PARADIGM pathway analysis of mRNASeq expression data

Prostate Adenocarcinoma (Primary solid tumor)

17 October 2014 | analyses__2014_10_17

Maintainer Information

Citation Information

Maintained by TCGA GDAC Team (Broad Institute/MD Anderson Cancer Center/Harvard Medical School)

Cite as Broad Institute TCGA Genome Data Analysis Center (2014): PARADIGM pathway analysis of mRNASeq expression data. Broad Institute of MIT and Harvard. doi:10.7908/C1RJ4HDH

Overview

Introduction

PAthway Representation and Analysis by Direct Inference on Graphical Models (PARADIGM) predicts the activity of a diverse set of molecular concepts such as genes, complexes, and processes. The predicted activities are called Inferred Pathway Levels (IPLs) and are derived from a probabilistic belief propagation strategy that incorporates multimodal data such as copy number and gene expression estimates with a concept's pathway context.

Summary

There were 49 significant pathways identified in this analysis.

Table 1. Get Full Table Top 10 out of 131 pathways in order of significance.

Pathway.Name	Avg.Num.Perturbations
Ephrin A reverse signaling	113
Glypican 2 network	106
FOXM1 transcription factor network	90
Angiopoietin receptor Tie2-mediated signaling	87
Aurora B signaling	82
Signaling mediated by p38-alpha and p38-beta	70
Endothelins	64
IL23-mediated signaling events	61
Syndecan-1-mediated signaling events	58
Glucocorticoid receptor regulatory network	56

Results

Summary Table

The following list describes the columns found in Table 2.

Pathway.Name = Full pathway name of curated PARADIGM pathway
Significance.Ratio = (Ave.Num.Perturbations)/ (Cohort Size) where Cohort Size is 486 . Pathway is significant if Significance.Ratio > 0.05 .
Avg.Num.Perturbations = Average number of samples with perturbations across the pathway concepts determined by a background permutation model (>2 standard deviations away from the permuted distribution)
Total.Perturbations = Total number of perturbed concepts across all samples (>2 standard deviations away from the permuted distribution)
Num.Entities = Number of concepts that belong to the pathway
Min.Mean.Truth = Minimum IPL for concepts in the pathway among real samples
Max.Mean.Truth = Maximum IPL for concepts in the pathway among real samples
Min.Mean.Within = Minimum IPL for concepts in the pathway among null samples using "within permutation" (values are permuted across genes)
Max.Mean.Within = Maximum IPL for concepts in the pathway among null samples using "within permutation" (values are permuted across genes)
Min.Mean.Any = Minimum IPL for concepts in the pathway among null samples using "any permutation" (values are permuted across samples and genes)
Max.Mean.Any = Maximum IPL for concepts in the pathway among null samples using "any permutation" (values are permuted across samples and genes).

Table 2. Get Full Table This summary table provides a report of cancer type specific pathway perturbations. Click on the links in the first column to display more detailed results for each pathway. A pathway is defined as significant (red number in Significance.Ratio column) if the Ave.Num.Perturbationsis > 5% of the cohort size ( 486 ).

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
Ephrin A reverse signaling	0.2325	113	791	7	-0.11	0	1000	-1000	-0.022	-1000
Glypican 2 network	0.2181	106	425	4	-0.14	-0.11	1000	-1000	-0.016	-1000
FOXM1 transcription factor network	0.1852	90	4637	51	-0.42	0.013	1000	-1000	-0.17	-1000
Angiopoietin receptor Tie2-mediated signaling	0.1790	87	7703	88	-0.32	0.06	1000	-1000	-0.077	-1000
Aurora B signaling	0.1687	82	5533	67	-0.26	0.013	1000	-1000	-0.052	-1000
Signaling mediated by p38-alpha and p38-beta	0.1440	70	3114	44	-0.18	0.013	1000	-1000	-0.04	-1000
Endothelins	0.1317	64	6178	96	-0.17	0.013	1000	-1000	-0.073	-1000
IL23-mediated signaling events	0.1255	61	3671	60	-0.42	0.013	1000	-1000	-0.16	-1000
Syndecan-1-mediated signaling events	0.1193	58	1997	34	-0.31	0.013	1000	-1000	-0.046	-1000
Glucocorticoid receptor regulatory network	0.1152	56	6469	114	-0.52	0.28	1000	-1000	-0.064	-1000
IL4-mediated signaling events	0.1091	53	4843	91	-0.6	0.5	1000	-1000	-0.16	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0967	47	3743	78	-0.18	0.17	1000	-1000	-0.056	-1000
Aurora C signaling	0.0947	46	325	7	-0.18	0.009	1000	-1000	-0.023	-1000
Integrins in angiogenesis	0.0947	46	3866	84	-0.22	0.027	1000	-1000	-0.084	-1000
Signaling events mediated by the Hedgehog family	0.0905	44	2319	52	-0.091	0.087	1000	-1000	-0.04	-1000
Glypican 1 network	0.0905	44	2150	48	-0.2	0.022	1000	-1000	-0.031	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0905	44	3043	68	-0.26	0.081	1000	-1000	-0.11	-1000
Ras signaling in the CD4+ TCR pathway	0.0905	44	749	17	-0.099	0.018	1000	-1000	-0.029	-1000
Thromboxane A2 receptor signaling	0.0885	43	4590	105	-0.13	0.035	1000	-1000	-0.061	-1000
IL6-mediated signaling events	0.0844	41	3078	75	-0.2	0.049	1000	-1000	-0.069	-1000
LPA receptor mediated events	0.0802	39	4045	102	-0.31	0.027	1000	-1000	-0.079	-1000
PLK1 signaling events	0.0782	38	3310	85	-0.21	0.03	1000	-1000	-0.038	-1000
amb2 Integrin signaling	0.0782	38	3154	82	-0.31	0.018	1000	-1000	-0.068	-1000
Reelin signaling pathway	0.0761	37	2110	56	-0.17	0.033	1000	-1000	-0.075	-1000
FOXA2 and FOXA3 transcription factor networks	0.0720	35	1630	46	-0.22	0.02	1000	-1000	-0.098	-1000
S1P1 pathway	0.0720	35	1290	36	-0.19	0.013	1000	-1000	-0.05	-1000
Nongenotropic Androgen signaling	0.0720	35	1825	52	-0.1	0.039	1000	-1000	-0.045	-1000
Signaling events mediated by PRL	0.0679	33	1130	34	-0.11	0.051	1000	-1000	-0.033	-1000
Aurora A signaling	0.0658	32	1941	60	-0.2	0.026	1000	-1000	-0.025	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0658	32	3897	120	-0.25	0.076	1000	-1000	-0.063	-1000
JNK signaling in the CD4+ TCR pathway	0.0638	31	537	17	-0.12	0.019	1000	-1000	-0.037	-1000
HIF-1-alpha transcription factor network	0.0638	31	2424	76	-0.22	0.048	1000	-1000	-0.16	-1000
S1P5 pathway	0.0638	31	532	17	-0.081	0.067	1000	-1000	-0.026	-1000
TCGA08_p53	0.0638	31	222	7	-0.081	0.045	1000	-1000	-0.013	-1000
BMP receptor signaling	0.0617	30	2478	81	-0.16	0.047	1000	-1000	-0.076	-1000
Signaling events regulated by Ret tyrosine kinase	0.0617	30	2494	82	-0.1	0.013	1000	-1000	-0.075	-1000
Calcium signaling in the CD4+ TCR pathway	0.0617	30	946	31	-0.16	0.013	1000	-1000	-0.058	-1000
IL12-mediated signaling events	0.0597	29	2589	87	-0.2	0.015	1000	-1000	-0.13	-1000
Osteopontin-mediated events	0.0597	29	1126	38	-0.08	0.014	1000	-1000	-0.088	-1000
Wnt signaling	0.0597	29	204	7	-0.085	0.013	1000	-1000	-0.03	-1000
p75(NTR)-mediated signaling	0.0556	27	3487	125	-0.15	0.039	1000	-1000	-0.094	-1000
EPHB forward signaling	0.0556	27	2341	85	-0.14	0.089	1000	-1000	-0.077	-1000
Syndecan-4-mediated signaling events	0.0556	27	1843	67	-0.31	0.02	1000	-1000	-0.064	-1000
S1P4 pathway	0.0556	27	676	25	-0.081	0.02	1000	-1000	-0.028	-1000
Effects of Botulinum toxin	0.0535	26	695	26	-0.097	0.014	1000	-1000	-0.048	-1000
IL27-mediated signaling events	0.0535	26	1356	51	-0.34	0.027	1000	-1000	-0.065	-1000
EGFR-dependent Endothelin signaling events	0.0535	26	551	21	-0.09	0.02	1000	-1000	-0.064	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.0514	25	879	34	-0.087	0.013	1000	-1000	-0.038	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0514	25	1357	54	-0.17	0.025	1000	-1000	-0.093	-1000
Noncanonical Wnt signaling pathway	0.0494	24	635	26	-0.085	0.013	1000	-1000	-0.048	-1000
PDGFR-alpha signaling pathway	0.0494	24	1083	44	-0.16	0.023	1000	-1000	-0.042	-1000
BCR signaling pathway	0.0494	24	2469	99	-0.15	0.041	1000	-1000	-0.08	-1000
ErbB4 signaling events	0.0473	23	1591	69	-0.16	0.041	1000	-1000	-0.078	-1000
Visual signal transduction: Cones	0.0473	23	894	38	-0.092	0.013	1000	-1000	-0.055	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0473	23	2003	85	-0.12	0.017	1000	-1000	-0.064	-1000
Signaling events mediated by PTP1B	0.0473	23	1772	76	-0.27	0.048	1000	-1000	-0.075	-1000
TCR signaling in naïve CD8+ T cells	0.0473	23	2142	93	-0.066	0.026	1000	-1000	-0.07	-1000
a4b1 and a4b7 Integrin signaling	0.0432	21	107	5	-0.014	0	1000	-1000	-0.02	-1000
Presenilin action in Notch and Wnt signaling	0.0432	21	1294	61	-0.22	0.04	1000	-1000	-0.062	-1000
Canonical Wnt signaling pathway	0.0432	21	1110	51	-0.22	0.11	1000	-1000	-0.057	-1000
Plasma membrane estrogen receptor signaling	0.0432	21	1883	86	-0.19	0.021	1000	-1000	-0.072	-1000
Visual signal transduction: Rods	0.0432	21	1136	52	-0.11	0.013	1000	-1000	-0.067	-1000
Regulation of nuclear SMAD2/3 signaling	0.0412	20	2831	136	-0.52	0.06	1000	-1000	-0.063	-1000
FAS signaling pathway (CD95)	0.0412	20	961	47	-0.27	0.02	1000	-1000	-0.04	-1000
TCGA08_retinoblastoma	0.0412	20	165	8	-0.11	0.029	1000	-1000	-0.017	-1000
Rapid glucocorticoid signaling	0.0412	20	412	20	-0.11	0.018	1000	-1000	-0.02	-1000
Syndecan-2-mediated signaling events	0.0391	19	1329	69	-0.067	0.031	1000	-1000	-0.023	-1000
Arf6 signaling events	0.0391	19	1225	62	-0.12	0.017	1000	-1000	-0.041	-1000
S1P3 pathway	0.0391	19	839	42	-0.078	0.02	1000	-1000	-0.034	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0370	18	684	37	-0.095	0.03	1000	-1000	-0.047	-1000
EPO signaling pathway	0.0350	17	957	55	-0.066	0.019	1000	-1000	-0.083	-1000
Fc-epsilon receptor I signaling in mast cells	0.0350	17	1741	97	-0.1	0.027	1000	-1000	-0.084	-1000
Regulation of p38-alpha and p38-beta	0.0350	17	919	54	-0.17	0.034	1000	-1000	-0.052	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0350	17	2175	125	-0.083	0.036	1000	-1000	-0.09	-1000
IL2 signaling events mediated by STAT5	0.0350	17	376	22	-0.078	0.034	1000	-1000	-0.043	-1000
Cellular roles of Anthrax toxin	0.0329	16	629	39	-0.038	0.014	1000	-1000	-0.017	-1000
Signaling events mediated by HDAC Class III	0.0329	16	666	40	-0.14	0.025	1000	-1000	-0.02	-1000
Ephrin B reverse signaling	0.0329	16	788	48	-0.14	0.049	1000	-1000	-0.051	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.0329	16	531	33	-0.13	0.033	1000	-1000	-0.032	-1000
BARD1 signaling events	0.0309	15	865	57	-0.039	0.033	1000	-1000	-0.047	-1000
Insulin Pathway	0.0309	15	1155	74	-0.22	0.027	1000	-1000	-0.083	-1000
ErbB2/ErbB3 signaling events	0.0288	14	918	65	-0.16	0.02	1000	-1000	-0.059	-1000
Coregulation of Androgen receptor activity	0.0288	14	1126	76	-0.15	0.025	1000	-1000	-0.028	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0288	14	409	28	-0.079	0.034	1000	-1000	-0.029	-1000
IL1-mediated signaling events	0.0288	14	885	62	-0.088	0.058	1000	-1000	-0.081	-1000
LPA4-mediated signaling events	0.0267	13	160	12	-0.03	0.018	1000	-1000	-0.023	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0267	13	721	52	-0.11	0.027	1000	-1000	-0.05	-1000
HIF-2-alpha transcription factor network	0.0267	13	575	43	-0.087	0.021	1000	-1000	-0.069	-1000
Signaling mediated by p38-gamma and p38-delta	0.0267	13	201	15	-0.01	0.016	1000	-1000	-0.029	-1000
IL2 signaling events mediated by PI3K	0.0267	13	784	58	-0.18	0.028	1000	-1000	-0.074	-1000
Nectin adhesion pathway	0.0247	12	810	63	-0.083	0.027	1000	-1000	-0.058	-1000
Retinoic acid receptors-mediated signaling	0.0247	12	722	58	-0.075	0.028	1000	-1000	-0.064	-1000
Syndecan-3-mediated signaling events	0.0247	12	445	35	-0.073	0.039	1000	-1000	-0.041	-1000
VEGFR1 specific signals	0.0247	12	704	56	-0.058	0.027	1000	-1000	-0.05	-1000
Caspase cascade in apoptosis	0.0226	11	841	74	-0.061	0.03	1000	-1000	-0.038	-1000
Class I PI3K signaling events	0.0226	11	825	73	-0.1	0.035	1000	-1000	-0.049	-1000
IGF1 pathway	0.0226	11	654	57	-0.048	0.027	1000	-1000	-0.09	-1000
Hedgehog signaling events mediated by Gli proteins	0.0206	10	687	65	-0.29	0.054	1000	-1000	-0.054	-1000
Regulation of Telomerase	0.0206	10	1043	102	-0.22	0.038	1000	-1000	-0.1	-1000
TRAIL signaling pathway	0.0185	9	473	48	-0.037	0.04	1000	-1000	-0.058	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0185	9	762	83	-0.097	0.055	1000	-1000	-0.07	-1000
TCGA08_rtk_signaling	0.0185	9	256	26	-0.033	0.043	1000	-1000	-0.02	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0165	8	630	74	-0.18	0.054	1000	-1000	-0.069	-1000
p38 MAPK signaling pathway	0.0165	8	370	44	-0.057	0.026	1000	-1000	-0.056	-1000
IFN-gamma pathway	0.0144	7	485	68	-0.085	0.051	1000	-1000	-0.083	-1000
Atypical NF-kappaB pathway	0.0144	7	222	31	-0.034	0.043	1000	-1000	-0.038	-1000
Class IB PI3K non-lipid kinase events	0.0144	7	21	3	-0.005	0.005	1000	-1000	-0.015	-1000
Regulation of Androgen receptor activity	0.0144	7	556	70	-0.11	0.063	1000	-1000	-0.049	-1000
PLK2 and PLK4 events	0.0123	6	20	3	0.007	0.013	1000	-1000	-0.015	-1000
Ceramide signaling pathway	0.0123	6	529	76	-0.056	0.039	1000	-1000	-0.041	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0123	6	286	45	-0.029	0.06	1000	-1000	-0.084	-1000
Canonical NF-kappaB pathway	0.0103	5	203	39	-0.029	0.063	1000	-1000	-0.074	-1000
Signaling events mediated by HDAC Class II	0.0103	5	426	75	-0.044	0.036	1000	-1000	-0.038	-1000
mTOR signaling pathway	0.0103	5	299	53	-0.016	0.027	1000	-1000	-0.058	-1000
FoxO family signaling	0.0103	5	350	64	-0.08	0.081	1000	-1000	-0.06	-1000
Paxillin-dependent events mediated by a4b1	0.0103	5	185	36	-0.024	0.025	1000	-1000	-0.065	-1000
ceramide signaling pathway	0.0082	4	227	49	-0.029	0.039	1000	-1000	-0.044	-1000
Arf6 trafficking events	0.0082	4	287	71	-0.091	0.04	1000	-1000	-0.062	-1000
Circadian rhythm pathway	0.0062	3	68	22	-0.023	0.04	1000	-1000	-0.046	-1000
Arf6 downstream pathway	0.0062	3	132	43	-0.022	0.024	1000	-1000	-0.031	-1000
Insulin-mediated glucose transport	0.0062	3	120	32	-0.036	0.029	1000	-1000	-0.045	-1000
PDGFR-beta signaling pathway	0.0062	3	355	97	-0.085	0.044	1000	-1000	-0.076	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0041	2	60	23	-0.013	0.042	1000	-1000	-0.04	-1000
E-cadherin signaling in keratinocytes	0.0041	2	119	43	-0.038	0.042	1000	-1000	-0.039	-1000
Class I PI3K signaling events mediated by Akt	0.0021	1	80	68	-0.036	0.046	1000	-1000	-0.037	-1000
Signaling events mediated by HDAC Class I	0.0021	1	118	104	-0.029	0.051	1000	-1000	-0.065	-1000
E-cadherin signaling in the nascent adherens junction	0.0021	1	125	76	-0.007	0.056	1000	-1000	-0.072	-1000
E-cadherin signaling events	0.0021	1	6	5	0.011	0.026	1000	-1000	-0.016	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	9	27	-0.001	0.034	1000	-1000	-0.048	-1000
Arf1 pathway	0.0000	0	28	54	-0.001	0.031	1000	-1000	-0.031	-1000
Alternative NF-kappaB pathway	0.0000	0	9	13	0	0.037	1000	-1000	-0.028	-1000
Total	NA	3120	177986	7203	-17	5	131000	-131000	-7.5	-131000

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.087	0.16	-9999	-0.31	154	154
EFNA5	-0.041	0.15	-9999	-0.47	54	54
FYN	-0.072	0.15	-9999	-0.28	154	154
neuron projection morphogenesis	-0.087	0.16	-9999	-0.31	154	154
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.087	0.16	-9999	-0.31	154	154
EPHA5	-0.11	0.21	-9999	-0.47	121	121

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.012	0.12	-9999	-0.57	21	21
GPC2	-0.14	0.26	-9999	-0.57	128	128
GPC2/Midkine	-0.11	0.21	-9999	-0.44	138	138
neuron projection morphogenesis	-0.11	0.21	-9999	-0.44	138	138

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.28	0.56	-9999	-1.1	114	114
PLK1	-0.12	0.23	-9999	-0.46	31	31
BIRC5	-0.14	0.24	-9999	-0.46	171	171
HSPA1B	-0.28	0.57	-9999	-1.1	109	109
MAP2K1	0.011	0.04	-9999	-10000	0	0
BRCA2	-0.3	0.59	-9999	-1.1	128	128
FOXM1	-0.41	0.82	-9999	-1.5	128	128
XRCC1	-0.28	0.56	-9999	-1.1	117	117
FOXM1B/p19	-0.4	0.5	-9999	-1.1	128	128
Cyclin D1/CDK4	-0.25	0.52	-9999	-1	100	100
CDC2	-0.3	0.6	-9999	-1.1	124	124
TGFA	-0.25	0.52	-9999	-1	105	105
SKP2	-0.28	0.57	-9999	-1.1	113	113
CCNE1	0.006	0.061	-9999	-0.59	5	5
CKS1B	-0.28	0.56	-9999	-1.1	114	114
RB1	-0.16	0.18	-9999	-0.49	51	51
FOXM1C/SP1	-0.34	0.66	-9999	-1.3	124	124
AURKB	-0.12	0.23	-9999	-0.45	152	152
CENPF	-0.33	0.62	-9999	-1.2	141	141
CDK4	0.012	0.015	-9999	-10000	0	0
MYC	-0.25	0.51	-9999	-0.98	116	116
CHEK2	0.01	0.049	-9999	-0.63	1	1
ONECUT1	-0.27	0.55	-9999	-1.1	113	113
CDKN2A	-0.11	0.24	-9999	-0.57	102	102
LAMA4	-0.28	0.57	-9999	-1.1	114	114
FOXM1B/HNF6	-0.34	0.66	-9999	-1.3	118	118
FOS	-0.36	0.64	-9999	-1.2	148	148
SP1	0.013	0.005	-9999	-10000	0	0
CDC25B	-0.28	0.57	-9999	-1.1	108	108
response to radiation	-0.003	0.036	-9999	-10000	0	0
CENPB	-0.28	0.56	-9999	-1.1	112	112
CENPA	-0.36	0.63	-9999	-1.2	149	149
NEK2	-0.36	0.62	-9999	-1.2	148	148
HIST1H2BA	-0.28	0.56	-9999	-1.1	112	112
CCNA2	-0.079	0.22	-9999	-0.59	75	75
EP300	0.01	0.038	-9999	-0.47	3	3
CCNB1/CDK1	-0.34	0.67	-9999	-1.3	120	120
CCNB2	-0.3	0.59	-9999	-1.2	116	116
CCNB1	-0.3	0.6	-9999	-1.2	118	118
ETV5	-0.3	0.6	-9999	-1.2	117	117
ESR1	-0.29	0.58	-9999	-1.1	118	118
CCND1	-0.26	0.53	-9999	-1	107	107
GSK3A	0.012	0.041	-9999	-0.51	1	1
Cyclin A-E1/CDK1-2	-0.035	0.16	-9999	-0.4	76	76
CDK2	0.012	0.009	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.005	0.043	-9999	-10000	0	0
FOXM1B/Cbp/p300	-0.42	0.52	-9999	-1.1	135	135
GAS1	-0.32	0.61	-9999	-1.2	126	126
MMP2	-0.29	0.58	-9999	-1.1	118	118
RB1/FOXM1C	-0.27	0.56	-9999	-1.1	111	111
CREBBP	0.013	0	-9999	-10000	0	0

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.18	0.41	-10000	0	-0.79	146	146
NCK1/PAK1/Dok-R	-0.12	0.18	-10000	0	-0.39	146	146
NCK1/Dok-R	-0.24	0.48	-10000	0	-0.95	146	146
PIK3CA	0.011	0.038	-10000	0	-0.47	3	3
mol:beta2-estradiol	0.06	0.11	0.23	144	-10000	0	144
RELA	0.013	0	-10000	0	-10000	0	0
SHC1	0.013	0.002	-10000	0	-10000	0	0
Rac/GDP	0.01	0	-10000	0	-10000	0	0
F2	0.036	0.17	0.24	122	-0.5	26	148
TNIP2	0.013	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.22	0.45	-10000	0	-0.89	146	146
FN1	-0.002	0.086	-10000	0	-0.5	14	14
PLD2	-0.25	0.5	-10000	0	-0.99	146	146
PTPN11	0.012	0.022	-10000	0	-0.47	1	1
GRB14	-0.098	0.23	-10000	0	-0.57	92	92
ELK1	-0.22	0.45	-10000	0	-0.89	146	146
GRB7	0.013	0	-10000	0	-10000	0	0
PAK1	0.007	0.053	-10000	0	-0.47	6	6
Tie2/Ang1/alpha5/beta1 Integrin	-0.24	0.48	-10000	0	-0.96	146	146
CDKN1A	-0.11	0.28	-10000	0	-0.58	74	74
ITGA5	-0.002	0.085	-10000	0	-0.48	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.24	0.48	-10000	0	-0.95	146	146
CRK	0.013	0	-10000	0	-10000	0	0
mol:NO	-0.13	0.32	-10000	0	-0.6	146	146
PLG	-0.27	0.5	-10000	0	-1	146	146
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.18	0.4	-10000	0	-0.77	146	146
GRB2	0.013	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.049	-10000	0	-0.48	5	5
ANGPT2	-0.11	0.24	-10000	0	-0.57	54	54
BMX	-0.28	0.51	-10000	0	-1	146	146
ANGPT1	-0.32	0.55	-10000	0	-1.2	145	145
tube development	-0.12	0.3	-10000	0	-0.57	138	138
ANGPT4	0.01	0.027	-10000	0	-0.57	1	1
response to hypoxia	-0.017	0.032	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.32	0.52	-10000	0	-1.1	146	146
alpha5/beta1 Integrin	0.009	0.061	-10000	0	-0.33	15	15
FGF2	-0.024	0.13	-10000	0	-0.47	37	37
STAT5A (dimer)	-0.14	0.34	-10000	0	-0.66	133	133
mol:L-citrulline	-0.13	0.32	-10000	0	-0.6	146	146
AGTR1	-0.12	0.24	-10000	0	-0.55	111	111
MAPK14	-0.24	0.48	-10000	0	-0.95	146	146
Tie2/SHP2	-0.072	0.26	-10000	0	-1.2	19	19
TEK	-0.085	0.29	-10000	0	-1.4	19	19
RPS6KB1	-0.18	0.39	-10000	0	-0.76	146	146
Angiotensin II/AT1	-0.082	0.18	-10000	0	-0.4	111	111
Tie2/Ang1/GRB2	-0.26	0.51	-10000	0	-1	146	146
MAPK3	-0.23	0.46	-10000	0	-0.91	146	146
MAPK1	-0.23	0.46	-10000	0	-0.91	146	146
Tie2/Ang1/GRB7	-0.26	0.51	-10000	0	-1	146	146
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.26	0.5	-10000	0	-1	146	146
PI3K	-0.22	0.46	-10000	0	-0.9	146	146
FES	-0.24	0.48	-10000	0	-0.95	146	146
Crk/Dok-R	-0.24	0.48	-10000	0	-0.95	146	146
Tie2/Ang1/ABIN2	-0.26	0.51	-10000	0	-1	146	146
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.16	0.37	-10000	0	-0.71	146	146
STAT5A	0.011	0.031	-10000	0	-0.47	2	2
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.18	0.39	-10000	0	-0.76	146	146
Tie2/Ang2	-0.18	0.39	-10000	0	-0.76	134	134
Tie2/Ang1	-0.28	0.54	-10000	0	-1.1	146	146
FOXO1	-0.16	0.37	-10000	0	-0.72	146	146
ELF1	0.008	0.068	-10000	0	-0.5	8	8
ELF2	-0.25	0.49	-10000	0	-0.98	146	146
mol:Choline	-0.24	0.47	-10000	0	-0.95	146	146
cell migration	-0.069	0.1	-10000	0	-0.22	146	146
FYN	-0.14	0.34	-10000	0	-0.65	134	134
DOK2	0.01	0.046	-10000	0	-0.58	3	3
negative regulation of cell cycle	-0.094	0.26	-10000	0	-0.51	88	88
ETS1	-0.05	0.12	-10000	0	-0.36	12	12
PXN	-0.14	0.33	-10000	0	-0.64	146	146
ITGB1	0.013	0	-10000	0	-10000	0	0
NOS3	-0.15	0.35	-10000	0	-0.68	146	146
RAC1	0.013	0	-10000	0	-10000	0	0
TNF	-0.088	0.17	-10000	0	-0.5	47	47
MAPKKK cascade	-0.24	0.47	-10000	0	-0.95	146	146
RASA1	0.01	0.038	-10000	0	-0.47	3	3
Tie2/Ang1/Shc	-0.26	0.51	-10000	0	-1	146	146
NCK1	0.012	0.027	-10000	0	-0.58	1	1
vasculogenesis	-0.11	0.29	-10000	0	-0.54	146	146
mol:Phosphatidic acid	-0.24	0.47	-10000	0	-0.95	146	146
mol:Angiotensin II	0.001	0.003	-10000	0	-10000	0	0
mol:NADP	-0.13	0.32	-10000	0	-0.6	146	146
Rac1/GTP	-0.22	0.33	-10000	0	-0.72	146	146
MMP2	-0.26	0.51	-10000	0	-1	146	146

Aurora B signaling

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
Condensin I complex	-0.11	0.19	-9999	-0.39	147	147
STMN1	-0.12	0.21	-9999	-0.42	159	159
Aurora B/RasGAP/Survivin	-0.21	0.31	-9999	-0.57	197	197
Chromosomal passenger complex/Cul3 protein complex	-0.089	0.17	-9999	-0.32	148	148
BIRC5	-0.21	0.29	-9999	-0.59	179	179
DES	-0.17	0.29	-9999	-0.75	88	88
Aurora C/Aurora B/INCENP	-0.087	0.16	-9999	-0.32	162	162
Aurora B/TACC1	-0.11	0.18	-9999	-0.36	161	161
Aurora B/PP2A	-0.12	0.2	-9999	-0.41	159	159
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.021	0.053	-9999	-10000	0	0
mitotic metaphase/anaphase transition	-0.001	0.004	-9999	-10000	0	0
NDC80	-0.12	0.2	-9999	-0.41	162	162
Cul3 protein complex	0.01	0.069	-9999	-0.27	28	28
KIF2C	-0.074	0.12	-9999	-0.23	164	164
PEBP1	0.008	0.006	-9999	-10000	0	0
KIF20A	-0.21	0.29	-9999	-0.58	185	185
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.12	0.21	-9999	-0.42	159	159
SEPT1	0.001	0.084	-9999	-0.58	10	10
SMC2	0.012	0.027	-9999	-0.58	1	1
SMC4	0.012	0.027	-9999	-0.58	1	1
NSUN2/NPM1/Nucleolin	-0.048	0.1	-9999	-10000	0	0
PSMA3	0.013	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	0	0.004	-9999	-10000	0	0
H3F3B	-0.062	0.11	-9999	-0.23	159	159
AURKB	-0.18	0.28	-9999	-0.58	159	159
AURKC	0.009	0.049	-9999	-0.52	4	4
CDCA8	-0.057	0.19	-9999	-0.6	53	53
cytokinesis	-0.14	0.24	-9999	-0.47	147	147
Aurora B/Septin1	-0.16	0.22	-9999	-0.47	146	146
AURKA	-0.029	0.15	-9999	-0.58	35	35
INCENP	0.007	0.008	-9999	-10000	0	0
KLHL13	-0.014	0.11	-9999	-0.47	27	27
BUB1	-0.12	0.25	-9999	-0.58	110	110
hSgo1/Aurora B/Survivin	-0.26	0.37	-9999	-0.66	204	204
EVI5	0.012	0.002	-9999	-10000	0	0
RhoA/GTP	-0.15	0.22	-9999	-0.45	143	143
SGOL1	-0.11	0.24	-9999	-0.58	102	102
CENPA	-0.14	0.19	-9999	-0.36	182	182
NCAPG	-0.18	0.28	-9999	-0.58	161	161
Aurora B/HC8 Proteasome	-0.12	0.2	-9999	-0.41	159	159
NCAPD2	0.013	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.12	0.2	-9999	-0.41	159	159
RHOA	0.013	0	-9999	-10000	0	0
NCAPH	-0.14	0.26	-9999	-0.58	130	130
NPM1	-0.062	0.11	-9999	-0.23	84	84
RASA1	0.01	0.038	-9999	-0.47	3	3
KLHL9	0.012	0.022	-9999	-0.47	1	1
mitotic prometaphase	-0.006	0.008	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.12	0.2	-9999	-0.41	159	159
PPP1CC	0.013	0	-9999	-10000	0	0
Centraspindlin	-0.15	0.26	-9999	-0.49	145	145
RhoA/GDP	0.01	0	-9999	-10000	0	0
NSUN2	-0.062	0.11	-9999	-0.24	53	53
MYLK	-0.15	0.21	-9999	-0.35	219	219
KIF23	-0.028	0.15	-9999	-0.59	32	32
VIM	-0.12	0.2	-9999	-0.41	159	159
RACGAP1	0.004	0.061	-9999	-0.59	5	5
mitosis	0	0	-9999	-10000	0	0
NCL	-0.062	0.11	-9999	-0.23	141	141
Chromosomal passenger complex	-0.15	0.22	-9999	-0.42	180	180
Chromosomal passenger complex/EVI5	-0.22	0.32	-9999	-0.65	151	151
TACC1	0.002	0.072	-9999	-0.47	11	11
PPP2R5D	0.013	0.001	-9999	-10000	0	0
CUL3	0.013	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	-0.18	0.41	-9999	-1	91	91
MKNK1	0.013	0	-9999	-10000	0	0
MAPK14	-0.053	0.14	-9999	-0.41	15	15
ATF2/c-Jun	-0.052	0.17	-9999	-0.55	31	31
MAPK11	-0.063	0.16	-9999	-0.32	114	114
MITF	-0.063	0.18	-9999	-0.36	110	110
MAPKAPK5	-0.06	0.17	-9999	-0.35	109	109
KRT8	-0.06	0.17	-9999	-0.35	110	110
MAPKAPK3	0.013	0	-9999	-10000	0	0
MAPKAPK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/CK2	-0.085	0.22	-9999	-0.44	114	114
CEBPB	-0.06	0.17	-9999	-0.35	109	109
SLC9A1	-0.06	0.17	-9999	-0.35	109	109
mol:GDP	0	0	-9999	-10000	0	0
ATF2	-0.076	0.21	-9999	-0.39	113	113
p38alpha-beta/MNK1	-0.056	0.18	-9999	-0.51	25	25
JUN	-0.051	0.17	-9999	-0.55	31	31
PPARGC1A	-0.17	0.29	-9999	-0.58	123	123
USF1	-0.06	0.17	-9999	-0.35	109	109
RAB5/GDP/GDI1	-0.04	0.12	-9999	-0.36	25	25
NOS2	-0.11	0.3	-9999	-0.71	66	66
DDIT3	-0.06	0.17	-9999	-0.35	109	109
RAB5A	0.013	0	-9999	-10000	0	0
HSPB1	-0.058	0.16	-9999	-0.45	31	31
p38alpha-beta/HBP1	-0.056	0.18	-9999	-0.49	28	28
CREB1	-0.066	0.19	-9999	-0.38	110	110
RAB5/GDP	0.01	0	-9999	-10000	0	0
EIF4E	-0.047	0.15	-9999	-0.52	18	18
RPS6KA4	-0.061	0.17	-9999	-0.36	110	110
PLA2G4A	-0.061	0.18	-9999	-0.54	36	36
GDI1	-0.06	0.17	-9999	-0.35	109	109
TP53	-0.081	0.21	-9999	-0.44	110	110
RPS6KA5	-0.07	0.19	-9999	-0.38	112	112
ESR1	-0.072	0.2	-9999	-0.39	110	110
HBP1	0.013	0	-9999	-10000	0	0
MEF2C	-0.063	0.18	-9999	-0.36	111	111
MEF2A	-0.062	0.18	-9999	-0.36	110	110
EIF4EBP1	-0.072	0.19	-9999	-0.4	111	111
KRT19	-0.092	0.22	-9999	-0.44	112	112
ELK4	-0.061	0.17	-9999	-0.35	110	110
ATF6	-0.06	0.17	-9999	-0.35	109	109
ATF1	-0.066	0.19	-9999	-0.38	111	111
p38alpha-beta/MAPKAPK2	-0.056	0.18	-9999	-0.49	28	28
p38alpha-beta/MAPKAPK3	-0.056	0.18	-9999	-0.51	25	25

Endothelins

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
AKT1	-0.04	0.21	0.27	18	-0.57	42	60
PTK2B	0.013	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.14	0.41	-10000	0	-0.95	93	93
EDN1	-0.025	0.17	-10000	0	-0.49	40	40
EDN3	-0.17	0.24	-10000	0	-0.47	184	184
EDN2	-0.022	0.13	-10000	0	-0.5	33	33
HRAS/GDP	-0.06	0.23	-10000	0	-0.52	75	75
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.025	0.17	-10000	0	-0.42	54	54
ADCY4	-0.091	0.24	-10000	0	-0.54	86	86
ADCY5	-0.12	0.3	-10000	0	-0.62	106	106
ADCY6	-0.09	0.24	-10000	0	-0.53	86	86
ADCY7	-0.09	0.24	-10000	0	-0.53	87	87
ADCY1	-0.12	0.25	-10000	0	-0.55	91	91
ADCY2	-0.1	0.25	-10000	0	-0.56	89	89
ADCY3	-0.09	0.24	-10000	0	-0.53	86	86
ADCY8	-0.099	0.24	-10000	0	-0.54	87	87
ADCY9	-0.09	0.24	-10000	0	-0.54	86	86
arachidonic acid secretion	-0.098	0.31	-10000	0	-0.56	117	117
ETB receptor/Endothelin-1/Gq/GTP	-0.039	0.16	-10000	0	-0.38	66	66
GNAO1	-0.079	0.19	-10000	0	-0.47	93	93
HRAS	0.006	0.059	-10000	0	-0.58	5	5
ETA receptor/Endothelin-1/G12/GTP	-0.024	0.22	0.3	56	-0.55	40	96
ETA receptor/Endothelin-1/Gs/GTP	-0.1	0.26	0.28	51	-0.57	86	137
mol:GTP	-0.001	0.007	-10000	0	-10000	0	0
COL3A1	-0.046	0.22	-10000	0	-0.58	48	48
EDNRB	-0.051	0.17	-10000	0	-0.47	67	67
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.083	0.28	-10000	0	-0.63	84	84
CYSLTR1	-0.06	0.26	-10000	0	-0.71	50	50
SLC9A1	-0.034	0.11	0.19	23	-0.3	40	63
mol:GDP	-0.069	0.25	-10000	0	-0.55	75	75
SLC9A3	-0.16	0.37	-10000	0	-0.84	90	90
RAF1	-0.076	0.25	-10000	0	-0.56	75	75
JUN	-0.069	0.29	-10000	0	-0.68	65	65
JAK2	-0.041	0.21	-10000	0	-0.58	42	42
mol:IP3	-0.03	0.17	-10000	0	-0.42	48	48
ETA receptor/Endothelin-1	-0.066	0.26	0.35	59	-0.61	51	110
PLCB1	0.008	0.044	-10000	0	-0.47	4	4
PLCB2	0.009	0.038	-10000	0	-0.57	2	2
ETA receptor/Endothelin-3	-0.15	0.23	-10000	0	-0.4	190	190
FOS	-0.13	0.38	-10000	0	-0.9	87	87
Gai/GDP	-0.14	0.36	-10000	0	-0.85	93	93
CRK	0.013	0.001	-10000	0	-10000	0	0
mol:Ca ++	-0.065	0.26	-10000	0	-0.64	59	59
BCAR1	0.013	0.001	-10000	0	-10000	0	0
PRKCB1	-0.033	0.16	-10000	0	-0.41	50	50
GNAQ	0.012	0.007	-10000	0	-10000	0	0
GNAZ	-0.033	0.14	-10000	0	-0.47	46	46
GNAL	-0.11	0.21	-10000	0	-0.47	124	124
Gs family/GDP	-0.15	0.24	-10000	0	-0.56	110	110
ETA receptor/Endothelin-1/Gq/GTP	-0.038	0.2	-10000	0	-0.46	63	63
MAPK14	-0.021	0.14	-10000	0	-0.4	35	35
TRPC6	-0.15	0.44	-10000	0	-1	92	92
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.005	0.065	-10000	0	-0.53	7	7
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.03	0.15	-10000	0	-0.38	50	50
ETB receptor/Endothelin-2	-0.051	0.15	-10000	0	-0.34	97	97
ETB receptor/Endothelin-3	-0.15	0.22	-10000	0	-0.4	201	201
ETB receptor/Endothelin-1	-0.05	0.18	-10000	0	-0.39	91	91
MAPK3	-0.12	0.35	-10000	0	-0.8	92	92
MAPK1	-0.12	0.35	-10000	0	-0.79	94	94
Rac1/GDP	-0.057	0.23	-10000	0	-0.52	71	71
cAMP biosynthetic process	-0.098	0.26	-10000	0	-0.56	91	91
MAPK8	-0.096	0.34	-10000	0	-0.68	101	101
SRC	0.013	0.001	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.075	0.21	-10000	0	-0.49	80	80
p130Cas/CRK/Src/PYK2	-0.083	0.29	-10000	0	-0.61	94	94
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.057	0.23	-10000	0	-0.52	69	69
COL1A2	-0.065	0.25	-10000	0	-0.64	56	56
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.047	0.17	-10000	0	-0.38	79	79
mol:DAG	-0.031	0.17	-10000	0	-0.42	48	48
MAP2K2	-0.094	0.29	-10000	0	-0.62	93	93
MAP2K1	-0.094	0.29	-10000	0	-0.62	92	92
EDNRA	-0.042	0.19	-10000	0	-0.5	60	60
positive regulation of muscle contraction	-0.029	0.19	-10000	0	-0.52	40	40
Gq family/GDP	-0.11	0.2	-10000	0	-0.53	71	71
HRAS/GTP	-0.064	0.22	-10000	0	-0.49	73	73
PRKCH	-0.026	0.16	-10000	0	-0.42	43	43
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.036	0.18	-10000	0	-0.46	52	52
PRKCB	-0.081	0.23	-10000	0	-0.5	84	84
PRKCE	-0.025	0.16	-10000	0	-0.42	43	43
PRKCD	-0.027	0.17	-10000	0	-0.43	43	43
PRKCG	-0.039	0.18	-10000	0	-0.43	54	54
regulation of vascular smooth muscle contraction	-0.16	0.44	-10000	0	-1.1	87	87
PRKCQ	-0.048	0.19	-10000	0	-0.47	56	56
PLA2G4A	-0.11	0.35	-10000	0	-0.63	117	117
GNA14	0.011	0.023	-10000	0	-0.48	1	1
GNA15	-0.012	0.11	-10000	0	-0.48	24	24
GNA12	0.013	0	-10000	0	-10000	0	0
GNA11	-0.004	0.087	-10000	0	-0.47	16	16
Rac1/GTP	-0.024	0.22	0.3	57	-0.55	40	97
MMP1	-0.068	0.26	-10000	0	-0.6	82	82

IL23-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
CCL2	-0.3	0.53	-10000	0	-1.2	89	89
IL23A	-0.31	0.54	-10000	0	-1.2	92	92
NF kappa B1 p50/RelA/I kappa B alpha	-0.35	0.47	-10000	0	-1.1	102	102
positive regulation of T cell mediated cytotoxicity	-0.34	0.6	-10000	0	-1.3	102	102
ITGA3	-0.29	0.52	-10000	0	-1.2	87	87
IL17F	-0.18	0.34	-10000	0	-0.74	80	80
IL12B	-0.029	0.15	-10000	0	-0.61	29	29
STAT1 (dimer)	-0.32	0.57	-10000	0	-1.2	102	102
CD4	-0.28	0.5	-10000	0	-1.1	89	89
IL23	-0.31	0.53	-10000	0	-1.2	95	95
IL23R	-0.031	0.1	-10000	0	-0.54	4	4
IL1B	-0.34	0.58	-10000	0	-1.3	99	99
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.28	0.5	-10000	0	-1.1	95	95
TYK2	0.006	0.023	-10000	0	-10000	0	0
STAT4	-0.008	0.11	-10000	0	-0.55	18	18
STAT3	0.013	0.001	-10000	0	-10000	0	0
IL18RAP	-0.023	0.14	-10000	0	-0.52	33	33
IL12RB1	-0.02	0.13	-10000	0	-0.59	22	22
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
IL12Rbeta1/TYK2	-0.011	0.098	-10000	0	-0.44	22	22
IL23R/JAK2	-0.034	0.13	-10000	0	-0.53	4	4
positive regulation of chronic inflammatory response	-0.34	0.6	-10000	0	-1.3	102	102
natural killer cell activation	0.003	0.009	0.046	5	-10000	0	5
JAK2	0.009	0.038	-10000	0	-0.47	1	1
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
NFKB1	0.012	0.004	-10000	0	-10000	0	0
RELA	0.012	0.004	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.29	0.5	-10000	0	-1.1	95	95
ALOX12B	-0.3	0.51	-10000	0	-1.1	110	110
CXCL1	-0.4	0.62	-10000	0	-1.3	140	140
T cell proliferation	-0.34	0.6	-10000	0	-1.3	102	102
NFKBIA	0.012	0.004	-10000	0	-10000	0	0
IL17A	-0.14	0.28	-10000	0	-0.6	66	66
PI3K	-0.37	0.48	-10000	0	-1.2	104	104
IFNG	-0.008	0.031	0.1	1	-0.1	7	8
STAT3 (dimer)	-0.35	0.45	-10000	0	-1.1	104	104
IL18R1	0.006	0.061	-10000	0	-0.47	8	8
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.34	-10000	0	-0.77	78	78
IL18/IL18R	-0.004	0.11	-10000	0	-0.4	19	19
macrophage activation	-0.018	0.018	-10000	0	-0.045	79	79
TNF	-0.32	0.56	-10000	0	-1.3	97	97
STAT3/STAT4	-0.37	0.49	-10000	0	-1.2	104	104
STAT4 (dimer)	-0.33	0.57	-10000	0	-1.2	104	104
IL18	0.002	0.075	-10000	0	-0.47	12	12
IL19	-0.28	0.49	-10000	0	-1.1	101	101
STAT5A (dimer)	-0.32	0.56	-10000	0	-1.2	102	102
STAT1	0.001	0.084	-10000	0	-0.58	10	10
SOCS3	-0.053	0.17	-10000	0	-0.48	65	65
CXCL9	-0.32	0.52	-10000	0	-1.2	84	84
MPO	-0.32	0.55	-10000	0	-1.1	123	123
positive regulation of humoral immune response	-0.34	0.6	-10000	0	-1.3	102	102
IL23/IL23R/JAK2/TYK2	-0.37	0.68	-10000	0	-1.4	102	102
IL6	-0.42	0.62	-10000	0	-1.2	149	149
STAT5A	0.011	0.031	-10000	0	-0.47	2	2
IL2	0.006	0.039	-10000	0	-0.59	2	2
positive regulation of tyrosine phosphorylation of STAT protein	0.003	0.009	0.046	5	-10000	0	5
CD3E	-0.28	0.51	-10000	0	-1.1	98	98
keratinocyte proliferation	-0.34	0.6	-10000	0	-1.3	102	102
NOS2	-0.32	0.54	-10000	0	-1.1	114	114

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.013	0	-9999	-10000	0	0
CCL5	-0.007	0.1	-9999	-0.5	19	19
SDCBP	0.013	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.16	0.15	-9999	-0.36	118	118
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.14	0.14	-9999	-0.42	55	55
Syndecan-1/Syntenin	-0.14	0.14	-9999	-0.42	55	55
MAPK3	-0.12	0.14	-9999	-0.4	49	49
HGF/MET	-0.039	0.15	-9999	-0.41	67	67
TGFB1/TGF beta receptor Type II	0.013	0	-9999	-10000	0	0
BSG	0.012	0.027	-9999	-0.58	1	1
keratinocyte migration	-0.14	0.14	-9999	-0.42	55	55
Syndecan-1/RANTES	-0.15	0.16	-9999	-0.44	64	64
Syndecan-1/CD147	-0.13	0.14	-9999	-0.41	59	59
Syndecan-1/Syntenin/PIP2	-0.14	0.14	-9999	-0.41	55	55
LAMA5	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	-0.13	0.14	-9999	-0.4	55	55
MMP7	-0.091	0.22	-9999	-0.53	93	93
HGF	-0.026	0.14	-9999	-0.5	37	37
Syndecan-1/CASK	-0.15	0.14	-9999	-0.34	118	118
Syndecan-1/HGF/MET	-0.17	0.18	-9999	-0.46	98	98
regulation of cell adhesion	-0.11	0.13	-9999	-0.41	39	39
HPSE	-0.015	0.12	-9999	-0.5	26	26
positive regulation of cell migration	-0.16	0.15	-9999	-0.36	118	118
SDC1	-0.16	0.15	-9999	-0.36	118	118
Syndecan-1/Collagen	-0.16	0.15	-9999	-0.36	118	118
PPIB	0.007	0.059	-9999	-0.58	5	5
MET	-0.033	0.14	-9999	-0.47	46	46
PRKACA	0.013	0	-9999	-10000	0	0
MMP9	-0.31	0.29	-9999	-0.57	270	270
MAPK1	-0.12	0.14	-9999	-0.4	49	49
homophilic cell adhesion	-0.15	0.15	-9999	-0.36	118	118
MMP1	-0.092	0.22	-9999	-0.54	92	92

Glucocorticoid receptor regulatory 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.02	0.081	0.32	11	-10000	0	11
SMARCC2	0.001	0.033	-10000	0	-10000	0	0
SMARCC1	0.001	0.033	-10000	0	-10000	0	0
TBX21	-0.098	0.21	-10000	0	-0.48	86	86
SUMO2	0.016	0.015	-10000	0	-10000	0	0
STAT1 (dimer)	0.005	0.094	-10000	0	-0.62	10	10
FKBP4	0.013	0	-10000	0	-10000	0	0
FKBP5	0.011	0.031	-10000	0	-0.47	2	2
GR alpha/HSP90/FKBP51/HSP90	0.11	0.12	0.3	72	-0.29	1	73
PRL	-0.077	0.13	-10000	0	-0.65	3	3
cortisol/GR alpha (dimer)/TIF2	0.2	0.29	0.57	132	-0.46	8	140
RELA	-0.053	0.1	-10000	0	-0.29	9	9
FGG	0.19	0.24	0.51	107	-0.54	11	118
GR beta/TIF2	0.071	0.18	0.32	80	-0.36	38	118
IFNG	-0.29	0.33	-10000	0	-0.73	139	139
apoptosis	0.067	0.23	0.51	67	-0.52	9	76
CREB1	-0.042	0.11	-10000	0	-0.33	28	28
histone acetylation	-0.06	0.18	0.36	10	-0.39	75	85
BGLAP	-0.086	0.18	-10000	0	-0.46	48	48
GR/PKAc	0.11	0.11	0.29	69	-10000	0	69
NF kappa B1 p50/RelA	-0.093	0.19	-10000	0	-0.45	63	63
SMARCD1	0.001	0.033	-10000	0	-10000	0	0
MDM2	0.1	0.1	0.26	101	-10000	0	101
GATA3	-0.13	0.22	-10000	0	-0.47	142	142
AKT1	0.004	0.003	-10000	0	-10000	0	0
CSF2	-0.081	0.14	0.34	1	-0.46	17	18
GSK3B	0.016	0.015	-10000	0	-10000	0	0
NR1I3	0.086	0.22	0.5	61	-0.63	7	68
CSN2	0.17	0.18	0.43	99	-0.55	2	101
BRG1/BAF155/BAF170/BAF60A	-0.007	0.11	-10000	0	-0.32	41	41
NFATC1	0.014	0.003	-10000	0	-10000	0	0
POU2F1	0.012	0.028	-10000	0	-0.57	1	1
CDKN1A	0.005	0.13	-10000	0	-1.3	4	4
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.003	0.014	-10000	0	-10000	0	0
SFN	-0.036	0.15	-10000	0	-0.47	49	49
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.082	0.12	0.3	53	-10000	0	53
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	0.035	0.29	0.48	59	-0.72	40	99
JUN	-0.17	0.21	-10000	0	-0.49	103	103
IL4	-0.09	0.16	-10000	0	-0.51	11	11
CDK5R1	-0.014	0.13	-10000	0	-0.57	24	24
PRKACA	0.013	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.13	0.22	0.22	2	-0.52	69	71
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.11	0.11	0.3	66	-10000	0	66
cortisol/GR alpha (monomer)	0.28	0.32	0.68	146	-10000	0	146
NCOA2	-0.047	0.16	-10000	0	-0.47	60	60
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.12	0.2	-10000	0	-0.53	88	88
AP-1/NFAT1-c-4	-0.31	0.35	-10000	0	-0.77	145	145
AFP	-0.14	0.19	-10000	0	-0.63	29	29
SUV420H1	0.013	0	-10000	0	-10000	0	0
IRF1	0.15	0.18	0.44	74	-0.53	4	78
TP53	0.021	0.071	-10000	0	-0.44	10	10
PPP5C	0.013	0	-10000	0	-10000	0	0
KRT17	-0.4	0.52	-10000	0	-1.2	134	134
KRT14	-0.39	0.58	0.41	2	-1.2	149	151
TBP	0.016	0.034	-10000	0	-0.24	1	1
CREBBP	0.045	0.13	0.28	60	-0.26	2	62
HDAC1	0.013	0.009	-10000	0	-10000	0	0
HDAC2	0.012	0.023	-10000	0	-0.47	1	1
AP-1	-0.31	0.36	-10000	0	-0.78	145	145
MAPK14	0.016	0.012	-10000	0	-10000	0	0
MAPK10	0.01	0.056	-10000	0	-0.48	6	6
MAPK11	0.007	0.077	-10000	0	-0.58	8	8
KRT5	-0.52	0.59	-10000	0	-1.2	188	188
interleukin-1 receptor activity	0	0.005	-10000	0	-10000	0	0
NCOA1	0.016	0.001	-10000	0	-10000	0	0
STAT1	0.005	0.094	-10000	0	-0.62	10	10
CGA	-0.24	0.38	-10000	0	-0.87	106	106
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.1	0.18	0.38	106	-0.49	4	110
MAPK3	0.016	0.014	-10000	0	-10000	0	0
MAPK1	0.016	0.012	-10000	0	-10000	0	0
ICAM1	-0.2	0.28	-10000	0	-0.66	92	92
NFKB1	-0.053	0.1	-10000	0	-0.29	5	5
MAPK8	-0.15	0.19	-10000	0	-0.44	108	108
MAPK9	0.016	0.012	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	0.06	0.23	0.51	68	-0.54	9	77
BAX	0.014	0.062	-10000	0	-0.4	4	4
POMC	-0.27	0.47	-10000	0	-1.3	67	67
EP300	0.042	0.14	0.28	60	-0.37	7	67
cortisol/GR alpha (dimer)/p53	0.24	0.26	0.58	133	-10000	0	133
proteasomal ubiquitin-dependent protein catabolic process	0.073	0.081	0.22	54	-10000	0	54
SGK1	-0.066	0.48	0.39	12	-1.1	77	89
IL13	-0.36	0.41	-10000	0	-0.87	161	161
IL6	-0.35	0.48	-10000	0	-0.96	161	161
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.3	0.33	-10000	0	-0.79	125	125
IL2	-0.28	0.32	-10000	0	-0.72	127	127
CDK5	0.015	0.006	-10000	0	-10000	0	0
PRKACB	0.013	0	-10000	0	-10000	0	0
HSP90AA1	0.013	0	-10000	0	-10000	0	0
IL8	-0.25	0.38	-10000	0	-0.82	114	114
CDK5R1/CDK5	0.001	0.095	-10000	0	-0.41	24	24
NF kappa B1 p50/RelA/PKAc	-0.048	0.14	-10000	0	-0.38	19	19
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.24	0.24	0.55	137	-10000	0	137
SMARCA4	0.001	0.033	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.21	0.39	90	-0.38	25	115
NF kappa B1 p50/RelA/Cbp	-0.043	0.21	0.34	21	-0.52	31	52
JUN (dimer)	-0.17	0.21	-10000	0	-0.49	103	103
YWHAH	0.013	0	-10000	0	-10000	0	0
VIPR1	-0.077	0.16	-10000	0	-0.45	53	53
NR3C1	0.17	0.2	0.48	103	-0.43	3	106
NR4A1	-0.053	0.18	-10000	0	-0.46	72	72
TIF2/SUV420H1	-0.023	0.11	-10000	0	-0.33	60	60
MAPKKK cascade	0.067	0.23	0.51	67	-0.52	9	76
cortisol/GR alpha (dimer)/Src-1	0.25	0.26	0.57	144	-10000	0	144
PBX1	0.011	0.032	-10000	0	-0.47	2	2
POU1F1	0.001	0.043	-10000	0	-0.64	2	2
SELE	-0.34	0.48	-10000	0	-1	141	141
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.21	0.39	90	-0.38	25	115
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.24	0.24	0.55	137	-10000	0	137
mol:cortisol	0.16	0.2	0.4	156	-0.21	7	163
MMP1	-0.18	0.31	-10000	0	-0.92	56	56

IL4-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.45	0.45	-10000	0	-1.2	95	95
STAT6 (cleaved dimer)	-0.48	0.46	-10000	0	-1.1	145	145
IGHG1	-0.16	0.14	-10000	0	-0.42	7	7
IGHG3	-0.44	0.43	-10000	0	-1.1	118	118
AKT1	-0.22	0.26	-10000	0	-0.71	55	55
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.17	0.23	-10000	0	-0.73	30	30
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.23	0.26	-10000	0	-0.76	38	38
THY1	-0.45	0.45	-10000	0	-1.2	87	87
MYB	-0.015	0.12	-10000	0	-0.58	23	23
HMGA1	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.3	0.33	-10000	0	-0.83	88	88
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.24	0.27	-10000	0	-0.76	50	50
SP1	0.021	0.002	-10000	0	-10000	0	0
INPP5D	-0.013	0.11	-10000	0	-0.47	26	26
SOCS5	0.028	0.015	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.45	0.48	-10000	0	-1.2	104	104
SOCS1	-0.29	0.3	-10000	0	-0.77	79	79
SOCS3	-0.33	0.42	-10000	0	-1.1	85	85
FCER2	-0.4	0.4	-10000	0	-1.1	92	92
PARP14	0.013	0.005	-10000	0	-10000	0	0
CCL17	-0.48	0.47	-10000	0	-1.2	102	102
GRB2	0.013	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.19	0.22	-10000	0	-0.7	39	39
T cell proliferation	-0.44	0.47	-10000	0	-1.2	99	99
IL4R/JAK1	-0.45	0.45	-10000	0	-1.2	97	97
EGR2	-0.49	0.48	-10000	0	-1.2	103	103
JAK2	-0.015	0.033	-10000	0	-0.51	1	1
JAK3	0	0.091	-10000	0	-0.55	13	13
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
JAK1	0.004	0.009	-10000	0	-10000	0	0
COL1A2	-0.14	0.15	-10000	0	-0.9	4	4
CCL26	-0.45	0.45	-10000	0	-1.2	88	88
IL4R	-0.48	0.48	-10000	0	-1.2	95	95
PTPN6	0.025	0.009	-10000	0	-10000	0	0
IL13RA2	-0.53	0.55	-10000	0	-1.4	119	119
IL13RA1	-0.014	0.024	-10000	0	-10000	0	0
IRF4	-0.18	0.34	-10000	0	-1	52	52
ARG1	-0.14	0.16	-10000	0	-0.64	11	11
CBL	-0.28	0.3	-10000	0	-0.79	82	82
GTF3A	0.018	0.012	-10000	0	-10000	0	0
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
IL13RA1/JAK2	-0.019	0.037	-10000	0	-0.37	1	1
IRF4/BCL6	-0.16	0.32	-10000	0	-0.95	52	52
CD40LG	-0.038	0.17	-10000	0	-0.54	49	49
MAPK14	-0.3	0.34	-10000	0	-0.91	82	82
mitosis	-0.21	0.24	-10000	0	-0.67	54	54
STAT6	-0.52	0.54	-10000	0	-1.3	102	102
SPI1	0.007	0.057	-10000	0	-0.57	4	4
RPS6KB1	-0.2	0.23	-10000	0	-0.65	49	49
STAT6 (dimer)	-0.52	0.54	-10000	0	-1.3	102	102
STAT6 (dimer)/PARP14	-0.48	0.49	-10000	0	-1.2	103	103
mast cell activation	0.012	0.011	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.22	0.26	-10000	0	-0.71	53	53
FRAP1	-0.22	0.26	-10000	0	-0.71	56	56
LTA	-0.46	0.46	-10000	0	-1.2	96	96
FES	0.008	0.049	-10000	0	-0.47	5	5
T-helper 1 cell differentiation	0.5	0.51	1.3	102	-10000	0	102
CCL11	-0.47	0.46	-10000	0	-1.1	118	118
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.22	0.26	-10000	0	-0.7	55	55
IL2RG	-0.01	0.12	-10000	0	-0.54	22	22
IL10	-0.48	0.48	-10000	0	-1.2	99	99
IRS1	-0.003	0.086	-10000	0	-0.47	16	16
IRS2	0.007	0.059	-10000	0	-0.58	5	5
IL4	-0.11	0.1	-10000	0	-10000	0	0
IL5	-0.46	0.45	-10000	0	-1.2	97	97
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.37	0.34	-10000	0	-0.88	93	93
COL1A1	-0.17	0.18	-10000	0	-0.6	32	32
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.45	0.46	-10000	0	-1.2	88	88
IL2R gamma/JAK3	-0.008	0.13	-10000	0	-0.56	24	24
TFF3	-0.53	0.48	-10000	0	-1.2	126	126
ALOX15	-0.58	0.48	-10000	0	-1.3	127	127
MYBL1	0.012	0.022	-10000	0	-0.47	1	1
T-helper 2 cell differentiation	-0.38	0.37	-10000	0	-0.95	100	100
SHC1	0.013	0	-10000	0	-10000	0	0
CEBPB	0.012	0.021	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.22	0.24	-10000	0	-0.73	35	35
mol:PI-3-4-5-P3	-0.22	0.26	-10000	0	-0.71	56	56
PI3K	-0.23	0.28	-10000	0	-0.76	56	56
DOK2	0.01	0.046	-10000	0	-0.58	3	3
ETS1	0.022	0.045	-10000	0	-0.46	4	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.18	0.21	-10000	0	-0.65	37	37
ITGB3	-0.57	0.6	-10000	0	-1.4	136	136
PIGR	-0.6	0.6	-10000	0	-1.4	153	153
IGHE	0.038	0.035	0.26	1	-10000	0	1
MAPKKK cascade	-0.17	0.2	-10000	0	-0.64	37	37
BCL6	0.014	0.004	-10000	0	-10000	0	0
OPRM1	-0.46	0.45	-10000	0	-1.2	93	93
RETNLB	-0.46	0.45	-10000	0	-1.2	95	95
SELP	-0.46	0.46	-10000	0	-1.2	94	94
AICDA	-0.44	0.43	-10000	0	-1.1	95	95

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

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
MAP4K1	-0.042	0.17	-10000	0	-0.42	65	65
CRKL	-0.033	0.17	-10000	0	-0.45	60	60
HRAS	-0.019	0.18	-10000	0	-0.5	38	38
mol:PIP3	-0.039	0.15	-10000	0	-0.42	58	58
SPRED1	0.007	0.053	-10000	0	-0.47	6	6
SPRED2	0.008	0.049	-10000	0	-0.47	5	5
GAB1	-0.041	0.17	-10000	0	-0.48	60	60
FOXO3	-0.023	0.15	-10000	0	-0.4	60	60
AKT1	-0.032	0.16	-10000	0	-0.43	60	60
BAD	-0.023	0.15	-10000	0	-0.4	61	61
megakaryocyte differentiation	-0.051	0.18	-10000	0	-0.48	68	68
GSK3B	-0.023	0.15	-10000	0	-0.4	60	60
RAF1	-0.005	0.14	-10000	0	-0.44	28	28
SHC1	0.013	0	-10000	0	-10000	0	0
STAT3	-0.041	0.17	-10000	0	-0.47	60	60
STAT1	-0.12	0.38	-10000	0	-1	68	68
HRAS/SPRED1	-0.008	0.15	-10000	0	-0.43	34	34
cell proliferation	-0.045	0.18	-10000	0	-0.48	62	62
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
TEC	0.013	0	-10000	0	-10000	0	0
RPS6KB1	-0.04	0.18	-10000	0	-0.47	61	61
HRAS/SPRED2	-0.008	0.14	-10000	0	-0.44	30	30
LYN/TEC/p62DOK	-0.025	0.16	-10000	0	-0.44	60	60
MAPK3	0.01	0.1	-10000	0	-0.3	26	26
STAP1	-0.11	0.22	-10000	0	-0.42	133	133
GRAP2	-0.008	0.1	-10000	0	-0.48	21	21
JAK2	-0.094	0.32	-10000	0	-0.85	68	68
STAT1 (dimer)	-0.11	0.37	-10000	0	-0.98	68	68
mol:Gleevec	0	0.006	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.037	0.18	-10000	0	-0.47	63	63
actin filament polymerization	-0.052	0.18	-10000	0	-0.48	63	63
LYN	0.013	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.13	0.28	-10000	0	-0.67	83	83
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
CBL/CRKL/GRB2	-0.016	0.15	-10000	0	-0.4	59	59
PI3K	-0.029	0.18	-10000	0	-0.46	62	62
PTEN	0	0.078	-10000	0	-0.47	13	13
SCF/KIT/EPO/EPOR	-0.15	0.44	-10000	0	-1.2	62	62
MAPK8	-0.046	0.18	-10000	0	-0.49	62	62
STAT3 (dimer)	-0.04	0.17	-10000	0	-0.46	60	60
positive regulation of transcription	0.013	0.088	-10000	0	-0.27	17	17
mol:GDP	-0.024	0.18	-10000	0	-0.45	62	62
PIK3C2B	-0.041	0.17	-10000	0	-0.47	60	60
CBL/CRKL	-0.024	0.16	-10000	0	-0.42	60	60
FER	-0.051	0.19	-10000	0	-0.49	68	68
SH2B3	-0.041	0.17	-10000	0	-0.47	60	60
PDPK1	-0.03	0.14	-10000	0	-0.39	55	55
SNAI2	-0.097	0.23	-10000	0	-0.59	73	73
positive regulation of cell proliferation	-0.078	0.29	-10000	0	-0.76	68	68
KITLG	-0.012	0.11	-10000	0	-0.5	24	24
cell motility	-0.078	0.29	-10000	0	-0.76	68	68
PTPN6	0.014	0.009	-10000	0	-10000	0	0
EPOR	-0.01	0.13	-10000	0	-0.46	1	1
STAT5A (dimer)	-0.065	0.24	-10000	0	-0.62	72	72
SOCS1	0.009	0.051	-10000	0	-0.55	4	4
cell migration	0.17	0.24	0.37	242	-10000	0	242
SOS1	0.013	0	-10000	0	-10000	0	0
EPO	-0.067	0.19	-10000	0	-0.52	74	74
VAV1	-0.01	0.1	-10000	0	-0.48	23	23
GRB10	-0.041	0.17	-10000	0	-0.47	60	60
PTPN11	0.013	0.022	-10000	0	-0.46	1	1
SCF/KIT	-0.05	0.18	-10000	0	-0.49	63	63
GO:0007205	0.001	0.009	-10000	0	-10000	0	0
MAP2K1	0.006	0.11	-10000	0	-0.34	26	26
CBL	0.012	0.022	-10000	0	-0.47	1	1
KIT	-0.12	0.42	-10000	0	-1.3	58	58
MAP2K2	0.006	0.12	-10000	0	-0.34	26	26
SHC/Grb2/SOS1	-0.025	0.16	-10000	0	-0.44	60	60
STAT5A	-0.068	0.25	-10000	0	-0.64	72	72
GRB2	0.013	0	-10000	0	-10000	0	0
response to radiation	-0.095	0.23	-10000	0	-0.57	73	73
SHC/GRAP2	0.004	0.073	-10000	0	-0.34	21	21
PTPRO	-0.052	0.19	-10000	0	-0.48	68	68
SH2B2	-0.053	0.19	-10000	0	-0.49	63	63
DOK1	0.013	0	-10000	0	-10000	0	0
MATK	-0.18	0.24	-10000	0	-0.38	242	242
CREBBP	0.027	0.027	-10000	0	-10000	0	0
BCL2	-0.05	0.3	-10000	0	-1.3	23	23

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.013	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.089	0.16	-9999	-0.32	162	162
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.03	0.042	-9999	-10000	0	0
AURKB	-0.18	0.28	-9999	-0.58	159	159
AURKC	0.009	0.049	-9999	-0.52	4	4

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.018	0.12	-9999	-0.36	48	48
alphaV beta3 Integrin	-0.053	0.17	-9999	-0.36	101	101
PTK2	-0.1	0.24	-9999	-0.53	92	92
IGF1R	0.011	0.035	-9999	-0.52	2	2
PI4KB	0.013	0	-9999	-10000	0	0
MFGE8	0.01	0.038	-9999	-0.47	3	3
SRC	0.013	0	-9999	-10000	0	0
CDKN1B	-0.083	0.19	-9999	-0.48	69	69
VEGFA	-0.019	0.12	-9999	-0.49	31	31
ILK	-0.083	0.19	-9999	-0.48	69	69
ROCK1	0.012	0.022	-9999	-0.47	1	1
AKT1	-0.07	0.18	-9999	-0.44	69	69
PTK2B	-0.042	0.14	-9999	-0.48	26	26
alphaV/beta3 Integrin/JAM-A	-0.091	0.2	-9999	-0.44	87	87
CBL	0.012	0.022	-9999	-0.47	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.18	0.22	-9999	-0.38	244	244
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.01	0.12	-9999	-0.4	28	28
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.064	0.15	-9999	-0.4	57	57
alphaV/beta3 Integrin/Syndecan-1	-0.045	0.14	-9999	-0.29	110	110
PI4KA	0.013	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.095	0.2	-9999	-0.61	51	51
PI4 Kinase	0.02	0	-9999	-10000	0	0
PIK3CA	0.01	0.038	-9999	-0.47	3	3
alphaV/beta3 Integrin/Osteopontin	-0.089	0.17	-9999	-0.32	160	160
RPS6KB1	-0.051	0.2	-9999	-0.56	51	51
TLN1	0.013	0	-9999	-10000	0	0
MAPK3	-0.11	0.28	-9999	-0.6	100	100
GPR124	-0.009	0.1	-9999	-0.47	22	22
MAPK1	-0.11	0.28	-9999	-0.6	100	100
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.008	0.049	-9999	-0.47	5	5
alphaV/beta3 Integrin/Tumstatin	-0.05	0.16	-9999	-0.33	106	106
cell adhesion	-0.14	0.19	-9999	-0.56	47	47
ANGPTL3	-0.22	0.29	-9999	-0.58	191	191
VEGFR2 homodimer/VEGFA homodimer/Src	-0.005	0.1	-9999	-0.3	48	48
IGF-1R heterotetramer	0.011	0.034	-9999	-0.52	2	2
Rac1/GDP	0.01	0	-9999	-10000	0	0
TGFBR2	-0.001	0.081	-9999	-0.47	14	14
ITGB3	-0.083	0.19	-9999	-0.47	97	97
IGF1	-0.046	0.17	-9999	-0.51	55	55
RAC1	0.013	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.045	0.15	-9999	-0.33	97	97
apoptosis	0.011	0.031	-9999	-0.47	2	2
CD47	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.033	0.12	-9999	-0.53	2	2
VCL	-0.016	0.12	-9999	-0.47	29	29
alphaV/beta3 Integrin/Del1	-0.089	0.2	-9999	-0.4	133	133
CSF1	0.003	0.069	-9999	-0.47	10	10
PIK3C2A	-0.083	0.19	-9999	-0.48	69	69
PI4 Kinase/Pyk2	-0.12	0.18	-9999	-0.5	66	66
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.049	0.16	-9999	-0.48	30	30
FAK1/Vinculin	-0.078	0.2	-9999	-0.49	70	70
alphaV beta3/Integrin/ppsTEM5	-0.045	0.15	-9999	-0.33	97	97
RHOA	0.013	0	-9999	-10000	0	0
VTN	-0.1	0.22	-9999	-0.52	104	104
BCAR1	0.013	0	-9999	-10000	0	0
FGF2	-0.024	0.13	-9999	-0.47	37	37
F11R	-0.006	0.093	-9999	-0.33	37	37
alphaV/beta3 Integrin/Lactadherin	-0.035	0.13	-9999	-0.28	97	97
alphaV/beta3 Integrin/TGFBR2	-0.041	0.14	-9999	-0.31	97	97
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.027	0.046	-9999	-0.48	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.029	0.11	-9999	-0.25	97	97
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.002	0.086	-9999	-0.5	14	14
alphaV/beta3 Integrin/Pyk2	-0.04	0.15	-9999	-0.48	26	26
SDC1	-0.007	0.096	-9999	-0.47	20	20
VAV3	0.001	0.098	-9999	-0.48	7	7
PTPN11	0.012	0.022	-9999	-0.47	1	1
IRS1	-0.003	0.086	-9999	-0.47	16	16
FAK1/Paxillin	-0.071	0.19	-9999	-0.45	64	64
cell migration	-0.063	0.19	-9999	-0.44	69	69
ITGAV	0.011	0.031	-9999	-0.47	2	2
PI3K	-0.11	0.17	-9999	-0.52	52	52
SPP1	-0.076	0.21	-9999	-0.57	74	74
KDR	-0.008	0.098	-9999	-0.47	21	21
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.011	0.031	-9999	-0.47	2	2
COL4A3	-0.017	0.12	-9999	-0.48	30	30
angiogenesis	-0.12	0.28	-9999	-0.6	101	101
Rac1/GTP	0.008	0.09	-9999	-0.44	7	7
EDIL3	-0.085	0.2	-9999	-0.47	98	98
cell proliferation	-0.041	0.14	-9999	-0.31	97	97

Signaling events mediated by the Hedgehog family

Figure S15. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S15. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.003	0.16	-10000	0	-0.65	22	22
IHH	-0.038	0.17	-10000	0	-0.53	52	52
SHH Np/Cholesterol/GAS1	-0.088	0.16	-10000	0	-0.3	167	167
LRPAP1	0.013	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.087	0.16	0.3	167	-10000	0	167
SMO/beta Arrestin2	0.002	0.11	-10000	0	-0.45	15	15
SMO	-0.005	0.12	-10000	0	-0.46	18	18
AKT1	0.014	0.08	-10000	0	-0.51	5	5
ARRB2	0.013	0	-10000	0	-10000	0	0
BOC	0.001	0.075	-10000	0	-0.47	12	12
ADRBK1	0.013	0	-10000	0	-10000	0	0
heart looping	-0.005	0.12	-10000	0	-0.46	18	18
STIL	-0.064	0.17	-10000	0	-0.46	37	37
DHH N/PTCH2	0.008	0.067	-10000	0	-0.36	15	15
DHH N/PTCH1	0.004	0.11	-10000	0	-0.44	13	13
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
DHH	0.003	0.073	-10000	0	-0.5	10	10
PTHLH	-0.003	0.2	-10000	0	-0.82	22	22
determination of left/right symmetry	-0.005	0.12	-10000	0	-0.46	18	18
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
skeletal system development	-0.002	0.2	-10000	0	-0.8	22	22
IHH N/Hhip	-0.05	0.16	-10000	0	-0.38	91	91
DHH N/Hhip	-0.024	0.12	-10000	0	-0.34	60	60
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.005	0.12	-10000	0	-0.46	18	18
pancreas development	-0.037	0.15	-10000	0	-0.48	50	50
HHAT	0.005	0.062	-10000	0	-0.47	8	8
PI3K	0.014	0.048	-10000	0	-0.37	7	7
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.039	0.15	-10000	0	-0.47	52	52
somite specification	-0.005	0.12	-10000	0	-0.46	18	18
SHH Np/Cholesterol/PTCH1	-0.059	0.16	-10000	0	-0.47	27	27
SHH Np/Cholesterol/PTCH2	-0.063	0.14	-10000	0	-0.28	138	138
SHH Np/Cholesterol/Megalin	-0.091	0.16	-10000	0	-0.3	171	171
SHH	-0.087	0.18	-10000	0	-0.37	135	135
catabolic process	0.004	0.12	-10000	0	-0.48	11	11
SMO/Vitamin D3	-0.05	0.16	-10000	0	-0.47	26	26
SHH Np/Cholesterol/Hhip	-0.087	0.17	-10000	0	-0.32	157	157
LRP2	-0.043	0.16	-10000	0	-0.49	54	54
receptor-mediated endocytosis	-0.065	0.17	-10000	0	-0.48	38	38
SHH Np/Cholesterol/BOC	-0.066	0.14	-10000	0	-0.33	62	62
SHH Np/Cholesterol/CDO	-0.064	0.14	-10000	0	-0.33	62	62
mesenchymal cell differentiation	0.086	0.17	0.32	157	-10000	0	157
mol:Vitamin D3	-0.057	0.16	-10000	0	-0.46	28	28
IHH N/PTCH2	-0.016	0.11	-10000	0	-0.32	56	56
CDON	0.006	0.063	-10000	0	-0.56	6	6
IHH N/PTCH1	0.005	0.12	-10000	0	-0.48	11	11
Megalin/LRPAP1	-0.021	0.12	-10000	0	-0.34	54	54
PTCH2	0.008	0.055	-10000	0	-0.53	5	5
SHH Np/Cholesterol	-0.068	0.14	-10000	0	-0.28	135	135
PTCH1	0.004	0.12	-10000	0	-0.48	11	11
HHIP	-0.037	0.15	-10000	0	-0.48	50	50

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.002	0.089	-10000	0	-0.3	37	37
fibroblast growth factor receptor signaling pathway	0.002	0.089	-10000	0	-0.3	37	37
LAMA1	-0.041	0.16	-10000	0	-0.53	48	48
PRNP	0.012	0.022	-10000	0	-0.47	1	1
GPC1/SLIT2	-0.024	0.12	-10000	0	-0.33	60	60
SMAD2	0.022	0.049	-10000	0	-0.48	1	1
GPC1/PrPc/Cu2+	0.017	0.019	-10000	0	-0.28	2	2
GPC1/Laminin alpha1	-0.02	0.12	-10000	0	-0.38	48	48
TDGF1	-0.052	0.17	-10000	0	-0.48	63	63
CRIPTO/GPC1	-0.028	0.12	-10000	0	-0.34	64	64
APP/GPC1	0.017	0.036	-10000	0	-0.42	3	3
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.015	0.1	-10000	0	-0.28	64	64
FLT1	0.006	0.061	-10000	0	-0.5	7	7
GPC1/TGFB/TGFBR1/TGFBR2	0.018	0.054	-10000	0	-0.29	14	14
SERPINC1	-0.022	0.13	-10000	0	-0.58	27	27
FYN	-0.015	0.1	-10000	0	-0.28	64	64
FGR	-0.017	0.1	-10000	0	-0.28	67	67
positive regulation of MAPKKK cascade	-0.036	0.14	-10000	0	-0.34	62	62
SLIT2	-0.047	0.16	-10000	0	-0.47	60	60
GPC1/NRG	-0.08	0.16	-10000	0	-0.33	139	139
NRG1	-0.12	0.22	-10000	0	-0.47	138	138
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.002	0.09	-10000	0	-0.31	36	36
LYN	-0.015	0.1	-10000	0	-0.28	64	64
mol:Spermine	0.01	0.016	-10000	0	-0.34	1	1
cell growth	0.002	0.089	-10000	0	-0.3	37	37
BMP signaling pathway	-0.012	0.022	0.47	1	-10000	0	1
SRC	-0.015	0.1	-10000	0	-0.28	64	64
TGFBR1	0.013	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.2	0.28	-10000	0	-0.56	183	183
GPC1	0.012	0.022	-10000	0	-0.47	1	1
TGFBR1 (dimer)	0.013	0	-10000	0	-10000	0	0
VEGFA	-0.019	0.12	-10000	0	-0.49	31	31
BLK	-0.086	0.17	-10000	0	-0.32	155	155
HCK	-0.017	0.1	-10000	0	-0.28	68	68
FGF2	-0.024	0.13	-10000	0	-0.47	37	37
FGFR1	0.01	0.038	-10000	0	-0.47	3	3
VEGFR1 homodimer	0.006	0.061	-10000	0	-0.5	7	7
TGFBR2	-0.001	0.081	-10000	0	-0.47	14	14
cell death	0.017	0.036	-10000	0	-0.42	3	3
ATIII/GPC1	-0.007	0.1	-10000	0	-0.41	28	28
PLA2G2A/GPC1	-0.14	0.21	-10000	0	-0.4	184	184
LCK	-0.021	0.11	-10000	0	-0.29	70	70
neuron differentiation	-0.08	0.16	-10000	0	-0.33	139	139
PrPc/Cu2+	0.009	0.016	-10000	0	-0.34	1	1
APP	0.01	0.038	-10000	0	-0.47	3	3
TGFBR2 (dimer)	-0.001	0.081	-10000	0	-0.47	14	14

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	-0.029	0.14	-10000	0	-0.68	19	19
NFATC2	-0.097	0.25	-10000	0	-0.66	44	44
NFATC3	-0.009	0.086	-10000	0	-10000	0	0
CD40LG	-0.22	0.4	-10000	0	-0.99	70	70
ITCH	-0.012	0.1	-10000	0	-10000	0	0
CBLB	-0.012	0.1	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.25	0.4	-10000	0	-0.89	107	107
JUNB	-0.016	0.12	-10000	0	-0.52	26	26
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.03	0.12	-10000	0	-10000	0	0
T cell anergy	-0.076	0.18	-10000	0	-0.42	88	88
TLE4	-0.049	0.18	-10000	0	-0.66	17	17
Jun/NFAT1-c-4/p21SNFT	-0.14	0.33	-10000	0	-0.88	49	49
AP-1/NFAT1-c-4	-0.23	0.45	-10000	0	-1.1	67	67
IKZF1	-0.063	0.21	-10000	0	-0.64	31	31
T-helper 2 cell differentiation	-0.21	0.31	-10000	0	-0.79	69	69
AP-1/NFAT1	-0.11	0.23	-10000	0	-0.57	66	66
CALM1	-0.011	0.07	-10000	0	-10000	0	0
EGR2	-0.13	0.36	-10000	0	-0.94	52	52
EGR3	-0.15	0.4	-10000	0	-1.1	54	54
NFAT1/FOXP3	-0.094	0.24	-10000	0	-0.65	48	48
EGR1	-0.059	0.18	-10000	0	-0.51	66	66
JUN	0	0.065	-10000	0	-0.51	7	7
EGR4	-0.15	0.26	-10000	0	-0.58	130	130
mol:Ca2+	-0.026	0.073	-10000	0	-10000	0	0
GBP3	-0.1	0.27	-10000	0	-0.73	61	61
FOSL1	-0.11	0.22	-10000	0	-0.5	113	113
NFAT1-c-4/MAF/IRF4	-0.13	0.33	-10000	0	-0.89	51	51
DGKA	-0.048	0.18	-10000	0	-0.63	18	18
CREM	0.013	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.14	0.32	-10000	0	-0.86	48	48
CTLA4	-0.11	0.28	-10000	0	-0.68	78	78
NFAT1-c-4 (dimer)/EGR1	-0.16	0.37	-10000	0	-0.93	66	66
NFAT1-c-4 (dimer)/EGR4	-0.21	0.36	-10000	0	-0.86	81	81
FOS	-0.084	0.2	-10000	0	-0.5	88	88
IFNG	-0.13	0.27	-10000	0	-0.73	50	50
T cell activation	-0.086	0.22	-10000	0	-0.7	25	25
MAF	0.006	0.058	-10000	0	-0.47	7	7
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.081	0.23	0.68	25	-10000	0	25
TNF	-0.22	0.38	-10000	0	-0.91	84	84
FASLG	-0.19	0.45	-10000	0	-1.3	50	50
TBX21	-0.016	0.13	-10000	0	-0.56	26	26
BATF3	-0.017	0.13	-10000	0	-0.57	25	25
PRKCQ	-0.03	0.15	-10000	0	-0.5	42	42
PTPN1	-0.048	0.18	-10000	0	-0.61	18	18
NFAT1-c-4/ICER1	-0.12	0.31	-10000	0	-0.85	46	46
GATA3	-0.13	0.22	-10000	0	-0.47	142	142
T-helper 1 cell differentiation	-0.12	0.27	-10000	0	-0.71	51	51
IL2RA	-0.26	0.33	-10000	0	-0.8	103	103
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.048	0.18	-10000	0	-0.61	18	18
E2F1	-0.008	0.12	-10000	0	-0.57	22	22
PPARG	-0.017	0.12	-10000	0	-0.48	30	30
SLC3A2	-0.048	0.18	-10000	0	-0.64	15	15
IRF4	-0.036	0.16	-10000	0	-0.53	44	44
PTGS2	-0.24	0.42	-10000	0	-1	80	80
CSF2	-0.21	0.38	-10000	0	-0.96	64	64
JunB/Fra1/NFAT1-c-4	-0.18	0.36	-10000	0	-0.95	58	58
IL4	-0.22	0.32	-10000	0	-0.83	69	69
IL5	-0.21	0.38	-10000	0	-0.95	66	66
IL2	-0.087	0.22	-10000	0	-0.71	25	25
IL3	-0.046	0.053	-10000	0	-10000	0	0
RNF128	-0.091	0.25	-10000	0	-0.54	111	111
NFATC1	-0.081	0.23	-10000	0	-0.69	25	25
CDK4	0.074	0.18	0.59	8	-10000	0	8
PTPRK	-0.048	0.18	-10000	0	-0.61	18	18
IL8	-0.23	0.41	-10000	0	-0.98	81	81
POU2F1	0.012	0.027	-10000	0	-0.58	1	1

Ras signaling in the CD4+ TCR pathway

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
ERK1-2/ELK1	-0.069	0.19	-9999	-0.5	55	55
MAP3K8	-0.001	0.08	-9999	-0.48	13	13
FOS	-0.056	0.16	-9999	-0.4	57	57
PRKCA	-0.008	0.096	-9999	-0.47	20	20
PTPN7	-0.014	0.12	-9999	-0.58	22	22
HRAS	0.007	0.059	-9999	-0.58	5	5
PRKCB	-0.099	0.2	-9999	-0.47	111	111
NRAS	0.012	0.022	-9999	-0.48	1	1
RAS family/GTP	0.018	0.038	-9999	-0.31	6	6
MAPK3	-0.027	0.091	-9999	-0.27	12	12
MAP2K1	-0.091	0.24	-9999	-0.48	113	113
ELK1	0.011	0.008	-9999	-10000	0	0
BRAF	-0.087	0.22	-9999	-0.46	113	113
mol:GTP	-0.001	0.002	-9999	-0.005	86	86
MAPK1	-0.027	0.091	-9999	-0.25	22	22
RAF1	-0.086	0.22	-9999	-0.45	113	113
KRAS	0.013	0.001	-9999	-10000	0	0

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.002	0.076	-10000	0	-0.55	9	9
GNB1/GNG2	-0.058	0.078	-10000	0	-0.19	84	84
AKT1	-0.023	0.11	-10000	0	-0.21	32	32
EGF	-0.056	0.18	-10000	0	-0.54	61	61
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	0.006	0.076	-10000	0	-0.32	7	7
mol:Ca2+	-0.054	0.15	-10000	0	-0.29	117	117
LYN	0.008	0.073	-10000	0	-0.31	5	5
RhoA/GTP	-0.036	0.052	-10000	0	-0.14	4	4
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.061	0.18	-10000	0	-0.34	117	117
GNG2	0.008	0.049	-10000	0	-0.47	5	5
ARRB2	0.013	0	-10000	0	-10000	0	0
TP alpha/Gq family/GDP/G beta5/gamma2	-0.003	0.11	-10000	0	-0.35	40	40
G beta5/gamma2	-0.075	0.1	-10000	0	-0.26	85	85
PRKCH	-0.062	0.17	-10000	0	-0.33	117	117
DNM1	0.011	0.035	-10000	0	-0.52	2	2
TXA2/TP beta/beta Arrestin3	-0.007	0.018	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
PTGDR	-0.023	0.13	-10000	0	-0.47	36	36
G12 family/GTP	-0.089	0.12	-10000	0	-0.3	116	116
ADRBK1	0.013	0	-10000	0	-10000	0	0
ADRBK2	0.012	0.022	-10000	0	-0.47	1	1
RhoA/GTP/ROCK1	0.017	0.013	-10000	0	-0.28	1	1
mol:GDP	0.035	0.11	0.29	33	-10000	0	33
mol:NADP	0.005	0.07	-10000	0	-0.57	7	7
RAB11A	0.013	0	-10000	0	-10000	0	0
PRKG1	-0.13	0.22	-10000	0	-0.47	139	139
mol:IP3	-0.072	0.18	-10000	0	-0.37	117	117
cell morphogenesis	0.017	0.013	-10000	0	-0.28	1	1
PLCB2	-0.1	0.24	-10000	0	-0.49	117	117
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.045	0.12	-10000	0	-0.34	36	36
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	0.006	0.078	-10000	0	-0.35	7	7
RHOA	0.013	0	-10000	0	-10000	0	0
PTGIR	-0.044	0.17	-10000	0	-0.57	48	48
PRKCB1	-0.071	0.18	-10000	0	-0.36	117	117
GNAQ	0.013	0	-10000	0	-10000	0	0
mol:L-citrulline	0.005	0.07	-10000	0	-0.57	7	7
TXA2/TXA2-R family	-0.11	0.25	-10000	0	-0.52	118	118
LCK	0.003	0.084	-10000	0	-0.34	11	11
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.025	0.079	-10000	0	-0.38	5	5
TXA2-R family/G12 family/GDP/G beta/gamma	0.017	0.034	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.004	0.083	-10000	0	-0.38	5	5
MAPK14	-0.032	0.12	-10000	0	-0.24	39	39
TGM2/GTP	-0.086	0.21	-10000	0	-0.42	117	117
MAPK11	-0.035	0.12	-10000	0	-0.23	81	81
ARHGEF1	-0.024	0.094	-10000	0	-0.19	19	19
GNAI2	0.013	0	-10000	0	-10000	0	0
JNK cascade	-0.073	0.19	-10000	0	-0.38	118	118
RAB11/GDP	0.013	0.002	-10000	0	-10000	0	0
ICAM1	-0.048	0.14	-10000	0	-0.28	119	119
cAMP biosynthetic process	-0.072	0.18	-10000	0	-0.35	117	117
Gq family/GTP/EBP50	0.007	0.066	-10000	0	-0.21	40	40
actin cytoskeleton reorganization	0.017	0.013	-10000	0	-0.28	1	1
SRC	0.008	0.073	-10000	0	-0.31	5	5
GNB5	0.013	0	-10000	0	-10000	0	0
GNB1	0.013	0	-10000	0	-10000	0	0
EGF/EGFR	-0.01	0.089	-10000	0	-0.26	15	15
VCAM1	-0.052	0.15	-10000	0	-0.29	116	116
TP beta/Gq family/GDP/G beta5/gamma2	-0.003	0.11	-10000	0	-0.35	40	40
platelet activation	-0.044	0.16	-10000	0	-0.3	116	116
PGI2/IP	-0.032	0.13	-10000	0	-0.42	48	48
PRKACA	-0.02	0.09	-10000	0	-0.22	83	83
Gq family/GDP/G beta5/gamma2	-0.003	0.1	-10000	0	-0.33	40	40
TXA2/TP beta/beta Arrestin2	-0.005	0.023	-10000	0	-0.45	1	1
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.017	0.094	-10000	0	-0.41	6	6
mol:DAG	-0.08	0.2	-10000	0	-0.41	117	117
EGFR	-0.026	0.13	-10000	0	-0.47	39	39
TXA2/TP alpha	-0.1	0.23	-10000	0	-0.48	117	117
Gq family/GTP	-0.01	0.052	-10000	0	-0.18	27	27
YES1	0.008	0.073	-10000	0	-0.31	5	5
GNAI2/GTP	-0.03	0.066	-10000	0	-0.35	5	5
PGD2/DP	-0.016	0.092	-10000	0	-0.34	36	36
SLC9A3R1	0.013	0	-10000	0	-10000	0	0
FYN	0.008	0.073	-10000	0	-0.31	5	5
mol:NO	0.005	0.07	-10000	0	-0.57	7	7
GNA15	-0.011	0.1	-10000	0	-0.47	24	24
PGK/cGMP	-0.072	0.14	-10000	0	-0.28	146	146
RhoA/GDP	0.013	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.003	0.095	-10000	0	-0.41	6	6
NOS3	0.005	0.07	-10000	0	-0.58	7	7
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCA	-0.067	0.18	-10000	0	-0.35	117	117
PRKCB	-0.093	0.2	-10000	0	-0.4	121	121
PRKCE	-0.06	0.17	-10000	0	-0.34	109	109
PRKCD	-0.07	0.18	-10000	0	-0.37	117	117
PRKCG	-0.075	0.19	-10000	0	-0.38	117	117
muscle contraction	-0.098	0.24	-10000	0	-0.48	118	118
PRKCZ	-0.059	0.17	-10000	0	-0.34	116	116
ARR3	0.002	0.038	-10000	0	-0.58	2	2
TXA2/TP beta	-0.009	0.086	-10000	0	-0.4	5	5
PRKCQ	-0.073	0.18	-10000	0	-0.36	120	120
MAPKKK cascade	-0.095	0.22	-10000	0	-0.45	118	118
SELE	-0.078	0.19	-10000	0	-0.39	119	119
TP beta/GNAI2/GDP/G beta/gamma	0.003	0.09	-10000	0	-0.41	6	6
ROCK1	0.012	0.022	-10000	0	-0.47	1	1
GNA14	0.012	0.022	-10000	0	-0.47	1	1
chemotaxis	-0.12	0.28	-10000	0	-0.6	118	118
GNA12	0.013	0	-10000	0	-10000	0	0
GNA13	0.013	0	-10000	0	-10000	0	0
GNA11	-0.003	0.086	-10000	0	-0.47	16	16
Rac1/GTP	0.008	0.004	-10000	0	-10000	0	0

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.058	0.22	-9999	-0.68	19	19
CRP	-0.077	0.24	-9999	-0.71	28	28
cell cycle arrest	-0.075	0.25	-9999	-0.67	39	39
TIMP1	-0.052	0.22	-9999	-0.74	17	17
IL6ST	-0.085	0.2	-9999	-0.47	100	100
Rac1/GDP	-0.11	0.23	-9999	-0.48	100	100
AP1	-0.017	0.14	-9999	-0.5	10	10
GAB2	0.014	0.002	-9999	-10000	0	0
TNFSF11	-0.068	0.24	-9999	-0.78	22	22
HSP90B1	0.018	0.044	-9999	-10000	0	0
GAB1	0.013	0.022	-9999	-0.47	1	1
MAPK14	-0.15	0.3	-9999	-0.64	107	107
AKT1	0.044	0.057	-9999	-1	1	1
FOXO1	0.049	0.053	-9999	-0.94	1	1
MAP2K6	-0.14	0.27	-9999	-0.56	112	112
mol:GTP	0	0.001	-9999	-10000	0	0
MAP2K4	-0.087	0.23	-9999	-0.52	75	75
MITF	-0.11	0.23	-9999	-0.47	111	111
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.013	0	-9999	-10000	0	0
A2M	0.016	0.05	-9999	-10000	0	0
CEBPB	0.02	0.002	-9999	-10000	0	0
GRB2/SOS1/GAB family/SHP2	-0.016	0.086	-9999	-0.41	2	2
STAT3	-0.076	0.26	-9999	-0.71	39	39
STAT1	-0.009	0.026	-9999	-10000	0	0
CEBPD	-0.063	0.23	-9999	-0.73	23	23
PIK3CA	0.012	0.038	-9999	-0.47	3	3
PI3K	0.017	0.048	-9999	-0.37	7	7
JUN	0.006	0.062	-9999	-0.5	7	7
PIAS3/MITF	-0.1	0.22	-9999	-0.46	104	104
MAPK11	-0.16	0.31	-9999	-0.65	110	110
STAT3 (dimer)/FOXO1	-0.014	0.2	-9999	-0.57	15	15
GRB2/SOS1/GAB family	-0.11	0.17	-9999	-0.47	57	57
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.12	0.22	-9999	-0.45	112	112
GRB2	0.014	0.001	-9999	-10000	0	0
JAK2	0.012	0.022	-9999	-0.47	1	1
LBP	-0.053	0.2	-9999	-0.64	15	15
PIK3R1	0.009	0.049	-9999	-0.47	5	5
JAK1	0.013	0.006	-9999	-10000	0	0
MYC	-0.073	0.24	-9999	-0.73	21	21
FGG	-0.072	0.23	-9999	-0.69	26	26
macrophage differentiation	-0.075	0.25	-9999	-0.67	39	39
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.12	0.21	-9999	-0.46	92	92
JUNB	-0.074	0.26	-9999	-0.82	30	30
FOS	-0.076	0.19	-9999	-0.48	88	88
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.13	0.24	-9999	-0.49	116	116
STAT1/PIAS1	-0.093	0.2	-9999	-0.46	78	78
GRB2/SOS1/GAB family/SHP2/PI3K	0.034	0.06	-9999	-1.1	1	1
STAT3 (dimer)	-0.073	0.26	-9999	-0.7	39	39
PRKCD	-0.071	0.24	-9999	-0.57	52	52
IL6R	-0.022	0.13	-9999	-0.47	36	36
SOCS3	-0.2	0.42	-9999	-1	82	82
gp130 (dimer)/JAK1/JAK1/LMO4	-0.032	0.13	-9999	-0.29	61	61
Rac1/GTP	-0.1	0.23	-9999	-0.52	84	84
HCK	0.009	0.046	-9999	-0.5	4	4
MAPKKK cascade	0.009	0.074	-9999	-0.85	1	1
bone resorption	-0.064	0.23	-9999	-0.72	23	23
IRF1	-0.063	0.23	-9999	-0.74	20	20
mol:GDP	-0.12	0.24	-9999	-0.49	114	114
SOS1	0.014	0.002	-9999	-10000	0	0
VAV1	-0.12	0.24	-9999	-0.5	114	114
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	-0.16	0.31	-9999	-0.67	110	110
PTPN11	-0.008	0.047	-9999	-1	1	1
IL6/IL6RA	-0.12	0.2	-9999	-0.38	180	180
gp130 (dimer)/TYK2/TYK2/LMO4	-0.034	0.12	-9999	-0.28	63	63
gp130 (dimer)/JAK2/JAK2/LMO4	-0.034	0.12	-9999	-0.29	44	44
IL6	-0.15	0.25	-9999	-0.51	155	155
PIAS3	0.013	0	-9999	-10000	0	0
PTPRE	0.007	0.042	-9999	-0.5	3	3
PIAS1	0.012	0.022	-9999	-0.47	1	1
RAC1	0.014	0.001	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.12	0.21	-9999	-0.43	118	118
LMO4	0.014	0.026	-9999	-0.51	1	1
STAT3 (dimer)/PIAS3	-0.078	0.25	-9999	-0.68	37	37
MCL1	0.049	0.049	-9999	-0.85	1	1

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.003	0.11	-9999	-0.48	12	12
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.12	-9999	-0.39	11	11
AP1	-0.099	0.16	-9999	-0.5	50	50
mol:PIP3	-0.069	0.14	-9999	-0.43	42	42
AKT1	0.027	0.084	-9999	-0.34	12	12
PTK2B	-0.006	0.09	-9999	-0.3	29	29
RHOA	0.018	0.034	-9999	-0.29	1	1
PIK3CB	0.012	0.027	-9999	-0.57	1	1
mol:Ca2+	-0.011	0.11	-9999	-0.34	21	21
MAGI3	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
apoptosis	-0.047	0.15	-9999	-0.3	108	108
HRAS/GDP	0.005	0.044	-9999	-0.42	5	5
positive regulation of microtubule depolymerization	0.006	0.082	-9999	-0.3	17	17
NF kappa B1 p50/RelA	-0.059	0.12	-9999	-0.46	22	22
endothelial cell migration	-0.018	0.14	-9999	-0.67	16	16
ADCY4	-0.056	0.22	-9999	-0.56	67	67
ADCY5	-0.096	0.3	-9999	-0.69	83	83
ADCY6	-0.055	0.22	-9999	-0.55	67	67
ADCY7	-0.055	0.22	-9999	-0.55	67	67
ADCY1	-0.066	0.22	-9999	-0.55	70	70
ADCY2	-0.066	0.24	-9999	-0.57	74	74
ADCY3	-0.055	0.22	-9999	-0.55	67	67
ADCY8	-0.059	0.22	-9999	-0.55	67	67
ADCY9	-0.056	0.22	-9999	-0.55	67	67
GSK3B	0.001	0.086	-9999	-0.31	22	22
arachidonic acid secretion	-0.055	0.22	-9999	-0.54	68	68
GNG2	0.008	0.049	-9999	-0.47	5	5
TRIP6	0.017	0.047	-9999	-0.36	7	7
GNAO1	-0.062	0.19	-9999	-0.4	99	99
HRAS	0.007	0.059	-9999	-0.58	5	5
NFKBIA	-0.016	0.13	-9999	-0.38	25	25
GAB1	0.012	0.022	-9999	-0.47	1	1
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0.02	0.071	-9999	-0.88	3	3
JUN	0.006	0.062	-9999	-0.5	7	7
LPA/LPA2/NHERF2	0.014	0.042	-9999	-0.34	6	6
TIAM1	-0.005	0.081	-9999	-1	3	3
PIK3R1	0.008	0.049	-9999	-0.47	5	5
mol:IP3	-0.012	0.11	-9999	-0.35	21	21
PLCB3	0.02	0.038	-9999	-0.31	6	6
FOS	-0.076	0.19	-9999	-0.48	88	88
positive regulation of mitosis	-0.055	0.22	-9999	-0.54	68	68
LPA/LPA1-2-3	-0.044	0.15	-9999	-0.47	28	28
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.013	0	-9999	-10000	0	0
stress fiber formation	-0.012	0.11	-9999	-0.38	23	23
GNAZ	-0.035	0.16	-9999	-0.38	70	70
EGFR/PI3K-beta/Gab1	-0.072	0.14	-9999	-0.45	42	42
positive regulation of dendritic cell cytokine production	-0.045	0.15	-9999	-0.47	28	28
LPA/LPA2/MAGI-3	0.018	0.019	-9999	-0.31	1	1
ARHGEF1	0.006	0.091	-9999	-0.43	9	9
GNAI2	-0.009	0.11	-9999	-0.31	49	49
GNAI3	-0.009	0.11	-9999	-0.3	51	51
GNAI1	-0.014	0.12	-9999	-0.32	55	55
LPA/LPA3	-0.046	0.13	-9999	-0.34	78	78
LPA/LPA2	0.01	0.023	-9999	-0.38	1	1
LPA/LPA1	-0.022	0.12	-9999	-0.36	52	52
HB-EGF/EGFR	-0.21	0.2	-9999	-0.37	286	286
HBEGF	-0.23	0.22	-9999	-0.42	274	274
mol:DAG	-0.012	0.11	-9999	-0.35	21	21
cAMP biosynthetic process	-0.069	0.24	-9999	-0.6	71	71
NFKB1	0.013	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
LYN	-0.016	0.13	-9999	-0.38	25	25
GNAQ	-0.022	0.099	-9999	-0.24	79	79
LPAR2	0.012	0.022	-9999	-0.47	1	1
LPAR3	-0.066	0.18	-9999	-0.48	78	78
LPAR1	-0.032	0.15	-9999	-0.5	45	45
IL8	-0.15	0.19	-9999	-0.46	105	105
PTK2	-0.035	0.14	-9999	-0.44	28	28
Rac1/GDP	0.01	0	-9999	-10000	0	0
CASP3	-0.047	0.15	-9999	-0.3	108	108
EGFR	-0.026	0.13	-9999	-0.47	39	39
PLCG1	-0.027	0.12	-9999	-0.29	73	73
PLD2	-0.035	0.14	-9999	-0.44	28	28
G12/G13	0.001	0.098	-9999	-0.46	9	9
PI3K-beta	-0.025	0.078	-9999	-0.38	15	15
cell migration	0.011	0.067	-9999	-0.24	8	8
SLC9A3R2	0.007	0.059	-9999	-0.58	5	5
PXN	-0.013	0.11	-9999	-0.38	23	23
HRAS/GTP	-0.058	0.23	-9999	-0.56	68	68
RAC1	0.013	0	-9999	-10000	0	0
MMP9	-0.31	0.29	-9999	-0.57	270	270
PRKCE	0.013	0	-9999	-10000	0	0
PRKCD	-0.005	0.1	-9999	-0.34	19	19
Gi(beta/gamma)	-0.05	0.21	-9999	-0.53	67	67
mol:LPA	0	0.024	-9999	-0.17	7	7
TRIP6/p130 Cas/FAK1/Paxillin	-0.056	0.12	-9999	-0.46	25	25
MAPKKK cascade	-0.055	0.22	-9999	-0.54	68	68
contractile ring contraction involved in cytokinesis	0.018	0.034	-9999	-0.29	1	1
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.022	0.1	-9999	-0.25	79	79
GNA15	-0.035	0.12	-9999	-0.27	95	95
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
MAPT	0.006	0.084	-9999	-0.3	17	17
GNA11	-0.031	0.12	-9999	-0.27	87	87
Rac1/GTP	0.02	0.075	-9999	-0.93	3	3
MMP2	-0.018	0.14	-9999	-0.67	16	16

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0.03	0.073	0.17	102	-10000	0	102
BUB1B	-0.056	0.12	-10000	0	-0.25	130	130
PLK1	-0.011	0.048	-10000	0	-0.14	35	35
PLK1S1	0	0.025	-10000	0	-0.13	2	2
KIF2A	-0.003	0.045	-10000	0	-0.25	3	3
regulation of mitotic centrosome separation	-0.011	0.048	-10000	0	-0.14	35	35
GOLGA2	0.013	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.084	0.17	-10000	0	-0.34	141	141
WEE1	-0.003	0.05	-10000	0	-0.28	4	4
cytokinesis	-0.1	0.15	-10000	0	-0.27	190	190
PP2A-alpha B56	0.001	0.069	-10000	0	-0.6	1	1
AURKA	-0.006	0.043	-10000	0	-0.15	35	35
PICH/PLK1	-0.024	0.14	-10000	0	-0.44	43	43
CENPE	-0.044	0.14	-10000	0	-0.4	62	62
RhoA/GTP	0.01	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.003	0.045	-10000	0	-0.25	3	3
PPP2CA	0.013	0	-10000	0	-10000	0	0
FZR1	0.013	0	-10000	0	-10000	0	0
TPX2	-0.032	0.067	-10000	0	-0.13	136	136
PAK1	0.007	0.055	-10000	0	-0.48	6	6
SPC24	-0.15	0.26	-10000	0	-0.58	138	138
FBXW11	0.013	0	-10000	0	-10000	0	0
CLSPN	-0.018	0.065	-10000	0	-0.17	67	67
GORASP1	0.013	0	-10000	0	-10000	0	0
metaphase	-0.002	0.005	-10000	0	-0.011	103	103
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.005	0.025	-10000	0	-0.068	35	35
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.009	19	19
STAG2	0.013	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.004	0.009	-10000	0	-10000	0	0
spindle elongation	-0.011	0.048	-10000	0	-0.14	35	35
ODF2	0.013	0.002	-10000	0	-10000	0	0
BUB1	-0.03	0.067	-10000	0	-0.66	1	1
TPT1	0	0.025	-10000	0	-0.13	2	2
CDC25C	-0.062	0.085	-10000	0	-0.16	157	157
CDC25B	0.011	0.035	-10000	0	-0.53	2	2
SGOL1	-0.03	0.073	-10000	0	-0.17	102	102
RHOA	0.013	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.022	0.071	-10000	0	-0.32	23	23
CDC14B	0.007	0.036	-10000	0	-0.34	5	5
CDC20	-0.19	0.28	-10000	0	-0.58	164	164
PLK1/PBIP1	-0.037	0.12	-10000	0	-0.39	48	48
mitosis	0.001	0.006	0.021	32	-0.021	3	35
FBXO5	0	0.037	-10000	0	-0.19	3	3
CDC2	0	0.004	-10000	0	-0.014	24	24
NDC80	0.01	0.038	-10000	0	-0.47	3	3
metaphase plate congression	-0.004	0.031	-10000	0	-0.14	2	2
ERCC6L	-0.019	0.13	-10000	0	-0.41	43	43
NLP/gamma Tubulin	-0.003	0.027	-10000	0	-0.13	3	3
microtubule cytoskeleton organization	0	0.025	-10000	0	-0.13	2	2
G2/M transition DNA damage checkpoint	0	0.001	0.009	4	-10000	0	4
PPP1R12A	0.013	0.001	-10000	0	-10000	0	0
interphase	0	0.001	0.009	4	-10000	0	4
PLK1/PRC1-2	-0.13	0.22	-10000	0	-0.38	185	185
GRASP65/GM130/RAB1/GTP/PLK1	0.011	0.038	-10000	0	-10000	0	0
RAB1A	0.013	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	-0.001	0.04	-10000	0	-0.22	3	3
mitotic prometaphase	-0.002	0.003	-10000	0	-0.009	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.009	0.062	-10000	0	-0.3	4	4
microtubule-based process	-0.13	0.19	-10000	0	-0.36	185	185
Golgi organization	-0.011	0.048	-10000	0	-0.14	35	35
Cohesin/SA2	-0.006	0.043	-10000	0	-0.23	2	2
PPP1CB/MYPT1	0.019	0.002	-10000	0	-10000	0	0
KIF20A	-0.21	0.29	-10000	0	-0.58	185	185
APC/C/CDC20	-0.11	0.19	-10000	0	-0.37	164	164
PPP2R1A	0.013	0	-10000	0	-10000	0	0
chromosome segregation	-0.036	0.12	-10000	0	-0.38	48	48
PRC1	-0.02	0.14	-10000	0	-0.58	27	27
ECT2	-0.013	0.082	-10000	0	-0.39	17	17
C13orf34	-0.002	0.04	-10000	0	-0.22	3	3
NUDC	-0.004	0.031	-10000	0	-0.14	2	2
regulation of attachment of spindle microtubules to kinetochore	-0.055	0.12	-10000	0	-0.24	130	130
spindle assembly	-0.006	0.038	-10000	0	-0.12	19	19
spindle stabilization	0	0.025	-10000	0	-0.13	2	2
APC/C/HCDH1	0.014	0.03	-10000	0	-0.28	5	5
MKLP2/PLK1	-0.13	0.19	-10000	0	-0.37	185	185
CCNB1	-0.013	0.12	-10000	0	-0.58	22	22
PPP1CB	0.013	0.001	-10000	0	-10000	0	0
BTRC	0.013	0	-10000	0	-10000	0	0
ROCK2	-0.032	0.12	-10000	0	-0.4	43	43
TUBG1	0	0.025	-10000	0	-0.13	2	2
G2/M transition of mitotic cell cycle	-0.023	0.069	-10000	0	-0.32	23	23
MLF1IP	-0.036	0.13	-10000	0	-0.44	48	48
INCENP	0.013	0.002	-10000	0	-10000	0	0

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.01	0.097	-9999	-0.38	23	23
alphaM/beta2 Integrin/GPIbA	-0.008	0.095	-9999	-0.39	20	20
alphaM/beta2 Integrin/proMMP-9	-0.2	0.2	-9999	-0.37	271	271
PLAUR	0.003	0.075	-9999	-0.58	8	8
HMGB1	0	0.023	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	0	0.073	-9999	-0.42	10	10
AGER	-0.027	0.12	-9999	-0.59	22	22
RAP1A	0.013	0	-9999	-10000	0	0
SELPLG	0.006	0.065	-9999	-0.58	6	6
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.05	0.14	-9999	-0.53	17	17
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.31	0.29	-9999	-0.57	270	270
CYR61	-0.006	0.1	-9999	-0.51	18	18
TLN1	0.013	0	-9999	-10000	0	0
Rap1/GTP	-0.065	0.098	-9999	-0.33	32	32
RHOA	0.013	0	-9999	-10000	0	0
P-selectin oligomer	0.004	0.065	-9999	-0.47	9	9
MYH2	-0.13	0.17	-9999	-0.42	85	85
MST1R	-0.006	0.096	-9999	-0.49	18	18
leukocyte activation during inflammatory response	-0.1	0.15	-9999	-0.35	83	83
APOB	-0.1	0.21	-9999	-0.47	117	117
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	-0.003	0.088	-9999	-0.48	16	16
JAM3	-0.006	0.094	-9999	-0.47	19	19
GP1BA	0	0.079	-9999	-0.5	12	12
alphaM/beta2 Integrin/CTGF	-0.013	0.096	-9999	-0.38	21	21
alphaM/beta2 Integrin	-0.068	0.13	-9999	-0.36	45	45
JAM3 homodimer	-0.006	0.094	-9999	-0.47	19	19
ICAM2	0.01	0.041	-9999	-0.51	3	3
ICAM1	0	0.088	-9999	-0.58	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.068	0.13	-9999	-0.35	45	45
cell adhesion	-0.008	0.094	-9999	-0.39	20	20
NFKB1	-0.09	0.21	-9999	-0.61	32	32
THY1	0.003	0.075	-9999	-0.58	8	8
RhoA/GDP	0.01	0	-9999	-10000	0	0
Lipoprotein(a)	-0.093	0.17	-9999	-0.32	161	161
alphaM/beta2 Integrin/LRP/tPA	-0.01	0.1	-9999	-0.36	35	35
IL6	-0.18	0.33	-9999	-0.7	119	119
ITGB2	-0.009	0.075	-9999	-0.6	7	7
elevation of cytosolic calcium ion concentration	-0.004	0.1	-9999	-0.39	21	21
alphaM/beta2 Integrin/JAM2/JAM3	-0.005	0.098	-9999	-0.39	21	21
JAM2	0.006	0.058	-9999	-0.47	7	7
alphaM/beta2 Integrin/ICAM1	-0.041	0.15	-9999	-0.39	38	38
alphaM/beta2 Integrin/uPA/Plg	-0.02	0.11	-9999	-0.35	38	38
RhoA/GTP	-0.08	0.15	-9999	-0.4	49	49
positive regulation of phagocytosis	-0.056	0.096	-9999	-0.42	15	15
Ron/MSP	-0.049	0.16	-9999	-0.41	77	77
alphaM/beta2 Integrin/uPAR/uPA	-0.004	0.1	-9999	-0.39	21	21
alphaM/beta2 Integrin/uPAR	-0.006	0.093	-9999	-0.43	17	17
PLAU	0	0.08	-9999	-0.48	13	13
PLAT	-0.018	0.13	-9999	-0.55	27	27
actin filament polymerization	-0.13	0.17	-9999	-0.4	85	85
MST1	-0.062	0.2	-9999	-0.58	62	62
alphaM/beta2 Integrin/lipoprotein(a)	-0.087	0.16	-9999	-0.34	92	92
TNF	-0.1	0.25	-9999	-0.72	47	47
RAP1B	0.013	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.008	0.093	-9999	-0.37	22	22
fibrinolysis	-0.02	0.11	-9999	-0.35	38	38
HCK	0.009	0.046	-9999	-0.5	4	4
dendritic cell antigen processing and presentation	-0.068	0.13	-9999	-0.35	45	45
VTN	-0.1	0.22	-9999	-0.52	104	104
alphaM/beta2 Integrin/CYR61	-0.012	0.1	-9999	-0.39	25	25
LPA	-0.055	0.17	-9999	-0.48	66	66
LRP1	0.01	0.041	-9999	-0.51	3	3
cell migration	-0.19	0.18	-9999	-0.34	272	272
FN1	-0.002	0.086	-9999	-0.5	14	14
alphaM/beta2 Integrin/Thy1	-0.006	0.09	-9999	-0.43	15	15
MPO	-0.027	0.13	-9999	-0.47	40	40
KNG1	-0.067	0.19	-9999	-0.58	60	60
RAP1/GDP	0.018	0	-9999	-10000	0	0
ROCK1	-0.07	0.14	-9999	-0.4	40	40
ELA2	0	0	-9999	-10000	0	0
PLG	-0.023	0.13	-9999	-0.58	24	24
CTGF	-0.007	0.097	-9999	-0.48	20	20
alphaM/beta2 Integrin/Hck	-0.003	0.083	-9999	-0.41	13	13
ITGAM	-0.006	0.059	-9999	-0.53	5	5
alphaM/beta2 Integrin/P-Selectin/PSGL1	0	0.098	-9999	-0.44	15	15
HP	-0.076	0.2	-9999	-0.54	78	78
leukocyte adhesion	-0.072	0.12	-9999	-0.43	30	30
SELP	0.004	0.065	-9999	-0.47	9	9

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	-0.002	0.094	-9999	-0.42	24	24
VLDLR	0.012	0.022	-9999	-0.47	1	1
CRKL	0.013	0	-9999	-10000	0	0
LRPAP1	0.013	0	-9999	-10000	0	0
FYN	0.013	0.001	-9999	-10000	0	0
ITGA3	0.003	0.069	-9999	-0.47	10	10
RELN/VLDLR/Fyn	-0.034	0.14	-9999	-0.35	74	74
MAPK8IP1/MKK7/MAP3K11/JNK1	0.033	0.04	-9999	-10000	0	0
AKT1	-0.086	0.14	-9999	-0.38	47	47
MAP2K7	0.013	0	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
DAB1	-0.17	0.24	-9999	-0.47	187	187
RELN/LRP8/DAB1	-0.14	0.19	-9999	-0.32	226	226
LRPAP1/LRP8	0.013	0.052	-9999	-0.42	7	7
RELN/LRP8/DAB1/Fyn	-0.12	0.18	-9999	-0.43	79	79
DAB1/alpha3/beta1 Integrin	-0.12	0.16	-9999	-0.52	47	47
long-term memory	-0.16	0.22	-9999	-0.54	85	85
DAB1/LIS1	-0.13	0.16	-9999	-0.51	46	46
DAB1/CRLK/C3G	-0.12	0.15	-9999	-0.49	46	46
PIK3CA	0.01	0.038	-9999	-0.47	3	3
DAB1/NCK2	-0.13	0.16	-9999	-0.51	46	46
ARHGEF2	0.013	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.093	0.2	-9999	-0.47	106	106
CDK5R1	-0.016	0.13	-9999	-0.58	24	24
RELN	-0.081	0.22	-9999	-0.57	79	79
PIK3R1	0.008	0.049	-9999	-0.47	5	5
RELN/LRP8/Fyn	-0.038	0.15	-9999	-0.36	83	83
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.17	0.23	-9999	-0.56	84	84
MAPK8	0.002	0.072	-9999	-0.47	11	11
RELN/VLDLR/DAB1	-0.13	0.19	-9999	-0.45	78	78
ITGB1	0.013	0	-9999	-10000	0	0
MAP1B	-0.14	0.2	-9999	-0.55	63	63
RELN/LRP8	-0.038	0.15	-9999	-0.36	83	83
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.12	0.19	-9999	-0.54	46	46
PI3K	0.014	0.048	-9999	-0.37	7	7
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	0.012	0.049	-9999	-0.33	10	10
RAP1A	-0.085	0.16	-9999	-0.46	46	46
PAFAH1B1	0.013	0	-9999	-10000	0	0
MAPK8IP1	0.012	0.027	-9999	-0.58	1	1
CRLK/C3G	0.02	0	-9999	-10000	0	0
GRIN2B	0.002	0.027	-9999	-0.58	1	1
NCK2	0.013	0	-9999	-10000	0	0
neuron differentiation	-0.065	0.12	-9999	-0.3	49	49
neuron adhesion	-0.074	0.17	-9999	-0.46	45	45
LRP8	0.005	0.07	-9999	-0.58	7	7
GSK3B	-0.076	0.14	-9999	-0.35	47	47
RELN/VLDLR/DAB1/Fyn	-0.12	0.18	-9999	-0.42	76	76
MAP3K11	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/P13K	-0.099	0.15	-9999	-0.4	47	47
CDK5	0.013	0	-9999	-10000	0	0
MAPT	0.02	0.043	-9999	-0.41	3	3
neuron migration	-0.088	0.17	-9999	-0.41	54	54
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.065	0.12	-9999	-0.3	49	49
RELN/VLDLR	-0.026	0.14	-9999	-0.32	78	78

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.15	0.33	-10000	0	-0.9	44	44
PCK1	-0.14	0.25	-10000	0	-0.72	39	39
HNF4A	-0.19	0.4	-10000	0	-1.2	42	42
KCNJ11	-0.15	0.35	-10000	0	-0.94	42	42
AKT1	-0.031	0.13	-10000	0	-0.44	7	7
response to starvation	-0.006	0.02	-10000	0	-10000	0	0
DLK1	-0.2	0.39	-10000	0	-0.93	73	73
NKX2-1	-0.15	0.26	0.48	1	-0.66	41	42
ACADM	-0.15	0.33	-10000	0	-0.92	44	44
TAT	-0.14	0.26	-10000	0	-0.82	36	36
CEBPB	0.007	0.015	-10000	0	-10000	0	0
CEBPA	0.01	0.013	-10000	0	-10000	0	0
TTR	-0.21	0.35	-10000	0	-0.89	68	68
PKLR	-0.18	0.36	-10000	0	-0.94	54	54
APOA1	-0.22	0.44	-10000	0	-1.2	54	54
CPT1C	-0.16	0.34	-10000	0	-0.94	49	49
ALAS1	-0.043	0.16	-10000	0	-10000	0	0
TFRC	-0.15	0.29	-10000	0	-0.8	45	45
FOXF1	0.002	0.14	-10000	0	-0.45	41	41
NF1	0.02	0	-10000	0	-10000	0	0
HNF1A (dimer)	-0.059	0.19	-10000	0	-0.58	57	57
CPT1A	-0.15	0.33	-10000	0	-0.92	41	41
HMGCS1	-0.15	0.33	-10000	0	-0.94	38	38
NR3C1	-0.001	0.082	-10000	0	-0.47	13	13
CPT1B	-0.19	0.36	-10000	0	-0.94	56	56
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.012	0.018	-10000	0	-10000	0	0
GCK	-0.17	0.37	-10000	0	-0.95	57	57
CREB1	0.008	0.03	-10000	0	-10000	0	0
IGFBP1	-0.078	0.2	-10000	0	-0.69	25	25
PDX1	-0.092	0.22	-10000	0	-0.77	15	15
UCP2	-0.15	0.33	-10000	0	-0.92	43	43
ALDOB	-0.16	0.37	-10000	0	-1	44	44
AFP	-0.087	0.2	-10000	0	-0.55	50	50
BDH1	-0.15	0.33	-10000	0	-0.92	41	41
HADH	-0.15	0.34	-10000	0	-0.95	39	39
F2	-0.2	0.4	-10000	0	-1.2	38	38
HNF1A	-0.06	0.19	-10000	0	-0.58	57	57
G6PC	-0.071	0.16	-10000	0	-0.59	19	19
SLC2A2	-0.11	0.23	-10000	0	-0.85	14	14
INS	-0.021	0.098	-10000	0	-0.58	14	14
FOXA1	-0.012	0.12	-10000	0	-0.34	13	13
FOXA3	-0.11	0.21	-10000	0	-0.54	71	71
FOXA2	-0.18	0.39	-10000	0	-1	46	46
ABCC8	-0.21	0.42	-10000	0	-0.97	84	84
ALB	-0.14	0.25	-10000	0	-0.58	75	75

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.02	0.12	-9999	-0.36	48	48
PDGFRB	0.009	0.038	-9999	-0.58	2	2
SPHK1	-0.02	0.034	-9999	-10000	0	0
mol:S1P	-0.024	0.039	-9999	-10000	0	0
S1P1/S1P/Gi	-0.1	0.25	-9999	-0.49	120	120
GNAO1	-0.081	0.19	-9999	-0.48	93	93
PDGFB-D/PDGFRB/PLCgamma1	-0.081	0.22	-9999	-0.52	72	72
PLCG1	-0.091	0.23	-9999	-0.45	120	120
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.009	0.038	-9999	-0.58	2	2
GNAI2	0.012	0.006	-9999	-10000	0	0
GNAI3	0.011	0.006	-9999	-10000	0	0
GNAI1	0.003	0.065	-9999	-0.53	7	7
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.018	0.099	-9999	-0.31	48	48
S1P1/S1P	-0.024	0.1	-9999	-0.39	17	17
negative regulation of cAMP metabolic process	-0.1	0.24	-9999	-0.47	120	120
MAPK3	-0.12	0.3	-9999	-0.6	120	120
calcium-dependent phospholipase C activity	-0.002	0.003	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
RhoA/GDP	0.01	0	-9999	-10000	0	0
KDR	-0.009	0.099	-9999	-0.47	21	21
PLCB2	-0.016	0.098	-9999	-0.34	17	17
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.041	0.077	-9999	-0.33	17	17
receptor internalization	-0.046	0.085	-9999	-0.36	17	17
PTGS2	-0.19	0.42	-9999	-0.99	96	96
Rac1/GTP	-0.041	0.077	-9999	-0.33	17	17
RHOA	0.013	0	-9999	-10000	0	0
VEGFA	-0.02	0.12	-9999	-0.49	31	31
negative regulation of T cell proliferation	-0.1	0.24	-9999	-0.47	120	120
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	-0.035	0.14	-9999	-0.48	46	46
MAPK1	-0.12	0.3	-9999	-0.6	120	120
S1P1/S1P/PDGFB-D/PDGFRB	-0.024	0.12	-9999	-0.41	19	19
ABCC1	0.012	0.003	-9999	-10000	0	0

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.01	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.002	0.081	-10000	0	-0.24	49	49
regulation of S phase of mitotic cell cycle	0.002	0.087	-10000	0	-0.24	46	46
GNAO1	-0.08	0.19	-10000	0	-0.47	93	93
HRAS	0.007	0.059	-10000	0	-0.58	5	5
SHBG/T-DHT	-0.001	0.055	-10000	0	-0.32	14	14
PELP1	0.013	0.001	-10000	0	-10000	0	0
AKT1	0.011	0	-10000	0	-10000	0	0
MAP2K1	-0.001	0.09	-10000	0	-0.38	11	11
T-DHT/AR	-0.022	0.1	-10000	0	-0.34	44	44
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	-10000	0	-0.007	88	88
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.005	0.065	-10000	0	-0.53	7	7
mol:GDP	-0.036	0.12	-10000	0	-0.4	44	44
cell proliferation	-0.037	0.17	-10000	0	-0.38	87	87
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
FOS	-0.1	0.31	-10000	0	-0.75	88	88
mol:Ca2+	-0.019	0.033	-10000	0	-0.087	78	78
MAPK3	-0.02	0.13	-10000	0	-0.46	11	11
MAPK1	-0.013	0.088	-10000	0	-0.19	84	84
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
mol:IP3	-0.001	0.002	-10000	0	-0.004	88	88
cAMP biosynthetic process	0.006	0.057	-10000	0	-0.28	14	14
GNG2	0.008	0.049	-10000	0	-0.47	5	5
potassium channel inhibitor activity	-0.001	0.002	-10000	0	-0.004	88	88
HRAS/GTP	-0.027	0.077	-10000	0	-0.38	11	11
actin cytoskeleton reorganization	-0.003	0.03	-10000	0	-0.43	1	1
SRC	0.013	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	-0.001	0.002	-10000	0	-0.004	88	88
PI3K	0.013	0.041	-10000	0	-0.31	7	7
apoptosis	0.039	0.17	0.38	87	-10000	0	87
T-DHT/AR/PELP1	-0.01	0.085	-10000	0	-0.28	44	44
HRAS/GDP	-0.036	0.12	-10000	0	-0.4	44	44
CREB1	-0.043	0.18	-10000	0	-0.41	87	87
RAC1-CDC42/GTP	0	0.032	-10000	0	-0.44	1	1
AR	-0.031	0.14	-10000	0	-0.47	44	44
GNB1	0.013	0	-10000	0	-10000	0	0
RAF1	-0.002	0.087	-10000	0	-0.38	11	11
RAC1-CDC42/GDP	-0.028	0.11	-10000	0	-0.36	43	43
T-DHT/AR/PELP1/Src	-0.002	0.078	-10000	0	-0.25	44	44
MAP2K2	-0.001	0.093	-10000	0	-0.4	11	11
T-DHT/AR/PELP1/Src/PI3K	0.001	0.088	-10000	0	-0.25	46	46
GNAZ	-0.033	0.14	-10000	0	-0.47	46	46
SHBG	-0.002	0.089	-10000	0	-0.52	14	14
Gi family/GNB1/GNG2/GDP	-0.051	0.18	-10000	0	-0.4	93	93
mol:T-DHT	0	0.001	0.002	1	-0.003	81	82
RAC1	0.013	0	-10000	0	-10000	0	0
GNRH1	0.001	0.062	-10000	0	-0.42	10	10
Gi family/GTP	-0.046	0.14	-10000	0	-0.36	59	59
CDC42	0.013	0	-10000	0	-10000	0	0

Signaling events mediated by PRL

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
CCNE1	0.007	0.059	-10000	0	-0.58	5	5
mol:Halofuginone	0.005	0.001	-10000	0	-10000	0	0
ITGA1	-0.023	0.13	-10000	0	-0.47	36	36
CDKN1A	0.008	0.069	-10000	0	-0.53	4	4
PRL-3/alpha Tubulin	-0.07	0.18	-10000	0	-0.42	100	100
mol:Ca2+	-0.014	0.18	0.25	86	-0.39	72	158
AGT	-0.07	0.2	-10000	0	-0.55	72	72
CCNA2	-0.048	0.15	-10000	0	-0.52	13	13
TUBA1B	0.013	0	-10000	0	-10000	0	0
EGR1	-0.029	0.13	-10000	0	-0.36	66	66
CDK2/Cyclin E1	0.019	0.07	-10000	0	-0.44	6	6
MAPK3	-0.069	0.18	-10000	0	-0.42	100	100
PRL-2 /Rab GGTase beta	0.02	0	-10000	0	-10000	0	0
MAPK1	-0.069	0.18	-10000	0	-0.42	100	100
PTP4A1	-0.006	0.1	-10000	0	-10000	0	0
PTP4A3	-0.11	0.24	-10000	0	-0.58	100	100
PTP4A2	0.013	0	-10000	0	-10000	0	0
ITGB1	-0.069	0.18	-10000	0	-0.42	100	100
SRC	0.013	0	-10000	0	-10000	0	0
RAC1	-0.015	0.071	-10000	0	-0.23	13	13
Rab GGTase beta/Rab GGTase alpha	0.02	0	-10000	0	-10000	0	0
PRL-1/ATF-5	-0.004	0.1	-10000	0	-0.51	1	1
RABGGTA	0.013	0	-10000	0	-10000	0	0
BCAR1	0.051	0.1	0.25	100	-10000	0	100
RHOC	-0.015	0.071	-10000	0	-10000	0	0
RHOA	-0.015	0.071	-10000	0	-0.23	13	13
cell motility	-0.012	0.074	-10000	0	-0.26	5	5
PRL-1/alpha Tubulin	0.001	0.094	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.094	0.2	-10000	0	-0.42	125	125
ROCK1	-0.012	0.075	-10000	0	-0.26	5	5
RABGGTB	0.013	0	-10000	0	-10000	0	0
CDK2	0.013	0	-10000	0	-10000	0	0
mitosis	-0.006	0.1	-10000	0	-10000	0	0
ATF5	0.003	0.075	-10000	0	-0.58	8	8

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.016	0.055	-9999	-0.26	2	2
BIRC5	-0.2	0.28	-9999	-0.57	179	179
NFKBIA	0.019	0.052	-9999	-10000	0	0
CPEB1	-0.12	0.22	-9999	-0.47	134	134
AKT1	0.019	0.052	-9999	-10000	0	0
NDEL1	0.013	0	-9999	-10000	0	0
Aurora A/BRCA1	0.014	0.055	-9999	-0.47	2	2
NDEL1/TACC3	-0.002	0.12	-9999	-0.37	40	40
GADD45A	0.011	0.031	-9999	-0.47	2	2
GSK3B	0.018	0.007	-9999	-10000	0	0
PAK1/Aurora A	0.014	0.064	-9999	-0.32	6	6
MDM2	0.013	0	-9999	-10000	0	0
JUB	-0.015	0.11	-9999	-0.47	28	28
TPX2	-0.12	0.2	-9999	-0.42	153	153
TP53	0.019	0.047	-9999	-0.27	6	6
DLG7	0.01	0.052	-9999	-0.18	35	35
AURKAIP1	0.003	0.075	-9999	-0.58	8	8
ARHGEF7	0.013	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	-0.003	0.12	-9999	-0.39	40	40
G2/M transition of mitotic cell cycle	0.014	0.055	-9999	-0.47	2	2
AURKA	0.014	0.065	-9999	-0.21	35	35
AURKB	-0.048	0.078	-9999	-0.16	143	143
CDC25B	0.013	0.055	-9999	-0.29	3	3
G2/M transition checkpoint	0	0.076	-9999	-0.24	28	28
mRNA polyadenylation	-0.058	0.13	-9999	-0.26	134	134
Aurora A/CPEB	-0.058	0.13	-9999	-0.26	134	134
Aurora A/TACC1/TRAP/chTOG	0.026	0.061	-9999	-0.37	3	3
BRCA1	0.011	0.038	-9999	-0.58	2	2
centrosome duplication	0.014	0.064	-9999	-0.32	6	6
regulation of centrosome cycle	-0.003	0.12	-9999	-0.37	40	40
spindle assembly	0.025	0.06	-9999	-0.36	3	3
TDRD7	0.013	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.087	0.17	-9999	-0.3	178	178
CENPA	-0.045	0.076	-9999	-0.15	143	143
Aurora A/PP2A	0.017	0.052	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.024	0.044	-9999	-10000	0	0
negative regulation of DNA binding	0.019	0.047	-9999	-0.27	6	6
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0.02	0	-9999	-10000	0	0
RASA1	0.01	0.038	-9999	-0.47	3	3
Ajuba/Aurora A	0	0.076	-9999	-0.24	28	28
mitotic prometaphase	0.013	0.02	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.064	-9999	-0.21	35	35
TACC1	0.002	0.072	-9999	-0.47	11	11
TACC3	-0.035	0.16	-9999	-0.58	40	40
Aurora A/Antizyme1	0.019	0.064	-9999	-0.31	8	8
Aurora A/RasGAP	0.016	0.057	-9999	-0.27	3	3
OAZ1	0.013	0	-9999	-10000	0	0
RAN	0.013	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.018	0.007	-9999	-10000	0	0
GIT1	0.013	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0.023	0.033	-9999	-0.27	6	6
Importin alpha/Importin beta/TPX2	-0.12	0.2	-9999	-0.42	153	153
PPP2R5D	0.013	0.001	-9999	-10000	0	0
Aurora A/TPX2	-0.083	0.18	-9999	-0.34	153	153
PAK1	0.007	0.053	-9999	-0.47	6	6
CKAP5	0.013	0	-9999	-10000	0	0

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.013	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.018	0.096	-10000	0	-0.26	42	42
NT3 (dimer)/TRKC	-0.085	0.2	-10000	0	-0.43	112	112
NT3 (dimer)/TRKB	-0.072	0.19	-10000	0	-0.37	121	121
SHC/Grb2/SOS1/GAB1/PI3K	0.031	0.036	-10000	0	-0.43	1	1
RAPGEF1	0.013	0	-10000	0	-10000	0	0
BDNF	-0.088	0.2	-10000	0	-0.47	102	102
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
DYNLT1	0.013	0.001	-10000	0	-10000	0	0
NTRK1	-0.029	0.14	-10000	0	-0.49	40	40
NTRK2	-0.056	0.17	-10000	0	-0.47	69	69
NTRK3	-0.081	0.19	-10000	0	-0.47	95	95
NT-4/5 (dimer)/TRKB	-0.1	0.21	-10000	0	-0.38	158	158
neuron apoptosis	0.076	0.19	0.5	60	-10000	0	60
SHC 2-3/Grb2	-0.084	0.21	-10000	0	-0.55	60	60
SHC1	0.013	0	-10000	0	-10000	0	0
SHC2	-0.088	0.16	-10000	0	-0.49	52	52
SHC3	-0.12	0.21	-10000	0	-0.56	73	73
STAT3 (dimer)	0.02	0.012	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.057	0.17	-10000	0	-0.34	110	110
RIN/GDP	-0.011	0.097	-10000	0	-0.25	23	23
GIPC1	0.013	0	-10000	0	-10000	0	0
KRAS	0.013	0	-10000	0	-10000	0	0
DNAJA3	-0.029	0.12	-10000	0	-0.34	43	43
RIN/GTP	-0.024	0.11	-10000	0	-0.42	34	34
CCND1	0.028	0.022	-10000	0	-0.47	1	1
MAGED1	0.012	0.027	-10000	0	-0.58	1	1
PTPN11	0.012	0.022	-10000	0	-0.47	1	1
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.099	0.2	-10000	0	-0.47	113	113
SHC/GRB2/SOS1	0.027	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.18	0.21	-10000	0	-0.37	251	251
TRKA/NEDD4-2	-0.024	0.13	-10000	0	-0.4	51	51
ELMO1	0.01	0.038	-10000	0	-0.47	3	3
RhoG/GTP/ELMO1/DOCK1	0.014	0.033	-10000	0	-0.28	6	6
NGF	-0.009	0.1	-10000	0	-0.48	22	22
HRAS	0.007	0.059	-10000	0	-0.58	5	5
DOCK1	0.01	0.038	-10000	0	-0.47	3	3
GAB2	0.013	0	-10000	0	-10000	0	0
RIT2	-0.033	0.15	-10000	0	-0.58	34	34
RIT1	0.013	0	-10000	0	-10000	0	0
FRS2	0.013	0	-10000	0	-10000	0	0
DNM1	0.011	0.035	-10000	0	-0.52	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.013	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.029	0.12	-10000	0	-0.34	43	43
mol:GDP	-0.003	0.12	-10000	0	-0.35	21	21
NGF (dimer)	-0.009	0.1	-10000	0	-0.48	22	22
RhoG/GDP	0.008	0.027	-10000	0	-0.34	3	3
RIT1/GDP	0.006	0.085	-10000	0	-0.24	15	15
TIAM1	0.01	0.038	-10000	0	-0.47	3	3
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
BDNF (dimer)/TRKB	-0.074	0.18	-10000	0	-0.36	126	126
KIDINS220/CRKL/C3G	0.02	0	-10000	0	-10000	0	0
SHC/RasGAP	0.017	0.027	-10000	0	-0.33	3	3
FRS2 family/SHP2	0.026	0.013	-10000	0	-0.27	1	1
SHC/GRB2/SOS1/GAB1	0.034	0.012	-10000	0	-10000	0	0
RIT1/GTP	0.01	0	-10000	0	-10000	0	0
NT3 (dimer)	-0.045	0.16	-10000	0	-0.47	58	58
RAP1/GDP	-0.027	0.053	-10000	0	-0.22	1	1
KIDINS220/CRKL	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.088	0.2	-10000	0	-0.47	102	102
ubiquitin-dependent protein catabolic process	-0.025	0.13	-10000	0	-0.32	71	71
Schwann cell development	-0.026	0.034	-10000	0	-10000	0	0
EHD4	0.013	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0.034	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0.037	0.011	-10000	0	-10000	0	0
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.13	0.21	-10000	0	-0.54	85	85
ABL1	0.013	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
Rap1/GTP	0.004	0.079	-10000	0	-10000	0	0
STAT3	0.02	0.012	-10000	0	-10000	0	0
axon guidance	-0.12	0.2	-10000	0	-0.51	85	85
MAPK3	-0.16	0.19	-10000	0	-0.34	228	228
MAPK1	-0.16	0.19	-10000	0	-0.34	228	228
CDC42/GDP	0.006	0.085	-10000	0	-0.24	12	12
NTF3	-0.045	0.16	-10000	0	-0.47	58	58
NTF4	-0.1	0.2	-10000	0	-0.47	113	113
NGF (dimer)/TRKA/FAIM	-0.013	0.11	-10000	0	-0.29	61	61
PI3K	0.014	0.048	-10000	0	-0.37	7	7
FRS3	0.013	0.001	-10000	0	-10000	0	0
FAIM	0.012	0.027	-10000	0	-0.58	1	1
GAB1	0.012	0.022	-10000	0	-0.47	1	1
RASGRF1	-0.073	0.17	-10000	0	-0.43	61	61
SOS1	0.013	0	-10000	0	-10000	0	0
MCF2L	-0.064	0.17	-10000	0	-0.36	112	112
RGS19	0.012	0.027	-10000	0	-0.58	1	1
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	0.017	0.066	-10000	0	-10000	0	0
Rac1/GDP	0.006	0.085	-10000	0	-0.23	17	17
NGF (dimer)/TRKA/GRIT	-0.021	0.11	-10000	0	-0.3	60	60
neuron projection morphogenesis	-0.016	0.12	-10000	0	-0.47	15	15
NGF (dimer)/TRKA/NEDD4-2	-0.025	0.13	-10000	0	-0.32	71	71
MAP2K1	0.035	0.011	-10000	0	-10000	0	0
NGFR	-0.028	0.14	-10000	0	-0.47	41	41
NGF (dimer)/TRKA/GIPC/GAIP	0.004	0.082	-10000	0	-0.43	2	2
RAS family/GTP/PI3K	0.023	0.045	-10000	0	-0.43	3	3
FRS2 family/SHP2/GRB2/SOS1	0.039	0.012	-10000	0	-10000	0	0
NRAS	0.012	0.022	-10000	0	-0.47	1	1
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
PRKCI	0.012	0.027	-10000	0	-0.58	1	1
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
PRKCZ	0.013	0	-10000	0	-10000	0	0
MAPKKK cascade	-0.079	0.19	-10000	0	-0.62	49	49
RASA1	0.01	0.038	-10000	0	-0.47	3	3
TRKA/c-Abl	-0.011	0.1	-10000	0	-0.35	40	40
SQSTM1	0.013	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.059	0.17	-10000	0	-0.48	46	46
NGF (dimer)/TRKA/p62/Atypical PKCs	0.005	0.093	-10000	0	-0.45	2	2
MATK	-0.25	0.29	-10000	0	-0.57	219	219
NEDD4L	-0.006	0.1	-10000	0	-0.58	16	16
RAS family/GDP	-0.026	0.052	-10000	0	-0.23	3	3
NGF (dimer)/TRKA	-0.053	0.12	-10000	0	-0.36	44	44
Rac1/GTP	-0.066	0.1	-10000	0	-0.33	46	46
FRS2 family/SHP2/CRK family	0.039	0.012	-10000	0	-10000	0	0

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	-0.012	0.14	-9999	-0.45	33	33
MAP4K1	-0.024	0.14	-9999	-0.56	32	32
MAP3K8	0	0.08	-9999	-0.48	13	13
PRKCB	-0.097	0.2	-9999	-0.47	111	111
DBNL	0.013	0	-9999	-10000	0	0
CRKL	0.013	0	-9999	-10000	0	0
MAP3K1	0.015	0.085	-9999	-0.5	6	6
JUN	-0.11	0.25	-9999	-0.53	121	121
MAP3K7	0.016	0.085	-9999	-0.5	6	6
GRAP2	-0.008	0.1	-9999	-0.48	21	21
CRK	0.013	0	-9999	-10000	0	0
MAP2K4	0.019	0.091	-9999	-0.44	9	9
LAT	-0.003	0.095	-9999	-0.55	14	14
LCP2	0.006	0.061	-9999	-0.54	6	6
MAPK8	-0.12	0.26	-9999	-0.56	120	120
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.009	0.089	-9999	-0.4	12	12
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.004	0.14	-9999	-0.42	33	33

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.1	0.43	-9999	-1.1	37	37
HDAC7	0.013	0.008	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.1	0.34	-9999	-0.9	39	39
SMAD4	0.014	0	-9999	-10000	0	0
ID2	-0.11	0.44	-9999	-1.2	34	34
AP1	-0.049	0.15	-9999	-0.36	88	88
ABCG2	-0.13	0.46	-9999	-1.2	44	44
HIF1A	0	0.077	-9999	-0.55	1	1
TFF3	-0.22	0.48	-9999	-1.1	70	70
GATA2	0.012	0.027	-9999	-0.57	1	1
AKT1	-0.002	0.086	-9999	-10000	0	0
response to hypoxia	-0.02	0.089	-9999	-0.24	12	12
MCL1	-0.1	0.43	-9999	-1.1	38	38
NDRG1	-0.1	0.43	-9999	-1.1	37	37
SERPINE1	-0.14	0.45	-9999	-1.1	46	46
FECH	-0.11	0.43	-9999	-1.1	39	39
FURIN	-0.1	0.43	-9999	-1.1	37	37
NCOA2	-0.048	0.16	-9999	-0.47	60	60
EP300	0.01	0.13	-9999	-0.35	22	22
HMOX1	-0.11	0.43	-9999	-1.1	41	41
BHLHE40	-0.11	0.44	-9999	-1.1	43	43
BHLHE41	-0.11	0.43	-9999	-1.1	38	38
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.013	0.076	-9999	-10000	0	0
ENG	0.048	0.091	-9999	-10000	0	0
JUN	0.006	0.062	-9999	-0.5	7	7
RORA	-0.1	0.43	-9999	-1.1	37	37
ABCB1	-0.06	0.19	-9999	-1.3	9	9
TFRC	-0.1	0.43	-9999	-1.1	40	40
CXCR4	-0.11	0.44	-9999	-1.1	42	42
TF	-0.16	0.48	-9999	-1.1	58	58
CITED2	-0.11	0.43	-9999	-1.1	36	36
HIF1A/ARNT	-0.14	0.47	-9999	-1.2	47	47
LDHA	-0.023	0.06	-9999	-0.53	3	3
ETS1	-0.11	0.43	-9999	-1.1	37	37
PGK1	-0.1	0.43	-9999	-1.1	36	36
NOS2	-0.14	0.46	-9999	-1.1	51	51
ITGB2	-0.11	0.43	-9999	-1.1	36	36
ALDOA	-0.1	0.43	-9999	-1.1	37	37
Cbp/p300/CITED2	-0.11	0.45	-9999	-1.2	37	37
FOS	-0.076	0.19	-9999	-0.48	88	88
HK2	-0.11	0.44	-9999	-1.1	39	39
SP1	0.021	0.003	-9999	-10000	0	0
GCK	-0.035	0.34	-9999	-1.3	25	25
HK1	-0.1	0.43	-9999	-1.1	37	37
NPM1	-0.1	0.43	-9999	-1.1	36	36
EGLN1	-0.1	0.43	-9999	-1.1	37	37
CREB1	0.02	0.002	-9999	-10000	0	0
PGM1	-0.1	0.43	-9999	-1.1	37	37
SMAD3	0.014	0	-9999	-10000	0	0
EDN1	-0.051	0.32	-9999	-1.1	33	33
IGFBP1	-0.13	0.44	-9999	-1.1	42	42
VEGFA	-0.053	0.34	-9999	-0.84	33	33
HIF1A/JAB1	-0.001	0.043	-9999	-0.39	1	1
CP	-0.16	0.47	-9999	-1.1	53	53
CXCL12	-0.11	0.44	-9999	-1.2	39	39
COPS5	0.011	0.009	-9999	-10000	0	0
SMAD3/SMAD4	0.022	0	-9999	-10000	0	0
BNIP3	-0.1	0.43	-9999	-1.1	38	38
EGLN3	-0.11	0.44	-9999	-1.1	41	41
CA9	-0.12	0.43	-9999	-1.1	40	40
TERT	-0.2	0.48	-9999	-1.1	69	69
ENO1	-0.1	0.43	-9999	-1.1	36	36
PFKL	-0.1	0.43	-9999	-1.1	37	37
NCOA1	0.012	0.005	-9999	-10000	0	0
ADM	-0.12	0.44	-9999	-1.1	44	44
ARNT	0.002	0.072	-9999	-10000	0	0
HNF4A	-0.029	0.14	-9999	-0.58	28	28
ADFP	-0.12	0.42	-9999	-1.1	46	46
SLC2A1	-0.041	0.33	-9999	-0.8	29	29
LEP	-0.12	0.43	-9999	-1.1	38	38
HIF1A/ARNT/Cbp/p300	-0.069	0.38	-9999	-0.94	36	36
EPO	-0.13	0.41	-9999	-0.95	63	63
CREBBP	0.012	0.13	-9999	-0.36	19	19
HIF1A/ARNT/Cbp/p300/HDAC7	-0.1	0.34	-9999	-0.91	37	37
PFKFB3	-0.11	0.43	-9999	-1.1	37	37
NT5E	-0.13	0.46	-9999	-1.2	46	46

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	0.067	0.18	0.5	56	-10000	0	56
GNAI2	0.013	0	-10000	0	-10000	0	0
S1P/S1P5/G12	-0.031	0.11	-10000	0	-0.28	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	-0.079	0.19	-10000	0	-0.47	93	93
RhoA/GTP	-0.068	0.19	-10000	0	-0.51	56	56
negative regulation of cAMP metabolic process	-0.08	0.2	-10000	0	-0.55	57	57
GNAZ	-0.033	0.14	-10000	0	-0.47	46	46
GNAI3	0.013	0	-10000	0	-10000	0	0
GNA12	0.013	0	-10000	0	-10000	0	0
S1PR5	-0.067	0.18	-10000	0	-0.47	80	80
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.081	0.2	-10000	0	-0.56	57	57
RhoA/GDP	0.01	0	-10000	0	-10000	0	0
RHOA	0.013	0	-10000	0	-10000	0	0
GNAI1	0.005	0.065	-10000	0	-0.53	7	7

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.081	0.18	-10000	0	-0.42	102	102
TP53	-0.027	0.056	-10000	0	-0.32	6	6
Senescence	-0.027	0.056	-10000	0	-0.32	6	6
Apoptosis	-0.027	0.056	-10000	0	-0.32	6	6
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.045	0.087	0.21	102	-10000	0	102
MDM4	0.013	0	-10000	0	-10000	0	0

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.037	0.14	-9999	-0.46	27	27
SMAD6-7/SMURF1	0.022	0.038	-9999	-0.27	8	8
NOG	-0.046	0.16	-9999	-0.47	59	59
SMAD9	-0.04	0.16	-9999	-0.47	52	52
SMAD4	0.013	0	-9999	-10000	0	0
SMAD5	-0.004	0.096	-9999	-0.38	15	15
BMP7/USAG1	-0.16	0.23	-9999	-0.41	201	201
SMAD5/SKI	0.004	0.092	-9999	-0.37	13	13
SMAD1	0.034	0.023	-9999	-10000	0	0
BMP2	-0.019	0.12	-9999	-0.47	32	32
SMAD1/SMAD1/SMAD4	-0.002	0.019	-9999	-10000	0	0
BMPR1A	0.012	0.022	-9999	-0.47	1	1
BMPR1B	0.006	0.063	-9999	-0.52	7	7
BMPR1A-1B/BAMBI	0.006	0.084	-9999	-0.33	28	28
AHSG	-0.035	0.14	-9999	-0.58	32	32
CER1	-0.008	0.082	-9999	-0.58	10	10
BMP2-4/CER1	-0.021	0.12	-9999	-0.36	53	53
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.007	0.13	-9999	-0.43	28	28
BMP2-4 (homodimer)	-0.02	0.13	-9999	-0.41	44	44
RGMB	0.005	0.062	-9999	-0.47	8	8
BMP6/BMPR2/BMPR1A-1B	-0.015	0.12	-9999	-0.31	66	66
RGMA	-0.009	0.1	-9999	-0.47	22	22
SMURF1	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.014	0.13	-9999	-0.44	28	28
BMP2-4/USAG1	-0.11	0.2	-9999	-0.34	174	174
SMAD6/SMURF1/SMAD5	0.004	0.092	-9999	-0.37	13	13
SOSTDC1	-0.15	0.23	-9999	-0.47	167	167
BMP7/BMPR2/BMPR1A-1B	-0.023	0.11	-9999	-0.34	5	5
SKI	0.013	0	-9999	-10000	0	0
BMP6 (homodimer)	-0.063	0.2	-9999	-0.57	63	63
HFE2	-0.052	0.18	-9999	-0.58	49	49
ZFYVE16	0.013	0	-9999	-10000	0	0
MAP3K7	0.013	0.001	-9999	-10000	0	0
BMP2-4/CHRD	-0.041	0.16	-9999	-0.37	84	84
SMAD5/SMAD5/SMAD4	0.004	0.092	-9999	-0.37	13	13
MAPK1	0.013	0	-9999	-10000	0	0
TAK1/TAB family	-0.036	0.094	-9999	-0.38	27	27
BMP7 (homodimer)	-0.081	0.19	-9999	-0.47	94	94
NUP214	0.013	0	-9999	-10000	0	0
BMP6/FETUA	-0.071	0.18	-9999	-0.43	91	91
SMAD1/SKI	0.04	0.022	-9999	-10000	0	0
SMAD6	0.005	0.062	-9999	-0.47	8	8
CTDSP2	0.013	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.037	0.14	-9999	-0.36	74	74
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.068	0.19	-9999	-0.52	74	74
BMPR2 (homodimer)	0.013	0	-9999	-10000	0	0
GADD34/PP1CA	0.024	0.034	-9999	-0.35	4	4
BMPR1A-1B (homodimer)	0.013	0.049	-9999	-0.36	8	8
CHRDL1	-0.11	0.21	-9999	-0.47	126	126
ENDOFIN/SMAD1	0.04	0.022	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.047	0.033	-9999	-10000	0	0
SMAD6/SMURF1	0.013	0	-9999	-10000	0	0
BAMBI	-0.011	0.12	-9999	-0.58	20	20
SMURF2	0.013	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.081	0.19	-9999	-0.6	36	36
BMP2-4/GREM1	-0.056	0.17	-9999	-0.35	107	107
SMAD7	0.013	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.031	0.15	-9999	-0.44	52	52
SMAD1/SMAD6	0.04	0.022	-9999	-10000	0	0
TAK1/SMAD6	0.02	0	-9999	-10000	0	0
BMP7	-0.081	0.19	-9999	-0.47	94	94
BMP6	-0.063	0.2	-9999	-0.58	63	63
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.007	0.12	-9999	-0.41	28	28
PPM1A	0.013	0	-9999	-10000	0	0
SMAD1/SMURF2	0.04	0.022	-9999	-10000	0	0
SMAD7/SMURF1	0.02	0	-9999	-10000	0	0
CTDSPL	0.013	0	-9999	-10000	0	0
PPP1CA	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
CTDSP1	0.013	0	-9999	-10000	0	0
PPP1R15A	0.008	0.053	-9999	-0.58	4	4
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.036	0.19	-9999	-0.6	38	38
CHRD	-0.042	0.17	-9999	-0.57	46	46
BMPR2	0.013	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.019	0.14	-9999	-0.49	28	28
BMP4	-0.012	0.11	-9999	-0.47	25	25
FST	-0.031	0.14	-9999	-0.48	44	44
BMP2-4/NOG	-0.041	0.17	-9999	-0.37	84	84
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.015	0.11	-9999	-0.45	1	1

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.022	0.042	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.062	0.11	-9999	-0.37	32	32
JUN	-0.033	0.13	-9999	-0.41	31	31
HRAS	0.007	0.059	-9999	-0.58	5	5
RET51/GFRalpha1/GDNF/GRB10	-0.072	0.17	-9999	-0.36	99	99
RAP1A	0.013	0	-9999	-10000	0	0
FRS2	0.013	0	-9999	-10000	0	0
RAP1A/GDP	0.01	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.072	0.17	-9999	-0.36	99	99
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.012	0.022	-9999	-0.47	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.022	0.12	-9999	-0.3	70	70
RHOA	0.013	0	-9999	-10000	0	0
RAP1A/GTP	-0.086	0.15	-9999	-0.45	34	34
GRB7	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF	-0.072	0.17	-9999	-0.36	99	99
MAPKKK cascade	-0.073	0.12	-9999	-0.45	26	26
BCAR1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	-0.023	0.12	-9999	-0.29	74	74
lamellipodium assembly	-0.058	0.1	-9999	-0.34	33	33
RET51/GFRalpha1/GDNF/SHC	-0.072	0.17	-9999	-0.36	99	99
PIK3CA	0.01	0.038	-9999	-0.47	3	3
RET9/GFRalpha1/GDNF/SHC	-0.015	0.1	-9999	-0.27	65	65
RET9/GFRalpha1/GDNF/Shank3	-0.015	0.1	-9999	-0.27	65	65
MAPK3	-0.054	0.15	-9999	-0.49	24	24
DOK1	0.013	0	-9999	-10000	0	0
DOK6	-0.024	0.14	-9999	-0.52	34	34
PXN	0.013	0	-9999	-10000	0	0
neurite development	-0.046	0.15	-9999	-0.47	27	27
DOK5	-0.02	0.13	-9999	-0.5	31	31
GFRA1	-0.03	0.14	-9999	-0.47	43	43
MAPK8	-0.037	0.13	-9999	-0.42	29	29
HRAS/GTP	-0.085	0.14	-9999	-0.52	26	26
tube development	-0.008	0.097	-9999	-0.42	8	8
MAPK1	-0.054	0.15	-9999	-0.49	24	24
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.007	0.093	-9999	-0.44	6	6
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	0.013	0	-9999	-10000	0	0
PDLIM7	-0.001	0.084	-9999	-0.49	14	14
RET51/GFRalpha1/GDNF/Dok6	-0.08	0.18	-9999	-0.36	114	114
SHC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Dok4	-0.075	0.18	-9999	-0.37	100	100
RET51/GFRalpha1/GDNF/Dok5	-0.089	0.19	-9999	-0.39	109	109
PRKCA	-0.007	0.096	-9999	-0.47	20	20
HRAS/GDP	0.005	0.044	-9999	-0.42	5	5
CREB1	-0.024	0.12	-9999	-0.41	22	22
PIK3R1	0.008	0.049	-9999	-0.47	5	5
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.007	0.095	-9999	-0.31	18	18
RET51/GFRalpha1/GDNF/Grb7	-0.072	0.17	-9999	-0.36	99	99
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.1	0.23	-9999	-0.56	96	96
DOK4	0.007	0.053	-9999	-0.47	6	6
JNK cascade	-0.032	0.13	-9999	-0.4	31	31
RET9/GFRalpha1/GDNF/FRS2	-0.015	0.1	-9999	-0.27	65	65
SHANK3	0.013	0	-9999	-10000	0	0
RASA1	0.01	0.038	-9999	-0.47	3	3
NCK1	0.012	0.027	-9999	-0.58	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.007	0.093	-9999	-0.44	6	6
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.04	0.13	-9999	-0.44	23	23
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.041	0.13	-9999	-0.44	24	24
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.041	0.13	-9999	-0.47	23	23
PI3K	-0.045	0.17	-9999	-0.53	33	33
SOS1	0.013	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.007	0.098	-9999	-0.42	8	8
GRB10	0.013	0	-9999	-10000	0	0
activation of MAPKK activity	-0.036	0.13	-9999	-0.36	40	40
RET51/GFRalpha1/GDNF/FRS2	-0.072	0.17	-9999	-0.36	99	99
GAB1	0.012	0.022	-9999	-0.47	1	1
IRS1	-0.003	0.086	-9999	-0.47	16	16
IRS2	0.007	0.059	-9999	-0.58	5	5
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.041	0.14	-9999	-0.49	23	23
RET51/GFRalpha1/GDNF/PKC alpha	-0.082	0.19	-9999	-0.39	103	103
GRB2	0.013	0	-9999	-10000	0	0
PRKACA	0.013	0	-9999	-10000	0	0
GDNF	-0.017	0.11	-9999	-0.48	28	28
RAC1	0.013	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.08	0.18	-9999	-0.37	104	104
Rac1/GTP	-0.068	0.12	-9999	-0.41	33	33
RET9/GFRalpha1/GDNF	-0.026	0.11	-9999	-0.3	65	65
GFRalpha1/GDNF	-0.032	0.13	-9999	-0.36	65	65

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	0.009	0.027	-9999	-10000	0	0
NFATC2	-0.046	0.12	-9999	-0.29	88	88
NFATC3	0.009	0.027	-9999	-10000	0	0
CD40LG	-0.14	0.29	-9999	-0.7	70	70
PTGS2	-0.16	0.31	-9999	-0.69	90	90
JUNB	-0.016	0.12	-9999	-0.52	26	26
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.015	-9999	-10000	0	0
CaM/Ca2+	0	0.015	-9999	-10000	0	0
CALM1	0.011	0.008	-9999	-10000	0	0
JUN	0.003	0.063	-9999	-0.51	7	7
mol:Ca2+	-0.006	0.011	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.007	0.005	-9999	-10000	0	0
FOSL1	-0.11	0.22	-9999	-0.5	113	113
CREM	0.013	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.059	0.16	-9999	-0.46	24	24
FOS	-0.079	0.19	-9999	-0.49	88	88
IFNG	-0.13	0.28	-9999	-0.7	58	58
AP-1/NFAT1-c-4	-0.14	0.32	-9999	-0.76	62	62
FASLG	-0.13	0.28	-9999	-0.72	56	56
NFAT1-c-4/ICER1	-0.044	0.11	-9999	-0.37	7	7
IL2RA	-0.16	0.31	-9999	-0.71	76	76
FKBP12/FK506	0.01	0	-9999	-10000	0	0
CSF2	-0.12	0.26	-9999	-0.67	52	52
JunB/Fra1/NFAT1-c-4	-0.097	0.17	-9999	-0.45	49	49
IL4	-0.12	0.26	-9999	-0.66	52	52
IL2	-0.004	0.03	-9999	-0.42	2	2
IL3	-0.017	0.022	-9999	-10000	0	0
FKBP1A	0.013	0	-9999	-10000	0	0
BATF3	-0.017	0.13	-9999	-0.57	25	25
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.012	0.027	-9999	-0.58	1	1

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.002	0.13	-10000	0	-0.42	23	23
TBX21	-0.088	0.37	-10000	0	-0.92	56	56
B2M	0.012	0.009	-10000	0	-10000	0	0
TYK2	0.015	0.02	-10000	0	-10000	0	0
IL12RB1	-0.011	0.12	-10000	0	-0.58	22	22
GADD45B	-0.06	0.31	-10000	0	-0.77	47	47
IL12RB2	-0.007	0.11	-10000	0	-0.5	21	21
GADD45G	-0.079	0.32	-10000	0	-0.76	54	54
natural killer cell activation	0.002	0.021	-10000	0	-10000	0	0
RELB	0.013	0	-10000	0	-10000	0	0
RELA	0.013	0	-10000	0	-10000	0	0
IL18	0.002	0.077	-10000	0	-0.48	12	12
IL2RA	-0.078	0.21	-10000	0	-0.57	76	76
IFNG	-0.026	0.14	-10000	0	-0.58	30	30
STAT3 (dimer)	-0.065	0.3	-10000	0	-0.7	59	59
HLA-DRB5	-0.01	0.11	-10000	0	-0.55	19	19
FASLG	-0.091	0.38	-10000	0	-1.1	41	41
NF kappa B2 p52/RelB	-0.15	0.28	-10000	0	-0.75	67	67
CD4	0.005	0.063	-10000	0	-0.56	6	6
SOCS1	0.009	0.051	-10000	0	-0.55	4	4
EntrezGene:6955	-0.005	0.014	-10000	0	-10000	0	0
CD3D	-0.03	0.14	-10000	0	-0.55	35	35
CD3E	-0.011	0.1	-10000	0	-0.52	19	19
CD3G	-0.046	0.16	-10000	0	-0.51	52	52
IL12Rbeta2/JAK2	0.007	0.087	-10000	0	-0.36	22	22
CCL3	-0.1	0.38	-10000	0	-0.9	63	63
CCL4	-0.083	0.35	-10000	0	-0.86	57	57
HLA-A	0	0.079	-10000	0	-0.51	11	11
IL18/IL18R	0.012	0.12	-10000	0	-0.37	29	29
NOS2	-0.12	0.41	-10000	0	-0.98	68	68
IL12/IL12R/TYK2/JAK2/SPHK2	-0.001	0.12	-10000	0	-0.4	21	21
IL1R1	-0.075	0.34	-10000	0	-0.84	52	52
IL4	0	0.021	-10000	0	-10000	0	0
JAK2	0.014	0.031	-10000	0	-0.49	1	1
EntrezGene:6957	-0.004	0.014	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.07	0.29	-10000	0	-0.79	47	47
RAB7A	-0.04	0.27	-10000	0	-0.72	27	27
lysosomal transport	-0.036	0.26	-10000	0	-0.68	28	28
FOS	-0.2	0.5	-10000	0	-1.1	99	99
STAT4 (dimer)	-0.061	0.32	-10000	0	-0.79	52	52
STAT5A (dimer)	-0.17	0.3	-10000	0	-0.8	69	69
GZMA	-0.086	0.36	-10000	0	-0.91	54	54
GZMB	-0.1	0.39	-10000	0	-0.94	64	64
HLX	-0.006	0.1	-10000	0	-0.58	16	16
LCK	-0.087	0.37	-10000	0	-0.85	64	64
TCR/CD3/MHC II/CD4	-0.055	0.18	-10000	0	-0.44	59	59
IL2/IL2R	-0.055	0.18	-10000	0	-0.4	85	85
MAPK14	-0.064	0.32	-10000	0	-0.76	54	54
CCR5	-0.061	0.32	-10000	0	-0.92	32	32
IL1B	-0.062	0.19	-10000	0	-0.52	72	72
STAT6	-0.005	0.11	-10000	0	-0.49	2	2
STAT4	-0.008	0.11	-10000	0	-0.55	18	18
STAT3	0.013	0	-10000	0	-10000	0	0
STAT1	0.001	0.084	-10000	0	-0.58	10	10
NFKB1	0.013	0	-10000	0	-10000	0	0
NFKB2	0.01	0.046	-10000	0	-0.58	3	3
IL12B	-0.022	0.14	-10000	0	-0.59	29	29
CD8A	-0.007	0.099	-10000	0	-0.51	18	18
CD8B	-0.01	0.11	-10000	0	-0.52	20	20
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.002	0.13	0.41	23	-10000	0	23
IL2RB	-0.017	0.12	-10000	0	-0.49	29	29
proteasomal ubiquitin-dependent protein catabolic process	-0.051	0.3	-10000	0	-0.72	51	51
IL2RG	-0.012	0.12	-10000	0	-0.55	22	22
IL12	-0.016	0.14	-10000	0	-0.45	41	41
STAT5A	0.011	0.031	-10000	0	-0.47	2	2
CD247	-0.014	0.12	-10000	0	-0.56	21	21
IL2	0.004	0.038	-10000	0	-0.58	2	2
SPHK2	0.013	0	-10000	0	-10000	0	0
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	-0.004	0.099	-10000	0	-0.53	16	16
IL12/IL12R/TYK2/JAK2	-0.095	0.38	-10000	0	-0.88	66	66
MAP2K3	-0.067	0.32	-10000	0	-0.74	57	57
RIPK2	0.002	0.079	-10000	0	-0.58	9	9
MAP2K6	-0.07	0.32	-10000	0	-0.75	58	58
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.006	0.056	-10000	0	-0.54	5	5
IL18RAP	-0.022	0.14	-10000	0	-0.53	33	33
IL12Rbeta1/TYK2	0.002	0.099	-10000	0	-0.43	22	22
EOMES	-0.058	0.24	-10000	0	-1.2	17	17
STAT1 (dimer)	-0.068	0.3	-10000	0	-0.71	58	58
T cell proliferation	-0.044	0.26	-10000	0	-0.59	56	56
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.007	0.063	-10000	0	-0.48	8	8
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.13	0.22	-10000	0	-0.64	54	54
ATF2	-0.065	0.31	-10000	0	-0.74	50	50

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.048	0.15	-9999	-0.44	18	18
NF kappa B1 p50/RelA/I kappa B alpha	-0.022	0.14	-9999	-0.42	18	18
alphaV/beta3 Integrin/Osteopontin/Src	-0.04	0.16	-9999	-0.4	76	76
AP1	-0.07	0.21	-9999	-0.56	41	41
ILK	-0.059	0.16	-9999	-0.5	14	14
bone resorption	-0.053	0.18	-9999	-0.45	53	53
PTK2B	0.013	0	-9999	-10000	0	0
PYK2/p130Cas	-0.044	0.15	-9999	-0.47	17	17
ITGAV	0.014	0.031	-9999	-0.47	2	2
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.019	0.11	-9999	-0.34	51	51
alphaV/beta3 Integrin/Osteopontin	-0.075	0.17	-9999	-0.37	78	78
MAP3K1	-0.061	0.16	-9999	-0.47	19	19
JUN	0.006	0.062	-9999	-0.5	7	7
MAPK3	-0.047	0.15	-9999	-0.46	18	18
MAPK1	-0.047	0.15	-9999	-0.46	18	18
Rac1/GDP	0.01	0	-9999	-10000	0	0
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	-0.054	0.16	-9999	-0.46	25	25
ITGB3	-0.08	0.19	-9999	-0.47	97	97
NFKBIA	-0.037	0.15	-9999	-0.46	18	18
FOS	-0.075	0.19	-9999	-0.48	88	88
CD44	0.002	0.072	-9999	-0.47	11	11
CHUK	0.013	0	-9999	-10000	0	0
PLAU	-0.047	0.22	-9999	-0.91	17	17
NF kappa B1 p50/RelA	-0.068	0.11	-9999	-0.43	16	16
BCAR1	0.013	0	-9999	-10000	0	0
RELA	0.013	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.044	0.14	-9999	-0.33	97	97
mol:GDP	0	0	-9999	-10000	0	0
SYK	-0.065	0.16	-9999	-0.34	83	83
VAV3	-0.08	0.18	-9999	-0.51	41	41
MAP3K14	-0.06	0.16	-9999	-0.48	18	18
ROCK2	-0.03	0.14	-9999	-0.47	43	43
SPP1	-0.072	0.21	-9999	-0.56	74	74
RAC1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.068	0.17	-9999	-0.47	41	41
MMP2	-0.058	0.19	-9999	-0.61	27	27

Wnt signaling

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
Noncanonical Wnts/FZD	-0.048	0.15	-9999	-0.46	28	28
FZD6	0.013	0	-9999	-10000	0	0
WNT6	-0.085	0.2	-9999	-0.48	97	97
WNT4	0.007	0.053	-9999	-0.47	6	6
FZD3	0.011	0.031	-9999	-0.47	2	2
WNT5A	-0.027	0.14	-9999	-0.51	38	38
WNT11	-0.025	0.14	-9999	-0.55	33	33

p75(NTR)-mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.02	0	-9999	-10000	0	0
Necdin/E2F1	-0.003	0.1	-9999	-0.44	24	24
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.006	0.088	-9999	-0.34	3	3
NGF (dimer)/p75(NTR)/BEX1	-0.1	0.18	-9999	-0.32	182	182
NT-4/5 (dimer)/p75(NTR)	-0.086	0.2	-9999	-0.41	121	121
IKBKB	0.012	0.027	-9999	-0.58	1	1
AKT1	-0.001	0.092	-9999	-0.45	3	3
IKBKG	0.013	0	-9999	-10000	0	0
BDNF	-0.088	0.2	-9999	-0.47	102	102
MGDIs/NGR/p75(NTR)/LINGO1	-0.039	0.14	-9999	-0.33	90	90
FURIN	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.059	0.16	-9999	-0.31	122	122
LINGO1	-0.052	0.18	-9999	-0.58	54	54
Sortilin/TRAF6/NRIF	0	0	-9999	-10000	0	0
proBDNF (dimer)	-0.088	0.2	-9999	-0.47	102	102
NTRK1	-0.029	0.14	-9999	-0.49	40	40
RTN4R	0.013	0	-9999	-10000	0	0
neuron apoptosis	-0.036	0.16	-9999	-0.45	36	36
IRAK1	0.012	0.027	-9999	-0.58	1	1
SHC1	-0.013	0.1	-9999	-0.28	62	62
ARHGDIA	0.013	0	-9999	-10000	0	0
RhoA/GTP	0.01	0	-9999	-10000	0	0
Gamma Secretase	0.039	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.007	0.1	-9999	-0.38	11	11
MAGEH1	0.003	0.076	-9999	-0.55	9	9
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.004	0.1	-9999	-0.43	7	7
Mammalian IAPs/DIABLO	0.03	0.034	-9999	-0.31	3	3
proNGF (dimer)	-0.009	0.1	-9999	-0.48	22	22
MAGED1	0.012	0.027	-9999	-0.58	1	1
APP	0.01	0.038	-9999	-0.47	3	3
NT-4/5 (dimer)	-0.099	0.2	-9999	-0.47	113	113
ZNF274	0.013	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.002	0.086	-9999	-0.34	3	3
NGF	-0.009	0.1	-9999	-0.48	22	22
cell cycle arrest	0.011	0.1	-9999	-0.38	2	2
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0	0.089	-9999	-0.39	5	5
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.065	0.17	-9999	-0.34	121	121
NCSTN	0.013	0	-9999	-10000	0	0
mol:GTP	-0.012	0.1	-9999	-0.28	62	62
PSENEN	0.013	0	-9999	-10000	0	0
mol:ceramide	-0.005	0.095	-9999	-0.39	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.01	0.077	-9999	-0.33	5	5
p75(NTR)/beta APP	-0.012	0.1	-9999	-0.34	42	42
BEX1	-0.14	0.23	-9999	-0.47	155	155
mol:GDP	-0.022	0.1	-9999	-0.28	62	62
NGF (dimer)	-0.059	0.15	-9999	-0.33	80	80
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.027	0.13	-9999	-0.29	90	90
PIK3R1	0.008	0.049	-9999	-0.47	5	5
RAC1/GTP	-0.009	0.086	-9999	-0.23	62	62
MYD88	0.013	0	-9999	-10000	0	0
CHUK	0.013	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.012	0.1	-9999	-0.28	62	62
RHOB	0.005	0.062	-9999	-0.47	8	8
RHOA	0.013	0	-9999	-10000	0	0
MAGE-G1/E2F1	0	0.091	-9999	-0.42	22	22
NT3 (dimer)	-0.045	0.16	-9999	-0.47	58	58
TP53	-0.032	0.13	-9999	-0.44	24	24
PRDM4	-0.004	0.092	-9999	-0.37	3	3
BDNF (dimer)	-0.15	0.2	-9999	-0.42	129	129
PIK3CA	0.01	0.038	-9999	-0.47	3	3
SORT1	0.013	0	-9999	-10000	0	0
activation of caspase activity	0.003	0.086	-9999	-0.34	3	3
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.001	0.093	-9999	-0.37	3	3
RHOC	0.013	0	-9999	-10000	0	0
XIAP	0.013	0	-9999	-10000	0	0
MAPK10	-0.018	0.14	-9999	-0.43	32	32
DIABLO	0.013	0	-9999	-10000	0	0
SMPD2	-0.006	0.095	-9999	-0.39	5	5
APH1B	0.013	0	-9999	-10000	0	0
APH1A	0.013	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.012	0.1	-9999	-0.28	62	62
PSEN1	0.013	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0.02	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.049	0.16	-9999	-0.38	84	84
MAPK8	-0.021	0.14	-9999	-0.41	31	31
MAPK9	-0.016	0.14	-9999	-0.41	30	30
APAF1	0.013	0	-9999	-10000	0	0
NTF3	-0.045	0.16	-9999	-0.47	58	58
NTF4	-0.1	0.2	-9999	-0.47	113	113
NDN	0.008	0.049	-9999	-0.47	5	5
RAC1/GDP	0.01	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.029	0.075	-9999	-0.42	4	4
p75 CTF/Sortilin/TRAF6/NRIF	0.031	0.027	-9999	-10000	0	0
RhoA-B-C/GTP	-0.012	0.1	-9999	-0.27	62	62
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.035	0.14	-9999	-0.45	21	21
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.044	0.14	-9999	-0.48	21	21
PRKACB	0.013	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.057	0.15	-9999	-0.33	105	105
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	0.007	0.06	-9999	-0.52	6	6
BIRC2	0.013	0	-9999	-10000	0	0
neuron projection morphogenesis	0.013	0.12	-9999	-0.34	8	8
BAD	-0.014	0.14	-9999	-0.4	33	33
RIPK2	0.002	0.079	-9999	-0.58	9	9
NGFR	-0.028	0.14	-9999	-0.47	41	41
CYCS	0.002	0.089	-9999	-0.48	2	2
ADAM17	0.008	0.049	-9999	-0.47	5	5
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.007	0.11	-9999	-0.38	12	12
BCL2L11	-0.013	0.14	-9999	-0.4	34	34
BDNF (dimer)/p75(NTR)	-0.08	0.18	-9999	-0.38	122	122
PI3K	-0.006	0.1	-9999	-0.41	5	5
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.001	0.093	-9999	-0.37	3	3
NDNL2	0.013	0	-9999	-10000	0	0
YWHAE	0.013	0	-9999	-10000	0	0
PRKCI	0.012	0.027	-9999	-0.58	1	1
NGF (dimer)/p75(NTR)	-0.026	0.12	-9999	-0.34	62	62
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.002	0.096	-9999	-0.41	4	4
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
PLG	-0.023	0.13	-9999	-0.58	24	24
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.052	0.15	-9999	-0.49	29	29
SQSTM1	0.013	0	-9999	-10000	0	0
NGFRAP1	0.013	0	-9999	-10000	0	0
CASP3	-0.01	0.13	-9999	-0.37	34	34
E2F1	-0.013	0.12	-9999	-0.58	22	22
CASP9	0.013	0	-9999	-10000	0	0
IKK complex	-0.039	0.088	-9999	-0.36	14	14
NGF (dimer)/TRKA	-0.027	0.12	-9999	-0.35	60	60
MMP7	-0.091	0.22	-9999	-0.53	93	93
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.006	0.088	-9999	-0.45	1	1
MMP3	-0.076	0.2	-9999	-0.51	81	81
APAF-1/Caspase 9	-0.021	0.056	-9999	-0.38	1	1

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.019	0.1	-10000	0	-0.3	57	57
cell-cell adhesion	0.089	0.13	0.43	41	-10000	0	41
Ephrin B/EPHB2/RasGAP	-0.012	0.13	-10000	0	-0.6	9	9
ITSN1	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
SHC1	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB3	0.013	0.038	-10000	0	-0.3	7	7
Ephrin B1/EPHB1	-0.079	0.14	-10000	0	-0.28	155	155
HRAS/GDP	-0.091	0.14	-10000	0	-0.43	42	42
Ephrin B/EPHB1/GRB7	-0.086	0.18	-10000	0	-0.51	40	40
Endophilin/SYNJ1	-0.012	0.12	-10000	0	-0.6	7	7
KRAS	0.013	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.086	0.18	-10000	0	-0.51	40	40
endothelial cell migration	0.014	0.068	-10000	0	-0.31	17	17
GRB2	0.013	0	-10000	0	-10000	0	0
GRB7	0.013	0	-10000	0	-10000	0	0
PAK1	-0.011	0.13	-10000	0	-0.62	9	9
HRAS	0.007	0.059	-10000	0	-0.58	5	5
RRAS	-0.015	0.12	-10000	0	-0.6	9	9
DNM1	0.011	0.035	-10000	0	-0.52	2	2
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.084	0.17	-10000	0	-0.48	40	40
lamellipodium assembly	-0.089	0.13	-10000	0	-0.43	41	41
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.075	0.16	-10000	0	-0.45	40	40
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
EPHB2	0.006	0.063	-10000	0	-0.52	7	7
EPHB3	0.011	0.038	-10000	0	-0.58	2	2
EPHB1	-0.14	0.23	-10000	0	-0.47	155	155
EPHB4	0.013	0	-10000	0	-10000	0	0
mol:GDP	-0.061	0.15	-10000	0	-0.44	40	40
Ephrin B/EPHB2	-0.018	0.12	-10000	0	-0.41	22	22
Ephrin B/EPHB3	-0.016	0.12	-10000	0	-0.38	20	20
JNK cascade	-0.05	0.13	-10000	0	-0.5	10	10
Ephrin B/EPHB1	-0.094	0.18	-10000	0	-0.48	48	48
RAP1/GDP	-0.042	0.13	-10000	0	-0.38	39	39
EFNB2	-0.006	0.1	-10000	0	-0.58	16	16
EFNB3	-0.05	0.16	-10000	0	-0.47	63	63
EFNB1	0.008	0.049	-10000	0	-0.47	5	5
Ephrin B2/EPHB1-2	-0.075	0.15	-10000	0	-0.27	165	165
RAP1B	0.013	0	-10000	0	-10000	0	0
RAP1A	0.013	0	-10000	0	-10000	0	0
CDC42/GTP	-0.096	0.15	-10000	0	-0.48	41	41
Rap1/GTP	-0.089	0.14	-10000	0	-0.43	41	41
axon guidance	-0.019	0.1	-10000	0	-0.3	57	57
MAPK3	-0.055	0.14	-10000	0	-0.39	40	40
MAPK1	-0.055	0.14	-10000	0	-0.39	40	40
Rac1/GDP	-0.05	0.14	-10000	0	-0.4	40	40
actin cytoskeleton reorganization	-0.07	0.11	-10000	0	-0.34	44	44
CDC42/GDP	-0.05	0.14	-10000	0	-0.4	40	40
PI3K	0.017	0.069	-10000	0	-0.31	17	17
EFNA5	-0.041	0.15	-10000	0	-0.47	54	54
Ephrin B2/EPHB4	0.006	0.067	-10000	0	-0.36	16	16
Ephrin B/EPHB2/Intersectin/N-WASP	-0.009	0.12	-10000	0	-0.64	7	7
CDC42	0.013	0	-10000	0	-10000	0	0
RAS family/GTP	-0.089	0.13	-10000	0	-0.42	44	44
PTK2	0.023	0.034	-10000	0	-10000	0	0
MAP4K4	-0.051	0.13	-10000	0	-0.5	10	10
SRC	0.013	0	-10000	0	-10000	0	0
KALRN	0.01	0.046	-10000	0	-0.58	3	3
Intersectin/N-WASP	0.02	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.035	0.14	-10000	0	-0.37	37	37
MAP2K1	-0.064	0.15	-10000	0	-0.42	40	40
WASL	0.013	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.059	0.14	-10000	0	-0.54	10	10
cell migration	-0.072	0.17	-10000	0	-0.47	40	40
NRAS	0.012	0.022	-10000	0	-0.47	1	1
SYNJ1	-0.012	0.12	-10000	0	-0.62	7	7
PXN	0.013	0	-10000	0	-10000	0	0
TF	-0.061	0.17	-10000	0	-0.46	44	44
HRAS/GTP	-0.099	0.15	-10000	0	-0.46	44	44
Ephrin B1/EPHB1-2	-0.067	0.14	-10000	0	-0.26	157	157
cell adhesion mediated by integrin	0.026	0.11	0.36	20	-10000	0	20
RAC1	0.013	0	-10000	0	-10000	0	0
mol:GTP	-0.08	0.17	-10000	0	-0.5	41	41
RAC1-CDC42/GTP	-0.089	0.14	-10000	0	-0.43	43	43
RASA1	0.01	0.038	-10000	0	-0.47	3	3
RAC1-CDC42/GDP	-0.042	0.13	-10000	0	-0.38	39	39
ruffle organization	-0.056	0.16	-10000	0	-0.43	41	41
NCK1	0.012	0.027	-10000	0	-0.58	1	1
receptor internalization	-0.007	0.11	-10000	0	-0.56	8	8
Ephrin B/EPHB2/KALRN	-0.012	0.13	-10000	0	-0.63	8	8
ROCK1	0.019	0.036	-10000	0	-0.26	8	8
RAS family/GDP	-0.065	0.1	-10000	0	-0.44	13	13
Rac1/GTP	-0.094	0.14	-10000	0	-0.46	41	41
Ephrin B/EPHB1/Src/Paxillin	-0.082	0.17	-10000	0	-0.48	40	40

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.007	0.074	-9999	-0.4	14	14
Syndecan-4/Syndesmos	-0.1	0.14	-9999	-0.46	28	28
positive regulation of JNK cascade	-0.1	0.15	-9999	-0.46	34	34
Syndecan-4/ADAM12	-0.12	0.16	-9999	-0.48	45	45
CCL5	-0.007	0.1	-9999	-0.5	19	19
Rac1/GDP	0.01	0	-9999	-10000	0	0
DNM2	0.013	0	-9999	-10000	0	0
ITGA5	-0.002	0.085	-9999	-0.48	15	15
SDCBP	0.013	0	-9999	-10000	0	0
PLG	-0.018	0.13	-9999	-0.57	24	24
ADAM12	-0.017	0.13	-9999	-0.56	26	26
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.062	0.054	-9999	-0.17	11	11
Syndecan-4/Laminin alpha1	-0.13	0.16	-9999	-0.48	51	51
Syndecan-4/CXCL12/CXCR4	-0.11	0.16	-9999	-0.49	34	34
Syndecan-4/Laminin alpha3	-0.12	0.16	-9999	-0.45	50	50
MDK	-0.012	0.12	-9999	-0.57	21	21
Syndecan-4/FZD7	-0.11	0.15	-9999	-0.47	34	34
Syndecan-4/Midkine	-0.12	0.16	-9999	-0.48	41	41
FZD7	-0.004	0.089	-9999	-0.47	17	17
Syndecan-4/FGFR1/FGF	-0.12	0.13	-9999	-0.47	31	31
THBS1	-0.011	0.11	-9999	-0.49	23	23
integrin-mediated signaling pathway	-0.11	0.15	-9999	-0.44	42	42
positive regulation of MAPKKK cascade	-0.1	0.15	-9999	-0.46	34	34
Syndecan-4/TACI	-0.14	0.17	-9999	-0.47	70	70
CXCR4	0.004	0.07	-9999	-0.54	8	8
cell adhesion	0.01	0.077	-9999	-0.35	13	13
Syndecan-4/Dynamin	-0.1	0.14	-9999	-0.46	28	28
Syndecan-4/TSP1	-0.12	0.15	-9999	-0.47	38	38
Syndecan-4/GIPC	-0.1	0.14	-9999	-0.46	28	28
Syndecan-4/RANTES	-0.11	0.15	-9999	-0.47	37	37
ITGB1	0.013	0	-9999	-10000	0	0
LAMA1	-0.041	0.16	-9999	-0.53	48	48
LAMA3	-0.03	0.14	-9999	-0.48	43	43
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.019	0.097	-9999	-0.42	20	20
Syndecan-4/alpha-Actinin	-0.11	0.15	-9999	-0.46	31	31
TFPI	-0.019	0.13	-9999	-0.52	29	29
F2	-0.03	0.13	-9999	-0.58	26	26
alpha5/beta1 Integrin	0.009	0.061	-9999	-0.33	15	15
positive regulation of cell adhesion	-0.14	0.17	-9999	-0.46	72	72
ACTN1	0.007	0.053	-9999	-0.47	6	6
TNC	-0.016	0.12	-9999	-0.47	29	29
Syndecan-4/CXCL12	-0.11	0.15	-9999	-0.48	35	35
FGF6	-0.001	0.037	-9999	-0.58	2	2
RHOA	0.013	0	-9999	-10000	0	0
CXCL12	-0.008	0.1	-9999	-0.48	21	21
TNFRSF13B	-0.052	0.18	-9999	-0.56	53	53
FGF2	-0.024	0.13	-9999	-0.47	37	37
FGFR1	0.01	0.038	-9999	-0.47	3	3
Syndecan-4/PI-4-5-P2	-0.11	0.14	-9999	-0.43	41	41
mol:GDP	0	0	-9999	-10000	0	0
FN1	0.005	0.085	-9999	-0.48	14	14
cell migration	-0.024	0.021	-9999	-10000	0	0
PRKCD	0.02	0.009	-9999	-10000	0	0
vasculogenesis	-0.11	0.15	-9999	-0.45	38	38
SDC4	-0.12	0.15	-9999	-0.45	41	41
Syndecan-4/Tenascin C	-0.12	0.16	-9999	-0.46	42	42
Syndecan-4/PI-4-5-P2/PKC alpha	-0.049	0.043	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.1	0.14	-9999	-0.46	28	28
MMP9	-0.31	0.29	-9999	-0.57	270	270
Rac1/GTP	0.009	0.078	-9999	-0.36	13	13
cytoskeleton organization	-0.1	0.14	-9999	-0.45	28	28
GIPC1	0.013	0	-9999	-10000	0	0
Syndecan-4/TFPI	-0.12	0.16	-9999	-0.5	42	42

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	-0.079	0.19	-9999	-0.47	93	93
CDC42/GTP	-0.033	0.14	-9999	-0.39	42	42
PLCG1	-0.034	0.14	-9999	-0.4	42	42
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.013	0	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.02	0	-9999	-10000	0	0
cell migration	-0.033	0.13	-9999	-0.38	42	42
S1PR5	-0.067	0.18	-9999	-0.47	80	80
S1PR4	-0.012	0.12	-9999	-0.57	21	21
MAPK3	-0.034	0.14	-9999	-0.4	42	42
MAPK1	-0.034	0.14	-9999	-0.4	42	42
S1P/S1P5/Gi	-0.081	0.2	-9999	-0.56	57	57
GNAI1	0.005	0.065	-9999	-0.53	7	7
CDC42/GDP	0.01	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.031	0.11	-9999	-0.28	80	80
RHOA	0.015	0.064	-9999	-0.29	20	20
S1P/S1P4/Gi	-0.044	0.15	-9999	-0.43	42	42
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	-0.033	0.14	-9999	-0.47	46	46
S1P/S1P4/G12/G13	0.011	0.069	-9999	-0.32	20	20
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
CDC42	0.013	0	-9999	-10000	0	0

Effects of Botulinum toxin

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
STX1A	0.009	0.028	-9999	-0.42	2	2
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	0.003	0.08	-9999	-0.38	20	20
STXBP1	0.01	0.041	-9999	-0.51	3	3
ACh/CHRNA1	-0.072	0.15	-9999	-0.38	90	90
RAB3GAP2/RIMS1/UNC13B	0.013	0.069	-9999	-0.32	20	20
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	-0.003	0.093	-9999	-0.52	15	15
mol:ACh	-0.01	0.044	-9999	-0.11	75	75
RAB3GAP2	0.013	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.029	0.071	-9999	-0.35	11	11
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.072	0.15	-9999	-0.38	90	90
UNC13B	0.007	0.059	-9999	-0.58	5	5
CHRNA1	-0.097	0.23	-9999	-0.58	90	90
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.058	0.14	-9999	-0.33	92	92
SNAP25	-0.035	0.099	-9999	-0.27	74	74
VAMP2	0.006	0	-9999	-10000	0	0
SYT1	-0.081	0.2	-9999	-0.48	92	92
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	0.014	0.035	-9999	-0.32	5	5
STX1A/SNAP25 fragment 1/VAMP2	-0.029	0.071	-9999	-0.35	11	11

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.038	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.027	0.17	0.61	22	-10000	0	22
IL27/IL27R/JAK1	0.002	0.25	0.4	1	-0.82	21	22
TBX21	0.009	0.22	0.35	1	-0.61	32	33
IL12B	-0.024	0.14	-10000	0	-0.58	29	29
IL12A	-0.003	0.069	-10000	0	-0.38	16	16
IL6ST	-0.084	0.2	-10000	0	-0.48	100	100
IL27RA/JAK1	0.002	0.17	-10000	0	-1	12	12
IL27	-0.01	0.11	-10000	0	-0.57	18	18
TYK2	0.015	0.006	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.087	0.15	-10000	0	-0.61	7	7
T-helper 2 cell differentiation	0.027	0.17	0.61	22	-10000	0	22
T cell proliferation during immune response	0.027	0.17	0.61	22	-10000	0	22
MAPKKK cascade	-0.027	0.17	-10000	0	-0.61	22	22
STAT3	0.013	0	-10000	0	-10000	0	0
STAT2	0.013	0	-10000	0	-10000	0	0
STAT1	0.003	0.084	-10000	0	-0.58	10	10
IL12RB1	-0.012	0.12	-10000	0	-0.55	22	22
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	0.011	0.21	0.35	1	-0.6	25	26
IL27/IL27R/JAK2/TYK2	-0.027	0.18	-10000	0	-0.62	22	22
positive regulation of T cell mediated cytotoxicity	-0.027	0.17	-10000	0	-0.61	22	22
STAT1 (dimer)	0.02	0.31	0.49	102	-0.86	19	121
JAK2	0.012	0.023	-10000	0	-0.47	1	1
JAK1	0.016	0.004	-10000	0	-10000	0	0
STAT2 (dimer)	-0.02	0.16	-10000	0	-0.58	22	22
T cell proliferation	-0.11	0.21	-10000	0	-0.5	66	66
IL12/IL12R/TYK2/JAK2	0.009	0.085	-10000	0	-0.43	6	6
IL17A	-0.09	0.14	-10000	0	-0.61	7	7
mast cell activation	0.027	0.17	0.61	22	-10000	0	22
IFNG	-0.001	0.032	-10000	0	-0.087	24	24
T cell differentiation	-0.003	0.006	0.015	1	-0.02	31	32
STAT3 (dimer)	-0.02	0.16	-10000	0	-0.58	22	22
STAT5A (dimer)	-0.021	0.17	-10000	0	-0.6	22	22
STAT4 (dimer)	-0.03	0.18	-10000	0	-0.57	33	33
STAT4	-0.008	0.11	-10000	0	-0.55	18	18
T cell activation	-0.007	0.02	0.12	12	-10000	0	12
IL27R/JAK2/TYK2	-0.051	0.19	-10000	0	-1.1	12	12
GATA3	-0.34	0.56	-10000	0	-1.2	142	142
IL18	0.002	0.054	-10000	0	-0.34	12	12
positive regulation of mast cell cytokine production	-0.019	0.16	-10000	0	-0.56	22	22
IL27/EBI3	-0.004	0.1	-10000	0	-0.41	30	30
IL27RA	-0.017	0.18	-10000	0	-1.1	12	12
IL6	-0.16	0.25	-10000	0	-0.51	155	155
STAT5A	0.011	0.031	-10000	0	-0.47	2	2
monocyte differentiation	0	0.001	-10000	0	-10000	0	0
IL2	0.012	0.075	0.48	11	-10000	0	11
IL1B	-0.045	0.13	-10000	0	-0.36	72	72
EBI3	0.002	0.089	-10000	0	-0.55	12	12
TNF	-0.02	0.1	-10000	0	-0.36	39	39

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.007	0.059	-9999	-0.58	5	5
EGFR	-0.026	0.13	-9999	-0.47	39	39
EGF/EGFR	-0.09	0.16	-9999	-0.4	69	69
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.019	0.12	-9999	-0.45	3	3
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	-0.039	0.15	-9999	-0.47	52	52
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.056	0.18	-9999	-0.54	61	61
EGF/EGFR dimer/SHC	-0.04	0.14	-9999	-0.31	97	97
mol:GDP	-0.021	0.12	-9999	-0.45	3	3
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.024	0.13	-9999	-0.5	35	35
GRB2/SOS1	0.02	0	-9999	-10000	0	0
HRAS/GTP	-0.048	0.098	-9999	-0.44	6	6
SHC1	0.013	0	-9999	-10000	0	0
HRAS/GDP	-0.049	0.1	-9999	-0.46	6	6
FRAP1	-0.022	0.11	-9999	-0.43	3	3
EGF/EGFR dimer	-0.059	0.16	-9999	-0.37	97	97
SOS1	0.013	0	-9999	-10000	0	0
GRB2	0.013	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.043	0.15	-9999	-0.39	75	75

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.067	0.15	0.35	109	-10000	0	109
KIRREL	-0.087	0.2	-10000	0	-0.48	99	99
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.068	0.15	-10000	0	-0.35	109	109
PLCG1	0.013	0	-10000	0	-10000	0	0
ARRB2	0.013	0	-10000	0	-10000	0	0
WASL	0.013	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.039	0.12	-10000	0	-0.54	2	2
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.029	0.1	-10000	0	-0.42	3	3
FYN	-0.041	0.11	-10000	0	-0.29	13	13
mol:Ca2+	-0.04	0.11	-10000	0	-0.32	14	14
mol:DAG	-0.04	0.12	-10000	0	-0.32	14	14
NPHS2	-0.011	0.05	-10000	0	-0.59	3	3
mol:IP3	-0.04	0.12	-10000	0	-0.32	14	14
regulation of endocytosis	-0.031	0.1	-10000	0	-0.47	2	2
Nephrin/NEPH1/podocin/Cholesterol	-0.048	0.12	-10000	0	-0.26	109	109
establishment of cell polarity	-0.067	0.15	-10000	0	-0.35	109	109
Nephrin/NEPH1/podocin/NCK1-2	-0.028	0.11	-10000	0	-0.5	3	3
Nephrin/NEPH1/beta Arrestin2	-0.03	0.1	-10000	0	-0.48	2	2
NPHS1	-0.016	0.087	-10000	0	-0.57	11	11
Nephrin/NEPH1/podocin	-0.041	0.11	-10000	0	-0.29	14	14
TJP1	0.013	0	-10000	0	-10000	0	0
NCK1	0.012	0.027	-10000	0	-0.58	1	1
NCK2	0.013	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.039	0.12	-10000	0	-0.33	14	14
CD2AP	0.013	0.001	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.039	0.12	-10000	0	-0.33	14	14
GRB2	0.013	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.079	0.16	-10000	0	-0.34	96	96
cytoskeleton organization	-0.029	0.12	-10000	0	-0.46	3	3
Nephrin/NEPH1	-0.045	0.11	-10000	0	-0.24	109	109
Nephrin/NEPH1/ZO-1	-0.043	0.12	-10000	0	-0.34	12	12

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.013	0	-9999	-10000	0	0
VLDLR	0.012	0.022	-9999	-0.47	1	1
LRPAP1	0.013	0	-9999	-10000	0	0
NUDC	0.013	0	-9999	-10000	0	0
RELN/LRP8	-0.038	0.15	-9999	-0.36	83	83
CaM/Ca2+	0.01	0	-9999	-10000	0	0
KATNA1	0.013	0.001	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.028	0.13	-9999	-0.32	78	78
IQGAP1/CaM	0.02	0	-9999	-10000	0	0
DAB1	-0.17	0.24	-9999	-0.47	187	187
IQGAP1	0.013	0	-9999	-10000	0	0
PLA2G7	-0.14	0.26	-9999	-0.57	124	124
CALM1	0.013	0	-9999	-10000	0	0
DYNLT1	0.013	0.001	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	0.013	0.052	-9999	-0.42	7	7
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.013	0	-9999	-10000	0	0
CDK5R1	-0.016	0.13	-9999	-0.58	24	24
LIS1/Poliovirus Protein 3A	0.016	0	-9999	-10000	0	0
CDK5R2	-0.053	0.18	-9999	-0.58	54	54
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.14	0.2	-9999	-0.34	224	224
YWHAE	0.013	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.022	0.13	-9999	-0.41	20	20
MAP1B	-0.022	0.074	-9999	-0.27	40	40
RAC1	0.02	0	-9999	-10000	0	0
p35/CDK5	-0.026	0.14	-9999	-0.61	9	9
RELN	-0.081	0.22	-9999	-0.57	79	79
PAFAH/LIS1	-0.069	0.16	-9999	-0.35	124	124
LIS1/CLIP170	0.025	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.045	0.084	-9999	-0.44	3	3
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.16	-9999	-0.44	58	58
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.031	0.14	-9999	-0.44	21	21
LIS1/IQGAP1	0.025	0	-9999	-10000	0	0
RHOA	0.02	0	-9999	-10000	0	0
PAFAH1B1	0.021	0	-9999	-10000	0	0
PAFAH1B3	-0.01	0.11	-9999	-0.57	19	19
PAFAH1B2	-0.002	0.084	-9999	-0.47	15	15
MAP1B/LIS1/Dynein heavy chain	0.009	0.051	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.015	0.13	-9999	-0.39	20	20
LRP8	0.005	0.07	-9999	-0.58	7	7
NDEL1/Katanin 60	-0.022	0.13	-9999	-0.41	21	21
P39/CDK5	-0.046	0.16	-9999	-0.55	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.025	0	-9999	-10000	0	0
CDK5	-0.02	0.12	-9999	-0.58	3	3
PPP2R5D	0.013	0.001	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.022	0	-9999	-10000	0	0
CSNK2A1	0.013	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.11	0.18	-9999	-0.52	43	43
RELN/VLDLR	-0.026	0.14	-9999	-0.32	78	78
CDC42	0.02	0	-9999	-10000	0	0

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	-0.075	0.19	-9999	-0.47	88	88
GNB1/GNG2	-0.031	0.14	-9999	-0.44	27	27
mol:DAG	-0.023	0.13	-9999	-0.44	19	19
PLCG1	-0.024	0.13	-9999	-0.46	19	19
YES1	-0.038	0.14	-9999	-0.45	25	25
FZD3	0.011	0.031	-9999	-0.47	2	2
FZD6	0.013	0	-9999	-10000	0	0
G protein	-0.024	0.13	-9999	-0.46	19	19
MAP3K7	-0.05	0.15	-9999	-0.4	38	38
mol:Ca2+	-0.022	0.12	-9999	-0.42	19	19
mol:IP3	-0.023	0.13	-9999	-0.44	19	19
NLK	-0.003	0.007	-9999	-10000	0	0
GNB1	0.013	0	-9999	-10000	0	0
CAMK2A	-0.06	0.16	-9999	-0.41	52	52
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.048	0.15	-9999	-0.46	28	28
CSNK1A1	0.013	0	-9999	-10000	0	0
GNAS	-0.038	0.14	-9999	-0.45	25	25
GO:0007205	-0.023	0.13	-9999	-0.43	19	19
WNT6	-0.085	0.2	-9999	-0.48	97	97
WNT4	0.007	0.053	-9999	-0.47	6	6
NFAT1/CK1 alpha	-0.056	0.16	-9999	-0.44	32	32
GNG2	0.008	0.049	-9999	-0.47	5	5
WNT5A	-0.027	0.14	-9999	-0.51	38	38
WNT11	-0.025	0.14	-9999	-0.55	33	33
CDC42	-0.03	0.13	-9999	-0.42	25	25

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.017	0.11	-9999	-0.5	25	25
PDGF/PDGFRA/CRKL	-0.001	0.08	-9999	-0.34	25	25
positive regulation of JUN kinase activity	0.017	0.061	-9999	-0.32	1	1
CRKL	0.013	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.088	0.17	-9999	-0.36	134	134
AP1	-0.16	0.34	-9999	-0.87	88	88
mol:IP3	-0.005	0.088	-9999	-0.37	25	25
PLCG1	-0.005	0.089	-9999	-0.37	25	25
PDGF/PDGFRA/alphaV Integrin	-0.003	0.087	-9999	-0.36	25	25
RAPGEF1	0.013	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
mol:Ca2+	-0.005	0.088	-9999	-0.37	25	25
CAV3	-0.1	0.21	-9999	-0.49	114	114
CAV1	-0.049	0.16	-9999	-0.47	62	62
SHC/Grb2/SOS1	0.018	0.061	-9999	-0.32	1	1
PDGF/PDGFRA/Shf	-0.003	0.086	-9999	-0.36	26	26
FOS	-0.13	0.35	-9999	-0.86	88	88
JUN	-0.017	0.054	-9999	-0.42	7	7
oligodendrocyte development	-0.003	0.087	-9999	-0.36	25	25
GRB2	0.013	0	-9999	-10000	0	0
PIK3R1	0.008	0.049	-9999	-0.47	5	5
mol:DAG	-0.005	0.088	-9999	-0.37	25	25
PDGF/PDGFRA	-0.017	0.11	-9999	-0.5	25	25
actin cytoskeleton reorganization	-0.004	0.09	-9999	-0.36	27	27
SRF	0.023	0.01	-9999	-10000	0	0
SHC1	0.013	0	-9999	-10000	0	0
PI3K	0.005	0.084	-9999	-0.34	21	21
PDGF/PDGFRA/Crk/C3G	0.009	0.068	-9999	-0.28	25	25
JAK1	0	0.08	-9999	-0.34	25	25
ELK1/SRF	0.017	0.067	-9999	-0.3	1	1
SHB	0.009	0.044	-9999	-0.47	4	4
SHF	0.011	0.035	-9999	-0.52	2	2
CSNK2A1	0.011	0.022	-9999	-10000	0	0
GO:0007205	-0.007	0.095	-9999	-0.4	25	25
SOS1	0.013	0	-9999	-10000	0	0
Ras protein signal transduction	0.017	0.061	-9999	-0.32	1	1
PDGF/PDGFRA/SHB	-0.004	0.09	-9999	-0.36	27	27
PDGF/PDGFRA/Caveolin-1	-0.044	0.16	-9999	-0.42	68	68
ITGAV	0.011	0.031	-9999	-0.47	2	2
ELK1	-0.004	0.091	-9999	-0.36	25	25
PIK3CA	0.01	0.038	-9999	-0.47	3	3
PDGF/PDGFRA/Crk	-0.001	0.08	-9999	-0.34	25	25
JAK-STAT cascade	0	0.08	-9999	-0.34	25	25
cell proliferation	-0.003	0.086	-9999	-0.36	26	26

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.029	0.12	-10000	0	-0.34	38	38
IKBKB	0.01	0.058	-10000	0	-0.22	6	6
AKT1	-0.015	0.097	0.2	8	-0.24	30	38
IKBKG	0.013	0.059	-10000	0	-0.24	6	6
CALM1	-0.006	0.08	0.23	11	-0.33	8	19
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
MAP3K1	-0.059	0.17	-10000	0	-0.41	68	68
MAP3K7	0.013	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.013	0.084	0.23	11	-0.28	22	33
DOK1	0.013	0	-10000	0	-10000	0	0
AP-1	-0.015	0.08	-10000	0	-0.23	22	22
LYN	0.013	0	-10000	0	-10000	0	0
BLNK	0.012	0.022	-10000	0	-0.47	1	1
SHC1	0.013	0	-10000	0	-10000	0	0
BCR complex	-0.064	0.19	-10000	0	-0.45	86	86
CD22	-0.076	0.17	-10000	0	-0.52	47	47
CAMK2G	0	0.076	0.22	11	-0.37	4	15
CSNK2A1	0.013	0	-10000	0	-10000	0	0
INPP5D	-0.013	0.11	-10000	0	-0.47	26	26
SHC/GRB2/SOS1	-0.051	0.12	-10000	0	-0.5	18	18
GO:0007205	-0.014	0.085	0.23	11	-0.29	22	33
SYK	0.006	0.06	-10000	0	-0.49	7	7
ELK1	-0.007	0.081	0.23	11	-0.3	13	24
NFATC1	-0.032	0.14	-10000	0	-0.34	60	60
B-cell antigen/BCR complex	-0.064	0.19	-10000	0	-0.45	86	86
PAG1/CSK	0.018	0.028	-10000	0	-0.42	2	2
NFKBIB	0.014	0.023	0.082	4	-10000	0	4
HRAS	-0.008	0.089	0.21	10	-0.32	17	27
NFKBIA	0.014	0.023	0.082	4	-10000	0	4
NF-kappa-B/RelA/I kappa B beta	0.018	0.02	-10000	0	-10000	0	0
RasGAP/Csk	-0.038	0.17	-10000	0	-0.61	25	25
mol:GDP	-0.012	0.08	0.24	11	-0.27	21	32
PTEN	0	0.078	-10000	0	-0.47	13	13
CD79B	-0.016	0.12	-10000	0	-0.53	26	26
NF-kappa-B/RelA/I kappa B alpha	0.018	0.019	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.057	0.17	-10000	0	-0.43	50	50
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
mol:IP3	-0.014	0.086	0.23	11	-0.29	22	33
CSK	0.013	0	-10000	0	-10000	0	0
FOS	-0.04	0.12	0.23	5	-0.37	25	30
CHUK	0.013	0.059	-10000	0	-0.24	6	6
IBTK	0.012	0.022	-10000	0	-0.47	1	1
CARD11/BCL10/MALT1/TAK1	-0.028	0.077	-10000	0	-0.43	11	11
PTPN6	-0.042	0.17	-10000	0	-0.52	42	42
RELA	0.013	0	-10000	0	-10000	0	0
BCL2A1	0.016	0.022	-10000	0	-0.11	8	8
VAV2	-0.079	0.19	-10000	0	-0.49	69	69
ubiquitin-dependent protein catabolic process	0.018	0.022	0.085	4	-10000	0	4
BTK	0.01	0.08	0.31	1	-0.79	1	2
CD19	-0.12	0.2	-10000	0	-0.53	72	72
MAP4K1	-0.024	0.14	-10000	0	-0.56	32	32
CD72	-0.013	0.12	-10000	0	-0.56	22	22
PAG1	0.011	0.038	-10000	0	-0.58	2	2
MAPK14	-0.044	0.15	-10000	0	-0.39	44	44
SH3BP5	0.013	0	-10000	0	-10000	0	0
PIK3AP1	-0.014	0.092	-10000	0	-0.32	21	21
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.015	0.12	-10000	0	-0.35	45	45
RAF1	-0.001	0.085	0.21	3	-0.34	9	12
RasGAP/p62DOK/SHIP	-0.076	0.16	-10000	0	-0.54	36	36
CD79A	-0.076	0.2	-10000	0	-0.55	77	77
re-entry into mitotic cell cycle	-0.015	0.079	-10000	0	-0.23	22	22
RASA1	0.01	0.038	-10000	0	-0.47	3	3
MAPK3	0.012	0.075	-10000	0	-0.32	5	5
MAPK1	0.012	0.075	-10000	0	-0.32	5	5
CD72/SHP1	-0.044	0.19	-10000	0	-0.56	46	46
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	-0.048	0.16	-10000	0	-0.38	60	60
actin cytoskeleton organization	-0.062	0.17	-10000	0	-0.42	69	69
NF-kappa-B/RelA	0.041	0.036	0.16	4	-10000	0	4
Calcineurin	0.003	0.066	-10000	0	-0.33	4	4
PI3K	-0.094	0.16	-10000	0	-0.43	73	73
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.017	0.089	-10000	0	-0.31	27	27
SOS1	0.013	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.12	0.3	-10000	0	-0.69	94	94
DAPP1	-0.15	0.31	-10000	0	-0.86	71	71
cytokine secretion	-0.029	0.13	0.19	2	-0.32	60	62
mol:DAG	-0.014	0.086	0.23	11	-0.29	22	33
PLCG2	0.004	0.069	-10000	0	-0.49	9	9
MAP2K1	0.006	0.08	-10000	0	-0.36	5	5
B-cell antigen/BCR complex/FcgammaRIIB	-0.059	0.19	-10000	0	-0.48	61	61
mol:PI-3-4-5-P3	-0.064	0.12	0.25	8	-0.3	68	76
ETS1	0.005	0.077	0.22	11	-0.38	5	16
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.029	0.15	-10000	0	-0.38	59	59
B-cell antigen/BCR complex/LYN	-0.062	0.14	-10000	0	-0.43	40	40
MALT1	0.009	0.051	-10000	0	-0.55	4	4
TRAF6	0.013	0	-10000	0	-10000	0	0
RAC1	-0.067	0.18	-10000	0	-0.45	69	69
B-cell antigen/BCR complex/LYN/SYK	-0.078	0.17	-10000	0	-0.55	42	42
CARD11	-0.015	0.1	0.23	8	-0.4	17	25
FCGR2B	-0.01	0.11	-10000	0	-0.53	21	21
PPP3CA	0.01	0.046	-10000	0	-0.58	3	3
BCL10	0.013	0	-10000	0	-10000	0	0
IKK complex	0.013	0.031	0.089	4	-10000	0	4
PTPRC	-0.013	0.11	-10000	0	-0.5	25	25
PDPK1	-0.019	0.094	0.18	8	-0.24	29	37
PPP3CB	0.013	0	-10000	0	-10000	0	0
PPP3CC	0.013	0	-10000	0	-10000	0	0
POU2F2	0.016	0.021	-10000	0	-0.1	2	2

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.011	0.075	-10000	0	-0.35	12	12
epithelial cell differentiation	-0.032	0.077	-10000	0	-0.4	5	5
ITCH	0.018	0.013	-10000	0	-10000	0	0
WWP1	0.018	0.054	-10000	0	-0.56	1	1
FYN	0.013	0.001	-10000	0	-10000	0	0
EGFR	-0.026	0.13	-10000	0	-0.47	39	39
PRL	-0.003	0.052	-10000	0	-0.58	4	4
neuron projection morphogenesis	-0.018	0.12	-10000	0	-0.41	11	11
PTPRZ1	-0.16	0.24	-10000	0	-0.48	174	174
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.033	0.13	-10000	0	-0.46	11	11
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.055	0.14	-10000	0	-0.35	36	36
ADAM17	0.012	0.049	-10000	0	-0.46	5	5
ErbB4/ErbB4	0.015	0.068	-10000	0	-0.43	4	4
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.026	0.11	-10000	0	-0.36	25	25
NCOR1	0.012	0.022	-10000	0	-0.47	1	1
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.044	0.13	-10000	0	-0.33	33	33
GRIN2B	-0.041	0.12	-10000	0	-0.57	2	2
ErbB4/ErbB2/betacellulin	0.009	0.1	-10000	0	-0.4	18	18
STAT1	0.001	0.084	-10000	0	-0.58	10	10
HBEGF	0.002	0.078	-10000	0	-0.53	10	10
PRLR	-0.042	0.16	-10000	0	-0.52	50	50
E4ICDs/ETO2	0.015	0.065	-10000	0	-0.38	5	5
axon guidance	0.033	0.077	-10000	0	-0.3	2	2
NEDD4	0.007	0.068	-10000	0	-0.46	10	10
Prolactin receptor/Prolactin receptor/Prolactin	-0.033	0.12	-10000	0	-0.38	54	54
CBFA2T3	0.008	0.049	-10000	0	-0.47	5	5
ErbB4/ErbB2/HBEGF	0.018	0.073	-10000	0	-0.37	6	6
MAPK3	-0.025	0.13	-10000	0	-0.43	11	11
STAT1 (dimer)	0.01	0.079	-10000	0	-0.36	14	14
MAPK1	-0.025	0.13	-10000	0	-0.43	11	11
JAK2	0.012	0.022	-10000	0	-0.47	1	1
ErbB4/ErbB2/neuregulin 1 beta	-0.047	0.13	-10000	0	-0.34	34	34
NRG1	-0.081	0.16	-10000	0	-0.33	142	142
NRG3	-0.048	0.16	-10000	0	-0.51	53	53
NRG2	-0.16	0.23	-10000	0	-0.47	172	172
NRG4	-0.15	0.23	-10000	0	-0.48	163	163
heart development	0.033	0.077	-10000	0	-0.3	2	2
neural crest cell migration	-0.046	0.13	-10000	0	-0.34	34	34
ERBB2	0.017	0.047	-10000	0	-0.32	9	9
WWOX/E4ICDs	0.017	0.06	-10000	0	-0.38	4	4
SHC1	0.013	0	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 4	-0.083	0.17	-10000	0	-0.47	40	40
apoptosis	0.029	0.11	0.34	38	-10000	0	38
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.08	0.16	-10000	0	-0.4	41	41
ErbB4/ErbB2/epiregulin	-0.01	0.098	-10000	0	-0.4	6	6
ErbB4/ErbB4/betacellulin/betacellulin	0	0.1	-10000	0	-0.43	17	17
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.006	0.12	-10000	0	-0.44	12	12
MDM2	0.02	0.059	-10000	0	-0.38	4	4
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.048	0.13	-10000	0	-0.31	33	33
STAT5A	0.041	0.072	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.064	0.16	-10000	0	-0.39	50	50
DLG4	0.001	0.075	-10000	0	-0.47	12	12
GRB2/SHC	0.02	0	-10000	0	-10000	0	0
E4ICDs/TAB2/NCoR1	0.015	0.058	-10000	0	-0.41	4	4
STAT5A (dimer)	-0.033	0.082	-10000	0	-0.43	5	5
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	0.04	0.068	-10000	0	-10000	0	0
LRIG1	0.012	0.027	-10000	0	-0.58	1	1
EREG	-0.041	0.16	-10000	0	-0.52	47	47
BTC	-0.018	0.12	-10000	0	-0.47	31	31
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	0.031	0.076	-10000	0	-0.3	2	2
ERBB4	0.015	0.068	-10000	0	-0.43	4	4
STAT5B	0.013	0	-10000	0	-10000	0	0
YAP1	0.011	0.067	-10000	0	-0.72	4	4
GRB2	0.013	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.061	0.14	-10000	0	-0.37	27	27
glial cell differentiation	-0.015	0.057	0.41	4	-10000	0	4
WWOX	0.012	0.022	-10000	0	-0.47	1	1
cell proliferation	-0.06	0.16	-10000	0	-0.5	25	25

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.002	0.078	-9999	-0.24	45	45
RGS9BP	0.009	0.049	-9999	-0.52	4	4
mol:GTP	0	0	-9999	-10000	0	0
GRK1	-0.001	0.053	-9999	-0.58	4	4
mol:Na +	-0.015	0.089	-9999	-0.37	28	28
mol:ADP	0.004	0.044	-9999	-0.42	5	5
GNAT2	0.005	0.059	-9999	-0.58	5	5
RGS9-1/Gbeta5/R9AP	-0.04	0.12	-9999	-0.27	109	109
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	0.003	0.054	-9999	-0.4	8	8
GRK7	0.006	0.027	-9999	-0.58	1	1
CNGB3	-0.014	0.1	-9999	-0.58	15	15
Cone Metarhodopsin II/X-Arrestin	0.001	0.028	-9999	-0.42	2	2
mol:Ca2+	-0.04	0.13	-9999	-0.34	72	72
Cone PDE6	-0.033	0.11	-9999	-0.52	2	2
Cone Metarhodopsin II	0.004	0.034	-9999	-0.33	5	5
Na + (4 Units)	-0.04	0.13	-9999	-0.34	72	72
GNAT2/GDP	-0.03	0.11	-9999	-0.36	10	10
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	0.004	0.049	-9999	-0.36	8	8
Cone Transducin	-0.002	0.083	-9999	-0.26	45	45
SLC24A2	-0.047	0.17	-9999	-0.58	46	46
GNB3/GNGT2	-0.01	0.099	-9999	-0.34	40	40
GNB3	-0.022	0.12	-9999	-0.47	35	35
GNAT2/GTP	0.004	0.044	-9999	-0.42	5	5
CNGA3	-0.011	0.098	-9999	-0.58	14	14
ARR3	0.002	0.038	-9999	-0.58	2	2
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.015	0.089	-9999	-0.37	28	28
mol:Pi	-0.04	0.12	-9999	-0.27	109	109
Cone CNG Channel	-0.022	0.081	-9999	-0.33	14	14
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.047	0.17	-9999	-0.57	46	46
RGS9	-0.092	0.2	-9999	-0.47	105	105
PDE6C	0.003	0.005	-9999	-10000	0	0
GNGT2	0.007	0.056	-9999	-0.49	6	6
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	-0.002	0.053	-9999	-0.58	4	4

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.013	0.1	-10000	0	-0.33	46	46
CRKL	-0.003	0.11	-10000	0	-0.44	17	17
mol:PIP3	-0.005	0.073	0.44	13	-10000	0	13
AKT1	0.01	0.051	0.32	13	-10000	0	13
PTK2B	0.013	0	-10000	0	-10000	0	0
RAPGEF1	0.004	0.11	-10000	0	-0.42	17	17
RANBP10	0.013	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
HGF/MET/SHIP2	-0.024	0.13	-10000	0	-0.34	67	67
MAP3K5	0.004	0.11	-10000	0	-0.41	19	19
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.013	0.12	-10000	0	-0.42	27	27
AP1	-0.05	0.14	-10000	0	-0.33	88	88
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	-0.12	0.29	-10000	0	-0.73	83	83
STAT3 (dimer)	-0.001	0.11	-10000	0	-0.44	18	18
GAB1/CRKL/SHP2/PI3K	0.012	0.12	-10000	0	-0.42	21	21
INPP5D	-0.013	0.11	-10000	0	-0.47	26	26
CBL/CRK	0.005	0.11	-10000	0	-0.43	17	17
PTPN11	0.012	0.022	-10000	0	-0.47	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.013	0	-10000	0	-10000	0	0
PTEN	0	0.078	-10000	0	-0.47	13	13
ELK1	-0.016	0.051	-10000	0	-0.17	46	46
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.023	0.065	-10000	0	-0.3	17	17
PAK1	0.012	0.054	0.3	13	-10000	0	13
HGF/MET/RANBP10	-0.024	0.13	-10000	0	-0.34	67	67
HRAS	-0.038	0.2	-10000	0	-0.63	46	46
DOCK1	0.003	0.11	-10000	0	-0.43	17	17
GAB1	-0.01	0.12	-10000	0	-0.32	47	47
CRK	-0.003	0.11	-10000	0	-0.44	17	17
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	-0.041	0.2	-10000	0	-0.58	57	57
JUN	0.006	0.061	-10000	0	-0.5	7	7
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	-0.022	0.099	-10000	0	-0.27	57	57
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
cell morphogenesis	0.017	0.13	-10000	0	-0.47	21	21
GRB2/SHC	-0.004	0.09	-10000	0	-0.36	16	16
FOS	-0.076	0.19	-10000	0	-0.48	88	88
GLMN	0	0	-10000	0	-10000	0	0
cell motility	-0.016	0.051	-10000	0	-0.17	46	46
HGF/MET/MUC20	-0.033	0.13	-10000	0	-0.35	67	67
cell migration	-0.004	0.088	-10000	0	-0.35	16	16
GRB2	0.013	0	-10000	0	-10000	0	0
CBL	0.012	0.022	-10000	0	-0.47	1	1
MET/RANBP10	-0.013	0.1	-10000	0	-0.33	46	46
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.006	0.11	-10000	0	-0.44	18	18
MET/MUC20	-0.023	0.1	-10000	0	-0.34	46	46
RAP1B	0.011	0.1	-10000	0	-0.38	17	17
RAP1A	0.011	0.1	-10000	0	-0.38	17	17
HGF/MET/RANBP9	-0.024	0.13	-10000	0	-0.34	67	67
RAF1	-0.029	0.19	-10000	0	-0.59	46	46
STAT3	-0.001	0.11	-10000	0	-0.44	18	18
cell proliferation	-0.005	0.15	-10000	0	-0.42	47	47
RPS6KB1	-0.001	0.038	-10000	0	-10000	0	0
MAPK3	-0.02	0.046	-10000	0	-10000	0	0
MAPK1	-0.02	0.046	-10000	0	-10000	0	0
RANBP9	0.013	0	-10000	0	-10000	0	0
MAPK8	0.012	0.12	-10000	0	-0.39	29	29
SRC	0.001	0.1	-10000	0	-0.41	18	18
PI3K	-0.008	0.1	-10000	0	-0.39	21	21
MET/Glomulin	-0.016	0.089	-10000	0	-0.29	46	46
SOS1	0.013	0	-10000	0	-10000	0	0
MAP2K1	-0.019	0.18	-10000	0	-0.54	46	46
MET	-0.033	0.14	-10000	0	-0.47	46	46
MAP4K1	-0.002	0.12	-10000	0	-0.44	19	19
PTK2	0.013	0	-10000	0	-10000	0	0
MAP2K2	-0.02	0.18	-10000	0	-0.54	47	47
BAD	0.014	0.049	0.3	13	-0.3	1	14
MAP2K4	0.011	0.1	-10000	0	-0.37	19	19
SHP2/GRB2/SOS1/GAB1	-0.04	0.11	-10000	0	-0.37	46	46
INPPL1	0.013	0	-10000	0	-10000	0	0
PXN	0.013	0	-10000	0	-10000	0	0
SH3KBP1	0.013	0	-10000	0	-10000	0	0
HGS	-0.014	0.092	-10000	0	-0.27	46	46
PLCgamma1/PKC	0.01	0	-10000	0	-10000	0	0
HGF	-0.026	0.14	-10000	0	-0.5	37	37
RASA1	0.01	0.038	-10000	0	-0.47	3	3
NCK1	0.012	0.027	-10000	0	-0.58	1	1
PTPRJ	0.013	0	-10000	0	-10000	0	0
NCK/PLCgamma1	-0.004	0.094	-10000	0	-0.37	17	17
PDPK1	0.002	0.058	0.35	13	-10000	0	13
HGF/MET/SHIP	-0.038	0.17	-10000	0	-0.41	73	73

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-10000	0	-0.58	2	2
Jak2/Leptin Receptor	-0.03	0.12	0.19	15	-0.41	19	34
PTP1B/AKT1	-0.037	0.081	-10000	0	-0.32	11	11
FYN	0.013	0.001	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.048	0.089	-10000	0	-0.3	23	23
EGFR	-0.028	0.13	-10000	0	-0.48	39	39
EGF/EGFR	-0.079	0.14	-10000	0	-0.36	69	69
CSF1	0.003	0.069	-10000	0	-0.47	10	10
AKT1	0.013	0.001	-10000	0	-10000	0	0
INSR	0.013	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.11	0.15	-10000	0	-0.34	100	100
Insulin Receptor/Insulin	-0.042	0.067	-10000	0	-0.31	12	12
HCK	0.009	0.046	-10000	0	-0.5	4	4
CRK	0.013	0	-10000	0	-10000	0	0
TYK2	-0.039	0.085	-10000	0	-0.32	13	13
EGF	-0.058	0.18	-10000	0	-0.54	61	61
YES1	0.013	0	-10000	0	-10000	0	0
CAV1	-0.062	0.12	-10000	0	-0.39	36	36
TXN	0.011	0.027	-10000	0	-0.58	1	1
PTP1B/IRS1/GRB2	-0.038	0.1	-10000	0	-0.38	17	17
cell migration	0.048	0.089	0.3	23	-10000	0	23
STAT3	0.013	0.001	-10000	0	-10000	0	0
PRLR	-0.041	0.16	-10000	0	-0.52	50	50
ITGA2B	-0.004	0.091	-10000	0	-0.51	15	15
CSF1R	0.011	0.035	-10000	0	-0.52	2	2
Prolactin Receptor/Prolactin	-0.033	0.13	-10000	0	-0.38	54	54
FGR	0.01	0.041	-10000	0	-0.51	3	3
PTP1B/p130 Cas	-0.039	0.085	-10000	0	-0.33	12	12
Crk/p130 Cas	-0.031	0.083	-10000	0	-0.32	11	11
DOK1	-0.029	0.079	-10000	0	-0.33	7	7
JAK2	-0.033	0.1	-10000	0	-0.41	16	16
Jak2/Leptin Receptor/Leptin	-0.085	0.14	-10000	0	-0.43	54	54
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
PTPN1	-0.049	0.09	-10000	0	-0.3	23	23
LYN	0.013	0	-10000	0	-10000	0	0
CDH2	-0.12	0.22	-10000	0	-0.48	136	136
SRC	-0.004	0.036	-10000	0	-10000	0	0
ITGB3	-0.084	0.19	-10000	0	-0.47	97	97
CAT1/PTP1B	-0.039	0.1	-10000	0	-0.41	9	9
CAPN1	0.013	0.002	-10000	0	-10000	0	0
CSK	0.013	0	-10000	0	-10000	0	0
PI3K	-0.035	0.074	-10000	0	-0.48	4	4
mol:H2O2	0.001	0.005	-10000	0	-10000	0	0
STAT3 (dimer)	-0.084	0.15	-10000	0	-0.42	70	70
negative regulation of transcription	-0.03	0.1	-10000	0	-0.4	16	16
FCGR2A	0.01	0.044	-10000	0	-0.54	3	3
FER	-0.009	0.1	-10000	0	-0.48	21	21
alphaIIb/beta3 Integrin	-0.062	0.16	-10000	0	-0.34	108	108
BLK	-0.1	0.22	-10000	0	-0.5	109	109
Insulin Receptor/Insulin/Shc	0.008	0.06	-10000	0	-0.34	14	14
RHOA	0.013	0.002	-10000	0	-10000	0	0
LEPR	-0.007	0.098	-10000	0	-0.47	21	21
BCAR1	0.013	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.013	0	-10000	0	-10000	0	0
mol:NADPH	-0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.013	0.097	-10000	0	-0.41	4	4
PRL	-0.002	0.053	-10000	0	-0.57	4	4
SOCS3	-0.14	0.41	-10000	0	-1.2	60	60
SPRY2	0.011	0.045	-10000	0	-0.48	4	4
Insulin Receptor/Insulin/IRS1	-0.002	0.081	-10000	0	-0.32	29	29
CSF1/CSF1R	-0.037	0.1	-10000	0	-0.45	14	14
Ras protein signal transduction	0.028	0.027	-10000	0	-10000	0	0
IRS1	-0.003	0.086	-10000	0	-0.47	16	16
INS	-0.016	0.096	-10000	0	-0.57	14	14
LEP	-0.006	0.083	-10000	0	-0.58	10	10
STAT5B	-0.037	0.087	-10000	0	-0.3	18	18
STAT5A	-0.037	0.087	-10000	0	-0.3	18	18
GRB2	0.013	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.04	0.087	-10000	0	-0.33	14	14
CSN2	-0.002	0.054	-10000	0	-10000	0	0
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
LAT	-0.012	0.063	-10000	0	-0.51	4	4
YBX1	0.021	0.002	-10000	0	-10000	0	0
LCK	0.003	0.075	-10000	0	-0.58	8	8
SHC1	0.013	0	-10000	0	-10000	0	0
NOX4	-0.27	0.29	-10000	0	-0.57	237	237

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	-0.049	0.14	-10000	0	-0.52	31	31
FYN	-0.011	0.2	-10000	0	-0.67	33	33
LAT/GRAP2/SLP76	-0.06	0.16	-10000	0	-0.54	40	40
IKBKB	0.012	0.027	-10000	0	-0.58	1	1
AKT1	0.001	0.14	-10000	0	-0.44	35	35
B2M	0.014	0.003	-10000	0	-10000	0	0
IKBKG	-0.012	0.036	-10000	0	-0.15	20	20
MAP3K8	0	0.08	-10000	0	-0.48	13	13
mol:Ca2+	-0.003	0.013	-10000	0	-0.13	2	2
integrin-mediated signaling pathway	0.004	0.061	-10000	0	-0.28	22	22
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.016	0.21	-10000	0	-0.65	37	37
TRPV6	-0.002	0.049	-10000	0	-0.53	4	4
CD28	-0.039	0.17	-10000	0	-0.56	45	45
SHC1	-0.016	0.2	-10000	0	-0.64	34	34
receptor internalization	-0.028	0.21	-10000	0	-0.6	43	43
PRF1	-0.016	0.23	-10000	0	-1.1	18	18
KRAS	0.013	0	-10000	0	-10000	0	0
GRB2	0.013	0	-10000	0	-10000	0	0
COT/AKT1	0.006	0.12	-10000	0	-0.38	30	30
LAT	-0.022	0.21	-10000	0	-0.64	40	40
EntrezGene:6955	0.001	0.002	-10000	0	-10000	0	0
CD3D	-0.026	0.14	-10000	0	-0.55	35	35
CD3E	-0.007	0.1	-10000	0	-0.52	19	19
CD3G	-0.042	0.16	-10000	0	-0.51	52	52
RASGRP2	0.001	0.04	-10000	0	-0.17	22	22
RASGRP1	0.004	0.14	-10000	0	-0.44	35	35
HLA-A	0.002	0.079	-10000	0	-0.51	11	11
RASSF5	-0.009	0.1	-10000	0	-0.47	22	22
RAP1A/GTP/RAPL	0.005	0.061	-10000	0	-0.28	22	22
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.02	0.048	-10000	0	-0.13	24	24
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.025	0.064	-10000	0	-0.26	27	27
PRKCA	-0.034	0.081	-10000	0	-0.29	34	34
GRAP2	-0.008	0.1	-10000	0	-0.48	21	21
mol:IP3	-0.047	0.12	0.2	3	-0.45	32	35
EntrezGene:6957	0.001	0.003	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.022	0.21	-10000	0	-0.65	34	34
ORAI1	0.005	0.027	0.29	4	-10000	0	4
CSK	-0.018	0.2	-10000	0	-0.66	34	34
B7 family/CD28	-0.036	0.23	-10000	0	-0.73	36	36
CHUK	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.03	0.23	-10000	0	-0.75	35	35
PTPN6	-0.015	0.2	-10000	0	-0.68	32	32
VAV1	-0.025	0.22	-10000	0	-0.68	37	37
Monovalent TCR/CD3	-0.029	0.16	-10000	0	-0.39	61	61
CBL	0.012	0.022	-10000	0	-0.47	1	1
LCK	-0.014	0.21	-10000	0	-0.69	34	34
PAG1	-0.018	0.2	-10000	0	-0.67	34	34
RAP1A	0.013	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.025	0.23	-10000	0	-0.72	36	36
CD80	-0.027	0.15	-10000	0	-0.58	33	33
CD86	0.004	0.074	-10000	0	-0.57	8	8
PDK1/CARD11/BCL10/MALT1	-0.03	0.078	-10000	0	-0.31	28	28
HRAS	0.007	0.059	-10000	0	-0.58	5	5
GO:0035030	-0.024	0.19	-10000	0	-0.58	36	36
CD8A	-0.005	0.099	-10000	0	-0.51	18	18
CD8B	-0.008	0.11	-10000	0	-0.52	20	20
PTPRC	-0.013	0.12	-10000	0	-0.5	25	25
PDK1/PKC theta	-0.004	0.18	-10000	0	-0.56	35	35
CSK/PAG1	-0.013	0.2	-10000	0	-0.67	31	31
SOS1	0.013	0	-10000	0	-10000	0	0
peptide-MHC class I	0.013	0.058	-10000	0	-0.37	11	11
GRAP2/SLP76	-0.066	0.19	-10000	0	-0.65	36	36
STIM1	0.003	0.014	-10000	0	-10000	0	0
RAS family/GTP	0.026	0.063	-10000	0	-0.17	26	26
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.032	0.23	-10000	0	-0.64	43	43
mol:DAG	-0.043	0.11	-10000	0	-0.39	35	35
RAP1A/GDP	0.01	0.021	-10000	0	-0.063	5	5
PLCG1	0.013	0	-10000	0	-10000	0	0
CD247	-0.01	0.12	-10000	0	-0.56	21	21
cytotoxic T cell degranulation	-0.013	0.22	-10000	0	-0.93	20	20
RAP1A/GTP	-0.004	0.013	-10000	0	-0.066	12	12
mol:PI-3-4-5-P3	-0.007	0.17	-10000	0	-0.52	37	37
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.06	0.16	0.22	2	-0.58	34	36
NRAS	0.012	0.022	-10000	0	-0.47	1	1
ZAP70	-0.054	0.19	-10000	0	-0.57	56	56
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.062	0.16	-10000	0	-0.54	40	40
MALT1	0.009	0.051	-10000	0	-0.55	4	4
TRAF6	0.013	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.007	0.12	-10000	0	-0.45	30	30
CARD11	-0.004	0.095	-10000	0	-0.52	16	16
PRKCB	-0.058	0.1	-10000	0	-0.29	58	58
PRKCE	-0.029	0.074	-10000	0	-0.28	29	29
PRKCQ	-0.016	0.2	-10000	0	-0.65	36	36
LCP2	0.006	0.061	-10000	0	-0.54	6	6
BCL10	0.013	0	-10000	0	-10000	0	0
regulation of survival gene product expression	0.006	0.12	-10000	0	-0.37	35	35
IKK complex	0.014	0.054	-10000	0	-0.12	28	28
RAS family/GDP	-0.003	0.01	-10000	0	-0.074	4	4
MAP3K14	0.014	0.095	-10000	0	-0.29	28	28
PDPK1	0.005	0.14	-10000	0	-0.44	31	31
TCR/CD3/MHC I/CD8/Fyn	-0.021	0.23	-10000	0	-0.74	34	34

a4b1 and a4b7 Integrin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.013	0	-9999	-10000	0	0
ITGB7	-0.007	0.1	-9999	-0.49	20	20
ITGA4	-0.013	0.12	-9999	-0.52	24	24
alpha4/beta7 Integrin	-0.014	0.12	-9999	-0.39	39	39
alpha4/beta1 Integrin	0	0.085	-9999	-0.37	24	24

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.027	0.12	-10000	0	-0.54	22	22
HDAC1	0.011	0.006	-10000	0	-10000	0	0
AES	0.013	0.002	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
DTX1	-0.011	0.12	-10000	0	-0.56	20	20
LRP6/FZD1	0.019	0.016	-10000	0	-0.33	1	1
TLE1	0.013	0.001	-10000	0	-10000	0	0
AP1	-0.051	0.16	-10000	0	-0.32	101	101
NCSTN	0.013	0	-10000	0	-10000	0	0
ADAM10	-0.007	0.096	-10000	0	-0.47	20	20
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.017	0.061	-10000	0	-10000	0	0
NICD/RBPSUH	0.008	0.12	-10000	0	-0.52	22	22
WIF1	-0.22	0.24	-10000	0	-0.47	236	236
NOTCH1	-0.025	0.12	-10000	0	-0.55	22	22
PSENEN	0.013	0	-10000	0	-10000	0	0
KREMEN2	-0.025	0.14	-10000	0	-0.54	34	34
DKK1	-0.089	0.2	-10000	0	-0.48	100	100
beta catenin/beta TrCP1	0.026	0.048	0.21	1	-10000	0	1
APH1B	0.013	0	-10000	0	-10000	0	0
APH1A	0.013	0	-10000	0	-10000	0	0
AXIN1	-0.008	0.045	-10000	0	-0.23	7	7
CtBP/CBP/TCF1/TLE1/AES	0.004	0.062	-10000	0	-10000	0	0
PSEN1	0.013	0	-10000	0	-10000	0	0
FOS	-0.076	0.19	-10000	0	-0.48	88	88
JUN	0.006	0.061	-10000	0	-0.5	7	7
MAP3K7	0.012	0.003	-10000	0	-10000	0	0
CTNNB1	0.02	0.05	0.22	1	-10000	0	1
MAPK3	0.013	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.12	-10000	0	-0.33	64	64
HNF1A	-0.057	0.19	-10000	0	-0.58	57	57
CTBP1	0.013	0.002	-10000	0	-10000	0	0
MYC	-0.009	0.11	-10000	0	-10000	0	0
NKD1	-0.035	0.15	-10000	0	-0.48	47	47
FZD1	0.012	0.022	-10000	0	-0.47	1	1
NOTCH1 precursor/Deltex homolog 1	-0.005	0.13	-10000	0	-0.52	22	22
apoptosis	-0.05	0.16	-10000	0	-0.32	101	101
Delta 1/NOTCHprecursor	0.004	0.12	-10000	0	-0.53	22	22
DLL1	0.006	0.058	-10000	0	-0.47	7	7
PPARD	0.021	0.014	-10000	0	-10000	0	0
Gamma Secretase	0.04	0.001	-10000	0	-10000	0	0
APC	-0.01	0.055	-10000	0	-0.29	10	10
DVL1	-0.002	0.034	-10000	0	-10000	0	0
CSNK2A1	0.013	0.001	-10000	0	-10000	0	0
MAP3K7IP1	-0.001	0.003	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.059	0.15	-10000	0	-0.31	126	126
LRP6	0.013	0	-10000	0	-10000	0	0
CSNK1A1	0.013	0.001	-10000	0	-10000	0	0
NLK	0.014	0.006	-10000	0	-10000	0	0
CCND1	0.02	0.024	-10000	0	-10000	0	0
WNT1	-0.002	0.087	-10000	0	-0.58	11	11
Axin1/APC/beta catenin	0.018	0.049	-10000	0	-10000	0	0
DKK2	-0.023	0.13	-10000	0	-0.51	34	34
NOTCH1 precursor/DVL1	-0.024	0.1	-10000	0	-0.5	22	22
GSK3B	0.013	0.001	-10000	0	-10000	0	0
FRAT1	0.013	0.001	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.035	0.12	-10000	0	-0.53	22	22
PPP2R5D	0.015	0.075	0.24	47	-10000	0	47
MAPK1	0.013	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.11	0.14	-10000	0	-0.37	19	19
RBPJ	0.013	0	-10000	0	-10000	0	0
CREBBP	0.015	0.005	-10000	0	-10000	0	0

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.011	0.013	-10000	0	-10000	0	0
AES	0.012	0.011	-10000	0	-10000	0	0
FBXW11	0.013	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.02	0.016	-10000	0	-0.33	1	1
SMAD4	0.013	0	-10000	0	-10000	0	0
DKK2	-0.023	0.13	-10000	0	-0.51	34	34
TLE1	0.012	0.011	-10000	0	-10000	0	0
MACF1	0.014	0	-10000	0	-10000	0	0
CTNNB1	0.087	0.081	0.26	15	-10000	0	15
WIF1	-0.22	0.24	-10000	0	-0.47	236	236
beta catenin/RanBP3	0.019	0.087	0.34	21	-10000	0	21
KREMEN2	-0.025	0.14	-10000	0	-0.54	34	34
DKK1	-0.089	0.2	-10000	0	-0.48	100	100
beta catenin/beta TrCP1	0.09	0.077	0.25	15	-10000	0	15
FZD1	0.013	0.022	-10000	0	-0.47	1	1
AXIN2	0.003	0.14	-10000	0	-1.3	5	5
AXIN1	0.014	0.001	-10000	0	-10000	0	0
RAN	0.013	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.028	0.039	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.066	0.076	-10000	0	-0.44	1	1
Axin1/APC/GSK3	0.02	0.054	0.21	17	-10000	0	17
Axin1/APC/GSK3/beta catenin/Macf1	0.064	0.055	-10000	0	-10000	0	0
HNF1A	-0.057	0.19	-10000	0	-0.57	57	57
CTBP1	0.012	0.011	-10000	0	-10000	0	0
MYC	-0.012	0.12	-10000	0	-0.54	2	2
RANBP3	0.013	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.02	0.12	-10000	0	-0.32	64	64
NKD1	-0.035	0.15	-10000	0	-0.48	47	47
TCF4	0.008	0.043	-10000	0	-0.45	4	4
TCF3	0.012	0.011	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	0.026	0.052	-10000	0	-0.31	11	11
Ran/GTP	0.01	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0	0.089	0.46	4	-0.43	1	5
LEF1	-0.02	0.13	-10000	0	-0.55	27	27
DVL1	0.066	0.043	-10000	0	-10000	0	0
CSNK2A1	0.013	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.068	0.082	-10000	0	-0.4	2	2
DKK1/LRP6/Kremen 2	-0.059	0.15	-10000	0	-0.31	123	123
LRP6	0.014	0.001	-10000	0	-10000	0	0
CSNK1A1	0.012	0.013	-10000	0	-10000	0	0
NLK	0.014	0.002	-10000	0	-10000	0	0
CCND1	0.014	0.041	-10000	0	-10000	0	0
WNT1	-0.002	0.087	-10000	0	-0.57	11	11
GSK3A	0.013	0.022	-10000	0	-0.47	1	1
GSK3B	0.013	0	-10000	0	-10000	0	0
FRAT1	0.013	0	-10000	0	-10000	0	0
PPP2R5D	0.059	0.078	0.29	47	-10000	0	47
APC	0.028	0.052	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.11	0.1	0.21	229	-10000	0	229
CREBBP	0.012	0.011	-10000	0	-10000	0	0

Plasma membrane estrogen receptor 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
GNB1/GNG2	0.006	0.083	-10000	0	-0.3	23	23
ER alpha/Gai/GDP/Gbeta gamma	-0.046	0.19	-10000	0	-0.48	55	55
AKT1	-0.007	0.16	-10000	0	-0.77	18	18
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.007	0.16	-10000	0	-0.77	18	18
mol:Ca2+	0.013	0.076	-10000	0	-0.5	3	3
IGF1R	0.011	0.035	-10000	0	-0.52	2	2
E2/ER alpha (dimer)/Striatin	-0.013	0.097	-10000	0	-0.3	48	48
SHC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.006	0.15	0.73	18	-10000	0	18
RhoA/GTP	-0.009	0.046	-10000	0	-0.46	1	1
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.06	0.13	-10000	0	-0.38	55	55
regulation of stress fiber formation	-0.017	0.086	0.38	12	-10000	0	12
E2/ERA-ERB (dimer)	-0.008	0.091	-10000	0	-0.32	37	37
KRAS	0.013	0	-10000	0	-10000	0	0
G13/GTP	0.008	0.048	-10000	0	-0.25	16	16
pseudopodium formation	0.017	0.086	-10000	0	-0.38	12	12
E2/ER alpha (dimer)/PELP1	0.008	0.054	-10000	0	-0.28	16	16
GRB2	0.013	0	-10000	0	-10000	0	0
GNG2	0.008	0.049	-10000	0	-0.47	5	5
GNAO1	-0.079	0.19	-10000	0	-0.47	93	93
HRAS	0.007	0.059	-10000	0	-0.58	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.017	0.14	-10000	0	-0.51	20	20
E2/ER beta (dimer)	-0.009	0.088	-10000	0	-0.42	21	21
mol:GDP	-0.021	0.074	-10000	0	-0.35	15	15
mol:NADP	-0.017	0.14	-10000	0	-0.51	20	20
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
mol:IP3	0.013	0.079	-10000	0	-0.52	3	3
IGF-1R heterotetramer	0.011	0.034	-10000	0	-0.52	2	2
PLCB1	0.008	0.079	-10000	0	-0.44	5	5
PLCB2	0.009	0.075	-10000	0	-0.43	3	3
IGF1	-0.046	0.17	-10000	0	-0.51	55	55
mol:L-citrulline	-0.017	0.14	-10000	0	-0.51	20	20
RHOA	0.013	0	-10000	0	-10000	0	0
Gai/GDP	-0.11	0.29	-10000	0	-0.7	93	93
JNK cascade	-0.009	0.088	-10000	0	-0.42	21	21
BCAR1	0.013	0	-10000	0	-10000	0	0
ESR2	-0.012	0.12	-10000	0	-0.58	21	21
GNAQ	0.013	0	-10000	0	-10000	0	0
ESR1	-0.003	0.088	-10000	0	-0.48	16	16
Gq family/GDP/Gbeta gamma	0.003	0.12	-10000	0	-0.38	40	40
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.017	0.056	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.06	0.13	-10000	0	-0.38	55	55
GNAZ	-0.033	0.14	-10000	0	-0.47	46	46
E2/ER alpha (dimer)	-0.002	0.063	-10000	0	-0.34	16	16
STRN	-0.023	0.13	-10000	0	-0.47	36	36
GNAL	-0.11	0.21	-10000	0	-0.47	124	124
PELP1	0.013	0	-10000	0	-10000	0	0
MAPK11	-0.005	0.088	-10000	0	-0.35	29	29
GNAI2	0.013	0	-10000	0	-10000	0	0
GNAI3	0.013	0	-10000	0	-10000	0	0
GNAI1	0.005	0.065	-10000	0	-0.53	7	7
HBEGF	-0.12	0.18	-10000	0	-0.46	77	77
cAMP biosynthetic process	-0.075	0.12	-10000	0	-0.24	146	146
SRC	-0.038	0.18	-10000	0	-0.45	55	55
PI3K	0.014	0.048	-10000	0	-0.37	7	7
GNB1	0.013	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.02	0.068	-10000	0	-0.5	2	2
SOS1	0.013	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.068	0.14	-10000	0	-0.42	46	46
Gs family/GTP	-0.076	0.12	-10000	0	-0.34	32	32
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.021	0.037	-10000	0	-0.3	6	6
vasodilation	-0.015	0.13	-10000	0	-0.48	20	20
mol:DAG	0.013	0.079	-10000	0	-0.52	3	3
Gs family/GDP/Gbeta gamma	-0.061	0.1	-10000	0	-0.42	18	18
MSN	0.016	0.093	-10000	0	-0.42	12	12
Gq family/GTP	0.003	0.077	-10000	0	-0.46	3	3
mol:PI-3-4-5-P3	-0.006	0.15	-10000	0	-0.74	18	18
NRAS	0.012	0.022	-10000	0	-0.47	1	1
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.015	0.13	0.48	20	-10000	0	20
GRB2/SOS1	0.02	0	-10000	0	-10000	0	0
RhoA/GDP	-0.02	0.069	-10000	0	-0.33	15	15
NOS3	-0.019	0.14	-10000	0	-0.54	20	20
GNA11	-0.003	0.086	-10000	0	-0.47	16	16
MAPKKK cascade	-0.019	0.16	-10000	0	-0.58	22	22
E2/ER alpha (dimer)/PELP1/Src	-0.063	0.14	-10000	0	-0.4	55	55
ruffle organization	0.017	0.086	-10000	0	-0.38	12	12
ROCK2	0.013	0.09	-10000	0	-0.44	9	9
GNA14	0.012	0.022	-10000	0	-0.47	1	1
GNA15	-0.011	0.1	-10000	0	-0.47	24	24
GNA13	0.013	0	-10000	0	-10000	0	0
MMP9	-0.19	0.2	-10000	0	-0.51	82	82
MMP2	-0.035	0.19	-10000	0	-0.5	48	48

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.013	0	-9999	-10000	0	0
GNAT1/GTP	0.001	0.028	-9999	-0.42	2	2
Metarhodopsin II/Arrestin	0.002	0.029	-9999	-0.36	3	3
PDE6G/GNAT1/GTP	-0.026	0.11	-9999	-0.36	48	48
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	0.001	0.038	-9999	-0.58	2	2
GRK1	-0.001	0.053	-9999	-0.58	4	4
CNG Channel	-0.072	0.13	-9999	-0.48	20	20
mol:Na +	-0.055	0.11	-9999	-0.53	7	7
mol:ADP	-0.001	0.053	-9999	-0.57	4	4
RGS9-1/Gbeta5/R9AP	-0.04	0.12	-9999	-0.27	109	109
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.056	0.12	-9999	-0.55	7	7
CNGB1	-0.003	0.079	-9999	-0.58	9	9
RDH5	-0.009	0.1	-9999	-0.48	22	22
SAG	0.001	0.027	-9999	-0.58	1	1
mol:Ca2+	-0.025	0.12	-9999	-0.51	7	7
Na + (4 Units)	-0.051	0.11	-9999	-0.5	7	7
RGS9	-0.092	0.2	-9999	-0.47	105	105
GNB1/GNGT1	0.009	0.027	-9999	-0.42	2	2
GNAT1/GDP	-0.033	0.11	-9999	-0.29	7	7
GUCY2D	-0.065	0.2	-9999	-0.55	67	67
GNGT1	-0.002	0.037	-9999	-0.58	2	2
GUCY2F	-0.001	0.026	-9999	-0.58	1	1
GNB5	0.013	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.051	0.14	-9999	-0.34	61	61
mol:11-cis-retinal	-0.009	0.1	-9999	-0.48	22	22
mol:cGMP	-0.035	0.13	-9999	-0.32	68	68
GNB1	0.013	0	-9999	-10000	0	0
Rhodopsin	-0.005	0.08	-9999	-0.35	24	24
SLC24A1	0.013	0	-9999	-10000	0	0
CNGA1	0.003	0.073	-9999	-0.53	9	9
Metarhodopsin II	0.001	0.037	-9999	-0.33	6	6
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.037	0.13	-9999	-0.34	72	72
RGS9BP	0.009	0.049	-9999	-0.52	4	4
Metarhodopsin II/Transducin	0.007	0.02	-9999	-10000	0	0
GCAP Family/Ca ++	0	0.067	-9999	-0.32	20	20
PDE6A/B	-0.041	0.15	-9999	-0.37	75	75
mol:Pi	-0.04	0.12	-9999	-0.27	109	109
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	0.008	0.03	-9999	-0.32	4	4
PDE6B	-0.047	0.16	-9999	-0.47	60	60
PDE6A	-0.013	0.11	-9999	-0.49	25	25
PDE6G	-0.043	0.17	-9999	-0.58	46	46
RHO	0.002	0.038	-9999	-0.58	2	2
PDE6	-0.11	0.16	-9999	-0.46	53	53
GUCA1A	0.005	0.038	-9999	-0.58	2	2
GC2/GCAP Family	-0.001	0.068	-9999	-0.32	20	20
GUCA1C	-0.001	0.026	-9999	-0.58	1	1
GUCA1B	-0.007	0.11	-9999	-0.57	17	17

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.013	0.039	-10000	0	-0.46	3	3
HSPA8	0.013	0.003	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	-0.006	0.064	-10000	0	-0.34	8	8
AKT1	0.016	0.004	-10000	0	-10000	0	0
GSC	-0.12	0.22	-10000	0	-0.51	48	48
NKX2-5	-0.045	0.16	-10000	0	-0.57	42	42
muscle cell differentiation	0.045	0.086	0.41	4	-10000	0	4
SMAD2-3/SMAD4/SP1	0.048	0.054	-10000	0	-0.42	1	1
SMAD4	0.01	0.035	-10000	0	-10000	0	0
CBFB	0.013	0	-10000	0	-10000	0	0
SAP18	0.013	0.001	-10000	0	-10000	0	0
Cbp/p300/MSG1	-0.039	0.13	-10000	0	-0.28	86	86
SMAD3/SMAD4/VDR	0.016	0.056	-10000	0	-0.34	1	1
MYC	-0.037	0.16	-10000	0	-0.58	39	39
CDKN2B	0.035	0.097	-10000	0	-1.3	2	2
AP1	0.004	0.13	-10000	0	-0.73	7	7
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.047	0.037	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.035	0.048	-10000	0	-0.61	1	1
SP3	0.016	0	-10000	0	-10000	0	0
CREB1	0.013	0	-10000	0	-10000	0	0
FOXH1	-0.12	0.24	-10000	0	-0.6	96	96
SMAD3/SMAD4/GR	0.023	0.068	-10000	0	-0.35	7	7
GATA3	-0.13	0.22	-10000	0	-0.47	142	142
SKI/SIN3/HDAC complex/NCoR1	0.042	0.019	-10000	0	-10000	0	0
MEF2C/TIF2	-0.092	0.2	-10000	0	-0.56	46	46
endothelial cell migration	0.059	0.24	0.66	43	-10000	0	43
MAX	0.016	0.012	-10000	0	-10000	0	0
RBBP7	0.013	0.001	-10000	0	-10000	0	0
RBBP4	0.011	0.031	-10000	0	-0.47	2	2
RUNX2	0.01	0.041	-10000	0	-0.51	3	3
RUNX3	0	0.084	-10000	0	-0.55	11	11
RUNX1	0.009	0.046	-10000	0	-0.5	4	4
CTBP1	0.013	0	-10000	0	-10000	0	0
NR3C1	0.003	0.08	-10000	0	-0.47	13	13
VDR	0.005	0.065	-10000	0	-0.5	8	8
CDKN1A	0.047	0.12	-10000	0	-1.2	4	4
KAT2B	0.014	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.072	0.18	-10000	0	-0.4	97	97
DCP1A	0.013	0	-10000	0	-10000	0	0
SKI	0.013	0.001	-10000	0	-10000	0	0
SERPINE1	-0.06	0.24	-10000	0	-0.68	41	41
SMAD3/SMAD4/ATF2	0.011	0.083	-10000	0	-0.37	2	2
SMAD3/SMAD4/ATF3	-0.025	0.14	-10000	0	-0.35	63	63
SAP30	0.013	0.001	-10000	0	-10000	0	0
Cbp/p300/PIAS3	0.032	0.036	-10000	0	-0.27	1	1
JUN	0.003	0.13	-10000	0	-0.72	7	7
SMAD3/SMAD4/IRF7	0.009	0.099	-10000	0	-0.37	26	26
TFE3	0.015	0.013	-10000	0	-10000	0	0
COL1A2	0.002	0.061	-10000	0	-0.56	4	4
mesenchymal cell differentiation	-0.027	0.048	0.34	3	-10000	0	3
DLX1	-0.52	0.18	-10000	0	-0.58	438	438
TCF3	0.013	0	-10000	0	-10000	0	0
FOS	-0.071	0.19	-10000	0	-0.48	88	88
SMAD3/SMAD4/Max	0.031	0.039	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0.026	0.026	-10000	0	-0.26	3	3
ZBTB17	0.011	0.004	-10000	0	-10000	0	0
LAMC1	0.038	0.036	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.03	0.039	-10000	0	-10000	0	0
IRF7	-0.018	0.13	-10000	0	-0.57	26	26
ESR1	-0.005	0.088	-10000	0	-0.48	16	16
HNF4A	-0.029	0.14	-10000	0	-0.58	28	28
MEF2C	-0.074	0.18	-10000	0	-0.56	20	20
SMAD2-3/SMAD4	0.023	0.047	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.028	0.029	-10000	0	-0.26	3	3
IGHV3OR16-13	-0.002	0.012	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.013	0	-10000	0	-10000	0	0
CREBBP	0.014	0.008	-10000	0	-10000	0	0
SKIL	0.001	0.078	-10000	0	-0.51	11	11
HDAC1	0.013	0.001	-10000	0	-10000	0	0
HDAC2	0.012	0.022	-10000	0	-0.47	1	1
SNIP1	0.013	0.002	-10000	0	-10000	0	0
GCN5L2	0.001	0.01	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.039	0.045	-10000	0	-10000	0	0
MSG1/HSC70	-0.063	0.15	-10000	0	-0.34	108	108
SMAD2	0.006	0.023	-10000	0	-10000	0	0
SMAD3	0.02	0.03	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.02	0.068	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.015	0.022	-10000	0	-10000	0	0
NCOR1	0.012	0.022	-10000	0	-0.47	1	1
NCOA2	-0.047	0.16	-10000	0	-0.47	60	60
NCOA1	0.013	0	-10000	0	-10000	0	0
MYOD/E2A	-0.002	0.073	-10000	0	-0.39	16	16
SMAD2-3/SMAD4/SP1/MIZ-1	0.06	0.051	-10000	0	-0.38	1	1
IFNB1	0.012	0.086	-10000	0	-0.39	5	5
SMAD3/SMAD4/MEF2C	-0.063	0.18	-10000	0	-0.57	17	17
CITED1	-0.097	0.21	-10000	0	-0.48	108	108
SMAD2-3/SMAD4/ARC105	0.031	0.044	-10000	0	-10000	0	0
RBL1	-0.015	0.11	-10000	0	-0.47	28	28
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.052	0.044	-10000	0	-0.53	2	2
RUNX1-3/PEBPB2	0.016	0.06	-10000	0	-0.35	9	9
SMAD7	0.028	0.12	-10000	0	-0.57	4	4
MYC/MIZ-1	-0.02	0.12	-10000	0	-0.42	39	39
SMAD3/SMAD4	0.018	0.12	0.35	1	-0.38	10	11
IL10	-0.061	0.18	-10000	0	-0.57	28	28
PIASy/HDAC complex	0.012	0.009	-10000	0	-10000	0	0
PIAS3	0.014	0.004	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.057	0.15	-10000	0	-0.48	18	18
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.012	0.009	-10000	0	-10000	0	0
ATF3	-0.074	0.19	-10000	0	-0.5	82	82
SMAD3/SMAD4/SP1	0.043	0.051	-10000	0	-0.4	1	1
FOXG1	-0.034	0.14	-10000	0	-0.58	30	30
FOXO3	0.025	0.006	-10000	0	-10000	0	0
FOXO1	0.025	0.006	-10000	0	-10000	0	0
FOXO4	0.024	0.02	-10000	0	-0.41	1	1
heart looping	-0.073	0.18	-10000	0	-0.56	20	20
CEBPB	0.015	0.002	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	-0.32	0.12	-10000	0	-0.36	438	438
MYOD1	-0.017	0.099	-10000	0	-0.55	16	16
SMAD3/SMAD4/HNF4	0.003	0.1	-10000	0	-0.37	28	28
SMAD3/SMAD4/GATA3	-0.067	0.16	-10000	0	-0.51	14	14
SnoN/SIN3/HDAC complex/NCoR1	0.001	0.078	-10000	0	-0.51	11	11
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.031	0.065	-10000	0	-0.35	2	2
SMAD3/SMAD4/SP1-3	0.054	0.048	-10000	0	-10000	0	0
MED15	0.013	0	-10000	0	-10000	0	0
SP1	0.021	0.015	-10000	0	-10000	0	0
SIN3B	0.013	0.001	-10000	0	-10000	0	0
SIN3A	0.013	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.084	0.19	-10000	0	-0.46	62	62
ITGB5	0.057	0.037	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.043	0.015	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	0.001	0.098	-10000	0	-0.34	9	9
AR	-0.031	0.14	-10000	0	-0.47	44	44
negative regulation of cell growth	0.008	0.087	-10000	0	-0.36	3	3
SMAD3/SMAD4/MYOD	0.011	0.076	-10000	0	-0.37	12	12
E2F5	-0.009	0.11	-10000	0	-0.58	18	18
E2F4	0.013	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.045	0.15	-10000	0	-0.4	45	45
SMAD2-3/SMAD4/FOXO1-3a-4	0.046	0.04	-10000	0	-0.4	2	2
TFDP1	0.013	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.004	0.13	-10000	0	-0.74	7	7
SMAD3/SMAD4/RUNX2	0.028	0.049	-10000	0	-0.34	3	3
TGIF2	0.013	0	-10000	0	-10000	0	0
TGIF1	0.013	0	-10000	0	-10000	0	0
ATF2	-0.016	0.12	-10000	0	-0.47	29	29

FAS signaling pathway (CD95)

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
SPTAN1	0.012	0.047	0.21	23	-10000	0	23
RFC1	0.012	0.047	0.21	23	-10000	0	23
PRKDC	0.011	0.049	0.21	23	-0.34	1	24
RIPK1	0.015	0.004	-10000	0	-10000	0	0
CASP7	-0.017	0.036	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.024	0.064	0.2	1	-0.26	24	25
MAP2K4	-0.038	0.14	-10000	0	-0.4	18	18
mol:ceramide	-0.025	0.11	-10000	0	-0.37	18	18
GSN	0.01	0.046	0.21	20	-0.26	1	21
FASLG/FAS/FADD/FAF1/Caspase 8	-0.014	0.081	-10000	0	-0.32	15	15
FAS	0	0.069	-10000	0	-0.48	10	10
BID	0.003	0.02	-10000	0	-10000	0	0
MAP3K1	-0.011	0.081	-10000	0	-0.24	4	4
MAP3K7	0.01	0.005	-10000	0	-10000	0	0
RB1	0.011	0.049	0.21	23	-0.26	1	24
CFLAR	0.015	0.004	-10000	0	-10000	0	0
HGF/MET	-0.025	0.14	-10000	0	-0.35	67	67
ARHGDIB	0.008	0.055	0.21	22	-0.31	4	26
FADD	0.01	0.007	-10000	0	-10000	0	0
actin filament polymerization	-0.01	0.046	0.26	1	-0.21	20	21
NFKB1	-0.058	0.084	-10000	0	-10000	0	0
MAPK8	-0.078	0.2	-10000	0	-0.42	108	108
DFFA	0.012	0.047	0.21	23	-10000	0	23
DNA fragmentation during apoptosis	0.012	0.047	0.21	23	-10000	0	23
FAS/FADD/MET	-0.014	0.099	-10000	0	-0.29	53	53
CFLAR/RIP1	0.013	0.009	-10000	0	-10000	0	0
FAIM3	0.002	0.084	-10000	0	-0.57	10	10
FAF1	0.01	0.007	-10000	0	-10000	0	0
PARP1	0.012	0.047	0.21	23	-10000	0	23
DFFB	0.012	0.047	0.21	23	-10000	0	23
CHUK	-0.05	0.074	-10000	0	-10000	0	0
FASLG	-0.022	0.13	-10000	0	-0.54	28	28
FAS/FADD	0.006	0.051	-10000	0	-0.34	10	10
HGF	-0.026	0.14	-10000	0	-0.5	37	37
LMNA	0.02	0.044	0.2	23	-0.31	1	24
CASP6	0.012	0.047	0.21	23	-10000	0	23
CASP10	0.002	0.06	-10000	0	-0.49	7	7
CASP3	0.014	0.055	0.25	23	-10000	0	23
PTPN13	0.011	0.031	-10000	0	-0.47	2	2
CASP8	0.005	0.035	0.25	10	-10000	0	10
IL6	-0.27	0.49	-10000	0	-1.2	105	105
MET	-0.033	0.14	-10000	0	-0.47	46	46
ICAD/CAD	0.011	0.044	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.025	0.11	-10000	0	-0.38	18	18
activation of caspase activity by cytochrome c	0.003	0.02	-10000	0	-10000	0	0
PAK2	0.012	0.047	0.21	23	-10000	0	23
BCL2	-0.009	0.1	-10000	0	-0.47	23	23

TCGA08_retinoblastoma

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
CDKN2B	0.011	0.034	-10000	0	-0.49	2	2
CDKN2C	0.019	0.056	-10000	0	-0.55	4	4
CDKN2A	-0.11	0.24	-10000	0	-0.59	102	102
CCND2	0.018	0.059	0.25	2	-0.13	21	23
RB1	-0.012	0.066	0.14	5	-0.23	4	9
CDK4	0.029	0.064	0.26	4	-10000	0	4
CDK6	0.02	0.067	0.24	4	-0.2	8	12
G1/S progression	0.012	0.066	0.23	4	-0.14	5	9

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	-0.043	0.12	-10000	0	-0.46	5	5
MAPK9	0.008	0	-10000	0	-10000	0	0
adrenocorticotropin secretion	-0.002	0.033	-10000	0	-0.42	3	3
GNB1/GNG2	0.015	0.03	-10000	0	-0.28	5	5
GNB1	0.013	0	-10000	0	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
MAPK14	0.008	0	-10000	0	-10000	0	0
Gs family/GTP	-0.059	0.12	-10000	0	-0.26	124	124
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	0.018	0.03	0.07	124	-10000	0	124
GNAL	-0.11	0.21	-10000	0	-0.47	124	124
GNG2	0.008	0.049	-10000	0	-0.47	5	5
CRH	-0.003	0.045	-10000	0	-0.58	3	3
mol:cortisol	0	0	-10000	0	-10000	0	0
MAPK8	0.001	0.047	-10000	0	-0.31	11	11
MAPK11	0.004	0.031	-10000	0	-0.24	8	8

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.011	0.066	-9999	-0.32	18	18
EPHB2	0.006	0.063	-9999	-0.52	7	7
Syndecan-2/TACI	-0.021	0.12	-9999	-0.33	59	59
LAMA1	-0.041	0.16	-9999	-0.53	48	48
Syndecan-2/alpha2 ITGB1	-0.02	0.13	-9999	-0.45	24	24
HRAS	0.007	0.059	-9999	-0.58	5	5
Syndecan-2/CASK	0.01	0.032	-9999	-0.28	6	6
ITGA5	-0.002	0.085	-9999	-0.48	15	15
BAX	0.025	0.06	-9999	-0.54	2	2
EPB41	0.013	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0.018	0.029	-9999	-0.24	6	6
LAMA3	-0.03	0.14	-9999	-0.48	43	43
EZR	0.013	0.001	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	-0.038	0.15	-9999	-0.47	51	51
Syndecan-2/MMP2	0.01	0.066	-9999	-0.3	20	20
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.024	0.12	-9999	-0.33	61	61
dendrite morphogenesis	0.015	0.056	-9999	-0.34	11	11
Syndecan-2/GM-CSF	0.009	0.052	-9999	-0.31	12	12
determination of left/right symmetry	0.014	0.039	-9999	-0.33	6	6
Syndecan-2/PKC delta	0.02	0.033	-9999	-0.27	6	6
GNB2L1	0.01	0.046	-9999	-0.58	3	3
MAPK3	0.017	0.047	-9999	-0.28	11	11
MAPK1	0.017	0.047	-9999	-0.28	12	12
Syndecan-2/RACK1	0.02	0.052	-9999	-0.28	13	13
NF1	0.013	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.014	0.039	-9999	-0.33	6	6
ITGA2	-0.048	0.16	-9999	-0.47	61	61
MAPK8	0.02	0.059	-9999	-0.28	17	17
Syndecan-2/alpha2/beta1 Integrin	-0.026	0.14	-9999	-0.36	40	40
Syndecan-2/Kininogen	-0.032	0.12	-9999	-0.34	66	66
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.025	0.05	-9999	-0.3	8	8
Syndecan-2/CASK/Protein 4.1	0.018	0.03	-9999	-0.24	6	6
extracellular matrix organization	0.02	0.033	-9999	-0.27	6	6
actin cytoskeleton reorganization	0.011	0.066	-9999	-0.32	18	18
Syndecan-2/Caveolin-2/Ras	-0.004	0.1	-9999	-0.28	55	55
Syndecan-2/Laminin alpha3	-0.007	0.093	-9999	-0.29	47	47
Syndecan-2/RasGAP	0.025	0.056	-9999	-0.32	9	9
alpha5/beta1 Integrin	0.009	0.061	-9999	-0.33	15	15
PRKCD	0.013	0	-9999	-10000	0	0
Syndecan-2 dimer	0.015	0.056	-9999	-0.34	11	11
GO:0007205	0.003	0.005	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	0.031	0.055	-9999	-0.31	9	9
RHOA	0.013	0	-9999	-10000	0	0
SDCBP	0.013	0	-9999	-10000	0	0
TNFRSF13B	-0.052	0.18	-9999	-0.56	53	53
RASA1	0.01	0.038	-9999	-0.47	3	3
alpha2/beta1 Integrin	-0.024	0.12	-9999	-0.33	61	61
Syndecan-2/Synbindin	0.02	0.033	-9999	-0.27	6	6
TGFB1	0.013	0	-9999	-10000	0	0
CASP3	0.026	0.03	-9999	-0.23	6	6
FN1	-0.002	0.086	-9999	-0.5	14	14
Syndecan-2/IL8	-0.022	0.11	-9999	-0.3	67	67
SDC2	0.014	0.039	-9999	-0.33	6	6
KNG1	-0.067	0.19	-9999	-0.58	60	60
Syndecan-2/Neurofibromin	0.02	0.033	-9999	-0.27	6	6
TRAPPC4	0.013	0	-9999	-10000	0	0
CSF2	-0.003	0.064	-9999	-0.58	6	6
Syndecan-2/TGFB1	0.02	0.033	-9999	-0.27	6	6
Syndecan-2/Syntenin/PI-4-5-P2	0.018	0.03	-9999	-0.24	6	6
Syndecan-2/Ezrin	0.027	0.03	-9999	-0.24	6	6
PRKACA	0.026	0.03	-9999	-0.23	6	6
angiogenesis	-0.022	0.11	-9999	-0.3	67	67
MMP2	-0.003	0.088	-9999	-0.48	16	16
IL8	-0.054	0.18	-9999	-0.51	62	62
calcineurin-NFAT signaling pathway	-0.021	0.12	-9999	-0.33	59	59

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.015	0.032	-9999	-0.34	4	4
ARNO/beta Arrestin1-2	0.013	0.036	-9999	-10000	0	0
EGFR	-0.026	0.13	-9999	-0.47	39	39
EPHA2	-0.036	0.15	-9999	-0.48	49	49
USP6	0.011	0.038	-9999	-0.58	2	2
IQSEC1	0.013	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.059	0.16	-9999	-0.37	97	97
ARRB2	0.008	0.022	-9999	-0.23	4	4
mol:GTP	0.012	0.019	-9999	-0.13	3	3
ARRB1	0.012	0.022	-9999	-0.47	1	1
FBXO8	0.013	0	-9999	-10000	0	0
TSHR	-0.009	0.1	-9999	-0.5	20	20
EGF	-0.056	0.18	-9999	-0.54	61	61
somatostatin receptor activity	0	0	-9999	-0.001	24	24
ARAP2	0.012	0.022	-9999	-0.47	1	1
mol:GDP	-0.025	0.084	-9999	-0.26	32	32
mol:PI-3-4-5-P3	0	0	-9999	-0.001	14	14
ITGA2B	-0.003	0.091	-9999	-0.51	15	15
ARF6	0.013	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	0.006	0.084	-9999	-0.31	4	4
ADAP1	0.009	0.051	-9999	-0.55	4	4
KIF13B	0.013	0	-9999	-10000	0	0
HGF/MET	-0.04	0.15	-9999	-0.41	67	67
PXN	0.013	0	-9999	-10000	0	0
ARF6/GTP	-0.018	0.088	-9999	-0.26	24	24
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.04	0.14	-9999	-0.31	97	97
ADRB2	0.006	0.065	-9999	-0.58	6	6
receptor agonist activity	0	0	-9999	0	18	18
actin filament binding	0	0	-9999	0	24	24
SRC	0.013	0	-9999	-10000	0	0
ITGB3	-0.083	0.19	-9999	-0.47	97	97
GNAQ	0.013	0	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	19	19
ARF6/GDP	0.014	0.066	-9999	-0.34	4	4
ARF6/GDP/GULP/ACAP1	-0.019	0.1	-9999	-0.35	20	20
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.029	0.12	-9999	-0.47	6	6
ACAP1	-0.015	0.12	-9999	-0.56	24	24
ACAP2	0.012	0.022	-9999	-0.47	1	1
LHCGR/beta Arrestin2	0.001	0.031	-9999	-0.33	4	4
EFNA1	0.013	0	-9999	-10000	0	0
HGF	-0.026	0.14	-9999	-0.5	37	37
CYTH3	0.006	0.044	-9999	-0.42	5	5
CYTH2	0.009	0.002	-9999	-10000	0	0
NCK1	0.012	0.027	-9999	-0.58	1	1
fibronectin binding	0	0	-9999	0	23	23
endosomal lumen acidification	0	0	-9999	0	25	25
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	0.009	0.049	-9999	-0.52	4	4
GNAQ/ARNO	0.017	0.004	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	9	9
MET	-0.033	0.14	-9999	-0.47	46	46
GNA14	0.012	0.022	-9999	-0.47	1	1
GNA15	-0.011	0.1	-9999	-0.47	24	24
GIT1	0.013	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	19	19
GNA11	-0.003	0.086	-9999	-0.47	16	16
LHCGR	-0.002	0.053	-9999	-0.58	4	4
AGTR1	-0.12	0.24	-9999	-0.55	111	111
desensitization of G-protein coupled receptor protein signaling pathway	0.001	0.031	-9999	-0.33	4	4
IPCEF1/ARNO	-0.028	0.1	-9999	-0.42	3	3
alphaIIb/beta3 Integrin	-0.061	0.15	-9999	-0.34	108	108

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.011	0.038	-9999	-0.58	2	2
mol:S1P	0.001	0.001	-9999	-10000	0	0
S1P1/S1P/Gi	-0.034	0.14	-9999	-0.4	47	47
GNAO1	-0.078	0.19	-9999	-0.47	93	93
S1P/S1P3/G12/G13	0.018	0.052	-9999	-0.25	15	15
AKT1	0.003	0.062	-9999	-10000	0	0
AKT3	-0.014	0.13	-9999	-0.85	4	4
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.011	0.038	-9999	-0.57	2	2
GNAI2	0.015	0.001	-9999	-10000	0	0
GNAI3	0.014	0.001	-9999	-10000	0	0
GNAI1	0.007	0.065	-9999	-0.53	7	7
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	-0.003	0.093	-9999	-0.48	18	18
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	-0.037	0.17	-9999	-0.48	48	48
MAPK3	-0.029	0.16	-9999	-0.45	48	48
MAPK1	-0.029	0.16	-9999	-0.45	48	48
JAK2	-0.03	0.17	-9999	-0.46	50	50
CXCR4	-0.033	0.17	-9999	-0.44	54	54
FLT1	0.008	0.062	-9999	-0.5	7	7
RhoA/GDP	0.01	0	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
SRC	-0.029	0.16	-9999	-0.45	48	48
S1P/S1P3/Gi	-0.037	0.17	-9999	-0.48	48	48
RAC1	0.013	0	-9999	-10000	0	0
RhoA/GTP	-0.028	0.16	-9999	-0.44	48	48
VEGFA	-0.016	0.12	-9999	-0.49	31	31
S1P/S1P2/Gi	-0.029	0.14	-9999	-0.42	41	41
VEGFR1 homodimer/VEGFA homodimer	-0.001	0.1	-9999	-0.37	35	35
RHOA	0.013	0	-9999	-10000	0	0
S1P/S1P3/Gq	-0.001	0.1	-9999	-0.55	10	10
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	-0.031	0.14	-9999	-0.47	46	46
G12/G13	0.02	0	-9999	-10000	0	0
GNA14	0.012	0.022	-9999	-0.47	1	1
GNA15	-0.011	0.1	-9999	-0.47	24	24
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.086	-9999	-0.47	16	16
Rac1/GTP	-0.028	0.16	-9999	-0.44	48	48

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.002	0.094	-9999	-0.35	24	24
CRKL	0.013	0	-9999	-10000	0	0
Rac1/GDP	0.01	0	-9999	-10000	0	0
DOCK1	0.01	0.038	-9999	-0.47	3	3
ITGA4	-0.013	0.12	-9999	-0.52	24	24
alpha4/beta7 Integrin/MAdCAM1	-0.055	0.16	-9999	-0.34	100	100
EPO	-0.067	0.19	-9999	-0.51	74	74
alpha4/beta7 Integrin	-0.014	0.12	-9999	-0.39	39	39
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin	0	0.085	-9999	-0.37	24	24
EPO/EPOR (dimer)	-0.047	0.15	-9999	-0.38	82	82
lamellipodium assembly	0.03	0.042	-9999	-0.44	2	2
PIK3CA	0.01	0.038	-9999	-0.47	3	3
PI3K	0.014	0.048	-9999	-0.37	7	7
ARF6	0.013	0	-9999	-10000	0	0
JAK2	-0.021	0.11	-9999	-0.46	7	7
PXN	0.013	0	-9999	-10000	0	0
PIK3R1	0.008	0.049	-9999	-0.47	5	5
MADCAM1	-0.095	0.23	-9999	-0.57	89	89
cell adhesion	-0.056	0.16	-9999	-0.34	100	100
CRKL/CBL	0.019	0.016	-9999	-0.33	1	1
ITGB1	0.013	0	-9999	-10000	0	0
SRC	0.008	0.091	-9999	-0.4	16	16
ITGB7	-0.007	0.1	-9999	-0.49	20	20
RAC1	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	0.002	0.1	-9999	-0.44	16	16
p130Cas/Crk/Dock1	0.027	0.084	-9999	-0.47	7	7
VCAM1	-0.001	0.086	-9999	-0.54	12	12
RHOA	0.013	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	0.019	0.066	-9999	-0.31	11	11
BCAR1	0.015	0.086	-9999	-0.55	5	5
EPOR	0.001	0.084	-9999	-0.58	10	10
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.012	0.022	-9999	-0.47	1	1
GIT1	0.013	0	-9999	-10000	0	0
Rac1/GTP	-0.002	0.041	-9999	-0.46	2	2

EPO signaling pathway

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
BCL2L1	0.013	0.13	-9999	-0.5	6	6
CRKL	-0.001	0.099	-9999	-0.43	3	3
mol:DAG	0	0.11	-9999	-0.37	8	8
HRAS	0.019	0.09	-9999	-0.39	2	2
MAPK8	-0.02	0.12	-9999	-0.31	39	39
RAP1A	-0.001	0.099	-9999	-0.43	3	3
GAB1	-0.002	0.1	-9999	-0.4	4	4
MAPK14	-0.014	0.11	-9999	-0.3	37	37
EPO	-0.065	0.19	-9999	-0.51	74	74
PLCG1	0	0.11	-9999	-0.38	8	8
EPOR/TRPC2/IP3 Receptors	-0.001	0.084	-9999	-0.57	10	10
RAPGEF1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.066	0.16	-9999	-0.31	136	136
GAB1/SHC/GRB2/SOS1	-0.031	0.069	-9999	-0.42	2	2
EPO/EPOR (dimer)	-0.043	0.15	-9999	-0.37	82	82
IRS2	-0.004	0.1	-9999	-0.43	5	5
STAT1	-0.001	0.12	-9999	-0.45	10	10
STAT5B	0.002	0.11	-9999	-0.41	8	8
cell proliferation	-0.012	0.11	-9999	-0.47	5	5
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.041	0.087	-9999	-0.41	10	10
TEC	-0.001	0.099	-9999	-0.43	3	3
SOCS3	-0.053	0.17	-9999	-0.48	65	65
STAT1 (dimer)	0	0.12	-9999	-0.44	10	10
JAK2	0.009	0.024	-9999	-0.47	1	1
PIK3R1	0.008	0.049	-9999	-0.47	5	5
EPO/EPOR (dimer)/JAK2	0.004	0.11	-9999	-0.35	8	8
EPO/EPOR	-0.043	0.15	-9999	-0.37	82	82
LYN	0.014	0.003	-9999	-10000	0	0
TEC/VAV2	0.007	0.098	-9999	-0.42	3	3
elevation of cytosolic calcium ion concentration	-0.001	0.084	-9999	-0.57	10	10
SHC1	0.013	0	-9999	-10000	0	0
EPO/EPOR (dimer)/LYN	-0.019	0.13	-9999	-0.29	82	82
mol:IP3	0	0.11	-9999	-0.37	8	8
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.005	0.12	-9999	-0.41	13	13
SH2B3	0.01	0.011	-9999	-10000	0	0
NFKB1	-0.014	0.11	-9999	-0.3	37	37
EPO/EPOR (dimer)/JAK2/SOCS3	-0.061	0.1	-9999	-0.27	56	56
PTPN6	-0.009	0.1	-9999	-0.35	8	8
TEC/VAV2/GRB2	0.013	0.095	-9999	-0.45	2	2
EPOR	-0.001	0.084	-9999	-0.58	10	10
INPP5D	-0.013	0.11	-9999	-0.47	26	26
mol:GDP	-0.032	0.07	-9999	-0.43	2	2
SOS1	0.013	0	-9999	-10000	0	0
PLCG2	0.004	0.069	-9999	-0.49	9	9
CRKL/CBL/C3G	0.013	0.096	-9999	-0.42	3	3
VAV2	-0.001	0.099	-9999	-0.43	3	3
CBL	-0.002	0.1	-9999	-0.43	4	4
SHC/Grb2/SOS1	-0.033	0.073	-9999	-0.45	2	2
STAT5A	0.001	0.12	-9999	-0.41	8	8
GRB2	0.013	0	-9999	-10000	0	0
STAT5 (dimer)	0.016	0.12	-9999	-0.44	8	8
LYN/PLCgamma2	0.013	0.05	-9999	-0.35	9	9
PTPN11	0.012	0.022	-9999	-0.47	1	1
BTK	-0.007	0.11	-9999	-0.44	4	4
BCL2	-0.01	0.21	-9999	-0.83	23	23

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.006	0.061	-10000	0	-0.54	6	6
LAT2	-0.007	0.12	-10000	0	-0.4	26	26
AP1	-0.069	0.14	-10000	0	-0.43	44	44
mol:PIP3	-0.005	0.15	-10000	0	-0.48	30	30
IKBKB	-0.007	0.1	0.15	2	-0.28	34	36
AKT1	0.012	0.11	-10000	0	-0.4	7	7
IKBKG	-0.007	0.1	0.15	2	-0.27	36	38
MS4A2	-0.016	0.12	-10000	0	-0.49	27	27
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
MAP3K1	0.013	0.12	-10000	0	-0.41	22	22
mol:Ca2+	0.002	0.12	-10000	0	-0.35	30	30
LYN	0.014	0.003	-10000	0	-10000	0	0
CBLB	-0.001	0.11	-10000	0	-0.42	18	18
SHC1	0.013	0	-10000	0	-10000	0	0
RasGAP/p62DOK	0.013	0.056	-10000	0	-10000	0	0
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	-0.013	0.11	-10000	0	-0.47	26	26
PLD2	-0.009	0.11	-10000	0	-0.42	14	14
PTPN13	0.004	0.11	-10000	0	-0.44	17	17
PTPN11	0.012	0.023	-10000	0	-0.48	1	1
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	0.027	0.097	-10000	0	-0.3	17	17
SYK	0.006	0.062	-10000	0	-0.5	7	7
GRB2	0.013	0	-10000	0	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.056	0.13	-10000	0	-0.49	29	29
LAT	-0.01	0.12	-10000	0	-0.4	27	27
PAK2	0.006	0.13	-10000	0	-0.42	28	28
NFATC2	-0.1	0.21	-10000	0	-0.52	88	88
HRAS	-0.001	0.14	-10000	0	-0.46	28	28
GAB2	0.013	0	-10000	0	-10000	0	0
PLA2G1B	0.023	0.018	-10000	0	-10000	0	0
Fc epsilon R1	-0.052	0.13	-10000	0	-0.34	66	66
Antigen/IgE/Fc epsilon R1	-0.026	0.12	-10000	0	-0.31	66	66
mol:GDP	-0.006	0.14	-10000	0	-0.49	27	27
JUN	0.006	0.061	-10000	0	-0.5	7	7
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
FOS	-0.076	0.19	-10000	0	-0.48	88	88
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.009	0.11	-10000	0	-0.41	22	22
CHUK	-0.007	0.1	0.15	2	-0.28	33	35
KLRG1	-0.004	0.1	-10000	0	-0.41	18	18
VAV1	-0.013	0.14	-10000	0	-0.49	26	26
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.002	0.11	-10000	0	-0.42	19	19
negative regulation of mast cell degranulation	-0.009	0.13	-10000	0	-0.46	28	28
BTK	-0.005	0.12	-10000	0	-0.45	22	22
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.029	0.17	-10000	0	-0.54	35	35
GAB2/PI3K/SHP2	-0.038	0.095	-10000	0	-0.39	19	19
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.013	0.13	-10000	0	-0.56	18	18
RAF1	0.015	0.019	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.035	0.17	-10000	0	-0.54	35	35
FCER1G	0.008	0.054	-10000	0	-0.59	4	4
FCER1A	-0.046	0.16	-10000	0	-0.48	59	59
Antigen/IgE/Fc epsilon R1/Fyn	-0.017	0.12	-10000	0	-0.4	21	21
MAPK3	0.024	0.017	-10000	0	-10000	0	0
MAPK1	0.024	0.017	-10000	0	-10000	0	0
NFKB1	0.013	0	-10000	0	-10000	0	0
MAPK8	0.009	0.11	-10000	0	-0.65	11	11
DUSP1	-0.006	0.094	-10000	0	-0.47	19	19
NF-kappa-B/RelA	-0.026	0.049	-10000	0	-0.22	1	1
actin cytoskeleton reorganization	-0.001	0.11	-10000	0	-0.46	16	16
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.046	0.12	-10000	0	-0.45	31	31
FER	-0.012	0.13	-10000	0	-0.46	23	23
RELA	0.013	0	-10000	0	-10000	0	0
ITK	-0.028	0.076	-10000	0	-0.37	15	15
SOS1	0.013	0	-10000	0	-10000	0	0
PLCG1	-0.003	0.14	-10000	0	-0.48	28	28
cytokine secretion	-0.019	0.035	-10000	0	-10000	0	0
SPHK1	-0.012	0.12	-10000	0	-0.37	33	33
PTK2	-0.002	0.11	-10000	0	-0.48	16	16
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.055	0.13	-10000	0	-0.51	28	28
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.15	-10000	0	-0.46	30	30
MAP2K2	0.02	0.021	-10000	0	-10000	0	0
MAP2K1	0.021	0.017	-10000	0	-10000	0	0
MAP2K7	0.013	0	-10000	0	-10000	0	0
KLRG1/SHP2	-0.003	0.099	-10000	0	-0.37	19	19
MAP2K4	0.021	0.008	-10000	0	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.031	0.15	-10000	0	-0.45	35	35
mol:Choline	-0.008	0.11	-10000	0	-0.42	14	14
SHC/Grb2/SOS1	0.011	0.1	-10000	0	-0.4	17	17
FYN	0.013	0.001	-10000	0	-10000	0	0
DOK1	0.013	0	-10000	0	-10000	0	0
PXN	0.005	0.11	-10000	0	-0.44	16	16
HCLS1	-0.004	0.11	-10000	0	-0.44	20	20
PRKCB	-0.023	0.14	-10000	0	-0.35	53	53
FCGR2B	-0.01	0.11	-10000	0	-0.53	21	21
IGHE	0	0.004	-10000	0	-10000	0	0
KLRG1/SHIP	-0.009	0.14	-10000	0	-0.47	28	28
LCP2	0.006	0.062	-10000	0	-0.54	6	6
PLA2G4A	-0.014	0.14	-10000	0	-0.48	28	28
RASA1	0.01	0.038	-10000	0	-0.47	3	3
mol:Phosphatidic acid	-0.008	0.11	-10000	0	-0.42	14	14
IKK complex	0.008	0.083	0.15	2	-0.22	20	22
WIPF1	0.008	0.049	-10000	0	-0.47	5	5

Regulation of p38-alpha and p38-beta

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.018	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.013	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	-0.003	0.095	-9999	-0.55	14	14
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.057	0.1	-9999	-0.19	187	187
response to UV	0	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.013	0	-9999	-10000	0	0
FYN	0.013	0.001	-9999	-10000	0	0
MAP3K12	0.007	0.053	-9999	-0.47	6	6
FGR	0.01	0.041	-9999	-0.51	3	3
p38 alpha/TAB1	-0.021	0.044	-9999	-0.27	4	4
PRKG1	-0.12	0.22	-9999	-0.47	139	139
DUSP8	0.007	0.059	-9999	-0.58	5	5
PGK/cGMP/p38 alpha	-0.074	0.1	-9999	-0.3	52	52
apoptosis	-0.02	0.042	-9999	-0.28	3	3
RAL/GTP	0.018	0	-9999	-10000	0	0
LYN	0.013	0	-9999	-10000	0	0
DUSP1	-0.006	0.094	-9999	-0.47	19	19
PAK1	0.007	0.053	-9999	-0.47	6	6
SRC	0.013	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0.034	0	-9999	-10000	0	0
TRAF6	0.013	0	-9999	-10000	0	0
RAC1	0.013	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.013	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0.018	0	-9999	-10000	0	0
MAPK11	-0.005	0.089	-9999	-0.36	7	7
BLK	-0.1	0.22	-9999	-0.5	109	109
HCK	0.009	0.046	-9999	-0.5	4	4
MAP2K3	0.013	0	-9999	-10000	0	0
DUSP16	0.012	0.022	-9999	-0.47	1	1
DUSP10	0.013	0	-9999	-10000	0	0
TRAF6/MEKK3	0.017	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.01	0.065	-9999	-0.29	4	4
positive regulation of innate immune response	0	0.094	-9999	-0.38	7	7
LCK	0.003	0.075	-9999	-0.58	8	8
p38alpha-beta/MKP7	0.007	0.092	-9999	-0.36	7	7
p38alpha-beta/MKP5	0.007	0.092	-9999	-0.37	6	6
PGK/cGMP	-0.089	0.16	-9999	-0.34	139	139
PAK2	0.013	0	-9999	-10000	0	0
p38alpha-beta/MKP1	-0.001	0.1	-9999	-0.41	7	7
CDC42	0.013	0	-9999	-10000	0	0
RALB	0.013	0	-9999	-10000	0	0
RALA	0.013	0	-9999	-10000	0	0
PAK3	-0.17	0.23	-9999	-0.47	182	182

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.051	0.14	-9999	-0.33	97	97
AKT1	0.027	0.16	-9999	-0.61	21	21
PTK2B	-0.036	0.18	-9999	-0.67	27	27
VEGFR2 homodimer/Frs2	0.006	0.13	-9999	-0.62	21	21
CAV1	-0.049	0.16	-9999	-0.47	62	62
CALM1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.001	0.15	-9999	-0.61	21	21
endothelial cell proliferation	0.003	0.17	-9999	-0.59	24	24
mol:Ca2+	0.006	0.15	-9999	-0.62	21	21
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.008	0.14	-9999	-0.57	21	21
RP11-342D11.1	-0.002	0.15	-9999	-0.62	21	21
CDH5	0.012	0.022	-9999	-0.47	1	1
VEGFA homodimer	0.016	0.071	-9999	-0.31	5	5
SHC1	0.013	0	-9999	-10000	0	0
SHC2	0	0.086	-9999	-0.57	11	11
HRAS/GDP	-0.036	0.12	-9999	-0.55	21	21
SH2D2A	-0.016	0.13	-9999	-0.56	25	25
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.035	0.11	-9999	-0.52	21	21
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.018	0.16	-9999	-0.62	22	22
VEGFR1 homodimer	0.006	0.061	-9999	-0.5	7	7
SHC/GRB2/SOS1	-0.037	0.13	-9999	-0.58	21	21
GRB10	0.007	0.15	-9999	-0.62	21	21
PTPN11	0.012	0.022	-9999	-0.47	1	1
GRB2	0.013	0	-9999	-10000	0	0
PAK1	0.007	0.053	-9999	-0.47	6	6
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.013	0.14	-9999	-0.56	21	21
HRAS	0.007	0.059	-9999	-0.58	5	5
VEGF/Rho/ROCK1/Integrin Complex	-0.023	0.15	-9999	-0.52	27	27
HIF1A	0.012	0.022	-9999	-0.47	1	1
FRS2	0.013	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	0.007	0.14	-9999	-0.56	21	21
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.01	0.041	-9999	-0.51	3	3
Nck/Pak	0.014	0.043	-9999	-0.34	7	7
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.001	0.15	-9999	-0.61	21	21
mol:GDP	-0.036	0.12	-9999	-0.56	21	21
mol:NADP	0.031	0.12	-9999	-0.44	21	21
eNOS/Hsp90	0.036	0.11	-9999	-0.44	15	15
PIK3R1	0.008	0.049	-9999	-0.47	5	5
mol:IP3	0.006	0.15	-9999	-0.63	21	21
HIF1A/ARNT	0.019	0.016	-9999	-0.33	1	1
SHB	0.009	0.044	-9999	-0.47	4	4
VEGFA	-0.017	0.12	-9999	-0.48	31	31
VEGFC	0.011	0.035	-9999	-0.52	2	2
FAK1/Vinculin	-0.031	0.22	-9999	-0.82	25	25
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.042	0.2	-9999	-0.71	27	27
PTPN6	0.013	0	-9999	-10000	0	0
EPAS1	0.005	0.085	-9999	-0.36	22	22
mol:L-citrulline	0.031	0.12	-9999	-0.44	21	21
ITGAV	0.011	0.031	-9999	-0.47	2	2
PIK3CA	0.01	0.038	-9999	-0.47	3	3
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.008	0.14	-9999	-0.57	21	21
VEGFR2 homodimer/VEGFA homodimer	0	0.16	-9999	-0.68	21	21
VEGFR2/3 heterodimer	0.004	0.14	-9999	-0.63	21	21
VEGFB	0.013	0	-9999	-10000	0	0
MAPK11	0.003	0.16	-9999	-0.66	21	21
VEGFR2 homodimer	0.001	0.15	-9999	-0.69	22	22
FLT1	0.006	0.061	-9999	-0.5	7	7
NEDD4	0.005	0.069	-9999	-0.47	10	10
MAPK3	-0.016	0.16	-9999	-0.63	22	22
MAPK1	-0.016	0.16	-9999	-0.63	22	22
VEGFA145/NRP2	-0.024	0.12	-9999	-0.35	60	60
VEGFR1/2 heterodimer	0.002	0.15	-9999	-0.67	21	21
KDR	0.001	0.15	-9999	-0.69	22	22
VEGFA165/NRP1/VEGFR2 homodimer	-0.008	0.18	-9999	-0.7	24	24
SRC	0.013	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.015	0.16	-9999	-0.65	22	22
PI3K	0.015	0.18	-9999	-0.74	21	21
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.001	0.15	-9999	-0.61	21	21
FES	0.003	0.16	-9999	-0.66	21	21
GAB1	-0.046	0.15	-9999	-0.68	22	22
VEGFR2 homodimer/VEGFA homodimer/Src	-0.001	0.15	-9999	-0.61	21	21
CTNNB1	0.013	0	-9999	-10000	0	0
SOS1	0.013	0	-9999	-10000	0	0
ARNT	0.013	0	-9999	-10000	0	0
eNOS/Caveolin-1	0.012	0.14	-9999	-0.53	20	20
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.001	0.15	-9999	-0.61	21	21
PI3K/GAB1	0.028	0.17	-9999	-0.62	22	22
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.01	0.14	-9999	-0.56	21	21
PRKACA	0.013	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	0.011	0.13	-9999	-0.58	21	21
HSP90AA1	0.013	0	-9999	-10000	0	0
CDC42	0.006	0.15	-9999	-0.64	21	21
actin cytoskeleton reorganization	-0.018	0.16	-9999	-0.61	22	22
PTK2	-0.029	0.21	-9999	-0.8	24	24
EDG1	-0.002	0.15	-9999	-0.62	21	21
mol:DAG	0.006	0.15	-9999	-0.63	21	21
CaM/Ca2+	0.012	0.14	-9999	-0.57	21	21
MAP2K3	0.007	0.15	-9999	-0.6	23	23
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.008	0.16	-9999	-0.64	21	21
PLCG1	0.006	0.15	-9999	-0.64	21	21
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.006	0.14	-9999	-0.57	21	21
IQGAP1	0.013	0	-9999	-10000	0	0
YES1	0.013	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.001	0.15	-9999	-0.62	21	21
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.001	0.15	-9999	-0.61	21	21
cell migration	-0.004	0.19	-9999	-0.68	25	25
mol:PI-3-4-5-P3	0.017	0.17	-9999	-0.66	21	21
FYN	0.013	0.001	-9999	-10000	0	0
VEGFB/NRP1	0.006	0.14	-9999	-0.59	21	21
mol:NO	0.031	0.12	-9999	-0.44	21	21
PXN	0.013	0	-9999	-10000	0	0
HRAS/GTP	-0.036	0.12	-9999	-0.55	21	21
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.007	0.16	-9999	-0.64	21	21
VHL	0.012	0.022	-9999	-0.47	1	1
ITGB3	-0.083	0.19	-9999	-0.47	97	97
NOS3	0.03	0.13	-9999	-0.5	21	21
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.007	0.17	-9999	-0.69	21	21
RAC1	0.013	0	-9999	-10000	0	0
PRKCA	0.003	0.16	-9999	-0.61	22	22
PRKCB	-0.042	0.19	-9999	-0.66	27	27
VCL	-0.016	0.12	-9999	-0.47	29	29
VEGFA165/NRP1	-0.001	0.15	-9999	-0.63	21	21
VEGFR1/2 heterodimer/VEGFA homodimer	-0.004	0.16	-9999	-0.66	22	22
VEGFA165/NRP2	-0.024	0.12	-9999	-0.35	60	60
MAPKKK cascade	0.028	0.14	-9999	-0.66	11	11
NRP2	-0.019	0.12	-9999	-0.47	32	32
VEGFC homodimer	0.011	0.034	-9999	-0.52	2	2
NCK1	0.012	0.027	-9999	-0.58	1	1
ROCK1	0.012	0.022	-9999	-0.47	1	1
FAK1/Paxillin	-0.019	0.19	-9999	-0.74	23	23
MAP3K13	0	0.16	-9999	-0.64	23	23
PDPK1	0.025	0.15	-9999	-0.57	21	21

IL2 signaling events mediated by STAT5

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
GAB2	0.014	0	-9999	-10000	0	0
ELF1	-0.028	0.11	-9999	-0.41	12	12
CCNA2	-0.078	0.21	-9999	-0.58	75	75
PIK3CA	0.011	0.038	-9999	-0.47	3	3
JAK3	-0.001	0.091	-9999	-0.55	13	13
PIK3R1	0.009	0.049	-9999	-0.47	5	5
JAK1	0.014	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	0.027	0.11	-9999	-0.48	11	11
SHC1	0.014	0	-9999	-10000	0	0
SP1	0	0.081	-9999	-0.32	29	29
IL2RA	-0.055	0.19	-9999	-0.48	76	76
IL2RB	-0.016	0.12	-9999	-0.49	29	29
SOS1	0.014	0	-9999	-10000	0	0
IL2RG	-0.011	0.12	-9999	-0.55	22	22
G1/S transition of mitotic cell cycle	-0.047	0.22	-9999	-0.76	35	35
PTPN11	0.013	0.022	-9999	-0.47	1	1
CCND2	-0.016	0.17	-9999	-0.69	30	30
LCK	0.004	0.075	-9999	-0.57	8	8
GRB2	0.014	0	-9999	-10000	0	0
IL2	0.004	0.038	-9999	-0.57	2	2
CDK6	-0.004	0.091	-9999	-0.48	17	17
CCND3	0.034	0.099	-9999	-0.44	8	8

Cellular roles of Anthrax toxin

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
ANTXR1	-0.003	0.088	-10000	0	-0.48	16	16
ANTXR2	0.001	0.075	-10000	0	-0.47	12	12
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.003	0.015	-10000	0	-0.065	26	26
monocyte activation	-0.016	0.1	-10000	0	-0.38	33	33
MAP2K2	-0.002	0.009	-10000	0	-10000	0	0
MAP2K1	-0.003	0.012	-10000	0	-10000	0	0
MAP2K7	-0.003	0.012	-10000	0	-10000	0	0
MAP2K6	-0.011	0.052	-10000	0	-0.3	14	14
CYAA	-0.001	0.062	-10000	0	-0.25	26	26
MAP2K4	-0.003	0.012	-10000	0	-10000	0	0
IL1B	-0.033	0.11	-10000	0	-0.28	76	76
Channel	0.002	0.067	-10000	0	-0.27	26	26
NLRP1	-0.009	0.043	-10000	0	-0.27	12	12
CALM1	0.013	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	-0.004	0.016	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.003	0.015	0.065	26	-10000	0	26
MAPK3	-0.003	0.012	-10000	0	-10000	0	0
MAPK1	-0.003	0.012	-10000	0	-10000	0	0
PGR	-0.038	0.09	-10000	0	-0.26	70	70
PA/Cellular Receptors	0.001	0.073	-10000	0	-0.3	26	26
apoptosis	-0.003	0.015	-10000	0	-0.065	26	26
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.002	0.063	-10000	0	-0.26	26	26
macrophage activation	0.014	0.014	-10000	0	-10000	0	0
TNF	-0.029	0.14	-10000	0	-0.5	39	39
VCAM1	-0.017	0.1	-10000	0	-0.38	33	33
platelet activation	-0.004	0.016	-10000	0	-10000	0	0
MAPKKK cascade	-0.009	0.021	0.1	4	-10000	0	4
IL18	0	0.067	-10000	0	-0.32	16	16
negative regulation of macrophage activation	-0.003	0.015	-10000	0	-0.065	26	26
LEF	-0.004	0.015	-10000	0	-0.065	26	26
CASP1	-0.01	0.044	-10000	0	-0.21	18	18
mol:cAMP	-0.004	0.016	-10000	0	-10000	0	0
necrosis	-0.003	0.015	-10000	0	-0.065	26	26
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.002	0.063	-10000	0	-0.26	26	26
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

Signaling events mediated by HDAC Class III

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
EP300	0.01	0.038	-10000	0	-0.47	3	3
HDAC4	0.013	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.012	0.06	0.42	9	-10000	0	9
CDKN1A	-0.007	0.069	-10000	0	-0.51	8	8
KAT2B	0.013	0	-10000	0	-10000	0	0
BAX	0.011	0.038	-10000	0	-0.58	2	2
FOXO3	0.002	0.03	0.38	3	-10000	0	3
FOXO1	0.013	0	-10000	0	-10000	0	0
FOXO4	0.019	0.025	-10000	0	-0.26	4	4
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
TAT	-0.02	0.13	-10000	0	-0.58	24	24
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.002	0.073	-10000	0	-0.4	16	16
PPARGC1A	-0.14	0.22	-10000	0	-0.47	150	150
FHL2	-0.01	0.1	-10000	0	-0.47	23	23
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.018	0.013	-10000	0	-10000	0	0
HIST2H4A	0.012	0.06	-10000	0	-0.42	9	9
SIRT1/FOXO3a	0.003	0.024	0.26	3	-10000	0	3
SIRT1	0.011	0.018	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.025	0.012	-10000	0	-10000	0	0
SIRT1/Histone H1b	-0.029	0.079	-10000	0	-0.21	6	6
apoptosis	-0.023	0.027	0.35	2	-10000	0	2
SIRT1/PGC1A	-0.075	0.14	-10000	0	-0.28	146	146
p53/SIRT1	0.001	0.056	0.32	8	-0.33	6	14
SIRT1/FOXO4	0.021	0.025	-10000	0	-0.21	4	4
FOXO1/FHL2/SIRT1	0.011	0.057	-10000	0	-0.24	22	22
HIST1H1E	-0.042	0.094	-10000	0	-0.18	151	151
SIRT1/p300	0.016	0.03	-10000	0	-0.33	3	3
muscle cell differentiation	-0.006	0.063	0.33	16	-10000	0	16
TP53	0.005	0.056	-10000	0	-0.47	6	6
KU70/SIRT1/BAX	0.024	0.027	-10000	0	-0.35	2	2
CREBBP	0.013	0	-10000	0	-10000	0	0
MEF2D	0.013	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.009	0.093	-10000	0	-0.41	24	24
ACSS2	0.02	0.011	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	0.006	0.063	-10000	0	-0.33	16	16

Ephrin B reverse signaling

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
EFNB2	-0.006	0.1	-10000	0	-0.58	16	16
EPHB2	0.005	0.064	-10000	0	-0.52	7	7
EFNB1	0.015	0.044	-10000	0	-0.35	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.042	0.13	-10000	0	-0.57	9	9
Ephrin B2/EPHB1-2	-0.074	0.15	-10000	0	-0.27	165	165
neuron projection morphogenesis	-0.067	0.11	-10000	0	-0.54	9	9
Ephrin B1/EPHB1-2/Tiam1	-0.051	0.14	-10000	0	-0.53	12	12
DNM1	0.011	0.035	-10000	0	-0.52	2	2
cell-cell signaling	0	0.001	-10000	0	-10000	0	0
MAP2K4	0.015	0.039	-10000	0	-0.57	2	2
YES1	-0.002	0.05	-10000	0	-0.78	2	2
Ephrin B1/EPHB1-2/NCK2	-0.049	0.14	-10000	0	-0.48	12	12
PI3K	0.015	0.061	-10000	0	-0.61	3	3
mol:GDP	-0.051	0.14	-10000	0	-0.52	12	12
ITGA2B	-0.003	0.091	-10000	0	-0.51	15	15
endothelial cell proliferation	0.005	0.066	-10000	0	-0.36	16	16
FYN	-0.002	0.05	-10000	0	-0.78	2	2
MAP3K7	0.009	0.041	-10000	0	-0.61	2	2
FGR	-0.002	0.052	-10000	0	-0.79	2	2
TIAM1	0.01	0.038	-10000	0	-0.47	3	3
PIK3R1	0.008	0.049	-10000	0	-0.47	5	5
RGS3	0.013	0	-10000	0	-10000	0	0
cell adhesion	-0.028	0.13	-10000	0	-0.54	11	11
LYN	-0.002	0.05	-10000	0	-0.78	2	2
Ephrin B1/EPHB1-2/Src Family Kinases	-0.004	0.048	-10000	0	-0.75	2	2
Ephrin B1/EPHB1-2	-0.005	0.042	-10000	0	-0.66	2	2
SRC	-0.001	0.051	-10000	0	-0.79	2	2
ITGB3	-0.083	0.19	-10000	0	-0.47	97	97
EPHB1	-0.14	0.23	-10000	0	-0.47	155	155
EPHB4	0.013	0	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0.006	0.067	-10000	0	-0.36	16	16
alphaIIb/beta3 Integrin	-0.061	0.15	-10000	0	-0.34	108	108
BLK	-0.03	0.076	-10000	0	-0.79	2	2
HCK	-0.002	0.053	-10000	0	-0.79	2	2
regulation of stress fiber formation	0.049	0.13	0.47	12	-10000	0	12
MAPK8	0.016	0.055	-10000	0	-0.64	2	2
Ephrin B1/EPHB1-2/RGS3	-0.049	0.14	-10000	0	-0.48	12	12
endothelial cell migration	0.004	0.065	-10000	0	-0.32	18	18
NCK2	0.013	0	-10000	0	-10000	0	0
PTPN13	0.012	0.039	-10000	0	-0.59	2	2
regulation of focal adhesion formation	0.049	0.13	0.47	12	-10000	0	12
chemotaxis	0.049	0.13	0.47	12	-10000	0	12
PIK3CA	0.01	0.038	-10000	0	-0.47	3	3
Rac1/GTP	-0.067	0.12	-10000	0	-0.56	9	9
angiogenesis	-0.005	0.042	-10000	0	-0.66	2	2
LCK	-0.002	0.051	-10000	0	-0.79	2	2

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.13	0.22	-9999	-0.47	142	142
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.005	0.07	-9999	-0.58	7	7
TCEB1	0.012	0.027	-9999	-0.58	1	1
HIF1A/p53	0.025	0.031	-9999	-0.28	1	1
HIF1A	0.021	0.016	-9999	-10000	0	0
COPS5	0.013	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	0.033	0.046	-9999	-0.52	1	1
FIH (dimer)	0.013	0	-9999	-10000	0	0
CDKN2A	-0.11	0.24	-9999	-0.58	102	102
ARNT/IPAS	-0.082	0.16	-9999	-0.33	142	142
HIF1AN	0.013	0	-9999	-10000	0	0
GNB2L1	0.01	0.046	-9999	-0.58	3	3
HIF1A/ARNT	0.028	0.015	-9999	-10000	0	0
CUL2	0.013	0	-9999	-10000	0	0
OS9	0.013	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	0.019	0.063	-9999	-0.42	9	9
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	0.028	0.015	-9999	-10000	0	0
PHD1-3/OS9	0.029	0.038	-9999	-10000	0	0
HIF1A/RACK1/Elongin B/Elongin C	0.032	0.052	-9999	-0.48	3	3
VHL	0.012	0.022	-9999	-0.47	1	1
HSP90AA1	0.013	0	-9999	-10000	0	0
HIF1A/JAB1	0.028	0.015	-9999	-10000	0	0
EGLN3	0.003	0.069	-9999	-0.47	10	10
EGLN2	0.013	0	-9999	-10000	0	0
EGLN1	0.013	0	-9999	-10000	0	0
TP53	0.007	0.053	-9999	-0.47	6	6
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.033	0.037	-9999	-0.65	1	1
ARNT	0.013	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.013	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.034	0.12	-9999	-0.27	102	102

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.018	0.11	-10000	0	-0.33	52	52
ATM	0.012	0.022	-10000	0	-0.47	1	1
UBE2D3	0.013	0	-10000	0	-10000	0	0
PRKDC	0.012	0.027	-10000	0	-0.58	1	1
ATR	0.012	0.027	-10000	0	-0.58	1	1
UBE2L3	0.013	0	-10000	0	-10000	0	0
FANCD2	0.022	0.031	-10000	0	-0.34	3	3
protein ubiquitination	0.004	0.09	-10000	0	-0.53	3	3
XRCC5	0.013	0	-10000	0	-10000	0	0
XRCC6	0.013	0	-10000	0	-10000	0	0
M/R/N Complex	0.027	0	-10000	0	-10000	0	0
MRE11A	0.013	0	-10000	0	-10000	0	0
DNA-PK	0.026	0.017	-10000	0	-0.35	1	1
FA complex/FANCD2/Ubiquitin	0.033	0.043	-10000	0	-0.34	1	1
FANCF	0.013	0	-10000	0	-10000	0	0
BRCA1	0.011	0.038	-10000	0	-0.58	2	2
CCNE1	0.007	0.059	-10000	0	-0.58	5	5
CDK2/Cyclin E1	0.015	0.044	-10000	0	-0.42	5	5
FANCG	0.013	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.02	0.11	-10000	0	-0.33	54	54
FANCE	0.013	0	-10000	0	-10000	0	0
FANCC	0.012	0.027	-10000	0	-0.58	1	1
NBN	0.013	0	-10000	0	-10000	0	0
FANCA	-0.031	0.16	-10000	0	-0.57	37	37
DNA repair	0.011	0.12	-10000	0	-0.49	10	10
BRCA1/BARD1/ubiquitin	-0.02	0.11	-10000	0	-0.33	54	54
BARD1/DNA-PK	0.004	0.085	-10000	0	-0.31	1	1
FANCL	0.013	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.018	0.11	0.33	52	-10000	0	52
BRCA1/BARD1/CTIP/M/R/N Complex	0.01	0.077	-10000	0	-0.34	2	2
BRCA1/BACH1/BARD1/TopBP1	-0.006	0.094	-10000	0	-0.27	54	54
BRCA1/BARD1/P53	0	0.093	-10000	0	-0.39	3	3
BARD1/CSTF1/BRCA1	-0.006	0.094	-10000	0	-0.27	54	54
BRCA1/BACH1	0.011	0.038	-10000	0	-0.57	2	2
BARD1	-0.039	0.15	-10000	0	-0.47	52	52
PCNA	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.006	0.094	-10000	0	-0.27	54	54
BRCA1/BARD1/UbcH7	-0.006	0.094	-10000	0	-0.27	54	54
BRCA1/BARD1/RAD51/PCNA	-0.023	0.13	-10000	0	-0.36	38	38
BARD1/DNA-PK/P53	0.008	0.083	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.02	0.11	-10000	0	-0.33	54	54
BRCA1/BARD1/CTIP	0.001	0.088	-10000	0	-0.37	3	3
FA complex	0.023	0.052	-10000	0	-0.29	1	1
BARD1/EWS	-0.018	0.11	-10000	0	-0.33	52	52
RBBP8	0.02	0.022	-10000	0	-0.33	2	2
TP53	0.007	0.053	-10000	0	-0.47	6	6
TOPBP1	0.013	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.001	0.092	0.39	3	-10000	0	3
BRCA1/BARD1	0.007	0.092	-10000	0	-0.54	3	3
CSTF1	0.013	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.027	0.11	-10000	0	-0.34	52	52
CDK2	0.013	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.033	0.16	-10000	0	-0.58	38	38
RAD50	0.013	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.02	0.11	-10000	0	-0.33	54	54
EWSR1	0.013	0	-10000	0	-10000	0	0

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.061	0.12	-9999	-0.47	20	20
TC10/GTP	-0.045	0.093	-9999	-0.46	6	6
Insulin Receptor/Insulin/IRS1/Shp2	0.01	0.075	-9999	-0.32	15	15
HRAS	0.007	0.059	-9999	-0.58	5	5
APS homodimer	-0.011	0.12	-9999	-0.57	20	20
GRB14	-0.098	0.23	-9999	-0.57	92	92
FOXO3	-0.08	0.22	-9999	-0.57	76	76
AKT1	-0.024	0.13	-9999	-0.43	14	14
INSR	0.014	0.005	-9999	-10000	0	0
Insulin Receptor/Insulin	0.027	0.047	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.013	0	-9999	-10000	0	0
SORBS1	-0.073	0.19	-9999	-0.47	87	87
CRK	0.013	0	-9999	-10000	0	0
PTPN1	0.023	0.045	-9999	-10000	0	0
CAV1	-0.024	0.11	-9999	-0.36	23	23
CBL/APS/CAP/Crk-II/C3G	-0.02	0.12	-9999	-0.51	6	6
Insulin Receptor/Insulin/IRS1/NCK2	0.011	0.073	-9999	-0.3	14	14
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.018	0.071	-9999	-0.48	5	5
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.024	0.049	-9999	-0.36	1	1
RPS6KB1	-0.016	0.12	-9999	-0.4	13	13
PARD6A	0.007	0.059	-9999	-0.58	5	5
CBL	0.012	0.022	-9999	-0.47	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0.001	0.006	-9999	-10000	0	0
PIK3R1	0.008	0.049	-9999	-0.47	5	5
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.052	0.1	-9999	-0.41	13	13
HRAS/GTP	-0.024	0.074	-9999	-0.42	8	8
Insulin Receptor	0.014	0.005	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.018	0.068	-9999	-0.5	1	1
PRKCI	-0.015	0.029	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.064	0.12	-9999	-0.47	14	14
SHC1	0.013	0	-9999	-10000	0	0
negative regulation of MAPKKK cascade	0.024	0.025	-9999	-10000	0	0
PI3K	-0.016	0.073	-9999	-0.49	5	5
NCK2	0.013	0	-9999	-10000	0	0
RHOQ	0.013	0	-9999	-10000	0	0
mol:H2O2	-0.001	0.005	-9999	-10000	0	0
HRAS/GDP	0.005	0.044	-9999	-0.42	5	5
AKT2	-0.024	0.13	-9999	-0.43	14	14
PRKCZ	-0.014	0.027	-9999	-10000	0	0
SH2B2	-0.011	0.12	-9999	-0.57	20	20
SHC/SHIP	0.004	0.091	-9999	-0.45	8	8
F2RL2	-0.22	0.29	-9999	-0.58	191	191
TRIP10	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	0.011	0.052	-9999	-0.29	14	14
TC10/GTP/CIP4/Exocyst	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.026	0.049	-9999	-10000	0	0
RAPGEF1	0.013	0	-9999	-10000	0	0
RASA1	0.01	0.038	-9999	-0.47	3	3
NCK1	0.012	0.027	-9999	-0.58	1	1
CBL/APS/CAP/Crk-II	-0.029	0.13	-9999	-0.38	20	20
TC10/GDP	0.01	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	0.02	0.052	-9999	-0.28	14	14
INPP5D	-0.005	0.095	-9999	-0.35	20	20
SOS1	0.013	0	-9999	-10000	0	0
SGK1	-0.13	0.3	-9999	-0.82	76	76
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.012	0.022	-9999	-0.47	1	1
IRS1	-0.003	0.086	-9999	-0.47	16	16
p62DOK/RasGAP	0.024	0.025	-9999	-10000	0	0
INS	-0.013	0.096	-9999	-0.57	14	14
mol:PI-3-4-P2	-0.005	0.094	-9999	-0.34	20	20
GRB2	0.013	0	-9999	-10000	0	0
EIF4EBP1	-0.041	0.15	-9999	-0.46	29	29
PTPRA	0.014	0.005	-9999	-10000	0	0
PIK3CA	0.01	0.038	-9999	-0.47	3	3
TC10/GTP/CIP4	0.018	0	-9999	-10000	0	0
PDPK1	0.013	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.019	0.053	-9999	-0.41	1	1
Insulin Receptor/Insulin/IRS1	0.002	0.072	-9999	-0.28	29	29
Insulin Receptor/Insulin/IRS3	0.001	0.071	-9999	-0.41	14	14
Par3/Par6	-0.099	0.16	-9999	-0.3	193	193

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.015	0.005	-10000	0	-10000	0	0
RAS family/GTP	-0.03	0.11	-10000	0	-0.36	5	5
NFATC4	-0.021	0.097	-10000	0	-0.32	7	7
ERBB2IP	0.013	0.022	-10000	0	-0.47	1	1
HSP90 (dimer)	0.013	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.04	0.11	-10000	0	-0.4	4	4
JUN	0.003	0.073	-10000	0	-0.33	1	1
HRAS	0.007	0.059	-10000	0	-0.58	5	5
DOCK7	-0.034	0.11	-10000	0	-0.37	4	4
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.05	0.12	-10000	0	-0.47	4	4
AKT1	0.009	0.003	-10000	0	-10000	0	0
BAD	0.016	0.017	-10000	0	-0.36	1	1
MAPK10	-0.006	0.07	-10000	0	-0.28	4	4
mol:GTP	-0.001	0.001	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.042	0.12	-10000	0	-0.43	4	4
RAF1	-0.024	0.11	-10000	0	-0.37	4	4
ErbB2/ErbB3/neuregulin 2	-0.082	0.13	-10000	0	-0.26	173	173
STAT3	0.004	0.006	-10000	0	-10000	0	0
cell migration	-0.001	0.073	-10000	0	-0.23	4	4
mol:PI-3-4-5-P3	-0.001	0.002	-10000	0	-10000	0	0
cell proliferation	-0.073	0.21	-10000	0	-0.56	25	25
FOS	-0.075	0.22	-10000	0	-0.49	85	85
NRAS	0.012	0.022	-10000	0	-0.47	1	1
mol:Ca2+	-0.04	0.11	-10000	0	-0.4	4	4
MAPK3	-0.053	0.17	-10000	0	-0.51	16	16
MAPK1	-0.053	0.17	-10000	0	-0.51	16	16
JAK2	-0.035	0.11	-10000	0	-0.38	5	5
NF2	-0.002	0.004	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.047	0.12	-10000	0	-0.26	33	33
NRG1	-0.12	0.22	-10000	0	-0.47	138	138
GRB2/SOS1	0.019	0.001	-10000	0	-10000	0	0
MAPK8	-0.044	0.12	-10000	0	-0.36	6	6
MAPK9	-0.004	0.065	-10000	0	-10000	0	0
ERBB2	-0.002	0.035	0.35	1	-0.35	4	5
ERBB3	0.011	0.022	-10000	0	-0.48	1	1
SHC1	0.013	0.001	-10000	0	-10000	0	0
RAC1	0.013	0	-10000	0	-10000	0	0
apoptosis	0.005	0.013	0.22	1	-10000	0	1
STAT3 (dimer)	0.018	0.006	-10000	0	-10000	0	0
RNF41	0.02	0.007	-10000	0	-10000	0	0
FRAP1	0.008	0.003	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.042	0.067	-10000	0	-0.27	4	4
ErbB2/ErbB2/HSP90 (dimer)	0.006	0.029	0.24	1	-0.28	4	5
CHRNA1	-0.055	0.17	-10000	0	-0.42	37	37
myelination	-0.019	0.095	-10000	0	-0.3	7	7
PPP3CB	-0.032	0.1	-10000	0	-0.35	4	4
KRAS	0.013	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.027	0.11	-10000	0	-0.34	4	4
NRG2	-0.16	0.23	-10000	0	-0.47	172	172
mol:GDP	-0.047	0.12	-10000	0	-0.26	33	33
SOS1	0.013	0.001	-10000	0	-10000	0	0
MAP2K2	-0.022	0.12	-10000	0	-0.35	9	9
SRC	0.013	0	-10000	0	-10000	0	0
mol:cAMP	-0.001	0.001	-10000	0	-10000	0	0
PTPN11	-0.031	0.11	-10000	0	-0.38	5	5
MAP2K1	-0.068	0.18	-10000	0	-0.42	67	67
heart morphogenesis	-0.04	0.11	-10000	0	-0.4	4	4
RAS family/GDP	-0.029	0.11	-10000	0	-0.36	5	5
GRB2	0.013	0.001	-10000	0	-10000	0	0
PRKACA	-0.004	0.007	-10000	0	-10000	0	0
CHRNE	0.009	0.02	-10000	0	-0.2	1	1
HSP90AA1	0.013	0	-10000	0	-10000	0	0
activation of caspase activity	-0.009	0.003	-10000	0	-10000	0	0
nervous system development	-0.04	0.11	-10000	0	-0.4	4	4
CDC42	0.013	0	-10000	0	-10000	0	0

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.012	0.033	-9999	-0.69	1	1
SVIL	-0.007	0.099	-9999	-0.47	21	21
ZNF318	0.012	0.018	-9999	-10000	0	0
JMJD2C	0.006	0.012	-9999	-0.097	6	6
T-DHT/AR/Ubc9	0.001	0.09	-9999	-0.27	44	44
CARM1	0.013	0.001	-9999	-10000	0	0
PRDX1	0.013	0.001	-9999	-10000	0	0
PELP1	0.013	0.003	-9999	-10000	0	0
CTNNB1	0.014	0.006	-9999	-10000	0	0
AKT1	0.013	0.005	-9999	-10000	0	0
PTK2B	0.013	0.005	-9999	-10000	0	0
MED1	0.013	0.006	-9999	-10000	0	0
MAK	-0.15	0.27	-9999	-0.58	137	137
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.001	0.079	-9999	-0.47	13	13
GSN	0.01	0.045	-9999	-0.47	4	4
NCOA2	-0.047	0.16	-9999	-0.47	60	60
NCOA6	0.014	0.007	-9999	-10000	0	0
DNA-PK	0.025	0.02	-9999	-10000	0	0
NCOA4	0.013	0.001	-9999	-10000	0	0
PIAS3	0.014	0.006	-9999	-10000	0	0
cell proliferation	-0.074	0.11	-9999	-0.29	21	21
XRCC5	0.013	0.004	-9999	-10000	0	0
UBE3A	0.014	0.013	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.01	0.11	-9999	-0.3	57	57
FHL2	-0.012	0.2	-9999	-0.86	23	23
RANBP9	0.014	0.007	-9999	-10000	0	0
JMJD1A	0.013	0.016	-9999	-0.13	6	6
CDK6	-0.004	0.091	-9999	-0.48	17	17
TGFB1I1	-0.027	0.14	-9999	-0.47	41	41
T-DHT/AR/CyclinD1	0.001	0.092	-9999	-0.28	45	45
XRCC6	0.013	0.004	-9999	-10000	0	0
T-DHT/AR	0.016	0.11	-9999	-0.28	44	44
CTDSP1	0.013	0.002	-9999	-10000	0	0
CTDSP2	0.013	0.013	-9999	-10000	0	0
BRCA1	0.011	0.041	-9999	-0.61	2	2
TCF4	0.009	0.045	-9999	-0.47	4	4
CDKN2A	-0.11	0.24	-9999	-0.57	102	102
SRF	0.014	0.031	-9999	-10000	0	0
NKX3-1	0.022	0.051	-9999	-10000	0	0
KLK3	0.023	0.15	-9999	-1.2	7	7
TMF1	0.013	0.001	-9999	-10000	0	0
HNRNPA1	0.013	0.007	-9999	-10000	0	0
AOF2	0.001	0.008	-9999	-0.069	6	6
APPL1	0.02	0.012	-9999	-10000	0	0
T-DHT/AR/Caspase 8	0.001	0.09	-9999	-0.27	44	44
AR	-0.027	0.14	-9999	-0.47	44	44
UBA3	0.013	0.002	-9999	-10000	0	0
PATZ1	0.013	0.007	-9999	-10000	0	0
PAWR	0.013	0.001	-9999	-10000	0	0
PRKDC	0.012	0.025	-9999	-0.52	1	1
PA2G4	0.013	0.008	-9999	-10000	0	0
UBE2I	0.013	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	0.002	0.082	-9999	-0.25	44	44
RPS6KA3	0.013	0.024	-9999	-0.47	1	1
T-DHT/AR/ARA70	0.001	0.09	-9999	-0.27	44	44
LATS2	0.013	0.006	-9999	-10000	0	0
T-DHT/AR/PRX1	0.002	0.082	-9999	-0.25	44	44
Cyclin D3/CDK11 p58	0.01	0.001	-9999	-10000	0	0
VAV3	-0.04	0.15	-9999	-0.47	54	54
KLK2	0.01	0.098	-9999	-0.74	6	6
CASP8	0.013	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.02	0.15	-9999	-0.4	63	63
TMPRSS2	0.013	0.11	-9999	-0.88	6	6
CCND1	0.012	0.027	-9999	-0.57	1	1
PIAS1	0.013	0.025	-9999	-0.47	1	1
mol:T-DHT	0.004	0.017	-9999	-0.062	29	29
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.014	0.017	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.01	0.11	-9999	-0.29	59	59
CMTM2	0.007	0.049	-9999	-0.52	4	4
SNURF	-0.006	0.094	-9999	-0.47	19	19
ZMIZ1	0.016	0.028	-9999	-0.5	1	1
CCND3	0.013	0.001	-9999	-10000	0	0
TGIF1	0.013	0.007	-9999	-10000	0	0
FKBP4	0.014	0.007	-9999	-10000	0	0

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	0.013	0	-9999	-10000	0	0
SPHK1	-0.006	0.1	-9999	-0.58	16	16
GNAI2	0.013	0	-9999	-10000	0	0
mol:S1P	0.015	0.035	-9999	-0.18	16	16
GNAO1	-0.079	0.19	-9999	-0.47	93	93
mol:Sphinganine-1-P	0.007	0.078	-9999	-0.42	16	16
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	0.034	0.026	-9999	-10000	0	0
GNAI3	0.013	0	-9999	-10000	0	0
G12/G13	0.02	0	-9999	-10000	0	0
S1PR3	-0.005	0.093	-9999	-0.48	18	18
S1PR2	0.013	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	0.009	0.029	-9999	-10000	0	0
S1PR5	-0.067	0.18	-9999	-0.47	80	80
S1PR4	-0.012	0.12	-9999	-0.57	21	21
GNAI1	0.005	0.065	-9999	-0.53	7	7
S1P/S1P5/G12	-0.017	0.099	-9999	-0.37	1	1
S1P/S1P3/Gq	0.004	0.1	-9999	-0.52	11	11
S1P/S1P4/Gi	-0.038	0.15	-9999	-0.42	43	43
GNAQ	0.013	0	-9999	-10000	0	0
GNAZ	-0.033	0.14	-9999	-0.47	46	46
GNA14	0.012	0.022	-9999	-0.47	1	1
GNA15	-0.011	0.1	-9999	-0.47	24	24
GNA12	0.013	0	-9999	-10000	0	0
GNA13	0.013	0	-9999	-10000	0	0
GNA11	-0.003	0.086	-9999	-0.47	16	16
ABCC1	0.013	0	-9999	-10000	0	0

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.013	0.005	-9999	-10000	0	0
PRKCZ	0.013	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.002	0.071	-9999	-0.28	9	9
IRAK/TOLLIP	0.026	0.016	-9999	-0.31	1	1
IKBKB	0.012	0.027	-9999	-0.58	1	1
IKBKG	0.013	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.059	0.14	-9999	-0.34	103	103
IL1A	0.001	0.059	-9999	-0.52	6	6
IL1B	-0.044	0.15	-9999	-0.38	79	79
IRAK/TRAF6/p62/Atypical PKCs	0.042	0.019	-9999	-10000	0	0
IL1R2	-0.083	0.19	-9999	-0.47	97	97
IL1R1	0.011	0.031	-9999	-0.47	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.017	0.063	-9999	-10000	0	0
TOLLIP	0.013	0	-9999	-10000	0	0
TICAM2	0.006	0.058	-9999	-0.47	7	7
MAP3K3	0.013	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0.009	0	-9999	-10000	0	0
IKK complex/ELKS	0.058	0.013	-9999	-10000	0	0
JUN	0.023	0.063	-9999	-0.39	2	2
MAP3K7	0.013	0.001	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.009	0.12	-9999	-0.47	11	11
IL1 alpha/IL1R1/IL1RAP/MYD88	0.024	0.048	-9999	-0.31	7	7
PIK3R1	0.008	0.049	-9999	-0.47	5	5
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.029	0.045	-9999	-0.33	4	4
IL1 beta fragment/IL1R1/IL1RAP	-0.022	0.12	-9999	-0.36	31	31
NFKB1	0.013	0	-9999	-10000	0	0
MAPK8	0.021	0.056	-9999	-10000	0	0
IRAK1	0.02	0.017	-9999	-0.35	1	1
IL1RN/IL1R1	-0.005	0.093	-9999	-0.35	33	33
IRAK4	0.013	0	-9999	-10000	0	0
PRKCI	0.012	0.027	-9999	-0.58	1	1
TRAF6	0.013	0	-9999	-10000	0	0
PI3K	0.014	0.048	-9999	-0.37	7	7
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.003	0.08	-9999	-0.31	9	9
CHUK	0.013	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.022	0.12	-9999	-0.36	31	31
IL1 beta/IL1R2	-0.088	0.18	-9999	-0.33	155	155
IRAK/TRAF6/TAK1/TAB1/TAB2	0.028	0.014	-9999	-0.26	1	1
NF kappa B1 p50/RelA	-0.04	0.092	-9999	-0.42	11	11
IRAK3	-0.011	0.1	-9999	-0.47	24	24
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.009	0.11	-9999	-0.43	9	9
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.027	0.038	-9999	-0.43	1	1
IL1 alpha/IL1R1/IL1RAP	0.016	0.052	-9999	-0.32	11	11
RELA	0.013	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.013	0	-9999	-10000	0	0
MYD88	0.013	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0.033	0.015	-9999	-0.28	1	1
IL1RAP	0.009	0.044	-9999	-0.47	4	4
UBE2N	0.013	0	-9999	-10000	0	0
IRAK/TRAF6	-0.036	0.08	-9999	-0.36	10	10
CASP1	-0.002	0.084	-9999	-0.47	15	15
IL1RN/IL1R2	-0.072	0.17	-9999	-0.36	118	118
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.012	0.12	-9999	-0.33	31	31
TMEM189-UBE2V1	0.005	0.006	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.033	0.037	-9999	-0.38	2	2
PIK3CA	0.01	0.038	-9999	-0.47	3	3
IL1RN	-0.019	0.12	-9999	-0.5	31	31
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.021	0.048	-9999	-0.27	11	11

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.016	0.023	-9999	-0.28	3	3
ADCY5	-0.03	0.11	-9999	-0.28	78	78
ADCY6	0.018	0	-9999	-10000	0	0
ADCY7	0.017	0.017	-9999	-0.36	1	1
ADCY1	-0.017	0.11	-9999	-0.35	46	46
ADCY2	0.004	0.064	-9999	-0.29	22	22
ADCY3	0.018	0	-9999	-10000	0	0
ADCY8	0.008	0.037	-9999	-0.36	5	5
PRKCE	0.01	0	-9999	-10000	0	0
ADCY9	0.016	0.019	-9999	-0.28	2	2
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	0.006	0.051	-9999	-0.24	3	3

RXR and RAR heterodimerization with other nuclear receptor

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