliferation	0.001	0.077	0.19	62	-0.18	5	67
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.024	0.05	-10000	0	-0.22	7	7
TEC	-0.012	0.062	0.24	3	-0.23	4	7
SOCS3	0.018	0.037	-10000	0	-0.32	6	6
STAT1 (dimer)	0	0.077	0.22	1	-0.24	33	34
JAK2	0.014	0.045	-10000	0	-0.32	8	8
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
EPO/EPOR (dimer)/JAK2	0.042	0.063	0.24	1	-0.19	10	11
EPO/EPOR	0.026	0.036	0.23	4	-0.23	3	7
LYN	0.016	0.016	-10000	0	-10000	0	0
TEC/VAV2	-0.016	0.059	0.21	5	-0.22	4	9
elevation of cytosolic calcium ion concentration	0.02	0.029	0.32	3	-10000	0	3
SHC1	0.019	0.009	-10000	0	-10000	0	0
EPO/EPOR (dimer)/LYN	0.032	0.04	0.22	3	-0.19	3	6
mol:IP3	0.006	0.056	0.21	1	-0.24	6	7
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.006	0.087	0.27	3	-0.25	15	18
SH2B3	0.02	0.022	-10000	0	-0.32	1	1
NFKB1	0.002	0.068	0.17	60	-0.18	4	64
EPO/EPOR (dimer)/JAK2/SOCS3	0.005	0.045	0.19	2	-0.2	15	17
PTPN6	-0.01	0.06	0.15	40	-0.19	9	49
TEC/VAV2/GRB2	0.023	0.056	0.27	1	-0.22	4	5
EPOR	0.02	0.029	0.32	3	-10000	0	3
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
mol:GDP	0.019	0.054	0.26	1	-0.23	5	6
SOS1	0.022	0.004	-10000	0	-10000	0	0
PLCG2	0.019	0.017	-10000	0	-0.32	1	1
CRKL/CBL/C3G	0.023	0.058	0.27	2	-0.23	3	5
VAV2	-0.013	0.059	0.24	3	-0.23	4	7
CBL	-0.012	0.06	0.28	2	-0.23	4	6
SHC/Grb2/SOS1	0.016	0.045	-10000	0	-0.23	4	4
STAT5A	0.003	0.068	0.22	1	-0.27	8	9
GRB2	0.021	0.006	-10000	0	-10000	0	0
STAT5 (dimer)	0.005	0.098	0.28	1	-0.31	31	32
LYN/PLCgamma2	0.023	0.022	-10000	0	-0.22	1	1
PTPN11	0.023	0.003	-10000	0	-10000	0	0
BTK	-0.013	0.063	0.18	7	-0.26	5	12
BCL2	-0.039	0.23	-10000	0	-0.72	48	48

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.015	0.01	-10000	0	-0.22	1	1
MAP4K4	0.001	0.06	0.23	2	-0.3	7	9
BAG4	0.019	0.022	-10000	0	-0.32	2	2
PKC zeta/ceramide	0.014	0.042	0.23	1	-0.19	17	18
NFKBIA	0.022	0.004	-10000	0	-10000	0	0
BIRC3	0.017	0.045	0.32	1	-0.32	8	9
BAX	0.005	0.046	-10000	0	-0.33	8	8
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AKT1	-0.001	0.089	0.65	9	-10000	0	9
BAD	-0.001	0.044	0.2	8	-0.18	18	26
SMPD1	0.01	0.059	0.18	15	-0.22	14	29
RB1	-0.004	0.036	0.2	1	-0.18	18	19
FADD/Caspase 8	0.003	0.07	0.25	3	-0.33	8	11
MAP2K4	-0.008	0.037	0.18	3	-0.18	18	21
NSMAF	0.021	0.007	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.003	0.048	0.2	12	-0.18	19	31
EGF	0.032	0.058	0.32	18	-0.32	1	19
mol:ceramide	0.001	0.038	-10000	0	-0.19	18	18
MADD	0.022	0.005	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.013	0.011	-10000	0	-0.22	1	1
ASAH1	0.02	0.008	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.004	0.036	0.2	1	-0.18	18	19
cell proliferation	-0.015	0.072	0.18	3	-0.22	19	22
BID	-0.014	0.16	-10000	0	-0.63	30	30
MAP3K1	-0.003	0.038	0.19	2	-0.18	18	20
EIF2A	0.003	0.059	0.18	37	-0.18	13	50
TRADD	0.02	0.008	-10000	0	-10000	0	0
CRADD	0.023	0.002	-10000	0	-10000	0	0
MAPK3	-0.006	0.048	0.19	11	-0.18	15	26
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.008	0.051	0.19	12	-0.18	16	28
Cathepsin D/ceramide	0.015	0.04	0.22	1	-0.18	17	18
FADD	0.002	0.061	0.21	5	-0.3	7	12
KSR1	-0.002	0.043	0.2	7	-0.18	19	26
MAPK8	-0.004	0.052	-10000	0	-0.24	8	8
PRKRA	-0.001	0.039	0.19	5	-0.18	16	21
PDGFA	0.021	0.016	-10000	0	-0.32	1	1
TRAF2	0.021	0.006	-10000	0	-10000	0	0
IGF1	-0.045	0.14	-10000	0	-0.32	101	101
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.001	0.038	-10000	0	-0.19	18	18
CTSD	0.022	0.014	0.32	1	-10000	0	1
regulation of nitric oxide biosynthetic process	0.032	0.014	-10000	0	-0.22	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.015	0.077	0.19	3	-0.23	19	22
PRKCD	0.022	0.004	-10000	0	-10000	0	0
PRKCZ	0.022	0.021	0.32	1	-0.32	1	2
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.013	0.011	-10000	0	-0.22	1	1
RelA/NF kappa B1	0.032	0.014	-10000	0	-0.22	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.023	0.002	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.007	0.051	0.17	4	-0.38	1	5
TNFR1A/BAG4/TNF-alpha	0.052	0.052	0.23	36	-0.19	1	37
mol:Sphingosine-1-phosphate	-0.015	0.01	-10000	0	-0.22	1	1
MAP2K1	-0.007	0.046	0.19	13	-0.18	17	30
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.023	0.003	-10000	0	-10000	0	0
CYCS	0.016	0.049	0.15	16	-0.16	4	20
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
TNFR1A/BAG4	0.029	0.02	-10000	0	-0.22	2	2
EIF2AK2	-0.002	0.046	0.19	14	-0.18	15	29
TNF-alpha/TNFR1A/FAN	0.053	0.051	0.23	36	-10000	0	36
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.013	0.062	-10000	0	-0.36	8	8
MAP2K2	-0.007	0.046	0.19	12	-0.17	17	29
SMPD3	0	0.091	0.19	6	-0.28	37	43
TNF	0.049	0.091	0.32	47	-0.32	2	49
PKC zeta/PAR4	0.032	0.016	0.24	1	-0.22	1	2
mol:PHOSPHOCHOLINE	-0.002	0.039	0.12	3	-0.14	13	16
NF kappa B1/RelA/I kappa B alpha	0.06	0.026	-10000	0	-0.17	2	2
AIFM1	0.015	0.05	0.14	39	-0.16	5	44
BCL2	-0.007	0.095	-10000	0	-0.32	43	43

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.019	0.022	-10000	0	-0.32	2	2
Caspase 8 (4 units)	0.027	0.048	-10000	0	-0.58	1	1
NEF	0.002	0.019	0.12	1	-0.19	3	4
NFKBIA	0.021	0.015	-10000	0	-10000	0	0
BIRC3	-0.019	0.056	0.19	11	-0.38	8	19
CYCS	0.019	0.069	0.16	69	-0.61	1	70
RIPK1	0.022	0.004	-10000	0	-10000	0	0
CD247	0.021	0.027	0.41	1	-0.23	2	3
MAP2K7	0.002	0.18	0.29	1	-0.66	31	32
protein ubiquitination	0.002	0.077	0.28	6	-0.29	9	15
CRADD	0.023	0.002	-10000	0	-10000	0	0
DAXX	0.022	0.003	-10000	0	-10000	0	0
FAS	0.019	0.031	-10000	0	-0.32	4	4
BID	0.027	0.07	0.17	71	-0.64	1	72
NF-kappa-B/RelA/I kappa B alpha	0.042	0.038	0.24	1	-0.22	9	10
TRADD	0.02	0.008	-10000	0	-10000	0	0
MAP3K5	0.022	0.016	-10000	0	-0.32	1	1
CFLAR	0.023	0.003	-10000	0	-10000	0	0
FADD	0.022	0.004	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.042	0.038	0.24	1	-0.22	9	10
MAPK8	0.003	0.18	0.37	6	-0.61	31	37
APAF1	0.023	0.002	-10000	0	-10000	0	0
TRAF1	0.021	0.006	-10000	0	-10000	0	0
TRAF2	0.021	0.006	-10000	0	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.035	0.073	0.18	71	-0.27	5	76
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	-0.004	0.088	-10000	0	-0.33	16	16
CHUK	0.002	0.08	0.28	6	-0.31	9	15
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.056	0.033	-10000	0	-0.17	5	5
TCRz/NEF	0.018	0.03	0.22	7	-0.22	2	9
TNF	0.049	0.091	0.32	47	-0.32	2	49
FASLG	0.013	0.05	0.36	8	-0.3	2	10
NFKB1	0.02	0.021	-10000	0	-0.32	1	1
TNFR1A/BAG4/TNF-alpha	0.052	0.052	0.23	36	-0.19	1	37
CASP6	0.037	0.11	-10000	0	-0.47	15	15
CASP7	0.02	0.1	0.42	5	-0.43	10	15
RELA	0.022	0.015	-10000	0	-10000	0	0
CASP2	0.022	0.005	-10000	0	-10000	0	0
CASP3	0.018	0.11	0.39	7	-0.4	14	21
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
TNFR1A/BAG4	0.029	0.02	-10000	0	-0.22	2	2
CASP8	0.023	0.003	-10000	0	-10000	0	0
CASP9	0.022	0.004	-10000	0	-10000	0	0
MAP3K14	0.001	0.081	-10000	0	-0.33	12	12
APAF-1/Caspase 9	-0.002	0.066	0.19	1	-0.29	8	9
BCL2	-0.008	0.16	0.35	5	-0.57	30	35

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.12	0.14	0.32	172	-10000	0	172
mol:Halofuginone	0.002	0	-10000	0	-10000	0	0
ITGA1	0.021	0.022	-10000	0	-0.32	2	2
CDKN1A	-0.003	0.045	-10000	0	-0.34	6	6
PRL-3/alpha Tubulin	0.03	0.011	-10000	0	-10000	0	0
mol:Ca2+	-0.035	0.071	0.19	6	-0.23	53	59
AGT	-0.02	0.12	0.32	5	-0.32	63	68
CCNA2	-0.013	0.067	0.25	8	-10000	0	8
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
EGR1	-0.028	0.081	-10000	0	-0.21	81	81
CDK2/Cyclin E1	0.09	0.11	0.31	12	-0.31	6	18
MAPK3	-0.013	0.005	-10000	0	-10000	0	0
PRL-2 /Rab GGTase beta	0.033	0.006	-10000	0	-10000	0	0
MAPK1	-0.013	0.005	-10000	0	-10000	0	0
PTP4A1	-0.034	0.055	-10000	0	-10000	0	0
PTP4A3	0.021	0.007	-10000	0	-10000	0	0
PTP4A2	0.022	0.004	-10000	0	-10000	0	0
ITGB1	-0.013	0.005	-10000	0	-10000	0	0
SRC	0.022	0.005	-10000	0	-10000	0	0
RAC1	-0.004	0.049	-10000	0	-0.35	7	7
Rab GGTase beta/Rab GGTase alpha	0.033	0.006	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.027	0.07	0.37	1	-10000	0	1
RABGGTA	0.022	0.004	-10000	0	-10000	0	0
BCAR1	-0.017	0.009	-10000	0	-10000	0	0
RHOC	-0.002	0.04	-10000	0	-0.35	4	4
RHOA	-0.007	0.058	-10000	0	-0.34	12	12
cell motility	0.006	0.062	0.27	1	-0.39	4	5
PRL-1/alpha Tubulin	-0.029	0.067	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	0.029	0.016	-10000	0	-0.22	1	1
ROCK1	0.006	0.061	0.27	1	-0.39	4	5
RABGGTB	0.023	0.002	-10000	0	-10000	0	0
CDK2	0.022	0.004	-10000	0	-10000	0	0
mitosis	-0.034	0.054	-10000	0	-10000	0	0
ATF5	0.025	0.027	0.32	4	-10000	0	4

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.037	0.056	-10000	0	-10000	0	0
epithelial cell differentiation	-0.006	0.085	-10000	0	-0.29	2	2
ITCH	0.009	0.028	-10000	0	-10000	0	0
WWP1	0.03	0.064	-10000	0	-10000	0	0
FYN	0.022	0.003	-10000	0	-10000	0	0
EGFR	0.013	0.054	-10000	0	-0.32	13	13
PRL	0.008	0.068	0.32	1	-0.32	20	21
neuron projection morphogenesis	0.038	0.098	0.28	32	-10000	0	32
PTPRZ1	0.036	0.069	0.32	27	-10000	0	27
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.031	0.052	0.28	1	-10000	0	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.015	0.043	0.31	1	-0.25	2	3
ADAM17	0.008	0.028	-10000	0	-10000	0	0
ErbB4/ErbB4	0.03	0.057	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	0.041	0.069	0.29	12	-10000	0	12
NCOR1	0.021	0.007	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.024	0.046	0.28	1	-10000	0	1
GRIN2B	0.015	0.068	0.25	19	-10000	0	19
ErbB4/ErbB2/betacellulin	0.026	0.058	0.25	7	-10000	0	7
STAT1	0.023	0.014	0.32	1	-10000	0	1
HBEGF	0.022	0.016	-10000	0	-0.32	1	1
PRLR	-0.041	0.13	-10000	0	-0.32	94	94
E4ICDs/ETO2	0.027	0.058	-10000	0	-0.28	1	1
axon guidance	0.017	0.055	-10000	0	-10000	0	0
NEDD4	-0.021	0.088	-10000	0	-0.32	37	37
Prolactin receptor/Prolactin receptor/Prolactin	-0.024	0.11	0.24	1	-0.23	106	107
CBFA2T3	-0.014	0.1	-10000	0	-0.32	51	51
ErbB4/ErbB2/HBEGF	0.032	0.05	0.25	7	-10000	0	7
MAPK3	0.035	0.088	0.27	18	-10000	0	18
STAT1 (dimer)	0.036	0.056	-10000	0	-10000	0	0
MAPK1	0.036	0.089	0.27	19	-10000	0	19
JAK2	0.016	0.045	-10000	0	-0.32	9	9
ErbB4/ErbB2/neuregulin 1 beta	0.015	0.05	0.25	8	-0.24	2	10
NRG1	-0.016	0.031	0.27	1	-0.23	7	8
NRG3	0.03	0.055	0.32	17	-10000	0	17
NRG2	-0.012	0.1	0.32	1	-0.32	51	52
NRG4	0.046	0.083	0.32	41	-10000	0	41
heart development	0.017	0.055	-10000	0	-10000	0	0
neural crest cell migration	0.015	0.05	0.25	8	-0.23	2	10
ERBB2	-0.005	0.048	0.28	13	-10000	0	13
WWOX/E4ICDs	0.034	0.052	-10000	0	-10000	0	0
SHC1	0.019	0.009	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	0.054	0.08	0.28	21	-0.26	2	23
apoptosis	-0.041	0.067	0.32	2	-0.27	9	11
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.029	0.065	-10000	0	-0.28	3	3
ErbB4/ErbB2/epiregulin	0.054	0.083	0.28	31	-10000	0	31
ErbB4/ErbB4/betacellulin/betacellulin	0.035	0.057	-10000	0	-10000	0	0
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.016	0.1	-10000	0	-0.3	6	6
MDM2	0.023	0.054	0.3	4	-10000	0	4
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.017	0.033	-10000	0	-10000	0	0
STAT5A	0.013	0.057	0.29	1	-10000	0	1
ErbB4/EGFR/neuregulin 1 beta	0.02	0.054	0.28	1	-0.3	3	4
DLG4	0.021	0.016	-10000	0	-0.32	1	1
GRB2/SHC	0.026	0.015	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.03	0.049	-10000	0	-10000	0	0
STAT5A (dimer)	0.003	0.097	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.028	0.062	-10000	0	-10000	0	0
LRIG1	0.02	0.027	-10000	0	-0.32	3	3
EREG	0.056	0.096	0.32	58	-10000	0	58
BTC	0.011	0.061	-10000	0	-0.32	17	17
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.014	0.051	-10000	0	-10000	0	0
ERBB4	0.03	0.057	-10000	0	-10000	0	0
STAT5B	0.021	0.016	-10000	0	-0.32	1	1
YAP1	0.013	0.083	-10000	0	-0.44	14	14
GRB2	0.021	0.006	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	0.049	0.078	0.3	28	-10000	0	28
glial cell differentiation	-0.03	0.049	-10000	0	-10000	0	0
WWOX	0.02	0.008	-10000	0	-10000	0	0
cell proliferation	0.016	0.092	0.29	11	-0.37	3	14

ceramide 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
MAP4K4	0.001	0.086	0.24	2	-0.4	12	14
BAG4	0.019	0.022	-10000	0	-0.32	2	2
BAD	0.001	0.042	0.17	8	-0.16	8	16
NFKBIA	0.022	0.004	-10000	0	-10000	0	0
BIRC3	0.017	0.045	0.32	1	-0.32	8	9
BAX	0	0.042	0.18	7	-0.16	9	16
EnzymeConsortium:3.1.4.12	0.002	0.024	0.08	2	-0.088	13	15
IKBKB	0.01	0.099	0.27	17	-0.37	10	27
MAP2K2	-0.003	0.042	0.21	8	-0.18	3	11
MAP2K1	-0.003	0.043	0.2	9	-0.19	3	12
SMPD1	-0.001	0.032	-10000	0	-0.14	14	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.007	0.088	0.24	4	-0.38	13	17
MAP2K4	-0.002	0.034	0.21	2	-0.16	5	7
protein ubiquitination	0.004	0.093	0.29	5	-0.38	11	16
EnzymeConsortium:2.7.1.37	-0.006	0.048	0.2	10	-0.2	3	13
response to UV	0	0.001	0.002	9	-0.002	2	11
RAF1	-0.001	0.046	0.21	9	-0.17	5	14
CRADD	0.023	0.002	-10000	0	-10000	0	0
mol:ceramide	0.002	0.039	0.11	5	-0.14	15	20
I-kappa-B-alpha/RELA/p50/ubiquitin	0.03	0.007	-10000	0	-10000	0	0
MADD	0.022	0.005	-10000	0	-10000	0	0
MAP3K1	-0.001	0.038	0.17	4	-0.16	8	12
TRADD	0.02	0.008	-10000	0	-10000	0	0
RELA/p50	0.023	0.003	-10000	0	-10000	0	0
MAPK3	-0.004	0.049	0.2	10	-0.18	6	16
MAPK1	-0.006	0.053	0.2	10	-0.2	10	20
p50/RELA/I-kappa-B-alpha	0.032	0.007	-10000	0	-10000	0	0
FADD	0.004	0.085	0.23	4	-0.37	13	17
KSR1	0	0.041	0.17	6	-0.16	7	13
MAPK8	-0.004	0.044	0.18	11	-0.16	3	14
TRAF2	0.021	0.006	-10000	0	-10000	0	0
response to radiation	0	0	0.002	4	-10000	0	4
CHUK	0.001	0.087	0.35	3	-0.4	9	12
TNF R/SODD	0.029	0.02	-10000	0	-0.22	2	2
TNF	0.049	0.091	0.32	47	-0.32	2	49
CYCS	0.009	0.048	0.14	21	-0.15	8	29
IKBKG	-0.003	0.088	0.3	4	-0.38	12	16
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.005	0.088	-10000	0	-0.32	25	25
RELA	0.023	0.003	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
AIFM1	0.008	0.046	0.14	18	-0.15	6	24
TNF/TNF R/SODD	0.052	0.052	0.22	36	-0.19	1	37
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
response to heat	0	0	0.002	4	-10000	0	4
CASP8	0.015	0.086	-10000	0	-0.61	8	8
NSMAF	0.012	0.091	0.26	11	-0.43	8	19
response to hydrogen peroxide	0	0.001	0.002	9	-0.002	2	11
BCL2	-0.007	0.095	-10000	0	-0.32	43	43

E-cadherin signaling in the nascent adherens junction

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
CTTN	-0.021	0.094	-10000	0	-0.28	58	58
KLHL20	-0.011	0.061	-10000	0	-0.2	30	30
CYFIP2	0.021	0.022	-10000	0	-0.32	2	2
Rac1/GDP	-0.007	0.069	0.27	1	-0.25	10	11
ENAH	-0.024	0.096	-10000	0	-0.28	59	59
AP1M1	0.022	0.005	-10000	0	-10000	0	0
RAP1B	0.023	0.002	-10000	0	-10000	0	0
RAP1A	0.023	0.001	-10000	0	-10000	0	0
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
CDC42/GTP	-0.024	0.022	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	-0.021	0.036	-10000	0	-0.14	33	33
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.048	0.029	0.23	2	-0.18	2	4
RAPGEF1	-0.02	0.079	0.22	1	-0.26	39	40
CTNND1	0.023	0.003	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.015	0.1	-10000	0	-0.28	63	63
CRK	-0.014	0.083	-10000	0	-0.27	41	41
E-cadherin/gamma catenin/alpha catenin	0.039	0.027	0.23	1	-0.27	2	3
alphaE/beta7 Integrin	0.031	0.014	0.24	1	-10000	0	1
IQGAP1	0.022	0.004	-10000	0	-10000	0	0
NCKAP1	0.023	0.003	-10000	0	-10000	0	0
Rap1/GTP/I-afadin	0.042	0.01	-10000	0	-10000	0	0
DLG1	-0.018	0.09	-10000	0	-0.28	51	51
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.017	-10000	0	-0.12	2	2
MLLT4	0.022	0.004	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	0.035	0.035	-10000	0	-0.17	13	13
PI3K	-0.028	0.021	-10000	0	-0.16	2	2
ARF6	0.022	0.003	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
E-cadherin/gamma catenin	0.028	0.027	0.24	1	-0.31	2	3
TIAM1	0.013	0.056	-10000	0	-0.32	14	14
E-cadherin(dimer)/Ca2+	0.046	0.025	0.21	1	-0.16	2	3
AKT1	-0.017	0.023	0.14	1	-10000	0	1
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
CDH1	0.019	0.026	0.32	1	-0.32	2	3
RhoA/GDP	-0.008	0.068	-10000	0	-0.24	8	8
actin cytoskeleton organization	-0.007	0.047	0.18	1	-0.15	30	31
CDC42/GDP	-0.006	0.069	0.27	1	-0.25	10	11
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.01	0.02	-10000	0	-0.27	2	2
ITGB7	0.023	0.014	0.32	1	-10000	0	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.049	0.027	0.23	1	-0.18	2	3
E-cadherin/Ca2+/beta catenin/alpha catenin	0.034	0.02	0.2	1	-0.16	2	3
mol:GDP	-0.02	0.074	0.28	1	-0.28	12	13
CDC42/GTP/IQGAP1	0.029	0.007	-10000	0	-10000	0	0
JUP	0.021	0.016	-10000	0	-0.32	1	1
p120 catenin/RhoA/GDP	0	0.071	-10000	0	-0.26	6	6
RAC1/GTP/IQGAP1	0.029	0.008	-10000	0	-10000	0	0
PIP5K1C/AP1M1	0.03	0.011	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
CDC42	0.022	0.004	-10000	0	-10000	0	0
CTNNA1	0.022	0.003	-10000	0	-10000	0	0
positive regulation of S phase of mitotic cell cycle	-0.001	0.034	0.13	3	-10000	0	3
NME1	0.022	0.005	-10000	0	-10000	0	0
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	-0.016	0.088	-10000	0	-0.28	49	49
regulation of cell-cell adhesion	-0.023	0.018	-10000	0	-10000	0	0
WASF2	-0.009	0.025	-10000	0	-0.086	6	6
Rap1/GTP	-0.019	0.038	-10000	0	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.055	0.034	0.23	2	-0.24	2	4
CCND1	-0.001	0.04	0.15	3	-0.14	1	4
VAV2	-0.036	0.17	-10000	0	-0.57	35	35
RAP1/GDP	0.01	0.058	-10000	0	-0.26	3	3
adherens junction assembly	-0.016	0.086	-10000	0	-0.27	49	49
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.022	0.005	-10000	0	-10000	0	0
PIP5K1C	0.021	0.006	-10000	0	-10000	0	0
regulation of heterotypic cell-cell adhesion	0.039	0.029	0.21	2	-0.23	2	4
E-cadherin/beta catenin	0.007	0.02	0.15	1	-0.28	2	3
mol:GTP	0	0	-10000	0	-10000	0	0
SRC	-0.022	0.095	-10000	0	-0.28	58	58
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
Rac1/GTP	-0.022	0.088	-10000	0	-0.31	32	32
E-cadherin/beta catenin/alpha catenin	0.039	0.024	0.23	1	-0.19	2	3
ITGAE	0.021	0.006	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.015	0.1	-10000	0	-0.29	63	63

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.012	0.015	0.15	1	-0.26	1	2
CRKL	0.022	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.016	0.003	-10000	0	-10000	0	0
DOCK1	0.018	0.037	-10000	0	-0.32	6	6
ITGA4	0.022	0.025	0.32	1	-0.32	2	3
alpha4/beta7 Integrin/MAdCAM1	0.065	0.054	0.23	41	-0.18	1	42
EPO	0.019	0.03	0.32	1	-0.32	3	4
alpha4/beta7 Integrin	0.033	0.018	0.24	2	-0.22	1	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.032	0.02	0.24	1	-0.22	2	3
EPO/EPOR (dimer)	0.03	0.029	0.24	4	-0.22	3	7
lamellipodium assembly	0.009	0.073	-10000	0	-0.38	10	10
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PI3K	0.027	0.028	-10000	0	-0.22	5	5
ARF6	0.022	0.003	-10000	0	-10000	0	0
JAK2	0.013	0.038	0.16	6	-0.23	9	15
PXN	0.022	0.003	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
MADCAM1	0.045	0.083	0.32	41	-10000	0	41
cell adhesion	0.063	0.052	0.22	41	-0.18	1	42
CRKL/CBL	0.031	0.009	-10000	0	-10000	0	0
ITGB1	0.022	0.004	-10000	0	-10000	0	0
SRC	-0.024	0.054	0.17	15	-0.18	32	47
ITGB7	0.023	0.014	0.32	1	-10000	0	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.027	0.064	0.23	1	-0.2	35	36
p130Cas/Crk/Dock1	-0.032	0.048	0.18	7	-0.34	2	9
VCAM1	-0.004	0.092	-10000	0	-0.32	40	40
RHOA	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.052	0.025	0.23	1	-0.18	2	3
BCAR1	-0.022	0.051	0.18	14	-0.18	25	39
EPOR	0.023	0.024	0.32	3	-10000	0	3
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.022	0.005	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	0.009	0.076	-10000	0	-0.39	10	10

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.021	0.006	-10000	0	-10000	0	0
HDAC4	0.022	0.003	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	0.012	0.036	0.22	2	-0.23	8	10
CDKN1A	-0.01	0.007	-10000	0	-10000	0	0
KAT2B	0.016	0.045	-10000	0	-0.32	9	9
BAX	0.022	0.004	-10000	0	-10000	0	0
FOXO3	-0.003	0.005	-10000	0	-10000	0	0
FOXO1	0.02	0.022	-10000	0	-0.32	2	2
FOXO4	0.007	0.014	-10000	0	-0.21	2	2
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.021	0.006	-10000	0	-10000	0	0
TAT	0.02	0.021	0.32	2	-10000	0	2
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.004	0.06	0.18	39	-0.22	8	47
PPARGC1A	-0.049	0.14	0.32	1	-0.32	106	107
FHL2	0.017	0.045	-10000	0	-0.32	9	9
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.029	0.021	0.25	1	-0.22	2	3
HIST2H4A	-0.012	0.036	0.23	8	-0.22	2	10
SIRT1/FOXO3a	0.019	0.033	0.22	2	-0.19	5	7
SIRT1	0.02	0.027	0.35	1	-0.32	2	3
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.035	0.026	0.24	1	-0.19	2	3
SIRT1/Histone H1b	0.016	0.051	0.33	1	-0.22	9	10
apoptosis	-0.039	0.022	0.19	2	-0.24	1	3
SIRT1/PGC1A	-0.016	0.088	0.22	2	-0.19	104	106
p53/SIRT1	0.027	0.03	0.55	1	-0.22	2	3
SIRT1/FOXO4	0.011	0.046	0.24	1	-0.2	12	13
FOXO1/FHL2/SIRT1	0.035	0.036	0.23	1	-0.17	12	13
HIST1H1E	0.014	0.028	0.19	2	-10000	0	2
SIRT1/p300	0.029	0.021	0.25	1	-0.22	2	3
muscle cell differentiation	-0.026	0.041	0.21	9	-0.24	3	12
TP53	0.021	0.021	0.34	2	-10000	0	2
KU70/SIRT1/BAX	0.04	0.023	0.24	1	-0.19	2	3
CREBBP	0.022	0.005	-10000	0	-10000	0	0
MEF2D	0.019	0.009	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	0.027	0.026	0.24	3	-0.22	2	5
ACSS2	-0.015	0.019	0.27	1	-0.22	2	3
SIRT1/PCAF/MYOD	0.026	0.041	0.24	3	-0.21	9	12

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.015	0.018	0.17	4	-10000	0	4
SNTA1	0.022	0.005	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.015	0.019	0.15	5	-10000	0	5
MAPK12	-0.005	0.048	0.2	4	-0.19	19	23
CCND1	0.006	0.032	-10000	0	-0.33	2	2
p38 gamma/SNTA1	0	0.059	0.21	10	-0.19	18	28
MAP2K3	0.021	0.006	-10000	0	-10000	0	0
PKN1	0.021	0.006	-10000	0	-10000	0	0
G2/M transition checkpoint	-0.004	0.05	0.2	7	-0.19	19	26
MAP2K6	0	0.053	0.23	2	-0.21	19	21
MAPT	-0.004	0.06	0.21	6	-0.23	20	26
MAPK13	-0.011	0.025	0.2	6	-10000	0	6
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	-0.002	0.05	-10000	0	-0.24	21	21

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.011	0.024	-10000	0	-0.17	8	8
epithelial cell differentiation	0.041	0.023	0.2	1	-0.16	2	3
CYFIP2	0.021	0.022	-10000	0	-0.32	2	2
ENAH	-0.014	0.055	0.26	9	-10000	0	9
EGFR	0.013	0.054	-10000	0	-0.32	13	13
EPHA2	0.022	0.004	-10000	0	-10000	0	0
MYO6	-0.018	0.023	0.17	5	-0.16	2	7
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
ABI1/Sra1/Nap1	0.043	0.016	-10000	0	-0.19	1	1
AQP5	0.097	0.091	0.26	8	-0.28	7	15
CTNND1	0.023	0.003	-10000	0	-10000	0	0
mol:PI-4-5-P2	-0.019	0.017	0.16	2	-10000	0	2
regulation of calcium-dependent cell-cell adhesion	-0.021	0.031	0.16	5	-0.29	1	6
EGF	0.032	0.058	0.32	18	-0.32	1	19
NCKAP1	0.023	0.003	-10000	0	-10000	0	0
AQP3	-0.014	0.061	-10000	0	-0.3	18	18
cortical microtubule organization	0.041	0.023	0.2	1	-0.16	2	3
GO:0000145	-0.018	0.016	0.15	2	-10000	0	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.046	0.025	0.21	1	-0.16	2	3
MLLT4	0.022	0.004	-10000	0	-10000	0	0
ARF6/GDP	-0.027	0.02	-10000	0	-0.16	4	4
ARF6	0.022	0.003	-10000	0	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.042	0.031	0.23	1	-0.18	2	3
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.01	0.019	-10000	0	-10000	0	0
PVRL2	0.022	0.005	-10000	0	-10000	0	0
ZYX	-0.018	0.023	0.17	5	-0.16	2	7
ARF6/GTP	0.046	0.033	0.22	1	-0.17	2	3
CDH1	0.019	0.026	0.32	1	-0.32	2	3
EGFR/EGFR/EGF/EGF	0.033	0.043	-10000	0	-0.17	11	11
RhoA/GDP	0.041	0.025	-10000	0	-0.16	2	2
actin cytoskeleton organization	-0.02	0.02	0.15	4	-0.16	2	6
IGF-1R heterotetramer	0.01	0.063	-10000	0	-0.32	18	18
GIT1	0.022	0.005	-10000	0	-10000	0	0
IGF1R	0.01	0.063	-10000	0	-0.32	18	18
IGF1	-0.045	0.14	-10000	0	-0.32	101	101
DIAPH1	0.027	0.1	-10000	0	-0.5	12	12
Wnt receptor signaling pathway	-0.041	0.023	0.16	2	-0.2	1	3
RHOA	0.022	0.005	-10000	0	-10000	0	0
RhoA/GTP	-0.026	0.02	-10000	0	-0.16	4	4
CTNNA1	0.022	0.003	-10000	0	-10000	0	0
VCL	-0.02	0.02	0.15	4	-0.17	2	6
EFNA1	0.019	0.016	0.32	1	-10000	0	1
LPP	-0.021	0.019	0.16	3	-10000	0	3
Ephrin A1/EPHA2	0.029	0.027	-10000	0	-0.16	2	2
SEC6/SEC8	-0.028	0.014	-10000	0	-0.16	1	1
MGAT3	-0.021	0.031	0.17	5	-0.29	1	6
HGF/MET	0.003	0.08	-10000	0	-0.16	85	85
HGF	-0.037	0.13	-10000	0	-0.32	88	88
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.011	0.025	-10000	0	-0.17	8	8
actin cable formation	0.036	0.1	0.29	31	-0.25	2	33
KIAA1543	-0.018	0.022	0.16	5	-0.15	3	8
KIFC3	-0.018	0.022	0.17	5	-10000	0	5
NCK1	0.021	0.022	-10000	0	-0.32	2	2
EXOC3	0.021	0.006	-10000	0	-10000	0	0
ACTN1	-0.019	0.021	0.17	4	-10000	0	4
NCK1/GIT1	0.03	0.019	-10000	0	-0.22	2	2
mol:GDP	0.041	0.023	0.2	1	-0.16	2	3
EXOC4	0.022	0.005	-10000	0	-10000	0	0
STX4	-0.018	0.024	0.17	6	-10000	0	6
PIP5K1C	-0.019	0.017	0.17	2	-10000	0	2
LIMA1	0.023	0.002	-10000	0	-10000	0	0
ABI1	0.022	0.005	-10000	0	-10000	0	0
ROCK1	0.01	0.087	0.31	15	-10000	0	15
adherens junction assembly	-0.051	0.14	-10000	0	-0.55	29	29
IGF-1R heterotetramer/IGF1	-0.007	0.088	-10000	0	-0.17	106	106
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.031	0.009	-10000	0	-10000	0	0
MET	0.022	0.041	0.32	4	-0.32	4	8
PLEKHA7	-0.019	0.023	0.17	5	-10000	0	5
mol:GTP	0.041	0.03	0.22	1	-0.17	2	3
establishment of epithelial cell apical/basal polarity	-0.011	0.07	0.35	8	-10000	0	8
cortical actin cytoskeleton stabilization	0.011	0.024	-10000	0	-0.17	8	8
regulation of cell-cell adhesion	-0.02	0.02	0.15	4	-0.16	2	6
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.011	0.025	-10000	0	-0.17	8	8

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.023	0.045	0.32	4	-0.32	6	10
PI3K Class IB/PDE3B	0.023	0.045	0.32	6	-0.32	4	10
PDE3B	0.023	0.045	0.32	6	-0.32	4	10

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.023	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.094	0.25	5	-0.31	17	22
ERC1	0.022	0.004	-10000	0	-10000	0	0
RIP2/NOD2	0.029	0.016	0.24	1	-10000	0	1
NFKBIA	-0.017	0.014	0.2	1	-10000	0	1
BIRC2	0.022	0.004	-10000	0	-10000	0	0
IKBKB	0.02	0.007	-10000	0	-10000	0	0
RIPK2	0.021	0.007	-10000	0	-10000	0	0
IKBKG	0.003	0.08	-10000	0	-0.34	23	23
IKK complex/A20	0.026	0.11	0.28	3	-0.33	33	36
NEMO/A20/RIP2	0.021	0.007	-10000	0	-10000	0	0
XPO1	0.022	0.003	-10000	0	-10000	0	0
NEMO/ATM	0.004	0.11	0.26	2	-0.34	41	43
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
Exportin 1/RanGTP	0.03	0.006	-10000	0	-10000	0	0
IKK complex/ELKS	0.007	0.1	-10000	0	-0.33	35	35
BCL10/MALT1/TRAF6	0.043	0.013	-10000	0	-10000	0	0
NOD2	0.021	0.015	0.32	1	-10000	0	1
NFKB1	0.022	0.016	-10000	0	-0.32	1	1
RELA	0.023	0.003	-10000	0	-10000	0	0
MALT1	0.022	0.005	-10000	0	-10000	0	0
cIAP1/UbcH5C	0.032	0.009	-10000	0	-10000	0	0
ATM	0.022	0.005	-10000	0	-10000	0	0
TNF/TNFR1A	0.05	0.06	0.24	46	-0.22	1	47
TRAF6	0.022	0.005	-10000	0	-10000	0	0
PRKCA	0.002	0.079	-10000	0	-0.32	29	29
CHUK	0.022	0.005	-10000	0	-10000	0	0
UBE2D3	0.022	0.004	-10000	0	-10000	0	0
TNF	0.049	0.091	0.32	47	-0.32	2	49
NF kappa B1 p50/RelA	0.047	0.016	-10000	0	-0.19	1	1
BCL10	0.023	0.002	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.017	0.014	0.2	1	-10000	0	1
beta TrCP1/SCF ubiquitin ligase complex	0.023	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
IKK complex	0.007	0.11	0.26	1	-0.34	35	36
CYLD	0.021	0.007	-10000	0	-10000	0	0
IKK complex/PKC alpha	0.006	0.11	-10000	0	-0.35	35	35

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.048	0.038	0.23	1	-0.18	10	11
HDAC3	0.022	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.016	0.004	-10000	0	-10000	0	0
GATA1/HDAC4	0.03	0.007	-10000	0	-10000	0	0
GATA1/HDAC5	0.029	0.009	-10000	0	-10000	0	0
GATA2/HDAC5	0.009	0.071	-10000	0	-0.22	44	44
HDAC5/BCL6/BCoR	0.039	0.02	-10000	0	-0.19	1	1
HDAC9	0.015	0.048	-10000	0	-0.32	10	10
Glucocorticoid receptor/Hsp90/HDAC6	0	0.09	-10000	0	-0.19	92	92
HDAC4/ANKRA2	0.031	0.014	-10000	0	-0.22	1	1
HDAC5/YWHAB	0.031	0.01	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.003	-10000	0	-10000	0	0
GATA2	-0.008	0.096	-10000	0	-0.32	44	44
HDAC4/RFXANK	0.032	0.016	0.24	2	-10000	0	2
BCOR	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.02	0.007	-10000	0	-10000	0	0
HDAC5	0.022	0.005	-10000	0	-10000	0	0
GNB1/GNG2	0.026	0.043	0.24	1	-0.22	14	15
Histones	0	0.06	-10000	0	-0.29	7	7
ADRBK1	0.022	0.004	-10000	0	-10000	0	0
HDAC4	0.022	0.003	-10000	0	-10000	0	0
XPO1	0.022	0.003	-10000	0	-10000	0	0
HDAC5/ANKRA2	0.031	0.015	-10000	0	-0.22	1	1
HDAC4/Ubc9	0.032	0.009	-10000	0	-10000	0	0
HDAC7	0.022	0.005	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.031	0.01	-10000	0	-10000	0	0
TUBA1B	0.023	0.002	-10000	0	-10000	0	0
HDAC6	0.022	0.004	-10000	0	-10000	0	0
HDAC5/RFXANK	0.032	0.016	0.24	2	-10000	0	2
CAMK4	0.024	0.037	0.32	5	-0.32	2	7
Tubulin/HDAC6	0.043	0.022	0.23	2	-0.19	2	4
SUMO1	0.023	0.003	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.022	0.005	-10000	0	-10000	0	0
GATA1	0.019	0.004	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.021	0.006	-10000	0	-10000	0	0
NR3C1	-0.04	0.13	-10000	0	-0.32	92	92
SUMO1/HDAC4	0.022	0.045	-10000	0	-0.19	11	11
SRF	0.022	0.004	-10000	0	-10000	0	0
HDAC4/YWHAB	0.032	0.009	-10000	0	-10000	0	0
Tubulin	0.032	0.024	0.24	2	-0.22	3	5
HDAC4/14-3-3 E	0.031	0.01	-10000	0	-10000	0	0
GNB1	0.022	0.004	-10000	0	-10000	0	0
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
BCL6/BCoR	0.03	0.016	-10000	0	-0.22	1	1
HDAC4/HDAC3/SMRT (N-CoR2)	0.044	0.011	-10000	0	-10000	0	0
HDAC4/SRF	0.044	0.023	0.23	4	-0.19	1	5
HDAC4/ER alpha	0.006	0.078	-10000	0	-0.22	53	53
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.001	0.059	-10000	0	-0.29	7	7
cell motility	0.043	0.022	0.22	2	-0.19	2	4
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
HDAC7/HDAC3	0.032	0.008	-10000	0	-10000	0	0
BCL6	0.02	0.017	-10000	0	-0.32	1	1
HDAC4/CaMK II delta B	0.022	0.003	-10000	0	-10000	0	0
Hsp90/HDAC6	0.032	0.008	-10000	0	-10000	0	0
ESR1	-0.013	0.1	-10000	0	-0.32	53	53
HDAC6/HDAC11	0.032	0.009	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.023	0.043	-10000	0	-0.18	10	10
NPC	0.013	0.001	-10000	0	-10000	0	0
MEF2C	-0.014	0.1	-10000	0	-0.32	53	53
RAN	0.023	0.003	-10000	0	-10000	0	0
HDAC4/MEF2C	0.038	0.071	-10000	0	-0.17	50	50
GNG2	0.013	0.058	0.32	1	-0.32	14	15
NCOR2	0.022	0.003	-10000	0	-10000	0	0
TUBB2A	0.021	0.033	0.32	2	-0.32	3	5
HDAC11	0.022	0.005	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
ANKRA2	0.021	0.016	-10000	0	-0.32	1	1
RFXANK	0.023	0.02	0.32	2	-10000	0	2
nuclear import	-0.023	0.009	-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.013	0.021	-10000	0	-0.15	1	1
TRAF2/ASK1	0.028	0.013	-10000	0	-0.18	1	1
ATM	0.022	0.005	-10000	0	-10000	0	0
MAP2K3	-0.003	0.093	0.23	2	-0.33	26	28
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.006	0.088	0.3	3	-0.34	16	19
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.014	0.05	-10000	0	-0.32	11	11
TXN	0.004	0.001	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
GADD45A	0.023	0.002	-10000	0	-10000	0	0
GADD45B	0.021	0.006	-10000	0	-10000	0	0
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
MAP3K6	0.022	0.004	-10000	0	-10000	0	0
MAP3K7	0.023	0.003	-10000	0	-10000	0	0
MAP3K4	0.022	0.004	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.013	-10000	0	-0.22	1	1
TAK1/TAB family	0.001	0.023	0.13	2	-0.16	3	5
RAC1/OSM/MEKK3	0.04	0.013	-10000	0	-10000	0	0
TRAF2	0.021	0.006	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.014	0.079	-10000	0	-0.29	20	20
TRAF6	0.004	0.001	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.076	0.12	0.32	91	-10000	0	91
CCM2	0.022	0.004	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.06	0.069	0.21	86	-10000	0	86
MAPK11	0.019	0.022	-10000	0	-0.32	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.068	0.067	0.21	83	-0.17	1	84
OSM/MEKK3	0.031	0.009	-10000	0	-10000	0	0
TAOK1	0.008	0.011	-10000	0	-0.24	1	1
TAOK2	0.008	0.003	-10000	0	-10000	0	0
TAOK3	0.009	0.002	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.022	0.004	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.022	0.016	-10000	0	-0.32	1	1
MAP3K10	0.022	0.005	-10000	0	-10000	0	0
MAP3K3	0.022	0.005	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.031	-10000	0	-0.17	1	1
GADD45/MTK1/MTK1	0.043	0.035	-10000	0	-0.16	10	10

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.15	0.17	-10000	0	-0.32	256	256
CLTC	0.008	0.061	-10000	0	-0.46	7	7
calcium ion-dependent exocytosis	0.005	0.03	-10000	0	-0.24	5	5
Dynamin 2/GTP	0.017	0.007	-10000	0	-10000	0	0
EXOC4	0.022	0.005	-10000	0	-10000	0	0
CD59	0.004	0.043	-10000	0	-0.37	6	6
CPE	-0.035	0.06	-10000	0	-0.18	69	69
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
membrane fusion	0.007	0.015	-10000	0	-10000	0	0
CTNND1	-0.013	0.029	0.17	11	-10000	0	11
DNM2	0.021	0.006	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.006	0.04	0.17	2	-0.31	4	6
TSHR	-0.007	0.035	0.17	17	-0.18	2	19
INS	-0.011	0.1	-10000	0	-0.47	23	23
BIN1	0.02	0.03	-10000	0	-0.32	4	4
mol:Choline	0.007	0.015	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.011	0.003	-10000	0	-10000	0	0
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.022	0.003	-10000	0	-10000	0	0
mol:Ca2+	0.017	0.007	-10000	0	-10000	0	0
JUP	0.005	0.036	-10000	0	-0.37	4	4
ASAP2/amphiphysin II	0.04	0.02	-10000	0	-0.17	3	3
ARF6/GTP	0.017	0.003	-10000	0	-10000	0	0
CDH1	0.004	0.036	-10000	0	-0.37	4	4
clathrin-independent pinocytosis	0.017	0.003	-10000	0	-10000	0	0
MAPK8IP3	0.022	0.005	-10000	0	-10000	0	0
positive regulation of endocytosis	0.017	0.003	-10000	0	-10000	0	0
EXOC2	0.022	0.005	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.006	0.036	-10000	0	-0.23	6	6
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.022	0.005	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.026	0.045	0.33	4	-10000	0	4
positive regulation of phagocytosis	-0.012	0.003	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.029	0.008	-10000	0	-10000	0	0
ACAP1	0.009	0.029	-10000	0	-0.19	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.005	0.038	-10000	0	-0.34	5	5
clathrin heavy chain/ACAP1	0.007	0.053	-10000	0	-0.36	7	7
JIP4/KLC1	0.04	0.013	-10000	0	-10000	0	0
EXOC1	0.022	0.003	-10000	0	-10000	0	0
exocyst	0.006	0.036	-10000	0	-0.23	6	6
RALA/GTP	0.017	0.003	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.029	0.008	-10000	0	-10000	0	0
receptor recycling	0.017	0.003	-10000	0	-10000	0	0
CTNNA1	-0.014	0.026	0.17	9	-10000	0	9
NME1	-0.011	0.003	-10000	0	-10000	0	0
clathrin coat assembly	0.008	0.064	0.26	1	-0.45	7	8
IL2RA	0.008	0.048	0.18	1	-0.37	6	7
VAMP3	-0.012	0.003	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.057	0.086	-10000	0	-0.36	8	8
EXOC6	0.022	0.006	-10000	0	-10000	0	0
PLD1	0.007	0.006	-10000	0	-10000	0	0
PLD2	0.007	0.005	-10000	0	-10000	0	0
EXOC5	0.022	0.004	-10000	0	-10000	0	0
PIP5K1C	0.004	0.034	-10000	0	-0.3	4	4
SDC1	0.028	0.054	0.19	1	-0.34	5	6
ARF6/GDP	0.018	0.005	-10000	0	-10000	0	0
EXOC7	0.021	0.006	-10000	0	-10000	0	0
E-cadherin/beta catenin	0.028	0.047	-10000	0	-0.34	4	4
mol:Phosphatidic acid	0.007	0.015	-10000	0	-10000	0	0
endocytosis	-0.038	0.019	0.17	3	-10000	0	3
SCAMP2	0.022	0.005	-10000	0	-10000	0	0
ADRB2	-0.017	0.079	0.3	1	-0.4	9	10
EXOC3	0.021	0.006	-10000	0	-10000	0	0
ASAP2	0.022	0.005	-10000	0	-10000	0	0
Dynamin 2/GDP	0.02	0.008	-10000	0	-10000	0	0
KLC1	0.022	0.004	-10000	0	-10000	0	0
AVPR2	-0.034	0.094	0.23	7	-0.42	9	16
RALA	0.022	0.004	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.016	0.045	0.32	1	-0.32	4	5

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.027	0.029	-10000	0	-10000	0	0
DAPP1	0.014	0.087	0.24	12	-0.33	10	22
Src family/SYK family/BLNK-LAT/BTK-ITK	0.01	0.11	0.3	5	-0.45	13	18
mol:DAG	0.003	0.062	0.26	11	-0.19	2	13
HRAS	0.022	0.007	-10000	0	-10000	0	0
RAP1A	0.024	0.005	-10000	0	-10000	0	0
ARF5/GDP	0.006	0.074	0.2	4	-0.24	25	29
PLCG2	0.019	0.017	-10000	0	-0.32	1	1
PLCG1	0.022	0.005	-10000	0	-10000	0	0
ARF5	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	-0.022	0.026	0.14	11	-10000	0	11
ARF1/GTP	-0.013	0.025	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
YES1	0.022	0.005	-10000	0	-10000	0	0
RAP1A/GTP	-0.022	0.028	0.15	11	-10000	0	11
ADAP1	-0.024	0.026	0.14	2	-10000	0	2
ARAP3	-0.022	0.026	0.14	11	-10000	0	11
INPPL1	0.022	0.003	-10000	0	-10000	0	0
PREX1	0.022	0.005	-10000	0	-10000	0	0
ARHGEF6	0.014	0.054	-10000	0	-0.32	13	13
ARHGEF7	0.021	0.006	-10000	0	-10000	0	0
ARF1	0.019	0.009	-10000	0	-10000	0	0
NRAS	0.023	0.005	-10000	0	-10000	0	0
FYN	0.022	0.003	-10000	0	-10000	0	0
ARF6	0.022	0.003	-10000	0	-10000	0	0
FGR	0.014	0.052	-10000	0	-0.32	12	12
mol:Ca2+	0.005	0.052	0.2	22	-10000	0	22
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.013	0.056	-10000	0	-0.32	14	14
ZAP70	0.03	0.056	0.32	15	-0.32	2	17
mol:IP3	0.003	0.063	0.23	24	-0.14	2	26
LYN	0.021	0.007	-10000	0	-10000	0	0
ARF1/GDP	0.003	0.071	0.19	2	-0.23	25	27
RhoA/GDP	-0.018	0.045	0.21	4	-0.21	1	5
PDK1/Src/Hsp90	0.041	0.015	-10000	0	-10000	0	0
BLNK	0.021	0.021	0.32	1	-0.32	1	2
actin cytoskeleton reorganization	-0.006	0.066	0.27	8	-0.28	6	14
SRC	0.022	0.005	-10000	0	-10000	0	0
PLEKHA2	-0.016	0.01	-10000	0	-0.19	1	1
RAC1	0.022	0.005	-10000	0	-10000	0	0
PTEN	0.022	0.01	-10000	0	-10000	0	0
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
ARF6/GTP	-0.027	0.03	-10000	0	-10000	0	0
RhoA/GTP	-0.024	0.026	-10000	0	-10000	0	0
Src family/SYK family/BLNK-LAT	0.016	0.067	0.23	5	-0.28	9	14
BLK	0.043	0.083	0.32	40	-10000	0	40
PDPK1	0.022	0.005	-10000	0	-10000	0	0
CYTH1	-0.024	0.026	0.14	1	-10000	0	1
HCK	0.022	0.015	0.32	1	-10000	0	1
CYTH3	-0.024	0.026	0.14	2	-10000	0	2
CYTH2	-0.024	0.026	0.14	2	-10000	0	2
KRAS	0.022	0.006	-10000	0	-10000	0	0
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	0.001	0.04	-10000	0	-0.37	3	3
SGK1	0.008	0.042	-10000	0	-0.39	3	3
INPP5D	0.022	0.016	-10000	0	-0.32	1	1
mol:GDP	-0.006	0.074	0.19	5	-0.25	26	31
SOS1	0.022	0.004	-10000	0	-10000	0	0
SYK	0.022	0.015	0.32	1	-10000	0	1
ARF6/GDP	-0.02	0.042	0.2	4	-0.2	2	6
mol:PI-3-4-5-P3	-0.022	0.025	0.15	1	-10000	0	1
ARAP3/RAP1A/GTP	-0.022	0.028	0.15	11	-10000	0	11
VAV1	0.024	0.034	0.32	5	-0.32	1	6
mol:PI-3-4-P2	-0.015	0.01	-10000	0	-0.22	1	1
RAS family/GTP/PI3K Class I	0.031	0.026	0.19	3	-10000	0	3
PLEKHA1	-0.017	0.009	-10000	0	-0.19	1	1
Rac1/GDP	0.006	0.074	0.2	4	-0.24	26	30
LAT	0.022	0.005	-10000	0	-10000	0	0
Rac1/GTP	-0.004	0.081	0.18	1	-0.28	31	32
ITK	-0.028	0.032	-10000	0	-0.16	10	10
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.001	0.068	0.26	8	-0.24	3	11
LCK	0.024	0.031	0.32	4	-0.32	1	5
BTK	-0.026	0.028	0.14	2	-0.16	4	6

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.02	0.025	-10000	0	-0.51	1	1
VEGFR1 homodimer/NRP1	-0.01	0.022	-10000	0	-0.5	1	1
mol:DAG	-0.016	0.027	0.18	3	-0.47	1	4
VEGFR1 homodimer/NRP1/VEGFR 121	0.019	0.023	-10000	0	-0.47	1	1
CaM/Ca2+	-0.02	0.025	-10000	0	-0.45	1	1
HIF1A	0.025	0.015	-10000	0	-0.3	1	1
GAB1	0.019	0.03	-10000	0	-0.32	4	4
AKT1	-0.007	0.054	0.47	1	-0.29	1	2
PLCG1	-0.016	0.027	0.18	3	-0.47	1	4
NOS3	0.006	0.054	0.43	2	-0.45	2	4
CBL	0.022	0.005	-10000	0	-10000	0	0
mol:NO	0.011	0.069	0.39	6	-0.44	2	8
FLT1	-0.013	0.026	-10000	0	-0.58	1	1
PGF	0.023	0.014	0.32	1	-10000	0	1
VEGFR1 homodimer/NRP2/VEGFR121	0.023	0.05	-10000	0	-0.47	1	1
CALM1	0.022	0.004	-10000	0	-10000	0	0
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
eNOS/Hsp90	0.02	0.06	0.39	1	-0.42	2	3
endothelial cell proliferation	-0.014	0.063	0.32	3	-0.32	4	7
mol:Ca2+	-0.016	0.026	0.18	3	-0.46	1	4
MAPK3	-0.025	0.047	0.34	4	-0.26	1	5
MAPK1	-0.025	0.048	0.3	5	-0.26	1	6
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
PLGF homodimer	0.023	0.014	0.32	1	-10000	0	1
PRKACA	0.022	0.005	-10000	0	-10000	0	0
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	-0.049	0.14	-10000	0	-0.32	105	105
VEGFA homodimer	0.022	0.004	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	0.02	0.025	-10000	0	-0.51	1	1
platelet activating factor biosynthetic process	-0.027	0.045	0.32	4	-0.25	1	5
PI3K	0.038	0.032	-10000	0	-0.28	1	1
PRKCA	-0.025	0.037	0.17	3	-0.27	1	4
PRKCB	-0.025	0.042	0.17	3	-0.57	1	4
VEGFR1 homodimer/PLGF homodimer	0.021	0.026	0.22	1	-0.51	1	2
VEGFA	0.022	0.004	-10000	0	-10000	0	0
VEGFB	0.022	0.004	-10000	0	-10000	0	0
mol:IP3	-0.016	0.027	0.18	3	-0.47	1	4
RASA1	-0.018	0.033	0.18	5	-0.47	1	6
NRP2	0.006	0.074	-10000	0	-0.32	25	25
VEGFR1 homodimer	-0.013	0.025	-10000	0	-0.58	1	1
VEGFB homodimer	0.022	0.004	-10000	0	-10000	0	0
NCK1	0.021	0.022	-10000	0	-0.32	2	2
eNOS/Caveolin-1	-0.008	0.092	0.44	4	-0.36	5	9
PTPN11	0.023	0.003	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.037	0.032	-10000	0	-0.28	1	1
mol:L-citrulline	0.011	0.069	0.39	6	-0.44	2	8
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.043	0.028	-10000	0	-0.45	1	1
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.031	0.023	-10000	0	-0.29	1	1
CD2AP	0.022	0.003	-10000	0	-10000	0	0
PI3K/GAB1	0.046	0.038	-10000	0	-0.27	1	1
PDPK1	-0.009	0.056	0.33	1	-0.26	1	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.032	0.025	-10000	0	-0.47	1	1
mol:NADP	0.011	0.069	0.39	6	-0.44	2	8
HSP90AA1	0.022	0.004	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.041	0.028	-10000	0	-0.45	1	1
VEGFR1 homodimer/NRP2	0.011	0.051	-10000	0	-0.2	22	22

Arf6 downstream 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
PLAUR	0.012	0.031	0.32	4	-10000	0	4
regulation of axonogenesis	-0.002	0.021	0.24	3	-10000	0	3
myoblast fusion	-0.019	0.029	-10000	0	-0.19	4	4
mol:GTP	0.017	0.024	-10000	0	-0.16	7	7
regulation of calcium-dependent cell-cell adhesion	-0.036	0.043	0.17	13	-10000	0	13
ARF1/GTP	0.024	0.024	-10000	0	-10000	0	0
mol:GM1	0.006	0.017	-10000	0	-10000	0	0
mol:Choline	-0.008	0.014	-10000	0	-0.17	1	1
lamellipodium assembly	0.006	0.051	-10000	0	-0.36	7	7
MAPK3	0.015	0.023	0.21	4	-10000	0	4
ARF6/GTP/NME1/Tiam1	0.036	0.044	0.19	4	-0.18	13	17
ARF1	0.019	0.009	-10000	0	-10000	0	0
ARF6/GDP	0.019	0.029	0.19	4	-10000	0	4
ARF1/GDP	0.017	0.039	-10000	0	-0.22	7	7
ARF6	0.03	0.01	-10000	0	-10000	0	0
RAB11A	0.022	0.005	-10000	0	-10000	0	0
TIAM1	0.011	0.057	-10000	0	-0.32	14	14
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.014	0.024	0.21	4	-10000	0	4
actin filament bundle formation	-0.024	0.037	0.22	6	-10000	0	6
KALRN	0.008	0.024	0.15	4	-0.16	4	8
RAB11FIP3/RAB11A	0.031	0.009	-10000	0	-10000	0	0
RhoA/GDP	0.024	0.038	-10000	0	-0.22	6	6
NME1	0.02	0.01	-10000	0	-10000	0	0
Rac1/GDP	0.025	0.04	-10000	0	-0.22	7	7
substrate adhesion-dependent cell spreading	0.017	0.024	-10000	0	-0.16	7	7
cortical actin cytoskeleton organization	0.006	0.051	-10000	0	-0.37	7	7
RAC1	0.022	0.005	-10000	0	-10000	0	0
liver development	0.017	0.024	-10000	0	-0.16	7	7
ARF6/GTP	0.017	0.024	-10000	0	-0.16	7	7
RhoA/GTP	0.028	0.022	-10000	0	-10000	0	0
mol:GDP	0.008	0.033	0.2	4	-0.23	6	10
ARF6/GTP/RAB11FIP3/RAB11A	0.041	0.021	-10000	0	-10000	0	0
RHOA	0.022	0.005	-10000	0	-10000	0	0
PLD1	0.011	0.018	-10000	0	-10000	0	0
RAB11FIP3	0.022	0.005	-10000	0	-10000	0	0
tube morphogenesis	0.006	0.051	-10000	0	-0.36	7	7
ruffle organization	0.002	0.021	-10000	0	-0.24	3	3
regulation of epithelial cell migration	0.017	0.024	-10000	0	-0.16	7	7
PLD2	0.012	0.018	-10000	0	-0.19	1	1
PIP5K1A	0.002	0.021	-10000	0	-0.25	3	3
mol:Phosphatidic acid	-0.008	0.014	-10000	0	-0.17	1	1
Rac1/GTP	0.006	0.052	-10000	0	-0.37	7	7

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.054	0.07	-10000	0	-0.23	4	4
Ran/GTP/Exportin 1/HDAC1	-0.016	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.028	0.06	-10000	0	-0.26	7	7
SUMO1	0.023	0.003	-10000	0	-10000	0	0
ZFPM1	0.019	0.017	-10000	0	-0.32	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.003	-10000	0	-10000	0	0
FKBP3	0.022	0.004	-10000	0	-10000	0	0
Histones	0.054	0.037	-10000	0	-10000	0	0
YY1/LSF	0.005	0.069	-10000	0	-0.24	25	25
SMG5	0.018	0.009	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	0.024	0.03	0.18	3	-0.18	1	4
I kappa B alpha/HDAC1	0.031	0.033	-10000	0	-10000	0	0
SAP18	0.022	0.005	-10000	0	-10000	0	0
RELA	0.024	0.035	0.24	2	-10000	0	2
HDAC1/Smad7	0.042	0.017	-10000	0	-0.19	1	1
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
HDAC3/TR2	0.031	0.036	-10000	0	-10000	0	0
NuRD/MBD3 Complex	0.023	0.043	-10000	0	-0.31	2	2
NF kappa B1 p50/RelA	0.021	0.068	0.23	1	-0.28	14	15
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.008	0.096	-10000	0	-0.32	44	44
GATA1	0.019	0.004	-10000	0	-10000	0	0
Mad/Max	0.032	0.007	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.011	0.075	-10000	0	-0.3	15	15
RBBP7	0.022	0.003	-10000	0	-10000	0	0
NPC	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.021	0.022	-10000	0	-0.32	2	2
MAX	0.022	0.004	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.022	0.004	-10000	0	-10000	0	0
NFKBIA	0.02	0.022	-10000	0	-10000	0	0
KAT2B	0.016	0.045	-10000	0	-0.32	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.008	0.028	-10000	0	-10000	0	0
SIN3 complex	0.051	0.021	-10000	0	-10000	0	0
SMURF1	0.022	0.004	-10000	0	-10000	0	0
CHD3	0.021	0.006	-10000	0	-10000	0	0
SAP30	0.022	0.005	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.021	0.007	-10000	0	-10000	0	0
YY1/HDAC3	0.011	0.056	-10000	0	-0.31	6	6
YY1/HDAC2	0.006	0.065	-10000	0	-0.23	25	25
YY1/HDAC1	0.009	0.062	-10000	0	-0.23	23	23
NuRD/MBD2 Complex (MeCP1)	0.023	0.044	-10000	0	-0.31	2	2
PPARG	0.009	0.066	0.23	1	-0.24	24	25
HDAC8/hEST1B	0.035	0.02	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-10000	0	-10000	0	0
TNFRSF1A	0.022	0.004	-10000	0	-10000	0	0
HDAC3/SMRT (N-CoR2)	0.031	0.035	-10000	0	-10000	0	0
MBD3L2	0.017	0.005	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.017	-10000	0	-0.19	1	1
CREBBP	0.022	0.005	-10000	0	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0.016	0.07	-10000	0	-0.3	13	13
HDAC1	0.022	0.004	-10000	0	-10000	0	0
HDAC3	0.02	0.023	-10000	0	-10000	0	0
HDAC2	0.022	0.003	-10000	0	-10000	0	0
YY1	0.007	0.024	-10000	0	-0.21	6	6
HDAC8	0.023	0.002	-10000	0	-10000	0	0
SMAD7	0.021	0.016	-10000	0	-0.32	1	1
NCOR2	0.022	0.003	-10000	0	-10000	0	0
MXD1	0.022	0.004	-10000	0	-10000	0	0
STAT3	0.012	0.005	-10000	0	-10000	0	0
NFKB1	0.021	0.016	-10000	0	-0.32	1	1
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
YY1/LSF/HDAC1	0.019	0.066	-10000	0	-0.23	18	18
YY1/SAP30/HDAC1	0.021	0.062	-10000	0	-0.22	15	15
EP300	0.021	0.006	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.012	0.005	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.022	-10000	0	-10000	0	0
histone deacetylation	0.023	0.043	-10000	0	-0.31	2	2
STAT3 (dimer non-phopshorylated)/HDAC3	0.019	0.032	-10000	0	-0.25	1	1
nuclear export	-0.034	0.02	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GATAD2B	0.018	0.009	-10000	0	-10000	0	0
GATAD2A	0.022	0.005	-10000	0	-10000	0	0
GATA2/HDAC3	0.015	0.061	-10000	0	-0.26	3	3
GATA1/HDAC1	0.03	0.008	-10000	0	-10000	0	0
GATA1/HDAC3	0.028	0.035	-10000	0	-10000	0	0
CHD4	0.022	0.004	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	0.05	0.06	0.24	46	-0.22	1	47
SIN3/HDAC complex/Mad/Max	0.013	0.05	-10000	0	-0.32	5	5
NuRD Complex	0.018	0.067	-10000	0	-0.3	11	11
positive regulation of chromatin silencing	0.052	0.036	-10000	0	-10000	0	0
SIN3B	0.021	0.006	-10000	0	-10000	0	0
MTA2	0.022	0.003	-10000	0	-10000	0	0
SIN3A	0.022	0.005	-10000	0	-10000	0	0
XPO1	0.022	0.003	-10000	0	-10000	0	0
SUMO1/HDAC1	0.023	0.043	-10000	0	-0.19	10	10
HDAC complex	0.054	0.021	-10000	0	-0.18	2	2
GATA1/Fog1	0.027	0.016	-10000	0	-0.22	1	1
FKBP25/HDAC1/HDAC2	0.044	0.012	-10000	0	-10000	0	0
TNF	0.049	0.091	0.32	47	-0.32	2	49
negative regulation of cell growth	0.013	0.049	-10000	0	-0.32	5	5
NuRD/MBD2/PRMT5 Complex	0.023	0.044	-10000	0	-0.31	2	2
Ran/GTP/Exportin 1	0.023	0.043	-10000	0	-0.18	10	10
NF kappa B/RelA/I kappa B alpha	0.016	0.055	0.21	1	-0.26	9	10
SIN3/HDAC complex/NCoR1	0.002	0.067	-10000	0	-0.39	9	9
TFCP2	0.019	0.034	-10000	0	-0.32	5	5
NR2C1	0.023	0.002	-10000	0	-10000	0	0
MBD3	0.021	0.006	-10000	0	-10000	0	0
MBD2	0.022	0.004	-10000	0	-10000	0	0

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.022	0.005	-10000	0	-10000	0	0
Rac1/GDP	0.021	0.013	-10000	0	-10000	0	0
DOCK1	0.018	0.037	-10000	0	-0.32	6	6
ITGA4	0.022	0.025	0.32	1	-0.32	2	3
RAC1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta7 Integrin	0.033	0.018	0.24	2	-0.22	1	3
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.021	0.006	-10000	0	-10000	0	0
alpha4/beta1 Integrin	0.041	0.022	0.23	1	-0.19	2	3
alpha4/beta7 Integrin/Paxillin	0.032	0.018	0.21	2	-0.18	1	3
lamellipodium assembly	-0.007	0.094	-10000	0	-0.4	22	22
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
PI3K	0.027	0.028	-10000	0	-0.22	5	5
ARF6	0.022	0.003	-10000	0	-10000	0	0
TLN1	0.022	0.005	-10000	0	-10000	0	0
PXN	-0.014	0.004	-10000	0	-10000	0	0
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
ARF6/GTP	0.039	0.023	-10000	0	-0.16	2	2
cell adhesion	0.039	0.023	0.21	1	-0.17	2	3
CRKL/CBL	0.031	0.009	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.03	0.019	0.21	1	-0.18	2	3
ITGB1	0.022	0.004	-10000	0	-10000	0	0
ITGB7	0.023	0.014	0.32	1	-10000	0	1
ARF6/GDP	0.021	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	0.028	0.057	0.22	1	-0.18	32	33
p130Cas/Crk/Dock1	0.035	0.031	-10000	0	-0.19	6	6
VCAM1	-0.004	0.092	-10000	0	-0.32	40	40
alpha4/beta1 Integrin/Paxillin/Talin	0.04	0.023	0.22	1	-0.17	2	3
alpha4/beta1 Integrin/Paxillin/GIT1	0.041	0.023	0.22	1	-0.17	2	3
BCAR1	0.02	0.008	-10000	0	-10000	0	0
mol:GDP	-0.039	0.023	0.17	2	-0.21	1	3
CBL	0.022	0.005	-10000	0	-10000	0	0
PRKACA	0.022	0.005	-10000	0	-10000	0	0
GIT1	0.022	0.005	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.04	0.023	0.22	1	-0.17	2	3
Rac1/GTP	-0.012	0.1	-10000	0	-0.44	22	22

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.021	0.016	-10000	0	-0.32	1	1
PLK4	0.025	0.03	0.32	5	-10000	0	5
regulation of centriole replication	-0.013	0.019	0.16	4	-0.22	1	5

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.019	0.022	-10000	0	-0.32	2	2
positive regulation of NF-kappaB transcription factor activity	0.022	0.037	-10000	0	-0.22	10	10
MAP2K4	0.002	0.04	0.22	1	-0.23	6	7
IKBKB	0.02	0.007	-10000	0	-10000	0	0
TNFRSF10B	0.02	0.008	-10000	0	-10000	0	0
TNFRSF10A	0.02	0.008	-10000	0	-10000	0	0
SMPD1	0.007	0.013	0.14	3	-0.14	1	4
IKBKG	0.023	0.003	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.013	0.048	-10000	0	-0.32	10	10
TRAIL/TRAILR2	0.026	0.018	-10000	0	-0.22	1	1
TRAIL/TRAILR3	0.025	0.024	-10000	0	-0.22	3	3
TRAIL/TRAILR1	0.026	0.018	-10000	0	-0.22	1	1
TRAIL/TRAILR4	0.022	0.037	-10000	0	-0.22	10	10
TRAIL/TRAILR1/DAP3/GTP	0.027	0.023	-10000	0	-0.17	1	1
IKK complex	0.009	0.033	-10000	0	-10000	0	0
RIPK1	0.022	0.004	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.014	0.007	-10000	0	-10000	0	0
MAPK3	-0.012	0.027	0.28	3	-0.22	2	5
MAP3K1	0.009	0.04	0.24	1	-0.23	5	6
TRAILR4 (trimer)	0.013	0.048	-10000	0	-0.32	10	10
TRADD	0.02	0.008	-10000	0	-10000	0	0
TRAILR1 (trimer)	0.02	0.008	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.011	0.026	-10000	0	-0.17	8	8
CFLAR	0.023	0.003	-10000	0	-10000	0	0
MAPK1	-0.013	0.023	0.28	2	-0.22	2	4
TRAIL/TRAILR1/FADD/TRADD/RIP	0.049	0.034	-10000	0	-0.17	1	1
mol:ceramide	0.007	0.013	0.14	3	-0.14	1	4
FADD	0.022	0.004	-10000	0	-10000	0	0
MAPK8	0.003	0.055	0.19	8	-0.22	5	13
TRAF2	0.021	0.006	-10000	0	-10000	0	0
TRAILR3 (trimer)	0.018	0.023	-10000	0	-0.32	2	2
CHUK	0.022	0.005	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	0.035	0.022	-10000	0	-0.19	1	1
DAP3	0.018	0.009	-10000	0	-10000	0	0
CASP10	0.007	0.058	0.21	14	-0.45	1	15
JNK cascade	0.022	0.037	-10000	0	-0.22	10	10
TRAIL (trimer)	0.019	0.022	-10000	0	-0.32	2	2
TNFRSF10C	0.018	0.023	-10000	0	-0.32	2	2
TRAIL/TRAILR1/DAP3/GTP/FADD	0.033	0.029	-10000	0	-0.16	1	1
TRAIL/TRAILR2/FADD	0.035	0.022	-10000	0	-0.19	1	1
cell death	0.007	0.013	0.14	3	-0.14	1	4
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.011	0.026	-10000	0	-0.17	8	8
TRAILR2 (trimer)	0.02	0.008	-10000	0	-10000	0	0
CASP8	0.012	0.039	-10000	0	-0.54	2	2
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.049	0.034	-10000	0	-0.17	1	1

Arf1 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
coatomer protein complex	0.005	0.031	0.15	21	-10000	0	21
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.026	0.056	0.14	76	-0.18	6	82
AP2	0.03	0.011	-10000	0	-10000	0	0
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.025	0.014	-10000	0	-10000	0	0
CLTB	0.022	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.01	0.007	-10000	0	-10000	0	0
CD4	0.023	0.014	0.32	1	-10000	0	1
CLTA	0.022	0.005	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-10000	0	0
ARFGAP1	-0.007	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.002	0.01	-10000	0	-0.13	1	1
ARF1/GTP	0.021	0.016	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.003	0.003	-10000	0	-10000	0	0
mol:Choline	-0.001	0.01	-10000	0	-0.14	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.021	0.011	-10000	0	-10000	0	0
DDEF1	0	0.01	-10000	0	-0.14	1	1
ARF1/GDP	0.001	0.016	-10000	0	-0.091	10	10
AP2M1	0.021	0.007	-10000	0	-10000	0	0
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.006	0.011	-10000	0	-10000	0	0
Rac/GTP	0.019	0.008	-10000	0	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0.024	0.015	-10000	0	-10000	0	0
ARFIP2	0.009	0.021	-10000	0	-10000	0	0
COPA	0.019	0.009	-10000	0	-10000	0	0
RAC1	0.022	0.005	-10000	0	-10000	0	0
ARF1/GTP/coatomer protein complex	0.008	0.028	-10000	0	-0.23	1	1
ARF1/GTP/ARHGAP10	0.013	0.008	-10000	0	-10000	0	0
GGA3	0.022	0.006	-10000	0	-10000	0	0
ARF1/GTP/Membrin	0.006	0.047	-10000	0	-0.21	20	20
AP2A1	0.022	0.004	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.005	0.022	-10000	0	-0.18	6	6
ARF1/GDP/Membrin	0.007	0.057	-10000	0	-0.24	23	23
Arfaptin 2/Rac/GDP	0.019	0.021	-10000	0	-10000	0	0
CYTH2	0.027	0.01	-10000	0	-10000	0	0
ARF1/GTP/GGA3	0.025	0.014	-10000	0	-10000	0	0
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.016	0.003	-10000	0	-10000	0	0
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.009	0.021	-10000	0	-0.17	1	1
PLD2	-0.001	0.01	-10000	0	-0.14	1	1
ARF-GAP1/v-SNARE	-0.007	0.002	-10000	0	-10000	0	0
PIP5K1A	0.002	0.01	-10000	0	-0.13	1	1
ARF1/GTP/Membrin/GBF1/p115	0.01	0.022	-10000	0	-0.12	3	3
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	-0.001	0.01	-10000	0	-0.14	1	1
KDEL Receptor/Ligand/ARF-GAP1	-0.007	0.002	-10000	0	-10000	0	0
GOSR2	0.005	0.026	-10000	0	-0.32	3	3
USO1	0.004	0.03	-10000	0	-0.32	4	4
GBF1	0.004	0.032	-10000	0	-0.35	4	4
ARF1/GTP/Arfaptin 2	0.025	0.015	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.04	0.018	0.23	1	-10000	0	1

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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
SMAD4	0.022	0.004	-10000	0	-10000	0	0
SMAD2	0	0.044	0.22	6	-0.26	4	10
SMAD3	0.006	0.03	-10000	0	-0.24	1	1
SMAD3/SMAD4	0.014	0.094	-10000	0	-0.49	15	15
SMAD4/Ubc9/PIASy	0.041	0.016	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.041	0.052	0.25	3	-0.25	2	5
PPM1A	0.022	0.004	-10000	0	-10000	0	0
CALM1	0.022	0.004	-10000	0	-10000	0	0
SMAD2/SMAD4	0.012	0.042	0.22	3	-0.24	5	8
MAP3K1	0.022	0.005	-10000	0	-10000	0	0
TRAP-1/SMAD4	0.029	0.032	-10000	0	-0.22	8	8
MAPK3	0.022	0.005	-10000	0	-10000	0	0
MAPK1	0.022	0.005	-10000	0	-10000	0	0
NUP214	0.021	0.006	-10000	0	-10000	0	0
CTDSP1	0.022	0.003	-10000	0	-10000	0	0
CTDSP2	0.023	0.001	-10000	0	-10000	0	0
CTDSPL	0.022	0.004	-10000	0	-10000	0	0
KPNB1	0.022	0.005	-10000	0	-10000	0	0
TGFBRAP1	0.017	0.043	-10000	0	-0.32	8	8
UBE2I	0.022	0.005	-10000	0	-10000	0	0
NUP153	0.021	0.016	-10000	0	-0.32	1	1
KPNA2	0.026	0.036	0.32	7	-10000	0	7
PIAS4	0.021	0.006	-10000	0	-10000	0	0

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.022	0.004	-10000	0	-10000	0	0
ITGB7	0.023	0.014	0.32	1	-10000	0	1
ITGA4	0.022	0.025	0.32	1	-0.32	2	3
alpha4/beta7 Integrin	0.033	0.018	0.24	2	-0.22	1	3
alpha4/beta1 Integrin	0.032	0.02	0.24	1	-0.22	2	3

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.022	0.004	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	-0.019	0.01	-10000	0	-10000	0	0
MDM2/SUMO1	0.021	0.046	-10000	0	-0.19	11	11
HDAC4	0.022	0.003	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	-0.018	0.01	-10000	0	-10000	0	0
SUMO1	0.023	0.003	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1	0.006	0.014	-10000	0	-0.27	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.004	0.021	-10000	0	-10000	0	0
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.023	0.003	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.023	0.002	-10000	0	-10000	0	0
SUMO1/HDAC4	0.022	0.045	-10000	0	-0.19	11	11
SUMO1/HDAC1	0.023	0.043	-10000	0	-0.19	10	10
RANGAP1	0.021	0.006	-10000	0	-10000	0	0
MDM2/SUMO1/SUMO1	0.053	0.018	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.007	0.003	-10000	0	-10000	0	0
Ran/GTP	0.012	0.04	-10000	0	-0.18	11	11
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.023	0.003	-10000	0	-10000	0	0
UBE2I	0.022	0.005	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.011	0.044	0.19	7	-0.18	10	17
NPC	0.013	0.001	-10000	0	-10000	0	0
PIAS2	0.022	0.005	-10000	0	-10000	0	0
PIAS1	0.022	0.005	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.038	0.028	0.23	1	-0.27	2	3
E-cadherin/beta catenin	0.029	0.022	0.24	1	-0.22	2	3
CTNNB1	0.022	0.004	-10000	0	-10000	0	0
JUP	0.021	0.016	-10000	0	-0.32	1	1
CDH1	0.019	0.026	0.32	1	-0.32	2	3

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.033	0.012	0.24	1	-10000	0	1
FBXW11	0.022	0.004	-10000	0	-10000	0	0
NF kappa B1 p50/c-Rel	0.018	0.012	-10000	0	-0.19	1	1
NF kappa B1 p50/RelA/I kappa B alpha	0.018	0.037	0.18	5	-0.22	2	7
NFKBIA	0.01	0.023	-10000	0	-10000	0	0
MAPK14	0.022	0.004	-10000	0	-10000	0	0
NF kappa B1 p105/p50	0.018	0.012	-10000	0	-0.19	1	1
ARRB2	0.008	0.003	-10000	0	-10000	0	0
REL	0.022	0.003	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.018	0.015	0.22	1	-0.19	1	2
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.018	0.012	-10000	0	-0.19	1	1
PIK3CA	0.02	0.017	-10000	0	-0.32	1	1
NF kappa B1 p50 dimer	-0.012	0.017	0.24	1	-0.22	1	2
PIK3R1	0.019	0.031	-10000	0	-0.32	4	4
NFKB1	-0.014	0.011	-10000	0	-0.22	1	1
RELA	0.023	0.003	-10000	0	-10000	0	0
positive regulation of anti-apoptosis	0.013	0.035	-10000	0	-0.23	4	4
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.017	0.037	-10000	0	-0.2	2	2
SRC	0.022	0.005	-10000	0	-10000	0	0
PI3K	0.027	0.028	-10000	0	-0.22	5	5
NF kappa B1 p50/RelA	0.014	0.033	-10000	0	-0.25	2	2
IKBKB	0.02	0.007	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-10000	0	-10000	0	0
SYK	0.022	0.015	0.32	1	-10000	0	1
I kappa B alpha/PIK3R1	0.021	0.041	0.19	7	-0.19	5	12
cell death	0.017	0.036	-10000	0	-0.19	2	2
NF kappa B1 p105/c-Rel	0.018	0.012	-10000	0	-0.19	1	1
LCK	0.024	0.031	0.32	4	-0.32	1	5
BCL3	0.023	0.014	0.32	1	-10000	0	1

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.035	0.022	-10000	0	-10000	0	0
CLOCK	0.023	0.004	-10000	0	-10000	0	0
TIMELESS/CRY2	0.026	0.023	-10000	0	-10000	0	0
DEC1/BMAL1	0.027	0.015	-10000	0	-0.22	1	1
ATR	0.022	0.005	-10000	0	-10000	0	0
NR1D1	0.009	0.014	-10000	0	-10000	0	0
ARNTL	0.022	0.016	-10000	0	-0.32	1	1
TIMELESS	0.01	0.023	0.41	1	-10000	0	1
NPAS2	0.02	0.034	-10000	0	-0.32	5	5
CRY2	0.022	0.005	-10000	0	-10000	0	0
mol:CO	-0.004	0.007	-10000	0	-0.12	2	2
CHEK1	0.022	0.005	-10000	0	-10000	0	0
mol:HEME	0.004	0.007	0.12	2	-10000	0	2
PER1	0.021	0.007	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.046	0.028	-10000	0	-0.19	5	5
BMAL1/CLOCK	0.008	0.055	-10000	0	-10000	0	0
S phase of mitotic cell cycle	0.035	0.022	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	0.036	0.022	-10000	0	-10000	0	0
mol:NADPH	0.004	0.007	0.12	2	-10000	0	2
PER1/TIMELESS	0.024	0.022	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.016	0.005	-10000	0	-10000	0	0

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.031	0.01	-9999	-10000	0	0
FBXW11	0.022	0.004	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.022	0.004	-9999	-10000	0	0
CHUK	0.022	0.005	-9999	-10000	0	0
NF kappa B2 p100/RelB	0.058	0.024	-9999	-10000	0	0
NFKB1	0.021	0.016	-9999	-0.32	1	1
MAP3K14	0.022	0.005	-9999	-10000	0	0
NF kappa B1 p50/RelB	0.031	0.014	-9999	-0.22	1	1
RELB	0.022	0.004	-9999	-10000	0	0
NFKB2	0.022	0.006	-9999	-10000	0	0
NF kappa B2 p52/RelB	0.028	0.009	-9999	-10000	0	0
regulation of B cell activation	0.028	0.009	-9999	-10000	0	0

pid_entity	TCGA.SL.A6JA	TCGA.SL.A6J9	TCGA.QS.A5YR	TCGA.QS.A5YQ
109_MAP3K5	0.013	0.013	0.013	-0.14
47_PPARGC1A	-0.32	-0.32	0.023	0.023
105_BMP4	0.023	-0.32	0.023	0.023
105_BMP6	0.023	0.023	0.023	0.023
105_BMP7	0.023	0	0.023	0.023
105_BMP2	0.023	-0.32	0.023	0.023
131_RELN/VLDLR	-0.18	0	0.059	0.059
30_TGFB1/TGF beta receptor Type II	-0.022	0.023	-0.023	0.023
84_STAT5B	-0.032	-0.062	0.02	-0.025
84_STAT5A	-0.032	-0.062	0.02	-0.025