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

Pathway.Name	Avg.Num.Perturbations
TCGA08_retinoblastoma	258
HIF-1-alpha transcription factor network	201
Nephrin/Neph1 signaling in the kidney podocyte	183
TCR signaling in naïve CD8+ T cells	148
TCGA08_p53	146
Syndecan-4-mediated signaling events	120
Aurora B signaling	119
FOXA2 and FOXA3 transcription factor networks	117
IL12-mediated signaling events	116
Glypican 1 network	106

Pathway.Name	Significance.Ratio	Avg.Num.Perturbations	Total.Perturbations	Num.Entities	Min.Mean.Truth	Max.Mean.Truth	Min.Mean.Within	Max.Mean.Within	Min.Mean.Any	Max.Mean.Within.1
TCGA08_retinoblastoma	0.4841	258	2071	8	-0.84	0.22	1000	-1000	-0.042	-1000
HIF-1-alpha transcription factor network	0.3771	201	15296	76	-1.3	0.026	1000	-1000	-0.18	-1000
Nephrin/Neph1 signaling in the kidney podocyte	0.3433	183	6222	34	-0.6	0.016	1000	-1000	-0.11	-1000
TCR signaling in naïve CD8+ T cells	0.2777	148	13797	93	-0.66	0.33	1000	-1000	-0.11	-1000
TCGA08_p53	0.2739	146	1027	7	-0.65	0.31	1000	-1000	-0.019	-1000
Syndecan-4-mediated signaling events	0.2251	120	8066	67	-0.64	0.11	1000	-1000	-0.14	-1000
Aurora B signaling	0.2233	119	8035	67	-0.4	0.016	1000	-1000	-0.11	-1000
FOXA2 and FOXA3 transcription factor networks	0.2195	117	5395	46	-1.2	0.025	1000	-1000	-0.095	-1000
IL12-mediated signaling events	0.2176	116	10111	87	-0.69	0.16	1000	-1000	-0.14	-1000
Glypican 1 network	0.1989	106	5123	48	-0.56	0.045	1000	-1000	-0.078	-1000
FOXM1 transcription factor network	0.1970	105	5382	51	-0.82	0.04	1000	-1000	-0.2	-1000
PDGFR-alpha signaling pathway	0.1951	104	4618	44	-0.27	0.034	1000	-1000	-0.096	-1000
amb2 Integrin signaling	0.1576	84	6888	82	-0.55	0.016	1000	-1000	-0.12	-1000
IL4-mediated signaling events	0.1463	78	7117	91	-0.84	0.54	1000	-1000	-0.17	-1000
Caspase cascade in apoptosis	0.1445	77	5751	74	-0.32	0.16	1000	-1000	-0.093	-1000
JNK signaling in the CD4+ TCR pathway	0.1445	77	1318	17	-0.41	0.016	1000	-1000	-0.092	-1000
EGFR-dependent Endothelin signaling events	0.1388	74	1567	21	-0.67	0.016	1000	-1000	-0.11	-1000
Aurora C signaling	0.1332	71	499	7	-0.39	0.012	1000	-1000	-0.064	-1000
VEGFR1 specific signals	0.1332	71	3991	56	-0.47	0.046	1000	-1000	-0.12	-1000
Glypican 2 network	0.1313	70	281	4	-0.12	-1000	1000	-1000	-0.052	-1000
Syndecan-1-mediated signaling events	0.1257	67	2303	34	-0.41	0.016	1000	-1000	-0.11	-1000
BMP receptor signaling	0.1182	63	5108	81	-0.69	0.016	1000	-1000	-0.13	-1000
HIF-2-alpha transcription factor network	0.1144	61	2637	43	-0.76	0.34	1000	-1000	-0.12	-1000
IL23-mediated signaling events	0.1144	61	3673	60	-0.39	0.021	1000	-1000	-0.19	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	0.1144	61	2013	33	-0.83	0.016	1000	-1000	-0.089	-1000
Signaling events mediated by the Hedgehog family	0.0957	51	2691	52	-0.44	0.12	1000	-1000	-0.11	-1000
Fc-epsilon receptor I signaling in mast cells	0.0901	48	4663	97	-0.32	0.04	1000	-1000	-0.13	-1000
IL27-mediated signaling events	0.0844	45	2319	51	-0.62	0.074	1000	-1000	-0.096	-1000
S1P1 pathway	0.0807	43	1551	36	-0.38	0.018	1000	-1000	-0.092	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	0.0788	42	2877	68	-0.55	0.063	1000	-1000	-0.17	-1000
Ephrin A reverse signaling	0.0769	41	292	7	-0.059	0	1000	-1000	-0.052	-1000
Effects of Botulinum toxin	0.0769	41	1091	26	-0.36	0.016	1000	-1000	-0.092	-1000
Arf6 signaling events	0.0750	40	2485	62	-0.67	0.016	1000	-1000	-0.086	-1000
Calcium signaling in the CD4+ TCR pathway	0.0713	38	1194	31	-0.46	0.016	1000	-1000	-0.16	-1000
p75(NTR)-mediated signaling	0.0675	36	4581	125	-0.41	0.016	1000	-1000	-0.15	-1000
IL2 signaling events mediated by PI3K	0.0657	35	2030	58	-0.43	0.032	1000	-1000	-0.11	-1000
LPA4-mediated signaling events	0.0638	34	417	12	-0.16	0.026	1000	-1000	-0.041	-1000
IL2 signaling events mediated by STAT5	0.0638	34	751	22	-0.44	0.038	1000	-1000	-0.081	-1000
Coregulation of Androgen receptor activity	0.0582	31	2356	76	-0.92	0.033	1000	-1000	-0.073	-1000
PLK1 signaling events	0.0582	31	2656	85	-0.38	0.016	1000	-1000	-0.08	-1000
Integrins in angiogenesis	0.0582	31	2613	84	-0.38	0.04	1000	-1000	-0.13	-1000
BCR signaling pathway	0.0582	31	3154	99	-0.34	0.035	1000	-1000	-0.14	-1000
Glucocorticoid receptor regulatory network	0.0563	30	3429	114	-0.41	0.16	1000	-1000	-0.098	-1000
Regulation of Telomerase	0.0563	30	3129	102	-0.67	0.051	1000	-1000	-0.14	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	0.0544	29	2279	78	-0.32	0.045	1000	-1000	-0.11	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	0.0525	28	1541	54	-0.65	0.031	1000	-1000	-0.13	-1000
EPO signaling pathway	0.0525	28	1566	55	-0.29	0.018	1000	-1000	-0.13	-1000
IL6-mediated signaling events	0.0507	27	2091	75	-0.29	0.076	1000	-1000	-0.13	-1000
Reelin signaling pathway	0.0450	24	1392	56	-0.24	0.016	1000	-1000	-0.12	-1000
Visual signal transduction: Rods	0.0450	24	1256	52	-0.29	0.016	1000	-1000	-0.12	-1000
Signaling events mediated by PTP1B	0.0432	23	1765	76	-0.67	0.049	1000	-1000	-0.12	-1000
Angiopoietin receptor Tie2-mediated signaling	0.0432	23	2094	88	-0.31	0.075	1000	-1000	-0.16	-1000
Aurora A signaling	0.0413	22	1323	60	-0.24	0.053	1000	-1000	-0.11	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	0.0413	22	1005	45	-0.57	0.062	1000	-1000	-0.13	-1000
Syndecan-2-mediated signaling events	0.0394	21	1454	69	-0.55	0.053	1000	-1000	-0.1	-1000
Neurotrophic factor-mediated Trk receptor signaling	0.0394	21	2530	120	-0.16	0.14	1000	-1000	-0.11	-1000
Endothelins	0.0338	18	1780	96	-0.35	0.086	1000	-1000	-0.1	-1000
Wnt signaling	0.0338	18	127	7	-0.068	0.016	1000	-1000	-0.085	-1000
Class I PI3K signaling events	0.0338	18	1325	73	-0.47	0.036	1000	-1000	-0.11	-1000
Regulation of nuclear SMAD2/3 signaling	0.0319	17	2404	136	-0.45	0.1	1000	-1000	-0.13	-1000
Presenilin action in Notch and Wnt signaling	0.0319	17	1039	61	-0.19	0.092	1000	-1000	-0.11	-1000
S1P3 pathway	0.0319	17	720	42	-0.37	0.062	1000	-1000	-0.089	-1000
Thromboxane A2 receptor signaling	0.0300	16	1776	105	-0.67	0.067	1000	-1000	-0.11	-1000
Paxillin-independent events mediated by a4b1 and a4b7	0.0300	16	610	37	-0.29	0.026	1000	-1000	-0.13	-1000
LPA receptor mediated events	0.0300	16	1665	102	-0.4	0.06	1000	-1000	-0.13	-1000
Sphingosine 1-phosphate (S1P) pathway	0.0281	15	426	28	-0.14	0.023	1000	-1000	-0.081	-1000
Ceramide signaling pathway	0.0281	15	1164	76	-0.67	0.23	1000	-1000	-0.091	-1000
FoxO family signaling	0.0281	15	997	64	-0.57	0.12	1000	-1000	-0.11	-1000
PLK2 and PLK4 events	0.0263	14	44	3	-0.016	0.011	1000	-1000	-0.036	-1000
E-cadherin signaling events	0.0263	14	71	5	-0.023	0.016	1000	-1000	-0.07	-1000
IFN-gamma pathway	0.0244	13	887	68	-0.37	0.018	1000	-1000	-0.13	-1000
FAS signaling pathway (CD95)	0.0244	13	647	47	-0.42	0.028	1000	-1000	-0.075	-1000
Canonical Wnt signaling pathway	0.0244	13	713	51	-0.19	0.096	1000	-1000	-0.088	-1000
Signaling events mediated by VEGFR1 and VEGFR2	0.0244	13	1729	125	-0.39	0.043	1000	-1000	-0.15	-1000
Regulation of Androgen receptor activity	0.0244	13	932	70	-0.96	0.04	1000	-1000	-0.094	-1000
Nongenotropic Androgen signaling	0.0225	12	639	52	-0.18	0.071	1000	-1000	-0.086	-1000
ErbB4 signaling events	0.0206	11	796	69	-0.18	0.1	1000	-1000	-0.13	-1000
S1P5 pathway	0.0206	11	197	17	-0.14	0.046	1000	-1000	-0.074	-1000
Stabilization and expansion of the E-cadherin adherens junction	0.0206	11	836	74	-0.67	0.099	1000	-1000	-0.14	-1000
S1P4 pathway	0.0206	11	287	25	-0.14	0.033	1000	-1000	-0.075	-1000
Visual signal transduction: Cones	0.0169	9	363	38	-0.041	0.016	1000	-1000	-0.095	-1000
Noncanonical Wnt signaling pathway	0.0169	9	254	26	-0.12	0.016	1000	-1000	-0.13	-1000
a4b1 and a4b7 Integrin signaling	0.0169	9	48	5	-0.02	0.016	1000	-1000	-0.051	-1000
TCGA08_rtk_signaling	0.0169	9	238	26	-0.28	0.041	1000	-1000	-0.033	-1000
Signaling events regulated by Ret tyrosine kinase	0.0150	8	692	82	-0.064	0.025	1000	-1000	-0.13	-1000
Class IB PI3K non-lipid kinase events	0.0150	8	24	3	-0.003	0.003	1000	-1000	-0.021	-1000
Signaling events mediated by PRL	0.0131	7	245	34	-0.055	0.045	1000	-1000	-0.091	-1000
Canonical NF-kappaB pathway	0.0113	6	268	39	-0.19	0.075	1000	-1000	-0.12	-1000
Insulin-mediated glucose transport	0.0113	6	192	32	-0.083	0.068	1000	-1000	-0.099	-1000
Signaling events mediated by HDAC Class III	0.0113	6	242	40	-0.058	0.032	1000	-1000	-0.066	-1000
IL1-mediated signaling events	0.0113	6	400	62	-0.09	0.059	1000	-1000	-0.14	-1000
Ephrin B reverse signaling	0.0113	6	335	48	-0.03	0.031	1000	-1000	-0.1	-1000
Signaling mediated by p38-alpha and p38-beta	0.0113	6	271	44	-0.046	0.049	1000	-1000	-0.069	-1000
Plasma membrane estrogen receptor signaling	0.0113	6	540	86	-0.16	0.07	1000	-1000	-0.13	-1000
p38 MAPK signaling pathway	0.0113	6	276	44	-0.099	0.049	1000	-1000	-0.1	-1000
ErbB2/ErbB3 signaling events	0.0094	5	387	65	-0.13	0.059	1000	-1000	-0.1	-1000
Arf6 downstream pathway	0.0094	5	225	43	-0.033	0.033	1000	-1000	-0.057	-1000
Signaling mediated by p38-gamma and p38-delta	0.0094	5	85	15	0	0.036	1000	-1000	-0.049	-1000
Syndecan-3-mediated signaling events	0.0094	5	209	35	-0.039	0.016	1000	-1000	-0.12	-1000
E-cadherin signaling in the nascent adherens junction	0.0094	5	407	76	-0.026	0.067	1000	-1000	-0.12	-1000
Arf6 trafficking events	0.0094	5	413	71	-0.12	0.058	1000	-1000	-0.11	-1000
Ras signaling in the CD4+ TCR pathway	0.0094	5	85	17	-0.037	0.055	1000	-1000	-0.064	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	0.0075	4	363	85	-0.037	0.079	1000	-1000	-0.11	-1000
EPHB forward signaling	0.0075	4	376	85	-0.075	0.069	1000	-1000	-0.14	-1000
BARD1 signaling events	0.0056	3	217	57	-0.17	0.044	1000	-1000	-0.1	-1000
Osteopontin-mediated events	0.0056	3	123	38	-0.03	0.096	1000	-1000	-0.15	-1000
Cellular roles of Anthrax toxin	0.0056	3	119	39	-0.022	0.027	1000	-1000	-0.042	-1000
Paxillin-dependent events mediated by a4b1	0.0056	3	138	36	-0.026	0.031	1000	-1000	-0.1	-1000
PDGFR-beta signaling pathway	0.0056	3	386	97	-0.058	0.087	1000	-1000	-0.12	-1000
E-cadherin signaling in keratinocytes	0.0056	3	133	43	-0.29	0.054	1000	-1000	-0.12	-1000
Hedgehog signaling events mediated by Gli proteins	0.0038	2	134	65	-0.06	0.093	1000	-1000	-0.097	-1000
ceramide signaling pathway	0.0038	2	131	49	-0.12	0.054	1000	-1000	-0.074	-1000
RXR and RAR heterodimerization with other nuclear receptor	0.0038	2	119	52	-0.031	0.093	1000	-1000	-0.11	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	0.0038	2	181	83	-0.083	0.081	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class I	0.0038	2	216	104	-0.029	0.063	1000	-1000	-0.1	-1000
Retinoic acid receptors-mediated signaling	0.0038	2	128	58	-0.025	0.062	1000	-1000	-0.11	-1000
Regulation of p38-alpha and p38-beta	0.0038	2	150	54	-0.041	0.073	1000	-1000	-0.094	-1000
Insulin Pathway	0.0038	2	200	74	-0.034	0.055	1000	-1000	-0.14	-1000
Signaling events mediated by HDAC Class II	0.0019	1	127	75	-0.027	0.051	1000	-1000	-0.092	-1000
Circadian rhythm pathway	0.0019	1	33	22	-0.019	0.064	1000	-1000	-0.089	-1000
mTOR signaling pathway	0.0019	1	102	53	-0.01	0.044	1000	-1000	-0.087	-1000
Class I PI3K signaling events mediated by Akt	0.0019	1	103	68	-0.083	0.059	1000	-1000	-0.1	-1000
Nectin adhesion pathway	0.0019	1	92	63	-0.016	0.078	1000	-1000	-0.11	-1000
Atypical NF-kappaB pathway	0.0019	1	55	31	-0.02	0.037	1000	-1000	-0.1	-1000
IGF1 pathway	0.0019	1	110	57	-0.065	0.071	1000	-1000	-0.14	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0.0000	0	2	23	-0.001	0.062	1000	-1000	-0.11	-1000
TRAIL signaling pathway	0.0000	0	32	48	-0.002	0.07	1000	-1000	-0.095	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0.0000	0	0	27	0	0.039	1000	-1000	-0.082	-1000
Rapid glucocorticoid signaling	0.0000	0	16	20	-0.006	0.016	1000	-1000	-0.065	-1000
Arf1 pathway	0.0000	0	31	54	-0.01	0.043	1000	-1000	-0.078	-1000
Alternative NF-kappaB pathway	0.0000	0	10	13	-0.005	0.016	1000	-1000	-0.11	-1000
Total	NA	4180	224701	7203	-40	-990	131000	-131000	-14	-131000

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.011	0.099	-10000	0	-0.87	7	7
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.84	0.17	-10000	0	-0.87	513	513
CCND2	0.18	0.049	0.47	7	-10000	0	7
RB1	-0.2	0.051	-10000	0	-0.21	512	512
CDK4	0.22	0.052	0.22	512	-10000	0	512
CDK6	0.2	0.055	0.51	7	-0.18	1	8
G1/S progression	0.2	0.054	0.21	512	-10000	0	512

×

HIF-1-alpha transcription factor 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
PKM2	-0.98	0.53	-9999	-1.4	305	305
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.94	277	277
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.98	0.53	-9999	-1.4	301	301
AP1	-0.014	0.087	-9999	-0.56	13	13
ABCG2	-0.98	0.53	-9999	-1.4	310	310
HIF1A	-0.1	0.068	-9999	-0.89	2	2
TFF3	-0.99	0.53	-9999	-1.4	308	308
GATA2	-0.001	0.12	-9999	-0.74	13	13
AKT1	-0.093	0.053	-9999	-10000	0	0
response to hypoxia	-0.13	0.058	-9999	-10000	0	0
MCL1	-0.98	0.53	-9999	-1.4	300	300
NDRG1	-0.98	0.53	-9999	-1.4	301	301
SERPINE1	-1	0.56	-9999	-1.4	308	308
FECH	-0.98	0.53	-9999	-1.4	306	306
FURIN	-0.98	0.53	-9999	-1.4	301	301
NCOA2	-0.004	0.11	-9999	-0.74	11	11
EP300	-0.1	0.075	-9999	-0.36	7	7
HMOX1	-1	0.54	-9999	-1.4	308	308
BHLHE40	-0.98	0.53	-9999	-1.4	302	302
BHLHE41	-1.1	0.58	-9999	-1.5	320	320
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.08	0.056	-9999	-0.6	2	2
ENG	-0.059	0.064	-9999	-10000	0	0
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.98	0.53	-9999	-1.4	306	306
ABCB1	-0.3	0.42	-9999	-1.3	70	70
TFRC	-0.98	0.53	-9999	-1.4	306	306
CXCR4	-1.1	0.59	-9999	-1.5	325	325
TF	-1	0.58	-9999	-1.4	320	320
CITED2	-0.98	0.53	-9999	-1.4	301	301
HIF1A/ARNT	-1.3	0.85	-9999	-1.8	343	343
LDHA	-0.086	0.062	-9999	-0.85	2	2
ETS1	-0.98	0.53	-9999	-1.4	301	301
PGK1	-0.98	0.53	-9999	-1.4	302	302
NOS2	-0.98	0.53	-9999	-1.4	304	304
ITGB2	-1	0.56	-9999	-1.4	316	316
ALDOA	-0.98	0.53	-9999	-1.4	301	301
Cbp/p300/CITED2	-0.98	0.53	-9999	-1.4	302	302
FOS	-0.002	0.12	-9999	-0.75	13	13
HK2	-1.2	0.58	-9999	-1.5	393	393
SP1	0.021	0.029	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.1	10	10
HK1	-0.98	0.53	-9999	-1.4	299	299
NPM1	-0.98	0.53	-9999	-1.4	301	301
EGLN1	-0.98	0.53	-9999	-1.4	300	300
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.98	0.53	-9999	-1.4	305	305
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.092	0.17	-9999	-0.8	19	19
IGFBP1	-1	0.57	-9999	-1.4	312	312
VEGFA	-0.77	0.41	-9999	-1.2	240	240
HIF1A/JAB1	-0.055	0.047	-9999	-0.69	2	2
CP	-1.2	0.59	-9999	-1.5	386	386
CXCL12	-0.99	0.53	-9999	-1.4	309	309
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.98	0.53	-9999	-1.4	301	301
EGLN3	-1.3	0.51	-9999	-1.5	413	413
CA9	-1.3	0.48	-9999	-1.5	426	426
TERT	-1	0.55	-9999	-1.4	317	317
ENO1	-0.98	0.53	-9999	-1.4	300	300
PFKL	-0.98	0.53	-9999	-1.4	306	306
NCOA1	0.015	0.003	-9999	-10000	0	0
ADM	-1.1	0.57	-9999	-1.4	321	321
ARNT	-0.1	0.047	-9999	-10000	0	0
HNF4A	-0.042	0.21	-9999	-0.74	44	44
ADFP	-0.99	0.53	-9999	-1.3	340	340
SLC2A1	-0.63	0.34	-9999	-1	144	144
LEP	-1	0.55	-9999	-1.4	308	308
HIF1A/ARNT/Cbp/p300	-0.71	0.34	-9999	-0.94	302	302
EPO	-0.61	0.4	-9999	-1.1	187	187
CREBBP	-0.099	0.074	-9999	-0.36	2	2
HIF1A/ARNT/Cbp/p300/HDAC7	-0.75	0.38	-9999	-1	300	300
PFKFB3	-0.98	0.53	-9999	-1.4	301	301
NT5E	-0.98	0.53	-9999	-1.4	301	301

×

Nephrin/Neph1 signaling in the kidney podocyte

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
positive regulation of NF-kappaB transcription factor activity	0.48	0.26	0.62	415	-10000	0	415
KIRREL	-0.056	0.11	-10000	0	-0.81	10	10
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.48	0.26	-10000	0	-0.62	415	415
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.52	0.31	-10000	0	-0.83	230	230
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.41	0.26	-10000	0	-0.66	230	230
FYN	-0.49	0.3	-10000	0	-0.79	230	230
mol:Ca2+	-0.52	0.3	-10000	0	-0.82	230	230
mol:DAG	-0.52	0.3	-10000	0	-0.83	230	230
NPHS2	-0.4	0.38	-10000	0	-0.8	254	254
mol:IP3	-0.52	0.3	-10000	0	-0.83	230	230
regulation of endocytosis	-0.46	0.28	-10000	0	-0.74	230	230
Nephrin/NEPH1/podocin/Cholesterol	-0.53	0.31	-10000	0	-0.65	434	434
establishment of cell polarity	-0.48	0.26	-10000	0	-0.62	415	415
Nephrin/NEPH1/podocin/NCK1-2	-0.48	0.29	-10000	0	-0.78	230	230
Nephrin/NEPH1/beta Arrestin2	-0.47	0.28	-10000	0	-0.76	230	230
NPHS1	-0.6	0.32	-10000	0	-0.78	412	412
Nephrin/NEPH1/podocin	-0.5	0.29	-10000	0	-0.8	230	230
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.014	0.033	-10000	0	-0.74	1	1
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.52	0.31	-10000	0	-0.83	230	230
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.52	0.31	-10000	0	-0.83	230	230
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.48	0.3	-10000	0	-0.78	230	230
cytoskeleton organization	-0.52	0.32	-10000	0	-0.84	230	230
Nephrin/NEPH1	-0.36	0.2	-10000	0	-0.46	415	415
Nephrin/NEPH1/ZO-1	-0.39	0.21	-10000	0	-0.54	230	230

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.34	0.33	-10000	0	-0.68	237	237
FYN	-0.41	0.49	-10000	0	-0.91	245	245
LAT/GRAP2/SLP76	-0.36	0.38	-10000	0	-0.75	244	244
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.25	0.29	-10000	0	-0.54	244	244
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.079	0.072	-10000	0	-0.19	83	83
MAP3K8	0.012	0.054	-10000	0	-0.86	2	2
mol:Ca2+	-0.11	0.045	-10000	0	-0.14	348	348
integrin-mediated signaling pathway	-0.02	0.1	-10000	0	-0.58	18	18
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.41	0.45	-10000	0	-0.85	255	255
TRPV6	-0.66	0.26	-10000	0	-0.76	461	461
CD28	-0.057	0.23	-10000	0	-0.87	40	40
SHC1	-0.44	0.49	-10000	0	-0.93	249	249
receptor internalization	-0.51	0.56	-10000	0	-1.1	253	253
PRF1	-0.48	0.59	-10000	0	-1.1	235	235
KRAS	0.016	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.18	0.22	-10000	0	-0.41	226	226
LAT	-0.5	0.53	-10000	0	-1	262	262
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	241	241
CD3E	-0.34	0.44	-10000	0	-0.87	215	215
CD3G	-0.33	0.43	-10000	0	-0.87	205	205
RASGRP2	-0.023	0.029	-10000	0	-0.14	3	3
RASGRP1	-0.23	0.27	-10000	0	-0.51	238	238
HLA-A	0.005	0.055	-10000	0	-0.87	2	2
RASSF5	-0.014	0.16	-10000	0	-0.86	18	18
RAP1A/GTP/RAPL	-0.02	0.11	-10000	0	-0.59	18	18
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.036	0.081	-10000	0	-0.13	4	4
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.15	0.13	-10000	0	-0.34	103	103
PRKCA	-0.14	0.17	-10000	0	-0.31	214	214
GRAP2	-0.042	0.22	-10000	0	-0.86	35	35
mol:IP3	-0.16	0.34	0.26	165	-0.5	225	390
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.52	0.63	-10000	0	-1.1	260	260
ORAI1	0.33	0.13	0.38	460	-10000	0	460
CSK	-0.45	0.51	-10000	0	-0.97	248	248
B7 family/CD28	-0.51	0.51	-10000	0	-1	247	247
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.56	0.62	-10000	0	-1.2	255	255
PTPN6	-0.43	0.52	-10000	0	-0.98	243	243
VAV1	-0.48	0.53	-10000	0	-1	258	258
Monovalent TCR/CD3	-0.45	0.53	-10000	0	-0.99	242	242
CBL	0.014	0.033	-10000	0	-0.74	1	1
LCK	-0.44	0.53	-10000	0	-0.98	243	243
PAG1	-0.46	0.51	-10000	0	-0.97	249	249
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.53	0.63	-10000	0	-1.2	247	247
CD80	-0.18	0.36	-10000	0	-0.87	117	117
CD86	-0.13	0.32	-10000	0	-0.87	82	82
PDK1/CARD11/BCL10/MALT1	-0.18	0.17	-10000	0	-0.41	117	117
HRAS	0.014	0.038	-10000	0	-0.86	1	1
GO:0035030	-0.35	0.41	-10000	0	-0.77	247	247
CD8A	-0.38	0.44	-10000	0	-0.87	236	236
CD8B	-0.3	0.42	-10000	0	-0.87	187	187
PTPRC	-0.083	0.27	-10000	0	-0.87	56	56
PDK1/PKC theta	-0.32	0.36	-10000	0	-0.68	246	246
CSK/PAG1	-0.44	0.49	-10000	0	-0.95	242	242
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.003	0.041	-10000	0	-0.68	2	2
GRAP2/SLP76	-0.43	0.44	-10000	0	-0.88	246	246
STIM1	0.17	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.064	0.11	-10000	0	-0.19	8	8
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.59	0.65	-10000	0	-1.2	253	253
mol:DAG	-0.2	0.26	-10000	0	-0.46	239	239
RAP1A/GDP	-0.014	0.035	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.41	-10000	0	-0.87	174	174
cytotoxic T cell degranulation	-0.44	0.55	-10000	0	-0.99	246	246
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.31	0.35	-10000	0	-0.66	253	253
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.26	0.44	0.3	108	-0.7	238	346
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.47	0.44	-10000	0	-0.86	296	296
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.38	0.35	-10000	0	-0.73	246	246
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.49	0.56	-10000	0	-1.1	242	242
CARD11	-0.17	0.36	-10000	0	-0.86	110	110
PRKCB	-0.14	0.17	-10000	0	-0.31	212	212
PRKCE	-0.14	0.17	-10000	0	-0.32	187	187
PRKCQ	-0.39	0.42	-10000	0	-0.8	254	254
LCP2	-0.038	0.21	-10000	0	-0.86	33	33
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.2	0.24	-10000	0	-0.45	243	243
IKK complex	-0.028	0.084	-10000	0	-10000	0	0
RAS family/GDP	-0.011	0.012	-10000	0	-0.11	1	1
MAP3K14	-0.13	0.18	-10000	0	-0.32	151	151
PDPK1	-0.23	0.27	-10000	0	-0.5	239	239
TCR/CD3/MHC I/CD8/Fyn	-0.55	0.65	-10000	0	-1.2	244	244

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.65	0.13	-10000	0	-0.68	513	513
TP53	-0.17	0.037	-10000	0	-10000	0	0
Senescence	-0.17	0.037	-10000	0	-10000	0	0
Apoptosis	-0.17	0.037	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.31	0.062	0.32	513	-10000	0	513
MDM4	0.014	0.038	-10000	0	-0.86	1	1

×

Syndecan-4-mediated signaling events

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
PTK2	-0.054	0.14	-9999	-0.54	39	39
Syndecan-4/Syndesmos	-0.46	0.39	-9999	-0.84	236	236
positive regulation of JNK cascade	-0.53	0.37	-9999	-0.84	287	287
Syndecan-4/ADAM12	-0.56	0.49	-9999	-1	260	260
CCL5	-0.35	0.43	-9999	-0.86	224	224
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.049	0.23	-9999	-0.86	39	39
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.36	0.37	-9999	-0.72	274	274
ADAM12	-0.22	0.39	-9999	-0.86	142	142
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.1	0.071	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.47	0.4	-9999	-0.86	238	238
Syndecan-4/CXCL12/CXCR4	-0.59	0.43	-9999	-0.94	287	287
Syndecan-4/Laminin alpha3	-0.46	0.39	-9999	-0.85	241	241
MDK	-0.049	0.23	-9999	-0.86	39	39
Syndecan-4/FZD7	-0.46	0.39	-9999	-0.84	237	237
Syndecan-4/Midkine	-0.49	0.41	-9999	-0.88	249	249
FZD7	0.014	0.033	-9999	-0.74	1	1
Syndecan-4/FGFR1/FGF	-0.43	0.33	-9999	-0.76	239	239
THBS1	0.011	0.057	-9999	-0.74	3	3
integrin-mediated signaling pathway	-0.44	0.36	-9999	-0.79	242	242
positive regulation of MAPKKK cascade	-0.53	0.37	-9999	-0.84	287	287
Syndecan-4/TACI	-0.5	0.42	-9999	-0.9	249	249
CXCR4	-0.29	0.42	-9999	-0.86	186	186
cell adhesion	-0.007	0.12	-9999	-0.51	15	15
Syndecan-4/Dynamin	-0.46	0.39	-9999	-0.84	236	236
Syndecan-4/TSP1	-0.46	0.39	-9999	-0.84	238	238
Syndecan-4/GIPC	-0.46	0.39	-9999	-0.84	237	237
Syndecan-4/RANTES	-0.64	0.46	-9999	-1	294	294
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.006	0.13	-9999	-0.75	15	15
LAMA3	0.004	0.1	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.066	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.46	0.39	-9999	-0.84	237	237
TFPI	0.002	0.11	-9999	-0.81	9	9
F2	-0.32	0.42	-9999	-0.87	199	199
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.66	39	39
positive regulation of cell adhesion	-0.45	0.38	-9999	-0.82	243	243
ACTN1	0.013	0.05	-9999	-0.8	2	2
TNC	-0.004	0.12	-9999	-0.74	14	14
Syndecan-4/CXCL12	-0.47	0.39	-9999	-0.84	242	242
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	-0.001	0.11	-9999	-0.74	12	12
TNFRSF13B	-0.072	0.26	-9999	-0.86	52	52
FGF2	0.008	0.075	-9999	-0.77	5	5
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.47	0.39	-9999	-0.85	236	236
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.039	0.22	-9999	-0.83	39	39
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.045	-9999	-0.85	1	1
vasculogenesis	-0.44	0.36	-9999	-0.79	238	238
SDC4	-0.5	0.43	-9999	-0.93	236	236
Syndecan-4/Tenascin C	-0.47	0.39	-9999	-0.84	242	242
Syndecan-4/PI-4-5-P2/PKC alpha	-0.079	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.46	0.39	-9999	-0.84	236	236
MMP9	-0.4	0.44	-9999	-0.86	251	251
Rac1/GTP	-0.008	0.12	-9999	-0.53	15	15
cytoskeleton organization	-0.43	0.36	-9999	-0.79	236	236
GIPC1	0.014	0.033	-9999	-0.74	1	1
Syndecan-4/TFPI	-0.47	0.39	-9999	-0.85	240	240

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.24	0.32	-9999	-0.68	163	163
STMN1	-0.29	0.34	-9999	-0.66	248	248
Aurora B/RasGAP/Survivin	-0.4	0.48	-9999	-0.87	253	253
Chromosomal passenger complex/Cul3 protein complex	-0.16	0.23	-9999	-0.49	151	151
BIRC5	-0.25	0.41	-9999	-0.89	154	154
DES	-0.38	0.34	-9999	-0.6	316	316
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	249	249
Aurora B/TACC1	-0.26	0.3	-9999	-0.57	248	248
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	248	248
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.072	0.09	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.4	0.5	-9999	-0.89	253	253
Cul3 protein complex	-0.015	0.083	-9999	-0.47	17	17
KIF2C	-0.15	0.18	-9999	-0.34	200	200
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.38	0.44	-9999	-0.86	238	238
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	249	249
SEPT1	-0.096	0.29	-9999	-0.86	68	68
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.18	0.24	-9999	-0.45	195	195
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.004	-9999	-10000	0	0
H3F3B	-0.17	0.21	-9999	-0.39	248	248
AURKB	-0.4	0.44	-9999	-0.87	248	248
AURKC	0.012	0.054	-9999	-0.86	2	2
CDCA8	-0.026	0.17	-9999	-0.89	20	20
cytokinesis	-0.34	0.37	-9999	-0.75	216	216
Aurora B/Septin1	-0.36	0.42	-9999	-0.83	210	210
AURKA	0.002	0.094	-9999	-0.87	6	6
INCENP	0.008	0.009	-9999	-10000	0	0
KLHL13	-0.008	0.13	-9999	-0.74	17	17
BUB1	-0.37	0.44	-9999	-0.86	232	232
hSgo1/Aurora B/Survivin	-0.39	0.48	-9999	-0.85	254	254
EVI5	0.01	0.008	-9999	-10000	0	0
RhoA/GTP	-0.31	0.34	-9999	-0.72	194	194
SGOL1	-0.014	0.16	-9999	-0.86	18	18
CENPA	-0.29	0.35	-9999	-0.63	255	255
NCAPG	-0.27	0.41	-9999	-0.86	176	176
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	248	248
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	248	248
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.13	0.33	-9999	-0.86	89	89
NPM1	-0.21	0.24	-9999	-0.47	248	248
RASA1	0.014	0.033	-9999	-0.74	1	1
KLHL9	0.016	0	-9999	-10000	0	0
mitotic prometaphase	-0.01	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.3	0.34	-9999	-0.66	248	248
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.34	0.38	-9999	-0.78	201	201
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.21	0.24	-9999	-0.47	248	248
MYLK	-0.17	0.21	-9999	-0.39	248	248
KIF23	-0.006	0.11	-9999	-0.88	8	8
VIM	-0.34	0.4	-9999	-0.73	263	263
RACGAP1	0.004	0.055	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.21	0.24	-9999	-0.47	248	248
Chromosomal passenger complex	-0.34	0.41	-9999	-0.76	240	240
Chromosomal passenger complex/EVI5	-0.36	0.48	-9999	-1	149	149
TACC1	0.016	0	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

FOXA2 and FOXA3 transcription factor networks

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	-0.44	0.47	-9999	-1.2	113	113
PCK1	-0.93	0.71	-9999	-1.4	310	310
HNF4A	-0.57	0.57	-9999	-1.4	138	138
KCNJ11	-0.44	0.5	-9999	-1.3	100	100
AKT1	-0.17	0.18	-9999	-10000	0	0
response to starvation	-0.02	0.038	-9999	-10000	0	0
DLK1	-0.55	0.57	-9999	-1.3	165	165
NKX2-1	-0.056	0.21	-9999	-0.84	4	4
ACADM	-0.44	0.47	-9999	-1.1	126	126
TAT	-0.51	0.35	-9999	-0.92	168	168
CEBPB	-0.024	0.14	-9999	-0.92	12	12
CEBPA	-0.019	0.12	-9999	-0.9	10	10
TTR	-0.88	0.48	-9999	-1.2	336	336
PKLR	-0.5	0.56	-9999	-1.3	124	124
APOA1	-0.55	0.56	-9999	-1.3	136	136
CPT1C	-0.44	0.47	-9999	-1.2	115	115
ALAS1	-0.17	0.19	-9999	-10000	0	0
TFRC	-0.62	0.42	-9999	-1	225	225
FOXF1	-0.001	0.12	-9999	-0.84	10	10
NF1	0.025	0.001	-9999	-10000	0	0
HNF1A (dimer)	-0.003	0.085	-9999	-0.79	5	5
CPT1A	-0.44	0.47	-9999	-1.2	110	110
HMGCS1	-0.44	0.47	-9999	-1.1	121	121
NR3C1	0.003	0.065	-9999	-0.96	1	1
CPT1B	-0.46	0.49	-9999	-1.2	120	120
chromatin remodeling	0	0	-9999	-10000	0	0
SP1	0.017	0.005	-9999	-10000	0	0
GCK	-0.45	0.48	-9999	-1.2	118	118
CREB1	-0.028	0.066	-9999	-10000	0	0
IGFBP1	-0.31	0.42	-9999	-1	120	120
PDX1	-0.19	0.22	-9999	-1	6	6
UCP2	-0.44	0.47	-9999	-1.2	114	114
ALDOB	-0.94	0.62	-9999	-1.3	361	361
AFP	-0.7	0.49	-9999	-0.97	327	327
BDH1	-0.59	0.57	-9999	-1.2	184	184
HADH	-0.43	0.48	-9999	-1.2	102	102
F2	-0.65	0.62	-9999	-1.3	191	191
HNF1A	-0.003	0.086	-9999	-0.79	5	5
G6PC	-0.81	0.66	-9999	-1.5	255	255
SLC2A2	-0.32	0.48	-9999	-1.7	48	48
INS	0.009	0.055	-9999	-10000	0	0
FOXA1	-0.36	0.38	-9999	-0.97	134	134
FOXA3	-0.61	0.37	-9999	-0.9	296	296
FOXA2	-0.51	0.56	-9999	-1.3	123	123
ABCC8	-0.44	0.49	-9999	-1.2	101	101
ALB	-1.2	0.48	-9999	-1.4	461	461

×

IL12-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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.16	0.26	-10000	0	-0.52	137	137
TBX21	-0.54	0.67	-10000	0	-1.2	246	246
B2M	0.011	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.021	-10000	0	-10000	0	0
IL12RB1	-0.26	0.42	-10000	0	-0.9	160	160
GADD45B	-0.29	0.42	-10000	0	-0.8	170	170
IL12RB2	-0.11	0.31	-10000	0	-0.87	76	76
GADD45G	-0.3	0.43	-10000	0	-0.79	187	187
natural killer cell activation	-0.01	0.03	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.003	0.1	-10000	0	-0.87	7	7
IL2RA	-0.16	0.35	-10000	0	-0.86	105	105
IFNG	-0.38	0.44	-10000	0	-0.86	239	239
STAT3 (dimer)	-0.37	0.46	-10000	0	-0.86	217	217
HLA-DRB5	-0.036	0.21	-10000	0	-0.86	32	32
FASLG	-0.6	0.7	-10000	0	-1.3	239	239
NF kappa B2 p52/RelB	-0.51	0.53	-10000	0	-1.1	220	220
CD4	0.002	0.11	-10000	0	-0.86	9	9
SOCS1	0.006	0.093	-10000	0	-0.86	6	6
EntrezGene:6955	-0.002	0.009	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	241	241
CD3E	-0.34	0.43	-10000	0	-0.87	215	215
CD3G	-0.32	0.43	-10000	0	-0.87	205	205
IL12Rbeta2/JAK2	-0.084	0.25	-10000	0	-0.68	76	76
CCL3	-0.48	0.63	-10000	0	-1.2	198	198
CCL4	-0.5	0.66	-10000	0	-1.2	220	220
HLA-A	0.007	0.054	-10000	0	-0.86	2	2
IL18/IL18R	-0.12	0.3	-10000	0	-0.6	149	149
NOS2	-0.36	0.49	-10000	0	-0.92	191	191
IL12/IL12R/TYK2/JAK2/SPHK2	-0.16	0.26	-10000	0	-0.56	100	100
IL1R1	-0.44	0.59	-10000	0	-1.1	190	190
IL4	0.013	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.021	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.009	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.69	0.81	-10000	0	-1.4	262	262
RAB7A	-0.23	0.37	-10000	0	-0.69	135	135
lysosomal transport	-0.22	0.36	-10000	0	-0.65	136	136
FOS	-0.37	0.5	-10000	0	-0.94	207	207
STAT4 (dimer)	-0.4	0.53	-10000	0	-0.96	217	217
STAT5A (dimer)	-0.65	0.61	-10000	0	-1.2	255	255
GZMA	-0.56	0.7	-10000	0	-1.3	234	234
GZMB	-0.53	0.67	-10000	0	-1.2	236	236
HLX	-0.091	0.29	-10000	0	-0.86	65	65
LCK	-0.51	0.69	-10000	0	-1.2	222	222
TCR/CD3/MHC II/CD4	-0.37	0.47	-10000	0	-0.86	232	232
IL2/IL2R	-0.41	0.42	-10000	0	-0.71	308	308
MAPK14	-0.3	0.44	-10000	0	-0.79	189	189
CCR5	-0.45	0.59	-10000	0	-1.1	204	204
IL1B	0.002	0.095	-10000	0	-0.86	6	6
STAT6	-0.083	0.15	-10000	0	-10000	0	0
STAT4	-0.035	0.21	-10000	0	-0.86	31	31
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.014	0.038	-10000	0	-0.86	1	1
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.092	0.29	-10000	0	-0.89	62	62
CD8A	-0.38	0.44	-10000	0	-0.87	236	236
CD8B	-0.3	0.42	-10000	0	-0.87	187	187
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.16	0.26	0.51	137	-10000	0	137
IL2RB	-0.44	0.44	-10000	0	-0.86	274	274
proteasomal ubiquitin-dependent protein catabolic process	-0.36	0.47	-10000	0	-0.85	217	217
IL2RG	-0.04	0.21	-10000	0	-0.86	34	34
IL12	-0.07	0.24	-10000	0	-0.71	63	63
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.27	0.41	-10000	0	-0.87	174	174
IL2	-0.007	0.12	-10000	0	-0.86	10	10
SPHK2	0.013	0.046	-10000	0	-0.74	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.046	-10000	0	-0.91	1	1
IL12/IL12R/TYK2/JAK2	-0.57	0.77	-10000	0	-1.4	222	222
MAP2K3	-0.3	0.44	-10000	0	-0.8	191	191
RIPK2	0.014	0.038	-10000	0	-0.86	1	1
MAP2K6	-0.3	0.44	-10000	0	-0.8	191	191
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.01	0.076	-10000	0	-0.86	4	4
IL18RAP	-0.21	0.39	-10000	0	-0.87	137	137
IL12Rbeta1/TYK2	-0.2	0.34	-10000	0	-0.72	160	160
EOMES	-0.29	0.37	-10000	0	-0.74	215	215
STAT1 (dimer)	-0.44	0.51	-10000	0	-0.95	239	239
T cell proliferation	-0.26	0.37	-10000	0	-0.66	200	200
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.002	0.1	-10000	0	-0.8	8	8
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.36	0.33	-10000	0	-0.74	201	201
ATF2	-0.27	0.41	-10000	0	-0.75	167	167

×

Glypican 1 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
GPC1/FGF2 dimer/FGFR1 dimer	-0.006	0.052	-10000	0	-0.49	6	6
fibroblast growth factor receptor signaling pathway	-0.005	0.052	-10000	0	-0.49	6	6
LAMA1	-0.006	0.13	-10000	0	-0.75	15	15
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.56	119	119
SMAD2	0.045	0.02	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.021	-10000	0	-0.48	1	1
GPC1/Laminin alpha1	-0.017	0.096	-10000	0	-0.56	16	16
TDGF1	-0.56	0.32	-10000	0	-0.74	401	401
CRIPTO/GPC1	-0.42	0.24	-10000	0	-0.56	401	401
APP/GPC1	-0.002	0.034	-10000	0	-0.56	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.35	0.22	-10000	0	-0.47	401	401
FLT1	0.007	0.085	-10000	0	-0.86	5	5
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.02	-10000	0	-0.47	1	1
SERPINC1	-0.053	0.22	-10000	0	-0.76	46	46
FYN	-0.35	0.22	-10000	0	-0.47	401	401
FGR	-0.35	0.22	-10000	0	-0.48	401	401
positive regulation of MAPKKK cascade	-0.36	0.24	-10000	0	-0.67	66	66
SLIT2	-0.15	0.32	-10000	0	-0.74	118	118
GPC1/NRG	-0.019	0.1	-10000	0	-0.56	18	18
NRG1	-0.008	0.13	-10000	0	-0.74	17	17
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.26	0.3	-10000	0	-0.58	240	240
LYN	-0.35	0.22	-10000	0	-0.47	401	401
mol:Spermine	0.014	0.025	-10000	0	-0.57	1	1
cell growth	-0.005	0.052	-10000	0	-0.49	6	6
BMP signaling pathway	-0.014	0.033	0.74	1	-10000	0	1
SRC	-0.35	0.22	-10000	0	-0.47	401	401
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.06	0.24	-10000	0	-0.86	43	43
GPC1	0.014	0.033	-10000	0	-0.74	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.38	0.44	-10000	0	-0.86	239	239
BLK	-0.38	0.26	-10000	0	-0.51	406	406
HCK	-0.38	0.24	-10000	0	-0.5	412	412
FGF2	0.008	0.075	-10000	0	-0.77	5	5
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.007	0.084	-10000	0	-0.86	5	5
TGFBR2	0.016	0	-10000	0	-10000	0	0
cell death	-0.002	0.034	-10000	0	-0.55	2	2
ATIII/GPC1	-0.05	0.16	-10000	0	-0.57	47	47
PLA2G2A/GPC1	-0.055	0.18	-10000	0	-0.66	44	44
LCK	-0.37	0.24	-10000	0	-0.49	409	409
neuron differentiation	-0.019	0.1	-10000	0	-0.55	18	18
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.033	-10000	0	-0.74	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

FOXM1 transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.18	0.67	-10000	0	-1.2	119	119
PLK1	-0.098	0.4	-10000	0	-0.8	129	129
BIRC5	-0.13	0.43	-10000	0	-0.79	154	154
HSPA1B	-0.18	0.67	-10000	0	-1.2	119	119
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.19	0.68	-10000	0	-1.2	121	121
FOXM1	-0.37	0.99	-10000	0	-1.9	128	128
XRCC1	-0.18	0.67	-10000	0	-1.2	117	117
FOXM1B/p19	-0.49	0.49	0.5	1	-1.2	133	134
Cyclin D1/CDK4	-0.18	0.61	-10000	0	-1.1	106	106
CDC2	-0.21	0.72	-10000	0	-1.3	127	127
TGFA	-0.16	0.6	-10000	0	-1.1	108	108
SKP2	-0.18	0.67	-10000	0	-1.2	120	120
CCNE1	0.002	0.11	-10000	0	-0.88	8	8
CKS1B	-0.18	0.67	-10000	0	-1.2	119	119
RB1	-0.19	0.26	-10000	0	-0.7	91	91
FOXM1C/SP1	-0.28	0.77	-10000	0	-1.5	124	124
AURKB	-0.25	0.46	-10000	0	-0.74	248	248
CENPF	-0.21	0.71	-10000	0	-1.3	121	121
CDK4	0.02	0.022	-10000	0	-10000	0	0
MYC	-0.15	0.6	-10000	0	-1.1	118	118
CHEK2	0.037	0.075	-10000	0	-0.91	2	2
ONECUT1	-0.19	0.65	-10000	0	-1.2	120	120
CDKN2A	-0.82	0.17	-10000	0	-0.86	513	513
LAMA4	-0.28	0.69	-10000	0	-1.3	126	126
FOXM1B/HNF6	-0.27	0.79	-10000	0	-1.5	120	120
FOS	-0.2	0.68	-10000	0	-1.2	122	122
SP1	0.016	0.005	-10000	0	-10000	0	0
CDC25B	-0.18	0.68	-10000	0	-1.2	119	119
response to radiation	0.014	0.05	-10000	0	-10000	0	0
CENPB	-0.18	0.67	-10000	0	-1.2	119	119
CENPA	-0.28	0.77	-10000	0	-1.4	146	146
NEK2	-0.24	0.75	-10000	0	-1.4	134	134
HIST1H2BA	-0.19	0.67	-10000	0	-1.2	119	119
CCNA2	-0.15	0.35	-10000	0	-0.88	102	102
EP300	0.014	0.033	-10000	0	-0.74	1	1
CCNB1/CDK1	-0.27	0.8	-10000	0	-1.5	123	123
CCNB2	-0.24	0.75	-10000	0	-1.4	131	131
CCNB1	-0.21	0.72	-10000	0	-1.3	120	120
ETV5	-0.18	0.67	-10000	0	-1.2	119	119
ESR1	-0.19	0.68	-10000	0	-1.2	120	120
CCND1	-0.17	0.63	-10000	0	-1.1	108	108
GSK3A	0.036	0.041	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.08	0.28	-10000	0	-0.64	103	103
CDK2	0.015	0.015	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.015	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.42	0.58	-10000	0	-1.4	134	134
GAS1	-0.23	0.7	-10000	0	-1.2	133	133
MMP2	-0.19	0.68	-10000	0	-1.2	119	119
RB1/FOXM1C	-0.21	0.67	-10000	0	-1.2	118	118
CREBBP	0.016	0	-10000	0	-10000	0	0

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.27	0.37	-9999	-0.74	205	205
PDGF/PDGFRA/CRKL	-0.21	0.26	-9999	-0.54	205	205
positive regulation of JUN kinase activity	-0.16	0.2	-9999	-0.52	1	1
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.22	0.27	-9999	-0.55	208	208
AP1	-0.16	0.24	-9999	-1.2	13	13
mol:IP3	-0.19	0.29	-9999	-0.55	205	205
PLCG1	-0.19	0.29	-9999	-0.55	205	205
PDGF/PDGFRA/alphaV Integrin	-0.21	0.26	-9999	-0.54	205	205
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.29	-9999	-0.55	205	205
CAV3	0	0.065	-9999	-0.86	3	3
CAV1	-0.045	0.22	-9999	-0.86	37	37
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/Shf	-0.21	0.26	-9999	-0.54	206	206
FOS	-0.12	0.27	-9999	-1.2	13	13
JUN	-0.013	0.017	-9999	-10000	0	0
oligodendrocyte development	-0.21	0.26	-9999	-0.54	205	205
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:DAG	-0.19	0.29	-9999	-0.55	205	205
PDGF/PDGFRA	-0.27	0.37	-9999	-0.74	205	205
actin cytoskeleton reorganization	-0.21	0.26	-9999	-0.54	205	205
SRF	0.034	0.009	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
PI3K	-0.18	0.22	-9999	-0.45	206	206
PDGF/PDGFRA/Crk/C3G	-0.17	0.22	-9999	-0.45	205	205
JAK1	-0.19	0.28	-9999	-0.54	205	205
ELK1/SRF	-0.15	0.19	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.033	-9999	-0.74	1	1
CSNK2A1	0.017	0.022	-9999	-10000	0	0
GO:0007205	-0.19	0.29	-9999	-0.56	205	205
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/SHB	-0.21	0.26	-9999	-0.54	205	205
PDGF/PDGFRA/Caveolin-1	-0.25	0.29	-9999	-0.57	234	234
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.26	-9999	-0.49	205	205
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PDGF/PDGFRA/Crk	-0.21	0.26	-9999	-0.54	205	205
JAK-STAT cascade	-0.19	0.28	-9999	-0.54	205	205
cell proliferation	-0.21	0.26	-9999	-0.54	206	206

×

amb2 Integrin 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
alphaM/beta2 Integrin/proMMP-2	-0.14	0.28	-9999	-0.67	109	109
alphaM/beta2 Integrin/GPIbA	-0.13	0.28	-9999	-0.67	104	104
alphaM/beta2 Integrin/proMMP-9	-0.39	0.43	-9999	-0.74	281	281
PLAUR	-0.029	0.19	-9999	-0.86	27	27
HMGB1	0.015	0.013	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.13	0.28	-9999	-0.67	103	103
AGER	-0.14	0.34	-9999	-0.86	95	95
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.04	0.22	-9999	-0.86	34	34
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.23	0.33	-9999	-0.94	62	62
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	251	251
CYR61	0.007	0.08	-9999	-0.74	6	6
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.25	0.2	-9999	-0.56	115	115
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.02	0.16	-9999	-0.74	25	25
MYH2	-0.34	0.26	-9999	-0.64	191	191
MST1R	0.005	0.09	-9999	-0.78	7	7
leukocyte activation during inflammatory response	-0.27	0.35	-9999	-0.63	223	223
APOB	-0.26	0.4	-9999	-0.86	169	169
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.004	0.098	-9999	-0.84	7	7
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.033	-9999	-0.74	1	1
alphaM/beta2 Integrin/CTGF	-0.14	0.29	-9999	-0.68	105	105
alphaM/beta2 Integrin	-0.3	0.25	-9999	-0.53	230	230
JAM3 homodimer	0.016	0	-9999	-10000	0	0
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	-0.002	0.12	-9999	-0.86	11	11
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.3	0.24	-9999	-0.52	230	230
cell adhesion	-0.13	0.28	-9999	-0.67	104	104
NFKB1	-0.18	0.36	-9999	-0.94	63	63
THY1	0.014	0.033	-9999	-0.74	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.19	0.28	-9999	-0.59	170	170
alphaM/beta2 Integrin/LRP/tPA	-0.13	0.27	-9999	-0.62	105	105
IL6	-0.2	0.41	-9999	-0.91	101	101
ITGB2	-0.15	0.34	-9999	-0.86	100	100
elevation of cytosolic calcium ion concentration	-0.15	0.29	-9999	-0.64	121	121
alphaM/beta2 Integrin/JAM2/JAM3	-0.12	0.26	-9999	-0.62	103	103
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.13	0.28	-9999	-0.85	41	41
alphaM/beta2 Integrin/uPA/Plg	-0.34	0.34	-9999	-0.85	109	109
RhoA/GTP	-0.36	0.27	-9999	-0.68	190	190
positive regulation of phagocytosis	-0.25	0.27	-9999	-0.7	107	107
Ron/MSP	-0.017	0.1	-9999	-0.62	15	15
alphaM/beta2 Integrin/uPAR/uPA	-0.15	0.3	-9999	-0.64	121	121
alphaM/beta2 Integrin/uPAR	-0.16	0.32	-9999	-0.7	120	120
PLAU	0.003	0.098	-9999	-0.74	9	9
PLAT	-0.004	0.12	-9999	-0.74	14	14
actin filament polymerization	-0.33	0.24	-9999	-0.6	191	191
MST1	0.003	0.1	-9999	-0.85	8	8
alphaM/beta2 Integrin/lipoprotein(a)	-0.27	0.36	-9999	-0.64	223	223
TNF	-0.15	0.34	-9999	-0.84	67	67
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.14	0.28	-9999	-0.66	108	108
fibrinolysis	-0.34	0.33	-9999	-0.84	109	109
HCK	-0.032	0.2	-9999	-0.86	29	29
dendritic cell antigen processing and presentation	-0.3	0.24	-9999	-0.52	230	230
VTN	-0.1	0.28	-9999	-0.75	82	82
alphaM/beta2 Integrin/CYR61	-0.14	0.28	-9999	-0.66	109	109
LPA	0.003	0.066	-9999	-0.86	3	3
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.37	0.4	-9999	-0.69	282	282
FN1	-0.049	0.23	-9999	-0.86	39	39
alphaM/beta2 Integrin/Thy1	-0.13	0.28	-9999	-0.67	104	104
MPO	-0.013	0.15	-9999	-0.86	17	17
KNG1	-0.55	0.32	-9999	-0.74	396	396
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.33	0.26	-9999	-0.63	181	181
ELA2	0	0	-9999	-10000	0	0
PLG	-0.38	0.38	-9999	-0.74	274	274
CTGF	0.006	0.086	-9999	-0.74	7	7
alphaM/beta2 Integrin/Hck	-0.16	0.35	-9999	-0.79	107	107
ITGAM	-0.021	0.18	-9999	-0.86	22	22
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.17	0.34	-9999	-0.74	111	111
HP	-0.2	0.38	-9999	-0.86	133	133
leukocyte adhesion	-0.18	0.27	-9999	-0.82	51	51
SELP	-0.02	0.16	-9999	-0.74	25	25

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.48	-10000	0	-1.2	114	114
STAT6 (cleaved dimer)	-0.58	0.49	-10000	0	-1.2	180	180
IGHG1	-0.17	0.18	-10000	0	-0.69	11	11
IGHG3	-0.48	0.46	-10000	0	-1.1	136	136
AKT1	-0.28	0.33	-10000	0	-0.84	86	86
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.24	0.31	-10000	0	-0.81	89	89
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.8	65	65
THY1	-0.48	0.48	-10000	0	-1.2	114	114
MYB	-0.21	0.39	-10000	0	-0.86	139	139
HMGA1	0.014	0.038	-10000	0	-0.86	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.39	0.42	-10000	0	-0.96	131	131
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.8	65	65
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.009	0.076	-10000	0	-0.86	4	4
SOCS5	0.026	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.48	-10000	0	-1.2	153	153
SOCS1	-0.33	0.34	-10000	0	-0.81	82	82
SOCS3	-0.3	0.34	-10000	0	-0.9	78	78
FCER2	-0.41	0.44	-10000	0	-1.1	85	85
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.5	0.5	-10000	0	-1.2	123	123
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.22	0.28	-10000	0	-0.79	54	54
T cell proliferation	-0.5	0.51	-10000	0	-1.2	130	130
IL4R/JAK1	-0.48	0.47	-10000	0	-1.2	114	114
EGR2	-0.49	0.5	-10000	0	-1.2	111	111
JAK2	0.006	0.023	-10000	0	-10000	0	0
JAK3	-0.16	0.35	-10000	0	-0.86	107	107
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
JAK1	0.007	0.015	-10000	0	-10000	0	0
COL1A2	-0.21	0.3	-10000	0	-0.89	67	67
CCL26	-0.49	0.49	-10000	0	-1.2	114	114
IL4R	-0.51	0.51	-10000	0	-1.2	117	117
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.56	0.56	-10000	0	-1.3	141	141
IL13RA1	0.006	0.023	-10000	0	-10000	0	0
IRF4	-0.27	0.42	-10000	0	-0.96	127	127
ARG1	-0.18	0.26	-10000	0	-0.76	52	52
CBL	-0.36	0.4	-10000	0	-0.94	116	116
GTF3A	0.01	0.03	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
IL13RA1/JAK2	-0.007	0.043	-10000	0	-10000	0	0
IRF4/BCL6	-0.26	0.37	-10000	0	-0.93	115	115
CD40LG	-0.078	0.29	-10000	0	-0.91	57	57
MAPK14	-0.35	0.39	-10000	0	-0.94	113	113
mitosis	-0.26	0.31	-10000	0	-0.78	86	86
STAT6	-0.55	0.56	-10000	0	-1.3	125	125
SPI1	-0.1	0.3	-10000	0	-0.86	73	73
RPS6KB1	-0.24	0.3	-10000	0	-0.77	74	74
STAT6 (dimer)	-0.56	0.56	-10000	0	-1.3	125	125
STAT6 (dimer)/PARP14	-0.51	0.51	-10000	0	-1.2	124	124
mast cell activation	0.012	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.3	0.36	-10000	0	-0.89	100	100
FRAP1	-0.28	0.33	-10000	0	-0.84	86	86
LTA	-0.6	0.56	-10000	0	-1.3	155	155
FES	0.013	0.046	-10000	0	-0.74	2	2
T-helper 1 cell differentiation	0.54	0.54	1.3	125	-10000	0	125
CCL11	-0.69	0.6	-10000	0	-1.3	231	231
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.29	0.34	-10000	0	-0.86	96	96
IL2RG	-0.035	0.21	-10000	0	-0.85	34	34
IL10	-0.5	0.5	-10000	0	-1.2	115	115
IRS1	0.01	0.065	-10000	0	-0.74	4	4
IRS2	0.003	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.12	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.2	111	111
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.37	-10000	0	-0.88	107	107
COL1A1	-0.41	0.43	-10000	0	-0.92	205	205
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.48	-10000	0	-1.2	97	97
IL2R gamma/JAK3	-0.16	0.36	-10000	0	-0.83	111	111
TFF3	-0.5	0.5	-10000	0	-1.2	126	126
ALOX15	-0.49	0.48	-10000	0	-1.2	111	111
MYBL1	-0.044	0.22	-10000	0	-0.86	36	36
T-helper 2 cell differentiation	-0.43	0.41	-10000	0	-0.97	130	130
SHC1	0.014	0.038	-10000	0	-0.86	1	1
CEBPB	0	0.13	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.29	-10000	0	-0.78	68	68
mol:PI-3-4-5-P3	-0.28	0.33	-10000	0	-0.84	86	86
PI3K	-0.3	0.36	-10000	0	-0.91	86	86
DOK2	-0.035	0.2	-10000	0	-0.86	31	31
ETS1	0.028	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.27	-10000	0	-0.77	54	54
ITGB3	-0.49	0.49	-10000	0	-1.2	115	115
PIGR	-0.84	0.7	-10000	0	-1.4	274	274
IGHE	0.028	0.089	0.29	14	-0.37	4	18
MAPKKK cascade	-0.2	0.26	-10000	0	-0.75	54	54
BCL6	0.014	0.004	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	111	111
RETNLB	-0.49	0.48	-10000	0	-1.2	114	114
SELP	-0.51	0.52	-10000	0	-1.3	119	119
AICDA	-0.62	0.54	-10000	0	-1.2	184	184

×

Caspase cascade in apoptosis

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
TOP1	-0.13	0.26	-10000	0	-0.49	172	172
ACTA1	-0.19	0.35	-10000	0	-0.67	173	173
NUMA1	-0.13	0.26	-10000	0	-0.49	172	172
SPTAN1	-0.19	0.35	-10000	0	-0.66	172	172
LIMK1	-0.19	0.35	-10000	0	-0.66	173	173
BIRC3	-0.12	0.31	-10000	0	-0.86	80	80
BIRC2	0.012	0.007	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.28	0.46	-10000	0	-0.86	190	190
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.016	0	-10000	0	-10000	0	0
PTK2	-0.13	0.26	-10000	0	-0.49	172	172
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.34	-10000	0	-0.65	172	172
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.19	0.35	-10000	0	-0.66	172	172
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.3	0.28	-10000	0	-0.54	294	294
BID	-0.09	0.17	-10000	0	-0.31	190	190
MAP3K1	-0.044	0.11	-10000	0	-0.22	78	78
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.19	0.35	-10000	0	-0.66	170	170
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.014	0.094	-10000	0	-0.21	35	35
neuron apoptosis	0.011	0.044	-10000	0	-0.61	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.17	0.34	-10000	0	-0.63	172	172
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.05	0.15	-10000	0	-0.39	28	28
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.17	0.34	-10000	0	-0.77	105	105
CASP7	0.05	0.12	0.34	80	-10000	0	80
KRT18	-0.002	0.046	-10000	0	-0.3	2	2
apoptosis	-0.17	0.32	-10000	0	-0.7	113	113
DFFA	-0.19	0.35	-10000	0	-0.66	172	172
DFFB	-0.19	0.35	-10000	0	-0.66	172	172
PARP1	-0.014	0.094	0.21	35	-10000	0	35
actin filament polymerization	0.16	0.32	0.72	106	-10000	0	106
TNF	0.003	0.1	-10000	0	-0.8	8	8
CYCS	-0.069	0.13	-10000	0	-0.28	105	105
SATB1	-0.037	0.15	-10000	0	-0.48	3	3
SLK	-0.19	0.35	-10000	0	-0.66	172	172
p15 BID/BAX	-0.073	0.15	-10000	0	-0.32	105	105
CASP2	0.031	0.088	-10000	0	-0.42	1	1
JNK cascade	0.044	0.11	0.22	78	-10000	0	78
CASP3	-0.21	0.37	-10000	0	-0.71	172	172
LMNB2	0.011	0.085	-10000	0	-0.39	4	4
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.078	0.19	-10000	0	-0.52	80	80
negative regulation of DNA binding	-0.29	0.28	-10000	0	-0.54	294	294
stress fiber formation	-0.18	0.35	-10000	0	-0.65	172	172
GZMB	-0.32	0.5	-10000	0	-0.97	190	190
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.009	0.089	-10000	0	-0.37	7	7
APP	0.011	0.045	-10000	0	-0.62	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	-0.17	0.31	-10000	0	-0.56	175	175
LMNA	0.011	0.085	-10000	0	-0.39	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.005	0.09	-10000	0	-0.41	7	7
LRDD	0.003	0.1	-10000	0	-0.85	8	8
SREBF1	-0.19	0.35	-10000	0	-0.66	173	173
APAF-1/Caspase 9	-0.01	0.062	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.13	0.26	-10000	0	-0.48	172	172
CFL2	-0.17	0.34	-10000	0	-0.75	106	106
GAS2	-0.2	0.36	-10000	0	-0.66	177	177
positive regulation of apoptosis	0.015	0.085	-10000	0	-0.38	4	4
PRF1	-0.2	0.38	-10000	0	-0.86	132	132

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.41	0.54	-9999	-0.9	245	245
MAP4K1	-0.34	0.43	-9999	-0.86	218	218
MAP3K8	0.012	0.054	-9999	-0.86	2	2
PRKCB	0.008	0.08	-9999	-0.81	5	5
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	-0.15	0.29	-9999	-0.62	124	124
JUN	0	0.087	-9999	-0.6	6	6
MAP3K7	-0.15	0.29	-9999	-0.62	124	124
GRAP2	-0.042	0.22	-9999	-0.86	35	35
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.14	0.28	-9999	-0.59	124	124
LAT	-0.23	0.39	-9999	-0.86	148	148
LCP2	-0.039	0.21	-9999	-0.86	33	33
MAPK8	-0.012	0.092	-9999	-0.64	6	6
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.2	0.29	-9999	-0.66	124	124
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.39	0.51	-9999	-1.2	124	124

×

EGFR-dependent Endothelin signaling events

Figure S17. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S17. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.014	0.038	-9999	-0.86	1	1
EGFR	0.001	0.11	-9999	-0.85	9	9
EGF/EGFR	-0.37	0.16	-9999	-0.86	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.36	0.14	-9999	-0.89	9	9
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.012	0.054	-9999	-0.86	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.74	480	480
EGF/EGFR dimer/SHC	-0.44	0.16	-9999	-0.48	481	481
mol:GDP	-0.36	0.13	-9999	-0.87	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.014	0.16	-9999	-0.86	18	18
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.32	0.12	-9999	-0.81	10	10
SHC1	0.014	0.038	-9999	-0.86	1	1
HRAS/GDP	-0.33	0.13	-9999	-0.82	10	10
FRAP1	-0.34	0.14	-9999	-0.85	9	9
EGF/EGFR dimer	-0.51	0.18	-9999	-0.56	481	481
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.025	0.12	-9999	-0.66	20	20

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.25	0.27	-9999	-0.53	249	249
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.063	0.068	-9999	-10000	0	0
AURKB	-0.39	0.44	-9999	-0.86	248	248
AURKC	0.012	0.054	-9999	-0.86	2	2

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.008	0.071	-9999	-0.68	5	5
VEGFR1 homodimer/NRP1	-0.008	0.072	-9999	-0.62	7	7
mol:DAG	-0.26	0.29	-9999	-0.52	294	294
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	240	240
CaM/Ca2+	-0.27	0.25	-9999	-0.92	7	7
HIF1A	0.02	0.057	-9999	-0.72	2	2
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.22	0.21	-9999	-0.94	6	6
PLCG1	-0.26	0.29	-9999	-0.52	294	294
NOS3	-0.18	0.24	-9999	-0.85	6	6
CBL	0.014	0.033	-9999	-0.74	1	1
mol:NO	-0.17	0.24	-9999	-0.8	6	6
FLT1	0.031	0.086	-9999	-0.71	7	7
PGF	-0.47	0.44	-9999	-0.86	293	293
VEGFR1 homodimer/NRP2/VEGFR121	-0.24	0.27	-9999	-0.53	245	245
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
eNOS/Hsp90	-0.16	0.23	-9999	-0.76	6	6
endothelial cell proliferation	-0.2	0.26	-9999	-0.82	9	9
mol:Ca2+	-0.26	0.29	-9999	-0.52	294	294
MAPK3	-0.21	0.26	-9999	-0.88	6	6
MAPK1	-0.21	0.26	-9999	-0.83	7	7
PIK3R1	0.014	0.033	-9999	-0.74	1	1
PLGF homodimer	-0.47	0.44	-9999	-0.86	293	293
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.045	0.22	-9999	-0.86	37	37
VEGFA homodimer	-0.38	0.44	-9999	-0.86	239	239
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	240	240
platelet activating factor biosynthetic process	-0.2	0.25	-9999	-0.85	6	6
PI3K	-0.27	0.25	-9999	-0.99	7	7
PRKCA	-0.23	0.27	-9999	-0.89	7	7
PRKCB	-0.24	0.28	-9999	-0.9	9	9
VEGFR1 homodimer/PLGF homodimer	-0.32	0.29	-9999	-0.58	294	294
VEGFA	-0.38	0.44	-9999	-0.86	239	239
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.52	294	294
RASA1	0.046	0.077	-9999	-0.65	6	6
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFR1 homodimer	0.031	0.086	-9999	-0.7	7	7
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
eNOS/Caveolin-1	-0.19	0.26	-9999	-0.8	31	31
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.27	0.25	-9999	-0.96	7	7
mol:L-citrulline	-0.17	0.24	-9999	-0.8	6	6
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.22	0.25	-9999	-0.94	6	6
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.24	0.27	-9999	-0.53	241	241
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.99	6	6
PDPK1	-0.22	0.27	-9999	-0.94	7	7
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-0.52	240	240
mol:NADP	-0.17	0.24	-9999	-0.8	6	6
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.22	0.25	-9999	-0.92	6	6
VEGFR1 homodimer/NRP2	-0.015	0.095	-9999	-0.61	12	12

×

Glypican 2 network

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
MDK	-0.049	0.23	-9999	-0.86	39	39
GPC2	-0.087	0.28	-9999	-0.86	62	62
GPC2/Midkine	-0.12	0.28	-9999	-0.73	90	90
neuron projection morphogenesis	-0.12	0.28	-9999	-0.73	90	90

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.085	-9999	-0.86	5	5
CCL5	-0.35	0.43	-9999	-0.86	224	224
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.22	0.23	-9999	-0.59	94	94
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.22	-9999	-0.56	95	95
Syndecan-1/Syntenin	-0.2	0.22	-9999	-0.55	94	94
MAPK3	-0.16	0.2	-9999	-0.7	15	15
HGF/MET	-0.032	0.15	-9999	-0.66	26	26
TGFB1/TGF beta receptor Type II	0.007	0.084	-9999	-0.86	5	5
BSG	0.014	0.038	-9999	-0.86	1	1
keratinocyte migration	-0.2	0.21	-9999	-0.55	95	95
Syndecan-1/RANTES	-0.41	0.33	-9999	-0.68	280	280
Syndecan-1/CD147	-0.2	0.18	-9999	-0.53	89	89
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	94	94
LAMA5	0.013	0.05	-9999	-0.8	2	2
positive regulation of cell-cell adhesion	-0.21	0.18	-9999	-0.52	94	94
MMP7	-0.13	0.3	-9999	-0.75	99	99
HGF	-0.019	0.17	-9999	-0.8	23	23
Syndecan-1/CASK	-0.21	0.22	-9999	-0.56	94	94
Syndecan-1/HGF/MET	-0.23	0.22	-9999	-0.58	104	104
regulation of cell adhesion	-0.15	0.2	-9999	-0.67	15	15
HPSE	0.013	0.046	-9999	-0.74	2	2
positive regulation of cell migration	-0.22	0.23	-9999	-0.59	94	94
SDC1	-0.22	0.23	-9999	-0.59	94	94
Syndecan-1/Collagen	-0.22	0.23	-9999	-0.59	94	94
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	251	251
MAPK1	-0.16	0.2	-9999	-0.7	15	15
homophilic cell adhesion	-0.22	0.22	-9999	-0.58	94	94
MMP1	-0.15	0.34	-9999	-0.83	106	106

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.59	0.31	-9999	-0.85	285	285
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.31	-9999	-0.84	85	85
SMAD9	-0.065	0.086	-9999	-0.57	11	11
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.18	0.17	-9999	-0.51	19	19
BMP7/USAG1	-0.69	0.34	-9999	-0.8	462	462
SMAD5/SKI	-0.17	0.16	-9999	-0.5	15	15
SMAD1	0.002	0.041	-9999	-10000	0	0
BMP2	0.01	0.068	-9999	-0.77	4	4
SMAD1/SMAD1/SMAD4	0	0.001	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.51	0.35	-9999	-0.74	367	367
BMPR1A-1B/BAMBI	-0.33	0.22	-9999	-0.48	371	371
AHSG	-0.014	0.13	-9999	-0.86	13	13
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.007	0.057	-9999	-0.5	7	7
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.11	-9999	-0.49	19	19
BMP2-4 (homodimer)	-0.008	0.065	-9999	-0.57	7	7
RGMB	0.012	0.054	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.78	5	5
RGMA	0.009	0.073	-9999	-0.74	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.15	0.15	-9999	-0.56	19	19
BMP2-4/USAG1	-0.31	0.24	-9999	-0.48	343	343
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	15	15
SOSTDC1	-0.47	0.36	-9999	-0.74	342	342
BMP7/BMPR2/BMPR1A-1B	-0.58	0.3	-9999	-0.85	264	264
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.004	0.092	-9999	-0.74	8	8
HFE2	-0.019	0.16	-9999	-0.86	19	19
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.017	0.097	-9999	-0.55	16	16
SMAD5/SMAD5/SMAD4	-0.17	0.16	-9999	-0.58	3	3
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.1	-9999	-0.5	15	15
BMP7 (homodimer)	-0.5	0.35	-9999	-0.74	358	358
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.025	0.12	-9999	-0.62	21	21
SMAD1/SKI	0.012	0.039	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.02	0.1	-9999	-0.55	20	20
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.18	0.33	-9999	-0.75	134	134
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.38	0.26	-9999	-0.56	367	367
CHRDL1	-0.38	0.38	-9999	-0.74	277	277
ENDOFIN/SMAD1	0.012	0.039	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.005	0.004	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	0.004	0.092	-9999	-0.74	8	8
SMURF2	0.014	0.033	-9999	-0.74	1	1
BMP2-4/CHRDL1	-0.25	0.24	-9999	-0.48	279	279
BMP2-4/GREM1	-0.13	0.22	-9999	-0.63	13	13
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.038	0.09	-9999	-0.56	9	9
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.5	0.35	-9999	-0.74	358	358
BMP6	0.004	0.092	-9999	-0.74	8	8
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.12	0.12	-9999	-0.46	19	19
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.011	0.042	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.2	0.19	-9999	-0.59	65	65
CHRD	-0.001	0.11	-9999	-0.78	11	11
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.17	0.13	-9999	-0.58	19	19
BMP4	0.011	0.057	-9999	-0.74	3	3
FST	-0.075	0.25	-9999	-0.76	62	62
BMP2-4/NOG	-0.095	0.21	-9999	-0.56	91	91
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.54	0.29	-9999	-0.8	264	264

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.03	0.088	-10000	0	-0.71	8	8
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.011	0.063	-10000	0	-0.82	3	3
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.23	0.14	-10000	0	-0.57	6	6
EPO	-0.4	0.41	-10000	0	-0.9	153	153
FIH (dimer)	0.014	0.02	-10000	0	-10000	0	0
APEX1	0.013	0.013	-10000	0	-10000	0	0
SERPINE1	-0.34	0.41	-10000	0	-0.93	120	120
FLT1	-0.019	0.077	-10000	0	-0.76	5	5
ADORA2A	-0.3	0.34	-10000	0	-0.82	83	83
germ cell development	-0.41	0.44	-10000	0	-0.93	177	177
SLC11A2	-0.29	0.34	-10000	0	-0.81	83	83
BHLHE40	-0.29	0.34	-10000	0	-0.81	83	83
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.56	146	146
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.023	0.056	-10000	0	-1.2	1	1
KDR	-0.015	0.065	-10000	0	-1.4	1	1
PGK1	-0.29	0.34	-10000	0	-0.81	83	83
SIRT1	0.014	0.005	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.35	0.42	-10000	0	-1	83	83
EPAS1	-0.27	0.19	-10000	0	-0.46	162	162
SP1	0.026	0.006	-10000	0	-10000	0	0
ABCG2	-0.29	0.34	-10000	0	-0.81	84	84
EFNA1	-0.29	0.34	-10000	0	-0.81	84	84
FXN	-0.3	0.34	-10000	0	-0.82	83	83
POU5F1	-0.43	0.47	-10000	0	-1	177	177
neuron apoptosis	0.34	0.4	0.96	83	-10000	0	83
EP300	0.014	0.033	-10000	0	-0.74	1	1
EGLN3	-0.76	0.29	-10000	0	-0.87	469	469
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.004	0.045	-10000	0	-0.52	4	4
VHL	0.014	0.033	-10000	0	-0.74	1	1
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.32	0.37	-10000	0	-0.9	85	85
TWIST1	-0.31	0.34	-10000	0	-0.83	86	86
ELK1	0.026	0.001	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.56	84	84
VEGFA	-0.47	0.49	-10000	0	-0.99	199	199
CREBBP	0.016	0	-10000	0	-10000	0	0

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.25	0.47	-10000	0	-1.1	70	70
IL23A	-0.24	0.47	-10000	0	-1.1	55	55
NF kappa B1 p50/RelA/I kappa B alpha	-0.32	0.39	-10000	0	-1	79	79
positive regulation of T cell mediated cytotoxicity	-0.28	0.52	-10000	0	-1.1	91	91
ITGA3	-0.24	0.46	-10000	0	-1.1	55	55
IL17F	-0.15	0.34	-10000	0	-0.74	36	36
IL12B	-0.085	0.29	-10000	0	-0.88	62	62
STAT1 (dimer)	-0.27	0.5	-10000	0	-1.1	89	89
CD4	-0.24	0.47	-10000	0	-1.1	66	66
IL23	-0.27	0.48	-10000	0	-1.1	70	70
IL23R	-0.012	0.15	-10000	0	-0.8	10	10
IL1B	-0.25	0.48	-10000	0	-1.1	67	67
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.24	0.47	-10000	0	-1.1	65	65
TYK2	0.016	0.024	-10000	0	-10000	0	0
STAT4	-0.035	0.21	-10000	0	-0.86	31	31
STAT3	0.016	0.001	-10000	0	-10000	0	0
IL18RAP	-0.22	0.39	-10000	0	-0.88	137	137
IL12RB1	-0.25	0.42	-10000	0	-0.89	160	160
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
IL12Rbeta1/TYK2	-0.2	0.33	-10000	0	-0.7	160	160
IL23R/JAK2	-0.011	0.16	-10000	0	-0.78	9	9
positive regulation of chronic inflammatory response	-0.28	0.52	-10000	0	-1.1	91	91
natural killer cell activation	0.002	0.012	0.063	10	-10000	0	10
JAK2	0.021	0.034	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
NFKB1	0.01	0.033	-10000	0	-0.73	1	1
RELA	0.012	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.26	0.46	-10000	0	-1.1	70	70
ALOX12B	-0.3	0.5	-10000	0	-1.1	85	85
CXCL1	-0.28	0.52	-10000	0	-1.1	83	83
T cell proliferation	-0.28	0.52	-10000	0	-1.1	91	91
NFKBIA	0.012	0.009	-10000	0	-10000	0	0
IL17A	-0.099	0.29	-10000	0	-0.61	3	3
PI3K	-0.33	0.4	-10000	0	-1	91	91
IFNG	-0.052	0.069	0.13	4	-0.12	221	225
STAT3 (dimer)	-0.31	0.38	-10000	0	-1	78	78
IL18R1	-0.003	0.1	-10000	0	-0.8	8	8
IL23/IL23R/JAK2/TYK2/SOCS3	-0.18	0.38	-10000	0	-0.79	87	87
IL18/IL18R	-0.17	0.28	-10000	0	-0.61	149	149
macrophage activation	-0.017	0.018	-10000	0	-0.045	10	10
TNF	-0.25	0.49	-10000	0	-1.1	68	68
STAT3/STAT4	-0.35	0.43	-10000	0	-1.1	96	96
STAT4 (dimer)	-0.3	0.53	-10000	0	-1.2	89	89
IL18	-0.002	0.099	-10000	0	-0.86	7	7
IL19	-0.25	0.46	-10000	0	-1	67	67
STAT5A (dimer)	-0.27	0.5	-10000	0	-1.1	88	88
STAT1	0.014	0.038	-10000	0	-0.86	1	1
SOCS3	0.009	0.076	-10000	0	-0.86	4	4
CXCL9	-0.39	0.59	-10000	0	-1.1	165	165
MPO	-0.25	0.48	-10000	0	-1.1	70	70
positive regulation of humoral immune response	-0.28	0.52	-10000	0	-1.1	91	91
IL23/IL23R/JAK2/TYK2	-0.3	0.54	-10000	0	-1.2	90	90
IL6	-0.3	0.53	-10000	0	-1.2	93	93
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.016	0.12	-10000	0	-0.86	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.063	10	-10000	0	10
CD3E	-0.38	0.6	-10000	0	-1.1	166	166
keratinocyte proliferation	-0.28	0.52	-10000	0	-1.1	91	91
NOS2	-0.25	0.47	-10000	0	-1.1	71	71

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.007	0.13	-9999	-0.77	15	15
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.011	0.063	-9999	-0.82	3	3
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.047	-9999	-0.39	1	1
HIF1A	-0.099	0.039	-9999	-0.42	1	1
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.003	0.038	-9999	-0.48	2	2
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	513	513
ARNT/IPAS	-0.016	0.097	-9999	-0.58	15	15
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.014	0.038	-9999	-0.86	1	1
HIF1A/ARNT	-0.08	0.047	-9999	-0.39	1	1
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.004	0.048	-9999	-0.55	4	4
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.047	-9999	-0.39	1	1
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	467	467
HIF1A/RACK1/Elongin B/Elongin C	-0.067	0.049	-9999	-0.54	4	4
VHL	0.014	0.033	-9999	-0.74	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.047	-9999	-0.39	1	1
EGLN3	-0.76	0.28	-9999	-0.86	469	469
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.003	0.038	-9999	-0.61	1	1
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.55	0.11	-9999	-0.57	513	513

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	-0.24	0.26	-10000	0	-0.74	32	32
IHH	-0.096	0.23	-10000	0	-0.82	47	47
SHH Np/Cholesterol/GAS1	-0.036	0.12	-10000	0	-0.45	43	43
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.036	0.12	0.45	43	-10000	0	43
SMO/beta Arrestin2	-0.14	0.15	-10000	0	-0.6	34	34
SMO	-0.13	0.19	-10000	0	-0.63	33	33
AKT1	-0.04	0.092	-10000	0	-0.46	1	1
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
BOC	0.016	0	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.13	0.19	-10000	0	-0.62	33	33
STIL	-0.093	0.16	-10000	0	-0.67	10	10
DHH N/PTCH2	-0.044	0.16	-10000	0	-0.63	37	37
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.62	37	37
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
DHH	-0.002	0.11	-10000	0	-0.74	12	12
PTHLH	-0.44	0.41	-10000	0	-0.74	328	328
determination of left/right symmetry	-0.13	0.19	-10000	0	-0.62	33	33
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
skeletal system development	-0.43	0.4	-10000	0	-0.73	328	328
IHH N/Hhip	-0.2	0.31	-10000	0	-0.65	164	164
DHH N/Hhip	-0.15	0.26	-10000	0	-0.57	142	142
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.13	0.19	-10000	0	-0.62	33	33
pancreas development	-0.18	0.33	-10000	0	-0.75	133	133
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.031	0.18	-10000	0	-0.74	33	33
somite specification	-0.13	0.19	-10000	0	-0.62	33	33
SHH Np/Cholesterol/PTCH1	-0.13	0.14	-10000	0	-0.55	36	36
SHH Np/Cholesterol/PTCH2	-0.034	0.13	-10000	0	-0.5	36	36
SHH Np/Cholesterol/Megalin	-0.047	0.15	-10000	0	-0.48	52	52
SHH	0.018	0.085	-10000	0	-0.57	11	11
catabolic process	-0.15	0.19	-10000	0	-0.65	32	32
SMO/Vitamin D3	-0.11	0.18	-10000	0	-0.58	36	36
SHH Np/Cholesterol/Hhip	-0.12	0.2	-10000	0	-0.46	139	139
LRP2	-0.05	0.21	-10000	0	-0.74	46	46
receptor-mediated endocytosis	-0.15	0.18	-10000	0	-0.62	44	44
SHH Np/Cholesterol/BOC	-0.009	0.063	-10000	0	-0.44	11	11
SHH Np/Cholesterol/CDO	-0.069	0.18	-10000	0	-0.52	70	70
mesenchymal cell differentiation	0.12	0.2	0.45	139	-10000	0	139
mol:Vitamin D3	-0.11	0.17	-10000	0	-0.56	36	36
IHH N/PTCH2	-0.081	0.21	-10000	0	-0.62	70	70
CDON	-0.083	0.28	-10000	0	-0.86	60	60
IHH N/PTCH1	-0.16	0.19	-10000	0	-0.66	32	32
Megalin/LRPAP1	-0.048	0.16	-10000	0	-0.56	46	46
PTCH2	-0.026	0.19	-10000	0	-0.86	25	25
SHH Np/Cholesterol	-0.009	0.065	-10000	0	-0.45	11	11
PTCH1	-0.15	0.19	-10000	0	-0.65	32	32
HHIP	-0.18	0.33	-10000	0	-0.75	133	133

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.016	0	-9999	-10000	0	0
LAT2	-0.16	0.23	-9999	-0.7	62	62
AP1	-0.16	0.21	-9999	-0.56	89	89
mol:PIP3	-0.23	0.34	-9999	-0.7	145	145
IKBKB	-0.086	0.16	-9999	-0.34	75	75
AKT1	-0.16	0.21	-9999	-0.72	22	22
IKBKG	-0.086	0.16	-9999	-0.34	84	84
MS4A2	-0.18	0.36	-9999	-0.86	117	117
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.011	0.033	-9999	-0.75	1	1
MAP3K1	-0.12	0.26	-9999	-0.59	89	89
mol:Ca2+	-0.16	0.24	-9999	-0.48	138	138
LYN	0.011	0.009	-9999	-10000	0	0
CBLB	-0.12	0.15	-9999	-0.54	21	21
SHC1	0.014	0.038	-9999	-0.86	1	1
RasGAP/p62DOK	-0.002	0.03	-9999	-0.48	2	2
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.009	0.076	-9999	-0.86	4	4
PLD2	-0.17	0.28	-9999	-0.56	100	100
PTPN13	-0.068	0.16	-9999	-0.49	21	21
PTPN11	0.014	0.006	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.043	0.17	-9999	-0.4	12	12
SYK	0.008	0.047	-9999	-0.75	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.29	0.32	-9999	-0.76	141	141
LAT	-0.25	0.29	-9999	-0.65	158	158
PAK2	-0.15	0.29	-9999	-0.64	115	115
NFATC2	-0.07	0.1	-9999	-0.68	5	5
HRAS	-0.18	0.32	-9999	-0.7	124	124
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.039	0.027	-9999	-10000	0	0
Fc epsilon R1	-0.25	0.32	-9999	-0.62	217	217
Antigen/IgE/Fc epsilon R1	-0.24	0.3	-9999	-0.58	217	217
mol:GDP	-0.2	0.35	-9999	-0.77	129	129
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.011	0.033	-9999	-0.74	1	1
FOS	-0.003	0.12	-9999	-0.75	13	13
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.12	0.16	-9999	-0.57	21	21
CHUK	-0.086	0.16	-9999	-0.34	73	73
KLRG1	-0.12	0.15	-9999	-0.55	21	21
VAV1	-0.2	0.32	-9999	-0.69	136	136
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.15	-9999	-0.55	22	22
negative regulation of mast cell degranulation	-0.11	0.15	-9999	-0.56	23	23
BTK	-0.18	0.24	-9999	-0.58	114	114
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.17	0.22	-9999	-0.58	85	85
GAB2/PI3K/SHP2	-0.18	0.24	-9999	-0.82	22	22
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.12	0.15	-9999	-0.55	21	21
RAF1	0.026	0.027	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.3	0.39	-9999	-0.87	122	122
FCER1G	-0.15	0.34	-9999	-0.87	98	98
FCER1A	-0.021	0.16	-9999	-0.77	22	22
Antigen/IgE/Fc epsilon R1/Fyn	-0.22	0.28	-9999	-0.54	203	203
MAPK3	0.04	0.025	-9999	-10000	0	0
MAPK1	0.04	0.025	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	-0.012	0.079	-9999	-0.58	2	2
DUSP1	0.014	0.038	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.069	0.074	-9999	-0.33	1	1
actin cytoskeleton reorganization	-0.073	0.16	-9999	-0.48	21	21
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.22	0.29	-9999	-0.72	116	116
FER	-0.12	0.15	-9999	-0.55	23	23
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.14	0.19	-9999	-0.42	165	165
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.2	0.36	-9999	-0.76	131	131
cytokine secretion	-0.051	0.053	-9999	-10000	0	0
SPHK1	-0.16	0.22	-9999	-0.64	60	60
PTK2	-0.076	0.16	-9999	-0.5	21	21
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.24	0.31	-9999	-0.77	110	110
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.18	0.31	-9999	-0.68	110	110
MAP2K2	0.034	0.031	-9999	-0.42	1	1
MAP2K1	0.035	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.11	0.15	-9999	-0.53	21	21
MAP2K4	0.017	0.015	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.32	0.4	-9999	-0.72	229	229
mol:Choline	-0.17	0.28	-9999	-0.55	100	100
SHC/Grb2/SOS1	-0.1	0.14	-9999	-0.52	16	16
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.061	0.15	-9999	-0.46	17	17
HCLS1	-0.13	0.19	-9999	-0.68	31	31
PRKCB	-0.14	0.23	-9999	-0.48	117	117
FCGR2B	-0.14	0.34	-9999	-0.86	96	96
IGHE	-0.005	0.01	-9999	-10000	0	0
KLRG1/SHIP	-0.11	0.15	-9999	-0.57	23	23
LCP2	-0.039	0.21	-9999	-0.87	33	33
PLA2G4A	-0.12	0.16	-9999	-0.54	27	27
RASA1	0.014	0.033	-9999	-0.74	1	1
mol:Phosphatidic acid	-0.17	0.28	-9999	-0.55	100	100
IKK complex	-0.046	0.13	-9999	-0.28	1	1
WIPF1	0.016	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.009	0.085	-10000	0	-0.86	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.074	0.2	0.6	34	-0.44	3	37
IL27/IL27R/JAK1	-0.079	0.35	0.58	1	-0.86	58	59
TBX21	-0.21	0.41	0.5	1	-0.72	184	185
IL12B	-0.093	0.28	-10000	0	-0.87	62	62
IL12A	0.008	0.031	-10000	0	-0.68	1	1
IL6ST	-0.016	0.14	-10000	0	-0.75	19	19
IL27RA/JAK1	0.011	0.062	-10000	0	-0.7	1	1
IL27	-0.043	0.21	-10000	0	-0.88	32	32
TYK2	0.011	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.025	0.13	-10000	0	-0.74	2	2
T-helper 2 cell differentiation	0.074	0.2	0.6	34	-0.44	3	37
T cell proliferation during immune response	0.074	0.2	0.6	34	-0.44	3	37
MAPKKK cascade	-0.074	0.2	0.44	3	-0.6	34	37
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.015	0.039	-10000	0	-0.86	1	1
IL12RB1	-0.25	0.4	-10000	0	-0.87	160	160
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.16	0.35	0.5	1	-0.7	108	109
IL27/IL27R/JAK2/TYK2	-0.078	0.2	0.44	3	-0.61	34	37
positive regulation of T cell mediated cytotoxicity	-0.074	0.2	0.44	3	-0.6	34	37
STAT1 (dimer)	-0.064	0.51	0.54	126	-0.98	73	199
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.08	0.18	0.39	3	-0.62	25	28
T cell proliferation	-0.12	0.25	0.4	1	-0.68	58	59
IL12/IL12R/TYK2/JAK2	-0.17	0.27	-10000	0	-0.68	62	62
IL17A	-0.025	0.13	-10000	0	-0.74	2	2
mast cell activation	0.074	0.2	0.6	34	-0.44	3	37
IFNG	-0.04	0.066	0.13	3	-0.11	239	242
T cell differentiation	-0.011	0.011	0.03	3	-0.026	142	145
STAT3 (dimer)	-0.08	0.18	0.39	3	-0.62	24	27
STAT5A (dimer)	-0.08	0.18	0.39	3	-0.61	26	29
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.76	44	46
STAT4	-0.035	0.21	-10000	0	-0.86	31	31
T cell activation	-0.012	0.007	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.043	0.1	-10000	0	-0.71	1	1
GATA3	-0.62	0.68	-10000	0	-1.3	264	264
IL18	0.005	0.079	-10000	0	-0.68	7	7
positive regulation of mast cell cytokine production	-0.08	0.18	0.38	3	-0.61	24	27
IL27/EBI3	-0.12	0.33	-10000	0	-0.83	86	86
IL27RA	-0.003	0.063	-10000	0	-0.76	1	1
IL6	-0.087	0.28	-10000	0	-0.81	67	67
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0.001	0.086	-10000	0	-0.59	10	10
IL1B	0.006	0.071	-10000	0	-0.66	6	6
EBI3	-0.12	0.31	-10000	0	-0.88	76	76
TNF	0.004	0.078	-10000	0	-0.62	8	8

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	239	239
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.031	0.1	-9999	-0.36	45	45
mol:S1P	-0.024	0.096	-9999	-0.36	16	16
S1P1/S1P/Gi	-0.047	0.14	-9999	-0.51	14	14
GNAO1	0.01	0.083	-9999	-0.84	5	5
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.087	-9999	-0.63	2	2
PLCG1	-0.028	0.13	-9999	-0.5	9	9
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.004	-9999	-10000	0	0
GNAI2	0.018	0.005	-9999	-10000	0	0
GNAI3	0.015	0.006	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.75	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.24	0.3	-9999	-0.58	239	239
S1P1/S1P	-0.21	0.21	-9999	-0.42	240	240
negative regulation of cAMP metabolic process	-0.046	0.14	-9999	-0.5	14	14
MAPK3	-0.038	0.16	-9999	-0.57	26	26
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.014	0.033	-9999	-0.74	1	1
PLCB2	-0.2	0.26	-9999	-0.6	78	78
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.17	-9999	-0.51	24	24
receptor internalization	-0.19	0.2	-9999	-0.39	240	240
PTGS2	-0.048	0.24	-9999	-0.99	27	27
Rac1/GTP	-0.17	0.17	-9999	-0.51	23	23
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	239	239
negative regulation of T cell proliferation	-0.046	0.14	-9999	-0.5	14	14
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
MAPK1	-0.038	0.16	-9999	-0.57	26	26
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.63	24	24
ABCC1	0.016	0.002	-9999	-10000	0	0

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.19	0.35	-10000	0	-1.1	70	70
NFATC2	-0.082	0.24	-10000	0	-0.75	23	23
NFATC3	-0.021	0.064	-10000	0	-10000	0	0
CD40LG	-0.24	0.44	-10000	0	-1.2	59	59
ITCH	0.054	0.057	-10000	0	-10000	0	0
CBLB	0.054	0.057	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.55	0.56	-10000	0	-1.2	207	207
JUNB	0.013	0.046	-10000	0	-0.74	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.011	0.057	-10000	0	-10000	0	0
T cell anergy	0.023	0.093	-10000	0	-0.6	1	1
TLE4	-0.032	0.18	-10000	0	-0.79	7	7
Jun/NFAT1-c-4/p21SNFT	-0.24	0.28	-10000	0	-1	26	26
AP-1/NFAT1-c-4	-0.3	0.37	-10000	0	-1.2	39	39
IKZF1	-0.13	0.36	-10000	0	-0.89	92	92
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.76	88	88
AP-1/NFAT1	-0.095	0.17	-10000	0	-0.7	14	14
CALM1	0.029	0.036	-10000	0	-10000	0	0
EGR2	-0.11	0.29	-10000	0	-1.3	10	10
EGR3	-0.11	0.29	-10000	0	-1.4	9	9
NFAT1/FOXP3	-0.28	0.4	-10000	0	-0.94	118	118
EGR1	0	0.11	-10000	0	-0.74	12	12
JUN	0.006	0.022	-10000	0	-10000	0	0
EGR4	0.004	0.084	-10000	0	-0.86	5	5
mol:Ca2+	0.011	0.04	-10000	0	-10000	0	0
GBP3	-0.036	0.19	-10000	0	-0.81	11	11
FOSL1	-0.029	0.19	-10000	0	-0.86	27	27
NFAT1-c-4/MAF/IRF4	-0.26	0.36	-10000	0	-0.94	87	87
DGKA	-0.036	0.2	-10000	0	-0.97	9	9
CREM	0.015	0.001	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.22	-10000	0	-1.1	9	9
CTLA4	-0.44	0.59	-10000	0	-1	243	243
NFAT1-c-4 (dimer)/EGR1	-0.17	0.24	-10000	0	-1.1	14	14
NFAT1-c-4 (dimer)/EGR4	-0.17	0.23	-10000	0	-1.1	10	10
FOS	-0.013	0.12	-10000	0	-0.75	13	13
IFNG	-0.5	0.52	-10000	0	-1	241	241
T cell activation	-0.05	0.22	-10000	0	-0.86	14	14
MAF	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.063	0.2	0.85	4	-10000	0	4
TNF	-0.097	0.28	-10000	0	-1.1	14	14
FASLG	-0.33	0.47	-10000	0	-1.1	35	35
TBX21	-0.3	0.44	-10000	0	-0.93	174	174
BATF3	-0.06	0.25	-10000	0	-0.86	46	46
PRKCQ	-0.034	0.13	-10000	0	-0.74	16	16
PTPN1	-0.032	0.18	-10000	0	-0.74	9	9
NFAT1-c-4/ICER1	-0.17	0.22	-10000	0	-1.1	8	8
GATA3	-0.36	0.38	-10000	0	-0.74	264	264
T-helper 1 cell differentiation	-0.48	0.5	-10000	0	-0.99	241	241
IL2RA	-0.38	0.46	-10000	0	-1.1	131	131
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.032	0.18	-10000	0	-0.76	8	8
E2F1	-0.081	0.28	-10000	0	-0.85	64	64
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.032	0.18	-10000	0	-0.82	6	6
IRF4	-0.18	0.36	-10000	0	-0.86	118	118
PTGS2	-0.21	0.4	-10000	0	-1.1	35	35
CSF2	-0.21	0.4	-10000	0	-1.1	34	34
JunB/Fra1/NFAT1-c-4	-0.18	0.23	-10000	0	-1	12	12
IL4	-0.37	0.29	-10000	0	-0.8	85	85
IL5	-0.2	0.38	-10000	0	-1	26	26
IL2	-0.051	0.23	-10000	0	-0.88	14	14
IL3	-0.049	0.049	-10000	0	-10000	0	0
RNF128	0.034	0.16	-10000	0	-0.78	19	19
NFATC1	-0.064	0.2	-10000	0	-0.85	4	4
CDK4	0.035	0.18	-10000	0	-10000	0	0
PTPRK	-0.033	0.18	-10000	0	-0.81	8	8
IL8	-0.22	0.42	-10000	0	-1.1	42	42
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.057	0.17	-9999	-0.52	58	58
EFNA5	-0.059	0.23	-9999	-0.75	52	52
FYN	-0.027	0.16	-9999	-0.47	58	58
neuron projection morphogenesis	-0.057	0.17	-9999	-0.52	58	58
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.057	0.17	-9999	-0.53	58	58
EPHA5	-0.008	0.11	-9999	-0.86	8	8

×

Effects of Botulinum toxin

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
STX1A	0.008	0.071	-9999	-0.66	6	6
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.02	0.11	-9999	-0.66	16	16
STXBP1	0.014	0.033	-9999	-0.74	1	1
ACh/CHRNA1	-0.27	0.31	-9999	-0.63	229	229
RAB3GAP2/RIMS1/UNC13B	-0.017	0.098	-9999	-0.57	16	16
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	-0.014	0.15	-9999	-0.86	16	16
mol:ACh	-0.01	0.053	-9999	-0.13	83	83
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.039	0.099	-9999	-0.62	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.27	0.31	-9999	-0.62	229	229
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.36	0.43	-9999	-0.86	229	229
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.082	0.2	-9999	-0.53	86	86
SNAP25	-0.04	0.12	-9999	-0.33	79	79
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.11	0.28	-9999	-0.74	86	86
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.007	0.063	-9999	-0.56	7	7
STX1A/SNAP25 fragment 1/VAMP2	-0.039	0.099	-9999	-0.62	4	4

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.042	-9999	-0.48	4	4
ARNO/beta Arrestin1-2	-0.019	0.064	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.74	1	1
USP6	0.014	0.038	-9999	-0.86	1	1
IQSEC1	0.015	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.51	0.18	-9999	-0.56	481	481
ARRB2	-0.017	0.11	-9999	-0.39	42	42
mol:GTP	-0.011	0.048	-9999	-0.23	2	2
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.085	0.28	-9999	-0.86	61	61
EGF	-0.67	0.23	-9999	-0.74	480	480
somatostatin receptor activity	0	0	-9999	-0.001	17	17
ARAP2	0.013	0.046	-9999	-0.74	2	2
mol:GDP	-0.057	0.095	-9999	-0.34	24	24
mol:PI-3-4-5-P3	0	0	-9999	-0.001	11	11
ITGA2B	-0.015	0.16	-9999	-0.86	19	19
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	-0.52	1	1
ADAP1	0.01	0.065	-9999	-0.74	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.032	0.15	-9999	-0.66	26	26
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.088	0.091	-9999	-0.34	22	22
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.43	0.16	-9999	-0.48	481	481
ADRB2	0.013	0.046	-9999	-0.74	2	2
receptor agonist activity	0	0	-9999	0	14	14
actin filament binding	0	0	-9999	-0.001	19	19
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.007	0.08	-9999	-0.74	6	6
GNAQ	0.015	0.001	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	11	11
ARF6/GDP	-0.069	0.14	-9999	-0.4	6	6
ARF6/GDP/GULP/ACAP1	-0.23	0.26	-9999	-0.53	207	207
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.023	0.11	-9999	-0.55	18	18
ACAP1	-0.32	0.43	-9999	-0.86	204	204
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.046	0.16	-9999	-0.59	42	42
EFNA1	0.014	0.038	-9999	-0.86	1	1
HGF	-0.02	0.17	-9999	-0.8	23	23
CYTH3	0.015	0	-9999	-10000	0	0
CYTH2	0.01	0.001	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
fibronectin binding	0	0	-9999	-0.001	13	13
endosomal lumen acidification	0	0	-9999	-0.001	22	22
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.011	0.14	-9999	-0.75	19	19
GNAQ/ARNO	0.009	0.01	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	2	2
MET	0.007	0.085	-9999	-0.86	5	5
GNA14	0.004	0.092	-9999	-0.74	8	8
GNA15	-0.009	0.14	-9999	-0.86	15	15
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	12	12
GNA11	0.011	0.057	-9999	-0.74	3	3
LHCGR	-0.061	0.23	-9999	-0.86	41	41
AGTR1	-0.026	0.17	-9999	-0.74	29	29
desensitization of G-protein coupled receptor protein signaling pathway	-0.046	0.16	-9999	-0.59	42	42
IPCEF1/ARNO	-0.34	0.12	-9999	-0.81	8	8
alphaIIb/beta3 Integrin	-0.03	0.14	-9999	-0.66	24	24

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.013	0.047	-9999	-10000	0	0
NFATC2	-0.019	0.073	-9999	-0.59	5	5
NFATC3	-0.013	0.047	-9999	-10000	0	0
CD40LG	-0.3	0.42	-9999	-0.94	103	103
PTGS2	-0.29	0.39	-9999	-0.86	96	96
JUNB	0.013	0.046	-9999	-0.74	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.02	0.018	-9999	-10000	0	0
CaM/Ca2+	-0.02	0.018	-9999	-10000	0	0
CALM1	0.006	0.013	-9999	-10000	0	0
JUN	0.006	0.013	-9999	-10000	0	0
mol:Ca2+	-0.02	0.019	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.003	-9999	-10000	0	0
FOSL1	-0.029	0.19	-9999	-0.86	27	27
CREM	0.015	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.74	37	37
FOS	-0.013	0.12	-9999	-0.76	13	13
IFNG	-0.43	0.52	-9999	-0.98	227	227
AP-1/NFAT1-c-4	-0.41	0.41	-9999	-1.1	94	94
FASLG	-0.46	0.52	-9999	-0.98	229	229
NFAT1-c-4/ICER1	-0.081	0.086	-9999	-0.6	4	4
IL2RA	-0.34	0.44	-9999	-1	107	107
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.28	0.38	-9999	-0.86	94	94
JunB/Fra1/NFAT1-c-4	-0.096	0.13	-9999	-0.68	9	9
IL4	-0.28	0.37	-9999	-0.83	91	91
IL2	-0.012	0.11	-9999	-0.77	10	10
IL3	-0.028	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.06	0.25	-9999	-0.86	46	46
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

p75(NTR)-mediated 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
Sortilin/TRAF6	-0.001	0.024	-9999	-0.56	1	1
Necdin/E2F1	-0.083	0.22	-9999	-0.68	65	65
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.078	0.2	-9999	-0.98	8	8
NGF (dimer)/p75(NTR)/BEX1	-0.26	0.3	-9999	-0.55	253	253
NT-4/5 (dimer)/p75(NTR)	-0.053	0.18	-9999	-0.67	42	42
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.032	0.22	-9999	-0.95	9	9
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.1	0.3	-9999	-0.86	71	71
MGDIs/NGR/p75(NTR)/LINGO1	-0.071	0.2	-9999	-0.61	62	62
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.12	0.25	-9999	-0.61	100	100
LINGO1	-0.022	0.18	-9999	-0.86	23	23
Sortilin/TRAF6/NRIF	-0.001	0.014	-9999	-10000	0	0
proBDNF (dimer)	-0.1	0.3	-9999	-0.86	71	71
NTRK1	-0.044	0.2	-9999	-0.75	41	41
RTN4R	0.004	0.098	-9999	-0.84	7	7
neuron apoptosis	-0.065	0.23	-9999	-0.67	31	31
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.059	0.24	-9999	-0.62	78	78
ARHGDIA	0.014	0.033	-9999	-0.74	1	1
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.084	0.21	-9999	-0.57	76	76
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.086	0.21	-9999	-0.58	77	77
Mammalian IAPs/DIABLO	-0.078	0.19	-9999	-0.52	80	80
proNGF (dimer)	-0.065	0.25	-9999	-0.86	49	49
MAGED1	0.014	0.038	-9999	-0.86	1	1
APP	0.014	0.033	-9999	-0.74	1	1
NT-4/5 (dimer)	-0.004	0.092	-9999	-0.86	6	6
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.079	0.2	-9999	-0.54	76	76
NGF	-0.065	0.25	-9999	-0.86	49	49
cell cycle arrest	-0.013	0.25	-9999	-0.59	59	59
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.044	0.11	-9999	-0.57	8	8
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.046	0.16	-9999	-0.58	42	42
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.09	0.23	-9999	-0.62	77	77
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.044	0.22	-9999	-0.57	76	76
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.034	0.085	-9999	-0.44	8	8
p75(NTR)/beta APP	-0.046	0.17	-9999	-0.66	37	37
BEX1	-0.26	0.37	-9999	-0.74	195	195
mol:GDP	-0.071	0.24	-9999	-0.64	77	77
NGF (dimer)	-0.34	0.3	-9999	-0.84	90	90
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.065	0.18	-9999	-0.56	62	62
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RAC1/GTP	-0.08	0.2	-9999	-0.56	76	76
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.091	0.23	-9999	-0.63	77	77
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.08	0.22	-9999	-0.66	64	64
NT3 (dimer)	0.005	0.09	-9999	-0.78	7	7
TP53	-0.041	0.22	-9999	-0.91	8	8
PRDM4	-0.044	0.22	-9999	-0.57	76	76
BDNF (dimer)	-0.41	0.36	-9999	-0.87	143	143
PIK3CA	0.014	0.033	-9999	-0.74	1	1
SORT1	0.014	0.033	-9999	-0.74	1	1
activation of caspase activity	-0.077	0.19	-9999	-0.96	8	8
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.084	0.21	-9999	-0.57	76	76
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.023	0.21	-9999	-0.63	23	23
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.044	0.22	-9999	-0.57	76	76
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.092	0.23	-9999	-0.63	78	78
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.052	0.18	-9999	-0.66	42	42
MAPK8	-0.021	0.2	-9999	-0.63	22	22
MAPK9	-0.02	0.2	-9999	-0.63	22	22
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.005	0.09	-9999	-0.78	7	7
NTF4	-0.004	0.092	-9999	-0.86	6	6
NDN	0.011	0.057	-9999	-0.74	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.071	0.18	-9999	-0.91	8	8
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.018	-9999	-10000	0	0
RhoA-B-C/GTP	-0.09	0.23	-9999	-0.62	77	77
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.098	0.21	-9999	-0.52	98	98
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.1	0.23	-9999	-0.56	98	98
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.088	0.22	-9999	-0.66	71	71
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.31	-9999	-0.86	80	80
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	0.008	0.24	-9999	-0.88	9	9
BAD	-0.01	0.2	-9999	-0.59	22	22
RIPK2	0.014	0.038	-9999	-0.86	1	1
NGFR	-0.044	0.22	-9999	-0.86	36	36
CYCS	-0.033	0.22	-9999	-0.54	77	77
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.084	0.21	-9999	-0.57	77	77
BCL2L11	-0.009	0.2	-9999	-0.59	22	22
BDNF (dimer)/p75(NTR)	-0.13	0.28	-9999	-0.7	100	100
PI3K	-0.084	0.21	-9999	-0.58	76	76
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.084	0.21	-9999	-0.57	76	76
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.1	0.26	-9999	-0.72	77	77
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.085	0.21	-9999	-0.57	77	77
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.057	-9999	-0.74	3	3
PLG	-0.38	0.38	-9999	-0.74	274	274
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.12	0.23	-9999	-0.67	44	44
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.004	0.18	-9999	-0.53	22	22
E2F1	-0.09	0.28	-9999	-0.86	64	64
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.069	0.14	-9999	-0.59	13	13
NGF (dimer)/TRKA	-0.1	0.24	-9999	-0.63	88	88
MMP7	-0.13	0.3	-9999	-0.75	99	99
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.078	0.2	-9999	-0.98	8	8
MMP3	-0.069	0.25	-9999	-0.86	47	47
APAF-1/Caspase 9	-0.11	0.17	-9999	-0.69	11	11

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.12	0.24	-10000	0	-0.77	35	35
UGCG	-0.024	0.055	-10000	0	-0.77	2	2
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.078	0.19	-10000	0	-0.48	57	57
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.009	0.064	-10000	0	-0.76	2	2
mol:DAG	-0.004	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.11	0.16	-10000	0	-0.56	36	36
FRAP1	-0.082	0.23	-10000	0	-0.61	51	51
FOXO3	-0.073	0.22	-10000	0	-0.66	33	33
AKT1	-0.09	0.24	-10000	0	-0.64	52	52
GAB2	0.016	0.003	-10000	0	-10000	0	0
SMPD1	-0.021	0.03	-10000	0	-10000	0	0
SGMS1	-0.021	0.03	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.026	0.032	-10000	0	-0.48	2	2
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.022	0.1	-10000	0	-0.49	2	2
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.55	2	2
RPS6KB1	-0.026	0.087	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.006	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.16	0.35	-10000	0	-0.86	107	107
PIK3R1	0.017	0.033	-10000	0	-0.74	1	1
JAK1	0.018	0.004	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MYC	-0.075	0.23	-10000	0	-0.66	37	37
MYB	-0.18	0.34	-10000	0	-0.74	139	139
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.12	0.26	-10000	0	-0.68	63	63
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.034	0.067	-10000	0	-0.47	2	2
mol:PI-3-4-5-P3	-0.11	0.25	-10000	0	-0.65	63	63
Rac1/GDP	0.02	0.033	-10000	0	-0.43	2	2
T cell proliferation	-0.093	0.23	-10000	0	-0.59	65	65
SHC1	0.014	0.038	-10000	0	-0.86	1	1
RAC1	0.015	0.002	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.008	0.026	-10000	0	-0.05	139	139
PRKCZ	-0.099	0.25	-10000	0	-0.62	65	65
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.56	34	34
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.14	0.26	-10000	0	-0.58	103	103
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.16	0.35	-10000	0	-0.86	105	105
IL2RB	-0.43	0.44	-10000	0	-0.86	274	274
TERT	-0.11	0.3	-10000	0	-0.86	75	75
E2F1	-0.099	0.2	-10000	0	-0.37	177	177
SOS1	0.016	0.003	-10000	0	-10000	0	0
RPS6	0.012	0.054	-10000	0	-0.86	2	2
mol:cAMP	0.003	0.013	0.025	139	-10000	0	139
PTPN11	0.016	0.003	-10000	0	-10000	0	0
IL2RG	-0.038	0.21	-10000	0	-0.86	34	34
actin cytoskeleton organization	-0.093	0.23	-10000	0	-0.59	65	65
GRB2	0.016	0.003	-10000	0	-10000	0	0
IL2	-0.004	0.12	-10000	0	-0.86	10	10
PIK3CA	0.017	0.033	-10000	0	-0.74	1	1
Rac1/GTP	0.032	0.034	-10000	0	-0.4	2	2
LCK	-0.017	0.17	-10000	0	-0.85	22	22
BCL2	-0.049	0.18	-10000	0	-0.52	28	28

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.026	0.022	-9999	-0.48	1	1
ADCY5	0.006	0.1	-9999	-0.48	22	22
ADCY6	0.026	0.041	-9999	-0.92	1	1
ADCY7	0.009	0.1	-9999	-0.58	16	16
ADCY1	0.013	0.084	-9999	-0.5	14	14
ADCY2	-0.13	0.27	-9999	-0.58	141	141
ADCY3	0.026	0.022	-9999	-0.48	1	1
ADCY8	-0.16	0.28	-9999	-0.59	165	165
PRKCE	0.014	0.025	-9999	-0.57	1	1
ADCY9	0.026	0.022	-9999	-0.48	1	1
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.092	0.17	-9999	-0.5	54	54

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.045	0.14	-9999	-0.72	1	1
CCNA2	-0.15	0.34	-9999	-0.86	102	102
PIK3CA	0.015	0.033	-9999	-0.74	1	1
JAK3	-0.16	0.35	-9999	-0.86	107	107
PIK3R1	0.015	0.033	-9999	-0.74	1	1
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.1	0.25	-9999	-0.66	59	59
SHC1	0.015	0.038	-9999	-0.86	1	1
SP1	0.025	0.022	-9999	-10000	0	0
IL2RA	-0.12	0.32	-9999	-0.77	106	106
IL2RB	-0.44	0.44	-9999	-0.86	274	274
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.039	0.21	-9999	-0.86	34	34
G1/S transition of mitotic cell cycle	-0.044	0.2	-9999	-0.55	13	13
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.05	-9999	-0.78	2	2
LCK	-0.019	0.17	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.006	0.12	-9999	-0.86	10	10
CDK6	0.014	0.033	-9999	-0.74	1	1
CCND3	-0.074	0.21	-9999	-0.72	17	17

×

Coregulation of Androgen receptor activity

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
NRIP1	0.013	0.035	-9999	-0.78	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.023	-9999	-10000	0	0
JMJD2C	-0.001	0.022	-9999	-0.11	19	19
T-DHT/AR/Ubc9	-0.078	0.11	-9999	-0.54	26	26
CARM1	0.015	0.003	-9999	-10000	0	0
PRDX1	0.016	0.001	-9999	-10000	0	0
PELP1	0.016	0.003	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
AKT1	0.017	0.006	-9999	-10000	0	0
PTK2B	0.015	0.003	-9999	-10000	0	0
MED1	0.013	0.009	-9999	-10000	0	0
MAK	0.014	0.044	-9999	-0.86	1	1
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.009	0.068	-9999	-0.77	4	4
GSN	0.015	0.008	-9999	-10000	0	0
NCOA2	0	0.11	-9999	-0.74	11	11
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.026	-9999	-10000	0	0
NCOA4	0.015	0.002	-9999	-10000	0	0
PIAS3	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.028	0.036	-9999	-0.61	1	1
XRCC5	0.016	0.005	-9999	-10000	0	0
UBE3A	0.014	0.013	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.15	-9999	-0.59	39	39
FHL2	-0.04	0.11	-9999	-1.1	5	5
RANBP9	0.016	0.003	-9999	-10000	0	0
JMJD1A	-0.12	0.056	-9999	-0.14	460	460
CDK6	0.014	0.033	-9999	-0.74	1	1
TGFB1I1	0.013	0.039	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.15	-9999	-0.59	46	46
XRCC6	0.016	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.58	26	26
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.015	0.017	-9999	-10000	0	0
BRCA1	0.015	0.007	-9999	-10000	0	0
TCF4	0.014	0.013	-9999	-10000	0	0
CDKN2A	-0.83	0.17	-9999	-0.86	513	513
SRF	0.026	0.012	-9999	-10000	0	0
NKX3-1	-0.19	0.07	-9999	-10000	0	0
KLK3	0.024	0.15	-9999	-0.7	21	21
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.013	-9999	-10000	0	0
AOF2	-0.001	0.01	-9999	-10000	0	0
APPL1	0.033	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.077	0.11	-9999	-0.54	26	26
AR	-0.07	0.16	-9999	-0.78	26	26
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.014	0.013	-9999	-10000	0	0
PAWR	0.014	0.033	-9999	-0.74	1	1
PRKDC	0.016	0.005	-9999	-10000	0	0
PA2G4	0.014	0.012	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.1	-9999	-0.5	26	26
RPS6KA3	0.013	0.035	-9999	-0.78	1	1
T-DHT/AR/ARA70	-0.078	0.11	-9999	-0.54	26	26
LATS2	0.014	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.069	0.1	-9999	-0.49	26	26
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.004	0.12	-9999	-0.74	14	14
KLK2	-0.085	0.14	-9999	-0.8	19	19
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.069	0.13	-9999	-0.56	32	32
TMPRSS2	-0.92	0.35	-9999	-1.1	460	460
CCND1	-0.018	0.17	-9999	-0.86	20	20
PIAS1	0.014	0.013	-9999	-10000	0	0
mol:T-DHT	-0.062	0.027	-9999	-0.072	449	449
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.013	0.019	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.11	-9999	-0.56	26	26
CMTM2	-0.004	0.13	-9999	-0.86	12	12
SNURF	-0.009	0.13	-9999	-0.74	17	17
ZMIZ1	-0.031	0.022	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.014	0.013	-9999	-10000	0	0
FKBP4	0.016	0.003	-9999	-10000	0	0

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.001	0.056	0.29	18	-10000	0	18
BUB1B	-0.022	0.12	-10000	0	-0.5	26	26
PLK1	-0.011	0.058	-10000	0	-0.2	10	10
PLK1S1	0.001	0.031	-10000	0	-10000	0	0
KIF2A	-0.003	0.072	-10000	0	-0.56	4	4
regulation of mitotic centrosome separation	-0.012	0.058	-10000	0	-0.2	10	10
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.18	0.33	-10000	0	-0.72	129	129
WEE1	-0.001	0.055	-10000	0	-0.28	7	7
cytokinesis	-0.2	0.27	-10000	0	-0.5	238	238
PP2A-alpha B56	-0.14	0.16	-10000	0	-10000	0	0
AURKA	-0.002	0.044	-10000	0	-0.3	6	6
PICH/PLK1	-0.044	0.16	-10000	0	-0.82	19	19
CENPE	-0.062	0.21	-10000	0	-0.62	62	62
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.003	0.071	-10000	0	-0.55	4	4
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.033	-10000	0	-0.74	1	1
TPX2	-0.049	0.12	-10000	0	-0.25	127	127
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.075	0.27	-10000	0	-0.86	55	55
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.025	0.096	-10000	0	-0.28	60	60
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.004	0.009	-10000	0	-0.02	129	129
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.006	0.031	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0	0.002	-10000	0	-0.014	6	6
STAG2	0.016	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.009	0.013	-10000	0	-10000	0	0
spindle elongation	-0.012	0.058	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.16	0.19	-10000	0	-0.45	10	10
TPT1	0.001	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	242	242
CDC25B	0.007	0.086	-10000	0	-0.88	5	5
SGOL1	0.001	0.057	-10000	0	-0.29	18	18
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.023	0.1	-10000	0	-0.74	9	9
CDC14B	0.016	0.002	-10000	0	-10000	0	0
CDC20	-0.055	0.24	-10000	0	-0.86	43	43
PLK1/PBIP1	-0.041	0.12	-10000	0	-0.59	19	19
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.003	0.044	-10000	0	-0.21	2	2
CDC2	-0.001	0.004	-10000	0	-0.023	9	9
NDC80	-0.17	0.36	-10000	0	-0.86	112	112
metaphase plate congression	-0.004	0.041	-10000	0	-10000	0	0
ERCC6L	-0.036	0.16	-10000	0	-0.81	19	19
NLP/gamma Tubulin	-0.003	0.034	-10000	0	-0.12	5	5
microtubule cytoskeleton organization	0.001	0.031	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.016	0.002	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.25	0.29	-10000	0	-0.56	238	238
GRASP65/GM130/RAB1/GTP/PLK1	-0.013	0.027	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.007	0.038	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	121	121
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.042	-10000	0	-10000	0	0
microtubule-based process	-0.24	0.3	-10000	0	-0.58	238	238
Golgi organization	-0.012	0.058	-10000	0	-0.2	10	10
Cohesin/SA2	-0.024	0.044	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.38	0.44	-10000	0	-0.86	238	238
APC/C/CDC20	-0.044	0.18	-10000	0	-0.64	43	43
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.04	0.11	-10000	0	-0.58	19	19
PRC1	0.006	0.093	-10000	0	-0.86	6	6
ECT2	0.001	0.053	-10000	0	-10000	0	0
C13orf34	0.004	0.042	-10000	0	-10000	0	0
NUDC	-0.004	0.041	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.022	0.12	-10000	0	-0.5	26	26
spindle assembly	-0.006	0.047	-10000	0	-0.16	8	8
spindle stabilization	0.001	0.031	-10000	0	-10000	0	0
APC/C/HCDH1	-0.001	0.021	-10000	0	-0.49	1	1
MKLP2/PLK1	-0.25	0.31	-10000	0	-0.59	238	238
CCNB1	0.002	0.11	-10000	0	-0.87	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.004	0.058	-10000	0	-0.48	4	4
TUBG1	0.001	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.025	0.097	-10000	0	-0.71	9	9
MLF1IP	-0.012	0.13	-10000	0	-0.69	19	19
INCENP	0.009	0.008	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	239	239
alphaV beta3 Integrin	-0.01	0.074	-9999	-0.53	10	10
PTK2	-0.15	0.23	-9999	-0.55	48	48
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.014	0.038	-9999	-0.86	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.084	0.19	-9999	-0.52	82	82
VEGFA	-0.38	0.44	-9999	-0.86	239	239
ILK	-0.084	0.19	-9999	-0.52	82	82
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.077	0.17	-9999	-0.49	74	74
PTK2B	-0.19	0.27	-9999	-0.48	239	239
alphaV/beta3 Integrin/JAM-A	-0.07	0.15	-9999	-0.52	10	10
CBL	0.014	0.033	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.47	254	254
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.066	-9999	-0.52	6	6
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.14	-9999	-0.47	46	46
alphaV/beta3 Integrin/Syndecan-1	-0.011	0.07	-9999	-0.47	12	12
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.047	0.14	-9999	-0.8	4	4
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
alphaV/beta3 Integrin/Osteopontin	-0.009	0.064	-9999	-0.47	10	10
RPS6KB1	-0.043	0.13	-9999	-0.73	4	4
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.044	0.1	-9999	-0.69	5	5
GPR124	0.011	0.066	-9999	-0.86	3	3
MAPK1	-0.044	0.1	-9999	-0.69	5	5
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
alphaV/beta3 Integrin/Tumstatin	-0.057	0.16	-9999	-0.49	63	63
cell adhesion	-0.17	0.18	-9999	-0.83	1	1
ANGPTL3	-0.34	0.38	-9999	-0.74	248	248
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	239	239
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.007	0.08	-9999	-0.74	6	6
IGF1	0.006	0.093	-9999	-0.86	6	6
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.009	0.065	-9999	-0.5	9	9
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.005	0.05	-9999	-0.47	6	6
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.019	0.099	-9999	-0.52	19	19
CSF1	0.014	0.033	-9999	-0.74	1	1
PIK3C2A	-0.086	0.2	-9999	-0.53	83	83
PI4 Kinase/Pyk2	-0.23	0.24	-9999	-0.75	47	47
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	239	239
FAK1/Vinculin	-0.11	0.18	-9999	-0.56	3	3
alphaV beta3/Integrin/ppsTEM5	-0.009	0.066	-9999	-0.51	9	9
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.1	0.28	-9999	-0.75	82	82
BCAR1	0.014	0.033	-9999	-0.74	1	1
FGF2	0.008	0.075	-9999	-0.77	5	5
F11R	0.025	0.059	-9999	-0.58	5	5
alphaV/beta3 Integrin/Lactadherin	-0.006	0.056	-9999	-0.49	7	7
alphaV/beta3 Integrin/TGFBR2	-0.005	0.05	-9999	-0.47	6	6
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.002	0.041	-9999	-0.85	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.005	0.046	-9999	-0.43	6	6
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.049	0.23	-9999	-0.86	39	39
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.88	1	1
SDC1	0.007	0.08	-9999	-0.74	6	6
VAV3	0.04	0.082	-9999	-0.79	1	1
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.065	-9999	-0.74	4	4
FAK1/Paxillin	-0.11	0.18	-9999	-0.56	3	3
cell migration	-0.091	0.17	-9999	-0.52	2	2
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.062	0.14	-9999	-1.1	1	1
SPP1	0.01	0.065	-9999	-0.74	4	4
KDR	0.014	0.033	-9999	-0.74	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	-0.068	0.24	-9999	-0.74	59	59
angiogenesis	0.002	0.15	-9999	-0.8	3	3
Rac1/GTP	-0.011	0.066	-9999	-0.72	1	1
EDIL3	-0.005	0.13	-9999	-0.78	14	14
cell proliferation	-0.005	0.05	-9999	-0.47	6	6

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	-0.054	0.16	-10000	0	-0.42	34	34
IKBKB	-0.023	0.1	-10000	0	-10000	0	0
AKT1	-0.023	0.12	-10000	0	-0.31	9	9
IKBKG	-0.022	0.11	-10000	0	-0.3	3	3
CALM1	-0.042	0.1	-10000	0	-0.5	3	3
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
MAP3K1	-0.11	0.25	-10000	0	-0.63	73	73
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.054	0.11	-10000	0	-0.5	4	4
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.011	0.09	-10000	0	-10000	0	0
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.033	-10000	0	-0.74	1	1
SHC1	0.014	0.038	-10000	0	-0.86	1	1
BCR complex	-0.17	0.29	-10000	0	-0.68	131	131
CD22	-0.15	0.23	-10000	0	-0.67	51	51
CAMK2G	-0.029	0.098	-10000	0	-0.49	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.009	0.076	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.1	0.19	-10000	0	-0.85	4	4
GO:0007205	-0.055	0.11	-10000	0	-0.5	4	4
SYK	0.013	0.046	-10000	0	-0.74	2	2
ELK1	-0.042	0.1	-10000	0	-0.51	3	3
NFATC1	-0.07	0.2	-10000	0	-0.51	58	58
B-cell antigen/BCR complex	-0.17	0.29	-10000	0	-0.68	131	131
PAG1/CSK	-0.002	0.041	-10000	0	-0.66	2	2
NFKBIB	0.005	0.039	-10000	0	-0.13	1	1
HRAS	-0.037	0.12	-10000	0	-0.49	4	4
NFKBIA	0.005	0.038	-10000	0	-0.14	1	1
NF-kappa-B/RelA/I kappa B beta	0.013	0.032	-10000	0	-0.18	1	1
RasGAP/Csk	-0.21	0.32	-10000	0	-0.99	47	47
mol:GDP	-0.05	0.1	0.29	1	-0.47	4	5
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	0.011	0.066	-10000	0	-0.86	3	3
NF-kappa-B/RelA/I kappa B alpha	0.014	0.032	-10000	0	-0.19	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.078	0.22	-10000	0	-0.57	65	65
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	-0.066	0.1	-10000	0	-0.51	4	4
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.04	0.11	-10000	0	-0.48	6	6
CHUK	-0.022	0.11	-10000	0	-10000	0	0
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.12	0.2	-10000	0	-0.56	63	63
PTPN6	-0.14	0.21	-10000	0	-0.68	39	39
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.01	0.068	-10000	0	-0.14	108	108
VAV2	-0.17	0.28	-10000	0	-0.8	75	75
ubiquitin-dependent protein catabolic process	0.011	0.037	-10000	0	-0.12	1	1
BTK	-0.086	0.17	0.46	1	-0.42	107	108
CD19	-0.19	0.32	-10000	0	-0.89	79	79
MAP4K1	-0.34	0.43	-10000	0	-0.86	218	218
CD72	-0.19	0.37	-10000	0	-0.86	124	124
PAG1	0.012	0.054	-10000	0	-0.86	2	2
MAPK14	-0.084	0.21	-10000	0	-0.53	64	64
SH3BP5	0.014	0.033	-10000	0	-0.74	1	1
PIK3AP1	-0.037	0.11	-10000	0	-0.54	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.11	0.23	-10000	0	-0.57	79	79
RAF1	-0.025	0.11	-10000	0	-0.53	2	2
RasGAP/p62DOK/SHIP	-0.2	0.31	-10000	0	-0.97	48	48
CD79A	-0.2	0.38	-10000	0	-0.86	131	131
re-entry into mitotic cell cycle	-0.012	0.089	-10000	0	-10000	0	0
RASA1	0.014	0.033	-10000	0	-0.74	1	1
MAPK3	-0.001	0.099	-10000	0	-10000	0	0
MAPK1	-0.001	0.099	-10000	0	-0.42	2	2
CD72/SHP1	-0.23	0.33	-10000	0	-0.82	101	101
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MAPK8	-0.085	0.21	-10000	0	-0.52	69	69
actin cytoskeleton organization	-0.095	0.26	-10000	0	-0.66	69	69
NF-kappa-B/RelA	0.035	0.059	-10000	0	-10000	0	0
Calcineurin	-0.042	0.07	-10000	0	-10000	0	0
PI3K	-0.14	0.22	-10000	0	-0.6	71	71
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.061	0.1	-10000	0	-0.55	4	4
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.27	0.32	-10000	0	-0.74	137	137
DAPP1	-0.11	0.18	-10000	0	-0.61	36	36
cytokine secretion	-0.064	0.19	-10000	0	-0.47	58	58
mol:DAG	-0.066	0.1	-10000	0	-0.51	4	4
PLCG2	0.003	0.1	-10000	0	-0.82	8	8
MAP2K1	-0.013	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.24	0.37	-10000	0	-0.72	180	180
mol:PI-3-4-5-P3	-0.097	0.15	-10000	0	-0.4	67	67
ETS1	-0.017	0.092	-10000	0	-10000	0	0
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.12	0.22	-10000	0	-0.98	3	3
B-cell antigen/BCR complex/LYN	-0.14	0.21	-10000	0	-0.59	63	63
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.1	0.28	-10000	0	-0.72	69	69
B-cell antigen/BCR complex/LYN/SYK	-0.16	0.25	-10000	0	-0.67	64	64
CARD11	-0.14	0.26	-10000	0	-0.62	110	110
FCGR2B	-0.14	0.34	-10000	0	-0.86	96	96
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.005	0.047	-10000	0	-10000	0	0
PTPRC	-0.077	0.27	-10000	0	-0.86	56	56
PDPK1	-0.06	0.1	-10000	0	-0.31	9	9
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	0.001	0.057	-10000	0	-0.14	66	66

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.019	0.11	-10000	0	-1.4	1	1
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.018	0	-10000	0	-10000	0	0
TBX21	-0.25	0.41	-10000	0	-0.82	179	179
SUMO2	0.011	0.007	-10000	0	-10000	0	0
STAT1 (dimer)	0.025	0.053	-10000	0	-1.2	1	1
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	0.004	0.098	-10000	0	-0.84	7	7
GR alpha/HSP90/FKBP51/HSP90	0.056	0.13	0.39	5	-0.57	8	13
PRL	-0.015	0.11	-10000	0	-0.56	1	1
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.57	83	-0.62	2	85
RELA	0.005	0.076	-10000	0	-10000	0	0
FGG	-0.14	0.43	0.58	12	-0.72	155	167
GR beta/TIF2	0.051	0.14	0.43	5	-0.52	10	15
IFNG	-0.41	0.44	-10000	0	-0.83	242	242
apoptosis	-0.093	0.21	-10000	0	-0.65	10	10
CREB1	-0.014	0.1	-10000	0	-0.38	13	13
histone acetylation	0.02	0.13	0.39	10	-0.44	7	17
BGLAP	-0.009	0.13	-10000	0	-0.74	3	3
GR/PKAc	0.066	0.1	0.4	2	-0.6	1	3
NF kappa B1 p50/RelA	0.011	0.14	-10000	0	-0.56	8	8
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.047	0.093	0.31	12	-10000	0	12
GATA3	-0.35	0.38	-10000	0	-0.74	264	264
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.027	0.15	-10000	0	-0.68	17	17
GSK3B	0.011	0.007	-10000	0	-10000	0	0
NR1I3	-0.057	0.22	-10000	0	-0.82	13	13
CSN2	0.045	0.19	0.5	4	-0.66	1	5
BRG1/BAF155/BAF170/BAF60A	0.004	0.014	-10000	0	-10000	0	0
NFATC1	0.018	0.005	-10000	0	-10000	0	0
POU2F1	0.019	0.005	-10000	0	-10000	0	0
CDKN1A	0.05	0.052	-10000	0	-0.72	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.003	0.21	0.39	1	-0.58	25	26
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.058	0.22	-10000	0	-0.85	13	13
JUN	-0.22	0.25	-10000	0	-0.61	94	94
IL4	-0.024	0.12	-10000	0	-0.63	1	1
CDK5R1	0.012	0.007	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.26	0.31	1	-0.7	81	82
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.062	0.12	0.39	3	-0.6	4	7
cortisol/GR alpha (monomer)	0.15	0.34	0.65	99	-0.8	1	100
NCOA2	0	0.11	-10000	0	-0.74	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.054	0.14	-10000	0	-0.82	13	13
AP-1/NFAT1-c-4	-0.32	0.34	-10000	0	-0.81	112	112
AFP	-0.35	0.56	-10000	0	-1.4	112	112
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.085	0.15	0.51	8	-0.62	1	9
TP53	0.044	0.021	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.25	0.41	-10000	0	-1.1	71	71
KRT14	-0.15	0.3	-10000	0	-0.83	81	81
TBP	0.028	0.01	-10000	0	-10000	0	0
CREBBP	0.049	0.082	-10000	0	-10000	0	0
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.011	0.014	-10000	0	-10000	0	0
AP-1	-0.33	0.34	-10000	0	-0.82	115	115
MAPK14	0.012	0.007	-10000	0	-10000	0	0
MAPK10	0.005	0.074	-10000	0	-0.75	5	5
MAPK11	0.008	0.055	-10000	0	-0.88	2	2
KRT5	-0.27	0.39	-10000	0	-0.93	111	111
interleukin-1 receptor activity	0	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.053	-10000	0	-1.2	1	1
CGA	-0.13	0.37	-10000	0	-1.2	52	52
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.091	0.15	0.45	35	-10000	0	35
MAPK3	0.012	0.007	-10000	0	-10000	0	0
MAPK1	0.012	0.007	-10000	0	-10000	0	0
ICAM1	-0.049	0.23	-10000	0	-0.76	29	29
NFKB1	0.003	0.085	-10000	0	-0.9	1	1
MAPK8	-0.14	0.2	-10000	0	-0.49	65	65
MAPK9	0.012	0.007	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.098	0.22	-10000	0	-0.68	10	10
BAX	0.052	0.028	-10000	0	-10000	0	0
POMC	-0.037	0.17	-10000	0	-0.86	6	6
EP300	0.047	0.087	-10000	0	-0.6	1	1
cortisol/GR alpha (dimer)/p53	0.16	0.29	0.58	92	-0.7	1	93
proteasomal ubiquitin-dependent protein catabolic process	0.026	0.071	0.28	2	-10000	0	2
SGK1	0.1	0.098	-10000	0	-10000	0	0
IL13	-0.36	0.28	-10000	0	-0.81	92	92
IL6	-0.12	0.38	-10000	0	-0.98	75	75
PRKACG	0.004	0.007	-10000	0	-10000	0	0
IL5	-0.29	0.21	-10000	0	-0.71	46	46
IL2	-0.17	0.25	-10000	0	-0.86	26	26
CDK5	0.012	0.007	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.077	0.3	-10000	0	-0.92	44	44
CDK5R1/CDK5	0	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.027	0.1	-10000	0	-0.62	1	1
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.15	0.26	0.56	73	-0.65	1	74
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.1	0.15	0.41	34	-10000	0	34
NF kappa B1 p50/RelA/Cbp	0.066	0.14	-10000	0	-0.93	1	1
JUN (dimer)	-0.21	0.25	-10000	0	-0.61	94	94
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.057	0.22	-10000	0	-1	16	16
NR3C1	0.081	0.19	0.5	32	-0.95	1	33
NR4A1	0.002	0.13	-10000	0	-0.73	16	16
TIF2/SUV420H1	-0.011	0.079	-10000	0	-0.56	11	11
MAPKKK cascade	-0.093	0.21	-10000	0	-0.65	10	10
cortisol/GR alpha (dimer)/Src-1	0.15	0.28	0.58	85	-0.8	1	86
PBX1	-0.003	0.13	-10000	0	-0.74	16	16
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.095	0.36	-10000	0	-1.3	39	39
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.1	0.15	0.41	34	-10000	0	34
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.15	0.26	0.56	73	-0.65	1	74
mol:cortisol	0.064	0.2	0.38	87	-0.26	14	101
MMP1	-0.23	0.4	-10000	0	-0.98	106	106

×

Regulation of Telomerase

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
Telomerase catalytic core complex	-0.24	0.28	-9999	-0.84	79	79
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.014	0.087	-9999	-0.56	13	13
IFNAR2	0.015	0.007	-9999	-10000	0	0
AKT1	0.013	0.069	-9999	-0.43	10	10
ER alpha/Oestrogen	-0.006	0.057	-9999	-0.59	5	5
NFX1/SIN3/HDAC complex	0.044	0.055	-9999	-10000	0	0
EGF	-0.67	0.23	-9999	-0.74	480	480
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.22	0.26	-9999	-0.79	77	77
SAP18	0.013	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.34	0.38	-9999	-0.74	248	248
WRN	0.016	0	-9999	-10000	0	0
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.18	0.23	-9999	-0.72	66	66
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.24	0.29	-9999	-0.88	79	79
CCND1	-0.22	0.27	-9999	-0.78	87	87
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.013	0.006	-9999	-10000	0	0
RBBP4	0.012	0.033	-9999	-0.74	1	1
TERF2	0	0.004	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.013	0.006	-9999	-10000	0	0
Telomerase/911	0.004	0.029	-9999	-10000	0	0
CDKN1B	-0.22	0.3	-9999	-0.55	239	239
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	-0.018	0.16	-9999	-0.86	19	19
TRF2/PARP2	0	0.004	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.014	0.006	-9999	-10000	0	0
E6	-0.001	0.003	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.005	0.12	-9999	-0.75	13	13
IFN-gamma/IRF1	-0.29	0.32	-9999	-0.65	239	239
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.004	0.13	-9999	-0.86	12	12
Telomerase	-0.021	0.16	-9999	-0.39	47	47
IRF1	0.016	0.039	-9999	-0.86	1	1
ESR1	0.006	0.076	-9999	-0.77	5	5
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	-0.001	0.021	-9999	-0.49	1	1
ubiquitin-dependent protein catabolic process	0.051	0.051	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.007	0.033	-9999	-10000	0	0
HDAC1	0.013	0.006	-9999	-10000	0	0
HDAC2	0.015	0.007	-9999	-10000	0	0
ATM	-0.001	0.023	-9999	-0.52	1	1
SMAD3	0.025	0.067	-9999	-0.66	5	5
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.006	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.17	0.25	-9999	-0.74	74	74
NR2F2	0.01	0.012	-9999	-10000	0	0
MAPK3	0.009	0.094	-9999	-0.67	10	10
MAPK1	0.009	0.094	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.008	0.084	-9999	-0.86	5	5
NFKB1	0.014	0.033	-9999	-0.74	1	1
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	-0.001	0.023	-9999	-0.52	1	1
NBN	0.016	0	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.51	0.18	-9999	-0.57	481	481
MYC	-0.021	0.17	-9999	-0.86	21	21
IL2	-0.008	0.12	-9999	-0.86	10	10
KU	0	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.008	0.084	-9999	-0.86	5	5
TRF2/BLM	-0.014	0.093	-9999	-0.62	12	12
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.21	0.26	-9999	-0.78	77	77
SP1/HDAC2	0.007	0.014	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.18	0.23	-9999	-0.72	66	66
Smad3/Myc	-0.021	0.13	-9999	-0.59	25	25
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.37	0.43	-9999	-0.85	239	239
Telomerase/PinX1	-0.18	0.23	-9999	-0.72	66	66
Telomerase/AKT1/mTOR/p70S6K	-0.012	0.079	-9999	-0.53	2	2
SIN3B	0.013	0.006	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.18	0.23	-9999	-0.72	65	65
response to DNA damage stimulus	0.004	0.006	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0.004	-9999	-10000	0	0
TRF2/WRN	0	0.004	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.18	0.23	-9999	-0.72	66	66
E2F1	-0.091	0.29	-9999	-0.87	64	64
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.14	0.33	-9999	-0.86	93	93
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	-0.18	0.27	-10000	0	-0.54	96	96
CRKL	0.016	0.12	-10000	0	-0.67	5	5
HRAS	-0.043	0.18	-10000	0	-0.51	41	41
mol:PIP3	-0.005	0.11	-10000	0	-0.44	24	24
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.014	0.033	-10000	0	-0.74	1	1
GAB1	0.005	0.12	-10000	0	-0.49	24	24
FOXO3	0.022	0.11	-10000	0	-0.59	5	5
AKT1	0.012	0.12	-10000	0	-0.45	24	24
BAD	0.021	0.11	-10000	0	-0.59	6	6
megakaryocyte differentiation	-0.074	0.22	-10000	0	-0.45	117	117
GSK3B	0.022	0.11	-10000	0	-0.59	5	5
RAF1	-0.012	0.15	-10000	0	-0.54	3	3
SHC1	0.014	0.038	-10000	0	-0.86	1	1
STAT3	0.005	0.12	-10000	0	-0.49	24	24
STAT1	-0.02	0.25	-10000	0	-1	24	24
HRAS/SPRED1	-0.068	0.12	-10000	0	-0.43	19	19
cell proliferation	0.004	0.13	-10000	0	-0.51	24	24
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.006	0.12	-10000	0	-0.48	26	26
HRAS/SPRED2	-0.068	0.12	-10000	0	-0.43	20	20
LYN/TEC/p62DOK	-0.02	0.1	-10000	0	-0.66	5	5
MAPK3	0.011	0.12	-10000	0	-0.37	2	2
STAP1	-0.32	0.22	-10000	0	-0.42	406	406
GRAP2	-0.042	0.22	-10000	0	-0.86	35	35
JAK2	-0.07	0.2	-10000	0	-0.9	24	24
STAT1 (dimer)	-0.018	0.24	-10000	0	-1	24	24
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.22	-10000	0	-0.55	49	49
actin filament polymerization	-0.002	0.14	-10000	0	-0.49	30	30
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.3	0.23	-10000	0	-0.88	33	33
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
CBL/CRKL/GRB2	-0.016	0.095	-10000	0	-0.59	5	5
PI3K	-0.022	0.11	-10000	0	-0.45	25	25
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.35	-10000	0	-1.3	26	26
MAPK8	0.003	0.13	-10000	0	-0.52	24	24
STAT3 (dimer)	0.005	0.12	-10000	0	-0.48	24	24
positive regulation of transcription	0.014	0.098	-10000	0	-0.31	1	1
mol:GDP	-0.11	0.19	-10000	0	-0.62	44	44
PIK3C2B	0.005	0.12	-10000	0	-0.49	24	24
CBL/CRKL	0.024	0.11	-10000	0	-0.62	5	5
FER	0.003	0.13	-10000	0	-0.5	26	26
SH2B3	0.005	0.12	-10000	0	-0.49	24	24
PDPK1	0.005	0.1	-10000	0	-0.4	25	25
SNAI2	0.004	0.13	-10000	0	-0.5	24	24
positive regulation of cell proliferation	-0.003	0.19	-10000	0	-0.7	31	31
KITLG	0	0.11	-10000	0	-0.76	10	10
cell motility	-0.003	0.19	-10000	0	-0.7	31	31
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.039	0.073	-10000	0	-10000	0	0
STAT5A (dimer)	0.001	0.16	-10000	0	-0.59	32	32
SOCS1	0.006	0.093	-10000	0	-0.86	6	6
cell migration	0.045	0.2	0.5	72	-10000	0	72
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.29	0.42	-10000	0	-0.86	187	187
VAV1	-0.19	0.37	-10000	0	-0.86	125	125
GRB10	0.005	0.12	-10000	0	-0.49	24	24
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.037	0.12	-10000	0	-0.47	33	33
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.005	0.13	-10000	0	-0.42	2	2
CBL	0.014	0.033	-10000	0	-0.74	1	1
KIT	-0.016	0.29	-10000	0	-1.2	31	31
MAP2K2	0.004	0.13	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.021	0.1	-10000	0	-0.66	5	5
STAT5A	0	0.17	-10000	0	-0.61	32	32
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.004	0.13	-10000	0	-0.49	24	24
SHC/GRAP2	-0.045	0.17	-10000	0	-0.66	36	36
PTPRO	-0.076	0.22	-10000	0	-0.46	117	117
SH2B2	-0.002	0.14	-10000	0	-0.5	30	30
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.046	0.2	-10000	0	-0.52	72	72
CREBBP	0.044	0.012	-10000	0	-10000	0	0
BCL2	0.041	0.071	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.22	-9999	-0.48	179	179
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0.001	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.11	0.22	-9999	-0.52	6	6
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.011	0.14	-9999	-0.86	13	13
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.65	0.38	-9999	-0.86	404	404
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0.001	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.099	0.29	-9999	-0.86	67	67
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.17	0.24	-9999	-0.49	190	190
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.13	0.16	-9999	-0.59	16	16
MAP1B	-0.001	0.02	-9999	-0.33	2	2
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.17	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.74	178	178
PAFAH/LIS1	-0.44	0.25	-9999	-0.57	404	404
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.098	0.12	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.14	-9999	-0.69	1	1
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.13	0.19	-9999	-0.64	16	16
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.031	0	-9999	-10000	0	0
PAFAH1B3	0.014	0.033	-9999	-0.74	1	1
PAFAH1B2	0.014	0.033	-9999	-0.74	1	1
MAP1B/LIS1/Dynein heavy chain	-0.001	0.013	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.12	0.15	-9999	-0.56	16	16
LRP8	0.014	0.038	-9999	-0.86	1	1
NDEL1/Katanin 60	-0.13	0.16	-9999	-0.59	16	16
P39/CDK5	-0.18	0.22	-9999	-0.86	16	16
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.094	0.21	-9999	-0.48	6	6
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.14	0.2	-9999	-0.89	1	1
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6
CDC42	0	0	-9999	-10000	0	0

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.02	0.18	-9999	-10000	0	0
CRKL	-0.094	0.22	-9999	-10000	0	0
mol:DAG	-0.12	0.17	-9999	-10000	0	0
HRAS	-0.11	0.15	-9999	-0.7	1	1
MAPK8	-0.14	0.26	-9999	-0.48	187	187
RAP1A	-0.094	0.22	-9999	-10000	0	0
GAB1	-0.094	0.22	-9999	-10000	0	0
MAPK14	-0.13	0.25	-9999	-0.48	187	187
EPO	-0.29	0.42	-9999	-0.85	187	187
PLCG1	-0.13	0.17	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.019	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.2	0.27	-9999	-0.55	188	188
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.31	-9999	-0.65	187	187
IRS2	-0.1	0.23	-9999	-0.88	2	2
STAT1	-0.065	0.21	-9999	-10000	0	0
STAT5B	-0.07	0.21	-9999	-10000	0	0
cell proliferation	-0.12	0.24	-9999	-0.85	1	1
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.11	0.15	-9999	-0.71	1	1
TEC	-0.094	0.22	-9999	-10000	0	0
SOCS3	0.009	0.076	-9999	-0.86	4	4
STAT1 (dimer)	-0.063	0.21	-9999	-10000	0	0
JAK2	0.006	0.018	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
EPO/EPOR (dimer)/JAK2	-0.1	0.24	-9999	-10000	0	0
EPO/EPOR	-0.23	0.31	-9999	-0.65	187	187
LYN	0.018	0.001	-9999	-10000	0	0
TEC/VAV2	-0.081	0.22	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.019	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
EPO/EPOR (dimer)/LYN	-0.16	0.28	-9999	-0.54	187	187
mol:IP3	-0.12	0.17	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.13	0.18	-9999	-0.79	3	3
SH2B3	0.006	0.018	-9999	-10000	0	0
NFKB1	-0.14	0.26	-9999	-0.48	187	187
EPO/EPOR (dimer)/JAK2/SOCS3	-0.11	0.15	-9999	-0.53	3	3
PTPN6	-0.11	0.23	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.12	0.17	-9999	-10000	0	0
EPOR	0.007	0.019	-9999	-10000	0	0
INPP5D	0.009	0.076	-9999	-0.86	4	4
mol:GDP	-0.12	0.16	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
CRKL/CBL/C3G	-0.12	0.17	-9999	-0.73	1	1
VAV2	-0.094	0.22	-9999	-10000	0	0
CBL	-0.095	0.22	-9999	-0.8	1	1
SHC/Grb2/SOS1	-0.12	0.17	-9999	-10000	0	0
STAT5A	-0.07	0.21	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.045	0.21	-9999	-10000	0	0
LYN/PLCgamma2	-0.009	0.076	-9999	-0.62	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.29	-9999	-0.88	30	30
BCL2	-0.02	0.18	-9999	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.3	-9999	-0.76	40	40
CRP	-0.2	0.39	-9999	-0.91	90	90
cell cycle arrest	-0.18	0.35	-9999	-0.8	79	79
TIMP1	-0.15	0.33	-9999	-0.77	70	70
IL6ST	-0.015	0.14	-9999	-0.74	19	19
Rac1/GDP	-0.14	0.26	-9999	-0.6	91	91
AP1	0.021	0.1	-9999	-0.55	3	3
GAB2	0.011	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.37	-9999	-0.91	61	61
HSP90B1	0.004	0.087	-9999	-10000	0	0
GAB1	0.014	0.006	-9999	-10000	0	0
MAPK14	0.014	0.14	-9999	-0.72	5	5
AKT1	0.06	0.034	-9999	-10000	0	0
FOXO1	0.076	0.023	-9999	-10000	0	0
MAP2K6	-0.02	0.14	-9999	-0.7	6	6
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.27	-9999	-0.65	70	70
MITF	-0.026	0.14	-9999	-0.69	5	5
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	0.028	0.005	-9999	-10000	0	0
CEBPB	0.003	0.13	-9999	-0.86	12	12
GRB2/SOS1/GAB family/SHP2	0	0.069	-9999	-10000	0	0
STAT3	-0.18	0.36	-9999	-0.85	75	75
STAT1	-0.005	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.3	-9999	-0.78	34	34
PIK3CA	0.017	0.033	-9999	-0.74	1	1
PI3K	-0.002	0.034	-9999	-0.55	2	2
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.02	0.13	-9999	-0.71	4	4
MAPK11	0.013	0.14	-9999	-0.78	6	6
STAT3 (dimer)/FOXO1	-0.072	0.27	-9999	-0.65	16	16
GRB2/SOS1/GAB family	-0.048	0.11	-9999	-0.66	4	4
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.04	0.16	-9999	-0.65	13	13
GRB2	0.014	0.006	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	-0.29	0.44	-9999	-0.88	165	165
PIK3R1	0.016	0.033	-9999	-0.74	1	1
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.32	-9999	-0.81	44	44
FGG	-0.27	0.43	-9999	-0.89	123	123
macrophage differentiation	-0.18	0.35	-9999	-0.8	79	79
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.07	0.17	-9999	-0.56	34	34
JUNB	-0.14	0.3	-9999	-0.77	34	34
FOS	-0.009	0.12	-9999	-0.75	13	13
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.037	0.15	-9999	-0.48	22	22
STAT1/PIAS1	-0.049	0.16	-9999	-0.51	20	20
GRB2/SOS1/GAB family/SHP2/PI3K	0.022	0.038	-9999	-10000	0	0
STAT3 (dimer)	-0.18	0.36	-9999	-0.84	79	79
PRKCD	-0.15	0.3	-9999	-0.72	58	58
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.028	0.14	-9999	-0.69	7	7
gp130 (dimer)/JAK1/JAK1/LMO4	-0.005	0.093	-9999	-0.47	15	15
Rac1/GTP	-0.18	0.23	-9999	-0.61	97	97
HCK	-0.033	0.2	-9999	-0.86	29	29
MAPKKK cascade	0.025	0.061	-9999	-10000	0	0
bone resorption	-0.18	0.35	-9999	-0.84	63	63
IRF1	-0.14	0.3	-9999	-0.76	40	40
mol:GDP	-0.15	0.27	-9999	-0.6	102	102
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.27	-9999	-0.61	102	102
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.01	0.13	-9999	-0.72	4	4
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.078	0.21	-9999	-0.63	67	67
gp130 (dimer)/TYK2/TYK2/LMO4	-0.014	0.088	-9999	-0.47	19	19
gp130 (dimer)/JAK2/JAK2/LMO4	-0.014	0.088	-9999	-0.47	19	19
IL6	-0.092	0.28	-9999	-0.82	67	67
PIAS3	0.016	0	-9999	-10000	0	0
PTPRE	0.016	0.04	-9999	-0.81	1	1
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.015	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.036	0.13	-9999	-0.45	15	15
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.29	-9999	-0.8	65	65
MCL1	0.075	0.022	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.012	0.054	-9999	-0.86	2	2
RELN/VLDLR/Fyn	-0.16	0.22	-9999	-0.48	178	178
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.004	0.045	-9999	-0.8	1	1
AKT1	-0.067	0.16	-9999	-0.57	2	2
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.011	0.14	-9999	-0.86	13	13
RELN/LRP8/DAB1	-0.16	0.22	-9999	-0.45	191	191
LRPAP1/LRP8	-0.001	0.029	-9999	-0.66	1	1
RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.52	19	19
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.82	1	1
long-term memory	-0.2	0.24	-9999	-0.88	24	24
DAB1/LIS1	-0.14	0.18	-9999	-0.85	1	1
DAB1/CRLK/C3G	-0.13	0.17	-9999	-0.82	1	1
PIK3CA	0.014	0.033	-9999	-0.74	1	1
DAB1/NCK2	-0.14	0.18	-9999	-0.86	1	1
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.1	0.3	-9999	-0.83	76	76
CDK5R1	0.016	0.001	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.74	178	178
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RELN/LRP8/Fyn	-0.16	0.22	-9999	-0.48	179	179
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.21	0.25	-9999	-0.62	77	77
MAPK8	0.013	0.046	-9999	-0.74	2	2
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.45	190	190
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.51	19	19
RELN/LRP8	-0.16	0.22	-9999	-0.48	179	179
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.15	0.2	-9999	-0.9	2	2
PI3K	-0.002	0.034	-9999	-0.56	2	2
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.002	0.041	-9999	-0.66	2	2
RAP1A	-0.11	0.17	-9999	-0.75	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.013	0.046	-9999	-0.74	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.008	0.054	-9999	-0.86	2	2
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.03	0.12	-9999	-0.53	3	3
neuron adhesion	-0.05	0.19	-9999	-0.7	1	1
LRP8	0.014	0.038	-9999	-0.86	1	1
GSK3B	-0.053	0.15	-9999	-0.53	2	2
RELN/VLDLR/DAB1/Fyn	-0.15	0.2	-9999	-0.52	18	18
MAP3K11	0.014	0.033	-9999	-0.74	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.15	-9999	-0.61	2	2
CDK5	0.016	0	-9999	-10000	0	0
MAPT	0.016	0.082	-9999	-0.69	6	6
neuron migration	-0.06	0.21	-9999	-0.61	1	1
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.03	0.12	-9999	-0.54	3	3
RELN/VLDLR	-0.14	0.2	-9999	-0.52	6	6

×

Visual signal transduction: Rods

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
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.01	0.082	-9999	-0.68	8	8
Metarhodopsin II/Arrestin	-0.018	0.1	-9999	-0.59	16	16
PDE6G/GNAT1/GTP	-0.014	0.086	-9999	-0.56	13	13
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.007	0.11	-9999	-0.86	8	8
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.11	0.21	-9999	-0.94	12	12
mol:Na +	-0.11	0.21	-9999	-0.81	22	22
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.22	-9999	-0.85	22	22
CNGB1	-0.008	0.12	-9999	-0.86	11	11
RDH5	-0.003	0.13	-9999	-0.83	12	12
SAG	0.001	0.038	-9999	-0.86	1	1
mol:Ca2+	-0.069	0.22	-9999	-0.78	22	22
Na + (4 Units)	-0.1	0.2	-9999	-0.74	22	22
RGS9	-0.008	0.14	-9999	-0.81	15	15
GNB1/GNGT1	-0.23	0.32	-9999	-0.66	183	183
GNAT1/GDP	-0.038	0.13	-9999	-0.53	16	16
GUCY2D	-0.031	0.19	-9999	-0.86	26	26
GNGT1	-0.29	0.42	-9999	-0.86	183	183
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.038	0.15	-9999	-0.59	29	29
mol:11-cis-retinal	-0.003	0.13	-9999	-0.83	12	12
mol:cGMP	-0.04	0.14	-9999	-0.58	14	14
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.033	0.14	-9999	-0.65	27	27
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.13	0.3	-9999	-0.74	100	100
Metarhodopsin II	-0.016	0.091	-9999	-0.55	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.043	0.15	-9999	-0.56	39	39
RGS9BP	-0.017	0.15	-9999	-0.74	23	23
Metarhodopsin II/Transducin	-0.12	0.16	-9999	-0.62	11	11
GCAP Family/Ca ++	-0.017	0.098	-9999	-0.56	16	16
PDE6A/B	-0.035	0.15	-9999	-0.66	28	28
mol:Pi	-0.035	0.13	-9999	-0.49	38	38
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.27	-9999	-0.55	186	186
PDE6B	0.007	0.08	-9999	-0.74	6	6
PDE6A	-0.024	0.18	-9999	-0.86	23	23
PDE6G	0.008	0.075	-9999	-0.77	5	5
RHO	-0.015	0.14	-9999	-0.86	15	15
PDE6	-0.056	0.16	-9999	-0.82	8	8
GUCA1A	-0.01	0.12	-9999	-0.86	10	10
GC2/GCAP Family	-0.017	0.098	-9999	-0.57	14	14
GUCA1C	0.001	0.046	-9999	-0.74	2	2
GUCA1B	0.007	0.085	-9999	-0.86	5	5

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.048	0.1	-10000	0	-0.46	10	10
PTP1B/AKT1	-0.032	0.047	-10000	0	-0.41	2	2
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.049	0.053	-10000	0	-0.37	6	6
EGFR	-0.013	0.11	-10000	0	-0.87	9	9
EGF/EGFR	-0.37	0.14	-10000	0	-0.41	477	477
CSF1	0.014	0.033	-10000	0	-0.74	1	1
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.05	0.091	-10000	0	-0.45	20	20
Insulin Receptor/Insulin	-0.008	0.035	-10000	0	-10000	0	0
HCK	-0.032	0.2	-10000	0	-0.86	29	29
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.035	0.05	-10000	0	-0.41	3	3
EGF	-0.67	0.23	-10000	0	-0.74	480	480
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	40	40
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.033	0.055	-10000	0	-0.45	6	6
cell migration	0.049	0.053	0.37	6	-10000	0	6
STAT3	0.015	0.002	-10000	0	-10000	0	0
PRLR	-0.087	0.26	-10000	0	-0.74	71	71
ITGA2B	-0.019	0.16	-10000	0	-0.86	19	19
CSF1R	0.004	0.1	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.075	0.19	-10000	0	-0.56	71	71
FGR	0.011	0.066	-10000	0	-0.86	3	3
PTP1B/p130 Cas	-0.036	0.052	-10000	0	-0.44	2	2
Crk/p130 Cas	-0.03	0.042	-10000	0	-0.42	1	1
DOK1	-0.019	0.046	-10000	0	-0.38	2	2
JAK2	-0.054	0.11	-10000	0	-0.42	17	17
Jak2/Leptin Receptor/Leptin	-0.054	0.13	-10000	0	-0.58	11	11
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
PTPN1	-0.049	0.053	-10000	0	-0.37	6	6
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.01	0.14	-10000	0	-0.74	18	18
SRC	0	0.021	-10000	0	-10000	0	0
ITGB3	0.003	0.08	-10000	0	-0.74	6	6
CAT1/PTP1B	-0.23	0.13	-10000	0	-0.58	36	36
CAPN1	0.002	0.006	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0.008	0.043	-10000	0	-0.63	1	1
mol:H2O2	-0.007	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.036	0.13	-10000	0	-0.71	5	5
negative regulation of transcription	-0.053	0.11	-10000	0	-0.41	17	17
FCGR2A	-0.024	0.18	-10000	0	-0.86	24	24
FER	-0.001	0.046	-10000	0	-0.75	2	2
alphaIIb/beta3 Integrin	-0.03	0.14	-10000	0	-0.66	24	24
BLK	-0.041	0.21	-10000	0	-0.86	34	34
Insulin Receptor/Insulin/Shc	-0.001	0.026	-10000	0	-0.59	1	1
RHOA	0.002	0.006	-10000	0	-10000	0	0
LEPR	0.014	0.004	-10000	0	-10000	0	0
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.22	0.15	-10000	0	-0.55	62	62
PRL	0.004	0.007	-10000	0	-10000	0	0
SOCS3	0.025	0.067	-10000	0	-0.73	4	4
SPRY2	0.002	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.004	0.042	-10000	0	-0.49	4	4
CSF1/CSF1R	-0.037	0.075	-10000	0	-0.53	10	10
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.01	0.065	-10000	0	-0.74	4	4
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.073	0.26	-10000	0	-0.86	51	51
STAT5B	-0.045	0.068	-10000	0	-0.46	5	5
STAT5A	-0.045	0.068	-10000	0	-0.46	5	5
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.035	0.05	-10000	0	-0.41	3	3
CSN2	-0.008	0.069	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
LAT	-0.1	0.17	-10000	0	-0.36	119	119
YBX1	0.003	0.008	-10000	0	-10000	0	0
LCK	-0.02	0.17	-10000	0	-0.85	22	22
SHC1	0.014	0.038	-10000	0	-0.86	1	1
NOX4	-0.006	0.073	-10000	0	-0.75	5	5

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.084	0.31	-10000	0	-0.9	30	30
NCK1/PAK1/Dok-R	-0.083	0.11	-10000	0	-0.42	27	27
NCK1/Dok-R	-0.083	0.26	-10000	0	-1	32	32
PIK3CA	0.005	0.033	-10000	0	-0.74	1	1
mol:beta2-estradiol	-0.006	0.038	0.32	5	-10000	0	5
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.007	0.039	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.31	0.42	-10000	0	-0.85	199	199
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.057	0.23	-10000	0	-0.96	31	31
FN1	-0.049	0.23	-10000	0	-0.86	39	39
PLD2	0.033	0.3	-10000	0	-1.1	31	31
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.024	0.17	-10000	0	-0.74	28	28
ELK1	0.061	0.27	-10000	0	-0.96	31	31
GRB7	0.004	0.092	-10000	0	-0.74	8	8
PAK1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.29	-10000	0	-1	43	43
CDKN1A	-0.11	0.31	-10000	0	-0.68	20	20
ITGA5	-0.049	0.23	-10000	0	-0.86	39	39
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.083	0.26	-10000	0	-1	32	32
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.049	0.26	-10000	0	-0.65	30	30
PLG	-0.19	0.34	-10000	0	-1.2	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.21	-10000	0	-0.84	30	30
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.007	0.034	-10000	0	-0.74	1	1
ANGPT2	-0.2	0.38	-10000	0	-0.65	169	169
BMX	-0.037	0.34	-10000	0	-1.1	31	31
ANGPT1	0.075	0.19	-10000	0	-1.2	8	8
tube development	-0.13	0.34	-10000	0	-0.74	25	25
ANGPT4	-0.018	0.15	-10000	0	-0.87	16	16
response to hypoxia	-0.003	0.017	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.024	0.32	-10000	0	-1.2	31	31
alpha5/beta1 Integrin	-0.049	0.17	-10000	0	-0.66	39	39
FGF2	0.01	0.077	-10000	0	-0.76	5	5
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	26	26
mol:L-citrulline	-0.049	0.26	-10000	0	-0.65	30	30
AGTR1	-0.036	0.17	-10000	0	-0.75	29	29
MAPK14	-0.003	0.31	-10000	0	-1.1	30	30
Tie2/SHP2	-0.061	0.25	-10000	0	-1.1	29	29
TEK	-0.046	0.29	-10000	0	-1.2	29	29
RPS6KB1	-0.047	0.28	-10000	0	-0.86	30	30
Angiotensin II/AT1	-0.043	0.13	-10000	0	-0.58	29	29
Tie2/Ang1/GRB2	-0.004	0.3	-10000	0	-1.1	31	31
MAPK3	0.045	0.27	-10000	0	-0.99	31	31
MAPK1	0.045	0.27	-10000	0	-0.99	31	31
Tie2/Ang1/GRB7	-0.009	0.31	-10000	0	-1.2	31	31
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
MAPK8	0.031	0.3	-10000	0	-1.1	31	31
PI3K	-0.07	0.32	-10000	0	-1	30	30
FES	-0.008	0.31	-10000	0	-1.1	31	31
Crk/Dok-R	-0.082	0.26	-10000	0	-1	31	31
Tie2/Ang1/ABIN2	-0.004	0.3	-10000	0	-1.1	31	31
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.073	0.29	-10000	0	-0.8	30	30
STAT5A	0.016	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.047	0.28	-10000	0	-0.86	30	30
Tie2/Ang2	-0.19	0.4	-10000	0	-1	26	26
Tie2/Ang1	0.024	0.33	-10000	0	-1.2	31	31
FOXO1	-0.11	0.31	-10000	0	-0.8	30	30
ELF1	0.023	0.035	-10000	0	-0.73	1	1
ELF2	0.029	0.3	-10000	0	-1.1	31	31
mol:Choline	0.035	0.28	-10000	0	-1	31	31
cell migration	-0.055	0.071	-10000	0	-10000	0	0
FYN	-0.15	0.36	-10000	0	-0.85	25	25
DOK2	-0.035	0.2	-10000	0	-0.86	31	31
negative regulation of cell cycle	-0.095	0.3	-10000	0	-0.61	20	20
ETS1	0.028	0.037	-10000	0	-10000	0	0
PXN	-0.025	0.25	-10000	0	-0.7	30	30
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.06	0.28	-10000	0	-0.74	30	30
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.009	0.1	-10000	0	-0.79	8	8
MAPKKK cascade	0.035	0.28	-10000	0	-1	31	31
RASA1	0.014	0.033	-10000	0	-0.74	1	1
Tie2/Ang1/Shc	-0.003	0.3	-10000	0	-1.1	31	31
NCK1	0.014	0.033	-10000	0	-0.74	1	1
vasculogenesis	-0.04	0.24	-10000	0	-0.58	30	30
mol:Phosphatidic acid	0.035	0.28	-10000	0	-1	31	31
mol:Angiotensin II	-0.016	0.022	-10000	0	-10000	0	0
mol:NADP	-0.049	0.26	-10000	0	-0.65	30	30
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	30	30
MMP2	0.026	0.3	-10000	0	-1.1	31	31

×

Aurora A signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.019	0.045	-9999	-10000	0	0
BIRC5	-0.24	0.4	-9999	-0.86	154	154
NFKBIA	0.047	0.039	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.76	109	109
AKT1	0.047	0.039	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.017	0.04	-9999	-10000	0	0
NDEL1/TACC3	0.016	0.074	-9999	-0.74	4	4
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.013	0.019	-9999	-10000	0	0
PAK1/Aurora A	0.019	0.045	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.011	0.057	-9999	-0.74	3	3
TPX2	-0.14	0.3	-9999	-0.67	127	127
TP53	0.024	0.036	-9999	-10000	0	0
DLG7	0.019	0.043	-9999	-10000	0	0
AURKAIP1	0.011	0.06	-9999	-0.78	3	3
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.017	0.078	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.017	0.04	-9999	-10000	0	0
AURKA	0.026	0.054	-9999	-10000	0	0
AURKB	-0.14	0.15	-9999	-0.29	248	248
CDC25B	0.017	0.061	-9999	-0.58	2	2
G2/M transition checkpoint	0.014	0.052	-9999	-0.43	3	3
mRNA polyadenylation	-0.075	0.19	-9999	-0.44	109	109
Aurora A/CPEB	-0.076	0.19	-9999	-0.44	109	109
Aurora A/TACC1/TRAP/chTOG	0.023	0.044	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.019	0.045	-9999	-10000	0	0
regulation of centrosome cycle	-0.006	0.064	-9999	-0.73	4	4
spindle assembly	-0.002	0.022	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.14	0.21	-9999	-0.73	7	7
CENPA	-0.12	0.14	-9999	-0.3	171	171
Aurora A/PP2A	0.019	0.045	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.053	0.035	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.036	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
Ajuba/Aurora A	0.015	0.053	-9999	-0.44	3	3
mitotic prometaphase	0.037	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.042	0.049	-9999	-10000	0	0
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.009	0.076	-9999	-0.86	4	4
Aurora A/Antizyme1	0.017	0.06	-9999	-0.52	2	2
Aurora A/RasGAP	0.018	0.049	-9999	-0.47	1	1
OAZ1	0.014	0.038	-9999	-0.86	1	1
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.013	0.019	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.3	-9999	-0.66	127	127
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.086	0.24	-9999	-0.52	127	127
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	0	-9999	-10000	0	0

×

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

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
BAG4	0.014	0.033	-9999	-0.74	1	1
Caspase 8 (4 units)	-0.096	0.092	-9999	-10000	0	0
NEF	-0.057	0.084	-9999	-10000	0	0
NFKBIA	0.002	0.044	-9999	-10000	0	0
BIRC3	-0.068	0.3	-9999	-0.79	80	80
CYCS	-0.077	0.14	-9999	-0.43	1	1
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.37	0.48	-9999	-1	174	174
MAP2K7	-0.04	0.11	-9999	-10000	0	0
protein ubiquitination	0.061	0.07	-9999	-0.44	1	1
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.016	0	-9999	-10000	0	0
BID	-0.091	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.049	0.12	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.05	0.12	-9999	-10000	0	0
MAPK8	-0.029	0.1	-9999	-0.51	1	1
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.014	0.038	-9999	-0.86	1	1
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.13	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.048	0.066	-9999	-10000	0	0
CHUK	0.062	0.074	-9999	-0.49	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.4	0.44	-9999	-0.74	284	284
TNF	0.003	0.1	-9999	-0.8	8	8
FASLG	-0.57	0.61	-9999	-1.1	284	284
NFKB1	0	0.054	-9999	-0.73	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.067	-9999	-0.52	9	9
CASP6	-0.047	0.052	-9999	-10000	0	0
CASP7	-0.058	0.21	-9999	-0.55	50	50
RELA	0.002	0.044	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.058	0.21	-9999	-0.55	50	50
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	-0.001	0.024	-9999	-0.56	1	1
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.054	0.079	-9999	-0.53	3	3
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.56	54	54
BCL2	-0.017	0.099	-9999	-0.46	1	1

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.042	0.15	-9999	-0.58	39	39
EPHB2	0	0.11	-9999	-0.76	11	11
Syndecan-2/TACI	-0.056	0.17	-9999	-0.58	52	52
LAMA1	-0.006	0.13	-9999	-0.75	15	15
Syndecan-2/alpha2 ITGB1	-0.01	0.067	-9999	-0.49	7	7
HRAS	0.014	0.038	-9999	-0.86	1	1
Syndecan-2/CASK	0	0	-9999	-10000	0	0
ITGA5	-0.049	0.23	-9999	-0.86	39	39
BAX	0.053	0.028	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
LAMA3	0.004	0.1	-9999	-0.86	7	7
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.001	0.11	-9999	-0.85	9	9
Syndecan-2/MMP2	-0.007	0.064	-9999	-0.56	7	7
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.005	0.054	-9999	-0.56	5	5
dendrite morphogenesis	-0.01	0.07	-9999	-0.49	11	11
Syndecan-2/GM-CSF	-0.016	0.095	-9999	-0.58	15	15
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.025	-9999	-0.58	1	1
GNB2L1	0.014	0.038	-9999	-0.86	1	1
MAPK3	0.022	0.093	-9999	-0.52	15	15
MAPK1	0.022	0.093	-9999	-0.52	15	15
Syndecan-2/RACK1	-0.002	0.03	-9999	-0.5	2	2
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.027	0	-9999	-10000	0	0
ITGA2	0.009	0.073	-9999	-0.74	5	5
MAPK8	0.045	0.031	-9999	-0.46	2	2
Syndecan-2/alpha2/beta1 Integrin	-0.015	0.08	-9999	-0.65	2	2
Syndecan-2/Kininogen	-0.35	0.21	-9999	-0.48	396	396
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.048	0.031	-9999	-0.46	2	2
Syndecan-2/CASK/Protein 4.1	0	0	-9999	-10000	0	0
extracellular matrix organization	-0.005	0.055	-9999	-0.57	5	5
actin cytoskeleton reorganization	-0.042	0.15	-9999	-0.57	39	39
Syndecan-2/Caveolin-2/Ras	-0.01	0.07	-9999	-0.51	10	10
Syndecan-2/Laminin alpha3	-0.008	0.066	-9999	-0.58	7	7
Syndecan-2/RasGAP	-0.003	0.043	-9999	-0.67	2	2
alpha5/beta1 Integrin	-0.049	0.17	-9999	-0.66	39	39
PRKCD	0.014	0.038	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.07	-9999	-0.49	11	11
GO:0007205	0.005	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.002	0.04	-9999	-0.83	1	1
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.072	0.26	-9999	-0.86	52	52
RASA1	0.014	0.033	-9999	-0.74	1	1
alpha2/beta1 Integrin	-0.005	0.054	-9999	-0.56	5	5
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.085	-9999	-0.86	5	5
CASP3	0.043	0.024	-9999	-0.52	1	1
FN1	-0.049	0.23	-9999	-0.86	39	39
Syndecan-2/IL8	-0.035	0.14	-9999	-0.56	34	34
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.55	0.32	-9999	-0.74	396	396
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.017	0.14	-9999	-0.86	15	15
Syndecan-2/TGFB1	-0.005	0.056	-9999	-0.58	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-2/Ezrin	0	0	-9999	-10000	0	0
PRKACA	0.044	0	-9999	-10000	0	0
angiogenesis	-0.035	0.14	-9999	-0.55	34	34
MMP2	0.004	0.098	-9999	-0.84	7	7
IL8	-0.039	0.21	-9999	-0.84	34	34
calcineurin-NFAT signaling pathway	-0.056	0.17	-9999	-0.57	52	52

×

Neurotrophic factor-mediated Trk receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.015	0.058	-10000	0	-0.62	1	1
NT3 (dimer)/TRKC	-0.04	0.15	-10000	0	-0.6	35	35
NT3 (dimer)/TRKB	-0.13	0.24	-10000	0	-0.54	132	132
SHC/Grb2/SOS1/GAB1/PI3K	-0.002	0.021	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.1	0.3	-10000	0	-0.86	71	71
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.044	0.2	-10000	0	-0.75	41	41
NTRK2	-0.13	0.3	-10000	0	-0.74	100	100
NTRK3	-0.029	0.18	-10000	0	-0.74	31	31
NT-4/5 (dimer)/TRKB	-0.13	0.25	-10000	0	-0.55	130	130
neuron apoptosis	0.14	0.18	0.56	51	-10000	0	51
SHC 2-3/Grb2	-0.15	0.2	-10000	0	-0.63	51	51
SHC1	0.014	0.038	-10000	0	-0.86	1	1
SHC2	-0.097	0.14	-10000	0	-0.46	48	48
SHC3	-0.16	0.24	-10000	0	-0.59	101	101
STAT3 (dimer)	0.013	0.067	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.082	0.2	-10000	0	-0.55	79	79
RIN/GDP	0.049	0.064	-10000	0	-0.32	1	1
GIPC1	0.014	0.033	-10000	0	-0.74	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.069	0.14	-10000	0	-0.63	13	13
RIN/GTP	-0.001	0.029	-10000	0	-0.68	1	1
CCND1	0.01	0.16	-10000	0	-0.78	20	20
MAGED1	0.014	0.038	-10000	0	-0.86	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.004	0.092	-10000	0	-0.86	6	6
SHC/GRB2/SOS1	-0.001	0.025	-10000	0	-0.57	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.15	0.27	-10000	0	-0.59	131	131
TRKA/NEDD4-2	-0.044	0.16	-10000	0	-0.57	41	41
ELMO1	0.012	0.054	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.003	0.041	-10000	0	-0.55	3	3
NGF	-0.065	0.25	-10000	0	-0.86	49	49
HRAS	0.014	0.038	-10000	0	-0.86	1	1
DOCK1	0.014	0.033	-10000	0	-0.74	1	1
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.002	0.038	-10000	0	-0.86	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.068	0.14	-10000	0	-0.59	15	15
mol:GDP	0.063	0.086	-10000	0	-0.48	2	2
NGF (dimer)	-0.065	0.25	-10000	0	-0.86	49	49
RhoG/GDP	-0.003	0.041	-10000	0	-0.68	2	2
RIT1/GDP	0.055	0.062	-10000	0	-0.31	1	1
TIAM1	0.014	0.033	-10000	0	-0.74	1	1
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
BDNF (dimer)/TRKB	-0.16	0.26	-10000	0	-0.55	159	159
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.002	0.037	-10000	0	-0.61	2	2
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.001	0.023	-10000	0	-0.52	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	0.005	0.09	-10000	0	-0.78	7	7
RAP1/GDP	-0.008	0.031	-10000	0	-10000	0	0
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.1	0.3	-10000	0	-0.86	71	71
ubiquitin-dependent protein catabolic process	-0.09	0.2	-10000	0	-0.54	88	88
Schwann cell development	-0.026	0.032	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.14	0.24	-10000	0	-0.81	31	31
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.049	0.078	-10000	0	-10000	0	0
STAT3	0.013	0.067	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.76	31	31
MAPK3	-0.098	0.26	-10000	0	-0.58	96	96
MAPK1	-0.098	0.26	-10000	0	-0.58	96	96
CDC42/GDP	0.055	0.062	-10000	0	-0.31	1	1
NTF3	0.005	0.09	-10000	0	-0.78	7	7
NTF4	-0.004	0.092	-10000	0	-0.86	6	6
NGF (dimer)/TRKA/FAIM	-0.089	0.2	-10000	0	-0.54	88	88
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.079	0.16	-10000	0	-0.61	24	24
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0.001	0.14	-10000	0	-0.52	35	35
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.049	0.066	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.062	-10000	0	-10000	0	0
NGF (dimer)/TRKA/GRIT	-0.091	0.21	-10000	0	-0.55	88	88
neuron projection morphogenesis	-0.021	0.14	-10000	0	-0.54	13	13
NGF (dimer)/TRKA/NEDD4-2	-0.09	0.21	-10000	0	-0.55	88	88
MAP2K1	0.053	0.023	-10000	0	-10000	0	0
NGFR	-0.044	0.22	-10000	0	-0.86	36	36
NGF (dimer)/TRKA/GIPC/GAIP	-0.055	0.12	-10000	0	-0.62	4	4
RAS family/GTP/PI3K	-0.002	0.029	-10000	0	-0.6	1	1
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
MAPKKK cascade	-0.094	0.18	-10000	0	-0.55	58	58
RASA1	0.014	0.033	-10000	0	-0.74	1	1
TRKA/c-Abl	-0.043	0.15	-10000	0	-0.56	41	41
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.15	0.24	-10000	0	-0.59	70	70
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.077	0.18	-10000	0	-0.51	52	52
MATK	-0.072	0.26	-10000	0	-0.86	53	53
NEDD4L	0.014	0.033	-10000	0	-0.74	1	1
RAS family/GDP	-0.008	0.031	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.074	0.15	-10000	0	-0.47	38	38
Rac1/GTP	-0.044	0.084	-10000	0	-0.4	8	8
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Endothelins

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
AKT1	0.008	0.22	-10000	0	-0.88	3	3
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.083	0.13	-10000	0	-0.83	3	3
EDN1	-0.015	0.19	-10000	0	-0.78	18	18
EDN3	-0.018	0.15	-10000	0	-0.86	17	17
EDN2	-0.091	0.28	-10000	0	-0.82	68	68
HRAS/GDP	0.052	0.17	-10000	0	-0.64	12	12
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.021	0.16	-10000	0	-0.48	18	18
ADCY4	0.01	0.17	-10000	0	-0.74	3	3
ADCY5	-0.007	0.2	-10000	0	-0.69	14	14
ADCY6	0.009	0.17	-10000	0	-0.74	3	3
ADCY7	-0.005	0.19	-10000	0	-0.72	7	7
ADCY1	-0.001	0.18	-10000	0	-0.74	4	4
ADCY2	-0.12	0.27	-10000	0	-0.7	31	31
ADCY3	0.01	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.28	-10000	0	-0.74	35	35
ADCY9	0.01	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.076	0.15	-10000	0	-0.53	10	10
ETB receptor/Endothelin-1/Gq/GTP	0.034	0.11	-10000	0	-0.46	12	12
GNAO1	0.008	0.082	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
ETA receptor/Endothelin-1/G12/GTP	-0.013	0.22	0.38	74	-0.82	3	77
ETA receptor/Endothelin-1/Gs/GTP	-0.013	0.21	0.36	74	-0.79	3	77
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.042	0.34	-10000	0	-0.95	53	53
EDNRB	0.007	0.068	-10000	0	-0.78	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.043	0.3	-10000	0	-0.75	51	51
CYSLTR1	0.008	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.014	0.11	-10000	0	-0.39	2	2
mol:GDP	0.045	0.18	-10000	0	-0.64	14	14
SLC9A3	-0.35	0.3	-10000	0	-0.66	152	152
RAF1	0.047	0.17	-10000	0	-0.61	14	14
JUN	0.086	0.12	-10000	0	-0.57	1	1
JAK2	0.008	0.22	-10000	0	-0.88	3	3
mol:IP3	0.018	0.17	-10000	0	-0.56	18	18
ETA receptor/Endothelin-1	-0.026	0.27	0.45	74	-0.65	19	93
PLCB1	0.001	0.11	-10000	0	-0.74	11	11
PLCB2	-0.078	0.27	-10000	0	-0.86	58	58
ETA receptor/Endothelin-3	-0.021	0.15	-10000	0	-0.68	19	19
FOS	0.06	0.2	-10000	0	-0.84	16	16
Gai/GDP	0.039	0.069	-10000	0	-0.62	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.003	0.24	-10000	0	-0.77	16	16
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
PRKCB1	0.019	0.16	-10000	0	-0.54	18	18
GNAQ	0.02	0.004	-10000	0	-10000	0	0
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
Gs family/GDP	-0.044	0.11	-10000	0	-0.59	12	12
ETA receptor/Endothelin-1/Gq/GTP	0.044	0.14	-10000	0	-0.48	11	11
MAPK14	0.024	0.13	-10000	0	-0.56	10	10
TRPC6	0.083	0.14	-10000	0	-0.89	3	3
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.014	0.14	-10000	0	-0.52	15	15
ETB receptor/Endothelin-2	-0.086	0.21	-10000	0	-0.62	71	71
ETB receptor/Endothelin-3	-0.028	0.12	-10000	0	-0.66	20	20
ETB receptor/Endothelin-1	-0.032	0.16	-10000	0	-0.62	19	19
MAPK3	0.06	0.19	-10000	0	-0.72	17	17
MAPK1	0.06	0.19	-10000	0	-0.72	17	17
Rac1/GDP	0.052	0.17	-10000	0	-0.71	8	8
cAMP biosynthetic process	-0.061	0.19	-10000	0	-0.6	14	14
MAPK8	0.078	0.13	-10000	0	-0.58	3	3
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	0.03	0.09	-10000	0	-0.57	3	3
p130Cas/CRK/Src/PYK2	0.072	0.17	-10000	0	-0.67	10	10
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.052	0.17	-10000	0	-0.65	10	10
COL1A2	-0.1	0.33	-10000	0	-0.9	65	65
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.081	0.23	-10000	0	-0.63	70	70
mol:DAG	0.018	0.17	-10000	0	-0.56	18	18
MAP2K2	0.057	0.18	-10000	0	-0.66	12	12
MAP2K1	0.058	0.17	-10000	0	-0.66	11	11
EDNRA	-0.007	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.019	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.035	0.14	-10000	0	-0.7	16	16
HRAS/GTP	0.036	0.17	-10000	0	-0.63	14	14
PRKCH	0.029	0.16	-10000	0	-0.58	13	13
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.029	0.16	-10000	0	-0.57	14	14
PRKCB	0.024	0.18	-10000	0	-0.67	15	15
PRKCE	0.028	0.16	-10000	0	-0.62	11	11
PRKCD	0.028	0.16	-10000	0	-0.6	12	12
PRKCG	0.003	0.2	-10000	0	-0.63	29	29
regulation of vascular smooth muscle contraction	0.059	0.23	-10000	0	-0.96	16	16
PRKCQ	0.016	0.18	-10000	0	-0.63	19	19
PLA2G4A	0.076	0.16	-10000	0	-0.57	10	10
GNA14	0.008	0.093	-10000	0	-0.74	8	8
GNA15	-0.006	0.14	-10000	0	-0.86	15	15
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.014	0.057	-10000	0	-0.74	3	3
Rac1/GTP	-0.013	0.22	0.38	74	-0.82	3	77
MMP1	-0.14	0.37	-10000	0	-0.85	106	106

×

Wnt 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
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.017	0.17	-9999	-0.86	20	20
WNT4	-0.068	0.24	-9999	-0.75	58	58
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.057	-9999	-0.74	3	3
WNT11	-0.04	0.2	-9999	-0.76	38	38

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.001	0.017	-9999	-10000	0	0
DAPP1	0.03	0.11	-9999	-0.54	9	9
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.14	0.26	-9999	-0.72	57	57
mol:DAG	-0.071	0.15	-9999	-0.31	78	78
HRAS	0.015	0.038	-9999	-0.86	1	1
RAP1A	0.017	0.001	-9999	-10000	0	0
ARF5/GDP	0.019	0.073	-9999	-10000	0	0
PLCG2	0.003	0.1	-9999	-0.82	8	8
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	-0.001	0.019	-9999	-0.43	1	1
ARF1/GTP	-0.001	0.017	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.001	0.018	-9999	-0.42	1	1
ADAP1	-0.003	0.036	-9999	-10000	0	0
ARAP3	-0.001	0.018	-9999	-0.42	1	1
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0.001	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.011	0.066	-9999	-0.86	3	3
mol:Ca2+	-0.023	0.077	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.014	0.033	-9999	-0.74	1	1
ZAP70	-0.47	0.44	-9999	-0.86	296	296
mol:IP3	-0.037	0.1	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.019	0.073	-9999	-10000	0	0
RhoA/GDP	-0.004	0.017	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.02	-9999	-0.47	1	1
BLNK	0.014	0.033	-9999	-0.74	1	1
actin cytoskeleton reorganization	0.045	0.081	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.036	0.053	-9999	-0.57	4	4
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0.002	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.001	0.017	-9999	-10000	0	0
RhoA/GTP	-0.001	0.017	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.2	0.24	-9999	-0.56	132	132
BLK	-0.041	0.21	-9999	-0.86	34	34
PDPK1	0.014	0.033	-9999	-0.74	1	1
CYTH1	-0.001	0.017	-9999	-10000	0	0
HCK	-0.032	0.2	-9999	-0.86	29	29
CYTH3	-0.001	0.017	-9999	-10000	0	0
CYTH2	-0.001	0.017	-9999	-10000	0	0
KRAS	0.017	0.001	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	-0.001	0.024	-9999	-0.54	1	1
SGK1	-0.001	0.026	-9999	-0.6	1	1
INPP5D	0.009	0.076	-9999	-0.86	4	4
mol:GDP	0.01	0.077	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.013	0.046	-9999	-0.74	2	2
ARF6/GDP	-0.004	0.016	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.001	0.019	-9999	-0.43	1	1
ARAP3/RAP1A/GTP	-0.001	0.019	-9999	-0.43	1	1
VAV1	-0.19	0.37	-9999	-0.86	125	125
mol:PI-3-4-P2	0.025	0.06	-9999	-0.66	4	4
RAS family/GTP/PI3K Class I	-0.001	0.019	-9999	-0.44	1	1
PLEKHA1	0.036	0.053	-9999	-0.57	4	4
Rac1/GDP	0.019	0.073	-9999	-10000	0	0
LAT	-0.23	0.39	-9999	-0.86	148	148
Rac1/GTP	0	0.1	-9999	-10000	0	0
ITK	-0.14	0.21	-9999	-0.46	165	165
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.11	0.2	-9999	-0.46	78	78
LCK	-0.02	0.17	-9999	-0.85	22	22
BTK	-0.095	0.18	-9999	-0.46	110	110

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.014	0.034	-10000	0	-0.73	1	1
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.02	0.089	-10000	0	-0.52	4	4
AKT1	0.02	0.007	-10000	0	-10000	0	0
GSC	-0.027	0.22	-10000	0	-0.76	44	44
NKX2-5	-0.046	0.21	-10000	0	-0.86	34	34
muscle cell differentiation	0.034	0.11	0.58	9	-10000	0	9
SMAD2-3/SMAD4/SP1	0.043	0.08	-10000	0	-10000	0	0
SMAD4	0.032	0.03	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.004	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.003	0.046	-10000	0	-0.57	2	2
SMAD3/SMAD4/VDR	0.01	0.05	-10000	0	-10000	0	0
MYC	-0.033	0.17	-10000	0	-0.86	21	21
CDKN2B	0.055	0.092	-10000	0	-0.68	6	6
AP1	0.064	0.073	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.012	0.049	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.051	0.069	-10000	0	-0.53	1	1
SP3	0.02	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.061	0.25	-10000	0	-0.88	46	46
SMAD3/SMAD4/GR	0.01	0.044	-10000	0	-0.6	1	1
GATA3	-0.36	0.38	-10000	0	-0.74	264	264
SKI/SIN3/HDAC complex/NCoR1	0.054	0.044	-10000	0	-10000	0	0
MEF2C/TIF2	-0.076	0.2	-10000	0	-0.88	16	16
endothelial cell migration	0.096	0.26	0.73	76	-10000	0	76
MAX	0.019	0.016	-10000	0	-10000	0	0
RBBP7	0.015	0.004	-10000	0	-10000	0	0
RBBP4	0.014	0.033	-10000	0	-0.74	1	1
RUNX2	-0.007	0.14	-10000	0	-0.86	14	14
RUNX3	-0.36	0.44	-10000	0	-0.86	229	229
RUNX1	-0.047	0.23	-10000	0	-0.86	38	38
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.017	0.042	-10000	0	-0.87	1	1
VDR	0.011	0.057	-10000	0	-0.74	3	3
CDKN1A	0.083	0.074	-10000	0	-0.64	2	2
KAT2B	0.013	0.033	-10000	0	-0.74	1	1
SMAD2/SMAD2/SMAD4/FOXH1	-0.054	0.18	-10000	0	-0.61	46	46
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.004	-10000	0	-10000	0	0
SERPINE1	-0.098	0.26	-10000	0	-0.74	76	76
SMAD3/SMAD4/ATF2	0.007	0.037	-10000	0	-0.48	1	1
SMAD3/SMAD4/ATF3	0.004	0.057	-10000	0	-0.48	5	5
SAP30	-0.016	0.16	-10000	0	-0.86	19	19
Cbp/p300/PIAS3	0.007	0.035	-10000	0	-10000	0	0
JUN	0.075	0.071	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.012	0.11	-10000	0	-0.56	18	18
TFE3	0.021	0.012	-10000	0	-10000	0	0
COL1A2	-0.092	0.25	-10000	0	-0.75	67	67
mesenchymal cell differentiation	0.007	0.1	0.59	14	-10000	0	14
DLX1	-0.45	0.44	-10000	0	-0.86	284	284
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.007	0.12	-10000	0	-0.74	13	13
SMAD3/SMAD4/Max	0.011	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	-0.001	0.02	-10000	0	-0.46	1	1
ZBTB17	-0.001	0.044	-10000	0	-0.71	2	2
LAMC1	0.071	0.042	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.008	0.031	-10000	0	-10000	0	0
IRF7	-0.013	0.16	-10000	0	-0.85	19	19
ESR1	0.001	0.077	-10000	0	-0.76	5	5
HNF4A	-0.047	0.21	-10000	0	-0.74	44	44
MEF2C	-0.007	0.22	-10000	0	-0.8	20	20
SMAD2-3/SMAD4	0.005	0.031	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.005	0.028	-10000	0	-10000	0	0
IGHV3OR16-13	-0.05	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.008	-10000	0	-10000	0	0
SKIL	0.016	0	-10000	0	-10000	0	0
HDAC1	0.015	0.004	-10000	0	-10000	0	0
HDAC2	0.015	0.004	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.01	0.036	-10000	0	-10000	0	0
MSG1/HSC70	0.002	0.043	-10000	0	-0.67	2	2
SMAD2	0.022	0.019	-10000	0	-10000	0	0
SMAD3	0.032	0.027	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.062	0.033	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.024	0.032	-10000	0	-0.52	1	1
NCOR1	0.015	0.004	-10000	0	-10000	0	0
NCOA2	0	0.11	-10000	0	-0.74	11	11
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.036	0.15	-10000	0	-0.66	29	29
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.084	-10000	0	-10000	0	0
IFNB1	0.045	0.11	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.009	0.21	-10000	0	-0.9	11	11
CITED1	0.011	0.054	-10000	0	-0.86	2	2
SMAD2-3/SMAD4/ARC105	0.007	0.03	-10000	0	-10000	0	0
RBL1	0.016	0.001	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.076	0.067	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.29	0.32	-10000	0	-0.61	251	251
SMAD7	0.1	0.079	-10000	0	-10000	0	0
MYC/MIZ-1	-0.027	0.13	-10000	0	-0.65	23	23
SMAD3/SMAD4	-0.021	0.12	-10000	0	-10000	0	0
IL10	-0.2	0.31	-10000	0	-0.98	32	32
PIASy/HDAC complex	0.018	0.01	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.17	0.25	-10000	0	-0.75	15	15
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.018	0.009	-10000	0	-10000	0	0
ATF3	0.009	0.073	-10000	0	-0.74	5	5
SMAD3/SMAD4/SP1	-0.012	0.053	-10000	0	-10000	0	0
FOXG1	-0.025	0.17	-10000	0	-0.86	20	20
FOXO3	0.036	0.01	-10000	0	-10000	0	0
FOXO1	0.036	0.009	-10000	0	-10000	0	0
FOXO4	0.036	0.009	-10000	0	-10000	0	0
heart looping	-0.007	0.22	-10000	0	-0.79	20	20
CEBPB	-0.002	0.13	-10000	0	-0.86	12	12
SMAD3/SMAD4/DLX1	-0.31	0.3	-10000	0	-0.58	284	284
MYOD1	-0.041	0.2	-10000	0	-0.86	29	29
SMAD3/SMAD4/HNF4	-0.033	0.14	-10000	0	-0.51	28	28
SMAD3/SMAD4/GATA3	-0.23	0.25	-10000	0	-0.8	17	17
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.23	0.28	-10000	0	-0.79	32	32
SMAD3/SMAD4/SP1-3	-0.005	0.043	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.013	0.049	-10000	0	-10000	0	0
SIN3B	0.015	0.004	-10000	0	-10000	0	0
SIN3A	0.015	0.004	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.078	0.22	-10000	0	-0.83	25	25
ITGB5	0.085	0.064	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.053	0.043	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.015	0.11	-10000	0	-0.5	22	22
AR	-0.021	0.16	-10000	0	-0.74	26	26
negative regulation of cell growth	0.065	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.024	0.14	-10000	0	-0.6	29	29
E2F5	0.014	0.033	-10000	0	-0.74	1	1
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.043	0.15	-10000	0	-0.67	13	13
SMAD2-3/SMAD4/FOXO1-3a-4	0.076	0.045	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.008	0.067	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.007	0.1	-10000	0	-0.59	14	14
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.014	0.033	-10000	0	-0.74	1	1

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.001	0.028	-10000	0	-0.66	1	1
HDAC1	0.003	0.011	-10000	0	-10000	0	0
AES	0.005	0.008	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.053	0.22	-10000	0	-0.74	48	48
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.015	0.002	-10000	0	-10000	0	0
AP1	-0.096	0.16	-10000	0	-0.34	151	151
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.014	0.033	-10000	0	-0.74	1	1
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.011	0.067	-10000	0	-0.45	1	1
NICD/RBPSUH	-0.001	0.027	-10000	0	-0.64	1	1
WIF1	0.001	0.075	-10000	0	-0.76	5	5
NOTCH1	-0.001	0.029	-10000	0	-0.68	1	1
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.091	0.28	-10000	0	-0.86	64	64
DKK1	-0.019	0.17	-10000	0	-0.82	22	22
beta catenin/beta TrCP1	0.084	0.084	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	-0.011	0.035	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.008	0.048	-10000	0	-10000	0	0
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	-0.003	0.12	-10000	0	-0.75	13	13
JUN	0.016	0	-10000	0	-10000	0	0
MAP3K7	0.002	0.008	-10000	0	-10000	0	0
CTNNB1	0.08	0.091	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.095	0.22	-10000	0	-0.57	89	89
HNF1A	-0.002	0.072	-10000	0	-0.74	5	5
CTBP1	0.005	0.008	-10000	0	-10000	0	0
MYC	0.002	0.15	-10000	0	-0.73	21	21
NKD1	-0.19	0.34	-10000	0	-0.74	142	142
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.036	0.11	-10000	0	-0.64	1	1
apoptosis	-0.096	0.16	-10000	0	-0.34	151	151
Delta 1/NOTCHprecursor	-0.001	0.027	-10000	0	-0.64	1	1
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.029	0.023	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.011	0.035	-10000	0	-10000	0	0
DVL1	-0.005	0.032	-10000	0	-0.47	2	2
CSNK2A1	0.015	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.091	0.22	-10000	0	-0.61	79	79
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
NLK	0.015	0.013	-10000	0	-10000	0	0
CCND1	0.003	0.15	-10000	0	-0.73	20	20
WNT1	-0.026	0.18	-10000	0	-0.86	25	25
Axin1/APC/beta catenin	0.081	0.052	-10000	0	-10000	0	0
DKK2	-0.026	0.18	-10000	0	-0.82	26	26
NOTCH1 precursor/DVL1	-0.003	0.033	-10000	0	-0.58	1	1
GSK3B	0.012	0.007	-10000	0	-10000	0	0
FRAT1	0.012	0.007	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.036	0.11	-10000	0	-0.66	1	1
PPP2R5D	0.092	0.16	0.35	141	-10000	0	141
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.029	0.12	-10000	0	-0.52	26	26
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.019	0.006	-10000	0	-10000	0	0

×

S1P3 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.04	0.044	-9999	-10000	0	0
GNAO1	0.01	0.082	-9999	-0.84	5	5
S1P/S1P3/G12/G13	-0.001	0.019	-9999	-0.43	1	1
AKT1	-0.002	0.012	-9999	-10000	0	0
AKT3	-0.025	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	0.013	0.057	-9999	-0.74	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.033	-9999	-0.74	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.054	0.048	-9999	-0.53	1	1
MAPK3	0.062	0.046	-9999	-0.5	1	1
MAPK1	0.062	0.046	-9999	-0.5	1	1
JAK2	-0.024	0.13	-9999	-0.48	2	2
CXCR4	-0.12	0.26	-9999	-0.47	187	187
FLT1	0.011	0.085	-9999	-0.86	5	5
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.062	0.046	-9999	-0.5	1	1
S1P/S1P3/Gi	0.054	0.049	-9999	-0.54	1	1
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.035	-9999	-0.49	1	1
VEGFA	-0.37	0.44	-9999	-0.86	239	239
S1P/S1P2/Gi	0.049	0.043	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	240	240
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.027	0.075	-9999	-0.6	1	1
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.057	-9999	-0.74	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.004	0.092	-9999	-0.74	8	8
GNA15	-0.009	0.14	-9999	-0.86	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.057	-9999	-0.74	3	3
Rac1/GTP	-0.005	0.035	-9999	-0.49	1	1

×

Thromboxane A2 receptor 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
TGM2	-0.004	0.12	-10000	0	-0.86	11	11
GNB1/GNG2	-0.034	0.063	-10000	0	-0.22	14	14
AKT1	0.055	0.1	-10000	0	-0.25	1	1
EGF	-0.67	0.23	-10000	0	-0.74	480	480
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.032	0.08	-10000	0	-0.61	2	2
mol:Ca2+	0.042	0.14	-10000	0	-0.33	28	28
LYN	-0.029	0.071	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.037	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.051	0.15	-10000	0	-0.37	25	25
GNG2	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.038	-10000	0	-0.86	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.029	0.079	-10000	0	-0.42	8	8
G beta5/gamma2	-0.044	0.083	-10000	0	-0.3	16	16
PRKCH	0.043	0.15	-10000	0	-0.39	21	21
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
TXA2/TP beta/beta Arrestin3	-0.014	0.045	-10000	0	-0.27	13	13
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.11	0.31	-10000	0	-0.86	77	77
G12 family/GTP	-0.042	0.091	-10000	0	-0.32	25	25
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.016	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.11	0.31	12	-10000	0	12
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	-0.006	0.12	-10000	0	-0.74	15	15
mol:IP3	0.038	0.17	-10000	0	-0.42	28	28
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.029	0.22	-10000	0	-0.58	28	28
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.054	0.13	-10000	0	-0.6	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.051	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.013	0.05	-10000	0	-0.8	2	2
PRKCB1	0.038	0.16	-10000	0	-0.38	42	42
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.037	0.21	-10000	0	-0.53	44	44
LCK	-0.045	0.12	-10000	0	-0.6	13	13
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.04	0.096	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.028	0.036	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.04	0.095	-10000	0	-10000	0	0
MAPK14	0.055	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.037	0.19	-10000	0	-0.48	30	30
MAPK11	0.054	0.11	-10000	0	-0.35	3	3
ARHGEF1	0.042	0.088	-10000	0	-0.32	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.045	0.17	-10000	0	-0.39	44	44
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.045	0.13	-10000	0	-0.35	20	20
cAMP biosynthetic process	0.035	0.16	-10000	0	-0.38	32	32
Gq family/GTP/EBP50	0.025	0.062	-10000	0	-0.34	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.029	0.071	-10000	0	-10000	0	0
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.085	0.1	-10000	0	-0.41	15	15
VCAM1	0.044	0.14	-10000	0	-0.34	26	26
TP beta/Gq family/GDP/G beta5/gamma2	0.029	0.079	-10000	0	-0.42	8	8
platelet activation	0.067	0.15	-10000	0	-0.34	15	15
PGI2/IP	-0.002	0.038	-10000	0	-0.62	2	2
PRKACA	-0.051	0.12	-10000	0	-0.34	79	79
Gq family/GDP/G beta5/gamma2	0.024	0.079	-10000	0	-0.41	8	8
TXA2/TP beta/beta Arrestin2	-0.015	0.065	-10000	0	-0.4	14	14
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.013	0.12	-10000	0	-10000	0	0
mol:DAG	0.038	0.18	-10000	0	-0.44	42	42
EGFR	0.001	0.11	-10000	0	-0.85	9	9
TXA2/TP alpha	0.034	0.21	-10000	0	-0.54	32	32
Gq family/GTP	-0.006	0.055	-10000	0	-0.29	8	8
YES1	-0.029	0.071	-10000	0	-10000	0	0
GNAI2/GTP	-0.034	0.082	-10000	0	-10000	0	0
PGD2/DP	-0.098	0.24	-10000	0	-0.68	77	77
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.029	0.071	-10000	0	-10000	0	0
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	-0.009	0.14	-10000	0	-0.86	15	15
PGK/cGMP	-0.014	0.08	-10000	0	-0.48	15	15
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.046	0.11	-10000	0	-0.71	1	1
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.043	0.15	-10000	0	-0.39	21	21
PRKCB	0.041	0.16	-10000	0	-0.43	22	22
PRKCE	0.044	0.16	-10000	0	-0.41	19	19
PRKCD	0.042	0.16	-10000	0	-0.41	22	22
PRKCG	0.03	0.18	-10000	0	-0.49	33	33
muscle contraction	0.043	0.2	-10000	0	-0.49	44	44
PRKCZ	0.05	0.15	-10000	0	-0.37	27	27
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.039	0.093	-10000	0	-10000	0	0
PRKCQ	0.036	0.16	-10000	0	-0.43	23	23
MAPKKK cascade	0.036	0.19	-10000	0	-0.49	29	29
SELE	0.038	0.15	-10000	0	-0.42	38	38
TP beta/GNAI2/GDP/G beta/gamma	-0.037	0.09	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.004	0.092	-10000	0	-0.74	8	8
chemotaxis	0.037	0.23	-10000	0	-0.61	43	43
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.011	0.057	-10000	0	-0.74	3	3
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.025	0.095	-9999	-0.52	16	16
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.014	0.033	-9999	-0.74	1	1
ITGA4	-0.011	0.15	-9999	-0.86	16	16
alpha4/beta7 Integrin/MAdCAM1	-0.027	0.12	-9999	-0.52	28	28
EPO	-0.29	0.42	-9999	-0.86	187	187
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	16	16
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.66	187	187
lamellipodium assembly	0	0.035	-9999	-0.53	2	2
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PI3K	-0.002	0.034	-9999	-0.56	2	2
ARF6	0.016	0	-9999	-10000	0	0
JAK2	-0.12	0.17	-9999	-0.66	6	6
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
MADCAM1	-0.007	0.13	-9999	-0.86	12	12
cell adhesion	-0.027	0.12	-9999	-0.52	28	28
CRKL/CBL	-0.001	0.024	-9999	-0.56	1	1
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.015	0.13	-9999	-0.52	25	25
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.031	0.13	-9999	-0.56	30	30
p130Cas/Crk/Dock1	-0.024	0.1	-9999	-0.8	1	1
VCAM1	-0.006	0.13	-9999	-0.82	14	14
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.016	0.089	-9999	-0.52	16	16
BCAR1	0.026	0.12	-9999	-0.89	1	1
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0	0.036	-9999	-0.55	2	2

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.021	0.088	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
AP1	-0.03	0.1	-9999	-0.52	2	2
mol:PIP3	-0.026	0.091	-9999	-0.54	1	1
AKT1	-0.014	0.058	-9999	-10000	0	0
PTK2B	0.032	0.059	-9999	-0.28	1	1
RHOA	0.036	0.037	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.05	0.052	-9999	-0.45	2	2
MAGI3	0.011	0.057	-9999	-0.74	3	3
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.022	0.085	-9999	-0.37	27	27
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
positive regulation of microtubule depolymerization	0.046	0.069	-9999	-0.41	1	1
NF kappa B1 p50/RelA	-0.019	0.073	-9999	-10000	0	0
endothelial cell migration	0.005	0.14	-9999	-0.54	30	30
ADCY4	0.031	0.12	-9999	-0.47	25	25
ADCY5	0.022	0.13	-9999	-0.49	28	28
ADCY6	0.031	0.12	-9999	-0.47	25	25
ADCY7	0.026	0.12	-9999	-0.48	25	25
ADCY1	0.026	0.13	-9999	-0.48	26	26
ADCY2	-0.019	0.14	-9999	-0.51	26	26
ADCY3	0.031	0.12	-9999	-0.47	25	25
ADCY8	-0.027	0.14	-9999	-0.48	25	25
ADCY9	0.031	0.12	-9999	-0.47	25	25
GSK3B	0.042	0.057	-9999	-10000	0	0
arachidonic acid secretion	0.038	0.11	-9999	-0.44	23	23
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0.001	0.008	-9999	-10000	0	0
GNAO1	0.007	0.12	-9999	-0.48	28	28
HRAS	0.014	0.038	-9999	-0.86	1	1
NFKBIA	0.06	0.062	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	-0.001	0.053	-9999	-0.86	2	2
JUN	0.016	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.002	0.023	-9999	-0.48	1	1
TIAM1	-0.002	0.062	-9999	-1	2	2
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	0.05	0.053	-9999	-0.46	2	2
PLCB3	0.037	0.023	-9999	-0.43	1	1
FOS	-0.003	0.12	-9999	-0.75	13	13
positive regulation of mitosis	0.038	0.11	-9999	-0.44	23	23
LPA/LPA1-2-3	-0.025	0.1	-9999	-0.44	27	27
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.74	1	1
stress fiber formation	0.039	0.076	-9999	-10000	0	0
GNAZ	0.009	0.12	-9999	-0.48	26	26
EGFR/PI3K-beta/Gab1	-0.027	0.094	-9999	-0.57	1	1
positive regulation of dendritic cell cytokine production	-0.025	0.099	-9999	-0.44	27	27
LPA/LPA2/MAGI-3	-0.004	0.037	-9999	-0.48	3	3
ARHGEF1	0.03	0.095	-9999	-0.49	1	1
GNAI2	0.012	0.11	-9999	-0.46	23	23
GNAI3	0.012	0.11	-9999	-0.46	23	23
GNAI1	0.009	0.12	-9999	-0.48	26	26
LPA/LPA3	-0.007	0.06	-9999	-0.67	4	4
LPA/LPA2	-0.002	0.014	-9999	-10000	0	0
LPA/LPA1	-0.028	0.12	-9999	-0.5	30	30
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	257	257
HBEGF	-0.3	0.35	-9999	-0.66	251	251
mol:DAG	0.05	0.053	-9999	-0.46	2	2
cAMP biosynthetic process	0.019	0.12	-9999	-0.46	25	25
NFKB1	0.014	0.033	-9999	-0.74	1	1
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.06	0.062	-9999	-10000	0	0
GNAQ	-0.004	0.035	-9999	-0.4	4	4
LPAR2	0.016	0	-9999	-10000	0	0
LPAR3	0.003	0.076	-9999	-0.86	4	4
LPAR1	-0.013	0.15	-9999	-0.73	23	23
IL8	-0.078	0.2	-9999	-0.49	44	44
PTK2	0.024	0.1	-9999	-0.48	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.022	0.085	-9999	-0.37	27	27
EGFR	0	0.11	-9999	-0.85	9	9
PLCG1	0.019	0.055	-9999	-0.38	5	5
PLD2	0.024	0.1	-9999	-0.48	4	4
G12/G13	-0.021	0.088	-9999	-0.42	23	23
PI3K-beta	-0.016	0.067	-9999	-10000	0	0
cell migration	-0.009	0.034	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-9999	-0.74	1	1
PXN	0.039	0.077	-9999	-10000	0	0
HRAS/GTP	-0.026	0.098	-9999	-0.45	23	23
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.4	0.44	-9999	-0.86	251	251
PRKCE	0.013	0.033	-9999	-0.74	1	1
PRKCD	0.058	0.055	-9999	-0.45	1	1
Gi(beta/gamma)	-0.026	0.097	-9999	-0.44	25	25
mol:LPA	0.003	0.025	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.018	0.08	-9999	-10000	0	0
MAPKKK cascade	0.038	0.11	-9999	-0.44	23	23
contractile ring contraction involved in cytokinesis	0.036	0.037	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.01	0.06	-9999	-0.4	12	12
GNA15	-0.015	0.078	-9999	-0.42	18	18
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.046	0.07	-9999	-0.42	1	1
GNA11	-0.006	0.045	-9999	-0.39	7	7
Rac1/GTP	-0.002	0.056	-9999	-0.91	2	2
MMP2	0.005	0.14	-9999	-0.54	30	30

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.013	0.046	-9999	-0.74	2	2
SPHK1	-0.058	0.24	-9999	-0.86	45	45
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.001	0.095	-9999	-0.31	47	47
GNAO1	0.008	0.082	-9999	-0.84	5	5
mol:Sphinganine-1-P	-0.03	0.2	-9999	-0.66	47	47
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.017	0.056	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.014	0.033	-9999	-0.74	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.023	0.075	-9999	-0.29	2	2
S1PR5	-0.14	0.33	-9999	-0.86	93	93
S1PR4	-0.034	0.2	-9999	-0.86	30	30
GNAI1	0.011	0.057	-9999	-0.74	3	3
S1P/S1P5/G12	-0.11	0.21	-9999	-0.54	93	93
S1P/S1P3/Gq	0.023	0.1	-9999	-0.44	16	16
S1P/S1P4/Gi	0.022	0.098	-9999	-0.38	13	13
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
GNA14	0.004	0.092	-9999	-0.74	8	8
GNA15	-0.009	0.14	-9999	-0.86	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.011	0.057	-9999	-0.74	3	3
ABCC1	0.016	0	-9999	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.027	0.044	-10000	0	-0.56	3	3
MAP4K4	0.026	0.093	-10000	0	-0.48	1	1
BAG4	0.014	0.033	-10000	0	-0.74	1	1
PKC zeta/ceramide	-0.098	0.046	-10000	0	-0.48	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.12	0.31	-10000	0	-0.86	80	80
BAX	-0.042	0.018	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.046	0.008	-10000	0	-10000	0	0
BAD	-0.098	0.043	-10000	0	-0.45	2	2
SMPD1	0.027	0.041	-10000	0	-0.28	1	1
RB1	-0.096	0.037	-10000	0	-10000	0	0
FADD/Caspase 8	0.04	0.087	-10000	0	-10000	0	0
MAP2K4	-0.08	0.035	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.084	0.056	-10000	0	-0.59	4	4
EGF	-0.67	0.23	-10000	0	-0.74	480	480
mol:ceramide	-0.11	0.039	0.2	2	-10000	0	2
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.03	0.025	-10000	0	-0.56	1	1
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.095	0.037	-10000	0	-10000	0	0
cell proliferation	-0.052	0.059	-10000	0	-0.46	10	10
BID	-0.011	0.065	-10000	0	-0.34	1	1
MAP3K1	-0.096	0.037	-10000	0	-10000	0	0
EIF2A	-0.067	0.034	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.065	0.052	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.065	0.052	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.097	0.035	-10000	0	-0.26	1	1
FADD	0.026	0.093	-10000	0	-0.48	1	1
KSR1	-0.1	0.059	-10000	0	-0.63	4	4
MAPK8	-0.076	0.041	-10000	0	-0.35	4	4
PRKRA	-0.096	0.037	-10000	0	-10000	0	0
PDGFA	0.014	0.033	-10000	0	-0.74	1	1
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.006	0.093	-10000	0	-0.86	6	6
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.11	0.039	0.2	2	-10000	0	2
CTSD	0.014	0.033	-10000	0	-0.74	1	1
regulation of nitric oxide biosynthetic process	-0.001	0.024	-10000	0	-0.55	1	1
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.055	0.065	-10000	0	-0.5	10	10
PRKCD	0.014	0.038	-10000	0	-0.86	1	1
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.03	0.025	-10000	0	-0.56	1	1
RelA/NF kappa B1	-0.001	0.024	-10000	0	-0.56	1	1
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.033	-10000	0	-0.74	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.033	0.077	-10000	0	-0.51	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.067	-10000	0	-0.52	9	9
mol:Sphingosine-1-phosphate	0.027	0.044	-10000	0	-0.56	3	3
MAP2K1	-0.07	0.054	-10000	0	-0.55	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	-0.063	0.023	-10000	0	-0.23	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.014	0.033	-10000	0	-0.74	1	1
TNFR1A/BAG4	-0.001	0.024	-10000	0	-0.56	1	1
EIF2AK2	-0.08	0.035	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.008	0.064	-10000	0	-0.52	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.037	-10000	0	-10000	0	0
MAP2K2	-0.071	0.053	-10000	0	-0.55	4	4
SMPD3	0.026	0.051	-10000	0	-0.33	2	2
TNF	0.003	0.1	-10000	0	-0.8	8	8
PKC zeta/PAR4	-0.004	0.048	-10000	0	-0.56	4	4
mol:PHOSPHOCHOLINE	0.23	0.083	0.26	482	-10000	0	482
NF kappa B1/RelA/I kappa B alpha	-0.004	0.038	-10000	0	-10000	0	0
AIFM1	-0.063	0.025	-10000	0	-0.23	1	1
BCL2	0.016	0	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.57	0.68	-9999	-1.3	250	250
PLK1	-0.12	0.37	-9999	-0.8	93	93
CDKN1B	0.062	0.16	-9999	-10000	0	0
FOXO3	-0.035	0.23	-9999	-0.66	14	14
KAT2B	0.012	0.04	-9999	-0.78	1	1
FOXO1/SIRT1	-0.14	0.21	-9999	-10000	0	0
CAT	-0.024	0.22	-9999	-0.89	7	7
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	-0.007	0.038	-9999	-10000	0	0
FOXO1	-0.16	0.23	-9999	-0.41	250	250
MAPK10	0.033	0.049	-9999	-0.43	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.048	-9999	-10000	0	0
response to oxidative stress	-0.028	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.029	0.2	-9999	-0.62	7	7
XPO1	0.017	0	-9999	-10000	0	0
EP300	-0.006	0.042	-9999	-0.74	1	1
BCL2L11	0.013	0.044	-9999	-10000	0	0
FOXO1/SKP2	-0.14	0.21	-9999	-0.4	3	3
mol:GDP	-0.028	0.045	-9999	-10000	0	0
RAN	0.018	0.001	-9999	-10000	0	0
GADD45A	0.12	0.098	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.031	0.085	-9999	-10000	0	0
MST1	0.001	0.11	-9999	-0.86	8	8
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.043	0.095	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.036	0.034	-9999	-0.43	2	2
MAPK9	0.037	0.019	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.035	0.028	-9999	-10000	0	0
SOD2	0.015	0.2	-9999	-0.71	6	6
RBL2	0.025	0.17	-9999	-1.3	1	1
RAL/GDP	0.009	0.024	-9999	-10000	0	0
CHUK	0.014	0.02	-9999	-10000	0	0
Ran/GTP	0.017	0.003	-9999	-10000	0	0
CSNK1G2	0.014	0.033	-9999	-0.74	1	1
RAL/GTP	0.024	0.026	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.34	0.39	-9999	-0.73	265	265
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.018	0.001	-9999	-10000	0	0
IKBKB	0.014	0.02	-9999	-10000	0	0
CCNB1	-0.027	0.23	-9999	-0.95	9	9
FOXO1-3a-4/beta catenin	-0.069	0.1	-9999	-0.43	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-9999	-0.4	3	3
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.014	0.02	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.024	0.014	-9999	-10000	0	0
ZFAND5	0.11	0.044	-9999	-10000	0	0
SFN	-0.083	0.27	-9999	-0.83	62	62
CDK2	-0.019	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.014	0.099	-9999	-10000	0	0
CREBBP	-0.019	0.041	-9999	-10000	0	0
FBXO32	-0.024	0.22	-9999	-0.79	8	8
BCL6	0.027	0.16	-9999	-10000	0	0
RALB	0.018	0	-9999	-10000	0	0
RALA	0.018	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.016	0.16	-9999	-0.86	19	19
PLK4	0.011	0.066	-9999	-0.86	3	3
regulation of centriole replication	0.002	0.14	-9999	-0.66	22	22

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.022	0.1	-9999	-0.49	24	24
E-cadherin/beta catenin	-0.023	0.11	-9999	-0.56	22	22
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.011	0.057	-9999	-0.74	3	3
CDH1	-0.016	0.15	-9999	-0.74	22	22

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.19	0.22	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.15	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.029	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.1	0.091	-9999	-0.37	1	1
CaM/Ca2+	-0.18	0.2	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.18	0.2	-9999	-1	1	1
AKT1	-0.16	0.17	-9999	-10000	0	0
MAP2K1	-0.12	0.22	-9999	-10000	0	0
MAP3K11	-0.14	0.23	-9999	-0.8	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.27	0.29	-9999	-0.73	117	117
Rap1/GTP	-0.13	0.14	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.21	0.23	-9999	-10000	0	0
CEBPB	-0.067	0.2	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.19	0.21	-9999	-1	2	2
STAT1	-0.14	0.23	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.37	0.43	-9999	-0.85	239	239
PIK3CA	0.014	0.033	-9999	-0.74	1	1
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.074	0.084	-9999	-0.47	1	1
mol:Ca2+	-0.19	0.21	-9999	-10000	0	0
MAPK3	-0.087	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.087	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
JAK1	0.001	0.019	-9999	-10000	0	0
CAMK2D	0.016	0	-9999	-10000	0	0
DAPK1	-0.024	0.15	-9999	-0.63	3	3
SMAD7	-0.02	0.082	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.17	0.19	-9999	-10000	0	0
IFNG	-0.37	0.43	-9999	-0.85	239	239
apoptosis	-0.036	0.12	-9999	-0.44	3	3
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.24	0.36	-9999	-0.74	180	180
CAMK2B	-0.098	0.27	-9999	-0.75	79	79
FRAP1	-0.1	0.2	-9999	-10000	0	0
PRKCD	-0.12	0.21	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.1	0.091	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.015	0.033	-9999	-0.74	1	1
IRF1	-0.057	0.18	-9999	-0.66	3	3
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.011	0.082	-9999	-0.73	6	6
mol:GDP	-0.15	0.17	-9999	-10000	0	0
CASP1	-0.02	0.082	-9999	-10000	0	0
PTGES2	0.013	0.046	-9999	-0.74	2	2
IRF9	0.018	0.076	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.18	-9999	-10000	0	0
RAP1/GDP	-0.13	0.14	-9999	-10000	0	0
CBL	-0.15	0.23	-9999	-10000	0	0
MAP3K1	-0.14	0.23	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.1	0.091	-9999	-0.37	1	1
PTPN11	-0.16	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

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
SPTAN1	0.012	0.043	-10000	0	-10000	0	0
RFC1	0.012	0.043	-10000	0	-10000	0	0
PRKDC	0.012	0.043	-10000	0	-10000	0	0
RIPK1	0.015	0.004	-10000	0	-10000	0	0
CASP7	-0.023	0.066	0.25	7	-10000	0	7
FASLG/FAS/FADD/FAF1	-0.13	0.16	-10000	0	-0.35	22	22
MAP2K4	-0.084	0.16	-10000	0	-0.43	23	23
mol:ceramide	-0.15	0.2	-10000	0	-0.48	32	32
GSN	0.012	0.043	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.17	0.18	-10000	0	-0.44	22	22
FAS	0.015	0.006	-10000	0	-10000	0	0
BID	0.018	0.066	-10000	0	-10000	0	0
MAP3K1	-0.035	0.1	-10000	0	-10000	0	0
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
RB1	0.012	0.043	-10000	0	-10000	0	0
CFLAR	0.015	0.004	-10000	0	-10000	0	0
HGF/MET	-0.036	0.14	-10000	0	-0.57	33	33
ARHGDIB	0.012	0.043	-10000	0	-10000	0	0
FADD	0.015	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.043	-10000	0	-10000	0	0
NFKB1	-0.065	0.077	-10000	0	-0.71	1	1
MAPK8	-0.084	0.18	-10000	0	-0.53	25	25
DFFA	0.012	0.043	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.012	0.043	-10000	0	-10000	0	0
FAS/FADD/MET	-0.005	0.055	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.045	0.22	-10000	0	-0.86	37	37
FAF1	0.015	0.006	-10000	0	-10000	0	0
PARP1	0.012	0.043	-10000	0	-10000	0	0
DFFB	0.012	0.043	-10000	0	-10000	0	0
CHUK	-0.052	0.067	-10000	0	-0.65	1	1
FASLG	-0.42	0.44	-10000	0	-0.86	265	265
FAS/FADD	0	0	-10000	0	-10000	0	0
HGF	-0.019	0.17	-10000	0	-0.8	23	23
LMNA	0.01	0.047	-10000	0	-0.52	1	1
CASP6	0.012	0.043	-10000	0	-10000	0	0
CASP10	0.015	0.006	-10000	0	-10000	0	0
CASP3	0.014	0.05	-10000	0	-10000	0	0
PTPN13	0.003	0.098	-10000	0	-0.74	9	9
CASP8	0.028	0.1	0.4	37	-10000	0	37
IL6	-0.13	0.34	-10000	0	-0.96	67	67
MET	0.007	0.085	-10000	0	-0.86	5	5
ICAD/CAD	0.012	0.042	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.15	0.2	-10000	0	-0.49	32	32
activation of caspase activity by cytochrome c	0.018	0.066	-10000	0	-10000	0	0
PAK2	0.012	0.042	-10000	0	-10000	0	0
BCL2	0.016	0.001	-10000	0	-10000	0	0

×

Canonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.005	0.019	-10000	0	-10000	0	0
AES	0.005	0.016	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.026	0.18	-10000	0	-0.82	26	26
TLE1	0.005	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.001	-10000	0	-10000	0	0
CTNNB1	0.048	0.1	-10000	0	-0.45	1	1
WIF1	-0.001	0.075	-10000	0	-0.77	5	5
beta catenin/RanBP3	0.004	0.11	0.35	20	-10000	0	20
KREMEN2	-0.091	0.28	-10000	0	-0.86	64	64
DKK1	-0.019	0.17	-10000	0	-0.82	22	22
beta catenin/beta TrCP1	0.056	0.094	-10000	0	-10000	0	0
FZD1	0.016	0.001	-10000	0	-10000	0	0
AXIN2	0.009	0.099	-10000	0	-1.4	2	2
AXIN1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.018	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.072	0.064	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.04	0.083	0.25	2	-10000	0	2
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.002	0.074	-10000	0	-0.74	5	5
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.01	0.15	-10000	0	-0.75	21	21
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.096	0.22	-10000	0	-0.57	89	89
NKD1	-0.19	0.33	-10000	0	-0.74	142	142
TCF4	0.005	0.017	-10000	0	-10000	0	0
TCF3	0.005	0.017	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.024	0.11	-10000	0	-0.52	25	25
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.02	0.11	0.52	3	-10000	0	3
LEF1	-0.021	0.15	-10000	0	-0.86	16	16
DVL1	0.004	0.034	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.082	0.07	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.091	0.22	-10000	0	-0.61	79	79
LRP6	0.016	0.002	-10000	0	-10000	0	0
CSNK1A1	0.005	0.019	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.009	0.15	-10000	0	-0.75	20	20
WNT1	-0.026	0.18	-10000	0	-0.86	25	25
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.016	0.002	-10000	0	-10000	0	0
FRAT1	0.015	0.004	-10000	0	-10000	0	0
PPP2R5D	0.096	0.15	0.35	141	-10000	0	141
APC	-0.005	0.11	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.012	0.063	0.27	5	-10000	0	5
CREBBP	0.005	0.017	-10000	0	-10000	0	0

×

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	-0.006	0.059	-9999	-0.56	6	6
AKT1	-0.054	0.2	-9999	-0.71	3	3
PTK2B	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.002	0.04	-9999	-0.83	1	1
CAV1	-0.045	0.22	-9999	-0.86	37	37
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.23	0.25	-9999	-1.2	1	1
endothelial cell proliferation	-0.04	0.19	-9999	-0.69	1	1
mol:Ca2+	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.21	0.24	-9999	-1.2	1	1
RP11-342D11.1	-0.17	0.26	-9999	-1.1	1	1
CDH5	0.014	0.038	-9999	-0.86	1	1
VEGFA homodimer	-0.23	0.26	-9999	-0.52	239	239
SHC1	0.014	0.038	-9999	-0.86	1	1
SHC2	0.006	0.089	-9999	-0.82	6	6
HRAS/GDP	-0.17	0.19	-9999	-0.82	2	2
SH2D2A	-0.27	0.41	-9999	-0.86	172	172
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.14	0.15	-9999	-0.78	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.39	0.33	-9999	-1	66	66
VEGFR1 homodimer	0.007	0.084	-9999	-0.86	5	5
SHC/GRB2/SOS1	-0.19	0.2	-9999	-1.1	1	1
GRB10	-0.16	0.26	-9999	-1.1	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.2	0.22	-9999	-1	2	2
HRAS	0.014	0.038	-9999	-0.86	1	1
VEGF/Rho/ROCK1/Integrin Complex	-0.086	0.094	-9999	-0.58	1	1
HIF1A	0.013	0.046	-9999	-0.74	2	2
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.21	0.23	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	-0.001	0.024	-9999	-0.56	1	1
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.23	0.25	-9999	-1.2	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.063	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.052	0.18	-9999	-0.57	1	1
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	-0.16	0.27	-9999	-1.1	1	1
HIF1A/ARNT	-0.002	0.034	-9999	-0.56	2	2
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.37	0.44	-9999	-0.86	239	239
VEGFC	0.014	0.038	-9999	-0.86	1	1
FAK1/Vinculin	-0.1	0.22	-9999	-0.99	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.22	0.24	-9999	-1.2	1	1
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	0.026	0.036	-9999	-0.71	1	1
mol:L-citrulline	-0.063	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.22	0.25	-9999	-1.2	1	1
VEGFR2/3 heterodimer	-0.002	0.04	-9999	-0.83	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.15	0.26	-9999	-0.83	2	2
VEGFR2 homodimer	0.043	0.049	-9999	-0.72	2	2
FLT1	0.007	0.085	-9999	-0.86	5	5
NEDD4	0.015	0.046	-9999	-0.74	2	2
MAPK3	-0.14	0.25	-9999	-0.76	2	2
MAPK1	-0.14	0.25	-9999	-0.76	2	2
VEGFA145/NRP2	-0.3	0.33	-9999	-0.66	244	244
VEGFR1/2 heterodimer	-0.008	0.068	-9999	-0.61	6	6
KDR	0.043	0.049	-9999	-0.73	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.21	0.23	-9999	-1.2	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.14	0.25	-9999	-0.77	2	2
PI3K	-0.16	0.18	-9999	-0.78	6	6
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.23	0.25	-9999	-1.2	1	1
FES	-0.17	0.27	-9999	-1	2	2
GAB1	-0.16	0.19	-9999	-0.8	5	5
VEGFR2 homodimer/VEGFA homodimer/Src	-0.23	0.25	-9999	-1.2	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.081	0.2	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.23	0.25	-9999	-1.2	1	1
PI3K/GAB1	-0.054	0.19	-9999	-0.69	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.2	0.22	-9999	-1.1	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.003	0.043	-9999	-0.64	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.16	0.27	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.39	0.33	-9999	-1	66	66
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.27	-9999	-1.1	1	1
CaM/Ca2+	-0.18	0.2	-9999	-1	1	1
MAP2K3	-0.14	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.21	0.23	-9999	-1.2	1	1
PLCG1	-0.16	0.27	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.21	0.24	-9999	-1.2	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.23	0.25	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.23	0.25	-9999	-0.5	239	239
cell migration	-0.053	0.2	-9999	-0.77	1	1
mol:PI-3-4-5-P3	-0.15	0.17	-9999	-0.7	6	6
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.19	0.21	-9999	-1	1	1
mol:NO	-0.063	0.19	-9999	-0.62	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.17	0.19	-9999	-0.82	2	2
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.21	0.23	-9999	-1.2	1	1
VHL	0.014	0.033	-9999	-0.74	1	1
ITGB3	0.007	0.08	-9999	-0.74	6	6
NOS3	-0.073	0.2	-9999	-0.73	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.23	0.26	-9999	-0.87	6	6
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.14	0.25	-9999	-1	1	1
PRKCB	-0.14	0.25	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.21	0.24	-9999	-1.2	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.23	0.26	-9999	-1.1	5	5
VEGFA165/NRP2	-0.3	0.33	-9999	-0.66	244	244
MAPKKK cascade	-0.16	0.18	-9999	-0.8	2	2
NRP2	0.004	0.1	-9999	-0.86	7	7
VEGFC homodimer	0.014	0.038	-9999	-0.86	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.1	0.22	-9999	-0.99	1	1
MAP3K13	-0.16	0.27	-9999	-1.2	1	1
PDPK1	-0.072	0.2	-9999	-0.65	6	6

×

Regulation of Androgen receptor activity

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
HDAC1	0.03	0.002	-9999	-10000	0	0
SMARCC1	0.026	0.01	-9999	-10000	0	0
REL	0.008	0.065	-9999	-0.74	4	4
HDAC7	-0.098	0.088	-9999	-0.66	3	3
JUN	0.015	0.003	-9999	-10000	0	0
EP300	0.014	0.033	-9999	-0.74	1	1
KAT2B	0.014	0.033	-9999	-0.74	1	1
KAT5	0.016	0	-9999	-10000	0	0
MAPK14	0.001	0.046	-9999	-0.59	3	3
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.091	-9999	-0.68	4	4
MAP2K6	-0.002	0.058	-9999	-0.76	3	3
BRM/BAF57	0	0	-9999	-10000	0	0
MAP2K4	0.002	0.006	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.12	0.13	-9999	-1.3	4	4
NCOA2	0	0.11	-9999	-0.74	11	11
CEBPA	-0.001	0.12	-9999	-0.86	10	10
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.093	0.098	-9999	-0.55	2	2
NR0B1	-0.051	0.21	-9999	-0.86	34	34
EGR1	-0.002	0.11	-9999	-0.74	12	12
RXRs/9cRA	-0.004	0.047	-9999	-0.54	4	4
AR/RACK1/Src	-0.016	0.064	-9999	-0.57	2	2
AR/GR	0	0.087	-9999	-0.69	4	4
GNB2L1	0.014	0.038	-9999	-0.86	1	1
PKN1	0.015	0.003	-9999	-10000	0	0
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.002	0.037	-9999	-0.57	2	2
T-DHT/AR/TIF2/CARM1	-0.022	0.098	-9999	-0.7	7	7
SRC	0.003	0.049	-9999	-10000	0	0
NR3C1	0.014	0.038	-9999	-0.86	1	1
KLK3	-0.052	0.19	-9999	-0.71	27	27
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.026	0.057	-9999	-0.57	4	4
TMPRSS2	-0.96	0.38	-9999	-1.1	460	460
RXRG	0.006	0.076	-9999	-0.86	4	4
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.016	0.001	-9999	-10000	0	0
RXRB	0.016	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.014	0.033	-9999	-0.74	1	1
KLK2	-0.025	0.14	-9999	-0.63	22	22
AR	-0.011	0.089	-9999	-0.43	14	14
SENP1	0.016	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.013	0.009	-9999	-10000	0	0
SRY	0.002	0.007	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.16	0.34	-9999	-0.86	104	104
T-DHT/AR/RACK1/Src	-0.016	0.062	-9999	-0.59	2	2
positive regulation of transcription	-0.003	0.12	-9999	-0.74	13	13
DNAJA1	0.002	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.002	-9999	-10000	0	0
NCOA1	0.024	0.005	-9999	-10000	0	0
SPDEF	-0.17	0.36	-9999	-0.86	114	114
T-DHT/AR/TIF2	0.018	0.076	-9999	-0.66	4	4
T-DHT/AR/Hsp90	-0.028	0.056	-9999	-0.57	4	4
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.011	0.053	-9999	-0.49	4	4
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.014	0.008	-9999	-10000	0	0
POU2F1	0.005	0.015	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.067	0.14	-9999	-0.6	29	29
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

Nongenotropic Androgen signaling

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
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.021	0.093	-10000	0	-0.43	26	26
regulation of S phase of mitotic cell cycle	-0.015	0.069	-10000	0	-0.62	1	1
GNAO1	0.008	0.082	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
SHBG/T-DHT	-0.05	0.15	-10000	0	-0.49	54	54
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.046	0.092	-10000	0	-10000	0	0
T-DHT/AR	-0.028	0.12	-10000	0	-0.57	26	26
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	13	13
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
mol:GDP	-0.027	0.12	-10000	0	-0.55	26	26
cell proliferation	0.071	0.11	-10000	0	-0.64	4	4
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
FOS	0.056	0.14	-10000	0	-0.81	13	13
mol:Ca2+	-0.003	0.014	-10000	0	-0.11	4	4
MAPK3	0.062	0.1	-10000	0	-0.57	4	4
MAPK1	0.044	0.054	-10000	0	-0.29	4	4
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	0	0.001	-10000	0	-0.004	13	13
cAMP biosynthetic process	-0.045	0.15	-10000	0	-0.48	54	54
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.004	13	13
HRAS/GTP	-0.02	0.086	-10000	0	-0.45	4	4
actin cytoskeleton reorganization	-0.001	0.023	-10000	0	-10000	0	0
SRC	0.016	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.004	13	13
PI3K	-0.002	0.03	-10000	0	-0.48	2	2
apoptosis	-0.06	0.094	0.43	12	-10000	0	12
T-DHT/AR/PELP1	-0.024	0.1	-10000	0	-0.48	26	26
HRAS/GDP	-0.026	0.12	-10000	0	-0.52	27	27
CREB1	0.061	0.1	-10000	0	-0.47	12	12
RAC1-CDC42/GTP	-0.001	0.023	-10000	0	-10000	0	0
AR	-0.021	0.16	-10000	0	-0.74	26	26
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.035	0.094	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.024	0.11	-10000	0	-0.49	26	26
T-DHT/AR/PELP1/Src	-0.021	0.094	-10000	0	-0.46	4	4
MAP2K2	0.046	0.094	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.015	0.069	-10000	0	-0.62	1	1
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
SHBG	-0.061	0.23	-10000	0	-0.74	54	54
Gi family/GNB1/GNG2/GDP	-0.008	0.044	-10000	0	-0.45	2	2
mol:T-DHT	0	0	-10000	0	-0.003	9	9
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.18	0.31	-10000	0	-0.68	148	148
Gi family/GTP	-0.013	0.058	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.07	-10000	0	-10000	0	0
epithelial cell differentiation	-0.052	0.11	-10000	0	-0.56	1	1
ITCH	0.055	0.017	-10000	0	-10000	0	0
WWP1	-0.097	0.066	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	0.001	0.11	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.019	0.08	-10000	0	-10000	0	0
PTPRZ1	-0.082	0.25	-10000	0	-0.75	65	65
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.053	0.074	-10000	0	-0.65	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.084	0.094	-10000	0	-0.57	10	10
ADAM17	0.055	0.017	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.085	-10000	0	-0.46	1	1
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.63	12	12
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.076	0.078	-10000	0	-0.71	1	1
GRIN2B	-0.057	0.091	-10000	0	-0.61	3	3
ErbB4/ErbB2/betacellulin	-0.13	0.16	-10000	0	-0.51	74	74
STAT1	0.014	0.038	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.085	0.26	-10000	0	-0.74	71	71
E4ICDs/ETO2	-0.11	0.079	-10000	0	-0.7	2	2
axon guidance	-0.017	0.071	-10000	0	-10000	0	0
NEDD4	0.052	0.051	-10000	0	-0.72	2	2
Prolactin receptor/Prolactin receptor/Prolactin	-0.075	0.19	-10000	0	-0.56	71	71
CBFA2T3	0.012	0.054	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.064	0.038	-10000	0	-0.51	1	1
MAPK3	-0.03	0.082	-10000	0	-0.6	1	1
STAT1 (dimer)	-0.11	0.072	-10000	0	-0.54	1	1
MAPK1	-0.03	0.082	-10000	0	-0.6	1	1
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.077	0.081	-10000	0	-0.53	11	11
NRG1	0.035	0.11	-10000	0	-0.56	17	17
NRG3	-0.004	0.13	-10000	0	-0.86	12	12
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
NRG4	-0.055	0.22	-10000	0	-0.76	47	47
heart development	-0.017	0.071	-10000	0	-10000	0	0
neural crest cell migration	-0.077	0.08	-10000	0	-0.52	11	11
ERBB2	0.052	0.039	-10000	0	-0.56	2	2
WWOX/E4ICDs	-0.11	0.074	-10000	0	-0.7	1	1
SHC1	0.014	0.038	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.14	0.15	-10000	0	-0.56	51	51
apoptosis	0.1	0.063	0.44	1	-10000	0	1
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.088	-10000	0	-0.53	10	10
ErbB4/ErbB2/epiregulin	-0.098	0.13	-10000	0	-0.57	35	35
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.19	-10000	0	-0.58	82	82
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.13	0.14	-10000	0	-0.72	1	1
MDM2	-0.1	0.073	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.054	0.078	-10000	0	-0.66	1	1
STAT5A	-0.005	0.067	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.085	0.1	-10000	0	-0.62	8	8
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.029	-10000	0	-0.66	1	1
E4ICDs/TAB2/NCoR1	-0.1	0.048	-10000	0	-10000	0	0
STAT5A (dimer)	-0.055	0.12	-10000	0	-0.62	1	1
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.007	0.064	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.041	0.21	-10000	0	-0.86	34	34
BTC	-0.1	0.27	-10000	0	-0.74	82	82
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.017	0.072	-10000	0	-10000	0	0
ERBB4	-0.14	0.085	-10000	0	-0.46	1	1
STAT5B	0.016	0	-10000	0	-10000	0	0
YAP1	-0.034	0.016	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.1	0.13	-10000	0	-0.52	37	37
glial cell differentiation	0.1	0.047	-10000	0	-10000	0	0
WWOX	0.014	0.038	-10000	0	-0.86	1	1
cell proliferation	-0.077	0.16	-10000	0	-0.67	8	8

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.046	0.093	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	93	93
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.008	0.082	-9999	-0.84	5	5
RhoA/GTP	-0.046	0.094	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.015	0.13	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	93	93
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.053	0.11	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.74	3	3

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.012	0.058	-9999	-10000	0	0
epithelial cell differentiation	-0.016	0.079	-9999	-10000	0	0
CYFIP2	0.004	0.092	-9999	-0.74	8	8
ENAH	0.078	0.065	-9999	-10000	0	0
EGFR	0.001	0.11	-9999	-0.85	9	9
EPHA2	0.014	0.033	-9999	-0.74	1	1
MYO6	0.032	0.096	-9999	-0.78	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.007	0.057	-9999	-0.47	8	8
AQP5	-0.17	0.24	-9999	-0.52	161	161
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.034	0.083	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.018	0.12	-9999	-0.84	1	1
EGF	-0.67	0.23	-9999	-0.74	480	480
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.05	0.16	-9999	-0.58	39	39
cortical microtubule organization	-0.016	0.079	-9999	-10000	0	0
GO:0000145	0.034	0.079	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.017	0.08	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GDP	-0.014	0.062	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.003	0.034	-9999	-0.52	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.05	0.084	-9999	-0.57	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.034	0.084	-9999	-10000	0	0
ARF6/GTP	-0.002	0.031	-9999	-10000	0	0
CDH1	-0.016	0.15	-9999	-0.74	22	22
EGFR/EGFR/EGF/EGF	-0.34	0.14	-9999	-0.77	28	28
RhoA/GDP	-0.015	0.073	-9999	-10000	0	0
actin cytoskeleton organization	0.042	0.092	-9999	-0.71	2	2
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
IGF1	0.006	0.093	-9999	-0.86	6	6
DIAPH1	-0.01	0.085	-9999	-0.69	8	8
Wnt receptor signaling pathway	0.016	0.079	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.014	0.063	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.042	0.094	-9999	-0.74	2	2
EFNA1	0.014	0.038	-9999	-0.86	1	1
LPP	0.043	0.089	-9999	-0.8	1	1
Ephrin A1/EPHA2	-0.016	0.074	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.062	-9999	-10000	0	0
MGAT3	0.018	0.12	-9999	-0.86	1	1
HGF/MET	-0.036	0.13	-9999	-0.95	4	4
HGF	-0.019	0.17	-9999	-0.8	23	23
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.012	0.059	-9999	-10000	0	0
actin cable formation	0.099	0.07	-9999	-10000	0	0
KIAA1543	0.036	0.12	-9999	-0.85	6	6
KIFC3	0.034	0.086	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.033	0.093	-9999	-0.86	1	1
NCK1/GIT1	-0.001	0.024	-9999	-0.56	1	1
mol:GDP	-0.016	0.079	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.034	0.084	-9999	-10000	0	0
PIP5K1C	0.034	0.084	-9999	-10000	0	0
LIMA1	0.016	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
ROCK1	-0.012	0.054	-9999	-10000	0	0
adherens junction assembly	0.058	0.12	-9999	-0.79	7	7
IGF-1R heterotetramer/IGF1	-0.019	0.083	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PLEKHA7	0.031	0.1	-9999	-0.78	3	3
mol:GTP	-0.003	0.034	-9999	-0.52	1	1
establishment of epithelial cell apical/basal polarity	0.07	0.076	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.058	-9999	-10000	0	0
regulation of cell-cell adhesion	0.042	0.092	-9999	-0.71	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.012	0.059	-9999	-10000	0	0

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.008	0.082	-9999	-0.84	5	5
CDC42/GTP	-0.018	0.063	-9999	-10000	0	0
PLCG1	0.033	0.08	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.018	0.062	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	93	93
S1PR4	-0.034	0.2	-9999	-0.86	30	30
MAPK3	0.033	0.08	-9999	-10000	0	0
MAPK1	0.033	0.08	-9999	-10000	0	0
S1P/S1P5/Gi	-0.053	0.11	-9999	-10000	0	0
GNAI1	0.011	0.057	-9999	-0.74	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	93	93
RHOA	0.013	0.12	-9999	-0.49	30	30
S1P/S1P4/Gi	-0.021	0.072	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.057	-9999	-0.74	3	3
S1P/S1P4/G12/G13	-0.03	0.12	-9999	-0.53	30	30
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	-0.031	0.12	-9999	-0.51	33	33
RGS9BP	-0.017	0.15	-9999	-0.74	23	23
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.012	0.084	-9999	-0.59	11	11
mol:ADP	0.012	0.043	-9999	-0.68	2	2
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	38	38
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.025	-9999	-0.59	1	1
GRK7	0.008	0.054	-9999	-0.86	2	2
CNGB3	-0.007	0.11	-9999	-0.86	8	8
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.11	-9999	-0.64	15	15
Cone PDE6	-0.033	0.12	-9999	-0.58	5	5
Cone Metarhodopsin II	-0.002	0.034	-9999	-0.55	2	2
Na + (4 Units)	-0.018	0.11	-9999	-0.64	15	15
GNAT2/GDP	-0.03	0.11	-9999	-0.5	9	9
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.043	-9999	-0.54	3	3
Cone Transducin	-0.033	0.13	-9999	-0.54	33	33
SLC24A2	-0.008	0.099	-9999	-0.86	7	7
GNB3/GNGT2	-0.041	0.16	-9999	-0.66	33	33
GNB3	-0.038	0.21	-9999	-0.86	32	32
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0	0.065	-9999	-0.86	3	3
ARR3	0.004	0.007	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.012	0.085	-9999	-0.6	11	11
mol:Pi	-0.035	0.13	-9999	-0.49	38	38
Cone CNG Channel	-0.013	0.083	-9999	-0.52	13	13
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.008	0.099	-9999	-0.86	7	7
RGS9	-0.008	0.14	-9999	-0.81	15	15
PDE6C	0.004	0.054	-9999	-0.86	2	2
GNGT2	0.014	0.038	-9999	-0.86	1	1
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.038	-9999	-0.86	1	1

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.008	0.078	-9999	-0.79	5	5
GNB1/GNG2	-0.054	0.11	-9999	-0.53	8	8
mol:DAG	0.009	0.13	-9999	-10000	0	0
PLCG1	0.009	0.13	-9999	-10000	0	0
YES1	-0.011	0.14	-9999	-0.56	8	8
FZD3	0.016	0	-9999	-10000	0	0
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.05	0.1	-9999	-10000	0	0
MAP3K7	-0.096	0.22	-9999	-0.55	40	40
mol:Ca2+	0.01	0.12	-9999	-10000	0	0
mol:IP3	0.009	0.13	-9999	-10000	0	0
NLK	-0.007	0.009	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.12	0.24	-9999	-0.6	50	50
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.064	0.13	-9999	-0.6	8	8
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.011	0.14	-9999	-0.56	8	8
GO:0007205	0.01	0.13	-9999	-10000	0	0
WNT6	-0.017	0.17	-9999	-0.86	20	20
WNT4	-0.068	0.24	-9999	-0.75	58	58
NFAT1/CK1 alpha	-0.051	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.057	-9999	-0.74	3	3
WNT11	-0.04	0.2	-9999	-0.76	38	38
CDC42	0	0.14	-9999	-0.52	8	8

×

a4b1 and a4b7 Integrin signaling

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
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ITGA4	-0.011	0.15	-9999	-0.86	16	16
alpha4/beta7 Integrin	-0.02	0.11	-9999	-0.66	16	16
alpha4/beta1 Integrin	-0.02	0.11	-9999	-0.66	16	16

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.37	-9999	-0.74	205	205
HRAS	0.014	0.038	-9999	-0.86	1	1
EGFR	0.001	0.11	-9999	-0.85	9	9
AKT	0.035	0.029	-9999	-10000	0	0
FOXO3	0.016	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
FOXO4	0.016	0	-9999	-10000	0	0
MET	0.007	0.085	-9999	-0.86	5	5
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PIK3CB	0.016	0	-9999	-10000	0	0
NRAS	0.016	0	-9999	-10000	0	0
PIK3CG	0.011	0.066	-9999	-0.86	3	3
PIK3R3	0.016	0	-9999	-10000	0	0
PIK3R2	0.016	0	-9999	-10000	0	0
NF1	0.016	0	-9999	-10000	0	0
RAS	-0.041	0.097	-9999	-0.38	5	5
ERBB2	0.013	0.046	-9999	-0.74	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.022	0.091	-9999	-0.29	6	6
PIK3R1	0.014	0.033	-9999	-0.74	1	1
KRAS	0.016	0	-9999	-10000	0	0
FOXO	0.041	0.034	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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
PTK2	-0.012	0.036	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.036	0.096	-9999	-0.48	7	7
JUN	0.025	0.12	-9999	-0.56	8	8
HRAS	0.014	0.038	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/GRB10	-0.052	0.16	-9999	-0.7	11	11
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.052	0.16	-9999	-0.7	11	11
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.041	0.13	-9999	-0.46	47	47
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.046	0.14	-9999	-0.82	5	5
GRB7	0.004	0.092	-9999	-0.74	8	8
RET51/GFRalpha1/GDNF	-0.052	0.16	-9999	-0.7	11	11
MAPKKK cascade	-0.041	0.12	-9999	-0.7	6	6
BCAR1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.04	0.13	-9999	-0.46	46	46
lamellipodium assembly	-0.034	0.091	-9999	-0.44	7	7
RET51/GFRalpha1/GDNF/SHC	-0.053	0.16	-9999	-0.69	12	12
PIK3CA	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC	-0.038	0.13	-9999	-0.46	44	44
RET9/GFRalpha1/GDNF/Shank3	-0.037	0.12	-9999	-0.46	43	43
MAPK3	0.006	0.14	-9999	-0.77	5	5
DOK1	0.016	0	-9999	-10000	0	0
DOK6	-0.001	0.11	-9999	-0.74	12	12
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.042	0.12	-9999	-0.73	5	5
DOK5	-0.006	0.13	-9999	-0.76	15	15
GFRA1	-0.042	0.2	-9999	-0.75	40	40
MAPK8	0.015	0.12	-9999	-0.6	8	8
HRAS/GTP	-0.048	0.14	-9999	-0.83	6	6
tube development	-0.034	0.12	-9999	-0.5	6	6
MAPK1	0.006	0.14	-9999	-0.77	5	5
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.024	0.082	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.009	0.076	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.057	0.17	-9999	-0.86	12	12
SHC1	0.014	0.038	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.052	0.16	-9999	-0.7	11	11
RET51/GFRalpha1/GDNF/Dok5	-0.064	0.19	-9999	-0.8	19	19
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
CREB1	-0.032	0.098	-9999	-0.53	5	5
PIK3R1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.025	0.083	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.058	0.18	-9999	-0.79	14	14
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.012	0.14	-9999	-0.76	19	19
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.025	0.11	-9999	-0.54	8	8
RET9/GFRalpha1/GDNF/FRS2	-0.037	0.12	-9999	-0.46	43	43
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.025	0.083	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.034	0.1	-9999	-0.6	5	5
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.035	0.11	-9999	-0.6	6	6
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.036	0.11	-9999	-0.76	5	5
PI3K	-0.051	0.14	-9999	-0.73	7	7
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.034	0.12	-9999	-0.5	6	6
GRB10	0.016	0	-9999	-10000	0	0
activation of MAPKK activity	-0.03	0.092	-9999	-0.52	5	5
RET51/GFRalpha1/GDNF/FRS2	-0.052	0.16	-9999	-0.7	11	11
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.065	-9999	-0.74	4	4
IRS2	0.003	0.11	-9999	-0.86	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.036	0.11	-9999	-0.76	5	5
RET51/GFRalpha1/GDNF/PKC alpha	-0.052	0.16	-9999	-0.7	11	11
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.001	0.065	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.055	0.16	-9999	-0.72	12	12
Rac1/GTP	-0.04	0.11	-9999	-0.54	7	7
RET9/GFRalpha1/GDNF	-0.041	0.14	-9999	-0.51	43	43
GFRalpha1/GDNF	-0.047	0.16	-9999	-0.58	43	43

×

Class IB PI3K non-lipid kinase 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.003	0.099	0.8	8	-10000	0	8
PI3K Class IB/PDE3B	0.003	0.1	-10000	0	-0.8	8	8
PDE3B	0.003	0.1	-10000	0	-0.8	8	8

×

Signaling events mediated by PRL

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
CCNE1	0.003	0.11	-10000	0	-0.86	8	8
mol:Halofuginone	0.007	0.001	-10000	0	-10000	0	0
ITGA1	0.016	0	-10000	0	-10000	0	0
CDKN1A	0.04	0.035	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.024	0.12	-10000	0	-0.66	19	19
mol:Ca2+	-0.016	0.16	0.4	19	-0.65	25	44
AGT	-0.024	0.18	-10000	0	-0.82	25	25
CCNA2	-0.055	0.23	-10000	0	-0.88	7	7
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.02	0.086	-10000	0	-0.55	12	12
CDK2/Cyclin E1	-0.01	0.063	-10000	0	-0.49	8	8
MAPK3	0.006	0.13	-10000	0	-0.66	19	19
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.13	-10000	0	-0.66	19	19
PTP4A1	0.041	0.069	-10000	0	-10000	0	0
PTP4A3	-0.016	0.16	-10000	0	-0.86	19	19
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.006	0.13	-10000	0	-0.66	19	19
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.03	0.062	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.002	0.034	-10000	0	-0.56	2	2
PRL-1/ATF-5	0.042	0.075	-10000	0	-10000	0	0
RABGGTA	0.013	0.046	-10000	0	-0.74	2	2
BCAR1	0.013	0.079	0.4	19	-0.57	1	20
RHOC	0.03	0.062	-10000	0	-10000	0	0
RHOA	0.03	0.062	-10000	0	-10000	0	0
cell motility	0.036	0.064	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.045	0.064	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.12	-10000	0	-0.66	19	19
ROCK1	0.036	0.064	-10000	0	-10000	0	0
RABGGTB	0.016	0	-10000	0	-10000	0	0
CDK2	0.016	0	-10000	0	-10000	0	0
mitosis	0.041	0.068	-10000	0	-10000	0	0
ATF5	0.011	0.066	-10000	0	-0.86	3	3

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.075	0.074	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.15	0.28	-9999	-0.67	123	123
NFKBIA	0.063	0.02	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.014	0.038	-9999	-0.86	1	1
IKBKG	-0.046	0.084	-9999	-10000	0	0
IKK complex/A20	-0.04	0.079	-9999	-0.58	2	2
NEMO/A20/RIP2	0.014	0.038	-9999	-0.86	1	1
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	-0.042	0.077	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.034	0.062	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.19	0.37	-9999	-0.86	123	123
NFKB1	0.019	0.033	-9999	-0.73	1	1
RELA	0.02	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.014	0.033	-9999	-0.74	1	1
TNF/TNFR1A	-0.009	0.075	-9999	-0.61	8	8
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
NF kappa B1 p50/RelA	-0.001	0.02	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.063	0.02	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	-0.038	0.069	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.035	0.063	-9999	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.006	0.034	-10000	0	-10000	0	0
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.066	0.09	0.32	36	-0.36	1	37
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.031	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	-0.072	0.26	-10000	0	-0.86	51	51
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.043	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.057	-10000	0	-0.74	3	3
TRIP10	0.016	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	0.033	0.083	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	0.068	0.094	0.33	36	-0.4	1	37
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.034	0	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
LNPEP	0.013	0.046	-10000	0	-0.74	2	2
YWHAE	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.014	0.033	-10000	0	-0.74	1	1
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.025	0.043	0.67	2	-10000	0	2
CDKN1A	-0.002	0.04	-10000	0	-0.65	2	2
KAT2B	0.014	0.033	-10000	0	-0.74	1	1
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0.001	0.023	0.53	1	-10000	0	1
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.03	0.016	-10000	0	-0.33	1	1
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	-0.005	0.12	-10000	0	-0.86	11	11
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.017	0.16	-10000	0	-0.66	30	30
PPARGC1A	-0.058	0.22	-10000	0	-0.74	52	52
FHL2	0.008	0.075	-10000	0	-0.77	5	5
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0	0.008	-10000	0	-10000	0	0
HIST2H4A	0.025	0.043	-10000	0	-0.67	2	2
SIRT1/FOXO3a	0.001	0.016	0.32	1	-10000	0	1
SIRT1	0.001	0.01	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	0	0.019	-10000	0	-10000	0	0
apoptosis	0	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.047	0.14	-10000	0	-0.48	52	52
p53/SIRT1	0.001	0.023	0.38	2	-10000	0	2
SIRT1/FOXO4	0	0.015	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.004	0.045	-10000	0	-0.46	5	5
HIST1H1E	0.029	0.022	-10000	0	-0.32	2	2
SIRT1/p300	-0.001	0.025	-10000	0	-0.56	1	1
muscle cell differentiation	0.032	0.13	0.57	30	-10000	0	30
TP53	0.001	0.01	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0	0.008	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.013	0.095	-10000	0	-0.67	11	11
ACSS2	0.027	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.032	0.13	-10000	0	-0.57	30	30

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.057	-9999	-0.74	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.004	0.029	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.086	0.22	-9999	-0.62	74	74
IL1A	-0.009	0.14	-9999	-0.86	14	14
IL1B	0.023	0.072	-9999	-0.65	6	6
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.026	-9999	-10000	0	0
IL1R2	-0.078	0.26	-9999	-0.79	62	62
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.003	0.025	-9999	-10000	0	0
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.016	0.001	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.039	0.046	-9999	-10000	0	0
JUN	0.059	0.037	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.01	0.068	-9999	-0.77	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.017	0.094	-9999	-0.52	17	17
PIK3R1	0.014	0.033	-9999	-0.74	1	1
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.016	0.087	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	-0.009	0.068	-9999	-0.52	8	8
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	0.05	0.039	-9999	-10000	0	0
IRAK1	0.03	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.021	0.12	-9999	-0.66	17	17
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.034	-9999	-0.56	2	2
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.004	0.031	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.009	0.068	-9999	-0.52	8	8
IL1 beta/IL1R2	-0.066	0.17	-9999	-0.51	68	68
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.009	0.069	-9999	-1	1	1
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.008	0.06	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.009	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.019	0.1	-9999	-0.57	18	18
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-9999	-10000	0	0
IL1RAP	0.009	0.073	-9999	-0.83	4	4
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.007	0.048	-9999	-10000	0	0
CASP1	0.016	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.09	0.22	-9999	-0.62	77	77
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.009	0.063	-9999	-10000	0	0
TMEM189-UBE2V1	0.007	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.006	0.034	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
IL1RN	-0.012	0.15	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.042	0.032	-9999	-10000	0	0

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0	0.11	-10000	0	-0.76	11	11
EFNB1	0.014	0.11	-10000	0	-0.66	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.022	0.11	-10000	0	-0.78	5	5
Ephrin B2/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
neuron projection morphogenesis	-0.021	0.1	-10000	0	-0.75	5	5
Ephrin B1/EPHB1-2/Tiam1	-0.024	0.12	-10000	0	-0.79	6	6
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.023	0.091	-10000	0	-0.67	9	9
YES1	-0.015	0.12	-10000	0	-0.89	9	9
Ephrin B1/EPHB1-2/NCK2	-0.024	0.11	-10000	0	-0.87	4	4
PI3K	-0.011	0.096	-10000	0	-0.69	10	10
mol:GDP	-0.024	0.12	-10000	0	-0.78	6	6
ITGA2B	-0.015	0.16	-10000	0	-0.86	19	19
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.015	0.12	-10000	0	-0.89	9	9
MAP3K7	-0.012	0.092	-10000	0	-0.71	9	9
FGR	-0.015	0.12	-10000	0	-0.88	9	9
TIAM1	0.014	0.033	-10000	0	-0.74	1	1
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	0.016	0.15	-10000	0	-0.56	26	26
LYN	-0.015	0.12	-10000	0	-0.89	9	9
Ephrin B1/EPHB1-2/Src Family Kinases	-0.015	0.11	-10000	0	-0.84	9	9
Ephrin B1/EPHB1-2	-0.015	0.1	-10000	0	-0.78	9	9
SRC	-0.014	0.11	-10000	0	-0.88	9	9
ITGB3	0.007	0.08	-10000	0	-0.74	6	6
EPHB1	0.009	0.071	-10000	0	-0.8	4	4
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.03	0.14	-10000	0	-0.66	24	24
BLK	-0.022	0.12	-10000	0	-0.88	9	9
HCK	-0.021	0.12	-10000	0	-0.93	9	9
regulation of stress fiber formation	0.023	0.11	0.85	4	-10000	0	4
MAPK8	0.031	0.091	-10000	0	-0.63	9	9
Ephrin B1/EPHB1-2/RGS3	-0.024	0.11	-10000	0	-0.79	5	5
endothelial cell migration	-0.009	0.079	-10000	0	-0.61	9	9
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.01	0.11	-10000	0	-0.85	9	9
regulation of focal adhesion formation	0.023	0.11	0.85	4	-10000	0	4
chemotaxis	0.023	0.11	0.78	5	-10000	0	5
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
Rac1/GTP	-0.022	0.11	-10000	0	-0.78	5	5
angiogenesis	-0.015	0.1	-10000	0	-0.77	9	9
LCK	-0.019	0.12	-10000	0	-0.9	9	9

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.006	0.26	-9999	-1.1	27	27
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.023	0.074	-9999	-0.44	1	1
ATF2/c-Jun	0.043	0.065	-9999	-0.61	1	1
MAPK11	0.019	0.091	-9999	-0.69	3	3
MITF	0.042	0.094	-9999	-0.46	2	2
MAPKAPK5	0.042	0.094	-9999	-0.46	2	2
KRT8	0.041	0.095	-9999	-0.46	2	2
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.03	0.12	-9999	-0.65	3	3
CEBPB	0.033	0.11	-9999	-0.55	1	1
SLC9A1	0.042	0.094	-9999	-0.46	2	2
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.049	0.098	-9999	-0.68	2	2
p38alpha-beta/MNK1	-0.021	0.079	-9999	-0.53	3	3
JUN	0.044	0.065	-9999	-0.6	1	1
PPARGC1A	0	0.16	-9999	-0.38	54	54
USF1	0.042	0.094	-9999	-0.46	2	2
RAB5/GDP/GDI1	-0.014	0.053	-9999	-0.41	1	1
NOS2	0.036	0.14	-9999	-0.87	8	8
DDIT3	0.04	0.098	-9999	-0.4	5	5
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.045	0.095	-9999	-0.65	4	4
p38alpha-beta/HBP1	-0.021	0.079	-9999	-0.53	3	3
CREB1	0.048	0.097	-9999	-0.55	1	1
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.046	0.083	-9999	-0.54	1	1
RPS6KA4	0.042	0.094	-9999	-0.46	2	2
PLA2G4A	0.04	0.11	-9999	-0.74	4	4
GDI1	0.042	0.094	-9999	-0.46	2	2
TP53	0.044	0.12	-9999	-0.56	3	3
RPS6KA5	0.042	0.094	-9999	-0.55	1	1
ESR1	0.038	0.1	-9999	-0.57	3	3
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.042	0.094	-9999	-0.55	1	1
MEF2A	0.042	0.094	-9999	-0.46	2	2
EIF4EBP1	0.041	0.1	-9999	-0.47	4	4
KRT19	-0.046	0.21	-9999	-0.4	109	109
ELK4	0.042	0.094	-9999	-0.46	2	2
ATF6	0.042	0.094	-9999	-0.46	2	2
ATF1	0.048	0.097	-9999	-0.55	1	1
p38alpha-beta/MAPKAPK2	-0.021	0.079	-9999	-0.53	3	3
p38alpha-beta/MAPKAPK3	-0.021	0.079	-9999	-0.53	3	3

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.01	0.067	-10000	0	-0.5	6	6
ER alpha/Gai/GDP/Gbeta gamma	0.053	0.057	-10000	0	-10000	0	0
AKT1	0.045	0.08	-10000	0	-0.8	4	4
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.04	0.08	-10000	0	-0.73	5	5
mol:Ca2+	-0.015	0.19	-10000	0	-0.46	67	67
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.008	0.07	-10000	0	-0.55	8	8
SHC1	0.014	0.038	-10000	0	-0.86	1	1
apoptosis	-0.045	0.076	0.68	5	-10000	0	5
RhoA/GTP	-0.004	0.039	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.008	0.048	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.066	0.053	0.54	2	-10000	0	2
E2/ERA-ERB (dimer)	-0.012	0.08	-10000	0	-0.54	12	12
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.004	0.045	-10000	0	-0.46	5	5
pseudopodium formation	0.066	0.053	-10000	0	-0.54	2	2
E2/ER alpha (dimer)/PELP1	-0.005	0.049	-10000	0	-0.5	5	5
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.008	0.082	-10000	0	-0.84	5	5
HRAS	0.014	0.038	-10000	0	-0.86	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.062	0.064	-10000	0	-0.46	5	5
E2/ER beta (dimer)	-0.008	0.074	-10000	0	-0.64	7	7
mol:GDP	-0.01	0.062	-10000	0	-0.41	12	12
mol:NADP	0.062	0.064	-10000	0	-0.46	5	5
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
mol:IP3	-0.018	0.19	-10000	0	-0.49	63	63
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.025	0.1	-10000	0	-0.56	12	12
PLCB2	-0.067	0.17	-10000	0	-0.48	68	68
IGF1	0.006	0.093	-10000	0	-0.86	6	6
mol:L-citrulline	0.062	0.064	-10000	0	-0.46	5	5
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.047	-10000	0	-0.63	1	1
JNK cascade	-0.008	0.073	-10000	0	-0.64	7	7
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
ESR2	0.005	0.096	-10000	0	-0.83	7	7
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.008	0.075	-10000	0	-0.77	5	5
Gq family/GDP/Gbeta gamma	-0.016	0.076	-10000	0	-0.59	2	2
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.051	0.035	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.008	0.049	-10000	0	-10000	0	0
GNAZ	0.011	0.057	-10000	0	-0.74	3	3
E2/ER alpha (dimer)	-0.006	0.057	-10000	0	-0.59	5	5
STRN	0.01	0.065	-10000	0	-0.74	4	4
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.015	0.076	-10000	0	-0.56	9	9
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.057	-10000	0	-0.74	3	3
HBEGF	-0.042	0.14	-10000	0	-0.51	6	6
cAMP biosynthetic process	-0.01	0.065	-10000	0	-0.43	12	12
SRC	0.062	0.054	-10000	0	-10000	0	0
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.008	0.054	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.01	0.051	-10000	0	-10000	0	0
Gs family/GTP	-0.01	0.066	-10000	0	-0.44	12	12
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	-0.001	0.023	-10000	0	-0.53	1	1
vasodilation	0.062	0.062	-10000	0	-0.44	5	5
mol:DAG	-0.018	0.19	-10000	0	-0.49	63	63
Gs family/GDP/Gbeta gamma	-0.008	0.049	-10000	0	-10000	0	0
MSN	0.068	0.057	-10000	0	-0.59	2	2
Gq family/GTP	-0.019	0.082	-10000	0	-0.49	11	11
mol:PI-3-4-5-P3	0.04	0.077	-10000	0	-0.7	5	5
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.062	0.062	0.44	5	-10000	0	5
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.009	0.058	-10000	0	-0.44	5	5
NOS3	0.063	0.067	-10000	0	-0.48	5	5
GNA11	0.011	0.057	-10000	0	-0.74	3	3
MAPKKK cascade	0.07	0.075	-10000	0	-0.58	5	5
E2/ER alpha (dimer)/PELP1/Src	-0.008	0.049	-10000	0	-10000	0	0
ruffle organization	0.066	0.053	-10000	0	-0.54	2	2
ROCK2	-0.006	0.055	-10000	0	-0.68	2	2
GNA14	0.004	0.092	-10000	0	-0.74	8	8
GNA15	-0.009	0.14	-10000	0	-0.86	15	15
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.16	0.25	-10000	0	-0.66	8	8
MMP2	0.064	0.083	-10000	0	-0.66	3	3

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-10000	0	-10000	0	0
TRAF2/ASK1	0	0	-10000	0	-10000	0	0
ATM	0.014	0.033	-10000	0	-0.74	1	1
MAP2K3	0.038	0.044	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.049	0.045	-10000	0	-10000	0	0
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	-0.002	0.12	-10000	0	-0.85	11	11
TXN	0.011	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
GADD45A	0.016	0	-10000	0	-10000	0	0
GADD45B	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
MAP3K6	0.014	0.033	-10000	0	-0.74	1	1
MAP3K7	0.016	0	-10000	0	-10000	0	0
MAP3K4	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	-0.001	0.024	-10000	0	-0.56	1	1
TAK1/TAB family	0.001	0.012	0.2	2	-10000	0	2
RAC1/OSM/MEKK3	0	0	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.004	0.014	-10000	0	-10000	0	0
TRAF6	0.011	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	-0.099	0.27	-10000	0	-0.75	79	79
CCM2	0.016	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.073	0.18	-10000	0	-0.49	79	79
MAPK11	0.012	0.054	-10000	0	-0.86	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.066	0.16	-10000	0	-0.44	79	79
OSM/MEKK3	0	0	-10000	0	-10000	0	0
TAOK1	0.016	0.053	-10000	0	-0.41	8	8
TAOK2	0.022	0.019	-10000	0	-0.41	1	1
TAOK3	0.022	0.019	-10000	0	-0.41	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.016	0	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.016	0	-10000	0	-10000	0	0
MAP3K10	0.014	0.033	-10000	0	-0.74	1	1
MAP3K3	0.016	0	-10000	0	-10000	0	0
TRX/ASK1	0	0	-10000	0	-10000	0	0
GADD45/MTK1/MTK1	-0.01	0.069	-10000	0	-0.5	10	10

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	0.028	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.073	-10000	0	-0.72	3	3
NFATC4	0.047	0.076	-10000	0	-0.54	2	2
ERBB2IP	0.008	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.016	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.017	0.077	-10000	0	-0.64	1	1
JUN	0.037	0.079	-10000	0	-0.41	2	2
HRAS	0.013	0.038	-10000	0	-0.86	1	1
DOCK7	0.02	0.091	-10000	0	-0.62	2	2
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.022	0.1	-10000	0	-0.87	2	2
AKT1	0.016	0.002	-10000	0	-10000	0	0
BAD	0.026	0.035	-10000	0	-0.54	2	2
MAPK10	-0.01	0.044	-10000	0	-0.39	1	1
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.019	0.083	-10000	0	-0.72	1	1
RAF1	0.039	0.094	-10000	0	-0.68	3	3
ErbB2/ErbB3/neuregulin 2	-0.019	0.095	-10000	0	-0.48	21	21
STAT3	0	0.002	-10000	0	-10000	0	0
cell migration	0.059	0.056	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.086	0.26	-10000	0	-0.6	9	9
FOS	-0.035	0.19	-10000	0	-0.48	15	15
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.017	0.077	-10000	0	-0.64	1	1
MAPK3	-0.056	0.21	-10000	0	-0.56	8	8
MAPK1	-0.056	0.21	-10000	0	-0.56	8	8
JAK2	0.021	0.087	-10000	0	-0.6	1	1
NF2	-0.001	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.006	0.089	-10000	0	-0.82	2	2
NRG1	-0.015	0.13	-10000	0	-0.74	17	17
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.024	0.086	-10000	0	-0.47	3	3
MAPK9	-0.008	0.036	-10000	0	-10000	0	0
ERBB2	-0.002	0.035	-10000	0	-0.57	2	2
ERBB3	-0.004	0.097	-10000	0	-0.74	9	9
SHC1	0.008	0.039	-10000	0	-0.86	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.002	0.022	0.35	2	-10000	0	2
STAT3 (dimer)	0	0.002	-10000	0	-10000	0	0
RNF41	0.038	0.005	-10000	0	-10000	0	0
FRAP1	0.014	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.012	0.052	-10000	0	-0.42	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.03	-10000	0	-0.49	2	2
CHRNA1	-0.13	0.28	-10000	0	-0.45	229	229
myelination	0.05	0.074	-10000	0	-0.48	2	2
PPP3CB	0.02	0.082	-10000	0	-0.55	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.014	0.068	-10000	0	-0.72	2	2
NRG2	-0.001	0.12	-10000	0	-0.85	10	10
mol:GDP	0.007	0.089	-10000	0	-0.81	2	2
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.046	0.096	-10000	0	-0.63	3	3
SRC	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.02	0.087	-10000	0	-0.6	1	1
MAP2K1	-0.039	0.18	-10000	0	-0.57	8	8
heart morphogenesis	-0.017	0.077	-10000	0	-0.64	1	1
RAS family/GDP	-0.014	0.073	-10000	0	-0.72	3	3
GRB2	0.009	0.008	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.021	0.026	-10000	0	-0.24	2	2
HSP90AA1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.016	0.002	-10000	0	-10000	0	0
nervous system development	-0.017	0.077	-10000	0	-0.64	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.02	0.17	-10000	0	-0.71	27	27
regulation of axonogenesis	-0.033	0.034	-10000	0	-10000	0	0
myoblast fusion	0.016	0.07	0.32	27	-10000	0	27
mol:GTP	-0.01	0.043	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.01	0.047	0.49	2	-10000	0	2
ARF1/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GM1	0.007	0.035	-10000	0	-10000	0	0
mol:Choline	0.033	0.031	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.073	-10000	0	-0.33	27	27
MAPK3	0.024	0.068	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.01	0.047	-10000	0	-0.5	2	2
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.07	-10000	0	-0.32	27	27
ARF1/GDP	0.02	0.07	-10000	0	-10000	0	0
ARF6	0.009	0.024	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.016	0.033	-10000	0	-0.74	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.024	0.068	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.012	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.024	-10000	0	-0.56	1	1
RhoA/GDP	-0.014	0.062	-10000	0	-10000	0	0
NME1	0.016	0.038	-10000	0	-0.86	1	1
Rac1/GDP	-0.014	0.062	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.016	0.074	-10000	0	-0.33	27	27
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.01	0.043	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.043	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.016	0.071	-10000	0	-0.32	27	27
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.029	-10000	0	-0.45	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.021	0.035	-10000	0	-10000	0	0
RAB11FIP3	0.014	0.033	-10000	0	-0.74	1	1
tube morphogenesis	-0.016	0.073	-10000	0	-0.33	27	27
ruffle organization	0.033	0.034	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.043	-10000	0	-10000	0	0
PLD2	0.021	0.035	-10000	0	-10000	0	0
PIP5K1A	0.033	0.034	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.031	-10000	0	-10000	0	0
Rac1/GTP	-0.016	0.074	-10000	0	-0.33	27	27

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.035	0.056	-9999	-0.49	6	6
SNTA1	0.013	0.05	-9999	-0.8	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.036	0.049	-9999	-0.47	5	5
MAPK12	0.029	0.084	-9999	-0.49	13	13
CCND1	0.014	0.07	-9999	-0.3	20	20
p38 gamma/SNTA1	0.033	0.088	-9999	-0.51	11	11
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.016	0	-9999	-10000	0	0
G2/M transition checkpoint	0.029	0.083	-9999	-0.49	13	13
MAP2K6	0.03	0.041	-9999	-0.47	3	3
MAPT	0.032	0.068	-9999	-0.49	6	6
MAPK13	0.025	0.057	-9999	-0.56	5	5
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.022	0.018	-9999	-0.39	1	1

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.013	0.068	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.013	0.077	-9999	-0.48	14	14
POMC	0.012	0.05	-9999	-0.8	2	2
EGFR	0.001	0.11	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.009	0.064	-9999	-0.47	10	10
AGRP	0.007	0.047	-9999	-0.74	2	2
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.01	0.14	-9999	-0.86	13	13
long-term memory	-0.001	0.016	-9999	-10000	0	0
Syndecan-3/IL8	-0.031	0.12	-9999	-0.47	35	35
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.001	0.018	-9999	-0.43	1	1
MC4R	-0.01	0.11	-9999	-0.86	9	9
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.75	19	19
FGFR/FGF/Syndecan-3	-0.001	0.019	-9999	-0.43	1	1
neuron projection morphogenesis	-0.023	0.09	-9999	-10000	0	0
Syndecan-3/AgRP	-0.002	0.03	-9999	-0.4	3	3
Syndecan-3/AgRP/MC4R	-0.01	0.066	-9999	-0.47	9	9
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.019	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.03	0.12	-9999	-0.46	35	35
IL8	-0.039	0.21	-9999	-0.84	34	34
Syndecan-3/Fyn/Cortactin	-0.001	0.016	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.018	-9999	-0.41	1	1
alpha-MSH/MC4R	-0.014	0.094	-9999	-0.66	11	11
Gamma Secretase	0	0	-9999	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.021	0.1	-9999	-0.51	22	22
KLHL20	-0.013	0.046	-9999	-0.35	2	2
CYFIP2	0.004	0.092	-9999	-0.74	8	8
Rac1/GDP	0.067	0.076	-9999	-10000	0	0
ENAH	-0.021	0.1	-9999	-0.51	22	22
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
CDC42/GTP	-0.01	0.047	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.01	0.036	-9999	-0.22	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.084	-9999	-10000	0	0
RAPGEF1	0.053	0.099	-9999	-10000	0	0
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.022	0.11	-9999	-0.53	22	22
CRK	0.042	0.11	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	-0.022	0.1	-9999	-0.49	24	24
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	-0.021	0.1	-9999	-0.51	22	22
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.008	0.035	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.002	0.03	-9999	-0.48	2	2
PI3K	-0.01	0.044	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.026	0.12	-9999	-0.57	24	24
TIAM1	0.014	0.033	-9999	-0.74	1	1
E-cadherin(dimer)/Ca2+	-0.017	0.08	-9999	-10000	0	0
AKT1	-0.005	0.025	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
CDH1	-0.016	0.15	-9999	-0.74	22	22
RhoA/GDP	0.067	0.076	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.034	-9999	-0.24	2	2
CDC42/GDP	0.067	0.076	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.068	-9999	-0.32	24	24
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.017	0.084	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.082	-9999	-0.41	22	22
mol:GDP	0.063	0.087	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.057	-9999	-0.74	3	3
p120 catenin/RhoA/GDP	-0.012	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.035	0.063	-9999	-0.26	20	20
NME1	0.014	0.038	-9999	-0.86	1	1
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.021	0.1	-9999	-0.51	22	22
regulation of cell-cell adhesion	-0.009	0.041	-9999	-10000	0	0
WASF2	-0.005	0.018	-9999	-10000	0	0
Rap1/GTP	-0.011	0.054	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.086	-9999	-0.8	1	1
CCND1	-0.016	0.065	-9999	-0.33	20	20
VAV2	0.049	0.1	-9999	-10000	0	0
RAP1/GDP	-0.011	0.056	-9999	-10000	0	0
adherens junction assembly	0.032	0.11	-9999	-0.49	22	22
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.081	-9999	-0.77	1	1
E-cadherin/beta catenin	-0.019	0.09	-9999	-0.45	22	22
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.021	0.1	-9999	-0.51	22	22
PIK3CA	0.014	0.033	-9999	-0.74	1	1
Rac1/GTP	-0.021	0.072	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.019	0.094	-9999	-0.47	22	22
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.023	0.11	-9999	-0.55	22	22

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.003	0.12	-10000	0	-0.81	12	12
CLTC	0.043	0.014	-10000	0	-10000	0	0
calcium ion-dependent exocytosis	0.036	0.001	-10000	0	-10000	0	0
Dynamin 2/GTP	-0.001	0.023	-10000	0	-0.53	1	1
EXOC4	0.016	0	-10000	0	-10000	0	0
CD59	0.039	0.009	-10000	0	-10000	0	0
CPE	0	0.12	-10000	0	-0.58	22	22
CTNNB1	0.016	0	-10000	0	-10000	0	0
membrane fusion	0	0	-10000	0	-10000	0	0
CTNND1	0.042	0.023	-10000	0	-0.49	1	1
DNM2	0.016	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.006	-10000	0	-10000	0	0
TSHR	-0.045	0.2	-10000	0	-0.59	61	61
INS	0.016	0.002	-10000	0	-10000	0	0
BIN1	0.016	0	-10000	0	-10000	0	0
mol:Choline	0	0	-10000	0	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	0.024	0.026	-10000	0	-0.58	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.001	0.023	-10000	0	-0.53	1	1
JUP	0.037	0.023	-10000	0	-10000	0	0
ASAP2/amphiphysin II	-0.001	0.019	-10000	0	-0.43	1	1
ARF6/GTP	0	0	-10000	0	-10000	0	0
CDH1	0.027	0.056	-10000	0	-10000	0	0
clathrin-independent pinocytosis	0	0	-10000	0	-10000	0	0
MAPK8IP3	-0.049	0.23	-10000	0	-0.86	39	39
positive regulation of endocytosis	0	0	-10000	0	-10000	0	0
EXOC2	0.016	0	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	0.058	0	-10000	0	-10000	0	0
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.016	0	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.007	0.035	-10000	0	-10000	0	0
positive regulation of phagocytosis	0.025	0	-10000	0	-10000	0	0
ARF6/GTP/JIP3	-0.043	0.15	-10000	0	-0.59	39	39
ACAP1	-0.019	0.025	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.032	0.015	-10000	0	-10000	0	0
clathrin heavy chain/ACAP1	0.042	0.017	-10000	0	-10000	0	0
JIP4/KLC1	0	0	-10000	0	-10000	0	0
EXOC1	0.016	0	-10000	0	-10000	0	0
exocyst	0	0	-10000	0	-10000	0	0
RALA/GTP	0	0	-10000	0	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-10000	0	-10000	0	0
receptor recycling	0	0	-10000	0	-10000	0	0
CTNNA1	0.042	0.023	-10000	0	-0.49	1	1
NME1	0.024	0.026	-10000	0	-0.59	1	1
clathrin coat assembly	0.042	0.014	-10000	0	-10000	0	0
IL2RA	-0.015	0.11	-10000	0	-10000	0	0
VAMP3	0.025	0	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.06	-10000	0	-0.43	7	7
EXOC6	0.016	0	-10000	0	-10000	0	0
PLD1	0	0	-10000	0	-10000	0	0
PLD2	0	0	-10000	0	-10000	0	0
EXOC5	0.016	0	-10000	0	-10000	0	0
PIP5K1C	0.044	0.006	-10000	0	-10000	0	0
SDC1	0.036	0.031	-10000	0	-10000	0	0
ARF6/GDP	-0.001	0.025	-10000	0	-0.58	1	1
EXOC7	0.016	0	-10000	0	-10000	0	0
E-cadherin/beta catenin	-0.007	0.036	-10000	0	-10000	0	0
mol:Phosphatidic acid	0	0	-10000	0	-10000	0	0
endocytosis	0.001	0.019	0.43	1	-10000	0	1
SCAMP2	0.016	0	-10000	0	-10000	0	0
ADRB2	0.049	0.029	-10000	0	-0.37	2	2
EXOC3	0.016	0	-10000	0	-10000	0	0
ASAP2	0.014	0.033	-10000	0	-0.74	1	1
Dynamin 2/GDP	-0.001	0.023	-10000	0	-0.53	1	1
KLC1	0.016	0	-10000	0	-10000	0	0
AVPR2	-0.12	0.21	-10000	0	-0.37	220	220
RALA	0.016	0	-10000	0	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.006	0.03	-10000	0	-10000	0	0

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.049	0.12	-9999	-0.68	5	5
MAP3K8	0.013	0.054	-9999	-0.86	2	2
FOS	0.041	0.11	-9999	-0.57	5	5
PRKCA	0.017	0.003	-9999	-10000	0	0
PTPN7	-0.037	0.21	-9999	-0.86	34	34
HRAS	0.014	0.038	-9999	-0.86	1	1
PRKCB	0.009	0.081	-9999	-0.82	5	5
NRAS	0.016	0.001	-9999	-10000	0	0
RAS family/GTP	-0.001	0.023	-9999	-0.53	1	1
MAPK3	0.029	0.085	-9999	-0.52	3	3
MAP2K1	0.055	0.055	-9999	-0.48	5	5
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.004	0.043	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-0.006	12	12
MAPK1	0.029	0.085	-9999	-0.52	3	3
RAF1	-0.004	0.043	-9999	-0.44	5	5
KRAS	0.016	0.001	-9999	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.006	0.064	-9999	-0.66	5	5
CRKL	0.04	0.064	-9999	-0.46	2	2
mol:PIP3	-0.03	0.003	-9999	-10000	0	0
AKT1	0	0.019	-9999	-0.44	1	1
PTK2B	0.016	0	-9999	-10000	0	0
RAPGEF1	0.049	0.061	-9999	-0.43	2	2
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
HGF/MET/SHIP2	-0.028	0.13	-9999	-0.57	26	26
MAP3K5	-0.025	0.12	-9999	-0.41	1	1
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.026	0.12	-9999	-0.61	15	15
AP1	-0.014	0.08	-9999	-0.51	13	13
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.038	-9999	-0.86	1	1
apoptosis	0.004	0.11	-9999	-0.7	12	12
STAT3 (dimer)	0.041	0.077	-9999	-0.53	3	3
GAB1/CRKL/SHP2/PI3K	-0.011	0.054	-9999	-0.58	2	2
INPP5D	0.009	0.076	-9999	-0.86	4	4
CBL/CRK	0.047	0.067	-9999	-0.51	3	3
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	0.001	0.029	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.038	-9999	-0.34	2	2
PAK1	0.01	0.018	-9999	-0.41	1	1
HGF/MET/RANBP10	-0.028	0.13	-9999	-0.57	26	26
HRAS	0.032	0.096	-9999	-0.71	3	3
DOCK1	0.049	0.067	-9999	-0.51	3	3
GAB1	0.031	0.067	-9999	-0.44	3	3
CRK	0.04	0.064	-9999	-0.46	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.1	-9999	-0.54	14	14
JUN	0.016	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.013	0.059	-9999	-0.4	5	5
PIK3R1	0.014	0.033	-9999	-0.74	1	1
cell morphogenesis	0.079	0.083	-9999	-0.65	2	2
GRB2/SHC	-0.011	0.056	-9999	-0.54	3	3
FOS	-0.003	0.12	-9999	-0.75	13	13
GLMN	0	0	-9999	-10000	0	0
cell motility	0.001	0.029	-9999	-0.29	5	5
HGF/MET/MUC20	-0.028	0.13	-9999	-0.58	26	26
cell migration	-0.011	0.055	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
MET/RANBP10	-0.006	0.064	-9999	-0.66	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.071	-9999	-0.58	3	3
MET/MUC20	-0.006	0.065	-9999	-0.68	5	5
RAP1B	0.058	0.058	-9999	-10000	0	0
RAP1A	0.058	0.058	-9999	-10000	0	0
HGF/MET/RANBP9	-0.028	0.13	-9999	-0.57	26	26
RAF1	0.041	0.092	-9999	-0.66	3	3
STAT3	-0.014	0.065	-9999	-0.54	3	3
cell proliferation	0.055	0.1	-9999	-0.62	4	4
RPS6KB1	-0.004	0.019	-9999	-10000	0	0
MAPK3	-0.006	0.026	-9999	-0.27	5	5
MAPK1	-0.006	0.026	-9999	-0.27	5	5
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.011	0.1	-9999	-0.56	2	2
SRC	0.042	0.077	-9999	-0.54	3	3
PI3K	-0.012	0.06	-9999	-0.53	4	4
MET/Glomulin	0.009	0.06	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.05	0.086	-9999	-0.6	3	3
MET	0.007	0.085	-9999	-0.86	5	5
MAP4K1	-0.037	0.12	-9999	-0.42	6	6
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.05	0.088	-9999	-0.6	3	3
BAD	0.008	0.044	-9999	-0.66	2	2
MAP2K4	-0.012	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.055	-9999	-0.57	2	2
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.011	0.053	-9999	-0.49	2	2
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.019	0.17	-9999	-0.8	23	23
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.012	0.058	-9999	-0.53	3	3
PDPK1	-0.014	0.021	-9999	-0.49	1	1
HGF/MET/SHIP	-0.032	0.14	-9999	-0.59	29	29

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	-0.058	0.16	-10000	0	-0.49	63	63
cell-cell adhesion	0.014	0.074	0.63	3	-10000	0	3
Ephrin B/EPHB2/RasGAP	-0.015	0.08	-10000	0	-0.8	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
SHC1	0.014	0.038	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.013	0.079	-10000	0	-0.49	14	14
Ephrin B1/EPHB1	-0.004	0.046	-10000	0	-0.53	4	4
HRAS/GDP	-0.009	0.055	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.015	0.076	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.035	0.086	-10000	0	-0.74	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.009	0.06	-10000	0	-10000	0	0
endothelial cell migration	-0.001	0.024	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.004	0.092	-10000	0	-0.74	8	8
PAK1	0.047	0.084	-10000	0	-0.75	1	1
HRAS	0.014	0.038	-10000	0	-0.86	1	1
RRAS	0.036	0.087	-10000	0	-0.76	1	1
DNM1	-0.006	0.14	-10000	0	-0.86	13	13
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.042	0.065	-10000	0	-10000	0	0
lamellipodium assembly	-0.014	0.074	-10000	0	-0.63	3	3
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.006	0.038	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
EPHB2	0	0.11	-10000	0	-0.76	11	11
EPHB3	-0.004	0.12	-10000	0	-0.75	14	14
EPHB1	0.01	0.071	-10000	0	-0.8	4	4
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	-0.004	0.061	-10000	0	-10000	0	0
Ephrin B/EPHB2	-0.015	0.08	-10000	0	-0.6	3	3
Ephrin B/EPHB3	-0.017	0.088	-10000	0	-0.71	3	3
JNK cascade	0.04	0.086	-10000	0	-0.78	2	2
Ephrin B/EPHB1	-0.009	0.062	-10000	0	-0.5	2	2
RAP1/GDP	-0.003	0.053	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.004	0.092	-10000	0	-0.74	8	8
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.016	0.082	-10000	0	-0.7	3	3
Rap1/GTP	-0.014	0.074	-10000	0	-0.64	3	3
axon guidance	-0.058	0.16	-10000	0	-0.49	63	63
MAPK3	0.065	0.042	-10000	0	-10000	0	0
MAPK1	0.065	0.042	-10000	0	-10000	0	0
Rac1/GDP	-0.004	0.056	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.011	0.059	-10000	0	-0.49	2	2
CDC42/GDP	-0.004	0.056	-10000	0	-10000	0	0
PI3K	-0.002	0.025	-10000	0	-10000	0	0
EFNA5	-0.059	0.23	-10000	0	-0.75	52	52
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.01	0.056	-10000	0	-0.6	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.015	0.077	-10000	0	-0.64	4	4
PTK2	0.003	0.017	-10000	0	-10000	0	0
MAP4K4	0.04	0.087	-10000	0	-0.79	2	2
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.011	0.059	-10000	0	-0.5	1	1
MAP2K1	0.056	0.044	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.013	0.085	-10000	0	-0.63	6	6
cell migration	0.066	0.05	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.035	0.088	-10000	0	-0.76	1	1
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.075	0.23	-10000	0	-0.79	3	3
HRAS/GTP	-0.016	0.086	-10000	0	-0.71	4	4
Ephrin B1/EPHB1-2	-0.013	0.085	-10000	0	-0.53	13	13
cell adhesion mediated by integrin	0.01	0.064	0.46	8	-10000	0	8
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.017	0.087	-10000	0	-0.74	3	3
RAC1-CDC42/GTP	-0.022	0.099	-10000	0	-0.77	5	5
RASA1	0.014	0.033	-10000	0	-0.74	1	1
RAC1-CDC42/GDP	-0.003	0.053	-10000	0	-10000	0	0
ruffle organization	0.069	0.09	-10000	0	-0.64	3	3
NCK1	0.014	0.033	-10000	0	-0.74	1	1
receptor internalization	0.033	0.12	-10000	0	-0.77	2	2
Ephrin B/EPHB2/KALRN	-0.014	0.079	-10000	0	-0.8	1	1
ROCK1	0.022	0.076	-10000	0	-0.44	14	14
RAS family/GDP	-0.011	0.059	-10000	0	-0.53	1	1
Rac1/GTP	-0.015	0.079	-10000	0	-0.68	3	3
Ephrin B/EPHB1/Src/Paxillin	-0.006	0.042	-10000	0	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.004	0.048	-10000	0	-0.56	4	4
ATM	0.014	0.033	-10000	0	-0.74	1	1
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.034	0.019	-10000	0	-0.4	1	1
protein ubiquitination	-0.011	0.074	-10000	0	-0.87	1	1
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.033	0.067	-10000	0	-0.52	1	1
FANCF	0.016	0	-10000	0	-10000	0	0
BRCA1	0.016	0	-10000	0	-10000	0	0
CCNE1	0.003	0.11	-10000	0	-0.86	8	8
CDK2/Cyclin E1	-0.01	0.081	-10000	0	-0.66	8	8
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.048	-10000	0	-0.56	4	4
FANCE	0.014	0.038	-10000	0	-0.86	1	1
FANCC	0.016	0	-10000	0	-10000	0	0
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.17	0.36	-10000	0	-0.86	110	110
DNA repair	0.044	0.13	-10000	0	-0.67	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.048	-10000	0	-0.56	4	4
BARD1/DNA-PK	-0.003	0.037	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.048	0.55	4	-10000	0	4
BRCA1/BARD1/CTIP/M/R/N Complex	-0.004	0.041	-10000	0	-0.78	1	1
BRCA1/BACH1/BARD1/TopBP1	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BARD1/P53	-0.003	0.037	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BACH1	0.016	0	-10000	0	-10000	0	0
BARD1	0.01	0.065	-10000	0	-0.74	4	4
PCNA	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.004	0.041	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH7	-0.004	0.041	-10000	0	-0.47	4	4
BRCA1/BARD1/RAD51/PCNA	-0.017	0.091	-10000	0	-0.52	14	14
BARD1/DNA-PK/P53	-0.003	0.034	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.048	-10000	0	-0.56	4	4
BRCA1/BARD1/CTIP	-0.005	0.052	-10000	0	-0.85	1	1
FA complex	-0.056	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.048	-10000	0	-0.56	4	4
RBBP8	0.029	0.045	-10000	0	-1	1	1
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.036	-10000	0	-10000	0	0
BRCA1/BARD1	-0.011	0.075	-10000	0	-0.89	1	1
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.049	-10000	0	-0.57	4	4
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.007	0.14	-10000	0	-0.86	14	14
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.048	-10000	0	-0.56	4	4
EWSR1	0.016	0	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.011	0.063	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.011	0.059	-9999	-0.67	1	1
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.047	-9999	-0.54	4	4
AP1	-0.019	0.092	-9999	-0.69	6	6
ILK	0.06	0.065	-9999	-10000	0	0
bone resorption	-0.026	0.1	-9999	-0.72	4	4
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.008	0.053	-9999	-10000	0	0
ITGAV	0.022	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.03	0.14	-9999	-0.65	25	25
alphaV/beta3 Integrin/Osteopontin	-0.009	0.061	-9999	-0.48	2	2
MAP3K1	0.06	0.065	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.072	0.081	-9999	-10000	0	0
MAPK1	0.072	0.081	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAPK8	0.072	0.078	-9999	-0.77	2	2
ITGB3	0.014	0.08	-9999	-0.73	6	6
NFKBIA	0.085	0.081	-9999	-10000	0	0
FOS	-0.002	0.12	-9999	-0.75	13	13
CD44	-0.019	0.17	-9999	-0.86	21	21
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.084	0.17	-9999	-1.1	9	9
NF kappa B1 p50/RelA	-0.012	0.06	-9999	-0.64	1	1
BCAR1	0.014	0.033	-9999	-0.74	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.006	0.057	-9999	-0.54	6	6
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.057	0.07	-9999	-10000	0	0
VAV3	0.055	0.1	-9999	-0.78	1	1
MAP3K14	0.059	0.082	-9999	-0.5	4	4
ROCK2	0.01	0.065	-9999	-0.74	4	4
SPP1	0.017	0.065	-9999	-0.73	4	4
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.016	0.075	-9999	-0.71	1	1
MMP2	0.096	0.13	-9999	-0.74	7	7

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.014	0.033	-10000	0	-0.74	1	1
ANTXR2	0.014	0.033	-10000	0	-0.74	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.006	-10000	0	-0.093	2	2
monocyte activation	0.006	0.083	-10000	0	-0.37	21	21
MAP2K2	-0.002	0.034	-10000	0	-0.8	1	1
MAP2K1	0	0.005	-10000	0	-10000	0	0
MAP2K7	0	0.005	-10000	0	-10000	0	0
MAP2K6	-0.003	0.032	-10000	0	-0.43	3	3
CYAA	0.02	0.027	-10000	0	-0.42	2	2
MAP2K4	0	0.005	-10000	0	-10000	0	0
IL1B	0.017	0.059	-10000	0	-0.49	6	6
Channel	-0.002	0.027	-10000	0	-0.44	2	2
NLRP1	-0.005	0.051	-10000	0	-0.52	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.006	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.006	0.093	2	-10000	0	2
MAPK3	0	0.005	-10000	0	-10000	0	0
MAPK1	0	0.005	-10000	0	-10000	0	0
PGR	-0.015	0.08	-10000	0	-0.44	18	18
PA/Cellular Receptors	-0.002	0.03	-10000	0	-0.48	2	2
apoptosis	0	0.006	-10000	0	-0.093	2	2
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.002	0.025	-10000	0	-0.42	2	2
macrophage activation	0.027	0.005	-10000	0	-10000	0	0
TNF	0.003	0.1	-10000	0	-0.8	8	8
VCAM1	-0.015	0.08	-10000	0	-0.37	21	21
platelet activation	0	0.006	-10000	0	-10000	0	0
MAPKKK cascade	-0.022	0.01	-10000	0	-10000	0	0
IL18	0.016	0.065	-10000	0	-0.52	7	7
negative regulation of macrophage activation	0	0.006	-10000	0	-0.093	2	2
LEF	0	0.006	-10000	0	-0.094	2	2
CASP1	-0.002	0.023	-10000	0	-0.23	5	5
mol:cAMP	0	0.007	-10000	0	-10000	0	0
necrosis	0	0.006	-10000	0	-0.093	2	2
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.002	0.026	-10000	0	-0.42	2	2
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-10000	0	-10000	0	0
Rac1/GDP	0.002	0.013	-10000	0	-10000	0	0
DOCK1	0.014	0.033	-10000	0	-0.74	1	1
ITGA4	-0.011	0.15	-10000	0	-0.86	16	16
RAC1	0.016	0	-10000	0	-10000	0	0
alpha4/beta7 Integrin	-0.02	0.11	-10000	0	-0.66	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin	-0.017	0.098	-10000	0	-0.57	16	16
alpha4/beta7 Integrin/Paxillin	-0.016	0.089	-10000	0	-0.52	16	16
lamellipodium assembly	-0.001	0.043	-10000	0	-0.77	1	1
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
PI3K	-0.002	0.034	-10000	0	-0.56	2	2
ARF6	0.016	0	-10000	0	-10000	0	0
TLN1	0.016	0	-10000	0	-10000	0	0
PXN	0.031	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
ARF6/GTP	-0.013	0.075	-10000	0	-10000	0	0
cell adhesion	-0.014	0.082	-10000	0	-10000	0	0
CRKL/CBL	-0.001	0.024	-10000	0	-0.56	1	1
alpha4/beta1 Integrin/Paxillin	-0.016	0.089	-10000	0	-0.52	16	16
ITGB1	0.016	0	-10000	0	-10000	0	0
ITGB7	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	0.002	0.013	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.026	0.11	-10000	0	-10000	0	0
p130Cas/Crk/Dock1	-0.002	0.029	-10000	0	-0.47	2	2
VCAM1	-0.006	0.13	-10000	0	-0.82	14	14
alpha4/beta1 Integrin/Paxillin/Talin	-0.015	0.083	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.015	0.083	-10000	0	-0.49	16	16
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
mol:GDP	0.014	0.082	0.48	16	-10000	0	16
CBL	0.014	0.033	-10000	0	-0.74	1	1
PRKACA	0.016	0	-10000	0	-10000	0	0
GIT1	0.016	0	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.015	0.083	-10000	0	-10000	0	0
Rac1/GTP	-0.001	0.05	-10000	0	-0.93	1	1

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.036	0.12	-9999	-0.42	45	45
PDGFB-D/PDGFRB/SLAP	-0.033	0.14	-9999	-0.67	26	26
PDGFB-D/PDGFRB/APS/CBL	-0.008	0.069	-9999	-0.56	8	8
AKT1	-0.002	0.022	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.012	0.14	-9999	-0.44	45	45
PIK3CA	0.014	0.033	-9999	-0.74	1	1
FGR	-0.004	0.029	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.041	0.14	-9999	-0.58	21	21
SHC1	0.014	0.038	-9999	-0.86	1	1
HRAS/GDP	-0.002	0.038	-9999	-0.88	1	1
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.038	0.041	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.004	0.092	-9999	-0.74	8	8
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	-0.033	0.14	-9999	-0.67	26	26
HRAS	0.014	0.038	-9999	-0.86	1	1
HIF1A	0.087	0.04	-9999	-0.59	1	1
GAB1	0.032	0.077	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.035	0.083	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.012	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.039	0.12	-9999	-0.48	19	19
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
mol:IP3	0.038	0.042	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.015	0.001	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.068	-9999	-0.56	8	8
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.087	-9999	-0.46	2	2
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.033	-9999	-0.74	1	1
VAV2	0.034	0.089	-9999	-10000	0	0
CBL	0.014	0.033	-9999	-0.74	1	1
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	-0.017	0.081	-9999	-0.5	6	6
PDGFRB	0.015	0.006	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.02	0.082	-9999	-10000	0	0
ABL1	0.033	0.06	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.032	0.071	-9999	-10000	0	0
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.014	0.038	-9999	-0.86	1	1
cell proliferation	0.042	0.13	-9999	-0.52	21	21
SLA	-0.027	0.19	-9999	-0.86	26	26
actin cytoskeleton reorganization	0.001	0.025	-9999	-10000	0	0
SRC	-0.002	0.014	-9999	-10000	0	0
PI3K	-0.002	0.024	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.008	0.063	-9999	-0.49	9	9
SH2B2	0.004	0.1	-9999	-0.86	7	7
PLCgamma1/SPHK1	0.011	0.14	-9999	-0.45	45	45
LYN	-0.001	0.014	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.023	-9999	-10000	0	0
SPHK1	-0.058	0.24	-9999	-0.86	45	45
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.038	0.042	-9999	-10000	0	0
PLCG1	0.038	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.02	-9999	-0.47	1	1
YES1	-0.001	0.014	-9999	-10000	0	0
cell migration	-0.001	0.02	-9999	-0.47	1	1
SHC/Grb2/SOS1	-0.001	0.02	-9999	-10000	0	0
SLC9A3R2	0.014	0.033	-9999	-0.74	1	1
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.018	-9999	-10000	0	0
FYN	-0.001	0.014	-9999	-10000	0	0
DOK1	0.044	0.009	-9999	-10000	0	0
HRAS/GTP	-0.001	0.029	-9999	-0.68	1	1
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	0.044	0.1	-9999	-0.52	2	2
PRKCD	0.042	0.028	-9999	-0.53	1	1
FER	0.041	0.032	-9999	-0.44	2	2
MAPKKK cascade	0	0.021	-9999	-10000	0	0
RASA1	0.042	0.025	-9999	-10000	0	0
NCK1	0.014	0.033	-9999	-0.74	1	1
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.033	0.059	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.02	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	0.057	0.052	-10000	0	-0.45	1	1
adherens junction organization	0.039	0.08	-10000	0	-0.53	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.06	-10000	0	-10000	0	0
FMN1	0.021	0.12	-10000	0	-0.66	2	2
mol:IP3	-0.008	0.04	-10000	0	-0.47	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.065	-10000	0	-0.71	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.054	0.056	-10000	0	-0.5	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.014	0.11	-10000	0	-0.55	17	17
CTNND1	0.016	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.044	0.074	-10000	0	-0.56	2	2
VASP	0.045	0.072	-10000	0	-0.66	1	1
ZYX	0.045	0.072	-10000	0	-0.66	1	1
JUB	0.042	0.079	-10000	0	-0.58	2	2
EGFR(dimer)	-0.02	0.082	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.021	0.1	-10000	0	-0.47	24	24
mol:PI-3-4-5-P3	-0.01	0.047	-10000	0	-0.54	1	1
PIK3CA	0.015	0.033	-10000	0	-0.74	1	1
PI3K	-0.01	0.048	-10000	0	-0.55	1	1
FYN	-0.23	0.13	-10000	0	-0.61	2	2
mol:Ca2+	-0.008	0.039	-10000	0	-0.46	1	1
JUP	-0.003	0.056	-10000	0	-0.74	3	3
PIK3R1	0.015	0.033	-10000	0	-0.74	1	1
mol:DAG	-0.008	0.04	-10000	0	-0.47	1	1
CDH1	-0.03	0.15	-10000	0	-0.74	22	22
RhoA/GDP	-0.013	0.06	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.044	0.071	-10000	0	-0.64	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	0.001	0.11	-10000	0	-0.85	9	9
CASR	-0.29	0.15	-10000	0	-0.54	18	18
RhoA/GTP	-0.007	0.034	-10000	0	-10000	0	0
AKT2	0.054	0.056	-10000	0	-0.5	1	1
actin cable formation	0.031	0.12	-10000	0	-0.63	2	2
apoptosis	0.009	0.043	0.48	1	-10000	0	1
CTNNA1	0.016	0.004	-10000	0	-10000	0	0
mol:GDP	-0.015	0.065	-10000	0	-10000	0	0
PIP5K1A	0.044	0.075	-10000	0	-0.58	2	2
PLCG1	-0.008	0.041	-10000	0	-0.49	1	1
Rac1/GTP	-0.018	0.073	-10000	0	-0.6	1	1
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.02	-9999	-10000	0	0
forebrain development	0.055	0.094	-9999	-0.5	2	2
GNAO1	0.008	0.083	-9999	-0.84	5	5
SMO/beta Arrestin2	-0.002	0.038	-9999	-0.61	2	2
SMO	0.016	0.033	-9999	-0.74	1	1
ARRB2	0.014	0.038	-9999	-0.86	1	1
GLI3/SPOP	0.061	0.024	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.004	-9999	-10000	0	0
SIN3/HDAC complex	-0.019	0.097	-9999	-0.52	19	19
GNAI1	0.011	0.057	-9999	-0.74	3	3
XPO1	0.019	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.013	0.061	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	19	19
mol:GDP	0.016	0.033	-9999	-0.74	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.033	-9999	-0.74	1	1
GNAI3	0.016	0.004	-9999	-10000	0	0
GLI2	0.057	0.032	-9999	-10000	0	0
GLI3	0.055	0.026	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0.033	-9999	-0.74	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.044	0.051	-9999	-0.55	1	1
SIN3B	0.015	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.074	0.034	-9999	-10000	0	0
GLI2/Su(fu)	0.074	0.037	-9999	-10000	0	0
FOXA2	-0.06	0.22	-9999	-0.83	38	38
neural tube patterning	0.055	0.094	-9999	-0.5	2	2
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.013	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.014	0.033	-9999	-0.74	1	1
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.023	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	0.055	0.094	-9999	-0.5	2	2
SUFU	0.038	0.021	-9999	-10000	0	0
LGALS3	-0.006	0.14	-9999	-0.86	13	13
catabolic process	0.093	0.031	-9999	-10000	0	0
GLI3A/CBP	0.017	0.056	-9999	-10000	0	0
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.055	0.095	-9999	-0.51	2	2
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.014	0.084	-9999	-0.54	13	13
GNAZ	0.011	0.057	-9999	-0.74	3	3
RBBP4	0.014	0.033	-9999	-0.74	1	1
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.061	0.029	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.052	0.047	-9999	-0.48	1	1
PTCH1	0.062	0.099	-9999	-1.1	1	1
MIM/GLI1	0.052	0.15	-9999	-0.71	1	1
CREBBP	0.017	0.056	-9999	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.056	0.048	-9999	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.028	0.1	-9999	-10000	0	0
BAG4	0.014	0.033	-9999	-0.74	1	1
BAD	0.03	0.045	-9999	-0.42	2	2
NFKBIA	0.016	0	-9999	-10000	0	0
BIRC3	-0.12	0.31	-9999	-0.86	80	80
BAX	0.032	0.036	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.012	0.027	-9999	-0.099	1	1
IKBKB	0.038	0.095	-9999	-10000	0	0
MAP2K2	0.047	0.052	-9999	-0.38	4	4
MAP2K1	0.047	0.05	-9999	-0.38	4	4
SMPD1	0.019	0.027	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.038	0.097	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.04	0.096	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.051	-9999	-0.38	4	4
response to UV	0.001	0	-9999	-10000	0	0
RAF1	0.039	0.052	-9999	-0.41	4	4
CRADD	0.016	0.001	-9999	-10000	0	0
mol:ceramide	0.022	0.037	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.016	0.001	-9999	-10000	0	0
MAP3K1	0.032	0.036	-9999	-10000	0	0
TRADD	0.016	0.001	-9999	-10000	0	0
RELA/p50	0.016	0	-9999	-10000	0	0
MAPK3	0.05	0.05	-9999	-0.37	4	4
MAPK1	0.05	0.05	-9999	-0.37	4	4
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.028	0.1	-9999	-10000	0	0
KSR1	0.03	0.055	-9999	-0.45	4	4
MAPK8	0.048	0.04	-9999	-10000	0	0
TRAF2	0.016	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.038	0.095	-9999	-10000	0	0
TNF R/SODD	-0.001	0.024	-9999	-0.56	1	1
TNF	0.004	0.1	-9999	-0.8	8	8
CYCS	0.033	0.038	-9999	-10000	0	0
IKBKG	0.038	0.095	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.018	0.1	-9999	-0.44	1	1
RELA	0.016	0	-9999	-10000	0	0
RIPK1	0.016	0.001	-9999	-10000	0	0
AIFM1	0.033	0.037	-9999	-10000	0	0
TNF/TNF R/SODD	-0.009	0.067	-9999	-0.52	9	9
TNFRSF1A	0.016	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.029	0.029	-9999	-10000	0	0
NSMAF	0.029	0.098	-9999	-10000	0	0
response to hydrogen peroxide	0.001	0	-9999	-10000	0	0
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.005	0.071	-9999	-0.73	5	5
VDR	0.011	0.057	-9999	-0.74	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.077	0.05	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.087	0.062	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.009	0.008	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.072	-9999	-10000	0	0
RXRs/NUR77	-0.007	0.087	-9999	-0.51	1	1
RXRs/PPAR	0.058	0.029	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.042	-9999	-0.57	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.039	-9999	-10000	0	0
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.057	-9999	-0.74	3	3
RARs/RARs/DNA/9cRA	-0.001	0.025	-9999	-0.41	2	2
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.034	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.072	-9999	-10000	0	0
THRA	0.014	0.033	-9999	-0.74	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.003	0.042	-9999	-0.57	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	0.005	0.056	-9999	-0.5	4	4
NR1H4	-0.009	0.13	-9999	-0.75	17	17
RXRs/LXRs/DNA	0.008	0.056	-9999	-10000	0	0
NR1H2	0.023	0.033	-9999	-0.73	1	1
NR1H3	0.025	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.052	-9999	-10000	0	0
NR4A1	-0.006	0.13	-9999	-0.75	15	15
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.067	-9999	-0.41	2	2
RXRG	0.015	0.076	-9999	-0.85	4	4
RXR alpha/CCPG	0	0.004	-9999	-10000	0	0
RXRA	0.024	0.004	-9999	-10000	0	0
RXRB	0.025	0.006	-9999	-10000	0	0
THRB	-0.031	0.18	-9999	-0.74	33	33
PPARG	0.016	0	-9999	-10000	0	0
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.084	0.13	-9999	-0.87	8	8
mol:Oxysterols	0.009	0.007	-9999	-10000	0	0
cholesterol transport	0.086	0.061	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.013	0.046	-9999	-0.74	2	2
RXRs/NUR77/BCL2	-0.01	0.054	-9999	-10000	0	0
SREBF1	0.093	0.064	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.056	-9999	-0.5	4	4
ABCA1	0.092	0.071	-9999	-0.66	2	2
RARs/THRs	-0.026	0.098	-9999	-10000	0	0
RXRs/FXR	-0.008	0.091	-9999	-0.5	5	5
BCL2	0.016	0	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.075	0.027	-10000	0	-10000	0	0
NFATC2	0.052	0.036	-10000	0	-0.32	2	2
NFATC3	0.029	0.039	-10000	0	-0.48	3	3
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.032	0.072	-10000	0	-0.46	4	4
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0.001	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.012	0.053	-10000	0	-0.52	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+	0	0.001	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0.003	-10000	0	-10000	0	0
BAD	0.013	0.05	-10000	0	-0.8	2	2
CABIN1/MEF2D	0.038	0.067	-10000	0	-0.43	4	4
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.033	-10000	0	-0.74	1	1
activation-induced cell death of T cells	-0.037	0.067	0.43	4	-10000	0	4
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.016	0	-10000	0	-10000	0	0
XPO1	0.016	0	-10000	0	-10000	0	0
SFN	-0.083	0.27	-10000	0	-0.83	62	62
MAP3K8	0.013	0.054	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.002	0.023	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.011	0.056	-10000	0	-10000	0	0
CABIN1	0.032	0.072	-10000	0	-0.47	4	4
CALM1	0.016	0.003	-10000	0	-10000	0	0
RAN	0.016	0	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0.013	0.046	-10000	0	-0.74	2	2
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.002	0.034	-10000	0	-0.56	2	2
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.013	0.046	-10000	0	-0.74	2	2
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.028	-10000	0	-10000	0	0
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	-0.001	0.024	-10000	0	-0.55	1	1
CASP3	0.016	0.003	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	-0.001	0.019	-10000	0	-0.39	1	1
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.03	0.076	-10000	0	-0.47	2	2
PRKCB	0.008	0.08	-10000	0	-0.81	5	5
PRKCE	0.014	0.033	-10000	0	-0.74	1	1
JNK2/NFAT4	-0.002	0.033	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.002	0.037	-10000	0	-0.61	2	2
PRKCD	0.014	0.038	-10000	0	-0.86	1	1
NUP214	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.012	0.057	-10000	0	-0.75	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.03	0.18	-10000	0	-0.86	23	23
PRKCQ	-0.007	0.13	-10000	0	-0.74	16	16
FKBP38/BCL2	-0.001	0.024	-10000	0	-0.56	1	1
EP300	0.015	0.033	-10000	0	-0.74	1	1
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.079	0.037	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.001	0.022	-10000	0	-0.5	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.029	-10000	0	-0.48	2	2
NFATc/ERK1	0.081	0.025	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.013	0.053	-10000	0	-0.52	2	2
NR4A1	0.073	0.13	-10000	0	-0.67	15	15
GSK3B	0.016	0.003	-10000	0	-10000	0	0
positive T cell selection	0.029	0.039	-10000	0	-0.48	3	3
NFAT1/CK1 alpha	-0.003	0.02	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0.003	-10000	0	-10000	0	0
AKAP5	0.013	0.046	-10000	0	-0.74	2	2
MEF2D	0.016	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.08	0.028	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.008	0.058	-9999	-0.55	1	1
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.047	-9999	-0.54	1	1
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.057	-9999	-0.74	3	3
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	-0.003	0.021	-9999	-10000	0	0
YY1/LSF	-0.001	0.031	-9999	-0.72	1	1
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.039	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.003	0.027	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.046	0.042	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	-0.003	0.027	-9999	-10000	0	0
NuRD/MBD3 Complex	0.062	0.025	-9999	-0.46	1	1
NF kappa B1 p50/RelA	0.048	0.047	-9999	-0.64	1	1
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
GATA1	-0.021	0.17	-9999	-0.86	21	21
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.008	0.045	-9999	-0.53	2	2
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.014	0.033	-9999	-0.74	1	1
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	-0.004	0.031	-9999	-10000	0	0
KAT2B	0.014	0.033	-9999	-0.74	1	1
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.008	0.038	-9999	-10000	0	0
SIN3 complex	-0.019	0.097	-9999	-0.52	19	19
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	19	19
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	-0.004	0.036	-9999	-0.64	1	1
YY1/HDAC2	-0.001	0.031	-9999	-0.72	1	1
YY1/HDAC1	-0.001	0.031	-9999	-0.72	1	1
NuRD/MBD2 Complex (MeCP1)	0.063	0.01	-9999	-10000	0	0
PPARG	-0.006	0.046	-9999	-0.39	4	4
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.003	0.027	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	-0.001	0.024	-9999	-0.52	1	1
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	-0.004	0.031	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.039	0.037	-9999	-0.81	1	1
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.034	0.019	-9999	-0.4	1	1
NFKB1	0.014	0.033	-9999	-0.74	1	1
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	-0.001	0.029	-9999	-0.67	1	1
YY1/SAP30/HDAC1	-0.019	0.098	-9999	-0.52	20	20
EP300	0.014	0.033	-9999	-0.74	1	1
STAT3 (dimer non-phopshorylated)	0.033	0.019	-9999	-0.4	1	1
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.031	-9999	-10000	0	0
histone deacetylation	0.063	0.01	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.026	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	-0.014	0.07	-9999	-0.42	13	13
GATA1/HDAC1	-0.026	0.13	-9999	-0.66	21	21
GATA1/HDAC3	-0.024	0.1	-9999	-0.52	21	21
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.009	0.075	-9999	-0.61	8	8
SIN3/HDAC complex/Mad/Max	0.056	0.041	-9999	-10000	0	0
NuRD Complex	-0.001	0.019	-9999	-0.41	1	1
positive regulation of chromatin silencing	-0.003	0.021	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	-0.001	0.018	-9999	-10000	0	0
GATA1/Fog1	-0.029	0.14	-9999	-0.65	24	24
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	0.003	0.1	-9999	-0.8	8	8
negative regulation of cell growth	0.056	0.04	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.063	0.01	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.044	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	0.053	0.041	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.013	0.05	-9999	-0.8	2	2
MBD2	0.016	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
VDR	0.011	0.057	-9999	-0.74	3	3
Cbp/p300/PCAF	-0.002	0.039	-9999	-0.91	1	1
EP300	0.014	0.033	-9999	-0.74	1	1
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.056	0.034	-9999	-0.43	1	1
KAT2B	0.014	0.033	-9999	-0.74	1	1
MAPK14	0.016	0	-9999	-10000	0	0
AKT1	0.03	0.038	-9999	-10000	0	0
RAR alpha/9cRA/Cyclin H	-0.009	0.038	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.052	0.036	-9999	-0.48	1	1
CDC2	0.001	0.001	-9999	-10000	0	0
response to UV	0.002	0.001	-9999	-10000	0	0
RAR alpha/Jnk1	-0.011	0.053	-9999	-0.58	2	2
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.003	0.042	-9999	-0.57	3	3
RXRs/RARs/NRIP1/9cRA	0.062	0.082	-9999	-0.52	1	1
NCOA2	0	0.11	-9999	-0.74	11	11
NCOA3	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.057	-9999	-0.74	3	3
RARG	0.017	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0.017	0.001	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
MAPK8	0.015	0.046	-9999	-0.74	2	2
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.018	0.073	-9999	-10000	0	0
RARA	0.025	0.06	-9999	-0.27	2	2
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.046	0.065	-9999	-0.44	5	5
PRKCA	0.021	0.001	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.054	0.083	-9999	-0.57	1	1
RXRG	0.013	0.09	-9999	-0.38	27	27
RXRA	0.036	0.056	-9999	-10000	0	0
RXRB	0.017	0.083	-9999	-0.37	23	23
VDR/Vit D3/DNA	-0.003	0.042	-9999	-0.57	3	3
RBP1	0.009	0.073	-9999	-0.83	4	4
CRBP1/9-cic-RA	-0.005	0.056	-9999	-0.65	4	4
RARB	0.016	0.046	-9999	-0.74	2	2
PRKCG	-0.025	0.18	-9999	-0.86	23	23
MNAT1	0.016	0	-9999	-10000	0	0
RAR alpha/RXRs	0.053	0.084	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.06	0.074	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.056	0.047	-9999	-0.33	1	1
RXRs/RARs/NRIP1/9cRA/HDAC3	0.054	0.083	-9999	-0.57	1	1
positive regulation of DNA binding	-0.008	0.037	-9999	-10000	0	0
NRIP1	0.053	0.091	-9999	-1.2	1	1
RXRs/RARs	0.046	0.081	-9999	-0.41	1	1
RXRs/RXRs/DNA/9cRA	-0.017	0.073	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
CDK7	0.016	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.006	0.026	-9999	-10000	0	0
CCNH	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.011	0.057	-9999	-0.74	3	3
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.006	0.037	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	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	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
MAP3K12	0.014	0.033	-9999	-0.74	1	1
FGR	0.011	0.066	-9999	-0.86	3	3
p38 alpha/TAB1	-0.012	0.037	-9999	-10000	0	0
PRKG1	-0.006	0.12	-9999	-0.74	15	15
DUSP8	0.014	0.033	-9999	-0.74	1	1
PGK/cGMP/p38 alpha	-0.02	0.064	-9999	-0.43	3	3
apoptosis	-0.012	0.036	-9999	-10000	0	0
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
DUSP1	0.014	0.038	-9999	-0.86	1	1
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	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	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.056	0.084	-9999	-0.42	2	2
BLK	-0.041	0.21	-9999	-0.86	34	34
HCK	-0.032	0.2	-9999	-0.86	29	29
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.011	0.066	-9999	-0.86	3	3
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.057	0.065	-9999	-0.34	2	2
positive regulation of innate immune response	0.067	0.091	-9999	-0.44	2	2
LCK	-0.02	0.17	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.073	0.087	-9999	-10000	0	0
p38alpha-beta/MKP5	0.07	0.092	-9999	-10000	0	0
PGK/cGMP	-0.016	0.094	-9999	-0.57	15	15
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.072	0.089	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.007	0.14	-9999	-0.83	14	14

×

Insulin Pathway

Figure S118. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S118. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.01	0.064	-9999	-10000	0	0
TC10/GTP	-0.007	0.054	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.003	0.038	-9999	-10000	0	0
HRAS	0.014	0.038	-9999	-0.86	1	1
APS homodimer	0.004	0.1	-9999	-0.86	7	7
GRB14	-0.024	0.17	-9999	-0.74	28	28
FOXO3	-0.003	0.012	-9999	-10000	0	0
AKT1	-0.021	0.084	-9999	-0.66	2	2
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
SORBS1	0.014	0.033	-9999	-0.74	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.005	0.14	-9999	-0.51	37	37
CBL/APS/CAP/Crk-II/C3G	-0.008	0.06	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.003	0.038	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.004	0.04	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.023	-9999	-10000	0	0
RPS6KB1	0.055	0.094	-9999	-0.58	2	2
PARD6A	0.011	0.057	-9999	-0.74	3	3
CBL	0.014	0.033	-9999	-0.74	1	1
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.018	0.073	-9999	-0.58	2	2
HRAS/GTP	-0.007	0.055	-9999	-0.73	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.004	0.041	-9999	-10000	0	0
PRKCI	-0.005	0.019	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.023	0.091	-9999	-0.72	2	2
SHC1	0.014	0.038	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	-0.001	0.035	-9999	-0.82	1	1
PI3K	-0.004	0.041	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	-0.001	0.029	-9999	-0.68	1	1
AKT2	-0.021	0.084	-9999	-0.66	2	2
PRKCZ	-0.008	0.055	-9999	-0.69	3	3
SH2B2	0.004	0.1	-9999	-0.86	7	7
SHC/SHIP	-0.007	0.062	-9999	-0.86	1	1
F2RL2	-0.034	0.2	-9999	-0.86	30	30
TRIP10	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.024	-9999	-0.55	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.022	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.014	0.033	-9999	-0.74	1	1
NCK1	0.014	0.033	-9999	-0.74	1	1
CBL/APS/CAP/Crk-II	-0.008	0.065	-9999	-0.52	7	7
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.023	-9999	-0.54	1	1
INPP5D	0.029	0.067	-9999	-0.61	4	4
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.001	0.006	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.01	0.065	-9999	-0.74	4	4
p62DOK/RasGAP	-0.001	0.036	-9999	-0.83	1	1
INS	0.005	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	0.029	0.066	-9999	-0.6	4	4
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.031	0.15	-9999	-0.73	6	6
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.014	0.033	-9999	-0.74	1	1
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.003	0.028	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.003	0.039	-9999	-0.45	4	4
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.03	0.12	-9999	-0.5	30	30

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.018	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.026	0.13	-9999	-0.66	21	21
GATA1/HDAC5	-0.027	0.13	-9999	-0.66	22	22
GATA2/HDAC5	-0.015	0.089	-9999	-0.56	14	14
HDAC5/BCL6/BCoR	-0.001	0.02	-9999	-0.47	1	1
HDAC9	0.016	0	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.025	-9999	-0.57	1	1
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	-0.001	0.024	-9999	-0.56	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	-0.003	0.12	-9999	-0.74	13	13
HDAC4/RFXANK	-0.001	0.029	-9999	-0.66	1	1
BCOR	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0.033	-9999	-0.74	1	1
HDAC5	0.014	0.033	-9999	-0.74	1	1
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	-0.003	0.039	-9999	-0.83	1	1
ADRBK1	0.016	0	-9999	-10000	0	0
HDAC4	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
HDAC5/ANKRA2	-0.001	0.024	-9999	-0.56	1	1
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.016	0	-9999	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.024	-9999	-0.56	1	1
TUBA1B	0.016	0	-9999	-10000	0	0
HDAC6	0.016	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.002	0.037	-9999	-0.61	2	2
CAMK4	0.013	0.046	-9999	-0.74	2	2
Tubulin/HDAC6	-0.001	0.02	-9999	-0.47	1	1
SUMO1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
GATA1	-0.021	0.17	-9999	-0.86	21	21
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
NR3C1	0.014	0.038	-9999	-0.86	1	1
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0.016	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.024	-9999	-0.56	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.002	0.029	-9999	-0.47	2	2
HDAC4/ER alpha	-0.005	0.056	-9999	-0.58	5	5
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.051	0.042	-9999	-0.82	1	1
cell motility	-0.001	0.02	-9999	-0.47	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.016	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	0.008	0.075	-9999	-0.77	5	5
HDAC6/HDAC11	-0.002	0.034	-9999	-0.56	2	2
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
HDAC4/MEF2C	0	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
TUBB2A	0.014	0.033	-9999	-0.74	1	1
HDAC11	0.013	0.046	-9999	-0.74	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
ANKRA2	0.016	0	-9999	-10000	0	0
RFXANK	0.014	0.038	-9999	-0.86	1	1
nuclear import	0.001	0.017	-9999	-10000	0	0

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.016	-10000	0	-10000	0	0
CLOCK	0.019	0.033	-10000	0	-0.74	1	1
TIMELESS/CRY2	0.056	0.025	-10000	0	-10000	0	0
DEC1/BMAL1	-0.001	0.029	-10000	0	-0.66	1	1
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.053	0.069	-10000	0	-1	2	2
ARNTL	0.02	0.003	-10000	0	-10000	0	0
TIMELESS	0.055	0.028	-10000	0	-10000	0	0
NPAS2	0.006	0.1	-10000	0	-0.74	10	10
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.009	0.12	2	-10000	0	2
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.009	-10000	0	-0.12	2	2
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.044	0.073	-10000	0	-0.46	11	11
BMAL1/CLOCK	0.064	0.055	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.016	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.016	-10000	0	-10000	0	0
mol:NADPH	0.019	0.009	-10000	0	-0.12	2	2
PER1/TIMELESS	0.056	0.025	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.001	0.038	-10000	0	-0.86	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.004	0.036	-10000	0	-0.4	2	2
FRAP1	0.02	0.012	-10000	0	-10000	0	0
AKT1	-0.004	0.036	-10000	0	-0.47	2	2
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.003	0.028	-10000	0	-0.46	1	1
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.001	0.009	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.002	0.025	-10000	0	-0.42	1	1
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.018	0.035	-10000	0	-0.39	4	4
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	-0.001	0.011	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.036	0.024	-10000	0	-0.33	1	1
MAP3K5	0.014	0.001	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
apoptosis	0.014	0.001	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	4	4
EIF4B	0.044	0.021	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.003	0.031	-10000	0	-0.45	2	2
eIF4E/eIF4G1/eIF4A1	0	0.004	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.004	0.038	-10000	0	-0.36	6	6
mTOR/RHEB/GTP/Raptor/GBL	0.042	0.018	-10000	0	-0.24	1	1
FKBP1A	0.016	0.001	-10000	0	-10000	0	0
RHEB/GTP	-0.002	0.024	-10000	0	-0.41	1	1
mol:Amino Acids	0	0	-10000	0	-0.002	4	4
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.004	0.043	-10000	0	-0.74	1	1
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.008	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.023	0.001	-10000	0	-10000	0	0
TSC1/TSC2	-0.003	0.03	-10000	0	-0.5	1	1
tumor necrosis factor receptor activity	0	0	0.002	4	-10000	0	4
RPS6	0.012	0.054	-10000	0	-0.86	2	2
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.008	0.037	-10000	0	-0.42	4	4
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0.015	0	-10000	0	-10000	0	0
PDK2	-0.003	0.033	-10000	0	-0.37	2	2
EIF4EBP1	-0.01	0.1	-10000	0	-0.46	28	28
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
PPP2R5D	0.029	0.011	-10000	0	-10000	0	0
peptide biosynthetic process	0.023	0.001	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0	0	-10000	0	-0.004	1	1
EEF2	0.023	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.001	0.094	-10000	0	-0.4	28	28

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.031	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.002	0.029	-9999	-0.52	1	1
CDKN1B	0.05	0.007	-9999	-10000	0	0
CDKN1A	0.048	0.032	-9999	-0.47	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.05	0.007	-9999	-10000	0	0
AKT1	0	0.006	-9999	-10000	0	0
BAD	0.013	0.05	-9999	-0.8	2	2
AKT3	0.022	0.019	-9999	-0.41	1	1
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.05	0.007	-9999	-10000	0	0
AKT1/ASK1	0	0.005	-9999	-10000	0	0
BAD/YWHAZ	-0.002	0.032	-9999	-0.52	2	2
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.016	0	-9999	-10000	0	0
JNK cascade	0	0.005	-9999	-10000	0	0
TSC1	0.05	0.007	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0.048	0.007	-9999	-10000	0	0
EP300	0.014	0.033	-9999	-0.74	1	1
mol:GDP	0	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.05	0.007	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.033	0.016	-9999	-0.34	1	1
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.041	0.052	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.05	0.007	-9999	-10000	0	0
CASP9	0.05	0.007	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.057	0.007	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	-0.001	0.02	-9999	-0.47	1	1
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.03	-9999	-0.44	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0.002	-9999	-10000	0	0
CHUK	0.05	0.007	-9999	-10000	0	0
BAD/BCL-XL	-0.002	0.028	-9999	-0.56	1	1
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.022	0.019	-9999	-0.41	1	1
FOXO1-3a-4/14-3-3 family	0.059	0.059	-9999	-10000	0	0
PDPK1	0.014	0.033	-9999	-0.74	1	1
MDM2	0.05	0.007	-9999	-10000	0	0
MAPKKK cascade	-0.048	0.007	-9999	-10000	0	0
MDM2/Cbp/p300	-0.001	0.021	-9999	-10000	0	0
TSC1/TSC2	0.059	0.007	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.001	0.02	-9999	-0.46	1	1
glucose import	0.03	0.079	-9999	-0.48	12	12
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0.005	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.03	0.079	-9999	-0.48	12	12
GSK3A	0.05	0.007	-9999	-10000	0	0
FOXO1	0.05	0.007	-9999	-10000	0	0
GSK3B	0.05	0.007	-9999	-10000	0	0
SFN	-0.083	0.27	-9999	-0.83	62	62
G1/S transition of mitotic cell cycle	0.059	0.007	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.036	0.078	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.006	0.059	-9999	-0.56	6	6
PTK2	-0.005	0.045	-9999	-0.77	1	1
positive regulation of JNK cascade	-0.003	0.027	-9999	-0.37	1	1
CDC42/GDP	0.076	0.041	-9999	-0.51	1	1
Rac1/GDP	0.078	0.04	-9999	-0.5	1	1
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.003	0.033	-9999	-0.46	1	1
nectin-3/I-afadin	-0.003	0.042	-9999	-0.56	3	3
RAPGEF1	0.073	0.044	-9999	-0.59	1	1
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.066	0.049	-9999	-0.57	3	3
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	0.045	0.018	-9999	-10000	0	0
Rap1/GTP	-0.002	0.025	-9999	-0.39	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.042	-9999	-0.56	3	3
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.077	0.049	-9999	-0.53	3	3
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.014	0.033	-9999	-0.74	1	1
PI3K	-0.004	0.038	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	-0.002	0.025	-9999	-0.39	1	1
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	0.011	0.057	-9999	-0.74	3	3
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.014	0.033	-9999	-0.74	1	1
CDH1	-0.016	0.15	-9999	-0.74	22	22
CLDN1	0.008	0.078	-9999	-0.79	5	5
JAM-A/CLDN1	-0.007	0.055	-9999	-0.52	2	2
SRC	-0.004	0.049	-9999	-0.64	3	3
ITGB3	0.007	0.08	-9999	-0.74	6	6
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.068	0.053	-9999	-0.53	4	4
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	-0.003	0.035	-9999	-0.47	3	3
nectin-1/I-afadin	0	0	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	-0.003	0.035	-9999	-0.47	3	3
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.016	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.003	0.027	-9999	-0.37	1	1
alphaV/beta3 Integrin/Talin	-0.005	0.043	-9999	-0.57	1	1
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	-0.001	0.017	-9999	-10000	0	0
VAV2	0.068	0.047	-9999	-0.54	3	3
RAP1/GDP	-0.003	0.03	-9999	-0.46	1	1
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	-0.003	0.035	-9999	-0.47	3	3
nectin-3(dimer)/I-afadin/I-afadin	-0.003	0.042	-9999	-0.56	3	3
Rac1/GTP	-0.003	0.031	-9999	-0.48	1	1
PTPRM	-0.001	0.02	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.073	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.002	0.041	-9999	-0.66	2	2
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.004	0.046	-9999	-0.47	5	5
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.038	-9999	-10000	0	0
NFKBIA	0.028	0.055	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	-0.001	0.02	-9999	-0.47	1	1
ARRB2	0.022	0.018	-9999	-0.39	1	1
REL	0.01	0.065	-9999	-0.74	4	4
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.003	0.041	-9999	-0.54	3	3
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	-0.001	0.02	-9999	-0.47	1	1
PIK3CA	0.014	0.033	-9999	-0.74	1	1
NF kappa B1 p50 dimer	0.025	0.025	-9999	-0.56	1	1
PIK3R1	0.014	0.033	-9999	-0.74	1	1
NFKB1	0.03	0.025	-9999	-0.56	1	1
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.037	0.054	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.008	0.036	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	-0.002	0.034	-9999	-0.56	2	2
NF kappa B1 p50/RelA	0.037	0.054	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.013	0.046	-9999	-0.74	2	2
I kappa B alpha/PIK3R1	0.034	0.054	-9999	-0.39	1	1
cell death	-0.008	0.035	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.004	0.046	-9999	-0.47	5	5
LCK	-0.02	0.17	-9999	-0.85	22	22
BCL3	0.012	0.054	-9999	-0.86	2	2

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.016	0	-10000	0	-10000	0	0
PTK2	0.016	0	-10000	0	-10000	0	0
CRKL	0.029	0.055	-10000	0	-0.41	6	6
GRB2/SOS1/SHC	-0.001	0.025	-10000	0	-0.57	1	1
HRAS	0.014	0.038	-10000	0	-0.86	1	1
IRS1/Crk	-0.007	0.05	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/PTP1B	-0.006	0.055	-10000	0	-0.52	6	6
AKT1	0.054	0.061	-10000	0	-0.71	1	1
BAD	0.062	0.071	-10000	0	-1	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.029	0.055	-10000	0	-0.41	6	6
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.051	-10000	0	-0.41	6	6
RAF1	0.067	0.057	-10000	0	-0.7	1	1
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.006	0.047	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.008	0.056	-10000	0	-0.45	6	6
PIK3CA	0.014	0.033	-10000	0	-0.74	1	1
RPS6KB1	0.054	0.061	-10000	0	-0.71	1	1
GNB2L1	0.014	0.038	-10000	0	-0.86	1	1
positive regulation of MAPKKK cascade	0.059	0.049	-10000	0	-0.56	1	1
PXN	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.014	0.033	-10000	0	-0.74	1	1
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
HRAS/GTP	-0.007	0.048	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.006	0.048	-10000	0	-0.5	1	1
IGF-1R heterotetramer	0.015	0.012	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.051	-10000	0	-0.41	6	6
Crk/p130 Cas/Paxillin	-0.007	0.046	-10000	0	-10000	0	0
IGF1R	0.015	0.012	-10000	0	-10000	0	0
IGF1	0.006	0.092	-10000	0	-0.85	6	6
IRS2/Crk	0.029	0.082	-10000	0	-0.48	8	8
PI3K	-0.008	0.052	-10000	0	-10000	0	0
apoptosis	-0.065	0.059	0.79	1	-10000	0	1
HRAS/GDP	-0.001	0.029	-10000	0	-0.68	1	1
PRKCD	0.05	0.056	-10000	0	-0.82	1	1
RAF1/14-3-3 E	0.071	0.05	-10000	0	-0.57	1	1
BAD/14-3-3	0.068	0.064	-10000	0	-0.89	1	1
PRKCZ	0.052	0.068	-10000	0	-0.71	1	1
Crk/p130 Cas/Paxillin/FAK1	-0.006	0.043	-10000	0	-0.56	1	1
PTPN1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.042	0.047	-10000	0	-10000	0	0
BCAR1	0.014	0.033	-10000	0	-0.74	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.006	0.053	-10000	0	-0.55	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IRS1/NCK2	-0.007	0.05	-10000	0	-10000	0	0
GRB10	0.016	0	-10000	0	-10000	0	0
PTPN11	0.029	0.055	-10000	0	-0.41	6	6
IRS1	0.018	0.059	-10000	0	-0.45	6	6
IRS2	0.02	0.086	-10000	0	-0.47	14	14
IGF-1R heterotetramer/IGF1	-0.008	0.069	-10000	0	-0.66	6	6
GRB2	0.016	0	-10000	0	-10000	0	0
PDPK1	0.045	0.064	-10000	0	-0.76	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0
PRKD1	0.05	0.049	-10000	0	-10000	0	0
SHC1	0.014	0.038	-10000	0	-0.86	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.016	0	-9999	-10000	0	0
SMAD2	0.019	0	-9999	-10000	0	0
SMAD3	0.056	0	-9999	-10000	0	0
SMAD3/SMAD4	0.062	0	-9999	-10000	0	0
SMAD4/Ubc9/PIASy	0	0	-9999	-10000	0	0
SMAD2/SMAD2/SMAD4	0	0	-9999	-10000	0	0
PPM1A	0.016	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
SMAD2/SMAD4	0.027	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
TRAP-1/SMAD4	-0.001	0.024	-9999	-0.56	1	1
MAPK3	0.016	0	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
NUP214	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
KPNB1	0.016	0	-9999	-10000	0	0
TGFBRAP1	0.014	0.033	-9999	-0.74	1	1
UBE2I	0.016	0	-9999	-10000	0	0
NUP153	0.016	0	-9999	-10000	0	0
KPNA2	0.016	0	-9999	-10000	0	0
PIAS4	0.016	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.014	0.033	-9999	-0.74	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.024	-9999	-0.55	1	1
MAP2K4	0.063	0.017	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.014	0.038	-9999	-0.86	1	1
TNFRSF10A	0.014	0.033	-9999	-0.74	1	1
SMPD1	-0.001	0.016	-9999	-0.27	2	2
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.002	0.037	-9999	-0.61	2	2
TRAIL/TRAILR3	-0.002	0.037	-9999	-0.61	2	2
TRAIL/TRAILR1	-0.002	0.034	-9999	-0.56	2	2
TRAIL/TRAILR4	-0.001	0.024	-9999	-0.56	1	1
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.027	-9999	-0.43	2	2
IKK complex	-0.001	0.009	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.03	0.025	-9999	-0.55	1	1
MAP3K1	-0.001	0.014	-9999	-10000	0	0
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.033	-9999	-0.74	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.018	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
MAPK1	0.03	0.025	-9999	-0.55	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.001	0.024	-9999	-10000	0	0
mol:ceramide	-0.001	0.016	-9999	-0.26	2	2
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.07	0.03	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.014	0.038	-9999	-0.86	1	1
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.029	-9999	-0.47	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.002	0.024	-9999	-0.45	1	1
JNK cascade	-0.001	0.024	-9999	-0.55	1	1
TRAIL (trimer)	0.014	0.033	-9999	-0.74	1	1
TNFRSF10C	0.014	0.038	-9999	-0.86	1	1
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.024	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.002	0.032	-9999	-0.52	2	2
cell death	-0.001	0.016	-9999	-0.26	2	2
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.017	-9999	-10000	0	0
TRAILR2 (trimer)	0.014	0.038	-9999	-0.86	1	1
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.002	0.027	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
HDAC1	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC4	0	-9999	-9999
MDM2/SUMO1	0	-9999	-9999
HDAC4	0.016	-9999	-9999
Ran/GTP/Exportin 1/HDAC1	0	-9999	-9999
SUMO1	0.016	-9999	-9999
NPC/RanGAP1/SUMO1	0.023	-9999	-9999
mol:GTP	0	-9999	-9999
XPO1	0.039	-9999	-9999
EntrezGene:23636	0	-9999	-9999
RAN	0.016	-9999	-9999
EntrezGene:8021	0	-9999	-9999
RANBP2	0.016	-9999	-9999
SUMO1/HDAC4	0	-9999	-9999
SUMO1/HDAC1	0	-9999	-9999
RANGAP1	0.016	-9999	-9999
MDM2/SUMO1/SUMO1	0	-9999	-9999
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0	-9999	-9999
Ran/GTP	0	-9999	-9999
EntrezGene:23225	0	-9999	-9999
MDM2	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
Ran/GTP/Exportin 1	0	-9999	-9999
NPC	0	-9999	-9999
PIAS2	0.016	-9999	-9999
PIAS1	0.016	-9999	-9999
EntrezGene:9972	0	-9999	-9999

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0	-9999	-10000	0	0
MAPK9	0.011	0	-9999	-10000	0	0
adrenocorticotropin secretion	-0.004	0.072	-9999	-0.68	6	6
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0	-9999	-10000	0	0
Gs family/GTP	0	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	-0.006	0.092	-9999	-0.86	6	6
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.01	0.027	-9999	-0.42	2	2
MAPK11	0.01	0.025	-9999	-0.4	2	2

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.022	-9999	-0.51	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.027	0.009	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0.002	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0.001	-9999	-10000	0	0
CD4	0.001	0.11	-9999	-0.86	9	9
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0.001	-9999	-10000	0	0
ARFGAP1	0.014	0.025	-9999	-0.57	1	1
mol:PI-4-5-P2	-0.001	0.017	-9999	-0.38	1	1
ARF1/GTP	0	0.009	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.02	-9999	-0.46	1	1
mol:Choline	-0.001	0.016	-9999	-0.38	1	1
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	-0.001	0.017	-9999	-0.38	1	1
ARF1/GDP	-0.001	0.02	-9999	-0.46	1	1
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0.001	-9999	-10000	0	0
Rac/GTP	0	0.001	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.018	-9999	-0.42	1	1
ARFIP2	0	0.003	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.034	0.005	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0.001	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0.005	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0	0.01	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0.005	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0.003	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0.002	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.043	0.034	-9999	-10000	0	0
PLD2	-0.001	0.016	-9999	-0.38	1	1
ARF-GAP1/v-SNARE	0.014	0.025	-9999	-0.57	1	1
PIP5K1A	-0.001	0.017	-9999	-0.38	1	1
ARF1/GTP/Membrin/GBF1/p115	0	0.009	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.001	0.016	-9999	-0.38	1	1
KDEL Receptor/Ligand/ARF-GAP1	0.014	0.025	-9999	-0.57	1	1
GOSR2	0	0.007	-9999	-10000	0	0
USO1	0	0.007	-9999	-10000	0	0
GBF1	0	0.007	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0.002	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.01	0.074	-9999	-0.57	9	9

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.005	0.057	-9999	-0.66	4	4
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.042	-9999	-10000	0	0
NFKB1	0.014	0.033	-9999	-0.74	1	1
MAP3K14	0.009	0.076	-9999	-0.86	4	4
NF kappa B1 p50/RelB	-0.001	0.024	-9999	-0.56	1	1
RELB	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.T7.A92I	TCGA.MW.A4EC	TCGA.MM.A84U	TCGA.MM.A564
109_MAP3K5	0.074	0.074	-0.13	0.074
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	0.016	-6.4e-15	-0.74	-0.74
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	-0.42	-0.42	0	-0.42
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.015	0.021
84_STAT5B	-0.03	-0.031	-0.14	-0.14
84_STAT5A	-0.03	-0.031	-0.14	-0.14