PARADIGM pathway analysis of mRNASeq expression data

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	173
IL23-mediated signaling events	161
FOXM1 transcription factor network	138
Ephrin A reverse signaling	132
Syndecan-1-mediated signaling events	123
Aurora B signaling	123
IL12-mediated signaling events	104
IL4-mediated signaling events	99
Effects of Botulinum toxin	93
Glypican 2 network	93

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
TCGA08_retinoblastoma	0.2586	173	1384	8	-0.15	0.11	1000	-1000	-0.026	-1000
IL23-mediated signaling events	0.2407	161	9716	60	-0.7	0.015	1000	-1000	-0.15	-1000
FOXM1 transcription factor network	0.2063	138	7068	51	-0.46	0.032	1000	-1000	-0.17	-1000
Ephrin A reverse signaling	0.1973	132	928	7	-0.12	0	1000	-1000	-0.035	-1000
Syndecan-1-mediated signaling events	0.1839	123	4201	34	-0.32	0.015	1000	-1000	-0.073	-1000
Aurora B signaling	0.1839	123	8287	67	-0.39	0.015	1000	-1000	-0.072	-1000
IL12-mediated signaling events	0.1555	104	9117	87	-0.51	0.1	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.1480	99	9055	91	-0.72	0.5	1000	-1000	-0.14	-1000
Effects of Botulinum toxin	0.1390	93	2420	26	-0.2	0.015	1000	-1000	-0.065	-1000
Glypican 2 network	0.1390	93	375	4	-0.085	-0.021	1000	-1000	-0.031	-1000
Syndecan-4-mediated signaling events	0.1360	91	6135	67	-0.27	0.048	1000	-1000	-0.097	-1000
Signaling events mediated by the Hedgehog family	0.1345	90	4703	52	-0.2	0.15	1000	-1000	-0.073	-1000
TCR signaling in naïve CD8+ T cells	0.1300	87	8175	93	-0.25	0.064	1000	-1000	-0.084	-1000
E-cadherin signaling events	0.1241	83	419	5	-0.11	0.015	1000	-1000	-0.051	-1000
HIF-1-alpha transcription factor network	0.1166	78	5976	76	-0.28	0.082	1000	-1000	-0.092	-1000
Signaling events regulated by Ret tyrosine kinase	0.1166	78	6475	82	-0.26	0.015	1000	-1000	-0.088	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.1166	78	5341	68	-0.43	0.16	1000	-1000	-0.13	-1000
a4b1 and a4b7 Integrin signaling	0.1076	72	363	5	-0.089	-0.027	1000	-1000	-0.038	-1000
Glypican 1 network	0.1046	70	3370	48	-0.22	0.034	1000	-1000	-0.05	-1000
amb2 Integrin signaling	0.1031	69	5703	82	-0.25	0.015	1000	-1000	-0.079	-1000
Reelin signaling pathway	0.1031	69	3897	56	-0.31	0.015	1000	-1000	-0.087	-1000
Aurora C signaling	0.1016	68	479	7	-0.18	0	1000	-1000	-0.048	-1000
Endothelins	0.1016	68	6568	96	-0.25	0.015	1000	-1000	-0.079	-1000
Osteopontin-mediated events	0.1001	67	2559	38	-0.22	0.016	1000	-1000	-0.11	-1000
Thromboxane A2 receptor signaling	0.1001	67	7104	105	-0.2	0.052	1000	-1000	-0.068	-1000
PLK1 signaling events	0.0942	63	5419	85	-0.23	0.054	1000	-1000	-0.051	-1000
Signaling mediated by p38-alpha and p38-beta	0.0942	63	2814	44	-0.15	0.015	1000	-1000	-0.055	-1000
TCGA08_p53	0.0927	62	440	7	-0.12	0.062	1000	-1000	-0.016	-1000
Caspase cascade in apoptosis	0.0912	61	4543	74	-0.17	0.05	1000	-1000	-0.06	-1000
Visual signal transduction: Cones	0.0897	60	2289	38	-0.18	0.018	1000	-1000	-0.063	-1000
Arf6 signaling events	0.0882	59	3712	62	-0.24	0.015	1000	-1000	-0.06	-1000
p75(NTR)-mediated signaling	0.0852	57	7159	125	-0.22	0.015	1000	-1000	-0.098	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0822	55	4756	85	-0.17	0.015	1000	-1000	-0.081	-1000
PDGFR-alpha signaling pathway	0.0822	55	2425	44	-0.15	0.029	1000	-1000	-0.057	-1000
FOXA2 and FOXA3 transcription factor networks	0.0807	54	2493	46	-0.3	0.019	1000	-1000	-0.058	-1000
IL1-mediated signaling events	0.0807	54	3365	62	-0.24	0.067	1000	-1000	-0.1	-1000
IL6-mediated signaling events	0.0807	54	4057	75	-0.24	0.066	1000	-1000	-0.086	-1000
Visual signal transduction: Rods	0.0792	53	2775	52	-0.19	0.015	1000	-1000	-0.081	-1000
Glucocorticoid receptor regulatory network	0.0747	50	5723	114	-0.41	0.24	1000	-1000	-0.069	-1000
LPA receptor mediated events	0.0747	50	5195	102	-0.25	0.027	1000	-1000	-0.081	-1000
Rapid glucocorticoid signaling	0.0732	49	981	20	-0.15	0.02	1000	-1000	-0.036	-1000
Ras signaling in the CD4+ TCR pathway	0.0732	49	845	17	-0.11	0.015	1000	-1000	-0.05	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0717	48	4237	88	-0.22	0.021	1000	-1000	-0.1	-1000
Integrins in angiogenesis	0.0703	47	3984	84	-0.15	0.019	1000	-1000	-0.094	-1000
S1P1 pathway	0.0688	46	1667	36	-0.13	0.015	1000	-1000	-0.055	-1000
Calcium signaling in the CD4+ TCR pathway	0.0688	46	1452	31	-0.22	0.014	1000	-1000	-0.088	-1000
IL2 signaling events mediated by STAT5	0.0673	45	1004	22	-0.16	0.024	1000	-1000	-0.046	-1000
Retinoic acid receptors-mediated signaling	0.0658	44	2590	58	-0.19	0.033	1000	-1000	-0.075	-1000
EGFR-dependent Endothelin signaling events	0.0658	44	944	21	-0.13	0.015	1000	-1000	-0.072	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0643	43	2269	52	-0.14	0.026	1000	-1000	-0.064	-1000
BMP receptor signaling	0.0628	42	3472	81	-0.19	0.052	1000	-1000	-0.099	-1000
Nongenotropic Androgen signaling	0.0613	41	2171	52	-0.082	0.015	1000	-1000	-0.058	-1000
BCR signaling pathway	0.0613	41	4157	99	-0.21	0.037	1000	-1000	-0.088	-1000
Fc-epsilon receptor I signaling in mast cells	0.0598	40	3902	97	-0.26	0.048	1000	-1000	-0.083	-1000
Syndecan-2-mediated signaling events	0.0583	39	2721	69	-0.22	0.038	1000	-1000	-0.056	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0568	38	1438	37	-0.13	0.015	1000	-1000	-0.065	-1000
Wnt signaling	0.0568	38	268	7	-0.042	-0.006	1000	-1000	-0.033	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0568	38	4644	120	-0.2	0.12	1000	-1000	-0.08	-1000
LPA4-mediated signaling events	0.0553	37	449	12	-0.048	0.015	1000	-1000	-0.02	-1000
ErbB2/ErbB3 signaling events	0.0553	37	2445	65	-0.16	0.026	1000	-1000	-0.068	-1000
Regulation of nuclear SMAD2/3 signaling	0.0553	37	5073	136	-0.29	0.28	1000	-1000	-0.068	-1000
Coregulation of Androgen receptor activity	0.0523	35	2690	76	-0.2	0.029	1000	-1000	-0.05	-1000
Syndecan-3-mediated signaling events	0.0508	34	1194	35	-0.22	0.015	1000	-1000	-0.065	-1000
Signaling events mediated by PTP1B	0.0493	33	2531	76	-0.24	0.028	1000	-1000	-0.078	-1000
IL2 signaling events mediated by PI3K	0.0493	33	1968	58	-0.17	0.034	1000	-1000	-0.086	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0478	32	1742	54	-0.19	0.032	1000	-1000	-0.1	-1000
S1P5 pathway	0.0478	32	547	17	-0.1	0.056	1000	-1000	-0.052	-1000
Presenilin action in Notch and Wnt signaling	0.0463	31	1951	61	-0.28	0.039	1000	-1000	-0.072	-1000
PLK2 and PLK4 events	0.0448	30	91	3	-0.007	-0.004	1000	-1000	-0.01	-1000
FAS signaling pathway (CD95)	0.0448	30	1418	47	-0.2	0.017	1000	-1000	-0.06	-1000
E-cadherin signaling in the nascent adherens junction	0.0448	30	2284	76	-0.11	0.02	1000	-1000	-0.083	-1000
ErbB4 signaling events	0.0433	29	2018	69	-0.14	0.082	1000	-1000	-0.088	-1000
Canonical Wnt signaling pathway	0.0419	28	1468	51	-0.28	0.1	1000	-1000	-0.051	-1000
JNK signaling in the CD4+ TCR pathway	0.0404	27	469	17	-0.072	0.019	1000	-1000	-0.068	-1000
Noncanonical Wnt signaling pathway	0.0404	27	712	26	-0.11	0.015	1000	-1000	-0.088	-1000
Signaling events mediated by HDAC Class III	0.0404	27	1115	40	-0.1	0.091	1000	-1000	-0.051	-1000
IL27-mediated signaling events	0.0404	27	1405	51	-0.17	0.02	1000	-1000	-0.071	-1000
Ceramide signaling pathway	0.0389	26	2010	76	-0.13	0.026	1000	-1000	-0.065	-1000
TCGA08_rtk_signaling	0.0389	26	698	26	-0.16	0.029	1000	-1000	-0.02	-1000
Cellular roles of Anthrax toxin	0.0374	25	981	39	-0.13	0.022	1000	-1000	-0.032	-1000
Aurora A signaling	0.0374	25	1501	60	-0.19	0.033	1000	-1000	-0.065	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0344	23	804	34	-0.056	0.015	1000	-1000	-0.07	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0344	23	1839	78	-0.067	0.045	1000	-1000	-0.081	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0329	22	617	28	-0.1	0.015	1000	-1000	-0.046	-1000
Ephrin B reverse signaling	0.0329	22	1076	48	-0.11	0.087	1000	-1000	-0.07	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0329	22	1833	83	-0.2	0.057	1000	-1000	-0.079	-1000
Plasma membrane estrogen receptor signaling	0.0329	22	1974	86	-0.13	0.04	1000	-1000	-0.079	-1000
S1P4 pathway	0.0329	22	552	25	-0.1	0.029	1000	-1000	-0.053	-1000
Signaling mediated by p38-gamma and p38-delta	0.0299	20	310	15	-0.017	0.034	1000	-1000	-0.027	-1000
EPHB forward signaling	0.0299	20	1723	85	-0.083	0.047	1000	-1000	-0.093	-1000
Nectin adhesion pathway	0.0284	19	1249	63	-0.11	0.04	1000	-1000	-0.075	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0284	19	855	45	-0.13	0.031	1000	-1000	-0.094	-1000
Regulation of Androgen receptor activity	0.0284	19	1331	70	-0.15	0.049	1000	-1000	-0.069	-1000
Insulin-mediated glucose transport	0.0269	18	599	32	-0.12	0.038	1000	-1000	-0.061	-1000
TRAIL signaling pathway	0.0269	18	885	48	-0.046	0.041	1000	-1000	-0.067	-1000
HIF-2-alpha transcription factor network	0.0269	18	806	43	-0.077	0.049	1000	-1000	-0.083	-1000
Paxillin-dependent events mediated by a4b1	0.0269	18	668	36	-0.11	0.042	1000	-1000	-0.07	-1000
Regulation of Telomerase	0.0269	18	1906	102	-0.13	0.052	1000	-1000	-0.11	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0269	18	625	33	-0.16	0.044	1000	-1000	-0.076	-1000
E-cadherin signaling in keratinocytes	0.0269	18	798	43	-0.11	0.029	1000	-1000	-0.071	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0254	17	1314	74	-0.19	0.062	1000	-1000	-0.097	-1000
EPO signaling pathway	0.0239	16	902	55	-0.18	0.067	1000	-1000	-0.097	-1000
Regulation of p38-alpha and p38-beta	0.0239	16	868	54	-0.13	0.026	1000	-1000	-0.06	-1000
S1P3 pathway	0.0239	16	685	42	-0.088	0.019	1000	-1000	-0.056	-1000
Arf6 downstream pathway	0.0224	15	656	43	-0.038	0.033	1000	-1000	-0.046	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0224	15	1942	125	-0.11	0.055	1000	-1000	-0.1	-1000
BARD1 signaling events	0.0209	14	836	57	-0.063	0.034	1000	-1000	-0.065	-1000
ceramide signaling pathway	0.0209	14	729	49	-0.12	0.026	1000	-1000	-0.045	-1000
p38 MAPK signaling pathway	0.0209	14	642	44	-0.068	0.024	1000	-1000	-0.06	-1000
Hedgehog signaling events mediated by Gli proteins	0.0179	12	817	65	-0.091	0.073	1000	-1000	-0.065	-1000
Atypical NF-kappaB pathway	0.0179	12	391	31	-0.098	0.032	1000	-1000	-0.038	-1000
Insulin Pathway	0.0179	12	961	74	-0.22	0.039	1000	-1000	-0.092	-1000
VEGFR1 specific signals	0.0179	12	686	56	-0.091	0.046	1000	-1000	-0.079	-1000
IFN-gamma pathway	0.0164	11	780	68	-0.22	0.076	1000	-1000	-0.093	-1000
Canonical NF-kappaB pathway	0.0149	10	412	39	-0.13	0.095	1000	-1000	-0.089	-1000
Class I PI3K signaling events	0.0149	10	789	73	-0.098	0.035	1000	-1000	-0.079	-1000
IGF1 pathway	0.0149	10	582	57	-0.049	0.053	1000	-1000	-0.096	-1000
Signaling events mediated by PRL	0.0149	10	370	34	-0.052	0.025	1000	-1000	-0.041	-1000
Circadian rhythm pathway	0.0135	9	198	22	-0.018	0.04	1000	-1000	-0.062	-1000
Class IB PI3K non-lipid kinase events	0.0135	9	27	3	-0.007	0.007	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class I	0.0120	8	856	104	-0.13	0.063	1000	-1000	-0.068	-1000
Signaling events mediated by HDAC Class II	0.0105	7	571	75	-0.15	0.042	1000	-1000	-0.062	-1000
Arf6 trafficking events	0.0105	7	563	71	-0.14	0.051	1000	-1000	-0.081	-1000
PDGFR-beta signaling pathway	0.0105	7	710	97	-0.057	0.072	1000	-1000	-0.09	-1000
Class I PI3K signaling events mediated by Akt	0.0090	6	419	68	-0.12	0.058	1000	-1000	-0.062	-1000
FoxO family signaling	0.0075	5	357	64	-0.12	0.1	1000	-1000	-0.064	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0030	2	59	23	-0.012	0.054	1000	-1000	-0.073	-1000
mTOR signaling pathway	0.0030	2	156	53	-0.004	0.038	1000	-1000	-0.065	-1000
Alternative NF-kappaB pathway	0.0030	2	27	13	-0.004	0.015	1000	-1000	-0.068	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0015	1	53	27	-0.007	0.035	1000	-1000	-0.057	-1000
Arf1 pathway	0.0000	0	28	54	-0.004	0.041	1000	-1000	-0.05	-1000
Total	NA	5380	295325	7203	-22	5.9	131000	-131000	-9.2	-131000

TCGA08_retinoblastoma

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
CDKN2B	-0.1	0.24	-10000	0	-0.58	134	134
CDKN2C	-0.042	0.18	-10000	0	-0.54	79	79
CDKN2A	-0.15	0.27	-10000	0	-0.58	186	186
CCND2	0.1	0.17	0.33	193	-0.15	3	196
RB1	-0.11	0.18	-10000	0	-0.35	196	196
CDK4	0.11	0.18	0.37	192	-10000	0	192
CDK6	0.11	0.19	0.37	190	-0.17	15	205
G1/S progression	0.093	0.18	0.34	196	-10000	0	196

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.62	0.58	-10000	0	-1.2	253	253
IL23A	-0.6	0.56	-10000	0	-1.2	262	262
NF kappa B1 p50/RelA/I kappa B alpha	-0.59	0.51	-10000	0	-1.1	262	262
positive regulation of T cell mediated cytotoxicity	-0.64	0.63	-10000	0	-1.3	266	266
ITGA3	-0.57	0.53	-10000	0	-1.1	258	258
IL17F	-0.36	0.34	-10000	0	-0.73	207	207
IL12B	-0.021	0.058	-10000	0	-0.65	4	4
STAT1 (dimer)	-0.62	0.6	-10000	0	-1.2	267	267
CD4	-0.54	0.51	-10000	0	-1.1	253	253
IL23	-0.59	0.53	-10000	0	-1.2	260	260
IL23R	-0.083	0.087	-10000	0	-0.6	1	1
IL1B	-0.65	0.61	-10000	0	-1.3	271	271
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.55	0.51	-10000	0	-1.1	252	252
TYK2	0.002	0.017	-10000	0	-10000	0	0
STAT4	-0.14	0.27	-10000	0	-0.6	165	165
STAT3	0.015	0	-10000	0	-10000	0	0
IL18RAP	-0.079	0.22	-10000	0	-0.6	102	102
IL12RB1	-0.033	0.15	-10000	0	-0.65	36	36
PIK3CA	0.015	0	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.029	0.11	-10000	0	-0.49	36	36
IL23R/JAK2	-0.094	0.11	-10000	0	-0.59	1	1
positive regulation of chronic inflammatory response	-0.64	0.63	-10000	0	-1.3	266	266
natural killer cell activation	0.008	0.008	0.052	1	-10000	0	1
JAK2	0.008	0.02	-10000	0	-10000	0	0
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
NFKB1	0.012	0.003	-10000	0	-10000	0	0
RELA	0.012	0.003	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.56	0.5	-10000	0	-1.1	263	263
ALOX12B	-0.62	0.57	-10000	0	-1.2	281	281
CXCL1	-0.61	0.56	-10000	0	-1.2	268	268
T cell proliferation	-0.64	0.63	-10000	0	-1.3	266	266
NFKBIA	0.011	0.023	-10000	0	-0.59	1	1
IL17A	-0.27	0.27	-10000	0	-0.58	151	151
PI3K	-0.6	0.53	-10000	0	-1.2	268	268
IFNG	-0.022	0.033	-10000	0	-0.1	16	16
STAT3 (dimer)	-0.57	0.49	-10000	0	-1.1	261	261
IL18R1	-0.048	0.19	-10000	0	-0.6	70	70
IL23/IL23R/JAK2/TYK2/SOCS3	-0.35	0.32	-10000	0	-0.72	182	182
IL18/IL18R	-0.1	0.22	-10000	0	-0.45	173	173
macrophage activation	-0.028	0.018	-10000	0	-0.044	254	254
TNF	-0.63	0.6	-10000	0	-1.2	269	269
STAT3/STAT4	-0.66	0.54	-10000	0	-1.2	298	298
STAT4 (dimer)	-0.67	0.6	-10000	0	-1.3	289	289
IL18	-0.026	0.16	-10000	0	-0.61	45	45
IL19	-0.55	0.51	-10000	0	-1.1	231	231
STAT5A (dimer)	-0.61	0.6	-10000	0	-1.2	263	263
STAT1	0.001	0.092	-10000	0	-0.59	16	16
SOCS3	-0.18	0.29	-10000	0	-0.6	214	214
CXCL9	-0.66	0.58	-10000	0	-1.2	305	305
MPO	-0.62	0.56	-10000	0	-1.2	276	276
positive regulation of humoral immune response	-0.64	0.63	-10000	0	-1.3	266	266
IL23/IL23R/JAK2/TYK2	-0.7	0.74	-10000	0	-1.4	266	266
IL6	-0.64	0.58	-10000	0	-1.2	277	277
STAT5A	0.005	0.081	-10000	0	-0.62	11	11
IL2	0.006	0.006	-10000	0	-10000	0	0
positive regulation of tyrosine phosphorylation of STAT protein	0.008	0.008	0.052	1	-10000	0	1
CD3E	-0.63	0.58	-10000	0	-1.2	292	292
keratinocyte proliferation	-0.64	0.63	-10000	0	-1.3	266	266
NOS2	-0.58	0.53	-10000	0	-1.2	251	251

×

FOXM1 transcription factor network

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
NFATC3	-0.24	0.68	-10000	0	-1.2	179	179
PLK1	-0.014	0.23	-10000	0	-1.5	7	7
BIRC5	-0.27	0.57	-10000	0	-0.99	217	217
HSPA1B	-0.26	0.68	-10000	0	-1.2	188	188
MAP2K1	0.028	0.049	-10000	0	-10000	0	0
BRCA2	-0.26	0.7	-10000	0	-1.3	185	185
FOXM1	-0.42	0.97	-10000	0	-1.8	195	195
XRCC1	-0.24	0.68	-10000	0	-1.2	174	174
FOXM1B/p19	-0.45	0.57	0.47	4	-1.3	202	206
Cyclin D1/CDK4	-0.23	0.63	-10000	0	-1.1	179	179
CDC2	-0.27	0.72	-10000	0	-1.3	195	195
TGFA	-0.21	0.61	-10000	0	-1	177	177
SKP2	-0.25	0.68	-10000	0	-1.2	179	179
CCNE1	0.011	0.055	-10000	0	-0.6	5	5
CKS1B	-0.25	0.68	-10000	0	-1.2	177	177
RB1	-0.19	0.28	-10000	0	-0.71	98	98
FOXM1C/SP1	-0.33	0.79	-10000	0	-1.4	190	190
AURKB	-0.28	0.59	-10000	0	-1.5	115	115
CENPF	-0.28	0.73	-10000	0	-1.3	186	186
CDK4	-0.015	0.14	-10000	0	-0.6	38	38
MYC	-0.2	0.6	-10000	0	-1	178	178
CHEK2	0.01	0.12	-10000	0	-0.64	20	20
ONECUT1	-0.25	0.66	-10000	0	-1.2	178	178
CDKN2A	-0.16	0.28	-10000	0	-0.61	186	186
LAMA4	-0.25	0.68	-10000	0	-1.2	180	180
FOXM1B/HNF6	-0.34	0.81	-10000	0	-1.5	183	183
FOS	-0.32	0.71	-10000	0	-1.2	219	219
SP1	0.016	0.005	-10000	0	-10000	0	0
CDC25B	-0.24	0.68	-10000	0	-1.2	176	176
response to radiation	0.009	0.046	-10000	0	-10000	0	0
CENPB	-0.24	0.68	-10000	0	-1.2	175	175
CENPA	-0.32	0.76	-10000	0	-1.3	207	207
NEK2	-0.32	0.77	-10000	0	-1.3	212	212
HIST1H2BA	-0.25	0.68	-10000	0	-1.2	174	174
CCNA2	-0.074	0.22	-10000	0	-0.61	97	97
EP300	0.012	0.043	-10000	0	-0.62	3	3
CCNB1/CDK1	-0.34	0.82	-10000	0	-1.5	187	187
CCNB2	-0.34	0.78	-10000	0	-1.4	214	214
CCNB1	-0.28	0.74	-10000	0	-1.3	187	187
ETV5	-0.26	0.69	-10000	0	-1.2	186	186
ESR1	-0.26	0.69	-10000	0	-1.2	183	183
CCND1	-0.23	0.64	-10000	0	-1.1	176	176
GSK3A	0.032	0.037	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.027	0.19	-10000	0	-0.43	104	104
CDK2	0.002	0.094	-10000	0	-0.61	15	15
G2/M transition of mitotic cell cycle	0.009	0.055	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.46	0.6	-10000	0	-1.3	201	201
GAS1	-0.26	0.69	-10000	0	-1.2	179	179
MMP2	-0.26	0.69	-10000	0	-1.2	179	179
RB1/FOXM1C	-0.25	0.67	-10000	0	-1.2	178	178
CREBBP	0.014	0.025	-10000	0	-0.62	1	1

×

Ephrin A reverse 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.12	0.22	-9999	-0.46	177	177
EFNA5	-0.068	0.21	-9999	-0.61	89	89
FYN	-0.088	0.21	-9999	-0.42	177	177
neuron projection morphogenesis	-0.12	0.22	-9999	-0.46	177	177
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.12	0.22	-9999	-0.46	177	177
EPHA5	-0.11	0.25	-9999	-0.61	131	131

×

Syndecan-1-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.006	0.077	-9999	-0.62	10	10
CCL5	-0.093	0.24	-9999	-0.6	117	117
SDCBP	0.015	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.22	0.23	-9999	-0.53	175	175
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.23	-9999	-0.54	155	155
Syndecan-1/Syntenin	-0.2	0.22	-9999	-0.53	154	154
MAPK3	-0.16	0.21	-9999	-0.49	140	140
HGF/MET	-0.19	0.26	-9999	-0.51	255	255
TGFB1/TGF beta receptor Type II	0.006	0.077	-9999	-0.62	10	10
BSG	0.015	0	-9999	-10000	0	0
keratinocyte migration	-0.2	0.22	-9999	-0.53	155	155
Syndecan-1/RANTES	-0.25	0.27	-9999	-0.59	200	200
Syndecan-1/CD147	-0.18	0.22	-9999	-0.52	141	141
Syndecan-1/Syntenin/PIP2	-0.2	0.2	-9999	-0.52	154	154
LAMA5	0.012	0.042	-9999	-0.61	3	3
positive regulation of cell-cell adhesion	-0.2	0.2	-9999	-0.5	154	154
MMP7	-0.22	0.3	-9999	-0.6	247	247
HGF	-0.088	0.23	-9999	-0.6	113	113
Syndecan-1/CASK	-0.21	0.22	-9999	-0.51	175	175
Syndecan-1/HGF/MET	-0.32	0.31	-9999	-0.64	263	263
regulation of cell adhesion	-0.15	0.2	-9999	-0.53	83	83
HPSE	-0.048	0.19	-9999	-0.62	67	67
positive regulation of cell migration	-0.22	0.23	-9999	-0.53	175	175
SDC1	-0.22	0.24	-9999	-0.56	162	162
Syndecan-1/Collagen	-0.22	0.23	-9999	-0.53	175	175
PPIB	0.015	0	-9999	-10000	0	0
MET	-0.16	0.28	-9999	-0.6	194	194
PRKACA	0.015	0	-9999	-10000	0	0
MMP9	-0.25	0.3	-9999	-0.6	285	285
MAPK1	-0.16	0.21	-9999	-0.49	140	140
homophilic cell adhesion	-0.21	0.23	-9999	-0.53	175	175
MMP1	-0.1	0.24	-9999	-0.6	124	124

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.15	0.3	-9999	-0.61	177	177
STMN1	-0.12	0.22	-9999	-0.45	210	210
Aurora B/RasGAP/Survivin	-0.22	0.33	-9999	-0.61	257	257
Chromosomal passenger complex/Cul3 protein complex	-0.14	0.24	-9999	-0.46	208	208
BIRC5	-0.2	0.3	-9999	-0.63	225	225
DES	-0.39	0.48	-9999	-0.88	260	260
Aurora C/Aurora B/INCENP	-0.11	0.19	-9999	-0.36	234	234
Aurora B/TACC1	-0.11	0.18	-9999	-0.38	209	209
Aurora B/PP2A	-0.13	0.22	-9999	-0.44	209	209
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.032	0.079	-9999	-0.18	115	115
mitotic metaphase/anaphase transition	-0.001	0.006	-9999	-10000	0	0
NDC80	-0.24	0.36	-9999	-0.68	251	251
Cul3 protein complex	-0.02	0.085	-9999	-0.38	35	35
KIF2C	-0.19	0.34	-9999	-0.52	255	255
PEBP1	0.008	0.037	-9999	-0.65	2	2
KIF20A	-0.23	0.31	-9999	-0.61	263	263
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.13	0.22	-9999	-0.44	209	209
SEPT1	0.013	0.033	-9999	-0.59	2	2
SMC2	0.015	0	-9999	-10000	0	0
SMC4	-0.015	0.13	-9999	-0.59	34	34
NSUN2/NPM1/Nucleolin	-0.18	0.34	-9999	-0.88	115	115
PSMA3	0.015	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.002	0.004	-9999	-10000	0	0
H3F3B	-0.085	0.16	-9999	-0.32	210	210
AURKB	-0.18	0.3	-9999	-0.62	209	209
AURKC	-0.015	0.13	-9999	-0.6	33	33
CDCA8	-0.12	0.25	-9999	-0.62	136	136
cytokinesis	-0.35	0.45	-9999	-0.88	247	247
Aurora B/Septin1	-0.3	0.43	-9999	-0.82	243	243
AURKA	-0.039	0.17	-9999	-0.59	59	59
INCENP	0.008	0.037	-9999	-0.64	2	2
KLHL13	0.012	0.043	-9999	-0.62	3	3
BUB1	-0.14	0.27	-9999	-0.61	170	170
hSgo1/Aurora B/Survivin	-0.3	0.42	-9999	-0.75	278	278
EVI5	0.013	0.003	-9999	-10000	0	0
RhoA/GTP	-0.31	0.41	-9999	-0.81	249	249
SGOL1	-0.16	0.28	-9999	-0.6	191	191
CENPA	-0.23	0.36	-9999	-0.63	254	254
NCAPG	-0.15	0.28	-9999	-0.61	180	180
Aurora B/HC8 Proteasome	-0.13	0.22	-9999	-0.44	209	209
NCAPD2	0.012	0.046	-9999	-0.59	4	4
Aurora B/PP1-gamma	-0.13	0.22	-9999	-0.44	209	209
RHOA	0.015	0	-9999	-10000	0	0
NCAPH	-0.091	0.23	-9999	-0.61	114	114
NPM1	-0.14	0.25	-9999	-0.64	116	116
RASA1	0.015	0	-9999	-10000	0	0
KLHL9	-0.015	0.14	-9999	-0.62	32	32
mitotic prometaphase	-0.008	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.13	0.21	-9999	-0.44	209	209
PPP1CC	0.015	0	-9999	-10000	0	0
Centraspindlin	-0.35	0.47	-9999	-0.89	257	257
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.14	0.25	-9999	-0.64	115	115
MYLK	-0.093	0.17	-9999	-0.32	222	222
KIF23	-0.17	0.28	-9999	-0.62	193	193
VIM	-0.19	0.27	-9999	-0.5	279	279
RACGAP1	0.006	0.048	-9999	-0.61	4	4
mitosis	0	0	-9999	-10000	0	0
NCL	-0.14	0.25	-9999	-0.64	115	115
Chromosomal passenger complex	-0.28	0.43	-9999	-0.76	255	255
Chromosomal passenger complex/EVI5	-0.25	0.38	-9999	-0.76	220	220
TACC1	0.015	0	-9999	-10000	0	0
PPP2R5D	0.015	0	-9999	-10000	0	0
CUL3	0.015	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.11	0.17	-10000	0	-0.42	81	81
TBX21	-0.42	0.48	-10000	0	-0.98	232	232
B2M	0.004	0.084	-10000	0	-0.59	13	13
TYK2	0.004	0.02	-10000	0	-10000	0	0
IL12RB1	-0.03	0.15	-10000	0	-0.65	36	36
GADD45B	-0.31	0.38	-10000	0	-0.86	142	142
IL12RB2	-0.11	0.24	-10000	0	-0.62	121	121
GADD45G	-0.35	0.43	-10000	0	-0.91	173	173
natural killer cell activation	-0.015	0.025	-10000	0	-10000	0	0
RELB	0.01	0.057	-10000	0	-0.59	6	6
RELA	0.015	0	-10000	0	-10000	0	0
IL18	-0.03	0.16	-10000	0	-0.62	45	45
IL2RA	-0.17	0.28	-10000	0	-0.6	193	193
IFNG	-0.002	0.061	-10000	0	-0.59	7	7
STAT3 (dimer)	-0.34	0.36	-10000	0	-0.73	250	250
HLA-DRB5	-0.13	0.26	-10000	0	-0.6	159	159
FASLG	-0.4	0.46	-10000	0	-0.96	200	200
NF kappa B2 p52/RelB	-0.42	0.41	-10000	0	-0.87	250	250
CD4	0.008	0.062	-10000	0	-0.59	7	7
SOCS1	-0.059	0.2	-10000	0	-0.59	82	82
EntrezGene:6955	-0.001	0.009	-10000	0	-10000	0	0
CD3D	-0.15	0.27	-10000	0	-0.61	173	173
CD3E	-0.15	0.27	-10000	0	-0.61	174	174
CD3G	-0.042	0.17	-10000	0	-0.6	58	58
IL12Rbeta2/JAK2	-0.079	0.18	-10000	0	-0.46	121	121
CCL3	-0.51	0.58	-10000	0	-1.2	247	247
CCL4	-0.49	0.57	-10000	0	-1.1	235	235
HLA-A	0.005	0.08	-10000	0	-0.59	12	12
IL18/IL18R	-0.088	0.24	-10000	0	-0.47	173	173
NOS2	-0.38	0.46	-10000	0	-0.96	190	190
IL12/IL12R/TYK2/JAK2/SPHK2	-0.077	0.14	-10000	0	-0.41	42	42
IL1R1	-0.41	0.47	-10000	0	-0.98	210	210
IL4	0.015	0.045	-10000	0	-0.54	3	3
JAK2	0.004	0.02	-10000	0	-10000	0	0
EntrezGene:6957	-0.001	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.14	0.28	-10000	0	-0.69	102	102
RAB7A	-0.26	0.32	-10000	0	-0.75	110	110
lysosomal transport	-0.24	0.31	-10000	0	-0.7	115	115
FOS	-0.32	0.44	-10000	0	-0.95	166	166
STAT4 (dimer)	-0.37	0.41	-10000	0	-0.84	221	221
STAT5A (dimer)	-0.43	0.42	-10000	0	-0.87	258	258
GZMA	-0.5	0.55	-10000	0	-1.1	265	265
GZMB	-0.46	0.52	-10000	0	-1.1	208	208
HLX	0.004	0.082	-10000	0	-0.6	12	12
LCK	-0.47	0.52	-10000	0	-0.99	274	274
TCR/CD3/MHC II/CD4	-0.18	0.28	-10000	0	-0.54	201	201
IL2/IL2R	-0.19	0.26	-10000	0	-0.5	207	207
MAPK14	-0.32	0.4	-10000	0	-0.83	176	176
CCR5	-0.38	0.47	-10000	0	-0.98	189	189
IL1B	-0.18	0.29	-10000	0	-0.63	191	191
STAT6	-0.095	0.12	0.25	1	-0.25	71	72
STAT4	-0.14	0.27	-10000	0	-0.6	165	165
STAT3	0.015	0	-10000	0	-10000	0	0
STAT1	0.001	0.092	-10000	0	-0.59	16	16
NFKB1	0.015	0	-10000	0	-10000	0	0
NFKB2	0.014	0.025	-10000	0	-0.62	1	1
IL12B	-0.011	0.054	-10000	0	-0.63	4	4
CD8A	-0.066	0.21	-10000	0	-0.61	88	88
CD8B	-0.032	0.17	-10000	0	-0.61	51	51
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.1	0.17	0.41	82	-10000	0	82
IL2RB	-0.11	0.25	-10000	0	-0.6	140	140
proteasomal ubiquitin-dependent protein catabolic process	-0.34	0.37	-10000	0	-0.76	221	221
IL2RG	-0.038	0.17	-10000	0	-0.6	58	58
IL12	-0.019	0.095	-10000	0	-0.48	24	24
STAT5A	0.005	0.081	-10000	0	-0.62	11	11
CD247	-0.02	0.14	-10000	0	-0.61	37	37
IL2	0.001	0.003	-10000	0	-10000	0	0
SPHK2	0.015	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.015	0.11	-10000	0	-0.63	20	20
IL12/IL12R/TYK2/JAK2	-0.46	0.55	-10000	0	-1	258	258
MAP2K3	-0.33	0.4	-10000	0	-0.83	183	183
RIPK2	0.015	0	-10000	0	-10000	0	0
MAP2K6	-0.33	0.4	-10000	0	-0.82	191	191
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	-0.1	0.24	-10000	0	-0.61	124	124
IL18RAP	-0.083	0.22	-10000	0	-0.61	102	102
IL12Rbeta1/TYK2	-0.022	0.12	-10000	0	-0.49	36	36
EOMES	-0.019	0.19	-10000	0	-0.81	19	19
STAT1 (dimer)	-0.33	0.36	-10000	0	-0.73	231	231
T cell proliferation	-0.27	0.3	-10000	0	-0.62	208	208
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	-0.052	0.19	-10000	0	-0.61	70	70
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.34	0.29	-10000	0	-0.69	206	206
ATF2	-0.3	0.37	-10000	0	-0.78	169	169

×

IL4-mediated signaling events

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
BCL2L1	-0.44	0.47	-10000	0	-1.1	144	144
STAT6 (cleaved dimer)	-0.53	0.47	-10000	0	-1.1	242	242
IGHG1	-0.17	0.2	-10000	0	-0.61	40	40
IGHG3	-0.44	0.45	-10000	0	-1	189	189
AKT1	-0.26	0.3	-10000	0	-0.73	117	117
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.24	0.3	-10000	0	-0.8	92	92
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.25	0.27	-10000	0	-0.68	100	100
THY1	-0.46	0.49	-10000	0	-1.2	152	152
MYB	-0.081	0.22	-10000	0	-0.6	104	104
HMGA1	0.007	0.07	-10000	0	-0.6	9	9
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.36	0.36	-10000	0	-0.81	187	187
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.25	0.28	-10000	0	-0.7	95	95
SP1	0.02	0.014	-10000	0	-10000	0	0
INPP5D	0.007	0.071	-10000	0	-0.6	9	9
SOCS5	0.03	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.52	0.49	-10000	0	-1.1	223	223
SOCS1	-0.35	0.35	-10000	0	-0.83	151	151
SOCS3	-0.44	0.48	-10000	0	-1	222	222
FCER2	-0.43	0.42	-10000	0	-1	149	149
PARP14	0.003	0.078	-10000	0	-0.6	11	11
CCL17	-0.46	0.48	-10000	0	-1.2	153	153
GRB2	0.014	0.023	-10000	0	-0.59	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.21	0.24	-10000	0	-0.69	69	69
T cell proliferation	-0.46	0.49	-10000	0	-1.2	163	163
IL4R/JAK1	-0.45	0.46	-10000	0	-1.1	147	147
EGR2	-0.54	0.55	-10000	0	-1.3	177	177
JAK2	-0.002	0.026	-10000	0	-10000	0	0
JAK3	-0.058	0.2	-10000	0	-0.6	78	78
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
JAK1	0.005	0.013	-10000	0	-10000	0	0
COL1A2	-0.21	0.31	-10000	0	-0.8	108	108
CCL26	-0.46	0.49	-10000	0	-1.2	155	155
IL4R	-0.48	0.5	-10000	0	-1.2	148	148
PTPN6	0.016	0.081	-10000	0	-0.61	11	11
IL13RA2	-0.72	0.61	-10000	0	-1.3	308	308
IL13RA1	-0.01	0.076	-10000	0	-0.66	8	8
IRF4	-0.17	0.31	-10000	0	-1.1	48	48
ARG1	-0.15	0.24	-10000	0	-0.84	41	41
CBL	-0.33	0.34	-10000	0	-0.78	172	172
GTF3A	0.007	0.048	-10000	0	-0.62	2	2
PIK3CA	0.015	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.014	0.065	-10000	0	-0.48	8	8
IRF4/BCL6	-0.14	0.29	-10000	0	-1	48	48
CD40LG	-0.028	0.16	-10000	0	-0.6	47	47
MAPK14	-0.37	0.38	-10000	0	-0.85	196	196
mitosis	-0.25	0.28	-10000	0	-0.69	117	117
STAT6	-0.51	0.55	-10000	0	-1.2	178	178
SPI1	-0.002	0.11	-10000	0	-0.61	19	19
RPS6KB1	-0.24	0.27	-10000	0	-0.68	100	100
STAT6 (dimer)	-0.52	0.55	-10000	0	-1.2	178	178
STAT6 (dimer)/PARP14	-0.49	0.5	-10000	0	-1.1	186	186
mast cell activation	0.012	0.012	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.33	-10000	0	-0.8	135	135
FRAP1	-0.26	0.3	-10000	0	-0.73	117	117
LTA	-0.47	0.5	-10000	0	-1.2	158	158
FES	0.011	0.048	-10000	0	-0.61	4	4
T-helper 1 cell differentiation	0.5	0.53	1.2	178	-10000	0	178
CCL11	-0.44	0.45	-10000	0	-1.1	148	148
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.28	0.32	-10000	0	-0.76	121	121
IL2RG	-0.04	0.17	-10000	0	-0.6	58	58
IL10	-0.55	0.59	-10000	0	-1.3	199	199
IRS1	0.009	0.065	-10000	0	-0.62	7	7
IRS2	0.014	0.023	-10000	0	-0.59	1	1
IL4	-0.11	0.12	-10000	0	-0.69	3	3
IL5	-0.45	0.47	-10000	0	-1.1	145	145
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.36	0.37	-10000	0	-0.86	153	153
COL1A1	-0.42	0.53	-10000	0	-1.1	218	218
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.45	0.48	-10000	0	-1.2	135	135
IL2R gamma/JAK3	-0.074	0.2	-10000	0	-0.49	120	120
TFF3	-0.47	0.49	-10000	0	-1.2	150	150
ALOX15	-0.46	0.48	-10000	0	-1.1	155	155
MYBL1	0.011	0.052	-10000	0	-0.59	5	5
T-helper 2 cell differentiation	-0.4	0.39	-10000	0	-0.92	169	169
SHC1	0.001	0.092	-10000	0	-0.59	16	16
CEBPB	-0.002	0.11	-10000	0	-0.61	19	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.24	0.26	-10000	0	-0.67	92	92
mol:PI-3-4-5-P3	-0.26	0.3	-10000	0	-0.73	117	117
PI3K	-0.28	0.32	-10000	0	-0.78	117	117
DOK2	-0.085	0.23	-10000	0	-0.6	109	109
ETS1	0.022	0.063	-10000	0	-0.58	7	7
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.19	0.23	-10000	0	-0.66	67	67
ITGB3	-0.51	0.54	-10000	0	-1.3	162	162
PIGR	-0.52	0.55	-10000	0	-1.3	183	183
IGHE	0.023	0.063	-10000	0	-0.28	7	7
MAPKKK cascade	-0.19	0.23	-10000	0	-0.64	67	67
BCL6	0.017	0.006	-10000	0	-10000	0	0
OPRM1	-0.46	0.47	-10000	0	-1.2	147	147
RETNLB	-0.46	0.47	-10000	0	-1.1	147	147
SELP	-0.46	0.48	-10000	0	-1.2	151	151
AICDA	-0.44	0.45	-10000	0	-1.1	163	163

×

Effects of Botulinum toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
STX1A	-0.042	0.15	-9999	-0.44	83	83
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.098	0.18	-9999	-0.44	147	147
STXBP1	-0.014	0.13	-9999	-0.59	32	32
ACh/CHRNA1	-0.16	0.2	-9999	-0.42	230	230
RAB3GAP2/RIMS1/UNC13B	-0.082	0.15	-9999	-0.37	147	147
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.12	0.26	-9999	-0.61	147	147
mol:ACh	-0.032	0.071	-9999	-0.14	190	190
RAB3GAP2	0.015	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.13	0.23	-9999	-0.55	127	127
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.16	0.2	-9999	-0.42	230	230
UNC13B	0.014	0.025	-9999	-0.62	1	1
CHRNA1	-0.2	0.29	-9999	-0.6	230	230
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.15	0.23	-9999	-0.46	229	229
SNAP25	-0.067	0.13	-9999	-0.27	184	184
VAMP2	0.008	0.007	-9999	-0.17	1	1
SYT1	-0.2	0.29	-9999	-0.6	229	229
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.043	0.18	-9999	-0.48	86	86
STX1A/SNAP25 fragment 1/VAMP2	-0.13	0.23	-9999	-0.55	127	127

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.071	0.21	-9999	-0.6	93	93
GPC2	-0.021	0.15	-9999	-0.61	38	38
GPC2/Midkine	-0.085	0.18	-9999	-0.47	122	122
neuron projection morphogenesis	-0.085	0.18	-9999	-0.46	122	122

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.017	0.084	-9999	-0.31	5	5
Syndecan-4/Syndesmos	-0.18	0.26	-9999	-0.58	137	137
positive regulation of JNK cascade	-0.2	0.23	-9999	-0.54	157	157
Syndecan-4/ADAM12	-0.27	0.3	-9999	-0.58	282	282
CCL5	-0.093	0.24	-9999	-0.6	117	117
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.015	0	-9999	-10000	0	0
ITGA5	-0.026	0.15	-9999	-0.59	46	46
SDCBP	0.015	0	-9999	-10000	0	0
PLG	0.002	0.046	-9999	-0.58	4	4
ADAM12	-0.17	0.28	-9999	-0.59	204	204
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.044	0.051	-9999	-0.21	1	1
Syndecan-4/Laminin alpha1	-0.22	0.28	-9999	-0.61	176	176
Syndecan-4/CXCL12/CXCR4	-0.19	0.27	-9999	-0.58	157	157
Syndecan-4/Laminin alpha3	-0.21	0.28	-9999	-0.6	170	170
MDK	-0.071	0.21	-9999	-0.6	93	93
Syndecan-4/FZD7	-0.21	0.29	-9999	-0.62	163	163
Syndecan-4/Midkine	-0.22	0.28	-9999	-0.59	196	196
FZD7	-0.046	0.19	-9999	-0.62	65	65
Syndecan-4/FGFR1/FGF	-0.19	0.22	-9999	-0.54	139	139
THBS1	-0.15	0.27	-9999	-0.6	176	176
integrin-mediated signaling pathway	-0.2	0.28	-9999	-0.6	170	170
positive regulation of MAPKKK cascade	-0.2	0.23	-9999	-0.54	157	157
Syndecan-4/TACI	-0.19	0.26	-9999	-0.59	141	141
CXCR4	-0.016	0.14	-9999	-0.61	33	33
cell adhesion	0.01	0.087	-9999	-0.33	27	27
Syndecan-4/Dynamin	-0.18	0.26	-9999	-0.58	137	137
Syndecan-4/TSP1	-0.26	0.3	-9999	-0.61	238	238
Syndecan-4/GIPC	-0.18	0.26	-9999	-0.57	146	146
Syndecan-4/RANTES	-0.23	0.29	-9999	-0.62	187	187
ITGB1	0.012	0.04	-9999	-0.59	3	3
LAMA1	-0.071	0.22	-9999	-0.62	91	91
LAMA3	-0.054	0.2	-9999	-0.61	74	74
RAC1	0.015	0	-9999	-10000	0	0
PRKCA	0.048	0.058	-9999	-0.51	2	2
Syndecan-4/alpha-Actinin	-0.2	0.28	-9999	-0.59	177	177
TFPI	-0.13	0.26	-9999	-0.61	154	154
F2	-0.008	0.061	-9999	-0.59	7	7
alpha5/beta1 Integrin	-0.031	0.12	-9999	-0.45	46	46
positive regulation of cell adhesion	-0.24	0.3	-9999	-0.6	210	210
ACTN1	-0.026	0.15	-9999	-0.59	46	46
TNC	-0.053	0.19	-9999	-0.61	73	73
Syndecan-4/CXCL12	-0.19	0.26	-9999	-0.58	145	145
FGF6	0.001	0.003	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
CXCL12	0	0.095	-9999	-0.61	16	16
TNFRSF13B	-0.003	0.069	-9999	-0.59	9	9
FGF2	0.013	0.034	-9999	-0.61	2	2
FGFR1	0.012	0.041	-9999	-0.6	3	3
Syndecan-4/PI-4-5-P2	-0.19	0.26	-9999	-0.58	148	148
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.023	0.16	-9999	-0.58	48	48
cell migration	-0.011	0.022	-9999	-10000	0	0
PRKCD	-0.002	0.12	-9999	-0.6	24	24
vasculogenesis	-0.25	0.29	-9999	-0.58	238	238
SDC4	-0.2	0.27	-9999	-0.61	148	148
Syndecan-4/Tenascin C	-0.21	0.29	-9999	-0.62	170	170
Syndecan-4/PI-4-5-P2/PKC alpha	-0.035	0.04	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.18	0.26	-9999	-0.58	137	137
MMP9	-0.25	0.3	-9999	-0.6	285	285
Rac1/GTP	-0.006	0.086	-9999	-0.34	27	27
cytoskeleton organization	-0.17	0.24	-9999	-0.55	146	146
GIPC1	0.014	0.023	-9999	-0.59	1	1
Syndecan-4/TFPI	-0.25	0.28	-9999	-0.62	181	181

×

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	-0.11	0.32	-10000	0	-0.63	171	171
IHH	-0.018	0.1	-10000	0	-0.58	14	14
SHH Np/Cholesterol/GAS1	-0.099	0.17	-10000	0	-0.37	181	181
LRPAP1	0.015	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.099	0.17	0.36	181	-10000	0	181
SMO/beta Arrestin2	-0.042	0.19	-10000	0	-0.61	36	36
SMO	-0.052	0.2	-10000	0	-0.65	37	37
AKT1	0.001	0.094	-10000	0	-0.36	6	6
ARRB2	0.015	0	-10000	0	-10000	0	0
BOC	0.009	0.064	-10000	0	-0.61	7	7
ADRBK1	0.015	0	-10000	0	-10000	0	0
heart looping	-0.051	0.2	-10000	0	-0.64	37	37
STIL	-0.1	0.23	-10000	0	-0.56	95	95
DHH N/PTCH2	-0.062	0.16	-10000	0	-0.45	93	93
DHH N/PTCH1	-0.084	0.22	-10000	0	-0.58	65	65
PIK3CA	0.015	0	-10000	0	-10000	0	0
DHH	-0.058	0.2	-10000	0	-0.6	79	79
PTHLH	-0.12	0.36	-10000	0	-0.87	95	95
determination of left/right symmetry	-0.051	0.2	-10000	0	-0.64	37	37
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
skeletal system development	-0.12	0.35	-10000	0	-0.86	95	95
IHH N/Hhip	-0.11	0.22	-10000	0	-0.5	159	159
DHH N/Hhip	-0.15	0.23	-10000	0	-0.48	208	208
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.051	0.2	-10000	0	-0.64	37	37
pancreas development	-0.12	0.26	-10000	0	-0.61	150	150
HHAT	-0.002	0.1	-10000	0	-0.62	18	18
PI3K	-0.002	0.03	-10000	0	-0.46	3	3
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.029	0.16	-10000	0	-0.59	49	49
somite specification	-0.051	0.2	-10000	0	-0.64	37	37
SHH Np/Cholesterol/PTCH1	-0.1	0.23	-10000	0	-0.57	81	81
SHH Np/Cholesterol/PTCH2	-0.084	0.15	-10000	0	-0.35	161	161
SHH Np/Cholesterol/Megalin	-0.19	0.22	-10000	0	-0.4	314	314
SHH	-0.079	0.2	-10000	0	-0.45	148	148
catabolic process	-0.055	0.21	-10000	0	-0.58	53	53
SMO/Vitamin D3	-0.092	0.23	-10000	0	-0.59	75	75
SHH Np/Cholesterol/Hhip	-0.15	0.21	-10000	0	-0.39	259	259
LRP2	-0.2	0.3	-10000	0	-0.61	225	225
receptor-mediated endocytosis	-0.19	0.23	-10000	0	-0.59	125	125
SHH Np/Cholesterol/BOC	-0.079	0.15	-10000	0	-0.35	152	152
SHH Np/Cholesterol/CDO	-0.092	0.16	-10000	0	-0.36	170	170
mesenchymal cell differentiation	0.15	0.2	0.39	259	-10000	0	259
mol:Vitamin D3	-0.099	0.23	-10000	0	-0.57	81	81
IHH N/PTCH2	-0.006	0.1	-10000	0	-0.44	30	30
CDON	-0.015	0.13	-10000	0	-0.61	32	32
IHH N/PTCH1	-0.056	0.21	-10000	0	-0.58	53	53
Megalin/LRPAP1	-0.15	0.21	-10000	0	-0.44	225	225
PTCH2	0	0.096	-10000	0	-0.62	16	16
SHH Np/Cholesterol	-0.077	0.15	-10000	0	-0.35	148	148
PTCH1	-0.055	0.21	-10000	0	-0.58	53	53
HHIP	-0.12	0.26	-10000	0	-0.61	150	150

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.15	0.21	-10000	0	-0.5	141	141
FYN	-0.16	0.29	-10000	0	-0.6	168	168
LAT/GRAP2/SLP76	-0.17	0.23	-10000	0	-0.53	156	156
IKBKB	0.015	0	-10000	0	-10000	0	0
AKT1	-0.11	0.2	-10000	0	-0.42	152	152
B2M	0	0.085	-10000	0	-0.6	13	13
IKBKG	-0.034	0.047	-10000	0	-0.16	11	11
MAP3K8	-0.005	0.11	-10000	0	-0.59	22	22
mol:Ca2+	-0.025	0.044	-10000	0	-0.12	87	87
integrin-mediated signaling pathway	-0.008	0.054	-10000	0	-0.38	14	14
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.17	0.28	-10000	0	-0.58	176	176
TRPV6	-0.11	0.24	-10000	0	-0.62	120	120
CD28	-0.089	0.23	-10000	0	-0.61	110	110
SHC1	-0.17	0.29	-10000	0	-0.6	172	172
receptor internalization	-0.14	0.26	-10000	0	-0.56	153	153
PRF1	-0.2	0.39	-10000	0	-0.93	120	120
KRAS	0.014	0.023	-10000	0	-0.59	1	1
GRB2	0.014	0.023	-10000	0	-0.59	1	1
COT/AKT1	-0.084	0.17	-10000	0	-0.36	121	121
LAT	-0.17	0.29	-10000	0	-0.6	176	176
EntrezGene:6955	-0.003	0.006	-10000	0	-10000	0	0
CD3D	-0.15	0.27	-10000	0	-0.61	173	173
CD3E	-0.15	0.28	-10000	0	-0.61	174	174
CD3G	-0.044	0.17	-10000	0	-0.6	58	58
RASGRP2	-0.005	0.026	-10000	0	-0.18	3	3
RASGRP1	-0.11	0.21	-10000	0	-0.42	149	149
HLA-A	0.001	0.08	-10000	0	-0.59	12	12
RASSF5	0.002	0.09	-10000	0	-0.61	14	14
RAP1A/GTP/RAPL	-0.008	0.055	-10000	0	-0.38	14	14
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.014	0.066	-10000	0	-0.12	50	50
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.064	0.082	-10000	0	-0.24	51	51
PRKCA	-0.079	0.11	-10000	0	-0.27	98	98
GRAP2	-0.034	0.17	-10000	0	-0.61	53	53
mol:IP3	-0.1	0.2	0.23	61	-0.42	126	187
EntrezGene:6957	-0.003	0.007	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.14	0.24	-10000	0	-0.53	150	150
ORAI1	0.064	0.13	0.33	118	-0.43	2	120
CSK	-0.17	0.29	-10000	0	-0.6	169	169
B7 family/CD28	-0.25	0.31	-10000	0	-0.66	203	203
CHUK	0.015	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.19	0.33	-10000	0	-0.67	178	178
PTPN6	-0.18	0.3	-10000	0	-0.62	171	171
VAV1	-0.17	0.3	-10000	0	-0.6	176	176
Monovalent TCR/CD3	-0.14	0.23	-10000	0	-0.42	233	233
CBL	0.014	0.025	-10000	0	-0.62	1	1
LCK	-0.18	0.32	-10000	0	-0.64	184	184
PAG1	-0.17	0.29	-10000	0	-0.6	170	170
RAP1A	0.015	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.19	0.33	-10000	0	-0.68	175	175
CD80	-0.095	0.24	-10000	0	-0.61	116	116
CD86	-0.017	0.14	-10000	0	-0.62	33	33
PDK1/CARD11/BCL10/MALT1	-0.078	0.099	-10000	0	-0.28	67	67
HRAS	0.015	0	-10000	0	-10000	0	0
GO:0035030	-0.18	0.28	-10000	0	-0.55	199	199
CD8A	-0.07	0.21	-10000	0	-0.61	88	88
CD8B	-0.036	0.17	-10000	0	-0.62	51	51
PTPRC	-0.028	0.15	-10000	0	-0.61	43	43
PDK1/PKC theta	-0.13	0.24	-10000	0	-0.51	150	150
CSK/PAG1	-0.16	0.28	-10000	0	-0.59	161	161
SOS1	0.015	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.092	-10000	0	-0.48	22	22
GRAP2/SLP76	-0.19	0.27	-10000	0	-0.59	174	174
STIM1	0.037	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.021	0.088	-10000	0	-0.18	30	30
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.15	0.28	-10000	0	-0.59	153	153
mol:DAG	-0.11	0.16	0.14	1	-0.37	139	140
RAP1A/GDP	-0.004	0.029	-10000	0	-10000	0	0
PLCG1	0.015	0	-10000	0	-10000	0	0
CD247	-0.021	0.14	-10000	0	-0.61	37	37
cytotoxic T cell degranulation	-0.19	0.36	-10000	0	-0.86	124	124
RAP1A/GTP	-0.003	0.006	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.14	0.24	-10000	0	-0.48	174	174
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.14	0.25	0.26	50	-0.54	129	179
NRAS	0.015	0	-10000	0	-10000	0	0
ZAP70	-0.038	0.17	-10000	0	-0.6	57	57
GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
LAT/GRAP2/SLP76/VAV1	-0.17	0.22	-10000	0	-0.52	154	154
MALT1	0.015	0	-10000	0	-10000	0	0
TRAF6	0.013	0.035	-10000	0	-0.62	2	2
CD8 heterodimer	-0.078	0.21	-10000	0	-0.52	116	116
CARD11	-0.001	0.1	-10000	0	-0.62	17	17
PRKCB	-0.11	0.12	-10000	0	-0.29	141	141
PRKCE	-0.083	0.11	-10000	0	-0.27	120	120
PRKCQ	-0.16	0.27	-10000	0	-0.56	166	166
LCP2	0.007	0.072	-10000	0	-0.61	9	9
BCL10	0.015	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.09	0.17	-10000	0	-0.35	151	151
IKK complex	-0.008	0.065	-10000	0	-0.12	11	11
RAS family/GDP	-0.007	0.009	-10000	0	-10000	0	0
MAP3K14	-0.056	0.13	-10000	0	-0.3	72	72
PDPK1	-0.1	0.19	-10000	0	-0.4	144	144
TCR/CD3/MHC I/CD8/Fyn	-0.2	0.34	-10000	0	-0.66	193	193

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.079	0.16	-9999	-0.38	139	139
E-cadherin/beta catenin	-0.09	0.18	-9999	-0.44	136	136
CTNNB1	0.015	0	-9999	-10000	0	0
JUP	0.008	0.069	-9999	-0.62	8	8
CDH1	-0.11	0.25	-9999	-0.61	136	136

×

HIF-1-alpha transcription factor network

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.11	0.55	-9999	-1.1	103	103
HDAC7	0.017	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.21	0.38	-9999	-0.93	108	108
SMAD4	0.017	0.002	-9999	-10000	0	0
ID2	-0.11	0.55	-9999	-1.1	107	107
AP1	-0.056	0.17	-9999	-0.46	97	97
ABCG2	-0.11	0.56	-9999	-1.1	108	108
HIF1A	0.01	0.1	-9999	-0.63	2	2
TFF3	-0.16	0.57	-9999	-1.1	124	124
GATA2	-0.002	0.11	-9999	-0.61	20	20
AKT1	0.007	0.11	-9999	-0.39	1	1
response to hypoxia	-0.01	0.12	-9999	-0.25	16	16
MCL1	-0.11	0.55	-9999	-1.1	103	103
NDRG1	-0.11	0.56	-9999	-1.1	105	105
SERPINE1	-0.21	0.62	-9999	-1.2	147	147
FECH	-0.11	0.55	-9999	-1.1	105	105
FURIN	-0.11	0.55	-9999	-1.1	104	104
NCOA2	-0.018	0.14	-9999	-0.63	36	36
EP300	0.023	0.18	-9999	-0.34	43	43
HMOX1	-0.13	0.58	-9999	-1.2	114	114
BHLHE40	-0.11	0.56	-9999	-1.1	104	104
BHLHE41	-0.11	0.56	-9999	-1.1	108	108
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.019	0.057	-9999	-0.41	5	5
ENG	0.082	0.14	-9999	-0.66	5	5
JUN	0.008	0.067	-9999	-0.6	8	8
RORA	-0.11	0.55	-9999	-1.1	107	107
ABCB1	-0.066	0.18	-9999	-1.4	10	10
TFRC	-0.11	0.56	-9999	-1.1	108	108
CXCR4	-0.12	0.57	-9999	-1.1	107	107
TF	-0.15	0.59	-9999	-1.2	124	124
CITED2	-0.11	0.55	-9999	-1.1	107	107
HIF1A/ARNT	-0.28	0.54	-9999	-1.3	115	115
LDHA	-0.06	0.15	-9999	-0.6	42	42
ETS1	-0.11	0.55	-9999	-1.1	107	107
PGK1	-0.11	0.56	-9999	-1.1	108	108
NOS2	-0.14	0.58	-9999	-1.1	123	123
ITGB2	-0.12	0.57	-9999	-1.1	112	112
ALDOA	-0.11	0.55	-9999	-1.1	103	103
Cbp/p300/CITED2	-0.19	0.55	-9999	-1.2	108	108
FOS	-0.073	0.22	-9999	-0.61	95	95
HK2	-0.12	0.56	-9999	-1.1	111	111
SP1	0.026	0.007	-9999	-10000	0	0
GCK	-0.084	0.47	-9999	-1.1	87	87
HK1	-0.11	0.55	-9999	-1.1	104	104
NPM1	-0.11	0.55	-9999	-1.1	107	107
EGLN1	-0.11	0.55	-9999	-1.1	102	102
CREB1	0.023	0.006	-9999	-10000	0	0
PGM1	-0.11	0.55	-9999	-1.1	107	107
SMAD3	0.017	0.002	-9999	-10000	0	0
EDN1	-0.032	0.3	-9999	-0.9	36	36
IGFBP1	-0.16	0.58	-9999	-1.1	119	119
VEGFA	-0.099	0.51	-9999	-0.97	118	118
HIF1A/JAB1	-0.014	0.036	-9999	-0.46	2	2
CP	-0.2	0.6	-9999	-1.2	130	130
CXCL12	-0.11	0.56	-9999	-1.1	104	104
COPS5	0.016	0.004	-9999	-10000	0	0
SMAD3/SMAD4	0	0.002	-9999	-10000	0	0
BNIP3	-0.11	0.55	-9999	-1.1	108	108
EGLN3	-0.11	0.56	-9999	-1.1	110	110
CA9	-0.19	0.62	-9999	-1.2	141	141
TERT	-0.18	0.56	-9999	-1.1	120	120
ENO1	-0.11	0.55	-9999	-1.1	107	107
PFKL	-0.11	0.55	-9999	-1.1	107	107
NCOA1	0.016	0.002	-9999	-10000	0	0
ADM	-0.18	0.62	-9999	-1.2	135	135
ARNT	0	0.088	-9999	-10000	0	0
HNF4A	-0.04	0.15	-9999	-0.59	42	42
ADFP	-0.16	0.52	-9999	-1.1	113	113
SLC2A1	-0.057	0.45	-9999	-0.86	91	91
LEP	-0.15	0.55	-9999	-1.1	105	105
HIF1A/ARNT/Cbp/p300	-0.23	0.39	-9999	-0.96	109	109
EPO	-0.031	0.41	-9999	-0.95	45	45
CREBBP	0.024	0.18	-9999	-0.34	40	40
HIF1A/ARNT/Cbp/p300/HDAC7	-0.23	0.41	-9999	-0.98	114	114
PFKFB3	-0.11	0.55	-9999	-1.1	103	103
NT5E	-0.11	0.56	-9999	-1.1	110	110

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.049	0.055	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.12	0.16	-9999	-0.46	82	82
JUN	-0.1	0.2	-9999	-0.53	80	80
HRAS	0.015	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.21	0.25	-9999	-0.49	222	222
RAP1A	0.015	0	-9999	-10000	0	0
FRS2	0.012	0.047	-9999	-0.6	4	4
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.21	0.25	-9999	-0.58	126	126
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.013	0.035	-9999	-0.62	2	2
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.14	0.21	-9999	-0.4	234	234
RHOA	0.015	0	-9999	-10000	0	0
RAP1A/GTP	-0.19	0.22	-9999	-0.66	81	81
GRB7	-0.038	0.16	-9999	-0.59	54	54
RET51/GFRalpha1/GDNF	-0.21	0.25	-9999	-0.58	125	125
MAPKKK cascade	-0.16	0.2	-9999	-0.61	80	80
BCAR1	0.014	0.025	-9999	-0.62	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.14	0.21	-9999	-0.4	231	231
lamellipodium assembly	-0.12	0.14	-9999	-0.42	83	83
RET51/GFRalpha1/GDNF/SHC	-0.21	0.26	-9999	-0.5	221	221
PIK3CA	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.14	0.21	-9999	-0.41	234	234
RET9/GFRalpha1/GDNF/Shank3	-0.14	0.21	-9999	-0.4	238	238
MAPK3	-0.15	0.23	-9999	-0.62	81	81
DOK1	0.014	0.025	-9999	-0.62	1	1
DOK6	-0.11	0.25	-9999	-0.62	134	134
PXN	0.015	0	-9999	-10000	0	0
neurite development	-0.15	0.24	-9999	-0.54	137	137
DOK5	0.004	0.085	-9999	-0.62	12	12
GFRA1	-0.16	0.28	-9999	-0.61	186	186
MAPK8	-0.11	0.21	-9999	-0.55	82	82
HRAS/GTP	-0.18	0.23	-9999	-0.69	78	78
tube development	-0.13	0.19	-9999	-0.47	94	94
MAPK1	-0.15	0.23	-9999	-0.62	81	81
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.075	0.17	-9999	-0.54	38	38
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.013	0.035	-9999	-0.62	2	2
PDLIM7	0.003	0.083	-9999	-0.59	13	13
RET51/GFRalpha1/GDNF/Dok6	-0.26	0.31	-9999	-0.79	134	134
SHC1	0.001	0.092	-9999	-0.59	16	16
RET51/GFRalpha1/GDNF/Dok4	-0.21	0.25	-9999	-0.48	223	223
RET51/GFRalpha1/GDNF/Dok5	-0.21	0.25	-9999	-0.48	228	228
PRKCA	0.013	0.035	-9999	-0.62	2	2
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.11	0.21	-9999	-0.58	77	77
PIK3R1	0.012	0.043	-9999	-0.62	3	3
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.078	0.18	-9999	-0.54	44	44
RET51/GFRalpha1/GDNF/Grb7	-0.23	0.27	-9999	-0.49	267	267
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.13	0.26	-9999	-0.61	151	151
DOK4	0.009	0.065	-9999	-0.62	7	7
JNK cascade	-0.1	0.2	-9999	-0.52	80	80
RET9/GFRalpha1/GDNF/FRS2	-0.14	0.2	-9999	-0.39	233	233
SHANK3	0.002	0.089	-9999	-0.6	14	14
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.078	0.17	-9999	-0.53	44	44
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.13	0.22	-9999	-0.6	80	80
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.13	0.22	-9999	-0.59	78	78
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.14	0.25	-9999	-0.68	83	83
PI3K	-0.14	0.27	-9999	-0.7	84	84
SOS1	0.015	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.13	0.19	-9999	-0.47	94	94
GRB10	0.006	0.075	-9999	-0.6	10	10
activation of MAPKK activity	-0.12	0.22	-9999	-0.51	109	109
RET51/GFRalpha1/GDNF/FRS2	-0.21	0.25	-9999	-0.48	220	220
GAB1	0.014	0.025	-9999	-0.62	1	1
IRS1	0.009	0.065	-9999	-0.62	7	7
IRS2	0.014	0.023	-9999	-0.59	1	1
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.14	0.25	-9999	-0.68	83	83
RET51/GFRalpha1/GDNF/PKC alpha	-0.21	0.25	-9999	-0.48	220	220
GRB2	0.014	0.023	-9999	-0.59	1	1
PRKACA	0.015	0	-9999	-10000	0	0
GDNF	-0.062	0.2	-9999	-0.62	79	79
RAC1	0.015	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.21	0.25	-9999	-0.49	220	220
Rac1/GTP	-0.14	0.18	-9999	-0.52	83	83
RET9/GFRalpha1/GDNF	-0.15	0.22	-9999	-0.44	231	231
GFRalpha1/GDNF	-0.17	0.25	-9999	-0.5	231	231

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.014	0.1	-10000	0	-0.65	12	12
NFATC2	-0.096	0.28	-10000	0	-0.72	75	75
NFATC3	-0.029	0.11	0.28	1	-0.31	9	10
CD40LG	-0.34	0.47	-10000	0	-1	153	153
ITCH	-0.02	0.12	-10000	0	-10000	0	0
CBLB	-0.021	0.12	-10000	0	-0.51	1	1
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.39	0.44	-10000	0	-0.95	198	198
JUNB	-0.029	0.16	-10000	0	-0.6	48	48
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.078	0.12	-10000	0	-10000	0	0
T cell anergy	-0.076	0.19	-10000	0	-0.43	93	93
TLE4	-0.048	0.23	-10000	0	-0.7	43	43
Jun/NFAT1-c-4/p21SNFT	-0.3	0.41	-10000	0	-1	134	134
AP-1/NFAT1-c-4	-0.42	0.55	-10000	0	-1.3	148	148
IKZF1	-0.058	0.25	-10000	0	-0.77	51	51
T-helper 2 cell differentiation	-0.16	0.28	-10000	0	-0.75	72	72
AP-1/NFAT1	-0.15	0.23	-10000	0	-0.57	119	119
CALM1	-0.018	0.079	-10000	0	-10000	0	0
EGR2	-0.22	0.52	-10000	0	-1.2	105	105
EGR3	-0.22	0.52	-10000	0	-1.2	109	109
NFAT1/FOXP3	-0.097	0.23	-10000	0	-0.65	68	68
EGR1	-0.086	0.23	-10000	0	-0.61	105	105
JUN	-0.007	0.071	-10000	0	-0.61	8	8
EGR4	-0.17	0.28	-10000	0	-0.61	192	192
mol:Ca2+	-0.037	0.086	-10000	0	-10000	0	0
GBP3	-0.14	0.35	-10000	0	-0.78	130	130
FOSL1	-0.14	0.27	-10000	0	-0.6	163	163
NFAT1-c-4/MAF/IRF4	-0.25	0.4	-10000	0	-1	112	112
DGKA	-0.042	0.21	-10000	0	-0.65	40	40
CREM	0.013	0.033	-10000	0	-0.59	2	2
NFAT1-c-4/PPARG	-0.26	0.42	-10000	0	-1	118	118
CTLA4	-0.099	0.28	-10000	0	-0.72	92	92
NFAT1-c-4 (dimer)/EGR1	-0.3	0.48	-10000	0	-1.1	138	138
NFAT1-c-4 (dimer)/EGR4	-0.34	0.44	-10000	0	-1.1	138	138
FOS	-0.09	0.22	-10000	0	-0.62	95	95
IFNG	-0.14	0.22	-10000	0	-0.71	52	52
T cell activation	-0.13	0.26	-10000	0	-0.81	36	36
MAF	0.012	0.043	-10000	0	-0.62	3	3
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.16	0.38	1.2	46	-10000	0	46
TNF	-0.38	0.49	-10000	0	-1.1	178	178
FASLG	-0.26	0.51	-10000	0	-1.3	98	98
TBX21	-0.044	0.18	-10000	0	-0.6	66	66
BATF3	-0.054	0.19	-10000	0	-0.6	76	76
PRKCQ	-0.021	0.15	-10000	0	-0.62	39	39
PTPN1	-0.042	0.21	-10000	0	-0.65	40	40
NFAT1-c-4/ICER1	-0.25	0.4	-10000	0	-0.99	118	118
GATA3	-0.11	0.25	-10000	0	-0.6	138	138
T-helper 1 cell differentiation	-0.13	0.23	-10000	0	-0.7	52	52
IL2RA	-0.37	0.4	-10000	0	-0.88	201	201
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.043	0.21	-10000	0	-0.66	41	41
E2F1	-0.01	0.13	-10000	0	-0.62	29	29
PPARG	-0.015	0.13	-10000	0	-0.61	32	32
SLC3A2	-0.042	0.21	-10000	0	-0.62	47	47
IRF4	-0.037	0.17	-10000	0	-0.6	56	56
PTGS2	-0.37	0.51	-10000	0	-1.1	172	172
CSF2	-0.33	0.45	-10000	0	-1.1	140	140
JunB/Fra1/NFAT1-c-4	-0.32	0.44	-10000	0	-1.1	127	127
IL4	-0.16	0.29	-10000	0	-0.8	70	70
IL5	-0.33	0.45	-10000	0	-1	140	140
IL2	-0.14	0.27	-10000	0	-0.84	35	35
IL3	-0.07	0.11	-10000	0	-0.88	9	9
RNF128	-0.14	0.3	-10000	0	-0.6	197	197
NFATC1	-0.16	0.39	-10000	0	-1.2	45	45
CDK4	0.077	0.26	0.67	22	-0.62	12	34
PTPRK	-0.042	0.21	-10000	0	-0.62	46	46
IL8	-0.43	0.51	-10000	0	-1.1	197	197
POU2F1	0.007	0.074	-10000	0	-0.62	9	9

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.012	0.04	-9999	-0.59	3	3
ITGB7	-0.027	0.16	-9999	-0.61	45	45
ITGA4	-0.07	0.21	-9999	-0.6	92	92
alpha4/beta7 Integrin	-0.089	0.18	-9999	-0.46	131	131
alpha4/beta1 Integrin	-0.062	0.16	-9999	-0.45	92	92

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.007	0.059	-10000	0	-0.46	10	10
fibroblast growth factor receptor signaling pathway	-0.007	0.059	-10000	0	-0.46	10	10
LAMA1	-0.071	0.22	-10000	0	-0.62	91	91
PRNP	0.014	0.025	-10000	0	-0.62	1	1
GPC1/SLIT2	-0.11	0.19	-10000	0	-0.44	163	163
SMAD2	0.034	0.047	-10000	0	-0.31	12	12
GPC1/PrPc/Cu2+	-0.005	0.047	-10000	0	-0.41	8	8
GPC1/Laminin alpha1	-0.066	0.16	-10000	0	-0.46	95	95
TDGF1	-0.087	0.23	-10000	0	-0.61	108	108
CRIPTO/GPC1	-0.076	0.18	-10000	0	-0.46	110	110
APP/GPC1	-0.005	0.046	-10000	0	-0.43	8	8
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.038	0.16	-10000	0	-0.39	112	112
FLT1	0.014	0.025	-10000	0	-0.62	1	1
GPC1/TGFB/TGFBR1/TGFBR2	-0.006	0.047	-10000	0	-0.36	12	12
SERPINC1	-0.004	0.1	-10000	0	-0.59	19	19
FYN	-0.037	0.16	-10000	0	-0.39	110	110
FGR	-0.04	0.16	-10000	0	-0.39	116	116
positive regulation of MAPKKK cascade	-0.065	0.19	-10000	0	-0.46	94	94
SLIT2	-0.13	0.26	-10000	0	-0.6	157	157
GPC1/NRG	-0.12	0.2	-10000	0	-0.44	188	188
NRG1	-0.15	0.28	-10000	0	-0.61	181	181
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.067	0.14	-10000	0	-0.36	122	122
LYN	-0.039	0.16	-10000	0	-0.39	114	114
mol:Spermine	0.008	0.049	-10000	0	-0.44	8	8
cell growth	-0.007	0.059	-10000	0	-0.46	10	10
BMP signaling pathway	-0.008	0.066	0.59	8	-10000	0	8
SRC	-0.038	0.16	-10000	0	-0.39	112	112
TGFBR1	0.014	0.025	-10000	0	-0.62	1	1
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.22	0.3	-10000	0	-0.61	250	250
GPC1	0.008	0.066	-10000	0	-0.59	8	8
TGFBR1 (dimer)	0.014	0.025	-10000	0	-0.62	1	1
VEGFA	-0.091	0.23	-10000	0	-0.59	118	118
BLK	-0.09	0.2	-10000	0	-0.4	188	188
HCK	-0.046	0.17	-10000	0	-0.4	121	121
FGF2	0.013	0.034	-10000	0	-0.61	2	2
FGFR1	0.012	0.041	-10000	0	-0.6	3	3
VEGFR1 homodimer	0.014	0.025	-10000	0	-0.62	1	1
TGFBR2	0.012	0.04	-10000	0	-0.59	3	3
cell death	-0.005	0.046	-10000	0	-0.42	8	8
ATIII/GPC1	-0.017	0.083	-10000	0	-0.42	27	27
PLA2G2A/GPC1	-0.17	0.22	-10000	0	-0.44	254	254
LCK	-0.11	0.22	-10000	0	-0.41	213	213
neuron differentiation	-0.12	0.2	-10000	0	-0.44	188	188
PrPc/Cu2+	-0.001	0.018	-10000	0	-0.46	1	1
APP	0.015	0	-10000	0	-10000	0	0
TGFBR2 (dimer)	0.012	0.04	-10000	0	-0.59	3	3

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.077	0.18	-9999	-0.48	93	93
alphaM/beta2 Integrin/GPIbA	-0.062	0.16	-9999	-0.52	67	67
alphaM/beta2 Integrin/proMMP-9	-0.21	0.23	-9999	-0.43	318	318
PLAUR	-0.073	0.21	-9999	-0.59	97	97
HMGB1	0	0.022	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.053	0.15	-9999	-0.54	53	53
AGER	-0.018	0.11	-9999	-0.64	19	19
RAP1A	0.015	0	-9999	-10000	0	0
SELPLG	-0.012	0.13	-9999	-0.62	29	29
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.12	0.18	-9999	-0.67	45	45
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.25	0.3	-9999	-0.6	285	285
CYR61	-0.096	0.24	-9999	-0.61	119	119
TLN1	0.015	0	-9999	-10000	0	0
Rap1/GTP	-0.1	0.14	-9999	-0.42	80	80
RHOA	0.015	0	-9999	-10000	0	0
P-selectin oligomer	-0.036	0.16	-9999	-0.59	52	52
MYH2	-0.1	0.18	-9999	-0.47	76	76
MST1R	-0.003	0.11	-9999	-0.62	19	19
leukocyte activation during inflammatory response	-0.1	0.18	-9999	-0.46	90	90
APOB	-0.078	0.22	-9999	-0.6	99	99
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.025	0.15	-9999	-0.6	44	44
JAM3	0.014	0.023	-9999	-0.59	1	1
GP1BA	0.001	0.094	-9999	-0.62	15	15
alphaM/beta2 Integrin/CTGF	-0.072	0.18	-9999	-0.51	82	82
alphaM/beta2 Integrin	-0.1	0.18	-9999	-0.47	87	87
JAM3 homodimer	0.014	0.023	-9999	-0.59	1	1
ICAM2	0.014	0.023	-9999	-0.59	1	1
ICAM1	-0.05	0.19	-9999	-0.6	72	72
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.1	0.18	-9999	-0.47	87	87
cell adhesion	-0.061	0.16	-9999	-0.52	67	67
NFKB1	-0.14	0.27	-9999	-0.71	76	76
THY1	0.003	0.088	-9999	-0.62	13	13
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.072	0.15	-9999	-0.38	127	127
alphaM/beta2 Integrin/LRP/tPA	-0.11	0.19	-9999	-0.44	113	113
IL6	-0.22	0.36	-9999	-0.86	114	114
ITGB2	-0.035	0.14	-9999	-0.64	36	36
elevation of cytosolic calcium ion concentration	-0.17	0.26	-9999	-0.55	171	171
alphaM/beta2 Integrin/JAM2/JAM3	-0.042	0.14	-9999	-0.49	53	53
JAM2	0.014	0.025	-9999	-0.62	1	1
alphaM/beta2 Integrin/ICAM1	-0.1	0.2	-9999	-0.55	73	73
alphaM/beta2 Integrin/uPA/Plg	-0.13	0.2	-9999	-0.45	150	150
RhoA/GTP	-0.1	0.18	-9999	-0.5	74	74
positive regulation of phagocytosis	-0.1	0.18	-9999	-0.6	55	55
Ron/MSP	-0.041	0.13	-9999	-0.46	60	60
alphaM/beta2 Integrin/uPAR/uPA	-0.17	0.26	-9999	-0.57	158	158
alphaM/beta2 Integrin/uPAR	-0.11	0.2	-9999	-0.47	140	140
PLAU	-0.13	0.26	-9999	-0.6	156	156
PLAT	-0.11	0.24	-9999	-0.59	136	136
actin filament polymerization	-0.096	0.17	-9999	-0.45	76	76
MST1	-0.025	0.15	-9999	-0.61	43	43
alphaM/beta2 Integrin/lipoprotein(a)	-0.1	0.19	-9999	-0.47	90	90
TNF	-0.2	0.35	-9999	-0.82	119	119
RAP1B	0.009	0.061	-9999	-0.59	7	7
alphaM/beta2 Integrin/uPA	-0.14	0.22	-9999	-0.45	195	195
fibrinolysis	-0.13	0.2	-9999	-0.44	150	150
HCK	0	0.096	-9999	-0.61	16	16
dendritic cell antigen processing and presentation	-0.1	0.18	-9999	-0.47	87	87
VTN	-0.017	0.14	-9999	-0.62	34	34
alphaM/beta2 Integrin/CYR61	-0.12	0.22	-9999	-0.49	153	153
LPA	-0.016	0.12	-9999	-0.59	29	29
LRP1	0.013	0.035	-9999	-0.62	2	2
cell migration	-0.2	0.24	-9999	-0.48	187	187
FN1	-0.028	0.16	-9999	-0.59	48	48
alphaM/beta2 Integrin/Thy1	-0.06	0.16	-9999	-0.52	66	66
MPO	-0.11	0.25	-9999	-0.61	136	136
KNG1	-0.018	0.11	-9999	-0.59	25	25
RAP1/GDP	-0.004	0.037	-9999	-0.36	7	7
ROCK1	-0.089	0.18	-9999	-0.48	67	67
ELA2	0	0	-9999	-10000	0	0
PLG	-0.002	0.046	-9999	-0.59	4	4
CTGF	-0.016	0.14	-9999	-0.61	34	34
alphaM/beta2 Integrin/Hck	-0.061	0.19	-9999	-0.62	55	55
ITGAM	-0.034	0.15	-9999	-0.65	35	35
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.083	0.21	-9999	-0.58	75	75
HP	-0.13	0.26	-9999	-0.6	153	153
leukocyte adhesion	-0.095	0.16	-9999	-0.57	54	54
SELP	-0.036	0.16	-9999	-0.59	52	52

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.037	0.12	-9999	-0.45	54	54
VLDLR	-0.004	0.11	-9999	-0.62	20	20
CRKL	0.014	0.023	-9999	-0.59	1	1
LRPAP1	0.015	0	-9999	-10000	0	0
FYN	0.015	0	-9999	-10000	0	0
ITGA3	-0.028	0.16	-9999	-0.59	48	48
RELN/VLDLR/Fyn	-0.13	0.19	-9999	-0.38	221	221
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.008	0.049	-9999	-10000	0	0
AKT1	-0.086	0.17	-9999	-0.48	57	57
MAP2K7	0.014	0.025	-9999	-0.62	1	1
RAPGEF1	0.013	0.035	-9999	-0.62	2	2
DAB1	-0.093	0.24	-9999	-0.62	114	114
RELN/LRP8/DAB1	-0.16	0.21	-9999	-0.39	281	281
LRPAP1/LRP8	-0.001	0.025	-9999	-0.46	2	2
RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.39	193	193
DAB1/alpha3/beta1 Integrin	-0.16	0.22	-9999	-0.63	83	83
long-term memory	-0.31	0.31	-9999	-0.72	208	208
DAB1/LIS1	-0.15	0.19	-9999	-0.61	58	58
DAB1/CRLK/C3G	-0.14	0.19	-9999	-0.59	59	59
PIK3CA	0.015	0	-9999	-10000	0	0
DAB1/NCK2	-0.15	0.19	-9999	-0.61	58	58
ARHGEF2	0.014	0.025	-9999	-0.62	1	1
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.17	0.28	-9999	-0.6	195	195
CDK5R1	-0.035	0.17	-9999	-0.62	53	53
RELN	-0.18	0.29	-9999	-0.61	211	211
PIK3R1	0.012	0.043	-9999	-0.62	3	3
RELN/LRP8/Fyn	-0.12	0.17	-9999	-0.37	211	211
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.24	0.27	-9999	-0.68	140	140
MAPK8	0.007	0.074	-9999	-0.62	9	9
RELN/VLDLR/DAB1	-0.17	0.22	-9999	-0.4	287	287
ITGB1	0.012	0.04	-9999	-0.59	3	3
MAP1B	-0.13	0.22	-9999	-0.63	58	58
RELN/LRP8	-0.12	0.17	-9999	-0.37	211	211
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.24	0.25	-9999	-0.66	131	131
PI3K	-0.002	0.03	-9999	-0.46	3	3
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.032	0.12	-9999	-0.44	49	49
RAP1A	-0.092	0.2	-9999	-0.55	59	59
PAFAH1B1	0.015	0	-9999	-10000	0	0
MAPK8IP1	0.009	0.06	-9999	-0.62	6	6
CRLK/C3G	-0.002	0.03	-9999	-0.44	3	3
GRIN2B	-0.17	0.28	-9999	-0.6	200	200
NCK2	0.015	0	-9999	-10000	0	0
neuron differentiation	-0.048	0.14	-9999	-0.42	44	44
neuron adhesion	-0.092	0.22	-9999	-0.55	84	84
LRP8	0.013	0.035	-9999	-0.62	2	2
GSK3B	-0.073	0.17	-9999	-0.49	44	44
RELN/VLDLR/DAB1/Fyn	-0.16	0.21	-9999	-0.41	200	200
MAP3K11	0.015	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.1	0.18	-9999	-0.5	62	62
CDK5	0.014	0.023	-9999	-0.59	1	1
MAPT	-0.009	0.14	-9999	-0.56	37	37
neuron migration	-0.089	0.22	-9999	-0.54	75	75
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.049	0.14	-9999	-0.42	44	44
RELN/VLDLR	-0.11	0.17	-9999	-0.69	11	11

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0.035	-9999	-0.62	2	2
Aurora C/Aurora B/INCENP	-0.12	0.17	-9999	-0.35	234	234
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.035	0.048	-9999	-0.24	1	1
AURKB	-0.18	0.29	-9999	-0.61	209	209
AURKC	-0.015	0.13	-9999	-0.6	33	33

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.1	0.23	-10000	0	-0.59	64	64
PTK2B	-0.005	0.11	-10000	0	-0.59	23	23
mol:Ca2+	-0.042	0.24	-10000	0	-0.7	52	52
EDN1	-0.083	0.19	-10000	0	-0.63	44	44
EDN3	-0.056	0.2	-10000	0	-0.62	75	75
EDN2	-0.029	0.14	-10000	0	-0.59	40	40
HRAS/GDP	-0.08	0.2	-10000	0	-0.51	60	60
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.045	0.16	-10000	0	-0.44	44	44
ADCY4	-0.15	0.26	-10000	0	-0.55	157	157
ADCY5	-0.18	0.3	-10000	0	-0.63	167	167
ADCY6	-0.15	0.26	-10000	0	-0.54	153	153
ADCY7	-0.15	0.26	-10000	0	-0.54	154	154
ADCY1	-0.2	0.28	-10000	0	-0.57	189	189
ADCY2	-0.17	0.29	-10000	0	-0.6	166	166
ADCY3	-0.15	0.26	-10000	0	-0.53	164	164
ADCY8	-0.18	0.28	-10000	0	-0.57	177	177
ADCY9	-0.15	0.26	-10000	0	-0.54	154	154
arachidonic acid secretion	-0.069	0.21	-10000	0	-0.53	68	68
ETB receptor/Endothelin-1/Gq/GTP	-0.031	0.15	-10000	0	-0.43	42	42
GNAO1	-0.012	0.13	-10000	0	-0.62	28	28
HRAS	0.014	0.005	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.094	0.22	0.35	35	-0.56	62	97
ETA receptor/Endothelin-1/Gs/GTP	-0.17	0.27	0.33	30	-0.56	164	194
mol:GTP	0.001	0.005	-10000	0	-10000	0	0
COL3A1	-0.25	0.37	-10000	0	-0.67	258	258
EDNRB	-0.035	0.16	-10000	0	-0.63	45	45
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.12	0.27	-10000	0	-0.76	59	59
CYSLTR1	-0.11	0.26	-10000	0	-0.71	59	59
SLC9A1	-0.067	0.11	0.21	20	-0.34	30	50
mol:GDP	-0.095	0.21	-10000	0	-0.51	82	82
SLC9A3	-0.085	0.26	-10000	0	-0.69	71	71
RAF1	-0.089	0.21	-10000	0	-0.54	72	72
JUN	-0.025	0.19	-10000	0	-0.67	20	20
JAK2	-0.1	0.23	-10000	0	-0.59	63	63
mol:IP3	-0.048	0.17	-10000	0	-0.48	46	46
ETA receptor/Endothelin-1	-0.14	0.27	0.4	36	-0.68	63	99
PLCB1	-0.03	0.16	-10000	0	-0.62	46	46
PLCB2	0.001	0.091	-10000	0	-0.62	14	14
ETA receptor/Endothelin-3	-0.099	0.2	-10000	0	-0.53	99	99
FOS	-0.11	0.31	-10000	0	-0.82	86	86
Gai/GDP	-0.022	0.2	-10000	0	-0.9	28	28
CRK	0.015	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.11	0.26	-10000	0	-0.58	96	96
BCAR1	0.015	0.025	-10000	0	-0.62	1	1
PRKCB1	-0.046	0.16	-10000	0	-0.46	48	48
GNAQ	0.015	0.007	-10000	0	-10000	0	0
GNAZ	0.012	0.043	-10000	0	-0.62	3	3
GNAL	-0.13	0.27	-10000	0	-0.62	149	149
Gs family/GDP	-0.18	0.22	-10000	0	-0.51	167	167
ETA receptor/Endothelin-1/Gq/GTP	-0.042	0.16	-10000	0	-0.41	46	46
MAPK14	-0.026	0.15	-10000	0	-0.49	33	33
TRPC6	-0.047	0.25	-10000	0	-0.78	48	48
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	-0.02	0.15	-10000	0	-0.62	37	37
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.036	0.16	-10000	0	-0.48	41	41
ETB receptor/Endothelin-2	-0.053	0.16	-10000	0	-0.47	82	82
ETB receptor/Endothelin-3	-0.082	0.19	-10000	0	-0.49	111	111
ETB receptor/Endothelin-1	-0.09	0.19	-10000	0	-0.51	82	82
MAPK3	-0.11	0.29	-10000	0	-0.73	88	88
MAPK1	-0.11	0.29	-10000	0	-0.74	86	86
Rac1/GDP	-0.08	0.2	-10000	0	-0.5	64	64
cAMP biosynthetic process	-0.17	0.28	-10000	0	-0.57	174	174
MAPK8	-0.038	0.2	-10000	0	-0.61	41	41
SRC	0.013	0.035	-10000	0	-0.63	2	2
ETB receptor/Endothelin-1/Gi/GTP	-0.03	0.14	-10000	0	-0.43	46	46
p130Cas/CRK/Src/PYK2	-0.084	0.23	-10000	0	-0.57	66	66
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.08	0.2	-10000	0	-0.5	65	65
COL1A2	-0.16	0.33	-10000	0	-0.7	142	142
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.077	0.16	-10000	0	-0.5	67	67
mol:DAG	-0.048	0.17	-10000	0	-0.48	46	46
MAP2K2	-0.092	0.24	-10000	0	-0.59	88	88
MAP2K1	-0.092	0.24	-10000	0	-0.58	90	90
EDNRA	-0.069	0.18	-10000	0	-0.67	29	29
positive regulation of muscle contraction	-0.078	0.2	-10000	0	-0.55	52	52
Gq family/GDP	-0.11	0.18	-10000	0	-0.56	58	58
HRAS/GTP	-0.09	0.2	-10000	0	-0.51	72	72
PRKCH	-0.038	0.16	-10000	0	-0.52	31	31
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCA	-0.039	0.16	-10000	0	-0.51	35	35
PRKCB	-0.083	0.2	-10000	0	-0.51	60	60
PRKCE	-0.044	0.17	-10000	0	-0.5	39	39
PRKCD	-0.05	0.19	-10000	0	-0.53	52	52
PRKCG	-0.15	0.23	-10000	0	-0.5	137	137
regulation of vascular smooth muscle contraction	-0.13	0.36	-10000	0	-0.97	82	82
PRKCQ	-0.057	0.19	-10000	0	-0.51	59	59
PLA2G4A	-0.077	0.23	-10000	0	-0.58	68	68
GNA14	-0.009	0.12	-10000	0	-0.61	26	26
GNA15	-0.009	0.12	-10000	0	-0.61	26	26
GNA12	0.014	0.025	-10000	0	-0.62	1	1
GNA11	0.005	0.078	-10000	0	-0.63	10	10
Rac1/GTP	-0.094	0.22	0.34	36	-0.55	62	98
MMP1	-0.051	0.28	-10000	0	-0.59	115	115

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.094	0.22	-9999	-0.62	57	57
NF kappa B1 p50/RelA/I kappa B alpha	-0.12	0.18	-9999	-0.58	57	57
alphaV/beta3 Integrin/Osteopontin/Src	-0.1	0.18	-9999	-0.44	156	156
AP1	-0.12	0.26	-9999	-0.64	86	86
ILK	-0.1	0.23	-9999	-0.65	51	51
bone resorption	-0.11	0.26	-9999	-0.61	107	107
PTK2B	-0.006	0.11	-9999	-0.59	23	23
PYK2/p130Cas	-0.14	0.2	-9999	-0.62	67	67
ITGAV	0.016	0.025	-9999	-0.61	1	1
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.061	0.16	-9999	-0.46	90	90
alphaV/beta3 Integrin/Osteopontin	-0.15	0.23	-9999	-0.54	115	115
MAP3K1	-0.11	0.23	-9999	-0.6	69	69
JUN	0.008	0.067	-9999	-0.6	8	8
MAPK3	-0.1	0.24	-9999	-0.53	112	112
MAPK1	-0.1	0.24	-9999	-0.54	108	108
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
MAPK8	-0.095	0.23	-9999	-0.59	69	69
ITGB3	-0.098	0.24	-9999	-0.6	125	125
NFKBIA	-0.093	0.24	-9999	-0.63	64	64
FOS	-0.074	0.22	-9999	-0.61	95	95
CD44	-0.055	0.2	-9999	-0.61	75	75
CHUK	0.015	0	-9999	-10000	0	0
PLAU	-0.17	0.37	-9999	-0.85	128	128
NF kappa B1 p50/RelA	-0.13	0.19	-9999	-0.61	57	57
BCAR1	0.014	0.025	-9999	-0.62	1	1
RELA	0.015	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.083	0.17	-9999	-0.44	126	126
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.11	0.25	-9999	-0.64	76	76
VAV3	-0.21	0.3	-9999	-0.7	134	134
MAP3K14	-0.11	0.24	-9999	-0.53	112	112
ROCK2	-0.001	0.1	-9999	-0.62	17	17
SPP1	-0.13	0.26	-9999	-0.6	155	155
RAC1	0.015	0	-9999	-10000	0	0
Rac1/GTP	-0.22	0.25	-9999	-0.64	133	133
MMP2	-0.11	0.25	-9999	-0.59	85	85

×

Thromboxane A2 receptor signaling

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
TGM2	0.006	0.061	-10000	0	-0.59	7	7
GNB1/GNG2	-0.077	0.08	-10000	0	-0.19	134	134
AKT1	-0.054	0.12	-10000	0	-0.22	81	81
EGF	-0.038	0.18	-10000	0	-0.61	57	57
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.016	0.084	-10000	0	-0.4	6	6
mol:Ca2+	-0.089	0.16	-10000	0	-0.3	186	186
LYN	0.016	0.085	-10000	0	-0.39	8	8
RhoA/GTP	-0.049	0.052	-10000	0	-0.16	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.1	0.19	-10000	0	-0.35	187	187
GNG2	0.009	0.06	-10000	0	-0.62	6	6
ARRB2	0.015	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	0.013	0.098	-10000	0	-0.39	30	30
G beta5/gamma2	-0.096	0.1	-10000	0	-0.25	122	122
PRKCH	-0.1	0.18	-10000	0	-0.34	174	174
DNM1	-0.083	0.22	-10000	0	-0.6	107	107
TXA2/TP beta/beta Arrestin3	-0.037	0.073	-10000	0	-0.25	31	31
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.034	0.16	-10000	0	-0.59	52	52
G12 family/GTP	-0.12	0.13	-10000	0	-0.3	190	190
ADRBK1	0.015	0	-10000	0	-10000	0	0
ADRBK2	0.011	0.049	-10000	0	-0.62	4	4
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	0.052	0.11	0.3	40	-10000	0	40
mol:NADP	0.009	0.06	-10000	0	-0.62	6	6
RAB11A	0.015	0	-10000	0	-10000	0	0
PRKG1	-0.032	0.17	-10000	0	-0.62	50	50
mol:IP3	-0.12	0.2	-10000	0	-0.37	190	190
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	-0.16	0.26	-10000	0	-0.5	190	190
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.028	0.12	-10000	0	-0.42	13	13
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.012	0.094	-10000	0	-0.41	11	11
RHOA	0.015	0	-10000	0	-10000	0	0
PTGIR	-0.043	0.18	-10000	0	-0.6	63	63
PRKCB1	-0.11	0.19	-10000	0	-0.36	198	198
GNAQ	0.015	0	-10000	0	-10000	0	0
mol:L-citrulline	0.009	0.06	-10000	0	-0.62	6	6
TXA2/TXA2-R family	-0.17	0.27	-10000	0	-0.52	203	203
LCK	-0.033	0.14	-10000	0	-0.41	38	38
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.032	0.077	-10000	0	-0.37	10	10
TXA2-R family/G12 family/GDP/G beta/gamma	0.024	0.046	-10000	0	-0.79	1	1
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.03	0.074	-10000	0	-0.36	9	9
MAPK14	-0.06	0.13	-10000	0	-0.24	120	120
TGM2/GTP	-0.13	0.22	-10000	0	-0.42	184	184
MAPK11	-0.061	0.13	-10000	0	-0.24	117	117
ARHGEF1	-0.045	0.1	-10000	0	-0.19	39	39
GNAI2	0.015	0	-10000	0	-10000	0	0
JNK cascade	-0.12	0.2	-10000	0	-0.38	203	203
RAB11/GDP	0.016	0.002	-10000	0	-10000	0	0
ICAM1	-0.092	0.17	-10000	0	-0.3	205	205
cAMP biosynthetic process	-0.11	0.19	-10000	0	-0.35	184	184
Gq family/GTP/EBP50	0.014	0.072	-10000	0	-0.26	29	29
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.018	0.08	-10000	0	-0.38	3	3
GNB5	0.015	0	-10000	0	-10000	0	0
GNB1	0.015	0	-10000	0	-10000	0	0
EGF/EGFR	-0.017	0.11	-10000	0	-0.33	24	24
VCAM1	-0.11	0.19	-10000	0	-0.37	194	194
TP beta/Gq family/GDP/G beta5/gamma2	0.013	0.098	-10000	0	-0.39	30	30
platelet activation	-0.08	0.17	-10000	0	-0.3	184	184
PGI2/IP	-0.041	0.13	-10000	0	-0.44	63	63
PRKACA	-0.018	0.099	-10000	0	-0.33	26	26
Gq family/GDP/G beta5/gamma2	0.011	0.093	-10000	0	-0.35	31	31
TXA2/TP beta/beta Arrestin2	-0.053	0.13	-10000	0	-0.51	38	38
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.01	0.1	-10000	0	-0.32	31	31
mol:DAG	-0.13	0.21	-10000	0	-0.41	198	198
EGFR	-0.11	0.25	-10000	0	-0.6	138	138
TXA2/TP alpha	-0.16	0.25	-10000	0	-0.48	186	186
Gq family/GTP	-0.013	0.063	-10000	0	-0.23	40	40
YES1	0.018	0.08	-10000	0	-0.38	3	3
GNAI2/GTP	-0.029	0.07	-10000	0	-0.45	3	3
PGD2/DP	-0.034	0.12	-10000	0	-0.44	52	52
SLC9A3R1	0.014	0.025	-10000	0	-0.62	1	1
FYN	0.018	0.078	-10000	0	-0.38	3	3
mol:NO	0.009	0.06	-10000	0	-0.62	6	6
GNA15	-0.009	0.12	-10000	0	-0.61	26	26
PGK/cGMP	-0.032	0.11	-10000	0	-0.39	55	55
RhoA/GDP	0.016	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.034	0.084	-10000	0	-0.47	8	8
NOS3	0.009	0.06	-10000	0	-0.62	6	6
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCA	-0.1	0.18	-10000	0	-0.34	181	181
PRKCB	-0.13	0.2	-10000	0	-0.38	203	203
PRKCE	-0.1	0.19	-10000	0	-0.35	176	176
PRKCD	-0.12	0.2	-10000	0	-0.38	196	196
PRKCG	-0.16	0.23	-10000	0	-0.43	230	230
muscle contraction	-0.16	0.25	-10000	0	-0.48	209	209
PRKCZ	-0.12	0.2	-10000	0	-0.36	206	206
ARR3	0.003	0.024	-10000	0	-0.59	1	1
TXA2/TP beta	-0.033	0.079	-10000	0	-0.38	10	10
PRKCQ	-0.11	0.19	-10000	0	-0.35	201	201
MAPKKK cascade	-0.14	0.23	-10000	0	-0.45	191	191
SELE	-0.11	0.18	-10000	0	-0.34	210	210
TP beta/GNAI2/GDP/G beta/gamma	-0.031	0.076	-10000	0	-0.48	4	4
ROCK1	0.015	0	-10000	0	-10000	0	0
GNA14	-0.009	0.12	-10000	0	-0.61	26	26
chemotaxis	-0.2	0.3	-10000	0	-0.6	208	208
GNA12	0.014	0.025	-10000	0	-0.62	1	1
GNA13	0.015	0	-10000	0	-10000	0	0
GNA11	0.006	0.078	-10000	0	-0.62	10	10
Rac1/GTP	0.004	0.006	-10000	0	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.054	0.11	0.22	191	-10000	0	191
BUB1B	-0.072	0.16	-10000	0	-0.33	174	174
PLK1	-0.006	0.054	-10000	0	-0.16	50	50
PLK1S1	0.004	0.027	-10000	0	-0.14	1	1
KIF2A	0.005	0.05	-10000	0	-0.26	3	3
regulation of mitotic centrosome separation	-0.005	0.054	-10000	0	-0.16	50	50
GOLGA2	0.014	0.025	-10000	0	-0.62	1	1
Hec1/SPC24	-0.18	0.28	-10000	0	-0.48	280	280
WEE1	-0.018	0.1	-10000	0	-0.37	34	34
cytokinesis	-0.14	0.23	-10000	0	-0.42	242	242
PP2A-alpha B56	-0.08	0.24	-10000	0	-0.67	86	86
AURKA	-0.005	0.055	-10000	0	-0.17	58	58
PICH/PLK1	-0.068	0.21	-10000	0	-0.5	105	105
CENPE	-0.053	0.16	-10000	0	-0.39	112	112
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	0.005	0.05	-10000	0	-0.26	3	3
PPP2CA	0.015	0	-10000	0	-10000	0	0
FZR1	0.015	0	-10000	0	-10000	0	0
TPX2	-0.025	0.091	-10000	0	-0.23	98	98
PAK1	-0.019	0.14	-10000	0	-0.59	37	37
SPC24	-0.17	0.28	-10000	0	-0.6	202	202
FBXW11	0.015	0	-10000	0	-10000	0	0
CLSPN	-0.046	0.11	-10000	0	-0.24	149	149
GORASP1	0.015	0	-10000	0	-10000	0	0
metaphase	0	0.005	-10000	0	-0.016	60	60
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.002	0.027	-10000	0	-0.077	49	49
G2 phase of mitotic cell cycle	-0.001	0.003	-10000	0	-0.011	22	22
STAG2	0.015	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.001	0.017	-10000	0	-0.29	1	1
spindle elongation	-0.005	0.054	-10000	0	-0.16	50	50
ODF2	0.014	0.004	-10000	0	-10000	0	0
BUB1	-0.12	0.25	-10000	0	-0.74	86	86
TPT1	0.004	0.029	-10000	0	-0.15	3	3
CDC25C	-0.072	0.15	-10000	0	-0.31	161	161
CDC25B	0.012	0.024	-10000	0	-0.58	1	1
SGOL1	-0.054	0.11	-10000	0	-0.22	191	191
RHOA	0.015	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.057	0.13	-10000	0	-0.36	86	86
CDC14B	0.013	0.004	-10000	0	-10000	0	0
CDC20	-0.17	0.28	-10000	0	-0.6	203	203
PLK1/PBIP1	-0.069	0.14	-10000	0	-0.38	114	114
mitosis	0.001	0.007	0.022	58	-0.034	1	59
FBXO5	0	0.052	-10000	0	-0.28	6	6
CDC2	-0.002	0.006	-10000	0	-0.015	83	83
NDC80	-0.17	0.28	-10000	0	-0.61	199	199
metaphase plate congression	0.003	0.033	-10000	0	-10000	0	0
ERCC6L	-0.093	0.19	-10000	0	-0.49	99	99
NLP/gamma Tubulin	0.001	0.03	-10000	0	-0.13	3	3
microtubule cytoskeleton organization	0.004	0.029	-10000	0	-0.15	3	3
G2/M transition DNA damage checkpoint	0	0.002	0.012	1	-0.011	1	2
PPP1R12A	0.015	0.001	-10000	0	-10000	0	0
interphase	0	0.002	0.012	1	-0.011	1	2
PLK1/PRC1-2	-0.13	0.22	-10000	0	-0.39	263	263
GRASP65/GM130/RAB1/GTP/PLK1	-0.008	0.032	-10000	0	-0.33	1	1
RAB1A	0.015	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.002	0.048	-10000	0	-0.44	1	1
mitotic prometaphase	-0.001	0.003	-10000	0	-0.011	45	45
proteasomal ubiquitin-dependent protein catabolic process	-0.005	0.071	-10000	0	-10000	0	0
microtubule-based process	-0.13	0.2	-10000	0	-0.38	263	263
Golgi organization	-0.005	0.054	-10000	0	-0.16	50	50
Cohesin/SA2	-0.016	0.038	-10000	0	-0.2	3	3
PPP1CB/MYPT1	0	0.024	-10000	0	-0.42	2	2
KIF20A	-0.23	0.3	-10000	0	-0.61	263	263
APC/C/CDC20	-0.1	0.19	-10000	0	-0.38	203	203
PPP2R1A	0.015	0	-10000	0	-10000	0	0
chromosome segregation	-0.068	0.14	-10000	0	-0.37	114	114
PRC1	-0.012	0.12	-10000	0	-0.59	30	30
ECT2	-0.007	0.094	-10000	0	-0.43	25	25
C13orf34	0.003	0.048	-10000	0	-0.44	1	1
NUDC	0.003	0.033	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.071	0.16	-10000	0	-0.32	174	174
spindle assembly	-0.001	0.043	-10000	0	-0.12	43	43
spindle stabilization	0.004	0.027	-10000	0	-0.14	1	1
APC/C/HCDH1	0.021	0.002	-10000	0	-10000	0	0
MKLP2/PLK1	-0.13	0.2	-10000	0	-0.38	263	263
CCNB1	-0.068	0.21	-10000	0	-0.59	92	92
PPP1CB	0.013	0.033	-10000	0	-0.59	2	2
BTRC	0.015	0	-10000	0	-10000	0	0
ROCK2	-0.001	0.08	-10000	0	-0.44	17	17
TUBG1	0.004	0.027	-10000	0	-0.13	2	2
G2/M transition of mitotic cell cycle	-0.058	0.12	-10000	0	-0.35	86	86
MLF1IP	-0.066	0.18	-10000	0	-0.46	114	114
INCENP	0.011	0.036	-10000	0	-0.63	2	2

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.15	0.38	-9999	-1.1	84	84
MKNK1	0.011	0.049	-9999	-0.62	4	4
MAPK14	-0.044	0.13	-9999	-0.35	24	24
ATF2/c-Jun	-0.021	0.13	-9999	-0.64	13	13
MAPK11	-0.046	0.13	-9999	-0.38	26	26
MITF	-0.041	0.16	-9999	-0.35	110	110
MAPKAPK5	-0.039	0.15	-9999	-0.34	108	108
KRT8	-0.11	0.22	-9999	-0.43	165	165
MAPKAPK3	0.013	0.035	-9999	-0.62	2	2
MAPKAPK2	0.015	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.065	0.19	-9999	-0.43	109	109
CEBPB	-0.051	0.18	-9999	-0.38	118	118
SLC9A1	-0.04	0.16	-9999	-0.35	108	108
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.041	0.17	-9999	-0.47	28	28
p38alpha-beta/MNK1	-0.039	0.16	-9999	-0.45	27	27
JUN	-0.021	0.13	-9999	-0.64	13	13
PPARGC1A	-0.051	0.18	-9999	-0.38	116	116
USF1	-0.039	0.15	-9999	-0.4	26	26
RAB5/GDP/GDI1	-0.053	0.09	-9999	-0.36	8	8
NOS2	-0.095	0.28	-9999	-0.98	40	40
DDIT3	-0.048	0.16	-9999	-0.42	29	29
RAB5A	0.015	0	-9999	-10000	0	0
HSPB1	-0.034	0.15	-9999	-0.44	32	32
p38alpha-beta/HBP1	-0.037	0.15	-9999	-0.42	23	23
CREB1	-0.043	0.17	-9999	-0.36	118	118
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	-0.026	0.14	-9999	-0.5	11	11
RPS6KA4	-0.039	0.15	-9999	-0.34	108	108
PLA2G4A	-0.042	0.16	-9999	-0.58	22	22
GDI1	-0.039	0.15	-9999	-0.34	108	108
TP53	-0.059	0.19	-9999	-0.43	113	113
RPS6KA5	-0.053	0.18	-9999	-0.37	125	125
ESR1	-0.052	0.17	-9999	-0.37	112	112
HBP1	0.015	0	-9999	-10000	0	0
MEF2C	-0.048	0.16	-9999	-0.36	113	113
MEF2A	-0.039	0.15	-9999	-0.34	108	108
EIF4EBP1	-0.045	0.17	-9999	-0.36	120	120
KRT19	-0.1	0.22	-9999	-0.42	161	161
ELK4	-0.039	0.15	-9999	-0.34	108	108
ATF6	-0.039	0.15	-9999	-0.34	108	108
ATF1	-0.043	0.17	-9999	-0.36	118	118
p38alpha-beta/MAPKAPK2	-0.037	0.15	-9999	-0.42	23	23
p38alpha-beta/MAPKAPK3	-0.038	0.16	-9999	-0.43	25	25

×

TCGA08_p53

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
CDKN2A	-0.12	0.21	-10000	0	-0.45	186	186
TP53	-0.037	0.093	0.23	4	-0.44	13	17
Senescence	-0.037	0.092	0.23	4	-0.44	13	17
Apoptosis	-0.037	0.092	0.23	4	-0.44	13	17
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.062	0.13	0.26	173	-0.32	13	186
MDM4	0	0.095	-10000	0	-0.59	17	17

×

Caspase cascade in apoptosis

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
TOP1	-0.049	0.16	-10000	0	-0.35	120	120
ACTA1	-0.072	0.2	0.26	3	-0.44	125	128
NUMA1	-0.052	0.17	-10000	0	-0.36	125	125
SPTAN1	-0.064	0.2	-10000	0	-0.43	119	119
LIMK1	-0.064	0.2	-10000	0	-0.43	119	119
BIRC3	-0.059	0.2	-10000	0	-0.6	81	81
BIRC2	0.015	0	-10000	0	-10000	0	0
BAX	0.015	0	-10000	0	-10000	0	0
CASP10	-0.1	0.23	-10000	0	-0.44	192	192
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.015	0	-10000	0	-10000	0	0
PTK2	-0.049	0.16	-10000	0	-0.35	120	120
DIABLO	0.015	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.062	0.2	-10000	0	-0.43	119	119
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.015	0	-10000	0	-10000	0	0
GSN	-0.068	0.2	-10000	0	-0.44	117	117
MADD	0.012	0.043	-10000	0	-0.62	3	3
TFAP2A	-0.17	0.29	-10000	0	-0.64	164	164
BID	-0.044	0.12	-10000	0	-0.25	125	125
MAP3K1	-0.015	0.076	-10000	0	-0.22	11	11
TRADD	0.014	0.025	-10000	0	-0.62	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.002	0.018	-10000	0	-0.42	1	1
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.065	0.2	-10000	0	-0.44	119	119
CASP9	0.015	0.023	-10000	0	-0.59	1	1
DNA repair	0	0.069	0.21	1	-0.18	41	42
neuron apoptosis	0.01	0.044	-10000	0	-0.3	6	6
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.057	0.2	-10000	0	-0.42	111	111
APAF1	0.015	0	-10000	0	-10000	0	0
CASP6	-0.027	0.12	-10000	0	-0.38	28	28
TRAF2	0.015	0	-10000	0	-10000	0	0
ICAD/CAD	-0.052	0.19	-10000	0	-0.43	94	94
CASP7	0.028	0.093	0.28	59	-10000	0	59
KRT18	-0.081	0.21	-10000	0	-0.58	91	91
apoptosis	-0.078	0.19	-10000	0	-0.52	50	50
DFFA	-0.063	0.2	-10000	0	-0.43	118	118
DFFB	-0.063	0.2	-10000	0	-0.43	115	115
PARP1	0	0.069	0.18	41	-0.22	1	42
actin filament polymerization	0.05	0.19	0.41	103	-10000	0	103
TNF	-0.13	0.26	-10000	0	-0.6	152	152
CYCS	-0.029	0.089	-10000	0	-0.24	46	46
SATB1	-0.029	0.13	-10000	0	-0.49	20	20
SLK	-0.064	0.2	-10000	0	-0.43	118	118
p15 BID/BAX	-0.032	0.11	-10000	0	-0.29	48	48
CASP2	-0.009	0.11	-10000	0	-0.41	14	14
JNK cascade	0.014	0.075	0.22	11	-10000	0	11
CASP3	-0.076	0.21	0.27	5	-0.46	119	124
LMNB2	-0.006	0.094	-10000	0	-0.4	11	11
RIPK1	0.015	0	-10000	0	-10000	0	0
CASP4	-0.053	0.19	-10000	0	-0.59	75	75
Mammalian IAPs/DIABLO	-0.039	0.1	-10000	0	-0.34	29	29
negative regulation of DNA binding	-0.17	0.29	-10000	0	-0.63	164	164
stress fiber formation	-0.063	0.2	0.26	1	-0.42	118	119
GZMB	-0.13	0.26	-10000	0	-0.52	192	192
CASP1	-0.027	0.13	-10000	0	-0.33	92	92
LMNB1	-0.014	0.1	-10000	0	-0.4	17	17
APP	0.01	0.045	-10000	0	-0.3	6	6
TNFRSF1A	0.002	0.09	-10000	0	-0.61	14	14
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.005	0.06	-10000	0	-0.44	12	12
VIM	-0.084	0.19	0.25	1	-0.41	112	113
LMNA	-0.007	0.095	-10000	0	-0.4	11	11
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.019	0.12	-10000	0	-0.41	19	19
LRDD	0.011	0.049	-10000	0	-0.62	4	4
SREBF1	-0.069	0.2	-10000	0	-0.43	124	124
APAF-1/Caspase 9	-0.004	0.047	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.051	0.17	-10000	0	-0.35	125	125
CFL2	-0.052	0.19	-10000	0	-0.42	98	98
GAS2	-0.082	0.21	-10000	0	-0.44	131	131
positive regulation of apoptosis	-0.006	0.097	-10000	0	-0.4	12	12
PRF1	-0.093	0.24	-10000	0	-0.6	118	118

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.035	0.1	-9999	-0.34	70	70
RGS9BP	0.003	0.088	-9999	-0.62	13	13
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.009	0.047	-9999	-0.59	4	4
mol:Na +	-0.11	0.17	-9999	-0.38	203	203
mol:ADP	0.018	0.05	-9999	-0.48	6	6
GNAT2	0.009	0.047	-9999	-0.59	4	4
RGS9-1/Gbeta5/R9AP	-0.056	0.14	-9999	-0.4	93	93
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.012	0.067	-9999	-0.38	21	21
GRK7	0.01	0.04	-9999	-0.59	3	3
CNGB3	-0.008	0.099	-9999	-0.59	19	19
Cone Metarhodopsin II/X-Arrestin	-0.001	0.017	-9999	-0.43	1	1
mol:Ca2+	-0.16	0.23	-9999	-0.4	294	294
Cone PDE6	-0.056	0.13	-9999	-0.42	26	26
Cone Metarhodopsin II	-0.003	0.038	-9999	-0.38	6	6
Na + (4 Units)	-0.18	0.22	-9999	-0.4	294	294
GNAT2/GDP	-0.049	0.13	-9999	-0.34	95	95
GNB5	0.015	0	-9999	-10000	0	0
mol:GMP (4 units)	0.006	0.068	-9999	-0.34	24	24
Cone Transducin	-0.037	0.11	-9999	-0.36	70	70
SLC24A2	-0.13	0.26	-9999	-0.61	151	151
GNB3/GNGT2	-0.046	0.14	-9999	-0.46	67	67
GNB3	-0.025	0.16	-9999	-0.62	43	43
GNAT2/GTP	-0.003	0.033	-9999	-0.43	4	4
CNGA3	-0.16	0.28	-9999	-0.6	185	185
ARR3	0.003	0.024	-9999	-0.59	1	1
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.12	0.18	-9999	-0.38	203	203
mol:Pi	-0.056	0.14	-9999	-0.4	93	93
Cone CNG Channel	-0.1	0.15	-9999	-0.63	11	11
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.13	0.26	-9999	-0.61	151	151
RGS9	-0.067	0.21	-9999	-0.62	87	87
PDE6C	0.004	0.04	-9999	-0.59	3	3
GNGT2	-0.009	0.12	-9999	-0.61	26	26
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.006	0.097	-9999	-0.59	18	18

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.032	0.11	-9999	-0.39	56	56
ARNO/beta Arrestin1-2	-0.02	0.079	-9999	-0.55	7	7
EGFR	-0.11	0.25	-9999	-0.6	138	138
EPHA2	-0.017	0.14	-9999	-0.59	35	35
USP6	0.002	0.087	-9999	-0.6	14	14
IQSEC1	0.012	0.04	-9999	-0.59	3	3
EGFR/EGFR/EGF/EGF	-0.13	0.21	-9999	-0.46	183	183
ARRB2	0.01	0.039	-9999	-0.25	15	15
mol:GTP	0.003	0.046	-9999	-0.15	37	37
ARRB1	0.003	0.088	-9999	-0.62	13	13
FBXO8	0.014	0.025	-9999	-0.62	1	1
TSHR	-0.24	0.31	-9999	-0.61	268	268
EGF	-0.038	0.18	-9999	-0.61	57	57
somatostatin receptor activity	0	0	-9999	-0.001	121	121
ARAP2	0.002	0.092	-9999	-0.62	14	14
mol:GDP	-0.083	0.12	-9999	-0.27	135	135
mol:PI-3-4-5-P3	0	0	-9999	-0.001	69	69
ITGA2B	-0.028	0.16	-9999	-0.62	46	46
ARF6	0.015	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.018	0.074	-9999	-0.34	6	6
ADAP1	-0.035	0.17	-9999	-0.61	54	54
KIF13B	0.012	0.043	-9999	-0.62	3	3
HGF/MET	-0.19	0.26	-9999	-0.51	255	255
PXN	0.015	0	-9999	-10000	0	0
ARF6/GTP	-0.075	0.12	-9999	-0.28	110	110
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.11	0.18	-9999	-0.39	184	184
ADRB2	-0.011	0.13	-9999	-0.62	27	27
receptor agonist activity	0	0	-9999	0	118	118
actin filament binding	0	0	-9999	-0.001	122	122
SRC	0.013	0.035	-9999	-0.62	2	2
ITGB3	-0.099	0.24	-9999	-0.6	125	125
GNAQ	0.015	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	82	82
ARF6/GDP	-0.011	0.11	-9999	-0.4	18	18
ARF6/GDP/GULP/ACAP1	-0.13	0.18	-9999	-0.43	132	132
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.083	0.15	-9999	-0.39	63	63
ACAP1	-0.046	0.18	-9999	-0.59	67	67
ACAP2	0.015	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	0.002	0.055	-9999	-0.36	15	15
EFNA1	0.012	0.041	-9999	-0.6	3	3
HGF	-0.088	0.23	-9999	-0.6	113	113
CYTH3	0.013	0	-9999	-10000	0	0
CYTH2	0.01	0.002	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	0	100	100
endosomal lumen acidification	0	0	-9999	0	117	117
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.06	0.2	-9999	-0.62	80	80
GNAQ/ARNO	0.014	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	46	46
MET	-0.16	0.28	-9999	-0.6	194	194
GNA14	-0.009	0.12	-9999	-0.61	26	26
GNA15	-0.009	0.12	-9999	-0.61	26	26
GIT1	0.014	0.025	-9999	-0.62	1	1
mol:PI-4-5-P2	0	0	-9999	-0.001	98	98
GNA11	0.006	0.078	-9999	-0.62	10	10
LHCGR	-0.005	0.089	-9999	-0.59	15	15
AGTR1	-0.078	0.22	-9999	-0.6	101	101
desensitization of G-protein coupled receptor protein signaling pathway	0.002	0.055	-9999	-0.36	15	15
IPCEF1/ARNO	-0.074	0.15	-9999	-0.57	12	12
alphaIIb/beta3 Integrin	-0.11	0.2	-9999	-0.46	160	160

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.003	0.035	-9999	-0.46	4	4
Necdin/E2F1	-0.077	0.18	-9999	-0.48	108	108
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.08	0.15	-9999	-0.63	19	19
NGF (dimer)/p75(NTR)/BEX1	-0.11	0.2	-9999	-0.43	176	176
NT-4/5 (dimer)/p75(NTR)	-0.078	0.17	-9999	-0.45	115	115
IKBKB	0.015	0	-9999	-10000	0	0
AKT1	-0.044	0.17	-9999	-0.63	18	18
IKBKG	0.015	0	-9999	-10000	0	0
BDNF	-0.079	0.22	-9999	-0.59	104	104
MGDIs/NGR/p75(NTR)/LINGO1	-0.1	0.19	-9999	-0.42	166	166
FURIN	0.015	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.11	0.19	-9999	-0.41	174	174
LINGO1	-0.024	0.15	-9999	-0.62	41	41
Sortilin/TRAF6/NRIF	-0.002	0.02	-9999	-10000	0	0
proBDNF (dimer)	-0.079	0.22	-9999	-0.59	104	104
NTRK1	-0.021	0.14	-9999	-0.59	40	40
RTN4R	-0.035	0.17	-9999	-0.61	54	54
neuron apoptosis	-0.058	0.19	-9999	-0.51	54	54
IRAK1	0.015	0	-9999	-10000	0	0
SHC1	-0.079	0.2	-9999	-0.41	169	169
ARHGDIA	0.015	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.095	0.17	-9999	-0.41	108	108
MAGEH1	-0.001	0.1	-9999	-0.62	17	17
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.13	0.21	-9999	-0.43	161	161
Mammalian IAPs/DIABLO	-0.039	0.1	-9999	-0.34	29	29
proNGF (dimer)	-0.062	0.2	-9999	-0.61	82	82
MAGED1	0.015	0	-9999	-10000	0	0
APP	0.015	0	-9999	-10000	0	0
NT-4/5 (dimer)	-0.015	0.11	-9999	-0.59	25	25
ZNF274	0.015	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.052	0.17	-9999	-0.38	89	89
NGF	-0.062	0.2	-9999	-0.61	82	82
cell cycle arrest	-0.076	0.16	-9999	-0.39	80	80
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.027	0.14	-9999	-0.5	21	21
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.066	0.15	-9999	-0.38	116	116
NCSTN	0.015	0	-9999	-10000	0	0
mol:GTP	-0.096	0.18	-9999	-0.4	159	159
PSENEN	0.015	0	-9999	-10000	0	0
mol:ceramide	-0.055	0.18	-9999	-0.36	159	159
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.023	0.13	-9999	-0.41	29	29
p75(NTR)/beta APP	-0.061	0.15	-9999	-0.44	94	94
BEX1	-0.013	0.13	-9999	-0.62	30	30
mol:GDP	-0.082	0.19	-9999	-0.41	159	159
NGF (dimer)	-0.16	0.2	-9999	-0.37	286	286
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.093	0.17	-9999	-0.37	166	166
PIK3R1	0.012	0.043	-9999	-0.62	3	3
RAC1/GTP	-0.083	0.16	-9999	-0.35	159	159
MYD88	0.008	0.07	-9999	-0.62	8	8
CHUK	0.015	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.096	0.18	-9999	-0.4	159	159
RHOB	0.014	0.023	-9999	-0.59	1	1
RHOA	0.015	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.019	0.088	-9999	-0.43	29	29
NT3 (dimer)	-0.012	0.11	-9999	-0.59	24	24
TP53	-0.049	0.18	-9999	-0.59	33	33
PRDM4	-0.056	0.18	-9999	-0.36	159	159
BDNF (dimer)	-0.21	0.24	-9999	-0.51	180	180
PIK3CA	0.015	0	-9999	-10000	0	0
SORT1	0.013	0.035	-9999	-0.62	2	2
activation of caspase activity	-0.079	0.15	-9999	-0.62	19	19
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.088	0.17	-9999	-0.37	160	160
RHOC	0.012	0.041	-9999	-0.6	3	3
XIAP	0.015	0	-9999	-10000	0	0
MAPK10	-0.036	0.18	-9999	-0.47	51	51
DIABLO	0.015	0	-9999	-10000	0	0
SMPD2	-0.056	0.18	-9999	-0.36	159	159
APH1B	0.015	0	-9999	-10000	0	0
APH1A	0.015	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.097	0.18	-9999	-0.41	159	159
PSEN1	0.015	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	-0.001	0.016	-9999	-0.42	1	1
NT3 (dimer)/p75(NTR)	-0.077	0.18	-9999	-0.46	111	111
MAPK8	-0.038	0.18	-9999	-0.46	51	51
MAPK9	-0.035	0.17	-9999	-0.46	48	48
APAF1	0.015	0	-9999	-10000	0	0
NTF3	-0.012	0.11	-9999	-0.59	24	24
NTF4	-0.016	0.11	-9999	-0.59	25	25
NDN	-0.068	0.22	-9999	-0.62	87	87
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.073	0.14	-9999	-0.58	17	17
p75 CTF/Sortilin/TRAF6/NRIF	-0.005	0.039	-9999	-0.34	9	9
RhoA-B-C/GTP	-0.095	0.18	-9999	-0.4	159	159
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.089	0.16	-9999	-0.62	27	27
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.097	0.18	-9999	-0.46	70	70
PRKACB	0.015	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.07	0.16	-9999	-0.44	107	107
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.059	0.2	-9999	-0.6	81	81
BIRC2	0.015	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.1	0.18	-9999	-0.44	106	106
BAD	-0.027	0.17	-9999	-0.48	37	37
RIPK2	0.015	0	-9999	-10000	0	0
NGFR	-0.072	0.22	-9999	-0.6	94	94
CYCS	-0.043	0.17	-9999	-0.6	20	20
ADAM17	0.01	0.055	-9999	-0.62	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.087	0.16	-9999	-0.4	90	90
BCL2L11	-0.027	0.17	-9999	-0.48	36	36
BDNF (dimer)/p75(NTR)	-0.12	0.22	-9999	-0.48	174	174
PI3K	-0.087	0.16	-9999	-0.4	94	94
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.087	0.16	-9999	-0.4	93	93
NDNL2	0.015	0	-9999	-10000	0	0
YWHAE	0.015	0	-9999	-10000	0	0
PRKCI	0.015	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.11	0.21	-9999	-0.48	159	159
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.087	0.16	-9999	-0.36	159	159
TRAF6	0.013	0.035	-9999	-0.62	2	2
RAC1	0.015	0	-9999	-10000	0	0
PRKCZ	-0.037	0.17	-9999	-0.62	55	55
PLG	-0.002	0.046	-9999	-0.59	4	4
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.092	0.21	-9999	-0.52	76	76
SQSTM1	0.015	0	-9999	-10000	0	0
NGFRAP1	0.015	0	-9999	-10000	0	0
CASP3	-0.022	0.16	-9999	-0.44	36	36
E2F1	-0.011	0.12	-9999	-0.6	29	29
CASP9	0.014	0.023	-9999	-0.59	1	1
IKK complex	-0.075	0.14	-9999	-0.5	32	32
NGF (dimer)/TRKA	-0.079	0.18	-9999	-0.46	116	116
MMP7	-0.22	0.3	-9999	-0.6	247	247
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.081	0.16	-9999	-0.63	20	20
MMP3	-0.054	0.18	-9999	-0.59	71	71
APAF-1/Caspase 9	-0.08	0.13	-9999	-0.48	40	40

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.13	0.2	-9999	-0.44	194	194
CRKL	-0.051	0.14	-9999	-0.46	14	14
mol:PIP3	-0.022	0.007	-9999	-10000	0	0
AKT1	0.002	0.02	-9999	-0.34	2	2
PTK2B	-0.006	0.11	-9999	-0.59	23	23
RAPGEF1	-0.041	0.13	-9999	-0.45	14	14
RANBP10	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.16	0.23	-9999	-0.43	255	255
MAP3K5	-0.041	0.14	-9999	-0.46	24	24
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.15	0.2	-9999	-0.64	52	52
AP1	-0.079	0.16	-9999	-0.44	97	97
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.001	0.092	-9999	-0.59	16	16
apoptosis	-0.084	0.22	-9999	-0.78	57	57
STAT3 (dimer)	-0.056	0.15	-9999	-0.35	53	53
GAB1/CRKL/SHP2/PI3K	-0.067	0.1	-9999	-0.47	10	10
INPP5D	0.007	0.071	-9999	-0.6	9	9
CBL/CRK	-0.04	0.13	-9999	-0.45	13	13
PTPN11	0.013	0.035	-9999	-0.62	2	2
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.015	0	-9999	-10000	0	0
PTEN	0.015	0	-9999	-10000	0	0
ELK1	-0.065	0.1	-9999	-0.22	194	194
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.055	0.08	-9999	-0.3	16	16
PAK1	-0.007	0.075	-9999	-0.31	39	39
HGF/MET/RANBP10	-0.16	0.23	-9999	-0.43	255	255
HRAS	-0.11	0.24	-9999	-0.66	81	81
DOCK1	-0.041	0.13	-9999	-0.46	13	13
GAB1	-0.063	0.14	-9999	-0.31	124	124
CRK	-0.051	0.14	-9999	-0.46	14	14
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.14	0.22	-9999	-0.6	103	103
JUN	0.008	0.067	-9999	-0.6	8	8
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.095	0.13	-9999	-0.31	145	145
PIK3R1	0.012	0.043	-9999	-0.62	3	3
cell morphogenesis	-0.025	0.15	-9999	-0.49	10	10
GRB2/SHC	-0.064	0.14	-9999	-0.5	27	27
FOS	-0.073	0.22	-9999	-0.61	95	95
GLMN	0	0	-9999	-10000	0	0
cell motility	-0.064	0.1	-9999	-0.22	194	194
HGF/MET/MUC20	-0.17	0.23	-9999	-0.44	255	255
cell migration	-0.063	0.14	-9999	-0.49	27	27
GRB2	0.014	0.023	-9999	-0.59	1	1
CBL	0.014	0.025	-9999	-0.62	1	1
MET/RANBP10	-0.13	0.2	-9999	-0.44	194	194
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.069	0.16	-9999	-0.38	70	70
MET/MUC20	-0.13	0.2	-9999	-0.45	194	194
RAP1B	-0.033	0.13	-9999	-0.46	16	16
RAP1A	-0.03	0.13	-9999	-0.42	13	13
HGF/MET/RANBP9	-0.16	0.23	-9999	-0.43	255	255
RAF1	-0.098	0.23	-9999	-0.61	81	81
STAT3	-0.057	0.15	-9999	-0.35	53	53
cell proliferation	-0.075	0.2	-9999	-0.59	29	29
RPS6KB1	-0.022	0.053	-9999	-10000	0	0
MAPK3	-0.065	0.092	-9999	-0.21	47	47
MAPK1	-0.065	0.092	-9999	-10000	0	0
RANBP9	0.015	0	-9999	-10000	0	0
MAPK8	-0.018	0.13	-9999	-0.44	22	22
SRC	-0.057	0.15	-9999	-0.36	53	53
PI3K	-0.058	0.13	-9999	-0.32	55	55
MET/Glomulin	-0.1	0.18	-9999	-0.39	194	194
SOS1	0.015	0	-9999	-10000	0	0
MAP2K1	-0.082	0.21	-9999	-0.56	81	81
MET	-0.16	0.28	-9999	-0.6	194	194
MAP4K1	-0.048	0.14	-9999	-0.46	23	23
PTK2	0.015	0	-9999	-10000	0	0
MAP2K2	-0.082	0.21	-9999	-0.56	81	81
BAD	0.011	0.019	-9999	-0.32	2	2
MAP2K4	-0.029	0.13	-9999	-0.42	22	22
SHP2/GRB2/SOS1/GAB1	-0.1	0.15	-9999	-0.39	85	85
INPPL1	0.015	0	-9999	-10000	0	0
PXN	0.015	0	-9999	-10000	0	0
SH3KBP1	0.015	0	-9999	-10000	0	0
HGS	-0.068	0.13	-9999	-0.3	123	123
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.088	0.23	-9999	-0.6	113	113
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
PTPRJ	0.013	0.034	-9999	-0.61	2	2
NCK/PLCgamma1	-0.056	0.13	-9999	-0.32	53	53
PDPK1	-0.008	0.016	-9999	-0.39	1	1
HGF/MET/SHIP	-0.17	0.23	-9999	-0.44	260	260

×

PDGFR-alpha 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.07	0.21	-9999	-0.62	88	88
PDGF/PDGFRA/CRKL	-0.058	0.15	-9999	-0.44	89	89
positive regulation of JUN kinase activity	-0.049	0.12	-9999	-0.46	14	14
CRKL	0.014	0.023	-9999	-0.59	1	1
PDGF/PDGFRA/Caveolin-3	-0.074	0.17	-9999	-0.46	106	106
AP1	-0.15	0.3	-9999	-0.81	96	96
mol:IP3	-0.039	0.16	-9999	-0.45	88	88
PLCG1	-0.039	0.16	-9999	-0.45	88	88
PDGF/PDGFRA/alphaV Integrin	-0.058	0.15	-9999	-0.44	88	88
RAPGEF1	0.013	0.035	-9999	-0.62	2	2
CRK	0.015	0	-9999	-10000	0	0
mol:Ca2+	-0.039	0.16	-9999	-0.45	88	88
CAV3	-0.014	0.11	-9999	-0.59	25	25
CAV1	-0.064	0.2	-9999	-0.59	88	88
SHC/Grb2/SOS1	-0.05	0.12	-9999	-0.47	14	14
PDGF/PDGFRA/Shf	-0.06	0.15	-9999	-0.44	91	91
FOS	-0.11	0.32	-9999	-0.79	96	96
JUN	-0.016	0.056	-9999	-0.49	8	8
oligodendrocyte development	-0.058	0.15	-9999	-0.44	88	88
GRB2	0.014	0.023	-9999	-0.59	1	1
PIK3R1	0.012	0.043	-9999	-0.62	3	3
mol:DAG	-0.039	0.16	-9999	-0.45	88	88
PDGF/PDGFRA	-0.07	0.21	-9999	-0.62	88	88
actin cytoskeleton reorganization	-0.06	0.15	-9999	-0.44	91	91
SRF	0.029	0.009	-9999	-10000	0	0
SHC1	0.001	0.092	-9999	-0.59	16	16
PI3K	-0.049	0.13	-9999	-0.37	89	89
PDGF/PDGFRA/Crk/C3G	-0.048	0.12	-9999	-0.36	89	89
JAK1	-0.034	0.16	-9999	-0.43	88	88
ELK1/SRF	-0.001	0.12	-9999	-0.38	5	5
SHB	0.011	0.049	-9999	-0.62	4	4
SHF	0.011	0.049	-9999	-0.62	4	4
CSNK2A1	0.013	0.022	-9999	-10000	0	0
GO:0007205	-0.039	0.16	-9999	-0.46	88	88
SOS1	0.015	0	-9999	-10000	0	0
Ras protein signal transduction	-0.049	0.12	-9999	-0.46	14	14
PDGF/PDGFRA/SHB	-0.06	0.15	-9999	-0.44	91	91
PDGF/PDGFRA/Caveolin-1	-0.11	0.22	-9999	-0.49	152	152
ITGAV	0.014	0.025	-9999	-0.62	1	1
ELK1	-0.028	0.15	-9999	-0.39	88	88
PIK3CA	0.015	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.057	0.15	-9999	-0.44	88	88
JAK-STAT cascade	-0.034	0.16	-9999	-0.43	88	88
cell proliferation	-0.06	0.15	-9999	-0.44	91	91

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.18	0.38	-9999	-0.98	70	70
PCK1	-0.22	0.4	-9999	-1.1	83	83
HNF4A	-0.21	0.41	-9999	-1.1	69	69
KCNJ11	-0.27	0.52	-9999	-1.2	120	120
AKT1	-0.08	0.17	-9999	-0.44	16	16
response to starvation	-0.002	0.022	-9999	-10000	0	0
DLK1	-0.28	0.47	-9999	-1.1	120	120
NKX2-1	-0.084	0.24	-9999	-0.8	21	21
ACADM	-0.18	0.38	-9999	-0.99	67	67
TAT	-0.23	0.41	-9999	-1.1	88	88
CEBPB	-0.002	0.1	-9999	-0.61	19	19
CEBPA	-0.008	0.12	-9999	-0.62	26	26
TTR	-0.16	0.29	-9999	-0.83	62	62
PKLR	-0.19	0.39	-9999	-0.98	75	75
APOA1	-0.23	0.46	-9999	-1.2	74	74
CPT1C	-0.18	0.38	-9999	-0.98	70	70
ALAS1	-0.062	0.2	-9999	-0.73	4	4
TFRC	-0.17	0.3	-9999	-0.78	60	60
FOXF1	-0.007	0.12	-9999	-0.6	24	24
NF1	0.019	0.055	-9999	-0.62	5	5
HNF1A (dimer)	0.012	0.042	-9999	-0.68	1	1
CPT1A	-0.18	0.38	-9999	-0.99	69	69
HMGCS1	-0.18	0.38	-9999	-0.98	71	71
NR3C1	-0.017	0.079	-9999	-0.3	2	2
CPT1B	-0.2	0.4	-9999	-1	84	84
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.008	0.031	-9999	-10000	0	0
GCK	-0.26	0.47	-9999	-1.1	126	126
CREB1	0.003	0.051	-9999	-10000	0	0
IGFBP1	-0.23	0.49	-9999	-1.3	98	98
PDX1	-0.096	0.23	-9999	-0.73	20	20
UCP2	-0.2	0.41	-9999	-1	81	81
ALDOB	-0.21	0.44	-9999	-1.2	75	75
AFP	-0.11	0.2	-9999	-0.57	67	67
BDH1	-0.22	0.44	-9999	-1.1	91	91
HADH	-0.19	0.4	-9999	-1	64	64
F2	-0.21	0.42	-9999	-1.1	62	62
HNF1A	0.012	0.042	-9999	-0.68	1	1
G6PC	-0.047	0.17	-9999	-0.71	15	15
SLC2A2	-0.098	0.23	-9999	-0.72	7	7
INS	0.008	0.088	-9999	-0.6	5	5
FOXA1	-0.067	0.19	-9999	-0.59	63	63
FOXA3	-0.12	0.25	-9999	-0.6	117	117
FOXA2	-0.22	0.46	-9999	-1.1	87	87
ABCC8	-0.3	0.55	-9999	-1.2	140	140
ALB	-0.15	0.34	-9999	-0.99	74	74

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	-0.001	0.016	-10000	0	-0.42	1	1
PRKCZ	-0.037	0.17	-10000	0	-0.62	55	55
MAP3K7IP2	0	0	-10000	0	-10000	0	0
ERC1	0.012	0.042	-10000	0	-0.61	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.087	0.13	-10000	0	-0.4	54	54
IRAK/TOLLIP	0.034	0.014	-10000	0	-10000	0	0
IKBKB	0.015	0	-10000	0	-10000	0	0
IKBKG	0.015	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	-0.2	0.25	-10000	0	-0.48	275	275
IL1A	-0.091	0.23	-10000	0	-0.61	114	114
IL1B	-0.13	0.24	-10000	0	-0.47	210	210
IRAK/TRAF6/p62/Atypical PKCs	-0.023	0.076	-10000	0	-10000	0	0
IL1R2	-0.16	0.28	-10000	0	-0.6	193	193
IL1R1	-0.037	0.17	-10000	0	-0.6	57	57
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.05	0.14	0.23	1	-0.45	33	34
TOLLIP	0.015	0	-10000	0	-10000	0	0
TICAM2	0.001	0.093	-10000	0	-0.61	15	15
MAP3K3	0.015	0	-10000	0	-10000	0	0
TAK1/TAB1/TAB2	0	0	-10000	0	-10000	0	0
IKK complex/ELKS	0.067	0.047	-10000	0	-0.53	1	1
JUN	0.045	0.056	-10000	0	-0.53	1	1
MAP3K7	0.015	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.16	0.2	-10000	0	-0.63	66	66
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.13	0.2	-10000	0	-0.46	109	109
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.12	0.19	-10000	0	-0.65	37	37
IL1 beta fragment/IL1R1/IL1RAP	-0.18	0.23	-10000	0	-0.49	150	150
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	0.042	0.045	-10000	0	-10000	0	0
IRAK1	0.028	0.016	-10000	0	-0.35	1	1
IL1RN/IL1R1	-0.16	0.24	-10000	0	-0.48	223	223
IRAK4	0.015	0	-10000	0	-10000	0	0
PRKCI	0.015	0	-10000	0	-10000	0	0
TRAF6	0.013	0.035	-10000	0	-0.62	2	2
PI3K	-0.002	0.03	-10000	0	-0.46	3	3
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.07	0.16	-10000	0	-0.43	63	63
CHUK	0.015	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.18	0.23	-10000	0	-0.49	150	150
IL1 beta/IL1R2	-0.23	0.25	-10000	0	-0.44	344	344
IRAK/TRAF6/TAK1/TAB1/TAB2	-0.001	0.019	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.14	0.18	-10000	0	-0.56	66	66
IRAK3	0.009	0.064	-10000	0	-0.61	7	7
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.16	0.21	-10000	0	-0.65	70	70
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.051	0.15	-10000	0	-0.45	37	37
IL1 alpha/IL1R1/IL1RAP	-0.14	0.22	-10000	0	-0.42	222	222
RELA	0.015	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.015	0	-10000	0	-10000	0	0
MYD88	0.008	0.07	-10000	0	-0.62	8	8
IRAK/TRAF6/MEKK3	0.041	0.023	-10000	0	-10000	0	0
IL1RAP	-0.067	0.21	-10000	0	-0.59	90	90
UBE2N	0.015	0	-10000	0	-10000	0	0
IRAK/TRAF6	-0.13	0.17	-10000	0	-0.53	71	71
CASP1	-0.017	0.14	-10000	0	-0.6	35	35
IL1RN/IL1R2	-0.24	0.29	-10000	0	-0.53	306	306
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.17	0.22	-10000	0	-0.68	65	65
TMEM189-UBE2V1	0.007	0.024	-10000	0	-0.59	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.027	0.13	-10000	0	-0.43	28	28
PIK3CA	0.015	0	-10000	0	-10000	0	0
IL1RN	-0.16	0.28	-10000	0	-0.6	193	193
TRAF6/TAK1/TAB1/TAB2	-0.001	0.02	-10000	0	-0.31	2	2
MAP2K6	0.038	0.025	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.061	0.25	-10000	0	-0.72	34	34
CRP	-0.07	0.25	-10000	0	-0.74	32	32
cell cycle arrest	-0.086	0.28	-10000	0	-0.72	64	64
TIMP1	-0.17	0.32	-10000	0	-0.71	109	109
IL6ST	-0.032	0.16	-10000	0	-0.62	46	46
Rac1/GDP	-0.096	0.21	-10000	0	-0.48	99	99
AP1	-0.023	0.15	-10000	0	-0.54	16	16
GAB2	0.013	0.043	-10000	0	-0.62	3	3
TNFSF11	-0.076	0.26	-10000	0	-0.77	36	36
HSP90B1	0.006	0.15	-10000	0	-0.97	13	13
GAB1	0.015	0.025	-10000	0	-0.62	1	1
MAPK14	-0.16	0.27	-10000	0	-0.54	183	183
AKT1	0.059	0.051	-10000	0	-0.67	2	2
FOXO1	0.066	0.051	-10000	0	-0.62	2	2
MAP2K6	-0.13	0.24	-10000	0	-0.49	143	143
mol:GTP	0	0.002	-10000	0	-10000	0	0
MAP2K4	-0.083	0.22	-10000	0	-0.54	77	77
MITF	-0.1	0.21	0.29	1	-0.44	123	124
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.015	0	-10000	0	-10000	0	0
A2M	0.022	0.049	-10000	0	-10000	0	0
CEBPB	0.007	0.11	-10000	0	-0.61	19	19
GRB2/SOS1/GAB family/SHP2	-0.01	0.091	-10000	0	-0.78	3	3
STAT3	-0.09	0.29	-10000	0	-0.76	65	65
STAT1	-0.009	0.04	-10000	0	-10000	0	0
CEBPD	-0.11	0.35	-10000	0	-0.95	74	74
PIK3CA	0.017	0	-10000	0	-10000	0	0
PI3K	0.024	0.032	-10000	0	-0.45	3	3
JUN	0.007	0.066	-10000	0	-0.6	8	8
PIAS3/MITF	-0.087	0.2	-10000	0	-0.44	98	98
MAPK11	-0.16	0.27	-10000	0	-0.54	184	184
STAT3 (dimer)/FOXO1	-0.008	0.23	-10000	0	-0.6	27	27
GRB2/SOS1/GAB family	-0.088	0.14	-10000	0	-0.51	36	36
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.09	0.19	-10000	0	-0.41	108	108
GRB2	0.015	0.023	-10000	0	-0.59	1	1
JAK2	0.015	0	-10000	0	-10000	0	0
LBP	-0.068	0.26	-10000	0	-0.67	58	58
PIK3R1	0.014	0.043	-10000	0	-0.62	3	3
JAK1	0.011	0.01	-10000	0	-10000	0	0
MYC	-0.079	0.29	-10000	0	-0.87	46	46
FGG	-0.072	0.25	-10000	0	-0.74	38	38
macrophage differentiation	-0.086	0.28	-10000	0	-0.72	64	64
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.14	0.19	-10000	0	-0.43	148	148
JUNB	-0.081	0.29	-10000	0	-0.84	47	47
FOS	-0.074	0.22	-10000	0	-0.61	95	95
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.12	0.21	0.31	1	-0.44	152	153
STAT1/PIAS1	-0.082	0.19	0.3	1	-0.44	96	97
GRB2/SOS1/GAB family/SHP2/PI3K	0.042	0.054	-10000	0	-0.5	4	4
STAT3 (dimer)	-0.088	0.29	-10000	0	-0.76	64	64
PRKCD	-0.084	0.26	-10000	0	-0.64	75	75
IL6R	-0.006	0.1	-10000	0	-0.62	19	19
SOCS3	-0.24	0.42	-10000	0	-0.85	172	172
gp130 (dimer)/JAK1/JAK1/LMO4	-0.007	0.11	-10000	0	-0.38	46	46
Rac1/GTP	-0.1	0.22	-10000	0	-0.5	98	98
HCK	0	0.096	-10000	0	-0.61	16	16
MAPKKK cascade	0.015	0.088	-10000	0	-0.79	4	4
bone resorption	-0.071	0.25	-10000	0	-0.73	36	36
IRF1	-0.071	0.26	-10000	0	-0.75	37	37
mol:GDP	-0.11	0.22	0.29	1	-0.47	123	124
SOS1	0.015	0.002	-10000	0	-10000	0	0
VAV1	-0.11	0.22	0.29	1	-0.48	123	124
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.15	0.26	-10000	0	-0.5	185	185
PTPN11	-0.005	0.053	-10000	0	-0.91	2	2
IL6/IL6RA	-0.14	0.24	-10000	0	-0.47	214	214
gp130 (dimer)/TYK2/TYK2/LMO4	-0.008	0.1	-10000	0	-0.38	46	46
gp130 (dimer)/JAK2/JAK2/LMO4	-0.008	0.1	-10000	0	-0.38	46	46
IL6	-0.18	0.29	-10000	0	-0.62	205	205
PIAS3	0.015	0	-10000	0	-10000	0	0
PTPRE	0.014	0.053	-10000	0	-0.62	4	4
PIAS1	0.013	0.035	-10000	0	-0.62	2	2
RAC1	0.015	0.001	-10000	0	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.092	0.17	0.28	1	-0.38	110	111
LMO4	0.012	0.013	-10000	0	-10000	0	0
STAT3 (dimer)/PIAS3	-0.14	0.23	0.37	1	-0.72	62	63
MCL1	0.066	0.046	-10000	0	-0.75	1	1

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.015	0	-9999	-10000	0	0
GNAT1/GTP	-0.019	0.09	-9999	-0.43	30	30
Metarhodopsin II/Arrestin	-0.02	0.084	-9999	-0.37	37	37
PDE6G/GNAT1/GTP	-0.046	0.12	-9999	-0.38	81	81
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.015	0.12	-9999	-0.59	30	30
GRK1	0.009	0.047	-9999	-0.59	4	4
CNG Channel	-0.18	0.22	-9999	-0.63	85	85
mol:Na +	-0.18	0.21	-9999	-0.6	94	94
mol:ADP	0.009	0.047	-9999	-0.59	4	4
RGS9-1/Gbeta5/R9AP	-0.056	0.14	-9999	-0.4	93	93
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.19	0.22	-9999	-0.62	94	94
CNGB1	-0.14	0.26	-9999	-0.6	171	171
RDH5	-0.028	0.16	-9999	-0.59	48	48
SAG	0.002	0.024	-9999	-0.59	1	1
mol:Ca2+	-0.15	0.22	-9999	-0.57	94	94
Na + (4 Units)	-0.17	0.2	-9999	-0.55	94	94
RGS9	-0.067	0.21	-9999	-0.62	87	87
GNB1/GNGT1	-0.004	0.04	-9999	-0.42	6	6
GNAT1/GDP	-0.061	0.13	-9999	-0.35	85	85
GUCY2D	-0.005	0.094	-9999	-0.59	17	17
GNGT1	-0.005	0.055	-9999	-0.59	6	6
GUCY2F	0.005	0.052	-9999	-0.59	5	5
GNB5	0.015	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.073	0.18	-9999	-0.53	34	34
mol:11-cis-retinal	-0.028	0.16	-9999	-0.59	48	48
mol:cGMP	-0.099	0.17	-9999	-0.53	38	38
GNB1	0.015	0	-9999	-10000	0	0
Rhodopsin	-0.053	0.14	-9999	-0.42	84	84
SLC24A1	0.015	0	-9999	-10000	0	0
CNGA1	-0.039	0.18	-9999	-0.61	57	57
Metarhodopsin II	-0.02	0.078	-9999	-0.33	40	40
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.11	0.18	-9999	-0.38	193	193
RGS9BP	0.003	0.088	-9999	-0.62	13	13
Metarhodopsin II/Transducin	-0.002	0.064	-9999	-0.35	2	2
GCAP Family/Ca ++	-0.1	0.18	-9999	-0.37	182	182
PDE6A/B	-0.087	0.18	-9999	-0.44	131	131
mol:Pi	-0.056	0.14	-9999	-0.4	93	93
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.018	0.076	-9999	-0.34	35	35
PDE6B	-0.029	0.16	-9999	-0.61	47	47
PDE6A	-0.064	0.2	-9999	-0.6	86	86
PDE6G	-0.034	0.17	-9999	-0.61	52	52
RHO	-0.02	0.14	-9999	-0.59	36	36
PDE6	-0.12	0.19	-9999	-0.62	49	49
GUCA1A	-0.14	0.27	-9999	-0.6	168	168
GC2/GCAP Family	-0.1	0.17	-9999	-0.37	187	187
GUCA1C	-0.01	0.091	-9999	-0.59	16	16
GUCA1B	-0.002	0.1	-9999	-0.62	18	18

×

Glucocorticoid receptor regulatory network

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
PCK2	0.024	0.1	0.34	3	-0.75	5	8
SMARCC2	0.016	0.026	-10000	0	-0.62	1	1
SMARCC1	0.017	0.007	-10000	0	-10000	0	0
TBX21	-0.11	0.25	-10000	0	-0.67	92	92
SUMO2	0.013	0.011	-10000	0	-10000	0	0
STAT1 (dimer)	0.003	0.11	-10000	0	-0.69	16	16
FKBP4	0.015	0	-10000	0	-10000	0	0
FKBP5	-0.068	0.21	-10000	0	-0.62	88	88
GR alpha/HSP90/FKBP51/HSP90	0.036	0.17	0.31	36	-0.36	46	82
PRL	-0.05	0.11	-10000	0	-0.65	3	3
cortisol/GR alpha (dimer)/TIF2	0.19	0.25	0.55	142	-0.44	8	150
RELA	-0.076	0.1	-10000	0	-0.29	6	6
FGG	0.17	0.18	0.5	65	-0.52	3	68
GR beta/TIF2	0.072	0.16	0.33	53	-0.41	36	89
IFNG	-0.23	0.23	-10000	0	-0.65	82	82
apoptosis	-0.014	0.19	0.56	25	-0.62	4	29
CREB1	0.012	0.032	-10000	0	-10000	0	0
histone acetylation	-0.04	0.12	-10000	0	-0.39	35	35
BGLAP	-0.049	0.13	-10000	0	-0.6	11	11
GR/PKAc	0.089	0.099	0.3	38	-10000	0	38
NF kappa B1 p50/RelA	-0.14	0.2	-10000	0	-0.46	96	96
SMARCD1	0.017	0.007	-10000	0	-10000	0	0
MDM2	0.08	0.091	0.28	44	-0.25	4	48
GATA3	-0.1	0.25	-10000	0	-0.6	138	138
AKT1	0	0.027	-10000	0	-0.6	1	1
CSF2	-0.065	0.11	-10000	0	-0.61	5	5
GSK3B	0.013	0.011	-10000	0	-10000	0	0
NR1I3	0.032	0.18	0.54	23	-0.8	2	25
CSN2	0.14	0.14	0.42	36	-10000	0	36
BRG1/BAF155/BAF170/BAF60A	0.037	0.047	-10000	0	-0.42	4	4
NFATC1	-0.006	0.12	-10000	0	-0.62	23	23
POU2F1	0.007	0.075	-10000	0	-0.62	9	9
CDKN1A	-0.044	0.31	-10000	0	-1.5	26	26
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.001	0.01	-10000	0	-10000	0	0
SFN	-0.12	0.25	-10000	0	-0.6	141	141
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.033	0.21	0.3	25	-0.48	45	70
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.039	0.31	0.53	22	-0.79	72	94
JUN	-0.17	0.2	-10000	0	-0.52	89	89
IL4	-0.079	0.15	-10000	0	-0.56	32	32
CDK5R1	-0.037	0.17	-10000	0	-0.62	53	53
PRKACA	0.015	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.15	0.21	0.26	2	-0.52	112	114
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.043	0.16	0.31	31	-0.35	14	45
cortisol/GR alpha (monomer)	0.24	0.27	0.64	154	-10000	0	154
NCOA2	-0.019	0.14	-10000	0	-0.62	36	36
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.12	0.22	-10000	0	-0.65	95	95
AP-1/NFAT1-c-4	-0.3	0.32	-10000	0	-0.73	165	165
AFP	-0.14	0.2	-10000	0	-0.67	46	46
SUV420H1	0.015	0	-10000	0	-10000	0	0
IRF1	0.12	0.17	0.48	22	-0.58	7	29
TP53	0.001	0.14	-10000	0	-0.52	38	38
PPP5C	0.015	0	-10000	0	-10000	0	0
KRT17	-0.41	0.48	-10000	0	-1	219	219
KRT14	-0.13	0.19	-10000	0	-0.63	54	54
TBP	0.025	0.026	-10000	0	-0.57	1	1
CREBBP	0.034	0.059	-10000	0	-0.63	1	1
HDAC1	0.005	0.05	-10000	0	-0.63	4	4
HDAC2	0.015	0.004	-10000	0	-10000	0	0
AP-1	-0.31	0.32	-10000	0	-0.74	165	165
MAPK14	0.012	0.025	-10000	0	-0.59	1	1
MAPK10	0.009	0.056	-10000	0	-0.63	5	5
MAPK11	0.011	0.044	-10000	0	-0.62	3	3
KRT5	-0.41	0.46	-10000	0	-1	203	203
interleukin-1 receptor activity	0	0.004	-10000	0	-10000	0	0
NCOA1	0.018	0.007	-10000	0	-10000	0	0
STAT1	0.003	0.11	-10000	0	-0.69	16	16
CGA	-0.073	0.14	-10000	0	-0.52	26	26
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.083	0.12	0.38	29	-10000	0	29
MAPK3	0.013	0.011	-10000	0	-10000	0	0
MAPK1	0.013	0.01	-10000	0	-10000	0	0
ICAM1	-0.24	0.33	-10000	0	-0.78	130	130
NFKB1	-0.076	0.1	-10000	0	-10000	0	0
MAPK8	-0.14	0.18	-10000	0	-0.46	86	86
MAPK9	0.013	0.01	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.019	0.19	0.56	25	-0.66	4	29
BAX	0.012	0.1	-10000	0	-10000	0	0
POMC	-0.13	0.25	-10000	0	-1.4	17	17
EP300	0.033	0.069	-10000	0	-0.62	3	3
cortisol/GR alpha (dimer)/p53	0.2	0.24	0.55	134	-10000	0	134
proteasomal ubiquitin-dependent protein catabolic process	0.053	0.078	0.28	19	-0.25	1	20
SGK1	0.08	0.17	-10000	0	-1.4	7	7
IL13	-0.24	0.25	-10000	0	-0.71	84	84
IL6	-0.35	0.44	-10000	0	-0.94	206	206
PRKACG	0.005	0.047	-10000	0	-0.59	4	4
IL5	-0.2	0.2	-10000	0	-0.65	47	47
IL2	-0.23	0.23	-10000	0	-0.7	53	53
CDK5	0.013	0.024	-10000	0	-0.59	1	1
PRKACB	0.015	0	-10000	0	-10000	0	0
HSP90AA1	0.015	0	-10000	0	-10000	0	0
IL8	-0.4	0.46	-10000	0	-0.95	231	231
CDK5R1/CDK5	-0.033	0.13	-10000	0	-0.46	54	54
NF kappa B1 p50/RelA/PKAc	-0.073	0.15	-10000	0	-0.43	10	10
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.21	0.21	0.52	150	-10000	0	150
SMARCA4	0.013	0.05	-10000	0	-0.62	4	4
chromatin remodeling	0.16	0.14	0.38	89	-0.43	3	92
NF kappa B1 p50/RelA/Cbp	-0.067	0.17	-10000	0	-0.48	18	18
JUN (dimer)	-0.17	0.2	-10000	0	-0.52	89	89
YWHAH	0.003	0.083	-10000	0	-0.59	13	13
VIPR1	-0.11	0.27	-10000	0	-0.77	81	81
NR3C1	0.14	0.16	0.45	89	-10000	0	89
NR4A1	-0.01	0.14	-10000	0	-0.54	38	38
TIF2/SUV420H1	-0.024	0.1	-10000	0	-0.46	36	36
MAPKKK cascade	-0.014	0.19	0.56	25	-0.62	4	29
cortisol/GR alpha (dimer)/Src-1	0.22	0.23	0.55	153	-10000	0	153
PBX1	0.015	0.027	-10000	0	-0.62	1	1
POU1F1	0.005	0.015	-10000	0	-10000	0	0
SELE	-0.3	0.39	-10000	0	-0.84	182	182
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.16	0.14	0.38	89	-0.43	3	92
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.21	0.21	0.52	150	-10000	0	150
mol:cortisol	0.13	0.16	0.36	159	-10000	0	159
MMP1	-0.19	0.31	-10000	0	-0.84	94	94

×

LPA receptor 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.05	0.12	-9999	-0.36	73	73
NF kappa B1 p50/RelA/I kappa B alpha	-0.035	0.082	-9999	-0.45	7	7
AP1	-0.11	0.18	-9999	-0.6	43	43
mol:PIP3	-0.11	0.16	-9999	-0.52	51	51
AKT1	0.027	0.1	-9999	-0.4	12	12
PTK2B	-0.009	0.11	-9999	-0.34	34	34
RHOA	0.016	0.059	-9999	-0.34	6	6
PIK3CB	0.014	0.025	-9999	-0.62	1	1
mol:Ca2+	0.014	0.084	-9999	-0.39	6	6
MAGI3	0.009	0.06	-9999	-0.62	6	6
RELA	0.015	0	-9999	-10000	0	0
apoptosis	-0.037	0.14	-9999	-0.36	68	68
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	-0.008	0.12	-9999	-0.36	35	35
NF kappa B1 p50/RelA	-0.061	0.13	-9999	-0.51	31	31
endothelial cell migration	-0.047	0.2	-9999	-0.48	106	106
ADCY4	-0.027	0.17	-9999	-0.44	73	73
ADCY5	-0.047	0.2	-9999	-0.47	102	102
ADCY6	-0.025	0.17	-9999	-0.44	73	73
ADCY7	-0.025	0.17	-9999	-0.45	73	73
ADCY1	-0.052	0.18	-9999	-0.46	91	91
ADCY2	-0.04	0.19	-9999	-0.46	91	91
ADCY3	-0.025	0.17	-9999	-0.44	73	73
ADCY8	-0.046	0.2	-9999	-0.51	85	85
ADCY9	-0.026	0.17	-9999	-0.44	73	73
GSK3B	0	0.1	-9999	-0.36	23	23
arachidonic acid secretion	-0.018	0.16	-9999	-0.41	73	73
GNG2	0.009	0.06	-9999	-0.62	6	6
TRIP6	0.015	0.063	-9999	-0.34	16	16
GNAO1	-0.042	0.16	-9999	-0.4	102	102
HRAS	0.015	0	-9999	-10000	0	0
NFKBIA	0.003	0.12	-9999	-0.42	22	22
GAB1	0.014	0.025	-9999	-0.62	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.003	0.075	-9999	-1	3	3
JUN	0.008	0.067	-9999	-0.6	8	8
LPA/LPA2/NHERF2	-0.009	0.044	-9999	-0.38	8	8
TIAM1	-0.006	0.097	-9999	-1.4	3	3
PIK3R1	0.012	0.043	-9999	-0.62	3	3
mol:IP3	0.014	0.085	-9999	-0.4	6	6
PLCB3	0.024	0.047	-9999	-0.34	9	9
FOS	-0.074	0.22	-9999	-0.61	95	95
positive regulation of mitosis	-0.018	0.16	-9999	-0.41	73	73
LPA/LPA1-2-3	-0.075	0.16	-9999	-0.38	119	119
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0.001	-9999	-10000	0	0
BCAR1	0.014	0.025	-9999	-0.62	1	1
stress fiber formation	-0.011	0.12	-9999	-0.37	35	35
GNAZ	-0.027	0.15	-9999	-0.39	79	79
EGFR/PI3K-beta/Gab1	-0.11	0.17	-9999	-0.55	51	51
positive regulation of dendritic cell cytokine production	-0.075	0.15	-9999	-0.37	119	119
LPA/LPA2/MAGI-3	-0.012	0.056	-9999	-0.38	14	14
ARHGEF1	-0.004	0.12	-9999	-0.34	59	59
GNAI2	-0.025	0.14	-9999	-0.38	77	77
GNAI3	-0.025	0.14	-9999	-0.38	77	77
GNAI1	-0.047	0.17	-9999	-0.4	110	110
LPA/LPA3	-0.038	0.12	-9999	-0.45	50	50
LPA/LPA2	-0.011	0.054	-9999	-0.45	8	8
LPA/LPA1	-0.064	0.16	-9999	-0.4	106	106
HB-EGF/EGFR	-0.22	0.27	-9999	-0.46	340	340
HBEGF	-0.18	0.24	-9999	-0.44	288	288
mol:DAG	0.014	0.085	-9999	-0.4	6	6
cAMP biosynthetic process	-0.033	0.18	-9999	-0.45	85	85
NFKB1	0.015	0	-9999	-10000	0	0
SRC	0.013	0.035	-9999	-0.62	2	2
GNB1	0.015	0.001	-9999	-10000	0	0
LYN	0.001	0.13	-9999	-0.45	24	24
GNAQ	-0.004	0.085	-9999	-0.27	57	57
LPAR2	0.007	0.069	-9999	-0.62	8	8
LPAR3	-0.037	0.16	-9999	-0.59	50	50
LPAR1	-0.054	0.2	-9999	-0.62	68	68
IL8	-0.23	0.24	-9999	-0.48	272	272
PTK2	-0.036	0.16	-9999	-0.38	72	72
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.038	0.14	-9999	-0.37	68	68
EGFR	-0.11	0.25	-9999	-0.6	138	138
PLCG1	-0.003	0.089	-9999	-0.32	20	20
PLD2	-0.037	0.16	-9999	-0.39	72	72
G12/G13	-0.048	0.12	-9999	-0.36	68	68
PI3K-beta	-0.037	0.094	-9999	-0.46	13	13
cell migration	-0.023	0.056	-9999	-0.25	11	11
SLC9A3R2	0.015	0	-9999	-10000	0	0
PXN	-0.012	0.13	-9999	-0.38	35	35
HRAS/GTP	-0.019	0.16	-9999	-0.42	73	73
RAC1	0.015	0	-9999	-10000	0	0
MMP9	-0.25	0.3	-9999	-0.6	285	285
PRKCE	0.002	0.09	-9999	-0.59	15	15
PRKCD	0.01	0.1	-9999	-0.39	18	18
Gi(beta/gamma)	-0.021	0.16	-9999	-0.42	75	75
mol:LPA	-0.006	0.043	-9999	-0.2	9	9
TRIP6/p130 Cas/FAK1/Paxillin	-0.059	0.13	-9999	-0.51	24	24
MAPKKK cascade	-0.018	0.16	-9999	-0.41	73	73
contractile ring contraction involved in cytokinesis	0.016	0.058	-9999	-0.34	6	6
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.016	0.1	-9999	-0.28	82	82
GNA15	-0.016	0.1	-9999	-0.28	79	79
GNA12	0.014	0.025	-9999	-0.62	1	1
GNA13	0.015	0	-9999	-10000	0	0
MAPT	-0.009	0.12	-9999	-0.37	35	35
GNA11	-0.009	0.094	-9999	-0.3	45	45
Rac1/GTP	-0.003	0.082	-9999	-1.2	3	3
MMP2	-0.048	0.2	-9999	-0.48	106	106

×

Rapid glucocorticoid 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
Gs family/GDP/Gbeta gamma	-0.076	0.14	-10000	0	-0.34	151	151
MAPK9	0.01	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.11	0.2	-10000	0	-0.45	179	179
GNB1/GNG2	-0.004	0.037	-10000	0	-0.39	6	6
GNB1	0.015	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.01	0.01	-10000	0	-0.26	1	1
Gs family/GTP	-0.081	0.15	-10000	0	-0.36	149	149
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	0.02	0.038	0.092	149	-10000	0	149
GNAL	-0.13	0.27	-10000	0	-0.62	149	149
GNG2	0.009	0.06	-10000	0	-0.62	6	6
CRH	-0.15	0.27	-10000	0	-0.6	179	179
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.005	0.045	-10000	0	-0.38	9	9
MAPK11	0.009	0.026	-10000	0	-0.38	3	3

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	-0.08	0.23	-9999	-0.54	98	98
MAP3K8	-0.006	0.11	-9999	-0.59	22	22
FOS	-0.075	0.21	-9999	-0.53	96	96
PRKCA	0.012	0.035	-9999	-0.62	2	2
PTPN7	-0.11	0.25	-9999	-0.61	135	135
HRAS	0.015	0.001	-9999	-10000	0	0
PRKCB	-0.072	0.22	-9999	-0.6	94	94
NRAS	0.015	0.001	-9999	-10000	0	0
RAS family/GTP	0	0.012	-9999	-0.32	1	1
MAPK3	-0.063	0.18	-9999	-0.5	88	88
MAP2K1	-0.011	0.13	-9999	-0.44	39	39
ELK1	0.014	0.006	-9999	-10000	0	0
BRAF	-0.048	0.12	-9999	-0.43	47	47
mol:GTP	0	0.002	-9999	-0.005	95	95
MAPK1	-0.063	0.18	-9999	-0.5	88	88
RAF1	-0.043	0.11	-9999	-0.43	39	39
KRAS	0.014	0.023	-9999	-0.59	1	1

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.12	0.31	-10000	0	-0.88	60	60
NCK1/PAK1/Dok-R	-0.11	0.14	-10000	0	-0.41	84	84
NCK1/Dok-R	-0.17	0.31	-10000	0	-1	58	58
PIK3CA	0.015	0.001	-10000	0	-10000	0	0
mol:beta2-estradiol	0.019	0.07	0.24	35	-10000	0	35
RELA	0.015	0	-10000	0	-10000	0	0
SHC1	0	0.092	-10000	0	-0.59	16	16
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	0.02	0.089	0.26	15	-0.5	7	22
TNIP2	0.015	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.12	0.28	-10000	0	-0.99	54	54
FN1	-0.028	0.16	-10000	0	-0.59	48	48
PLD2	-0.094	0.33	-10000	0	-1.1	54	54
PTPN11	0.013	0.035	-10000	0	-0.62	2	2
GRB14	-0.22	0.3	-10000	0	-0.6	252	252
ELK1	-0.065	0.3	-10000	0	-0.98	54	54
GRB7	-0.038	0.16	-10000	0	-0.59	54	54
PAK1	-0.018	0.14	-10000	0	-0.59	37	37
Tie2/Ang1/alpha5/beta1 Integrin	-0.16	0.31	-10000	0	-1	68	68
CDKN1A	-0.13	0.3	-10000	0	-0.71	93	93
ITGA5	-0.026	0.15	-10000	0	-0.59	46	46
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.17	0.31	-10000	0	-1	58	58
CRK	0.015	0	-10000	0	-10000	0	0
mol:NO	-0.081	0.24	-10000	0	-0.64	61	61
PLG	-0.1	0.33	-10000	0	-1.1	55	55
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.1	0.28	-10000	0	-0.83	62	62
GRB2	0.014	0.023	-10000	0	-0.59	1	1
PIK3R1	0.011	0.043	-10000	0	-0.63	3	3
ANGPT2	-0.18	0.33	-10000	0	-0.83	93	93
BMX	-0.12	0.33	-10000	0	-1.1	56	56
ANGPT1	-0.14	0.36	-10000	0	-1.2	57	57
tube development	-0.12	0.28	-10000	0	-0.66	100	100
ANGPT4	-0.048	0.18	-10000	0	-0.61	64	64
response to hypoxia	-0.009	0.023	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.22	0.37	-10000	0	-1.2	62	62
alpha5/beta1 Integrin	-0.031	0.12	-10000	0	-0.45	46	46
FGF2	0.015	0.034	-10000	0	-0.61	2	2
STAT5A (dimer)	-0.15	0.33	-10000	0	-0.81	85	85
mol:L-citrulline	-0.081	0.24	-10000	0	-0.64	61	61
AGTR1	-0.08	0.22	-10000	0	-0.6	101	101
MAPK14	-0.1	0.32	-10000	0	-1.1	54	54
Tie2/SHP2	-0.047	0.16	-10000	0	-1.1	12	12
TEK	-0.025	0.19	-10000	0	-1	16	16
RPS6KB1	-0.099	0.28	-10000	0	-0.83	60	60
Angiotensin II/AT1	-0.061	0.16	-10000	0	-0.45	101	101
Tie2/Ang1/GRB2	-0.099	0.34	-10000	0	-1.1	54	54
MAPK3	-0.074	0.3	-10000	0	-1	54	54
MAPK1	-0.074	0.3	-10000	0	-1	54	54
Tie2/Ang1/GRB7	-0.13	0.34	-10000	0	-1.1	57	57
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	-0.098	0.33	-10000	0	-1.1	54	54
PI3K	-0.13	0.33	-10000	0	-1	60	60
FES	-0.11	0.32	-10000	0	-1.1	54	54
Crk/Dok-R	-0.17	0.31	-10000	0	-1	58	58
Tie2/Ang1/ABIN2	-0.098	0.34	-10000	0	-1.1	54	54
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.1	0.28	-10000	0	-0.77	62	62
STAT5A	0.004	0.081	-10000	0	-0.62	11	11
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.099	0.28	-10000	0	-0.83	60	60
Tie2/Ang2	-0.18	0.37	-10000	0	-0.91	99	99
Tie2/Ang1	-0.11	0.35	-10000	0	-1.2	54	54
FOXO1	-0.12	0.3	-10000	0	-0.77	68	68
ELF1	0.021	0.015	-10000	0	-10000	0	0
ELF2	-0.097	0.32	-10000	0	-1.1	54	54
mol:Choline	-0.085	0.32	-10000	0	-1.1	54	54
cell migration	-0.066	0.081	-10000	0	-0.24	45	45
FYN	-0.14	0.32	-10000	0	-0.76	99	99
DOK2	-0.085	0.23	-10000	0	-0.6	109	109
negative regulation of cell cycle	-0.12	0.27	-10000	0	-0.63	93	93
ETS1	-0.007	0.09	-10000	0	-0.62	7	7
PXN	-0.074	0.24	-10000	0	-0.68	59	59
ITGB1	0.012	0.04	-10000	0	-0.59	3	3
NOS3	-0.094	0.27	-10000	0	-0.74	61	61
RAC1	0.015	0	-10000	0	-10000	0	0
TNF	-0.14	0.27	-10000	0	-0.63	152	152
MAPKKK cascade	-0.085	0.32	-10000	0	-1.1	54	54
RASA1	0.015	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	-0.11	0.34	-10000	0	-1.1	55	55
NCK1	0.015	0	-10000	0	-10000	0	0
vasculogenesis	-0.071	0.22	-10000	0	-0.57	61	61
mol:Phosphatidic acid	-0.085	0.32	-10000	0	-1.1	54	54
mol:Angiotensin II	-0.003	0.009	-10000	0	-10000	0	0
mol:NADP	-0.081	0.24	-10000	0	-0.64	61	61
Rac1/GTP	-0.14	0.23	-10000	0	-0.77	60	60
MMP2	-0.11	0.34	-10000	0	-1.1	56	56

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.077	0.16	-9999	-0.43	121	121
alphaV beta3 Integrin	-0.068	0.14	-9999	-0.36	127	127
PTK2	-0.068	0.2	-9999	-0.52	54	54
IGF1R	0.005	0.081	-9999	-0.62	11	11
PI4KB	0.015	0	-9999	-10000	0	0
MFGE8	0.011	0.049	-9999	-0.62	4	4
SRC	0.013	0.035	-9999	-0.62	2	2
CDKN1B	-0.047	0.13	-9999	-0.58	28	28
VEGFA	-0.091	0.23	-9999	-0.59	118	118
ILK	-0.047	0.13	-9999	-0.58	28	28
ROCK1	0.015	0	-9999	-10000	0	0
AKT1	-0.008	0.13	-9999	-0.54	28	28
PTK2B	-0.085	0.22	-9999	-0.59	67	67
alphaV/beta3 Integrin/JAM-A	-0.076	0.14	-9999	-0.64	12	12
CBL	0.014	0.025	-9999	-0.62	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.069	0.14	-9999	-0.36	127	127
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.021	0.1	-9999	-0.44	27	27
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.025	0.13	-9999	-0.45	12	12
alphaV/beta3 Integrin/Syndecan-1	-0.11	0.2	-9999	-0.44	165	165
PI4KA	0.009	0.061	-9999	-0.59	7	7
IGF-1R heterotetramer/IGF1/IRS1	-0.085	0.17	-9999	-0.58	48	48
PI4 Kinase	-0.004	0.043	-9999	-0.42	7	7
PIK3CA	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.15	0.22	-9999	-0.44	231	231
RPS6KB1	-0.027	0.18	-9999	-0.54	48	48
TLN1	0.015	0	-9999	-10000	0	0
MAPK3	-0.068	0.13	-9999	-0.46	37	37
GPR124	0.01	0.057	-9999	-0.59	6	6
MAPK1	-0.068	0.13	-9999	-0.46	36	36
PXN	0.015	0	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.62	3	3
alphaV/beta3 Integrin/Tumstatin	-0.13	0.2	-9999	-0.41	216	216
cell adhesion	-0.058	0.12	-9999	-0.54	1	1
ANGPTL3	0.005	0.024	-9999	-0.59	1	1
VEGFR2 homodimer/VEGFA homodimer/Src	-0.065	0.14	-9999	-0.36	122	122
IGF-1R heterotetramer	0.005	0.081	-9999	-0.62	11	11
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.012	0.04	-9999	-0.59	3	3
ITGB3	-0.099	0.24	-9999	-0.6	125	125
IGF1	-0.005	0.11	-9999	-0.61	22	22
RAC1	0.015	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.07	0.14	-9999	-0.36	129	129
apoptosis	0.014	0.025	-9999	-0.62	1	1
CD47	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.067	0.14	-9999	-0.36	126	126
VCL	0.011	0.053	-9999	-0.6	5	5
alphaV/beta3 Integrin/Del1	-0.12	0.2	-9999	-0.42	201	201
CSF1	0.004	0.085	-9999	-0.62	12	12
PIK3C2A	-0.048	0.13	-9999	-0.58	28	28
PI4 Kinase/Pyk2	-0.11	0.18	-9999	-0.53	80	80
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.12	0.21	-9999	-0.53	97	97
FAK1/Vinculin	-0.047	0.17	-9999	-0.42	40	40
alphaV beta3/Integrin/ppsTEM5	-0.071	0.15	-9999	-0.37	129	129
RHOA	0.015	0	-9999	-10000	0	0
VTN	-0.017	0.14	-9999	-0.62	34	34
BCAR1	0.014	0.025	-9999	-0.62	1	1
FGF2	0.013	0.034	-9999	-0.61	2	2
F11R	0.019	0.061	-9999	-0.43	12	12
alphaV/beta3 Integrin/Lactadherin	-0.07	0.14	-9999	-0.36	129	129
alphaV/beta3 Integrin/TGFBR2	-0.069	0.14	-9999	-0.36	127	127
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.008	0.053	-9999	-0.36	14	14
HSP90AA1	0.015	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.061	0.13	-9999	-0.33	126	126
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.028	0.16	-9999	-0.59	48	48
alphaV/beta3 Integrin/Pyk2	-0.085	0.22	-9999	-0.6	67	67
SDC1	-0.055	0.2	-9999	-0.6	77	77
VAV3	-0.08	0.17	-9999	-0.7	4	4
PTPN11	0.013	0.035	-9999	-0.62	2	2
IRS1	0.009	0.065	-9999	-0.62	7	7
FAK1/Paxillin	-0.045	0.17	-9999	-0.42	39	39
cell migration	-0.032	0.16	-9999	-0.44	17	17
ITGAV	0.014	0.025	-9999	-0.62	1	1
PI3K	-0.067	0.13	-9999	-0.58	14	14
SPP1	-0.13	0.26	-9999	-0.6	155	155
KDR	0.011	0.048	-9999	-0.61	4	4
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.014	0.025	-9999	-0.62	1	1
COL4A3	-0.097	0.24	-9999	-0.6	121	121
angiogenesis	-0.019	0.16	-9999	-0.48	42	42
Rac1/GTP	-0.098	0.13	-9999	-0.64	4	4
EDIL3	-0.084	0.23	-9999	-0.62	105	105
cell proliferation	-0.069	0.14	-9999	-0.36	127	127

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.077	0.16	-9999	-0.43	121	121
PDGFRB	0.009	0.053	-9999	-0.6	5	5
SPHK1	-0.039	0.13	-9999	-0.64	24	24
mol:S1P	-0.039	0.12	-9999	-0.55	27	27
S1P1/S1P/Gi	-0.052	0.2	-9999	-0.4	116	116
GNAO1	-0.013	0.13	-9999	-0.63	28	28
PDGFB-D/PDGFRB/PLCgamma1	-0.034	0.18	-9999	-0.54	36	36
PLCG1	-0.041	0.18	-9999	-0.54	39	39
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.053	-9999	-0.59	5	5
GNAI2	0.014	0.007	-9999	-10000	0	0
GNAI3	0.013	0.007	-9999	-10000	0	0
GNAI1	-0.022	0.15	-9999	-0.63	37	37
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.05	0.15	-9999	-0.36	121	121
S1P1/S1P	-0.083	0.14	-9999	-0.39	79	79
negative regulation of cAMP metabolic process	-0.05	0.19	-9999	-0.39	116	116
MAPK3	-0.067	0.24	-9999	-0.53	113	113
calcium-dependent phospholipase C activity	-0.001	0.004	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.01	0.048	-9999	-0.6	4	4
PLCB2	-0.042	0.15	-9999	-0.38	66	66
RAC1	0.015	0	-9999	-10000	0	0
RhoA/GTP	-0.07	0.12	-9999	-0.35	63	63
receptor internalization	-0.078	0.13	-9999	-0.36	79	79
PTGS2	-0.13	0.37	-9999	-0.91	106	106
Rac1/GTP	-0.07	0.12	-9999	-0.35	63	63
RHOA	0.015	0	-9999	-10000	0	0
VEGFA	-0.092	0.23	-9999	-0.59	118	118
negative regulation of T cell proliferation	-0.05	0.19	-9999	-0.39	116	116
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.01	0.044	-9999	-0.63	3	3
MAPK1	-0.067	0.24	-9999	-0.55	100	100
S1P1/S1P/PDGFB-D/PDGFRB	-0.046	0.17	-9999	-0.4	79	79
ABCC1	0.012	0.041	-9999	-0.59	3	3

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.005	0.08	-9999	-0.4	23	23
NFATC2	-0.036	0.13	-9999	-0.4	73	73
NFATC3	0.009	0.03	-9999	-10000	0	0
CD40LG	-0.16	0.3	-9999	-0.78	76	76
PTGS2	-0.2	0.34	-9999	-0.76	131	131
JUNB	-0.029	0.16	-9999	-0.6	48	48
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.006	0.011	-9999	-10000	0	0
CaM/Ca2+	-0.006	0.011	-9999	-10000	0	0
CALM1	0.012	0.008	-9999	-10000	0	0
JUN	0.004	0.067	-9999	-0.6	8	8
mol:Ca2+	-0.007	0.013	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0.015	-9999	-0.38	1	1
FOSL1	-0.14	0.27	-9999	-0.6	163	163
CREM	0.013	0.033	-9999	-0.59	2	2
Jun/NFAT1-c-4/p21SNFT	-0.13	0.18	-9999	-0.54	80	80
FOS	-0.078	0.22	-9999	-0.62	95	95
IFNG	-0.15	0.27	-9999	-0.73	62	62
AP-1/NFAT1-c-4	-0.22	0.29	-9999	-0.76	104	104
FASLG	-0.16	0.29	-9999	-0.78	65	65
NFAT1-c-4/ICER1	-0.069	0.13	-9999	-0.45	36	36
IL2RA	-0.22	0.35	-9999	-0.72	164	164
FKBP12/FK506	-0.001	0.017	-9999	-0.43	1	1
CSF2	-0.15	0.28	-9999	-0.74	61	61
JunB/Fra1/NFAT1-c-4	-0.16	0.21	-9999	-0.56	97	97
IL4	-0.15	0.27	-9999	-0.7	67	67
IL2	-0.009	0.015	-9999	-10000	0	0
IL3	-0.029	0.1	-9999	-0.89	9	9
FKBP1A	0.014	0.023	-9999	-0.59	1	1
BATF3	-0.054	0.19	-9999	-0.6	76	76
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.007	0.074	-9999	-0.62	9	9

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.013	0.043	-9999	-0.62	3	3
ELF1	-0.067	0.14	-9999	-0.35	75	75
CCNA2	-0.074	0.22	-9999	-0.6	97	97
PIK3CA	0.016	0.001	-9999	-10000	0	0
JAK3	-0.056	0.2	-9999	-0.6	78	78
PIK3R1	0.013	0.043	-9999	-0.62	3	3
JAK1	0.016	0.001	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.063	0.19	-9999	-0.5	55	55
SHC1	0.002	0.092	-9999	-0.59	16	16
SP1	0.019	0.043	-9999	-0.35	6	6
IL2RA	-0.16	0.32	-9999	-0.64	193	193
IL2RB	-0.11	0.25	-9999	-0.6	140	140
SOS1	0.016	0.001	-9999	-10000	0	0
IL2RG	-0.038	0.17	-9999	-0.6	58	58
G1/S transition of mitotic cell cycle	-0.044	0.19	-9999	-0.52	63	63
PTPN11	0.014	0.035	-9999	-0.62	2	2
CCND2	0.024	0.098	-9999	-0.68	12	12
LCK	-0.097	0.24	-9999	-0.6	123	123
GRB2	0.015	0.023	-9999	-0.59	1	1
IL2	0.001	0.003	-9999	-10000	0	0
CDK6	-0.037	0.17	-9999	-0.6	57	57
CCND3	-0.044	0.17	-9999	-0.51	22	22

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.049	-10000	0	-0.62	4	4
HDAC3	0.015	0	-10000	0	-10000	0	0
VDR	-0.11	0.24	-10000	0	-0.6	132	132
Cbp/p300/PCAF	-0.004	0.038	-10000	0	-0.38	7	7
EP300	0.012	0.043	-10000	0	-0.62	3	3
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.02	0.064	-10000	0	-0.41	6	6
KAT2B	0.012	0.042	-10000	0	-0.61	3	3
MAPK14	0.014	0.023	-10000	0	-0.59	1	1
AKT1	0.033	0.086	0.23	17	-0.37	3	20
RAR alpha/9cRA/Cyclin H	-0.052	0.08	-10000	0	-0.49	2	2
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.017	0.069	-10000	0	-0.45	6	6
CDC2	0.001	0	-10000	0	-10000	0	0
response to UV	0.001	0	-10000	0	-10000	0	0
RAR alpha/Jnk1	-0.06	0.094	-10000	0	-0.5	10	10
NCOR2	0.013	0.035	-10000	0	-0.62	2	2
VDR/VDR/Vit D3	-0.088	0.18	-10000	0	-0.44	132	132
RXRs/RARs/NRIP1/9cRA	-0.056	0.21	-10000	0	-0.5	78	78
NCOA2	-0.019	0.14	-10000	0	-0.62	36	36
NCOA3	0.015	0	-10000	0	-10000	0	0
NCOA1	0.015	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.11	0.24	-10000	0	-0.6	132	132
RARG	0.013	0.047	-10000	0	-0.59	4	4
RAR gamma1/9cRA	-0.002	0.028	-10000	0	-0.36	4	4
MAPK3	0.016	0	-10000	0	-10000	0	0
MAPK1	0.015	0	-10000	0	-10000	0	0
MAPK8	0.008	0.074	-10000	0	-0.62	9	9
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.18	0.24	-10000	0	-0.59	133	133
RARA	-0.047	0.12	-10000	0	-0.26	119	119
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.003	0.093	-10000	0	-0.38	19	19
PRKCA	0.017	0.035	-10000	0	-0.62	2	2
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.076	0.21	-10000	0	-0.49	110	110
RXRG	-0.15	0.24	-10000	0	-0.46	175	175
RXRA	-0.032	0.11	-10000	0	-0.42	3	3
RXRB	-0.077	0.16	-10000	0	-0.36	110	110
VDR/Vit D3/DNA	-0.088	0.18	-10000	0	-0.44	132	132
RBP1	-0.18	0.28	-10000	0	-0.59	211	211
CRBP1/9-cic-RA	-0.14	0.2	-10000	0	-0.44	211	211
RARB	0.013	0.053	-10000	0	-0.59	5	5
PRKCG	-0.19	0.3	-10000	0	-0.6	230	230
MNAT1	0.014	0.023	-10000	0	-0.59	1	1
RAR alpha/RXRs	-0.048	0.22	-10000	0	-0.53	79	79
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.041	0.18	-10000	0	-0.42	79	79
proteasomal ubiquitin-dependent protein catabolic process	-0.002	0.096	-10000	0	-0.4	8	8
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.076	0.21	-10000	0	-0.49	110	110
positive regulation of DNA binding	-0.05	0.076	-10000	0	-0.46	2	2
NRIP1	-0.066	0.19	-10000	0	-0.6	37	37
RXRs/RARs	-0.083	0.21	-10000	0	-0.49	110	110
RXRs/RXRs/DNA/9cRA	-0.13	0.21	-10000	0	-0.55	110	110
PRKACA	0.015	0	-10000	0	-10000	0	0
CDK7	0.015	0	-10000	0	-10000	0	0
TFIIH	-0.001	0.014	-10000	0	-0.35	1	1
RAR alpha/9cRA	-0.036	0.055	-10000	0	-0.42	1	1
CCNH	0.015	0	-10000	0	-10000	0	0
CREBBP	0.014	0.025	-10000	0	-0.62	1	1
RAR gamma2/9cRA	-0.002	0.024	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.015	0	-9999	-10000	0	0
EGFR	-0.11	0.25	-9999	-0.6	138	138
EGF/EGFR	-0.12	0.17	-9999	-0.37	131	131
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.094	0.16	-9999	-0.64	18	18
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.011	0.12	-9999	-0.61	28	28
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.038	0.18	-9999	-0.61	57	57
EGF/EGFR dimer/SHC	-0.11	0.19	-9999	-0.4	192	192
mol:GDP	-0.093	0.16	-9999	-0.64	18	18
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.023	0.15	-9999	-0.6	41	41
GRB2/SOS1	-0.001	0.016	-9999	-0.42	1	1
HRAS/GTP	-0.085	0.14	-9999	-0.59	18	18
SHC1	0.001	0.092	-9999	-0.59	16	16
HRAS/GDP	-0.086	0.15	-9999	-0.6	18	18
FRAP1	-0.058	0.17	-9999	-0.61	18	18
EGF/EGFR dimer	-0.13	0.21	-9999	-0.46	183	183
SOS1	0.015	0	-9999	-10000	0	0
GRB2	0.014	0.023	-9999	-0.59	1	1
ETA receptor/Endothelin-1	-0.045	0.14	-9999	-0.45	66	66

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.003	0.15	-10000	0	-1.3	9	9
VDR	-0.11	0.24	-10000	0	-0.6	132	132
FAM120B	0.014	0.023	-10000	0	-0.59	1	1
RXRs/LXRs/DNA/9cRA	-0.035	0.16	-10000	0	-0.45	34	34
RXRs/LXRs/DNA/Oxysterols	-0.049	0.2	-10000	0	-0.45	93	93
MED1	0.015	0	-10000	0	-10000	0	0
mol:9cRA	-0.004	0.022	-10000	0	-10000	0	0
RARs/THRs/DNA/Src-1	0.026	0.075	-10000	0	-0.61	3	3
RXRs/NUR77	-0.039	0.16	-10000	0	-0.36	115	115
RXRs/PPAR	-0.021	0.13	-10000	0	-0.4	25	25
NCOR2	0.013	0.035	-10000	0	-0.62	2	2
VDR/VDR/Vit D3	-0.088	0.18	-10000	0	-0.44	132	132
RARs/VDR/DNA/Vit D3	-0.064	0.13	-10000	0	-0.35	53	53
RARA	0.015	0	-10000	0	-10000	0	0
NCOA1	0.015	0	-10000	0	-10000	0	0
VDR/VDR/DNA	-0.11	0.24	-10000	0	-0.6	132	132
RARs/RARs/DNA/9cRA	-0.004	0.043	-10000	0	-0.4	7	7
RARG	0.012	0.046	-10000	0	-0.59	4	4
RPS6KB1	0.024	0.066	-10000	0	-0.41	9	9
RARs/THRs/DNA/SMRT	0.025	0.077	-10000	0	-0.61	3	3
THRA	0.001	0.095	-10000	0	-0.62	15	15
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	-0.088	0.18	-10000	0	-0.44	132	132
RXRs/PPAR/9cRA/PGJ2/DNA	-0.04	0.16	0.31	4	-0.36	111	115
NR1H4	-0.12	0.25	-10000	0	-0.6	142	142
RXRs/LXRs/DNA	-0.022	0.16	-10000	0	-0.45	29	29
NR1H2	0.015	0.015	-10000	0	-10000	0	0
NR1H3	0.014	0.018	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.091	0.2	-10000	0	-0.4	156	156
NR4A1	-0.009	0.12	-10000	0	-0.59	27	27
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	-0.065	0.15	-10000	0	-0.34	98	98
RXRG	-0.091	0.24	-10000	0	-0.62	111	111
RXR alpha/CCPG	0.02	0.028	-10000	0	-0.43	2	2
RXRA	0.014	0.029	-10000	0	-0.62	1	1
RXRB	0.014	0.018	-10000	0	-10000	0	0
THRB	-0.008	0.12	-10000	0	-0.6	25	25
PPARG	-0.015	0.13	-10000	0	-0.61	32	32
PPARD	0.015	0	-10000	0	-10000	0	0
TNF	-0.14	0.39	-10000	0	-1	88	88
mol:Oxysterols	-0.003	0.02	-10000	0	-10000	0	0
cholesterol transport	-0.048	0.2	-10000	0	-0.44	93	93
PPARA	0.015	0	-10000	0	-10000	0	0
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.011	0.053	-10000	0	-0.6	5	5
RXRs/NUR77/BCL2	-0.024	0.12	-10000	0	-0.28	106	106
SREBF1	-0.045	0.23	-10000	0	-0.82	27	27
RXRs/RXRs/DNA/9cRA	-0.04	0.16	0.3	4	-0.36	111	115
ABCA1	-0.049	0.24	-10000	0	-0.88	30	30
RARs/THRs	-0.022	0.089	-10000	0	-0.82	3	3
RXRs/FXR	-0.1	0.21	-10000	0	-0.42	160	160
BCL2	0.012	0.043	-10000	0	-0.62	3	3

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.069	0.14	-9999	-0.66	11	11
SMAD6-7/SMURF1	-0.004	0.041	-9999	-0.37	8	8
NOG	-0.094	0.24	-9999	-0.62	116	116
SMAD9	-0.053	0.16	-9999	-0.58	51	51
SMAD4	0.015	0	-9999	-10000	0	0
SMAD5	0.004	0.11	-9999	-0.45	19	19
BMP7/USAG1	-0.093	0.18	-9999	-0.44	140	140
SMAD5/SKI	0.012	0.11	-9999	-0.43	17	17
SMAD1	0.045	0.043	-9999	-10000	0	0
BMP2	-0.098	0.24	-9999	-0.62	119	119
SMAD1/SMAD1/SMAD4	-0.006	0.033	-9999	-10000	0	0
BMPR1A	0.014	0.025	-9999	-0.62	1	1
BMPR1B	-0.016	0.14	-9999	-0.62	33	33
BMPR1A-1B/BAMBI	-0.024	0.097	-9999	-0.4	39	39
AHSG	-0.066	0.21	-9999	-0.61	86	86
CER1	-0.034	0.15	-9999	-0.59	47	47
BMP2-4/CER1	-0.1	0.21	-9999	-0.45	157	157
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.009	0.14	-9999	-0.45	38	38
BMP2-4 (homodimer)	-0.096	0.21	-9999	-0.51	126	126
RGMB	0.009	0.063	-9999	-0.6	7	7
BMP6/BMPR2/BMPR1A-1B	-0.029	0.1	-9999	-0.37	42	42
RGMA	0.002	0.091	-9999	-0.62	14	14
SMURF1	0.015	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.016	0.14	-9999	-0.44	37	37
BMP2-4/USAG1	-0.15	0.23	-9999	-0.45	224	224
SMAD6/SMURF1/SMAD5	0.012	0.11	-9999	-0.43	17	17
SOSTDC1	-0.11	0.24	-9999	-0.6	132	132
BMP7/BMPR2/BMPR1A-1B	-0.023	0.089	-9999	-0.35	43	43
SKI	0.015	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.007	0.12	-9999	-0.6	24	24
HFE2	0.002	0.073	-9999	-0.59	10	10
ZFYVE16	0.015	0	-9999	-10000	0	0
MAP3K7	0.015	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.088	0.18	-9999	-0.43	138	138
SMAD5/SMAD5/SMAD4	0.012	0.11	-9999	-0.43	17	17
MAPK1	0.015	0	-9999	-10000	0	0
TAK1/TAB family	-0.044	0.095	-9999	-0.37	34	34
BMP7 (homodimer)	0.005	0.081	-9999	-0.62	11	11
NUP214	0.015	0	-9999	-10000	0	0
BMP6/FETUA	-0.073	0.16	-9999	-0.44	109	109
SMAD1/SKI	0.052	0.041	-9999	-10000	0	0
SMAD6	0.01	0.059	-9999	-0.61	6	6
CTDSP2	0.001	0.092	-9999	-0.59	16	16
BMP2-4/FETUA	-0.13	0.22	-9999	-0.44	195	195
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.17	0.28	-9999	-0.61	195	195
BMPR2 (homodimer)	0.015	0	-9999	-10000	0	0
GADD34/PP1CA	-0.005	0.04	-9999	-0.35	9	9
BMPR1A-1B (homodimer)	-0.023	0.1	-9999	-0.46	34	34
CHRDL1	-0.073	0.22	-9999	-0.62	93	93
ENDOFIN/SMAD1	0.052	0.041	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	-0.006	0.039	-9999	-0.42	1	1
SMAD6/SMURF1	0.015	0	-9999	-10000	0	0
BAMBI	0.008	0.067	-9999	-0.6	8	8
SMURF2	0.015	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.13	0.23	-9999	-0.46	193	193
BMP2-4/GREM1	-0.19	0.24	-9999	-0.44	281	281
SMAD7	0.013	0.035	-9999	-0.62	2	2
SMAD8A/SMAD8A/SMAD4	-0.021	0.16	-9999	-0.54	51	51
SMAD1/SMAD6	0.052	0.041	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	0.005	0.081	-9999	-0.62	11	11
BMP6	-0.007	0.12	-9999	-0.6	24	24
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.011	0.13	-9999	-0.4	39	39
PPM1A	0.015	0	-9999	-10000	0	0
SMAD1/SMURF2	0.052	0.041	-9999	-10000	0	0
SMAD7/SMURF1	-0.001	0.025	-9999	-0.46	2	2
CTDSPL	0.014	0.025	-9999	-0.62	1	1
PPP1CA	0.014	0.023	-9999	-0.59	1	1
XIAP	0.015	0	-9999	-10000	0	0
CTDSP1	0.015	0	-9999	-10000	0	0
PPP1R15A	0.008	0.065	-9999	-0.59	8	8
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.052	0.18	-9999	-0.47	65	65
CHRD	0.003	0.088	-9999	-0.62	13	13
BMPR2	0.015	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.026	0.15	-9999	-0.48	37	37
BMP4	-0.009	0.12	-9999	-0.62	25	25
FST	-0.084	0.23	-9999	-0.61	107	107
BMP2-4/NOG	-0.14	0.26	-9999	-0.52	186	186
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.021	0.082	-9999	-0.64	2	2

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.014	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.054	0.13	-10000	0	-0.34	108	108
regulation of S phase of mitotic cell cycle	-0.009	0.11	-10000	0	-0.28	85	85
GNAO1	-0.012	0.13	-10000	0	-0.62	28	28
HRAS	0.015	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.012	0.069	-10000	0	-0.4	21	21
PELP1	0.013	0.035	-10000	0	-0.62	2	2
AKT1	0.013	0.017	-10000	0	-0.43	1	1
MAP2K1	-0.005	0.13	-10000	0	-0.39	25	25
T-DHT/AR	-0.07	0.17	-10000	0	-0.46	102	102
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.002	-10000	0	-0.006	94	94
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	-0.02	0.15	-10000	0	-0.62	37	37
mol:GDP	-0.067	0.16	-10000	0	-0.43	103	103
cell proliferation	-0.011	0.17	-10000	0	-0.56	25	25
PIK3CA	0.015	0	-10000	0	-10000	0	0
FOS	-0.049	0.26	-10000	0	-0.64	95	95
mol:Ca2+	-0.012	0.024	-10000	0	-0.067	74	74
MAPK3	-0.006	0.15	-10000	0	-0.49	25	25
MAPK1	0.002	0.087	-10000	0	-0.28	18	18
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
mol:IP3	0	0.002	-10000	0	-0.004	95	95
cAMP biosynthetic process	0	0.07	-10000	0	-0.37	21	21
GNG2	0.009	0.06	-10000	0	-0.62	6	6
potassium channel inhibitor activity	0	0.002	-10000	0	-0.004	95	95
HRAS/GTP	-0.05	0.12	-10000	0	-0.33	86	86
actin cytoskeleton reorganization	-0.001	0.02	-10000	0	-0.3	3	3
SRC	0.013	0.035	-10000	0	-0.62	2	2
voltage-gated calcium channel activity	0	0.002	-10000	0	-0.004	95	95
PI3K	-0.002	0.026	-10000	0	-0.39	3	3
apoptosis	0.011	0.16	0.42	63	-10000	0	63
T-DHT/AR/PELP1	-0.059	0.14	-10000	0	-0.39	103	103
HRAS/GDP	-0.062	0.15	-10000	0	-0.45	82	82
CREB1	-0.014	0.17	-10000	0	-0.45	63	63
RAC1-CDC42/GTP	-0.001	0.02	-10000	0	-0.3	3	3
AR	-0.082	0.23	-10000	0	-0.62	102	102
GNB1	0.015	0	-10000	0	-10000	0	0
RAF1	-0.012	0.13	-10000	0	-0.39	25	25
RAC1-CDC42/GDP	-0.059	0.14	-10000	0	-0.42	82	82
T-DHT/AR/PELP1/Src	-0.053	0.13	-10000	0	-0.36	103	103
MAP2K2	-0.005	0.13	-10000	0	-0.4	24	24
T-DHT/AR/PELP1/Src/PI3K	-0.01	0.11	-10000	0	-0.28	85	85
GNAZ	0.012	0.043	-10000	0	-0.62	3	3
SHBG	-0.005	0.11	-10000	0	-0.62	21	21
Gi family/GNB1/GNG2/GDP	0.008	0.12	-10000	0	-0.46	30	30
mol:T-DHT	0	0.001	-10000	0	-0.003	71	71
RAC1	0.015	0	-10000	0	-10000	0	0
GNRH1	0.003	0.07	-10000	0	-0.46	15	15
Gi family/GTP	-0.044	0.097	-10000	0	-0.31	44	44
CDC42	0.015	0	-10000	0	-10000	0	0

×

BCR signaling pathway

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
JUN	-0.028	0.14	-10000	0	-0.38	56	56
IKBKB	-0.005	0.075	-10000	0	-0.27	15	15
AKT1	-0.046	0.1	-10000	0	-0.26	50	50
IKBKG	-0.003	0.079	-10000	0	-0.29	15	15
CALM1	-0.043	0.14	-10000	0	-0.41	59	59
PIK3CA	0.015	0	-10000	0	-10000	0	0
MAP3K1	-0.056	0.18	-10000	0	-0.51	65	65
MAP3K7	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	-0.055	0.15	0.22	2	-0.42	71	73
DOK1	0.014	0.025	-10000	0	-0.62	1	1
AP-1	-0.02	0.097	-10000	0	-0.27	27	27
LYN	0.011	0.053	-10000	0	-0.6	5	5
BLNK	-0.036	0.17	-10000	0	-0.62	54	54
SHC1	0.001	0.092	-10000	0	-0.59	16	16
BCR complex	-0.084	0.19	-10000	0	-0.48	118	118
CD22	-0.18	0.22	-10000	0	-0.53	129	129
CAMK2G	-0.033	0.14	-10000	0	-0.54	23	23
CSNK2A1	0.015	0	-10000	0	-10000	0	0
INPP5D	0.007	0.071	-10000	0	-0.6	9	9
SHC/GRB2/SOS1	-0.085	0.16	-10000	0	-0.61	38	38
GO:0007205	-0.056	0.16	0.22	2	-0.42	71	73
SYK	-0.004	0.11	-10000	0	-0.62	20	20
ELK1	-0.044	0.15	-10000	0	-0.42	60	60
NFATC1	-0.054	0.17	-10000	0	-0.49	64	64
B-cell antigen/BCR complex	-0.084	0.19	-10000	0	-0.48	118	118
PAG1/CSK	-0.001	0.018	-10000	0	-0.46	1	1
NFKBIB	0.01	0.028	-10000	0	-10000	0	0
HRAS	-0.035	0.15	-10000	0	-0.47	40	40
NFKBIA	0.01	0.028	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.016	0.023	-10000	0	-10000	0	0
RasGAP/Csk	-0.17	0.21	-10000	0	-0.64	62	62
mol:GDP	-0.049	0.15	0.22	4	-0.42	64	68
PTEN	0.015	0	-10000	0	-10000	0	0
CD79B	-0.06	0.2	-10000	0	-0.6	81	81
NF-kappa-B/RelA/I kappa B alpha	0.016	0.023	-10000	0	-10000	0	0
GRB2	0.014	0.023	-10000	0	-0.59	1	1
PI3K/BCAP/CD19	-0.079	0.19	-10000	0	-0.51	80	80
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
mol:IP3	-0.061	0.16	0.22	2	-0.43	71	73
CSK	0.015	0	-10000	0	-10000	0	0
FOS	-0.075	0.18	-10000	0	-0.55	44	44
CHUK	-0.003	0.079	-10000	0	-0.29	15	15
IBTK	0.015	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.054	0.13	-10000	0	-0.54	28	28
PTPN6	-0.17	0.21	-10000	0	-0.52	128	128
RELA	0.015	0	-10000	0	-10000	0	0
BCL2A1	-0.008	0.051	-10000	0	-0.1	66	66
VAV2	-0.11	0.19	-10000	0	-0.58	67	67
ubiquitin-dependent protein catabolic process	0.015	0.027	-10000	0	-10000	0	0
BTK	-0.039	0.2	0.37	6	-1.1	21	27
CD19	-0.11	0.19	-10000	0	-0.55	74	74
MAP4K1	-0.011	0.13	-10000	0	-0.62	28	28
CD72	-0.019	0.14	-10000	0	-0.59	38	38
PAG1	0.014	0.025	-10000	0	-0.62	1	1
MAPK14	-0.039	0.16	-10000	0	-0.43	62	62
SH3BP5	0.011	0.049	-10000	0	-0.62	4	4
PIK3AP1	-0.054	0.18	0.25	2	-0.51	59	61
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.049	0.2	-10000	0	-0.54	67	67
RAF1	-0.024	0.14	-10000	0	-0.51	27	27
RasGAP/p62DOK/SHIP	-0.16	0.2	-10000	0	-0.62	64	64
CD79A	-0.031	0.16	-10000	0	-0.6	50	50
re-entry into mitotic cell cycle	-0.021	0.097	-10000	0	-0.28	27	27
RASA1	0.015	0	-10000	0	-10000	0	0
MAPK3	-0.002	0.12	-10000	0	-0.45	20	20
MAPK1	-0.002	0.12	-10000	0	-0.45	20	20
CD72/SHP1	-0.15	0.23	-10000	0	-0.59	92	92
NFKB1	0.015	0	-10000	0	-10000	0	0
MAPK8	-0.042	0.16	-10000	0	-0.44	65	65
actin cytoskeleton organization	-0.062	0.18	-10000	0	-0.52	56	56
NF-kappa-B/RelA	0.037	0.044	-10000	0	-10000	0	0
Calcineurin	-0.049	0.11	-10000	0	-0.49	23	23
PI3K	-0.13	0.17	-10000	0	-0.5	79	79
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.071	0.16	0.25	2	-0.46	71	73
SOS1	0.015	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.1	0.26	-10000	0	-0.79	69	69
DAPP1	-0.13	0.28	-10000	0	-0.9	63	63
cytokine secretion	-0.049	0.16	-10000	0	-0.46	64	64
mol:DAG	-0.061	0.16	0.22	2	-0.43	71	73
PLCG2	0.004	0.083	-10000	0	-0.61	12	12
MAP2K1	-0.013	0.13	-10000	0	-0.5	22	22
B-cell antigen/BCR complex/FcgammaRIIB	-0.2	0.24	-10000	0	-0.44	305	305
mol:PI-3-4-5-P3	-0.098	0.12	-10000	0	-0.36	73	73
ETS1	-0.024	0.13	-10000	0	-0.48	24	24
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.095	0.19	-10000	0	-0.7	36	36
B-cell antigen/BCR complex/LYN	-0.11	0.18	-10000	0	-0.52	80	80
MALT1	0.015	0	-10000	0	-10000	0	0
TRAF6	0.013	0.035	-10000	0	-0.62	2	2
RAC1	-0.067	0.19	-10000	0	-0.56	56	56
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.23	-10000	0	-0.64	86	86
CARD11	-0.052	0.17	-10000	0	-0.57	41	41
FCGR2B	-0.21	0.3	-10000	0	-0.6	244	244
PPP3CA	0.013	0.033	-10000	0	-0.59	2	2
BCL10	0.015	0	-10000	0	-10000	0	0
IKK complex	0.006	0.036	-10000	0	-0.12	2	2
PTPRC	-0.025	0.15	-10000	0	-0.61	43	43
PDPK1	-0.047	0.098	-10000	0	-0.26	45	45
PPP3CB	0.013	0.033	-10000	0	-0.59	2	2
PPP3CC	0.015	0	-10000	0	-10000	0	0
POU2F2	0.016	0.024	-10000	0	-0.11	10	10

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.014	0.023	-9999	-0.59	1	1
LAT2	-0.056	0.18	-9999	-0.63	37	37
AP1	-0.1	0.17	-9999	-0.57	56	56
mol:PIP3	-0.065	0.2	-9999	-0.62	42	42
IKBKB	-0.031	0.12	-9999	-0.3	45	45
AKT1	-0.053	0.17	-9999	-0.48	40	40
IKBKG	-0.031	0.12	-9999	-0.3	41	41
MS4A2	-0.026	0.13	-9999	-0.59	32	32
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.015	0.001	-9999	-10000	0	0
MAP3K1	-0.016	0.15	-9999	-0.57	30	30
mol:Ca2+	-0.044	0.15	-9999	-0.44	41	41
LYN	0.009	0.055	-9999	-0.62	5	5
CBLB	-0.044	0.14	-9999	-0.53	26	26
SHC1	0.001	0.092	-9999	-0.59	16	16
RasGAP/p62DOK	-0.019	0.077	-9999	-0.33	39	39
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.007	0.071	-9999	-0.6	9	9
PLD2	-0.094	0.19	-9999	-0.56	42	42
PTPN13	-0.033	0.14	-9999	-0.59	20	20
PTPN11	0.009	0.037	-9999	-0.64	2	2
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.009	0.13	-9999	-0.35	22	22
SYK	-0.005	0.11	-9999	-0.64	20	20
GRB2	0.014	0.023	-9999	-0.59	1	1
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.18	-9999	-0.6	47	47
LAT	-0.058	0.15	-9999	-0.44	53	53
PAK2	-0.028	0.17	-9999	-0.64	32	32
NFATC2	-0.1	0.19	-9999	-0.58	73	73
HRAS	-0.041	0.19	-9999	-0.7	35	35
GAB2	0.012	0.043	-9999	-0.62	3	3
PLA2G1B	0.048	0.024	-9999	-10000	0	0
Fc epsilon R1	-0.16	0.22	-9999	-0.42	247	247
Antigen/IgE/Fc epsilon R1	-0.14	0.2	-9999	-0.38	247	247
mol:GDP	-0.05	0.2	-9999	-0.74	37	37
JUN	0.008	0.067	-9999	-0.6	8	8
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.63	3	3
FOS	-0.073	0.22	-9999	-0.61	95	95
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.08	0.14	-9999	-0.4	62	62
CHUK	-0.031	0.12	-9999	-0.3	41	41
KLRG1	-0.049	0.14	-9999	-0.41	50	50
VAV1	-0.056	0.18	-9999	-0.68	33	33
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.044	0.14	-9999	-0.54	26	26
negative regulation of mast cell degranulation	-0.041	0.14	-9999	-0.51	31	31
BTK	-0.078	0.2	-9999	-0.73	38	38
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.15	0.22	-9999	-0.48	136	136
GAB2/PI3K/SHP2	-0.11	0.15	-9999	-0.53	40	40
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.063	0.16	-9999	-0.45	56	56
RAF1	0.036	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.24	0.26	-9999	-0.68	138	138
FCER1G	-0.037	0.17	-9999	-0.61	55	55
FCER1A	-0.17	0.28	-9999	-0.6	200	200
Antigen/IgE/Fc epsilon R1/Fyn	-0.13	0.18	-9999	-0.4	138	138
MAPK3	0.047	0.024	-9999	-10000	0	0
MAPK1	0.047	0.024	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
MAPK8	0.005	0.086	-9999	-0.57	10	10
DUSP1	-0.02	0.14	-9999	-0.6	38	38
NF-kappa-B/RelA	-0.036	0.051	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.039	0.14	-9999	-0.52	25	25
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.072	0.16	-9999	-0.69	30	30
FER	-0.05	0.15	-9999	-0.49	38	38
RELA	0.015	0	-9999	-10000	0	0
ITK	-0.092	0.15	-9999	-0.37	121	121
SOS1	0.015	0	-9999	-10000	0	0
PLCG1	-0.048	0.2	-9999	-0.73	37	37
cytokine secretion	-0.026	0.037	-9999	-10000	0	0
SPHK1	-0.064	0.17	-9999	-0.5	52	52
PTK2	-0.041	0.14	-9999	-0.55	25	25
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.11	0.19	-9999	-0.58	59	59
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.054	0.19	-9999	-0.61	37	37
MAP2K2	0.042	0.025	-9999	-10000	0	0
MAP2K1	0.042	0.025	-9999	-10000	0	0
MAP2K7	0.014	0.025	-9999	-0.62	1	1
KLRG1/SHP2	-0.072	0.12	-9999	-0.46	33	33
MAP2K4	0.02	0.038	-9999	-0.94	1	1
Fc epsilon R1/FcgammaRIIB	-0.26	0.28	-9999	-0.5	307	307
mol:Choline	-0.092	0.19	-9999	-0.55	43	43
SHC/Grb2/SOS1	-0.07	0.12	-9999	-0.49	35	35
FYN	0.015	0	-9999	-10000	0	0
DOK1	0.014	0.025	-9999	-0.62	1	1
PXN	-0.03	0.13	-9999	-0.51	23	23
HCLS1	-0.056	0.17	-9999	-0.58	39	39
PRKCB	-0.056	0.15	-9999	-0.4	61	61
FCGR2B	-0.21	0.3	-9999	-0.6	244	244
IGHE	-0.002	0.006	-9999	-10000	0	0
KLRG1/SHIP	-0.042	0.15	-9999	-0.52	31	31
LCP2	0.007	0.072	-9999	-0.61	9	9
PLA2G4A	-0.058	0.16	-9999	-0.51	44	44
RASA1	0.015	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.092	0.19	-9999	-0.55	43	43
IKK complex	-0.007	0.092	-9999	-0.24	23	23
WIPF1	0.014	0.023	-9999	-0.59	1	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.013	0.12	-9999	-0.37	72	72
EPHB2	0.007	0.071	-9999	-0.6	9	9
Syndecan-2/TACI	-0.01	0.088	-9999	-0.38	34	34
LAMA1	-0.071	0.22	-9999	-0.62	91	91
Syndecan-2/alpha2 ITGB1	-0.071	0.15	-9999	-0.65	20	20
HRAS	0.015	0	-9999	-10000	0	0
Syndecan-2/CASK	-0.015	0.073	-9999	-0.38	26	26
ITGA5	-0.026	0.15	-9999	-0.59	46	46
BAX	0.029	0.081	-9999	-10000	0	0
EPB41	0.01	0.054	-9999	-0.62	5	5
positive regulation of cell-cell adhesion	-0.013	0.065	-9999	-0.33	26	26
LAMA3	-0.054	0.2	-9999	-0.61	74	74
EZR	0.009	0.06	-9999	-0.62	6	6
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.04	0.17	-9999	-0.59	61	61
Syndecan-2/MMP2	-0.012	0.13	-9999	-0.39	65	65
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.038	0.12	-9999	-0.45	57	57
dendrite morphogenesis	0.009	0.09	-9999	-0.38	34	34
Syndecan-2/GM-CSF	-0.016	0.085	-9999	-0.38	33	33
determination of left/right symmetry	0.006	0.09	-9999	-0.44	26	26
Syndecan-2/PKC delta	-0.001	0.12	-9999	-0.42	44	44
GNB2L1	0.015	0	-9999	-10000	0	0
MAPK3	0.011	0.08	-9999	-0.34	33	33
MAPK1	0.011	0.08	-9999	-0.34	33	33
Syndecan-2/RACK1	-0.012	0.06	-9999	-0.31	26	26
NF1	0.01	0.055	-9999	-0.62	5	5
FGFR/FGF/Syndecan-2	0.006	0.09	-9999	-0.44	26	26
ITGA2	-0.036	0.17	-9999	-0.61	55	55
MAPK8	0.02	0.09	-9999	-0.36	35	35
Syndecan-2/alpha2/beta1 Integrin	-0.08	0.17	-9999	-0.61	30	30
Syndecan-2/Kininogen	-0.02	0.1	-9999	-0.36	51	51
ITGB1	0.012	0.04	-9999	-0.59	3	3
SRC	0.03	0.07	-9999	-0.6	2	2
Syndecan-2/CASK/Protein 4.1	-0.016	0.073	-9999	-0.35	30	30
extracellular matrix organization	0.008	0.096	-9999	-0.4	33	33
actin cytoskeleton reorganization	-0.013	0.12	-9999	-0.37	72	72
Syndecan-2/Caveolin-2/Ras	-0.041	0.12	-9999	-0.34	81	81
Syndecan-2/Laminin alpha3	-0.03	0.15	-9999	-0.4	92	92
Syndecan-2/RasGAP	-0.011	0.055	-9999	-10000	0	0
alpha5/beta1 Integrin	-0.031	0.12	-9999	-0.45	46	46
PRKCD	-0.008	0.12	-9999	-0.62	24	24
Syndecan-2 dimer	0.009	0.091	-9999	-0.38	34	34
GO:0007205	0.004	0.001	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.038	0.069	-9999	-0.57	2	2
RHOA	0.015	0	-9999	-10000	0	0
SDCBP	0.015	0	-9999	-10000	0	0
TNFRSF13B	-0.003	0.069	-9999	-0.59	9	9
RASA1	0.015	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.038	0.12	-9999	-0.45	57	57
Syndecan-2/Synbindin	0.014	0.077	-9999	-0.37	26	26
TGFB1	0.006	0.077	-9999	-0.62	10	10
CASP3	0.011	0.11	-9999	-0.37	46	46
FN1	-0.028	0.16	-9999	-0.59	48	48
Syndecan-2/IL8	-0.14	0.21	-9999	-0.38	270	270
SDC2	0.006	0.09	-9999	-0.44	26	26
KNG1	-0.018	0.11	-9999	-0.59	25	25
Syndecan-2/Neurofibromin	0.011	0.084	-9999	-0.37	31	31
TRAPPC4	0.015	0	-9999	-10000	0	0
CSF2	-0.006	0.064	-9999	-0.59	8	8
Syndecan-2/TGFB1	0.008	0.096	-9999	-0.4	33	33
Syndecan-2/Syntenin/PI-4-5-P2	-0.013	0.065	-9999	-0.34	26	26
Syndecan-2/Ezrin	-0.015	0.078	-9999	-0.36	29	29
PRKACA	0.022	0.077	-9999	-0.33	31	31
angiogenesis	-0.14	0.2	-9999	-0.38	270	270
MMP2	-0.025	0.15	-9999	-0.6	44	44
IL8	-0.22	0.3	-9999	-0.6	256	256
calcineurin-NFAT signaling pathway	-0.01	0.088	-9999	-0.38	34	34

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.038	0.16	-9999	-0.36	117	117
CRKL	0.014	0.023	-9999	-0.59	1	1
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.014	0.025	-9999	-0.62	1	1
ITGA4	-0.07	0.21	-9999	-0.6	92	92
alpha4/beta7 Integrin/MAdCAM1	-0.13	0.19	-9999	-0.65	32	32
EPO	-0.026	0.15	-9999	-0.59	43	43
alpha4/beta7 Integrin	-0.089	0.18	-9999	-0.46	131	131
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.062	0.16	-9999	-0.45	92	92
EPO/EPOR (dimer)	-0.028	0.11	-9999	-0.43	44	44
lamellipodium assembly	0.009	0.031	-9999	-0.34	1	1
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	-0.002	0.03	-9999	-0.46	3	3
ARF6	0.015	0	-9999	-10000	0	0
JAK2	-0.013	0.11	-9999	-0.39	11	11
PXN	0.015	0	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.62	3	3
MADCAM1	-0.11	0.24	-9999	-0.6	133	133
cell adhesion	-0.13	0.19	-9999	-0.64	32	32
CRKL/CBL	-0.001	0.024	-9999	-0.44	2	2
ITGB1	0.012	0.04	-9999	-0.59	3	3
SRC	-0.087	0.19	-9999	-0.35	218	218
ITGB7	-0.027	0.16	-9999	-0.61	45	45
RAC1	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.13	0.19	-9999	-0.4	216	216
p130Cas/Crk/Dock1	-0.05	0.17	-9999	-0.57	17	17
VCAM1	-0.11	0.26	-9999	-0.62	137	137
RHOA	0.015	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.046	0.12	-9999	-0.36	44	44
BCAR1	-0.072	0.18	-9999	-0.63	16	16
EPOR	0.014	0.023	-9999	-0.59	1	1
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0.025	-9999	-0.62	1	1
GIT1	0.014	0.025	-9999	-0.62	1	1
Rac1/GTP	0.009	0.031	-9999	-0.35	1	1

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.036	0.14	-9999	-0.42	39	39
FZD6	-0.033	0.16	-9999	-0.59	53	53
WNT6	-0.027	0.16	-9999	-0.6	46	46
WNT4	-0.042	0.18	-9999	-0.6	62	62
FZD3	0.012	0.043	-9999	-0.62	3	3
WNT5A	-0.006	0.11	-9999	-0.61	23	23
WNT11	-0.024	0.15	-9999	-0.61	42	42

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.014	0.023	-10000	0	-0.59	1	1
RAS family/GTP/Tiam1	0.005	0.045	-10000	0	-0.54	1	1
NT3 (dimer)/TRKC	-0.021	0.1	-10000	0	-0.48	29	29
NT3 (dimer)/TRKB	-0.1	0.19	-10000	0	-0.42	159	159
SHC/Grb2/SOS1/GAB1/PI3K	0.038	0.044	-10000	0	-0.48	2	2
RAPGEF1	0.013	0.035	-10000	0	-0.62	2	2
BDNF	-0.079	0.22	-10000	0	-0.59	104	104
PIK3CA	0.015	0	-10000	0	-10000	0	0
DYNLT1	0.01	0.058	-10000	0	-0.6	6	6
NTRK1	-0.021	0.14	-10000	0	-0.59	40	40
NTRK2	-0.046	0.19	-10000	0	-0.62	64	64
NTRK3	0.007	0.074	-10000	0	-0.62	9	9
NT-4/5 (dimer)/TRKB	-0.1	0.19	-10000	0	-0.42	162	162
neuron apoptosis	0.12	0.16	0.42	98	-10000	0	98
SHC 2-3/Grb2	-0.13	0.17	-10000	0	-0.46	98	98
SHC1	0.001	0.092	-10000	0	-0.59	16	16
SHC2	-0.08	0.13	-10000	0	-0.43	49	49
SHC3	-0.14	0.21	-10000	0	-0.54	108	108
STAT3 (dimer)	0.014	0.057	-10000	0	-0.35	8	8
NT3 (dimer)/TRKA	-0.085	0.17	-10000	0	-0.4	141	141
RIN/GDP	-0.04	0.12	-10000	0	-0.29	34	34
GIPC1	0.014	0.023	-10000	0	-0.59	1	1
KRAS	0.014	0.023	-10000	0	-0.59	1	1
DNAJA3	-0.073	0.13	-10000	0	-0.38	63	63
RIN/GTP	-0.16	0.22	-10000	0	-0.45	231	231
CCND1	0.013	0.13	-10000	0	-0.62	24	24
MAGED1	0.015	0	-10000	0	-10000	0	0
PTPN11	0.013	0.035	-10000	0	-0.62	2	2
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.015	0.11	-10000	0	-0.59	25	25
SHC/GRB2/SOS1	-0.009	0.055	-10000	0	-0.35	17	17
GRB2	0.014	0.023	-10000	0	-0.59	1	1
NGF (dimer)/TRKA/MATK	-0.13	0.2	-10000	0	-0.41	208	208
TRKA/NEDD4-2	-0.033	0.12	-10000	0	-0.44	50	50
ELMO1	-0.001	0.1	-10000	0	-0.62	17	17
RhoG/GTP/ELMO1/DOCK1	-0.011	0.063	-10000	0	-0.39	18	18
NGF	-0.062	0.2	-10000	0	-0.61	82	82
HRAS	0.015	0	-10000	0	-10000	0	0
DOCK1	0.014	0.025	-10000	0	-0.62	1	1
GAB2	0.012	0.043	-10000	0	-0.62	3	3
RIT2	-0.2	0.3	-10000	0	-0.61	231	231
RIT1	0.015	0	-10000	0	-10000	0	0
FRS2	0.012	0.047	-10000	0	-0.6	4	4
DNM1	-0.083	0.22	-10000	0	-0.6	107	107
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.078	0.14	-10000	0	-0.39	76	76
mol:GDP	0.038	0.095	-10000	0	-0.46	11	11
NGF (dimer)	-0.062	0.2	-10000	0	-0.61	82	82
RhoG/GDP	-0.012	0.073	-10000	0	-0.46	17	17
RIT1/GDP	0.037	0.066	-10000	0	-0.31	8	8
TIAM1	0.013	0.035	-10000	0	-0.62	2	2
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
BDNF (dimer)/TRKB	-0.093	0.18	-10000	0	-0.4	155	155
KIDINS220/CRKL/C3G	-0.002	0.03	-10000	0	-0.44	3	3
SHC/RasGAP	-0.01	0.065	-10000	0	-0.42	16	16
FRS2 family/SHP2	-0.003	0.035	-10000	0	-0.37	6	6
SHC/GRB2/SOS1/GAB1	-0.008	0.054	-10000	0	-0.66	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.012	0.11	-10000	0	-0.59	24	24
RAP1/GDP	-0.011	0.042	-10000	0	-0.29	8	8
KIDINS220/CRKL	0.014	0.023	-10000	0	-0.59	1	1
BDNF (dimer)	-0.079	0.22	-10000	0	-0.59	104	104
ubiquitin-dependent protein catabolic process	-0.072	0.16	-10000	0	-0.39	124	124
Schwann cell development	-0.026	0.031	-10000	0	-10000	0	0
EHD4	0.012	0.04	-10000	0	-0.59	3	3
FRS2 family/GRB2/SOS1	-0.002	0.027	-10000	0	-0.34	1	1
FRS2 family/SHP2/CRK family/C3G/GAB2	0.044	0.048	-10000	0	-0.72	2	2
RAP1B	0.009	0.061	-10000	0	-0.59	7	7
RAP1A	0.015	0	-10000	0	-10000	0	0
CDC42/GTP	-0.083	0.16	-10000	0	-0.65	29	29
ABL1	0.014	0.025	-10000	0	-0.62	1	1
SH2B family/GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
Rap1/GTP	-0.032	0.077	-10000	0	-0.74	3	3
STAT3	0.014	0.057	-10000	0	-0.35	8	8
axon guidance	-0.079	0.16	-10000	0	-0.61	29	29
MAPK3	-0.086	0.2	-10000	0	-0.37	208	208
MAPK1	-0.086	0.2	-10000	0	-0.41	115	115
CDC42/GDP	0.037	0.066	-10000	0	-0.3	9	9
NTF3	-0.012	0.11	-10000	0	-0.59	24	24
NTF4	-0.016	0.11	-10000	0	-0.59	25	25
NGF (dimer)/TRKA/FAIM	-0.069	0.15	-10000	0	-0.39	119	119
PI3K	-0.002	0.03	-10000	0	-0.46	3	3
FRS3	0.015	0	-10000	0	-10000	0	0
FAIM	0.011	0.049	-10000	0	-0.62	4	4
GAB1	0.014	0.025	-10000	0	-0.62	1	1
RASGRF1	-0.15	0.2	-10000	0	-0.4	211	211
SOS1	0.015	0	-10000	0	-10000	0	0
MCF2L	0.004	0.11	-10000	0	-0.43	36	36
RGS19	0.015	0	-10000	0	-10000	0	0
CDC42	0.015	0	-10000	0	-10000	0	0
RAS family/GTP	0.005	0.088	-10000	0	-10000	0	0
Rac1/GDP	0.037	0.066	-10000	0	-0.31	8	8
NGF (dimer)/TRKA/GRIT	-0.068	0.15	-10000	0	-0.39	116	116
neuron projection morphogenesis	-0.034	0.14	-10000	0	-0.5	16	16
NGF (dimer)/TRKA/NEDD4-2	-0.072	0.16	-10000	0	-0.39	124	124
MAP2K1	0.038	0.056	-10000	0	-0.61	1	1
NGFR	-0.072	0.22	-10000	0	-0.6	94	94
NGF (dimer)/TRKA/GIPC/GAIP	-0.04	0.14	-10000	0	-0.46	27	27
RAS family/GTP/PI3K	0.036	0.021	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	-0.003	0.03	-10000	0	-10000	0	0
NRAS	0.015	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
PRKCI	0.015	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.015	0	-10000	0	-10000	0	0
PRKCZ	-0.037	0.17	-10000	0	-0.62	55	55
MAPKKK cascade	-0.075	0.18	-10000	0	-0.58	65	65
RASA1	0.015	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.026	0.1	-10000	0	-0.43	41	41
SQSTM1	0.015	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.085	0.16	-10000	0	-0.42	77	77
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.08	0.16	-10000	0	-0.67	18	18
MATK	-0.09	0.23	-10000	0	-0.61	113	113
NEDD4L	0.005	0.079	-10000	0	-0.6	11	11
RAS family/GDP	-0.009	0.037	-10000	0	-0.26	6	6
NGF (dimer)/TRKA	-0.079	0.14	-10000	0	-0.35	107	107
Rac1/GTP	-0.082	0.11	-10000	0	-0.33	67	67
FRS2 family/SHP2/CRK family	-0.003	0.03	-10000	0	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.01	0.071	-9999	-0.37	23	23
ADCY5	-0.021	0.13	-9999	-0.4	71	71
ADCY6	0.015	0.058	-9999	-0.36	15	15
ADCY7	0.014	0.06	-9999	-0.37	16	16
ADCY1	-0.048	0.17	-9999	-0.42	108	108
ADCY2	-0.013	0.12	-9999	-0.39	59	59
ADCY3	0.015	0.058	-9999	-0.36	15	15
ADCY8	-0.025	0.13	-9999	-0.39	79	79
PRKCE	0.003	0.067	-9999	-0.44	15	15
ADCY9	0.014	0.064	-9999	-0.39	16	16
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.011	0.11	-9999	-0.38	32	32

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.02	0.016	-10000	0	-0.36	1	1
RAS family/GTP	-0.071	0.17	-10000	0	-0.55	41	41
NFATC4	-0.059	0.14	-10000	0	-0.39	47	47
ERBB2IP	0.016	0.025	-10000	0	-0.62	1	1
HSP90 (dimer)	0.015	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.09	0.16	-10000	0	-0.52	33	33
JUN	-0.009	0.099	-10000	0	-0.37	20	20
HRAS	0.015	0.001	-10000	0	-10000	0	0
DOCK7	-0.082	0.16	-10000	0	-0.51	36	36
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.14	0.2	-10000	0	-0.4	192	192
AKT1	0.011	0.018	-10000	0	-0.43	1	1
BAD	0.022	0.015	-10000	0	-0.36	1	1
MAPK10	-0.052	0.074	-10000	0	-0.25	30	30
mol:GTP	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.095	0.18	-10000	0	-0.57	33	33
RAF1	-0.062	0.17	-10000	0	-0.52	41	41
ErbB2/ErbB3/neuregulin 2	-0.057	0.14	-10000	0	-0.38	101	101
STAT3	0.001	0.059	-10000	0	-1.1	2	2
cell migration	-0.013	0.099	-10000	0	-0.25	20	20
mol:PI-3-4-5-P3	-0.002	0.003	-10000	0	-10000	0	0
cell proliferation	-0.15	0.28	-10000	0	-0.62	126	126
FOS	-0.1	0.22	-10000	0	-0.41	167	167
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.09	0.16	-10000	0	-0.52	33	33
MAPK3	-0.12	0.24	-10000	0	-0.57	71	71
MAPK1	-0.12	0.24	-10000	0	-0.57	70	70
JAK2	-0.078	0.16	-10000	0	-0.49	33	33
NF2	-0.003	0.005	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.094	0.19	-10000	0	-0.38	162	162
NRG1	-0.16	0.28	-10000	0	-0.61	181	181
GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
MAPK8	-0.067	0.15	-10000	0	-0.41	39	39
MAPK9	-0.051	0.071	-10000	0	-0.24	33	33
ERBB2	-0.007	0.059	0.4	1	-0.45	11	12
ERBB3	-0.074	0.22	-10000	0	-0.62	92	92
SHC1	0	0.092	-10000	0	-0.59	16	16
RAC1	0.015	0	-10000	0	-10000	0	0
apoptosis	0	0.017	0.33	1	-10000	0	1
STAT3 (dimer)	0.002	0.057	-10000	0	-1	2	2
RNF41	0.026	0.016	-10000	0	-0.32	1	1
FRAP1	0.01	0.015	-10000	0	-0.37	1	1
RAC1-CDC42/GTP	-0.073	0.1	-10000	0	-0.35	35	35
ErbB2/ErbB2/HSP90 (dimer)	-0.006	0.049	0.27	1	-0.37	11	12
CHRNA1	-0.15	0.28	-10000	0	-0.58	163	163
myelination	-0.05	0.14	-10000	0	-0.38	47	47
PPP3CB	-0.074	0.15	-10000	0	-0.45	35	35
KRAS	0.014	0.023	-10000	0	-0.59	1	1
RAC1-CDC42/GDP	-0.065	0.17	-10000	0	-0.55	42	42
NRG2	0.009	0.065	-10000	0	-0.62	7	7
mol:GDP	-0.093	0.19	-10000	0	-0.37	162	162
SOS1	0.015	0.001	-10000	0	-10000	0	0
MAP2K2	-0.059	0.17	-10000	0	-0.52	33	33
SRC	0.013	0.035	-10000	0	-0.62	2	2
mol:cAMP	-0.002	0.002	-10000	0	-10000	0	0
PTPN11	-0.08	0.16	-10000	0	-0.49	34	34
MAP2K1	-0.12	0.23	-10000	0	-0.52	103	103
heart morphogenesis	-0.09	0.16	-10000	0	-0.52	33	33
RAS family/GDP	-0.069	0.17	-10000	0	-0.55	40	40
GRB2	0.014	0.023	-10000	0	-0.59	1	1
PRKACA	-0.007	0.009	-10000	0	-10000	0	0
CHRNE	0.007	0.042	-10000	0	-0.2	20	20
HSP90AA1	0.015	0	-10000	0	-10000	0	0
activation of caspase activity	-0.011	0.018	0.43	1	-10000	0	1
nervous system development	-0.09	0.16	-10000	0	-0.52	33	33
CDC42	0.015	0	-10000	0	-10000	0	0

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.012	0.046	-10000	0	-0.62	3	3
HSPA8	0.014	0.025	-10000	0	-0.62	1	1
SMAD3/SMAD4/ER alpha	-0.014	0.11	0.23	4	-0.41	22	26
AKT1	0.004	0.039	-10000	0	-0.68	1	1
GSC	-0.17	0.5	-10000	0	-1.4	96	96
NKX2-5	-0.24	0.3	-10000	0	-0.6	270	270
muscle cell differentiation	0.16	0.18	0.54	86	-10000	0	86
SMAD2-3/SMAD4/SP1	-0.018	0.12	-10000	0	-0.44	10	10
SMAD4	-0.016	0.067	-10000	0	-0.34	2	2
CBFB	0.015	0	-10000	0	-10000	0	0
SAP18	0.015	0.003	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.032	0.13	-10000	0	-0.37	81	81
SMAD3/SMAD4/VDR	-0.058	0.15	-10000	0	-0.41	47	47
MYC	0.007	0.11	-10000	0	-0.6	21	21
CDKN2B	-0.22	0.56	-10000	0	-1.4	115	115
AP1	-0.016	0.15	-10000	0	-0.57	19	19
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.048	0.052	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.032	0.16	-10000	0	-0.46	35	35
SP3	0.018	0.008	-10000	0	-10000	0	0
CREB1	0.015	0	-10000	0	-10000	0	0
FOXH1	-0.011	0.099	-10000	0	-0.61	15	15
SMAD3/SMAD4/GR	-0.005	0.065	-10000	0	-0.36	2	2
GATA3	-0.13	0.26	-10000	0	-0.63	138	138
SKI/SIN3/HDAC complex/NCoR1	0.05	0.035	-10000	0	-10000	0	0
MEF2C/TIF2	-0.14	0.21	-10000	0	-0.54	73	73
endothelial cell migration	0.28	0.51	1.1	153	-10000	0	153
MAX	0.027	0.021	-10000	0	-10000	0	0
RBBP7	0.015	0.003	-10000	0	-10000	0	0
RBBP4	0.015	0.003	-10000	0	-10000	0	0
RUNX2	0	0.097	-10000	0	-0.6	17	17
RUNX3	-0.027	0.16	-10000	0	-0.61	45	45
RUNX1	-0.057	0.2	-10000	0	-0.6	78	78
CTBP1	0.015	0	-10000	0	-10000	0	0
NR3C1	0.027	0.021	-10000	0	-10000	0	0
VDR	-0.11	0.24	-10000	0	-0.6	132	132
CDKN1A	-0.041	0.29	-10000	0	-1.1	35	35
KAT2B	0.012	0.042	-10000	0	-0.6	3	3
SMAD2/SMAD2/SMAD4/FOXH1	-0.033	0.11	-10000	0	-0.39	19	19
DCP1A	0.015	0	-10000	0	-10000	0	0
SKI	0.015	0.003	-10000	0	-10000	0	0
SERPINE1	-0.29	0.52	-10000	0	-1.1	145	145
SMAD3/SMAD4/ATF2	-0.024	0.078	-10000	0	-0.39	14	14
SMAD3/SMAD4/ATF3	-0.055	0.14	-10000	0	-0.43	66	66
SAP30	0.014	0.025	-10000	0	-0.63	1	1
Cbp/p300/PIAS3	0.017	0.056	-10000	0	-0.37	4	4
JUN	-0.008	0.15	-10000	0	-0.62	15	15
SMAD3/SMAD4/IRF7	-0.034	0.1	-10000	0	-0.42	28	28
TFE3	0.005	0.035	-10000	0	-10000	0	0
COL1A2	-0.091	0.23	-10000	0	-0.56	116	116
mesenchymal cell differentiation	0.027	0.091	0.45	18	-10000	0	18
DLX1	-0.15	0.28	-10000	0	-0.61	177	177
TCF3	0.014	0.025	-10000	0	-0.62	1	1
FOS	-0.07	0.22	-10000	0	-0.61	95	95
SMAD3/SMAD4/Max	-0.005	0.065	-10000	0	-0.36	2	2
Cbp/p300/SNIP1	0.006	0.036	-10000	0	-0.37	4	4
ZBTB17	0.023	0.032	-10000	0	-0.53	1	1
LAMC1	-0.01	0.14	-10000	0	-0.59	32	32
TGIF2/HDAC complex/SMAD3/SMAD4	-0.02	0.071	-10000	0	-0.43	7	7
IRF7	-0.011	0.12	-10000	0	-0.6	29	29
ESR1	-0.003	0.11	-10000	0	-0.59	23	23
HNF4A	-0.031	0.14	-10000	0	-0.59	42	42
MEF2C	-0.13	0.21	-10000	0	-0.54	67	67
SMAD2-3/SMAD4	-0.036	0.075	-10000	0	-0.37	6	6
Cbp/p300/Src-1	0.013	0.044	-10000	0	-0.37	4	4
IGHV3OR16-13	-0.015	0.033	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.01	0.054	-10000	0	-0.62	5	5
CREBBP	0.013	0.027	-10000	0	-0.61	1	1
SKIL	0.012	0.043	-10000	0	-0.62	3	3
HDAC1	0.011	0.049	-10000	0	-0.62	4	4
HDAC2	0.015	0.003	-10000	0	-10000	0	0
SNIP1	0.015	0.006	-10000	0	-10000	0	0
GCN5L2	-0.001	0.017	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	-0.025	0.09	-10000	0	-0.4	11	11
MSG1/HSC70	-0.043	0.14	-10000	0	-0.43	80	80
SMAD2	-0.006	0.048	-10000	0	-10000	0	0
SMAD3	-0.005	0.06	-10000	0	-0.28	1	1
SMAD3/E2F4-5/DP1/p107/SMAD4	0.013	0.068	-10000	0	-0.31	6	6
SMAD2/SMAD2/SMAD4	-0.004	0.042	-10000	0	-0.42	2	2
NCOR1	0.013	0.035	-10000	0	-0.62	2	2
NCOA2	-0.019	0.14	-10000	0	-0.62	36	36
NCOA1	0.015	0	-10000	0	-10000	0	0
MYOD/E2A	-0.12	0.2	-10000	0	-0.44	179	179
SMAD2-3/SMAD4/SP1/MIZ-1	-0.009	0.12	-10000	0	-0.45	8	8
IFNB1	-0.006	0.11	-10000	0	-0.5	13	13
SMAD3/SMAD4/MEF2C	-0.14	0.21	-10000	0	-0.52	77	77
CITED1	-0.058	0.2	-10000	0	-0.6	79	79
SMAD2-3/SMAD4/ARC105	-0.024	0.064	-10000	0	-0.4	2	2
RBL1	0.001	0.095	-10000	0	-0.62	15	15
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.056	0.22	-10000	0	-0.51	116	116
RUNX1-3/PEBPB2	-0.067	0.15	-10000	0	-0.38	117	117
SMAD7	-0.012	0.15	-10000	0	-0.62	9	9
MYC/MIZ-1	0.015	0.1	-10000	0	-0.43	21	21
SMAD3/SMAD4	-0.056	0.2	0.31	48	-0.42	98	146
IL10	-0.16	0.32	-10000	0	-0.67	150	150
PIASy/HDAC complex	0.017	0.028	-10000	0	-0.62	1	1
PIAS3	0.013	0.009	-10000	0	-10000	0	0
CDK2	0	0.092	-10000	0	-0.6	15	15
IL5	-0.088	0.21	-10000	0	-0.57	59	59
CDK4	-0.019	0.14	-10000	0	-0.59	38	38
PIAS4	0.017	0.028	-10000	0	-0.62	1	1
ATF3	-0.045	0.18	-10000	0	-0.6	65	65
SMAD3/SMAD4/SP1	-0.033	0.1	-10000	0	-0.41	11	11
FOXG1	-0.026	0.16	-10000	0	-0.62	43	43
FOXO3	0.012	0.048	-10000	0	-0.5	2	2
FOXO1	0.012	0.048	-10000	0	-0.5	2	2
FOXO4	0.01	0.057	-10000	0	-0.52	4	4
heart looping	-0.13	0.21	-10000	0	-0.53	67	67
CEBPB	-0.007	0.11	-10000	0	-0.62	19	19
SMAD3/SMAD4/DLX1	-0.12	0.18	-10000	0	-0.4	179	179
MYOD1	-0.16	0.27	-10000	0	-0.61	178	178
SMAD3/SMAD4/HNF4	-0.044	0.11	-10000	0	-0.39	44	44
SMAD3/SMAD4/GATA3	-0.13	0.21	-10000	0	-0.51	113	113
SnoN/SIN3/HDAC complex/NCoR1	0.012	0.043	-10000	0	-0.62	3	3
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.064	0.15	-10000	0	-0.44	58	58
SMAD3/SMAD4/SP1-3	-0.01	0.1	-10000	0	-0.46	5	5
MED15	0.015	0	-10000	0	-10000	0	0
SP1	-0.001	0.05	-10000	0	-10000	0	0
SIN3B	0.014	0.025	-10000	0	-0.62	1	1
SIN3A	0.015	0.003	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.16	0.21	-10000	0	-0.45	121	121
ITGB5	0.019	0.12	-10000	0	-0.63	7	7
TGIF/SIN3/HDAC complex/CtBP	0.047	0.046	-10000	0	-0.46	1	1
SMAD3/SMAD4/AR	-0.078	0.16	-10000	0	-0.42	103	103
AR	-0.081	0.23	-10000	0	-0.62	102	102
negative regulation of cell growth	-0.006	0.12	-10000	0	-0.46	19	19
SMAD3/SMAD4/MYOD	-0.12	0.18	-10000	0	-0.39	180	180
E2F5	0.013	0.035	-10000	0	-0.62	2	2
E2F4	0.015	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.018	0.085	-10000	0	-0.37	9	9
SMAD2-3/SMAD4/FOXO1-3a-4	-0.029	0.15	-10000	0	-0.4	43	43
TFDP1	0.011	0.049	-10000	0	-0.62	4	4
SMAD3/SMAD4/AP1	-0.018	0.15	-10000	0	-0.63	15	15
SMAD3/SMAD4/RUNX2	-0.027	0.092	-10000	0	-0.46	18	18
TGIF2	0.01	0.054	-10000	0	-0.62	5	5
TGIF1	-0.005	0.11	-10000	0	-0.62	21	21
ATF2	0.004	0.085	-10000	0	-0.62	12	12

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.014	0.004	-9999	-10000	0	0
SVIL	-0.008	0.12	-9999	-0.59	25	25
ZNF318	0.019	0.019	-9999	-10000	0	0
JMJD2C	-0.002	0.021	-9999	-0.089	36	36
T-DHT/AR/Ubc9	-0.052	0.16	-9999	-0.41	102	102
CARM1	0.015	0.001	-9999	-10000	0	0
PRDX1	-0.01	0.13	-9999	-0.62	27	27
PELP1	0.014	0.035	-9999	-0.62	2	2
CTNNB1	0.014	0.004	-9999	-10000	0	0
AKT1	0.015	0.024	-9999	-0.59	1	1
PTK2B	-0.006	0.11	-9999	-0.59	23	23
MED1	0.016	0.005	-9999	-10000	0	0
MAK	-0.057	0.2	-9999	-0.59	84	84
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.005	0.078	-9999	-0.63	10	10
GSN	0.006	0.074	-9999	-0.62	9	9
NCOA2	-0.019	0.14	-9999	-0.62	36	36
NCOA6	0.013	0.035	-9999	-0.62	2	2
DNA-PK	0.007	0.026	-9999	-10000	0	0
NCOA4	0.015	0.001	-9999	-10000	0	0
PIAS3	0.014	0.004	-9999	-10000	0	0
cell proliferation	-0.055	0.13	-9999	-0.37	71	71
XRCC5	0.016	0.004	-9999	-10000	0	0
UBE3A	0.013	0.01	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.062	0.17	-9999	-0.42	114	114
FHL2	-0.056	0.21	-9999	-0.62	63	63
RANBP9	0.015	0.004	-9999	-10000	0	0
JMJD1A	-0.007	0.055	-9999	-0.12	118	118
CDK6	-0.037	0.17	-9999	-0.6	57	57
TGFB1I1	0.004	0.079	-9999	-0.6	11	11
T-DHT/AR/CyclinD1	-0.066	0.18	-9999	-0.44	115	115
XRCC6	0.016	0.004	-9999	-10000	0	0
T-DHT/AR	-0.061	0.19	-9999	-0.42	115	115
CTDSP1	0.014	0.004	-9999	-10000	0	0
CTDSP2	0.004	0.093	-9999	-0.59	16	16
BRCA1	0.012	0.04	-9999	-0.59	3	3
TCF4	0.016	0.026	-9999	-0.62	1	1
CDKN2A	-0.16	0.28	-9999	-0.61	186	186
SRF	0.017	0.031	-9999	-10000	0	0
NKX3-1	-0.075	0.18	-9999	-1.1	16	16
KLK3	-0.012	0.12	-9999	-0.49	9	9
TMF1	0.014	0.004	-9999	-10000	0	0
HNRNPA1	0.017	0.007	-9999	-10000	0	0
AOF2	-0.002	0.008	-9999	-10000	0	0
APPL1	0.029	0.021	-9999	-0.42	1	1
T-DHT/AR/Caspase 8	-0.06	0.16	-9999	-0.41	113	113
AR	-0.09	0.23	-9999	-0.63	102	102
UBA3	0.014	0.004	-9999	-10000	0	0
PATZ1	0.017	0.007	-9999	-10000	0	0
PAWR	-0.037	0.17	-9999	-0.6	56	56
PRKDC	0.016	0.004	-9999	-10000	0	0
PA2G4	0.017	0.008	-9999	-10000	0	0
UBE2I	0.015	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.046	0.14	-9999	-0.37	103	103
RPS6KA3	0.014	0.025	-9999	-0.62	1	1
T-DHT/AR/ARA70	-0.053	0.16	-9999	-0.41	102	102
LATS2	0.006	0.079	-9999	-0.6	11	11
T-DHT/AR/PRX1	-0.061	0.17	-9999	-0.4	117	117
Cyclin D3/CDK11 p58	-0.001	0.017	-9999	-0.43	1	1
VAV3	-0.2	0.29	-9999	-0.6	236	236
KLK2	-0.061	0.12	-9999	-0.51	37	37
CASP8	0.005	0.081	-9999	-0.59	12	12
T-DHT/AR/TIF2/CARM1	-0.057	0.18	-9999	-0.4	125	125
TMPRSS2	-0.15	0.31	-9999	-0.75	116	116
CCND1	-0.007	0.11	-9999	-0.6	24	24
PIAS1	0.011	0.036	-9999	-0.62	2	2
mol:T-DHT	-0.011	0.033	-9999	-0.083	68	68
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.011	0.03	-9999	-0.62	1	1
T-DHT/AR/CDK6	-0.087	0.19	-9999	-0.42	147	147
CMTM2	-0.001	0.1	-9999	-0.62	18	18
SNURF	-0.002	0.1	-9999	-0.62	18	18
ZMIZ1	0.003	0.061	-9999	-0.63	5	5
CCND3	0.014	0.023	-9999	-0.59	1	1
TGIF1	-0.003	0.11	-9999	-0.61	21	21
FKBP4	0.015	0.004	-9999	-10000	0	0

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.015	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.007	0.06	-9999	-0.76	3	3
Syndecan-3/Neurocan	-0.024	0.098	-9999	-0.36	45	45
POMC	-0.004	0.11	-9999	-0.61	21	21
EGFR	-0.11	0.25	-9999	-0.6	138	138
Syndecan-3/EGFR	-0.065	0.13	-9999	-0.31	141	141
AGRP	-0.001	0.083	-9999	-0.59	13	13
NCSTN	0.015	0	-9999	-10000	0	0
PSENEN	0.015	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.015	0	-9999	-10000	0	0
APH1A	0.015	0	-9999	-10000	0	0
NCAN	-0.028	0.16	-9999	-0.62	45	45
long-term memory	-0.003	0.039	-9999	-0.57	3	3
Syndecan-3/IL8	-0.12	0.15	-9999	-0.33	101	101
PSEN1	0.015	0	-9999	-10000	0	0
Src/Cortactin	-0.001	0.025	-9999	-0.46	2	2
FYN	0.015	0	-9999	-10000	0	0
limb bud formation	-0.004	0.044	-9999	-0.64	3	3
MC4R	-0.1	0.24	-9999	-0.61	126	126
SRC	0.013	0.035	-9999	-0.62	2	2
PTN	0.007	0.071	-9999	-0.6	9	9
FGFR/FGF/Syndecan-3	-0.004	0.045	-9999	-0.65	3	3
neuron projection morphogenesis	-0.025	0.1	-9999	-0.7	8	8
Syndecan-3/AgRP	-0.009	0.058	-9999	-0.35	16	16
Syndecan-3/AgRP/MC4R	-0.063	0.13	-9999	-0.6	8	8
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.004	0.045	-9999	-0.65	3	3
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.12	0.15	-9999	-0.32	101	101
IL8	-0.22	0.3	-9999	-0.6	256	256
Syndecan-3/Fyn/Cortactin	-0.003	0.04	-9999	-0.59	3	3
Syndecan-3/CASK	-0.003	0.043	-9999	-0.62	3	3
alpha-MSH/MC4R	-0.096	0.19	-9999	-0.46	141	141
Gamma Secretase	0	0	-9999	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.011	0.052	-10000	0	-0.59	5	5
Jak2/Leptin Receptor	0	0.1	0.21	46	-0.39	14	60
PTP1B/AKT1	-0.017	0.095	-10000	0	-0.32	16	16
FYN	0.015	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.028	0.1	-10000	0	-0.29	35	35
EGFR	-0.11	0.25	-10000	0	-0.61	138	138
EGF/EGFR	-0.12	0.17	-10000	0	-0.39	153	153
CSF1	0.004	0.085	-10000	0	-0.62	12	12
AKT1	0.014	0.023	-10000	0	-0.59	1	1
INSR	0.014	0.025	-10000	0	-0.63	1	1
PTP1B/N-cadherin	-0.019	0.099	-10000	0	-0.33	17	17
Insulin Receptor/Insulin	-0.032	0.064	-10000	0	-0.34	7	7
HCK	0	0.096	-10000	0	-0.61	16	16
CRK	0.015	0	-10000	0	-10000	0	0
TYK2	-0.017	0.099	-10000	0	-0.33	13	13
EGF	-0.041	0.18	-10000	0	-0.62	57	57
YES1	0.013	0.035	-10000	0	-0.62	2	2
CAV1	-0.045	0.14	-10000	0	-0.37	50	50
TXN	0.013	0.007	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.022	0.097	-10000	0	-0.36	16	16
cell migration	0.028	0.1	0.29	35	-10000	0	35
STAT3	0.014	0.001	-10000	0	-10000	0	0
PRLR	-0.021	0.15	-10000	0	-0.6	42	42
ITGA2B	-0.029	0.16	-10000	0	-0.62	46	46
CSF1R	-0.013	0.13	-10000	0	-0.62	30	30
Prolactin Receptor/Prolactin	-0.018	0.12	-10000	0	-0.45	47	47
FGR	0.01	0.057	-10000	0	-0.59	6	6
PTP1B/p130 Cas	-0.019	0.099	-10000	0	-0.34	12	12
Crk/p130 Cas	-0.018	0.089	-10000	0	-0.34	10	10
DOK1	-0.007	0.094	-10000	0	-0.33	10	10
JAK2	0.001	0.089	-10000	0	-0.37	10	10
Jak2/Leptin Receptor/Leptin	-0.17	0.23	-10000	0	-0.49	205	205
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
PTPN1	-0.028	0.1	-10000	0	-0.29	35	35
LYN	0.011	0.053	-10000	0	-0.6	5	5
CDH2	0.014	0.025	-10000	0	-0.62	1	1
SRC	0.007	0.051	-10000	0	-0.52	2	2
ITGB3	-0.099	0.24	-10000	0	-0.6	125	125
CAT1/PTP1B	-0.057	0.14	-10000	0	-0.4	46	46
CAPN1	0.015	0.025	-10000	0	-0.63	1	1
CSK	0.015	0	-10000	0	-10000	0	0
PI3K	-0.024	0.06	-10000	0	-0.43	1	1
mol:H2O2	0	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.17	0.23	-10000	0	-0.49	214	214
negative regulation of transcription	0.001	0.089	-10000	0	-0.36	10	10
FCGR2A	-0.05	0.19	-10000	0	-0.6	70	70
FER	0	0.089	-10000	0	-0.63	13	13
alphaIIb/beta3 Integrin	-0.11	0.2	-10000	0	-0.46	160	160
BLK	-0.07	0.21	-10000	0	-0.59	91	91
Insulin Receptor/Insulin/Shc	-0.012	0.066	-10000	0	-0.37	22	22
RHOA	0.016	0.003	-10000	0	-10000	0	0
LEPR	0.008	0.075	-10000	0	-0.6	10	10
BCAR1	0.014	0.025	-10000	0	-0.62	1	1
p210 bcr-abl/Grb2	0.014	0.023	-10000	0	-0.59	1	1
mol:NADPH	0	0.004	-10000	0	-10000	0	0
TRPV6	-0.05	0.14	-10000	0	-0.45	36	36
PRL	0	0.056	-10000	0	-0.58	6	6
SOCS3	-0.24	0.44	-10000	0	-1.2	92	92
SPRY2	0.008	0.07	-10000	0	-0.59	9	9
Insulin Receptor/Insulin/IRS1	-0.007	0.053	-10000	0	-0.38	13	13
CSF1/CSF1R	-0.038	0.13	-10000	0	-0.46	33	33
Ras protein signal transduction	0.025	0.039	-10000	0	-0.5	1	1
IRS1	0.009	0.065	-10000	0	-0.62	7	7
INS	-0.004	0.053	-10000	0	-0.62	5	5
LEP	-0.015	0.11	-10000	0	-0.59	23	23
STAT5B	-0.011	0.093	-10000	0	-0.28	16	16
STAT5A	-0.013	0.095	-10000	0	-0.3	16	16
GRB2	0.014	0.023	-10000	0	-0.59	1	1
PDGFB-D/PDGFRB	-0.02	0.1	-10000	0	-0.37	18	18
CSN2	0.002	0.045	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
LAT	-0.046	0.16	-10000	0	-0.48	63	63
YBX1	0.022	0.035	-10000	0	-0.61	2	2
LCK	-0.098	0.24	-10000	0	-0.6	123	123
SHC1	0.001	0.092	-10000	0	-0.59	16	16
NOX4	-0.16	0.27	-10000	0	-0.6	188	188

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.043	0.18	-10000	0	-0.53	32	32
UGCG	-0.023	0.12	-10000	0	-0.65	21	21
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.049	0.16	-10000	0	-0.43	51	51
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.02	0.12	-10000	0	-0.63	22	22
mol:DAG	-0.003	0.005	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.076	0.12	-10000	0	-0.43	37	37
FRAP1	-0.042	0.18	-10000	0	-0.5	39	39
FOXO3	-0.036	0.18	-10000	0	-0.5	35	35
AKT1	-0.048	0.19	-10000	0	-0.51	44	44
GAB2	0.013	0.043	-10000	0	-0.63	3	3
SMPD1	-0.001	0.038	-10000	0	-10000	0	0
SGMS1	-0.001	0.038	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.028	-10000	0	-0.38	3	3
CALM1	0.015	0	-10000	0	-10000	0	0
cell proliferation	-0.018	0.1	-10000	0	-0.3	40	40
EIF3A	0.014	0.025	-10000	0	-0.62	1	1
PI3K	0.025	0.033	-10000	0	-0.45	3	3
RPS6KB1	-0.006	0.065	-10000	0	-0.24	3	3
mol:sphingomyelin	-0.003	0.005	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-0.012	8	8
JAK3	-0.054	0.2	-10000	0	-0.6	78	78
PIK3R1	0.015	0.043	-10000	0	-0.62	3	3
JAK1	0.018	0.003	-10000	0	-10000	0	0
NFKB1	0.015	0	-10000	0	-10000	0	0
MYC	-0.045	0.22	-10000	0	-0.84	26	26
MYB	-0.094	0.34	-10000	0	-0.76	109	109
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.065	0.19	-10000	0	-0.5	59	59
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.011	0.063	-10000	0	-0.38	1	1
mol:PI-3-4-5-P3	-0.062	0.19	-10000	0	-0.48	59	59
Rac1/GDP	0.031	0.026	-10000	0	-0.34	3	3
T cell proliferation	-0.073	0.2	-10000	0	-0.51	75	75
SHC1	0.001	0.092	-10000	0	-0.59	16	16
RAC1	0.015	0	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.002	0.021	-10000	0	-0.05	104	104
PRKCZ	-0.076	0.21	-10000	0	-0.53	75	75
NF kappa B1 p50/RelA	-0.07	0.12	-10000	0	-0.44	30	30
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.058	0.19	-10000	0	-0.49	76	76
HSP90AA1	0.015	0	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
IL2RA	-0.17	0.28	-10000	0	-0.6	193	193
IL2RB	-0.11	0.25	-10000	0	-0.6	140	140
TERT	-0.079	0.22	-10000	0	-0.61	94	94
E2F1	-0.034	0.15	-10000	0	-0.35	109	109
SOS1	0.016	0.003	-10000	0	-10000	0	0
RPS6	0.013	0.033	-10000	0	-0.59	2	2
mol:cAMP	0.001	0.01	0.024	104	-10000	0	104
PTPN11	0.014	0.035	-10000	0	-0.62	2	2
IL2RG	-0.036	0.17	-10000	0	-0.6	58	58
actin cytoskeleton organization	-0.073	0.2	-10000	0	-0.51	75	75
GRB2	0.015	0.023	-10000	0	-0.59	1	1
IL2	0.004	0.004	-10000	0	-10000	0	0
PIK3CA	0.018	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.034	0.029	-10000	0	-0.32	3	3
LCK	-0.095	0.24	-10000	0	-0.6	123	123
BCL2	-0.022	0.16	-10000	0	-0.64	8	8

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.011	0.049	-9999	-0.62	4	4
VLDLR	-0.004	0.11	-9999	-0.62	20	20
LRPAP1	0.015	0	-9999	-10000	0	0
NUDC	0.015	0	-9999	-10000	0	0
RELN/LRP8	-0.12	0.17	-9999	-0.37	211	211
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.015	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.076	0.17	-9999	-0.67	3	3
IQGAP1/CaM	-0.005	0.045	-9999	-0.44	7	7
DAB1	-0.093	0.24	-9999	-0.62	114	114
IQGAP1	0.009	0.064	-9999	-0.61	7	7
PLA2G7	-0.039	0.18	-9999	-0.61	58	58
CALM1	0.015	0	-9999	-10000	0	0
DYNLT1	0.01	0.058	-9999	-0.6	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.025	-9999	-0.46	2	2
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.014	0.025	-9999	-0.62	1	1
CDK5R1	-0.035	0.17	-9999	-0.62	53	53
LIS1/Poliovirus Protein 3A	0.02	0	-9999	-10000	0	0
CDK5R2	-0.1	0.24	-9999	-0.61	124	124
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.19	0.24	-9999	-0.44	287	287
YWHAE	0.015	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.092	0.22	-9999	-0.56	82	82
MAP1B	-0.001	0.015	-9999	-0.27	2	2
RAC1	-0.002	0.017	-9999	-10000	0	0
p35/CDK5	-0.076	0.2	-9999	-0.63	34	34
RELN	-0.18	0.29	-9999	-0.61	211	211
PAFAH/LIS1	-0.003	0.11	-9999	-0.37	58	58
LIS1/CLIP170	0.031	0.016	-9999	-0.38	1	1
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.1	0.15	-9999	-0.56	37	37
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.098	0.21	-9999	-0.6	61	61
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.11	0.24	-9999	-0.62	82	82
LIS1/IQGAP1	0.027	0.041	-9999	-0.37	7	7
RHOA	-0.002	0.017	-9999	-10000	0	0
PAFAH1B1	0.027	0	-9999	-10000	0	0
PAFAH1B3	0.015	0	-9999	-10000	0	0
PAFAH1B2	0.003	0.088	-9999	-0.62	13	13
MAP1B/LIS1/Dynein heavy chain	0.027	0.03	-9999	-0.33	4	4
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.19	-9999	-0.61	60	60
LRP8	0.013	0.035	-9999	-0.62	2	2
NDEL1/Katanin 60	-0.092	0.22	-9999	-0.63	59	59
P39/CDK5	-0.11	0.22	-9999	-0.6	60	60
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.032	0	-9999	-10000	0	0
CDK5	-0.062	0.16	-9999	-0.63	3	3
PPP2R5D	0.015	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0.013	-9999	-0.33	1	1
CSNK2A1	0.015	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.16	0.2	-9999	-0.63	57	57
RELN/VLDLR	-0.11	0.17	-9999	-0.69	11	11
CDC42	-0.002	0.017	-9999	-10000	0	0

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.056	0.11	0.48	17	-10000	0	17
GNAI2	0.015	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.073	0.15	-10000	0	-0.38	128	128
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.012	0.13	-10000	0	-0.62	28	28
RhoA/GTP	-0.057	0.11	-10000	0	-0.49	17	17
negative regulation of cAMP metabolic process	-0.035	0.14	-10000	0	-0.3	94	94
GNAZ	0.012	0.043	-10000	0	-0.62	3	3
GNAI3	0.015	0	-10000	0	-10000	0	0
GNA12	0.014	0.025	-10000	0	-0.62	1	1
S1PR5	-0.1	0.24	-10000	0	-0.61	128	128
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.035	0.14	-10000	0	-0.31	94	94
RhoA/GDP	0	0	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
GNAI1	-0.02	0.15	-10000	0	-0.62	37	37

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.051	0.15	-10000	0	-0.74	18	18
HDAC1	0.008	0.049	-10000	0	-0.62	4	4
AES	0.014	0.003	-10000	0	-10000	0	0
FBXW11	0.015	0	-10000	0	-10000	0	0
DTX1	0.006	0.077	-10000	0	-0.62	10	10
LRP6/FZD1	-0.006	0.051	-10000	0	-0.42	10	10
TLE1	0.013	0.035	-10000	0	-0.63	2	2
AP1	-0.027	0.13	-10000	0	-0.32	87	87
NCSTN	0.015	0	-10000	0	-10000	0	0
ADAM10	0.005	0.081	-10000	0	-0.62	11	11
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.039	0.065	-10000	0	-0.55	1	1
NICD/RBPSUH	-0.017	0.098	-10000	0	-0.6	18	18
WIF1	-0.28	0.31	-10000	0	-0.6	322	322
NOTCH1	-0.017	0.1	-10000	0	-0.64	18	18
PSENEN	0.015	0	-10000	0	-10000	0	0
KREMEN2	-0.042	0.18	-10000	0	-0.6	63	63
DKK1	-0.13	0.26	-10000	0	-0.6	160	160
beta catenin/beta TrCP1	0.028	0.055	0.27	4	-10000	0	4
APH1B	0.015	0	-10000	0	-10000	0	0
APH1A	0.015	0	-10000	0	-10000	0	0
AXIN1	0	0.062	0.27	7	-0.46	4	11
CtBP/CBP/TCF1/TLE1/AES	0.029	0.045	0.29	2	-10000	0	2
PSEN1	0.015	0	-10000	0	-10000	0	0
FOS	-0.073	0.22	-10000	0	-0.61	95	95
JUN	0.008	0.067	-10000	0	-0.6	8	8
MAP3K7	0.014	0.004	-10000	0	-10000	0	0
CTNNB1	0.02	0.058	0.28	5	-10000	0	5
MAPK3	0.015	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.098	0.18	-10000	0	-0.39	168	168
HNF1A	0.013	0.025	-10000	0	-0.63	1	1
CTBP1	0.014	0.003	-10000	0	-10000	0	0
MYC	-0.012	0.23	-10000	0	-1.3	20	20
NKD1	-0.023	0.15	-10000	0	-0.62	40	40
FZD1	0.007	0.069	-10000	0	-0.59	9	9
NOTCH1 precursor/Deltex homolog 1	-0.021	0.11	-10000	0	-0.66	18	18
apoptosis	-0.027	0.13	-10000	0	-0.32	87	87
Delta 1/NOTCHprecursor	-0.051	0.15	-10000	0	-0.73	18	18
DLL1	-0.057	0.2	-10000	0	-0.62	76	76
PPARD	0.025	0.022	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	0.001	0.048	0.27	7	-0.27	4	11
DVL1	-0.022	0.033	-10000	0	-0.58	1	1
CSNK2A1	0.015	0.003	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.12	0.18	-10000	0	-0.38	212	212
LRP6	0.014	0.023	-10000	0	-0.59	1	1
CSNK1A1	0.015	0.003	-10000	0	-10000	0	0
NLK	0.017	0.01	-10000	0	-10000	0	0
CCND1	-0.001	0.18	-10000	0	-1.3	9	9
WNT1	-0.022	0.14	-10000	0	-0.59	38	38
Axin1/APC/beta catenin	0.03	0.064	0.3	8	-0.72	1	9
DKK2	-0.093	0.24	-10000	0	-0.6	117	117
NOTCH1 precursor/DVL1	-0.017	0.098	-10000	0	-0.6	18	18
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.006	0.072	-10000	0	-0.61	9	9
NOTCH/Deltex homolog 1	-0.021	0.11	-10000	0	-0.67	18	18
PPP2R5D	0.006	0.073	0.29	39	-10000	0	39
MAPK1	0.015	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.18	0.19	-10000	0	-0.39	181	181
RBPJ	0.014	0.023	-10000	0	-0.59	1	1
CREBBP	0.018	0.025	-10000	0	-0.63	1	1

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.005	0.11	-9999	-0.59	22	22
PLK4	-0.007	0.11	-9999	-0.6	24	24
regulation of centriole replication	-0.004	0.12	-9999	-0.44	45	45

×

FAS signaling pathway (CD95)

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
SPTAN1	0.005	0.05	0.26	3	-0.38	1	4
RFC1	0.005	0.048	0.26	3	-10000	0	3
PRKDC	0.005	0.048	0.26	3	-10000	0	3
RIPK1	0.017	0.004	-10000	0	-10000	0	0
CASP7	-0.011	0.068	0.26	14	-0.37	5	19
FASLG/FAS/FADD/FAF1	-0.02	0.091	0.23	17	-0.33	18	35
MAP2K4	-0.015	0.13	-10000	0	-0.4	13	13
mol:ceramide	-0.011	0.11	-10000	0	-0.41	12	12
GSN	0	0.063	0.26	3	-0.38	8	11
FASLG/FAS/FADD/FAF1/Caspase 8	-0.007	0.095	-10000	0	-0.39	11	11
FAS	-0.023	0.14	-10000	0	-0.61	37	37
BID	0.005	0.076	0.31	19	-0.35	13	32
MAP3K1	0.002	0.093	-10000	0	-0.34	5	5
MAP3K7	0.011	0.007	-10000	0	-10000	0	0
RB1	0.005	0.05	0.26	3	-0.38	1	4
CFLAR	0.017	0.004	-10000	0	-10000	0	0
HGF/MET	-0.17	0.23	-10000	0	-0.44	257	257
ARHGDIB	0.003	0.053	0.26	3	-0.32	3	6
FADD	0.011	0.008	-10000	0	-10000	0	0
actin filament polymerization	0	0.063	0.37	8	-0.26	3	11
NFKB1	-0.05	0.075	-10000	0	-10000	0	0
MAPK8	-0.043	0.19	-10000	0	-0.43	75	75
DFFA	0.005	0.048	0.26	3	-10000	0	3
DNA fragmentation during apoptosis	0.005	0.048	0.26	3	-10000	0	3
FAS/FADD/MET	-0.13	0.2	-10000	0	-0.41	208	208
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.016	0.14	-10000	0	-0.61	35	35
FAF1	0.01	0.036	-10000	0	-0.62	2	2
PARP1	0.005	0.05	0.26	3	-0.35	1	4
DFFB	0.005	0.048	0.26	3	-10000	0	3
CHUK	-0.042	0.064	-10000	0	-10000	0	0
FASLG	-0.023	0.13	-10000	0	-0.6	33	33
FAS/FADD	-0.025	0.1	-10000	0	-0.44	37	37
HGF	-0.088	0.23	-10000	0	-0.6	113	113
LMNA	0.001	0.061	0.24	3	-0.36	9	12
CASP6	0.001	0.062	0.26	3	-0.38	7	10
CASP10	0.011	0.008	-10000	0	-10000	0	0
CASP3	0.006	0.056	0.24	22	-0.24	8	30
PTPN13	0.009	0.065	-10000	0	-0.62	7	7
CASP8	0.009	0.095	0.36	31	-0.4	12	43
IL6	-0.2	0.43	-10000	0	-1.1	90	90
MET	-0.16	0.28	-10000	0	-0.6	194	194
ICAD/CAD	0.005	0.045	0.24	3	-10000	0	3
FASLG/FAS/FADD/FAF1/Caspase 10	-0.012	0.11	-10000	0	-0.41	12	12
activation of caspase activity by cytochrome c	0.005	0.076	0.31	19	-0.35	13	32
PAK2	0.005	0.048	0.26	3	-10000	0	3
BCL2	0.013	0.043	-10000	0	-0.62	3	3

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.032	0.17	-9999	-0.48	78	78
KLHL20	-0.026	0.057	-9999	-0.29	11	11
CYFIP2	0.008	0.068	-9999	-0.61	8	8
Rac1/GDP	0.014	0.12	-9999	-0.58	3	3
ENAH	-0.032	0.18	-9999	-0.48	78	78
AP1M1	0.015	0	-9999	-10000	0	0
RAP1B	0.009	0.061	-9999	-0.59	7	7
RAP1A	0.015	0	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
CDC42/GTP	-0.038	0.079	-9999	-0.5	4	4
ABI1/Sra1/Nap1	-0.017	0.04	-9999	-0.2	14	14
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.09	0.16	-9999	-0.36	167	167
RAPGEF1	-0.009	0.16	-9999	-0.41	79	79
CTNND1	0.015	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.075	0.16	-9999	-0.5	78	78
CRK	-0.02	0.17	-9999	-0.44	78	78
E-cadherin/gamma catenin/alpha catenin	-0.079	0.16	-9999	-0.38	139	139
alphaE/beta7 Integrin	-0.032	0.11	-9999	-0.44	48	48
IQGAP1	0.009	0.064	-9999	-0.61	7	7
NCKAP1	0.015	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	-0.004	0.035	-9999	-0.32	8	8
DLG1	-0.032	0.17	-9999	-0.48	78	78
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.027	0.056	-9999	-0.33	4	4
MLLT4	0.014	0.025	-9999	-0.62	1	1
ARF6/GTP/NME1/Tiam1	-0.003	0.031	-9999	-0.33	6	6
PI3K	-0.035	0.072	-9999	-0.45	4	4
ARF6	0.015	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.094	0.19	-9999	-0.46	139	139
TIAM1	0.013	0.035	-9999	-0.62	2	2
E-cadherin(dimer)/Ca2+	-0.062	0.12	-9999	-10000	0	0
AKT1	-0.02	0.04	-9999	-0.23	4	4
PIK3R1	0.012	0.043	-9999	-0.62	3	3
CDH1	-0.11	0.25	-9999	-0.61	136	136
RhoA/GDP	0.013	0.12	-9999	-0.58	3	3
actin cytoskeleton organization	-0.019	0.042	-9999	-0.21	11	11
CDC42/GDP	0.013	0.12	-9999	-0.58	3	3
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.026	0.11	-9999	-0.28	82	82
ITGB7	-0.027	0.16	-9999	-0.61	45	45
RAC1	0.015	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.066	0.13	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.064	0.13	-9999	-0.32	136	136
mol:GDP	0.003	0.14	-9999	-0.75	3	3
CDC42/GTP/IQGAP1	-0.004	0.038	-9999	-0.38	7	7
JUP	0.008	0.069	-9999	-0.62	8	8
p120 catenin/RhoA/GDP	-0.045	0.097	-9999	-0.59	3	3
RAC1/GTP/IQGAP1	-0.004	0.038	-9999	-0.38	7	7
PIP5K1C/AP1M1	-0.001	0.018	-9999	-0.46	1	1
RHOA	0.015	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0
CTNNA1	0.015	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.018	0.06	-9999	-0.23	24	24
NME1	0.012	0.046	-9999	-0.59	4	4
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.032	0.17	-9999	-0.48	78	78
regulation of cell-cell adhesion	-0.034	0.07	-9999	-0.42	4	4
WASF2	-0.008	0.021	-9999	-10000	0	0
Rap1/GTP	-0.044	0.093	-9999	-0.6	4	4
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.086	0.16	-9999	-0.65	22	22
CCND1	0.02	0.073	-9999	-0.29	24	24
VAV2	-0.016	0.17	-9999	-0.45	80	80
RAP1/GDP	-0.043	0.095	-9999	-0.58	4	4
adherens junction assembly	-0.029	0.17	-9999	-0.46	78	78
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.015	0	-9999	-10000	0	0
PIP5K1C	0.014	0.025	-9999	-0.62	1	1
regulation of heterotypic cell-cell adhesion	-0.081	0.15	-9999	-0.62	22	22
E-cadherin/beta catenin	-0.067	0.14	-9999	-0.33	137	137
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.032	0.18	-9999	-0.48	79	79
PIK3CA	0.015	0	-9999	-10000	0	0
Rac1/GTP	-0.041	0.095	-9999	-0.49	13	13
E-cadherin/beta catenin/alpha catenin	-0.075	0.15	-9999	-0.37	136	136
ITGAE	0.012	0.04	-9999	-0.59	3	3
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.077	0.17	-9999	-0.51	78	78

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.015	0.081	-10000	0	-0.45	6	6
epithelial cell differentiation	-0.042	0.09	-10000	0	-0.47	8	8
ITCH	0.021	0.015	-10000	0	-10000	0	0
WWP1	0.025	0.056	-10000	0	-10000	0	0
FYN	0.015	0	-10000	0	-10000	0	0
EGFR	-0.11	0.25	-10000	0	-0.6	138	138
PRL	-0.003	0.056	-10000	0	-0.59	6	6
neuron projection morphogenesis	-0.027	0.16	-10000	0	-0.52	13	13
PTPRZ1	0.007	0.074	-10000	0	-0.62	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.091	0.14	-10000	0	-0.58	13	13
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.071	0.17	-10000	0	-0.36	117	117
ADAM17	0.016	0.057	-10000	0	-0.62	5	5
ErbB4/ErbB4	0.02	0.071	-10000	0	-0.42	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.041	0.17	-10000	0	-0.41	110	110
NCOR1	0.013	0.035	-10000	0	-0.62	2	2
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.059	0.16	-10000	0	-0.43	28	28
GRIN2B	-0.14	0.22	-10000	0	-0.53	95	95
ErbB4/ErbB2/betacellulin	-0.035	0.15	-10000	0	-0.45	26	26
STAT1	0.001	0.092	-10000	0	-0.59	16	16
HBEGF	0.003	0.084	-10000	0	-0.59	13	13
PRLR	-0.024	0.15	-10000	0	-0.61	42	42
E4ICDs/ETO2	0.004	0.1	-10000	0	-0.4	29	29
axon guidance	-0.009	0.075	-10000	0	-0.36	3	3
NEDD4	0.014	0.065	-10000	0	-0.6	7	7
Prolactin receptor/Prolactin receptor/Prolactin	-0.032	0.12	-10000	0	-0.45	47	47
CBFA2T3	-0.014	0.13	-10000	0	-0.62	31	31
ErbB4/ErbB2/HBEGF	0.022	0.085	-10000	0	-0.38	12	12
MAPK3	-0.037	0.16	-10000	0	-0.54	13	13
STAT1 (dimer)	0.014	0.082	-10000	0	-0.35	17	17
MAPK1	-0.037	0.16	-10000	0	-0.54	13	13
JAK2	0.015	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.064	0.17	-10000	0	-0.45	31	31
NRG1	-0.1	0.22	-10000	0	-0.45	183	183
NRG3	-0.09	0.24	-10000	0	-0.62	110	110
NRG2	0.009	0.065	-10000	0	-0.62	7	7
NRG4	-0.031	0.16	-10000	0	-0.59	50	50
heart development	-0.009	0.075	-10000	0	-0.36	3	3
neural crest cell migration	-0.064	0.17	-10000	0	-0.44	31	31
ERBB2	0.02	0.072	-10000	0	-0.43	16	16
WWOX/E4ICDs	0.022	0.059	-10000	0	-0.37	1	1
SHC1	0.001	0.092	-10000	0	-0.59	16	16
ErbB4/EGFR/neuregulin 4	-0.1	0.16	-10000	0	-0.49	47	47
apoptosis	0.082	0.17	0.44	110	-10000	0	110
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.018	0.076	-10000	0	-0.45	8	8
ErbB4/ErbB2/epiregulin	-0.008	0.12	-10000	0	-0.4	26	26
ErbB4/ErbB4/betacellulin/betacellulin	-0.046	0.15	-10000	0	-0.36	110	110
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.037	0.097	-10000	0	-0.52	12	12
MDM2	0.02	0.083	-10000	0	-0.39	13	13
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.092	0.14	-10000	0	-0.42	28	28
STAT5A	-0.005	0.087	-10000	0	-0.41	10	10
ErbB4/EGFR/neuregulin 1 beta	-0.13	0.22	-10000	0	-0.55	73	73
DLG4	0.005	0.077	-10000	0	-0.59	11	11
GRB2/SHC	-0.011	0.066	-10000	0	-0.42	17	17
E4ICDs/TAB2/NCoR1	-0.016	0.047	-10000	0	-0.43	3	3
STAT5A (dimer)	-0.045	0.096	-10000	0	-0.52	7	7
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0	0.07	-10000	0	-0.35	2	2
LRIG1	0.003	0.088	-10000	0	-0.62	13	13
EREG	-0.038	0.16	-10000	0	-0.59	55	55
BTC	-0.089	0.23	-10000	0	-0.61	109	109
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.009	0.076	-10000	0	-0.36	3	3
ERBB4	0.02	0.071	-10000	0	-0.43	1	1
STAT5B	0.015	0	-10000	0	-10000	0	0
YAP1	-0.031	0.12	-10000	0	-0.6	29	29
GRB2	0.014	0.023	-10000	0	-0.59	1	1
ErbB4/ErbB2/neuregulin 4	0.001	0.11	-10000	0	-0.44	15	15
glial cell differentiation	0.016	0.047	0.42	3	-10000	0	3
WWOX	0.015	0	-10000	0	-10000	0	0
cell proliferation	-0.093	0.19	-10000	0	-0.54	44	44

×

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	0.001	0.052	-10000	0	-0.61	4	4
AES	0.004	0.018	-10000	0	-10000	0	0
FBXW11	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	-0.006	0.051	-10000	0	-0.42	10	10
SMAD4	0.015	0	-10000	0	-10000	0	0
DKK2	-0.094	0.24	-10000	0	-0.6	117	117
TLE1	0.003	0.039	-10000	0	-0.63	2	2
MACF1	0.013	0.043	-10000	0	-0.62	3	3
CTNNB1	0.071	0.092	0.33	5	-0.35	1	6
WIF1	-0.28	0.31	-10000	0	-0.6	322	322
beta catenin/RanBP3	0.01	0.097	0.42	25	-10000	0	25
KREMEN2	-0.042	0.18	-10000	0	-0.6	63	63
DKK1	-0.13	0.26	-10000	0	-0.6	160	160
beta catenin/beta TrCP1	0.076	0.087	0.39	2	-10000	0	2
FZD1	0.008	0.069	-10000	0	-0.58	9	9
AXIN2	0.008	0.1	-10000	0	-1.2	3	3
AXIN1	0.015	0.025	-10000	0	-0.63	1	1
RAN	0.015	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.009	0.035	-10000	0	-0.49	1	1
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.096	0.054	0.35	1	-10000	0	1
Axin1/APC/GSK3	0.012	0.052	0.26	11	-10000	0	11
Axin1/APC/GSK3/beta catenin/Macf1	0.058	0.082	-10000	0	-0.48	4	4
HNF1A	0.004	0.031	-10000	0	-0.63	1	1
CTBP1	0.005	0.02	-10000	0	-10000	0	0
MYC	-0.023	0.24	-10000	0	-1.4	20	20
RANBP3	0.015	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.098	0.18	-10000	0	-0.39	168	168
NKD1	-0.023	0.15	-10000	0	-0.62	40	40
TCF4	0.004	0.029	-10000	0	-0.58	1	1
TCF3	0.004	0.026	-10000	0	-0.49	1	1
WNT1/LRP6/FZD1/Axin1	-0.023	0.084	-10000	0	-0.48	4	4
Ran/GTP	0.001	0.004	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.021	0.11	0.49	24	-10000	0	24
LEF1	-0.003	0.068	-10000	0	-0.59	8	8
DVL1	0.056	0.055	0.23	1	-10000	0	1
CSNK2A1	0.015	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.1	0.069	-10000	0	-0.48	1	1
DKK1/LRP6/Kremen 2	-0.12	0.18	-10000	0	-0.38	212	212
LRP6	0.015	0.023	-10000	0	-0.59	1	1
CSNK1A1	0.005	0.021	-10000	0	-10000	0	0
NLK	0.016	0.004	-10000	0	-10000	0	0
CCND1	-0.012	0.19	-10000	0	-1.4	9	9
WNT1	-0.021	0.14	-10000	0	-0.59	38	38
GSK3A	0.016	0.001	-10000	0	-10000	0	0
GSK3B	0.015	0.001	-10000	0	-10000	0	0
FRAT1	0.007	0.072	-10000	0	-0.61	9	9
PPP2R5D	0.053	0.07	0.31	40	-10000	0	40
APC	0.024	0.088	-10000	0	-0.58	2	2
WNT1/LRP6/FZD1	0.098	0.11	0.25	143	-10000	0	143
CREBBP	0.004	0.031	-10000	0	-0.63	1	1

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.058	0.14	-9999	-0.4	80	80
MAP4K1	-0.011	0.13	-9999	-0.62	28	28
MAP3K8	-0.005	0.11	-9999	-0.59	22	22
PRKCB	-0.072	0.22	-9999	-0.6	94	94
DBNL	0.015	0	-9999	-10000	0	0
CRKL	0.014	0.023	-9999	-0.59	1	1
MAP3K1	0.012	0.11	-9999	-0.47	10	10
JUN	-0.021	0.16	-9999	-0.53	47	47
MAP3K7	0.014	0.1	-9999	-0.47	10	10
GRAP2	-0.034	0.17	-9999	-0.61	53	53
CRK	0.015	0	-9999	-10000	0	0
MAP2K4	0.019	0.11	-9999	-0.44	13	13
LAT	-0.011	0.13	-9999	-0.62	28	28
LCP2	0.007	0.072	-9999	-0.61	9	9
MAPK8	-0.028	0.16	-9999	-0.56	46	46
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.004	0.11	-9999	-0.45	14	14
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.054	0.14	-9999	-0.65	14	14

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.053	0.2	-9999	-0.61	73	73
GNB1/GNG2	-0.059	0.12	-9999	-0.5	20	20
mol:DAG	-0.007	0.13	-9999	-0.45	20	20
PLCG1	-0.008	0.13	-9999	-0.46	20	20
YES1	-0.025	0.14	-9999	-0.46	25	25
FZD3	0.012	0.043	-9999	-0.62	3	3
FZD6	-0.033	0.16	-9999	-0.59	53	53
G protein	-0.008	0.13	-9999	-0.47	20	20
MAP3K7	-0.096	0.17	-9999	-0.45	48	48
mol:Ca2+	-0.006	0.12	-9999	-0.43	20	20
mol:IP3	-0.007	0.13	-9999	-0.45	20	20
NLK	-0.006	0.007	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
CAMK2A	-0.11	0.18	-9999	-0.47	64	64
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.036	0.14	-9999	-0.42	39	39
CSNK1A1	0.015	0	-9999	-10000	0	0
GNAS	-0.024	0.14	-9999	-0.46	23	23
GO:0007205	-0.006	0.13	-9999	-0.44	20	20
WNT6	-0.027	0.16	-9999	-0.6	46	46
WNT4	-0.042	0.18	-9999	-0.6	62	62
NFAT1/CK1 alpha	-0.079	0.13	-9999	-0.46	43	43
GNG2	0.009	0.06	-9999	-0.62	6	6
WNT5A	-0.006	0.11	-9999	-0.61	23	23
WNT11	-0.024	0.15	-9999	-0.61	42	42
CDC42	-0.015	0.13	-9999	-0.45	22	22

×

Signaling events mediated by HDAC Class III

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
EP300	0.012	0.043	-10000	0	-0.62	3	3
HDAC4	0.014	0.025	-10000	0	-0.62	1	1
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.025	0.055	0.42	8	-10000	0	8
CDKN1A	-0.045	0.17	-10000	0	-0.6	53	53
KAT2B	0.012	0.042	-10000	0	-0.61	3	3
BAX	0.015	0	-10000	0	-10000	0	0
FOXO3	0.002	0.033	0.47	3	-0.28	1	4
FOXO1	0.014	0.025	-10000	0	-0.62	1	1
FOXO4	0.024	0.041	-10000	0	-0.38	6	6
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.015	0	-10000	0	-10000	0	0
TAT	-0.088	0.23	-10000	0	-0.6	111	111
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.1	0.21	-10000	0	-0.45	178	178
PPARGC1A	-0.002	0.1	-10000	0	-0.62	18	18
FHL2	-0.042	0.18	-10000	0	-0.59	63	63
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.01	0.034	-10000	0	-10000	0	0
HIST2H4A	0.025	0.055	-10000	0	-0.42	8	8
SIRT1/FOXO3a	0.01	0.037	0.3	3	-10000	0	3
SIRT1	0.013	0.044	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.008	0.04	-10000	0	-0.38	2	2
SIRT1/Histone H1b	-0.005	0.07	-10000	0	-0.47	2	2
apoptosis	-0.009	0.033	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.002	0.07	-10000	0	-0.38	18	18
p53/SIRT1	0.018	0.12	0.35	52	-0.46	12	64
SIRT1/FOXO4	0.008	0.051	-10000	0	-0.66	1	1
FOXO1/FHL2/SIRT1	-0.023	0.1	-10000	0	-0.32	63	63
HIST1H1E	0.006	0.076	-10000	0	-0.33	20	20
SIRT1/p300	0.008	0.046	-10000	0	-0.46	3	3
muscle cell differentiation	0.091	0.17	0.37	178	-10000	0	178
TP53	0	0.098	-10000	0	-0.62	13	13
KU70/SIRT1/BAX	0.01	0.034	-10000	0	-10000	0	0
CREBBP	0.014	0.025	-10000	0	-0.62	1	1
MEF2D	0.014	0.025	-10000	0	-0.62	1	1
HIV-1 Tat/SIRT1	-0.064	0.17	-10000	0	-0.43	111	111
ACSS2	0.031	0.024	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.091	0.17	-10000	0	-0.37	178	178

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.006	0.077	-10000	0	-0.62	10	10
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.004	0.11	0.51	7	-10000	0	7
IL27/IL27R/JAK1	-0.029	0.16	-10000	0	-0.65	9	9
TBX21	-0.038	0.22	-10000	0	-0.58	56	56
IL12B	0.001	0.047	-10000	0	-0.6	4	4
IL12A	0	0.08	-10000	0	-0.46	20	20
IL6ST	-0.029	0.16	-10000	0	-0.63	46	46
IL27RA/JAK1	0.02	0.067	-10000	0	-1.3	1	1
IL27	-0.012	0.12	-10000	0	-0.59	28	28
TYK2	0.016	0.004	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.075	0.14	-10000	0	-0.75	5	5
T-helper 2 cell differentiation	-0.004	0.11	0.51	7	-10000	0	7
T cell proliferation during immune response	-0.004	0.11	0.51	7	-10000	0	7
MAPKKK cascade	0.004	0.11	-10000	0	-0.51	7	7
STAT3	0.015	0	-10000	0	-10000	0	0
STAT2	0.012	0.04	-10000	0	-0.59	3	3
STAT1	0.001	0.093	-10000	0	-0.59	16	16
IL12RB1	-0.019	0.14	-10000	0	-0.62	36	36
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.059	0.24	-10000	0	-0.56	61	61
IL27/IL27R/JAK2/TYK2	0.004	0.11	-10000	0	-0.51	7	7
positive regulation of T cell mediated cytotoxicity	0.004	0.11	-10000	0	-0.51	7	7
STAT1 (dimer)	-0.046	0.25	0.53	35	-0.72	19	54
JAK2	0.016	0.004	-10000	0	-10000	0	0
JAK1	0.015	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	0.011	0.1	-10000	0	-0.48	8	8
T cell proliferation	-0.087	0.18	-10000	0	-0.51	39	39
IL12/IL12R/TYK2/JAK2	0.008	0.083	-10000	0	-0.59	3	3
IL17A	-0.075	0.14	-10000	0	-0.75	5	5
mast cell activation	-0.004	0.11	0.51	7	-10000	0	7
IFNG	0.004	0.021	-10000	0	-0.095	5	5
T cell differentiation	-0.004	0.005	-10000	0	-0.023	4	4
STAT3 (dimer)	0.012	0.1	-10000	0	-0.48	7	7
STAT5A (dimer)	0.007	0.11	-10000	0	-0.5	12	12
STAT4 (dimer)	-0.069	0.18	-10000	0	-0.52	23	23
STAT4	-0.14	0.27	-10000	0	-0.6	165	165
T cell activation	-0.009	0.01	0.079	7	-10000	0	7
IL27R/JAK2/TYK2	-0.013	0.1	-10000	0	-1.2	1	1
GATA3	-0.15	0.39	-10000	0	-1.4	54	54
IL18	-0.018	0.12	-10000	0	-0.45	45	45
positive regulation of mast cell cytokine production	0.012	0.1	-10000	0	-0.47	7	7
IL27/EBI3	-0.011	0.12	-10000	0	-0.44	44	44
IL27RA	0.014	0.07	-10000	0	-1.3	1	1
IL6	-0.17	0.28	-10000	0	-0.6	205	205
STAT5A	0.005	0.081	-10000	0	-0.62	11	11
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	0.002	0.032	0.47	1	-10000	0	1
IL1B	-0.12	0.21	-10000	0	-0.45	191	191
EBI3	-0.002	0.1	-10000	0	-0.62	17	17
TNF	-0.091	0.19	-10000	0	-0.45	152	152

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	-0.01	0.12	-10000	0	-0.42	55	55
MAP4K4	-0.015	0.12	-10000	0	-0.46	18	18
BAG4	0.003	0.088	-10000	0	-0.62	13	13
PKC zeta/ceramide	-0.022	0.097	0.18	11	-0.3	55	66
NFKBIA	0.014	0.023	-10000	0	-0.59	1	1
BIRC3	-0.059	0.2	-10000	0	-0.6	81	81
BAX	0.008	0.029	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
AKT1	0.025	0.029	-10000	0	-0.55	1	1
BAD	0.007	0.053	0.19	18	-10000	0	18
SMPD1	-0.018	0.088	-10000	0	-0.27	13	13
RB1	0.007	0.055	0.19	18	-0.43	1	19
FADD/Caspase 8	-0.003	0.12	-10000	0	-0.43	21	21
MAP2K4	0.014	0.056	0.19	15	-0.32	4	19
NSMAF	0.015	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	0.013	0.057	-10000	0	-0.3	5	5
EGF	-0.038	0.18	-10000	0	-0.61	57	57
mol:ceramide	-0.003	0.057	0.18	50	-10000	0	50
MADD	0.012	0.043	-10000	0	-0.62	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.01	0.12	-10000	0	-0.42	55	55
ASAH1	0.015	0	-10000	0	-10000	0	0
negative regulation of cell cycle	0.006	0.055	0.19	18	-0.42	1	19
cell proliferation	-0.021	0.078	-10000	0	-0.33	32	32
BID	-0.004	0.093	-10000	0	-0.44	9	9
MAP3K1	0.005	0.059	0.19	18	-0.35	4	22
EIF2A	0.022	0.053	-10000	0	-0.33	3	3
TRADD	0.014	0.025	-10000	0	-0.62	1	1
CRADD	0.015	0	-10000	0	-10000	0	0
MAPK3	0.026	0.054	-10000	0	-0.29	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	0.026	0.054	-10000	0	-0.29	4	4
Cathepsin D/ceramide	0.005	0.052	0.17	22	-0.32	1	23
FADD	-0.015	0.12	-10000	0	-0.46	18	18
KSR1	0.005	0.06	0.19	18	-0.33	5	23
MAPK8	-0.002	0.079	0.19	11	-0.25	38	49
PRKRA	0.007	0.053	0.19	18	-10000	0	18
PDGFA	-0.034	0.17	-10000	0	-0.59	55	55
TRAF2	0.015	0	-10000	0	-10000	0	0
IGF1	-0.005	0.11	-10000	0	-0.61	22	22
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.003	0.057	0.17	50	-10000	0	50
CTSD	0.014	0.023	-10000	0	-0.59	1	1
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.005	0.092	-10000	0	-0.36	32	32
PRKCD	-0.008	0.12	-10000	0	-0.62	24	24
PRKCZ	-0.037	0.17	-10000	0	-0.62	55	55
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.01	0.12	-10000	0	-0.42	55	55
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	-0.036	0.17	-10000	0	-0.6	56	56
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.026	0.13	-10000	0	-0.5	18	18
TNFR1A/BAG4/TNF-alpha	-0.098	0.17	-10000	0	-0.38	171	171
mol:Sphingosine-1-phosphate	-0.01	0.12	-10000	0	-0.42	55	55
MAP2K1	0.021	0.055	-10000	0	-0.3	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.015	0	-10000	0	-10000	0	0
CYCS	0.009	0.04	0.15	17	-10000	0	17
TNFRSF1A	0.002	0.09	-10000	0	-0.61	14	14
NFKB1	0.015	0	-10000	0	-10000	0	0
TNFR1A/BAG4	-0.018	0.091	-10000	0	-0.46	26	26
EIF2AK2	0.014	0.056	-10000	0	-0.36	3	3
TNF-alpha/TNFR1A/FAN	-0.091	0.16	-10000	0	-0.37	164	164
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.004	0.08	-10000	0	-0.41	4	4
MAP2K2	0.021	0.055	-10000	0	-0.3	4	4
SMPD3	-0.054	0.15	-10000	0	-0.3	140	140
TNF	-0.13	0.26	-10000	0	-0.6	152	152
PKC zeta/PAR4	-0.072	0.18	-10000	0	-0.47	102	102
mol:PHOSPHOCHOLINE	0.001	0.077	0.22	51	-10000	0	51
NF kappa B1/RelA/I kappa B alpha	-0.05	0.12	-10000	0	-0.62	10	10
AIFM1	0.009	0.04	0.23	2	-10000	0	2
BCL2	0.012	0.043	-10000	0	-0.62	3	3

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.068	0.21	-10000	0	-0.62	88	88
HRAS	0.015	0	-10000	0	-10000	0	0
EGFR	-0.11	0.25	-10000	0	-0.6	138	138
AKT	0.021	0.05	-10000	0	-0.38	7	7
FOXO3	0.014	0.025	-10000	0	-0.62	1	1
AKT1	0.014	0.023	-10000	0	-0.59	1	1
FOXO1	0.014	0.025	-10000	0	-0.62	1	1
AKT3	0.01	0.06	-10000	0	-0.62	6	6
FOXO4	0.012	0.043	-10000	0	-0.62	3	3
MET	-0.16	0.28	-10000	0	-0.6	194	194
PIK3CA	0.015	0	-10000	0	-10000	0	0
PIK3CB	0.014	0.025	-10000	0	-0.62	1	1
NRAS	0.015	0	-10000	0	-10000	0	0
PIK3CG	-0.037	0.17	-10000	0	-0.61	56	56
PIK3R3	0.012	0.041	-10000	0	-0.6	3	3
PIK3R2	0.015	0	-10000	0	-10000	0	0
NF1	0.01	0.055	-10000	0	-0.62	5	5
RAS	-0.062	0.12	0.24	1	-0.32	71	72
ERBB2	0.005	0.078	-10000	0	-0.59	11	11
proliferation/survival/translation	-0.012	0.05	0.22	5	-10000	0	5
PI3K	-0.038	0.12	-10000	0	-0.27	102	102
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
KRAS	0.014	0.023	-10000	0	-0.59	1	1
FOXO	0.029	0.033	-10000	0	-10000	0	0
AKT2	0.015	0	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.013	0.035	-10000	0	-0.62	2	2
ANTXR2	0.004	0.081	-10000	0	-0.59	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0.011	-10000	0	-0.074	14	14
monocyte activation	-0.13	0.24	-10000	0	-0.52	155	155
MAP2K2	-0.001	0.004	-10000	0	-10000	0	0
MAP2K1	-0.001	0.008	-10000	0	-10000	0	0
MAP2K7	-0.002	0.016	-10000	0	-0.34	1	1
MAP2K6	-0.002	0.016	-10000	0	-0.34	1	1
CYAA	0.011	0.048	-10000	0	-0.32	14	14
MAP2K4	-0.001	0.008	-10000	0	-10000	0	0
IL1B	-0.079	0.15	-10000	0	-0.32	192	192
Channel	-0.007	0.048	-10000	0	-0.34	14	14
NLRP1	-0.003	0.028	-10000	0	-0.34	4	4
CALM1	0.015	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.002	0.012	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0.011	0.074	14	-10000	0	14
MAPK3	-0.001	0.008	-10000	0	-10000	0	0
MAPK1	-0.001	0.008	-10000	0	-10000	0	0
PGR	-0.054	0.12	-10000	0	-0.35	103	103
PA/Cellular Receptors	-0.008	0.053	-10000	0	-0.37	14	14
apoptosis	-0.002	0.011	-10000	0	-0.074	14	14
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.012	0.046	-10000	0	-0.3	14	14
macrophage activation	0.022	0.01	-10000	0	-10000	0	0
TNF	-0.13	0.26	-10000	0	-0.6	152	152
VCAM1	-0.13	0.24	-10000	0	-0.52	155	155
platelet activation	-0.002	0.012	-10000	0	-10000	0	0
MAPKKK cascade	-0.018	0.012	-10000	0	-10000	0	0
IL18	-0.006	0.09	-10000	0	-0.33	46	46
negative regulation of macrophage activation	-0.002	0.011	-10000	0	-0.074	14	14
LEF	-0.002	0.011	-10000	0	-0.074	14	14
CASP1	-0.004	0.02	-10000	0	-0.19	4	4
mol:cAMP	-0.002	0.012	-10000	0	-10000	0	0
necrosis	-0.002	0.011	-10000	0	-0.074	14	14
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.012	0.048	-10000	0	-0.32	14	14
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0	0.11	-9999	-0.37	42	42
BIRC5	-0.19	0.29	-9999	-0.6	225	225
NFKBIA	0.028	0.068	-9999	-0.32	2	2
CPEB1	0	0.098	-9999	-0.62	16	16
AKT1	0.028	0.068	-9999	-0.31	2	2
NDEL1	0.015	0	-9999	-10000	0	0
Aurora A/BRCA1	0.002	0.06	-9999	-0.3	4	4
NDEL1/TACC3	-0.01	0.1	-9999	-0.39	31	31
GADD45A	-0.022	0.14	-9999	-0.59	41	41
GSK3B	0.021	0.016	-9999	-10000	0	0
PAK1/Aurora A	0.002	0.1	-9999	-0.34	33	33
MDM2	0.003	0.083	-9999	-0.59	13	13
JUB	-0.007	0.12	-9999	-0.62	23	23
TPX2	-0.041	0.17	-9999	-0.44	98	98
TP53	0.021	0.069	-9999	-0.28	19	19
DLG7	0.016	0.066	-9999	-0.3	1	1
AURKAIP1	0.014	0.023	-9999	-0.59	1	1
ARHGEF7	0.015	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.011	0.11	-9999	-0.41	31	31
G2/M transition of mitotic cell cycle	0.002	0.06	-9999	-0.3	4	4
AURKA	0.022	0.082	-9999	-0.36	1	1
AURKB	-0.099	0.14	-9999	-0.3	205	205
CDC25B	0.023	0.063	-9999	-0.28	2	2
G2/M transition checkpoint	-0.009	0.082	-9999	-0.33	23	23
mRNA polyadenylation	-0.006	0.083	-9999	-0.39	17	17
Aurora A/CPEB	-0.006	0.084	-9999	-0.4	17	17
Aurora A/TACC1/TRAP/chTOG	0.009	0.059	-9999	-0.47	1	1
BRCA1	0.012	0.04	-9999	-0.59	3	3
centrosome duplication	0.002	0.1	-9999	-0.34	33	33
regulation of centrosome cycle	-0.02	0.093	-9999	-0.39	31	31
spindle assembly	-0.003	0.048	-9999	-0.46	1	1
TDRD7	0.013	0.035	-9999	-0.62	2	2
Aurora A/RasGAP/Survivin	-0.1	0.15	-9999	-0.38	90	90
CENPA	-0.093	0.14	-9999	-0.3	175	175
Aurora A/PP2A	0.023	0.064	-9999	-0.29	1	1
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.033	0.059	-9999	-0.27	1	1
negative regulation of DNA binding	0.021	0.069	-9999	-0.28	19	19
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	-0.001	0.018	-9999	-0.46	1	1
RASA1	0.015	0	-9999	-10000	0	0
Ajuba/Aurora A	-0.009	0.082	-9999	-0.33	23	23
mitotic prometaphase	0.022	0.037	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.022	0.082	-9999	-0.36	1	1
TACC1	0.015	0	-9999	-10000	0	0
TACC3	-0.016	0.13	-9999	-0.59	34	34
Aurora A/Antizyme1	0.006	0.059	-9999	-10000	0	0
Aurora A/RasGAP	0.023	0.064	-9999	-0.29	1	1
OAZ1	0.015	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.021	0.016	-9999	-10000	0	0
GIT1	0.014	0.025	-9999	-0.62	1	1
GIT1/beta-PIX/PAK1	-0.02	0.083	-9999	-0.36	38	38
Importin alpha/Importin beta/TPX2	-0.041	0.16	-9999	-0.44	98	98
PPP2R5D	0.015	0	-9999	-10000	0	0
Aurora A/TPX2	-0.019	0.15	-9999	-0.42	59	59
PAK1	-0.018	0.14	-9999	-0.59	37	37
CKAP5	0.015	0	-9999	-10000	0	0

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.055	0.15	0.46	81	-10000	0	81
KIRREL	-0.032	0.16	-10000	0	-0.63	47	47
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.056	0.15	-10000	0	-0.46	81	81
PLCG1	0.015	0	-10000	0	-10000	0	0
ARRB2	0.015	0	-10000	0	-10000	0	0
WASL	0.015	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.041	0.11	-10000	0	-0.64	4	4
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.003	0.092	-10000	0	-0.47	4	4
FYN	-0.018	0.11	-10000	0	-0.35	43	43
mol:Ca2+	-0.041	0.11	-10000	0	-0.44	12	12
mol:DAG	-0.041	0.11	-10000	0	-0.44	12	12
NPHS2	-0.005	0.044	-10000	0	-0.59	3	3
mol:IP3	-0.041	0.11	-10000	0	-0.44	12	12
regulation of endocytosis	-0.035	0.096	-10000	0	-0.57	4	4
Nephrin/NEPH1/podocin/Cholesterol	-0.043	0.12	-10000	0	-0.34	84	84
establishment of cell polarity	-0.055	0.15	-10000	0	-0.46	81	81
Nephrin/NEPH1/podocin/NCK1-2	-0.037	0.1	-10000	0	-0.59	4	4
Nephrin/NEPH1/beta Arrestin2	-0.009	0.11	-10000	0	-0.58	4	4
NPHS1	-0.026	0.14	-10000	0	-0.59	38	38
Nephrin/NEPH1/podocin	-0.036	0.11	-10000	0	-0.35	43	43
TJP1	0.015	0	-10000	0	-10000	0	0
NCK1	0.015	0	-10000	0	-10000	0	0
NCK2	0.015	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.041	0.11	-10000	0	-0.44	12	12
CD2AP	0.015	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.042	0.11	-10000	0	-0.44	13	13
GRB2	0.014	0.023	-10000	0	-0.59	1	1
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.038	0.14	-10000	0	-0.39	55	55
cytoskeleton organization	0.005	0.11	-10000	0	-0.57	4	4
Nephrin/NEPH1	-0.04	0.11	-10000	0	-0.33	81	81
Nephrin/NEPH1/ZO-1	-0.044	0.12	-10000	0	-0.36	81	81

×

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

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
MAP4K1	0.021	0.12	-10000	0	-0.39	28	28
CRKL	0.027	0.11	-10000	0	-0.42	27	27
HRAS	0.005	0.14	-10000	0	-0.5	17	17
mol:PIP3	0.003	0.11	-10000	0	-0.41	29	29
SPRED1	0.015	0	-10000	0	-10000	0	0
SPRED2	0.011	0.054	-10000	0	-0.61	5	5
GAB1	0.019	0.12	-10000	0	-0.45	27	27
FOXO3	0.028	0.11	-10000	0	-0.38	28	28
AKT1	0.02	0.11	-10000	0	-0.42	28	28
BAD	0.028	0.11	-10000	0	-0.38	28	28
megakaryocyte differentiation	0.012	0.12	-10000	0	-0.45	30	30
GSK3B	0.028	0.11	-10000	0	-0.38	28	28
RAF1	0.017	0.12	-10000	0	-0.41	14	14
SHC1	0.001	0.092	-10000	0	-0.59	16	16
STAT3	0.019	0.11	-10000	0	-0.44	28	28
STAT1	0.013	0.24	-10000	0	-1	29	29
HRAS/SPRED1	-0.043	0.089	-10000	0	-0.39	17	17
cell proliferation	0.015	0.12	-10000	0	-0.44	30	30
PIK3CA	0.015	0	-10000	0	-10000	0	0
TEC	-0.012	0.13	-10000	0	-0.6	30	30
RPS6KB1	0.018	0.12	0.24	1	-0.4	36	37
HRAS/SPRED2	-0.045	0.093	-10000	0	-0.39	20	20
LYN/TEC/p62DOK	-0.037	0.11	-10000	0	-0.45	29	29
MAPK3	0.03	0.094	0.22	1	-0.32	6	7
STAP1	-0.007	0.15	-10000	0	-0.45	42	42
GRAP2	-0.034	0.17	-10000	0	-0.61	53	53
JAK2	-0.049	0.18	-10000	0	-0.84	28	28
STAT1 (dimer)	0.014	0.24	-10000	0	-0.98	30	30
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.065	0.13	-10000	0	-0.48	35	35
actin filament polymerization	0.012	0.12	-10000	0	-0.44	29	29
LYN	0.011	0.053	-10000	0	-0.6	5	5
STAP1/STAT5A (dimer)	0	0.18	-10000	0	-0.63	32	32
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
CBL/CRKL/GRB2	0.037	0.1	-10000	0	-0.37	25	25
PI3K	0.026	0.11	-10000	0	-0.41	27	27
PTEN	0.015	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.002	0.29	-10000	0	-1.3	28	28
MAPK8	0.015	0.12	-10000	0	-0.45	30	30
STAT3 (dimer)	0.02	0.11	-10000	0	-0.43	28	28
positive regulation of transcription	0.03	0.081	0.21	1	-0.26	5	6
mol:GDP	-0.067	0.13	0.23	2	-0.5	28	30
PIK3C2B	0.012	0.13	-10000	0	-0.44	36	36
CBL/CRKL	0.034	0.11	-10000	0	-0.39	27	27
FER	0.013	0.12	-10000	0	-0.4	41	41
SH2B3	0.018	0.12	-10000	0	-0.45	27	27
PDPK1	0.012	0.1	-10000	0	-0.37	29	29
SNAI2	-0.015	0.15	-10000	0	-0.46	38	38
positive regulation of cell proliferation	0.02	0.18	-10000	0	-0.73	29	29
KITLG	0.011	0.076	-10000	0	-0.64	9	9
cell motility	0.02	0.18	-10000	0	-0.73	29	29
PTPN6	-0.006	0.08	-10000	0	-0.62	11	11
EPOR	0.045	0.082	-10000	0	-0.62	2	2
STAT5A (dimer)	0.02	0.15	-10000	0	-0.61	28	28
SOCS1	-0.059	0.2	-10000	0	-0.59	82	82
cell migration	0.035	0.16	0.42	43	-10000	0	43
SOS1	0.015	0	-10000	0	-10000	0	0
EPO	-0.023	0.15	-10000	0	-0.59	43	43
VAV1	-0.01	0.12	-10000	0	-0.62	27	27
GRB10	0.015	0.12	-10000	0	-0.46	29	29
PTPN11	0.011	0.035	-10000	0	-0.62	2	2
SCF/KIT	0.01	0.12	0.25	1	-0.42	36	37
GO:0007205	-0.002	0.006	-10000	0	-10000	0	0
MAP2K1	0.026	0.1	-10000	0	-0.36	6	6
CBL	0.014	0.025	-10000	0	-0.62	1	1
KIT	-0.007	0.29	-10000	0	-1.3	27	27
MAP2K2	0.026	0.1	-10000	0	-0.36	6	6
SHC/Grb2/SOS1	-0.03	0.1	-10000	0	-0.45	27	27
STAT5A	0.019	0.16	-10000	0	-0.63	28	28
GRB2	0.014	0.023	-10000	0	-0.59	1	1
response to radiation	-0.014	0.15	-10000	0	-0.46	38	38
SHC/GRAP2	-0.045	0.14	-10000	0	-0.45	67	67
PTPRO	0.012	0.13	-10000	0	-0.46	30	30
SH2B2	0.012	0.13	-10000	0	-0.45	29	29
DOK1	0.014	0.025	-10000	0	-0.62	1	1
MATK	-0.036	0.16	-10000	0	-0.44	41	41
CREBBP	0.042	0.028	-10000	0	-0.62	1	1
BCL2	0.041	0.12	-10000	0	-1.2	4	4

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.015	0	-9999	-10000	0	0
SPHK1	-0.025	0.15	-9999	-0.6	44	44
GNAI2	0.015	0	-9999	-10000	0	0
mol:S1P	0.009	0.069	-9999	-0.31	19	19
GNAO1	-0.012	0.13	-9999	-0.62	28	28
mol:Sphinganine-1-P	-0.003	0.12	-9999	-0.44	44	44
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.013	0.053	-9999	-0.43	4	4
GNAI3	0.015	0	-9999	-10000	0	0
G12/G13	-0.001	0.018	-9999	-0.46	1	1
S1PR3	-0.023	0.15	-9999	-0.6	41	41
S1PR2	0.011	0.053	-9999	-0.6	5	5
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.014	0.054	-9999	-0.27	19	19
S1PR5	-0.1	0.24	-9999	-0.61	128	128
S1PR4	0	0.096	-9999	-0.6	17	17
GNAI1	-0.02	0.15	-9999	-0.62	37	37
S1P/S1P5/G12	-0.045	0.15	-9999	-0.34	129	129
S1P/S1P3/Gq	0.001	0.11	-9999	-0.46	13	13
S1P/S1P4/Gi	0.012	0.11	-9999	-0.47	19	19
GNAQ	0.015	0	-9999	-10000	0	0
GNAZ	0.012	0.043	-9999	-0.62	3	3
GNA14	-0.009	0.12	-9999	-0.61	26	26
GNA15	-0.009	0.12	-9999	-0.61	26	26
GNA12	0.014	0.025	-9999	-0.62	1	1
GNA13	0.015	0	-9999	-10000	0	0
GNA11	0.006	0.078	-9999	-0.62	10	10
ABCC1	0.012	0.04	-9999	-0.59	3	3

×

Ephrin B reverse signaling

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
EFNB2	0.003	0.085	-10000	0	-0.6	13	13
EPHB2	0.007	0.072	-10000	0	-0.6	9	9
EFNB1	-0.049	0.17	-10000	0	-0.44	110	110
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.084	0.15	-10000	0	-0.64	15	15
Ephrin B2/EPHB1-2	-0.054	0.14	-10000	0	-0.37	97	97
neuron projection morphogenesis	-0.08	0.14	-10000	0	-0.61	15	15
Ephrin B1/EPHB1-2/Tiam1	-0.086	0.16	-10000	0	-0.7	15	15
DNM1	-0.083	0.22	-10000	0	-0.6	107	107
cell-cell signaling	0	0.002	-10000	0	-10000	0	0
MAP2K4	0.017	0.073	-10000	0	-0.73	6	6
YES1	-0.006	0.095	-10000	0	-0.99	6	6
Ephrin B1/EPHB1-2/NCK2	-0.085	0.16	-10000	0	-0.68	14	14
PI3K	0.016	0.077	-10000	0	-0.74	6	6
mol:GDP	-0.087	0.16	-10000	0	-0.68	15	15
ITGA2B	-0.028	0.16	-10000	0	-0.62	46	46
endothelial cell proliferation	-0.01	0.062	-10000	0	-0.39	17	17
FYN	-0.005	0.092	-10000	0	-0.97	6	6
MAP3K7	-0.004	0.075	-10000	0	-0.78	6	6
FGR	-0.006	0.092	-10000	0	-0.96	6	6
TIAM1	0.013	0.035	-10000	0	-0.62	2	2
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
RGS3	0.012	0.046	-10000	0	-0.59	4	4
cell adhesion	-0.048	0.16	-10000	0	-0.63	19	19
LYN	-0.006	0.093	-10000	0	-0.97	6	6
Ephrin B1/EPHB1-2/Src Family Kinases	-0.008	0.088	-10000	0	-0.92	6	6
Ephrin B1/EPHB1-2	-0.011	0.081	-10000	0	-0.85	6	6
SRC	-0.005	0.092	-10000	0	-0.96	6	6
ITGB3	-0.099	0.24	-10000	0	-0.6	125	125
EPHB1	-0.066	0.21	-10000	0	-0.62	84	84
EPHB4	0.011	0.052	-10000	0	-0.59	5	5
RAC1	0.015	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	-0.01	0.063	-10000	0	-0.39	17	17
alphaIIb/beta3 Integrin	-0.11	0.2	-10000	0	-0.46	160	160
BLK	-0.016	0.099	-10000	0	-1	6	6
HCK	-0.008	0.1	-10000	0	-1	6	6
regulation of stress fiber formation	0.086	0.16	0.67	14	-10000	0	14
MAPK8	0.021	0.083	-10000	0	-0.74	6	6
Ephrin B1/EPHB1-2/RGS3	-0.087	0.16	-10000	0	-0.67	17	17
endothelial cell migration	-0.009	0.084	-10000	0	-0.56	10	10
NCK2	0.015	0	-10000	0	-10000	0	0
PTPN13	0.004	0.076	-10000	0	-0.72	7	7
regulation of focal adhesion formation	0.086	0.16	0.67	14	-10000	0	14
chemotaxis	0.087	0.16	0.66	17	-10000	0	17
PIK3CA	0.015	0	-10000	0	-10000	0	0
Rac1/GTP	-0.082	0.14	-10000	0	-0.63	15	15
angiogenesis	-0.011	0.08	-10000	0	-0.84	6	6
LCK	-0.025	0.1	-10000	0	-0.98	6	6

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.014	0.023	-10000	0	-0.59	1	1
NFATC1	0.032	0.099	-10000	0	-0.45	1	1
NFATC2	0.015	0.075	-10000	0	-0.27	16	16
NFATC3	-0.005	0.11	-10000	0	-0.38	55	55
YWHAE	0.015	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	-0.069	0.18	-10000	0	-0.54	57	57
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.15	0.2	-10000	0	-0.49	124	124
BCL2/BAX	-0.002	0.03	-10000	0	-0.46	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.013	0.003	-10000	0	-10000	0	0
CaM/Ca2+	0.013	0.003	-10000	0	-10000	0	0
BAX	0.015	0	-10000	0	-10000	0	0
MAPK14	0.014	0.023	-10000	0	-0.59	1	1
BAD	0.015	0	-10000	0	-10000	0	0
CABIN1/MEF2D	-0.058	0.18	-10000	0	-0.52	57	57
Calcineurin A alpha-beta B1/BCL2	0.012	0.043	-10000	0	-0.62	3	3
FKBP8	0.015	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.057	0.18	0.5	57	-10000	0	57
KPNB1	0.015	0	-10000	0	-10000	0	0
KPNA2	0.014	0.023	-10000	0	-0.59	1	1
XPO1	0.015	0	-10000	0	-10000	0	0
SFN	-0.12	0.25	-10000	0	-0.6	141	141
MAP3K8	-0.005	0.11	-10000	0	-0.59	22	22
NFAT4/CK1 alpha	-0.021	0.069	-10000	0	-0.55	1	1
MEF2D/NFAT1/Cbp/p300	-0.024	0.073	-10000	0	-0.42	9	9
CABIN1	-0.07	0.19	-10000	0	-0.55	57	57
CALM1	0.015	0.003	-10000	0	-10000	0	0
RAN	0.015	0	-10000	0	-10000	0	0
MAP3K1	0.012	0.046	-10000	0	-0.59	4	4
CAMK4	-0.15	0.28	-10000	0	-0.61	176	176
mol:Ca2+	0.001	0.003	-10000	0	-10000	0	0
MAPK3	0.015	0	-10000	0	-10000	0	0
YWHAH	0.003	0.083	-10000	0	-0.59	13	13
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.03	0.11	-10000	0	-0.42	48	48
YWHAB	0.015	0	-10000	0	-10000	0	0
MAPK8	0.007	0.074	-10000	0	-0.62	9	9
MAPK9	0.015	0	-10000	0	-10000	0	0
YWHAG	0.012	0.04	-10000	0	-0.59	3	3
FKBP1A	0.014	0.023	-10000	0	-0.59	1	1
NFAT1-c-4/YWHAQ	-0.026	0.087	-10000	0	-0.4	5	5
PRKCH	0.015	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.002	0.035	-10000	0	-0.45	4	4
CASP3	0.013	0.033	-10000	0	-0.59	2	2
PIM1	0.009	0.061	-10000	0	-0.59	7	7
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.001	0.014	-10000	0	-0.37	1	1
apoptosis	-0.001	0.017	-10000	0	-0.4	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.014	0.073	-10000	0	-0.33	1	1
PRKCB	-0.072	0.22	-10000	0	-0.6	94	94
PRKCE	0.002	0.09	-10000	0	-0.59	15	15
JNK2/NFAT4	0.004	0.1	-10000	0	-0.38	42	42
BAD/BCL-XL	-0.001	0.016	-10000	0	-0.42	1	1
PRKCD	-0.008	0.12	-10000	0	-0.62	24	24
NUP214	0.015	0	-10000	0	-10000	0	0
PRKCZ	-0.037	0.17	-10000	0	-0.62	55	55
PRKCA	0.013	0.035	-10000	0	-0.62	2	2
PRKCG	-0.2	0.3	-10000	0	-0.6	230	230
PRKCQ	-0.022	0.15	-10000	0	-0.62	39	39
FKBP38/BCL2	-0.002	0.03	-10000	0	-0.46	3	3
EP300	0.013	0.043	-10000	0	-0.62	3	3
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.015	0	-10000	0	-10000	0	0
NFATc/JNK1	0.034	0.1	-10000	0	-0.42	1	1
CaM/Ca2+/FKBP38	0	0	-10000	0	-10000	0	0
FKBP12/FK506	-0.001	0.017	-10000	0	-0.43	1	1
CSNK1A1	0.024	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.099	0.17	-10000	0	-0.38	176	176
NFATc/ERK1	0.039	0.094	-10000	0	-0.42	1	1
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.14	0.19	-10000	0	-0.48	124	124
NR4A1	0.034	0.13	-10000	0	-0.52	28	28
GSK3B	0.015	0.003	-10000	0	-10000	0	0
positive T cell selection	-0.005	0.11	-10000	0	-0.38	55	55
NFAT1/CK1 alpha	-0.018	0.041	-10000	0	-0.3	2	2
RCH1/ KPNB1	-0.001	0.016	-10000	0	-0.42	1	1
YWHAQ	0.015	0	-10000	0	-10000	0	0
PRKACA	0.015	0.003	-10000	0	-10000	0	0
AKAP5	-0.028	0.16	-10000	0	-0.59	48	48
MEF2D	0.015	0.025	-10000	0	-0.62	1	1
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.015	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.038	0.096	-10000	0	-0.4	2	2
CREBBP	0.015	0.025	-10000	0	-0.62	1	1
BCL2	0.012	0.043	-10000	0	-0.62	3	3

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.03	0.094	-10000	0	-0.34	29	29
ER alpha/Gai/GDP/Gbeta gamma	0.015	0.12	-10000	0	-0.41	32	32
AKT1	0.022	0.11	-10000	0	-0.76	12	12
PIK3CA	0.015	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.019	0.11	-10000	0	-0.77	12	12
mol:Ca2+	-0.008	0.14	-10000	0	-0.49	29	29
IGF1R	0.005	0.081	-10000	0	-0.62	11	11
E2/ER alpha (dimer)/Striatin	-0.027	0.1	-10000	0	-0.39	46	46
SHC1	0.001	0.092	-10000	0	-0.59	16	16
apoptosis	-0.022	0.11	0.72	12	-10000	0	12
RhoA/GTP	-0.009	0.048	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.03	0.096	-10000	0	-0.43	26	26
regulation of stress fiber formation	-0.03	0.098	0.46	9	-10000	0	9
E2/ERA-ERB (dimer)	-0.033	0.11	-10000	0	-0.38	59	59
KRAS	0.014	0.023	-10000	0	-0.59	1	1
G13/GTP	-0.012	0.062	-10000	0	-0.34	23	23
pseudopodium formation	0.03	0.098	-10000	0	-0.46	9	9
E2/ER alpha (dimer)/PELP1	-0.014	0.072	-10000	0	-0.38	25	25
GRB2	0.014	0.023	-10000	0	-0.59	1	1
GNG2	0.009	0.06	-10000	0	-0.62	6	6
GNAO1	-0.012	0.13	-10000	0	-0.62	28	28
HRAS	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.023	0.11	-10000	0	-0.4	26	26
E2/ER beta (dimer)	-0.024	0.1	-10000	0	-0.44	37	37
mol:GDP	-0.025	0.083	-10000	0	-0.38	23	23
mol:NADP	0.023	0.11	-10000	0	-0.4	26	26
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
mol:IP3	-0.009	0.15	-10000	0	-0.51	29	29
IGF-1R heterotetramer	0.005	0.081	-10000	0	-0.62	11	11
PLCB1	-0.012	0.14	-10000	0	-0.49	26	26
PLCB2	0.004	0.12	-10000	0	-0.56	18	18
IGF1	-0.005	0.11	-10000	0	-0.61	22	22
mol:L-citrulline	0.023	0.11	-10000	0	-0.4	26	26
RHOA	0.015	0	-10000	0	-10000	0	0
Gai/GDP	-0.042	0.16	-10000	0	-0.77	28	28
JNK cascade	-0.024	0.1	-10000	0	-0.44	37	37
BCAR1	0.014	0.025	-10000	0	-0.62	1	1
ESR2	-0.019	0.14	-10000	0	-0.6	37	37
GNAQ	0.015	0	-10000	0	-10000	0	0
ESR1	-0.006	0.11	-10000	0	-0.61	23	23
Gq family/GDP/Gbeta gamma	0.016	0.11	-10000	0	-0.44	30	30
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.031	0.061	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.036	0.11	-10000	0	-0.47	32	32
GNAZ	0.012	0.043	-10000	0	-0.62	3	3
E2/ER alpha (dimer)	-0.015	0.082	-10000	0	-0.45	23	23
STRN	-0.008	0.12	-10000	0	-0.62	24	24
GNAL	-0.13	0.27	-10000	0	-0.62	149	149
PELP1	0.013	0.035	-10000	0	-0.62	2	2
MAPK11	-0.001	0.093	-10000	0	-0.37	40	40
GNAI2	0.015	0	-10000	0	-10000	0	0
GNAI3	0.015	0	-10000	0	-10000	0	0
GNAI1	-0.02	0.15	-10000	0	-0.62	37	37
HBEGF	-0.047	0.16	-10000	0	-0.52	36	36
cAMP biosynthetic process	-0.095	0.16	-10000	0	-0.34	185	185
SRC	0.023	0.12	-10000	0	-0.42	26	26
PI3K	-0.002	0.03	-10000	0	-0.46	3	3
GNB1	0.015	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.023	0.076	-10000	0	-0.37	14	14
SOS1	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.038	0.1	-10000	0	-0.45	25	25
Gs family/GTP	-0.097	0.17	-10000	0	-0.35	185	185
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0.012	-10000	0	-0.32	1	1
vasodilation	0.023	0.11	-10000	0	-0.38	26	26
mol:DAG	-0.009	0.15	-10000	0	-0.51	29	29
Gs family/GDP/Gbeta gamma	-0.075	0.13	-10000	0	-0.42	38	38
MSN	0.03	0.1	-10000	0	-0.51	9	9
Gq family/GTP	-0.034	0.098	-10000	0	-0.45	21	21
mol:PI-3-4-5-P3	0.02	0.11	-10000	0	-0.74	12	12
NRAS	0.015	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.023	0.11	0.38	26	-10000	0	26
GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
RhoA/GDP	-0.023	0.077	-10000	0	-0.39	13	13
NOS3	0.022	0.12	-10000	0	-0.42	26	26
GNA11	0.006	0.078	-10000	0	-0.62	10	10
MAPKKK cascade	0.027	0.12	-10000	0	-0.52	16	16
E2/ER alpha (dimer)/PELP1/Src	-0.032	0.099	-10000	0	-0.45	26	26
ruffle organization	0.03	0.098	-10000	0	-0.46	9	9
ROCK2	0.04	0.076	-10000	0	-0.55	2	2
GNA14	-0.009	0.12	-10000	0	-0.61	26	26
GNA15	-0.009	0.12	-10000	0	-0.61	26	26
GNA13	0.015	0	-10000	0	-10000	0	0
MMP9	-0.099	0.2	-10000	0	-0.53	62	62
MMP2	0.011	0.14	-10000	0	-0.51	22	22

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.012	0.13	-9999	-0.62	28	28
CDC42/GTP	-0.026	0.086	-9999	-0.5	12	12
PLCG1	0.018	0.1	-9999	-0.51	12	12
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0	-9999	-10000	0	0
G12/G13	-0.001	0.018	-9999	-0.46	1	1
cell migration	-0.025	0.084	-9999	-0.48	12	12
S1PR5	-0.1	0.24	-9999	-0.61	128	128
S1PR4	0	0.096	-9999	-0.6	17	17
MAPK3	0.018	0.1	-9999	-0.51	12	12
MAPK1	0.018	0.1	-9999	-0.51	12	12
S1P/S1P5/Gi	-0.035	0.14	-9999	-0.31	94	94
GNAI1	-0.02	0.15	-9999	-0.62	37	37
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.073	0.15	-9999	-0.38	128	128
RHOA	0.029	0.054	-9999	-0.32	5	5
S1P/S1P4/Gi	0.008	0.11	-9999	-0.37	32	32
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.012	0.043	-9999	-0.62	3	3
S1P/S1P4/G12/G13	-0.009	0.053	-9999	-0.33	18	18
GNA12	0.014	0.025	-9999	-0.62	1	1
GNA13	0.015	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.003	0.12	-9999	-0.36	64	64
SNTA1	-0.015	0.13	-9999	-0.61	32	32
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	-0.004	0.12	-9999	-0.37	66	66
MAPK12	0.034	0.029	-9999	-0.34	3	3
CCND1	0.017	0.056	-9999	-0.42	8	8
p38 gamma/SNTA1	0.023	0.079	-9999	-0.32	26	26
MAP2K3	0.013	0.033	-9999	-0.59	2	2
PKN1	0.015	0	-9999	-10000	0	0
G2/M transition checkpoint	0.034	0.029	-9999	-0.34	3	3
MAP2K6	0.028	0.022	-9999	-0.34	2	2
MAPT	-0.005	0.13	-9999	-0.44	38	38
MAPK13	-0.017	0.14	-9999	-0.44	64	64
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.02	0.018	-9999	-0.31	2	2

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.055	0.14	-10000	0	-0.39	95	95
cell-cell adhesion	0.047	0.12	0.57	16	-10000	0	16
Ephrin B/EPHB2/RasGAP	-0.02	0.08	-10000	0	-0.64	3	3
ITSN1	0.015	0	-10000	0	-10000	0	0
PIK3CA	0.015	0	-10000	0	-10000	0	0
SHC1	0.001	0.092	-10000	0	-0.59	16	16
Ephrin B1/EPHB3	-0.004	0.04	-10000	0	-0.37	8	8
Ephrin B1/EPHB1	-0.051	0.13	-10000	0	-0.4	86	86
HRAS/GDP	-0.045	0.11	-10000	0	-0.54	16	16
Ephrin B/EPHB1/GRB7	-0.078	0.16	-10000	0	-0.65	24	24
Endophilin/SYNJ1	0.023	0.086	-10000	0	-0.59	3	3
KRAS	0.014	0.023	-10000	0	-0.59	1	1
Ephrin B/EPHB1/Src	-0.056	0.14	-10000	0	-0.63	15	15
endothelial cell migration	-0.009	0.057	-10000	0	-0.39	8	8
GRB2	0.014	0.023	-10000	0	-0.59	1	1
GRB7	-0.038	0.16	-10000	0	-0.59	54	54
PAK1	0.007	0.14	-10000	0	-0.57	21	21
HRAS	0.015	0	-10000	0	-10000	0	0
RRAS	0.02	0.096	-10000	0	-0.6	5	5
DNM1	-0.083	0.22	-10000	0	-0.6	107	107
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.014	0.14	-10000	0	-0.6	14	14
lamellipodium assembly	-0.047	0.12	-10000	0	-0.57	16	16
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.007	0.14	-10000	0	-0.53	23	23
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
EPHB2	0.007	0.071	-10000	0	-0.6	9	9
EPHB3	0.011	0.048	-10000	0	-0.61	4	4
EPHB1	-0.065	0.21	-10000	0	-0.62	84	84
EPHB4	0.011	0.052	-10000	0	-0.59	5	5
mol:GDP	-0.042	0.11	-10000	0	-0.48	20	20
Ephrin B/EPHB2	-0.02	0.082	-10000	0	-0.37	19	19
Ephrin B/EPHB3	-0.018	0.08	-10000	0	-0.63	4	4
JNK cascade	-0.004	0.13	-10000	0	-0.68	5	5
Ephrin B/EPHB1	-0.056	0.14	-10000	0	-0.36	95	95
RAP1/GDP	-0.038	0.095	-10000	0	-0.45	17	17
EFNB2	0.003	0.085	-10000	0	-0.6	13	13
EFNB3	-0.002	0.1	-10000	0	-0.61	18	18
EFNB1	0.012	0.046	-10000	0	-0.59	4	4
Ephrin B2/EPHB1-2	-0.054	0.14	-10000	0	-0.38	97	97
RAP1B	0.009	0.061	-10000	0	-0.59	7	7
RAP1A	0.015	0	-10000	0	-10000	0	0
CDC42/GTP	-0.047	0.12	-10000	0	-0.57	15	15
Rap1/GTP	-0.047	0.11	-10000	0	-0.53	18	18
axon guidance	-0.055	0.14	-10000	0	-0.39	95	95
MAPK3	0.012	0.12	-10000	0	-0.48	21	21
MAPK1	0.012	0.12	-10000	0	-0.48	21	21
Rac1/GDP	0.013	0.12	-10000	0	-0.48	15	15
actin cytoskeleton reorganization	-0.035	0.087	-10000	0	-0.43	16	16
CDC42/GDP	0.013	0.12	-10000	0	-0.48	15	15
PI3K	-0.009	0.058	-10000	0	-0.39	8	8
EFNA5	-0.068	0.21	-10000	0	-0.61	89	89
Ephrin B2/EPHB4	-0.01	0.062	-10000	0	-0.39	17	17
Ephrin B/EPHB2/Intersectin/N-WASP	0.028	0.069	-10000	0	-0.53	3	3
CDC42	0.015	0	-10000	0	-10000	0	0
RAS family/GTP	-0.044	0.11	-10000	0	-0.52	15	15
PTK2	0.013	0.032	-10000	0	-10000	0	0
MAP4K4	-0.004	0.13	-10000	0	-0.69	5	5
SRC	0.013	0.035	-10000	0	-0.62	2	2
KALRN	-0.001	0.097	-10000	0	-0.59	18	18
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	0.02	0.14	-10000	0	-0.47	11	11
MAP2K1	0.003	0.13	-10000	0	-0.51	21	21
WASL	0.015	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.049	0.12	-10000	0	-0.35	92	92
cell migration	0.005	0.14	-10000	0	-0.53	21	21
NRAS	0.015	0	-10000	0	-10000	0	0
SYNJ1	0.023	0.088	-10000	0	-0.6	3	3
PXN	0.015	0	-10000	0	-10000	0	0
TF	-0.015	0.15	-10000	0	-0.62	12	12
HRAS/GTP	-0.049	0.12	-10000	0	-0.57	15	15
Ephrin B1/EPHB1-2	-0.05	0.13	-10000	0	-0.36	92	92
cell adhesion mediated by integrin	0.008	0.078	0.34	27	-10000	0	27
RAC1	0.015	0	-10000	0	-10000	0	0
mol:GTP	-0.053	0.13	-10000	0	-0.62	15	15
RAC1-CDC42/GTP	-0.046	0.12	-10000	0	-0.55	17	17
RASA1	0.015	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.035	0.091	-10000	0	-0.46	14	14
ruffle organization	0.016	0.14	-10000	0	-0.58	16	16
NCK1	0.015	0	-10000	0	-10000	0	0
receptor internalization	-0.018	0.14	-10000	0	-0.7	7	7
Ephrin B/EPHB2/KALRN	-0.027	0.092	-10000	0	-0.62	4	4
ROCK1	0.026	0.039	-10000	0	-0.32	8	8
RAS family/GDP	-0.032	0.081	-10000	0	-0.48	8	8
Rac1/GTP	-0.05	0.12	-10000	0	-0.61	16	16
Ephrin B/EPHB1/Src/Paxillin	-0.007	0.13	-10000	0	-0.52	15	15

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.052	-9999	-0.59	5	5
alphaV beta3 Integrin	-0.081	0.17	-9999	-0.43	126	126
PTK2	-0.05	0.13	-9999	-0.54	32	32
positive regulation of JNK cascade	-0.014	0.061	-9999	-0.33	22	22
CDC42/GDP	0.038	0.1	-9999	-0.45	22	22
Rac1/GDP	0.04	0.1	-9999	-0.45	22	22
RAP1B	0.009	0.061	-9999	-0.59	7	7
RAP1A	0.015	0	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
CDC42/GTP	-0.018	0.075	-9999	-0.41	22	22
nectin-3/I-afadin	-0.015	0.081	-9999	-0.45	22	22
RAPGEF1	0.029	0.11	-9999	-0.52	22	22
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.021	0.12	-9999	-0.58	22	22
PDGFB-D/PDGFRB	0.011	0.052	-9999	-0.59	5	5
TLN1	0.029	0.057	-9999	-0.4	6	6
Rap1/GTP	-0.017	0.072	-9999	-0.37	22	22
IQGAP1	0.009	0.064	-9999	-0.61	7	7
Rap1/GTP/I-afadin	-0.004	0.035	-9999	-0.32	8	8
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.015	0.081	-9999	-0.45	22	22
PVR	0.015	0	-9999	-10000	0	0
Necl-5(dimer)	0.015	0	-9999	-10000	0	0
mol:GDP	0.033	0.12	-9999	-0.57	22	22
MLLT4	0.014	0.025	-9999	-0.62	1	1
PIK3CA	0.015	0	-9999	-10000	0	0
PI3K	-0.014	0.072	-9999	-0.76	2	2
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	-0.018	0.089	-9999	-0.46	27	27
positive regulation of lamellipodium assembly	-0.016	0.067	-9999	-0.35	23	23
PVRL1	-0.01	0.12	-9999	-0.62	26	26
PVRL3	-0.005	0.11	-9999	-0.62	21	21
PVRL2	0.014	0.025	-9999	-0.62	1	1
PIK3R1	0.012	0.043	-9999	-0.62	3	3
CDH1	-0.11	0.25	-9999	-0.61	136	136
CLDN1	-0.022	0.15	-9999	-0.6	40	40
JAM-A/CLDN1	-0.035	0.1	-9999	-0.36	35	35
SRC	-0.033	0.12	-9999	-0.66	22	22
ITGB3	-0.099	0.24	-9999	-0.6	125	125
nectin-1(dimer)/I-afadin/I-afadin	-0.018	0.089	-9999	-0.46	27	27
FARP2	0.026	0.12	-9999	-0.55	22	22
RAC1	0.015	0	-9999	-10000	0	0
CTNNA1	0.015	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.012	0.067	-9999	-0.38	22	22
nectin-1/I-afadin	-0.018	0.089	-9999	-0.46	27	27
nectin-2/I-afadin	-0.001	0.025	-9999	-0.46	2	2
RAC1/GTP/IQGAP1/filamentous actin	-0.004	0.038	-9999	-0.38	7	7
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.027	0.1	-9999	-0.39	47	47
CDC42/GTP/IQGAP1/filamentous actin	-0.004	0.038	-9999	-0.38	7	7
F11R	0.006	0.074	-9999	-0.59	10	10
positive regulation of filopodium formation	-0.014	0.061	-9999	-0.33	22	22
alphaV/beta3 Integrin/Talin	-0.014	0.14	-9999	-0.48	17	17
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.025	-9999	-0.46	2	2
nectin-2(dimer)/I-afadin/I-afadin	-0.001	0.025	-9999	-0.46	2	2
PIP5K1C	0.021	0.061	-9999	-0.44	6	6
VAV2	0.024	0.13	-9999	-0.58	23	23
RAP1/GDP	-0.02	0.083	-9999	-0.43	22	22
ITGAV	0.014	0.025	-9999	-0.62	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.013	0.069	-9999	-0.38	23	23
nectin-3(dimer)/I-afadin/I-afadin	-0.015	0.081	-9999	-0.45	22	22
Rac1/GTP	-0.019	0.082	-9999	-0.43	23	23
PTPRM	0.012	0.064	-9999	-0.28	25	25
E-cadherin/beta catenin/alpha catenin	-0.069	0.14	-9999	-0.61	12	12
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.015	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.003	0.088	-9999	-0.62	13	13
Caspase 8 (4 units)	-0.026	0.076	-9999	-0.4	13	13
NEF	-0.002	0.031	-9999	-10000	0	0
NFKBIA	0.005	0.042	-9999	-0.58	1	1
BIRC3	-0.022	0.2	-9999	-0.57	81	81
CYCS	0.026	0.089	-9999	-0.4	8	8
RIPK1	0.015	0	-9999	-10000	0	0
CD247	-0.023	0.16	-9999	-0.66	37	37
MAP2K7	0.02	0.081	-9999	-0.39	5	5
protein ubiquitination	0.027	0.091	-9999	-0.41	5	5
CRADD	0.015	0	-9999	-10000	0	0
DAXX	0.015	0	-9999	-10000	0	0
FAS	-0.019	0.14	-9999	-0.6	37	37
BID	0.018	0.093	-9999	-0.41	10	10
NF-kappa-B/RelA/I kappa B alpha	-0.032	0.087	-9999	-10000	0	0
TRADD	0.014	0.025	-9999	-0.62	1	1
MAP3K5	0.005	0.081	-9999	-0.62	11	11
CFLAR	0.015	0	-9999	-10000	0	0
FADD	0.015	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.033	0.088	-9999	-10000	0	0
MAPK8	0.024	0.084	-9999	-0.44	2	2
APAF1	0.015	0	-9999	-10000	0	0
TRAF1	0.003	0.086	-9999	-0.61	13	13
TRAF2	0.015	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.009	0.096	-9999	-0.41	12	12
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.009	0.11	-9999	-0.54	6	6
CHUK	0.027	0.096	-9999	-0.46	5	5
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	-0.027	0.091	-9999	-0.59	4	4
TCRz/NEF	-0.038	0.13	-9999	-0.54	37	37
TNF	-0.13	0.26	-9999	-0.6	152	152
FASLG	-0.022	0.17	-9999	-0.6	46	46
NFKB1	0.006	0.035	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.098	0.17	-9999	-0.38	171	171
CASP6	-0.02	0.069	-9999	-0.52	5	5
CASP7	0.023	0.18	-9999	-0.53	38	38
RELA	0.006	0.035	-9999	-10000	0	0
CASP2	0.015	0	-9999	-10000	0	0
CASP3	0.024	0.18	-9999	-0.53	39	39
TNFRSF1A	0.002	0.09	-9999	-0.61	14	14
TNFR1A/BAG4	-0.018	0.091	-9999	-0.46	26	26
CASP8	0.004	0.08	-9999	-0.59	12	12
CASP9	0.014	0.023	-9999	-0.59	1	1
MAP3K14	0.018	0.1	-9999	-0.52	5	5
APAF-1/Caspase 9	-0.053	0.13	-9999	-0.43	43	43
BCL2	0.031	0.082	-9999	-0.4	2	2

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.024	0.037	-9999	-0.46	4	4
SMARCC1	0.009	0.014	-9999	-10000	0	0
REL	-0.009	0.12	-9999	-0.61	27	27
HDAC7	0.039	0.094	-9999	-0.37	2	2
JUN	0.007	0.067	-9999	-0.6	8	8
EP300	0.012	0.043	-9999	-0.62	3	3
KAT2B	0.012	0.042	-9999	-0.61	3	3
KAT5	0.015	0	-9999	-10000	0	0
MAPK14	0.025	0.028	-9999	-0.43	2	2
FOXO1	0.014	0.025	-9999	-0.62	1	1
T-DHT/AR	0.035	0.1	-9999	-0.4	6	6
MAP2K6	0.014	0.025	-9999	-0.62	1	1
BRM/BAF57	-0.003	0.035	-9999	-0.46	4	4
MAP2K4	0.015	0.006	-9999	-10000	0	0
SMARCA2	0.011	0.049	-9999	-0.62	4	4
PDE9A	-0.032	0.13	-9999	-0.8	13	13
NCOA2	-0.02	0.14	-9999	-0.62	36	36
CEBPA	-0.009	0.12	-9999	-0.62	26	26
EHMT2	0.012	0.035	-9999	-0.62	2	2
cell proliferation	0.049	0.12	-9999	-0.49	7	7
NR0B1	-0.15	0.27	-9999	-0.61	173	173
EGR1	-0.084	0.23	-9999	-0.61	105	105
RXRs/9cRA	-0.058	0.13	-9999	-0.34	112	112
AR/RACK1/Src	-0.003	0.069	-9999	-0.38	8	8
AR/GR	0.002	0.11	-9999	-0.38	16	16
GNB2L1	0.015	0.001	-9999	-10000	0	0
PKN1	0.015	0	-9999	-10000	0	0
RCHY1	0.015	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.02	0.057	-9999	-0.45	9	9
T-DHT/AR/TIF2/CARM1	-0.016	0.11	-9999	-0.56	16	16
SRC	0.039	0.056	-9999	-0.32	1	1
NR3C1	0.015	0	-9999	-10000	0	0
KLK3	-0.053	0.15	-9999	-0.54	22	22
APPBP2	0.015	0.007	-9999	-10000	0	0
TRIM24	0.014	0.024	-9999	-0.59	1	1
T-DHT/AR/TIP60	0.028	0.073	-9999	-0.42	7	7
TMPRSS2	-0.13	0.32	-9999	-1	61	61
RXRG	-0.091	0.24	-9999	-0.62	111	111
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.014	0.025	-9999	-0.62	1	1
RXRB	0.015	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.008	0.065	-9999	-0.62	7	7
KLK2	0.009	0.14	-9999	-0.49	28	28
AR	-0.005	0.12	-9999	-0.29	82	82
SENP1	0.015	0.001	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
MDM2	0.004	0.084	-9999	-0.59	13	13
SRY	-0.052	0.18	-9999	-0.59	64	64
GATA2	-0.003	0.11	-9999	-0.61	20	20
MYST2	0.015	0.001	-9999	-10000	0	0
HOXB13	-0.12	0.25	-9999	-0.6	145	145
T-DHT/AR/RACK1/Src	0.034	0.076	-9999	-0.4	7	7
positive regulation of transcription	-0.003	0.11	-9999	-0.61	20	20
DNAJA1	0.015	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.03	0.036	-9999	-10000	0	0
NCOA1	0.018	0.005	-9999	-10000	0	0
SPDEF	-0.039	0.17	-9999	-0.61	57	57
T-DHT/AR/TIF2	0.032	0.097	-9999	-0.51	12	12
T-DHT/AR/Hsp90	0.028	0.073	-9999	-0.42	7	7
GSK3B	0.015	0.004	-9999	-10000	0	0
NR2C1	0.015	0.001	-9999	-10000	0	0
mol:T-DHT	0.034	0.055	-9999	-0.34	10	10
SIRT1	0.015	0	-9999	-10000	0	0
ZMIZ2	0.016	0.005	-9999	-10000	0	0
POU2F1	0.019	0.076	-9999	-0.62	9	9
T-DHT/AR/DAX-1	-0.062	0.17	-9999	-0.41	57	57
CREBBP	0.014	0.025	-9999	-0.62	1	1
SMARCE1	0.014	0.004	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	-0.039	0.1	-10000	0	-0.37	41	41
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.014	0.023	-10000	0	-0.59	1	1
AKT2	0.015	0	-10000	0	-10000	0	0
STXBP4	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.017	0.15	0.27	69	-0.41	38	107
YWHAZ	0.015	0	-10000	0	-10000	0	0
CALM1	0.015	0	-10000	0	-10000	0	0
YWHAQ	0.015	0	-10000	0	-10000	0	0
TBC1D4	0.027	0.017	-10000	0	-0.42	1	1
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.003	0.083	-10000	0	-0.59	13	13
YWHAB	0.015	0	-10000	0	-10000	0	0
SNARE/Synip	-0.001	0.014	-10000	0	-0.35	1	1
YWHAG	0.012	0.04	-10000	0	-0.59	3	3
ASIP	-0.083	0.23	-10000	0	-0.62	104	104
PRKCI	0.015	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.015	0	-10000	0	-10000	0	0
GYS1	0.038	0.009	-10000	0	-10000	0	0
PRKCZ	-0.037	0.17	-10000	0	-0.62	55	55
TRIP10	0.009	0.065	-10000	0	-0.62	7	7
TC10/GTP/CIP4/Exocyst	-0.004	0.039	-10000	0	-0.39	7	7
AS160/14-3-3	0.012	0.084	-10000	0	-0.34	1	1
VAMP2	0.014	0.023	-10000	0	-0.59	1	1
SLC2A4	0.014	0.16	0.28	64	-0.46	38	102
STX4	0.015	0	-10000	0	-10000	0	0
GSK3B	0.031	0.01	-10000	0	-10000	0	0
SFN	-0.12	0.25	-10000	0	-0.6	141	141
LNPEP	0.002	0.092	-10000	0	-0.62	14	14
YWHAE	0.015	0	-10000	0	-10000	0	0

×

TRAIL signaling pathway

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
TNFSF10	-0.011	0.12	-10000	0	-0.6	28	28
positive regulation of NF-kappaB transcription factor activity	-0.027	0.11	-10000	0	-0.44	41	41
MAP2K4	0.038	0.06	-10000	0	-0.38	1	1
IKBKB	0.015	0	-10000	0	-10000	0	0
TNFRSF10B	0.012	0.043	-10000	0	-0.62	3	3
TNFRSF10A	-0.024	0.15	-10000	0	-0.61	42	42
SMPD1	0.014	0.048	-10000	0	-0.24	14	14
IKBKG	0.015	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.002	0.087	-10000	0	-0.59	14	14
TRAIL/TRAILR2	-0.02	0.094	-10000	0	-0.45	30	30
TRAIL/TRAILR3	-0.045	0.15	-10000	0	-0.48	63	63
TRAIL/TRAILR1	-0.046	0.14	-10000	0	-0.46	66	66
TRAIL/TRAILR4	-0.027	0.11	-10000	0	-0.44	41	41
TRAIL/TRAILR1/DAP3/GTP	-0.035	0.11	-10000	0	-0.36	66	66
IKK complex	-0.01	0.031	-10000	0	-10000	0	0
RIPK1	0.015	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0	0	-10000	0	-10000	0	0
MAPK3	0.008	0.093	-10000	0	-0.44	28	28
MAP3K1	0.03	0.063	-10000	0	-0.34	2	2
TRAILR4 (trimer)	0.002	0.087	-10000	0	-0.59	14	14
TRADD	0.014	0.025	-10000	0	-0.62	1	1
TRAILR1 (trimer)	-0.024	0.15	-10000	0	-0.61	42	42
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.018	0.083	-10000	0	-0.35	4	4
CFLAR	0.015	0	-10000	0	-10000	0	0
MAPK1	0.008	0.093	-10000	0	-0.44	28	28
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.032	0.098	-10000	0	-0.59	4	4
mol:ceramide	0.014	0.047	-10000	0	-0.24	14	14
FADD	0.015	0	-10000	0	-10000	0	0
MAPK8	0.041	0.072	-10000	0	-0.4	5	5
TRAF2	0.015	0	-10000	0	-10000	0	0
TRAILR3 (trimer)	-0.024	0.15	-10000	0	-0.6	43	43
CHUK	0.015	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD	-0.038	0.12	-10000	0	-0.39	66	66
DAP3	0.015	0	-10000	0	-10000	0	0
CASP10	-0.021	0.085	0.24	7	-0.4	15	22
JNK cascade	-0.027	0.11	-10000	0	-0.44	41	41
TRAIL (trimer)	-0.011	0.12	-10000	0	-0.6	28	28
TNFRSF10C	-0.024	0.15	-10000	0	-0.6	43	43
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.032	0.1	-10000	0	-0.35	41	41
TRAIL/TRAILR2/FADD	-0.017	0.079	-10000	0	-0.38	30	30
cell death	0.014	0.047	-10000	0	-0.24	14	14
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.033	0.057	-10000	0	-0.54	1	1
TRAILR2 (trimer)	0.012	0.043	-10000	0	-0.62	3	3
CASP8	-0.001	0.048	-10000	0	-0.82	1	1
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.014	0.066	-10000	0	-0.64	1	1

×

HIF-2-alpha transcription factor network

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
MMP14	-0.07	0.25	-10000	0	-1.1	31	31
oxygen homeostasis	0.004	0.022	-10000	0	-10000	0	0
TCEB2	0.015	0	-10000	0	-10000	0	0
TCEB1	0.015	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.013	0.055	-10000	0	-0.41	1	1
EPO	0.035	0.3	-10000	0	-0.75	41	41
FIH (dimer)	0.02	0.019	-10000	0	-10000	0	0
APEX1	0.017	0.021	-10000	0	-10000	0	0
SERPINE1	-0.077	0.4	-10000	0	-0.79	83	83
FLT1	0	0.073	-10000	0	-0.72	5	5
ADORA2A	0.034	0.3	-10000	0	-0.73	36	36
germ cell development	0.024	0.3	-10000	0	-0.71	42	42
SLC11A2	0.036	0.3	-10000	0	-0.73	36	36
BHLHE40	0.029	0.31	-10000	0	-0.76	41	41
HIF1AN	0.02	0.019	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.046	0.1	-10000	0	-0.39	16	16
ETS1	0.027	0.066	-10000	0	-0.61	7	7
CITED2	0.002	0.023	-10000	0	-10000	0	0
KDR	-0.002	0.089	-10000	0	-0.73	8	8
PGK1	0.033	0.31	-10000	0	-0.78	37	37
SIRT1	0.015	0.001	-10000	0	-10000	0	0
response to hypoxia	0	0.002	-10000	0	-10000	0	0
HIF2A/ARNT	0.032	0.34	-10000	0	-0.9	36	36
EPAS1	0.049	0.13	-10000	0	-0.37	5	5
SP1	0.02	0.018	-10000	0	-10000	0	0
ABCG2	0.032	0.31	-10000	0	-0.79	36	36
EFNA1	0.034	0.3	-10000	0	-0.74	37	37
FXN	0.035	0.3	-10000	0	-0.73	35	35
POU5F1	0.022	0.32	-10000	0	-0.74	42	42
neuron apoptosis	-0.032	0.33	0.86	36	-10000	0	36
EP300	0.012	0.043	-10000	0	-0.62	3	3
EGLN3	0.007	0.091	-10000	0	-0.62	13	13
EGLN2	0.02	0.02	-10000	0	-10000	0	0
EGLN1	0.02	0.019	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	0	0	-10000	0	-10000	0	0
VHL	0.015	0	-10000	0	-10000	0	0
ARNT	0.017	0.021	-10000	0	-10000	0	0
SLC2A1	0.034	0.3	-10000	0	-0.74	36	36
TWIST1	-0.012	0.36	-10000	0	-0.82	65	65
ELK1	0.025	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.043	0.1	-10000	0	-0.47	6	6
VEGFA	-0.009	0.37	-10000	0	-0.82	71	71
CREBBP	0.014	0.025	-10000	0	-0.62	1	1

×

Paxillin-dependent events mediated by a4b1

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
CRKL	0.014	0.023	-10000	0	-0.59	1	1
Rac1/GDP	0.008	0.02	-10000	0	-10000	0	0
DOCK1	0.014	0.025	-10000	0	-0.62	1	1
ITGA4	-0.07	0.21	-10000	0	-0.6	92	92
RAC1	0.015	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.089	0.18	-10000	0	-0.46	131	131
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.015	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.052	0.13	-10000	0	-0.38	92	92
alpha4/beta7 Integrin/Paxillin	-0.066	0.14	-10000	0	-0.36	69	69
lamellipodium assembly	0.006	0.041	-10000	0	-0.41	4	4
PIK3CA	0.015	0	-10000	0	-10000	0	0
PI3K	-0.002	0.03	-10000	0	-0.46	3	3
ARF6	0.015	0	-10000	0	-10000	0	0
TLN1	0.015	0	-10000	0	-10000	0	0
PXN	0.027	0	-10000	0	-10000	0	0
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
ARF6/GTP	-0.038	0.096	-10000	0	-0.54	3	3
cell adhesion	-0.042	0.11	-10000	0	-0.58	3	3
CRKL/CBL	-0.001	0.024	-10000	0	-0.44	2	2
alpha4/beta1 Integrin/Paxillin	-0.046	0.12	-10000	0	-0.36	43	43
ITGB1	0.012	0.04	-10000	0	-0.59	3	3
ITGB7	-0.027	0.16	-10000	0	-0.61	45	45
ARF6/GDP	0.008	0.02	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.1	0.16	-10000	0	-0.64	15	15
p130Cas/Crk/Dock1	-0.001	0.021	-10000	0	-0.38	2	2
VCAM1	-0.11	0.26	-10000	0	-0.62	137	137
alpha4/beta1 Integrin/Paxillin/Talin	-0.042	0.11	-10000	0	-0.59	3	3
alpha4/beta1 Integrin/Paxillin/GIT1	-0.042	0.11	-10000	0	-0.59	3	3
BCAR1	0.014	0.025	-10000	0	-0.62	1	1
mol:GDP	0.042	0.11	0.58	3	-10000	0	3
CBL	0.014	0.025	-10000	0	-0.62	1	1
PRKACA	0.015	0	-10000	0	-10000	0	0
GIT1	0.014	0.025	-10000	0	-0.62	1	1
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.042	0.11	-10000	0	-0.59	3	3
Rac1/GTP	0.006	0.045	-10000	0	-0.45	4	4

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.11	0.38	-9999	-1.2	71	71
RAD9A	0.015	0	-9999	-10000	0	0
AP1	-0.056	0.17	-9999	-0.46	97	97
IFNAR2	0.014	0.007	-9999	-10000	0	0
AKT1	0.006	0.047	-9999	-0.28	2	2
ER alpha/Oestrogen	-0.009	0.084	-9999	-0.45	23	23
NFX1/SIN3/HDAC complex	0.047	0.031	-9999	-10000	0	0
EGF	-0.039	0.18	-9999	-0.61	57	57
SMG5	0.015	0	-9999	-10000	0	0
SMG6	0.014	0.025	-9999	-0.62	1	1
SP3/HDAC2	0.019	0.013	-9999	-10000	0	0
TERT/c-Abl	-0.13	0.34	-9999	-1.1	72	72
SAP18	0.014	0.005	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.067	0.2	-9999	-0.59	83	83
WRN	0.013	0.035	-9999	-0.62	2	2
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.015	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.12	0.29	-9999	-0.93	69	69
Mad/Max	0.013	0.013	-9999	-10000	0	0
TERT	-0.12	0.4	-9999	-1.2	71	71
CCND1	-0.096	0.34	-9999	-1	74	74
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.014	0.005	-9999	-10000	0	0
RBBP4	0.014	0.005	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.015	0	-9999	-10000	0	0
SIN3A	0.014	0.005	-9999	-10000	0	0
Telomerase/911	0.039	0.039	-9999	-10000	0	0
CDKN1B	0.013	0.09	-9999	-0.66	2	2
RAD1	0.015	0	-9999	-10000	0	0
XRCC5	0.015	0	-9999	-10000	0	0
XRCC6	0.015	0	-9999	-10000	0	0
SAP30	0.013	0.025	-9999	-0.62	1	1
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.007	0.067	-9999	-0.6	8	8
E6	-0.001	0.005	-9999	-10000	0	0
HPV-16 E6/E6AP	0.011	0.007	-9999	-10000	0	0
FOS	-0.075	0.22	-9999	-0.61	95	95
IFN-gamma/IRF1	-0.023	0.099	-9999	-0.43	36	36
PARP2	0.015	0	-9999	-10000	0	0
BLM	-0.026	0.16	-9999	-0.62	44	44
Telomerase	-0.037	0.12	-9999	-0.42	43	43
IRF1	-0.009	0.12	-9999	-0.57	31	31
ESR1	-0.007	0.11	-9999	-0.61	23	23
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.052	0.033	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.052	0.033	-9999	-10000	0	0
HDAC1	0.01	0.049	-9999	-0.62	4	4
HDAC2	0.014	0.009	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.021	0.058	-9999	-0.45	10	10
ABL1	0.014	0.025	-9999	-0.62	1	1
MXD1	0.014	0.006	-9999	-10000	0	0
MRE11A	0.015	0	-9999	-10000	0	0
HUS1	0.014	0.023	-9999	-0.59	1	1
RPS6KB1	0.015	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.12	0.32	-9999	-1	69	69
NR2F2	-0.001	0.1	-9999	-0.6	20	20
MAPK3	0.014	0.007	-9999	-10000	0	0
MAPK1	0.014	0.007	-9999	-10000	0	0
TGFB1/TGF beta receptor Type II	0.006	0.077	-9999	-0.62	10	10
NFKB1	0.015	0	-9999	-10000	0	0
HNRNPC	0.015	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.015	0	-9999	-10000	0	0
EGFR	-0.11	0.25	-9999	-0.6	138	138
mol:Oestrogen	-0.001	0.003	-9999	-10000	0	0
EGF/EGFR	-0.13	0.21	-9999	-0.46	183	183
MYC	-0.006	0.11	-9999	-0.62	21	21
IL2	-0.002	0.014	-9999	-10000	0	0
KU	0	0	-9999	-10000	0	0
RAD50	0.015	0	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
TGFB1	0.006	0.077	-9999	-0.62	10	10
TRF2/BLM	-0.027	0.1	-9999	-0.42	44	44
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.11	0.34	-9999	-1.1	71	71
SP1/HDAC2	0.022	0.017	-9999	-10000	0	0
PINX1	0.015	0	-9999	-10000	0	0
Telomerase/EST1A	-0.12	0.29	-9999	-0.92	70	70
Smad3/Myc	0.014	0.088	-9999	-0.39	30	30
911 complex	-0.001	0.014	-9999	-0.35	1	1
IFNG	0.003	0.061	-9999	-0.58	7	7
Telomerase/PinX1	-0.12	0.29	-9999	-0.93	69	69
Telomerase/AKT1/mTOR/p70S6K	0.017	0.073	-9999	-10000	0	0
SIN3B	0.013	0.025	-9999	-0.63	1	1
YWHAE	0.015	0	-9999	-10000	0	0
Telomerase/EST1B	-0.12	0.29	-9999	-0.92	70	70
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	-0.001	0.023	-9999	-0.42	2	2
Telomerase/hnRNP C1/C2	-0.12	0.29	-9999	-0.92	70	70
E2F1	-0.012	0.12	-9999	-0.6	29	29
ZNFX1	0.014	0.005	-9999	-10000	0	0
PIF1	-0.05	0.19	-9999	-0.61	70	70
NCL	0.015	0	-9999	-10000	0	0
DKC1	0.015	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.09	0.23	-9999	-0.61	112	112
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.015	0	-9999	-10000	0	0
TCEB1	0.015	0	-9999	-10000	0	0
HIF1A/p53	0.026	0.052	-9999	-0.29	13	13
HIF1A	0.024	0.028	-9999	-0.25	1	1
COPS5	0.015	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.015	-9999	-10000	0	0
FIH (dimer)	0.015	0	-9999	-10000	0	0
CDKN2A	-0.16	0.28	-9999	-0.61	186	186
ARNT/IPAS	-0.074	0.16	-9999	-0.44	112	112
HIF1AN	0.015	0	-9999	-10000	0	0
GNB2L1	0.015	0	-9999	-10000	0	0
HIF1A/ARNT	0.032	0.027	-9999	-10000	0	0
CUL2	0.015	0	-9999	-10000	0	0
OS9	-0.007	0.11	-9999	-0.59	25	25
RACK1/Elongin B/Elongin C	0	0	-9999	-10000	0	0
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.032	0.027	-9999	-10000	0	0
PHD1-3/OS9	-0.018	0.074	-9999	-0.34	13	13
HIF1A/RACK1/Elongin B/Elongin C	-0.003	0.015	-9999	-10000	0	0
VHL	0.015	0	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
HIF1A/JAB1	0.032	0.027	-9999	-10000	0	0
EGLN3	0.003	0.088	-9999	-0.62	13	13
EGLN2	0.015	0	-9999	-10000	0	0
EGLN1	0.015	0	-9999	-10000	0	0
TP53	0.003	0.088	-9999	-0.62	13	13
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.044	0.012	-9999	-10000	0	0
ARNT	0.015	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0.033	-9999	-0.59	2	2
HIF1A/p19ARF	-0.056	0.15	-9999	-0.31	135	135

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	0.026	0.074	-10000	0	-0.48	3	3
adherens junction organization	-0.017	0.12	-10000	0	-0.41	20	20
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.028	0.14	-10000	0	-0.41	23	23
FMN1	-0.045	0.16	-10000	0	-0.55	19	19
mol:IP3	-0.024	0.056	-10000	0	-0.48	3	3
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.009	0.11	-10000	0	-0.57	5	5
CTNNB1	0.017	0.004	-10000	0	-10000	0	0
AKT1	0.019	0.083	-10000	0	-0.5	3	3
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.026	0.16	-10000	0	-0.43	80	80
CTNND1	0.016	0.002	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.001	0.11	-10000	0	-0.52	5	5
VASP	0.001	0.11	-10000	0	-0.53	5	5
ZYX	-0.007	0.12	-10000	0	-0.53	6	6
JUB	-0.01	0.13	-10000	0	-0.62	8	8
EGFR(dimer)	-0.066	0.17	-10000	0	-0.5	35	35
E-cadherin/beta catenin-gamma catenin	-0.077	0.15	-10000	0	-0.37	139	139
mol:PI-3-4-5-P3	-0.03	0.068	-10000	0	-0.46	5	5
PIK3CA	0.016	0.002	-10000	0	-10000	0	0
PI3K	-0.03	0.069	-10000	0	-0.47	5	5
FYN	0.029	0.072	-10000	0	-0.5	1	1
mol:Ca2+	0.016	0.073	-10000	0	-0.47	3	3
JUP	0.009	0.069	-10000	0	-0.61	8	8
PIK3R1	0.013	0.043	-10000	0	-0.63	3	3
mol:DAG	-0.024	0.056	-10000	0	-0.48	3	3
CDH1	-0.11	0.25	-10000	0	-0.61	136	136
RhoA/GDP	-0.028	0.14	-10000	0	-0.41	23	23
establishment of polarity of embryonic epithelium	0.001	0.11	-10000	0	-0.52	5	5
SRC	0.013	0.035	-10000	0	-0.62	2	2
RAC1	0.015	0	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
EGFR	-0.11	0.25	-10000	0	-0.6	138	138
CASR	0.017	0.08	-10000	0	-0.4	6	6
RhoA/GTP	-0.02	0.048	-10000	0	-0.42	3	3
AKT2	0.02	0.083	-10000	0	-0.5	3	3
actin cable formation	-0.035	0.15	-10000	0	-0.53	19	19
apoptosis	0.026	0.06	0.42	5	-10000	0	5
CTNNA1	0.016	0.002	-10000	0	-10000	0	0
mol:GDP	-0.039	0.15	-10000	0	-0.42	33	33
PIP5K1A	0.001	0.11	-10000	0	-0.53	5	5
PLCG1	-0.024	0.057	-10000	0	-0.49	3	3
Rac1/GTP	-0.089	0.13	-10000	0	-0.46	35	35
homophilic cell adhesion	0.001	0.002	-10000	0	-10000	0	0

×

Stabilization and expansion of the E-cadherin adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.019	0.11	-9999	-0.73	1	1
epithelial cell differentiation	-0.062	0.12	-9999	-10000	0	0
CYFIP2	0.008	0.068	-9999	-0.61	8	8
ENAH	0.018	0.11	-9999	-0.39	2	2
EGFR	-0.11	0.25	-9999	-0.6	138	138
EPHA2	-0.017	0.14	-9999	-0.59	35	35
MYO6	-0.021	0.13	-9999	-10000	0	0
CTNNB1	0.015	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.004	0.04	-9999	-0.37	8	8
AQP5	-0.19	0.2	-9999	-0.51	163	163
CTNND1	0.015	0	-9999	-10000	0	0
mol:PI-4-5-P2	-0.021	0.13	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.035	0.15	-9999	-0.6	7	7
EGF	-0.038	0.18	-9999	-0.61	57	57
NCKAP1	0.015	0	-9999	-10000	0	0
AQP3	-0.077	0.14	-9999	-0.54	34	34
cortical microtubule organization	-0.062	0.12	-9999	-10000	0	0
GO:0000145	-0.02	0.12	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.062	0.12	-9999	-10000	0	0
MLLT4	0.014	0.025	-9999	-0.62	1	1
ARF6/GDP	-0.058	0.11	-9999	-0.49	11	11
ARF6	0.015	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.018	0.074	-9999	-0.34	6	6
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	-0.022	0.14	-9999	-0.42	12	12
PVRL2	0.014	0.025	-9999	-0.62	1	1
ZYX	-0.029	0.14	-9999	-0.6	1	1
ARF6/GTP	-0.017	0.066	-9999	-10000	0	0
CDH1	-0.11	0.25	-9999	-0.61	136	136
EGFR/EGFR/EGF/EGF	-0.14	0.18	-9999	-0.59	53	53
RhoA/GDP	-0.057	0.11	-9999	-10000	0	0
actin cytoskeleton organization	-0.014	0.13	-9999	-0.58	1	1
IGF-1R heterotetramer	0.005	0.081	-9999	-0.62	11	11
GIT1	0.014	0.025	-9999	-0.62	1	1
IGF1R	0.005	0.081	-9999	-0.62	11	11
IGF1	-0.005	0.11	-9999	-0.61	22	22
DIAPH1	-0.003	0.065	-9999	-0.72	5	5
Wnt receptor signaling pathway	0.062	0.12	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
RhoA/GTP	-0.058	0.11	-9999	-0.49	11	11
CTNNA1	0.015	0	-9999	-10000	0	0
VCL	-0.015	0.13	-9999	-0.6	1	1
EFNA1	0.012	0.041	-9999	-0.6	3	3
LPP	-0.035	0.15	-9999	-0.56	11	11
Ephrin A1/EPHA2	-0.069	0.13	-9999	-0.56	10	10
SEC6/SEC8	-0.049	0.098	-9999	-0.54	2	2
MGAT3	-0.035	0.15	-9999	-0.62	7	7
HGF/MET	-0.18	0.21	-9999	-0.61	91	91
HGF	-0.088	0.23	-9999	-0.6	113	113
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.019	0.11	-9999	-0.74	1	1
actin cable formation	0.03	0.11	-9999	-0.37	5	5
KIAA1543	-0.077	0.2	-9999	-0.6	39	39
KIFC3	-0.022	0.13	-9999	-0.62	1	1
NCK1	0.015	0	-9999	-10000	0	0
EXOC3	0.015	0	-9999	-10000	0	0
ACTN1	-0.043	0.16	-9999	-0.59	10	10
NCK1/GIT1	-0.001	0.018	-9999	-0.46	1	1
mol:GDP	-0.062	0.12	-9999	-10000	0	0
EXOC4	0.015	0	-9999	-10000	0	0
STX4	-0.021	0.13	-9999	-10000	0	0
PIP5K1C	-0.022	0.13	-9999	-10000	0	0
LIMA1	0.008	0.07	-9999	-0.62	8	8
ABI1	0.015	0	-9999	-10000	0	0
ROCK1	-0.05	0.093	-9999	-0.42	11	11
adherens junction assembly	-0.056	0.19	-9999	-0.58	40	40
IGF-1R heterotetramer/IGF1	-0.068	0.13	-9999	-0.61	12	12
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	-0.001	0.025	-9999	-0.46	2	2
MET	-0.16	0.28	-9999	-0.6	194	194
PLEKHA7	-0.026	0.14	-9999	-0.62	5	5
mol:GTP	-0.018	0.073	-9999	-0.34	6	6
establishment of epithelial cell apical/basal polarity	0.014	0.12	-9999	-0.51	2	2
cortical actin cytoskeleton stabilization	-0.019	0.11	-9999	-0.73	1	1
regulation of cell-cell adhesion	-0.014	0.13	-9999	-0.58	1	1
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.019	0.11	-9999	-0.74	1	1

×

EPO 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.069	0.091	-9999	-0.67	2	2
CRKL	0.035	0.084	-9999	-0.46	2	2
mol:DAG	0.043	0.081	-9999	-0.43	4	4
HRAS	0.056	0.091	-9999	-0.47	6	6
MAPK8	0.016	0.1	-9999	-0.38	16	16
RAP1A	0.035	0.084	-9999	-0.46	2	2
GAB1	0.035	0.087	-9999	-0.62	2	2
MAPK14	0.021	0.089	-9999	-0.33	12	12
EPO	-0.021	0.15	-9999	-0.58	43	43
PLCG1	0.043	0.083	-9999	-0.44	4	4
EPOR/TRPC2/IP3 Receptors	0.016	0.024	-9999	-0.58	1	1
RAPGEF1	0.013	0.035	-9999	-0.62	2	2
EPO/EPOR (dimer)/SOCS3	-0.14	0.2	-9999	-0.4	234	234
GAB1/SHC/GRB2/SOS1	-0.022	0.073	-9999	-0.52	6	6
EPO/EPOR (dimer)	-0.001	0.11	-9999	-0.42	44	44
IRS2	0.035	0.084	-9999	-0.46	2	2
STAT1	0.048	0.097	-9999	-0.46	7	7
STAT5B	0.049	0.084	-9999	-0.46	4	4
cell proliferation	0.025	0.095	-9999	-0.5	3	3
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.025	0.082	-9999	-0.49	11	11
TEC	0.021	0.11	-9999	-0.51	7	7
SOCS3	-0.18	0.29	-9999	-0.6	214	214
STAT1 (dimer)	0.048	0.095	-9999	-0.45	7	7
JAK2	0.016	0.008	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.62	3	3
EPO/EPOR (dimer)/JAK2	0.041	0.092	-9999	-0.5	2	2
EPO/EPOR	-0.001	0.11	-9999	-0.42	44	44
LYN	0.013	0.053	-9999	-0.6	5	5
TEC/VAV2	0.029	0.11	-9999	-0.52	6	6
elevation of cytosolic calcium ion concentration	0.016	0.024	-9999	-0.58	1	1
SHC1	0.001	0.092	-9999	-0.59	16	16
EPO/EPOR (dimer)/LYN	0.017	0.1	-9999	-0.34	49	49
mol:IP3	0.043	0.081	-9999	-0.43	4	4
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.022	0.073	-9999	-0.5	6	6
SH2B3	0.013	0.046	-9999	-0.58	4	4
NFKB1	0.021	0.088	-9999	-0.35	6	6
EPO/EPOR (dimer)/JAK2/SOCS3	-0.067	0.1	-9999	-0.34	25	25
PTPN6	0.027	0.087	-9999	-0.49	2	2
TEC/VAV2/GRB2	0.035	0.11	-9999	-0.49	6	6
EPOR	0.016	0.024	-9999	-0.58	1	1
INPP5D	0.007	0.071	-9999	-0.6	9	9
mol:GDP	-0.023	0.074	-9999	-0.52	6	6
SOS1	0.015	0	-9999	-10000	0	0
PLCG2	0.004	0.083	-9999	-0.61	12	12
CRKL/CBL/C3G	0.048	0.084	-9999	-0.53	2	2
VAV2	0.034	0.086	-9999	-0.46	2	2
CBL	0.035	0.084	-9999	-0.46	2	2
SHC/Grb2/SOS1	-0.024	0.075	-9999	-0.5	6	6
STAT5A	0.042	0.11	-9999	-0.54	10	10
GRB2	0.014	0.023	-9999	-0.59	1	1
STAT5 (dimer)	0.064	0.1	-9999	-0.52	9	9
LYN/PLCgamma2	-0.011	0.08	-9999	-0.55	13	13
PTPN11	0.013	0.035	-9999	-0.62	2	2
BTK	0.024	0.11	-9999	-0.57	9	9
BCL2	0.067	0.11	-9999	-0.88	4	4

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.015	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.014	0.025	-9999	-0.62	1	1
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.015	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.031	0.11	-9999	-0.24	131	131
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0.035	-9999	-0.62	2	2
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.015	0	-9999	-10000	0	0
FYN	0.015	0	-9999	-10000	0	0
MAP3K12	0.015	0	-9999	-10000	0	0
FGR	0.01	0.057	-9999	-0.59	6	6
p38 alpha/TAB1	-0.021	0.052	-9999	-0.33	8	8
PRKG1	-0.032	0.17	-9999	-0.62	50	50
DUSP8	-0.006	0.11	-9999	-0.61	23	23
PGK/cGMP/p38 alpha	-0.037	0.086	-9999	-0.32	34	34
apoptosis	-0.02	0.05	-9999	-0.32	7	7
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.011	0.053	-9999	-0.6	5	5
DUSP1	-0.02	0.14	-9999	-0.6	38	38
PAK1	-0.018	0.14	-9999	-0.59	37	37
SRC	0.013	0.035	-9999	-0.62	2	2
RAC1/OSM/MEKK3/MKK3	-0.001	0.021	-9999	-10000	0	0
TRAF6	0.013	0.035	-9999	-0.62	2	2
RAC1	0.015	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.014	0.023	-9999	-0.59	1	1
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.012	0.092	-9999	-0.4	8	8
BLK	-0.07	0.21	-9999	-0.59	91	91
HCK	0	0.096	-9999	-0.61	16	16
MAP2K3	0.013	0.033	-9999	-0.59	2	2
DUSP16	0.015	0	-9999	-10000	0	0
DUSP10	-0.006	0.12	-9999	-0.62	23	23
TRAF6/MEKK3	-0.001	0.019	-9999	-0.36	2	2
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.02	0.078	-9999	-0.33	10	10
positive regulation of innate immune response	0.018	0.1	-9999	-0.43	9	9
LCK	-0.098	0.24	-9999	-0.6	123	123
p38alpha-beta/MKP7	0.026	0.098	-9999	-0.43	7	7
p38alpha-beta/MKP5	0.016	0.11	-9999	-0.43	11	11
PGK/cGMP	-0.034	0.12	-9999	-0.46	50	50
PAK2	0.015	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.009	0.12	-9999	-0.45	11	11
CDC42	0.015	0	-9999	-10000	0	0
RALB	0.015	0	-9999	-10000	0	0
RALA	0.015	0	-9999	-10000	0	0
PAK3	-0.13	0.27	-9999	-0.61	158	158

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.052	-9999	-0.59	5	5
mol:S1P	0.002	0.003	-9999	-10000	0	0
S1P1/S1P/Gi	0.012	0.099	-9999	-0.32	40	40
GNAO1	-0.01	0.13	-9999	-0.62	28	28
S1P/S1P3/G12/G13	0.008	0.09	-9999	-0.34	41	41
AKT1	-0.013	0.038	-9999	-0.35	3	3
AKT3	0.008	0.14	-9999	-1.2	6	6
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.052	-9999	-0.59	5	5
GNAI2	0.017	0.002	-9999	-10000	0	0
GNAI3	0.017	0.002	-9999	-10000	0	0
GNAI1	-0.019	0.15	-9999	-0.62	37	37
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.021	0.15	-9999	-0.6	41	41
S1PR2	0.011	0.053	-9999	-0.6	5	5
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.01	0.12	-9999	-0.52	14	14
MAPK3	0.019	0.11	-9999	-0.49	14	14
MAPK1	0.019	0.11	-9999	-0.49	14	14
JAK2	0.014	0.13	-9999	-0.48	24	24
CXCR4	0.002	0.14	-9999	-0.55	23	23
FLT1	0.018	0.025	-9999	-0.62	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.018	0.12	-9999	-0.52	15	15
S1P/S1P3/Gi	0.01	0.12	-9999	-0.53	14	14
RAC1	0.015	0	-9999	-10000	0	0
RhoA/GTP	-0.033	0.09	-9999	-0.48	14	14
VEGFA	-0.088	0.23	-9999	-0.58	118	118
S1P/S1P2/Gi	0.019	0.1	-9999	-0.5	13	13
VEGFR1 homodimer/VEGFA homodimer	-0.048	0.17	-9999	-0.42	119	119
RHOA	0.015	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.001	0.1	-9999	-0.45	10	10
GNAQ	0.015	0	-9999	-10000	0	0
GNAZ	0.014	0.043	-9999	-0.63	3	3
G12/G13	-0.001	0.018	-9999	-0.46	1	1
GNA14	-0.009	0.12	-9999	-0.61	26	26
GNA15	-0.009	0.12	-9999	-0.61	26	26
GNA12	0.014	0.025	-9999	-0.62	1	1
GNA13	0.015	0	-9999	-10000	0	0
GNA11	0.006	0.078	-9999	-0.62	10	10
Rac1/GTP	-0.033	0.09	-9999	-0.48	14	14

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.031	0.22	-10000	0	-0.52	97	97
regulation of axonogenesis	-0.003	0.074	0.37	4	-10000	0	4
myoblast fusion	0.018	0.098	0.25	95	-10000	0	95
mol:GTP	-0.023	0.056	-10000	0	-0.23	11	11
regulation of calcium-dependent cell-cell adhesion	-0.013	0.071	0.39	6	-10000	0	6
ARF1/GTP	-0.015	0.037	-10000	0	-10000	0	0
mol:GM1	-0.006	0.046	-10000	0	-0.18	10	10
mol:Choline	-0.006	0.1	-10000	0	-0.37	42	42
lamellipodium assembly	-0.038	0.092	-10000	0	-0.44	11	11
MAPK3	-0.001	0.089	-10000	0	-0.33	11	11
ARF6/GTP/NME1/Tiam1	0.014	0.071	-10000	0	-0.39	6	6
ARF1	0.015	0	-10000	0	-10000	0	0
ARF6/GDP	-0.018	0.098	-10000	0	-0.25	95	95
ARF1/GDP	-0.005	0.09	-10000	0	-0.37	11	11
ARF6	0.001	0.032	-10000	0	-10000	0	0
RAB11A	0.015	0	-10000	0	-10000	0	0
TIAM1	0.013	0.035	-10000	0	-0.62	2	2
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	-0.001	0.089	-10000	0	-0.34	10	10
actin filament bundle formation	0.033	0.079	0.37	11	-10000	0	11
KALRN	-0.035	0.082	-10000	0	-0.3	28	28
RAB11FIP3/RAB11A	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.033	0.079	-10000	0	-0.38	11	11
NME1	0.011	0.048	-10000	0	-0.6	4	4
Rac1/GDP	-0.033	0.079	-10000	0	-0.38	11	11
substrate adhesion-dependent cell spreading	-0.023	0.056	-10000	0	-0.23	11	11
cortical actin cytoskeleton organization	-0.038	0.093	-10000	0	-0.44	11	11
RAC1	0.015	0	-10000	0	-10000	0	0
liver development	-0.023	0.056	-10000	0	-0.23	11	11
ARF6/GTP	-0.023	0.056	-10000	0	-0.23	11	11
RhoA/GTP	-0.015	0.037	-10000	0	-10000	0	0
mol:GDP	-0.037	0.09	-10000	0	-0.42	11	11
ARF6/GTP/RAB11FIP3/RAB11A	-0.011	0.028	-10000	0	-10000	0	0
RHOA	0.015	0	-10000	0	-10000	0	0
PLD1	-0.02	0.11	-10000	0	-0.43	41	41
RAB11FIP3	0.015	0	-10000	0	-10000	0	0
tube morphogenesis	-0.038	0.092	-10000	0	-0.44	11	11
ruffle organization	0.003	0.074	-10000	0	-0.37	4	4
regulation of epithelial cell migration	-0.023	0.056	-10000	0	-0.23	11	11
PLD2	0.006	0.049	-10000	0	-0.42	1	1
PIP5K1A	0.002	0.074	-10000	0	-0.37	4	4
mol:Phosphatidic acid	-0.006	0.1	-10000	0	-0.37	42	42
Rac1/GTP	-0.038	0.093	-10000	0	-0.45	11	11

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.081	0.17	-9999	-0.43	126	126
AKT1	0.055	0.11	-9999	-0.57	3	3
PTK2B	-0.061	0.21	-9999	-0.56	70	70
VEGFR2 homodimer/Frs2	0.036	0.06	-9999	-0.58	4	4
CAV1	-0.064	0.2	-9999	-0.59	88	88
CALM1	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.059	0.13	-9999	-0.55	11	11
endothelial cell proliferation	0.041	0.13	-9999	-0.47	6	6
mol:Ca2+	0	0.14	-9999	-0.56	10	10
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.056	0.12	-9999	-0.52	11	11
RP11-342D11.1	-0.01	0.14	-9999	-0.57	10	10
CDH5	0.01	0.057	-9999	-0.59	6	6
VEGFA homodimer	-0.055	0.12	-9999	-0.36	6	6
SHC1	0.001	0.092	-9999	-0.59	16	16
SHC2	0.012	0.043	-9999	-0.62	3	3
HRAS/GDP	-0.05	0.11	-9999	-0.48	20	20
SH2D2A	-0.092	0.23	-9999	-0.6	116	116
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.039	0.086	-9999	-0.56	5	5
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.11	0.18	-9999	-0.64	40	40
VEGFR1 homodimer	0.014	0.025	-9999	-0.62	1	1
SHC/GRB2/SOS1	-0.056	0.12	-9999	-0.54	20	20
GRB10	-0.004	0.16	-9999	-0.7	14	14
PTPN11	0.013	0.035	-9999	-0.62	2	2
GRB2	0.014	0.023	-9999	-0.59	1	1
PAK1	-0.018	0.14	-9999	-0.59	37	37
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.054	0.12	-9999	-0.58	11	11
HRAS	0.015	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.004	0.12	-9999	-0.34	6	6
HIF1A	0.013	0.034	-9999	-0.61	2	2
FRS2	0.012	0.047	-9999	-0.6	4	4
oxygen and reactive oxygen species metabolic process	-0.055	0.12	-9999	-0.51	11	11
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.005	0.078	-9999	-0.6	11	11
Nck/Pak	-0.024	0.098	-9999	-0.43	37	37
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.058	0.12	-9999	-0.54	9	9
mol:GDP	-0.054	0.12	-9999	-0.52	20	20
mol:NADP	0.042	0.11	-9999	-0.52	5	5
eNOS/Hsp90	0.047	0.11	-9999	-0.48	5	5
PIK3R1	0.012	0.043	-9999	-0.62	3	3
mol:IP3	0	0.14	-9999	-0.57	10	10
HIF1A/ARNT	-0.001	0.024	-9999	-0.44	2	2
SHB	0.011	0.049	-9999	-0.62	4	4
VEGFA	-0.089	0.23	-9999	-0.59	118	118
VEGFC	-0.005	0.11	-9999	-0.6	22	22
FAK1/Vinculin	-0.007	0.16	-9999	-0.54	9	9
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.11	0.19	-9999	-0.58	71	71
PTPN6	0.005	0.081	-9999	-0.62	11	11
EPAS1	0.024	0.035	-9999	-0.43	3	3
mol:L-citrulline	0.042	0.11	-9999	-0.52	5	5
ITGAV	0.014	0.025	-9999	-0.62	1	1
PIK3CA	0.015	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.055	0.12	-9999	-0.52	11	11
VEGFR2 homodimer/VEGFA homodimer	-0.062	0.13	-9999	-0.62	10	10
VEGFR2/3 heterodimer	0.032	0.077	-9999	-0.58	7	7
VEGFB	0.015	0	-9999	-10000	0	0
MAPK11	0.004	0.14	-9999	-0.55	11	11
VEGFR2 homodimer	0.037	0.06	-9999	-0.62	5	5
FLT1	0.014	0.025	-9999	-0.62	1	1
NEDD4	0.011	0.063	-9999	-0.6	7	7
MAPK3	-0.006	0.14	-9999	-0.53	10	10
MAPK1	-0.006	0.14	-9999	-0.53	10	10
VEGFA145/NRP2	-0.081	0.17	-9999	-0.43	125	125
VEGFR1/2 heterodimer	0.037	0.058	-9999	-0.61	5	5
KDR	0.037	0.06	-9999	-0.62	5	5
VEGFA165/NRP1/VEGFR2 homodimer	-0.058	0.12	-9999	-0.59	12	12
SRC	0.013	0.035	-9999	-0.62	2	2
platelet activating factor biosynthetic process	-0.003	0.14	-9999	-0.54	10	10
PI3K	-0.041	0.091	-9999	-0.54	7	7
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.058	0.12	-9999	-0.54	9	9
FES	-0.002	0.15	-9999	-0.58	11	11
GAB1	-0.042	0.095	-9999	-0.58	6	6
VEGFR2 homodimer/VEGFA homodimer/Src	-0.059	0.13	-9999	-0.55	10	10
CTNNB1	0.015	0	-9999	-10000	0	0
SOS1	0.015	0	-9999	-10000	0	0
ARNT	0.015	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.013	0.16	-9999	-0.51	13	13
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.058	0.12	-9999	-0.54	9	9
PI3K/GAB1	0.054	0.11	-9999	-0.51	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.064	0.12	-9999	-0.56	6	6
PRKACA	0.015	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.019	0.086	-9999	-0.68	5	5
HSP90AA1	0.015	0	-9999	-10000	0	0
CDC42	0	0.15	-9999	-0.58	10	10
actin cytoskeleton reorganization	-0.11	0.18	-9999	-0.63	40	40
PTK2	-0.014	0.16	-9999	-0.56	8	8
EDG1	-0.01	0.14	-9999	-0.57	10	10
mol:DAG	0	0.14	-9999	-0.57	10	10
CaM/Ca2+	-0.049	0.1	-9999	-0.52	10	10
MAP2K3	0.001	0.15	-9999	-0.55	15	15
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.006	0.16	-9999	-0.72	14	14
PLCG1	0	0.15	-9999	-0.58	10	10
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.055	0.12	-9999	-0.55	10	10
IQGAP1	0.009	0.064	-9999	-0.61	7	7
YES1	0.013	0.035	-9999	-0.62	2	2
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.059	0.13	-9999	-0.56	11	11
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.063	0.13	-9999	-0.54	9	9
cell migration	0.025	0.15	-9999	-0.52	5	5
mol:PI-3-4-5-P3	0.035	0.12	-9999	-0.5	7	7
FYN	0.015	0	-9999	-10000	0	0
VEGFB/NRP1	0	0.14	-9999	-0.54	10	10
mol:NO	0.042	0.11	-9999	-0.52	5	5
PXN	0.015	0	-9999	-10000	0	0
HRAS/GTP	-0.05	0.11	-9999	-0.48	20	20
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.006	0.16	-9999	-0.72	14	14
VHL	0.015	0	-9999	-10000	0	0
ITGB3	-0.099	0.24	-9999	-0.6	125	125
NOS3	0.041	0.12	-9999	-0.59	5	5
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.059	0.13	-9999	-0.55	10	10
RAC1	0.015	0	-9999	-10000	0	0
PRKCA	0.01	0.14	-9999	-0.53	11	11
PRKCB	-0.035	0.18	-9999	-0.56	30	30
VCL	0.011	0.053	-9999	-0.6	5	5
VEGFA165/NRP1	-0.011	0.14	-9999	-0.58	10	10
VEGFR1/2 heterodimer/VEGFA homodimer	-0.058	0.13	-9999	-0.55	10	10
VEGFA165/NRP2	-0.081	0.17	-9999	-0.43	125	125
MAPKKK cascade	0.022	0.15	-9999	-0.62	12	12
NRP2	0.006	0.075	-9999	-0.61	10	10
VEGFC homodimer	-0.005	0.11	-9999	-0.6	22	22
NCK1	0.015	0	-9999	-10000	0	0
ROCK1	0.015	0	-9999	-10000	0	0
FAK1/Paxillin	-0.005	0.16	-9999	-0.53	7	7
MAP3K13	-0.009	0.16	-9999	-0.58	14	14
PDPK1	0.043	0.11	-9999	-0.56	3	3

×

BARD1 signaling events

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
BARD1/CSTF1	-0.021	0.095	-10000	0	-0.45	31	31
ATM	0.015	0	-10000	0	-10000	0	0
UBE2D3	0.015	0	-10000	0	-10000	0	0
PRKDC	0.015	0	-10000	0	-10000	0	0
ATR	0.015	0	-10000	0	-10000	0	0
UBE2L3	0.015	0	-10000	0	-10000	0	0
FANCD2	0.018	0.063	-10000	0	-0.28	27	27
protein ubiquitination	-0.024	0.091	-10000	0	-0.67	4	4
XRCC5	0.015	0	-10000	0	-10000	0	0
XRCC6	0.015	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.015	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.012	0.053	-10000	0	-0.4	8	8
FANCF	0.015	0	-10000	0	-10000	0	0
BRCA1	0.012	0.04	-10000	0	-0.59	3	3
CCNE1	0.011	0.052	-10000	0	-0.59	5	5
CDK2/Cyclin E1	-0.013	0.079	-10000	0	-0.47	18	18
FANCG	0.014	0.023	-10000	0	-0.59	1	1
BRCA1/BACH1/BARD1	-0.023	0.1	-10000	0	-0.46	33	33
FANCE	0.015	0	-10000	0	-10000	0	0
FANCC	0.014	0.025	-10000	0	-0.62	1	1
NBN	0.015	0	-10000	0	-10000	0	0
FANCA	-0.023	0.15	-10000	0	-0.6	42	42
DNA repair	0.019	0.15	-10000	0	-0.53	16	16
BRCA1/BARD1/ubiquitin	-0.023	0.1	-10000	0	-0.46	33	33
BARD1/DNA-PK	-0.016	0.071	-10000	0	-0.34	30	30
FANCL	0.015	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.021	0.095	0.45	31	-10000	0	31
BRCA1/BARD1/CTIP/M/R/N Complex	0.034	0.066	-10000	0	-0.43	2	2
BRCA1/BACH1/BARD1/TopBP1	-0.019	0.085	-10000	0	-0.39	33	33
BRCA1/BARD1/P53	-0.024	0.092	-10000	0	-0.36	42	42
BARD1/CSTF1/BRCA1	-0.019	0.085	-10000	0	-0.39	33	33
BRCA1/BACH1	0.012	0.04	-10000	0	-0.59	3	3
BARD1	-0.014	0.13	-10000	0	-0.62	31	31
PCNA	0.009	0.061	-10000	0	-0.59	7	7
BRCA1/BARD1/UbcH5C	-0.019	0.085	-10000	0	-0.39	33	33
BRCA1/BARD1/UbcH7	-0.019	0.085	-10000	0	-0.39	33	33
BRCA1/BARD1/RAD51/PCNA	-0.061	0.14	-10000	0	-0.65	12	12
BARD1/DNA-PK/P53	-0.02	0.081	-10000	0	-0.64	2	2
BRCA1/BARD1/Ubiquitin	-0.023	0.1	-10000	0	-0.46	33	33
BRCA1/BARD1/CTIP	-0.018	0.084	-10000	0	-0.37	31	31
FA complex	0.034	0.058	-10000	0	-0.32	1	1
BARD1/EWS	-0.021	0.095	-10000	0	-0.45	31	31
RBBP8	0.025	0.03	-10000	0	-0.42	3	3
TP53	0.003	0.088	-10000	0	-0.62	13	13
TOPBP1	0.015	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.023	0.091	0.36	42	-10000	0	42
BRCA1/BARD1	-0.024	0.092	-10000	0	-0.68	4	4
CSTF1	0.015	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.022	0.098	-10000	0	-0.46	31	31
CDK2	0.001	0.091	-10000	0	-0.6	15	15
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.063	0.2	-10000	0	-0.6	85	85
RAD50	0.015	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.023	0.1	-10000	0	-0.46	33	33
EWSR1	0.015	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	-0.01	0.13	-10000	0	-0.51	18	18
BAG4	0.003	0.088	-10000	0	-0.62	13	13
BAD	0.013	0.045	-10000	0	-0.2	1	1
NFKBIA	0.014	0.023	-10000	0	-0.59	1	1
BIRC3	-0.059	0.2	-10000	0	-0.6	81	81
BAX	0.013	0.045	-10000	0	-0.2	1	1
EnzymeConsortium:3.1.4.12	-0.001	0.034	-10000	0	-0.11	18	18
IKBKB	-0.001	0.12	-10000	0	-0.48	17	17
MAP2K2	0.023	0.058	-10000	0	-0.37	4	4
MAP2K1	0.023	0.058	-10000	0	-0.37	4	4
SMPD1	0.006	0.034	-10000	0	-0.14	1	1
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	-0.002	0.12	-10000	0	-0.5	17	17
MAP2K4	0.018	0.052	-10000	0	-0.29	4	4
protein ubiquitination	0.001	0.12	-10000	0	-0.49	17	17
EnzymeConsortium:2.7.1.37	0.026	0.063	-10000	0	-0.39	4	4
response to UV	0	0.001	-10000	0	-0.003	5	5
RAF1	0.017	0.058	-10000	0	-0.37	5	5
CRADD	0.015	0	-10000	0	-10000	0	0
mol:ceramide	0.004	0.047	-10000	0	-0.16	14	14
I-kappa-B-alpha/RELA/p50/ubiquitin	-0.001	0.014	-10000	0	-0.36	1	1
MADD	0.013	0.043	-10000	0	-0.63	3	3
MAP3K1	0.011	0.053	-10000	0	-0.29	5	5
TRADD	0.015	0.025	-10000	0	-0.63	1	1
RELA/p50	0.015	0	-10000	0	-10000	0	0
MAPK3	0.026	0.057	-10000	0	-0.36	4	4
MAPK1	0.026	0.057	-10000	0	-0.36	4	4
p50/RELA/I-kappa-B-alpha	-0.001	0.016	-10000	0	-0.42	1	1
FADD	-0.01	0.13	-10000	0	-0.51	18	18
KSR1	0.01	0.058	-10000	0	-0.36	6	6
MAPK8	0.022	0.061	-10000	0	-0.29	11	11
TRAF2	0.015	0.001	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-0.002	1	1
CHUK	-0.001	0.12	-10000	0	-0.48	17	17
TNF R/SODD	-0.018	0.091	-10000	0	-0.46	26	26
TNF	-0.12	0.26	-10000	0	-0.6	152	152
CYCS	0.015	0.045	0.15	2	-0.19	1	3
IKBKG	-0.001	0.12	-10000	0	-0.48	17	17
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	-0.02	0.13	-10000	0	-0.55	18	18
RELA	0.015	0	-10000	0	-10000	0	0
RIPK1	0.015	0.001	-10000	0	-10000	0	0
AIFM1	0.015	0.045	0.15	2	-0.19	1	3
TNF/TNF R/SODD	-0.097	0.17	-10000	0	-0.38	171	171
TNFRSF1A	0.002	0.09	-10000	0	-0.61	14	14
response to heat	0	0	-10000	0	-0.002	1	1
CASP8	0.013	0.05	-10000	0	-0.73	1	1
NSMAF	-0.01	0.12	-10000	0	-0.5	18	18
response to hydrogen peroxide	0	0.001	-10000	0	-0.003	5	5
BCL2	0.012	0.043	-10000	0	-0.62	3	3

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	-0.006	0.045	-10000	0	-0.33	13	13
TRAF2/ASK1	-0.006	0.05	-10000	0	-0.39	11	11
ATM	0.015	0	-10000	0	-10000	0	0
MAP2K3	0.024	0.057	-10000	0	-0.3	5	5
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.023	0.075	-10000	0	-0.39	12	12
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.043	0.18	-10000	0	-0.61	63	63
TXN	0.01	0	-10000	0	-10000	0	0
CALM1	0.015	0	-10000	0	-10000	0	0
GADD45A	-0.022	0.14	-10000	0	-0.59	41	41
GADD45B	-0.018	0.14	-10000	0	-0.6	36	36
MAP3K1	0.012	0.046	-10000	0	-0.59	4	4
MAP3K6	0.01	0.057	-10000	0	-0.59	6	6
MAP3K7	0.015	0	-10000	0	-10000	0	0
MAP3K4	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.011	0.07	-10000	0	-0.44	17	17
TAK1/TAB family	0.001	0.017	0.19	3	-0.18	2	5
RAC1/OSM/MEKK3	0	0.012	-10000	0	-0.32	1	1
TRAF2	0.015	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.008	0.029	-10000	0	-10000	0	0
TRAF6	0.009	0.021	-10000	0	-0.38	2	2
RAC1	0.015	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.068	0.21	-10000	0	-0.61	89	89
CCM2	0.014	0.023	-10000	0	-0.59	1	1
CaM/Ca2+/CAMKIIB	-0.05	0.13	-10000	0	-0.38	89	89
MAPK11	0.012	0.043	-10000	0	-0.62	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.05	0.13	-10000	0	-0.35	95	95
OSM/MEKK3	-0.001	0.016	-10000	0	-0.42	1	1
TAOK1	-0.012	0.11	-10000	0	-0.36	56	56
TAOK2	0.019	0.021	-10000	0	-0.37	2	2
TAOK3	0.021	0	-10000	0	-10000	0	0
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.014	0.023	-10000	0	-0.59	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.005	0.081	-10000	0	-0.62	11	11
MAP3K10	0.008	0.066	-10000	0	-0.59	8	8
MAP3K3	0.015	0	-10000	0	-10000	0	0
TRX/ASK1	0.012	0.051	-10000	0	-0.38	11	11
GADD45/MTK1/MTK1	-0.063	0.14	-10000	0	-0.41	59	59

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.049	-9999	-0.62	4	4
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.009	0.057	-9999	-0.38	16	16
forebrain development	-0.023	0.18	-9999	-0.46	70	70
GNAO1	-0.012	0.13	-9999	-0.63	28	28
SMO/beta Arrestin2	0.017	0.058	-9999	-0.44	10	10
SMO	0.006	0.077	-9999	-0.61	10	10
ARRB2	0.015	0.005	-9999	-10000	0	0
GLI3/SPOP	0.045	0.068	-9999	-0.61	1	1
mol:GTP	0	0.002	-9999	-10000	0	0
GSK3B	0.015	0	-9999	-10000	0	0
GNAI2	0.015	0.004	-9999	-10000	0	0
SIN3/HDAC complex	0.004	0.023	-9999	-0.34	2	2
GNAI1	-0.021	0.15	-9999	-0.63	37	37
XPO1	0.016	0.006	-9999	-10000	0	0
GLI1/Su(fu)	-0.057	0.12	-9999	-0.55	23	23
SAP30	0.014	0.025	-9999	-0.62	1	1
mol:GDP	0.006	0.076	-9999	-0.61	10	10
MIM/GLI2A	0.015	0.042	-9999	-0.61	3	3
IFT88	0.015	0	-9999	-10000	0	0
GNAI3	0.015	0.004	-9999	-10000	0	0
GLI2	0.05	0.032	-9999	-10000	0	0
GLI3	0.038	0.071	-9999	-0.41	4	4
CSNK1D	0.015	0	-9999	-10000	0	0
CSNK1E	0.015	0	-9999	-10000	0	0
SAP18	0.015	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.015	0	-9999	-10000	0	0
GNG2	0.009	0.06	-9999	-0.62	6	6
Gi family/GTP	0.01	0.11	-9999	-0.44	20	20
SIN3B	0.014	0.025	-9999	-0.62	1	1
SIN3A	0.015	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.055	0.062	-9999	-0.43	2	2
GLI2/Su(fu)	0.06	0.05	-9999	-10000	0	0
FOXA2	-0.042	0.13	-9999	-0.54	24	24
neural tube patterning	-0.023	0.18	-9999	-0.46	70	70
SPOP	0.015	0	-9999	-10000	0	0
Su(fu)/PIAS1	0.031	0.042	-9999	-0.37	4	4
GNB1	0.015	0	-9999	-10000	0	0
CSNK1G2	0.015	0	-9999	-10000	0	0
CSNK1G3	0.015	0	-9999	-10000	0	0
MTSS1	0.015	0.043	-9999	-0.61	3	3
embryonic limb morphogenesis	-0.023	0.18	-9999	-0.46	70	70
SUFU	0.028	0.04	-9999	-0.45	2	2
LGALS3	-0.091	0.23	-9999	-0.59	118	118
catabolic process	0.073	0.065	-9999	-0.5	1	1
GLI3A/CBP	-0.027	0.12	-9999	-0.35	46	46
KIF3A	0.011	0.049	-9999	-0.62	4	4
GLI1	-0.024	0.18	-9999	-0.47	70	70
RAB23	0.014	0.025	-9999	-0.62	1	1
CSNK1A1	0.015	0	-9999	-10000	0	0
IFT172	0.012	0.043	-9999	-0.62	3	3
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.028	0.14	-9999	-0.4	19	19
GNAZ	0.012	0.043	-9999	-0.63	3	3
RBBP4	0.015	0.001	-9999	-10000	0	0
CSNK1G1	0.014	0.023	-9999	-0.59	1	1
PIAS1	0.013	0.035	-9999	-0.62	2	2
PRKACA	0.015	0	-9999	-10000	0	0
GLI2/SPOP	0.054	0.03	-9999	-10000	0	0
STK36	0.016	0.006	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.018	0.1	-9999	-0.5	13	13
PTCH1	-0.033	0.25	-9999	-0.99	28	28
MIM/GLI1	-0.024	0.2	-9999	-0.59	39	39
CREBBP	-0.027	0.12	-9999	-0.35	46	46
Su(fu)/SIN3/HDAC complex	0.057	0.029	-9999	-0.29	2	2

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.024	0.098	-9999	-0.42	38	38
FBXW11	0.015	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	0.015	0.079	-9999	-0.37	27	27
NF kappa B1 p50/RelA/I kappa B alpha	0.017	0.084	-9999	-0.43	4	4
NFKBIA	-0.01	0.095	-9999	-0.35	11	11
MAPK14	0.014	0.023	-9999	-0.59	1	1
NF kappa B1 p105/p50	0.032	0	-9999	-10000	0	0
ARRB2	0.02	0.01	-9999	-0.25	1	1
REL	-0.01	0.12	-9999	-0.61	27	27
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	0.01	0.089	-9999	-0.35	38	38
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0.032	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.024	0	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.62	3	3
NFKB1	0.027	0	-9999	-10000	0	0
RELA	0.015	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	-0.001	0.091	-9999	-0.36	7	7
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.022	0.082	-9999	-0.5	2	2
SRC	0.013	0.035	-9999	-0.62	2	2
PI3K	-0.002	0.03	-9999	-0.46	3	3
NF kappa B1 p50/RelA	-0.001	0.092	-9999	-0.36	7	7
IKBKB	0.015	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
SYK	-0.004	0.11	-9999	-0.62	20	20
I kappa B alpha/PIK3R1	-0.003	0.093	-9999	-0.39	10	10
cell death	0.021	0.079	-9999	-0.48	2	2
NF kappa B1 p105/c-Rel	0.015	0.079	-9999	-0.37	27	27
LCK	-0.098	0.24	-9999	-0.6	123	123
BCL3	-0.019	0.14	-9999	-0.59	38	38

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.013	0.067	-9999	-0.76	2	2
TC10/GTP	-0.008	0.056	-9999	-0.73	2	2
Insulin Receptor/Insulin/IRS1/Shp2	-0.008	0.056	-9999	-0.44	8	8
HRAS	0.015	0	-9999	-10000	0	0
APS homodimer	0.001	0.094	-9999	-0.62	15	15
GRB14	-0.22	0.3	-9999	-0.6	252	252
FOXO3	-0.022	0.074	-9999	-0.66	8	8
AKT1	-0.059	0.15	-9999	-0.5	8	8
INSR	0.016	0.025	-9999	-0.62	1	1
Insulin Receptor/Insulin	0.039	0.03	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.006	0.075	-9999	-0.6	10	10
SORBS1	0.014	0.025	-9999	-0.62	1	1
CRK	0.015	0	-9999	-10000	0	0
PTPN1	0.039	0.03	-9999	-10000	0	0
CAV1	-0.018	0.12	-9999	-0.41	11	11
CBL/APS/CAP/Crk-II/C3G	-0.009	0.062	-9999	-0.8	2	2
Insulin Receptor/Insulin/IRS1/NCK2	-0.006	0.046	-9999	-0.35	7	7
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.044	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.036	0.051	-9999	-0.52	1	1
RPS6KB1	-0.045	0.14	-9999	-0.45	8	8
PARD6A	0.013	0.035	-9999	-0.62	2	2
CBL	0.014	0.025	-9999	-0.62	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.035	-9999	-0.84	1	1
PIK3R1	0.012	0.043	-9999	-0.62	3	3
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.083	0.11	-9999	-0.46	9	9
HRAS/GTP	-0.014	0.058	-9999	-0.5	2	2
Insulin Receptor	0.016	0.025	-9999	-0.62	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.013	0.062	-9999	-10000	0	0
PRKCI	-0.027	0.06	-9999	-0.58	6	6
Insulin Receptor/Insulin/GRB14/PDK1	-0.1	0.13	-9999	-0.54	7	7
SHC1	0.001	0.092	-9999	-0.59	16	16
negative regulation of MAPKKK cascade	0.002	0.031	-9999	-0.71	1	1
PI3K	-0.007	0.045	-9999	-10000	0	0
NCK2	0.015	0	-9999	-10000	0	0
RHOQ	0.015	0	-9999	-10000	0	0
mol:H2O2	0	0.003	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.058	0.15	-9999	-0.5	7	7
PRKCZ	-0.067	0.16	-9999	-0.6	48	48
SH2B2	0.001	0.094	-9999	-0.62	15	15
SHC/SHIP	0.022	0.079	-9999	-0.59	2	2
F2RL2	-0.14	0.26	-9999	-0.6	168	168
TRIP10	0.009	0.065	-9999	-0.62	7	7
Insulin Receptor/Insulin/Shc	-0.011	0.059	-9999	-0.33	22	22
TC10/GTP/CIP4/Exocyst	-0.004	0.039	-9999	-0.39	7	7
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.01	0.053	-9999	-10000	0	0
RAPGEF1	0.013	0.035	-9999	-0.62	2	2
RASA1	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.009	0.059	-9999	-0.39	13	13
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.016	0.072	-9999	-0.41	5	5
INPP5D	0.021	0.064	-9999	-0.33	20	20
SOS1	0.015	0	-9999	-10000	0	0
SGK1	-0.016	0.093	-9999	-0.92	7	7
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.013	0.035	-9999	-0.62	2	2
IRS1	0.009	0.065	-9999	-0.62	7	7
p62DOK/RasGAP	0.002	0.031	-9999	-0.72	1	1
INS	-0.001	0.053	-9999	-0.61	5	5
mol:PI-3-4-P2	0.021	0.063	-9999	-0.33	20	20
GRB2	0.014	0.023	-9999	-0.59	1	1
EIF4EBP1	-0.049	0.15	-9999	-0.49	14	14
PTPRA	0.017	0.003	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
TC10/GTP/CIP4	-0.004	0.039	-9999	-0.39	7	7
PDPK1	0.014	0.025	-9999	-0.62	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.03	0.051	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.007	0.047	-9999	-0.34	13	13
Insulin Receptor/Insulin/IRS3	-0.004	0.042	-9999	-0.44	6	6
Par3/Par6	-0.079	0.13	-9999	-0.3	176	176

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.036	0.037	-9999	-0.56	2	2
VEGFR1 homodimer/NRP1	0.025	0.037	-9999	-0.49	3	3
mol:DAG	-0.002	0.13	-9999	-0.68	1	1
VEGFR1 homodimer/NRP1/VEGFR 121	-0.057	0.12	-9999	-0.7	1	1
CaM/Ca2+	0.006	0.12	-9999	-0.64	1	1
HIF1A	0.022	0.036	-9999	-0.51	3	3
GAB1	0.014	0.025	-9999	-0.62	1	1
AKT1	0.023	0.12	-9999	-0.58	2	2
PLCG1	-0.002	0.13	-9999	-0.69	1	1
NOS3	0.028	0.12	-9999	-0.56	3	3
CBL	0.014	0.025	-9999	-0.62	1	1
mol:NO	0.028	0.12	-9999	-0.54	3	3
FLT1	0.034	0.042	-9999	-0.56	3	3
PGF	-0.067	0.21	-9999	-0.61	88	88
VEGFR1 homodimer/NRP2/VEGFR121	-0.06	0.13	-9999	-0.64	4	4
CALM1	0.015	0	-9999	-10000	0	0
PIK3CA	0.015	0	-9999	-10000	0	0
eNOS/Hsp90	0.036	0.12	-9999	-0.52	3	3
endothelial cell proliferation	-0.019	0.16	-9999	-0.57	17	17
mol:Ca2+	-0.002	0.13	-9999	-0.68	1	1
MAPK3	0.016	0.11	-9999	-0.59	1	1
MAPK1	0.016	0.11	-9999	-0.59	1	1
PIK3R1	0.012	0.043	-9999	-0.62	3	3
PLGF homodimer	-0.067	0.21	-9999	-0.61	88	88
PRKACA	0.015	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.064	0.2	-9999	-0.59	88	88
VEGFA homodimer	-0.091	0.23	-9999	-0.59	118	118
VEGFR1 homodimer/VEGFA homodimer	-0.031	0.15	-9999	-0.56	2	2
platelet activating factor biosynthetic process	0.024	0.11	-9999	-0.57	1	1
PI3K	-0.042	0.1	-9999	-0.65	1	1
PRKCA	0.007	0.12	-9999	-0.63	1	1
PRKCB	-0.04	0.17	-9999	-0.62	17	17
VEGFR1 homodimer/PLGF homodimer	-0.016	0.14	-9999	-0.38	55	55
VEGFA	-0.091	0.23	-9999	-0.59	118	118
VEGFB	0.015	0	-9999	-10000	0	0
mol:IP3	-0.002	0.13	-9999	-0.68	1	1
RASA1	0.046	0.034	-9999	-0.69	1	1
NRP2	0.006	0.075	-9999	-0.61	10	10
VEGFR1 homodimer	0.034	0.042	-9999	-0.56	3	3
VEGFB homodimer	0.015	0	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.003	0.15	-9999	-0.51	13	13
PTPN11	0.013	0.035	-9999	-0.62	2	2
mol:PI-3-4-5-P3	-0.041	0.1	-9999	-0.64	1	1
mol:L-citrulline	0.028	0.12	-9999	-0.54	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.051	0.11	-9999	-0.63	2	2
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.056	0.12	-9999	-0.69	1	1
CD2AP	0.015	0	-9999	-10000	0	0
PI3K/GAB1	-0.039	0.096	-9999	-0.61	1	1
PDPK1	0.014	0.12	-9999	-0.6	2	2
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.057	0.12	-9999	-0.84	2	2
mol:NADP	0.028	0.12	-9999	-0.54	3	3
HSP90AA1	0.015	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.051	0.11	-9999	-0.62	2	2
VEGFR1 homodimer/NRP2	0.03	0.061	-9999	-0.43	7	7

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.037	0.04	-9999	-0.32	1	1
positive regulation of NF-kappaB transcription factor activity	0	0.002	-9999	-10000	0	0
CRKL	0.014	0.023	-9999	-0.59	1	1
STAT1 (dimer)/Cbp/p300	0.029	0.1	-9999	-0.5	12	12
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0	0.004	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.053	0.083	-9999	-0.35	27	27
CaM/Ca2+	-0.003	0.028	-9999	-10000	0	0
RAP1A	0.015	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	0.039	0.068	-9999	-0.38	3	3
AKT1	0.057	0.041	-9999	-10000	0	0
MAP2K1	0.055	0.045	-9999	-10000	0	0
MAP3K11	0.046	0.037	-9999	-10000	0	0
IFNGR1	0.017	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.13	0.19	-9999	-0.47	117	117
Rap1/GTP	-0.006	0.045	-9999	-0.65	2	2
CRKL/C3G	-0.002	0.03	-9999	-0.44	3	3
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.003	0.028	-9999	-10000	0	0
CEBPB	0.076	0.094	-9999	-0.61	5	5
STAT3	0.015	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.061	0.19	-9999	-1.1	14	14
STAT1	0.04	0.068	-9999	-0.37	5	5
CALM1	0.015	0	-9999	-10000	0	0
IFN-gamma (dimer)	0.001	0.06	-9999	-0.58	7	7
PIK3CA	0.015	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	0.046	0.067	-9999	-0.36	3	3
CEBPB/PTGES2/Cbp/p300	-0.011	0.048	-9999	-0.35	5	5
mol:Ca2+	-0.004	0.031	-9999	-0.32	1	1
MAPK3	0.065	0.049	-9999	-10000	0	0
STAT1 (dimer)	-0.071	0.12	-9999	-0.52	27	27
MAPK1	0.065	0.049	-9999	-10000	0	0
JAK2	0.017	0.003	-9999	-10000	0	0
PIK3R1	0.012	0.043	-9999	-0.62	3	3
JAK1	0.017	0.003	-9999	-10000	0	0
CAMK2D	0.014	0.025	-9999	-0.62	1	1
DAPK1	0.067	0.12	-9999	-0.63	16	16
SMAD7	0.016	0.074	-9999	-0.25	7	7
CBL/CRKL/C3G	-0.003	0.042	-9999	-0.8	1	1
PI3K	-0.004	0.032	-9999	-10000	0	0
IFNG	0.001	0.06	-9999	-0.58	7	7
apoptosis	0.044	0.085	-9999	-0.45	16	16
CAMK2G	0.012	0.043	-9999	-0.62	3	3
STAT3 (dimer)	0.015	0	-9999	-10000	0	0
CAMK2A	-0.22	0.3	-9999	-0.6	251	251
CAMK2B	-0.068	0.21	-9999	-0.61	89	89
FRAP1	0.056	0.039	-9999	-10000	0	0
PRKCD	0.048	0.072	-9999	-10000	0	0
RAP1B	0.009	0.061	-9999	-0.59	7	7
negative regulation of cell growth	-0.053	0.083	-9999	-0.35	27	27
PTPN2	0.015	0	-9999	-10000	0	0
EP300	0.013	0.043	-9999	-0.63	3	3
IRF1	0.031	0.17	-9999	-0.67	25	25
STAT1 (dimer)/PIASy	0.005	0.071	-9999	-0.36	2	2
SOCS1	-0.074	0.24	-9999	-1.4	13	13
mol:GDP	-0.004	0.04	-9999	-0.74	1	1
CASP1	0.007	0.098	-9999	-0.32	35	35
PTGES2	0.015	0	-9999	-10000	0	0
IRF9	0.06	0.042	-9999	-0.27	3	3
mol:PI-3-4-5-P3	-0.004	0.031	-9999	-10000	0	0
RAP1/GDP	-0.006	0.047	-9999	-0.68	2	2
CBL	0.045	0.042	-9999	-0.57	1	1
MAP3K1	0.045	0.046	-9999	-10000	0	0
PIAS1	0.013	0.035	-9999	-0.62	2	2
PIAS4	0.015	0.025	-9999	-0.62	1	1
antigen processing and presentation of peptide antigen via MHC class II	-0.053	0.083	-9999	-0.35	27	27
PTPN11	0.038	0.038	-9999	-0.32	1	1
CREBBP	0.014	0.025	-9999	-0.62	1	1
RAPGEF1	0.013	0.035	-9999	-0.62	2	2

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.019	0.004	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.095	0.037	-9999	-0.38	1	1
ERC1	0.012	0.042	-9999	-0.61	3	3
RIP2/NOD2	-0.019	0.089	-9999	-0.44	29	29
NFKBIA	0.055	0.023	-9999	-0.53	1	1
BIRC2	0.015	0	-9999	-10000	0	0
IKBKB	0.015	0	-9999	-10000	0	0
RIPK2	0.015	0	-9999	-10000	0	0
IKBKG	-0.007	0.041	-9999	-0.72	1	1
IKK complex/A20	-0.064	0.11	-9999	-0.51	6	6
NEMO/A20/RIP2	0.015	0	-9999	-10000	0	0
XPO1	0.015	0	-9999	-10000	0	0
NEMO/ATM	0.052	0.049	-9999	-0.68	1	1
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.006	0.035	-9999	-0.6	1	1
BCL10/MALT1/TRAF6	-0.001	0.021	-9999	-0.38	2	2
NOD2	-0.012	0.13	-9999	-0.6	29	29
NFKB1	0.019	0.004	-9999	-10000	0	0
RELA	0.019	0.004	-9999	-10000	0	0
MALT1	0.015	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.015	0	-9999	-10000	0	0
TNF/TNFR1A	-0.11	0.19	-9999	-0.44	164	164
TRAF6	0.013	0.035	-9999	-0.62	2	2
PRKCA	0.013	0.035	-9999	-0.62	2	2
CHUK	0.015	0	-9999	-10000	0	0
UBE2D3	0.015	0	-9999	-10000	0	0
TNF	-0.13	0.26	-9999	-0.6	152	152
NF kappa B1 p50/RelA	0	0.01	-9999	-10000	0	0
BCL10	0.015	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.055	0.023	-9999	-0.53	1	1
beta TrCP1/SCF ubiquitin ligase complex	0.019	0.004	-9999	-10000	0	0
TNFRSF1A	0.002	0.09	-9999	-0.61	14	14
IKK complex	-0.006	0.035	-9999	-0.65	1	1
CYLD	0.014	0.025	-9999	-0.62	1	1
IKK complex/PKC alpha	-0.006	0.042	-9999	-0.89	1	1

×

Class I PI3K signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.022	0.067	-9999	-10000	0	0
DAPP1	-0.016	0.13	-9999	-0.43	33	33
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.058	0.2	-9999	-0.59	52	52
mol:DAG	-0.017	0.1	-9999	-0.28	31	31
HRAS	0.015	0.004	-9999	-10000	0	0
RAP1A	0.015	0.004	-9999	-10000	0	0
ARF5/GDP	0.035	0.054	-9999	-0.28	6	6
PLCG2	0.004	0.083	-9999	-0.61	12	12
PLCG1	0.015	0	-9999	-10000	0	0
ARF5	0.015	0	-9999	-10000	0	0
mol:GTP	-0.025	0.076	-9999	-10000	0	0
ARF1/GTP	-0.021	0.065	-9999	-0.41	1	1
RHOA	0.015	0	-9999	-10000	0	0
YES1	0.013	0.035	-9999	-0.62	2	2
RAP1A/GTP	-0.024	0.075	-9999	-10000	0	0
ADAP1	-0.046	0.12	-9999	-0.56	16	16
ARAP3	-0.025	0.076	-9999	-10000	0	0
INPPL1	0.015	0	-9999	-10000	0	0
PREX1	0.007	0.074	-9999	-0.62	9	9
ARHGEF6	0.013	0.035	-9999	-0.62	2	2
ARHGEF7	0.015	0	-9999	-10000	0	0
ARF1	0.015	0	-9999	-10000	0	0
NRAS	0.015	0.004	-9999	-10000	0	0
FYN	0.015	0	-9999	-10000	0	0
ARF6	0.015	0	-9999	-10000	0	0
FGR	0.01	0.057	-9999	-0.59	6	6
mol:Ca2+	0.001	0.057	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.013	0.035	-9999	-0.62	2	2
ZAP70	-0.038	0.17	-9999	-0.6	57	57
mol:IP3	-0.002	0.076	-9999	-0.22	4	4
LYN	0.011	0.053	-9999	-0.6	5	5
ARF1/GDP	0.035	0.054	-9999	-0.28	6	6
RhoA/GDP	-0.022	0.062	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.002	0.025	-9999	-0.38	3	3
BLNK	-0.036	0.17	-9999	-0.62	54	54
actin cytoskeleton reorganization	0.045	0.085	-9999	-10000	0	0
SRC	0.013	0.035	-9999	-0.62	2	2
PLEKHA2	0.03	0.046	-9999	-0.36	9	9
RAC1	0.015	0	-9999	-10000	0	0
PTEN	0.004	0.011	-9999	-10000	0	0
HSP90AA1	0.015	0	-9999	-10000	0	0
ARF6/GTP	-0.022	0.067	-9999	-10000	0	0
RhoA/GTP	-0.023	0.07	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.046	0.18	-9999	-0.55	47	47
BLK	-0.07	0.21	-9999	-0.59	91	91
PDPK1	0.014	0.025	-9999	-0.62	1	1
CYTH1	-0.024	0.075	-9999	-0.56	1	1
HCK	0	0.096	-9999	-0.61	16	16
CYTH3	-0.023	0.07	-9999	-10000	0	0
CYTH2	-0.023	0.07	-9999	-10000	0	0
KRAS	0.014	0.024	-9999	-0.58	1	1
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.016	0.058	-9999	-0.46	7	7
SGK1	-0.018	0.063	-9999	-0.5	7	7
INPP5D	0.007	0.071	-9999	-0.6	9	9
mol:GDP	0.027	0.056	-9999	-0.3	6	6
SOS1	0.015	0	-9999	-10000	0	0
SYK	-0.004	0.11	-9999	-0.62	20	20
ARF6/GDP	-0.022	0.062	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.024	0.076	-9999	-10000	0	0
ARAP3/RAP1A/GTP	-0.025	0.076	-9999	-10000	0	0
VAV1	-0.01	0.12	-9999	-0.62	27	27
mol:PI-3-4-P2	0.021	0.053	-9999	-0.44	9	9
RAS family/GTP/PI3K Class I	0.009	0.087	-9999	-10000	0	0
PLEKHA1	0.028	0.055	-9999	-0.36	13	13
Rac1/GDP	0.035	0.054	-9999	-0.28	6	6
LAT	-0.011	0.13	-9999	-0.62	28	28
Rac1/GTP	0.033	0.073	-9999	-0.54	6	6
ITK	-0.092	0.15	-9999	-0.53	25	25
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.031	0.14	-9999	-0.4	34	34
LCK	-0.098	0.24	-9999	-0.6	123	123
BTK	-0.032	0.085	-9999	-10000	0	0

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.015	0	-10000	0	-10000	0	0
PTK2	0.015	0	-10000	0	-10000	0	0
CRKL	0.013	0.09	-10000	0	-0.38	25	25
GRB2/SOS1/SHC	-0.009	0.055	-10000	0	-0.35	17	17
HRAS	0.015	0	-10000	0	-10000	0	0
IRS1/Crk	0.013	0.089	-10000	0	-0.38	24	24
IGF-1R heterotetramer/IGF1/PTP1B	-0.018	0.083	-10000	0	-0.4	24	24
AKT1	0.036	0.081	-10000	0	-0.63	4	4
BAD	0.044	0.077	-10000	0	-0.57	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.014	0.089	-10000	0	-0.38	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.012	0.097	-10000	0	-0.41	24	24
RAF1	0.048	0.074	-10000	0	-0.53	4	4
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.016	0.078	-10000	0	-0.72	4	4
YWHAZ	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.003	0.095	-10000	0	-0.37	34	34
PIK3CA	0.015	0	-10000	0	-10000	0	0
RPS6KB1	0.037	0.081	-10000	0	-0.63	4	4
GNB2L1	0.015	0	-10000	0	-10000	0	0
positive regulation of MAPKKK cascade	0.041	0.065	-10000	0	-0.45	4	4
PXN	0.015	0	-10000	0	-10000	0	0
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	-0.001	0.016	-10000	0	-0.42	1	1
HRAS/GTP	-0.02	0.079	-10000	0	-0.59	6	6
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.021	0.082	-10000	0	-0.52	6	6
IGF-1R heterotetramer	0.002	0.087	-10000	0	-0.66	11	11
IGF-1R heterotetramer/IGF1/IRS/Nck	0.013	0.089	-10000	0	-0.38	24	24
Crk/p130 Cas/Paxillin	-0.015	0.078	-10000	0	-0.76	4	4
IGF1R	0.002	0.088	-10000	0	-0.66	11	11
IGF1	-0.007	0.12	-10000	0	-0.63	22	22
IRS2/Crk	0.022	0.086	-10000	0	-0.72	4	4
PI3K	-0.017	0.08	-10000	0	-0.54	7	7
apoptosis	-0.049	0.068	0.48	4	-10000	0	4
HRAS/GDP	0	0	-10000	0	-10000	0	0
PRKCD	0.016	0.12	-10000	0	-0.52	18	18
RAF1/14-3-3 E	0.053	0.066	-10000	0	-0.45	4	4
BAD/14-3-3	0.051	0.072	-10000	0	-0.52	4	4
PRKCZ	0.01	0.13	-10000	0	-0.59	11	11
Crk/p130 Cas/Paxillin/FAK1	-0.012	0.059	-10000	0	-0.56	4	4
PTPN1	0.015	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.02	0.095	-10000	0	-0.42	25	25
BCAR1	0.014	0.025	-10000	0	-0.62	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.028	0.1	-10000	0	-0.42	29	29
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.015	0	-10000	0	-10000	0	0
IRS1/NCK2	0.013	0.088	-10000	0	-0.38	24	24
GRB10	0.006	0.075	-10000	0	-0.6	10	10
PTPN11	0.013	0.097	-10000	0	-0.41	24	24
IRS1	0.004	0.095	-10000	0	-0.37	34	34
IRS2	0.013	0.09	-10000	0	-0.38	25	25
IGF-1R heterotetramer/IGF1	-0.023	0.11	-10000	0	-0.49	31	31
GRB2	0.014	0.023	-10000	0	-0.59	1	1
PDPK1	0.028	0.085	-10000	0	-0.67	4	4
YWHAE	0.015	0	-10000	0	-10000	0	0
PRKD1	0.029	0.091	-10000	0	-0.43	18	18
SHC1	0.001	0.092	-10000	0	-0.59	16	16

×

Signaling events mediated by PRL

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
CCNE1	0.011	0.052	-10000	0	-0.59	5	5
mol:Halofuginone	0.006	0.001	-10000	0	-10000	0	0
ITGA1	-0.02	0.14	-10000	0	-0.6	38	38
CDKN1A	-0.011	0.12	-10000	0	-0.47	31	31
PRL-3/alpha Tubulin	-0.003	0.036	-10000	0	-0.42	5	5
mol:Ca2+	-0.017	0.093	0.28	3	-0.47	26	29
AGT	-0.01	0.12	-10000	0	-0.62	26	26
CCNA2	-0.052	0.17	-10000	0	-0.61	11	11
TUBA1B	0.013	0.033	-10000	0	-0.59	2	2
EGR1	-0.044	0.17	-10000	0	-0.44	105	105
CDK2/Cyclin E1	-0.003	0.13	-10000	0	-0.47	30	30
MAPK3	0.025	0.03	-10000	0	-0.42	3	3
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.025	0.03	-10000	0	-0.42	3	3
PTP4A1	-0.013	0.13	-10000	0	-10000	0	0
PTP4A3	0.012	0.04	-10000	0	-0.59	3	3
PTP4A2	0.015	0	-10000	0	-10000	0	0
ITGB1	0.023	0.042	-10000	0	-0.42	6	6
SRC	0.013	0.035	-10000	0	-0.62	2	2
RAC1	0.014	0.06	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	0	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.01	0.13	-10000	0	-10000	0	0
RABGGTA	0.015	0	-10000	0	-10000	0	0
BCAR1	0.001	0.026	0.28	3	-0.47	1	4
RHOC	0.013	0.063	-10000	0	-0.35	2	2
RHOA	0.014	0.06	-10000	0	-10000	0	0
cell motility	0.017	0.065	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	-0.006	0.12	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.026	0.1	-10000	0	-0.44	40	40
ROCK1	0.017	0.065	-10000	0	-10000	0	0
RABGGTB	0.015	0	-10000	0	-10000	0	0
CDK2	0.001	0.091	-10000	0	-0.6	15	15
mitosis	-0.013	0.13	-10000	0	-10000	0	0
ATF5	0.006	0.073	-10000	0	-0.59	10	10

×

Circadian rhythm 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
chromatin modification	-0.009	0.068	-10000	0	-0.98	2	2
CLOCK	-0.006	0.12	-10000	0	-0.62	26	26
TIMELESS/CRY2	0.037	0.087	-10000	0	-1.1	2	2
DEC1/BMAL1	-0.018	0.085	-10000	0	-0.42	29	29
ATR	0.015	0	-10000	0	-10000	0	0
NR1D1	0.04	0.077	-10000	0	-1	2	2
ARNTL	0.019	0.004	-10000	0	-10000	0	0
TIMELESS	0.038	0.086	-10000	0	-0.94	3	3
NPAS2	0.008	0.08	-10000	0	-0.61	11	11
CRY2	0.009	0.065	-10000	0	-0.62	7	7
mol:CO	-0.015	0.014	0.096	10	-10000	0	10
CHEK1	0.013	0.033	-10000	0	-0.59	2	2
mol:HEME	0.015	0.014	-10000	0	-0.096	10	10
PER1	0.007	0.074	-10000	0	-0.62	9	9
BMAL/CLOCK/NPAS2	0.027	0.098	-10000	0	-0.37	37	37
BMAL1/CLOCK	0.032	0.12	-10000	0	-1.1	3	3
S phase of mitotic cell cycle	-0.009	0.068	-10000	0	-0.98	2	2
TIMELESS/CHEK1/ATR	-0.009	0.07	-10000	0	-1	2	2
mol:NADPH	0.015	0.014	-10000	0	-0.096	10	10
PER1/TIMELESS	0.036	0.09	-10000	0	-1.1	2	2
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	-0.016	0.12	-10000	0	-0.59	29	29

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.007	0.073	0.61	9	-10000	0	9
PI3K Class IB/PDE3B	0.007	0.073	-10000	0	-0.62	9	9
PDE3B	0.007	0.073	-10000	0	-0.62	9	9

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	-0.074	0.13	-10000	0	-0.36	78	78
Ran/GTP/Exportin 1/HDAC1	-0.002	0.022	-10000	0	-0.28	4	4
NF kappa B1 p50/RelA/I kappa B alpha	-0.017	0.14	-10000	0	-0.46	3	3
SUMO1	0.015	0	-10000	0	-10000	0	0
ZFPM1	0.014	0.025	-10000	0	-0.62	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.026	0	-10000	0	-10000	0	0
FKBP3	0.015	0	-10000	0	-10000	0	0
Histones	-0.033	0.065	-10000	0	-0.47	4	4
YY1/LSF	0.033	0.041	-10000	0	-0.44	3	3
SMG5	0.015	0	-10000	0	-10000	0	0
RAN	0.015	0	-10000	0	-10000	0	0
I kappa B alpha/HDAC3	-0.027	0.12	-10000	0	-0.46	2	2
I kappa B alpha/HDAC1	-0.013	0.094	-10000	0	-0.43	6	6
SAP18	0.015	0	-10000	0	-10000	0	0
RELA	-0.016	0.11	-10000	0	-0.26	78	78
HDAC1/Smad7	-0.003	0.036	-10000	0	-0.38	6	6
RANGAP1	0.015	0	-10000	0	-10000	0	0
HDAC3/TR2	-0.01	0.087	-10000	0	-0.3	2	2
NuRD/MBD3 Complex	0.053	0.029	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.008	0.1	-10000	0	-0.37	3	3
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	-0.003	0.11	-10000	0	-0.61	20	20
GATA1	0.004	0.061	-10000	0	-0.59	7	7
Mad/Max	0	0	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	0.062	0.035	-10000	0	-10000	0	0
RBBP7	0.015	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
RBBP4	0.015	0	-10000	0	-10000	0	0
MAX	0.015	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.015	0	-10000	0	-10000	0	0
NFKBIA	-0.021	0.098	-10000	0	-0.34	2	2
KAT2B	0.012	0.042	-10000	0	-0.61	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	0.05	0.024	-10000	0	-10000	0	0
SIN3 complex	-0.001	0.018	-10000	0	-0.34	2	2
SMURF1	0.015	0	-10000	0	-10000	0	0
CHD3	0.008	0.07	-10000	0	-0.62	8	8
SAP30	0.014	0.025	-10000	0	-0.62	1	1
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.013	0.035	-10000	0	-0.62	2	2
YY1/HDAC3	0.005	0.084	-10000	0	-0.33	2	2
YY1/HDAC2	0.034	0.027	-10000	0	-10000	0	0
YY1/HDAC1	0.032	0.041	-10000	0	-0.36	4	4
NuRD/MBD2 Complex (MeCP1)	0.053	0.029	-10000	0	-10000	0	0
PPARG	-0.08	0.14	-10000	0	-0.38	81	81
HDAC8/hEST1B	-0.001	0.015	-10000	0	-0.38	1	1
UBE2I	0.015	0	-10000	0	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-10000	0	-10000	0	0
TNFRSF1A	0.002	0.09	-10000	0	-0.61	14	14
HDAC3/SMRT (N-CoR2)	-0.011	0.089	-10000	0	-0.32	4	4
MBD3L2	0	0.001	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.003	0.036	-10000	0	-0.38	6	6
CREBBP	0.014	0.025	-10000	0	-0.62	1	1
NuRD/MBD3/MBD3L2 Complex	0.057	0.031	-10000	0	-10000	0	0
HDAC1	0.011	0.049	-10000	0	-0.62	4	4
HDAC3	-0.021	0.098	-10000	0	-0.34	2	2
HDAC2	0.015	0	-10000	0	-10000	0	0
YY1	0.033	0.032	-10000	0	-0.29	6	6
HDAC8	0.014	0.025	-10000	0	-0.62	1	1
SMAD7	0.013	0.035	-10000	0	-0.62	2	2
NCOR2	0.013	0.035	-10000	0	-0.62	2	2
MXD1	0.015	0	-10000	0	-10000	0	0
STAT3	0.029	0.03	-10000	0	-0.36	4	4
NFKB1	0.015	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.015	0	-10000	0	-10000	0	0
YY1/LSF/HDAC1	-0.006	0.042	-10000	0	-0.36	7	7
YY1/SAP30/HDAC1	-0.005	0.035	-10000	0	-0.33	5	5
EP300	0.012	0.043	-10000	0	-0.62	3	3
STAT3 (dimer non-phopshorylated)	0.029	0.03	-10000	0	-0.35	4	4
proteasomal ubiquitin-dependent protein catabolic process	-0.021	0.098	-10000	0	-0.34	2	2
histone deacetylation	0.053	0.029	-10000	0	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	0.002	0.084	-10000	0	-0.39	1	1
nuclear export	0.001	0.015	0.38	1	-10000	0	1
PRKACA	0.015	0	-10000	0	-10000	0	0
GATAD2B	0.015	0	-10000	0	-10000	0	0
GATAD2A	0.015	0	-10000	0	-10000	0	0
GATA2/HDAC3	-0.021	0.1	-10000	0	-0.35	22	22
GATA1/HDAC1	-0.007	0.055	-10000	0	-0.44	11	11
GATA1/HDAC3	-0.024	0.091	-10000	0	-0.35	9	9
CHD4	0.015	0	-10000	0	-10000	0	0
TNF-alpha/TNFR1A	-0.11	0.19	-10000	0	-0.44	164	164
SIN3/HDAC complex/Mad/Max	0.055	0.021	-10000	0	-10000	0	0
NuRD Complex	0.063	0.031	-10000	0	-10000	0	0
positive regulation of chromatin silencing	-0.033	0.064	-10000	0	-0.46	4	4
SIN3B	0.014	0.025	-10000	0	-0.62	1	1
MTA2	0.015	0	-10000	0	-10000	0	0
SIN3A	0.015	0	-10000	0	-10000	0	0
XPO1	0.015	0	-10000	0	-10000	0	0
SUMO1/HDAC1	0.034	0.026	-10000	0	-0.31	4	4
HDAC complex	-0.002	0.026	-10000	0	-0.34	4	4
GATA1/Fog1	-0.005	0.047	-10000	0	-0.43	8	8
FKBP25/HDAC1/HDAC2	-0.002	0.029	-10000	0	-0.38	4	4
TNF	-0.13	0.26	-10000	0	-0.6	152	152
negative regulation of cell growth	0.055	0.02	-10000	0	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.053	0.029	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.065	0.12	-10000	0	-0.34	78	78
SIN3/HDAC complex/NCoR1	0.052	0.024	-10000	0	-10000	0	0
TFCP2	0.012	0.043	-10000	0	-0.62	3	3
NR2C1	0.015	0	-10000	0	-10000	0	0
MBD3	0.015	0	-10000	0	-10000	0	0
MBD2	0.015	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	-0.004	0.034	-10000	0	-0.34	7	7
HDAC3	0.015	0	-10000	0	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0.011	-10000	0	-0.28	1	1
GATA1/HDAC4	-0.005	0.047	-10000	0	-0.43	8	8
GATA1/HDAC5	-0.005	0.047	-10000	0	-0.43	8	8
GATA2/HDAC5	-0.014	0.08	-10000	0	-0.46	20	20
HDAC5/BCL6/BCoR	-0.002	0.035	-10000	0	-0.49	3	3
HDAC9	0.005	0.081	-10000	0	-0.62	11	11
Glucocorticoid receptor/Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
HDAC4/ANKRA2	-0.001	0.018	-10000	0	-0.46	1	1
HDAC5/YWHAB	-0.001	0.018	-10000	0	-0.46	1	1
NPC/RanGAP1/SUMO1/Ubc9	0.026	0	-10000	0	-10000	0	0
GATA2	-0.003	0.11	-10000	0	-0.61	20	20
HDAC4/RFXANK	-0.001	0.024	-10000	0	-0.44	2	2
BCOR	0.012	0.042	-10000	0	-0.61	3	3
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0.014	0.025	-10000	0	-0.62	1	1
HDAC5	0.014	0.025	-10000	0	-0.62	1	1
GNB1/GNG2	-0.004	0.043	-10000	0	-0.46	6	6
Histones	0.042	0.046	-10000	0	-0.73	1	1
ADRBK1	0.015	0	-10000	0	-10000	0	0
HDAC4	0.014	0.025	-10000	0	-0.62	1	1
XPO1	0.015	0	-10000	0	-10000	0	0
HDAC5/ANKRA2	-0.001	0.018	-10000	0	-0.46	1	1
HDAC4/Ubc9	-0.001	0.018	-10000	0	-0.46	1	1
HDAC7	0.015	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.018	-10000	0	-0.46	1	1
TUBA1B	0.013	0.033	-10000	0	-0.59	2	2
HDAC6	0.015	0	-10000	0	-10000	0	0
HDAC5/RFXANK	-0.001	0.024	-10000	0	-0.44	2	2
CAMK4	-0.15	0.28	-10000	0	-0.61	176	176
Tubulin/HDAC6	-0.003	0.032	-10000	0	-0.37	5	5
SUMO1	0.015	0	-10000	0	-10000	0	0
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.015	0	-10000	0	-10000	0	0
GATA1	0.004	0.061	-10000	0	-0.59	7	7
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.015	0	-10000	0	-10000	0	0
NR3C1	0.015	0	-10000	0	-10000	0	0
SUMO1/HDAC4	0.035	0.013	-10000	0	-0.31	1	1
SRF	0.015	0	-10000	0	-10000	0	0
HDAC4/YWHAB	-0.001	0.018	-10000	0	-0.46	1	1
Tubulin	-0.003	0.038	-10000	0	-0.44	5	5
HDAC4/14-3-3 E	-0.001	0.018	-10000	0	-0.46	1	1
GNB1	0.015	0	-10000	0	-10000	0	0
RANGAP1	0.015	0	-10000	0	-10000	0	0
BCL6/BCoR	-0.002	0.03	-10000	0	-0.44	3	3
HDAC4/HDAC3/SMRT (N-CoR2)	-0.002	0.025	-10000	0	-0.38	3	3
HDAC4/SRF	-0.097	0.16	-10000	0	-0.37	176	176
HDAC4/ER alpha	-0.016	0.082	-10000	0	-0.44	24	24
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.042	0.046	-10000	0	-0.72	1	1
cell motility	-0.003	0.032	-10000	0	-0.37	5	5
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.015	0	-10000	0	-10000	0	0
HDAC7/HDAC3	0	0	-10000	0	-10000	0	0
BCL6	0.015	0	-10000	0	-10000	0	0
HDAC4/CaMK II delta B	0.014	0.025	-10000	0	-0.62	1	1
Hsp90/HDAC6	0	0	-10000	0	-10000	0	0
ESR1	-0.006	0.11	-10000	0	-0.61	23	23
HDAC6/HDAC11	-0.001	0.025	-10000	0	-0.46	2	2
Ran/GTP/Exportin 1	0	0	-10000	0	-10000	0	0
NPC	0	0	-10000	0	-10000	0	0
MEF2C	-0.002	0.1	-10000	0	-0.59	19	19
RAN	0.015	0	-10000	0	-10000	0	0
HDAC4/MEF2C	-0.01	0.052	-10000	0	-10000	0	0
GNG2	0.009	0.06	-10000	0	-0.62	6	6
NCOR2	0.013	0.035	-10000	0	-0.62	2	2
TUBB2A	0.012	0.043	-10000	0	-0.62	3	3
HDAC11	0.013	0.035	-10000	0	-0.62	2	2
HSP90AA1	0.015	0	-10000	0	-10000	0	0
RANBP2	0.015	0	-10000	0	-10000	0	0
ANKRA2	0.015	0	-10000	0	-10000	0	0
RFXANK	0.014	0.023	-10000	0	-0.59	1	1
nuclear import	-0.034	0.02	0.34	2	-10000	0	2

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.062	0.2	-10000	0	-0.6	83	83
CLTC	0.034	0.024	-10000	0	-0.35	1	1
calcium ion-dependent exocytosis	0.022	0.041	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.002	0.025	-10000	0	-0.32	4	4
EXOC4	0.015	0	-10000	0	-10000	0	0
CD59	0.029	0.021	-10000	0	-10000	0	0
CPE	0.013	0.063	-10000	0	-0.39	16	16
CTNNB1	0.015	0	-10000	0	-10000	0	0
membrane fusion	0.02	0.044	-10000	0	-10000	0	0
CTNND1	0.036	0.025	-10000	0	-10000	0	0
DNM2	0.015	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.032	0.029	-10000	0	-0.41	1	1
TSHR	-0.14	0.2	-10000	0	-0.38	268	268
INS	0.009	0.043	-10000	0	-0.53	4	4
BIN1	0.014	0.025	-10000	0	-0.62	1	1
mol:Choline	0.02	0.044	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.03	-10000	0	-0.36	4	4
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.015	0	-10000	0	-10000	0	0
mol:Ca2+	-0.002	0.024	-10000	0	-0.32	4	4
JUP	0.026	0.035	-10000	0	-0.3	3	3
ASAP2/amphiphysin II	-0.001	0.013	-10000	0	-0.35	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	-0.015	0.095	-10000	0	-0.32	15	15
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	0.007	0.074	-10000	0	-0.62	9	9
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.015	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.051	0.01	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.015	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.026	0.058	0.41	2	-10000	0	2
positive regulation of phagocytosis	0.022	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.005	0.045	-10000	0	-0.39	9	9
ACAP1	0.016	0.041	-10000	0	-0.29	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.009	0.083	-10000	0	-0.3	4	4
clathrin heavy chain/ACAP1	0.036	0.033	-10000	0	-0.34	1	1
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.013	0.033	-10000	0	-0.59	2	2
exocyst	0.051	0.01	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.036	0.025	-10000	0	-10000	0	0
NME1	0.02	0.03	-10000	0	-0.36	4	4
clathrin coat assembly	0.034	0.024	-10000	0	-0.35	1	1
IL2RA	-0.031	0.094	-10000	0	-0.29	5	5
VAMP3	0.022	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.037	0.088	-10000	0	-0.28	39	39
EXOC6	0.015	0	-10000	0	-10000	0	0
PLD1	-0.016	0.063	-10000	0	-0.29	31	31
PLD2	0	0.011	-10000	0	-0.29	1	1
EXOC5	0.015	0	-10000	0	-10000	0	0
PIP5K1C	0.032	0.03	-10000	0	-0.41	1	1
SDC1	0.007	0.064	-10000	0	-0.29	1	1
ARF6/GDP	0.019	0.029	-10000	0	-0.36	4	4
EXOC7	0.014	0.023	-10000	0	-0.59	1	1
E-cadherin/beta catenin	-0.026	0.059	-10000	0	-0.42	2	2
mol:Phosphatidic acid	0.02	0.044	-10000	0	-10000	0	0
endocytosis	0.001	0.013	0.34	1	-10000	0	1
SCAMP2	0.015	0	-10000	0	-10000	0	0
ADRB2	0.028	0.071	-10000	0	-0.3	27	27
EXOC3	0.015	0	-10000	0	-10000	0	0
ASAP2	0.015	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.028	0.027	-10000	0	-0.32	4	4
KLC1	0.015	0	-10000	0	-10000	0	0
AVPR2	0.03	0.06	-10000	0	-0.32	5	5
RALA	0.015	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.021	0.05	-10000	0	-0.38	2	2

×

PDGFR-beta signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.019	0.078	-9999	-0.42	9	9
PDGFB-D/PDGFRB/SLAP	-0.02	0.097	-9999	-0.44	34	34
PDGFB-D/PDGFRB/APS/CBL	-0.012	0.071	-9999	-0.41	19	19
AKT1	0.067	0.038	-9999	-0.47	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.017	0.091	-9999	-0.43	9	9
PIK3CA	0.015	0	-9999	-10000	0	0
FGR	0	0.035	-9999	-10000	0	0
mol:Ca2+	0.027	0.043	-9999	-10000	0	0
MYC	0.026	0.15	-9999	-0.81	18	18
SHC1	0.001	0.092	-9999	-0.59	16	16
HRAS/GDP	0.011	0.032	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	-0.004	0.043	-9999	-0.41	7	7
GRB10	0.006	0.075	-9999	-0.6	10	10
PTPN11	0.013	0.035	-9999	-0.62	2	2
GO:0007205	0.027	0.043	-9999	-10000	0	0
PTEN	0.015	0	-9999	-10000	0	0
GRB2	0.014	0.023	-9999	-0.59	1	1
GRB7	-0.038	0.16	-9999	-0.59	54	54
PDGFB-D/PDGFRB/SHP2	-0.002	0.045	-9999	-0.43	7	7
PDGFB-D/PDGFRB/GRB10	-0.007	0.068	-9999	-0.46	14	14
cell cycle arrest	-0.02	0.097	-9999	-0.44	34	34
HRAS	0.015	0	-9999	-10000	0	0
HIF1A	0.072	0.038	-9999	-0.41	1	1
GAB1	0.018	0.071	-9999	-0.4	4	4
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.022	0.074	-9999	-0.4	4	4
PDGFB-D/PDGFRB	0.008	0.037	-9999	-0.36	5	5
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	-0.001	0.037	-9999	-0.42	5	5
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.022	0.085	-9999	-0.46	10	10
positive regulation of MAPKKK cascade	-0.002	0.045	-9999	-0.43	7	7
PIK3R1	0.012	0.043	-9999	-0.62	3	3
mol:IP3	0.027	0.044	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.035	0.12	-9999	-0.44	57	57
SHB	0.011	0.049	-9999	-0.62	4	4
BLK	-0.026	0.074	-9999	-0.52	5	5
PTPN2	0.015	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	-0.001	0.037	-9999	-0.42	5	5
BCAR1	0.014	0.025	-9999	-0.62	1	1
VAV2	0.022	0.081	-9999	-0.45	3	3
CBL	0.014	0.025	-9999	-0.62	1	1
PDGFB-D/PDGFRB/DEP1	-0.002	0.044	-9999	-0.43	7	7
LCK	-0.057	0.15	-9999	-0.54	48	48
PDGFRB	0.011	0.053	-9999	-0.59	5	5
ACP1	0.015	0	-9999	-10000	0	0
HCK	-0.008	0.084	-9999	-0.62	10	10
ABL1	0.018	0.062	-9999	-0.36	4	4
PDGFB-D/PDGFRB/CBL	0.018	0.068	-9999	-0.42	1	1
PTPN1	0.015	0.003	-9999	-10000	0	0
SNX15	0.015	0	-9999	-10000	0	0
STAT3	0.015	0	-9999	-10000	0	0
STAT1	0.001	0.092	-9999	-0.59	16	16
cell proliferation	0.028	0.14	-9999	-0.7	18	18
SLA	-0.012	0.13	-9999	-0.61	29	29
actin cytoskeleton reorganization	0.052	0.046	-9999	-0.6	1	1
SRC	0	0.046	-9999	-0.61	2	2
PI3K	-0.003	0.032	-9999	-0.53	1	1
PDGFB-D/PDGFRB/GRB7/SHC	-0.039	0.12	-9999	-0.39	67	67
SH2B2	0.001	0.094	-9999	-0.62	15	15
PLCgamma1/SPHK1	0.017	0.094	-9999	-0.44	9	9
LYN	0	0.049	-9999	-0.64	2	2
LRP1	0.013	0.035	-9999	-0.62	2	2
SOS1	0.015	0	-9999	-10000	0	0
STAT5B	0.015	0	-9999	-10000	0	0
STAT5A	0.005	0.081	-9999	-0.62	11	11
NCK1-2/p130 Cas	0.002	0.03	-9999	-10000	0	0
SPHK1	-0.025	0.15	-9999	-0.6	44	44
EDG1	0	0.002	-9999	-10000	0	0
mol:DAG	0.027	0.044	-9999	-10000	0	0
PLCG1	0.027	0.044	-9999	-10000	0	0
NHERF/PDGFRB	-0.003	0.033	-9999	-0.35	6	6
YES1	0	0.045	-9999	-0.58	2	2
cell migration	-0.003	0.033	-9999	-0.35	6	6
SHC/Grb2/SOS1	-0.004	0.058	-9999	-0.57	3	3
SLC9A3R2	0.015	0	-9999	-10000	0	0
SLC9A3R1	0.014	0.025	-9999	-0.62	1	1
NHERF1-2/PDGFRB/PTEN	-0.003	0.03	-9999	-0.34	1	1
FYN	0.003	0.031	-9999	-10000	0	0
DOK1	0.036	0.035	-9999	-10000	0	0
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.014	0.023	-9999	-0.59	1	1
RAC1	0.03	0.1	-9999	-0.49	6	6
PRKCD	0.023	0.078	-9999	-0.36	6	6
FER	0.029	0.061	-9999	-0.34	13	13
MAPKKK cascade	-0.009	0.055	-9999	-0.56	3	3
RASA1	0.037	0.032	-9999	-10000	0	0
NCK1	0.015	0	-9999	-10000	0	0
NCK2	0.015	0	-9999	-10000	0	0
p62DOK/Csk	0.014	0.036	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	-0.004	0.051	-9999	-0.44	9	9
chemotaxis	0.018	0.061	-9999	-0.36	4	4
STAT1-3-5/STAT1-3-5	-0.012	0.056	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	-0.002	0.038	-9999	-0.44	5	5
PTPRJ	0.013	0.034	-9999	-0.61	2	2

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	0.027	0.017	-10000	0	-0.42	1	1
BAD/BCL-XL/YWHAZ	0	0.012	-10000	0	-10000	0	0
CDKN1B	0.044	0.013	-10000	0	-10000	0	0
CDKN1A	0.018	0.089	-10000	0	-0.3	26	26
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.015	0	-10000	0	-10000	0	0
FOXO3	0.043	0.019	-10000	0	-0.3	1	1
AKT1	-0.001	0.01	-10000	0	-10000	0	0
BAD	0.015	0	-10000	0	-10000	0	0
AKT3	0.017	0.047	-10000	0	-0.44	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	0.042	0.031	-10000	0	-0.39	3	3
AKT1/ASK1	-0.005	0.037	-10000	0	-0.29	11	11
BAD/YWHAZ	0	0	-10000	0	-10000	0	0
RICTOR	0.013	0.035	-10000	0	-0.62	2	2
RAF1	0.015	0	-10000	0	-10000	0	0
JNK cascade	0.005	0.036	0.28	11	-10000	0	11
TSC1	0.043	0.023	-10000	0	-0.3	2	2
YWHAZ	0.015	0	-10000	0	-10000	0	0
AKT1/RAF1	0.043	0.013	-10000	0	-10000	0	0
EP300	0.012	0.043	-10000	0	-0.62	3	3
mol:GDP	0.036	0.014	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	0.043	0.022	-10000	0	-0.43	1	1
YWHAQ	0.015	0	-10000	0	-10000	0	0
TBC1D4	0.029	0.013	-10000	0	-0.31	1	1
MAP3K5	0.005	0.081	-10000	0	-0.62	11	11
MAPKAP1	0.015	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.021	0.057	0.24	1	-10000	0	1
YWHAH	0.003	0.083	-10000	0	-0.59	13	13
AKT1S1	0.044	0.013	-10000	0	-10000	0	0
CASP9	0.043	0.018	-10000	0	-10000	0	0
YWHAB	0.015	0	-10000	0	-10000	0	0
p27Kip1/KPNA1	0.051	0.013	-10000	0	-10000	0	0
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	-0.002	0.025	-10000	0	-0.38	3	3
YWHAE	0.015	0	-10000	0	-10000	0	0
SRC	0.013	0.035	-10000	0	-0.62	2	2
AKT2/p21CIP1	-0.022	0.073	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.022	0.005	-10000	0	-10000	0	0
CHUK	0.044	0.013	-10000	0	-10000	0	0
BAD/BCL-XL	0.058	0.017	-10000	0	-10000	0	0
mTORC2	-0.001	0.019	-10000	0	-0.36	2	2
AKT2	0.02	0.015	-10000	0	-0.37	1	1
FOXO1-3a-4/14-3-3 family	0.039	0.063	-10000	0	-10000	0	0
PDPK1	0.014	0.025	-10000	0	-0.62	1	1
MDM2	0.038	0.046	-10000	0	-0.35	1	1
MAPKKK cascade	-0.042	0.013	-10000	0	-10000	0	0
MDM2/Cbp/p300	0.05	0.05	-10000	0	-0.39	1	1
TSC1/TSC2	0.05	0.028	-10000	0	-0.41	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.039	-10000	0	-0.37	1	1
glucose import	-0.008	0.12	-10000	0	-0.32	83	83
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.037	0.01	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.008	0.12	-10000	0	-0.32	83	83
GSK3A	0.044	0.013	-10000	0	-10000	0	0
FOXO1	0.043	0.019	-10000	0	-0.3	1	1
GSK3B	0.044	0.013	-10000	0	-10000	0	0
SFN	-0.12	0.25	-10000	0	-0.6	141	141
G1/S transition of mitotic cell cycle	0.051	0.013	-10000	0	-10000	0	0
p27Kip1/14-3-3 family	0.016	0.08	-10000	0	-0.37	1	1
PRKACA	0.015	0	-10000	0	-10000	0	0
KPNA1	0.015	0	-10000	0	-10000	0	0
HSP90AA1	0.015	0	-10000	0	-10000	0	0
YWHAG	0.012	0.04	-10000	0	-0.59	3	3
RHEB	0.015	0	-10000	0	-10000	0	0
CREBBP	0.014	0.025	-10000	0	-0.62	1	1

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.031	0.094	-9999	-10000	0	0
PLK1	0.035	0.25	-9999	-1	13	13
CDKN1B	0.095	0.13	-9999	-10000	0	0
FOXO3	0.057	0.18	-9999	-0.6	9	9
KAT2B	0.02	0.045	-9999	-0.6	3	3
FOXO1/SIRT1	0.003	0.056	-9999	-10000	0	0
CAT	0.062	0.18	-9999	-0.66	7	7
CTNNB1	0.015	0	-9999	-10000	0	0
AKT1	0.025	0.03	-9999	-0.6	1	1
FOXO1	0.036	0.067	-9999	-0.3	1	1
MAPK10	0.04	0.035	-9999	-0.32	5	5
mol:GTP	0.002	0.002	-9999	-10000	0	0
FOXO4	0.1	0.067	-9999	-0.51	1	1
response to oxidative stress	0.01	0.022	-9999	-10000	0	0
FOXO3A/SIRT1	-0.007	0.15	-9999	-0.56	10	10
XPO1	0.016	0.001	-9999	-10000	0	0
EP300	0.014	0.043	-9999	-0.62	3	3
BCL2L11	0.034	0.086	-9999	-1.4	2	2
FOXO1/SKP2	0.035	0.07	-9999	-0.5	1	1
mol:GDP	0.01	0.022	-9999	-10000	0	0
RAN	0.017	0.002	-9999	-10000	0	0
GADD45A	0.077	0.16	-9999	-0.52	19	19
YWHAQ	0.015	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.055	0.069	-9999	-10000	0	0
MST1	-0.018	0.16	-9999	-0.61	43	43
CSNK1D	0.015	0	-9999	-10000	0	0
CSNK1E	0.015	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.02	0.1	-9999	-0.42	1	1
YWHAB	0.015	0	-9999	-10000	0	0
MAPK8	0.038	0.045	-9999	-0.32	9	9
MAPK9	0.043	0.016	-9999	-10000	0	0
YWHAG	0.012	0.04	-9999	-0.59	3	3
YWHAE	0.015	0	-9999	-10000	0	0
YWHAZ	0.015	0	-9999	-10000	0	0
SIRT1	0.007	0.012	-9999	-10000	0	0
SOD2	0.083	0.2	-9999	-0.55	19	19
RBL2	0.083	0.14	-9999	-1.2	1	1
RAL/GDP	0.03	0.021	-9999	-10000	0	0
CHUK	0.023	0.017	-9999	-10000	0	0
Ran/GTP	0.015	0.006	-9999	-10000	0	0
CSNK1G2	0.015	0	-9999	-10000	0	0
RAL/GTP	0.038	0.022	-9999	-10000	0	0
CSNK1G1	0.014	0.023	-9999	-0.59	1	1
FASLG	0.01	0.11	-9999	-10000	0	0
SKP2	0.009	0.064	-9999	-0.61	7	7
USP7	0.017	0.002	-9999	-10000	0	0
IKBKB	0.023	0.017	-9999	-10000	0	0
CCNB1	0.032	0.24	-9999	-0.66	15	15
FOXO1-3a-4/beta catenin	0.019	0.11	-9999	-0.42	1	1
proteasomal ubiquitin-dependent protein catabolic process	0.035	0.07	-9999	-0.49	1	1
CSNK1A1	0.015	0	-9999	-10000	0	0
SGK1	0.016	0.067	-9999	-0.61	7	7
CSNK1G3	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.026	0.01	-9999	-10000	0	0
ZFAND5	0.1	0.06	-9999	-10000	0	0
SFN	-0.12	0.25	-9999	-0.6	141	141
CDK2	0.002	0.092	-9999	-0.6	15	15
FOXO3A/14-3-3	0.031	0.089	-9999	-10000	0	0
CREBBP	0.015	0.027	-9999	-0.62	1	1
FBXO32	0.053	0.2	-9999	-1.1	4	4
BCL6	0.085	0.13	-9999	-10000	0	0
RALB	0.017	0.001	-9999	-10000	0	0
RALA	0.017	0.001	-9999	-10000	0	0
YWHAH	0.003	0.083	-9999	-0.59	13	13

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.015	0	-9999	-10000	0	0
SMAD2	0.019	0.018	-9999	-0.26	1	1
SMAD3	0.045	0.033	-9999	-10000	0	0
SMAD3/SMAD4	0.054	0.013	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	-0.001	0.015	-9999	-0.38	1	1
SMAD2/SMAD2/SMAD4	-0.001	0.012	-9999	-10000	0	0
PPM1A	0.015	0	-9999	-10000	0	0
CALM1	0.015	0	-9999	-10000	0	0
SMAD2/SMAD4	0.026	0.015	-9999	-10000	0	0
MAP3K1	0.012	0.046	-9999	-0.59	4	4
TRAP-1/SMAD4	-0.012	0.072	-9999	-0.46	17	17
MAPK3	0.015	0	-9999	-10000	0	0
MAPK1	0.015	0	-9999	-10000	0	0
NUP214	0.015	0	-9999	-10000	0	0
CTDSP1	0.015	0	-9999	-10000	0	0
CTDSP2	0.001	0.092	-9999	-0.59	16	16
CTDSPL	0.014	0.025	-9999	-0.62	1	1
KPNB1	0.015	0	-9999	-10000	0	0
TGFBRAP1	-0.001	0.1	-9999	-0.62	17	17
UBE2I	0.015	0	-9999	-10000	0	0
NUP153	0.015	0	-9999	-10000	0	0
KPNA2	0.014	0.023	-9999	-0.59	1	1
PIAS4	0.014	0.025	-9999	-0.62	1	1

×

mTOR signaling pathway

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
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.011	0.049	-10000	0	-0.62	4	4
mol:PIP3	-0.004	0.036	-10000	0	-0.3	10	10
FRAP1	0.017	0.015	-10000	0	-10000	0	0
AKT1	0.03	0.036	-10000	0	-0.29	3	3
INSR	0.014	0.025	-10000	0	-0.62	1	1
Insulin Receptor/Insulin	-0.003	0.037	-10000	0	-0.39	6	6
mol:GTP	-0.004	0.031	-10000	0	-0.4	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.009	-10000	0	-10000	0	0
TSC2	0.014	0.025	-10000	0	-0.62	1	1
RHEB/GDP	-0.004	0.027	-10000	0	-0.35	1	1
TSC1	0.013	0.035	-10000	0	-0.62	2	2
Insulin Receptor/IRS1	0.015	0.041	-10000	0	-0.36	8	8
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.009	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.014	0.025	-10000	0	-0.62	1	1
RPS6KB1	0.031	0.021	-10000	0	-10000	0	0
MAP3K5	0.006	0.052	-10000	0	-0.4	11	11
PIK3R1	0.012	0.043	-10000	0	-0.62	3	3
apoptosis	0.006	0.052	-10000	0	-0.4	11	11
mol:LY294002	0	0	-10000	0	-0.002	7	7
EIF4B	0.038	0.019	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.019	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1	-0.001	0.015	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.024	0.042	-10000	0	-0.32	10	10
mTOR/RHEB/GTP/Raptor/GBL	0.035	0.02	-10000	0	-10000	0	0
FKBP1A	0.015	0.023	-10000	0	-0.59	1	1
RHEB/GTP	-0.004	0.026	-10000	0	-0.34	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	7	7
FKBP12/Rapamycin	-0.001	0.017	-10000	0	-0.43	1	1
PDPK1	-0.004	0.035	-10000	0	-0.29	4	4
EIF4E	0.015	0	-10000	0	-10000	0	0
ASK1/PP5C	0.015	0.081	-10000	0	-0.61	11	11
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.02	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.004	0.033	-10000	0	-0.44	1	1
tumor necrosis factor receptor activity	0	0	0.002	7	-10000	0	7
RPS6	0.013	0.033	-10000	0	-0.59	2	2
PPP5C	0.015	0	-10000	0	-10000	0	0
EIF4G1	0.015	0	-10000	0	-10000	0	0
IRS1	0.006	0.041	-10000	0	-0.39	7	7
INS	-0.004	0.053	-10000	0	-0.62	5	5
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.004	0.033	-10000	0	-0.29	3	3
EIF4EBP1	0.001	0.12	-10000	0	-1.1	7	7
PIK3CA	0.015	0	-10000	0	-10000	0	0
PPP2R5D	0.025	0.014	-10000	0	-10000	0	0
peptide biosynthetic process	0.017	0.034	-10000	0	-0.34	6	6
RHEB	0.015	0	-10000	0	-10000	0	0
EIF4A1	0.015	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-10000	0	0
EEF2	0.018	0.034	-10000	0	-0.34	6	6
eIF4E/4E-BP1	0.01	0.11	-10000	0	-1.1	7	7

×

Alternative 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0	0	-9999	-10000	0	0
FBXW11	0.015	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.015	0	-9999	-10000	0	0
CHUK	0.015	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.003	0.03	-9999	-10000	0	0
NFKB1	0.015	0	-9999	-10000	0	0
MAP3K14	0.015	0	-9999	-10000	0	0
NF kappa B1 p50/RelB	-0.004	0.04	-9999	-0.43	6	6
RELB	0.01	0.057	-9999	-0.59	6	6
NFKB2	0.014	0.025	-9999	-0.62	1	1
NF kappa B2 p52/RelB	-0.004	0.038	-9999	-0.37	7	7
regulation of B cell activation	-0.004	0.037	-9999	-0.37	7	7

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.049	-9999	-0.62	4	4
Ran/GTP/Exportin 1/HDAC4	0	0.01	-9999	-10000	0	0
MDM2/SUMO1	0.03	0.044	-9999	-0.28	13	13
HDAC4	0.014	0.025	-9999	-0.62	1	1
Ran/GTP/Exportin 1/HDAC1	-0.002	0.02	-9999	-10000	0	0
SUMO1	0.015	0	-9999	-10000	0	0
NPC/RanGAP1/SUMO1	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
XPO1	0.034	0	-9999	-10000	0	0
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.015	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.015	0	-9999	-10000	0	0
SUMO1/HDAC4	0.035	0.013	-9999	-0.31	1	1
SUMO1/HDAC1	0.034	0.026	-9999	-0.31	4	4
RANGAP1	0.015	0	-9999	-10000	0	0
MDM2/SUMO1/SUMO1	-0.007	0.046	-9999	-0.31	15	15
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.026	0	-9999	-10000	0	0
Ran/GTP	0.032	0	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.003	0.083	-9999	-0.59	13	13
UBE2I	0.015	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
PIAS2	0.015	0	-9999	-10000	0	0
PIAS1	0.013	0.035	-9999	-0.62	2	2
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Arf1 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
coatomer protein complex	0	0.01	-9999	-0.26	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.024	0.008	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.001	-9999	-10000	0	0
CLTB	0.015	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0.031	0	-9999	-10000	0	0
CD4	0.009	0.062	-9999	-0.59	7	7
CLTA	0.015	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.013	0.017	-9999	-0.43	1	1
mol:PI-4-5-P2	0	0.008	-9999	-0.2	1	1
ARF1/GTP	0	0.004	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	0.032	0.012	-9999	-0.28	1	1
mol:Choline	0	0.008	-9999	-0.21	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.015	0	-9999	-10000	0	0
DDEF1	0	0.008	-9999	-0.21	1	1
ARF1/GDP	-0.001	0.012	-9999	-0.3	1	1
AP2M1	0.015	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0.02	0	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	0	0.012	-9999	-0.3	1	1
ARFIP2	0	0.001	-9999	-10000	0	0
COPA	0.015	0	-9999	-10000	0	0
RAC1	0.015	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.031	0.002	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.015	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.002	-9999	-10000	0	0
AP2A1	0.015	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.033	0.007	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.002	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.001	-9999	-10000	0	0
CYTH2	0.015	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.001	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.041	0.019	-9999	-10000	0	0
PLD2	0	0.008	-9999	-0.21	1	1
ARF-GAP1/v-SNARE	0.013	0.017	-9999	-0.43	1	1
PIP5K1A	0	0.008	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0.006	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0.008	-9999	-0.21	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.013	0.017	-9999	-0.43	1	1
GOSR2	0	0.003	-9999	-10000	0	0
USO1	0	0.003	-9999	-10000	0	0
GBF1	-0.001	0.024	-9999	-0.43	2	2
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.004	0.036	-9999	-0.36	7	7

pid_entity	TCGA.WY.A85E	TCGA.WY.A85D	TCGA.WY.A85C	TCGA.WY.A85B
109_MAP3K5	0.065	-0.22	0.065	-0.22
47_PPARGC1A	0.015	0.015	0.015	0.015
105_BMP4	0.015	0.015	0.015	0.015
105_BMP6	0.015	0.015	0.015	0.015
105_BMP7	0.015	0.015	0.015	0.015
105_BMP2	0.015	0.015	0.015	0.015
131_RELN/VLDLR	0	0	-0.34	0
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.015	0.015
84_STAT5B	0.014	0.054	-0.12	0.13
84_STAT5A	0.014	0.054	-0.12	0.13