Glioblastoma Multiforme: PARADIGM pathway analysis of mRNA expression and copy number data

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	122
FOXM1 transcription factor network	104
Angiopoietin receptor Tie2-mediated signaling	91
Syndecan-4-mediated signaling events	87
Endothelins	83
TCGA08_rtk_signaling	75
Thromboxane A2 receptor signaling	74
TCGA08_p53	73
EGFR-dependent Endothelin signaling events	71
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	71

Pathway.Name	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
HIF-1-alpha transcription factor network	122	9290	76	-0.078	0.1	1000	-1000	-0.007	-1000
FOXM1 transcription factor network	104	5349	51	-0.32	0.061	1000	-1000	-0.052	-1000
Angiopoietin receptor Tie2-mediated signaling	91	8014	88	-0.29	0.053	1000	-1000	-0.041	-1000
Syndecan-4-mediated signaling events	87	5850	67	-0.14	0.036	1000	-1000	-0.029	-1000
Endothelins	83	8043	96	-0.14	0.036	1000	-1000	-0.025	-1000
TCGA08_rtk_signaling	75	1957	26	-0.024	0.093	1000	-1000	-0.014	-1000
Thromboxane A2 receptor signaling	74	7780	105	-0.069	0.044	1000	-1000	-0.025	-1000
TCGA08_p53	73	512	7	-0.001	0.034	1000	-1000	-0.01	-1000
EGFR-dependent Endothelin signaling events	71	1491	21	-0.005	0.093	1000	-1000	-0.01	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	71	2364	33	-0.075	0.068	1000	-1000	-0.011	-1000
Effects of Botulinum toxin	68	1776	26	-0.007	0.052	1000	-1000	-0.011	-1000
PDGFR-alpha signaling pathway	67	2953	44	-0.093	0.036	1000	-1000	-0.021	-1000
Arf6 signaling events	65	4036	62	-0.005	0.092	1000	-1000	-0.007	-1000
Syndecan-3-mediated signaling events	65	2287	35	-0.071	0.08	1000	-1000	-0.028	-1000
Canonical Wnt signaling pathway	65	3341	51	-0.097	0.071	1000	-1000	-0.019	-1000
Wnt signaling	65	461	7	-0.006	0.037	1000	-1000	-0.002	-1000
HIF-2-alpha transcription factor network	64	2793	43	-0.074	0.047	1000	-1000	-0.039	-1000
S1P5 pathway	62	1069	17	-0.007	0.036	1000	-1000	-0.015	-1000
S1P4 pathway	62	1560	25	-0.012	0.043	1000	-1000	-0.007	-1000
TCGA08_retinoblastoma	61	495	8	-0.045	0.053	1000	-1000	-0.003	-1000
LPA receptor mediated events	58	5977	102	-0.13	0.039	1000	-1000	-0.057	-1000
Ras signaling in the CD4+ TCR pathway	58	995	17	-0.001	0.042	1000	-1000	-0.01	-1000
Nongenotropic Androgen signaling	55	2907	52	-0.087	0.06	1000	-1000	-0.017	-1000
Syndecan-1-mediated signaling events	54	1865	34	-0.004	0.035	1000	-1000	-0.018	-1000
IL2 signaling events mediated by STAT5	53	1168	22	-0.074	0.042	1000	-1000	-0.016	-1000
Syndecan-2-mediated signaling events	52	3590	69	-0.026	0.037	1000	-1000	-0.027	-1000
EPO signaling pathway	52	2881	55	-0.001	0.082	1000	-1000	-0.016	-1000
amb2 Integrin signaling	52	4340	82	-0.015	0.077	1000	-1000	-0.019	-1000
Glypican 2 network	51	206	4	0	0.007	1000	-1000	0	-1000
JNK signaling in the CD4+ TCR pathway	50	852	17	-0.14	0.063	1000	-1000	-0.01	-1000
IL23-mediated signaling events	50	3005	60	-0.064	0.15	1000	-1000	-0.035	-1000
Fc-epsilon receptor I signaling in mast cells	49	4835	97	-0.12	0.048	1000	-1000	-0.041	-1000
PLK2 and PLK4 events	48	146	3	-0.011	0.035	1000	-1000	-0.015	-1000
Osteopontin-mediated events	48	1831	38	-0.071	0.05	1000	-1000	-0.02	-1000
Signaling events mediated by VEGFR1 and VEGFR2	48	6101	125	-0.045	0.06	1000	-1000	-0.038	-1000
Ephrin B reverse signaling	45	2196	48	-0.067	0.066	1000	-1000	-0.043	-1000
FoxO family signaling	45	2923	64	-0.16	0.052	1000	-1000	-0.029	-1000
Presenilin action in Notch and Wnt signaling	44	2739	61	-0.079	0.08	1000	-1000	-0.029	-1000
IL2 signaling events mediated by PI3K	44	2555	58	-0.065	0.038	1000	-1000	-0.025	-1000
FAS signaling pathway (CD95)	43	2061	47	-0.16	0.048	1000	-1000	-0.025	-1000
BCR signaling pathway	43	4320	99	-0.061	0.05	1000	-1000	-0.036	-1000
S1P3 pathway	43	1841	42	-0.018	0.036	1000	-1000	-0.009	-1000
Sphingosine 1-phosphate (S1P) pathway	42	1188	28	-0.012	0.036	1000	-1000	-0.015	-1000
Reelin signaling pathway	42	2388	56	-0.014	0.068	1000	-1000	-0.016	-1000
Regulation of nuclear SMAD2/3 signaling	41	5680	136	-0.21	0.19	1000	-1000	-0.042	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	41	2231	54	-0.034	0.082	1000	-1000	-0.027	-1000
Paxillin-dependent events mediated by a4b1	41	1485	36	-0.057	0.059	1000	-1000	-0.043	-1000
EPHB forward signaling	41	3545	85	-0.052	0.082	1000	-1000	-0.044	-1000
ErbB2/ErbB3 signaling events	40	2663	65	-0.044	0.036	1000	-1000	-0.042	-1000
Noncanonical Wnt signaling pathway	40	1042	26	-0.039	0.037	1000	-1000	-0.047	-1000
BMP receptor signaling	40	3258	81	-0.031	0.058	1000	-1000	-0.011	-1000
IL1-mediated signaling events	40	2487	62	-0.045	0.074	1000	-1000	-0.035	-1000
IL12-mediated signaling events	39	3474	87	-0.11	0.094	1000	-1000	-0.016	-1000
Paxillin-independent events mediated by a4b1 and a4b7	39	1462	37	-0.034	0.083	1000	-1000	-0.014	-1000
Class I PI3K signaling events	39	2880	73	-0.053	0.062	1000	-1000	-0.017	-1000
Signaling events mediated by PTP1B	38	2913	76	-0.033	0.059	1000	-1000	-0.018	-1000
Glypican 1 network	38	1851	48	-0.038	0.051	1000	-1000	-0.033	-1000
S1P1 pathway	38	1395	36	-0.005	0.052	1000	-1000	-0.008	-1000
E-cadherin signaling in keratinocytes	38	1655	43	-0.042	0.064	1000	-1000	-0.012	-1000
p38 MAPK signaling pathway	38	1704	44	0	0.043	1000	-1000	-0.013	-1000
PLK1 signaling events	37	3172	85	-0.048	0.051	1000	-1000	-0.017	-1000
mTOR signaling pathway	37	1989	53	-0.034	0.046	1000	-1000	-0.028	-1000
Stabilization and expansion of the E-cadherin adherens junction	37	2801	74	-0.12	0.079	1000	-1000	-0.048	-1000
Arf6 downstream pathway	36	1571	43	-0.026	0.051	1000	-1000	-0.024	-1000
Class I PI3K signaling events mediated by Akt	36	2460	68	-0.03	0.063	1000	-1000	-0.014	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	36	2503	68	-0.1	0.046	1000	-1000	-0.047	-1000
Neurotrophic factor-mediated Trk receptor signaling	36	4383	120	-0.035	0.087	1000	-1000	-0.028	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	35	3038	85	-0.12	0.12	1000	-1000	-0.04	-1000
Regulation of p38-alpha and p38-beta	35	1902	54	-0.002	0.047	1000	-1000	-0.01	-1000
IL6-mediated signaling events	35	2686	75	-0.076	0.11	1000	-1000	-0.032	-1000
IGF1 pathway	35	2002	57	-0.046	0.066	1000	-1000	-0.028	-1000
Plasma membrane estrogen receptor signaling	35	3063	86	-0.066	0.053	1000	-1000	-0.033	-1000
IFN-gamma pathway	34	2375	68	-0.041	0.064	1000	-1000	-0.035	-1000
Alternative NF-kappaB pathway	34	451	13	0	0.066	1000	-1000	0	-1000
TCR signaling in naïve CD8+ T cells	33	3113	93	-0.35	0.4	1000	-1000	-0.026	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	33	1509	45	-0.032	0.075	1000	-1000	-0.019	-1000
PDGFR-beta signaling pathway	33	3275	97	-0.055	0.068	1000	-1000	-0.04	-1000
a4b1 and a4b7 Integrin signaling	32	162	5	0.027	0.052	1000	-1000	0.033	-1000
Signaling events regulated by Ret tyrosine kinase	32	2699	82	-0.057	0.063	1000	-1000	-0.023	-1000
Hedgehog signaling events mediated by Gli proteins	31	2039	65	-0.015	0.057	1000	-1000	-0.028	-1000
E-cadherin signaling in the nascent adherens junction	31	2356	76	-0.043	0.09	1000	-1000	-0.036	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	31	2423	78	-0.022	0.072	1000	-1000	-0.033	-1000
Caspase cascade in apoptosis	30	2258	74	-0.079	0.067	1000	-1000	-0.025	-1000
ErbB4 signaling events	30	2134	69	-0.071	0.062	1000	-1000	-0.018	-1000
Visual signal transduction: Cones	30	1157	38	-0.014	0.058	1000	-1000	-0.013	-1000
Regulation of Telomerase	30	3110	102	-0.027	0.077	1000	-1000	-0.026	-1000
p75(NTR)-mediated signaling	29	3693	125	-0.022	0.087	1000	-1000	-0.038	-1000
Signaling events mediated by HDAC Class III	29	1193	40	-0.049	0.05	1000	-1000	-0.049	-1000
Integrins in angiogenesis	29	2481	84	-0.044	0.071	1000	-1000	-0.021	-1000
Insulin Pathway	29	2201	74	-0.036	0.082	1000	-1000	-0.031	-1000
Signaling events mediated by PRL	29	1008	34	-0.034	0.047	1000	-1000	-0.025	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	28	654	23	-0.016	0.054	1000	-1000	-0.009	-1000
IL4-mediated signaling events	28	2619	91	-0.32	0.067	1000	-1000	-0.074	-1000
Aurora B signaling	28	1909	67	-0.032	0.062	1000	-1000	-0.02	-1000
Aurora A signaling	27	1656	60	-0.028	0.058	1000	-1000	-0.016	-1000
TRAIL signaling pathway	27	1332	48	-0.033	0.086	1000	-1000	-0.015	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	27	2242	83	-0.034	0.068	1000	-1000	-0.015	-1000
Signaling mediated by p38-gamma and p38-delta	27	417	15	-0.025	0.036	1000	-1000	-0.017	-1000
Retinoic acid receptors-mediated signaling	27	1581	58	-0.053	0.059	1000	-1000	-0.015	-1000
BARD1 signaling events	26	1513	57	-0.064	0.085	1000	-1000	-0.057	-1000
Nectin adhesion pathway	26	1698	63	-0.01	0.084	1000	-1000	-0.021	-1000
Glucocorticoid receptor regulatory network	25	2962	114	-0.13	0.064	1000	-1000	-0.041	-1000
Calcium signaling in the CD4+ TCR pathway	24	762	31	-0.017	0.093	1000	-1000	-0.02	-1000
Signaling events mediated by HDAC Class I	23	2469	104	-0.029	0.066	1000	-1000	-0.025	-1000
Coregulation of Androgen receptor activity	22	1727	76	-0.011	0.07	1000	-1000	-0.01	-1000
Insulin-mediated glucose transport	22	706	32	-0.016	0.041	1000	-1000	-0.016	-1000
IL27-mediated signaling events	22	1152	51	-0.015	0.064	1000	-1000	-0.042	-1000
E-cadherin signaling events	22	110	5	0.033	0.062	1000	-1000	0.033	-1000
Regulation of Androgen receptor activity	22	1583	70	-0.031	0.067	1000	-1000	-0.032	-1000
Ceramide signaling pathway	21	1660	76	-0.04	0.07	1000	-1000	-0.016	-1000
Signaling mediated by p38-alpha and p38-beta	20	893	44	-0.015	0.086	1000	-1000	-0.014	-1000
Signaling events mediated by HDAC Class II	19	1461	75	-0.03	0.093	1000	-1000	-0.026	-1000
Cellular roles of Anthrax toxin	19	747	39	-0.069	0.036	1000	-1000	-0.017	-1000
RXR and RAR heterodimerization with other nuclear receptor	19	1025	52	-0.043	0.1	1000	-1000	-0.017	-1000
Atypical NF-kappaB pathway	19	596	31	-0.021	0.036	1000	-1000	-0.014	-1000
Circadian rhythm pathway	18	402	22	-0.01	0.056	1000	-1000	-0.028	-1000
Signaling events mediated by the Hedgehog family	18	958	52	-0.014	0.09	1000	-1000	-0.019	-1000
ceramide signaling pathway	18	886	49	-0.014	0.053	1000	-1000	-0.012	-1000
Arf6 trafficking events	18	1315	71	-0.038	0.046	1000	-1000	-0.031	-1000
Arf1 pathway	18	1019	54	-0.075	0.044	1000	-1000	-0.013	-1000
Canonical NF-kappaB pathway	17	694	39	-0.033	0.065	1000	-1000	-0.019	-1000
VEGFR1 specific signals	17	971	56	-0.032	0.041	1000	-1000	-0.028	-1000
Sumoylation by RanBP2 regulates transcriptional repression	15	420	27	-0.032	0.077	1000	-1000	-0.027	-1000
Rapid glucocorticoid signaling	15	315	20	-0.011	0.036	1000	-1000	-0.01	-1000
Nephrin/Neph1 signaling in the kidney podocyte	14	505	34	-0.054	0.096	1000	-1000	-0.039	-1000
FOXA2 and FOXA3 transcription factor networks	13	609	46	0	0.094	1000	-1000	-0.025	-1000
Aurora C signaling	10	75	7	0	0.063	1000	-1000	-0.001	-1000
Class IB PI3K non-lipid kinase events	9	27	3	-0.036	0.036	1000	-1000	-0.033	-1000
LPA4-mediated signaling events	8	104	12	-0.017	0.018	1000	-1000	-0.012	-1000
Visual signal transduction: Rods	8	440	52	-0.033	0.084	1000	-1000	-0.009	-1000
Ephrin A reverse signaling	2	18	7	-0.019	0.048	1000	-1000	-0.009	-1000
Total	5102	287495	7203	-6.9	8.6	131000	-131000	-3	-131000

HIF-1-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	0.027	0.46	0.62	78	-0.74	86	164
HDAC7	-0.001	0.005	-10000	0	-0.049	3	3
HIF1A/ARNT/Cbp/p300/Src-1	-0.025	0.38	0.58	39	-0.69	73	112
SMAD4	0.033	0.014	0.079	10	-10000	0	10
ID2	0.048	0.47	0.63	98	-0.74	85	183
AP1	0.015	0.079	-10000	0	-0.17	71	71
ABCG2	0.014	0.46	0.62	88	-0.74	88	176
HIF1A	0.044	0.13	0.24	77	-0.15	63	140
TFF3	0.043	0.46	0.63	91	-0.74	84	175
GATA2	0.039	0.014	0.075	22	-0.079	2	24
AKT1	0.052	0.13	0.24	90	-0.18	44	134
response to hypoxia	0.011	0.088	0.17	81	-0.12	52	133
MCL1	0.055	0.47	0.62	105	-0.74	86	191
NDRG1	-0.001	0.45	0.62	69	-0.76	88	157
SERPINE1	-0.065	0.38	0.6	30	-0.76	81	111
FECH	0.044	0.46	0.63	91	-0.74	84	175
FURIN	0.051	0.47	0.63	99	-0.74	86	185
NCOA2	0.037	0.006	-10000	0	-10000	0	0
EP300	0.073	0.18	0.36	95	-0.3	28	123
HMOX1	-0.019	0.45	0.63	61	-0.77	87	148
BHLHE40	-0.054	0.4	0.55	73	-0.72	89	162
BHLHE41	-0.054	0.4	0.55	73	-0.72	89	162
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.07	0.18	0.35	46	-0.23	38	84
ENG	0.03	0.15	0.3	45	-0.25	17	62
JUN	0.035	0.013	-10000	0	-0.052	2	2
RORA	0.024	0.46	0.62	85	-0.74	87	172
ABCB1	-0.055	0.21	-10000	0	-0.83	29	29
TFRC	0.033	0.46	0.63	89	-0.75	85	174
CXCR4	0.016	0.46	0.63	79	-0.75	91	170
TF	-0.078	0.4	0.63	41	-0.75	88	129
CITED2	0.014	0.45	0.61	84	-0.74	88	172
HIF1A/ARNT	-0.073	0.44	0.67	16	-0.87	76	92
LDHA	-0.066	0.28	-10000	0	-0.96	40	40
ETS1	0.059	0.47	0.63	105	-0.74	86	191
PGK1	0.048	0.48	0.62	101	-0.76	86	187
NOS2	-0.054	0.4	0.55	73	-0.72	89	162
ITGB2	0.006	0.46	0.62	78	-0.76	86	164
ALDOA	0.055	0.47	0.64	96	-0.74	86	182
Cbp/p300/CITED2	-0.021	0.45	0.6	67	-0.78	86	153
FOS	0.026	0.018	-10000	0	-0.043	1	1
HK2	0.058	0.48	0.62	109	-0.74	85	194
SP1	0.033	0.059	0.11	39	-0.15	40	79
GCK	0.1	0.24	0.55	61	-0.46	13	74
HK1	0.002	0.44	0.64	72	-0.74	84	156
NPM1	0.053	0.47	0.63	99	-0.74	84	183
EGLN1	0.05	0.47	0.62	98	-0.74	85	183
CREB1	0.032	0.034	-10000	0	-0.1	30	30
PGM1	0.052	0.47	0.63	99	-0.74	87	186
SMAD3	0.037	0.008	0.079	10	-10000	0	10
EDN1	0.057	0.21	0.47	26	-0.55	17	43
IGFBP1	-0.01	0.41	0.63	56	-0.74	76	132
VEGFA	-0.016	0.34	0.48	78	-0.56	84	162
HIF1A/JAB1	0.045	0.1	0.2	58	-0.13	45	103
CP	-0.033	0.44	0.61	62	-0.75	93	155
CXCL12	-0.033	0.41	0.62	45	-0.74	83	128
COPS5	0.036	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.039	0.052	0.14	5	-0.14	35	40
BNIP3	-0.005	0.44	0.64	71	-0.75	84	155
EGLN3	0.006	0.45	0.63	71	-0.74	85	156
CA9	-0.015	0.42	0.61	59	-0.74	83	142
TERT	0.051	0.47	0.63	100	-0.74	86	186
ENO1	0.049	0.47	0.63	101	-0.74	85	186
PFKL	0.055	0.47	0.62	108	-0.74	85	193
NCOA1	0.033	0.011	-10000	0	-10000	0	0
ADM	-0.018	0.45	0.61	72	-0.76	91	163
ARNT	0.047	0.13	0.24	82	-0.14	67	149
HNF4A	0.038	0.01	0.083	10	-10000	0	10
ADFP	-0.029	0.44	0.64	51	-0.76	86	137
SLC2A1	0.015	0.37	0.54	72	-0.6	79	151
LEP	0.009	0.42	0.63	68	-0.74	76	144
HIF1A/ARNT/Cbp/p300	-0.036	0.38	0.59	36	-0.69	77	113
EPO	0.021	0.31	0.55	50	-0.58	42	92
CREBBP	0.078	0.18	0.35	97	-0.27	27	124
HIF1A/ARNT/Cbp/p300/HDAC7	-0.041	0.37	0.55	37	-0.68	76	113
PFKFB3	0.009	0.45	0.65	75	-0.76	83	158
NT5E	-0.026	0.44	0.63	61	-0.73	94	155

×

FOXM1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC3	-0.087	0.66	1	33	-1.2	95	128
PLK1	0.061	0.16	0.64	16	-0.82	5	21
BIRC5	-0.062	0.44	0.65	15	-1.2	57	72
HSPA1B	-0.088	0.65	0.96	35	-1.2	101	136
MAP2K1	0.045	0.1	0.25	56	-10000	0	56
BRCA2	-0.086	0.66	1	32	-1.2	93	125
FOXM1	-0.23	0.97	1.2	30	-1.9	101	131
XRCC1	-0.084	0.66	1	34	-1.2	94	128
FOXM1B/p19	-0.32	0.57	-10000	0	-1.4	99	99
Cyclin D1/CDK4	-0.11	0.59	0.86	28	-1.1	102	130
CDC2	-0.11	0.73	1.1	33	-1.3	102	135
TGFA	-0.071	0.58	0.89	36	-1	98	134
SKP2	-0.089	0.66	1	33	-1.2	95	128
CCNE1	0.024	0.037	0.1	21	-0.034	114	135
CKS1B	-0.097	0.68	1	33	-1.2	100	133
RB1	-0.073	0.37	0.49	16	-1	47	63
FOXM1C/SP1	-0.17	0.76	0.9	27	-1.5	102	129
AURKB	0.061	0.15	0.68	13	-0.97	2	15
CENPF	-0.11	0.71	1.1	33	-1.2	109	142
CDK4	0.025	0.052	0.15	30	-10000	0	30
MYC	-0.1	0.56	0.81	34	-1	103	137
CHEK2	0.037	0.092	0.23	50	-10000	0	50
ONECUT1	-0.089	0.63	0.93	35	-1.2	101	136
CDKN2A	0.003	0.018	-10000	0	-0.13	4	4
LAMA4	-0.092	0.66	0.97	35	-1.2	96	131
FOXM1B/HNF6	-0.16	0.77	0.96	32	-1.5	101	133
FOS	-0.15	0.7	0.99	32	-1.2	123	155
SP1	0.034	0.019	0.072	3	-0.045	24	27
CDC25B	-0.093	0.67	0.98	35	-1.2	99	134
response to radiation	0.023	0.067	0.15	72	-10000	0	72
CENPB	-0.085	0.67	0.98	37	-1.2	96	133
CENPA	-0.09	0.67	1	34	-1.2	95	129
NEK2	-0.079	0.67	1.1	33	-1.2	95	128
HIST1H2BA	-0.088	0.65	0.96	35	-1.2	101	136
CCNA2	0.022	0.031	0.096	4	-0.034	79	83
EP300	0.033	0.011	-10000	0	-10000	0	0
CCNB1/CDK1	-0.19	0.84	1.1	29	-1.6	109	138
CCNB2	-0.11	0.69	1	35	-1.3	100	135
CCNB1	-0.12	0.74	1.1	34	-1.4	105	139
ETV5	-0.12	0.69	0.99	33	-1.2	117	150
ESR1	-0.09	0.65	0.99	32	-1.2	100	132
CCND1	-0.098	0.62	0.92	36	-1.1	101	137
GSK3A	0.037	0.084	0.2	54	-10000	0	54
Cyclin A-E1/CDK1-2	0.047	0.1	0.25	24	-0.16	42	66
CDK2	0.024	0.037	0.1	16	-0.034	120	136
G2/M transition of mitotic cell cycle	0.027	0.081	0.18	74	-10000	0	74
FOXM1B/Cbp/p300	-0.16	0.68	0.8	18	-1.4	101	119
GAS1	-0.092	0.67	1	36	-1.2	98	134
MMP2	-0.11	0.7	1	36	-1.2	109	145
RB1/FOXM1C	-0.14	0.61	0.86	24	-1.2	100	124
CREBBP	0.036	0.005	-10000	0	0	8	8

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.23	0.41	-10000	0	-0.78	163	163
NCK1/PAK1/Dok-R	-0.12	0.17	-10000	0	-0.37	140	140
NCK1/Dok-R	-0.14	0.35	-10000	0	-0.86	96	96
PIK3CA	0.031	0.013	-10000	0	0	80	80
mol:beta2-estradiol	0.032	0.098	0.23	96	-10000	0	96
RELA	0.036	0.005	-10000	0	0	9	9
SHC1	0.032	0.011	-10000	0	0	52	52
Rac/GDP	0.017	0.019	-10000	0	-0.13	5	5
F2	0.053	0.11	0.28	87	-0.09	64	151
TNIP2	0.036	0.006	-10000	0	0	13	13
NF kappa B/RelA	-0.12	0.36	-10000	0	-0.83	96	96
FN1	0.035	0.009	-10000	0	0	29	29
PLD2	-0.15	0.36	-10000	0	-0.89	96	96
PTPN11	0.036	0.005	-10000	0	0	11	11
GRB14	0.032	0.013	-10000	0	0	70	70
ELK1	-0.15	0.33	-10000	0	-0.82	96	96
GRB7	0.036	0.006	-10000	0	0	14	14
PAK1	0.036	0.006	-10000	0	0	15	15
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.36	-10000	0	-0.86	96	96
CDKN1A	-0.19	0.35	0.4	2	-0.65	175	177
ITGA5	0.033	0.011	-10000	0	0	56	56
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.14	0.36	-10000	0	-0.86	96	96
CRK	0.035	0.008	-10000	0	0	23	23
mol:NO	-0.12	0.32	0.37	4	-0.57	152	156
PLG	-0.15	0.36	-10000	0	-0.89	96	96
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.37	-10000	0	-0.74	128	128
GRB2	0.035	0.007	-10000	0	0	17	17
PIK3R1	0.032	0.012	-10000	0	0	63	63
ANGPT2	-0.22	0.45	-10000	0	-0.86	142	142
BMX	-0.15	0.36	-10000	0	-0.89	96	96
ANGPT1	-0.16	0.42	-10000	0	-1	95	95
tube development	-0.21	0.36	-10000	0	-0.69	167	167
ANGPT4	0.023	0.028	-10000	0	-0.03	107	107
response to hypoxia	-0.013	0.026	-10000	0	-0.063	96	96
Tie2/Ang1/GRB14	-0.14	0.37	-10000	0	-0.9	96	96
alpha5/beta1 Integrin	0.029	0.042	-10000	0	-0.14	20	20
FGF2	0.035	0.016	-10000	0	-0.012	43	43
STAT5A (dimer)	-0.24	0.44	-10000	0	-0.8	177	177
mol:L-citrulline	-0.12	0.32	0.37	4	-0.57	152	156
AGTR1	0.022	0.034	-10000	0	-0.038	112	112
MAPK14	-0.16	0.37	-10000	0	-0.9	96	96
Tie2/SHP2	-0.079	0.24	-10000	0	-0.81	35	35
TEK	-0.087	0.25	-10000	0	-0.9	33	33
RPS6KB1	-0.2	0.37	-10000	0	-0.76	139	139
Angiotensin II/AT1	0.015	0.036	0.077	4	-0.056	89	93
Tie2/Ang1/GRB2	-0.14	0.38	-10000	0	-0.91	96	96
MAPK3	-0.15	0.34	-10000	0	-0.84	96	96
MAPK1	-0.15	0.34	-10000	0	-0.84	96	96
Tie2/Ang1/GRB7	-0.14	0.38	-10000	0	-0.91	96	96
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.16	0.36	-10000	0	-0.88	96	96
PI3K	-0.24	0.44	-10000	0	-0.9	136	136
FES	-0.16	0.38	-10000	0	-0.9	97	97
Crk/Dok-R	-0.14	0.36	-10000	0	-0.86	96	96
Tie2/Ang1/ABIN2	-0.14	0.38	-10000	0	-0.9	96	96
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.2	0.36	-10000	0	-0.69	164	164
STAT5A	0.036	0.004	-10000	0	0	5	5
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.2	0.37	-10000	0	-0.76	138	138
Tie2/Ang2	-0.29	0.5	-10000	0	-0.96	165	165
Tie2/Ang1	-0.15	0.38	-10000	0	-0.93	96	96
FOXO1	-0.22	0.39	-10000	0	-0.75	167	167
ELF1	0.028	0.036	0.11	4	-0.046	81	85
ELF2	-0.14	0.36	-10000	0	-0.87	96	96
mol:Choline	-0.15	0.35	-10000	0	-0.86	96	96
cell migration	-0.066	0.097	-10000	0	-0.21	137	137
FYN	-0.24	0.41	-10000	0	-0.8	167	167
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.17	0.32	0.39	3	-0.58	175	178
ETS1	-0.002	0.12	0.12	2	-0.25	93	95
PXN	-0.17	0.31	0.36	1	-0.64	138	139
ITGB1	0.027	0.016	-10000	0	0	138	138
NOS3	-0.15	0.35	0.38	3	-0.64	150	153
RAC1	0.024	0.017	-10000	0	0	173	173
TNF	-0.004	0.12	-10000	0	-0.25	92	92
MAPKKK cascade	-0.15	0.35	-10000	0	-0.86	96	96
RASA1	0.034	0.009	-10000	0	0	32	32
Tie2/Ang1/Shc	-0.15	0.37	-10000	0	-0.91	96	96
NCK1	0.035	0.008	-10000	0	0	27	27
vasculogenesis	-0.1	0.29	0.35	5	-0.51	153	158
mol:Phosphatidic acid	-0.15	0.35	-10000	0	-0.86	96	96
mol:Angiotensin II	-0.004	0.013	-10000	0	-0.032	73	73
mol:NADP	-0.12	0.32	0.37	4	-0.57	152	156
Rac1/GTP	-0.18	0.34	-10000	0	-0.69	134	134
MMP2	-0.15	0.37	-10000	0	-0.9	96	96

×

Syndecan-4-mediated signaling events

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
PTK2	-0.031	0.16	-10000	0	-0.45	43	43
Syndecan-4/Syndesmos	-0.14	0.28	-10000	0	-0.48	149	149
positive regulation of JNK cascade	-0.13	0.26	-10000	0	-0.49	124	124
Syndecan-4/ADAM12	-0.13	0.29	-10000	0	-0.52	124	124
CCL5	0.033	0.011	-10000	0	0	53	53
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
DNM2	0.035	0.009	-10000	0	0	29	29
ITGA5	0.033	0.011	-10000	0	0	56	56
SDCBP	0.035	0.007	-10000	0	0	21	21
PLG	0.03	0.021	-10000	0	-0.047	17	17
ADAM12	0.024	0.017	-10000	0	0	168	168
mol:GTP	0	0	-10000	0	-10000	0	0
NUDT16L1	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
Syndecan-4/PKC alpha	-0.025	0.022	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.28	-10000	0	-0.48	149	149
Syndecan-4/CXCL12/CXCR4	-0.14	0.28	-10000	0	-0.53	122	122
Syndecan-4/Laminin alpha3	-0.13	0.29	-10000	0	-0.49	142	142
MDK	0.03	0.014	-10000	0	0	92	92
Syndecan-4/FZD7	-0.14	0.3	-10000	0	-0.5	152	152
Syndecan-4/Midkine	-0.13	0.3	-10000	0	-0.49	154	154
FZD7	0.026	0.016	-10000	0	0	143	143
Syndecan-4/FGFR1/FGF	-0.098	0.28	-10000	0	-0.47	136	136
THBS1	0.03	0.014	-10000	0	0	97	97
integrin-mediated signaling pathway	-0.13	0.28	-10000	0	-0.47	153	153
positive regulation of MAPKKK cascade	-0.13	0.26	-10000	0	-0.49	124	124
Syndecan-4/TACI	-0.12	0.3	-10000	0	-0.48	149	149
CXCR4	0.029	0.015	-10000	0	0	103	103
cell adhesion	-0.009	0.054	0.2	3	-0.25	17	20
Syndecan-4/Dynamin	-0.12	0.29	-10000	0	-0.48	146	146
Syndecan-4/TSP1	-0.13	0.28	-10000	0	-0.5	135	135
Syndecan-4/GIPC	-0.12	0.29	-10000	0	-0.48	146	146
Syndecan-4/RANTES	-0.13	0.29	-10000	0	-0.49	144	144
ITGB1	0.027	0.016	-10000	0	0	138	138
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.033	0.011	-10000	0	0	48	48
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	0.001	0.11	0.98	6	-10000	0	6
Syndecan-4/alpha-Actinin	-0.14	0.3	-10000	0	-0.5	151	151
TFPI	0.029	0.015	-10000	0	0	103	103
F2	0.01	0.041	-10000	0	-0.045	168	168
alpha5/beta1 Integrin	0.029	0.042	-10000	0	-0.14	20	20
positive regulation of cell adhesion	-0.13	0.27	-10000	0	-0.47	142	142
ACTN1	0.028	0.016	-10000	0	0	119	119
TNC	0.028	0.016	-10000	0	0	122	122
Syndecan-4/CXCL12	-0.14	0.28	-10000	0	-0.53	120	120
FGF6	0.035	0.008	-10000	0	0	27	27
RHOA	0.035	0.007	-10000	0	0	18	18
CXCL12	0.022	0.018	-10000	0	0	202	202
TNFRSF13B	0.036	0.005	-10000	0	0	8	8
FGF2	0.035	0.008	-10000	0	0	25	25
FGFR1	0.036	0.005	-10000	0	0	9	9
Syndecan-4/PI-4-5-P2	-0.14	0.28	-10000	0	-0.48	149	149
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.03	0.021	-10000	0	-0.045	27	27
cell migration	-0.011	0.016	-10000	0	-10000	0	0
PRKCD	0.031	0.021	-10000	0	-0.044	24	24
vasculogenesis	-0.13	0.27	-10000	0	-0.48	135	135
SDC4	-0.14	0.3	-10000	0	-0.51	148	148
Syndecan-4/Tenascin C	-0.14	0.3	-10000	0	-0.5	153	153
Syndecan-4/PI-4-5-P2/PKC alpha	-0.02	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.3	-10000	0	-0.49	146	146
MMP9	0.012	0.024	-10000	0	-0.043	37	37
Rac1/GTP	-0.009	0.055	0.2	3	-0.26	17	20
cytoskeleton organization	-0.13	0.27	-10000	0	-0.46	149	149
GIPC1	0.035	0.008	-10000	0	0	24	24
Syndecan-4/TFPI	-0.13	0.29	-10000	0	-0.5	143	143

×

Endothelins

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
AKT1	-0.02	0.14	0.21	77	-0.26	85	162
PTK2B	0.036	0.006	-10000	0	0	16	16
mol:Ca2+	-0.1	0.25	0.4	1	-0.53	78	79
EDN1	0.005	0.092	0.14	9	-0.16	103	112
EDN3	0.033	0.011	-10000	0	0	52	52
EDN2	0.036	0.006	-10000	0	0	12	12
HRAS/GDP	-0.016	0.17	0.3	18	-0.37	57	75
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0	0.12	0.2	17	-0.25	59	76
ADCY4	-0.035	0.097	0.14	39	-0.2	99	138
ADCY5	-0.035	0.097	0.14	39	-0.2	99	138
ADCY6	-0.007	0.13	0.22	41	-0.23	62	103
ADCY7	-0.014	0.13	0.21	39	-0.24	66	105
ADCY1	-0.002	0.11	0.21	26	-0.25	42	68
ADCY2	-0.007	0.13	0.21	46	-0.24	65	111
ADCY3	-0.035	0.097	0.14	39	-0.2	99	138
ADCY8	-0.011	0.12	0.22	38	-0.23	57	95
ADCY9	-0.009	0.13	0.22	43	-0.23	65	108
arachidonic acid secretion	-0.08	0.26	0.32	26	-0.51	102	128
ETB receptor/Endothelin-1/Gq/GTP	-0.007	0.11	0.19	10	-0.25	47	57
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	32	32
ETA receptor/Endothelin-1/G12/GTP	0.004	0.12	-10000	0	-0.22	76	76
ETA receptor/Endothelin-1/Gs/GTP	0.005	0.12	-10000	0	-0.2	105	105
mol:GTP	0	0.006	0.026	3	-0.025	4	7
COL3A1	-0.074	0.15	0.18	9	-0.36	100	109
EDNRB	0.023	0.045	0.096	62	-0.082	48	110
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.017	0.14	0.21	76	-0.27	68	144
CYSLTR1	-0.034	0.12	0.19	41	-0.24	97	138
SLC9A1	-0.014	0.086	0.13	28	-0.16	107	135
mol:GDP	-0.024	0.17	0.29	21	-0.38	57	78
SLC9A3	-0.12	0.29	-10000	0	-0.66	81	81
RAF1	-0.036	0.2	0.31	24	-0.41	83	107
JUN	-0.14	0.33	0.5	1	-0.7	90	91
JAK2	-0.021	0.14	0.21	66	-0.25	86	152
mol:IP3	-0.004	0.12	0.22	19	-0.27	47	66
ETA receptor/Endothelin-1	-0.02	0.15	-10000	0	-0.27	113	113
PLCB1	0.033	0.013	-10000	0	-0.008	38	38
PLCB2	0.028	0.023	-10000	0	-0.022	80	80
ETA receptor/Endothelin-3	0.008	0.087	-10000	0	-0.14	104	104
FOS	-0.094	0.35	0.41	15	-0.84	82	97
Gai/GDP	-0.068	0.27	-10000	0	-0.73	66	66
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca ++	-0.02	0.17	0.25	55	-0.33	80	135
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.004	0.12	0.23	25	-0.29	47	72
GNAQ	0.027	0.026	-10000	0	-0.034	70	70
GNAZ	0.031	0.013	-10000	0	0	81	81
GNAL	0.036	0.006	-10000	0	0	13	13
Gs family/GDP	-0.014	0.16	0.29	19	-0.35	56	75
ETA receptor/Endothelin-1/Gq/GTP	-0.006	0.12	0.21	10	-0.27	57	67
MAPK14	-0.014	0.099	0.18	7	-0.25	44	51
TRPC6	-0.1	0.26	-10000	0	-0.56	77	77
GNAI2	0.034	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.004	0.1	0.18	15	-0.24	48	63
ETB receptor/Endothelin-2	0.017	0.071	-10000	0	-0.11	99	99
ETB receptor/Endothelin-3	0.016	0.069	-10000	0	-0.11	84	84
ETB receptor/Endothelin-1	0	0.1	0.18	26	-0.16	113	139
MAPK3	-0.077	0.32	0.39	18	-0.73	82	100
MAPK1	-0.091	0.34	0.4	16	-0.79	82	98
Rac1/GDP	-0.012	0.15	0.31	15	-0.37	40	55
cAMP biosynthetic process	0.02	0.12	0.22	54	-0.21	46	100
MAPK8	-0.14	0.31	0.36	1	-0.58	138	139
SRC	0.036	0.006	-10000	0	0	14	14
ETB receptor/Endothelin-1/Gi/GTP	-0.029	0.14	0.16	6	-0.34	59	65
p130Cas/CRK/Src/PYK2	-0.024	0.18	0.35	13	-0.47	43	56
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.015	0.15	0.31	13	-0.38	44	57
COL1A2	-0.052	0.17	0.22	2	-0.47	61	63
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.006	0.091	-10000	0	-0.14	115	115
mol:DAG	-0.004	0.12	0.22	19	-0.27	47	66
MAP2K2	-0.052	0.26	0.34	36	-0.55	82	118
MAP2K1	-0.064	0.26	0.33	23	-0.58	84	107
EDNRA	-0.008	0.1	0.14	6	-0.2	99	105
positive regulation of muscle contraction	0.033	0.15	0.22	150	-0.24	54	204
Gq family/GDP	0.002	0.16	0.3	6	-0.35	56	62
HRAS/GTP	-0.016	0.16	0.27	26	-0.35	59	85
PRKCH	-0.009	0.12	0.24	19	-0.29	44	63
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	-0.012	0.12	0.22	18	-0.28	49	67
PRKCB	-0.008	0.12	0.21	19	-0.27	50	69
PRKCE	-0.013	0.12	0.22	17	-0.29	48	65
PRKCD	-0.007	0.12	0.25	24	-0.28	47	71
PRKCG	-0.014	0.12	0.22	18	-0.29	50	68
regulation of vascular smooth muscle contraction	-0.12	0.41	0.45	11	-1	82	93
PRKCQ	-0.003	0.11	0.25	19	-0.3	32	51
PLA2G4A	-0.09	0.28	0.32	25	-0.56	102	127
GNA14	0.027	0.026	-10000	0	-0.034	70	70
GNA15	0.03	0.019	-10000	0	-0.034	25	25
GNA12	0.023	0.018	-10000	0	0	193	193
GNA11	0.031	0.017	-10000	0	-0.035	16	16
Rac1/GTP	0.006	0.11	-10000	0	-0.22	70	70
MMP1	0.019	0.074	0.18	54	-10000	0	54

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.025	0.017	-10000	0	0	167	167
HRAS	0.034	0.009	-10000	0	0	32	32
EGFR	0.009	0.016	-10000	0	0	381	381
AKT	0.09	0.12	0.24	125	-0.18	9	134
FOXO3	0	0	-10000	0	-10000	0	0
AKT1	0.033	0.011	-10000	0	0	53	53
FOXO1	0	0	-10000	0	-10000	0	0
AKT3	0.035	0.008	-10000	0	0	23	23
FOXO4	0	0	-10000	0	-10000	0	0
MET	0.023	0.018	-10000	0	0	191	191
PIK3CA	0.031	0.013	-10000	0	0	80	80
PIK3CB	0.035	0.007	-10000	0	0	18	18
NRAS	0.032	0.012	-10000	0	0	63	63
PIK3CG	0.025	0.017	-10000	0	0	163	163
PIK3R3	0.036	0.006	-10000	0	0	15	15
PIK3R2	0.035	0.008	-10000	0	0	23	23
NF1	0.036	0.003	-10000	0	0	4	4
RAS	-0.003	0.057	0.12	7	-0.13	50	57
ERBB2	0.036	0.004	-10000	0	0	5	5
proliferation/survival/translation	-0.024	0.051	0.22	4	-0.19	15	19
PI3K	0.041	0.092	0.22	79	-0.15	12	91
PIK3R1	0.032	0.012	-10000	0	0	63	63
KRAS	0.034	0.009	-10000	0	0	35	35
FOXO	0.093	0.091	0.2	164	-10000	0	164
AKT2	0.035	0.008	-10000	0	0	28	28
PTEN	0.026	0.017	-10000	0	0	148	148

×

Thromboxane A2 receptor 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.035	0.008	-10000	0	0	23	23
GNB1/GNG2	-0.046	0.078	-10000	0	-0.17	131	131
AKT1	-0.003	0.16	0.28	34	-0.31	35	69
EGF	0.035	0.008	-10000	0	0	25	25
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.015	0.07	0.27	21	-0.17	3	24
mol:Ca2+	-0.001	0.19	0.34	28	-0.27	122	150
LYN	-0.015	0.07	0.28	18	-0.17	6	24
RhoA/GTP	0.002	0.084	0.16	28	-0.13	87	115
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.017	0.21	0.36	30	-0.32	124	154
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.035	0.008	-10000	0	0	26	26
TP alpha/Gq family/GDP/G beta5/gamma2	0.001	0.078	-10000	0	-0.25	30	30
G beta5/gamma2	-0.054	0.1	-10000	0	-0.23	128	128
PRKCH	-0.016	0.21	0.36	25	-0.32	127	152
DNM1	0.035	0.008	-10000	0	0	26	26
TXA2/TP beta/beta Arrestin3	0.014	0.018	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	0.006	57	-0.002	2	59
PTGDR	0.035	0.008	-10000	0	0	26	26
G12 family/GTP	-0.045	0.14	-10000	0	-0.29	93	93
ADRBK1	0.036	0.006	-10000	0	0	13	13
ADRBK2	0.035	0.009	-10000	0	0	29	29
RhoA/GTP/ROCK1	0.044	0.026	-10000	0	-0.12	10	10
mol:GDP	-0.008	0.13	0.41	15	-0.28	17	32
mol:NADP	0.024	0.017	-10000	0	0	175	175
RAB11A	0.035	0.007	-10000	0	0	18	18
PRKG1	0.027	0.017	-10000	0	0	141	141
mol:IP3	-0.013	0.22	0.38	25	-0.34	125	150
cell morphogenesis	0.044	0.026	-10000	0	-0.12	10	10
PLCB2	-0.037	0.27	0.43	18	-0.45	125	143
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.013	0.072	0.26	23	-10000	0	23
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.018	0.06	0.25	14	-0.17	8	22
RHOA	0.035	0.007	-10000	0	0	18	18
PTGIR	0.034	0.009	-10000	0	0	33	33
PRKCB1	-0.017	0.22	0.37	25	-0.34	125	150
GNAQ	0.034	0.009	-10000	0	0	31	31
mol:L-citrulline	0.024	0.017	-10000	0	0	175	175
TXA2/TXA2-R family	-0.048	0.28	0.41	23	-0.47	133	156
LCK	-0.015	0.07	0.27	21	-10000	0	21
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.033	0.038	0.19	5	-10000	0	5
TXA2-R family/G12 family/GDP/G beta/gamma	-0.02	0.14	-10000	0	-0.46	45	45
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.03	0.041	0.19	5	-0.15	1	6
MAPK14	-0.004	0.15	0.28	36	-0.22	120	156
TGM2/GTP	-0.012	0.24	0.41	24	-0.38	114	138
MAPK11	-0.006	0.15	0.29	34	-0.22	122	156
ARHGEF1	0.011	0.12	0.22	46	-0.18	89	135
GNAI2	0.034	0.01	-10000	0	0	43	43
JNK cascade	-0.021	0.22	0.38	25	-0.35	133	158
RAB11/GDP	0.034	0.01	-10000	0	-0.009	25	25
ICAM1	-0.005	0.18	0.32	38	-0.27	126	164
cAMP biosynthetic process	-0.013	0.2	0.35	26	-0.32	109	135
Gq family/GTP/EBP50	0.013	0.051	0.24	7	-0.15	30	37
actin cytoskeleton reorganization	0.044	0.026	-10000	0	-0.12	10	10
SRC	-0.018	0.062	0.25	16	-10000	0	16
GNB5	0.035	0.008	-10000	0	0	24	24
GNB1	0.035	0.007	-10000	0	0	20	20
EGF/EGFR	-0.011	0.1	0.26	23	-0.23	40	63
VCAM1	-0.023	0.21	0.33	34	-0.33	135	169
TP beta/Gq family/GDP/G beta5/gamma2	0.001	0.078	-10000	0	-0.25	30	30
platelet activation	-0.009	0.19	0.36	30	-0.28	120	150
PGI2/IP	0.025	0.007	-10000	0	-10000	0	0
PRKACA	0.015	0.02	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.004	0.069	-10000	0	-0.22	29	29
TXA2/TP beta/beta Arrestin2	0.004	0.047	-10000	0	-0.29	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.006	0.02	-10000	0	-10000	0	0
mol:DAG	-0.022	0.24	0.39	25	-0.38	126	151
EGFR	0.009	0.016	-10000	0	0	381	381
TXA2/TP alpha	-0.029	0.26	0.42	19	-0.42	119	138
Gq family/GTP	0.009	0.048	0.2	12	-0.13	28	40
YES1	-0.014	0.071	0.28	19	-0.16	3	22
GNAI2/GTP	0.008	0.048	-10000	0	-0.14	2	2
PGD2/DP	0.026	0.006	-10000	0	-10000	0	0
SLC9A3R1	0.034	0.01	-10000	0	0	37	37
FYN	-0.015	0.072	0.28	19	-0.17	7	26
mol:NO	0.024	0.017	-10000	0	0	175	175
GNA15	0.033	0.012	-10000	0	0	57	57
PGK/cGMP	0.027	0.025	-10000	0	-10000	0	0
RhoA/GDP	0.034	0.01	-10000	0	-0.009	25	25
TP alpha/TGM2/GDP/G beta/gamma	0.031	0.042	0.18	4	-0.15	1	5
NOS3	0.024	0.017	-10000	0	0	175	175
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	-0.015	0.21	0.35	26	-0.32	126	152
PRKCB	-0.016	0.21	0.35	26	-0.32	131	157
PRKCE	-0.018	0.21	0.36	26	-0.33	127	153
PRKCD	-0.019	0.22	0.36	30	-0.35	129	159
PRKCG	-0.022	0.22	0.37	25	-0.35	131	156
muscle contraction	-0.042	0.26	0.4	24	-0.44	133	157
PRKCZ	-0.016	0.2	0.35	27	-0.31	133	160
ARR3	0.037	0	-10000	0	-10000	0	0
TXA2/TP beta	0.036	0.039	0.19	4	-0.14	1	5
PRKCQ	-0.026	0.2	0.35	27	-0.32	123	150
MAPKKK cascade	-0.032	0.24	0.39	24	-0.4	125	149
SELE	-0.01	0.18	0.32	30	-0.27	134	164
TP beta/GNAI2/GDP/G beta/gamma	0.026	0.053	0.19	4	-0.17	13	17
ROCK1	0.036	0.006	-10000	0	0	15	15
GNA14	0.034	0.009	-10000	0	0	30	30
chemotaxis	-0.069	0.32	0.45	17	-0.56	135	152
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
Rac1/GTP	0.017	0.02	-10000	0	-0.13	5	5

×

TCGA08_p53

Figure S8. Get High-res Image This plot shows pathway concept perturbations across all samples against a permutation model. The concepts along the x-axis are sorted by lowest to highest mean activity for the real patient samples. Mean inferred activities are plotted along the y-axis as a colored band showing the average level and one standard deviation range. Real samples are shown in red and permuted samples in black.

Table S8. Get Full Table This table displays mean, standard deviation, and perturbation statistics for Inferred Pathway Levels (IPLs). A mean perturbation of -9999 implies that the IPLs across all the real samples did not differ enough from the IPLs generated by a background model of permuted samples (> 1 Std.Dev from the permuted sample IPLs).

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.001	0.004	0	444	-10000	0	444
TP53	0.004	0.034	-10000	0	-0.22	9	9
Senescence	0.004	0.034	-10000	0	-0.22	9	9
Apoptosis	0.004	0.034	-10000	0	-0.22	9	9
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0	0.023	0.3	3	-10000	0	3
MDM4	0.034	0.01	-10000	0	0	38	38

×

EGFR-dependent Endothelin 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
HRAS	0.034	0.009	-10000	0	0	32	32
EGFR	0.009	0.016	-10000	0	0	381	381
EGF/EGFR	0.001	0.052	-10000	0	-0.11	64	64
EGF/EGFR dimer/SHC/GRB2/SOS1	0.006	0.057	-10000	0	-0.11	61	61
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.028	0.016	-10000	0	0	122	122
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.035	0.008	-10000	0	0	25	25
EGF/EGFR dimer/SHC	0	0.055	-10000	0	-0.12	61	61
mol:GDP	0.004	0.055	-10000	0	-0.11	61	61
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.033	0.011	-10000	0	0	53	53
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
HRAS/GTP	-0.004	0.051	-10000	0	-0.11	67	67
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0	0.057	-10000	0	-0.12	67	67
FRAP1	0.093	0.12	0.18	302	-0.18	4	306
EGF/EGFR dimer	-0.005	0.056	-10000	0	-0.14	64	64
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	17	17
ETA receptor/Endothelin-1	0.023	0.059	-10000	0	-0.14	50	50

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.034	0.01	-10000	0	0	41	41
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.036	0.004	-10000	0	0	6	6
TCEB1	0.035	0.007	-10000	0	0	22	22
HIF1A/p53	-0.063	0.14	-10000	0	-0.27	139	139
HIF1A	-0.057	0.12	0.16	1	-0.28	118	119
COPS5	0.036	0.006	-10000	0	0	14	14
VHL/Elongin B/Elongin C/RBX1/CUL2	0.048	0.059	-10000	0	-0.13	22	22
FIH (dimer)	0.025	0.017	-10000	0	0	156	156
CDKN2A	0.004	0.012	-10000	0	0	444	444
ARNT/IPAS	0.05	0.015	-10000	0	-10000	0	0
HIF1AN	0.025	0.017	-10000	0	0	156	156
GNB2L1	0.036	0.002	-10000	0	0	2	2
HIF1A/ARNT	-0.061	0.14	-10000	0	-0.27	139	139
CUL2	0.026	0.017	-10000	0	0	153	153
OS9	0.031	0.013	-10000	0	0	73	73
RACK1/Elongin B/Elongin C	0.068	0.032	-10000	0	-0.13	10	10
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.075	0.13	-10000	0	-0.27	141	141
PHD1-3/OS9	0.063	0.064	-10000	0	-0.14	31	31
HIF1A/RACK1/Elongin B/Elongin C	-0.043	0.15	-10000	0	-0.27	141	141
VHL	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
HIF1A/JAB1	-0.063	0.14	-10000	0	-0.27	143	143
EGLN3	0.03	0.014	-10000	0	0	91	91
EGLN2	0.034	0.009	-10000	0	0	30	30
EGLN1	0.034	0.009	-10000	0	0	33	33
TP53	0.031	0.013	-10000	0	0	73	73
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.005	0.1	-10000	0	-0.61	12	12
ARNT	0.036	0.004	-10000	0	0	5	5
ARD1A	0.036	0.003	-10000	0	0	4	4
RBX1	0.033	0.01	-10000	0	0	45	45
HIF1A/p19ARF	-0.064	0.12	-10000	0	-0.26	119	119

×

Effects of Botulinum toxin

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
STX1A	-0.007	0.006	0	180	-10000	0	180
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.04	0.04	-10000	0	-0.14	19	19
STXBP1	0.029	0.015	-10000	0	0	106	106
ACh/CHRNA1	0.026	0.053	0.095	40	-0.075	91	131
RAB3GAP2/RIMS1/UNC13B	0.052	0.05	-10000	0	-0.13	25	25
mol:Ca2+	0	0	-10000	0	-10000	0	0
UniProt:P30996	0	0	-10000	0	-10000	0	0
UniProt:Q60393	0	0	-10000	0	-10000	0	0
CST086	0	0	-10000	0	-10000	0	0
RIMS1	0.035	0.008	-10000	0	0	23	23
mol:ACh	0.016	0.063	0.093	145	-0.089	88	233
RAB3GAP2	0.035	0.009	-10000	0	0	29	29
STX1A/SNAP25/VAMP2	0.026	0.1	0.18	19	-0.16	76	95
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.026	0.053	0.095	40	-0.075	91	131
UNC13B	0.032	0.013	-10000	0	0	70	70
CHRNA1	0.035	0.007	-10000	0	0	18	18
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.012	0.041	0.096	9	-0.085	40	49
SNAP25	0.002	0.003	-10000	0	0	262	262
VAMP2	0.004	0.001	-10000	0	0	48	48
SYT1	0.018	0.018	-10000	0	0	262	262
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.017	0.016	-10000	0	-10000	0	0
STX1A/SNAP25 fragment 1/VAMP2	0.026	0.1	0.18	19	-0.16	76	95

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.017	0.031	0.081	3	-0.056	51	54
PDGF/PDGFRA/CRKL	0.007	0.067	-10000	0	-0.14	68	68
positive regulation of JUN kinase activity	0.023	0.062	-10000	0	-0.11	69	69
CRKL	0.035	0.009	-10000	0	0	29	29
PDGF/PDGFRA/Caveolin-3	0.009	0.068	-10000	0	-0.14	68	68
AP1	-0.08	0.24	0.29	12	-0.59	77	89
mol:IP3	-0.015	0.046	0.095	25	-0.1	49	74
PLCG1	-0.015	0.046	0.095	25	-0.1	49	74
PDGF/PDGFRA/alphaV Integrin	0.004	0.075	-10000	0	-0.15	78	78
RAPGEF1	0.035	0.007	-10000	0	0	19	19
CRK	0.035	0.008	-10000	0	0	23	23
mol:Ca2+	-0.015	0.046	0.095	25	-0.1	49	74
CAV3	0.036	0.005	-10000	0	0	11	11
CAV1	0.016	0.018	-10000	0	0	290	290
SHC/Grb2/SOS1	0.028	0.064	-10000	0	-0.11	69	69
PDGF/PDGFRA/Shf	-0.005	0.054	-10000	0	-0.1	96	96
FOS	-0.093	0.22	0.42	1	-0.6	71	72
JUN	-0.026	0.056	0.2	10	-0.2	16	26
oligodendrocyte development	0.003	0.075	-10000	0	-0.15	78	78
GRB2	0.035	0.007	-10000	0	0	17	17
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:DAG	-0.015	0.046	0.095	25	-0.1	49	74
PDGF/PDGFRA	0.017	0.031	0.081	3	-0.056	51	54
actin cytoskeleton reorganization	0.007	0.065	-10000	0	-0.14	65	65
SRF	-0.016	0.021	0.033	70	-10000	0	70
SHC1	0.033	0.011	-10000	0	0	52	52
PI3K	0.007	0.09	-10000	0	-0.15	108	108
PDGF/PDGFRA/Crk/C3G	0.027	0.071	-10000	0	-0.13	75	75
JAK1	-0.007	0.029	0.083	30	-10000	0	30
ELK1/SRF	-0.02	0.083	0.14	67	-0.16	59	126
SHB	0.033	0.011	-10000	0	0	51	51
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.027	0.034	-10000	0	-0.032	102	102
GO:0007205	-0.027	0.068	0.1	25	-0.19	55	80
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	0.023	0.062	-10000	0	-0.11	69	69
PDGF/PDGFRA/SHB	0.007	0.065	-10000	0	-0.14	65	65
PDGF/PDGFRA/Caveolin-1	-0.016	0.077	-10000	0	-0.17	87	87
ITGAV	0.034	0.009	-10000	0	0	31	31
ELK1	-0.032	0.066	0.13	7	-0.15	84	91
PIK3CA	0.031	0.013	-10000	0	0	80	80
PDGF/PDGFRA/Crk	0.006	0.072	-10000	0	-0.15	76	76
JAK-STAT cascade	-0.007	0.029	0.082	30	-10000	0	30
cell proliferation	-0.005	0.054	-10000	0	-0.1	96	96

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.014	0.035	-10000	0	-0.11	38	38
ARNO/beta Arrestin1-2	0.042	0.025	-10000	0	-0.094	7	7
EGFR	0.009	0.016	-10000	0	0	381	381
EPHA2	0.033	0.011	-10000	0	0	54	54
USP6	0.035	0.007	-10000	0	0	18	18
IQSEC1	0.035	0.007	-10000	0	0	19	19
EGFR/EGFR/EGF/EGF	-0.005	0.056	-10000	0	-0.14	64	64
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
mol:GTP	0.002	0.012	-10000	0	-0.063	3	3
ARRB1	0.036	0.005	-10000	0	0	10	10
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.033	0.011	-10000	0	0	48	48
EGF	0.035	0.008	-10000	0	0	25	25
somatostatin receptor activity	0	0	0.001	155	0	6	161
ARAP2	0	0	0	129	0	2	131
mol:GDP	0.068	0.068	0.16	127	-0.16	4	131
mol:PI-3-4-5-P3	0	0	0	139	0	5	144
ITGA2B	0.036	0.004	-10000	0	0	5	5
ARF6	0.035	0.008	-10000	0	0	27	27
Ephrin A1/EPHA2/NCK1/GIT1	0.076	0.052	-10000	0	-0.12	24	24
ADAP1	0	0	0	61	0	1	62
KIF13B	0.032	0.012	-10000	0	0	63	63
HGF/MET	0.032	0.027	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
ARF6/GTP	0.083	0.087	0.19	138	-0.2	5	143
EGFR/EGFR/EGF/EGF/ARFGEP100	0.001	0.055	-10000	0	-0.12	62	62
ADRB2	0.034	0.01	-10000	0	0	42	42
receptor agonist activity	0	0	0	141	0	5	146
actin filament binding	0	0	0	142	0	7	149
SRC	0.036	0.006	-10000	0	0	14	14
ITGB3	0.036	0.003	-10000	0	0	4	4
GNAQ	0.035	0.009	-10000	0	0	31	31
EFA6/PI-4-5-P2	0.001	0.001	0.001	169	-0.001	4	173
ARF6/GDP	0.036	0.063	0.17	12	-0.22	11	23
ARF6/GDP/GULP/ACAP1	0.055	0.075	0.2	23	-0.2	3	26
alphaIIb/beta3 Integrin/paxillin/GIT1	0.092	0.012	-10000	0	-10000	0	0
ACAP1	0	0	0	58	-10000	0	58
ACAP2	0	0	0	70	0	3	73
LHCGR/beta Arrestin2	0.03	0.024	-10000	0	-0.14	7	7
EFNA1	0.033	0.011	-10000	0	0	50	50
HGF	0.024	0.017	-10000	0	0	177	177
CYTH3	0	0	0.001	148	-0.001	4	152
CYTH2	0	0.001	0.003	1	-0.003	6	7
NCK1	0.035	0.008	-10000	0	0	27	27
fibronectin binding	0	0	0	145	0	5	150
endosomal lumen acidification	0	0	0	145	0	6	151
microtubule-based process	0	0	-10000	0	0	1	1
GULP1	0.024	0.017	-10000	0	0	168	168
GNAQ/ARNO	0.026	0.008	0.04	5	0	31	36
mol:Phosphatidic acid	0	0	0	70	0	3	73
PIP3-E	0.03	0.014	-10000	0	0	89	89
MET	0.023	0.018	-10000	0	0	191	191
GNA14	0.035	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GIT1	0.036	0.003	-10000	0	0	4	4
mol:PI-4-5-P2	0	0	0.001	152	-0.001	4	156
GNA11	0.033	0.011	-10000	0	0	54	54
LHCGR	0.037	0.003	-10000	0	0	3	3
AGTR1	0.035	0.008	-10000	0	0	22	22
desensitization of G-protein coupled receptor protein signaling pathway	0.03	0.024	-10000	0	-0.14	7	7
IPCEF1/ARNO	0.007	0.043	-10000	0	-0.09	51	51
alphaIIb/beta3 Integrin	0.054	0.006	-10000	0	-10000	0	0

×

Syndecan-3-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.036	0.006	-9999	0	13	13
Syndecan-3/Src/Cortactin	-0.025	0.18	-9999	-0.43	75	75
Syndecan-3/Neurocan	-0.065	0.18	-9999	-0.48	78	78
POMC	0.036	0.006	-9999	0	14	14
EGFR	0.009	0.016	-9999	0	381	381
Syndecan-3/EGFR	-0.057	0.16	-9999	-0.42	77	77
AGRP	0.036	0.005	-9999	0	9	9
NCSTN	0.035	0.008	-9999	0	28	28
PSENEN	0.035	0.008	-9999	0	28	28
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.035	0.006	-9999	0	16	16
APH1A	0.036	0.005	-9999	0	11	11
NCAN	0	0	-9999	-10000	0	0
long-term memory	-0.033	0.2	-9999	-0.49	78	78
Syndecan-3/IL8	-0.056	0.18	-9999	-0.48	78	78
PSEN1	0.033	0.011	-9999	0	46	46
Src/Cortactin	0.051	0.015	-9999	-0.14	1	1
FYN	0.03	0.014	-9999	0	90	90
limb bud formation	-0.066	0.18	-9999	-0.5	78	78
MC4R	0.035	0.007	-9999	0	20	20
SRC	0.036	0.006	-9999	0	14	14
PTN	0.021	0.018	-9999	0	209	209
FGFR/FGF/Syndecan-3	-0.067	0.19	-9999	-0.5	78	78
neuron projection morphogenesis	-0.071	0.15	-9999	-0.43	73	73
Syndecan-3/AgRP	-0.044	0.19	-9999	-0.49	78	78
Syndecan-3/AgRP/MC4R	-0.025	0.19	-9999	-0.47	78	78
Fyn/Cortactin	0.029	0.061	-9999	-0.14	53	53
SDC3	-0.068	0.19	-9999	-0.51	78	78
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.055	0.18	-9999	-0.47	78	78
IL8	0.019	0.018	-9999	0	243	243
Syndecan-3/Fyn/Cortactin	-0.034	0.21	-9999	-0.51	78	78
Syndecan-3/CASK	-0.065	0.18	-9999	-0.48	78	78
alpha-MSH/MC4R	0.051	0.014	-9999	-10000	0	0
Gamma Secretase	0.08	0.069	-9999	-0.15	28	28

×

Canonical Wnt signaling pathway

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
HDAC1	0.033	0.045	0.12	67	-0.039	84	151
AES	0.031	0.042	0.11	63	-0.036	80	143
FBXW11	0.035	0.008	-10000	0	0	25	25
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.026	-10000	0	-10000	0	0
SMAD4	0.032	0.012	-10000	0	0	58	58
DKK2	0.034	0.009	-10000	0	0	31	31
TLE1	0.031	0.041	0.11	64	-0.036	84	148
MACF1	0.033	0.011	-10000	0	0	49	49
CTNNB1	0.045	0.11	0.25	25	-0.36	14	39
WIF1	0.028	0.015	-10000	0	0	112	112
beta catenin/RanBP3	0.071	0.16	0.42	62	-0.35	9	71
KREMEN2	0.036	0.004	-10000	0	0	7	7
DKK1	0.017	0.018	-10000	0	0	271	271
beta catenin/beta TrCP1	0.06	0.11	0.26	22	-0.34	16	38
FZD1	0.024	0.017	-10000	0	0	173	173
AXIN2	-0.024	0.093	0.11	4	-0.24	67	71
AXIN1	0.037	0.001	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
Axin1/APC/GSK3/beta catenin	0.015	0.16	-10000	0	-0.6	29	29
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.024	0.13	0.25	13	-0.39	23	36
Axin1/APC/GSK3	0.005	0.09	0.23	5	-0.38	17	22
Axin1/APC/GSK3/beta catenin/Macf1	0.032	0.14	0.22	24	-0.34	39	63
HNF1A	0.006	0.03	0.071	74	-0.035	4	78
CTBP1	0.031	0.041	0.11	61	-0.037	83	144
MYC	-0.097	0.4	0.74	14	-1.3	49	63
RANBP3	0.035	0.008	-10000	0	0	23	23
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.12	1	1
NKD1	0	0.001	-10000	0	-10000	0	0
TCF4	0.03	0.038	0.11	59	-0.036	68	127
TCF3	0.032	0.042	0.11	64	-0.036	83	147
WNT1/LRP6/FZD1/Axin1	0.059	0.046	-10000	0	-10000	0	0
Ran/GTP	0.026	0.016	-10000	0	-0.13	5	5
CtBP/CBP/TCF/TLE1/AES	0.035	0.19	0.46	65	-0.34	20	85
LEF1	0.033	0.044	0.11	71	-0.037	86	157
DVL1	0.01	0.098	-10000	0	-0.42	18	18
CSNK2A1	0.035	0.009	-10000	0	0	31	31
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.01	0.16	0.25	10	-0.48	32	42
DKK1/LRP6/Kremen 2	0.031	0.037	-10000	0	-10000	0	0
LRP6	0.034	0.01	-10000	0	0	40	40
CSNK1A1	0.034	0.046	0.12	68	-0.038	86	154
NLK	0.026	0.023	-10000	0	-0.032	56	56
CCND1	-0.08	0.35	0.79	3	-1.3	38	41
WNT1	0.036	0.007	-10000	0	0	16	16
GSK3A	0.035	0.009	-10000	0	0	28	28
GSK3B	0.034	0.01	-10000	0	0	40	40
FRAT1	0.025	0.017	-10000	0	0	161	161
PPP2R5D	0.023	0.044	-10000	0	-0.24	8	8
APC	0.04	0.1	0.18	161	-10000	0	161
WNT1/LRP6/FZD1	0.001	0.049	-10000	0	-0.25	12	12
CREBBP	0.033	0.043	0.11	70	-0.036	86	156

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.006	0.089	-9999	-0.17	89	89
FZD6	0.027	0.016	-9999	0	130	130
WNT6	0.037	0.002	-9999	0	1	1
WNT4	0.035	0.007	-9999	0	18	18
FZD3	0.029	0.015	-9999	0	110	110
WNT5A	0.029	0.015	-9999	0	99	99
WNT11	0.036	0.006	-9999	0	14	14

×

HIF-2-alpha transcription factor network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MMP14	-0.019	0.17	-10000	0	-0.66	31	31
oxygen homeostasis	0.004	0.02	0.044	66	-0.024	23	89
TCEB2	0.036	0.004	-10000	0	0	6	6
TCEB1	0.035	0.007	-10000	0	0	22	22
VHL/Elongin B/Elongin C/HIF2A	0.003	0.14	0.3	23	-0.24	45	68
EPO	-0.04	0.2	0.4	17	-0.44	52	69
FIH (dimer)	0.016	0.038	0.11	18	-0.04	50	68
APEX1	0.016	0.043	0.1	8	-0.053	23	31
SERPINE1	-0.074	0.2	0.37	2	-0.47	76	78
FLT1	-0.012	0.16	-10000	0	-0.67	23	23
ADORA2A	-0.037	0.24	0.44	35	-0.45	59	94
germ cell development	-0.036	0.23	0.43	33	-0.42	69	102
SLC11A2	-0.034	0.24	0.45	34	-0.44	67	101
BHLHE40	-0.039	0.23	0.43	32	-0.43	69	101
HIF1AN	0.016	0.038	0.11	18	-0.04	50	68
HIF2A/ARNT/SIRT1	-0.016	0.16	0.35	25	-0.3	52	77
ETS1	0.047	0.032	0.12	15	-0.11	11	26
CITED2	-0.058	0.26	-10000	0	-0.8	51	51
KDR	-0.001	0.16	-10000	0	-0.83	16	16
PGK1	-0.039	0.25	0.45	34	-0.45	75	109
SIRT1	0.024	0.017	-10000	0	0	171	171
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.028	0.27	0.48	12	-0.49	68	80
EPAS1	0	0.13	0.3	35	-0.26	39	74
SP1	0.041	0.011	0.11	8	-10000	0	8
ABCG2	-0.045	0.26	0.45	34	-0.46	82	116
EFNA1	-0.04	0.24	0.43	30	-0.45	70	100
FXN	-0.039	0.23	0.43	35	-0.43	68	103
POU5F1	-0.039	0.23	0.43	32	-0.43	69	101
neuron apoptosis	0.027	0.26	0.48	68	-0.47	12	80
EP300	0.033	0.011	-10000	0	0	49	49
EGLN3	0.019	0.039	0.11	15	-0.041	49	64
EGLN2	0.022	0.041	0.11	19	-0.041	38	57
EGLN1	0.023	0.041	0.11	19	-0.04	59	78
VHL/Elongin B/Elongin C	0.045	0.023	-10000	0	-0.12	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.016	0.043	0.11	7	-0.053	25	32
SLC2A1	-0.051	0.23	0.43	27	-0.45	71	98
TWIST1	-0.064	0.21	0.41	15	-0.43	85	100
ELK1	0.038	0.035	0.11	29	-0.095	25	54
HIF2A/ARNT/Cbp/p300	0.001	0.19	0.38	31	-0.32	49	80
VEGFA	-0.039	0.23	0.43	32	-0.43	69	101
CREBBP	0.036	0.005	-10000	0	0	8	8

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.006	0.1	0.19	87	-10000	0	87
GNAI2	0.034	0.01	-10000	0	0	43	43
S1P/S1P5/G12	0.009	0.03	-10000	0	-0.11	28	28
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
RhoA/GTP	0.007	0.11	-10000	0	-0.2	87	87
negative regulation of cAMP metabolic process	-0.007	0.099	-10000	0	-0.21	80	80
GNAZ	0.031	0.013	-10000	0	0	81	81
GNAI3	0.036	0.006	-10000	0	0	15	15
GNA12	0.023	0.018	-10000	0	0	193	193
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.007	0.1	-10000	0	-0.21	80	80
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
RHOA	0.035	0.007	-10000	0	0	18	18
GNAI1	0.018	0.018	-10000	0	0	263	263

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
CDC42/GTP	0.007	0.1	-10000	0	-0.19	84	84
PLCG1	-0.011	0.097	0.12	5	-0.2	83	88
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.034	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
cell migration	0.006	0.1	-10000	0	-0.19	84	84
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.012	0.098	0.12	4	-0.2	85	89
MAPK1	-0.006	0.094	0.12	5	-0.2	77	82
S1P/S1P5/Gi	-0.007	0.1	-10000	0	-0.21	80	80
GNAI1	0.018	0.018	-10000	0	0	263	263
CDC42/GDP	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.009	0.03	-10000	0	-0.11	28	28
RHOA	0.043	0.1	0.19	161	-0.18	3	164
S1P/S1P4/Gi	-0.007	0.1	-10000	0	-0.21	80	80
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.031	0.013	-10000	0	0	81	81
S1P/S1P4/G12/G13	0.023	0.037	-10000	0	-0.1	28	28
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
CDC42	0.035	0.008	-10000	0	0	24	24

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	0.003	0.026	-10000	0	-0.052	56	56
CDKN2C	-0.009	0.021	-10000	0	-0.035	121	121
CDKN2A	0.005	0.015	-10000	0	-0.043	1	1
CCND2	-0.001	0.018	0.11	6	-10000	0	6
RB1	-0.045	0.09	0.16	2	-0.18	139	141
CDK4	-0.001	0.02	0.13	6	-10000	0	6
CDK6	-0.001	0.02	0.13	6	-10000	0	6
G1/S progression	0.053	0.095	0.19	156	-0.16	2	158

×

LPA receptor mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.006	0.057	-10000	0	-0.14	60	60
NF kappa B1 p50/RelA/I kappa B alpha	0.007	0.096	0.21	11	-0.21	39	50
AP1	-0.009	0.073	0.089	13	-0.14	89	102
mol:PIP3	-0.024	0.05	-10000	0	-0.13	77	77
AKT1	0.002	0.094	0.2	19	-0.24	27	46
PTK2B	-0.002	0.058	0.13	3	-0.15	57	60
RHOA	0.022	0.078	0.17	26	-0.34	11	37
PIK3CB	0.035	0.007	-10000	0	0	18	18
mol:Ca2+	-0.009	0.04	0.19	5	-0.14	18	23
MAGI3	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
apoptosis	0.002	0.062	0.1	36	-0.16	53	89
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
positive regulation of microtubule depolymerization	-0.02	0.074	0.17	11	-0.21	36	47
NF kappa B1 p50/RelA	-0.021	0.066	0.08	51	-0.17	52	103
endothelial cell migration	-0.017	0.097	-10000	0	-0.3	53	53
ADCY4	-0.004	0.091	0.14	13	-0.26	36	49
ADCY5	-0.004	0.091	0.14	13	-0.26	36	49
ADCY6	0.001	0.092	0.16	14	-0.25	37	51
ADCY7	-0.002	0.096	0.15	16	-0.25	42	58
ADCY1	-0.009	0.083	0.15	9	-0.26	34	43
ADCY2	-0.001	0.094	0.16	14	-0.25	40	54
ADCY3	-0.004	0.091	0.14	13	-0.26	36	49
ADCY8	-0.002	0.091	0.15	17	-0.25	38	55
ADCY9	0	0.091	0.16	15	-0.24	39	54
GSK3B	-0.009	0.065	0.19	7	-0.19	25	32
arachidonic acid secretion	-0.016	0.11	0.15	14	-0.24	66	80
GNG2	0	0.001	0.002	1	-0.003	8	9
TRIP6	-0.016	0.085	-10000	0	-0.25	57	57
GNAO1	0.003	0.057	0.12	24	-0.16	47	71
HRAS	0.034	0.009	-10000	0	0	32	32
NFKBIA	-0.017	0.083	0.17	16	-0.22	37	53
GAB1	0.032	0.012	-10000	0	0	59	59
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.009	0.21	-10000	0	-0.8	31	31
JUN	0.034	0.01	-10000	0	0	40	40
LPA/LPA2/NHERF2	0.019	0.029	-10000	0	-0.061	53	53
TIAM1	-0.015	0.25	-10000	0	-0.98	31	31
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.008	0.039	0.22	3	-0.14	19	22
PLCB3	0.006	0.035	0.2	5	-10000	0	5
FOS	0.025	0.017	-10000	0	0	158	158
positive regulation of mitosis	-0.016	0.11	0.15	14	-0.24	66	80
LPA/LPA1-2-3	-0.008	0.04	-10000	0	-0.12	53	53
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	0.009	0.066	-10000	0	-0.28	9	9
GNAZ	0.003	0.063	0.12	28	-0.17	48	76
EGFR/PI3K-beta/Gab1	-0.02	0.054	-10000	0	-0.13	77	77
positive regulation of dendritic cell cytokine production	-0.008	0.04	-10000	0	-0.12	53	53
LPA/LPA2/MAGI-3	-0.004	0.017	-10000	0	-0.052	53	53
ARHGEF1	0.039	0.12	0.19	153	-0.17	34	187
GNAI2	0.004	0.069	0.12	40	-0.17	53	93
GNAI3	0.007	0.063	0.12	39	-0.15	53	92
GNAI1	0.002	0.047	0.12	19	-0.16	29	48
LPA/LPA3	-0.006	0.021	-10000	0	-0.066	53	53
LPA/LPA2	-0.005	0.021	-10000	0	-0.065	53	53
LPA/LPA1	-0.012	0.054	-10000	0	-0.17	53	53
HB-EGF/EGFR	-0.01	0.056	-10000	0	-0.14	66	66
HBEGF	0.011	0.046	0.092	116	-10000	0	116
mol:DAG	-0.008	0.039	0.22	3	-0.14	19	22
cAMP biosynthetic process	0.003	0.11	0.18	33	-0.26	43	76
NFKB1	0.035	0.007	-10000	0	0	18	18
SRC	0.036	0.006	-10000	0	0	14	14
GNB1	0.035	0.007	-10000	0	0	20	20
LYN	-0.023	0.095	0.17	19	-0.23	62	81
GNAQ	0.008	0.026	0.056	38	-0.058	55	93
LPAR2	0	0.001	-10000	0	-0.003	3	3
LPAR3	0	0.001	-10000	0	-0.002	1	1
LPAR1	-0.009	0.033	-10000	0	-0.1	53	53
IL8	-0.13	0.2	0.33	7	-0.39	157	164
PTK2	0.014	0.057	0.12	39	-0.14	50	89
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
CASP3	0.002	0.062	0.1	36	-0.16	53	89
EGFR	0.009	0.016	-10000	0	0	381	381
PLCG1	0.005	0.038	0.072	8	-0.1	35	43
PLD2	0.015	0.053	0.12	38	-0.12	52	90
G12/G13	0.018	0.062	-10000	0	-0.15	45	45
PI3K-beta	-0.014	0.069	-10000	0	-0.24	28	28
cell migration	-0.002	0.073	-10000	0	-0.25	29	29
SLC9A3R2	0.036	0.005	-10000	0	0	9	9
PXN	0.009	0.067	-10000	0	-0.29	9	9
HRAS/GTP	-0.018	0.11	0.16	8	-0.25	66	74
RAC1	0.024	0.017	-10000	0	0	173	173
MMP9	0.017	0.018	-10000	0	0	267	267
PRKCE	0.036	0.003	-10000	0	0	4	4
PRKCD	-0.005	0.054	0.18	14	-0.2	3	17
Gi(beta/gamma)	-0.009	0.12	0.17	11	-0.26	60	71
mol:LPA	-0.009	0.033	-10000	0	-0.1	53	53
TRIP6/p130 Cas/FAK1/Paxillin	-0.008	0.081	-10000	0	-0.22	43	43
MAPKKK cascade	-0.016	0.11	0.15	14	-0.24	66	80
contractile ring contraction involved in cytokinesis	0.021	0.08	0.18	21	-0.34	12	33
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.008	0.026	0.056	37	-0.058	55	92
GNA15	0.008	0.025	0.056	33	-0.057	51	84
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
MAPT	-0.02	0.075	0.17	11	-0.21	37	48
GNA11	0.011	0.022	0.056	37	-0.057	34	71
Rac1/GTP	-0.01	0.22	-10000	0	-0.85	31	31
MMP2	-0.017	0.097	-10000	0	-0.3	53	53

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.024	0.14	-10000	0	-0.37	21	21
MAP3K8	0.022	0.018	-10000	0	0	197	197
FOS	0.019	0.1	-10000	0	-0.36	13	13
PRKCA	0.029	0.025	-10000	0	-0.032	70	70
PTPN7	0.028	0.029	0.067	24	-0.037	72	96
HRAS	0.034	0.009	-10000	0	0	32	32
PRKCB	0	0.008	0.016	61	-0.013	76	137
NRAS	0.032	0.012	-10000	0	0	63	63
RAS family/GTP	0.042	0.065	-10000	0	-0.13	53	53
MAPK3	0.035	0.052	-10000	0	-0.33	2	2
MAP2K1	0.012	0.055	-10000	0	-0.22	12	12
ELK1	0.026	0.029	-10000	0	-0.04	80	80
BRAF	0.007	0.021	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.002	60	-0.004	77	137
MAPK1	0.008	0.13	-10000	0	-0.44	30	30
RAF1	-0.001	0.067	-10000	0	-0.34	17	17
KRAS	0.034	0.009	-10000	0	0	35	35

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.003	0	32	-10000	0	32
GNB1/GNG2	0.039	0.03	-10000	0	-0.1	20	20
regulation of S phase of mitotic cell cycle	-0.004	0.081	-10000	0	-0.18	72	72
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	32	32
SHBG/T-DHT	0.024	0.004	-10000	0	-10000	0	0
PELP1	0.035	0.007	-10000	0	0	17	17
AKT1	-0.01	0.004	0	53	-10000	0	53
MAP2K1	-0.035	0.076	0.18	14	-0.18	67	81
T-DHT/AR	0.025	0.008	-10000	0	-0.023	6	6
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	0.003	12	-0.006	76	88
GNAI2	0.033	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
mol:GDP	-0.02	0.036	-10000	0	-0.12	26	26
cell proliferation	-0.059	0.18	0.29	9	-0.42	85	94
PIK3CA	0.031	0.013	-10000	0	0	80	80
FOS	-0.087	0.28	0.38	3	-0.69	83	86
mol:Ca2+	-0.004	0.02	0.027	6	-0.053	59	65
MAPK3	-0.043	0.13	0.26	13	-0.3	78	91
MAPK1	-0.04	0.16	0.25	3	-0.49	37	40
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0	0.002	0.003	59	-0.004	74	133
cAMP biosynthetic process	-0.002	0.013	-10000	0	-10000	0	0
GNG2	0	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.002	0.003	59	-0.004	74	133
HRAS/GTP	0.043	0.065	-10000	0	-0.093	78	78
actin cytoskeleton reorganization	0.019	0.054	-10000	0	-0.12	45	45
SRC	0.035	0.006	-10000	0	0	14	14
voltage-gated calcium channel activity	0	0.002	0.003	59	-0.004	74	133
PI3K	0.019	0.063	-10000	0	-0.13	73	73
apoptosis	0.048	0.19	0.43	84	-0.3	5	89
T-DHT/AR/PELP1	0.043	0.023	-10000	0	-0.1	9	9
HRAS/GDP	0.007	0.06	-10000	0	-0.15	28	28
CREB1	-0.068	0.19	0.3	5	-0.46	84	89
RAC1-CDC42/GTP	0.027	0.06	-10000	0	-0.12	45	45
AR	0.035	0.008	-10000	0	0	22	22
GNB1	0.035	0.007	-10000	0	0	20	20
RAF1	-0.026	0.068	0.19	14	-0.22	13	27
RAC1-CDC42/GDP	0.02	0.053	-10000	0	-0.17	13	13
T-DHT/AR/PELP1/Src	0.06	0.032	-10000	0	-0.086	13	13
MAP2K2	-0.038	0.069	0.16	8	-0.17	67	75
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.081	-10000	0	-0.19	72	72
GNAZ	0.031	0.013	-10000	0	0	81	81
SHBG	0.036	0.006	-10000	0	0	14	14
Gi family/GNB1/GNG2/GDP	-0.038	0.17	-10000	0	-0.45	53	53
mol:T-DHT	0	0.001	0.002	1	-0.004	21	22
RAC1	0.024	0.017	-10000	0	0	173	173
GNRH1	-0.011	0.002	0	12	-0.017	1	13
Gi family/GTP	-0.005	0.082	-10000	0	-0.19	62	62
CDC42	0.035	0.008	-10000	0	0	24	24

×

Syndecan-1-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
TGFB1	0.032	0.012	-10000	0	0	66	66
CCL5	0.033	0.011	-10000	0	0	53	53
SDCBP	0.035	0.007	-10000	0	0	21	21
FGFR/FGF2/Syndecan-1	0.014	0.1	0.21	24	-0.24	10	34
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
RP11-540L11.1	0	0	-10000	0	-10000	0	0
Syndecan-1/Laminin-5	0.02	0.1	0.22	19	-0.25	11	30
Syndecan-1/Syntenin	0.025	0.11	0.23	25	-0.25	13	38
MAPK3	0.003	0.1	0.2	19	-0.23	18	37
HGF/MET	0.032	0.027	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.032	0.012	-10000	0	0	66	66
BSG	0.032	0.012	-10000	0	0	66	66
keratinocyte migration	0.02	0.1	0.22	19	-0.24	11	30
Syndecan-1/RANTES	0.019	0.1	0.23	18	-0.25	10	28
Syndecan-1/CD147	0.023	0.11	0.24	14	-0.24	18	32
Syndecan-1/Syntenin/PIP2	0.022	0.1	0.21	25	-0.24	13	38
LAMA5	0.032	0.012	-10000	0	0	65	65
positive regulation of cell-cell adhesion	0.022	0.1	0.21	25	-0.23	13	38
MMP7	0.027	0.016	-10000	0	0	137	137
HGF	0.024	0.017	-10000	0	0	177	177
Syndecan-1/CASK	-0.001	0.085	0.15	5	-0.24	10	15
Syndecan-1/HGF/MET	0.024	0.089	0.24	9	-0.25	5	14
regulation of cell adhesion	-0.004	0.11	0.24	27	-0.25	14	41
HPSE	0.032	0.012	-10000	0	0	59	59
positive regulation of cell migration	0.014	0.1	0.21	24	-0.24	10	34
SDC1	0.01	0.095	0.17	36	-0.25	9	45
Syndecan-1/Collagen	0.014	0.1	0.21	24	-0.24	10	34
PPIB	0.034	0.01	-10000	0	0	39	39
MET	0.023	0.018	-10000	0	0	191	191
PRKACA	0.035	0.008	-10000	0	0	25	25
MMP9	0.017	0.018	-10000	0	0	267	267
MAPK1	0.003	0.098	0.2	18	-0.24	18	36
homophilic cell adhesion	0.016	0.1	0.21	29	-0.25	9	38
MMP1	0.031	0.013	-10000	0	0	71	71

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.032	0.014	-10000	0	-0.005	56	56
ELF1	0.042	0.016	-10000	0	-10000	0	0
CCNA2	0.028	0.015	-10000	0	0	117	117
PIK3CA	0.03	0.015	-10000	0	-0.002	87	87
JAK3	0.034	0.012	-10000	0	-0.009	31	31
PIK3R1	0.032	0.014	-10000	0	-0.002	68	68
JAK1	0.033	0.012	-10000	0	-0.003	46	46
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.02	0.18	0.24	2	-0.53	39	41
SHC1	0.032	0.014	-10000	0	-0.004	60	60
SP1	-0.011	0.12	-10000	0	-0.27	89	89
IL2RA	0.011	0.012	-10000	0	-10000	0	0
IL2RB	0.032	0.014	-10000	0	-0.004	61	61
SOS1	0	0.002	-10000	0	-10000	0	0
IL2RG	0.034	0.011	-10000	0	-0.006	30	30
G1/S transition of mitotic cell cycle	-0.069	0.27	0.27	10	-0.58	95	105
PTPN11	0.035	0.01	-10000	0	-0.012	18	18
CCND2	-0.074	0.19	-10000	0	-0.49	89	89
LCK	0.035	0.01	-10000	0	-0.009	24	24
GRB2	0.035	0.01	-10000	0	-0.009	24	24
IL2	0.035	0.009	-10000	0	-0.012	17	17
CDK6	0.024	0.017	-10000	0	0	176	176
CCND3	-0.026	0.2	0.38	2	-0.74	27	29

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	0.014	0.061	0.14	1	-0.13	69	70
EPHB2	0.034	0.01	-10000	0	0	42	42
Syndecan-2/TACI	0.017	0.055	0.14	1	-0.12	66	67
LAMA1	0	0	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.022	0.073	-10000	0	-0.12	83	83
HRAS	0.034	0.009	-10000	0	0	32	32
Syndecan-2/CASK	-0.009	0.041	-10000	0	-0.11	69	69
ITGA5	0.033	0.011	-10000	0	0	56	56
BAX	-0.009	0.073	-10000	0	-0.9	3	3
EPB41	0.036	0.005	-10000	0	0	9	9
positive regulation of cell-cell adhesion	0.013	0.054	-10000	0	-0.11	73	73
LAMA3	0.033	0.011	-10000	0	0	48	48
EZR	0	0	-10000	0	-10000	0	0
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
CAV2	0.019	0.018	-10000	0	0	246	246
Syndecan-2/MMP2	0.009	0.062	0.14	1	-0.14	65	66
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.019	0.054	-10000	0	-0.14	42	42
dendrite morphogenesis	0.015	0.054	0.14	1	-0.12	62	63
Syndecan-2/GM-CSF	0.017	0.055	0.14	1	-0.12	64	65
determination of left/right symmetry	0.007	0.024	0.085	5	-0.24	4	9
Syndecan-2/PKC delta	0.016	0.054	0.14	1	-0.12	62	63
GNB2L1	0.036	0.002	-10000	0	0	2	2
MAPK3	-0.023	0.051	0.11	34	-0.12	20	54
MAPK1	-0.02	0.05	0.12	31	-0.13	18	49
Syndecan-2/RACK1	0.03	0.063	0.14	3	-0.11	77	80
NF1	0.036	0.003	-10000	0	0	4	4
FGFR/FGF/Syndecan-2	0.007	0.024	0.085	5	-0.24	4	9
ITGA2	0.029	0.015	-10000	0	0	112	112
MAPK8	-0.005	0.038	0.13	3	-0.39	3	6
Syndecan-2/alpha2/beta1 Integrin	0.007	0.063	0.14	1	-0.11	92	93
Syndecan-2/Kininogen	0.016	0.054	0.14	1	-0.12	63	64
ITGB1	0.027	0.016	-10000	0	0	138	138
SRC	-0.026	0.051	0.17	11	-0.19	8	19
Syndecan-2/CASK/Protein 4.1	0.015	0.05	-10000	0	-0.1	68	68
extracellular matrix organization	0.014	0.051	-10000	0	-0.12	57	57
actin cytoskeleton reorganization	0.014	0.061	0.14	1	-0.13	69	70
Syndecan-2/Caveolin-2/Ras	0.007	0.067	0.15	2	-0.13	75	77
Syndecan-2/Laminin alpha3	0.016	0.052	0.14	1	-0.12	60	61
Syndecan-2/RasGAP	0.037	0.078	-10000	0	-0.12	89	89
alpha5/beta1 Integrin	0.029	0.042	-10000	0	-0.14	20	20
PRKCD	0.034	0.01	-10000	0	0	40	40
Syndecan-2 dimer	0.015	0.054	0.14	1	-0.12	62	63
GO:0007205	0.001	0.011	-10000	0	-0.12	4	4
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.014	0.067	0.19	1	-0.13	75	76
RHOA	0.035	0.007	-10000	0	0	18	18
SDCBP	0.035	0.007	-10000	0	0	21	21
TNFRSF13B	0.036	0.005	-10000	0	0	8	8
RASA1	0.034	0.009	-10000	0	0	32	32
alpha2/beta1 Integrin	0.019	0.054	-10000	0	-0.14	42	42
Syndecan-2/Synbindin	0.016	0.059	0.14	1	-0.13	67	68
TGFB1	0.032	0.012	-10000	0	0	66	66
CASP3	-0.016	0.052	0.11	32	-0.2	4	36
FN1	0.035	0.009	-10000	0	0	29	29
Syndecan-2/IL8	-0.003	0.069	-10000	0	-0.17	61	61
SDC2	0.007	0.024	0.085	5	-0.24	4	9
KNG1	0.035	0.008	-10000	0	0	28	28
Syndecan-2/Neurofibromin	0.017	0.056	0.14	1	-0.12	68	69
TRAPPC4	0.036	0.006	-10000	0	0	15	15
CSF2	0.036	0.005	-10000	0	0	10	10
Syndecan-2/TGFB1	0.015	0.051	-10000	0	-0.12	57	57
Syndecan-2/Syntenin/PI-4-5-P2	0.013	0.055	-10000	0	-0.11	73	73
Syndecan-2/Ezrin	0.014	0.053	-10000	0	-0.11	70	70
PRKACA	-0.021	0.051	0.12	35	-0.18	3	38
angiogenesis	-0.003	0.068	-10000	0	-0.17	61	61
MMP2	0.029	0.015	-10000	0	0	108	108
IL8	0.019	0.018	-10000	0	0	243	243
calcineurin-NFAT signaling pathway	0.017	0.055	0.14	1	-0.12	66	67

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.047	0.082	0.37	1	-10000	0	1
CRKL	0.043	0.09	0.16	146	-10000	0	146
mol:DAG	0.016	0.063	0.21	2	-0.19	28	30
HRAS	0.043	0.1	0.23	61	-0.19	2	63
MAPK8	0.012	0.076	0.16	83	-0.13	7	90
RAP1A	0.049	0.093	0.16	186	-10000	0	186
GAB1	0.04	0.087	0.16	161	-10000	0	161
MAPK14	0.034	0.1	0.17	153	-0.13	8	161
EPO	0.027	0.02	-10000	0	-0.032	2	2
PLCG1	0.016	0.063	0.21	2	-0.19	28	30
EPOR/TRPC2/IP3 Receptors	0.041	0.013	-10000	0	-0.032	2	2
RAPGEF1	0.035	0.007	-10000	0	0	19	19
EPO/EPOR (dimer)/SOCS3	0.051	0.038	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.06	0.072	0.21	28	-10000	0	28
EPO/EPOR (dimer)	0.039	0.03	-10000	0	-10000	0	0
IRS2	0.038	0.088	0.16	130	-0.16	4	134
STAT1	0.02	0.066	0.23	4	-0.21	12	16
STAT5B	0.019	0.066	0.23	3	-0.19	29	32
cell proliferation	0.008	0.075	0.16	84	-0.12	7	91
GAB1/SHIP/PIK3R1/SHP2/SHC	0.037	0.064	0.16	3	-0.18	6	9
TEC	0.049	0.093	0.16	160	-10000	0	160
SOCS3	0.036	0.004	-10000	0	0	7	7
STAT1 (dimer)	0.02	0.065	0.23	4	-0.22	8	12
JAK2	0.037	0.018	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPO/EPOR (dimer)/JAK2	0.047	0.053	0.22	11	-10000	0	11
EPO/EPOR	0.039	0.03	-10000	0	-10000	0	0
LYN	0.032	0.014	-10000	0	-10000	0	0
TEC/VAV2	0.036	0.085	0.2	37	-10000	0	37
elevation of cytosolic calcium ion concentration	0.041	0.013	-10000	0	-0.032	2	2
SHC1	0.033	0.011	-10000	0	0	52	52
EPO/EPOR (dimer)/LYN	0.04	0.059	-10000	0	-0.13	29	29
mol:IP3	0.016	0.063	0.21	2	-0.19	28	30
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.023	0.093	0.16	135	-0.17	11	146
SH2B3	-0.001	0.006	0.026	8	-10000	0	8
NFKB1	0.034	0.1	0.17	149	-0.14	8	157
EPO/EPOR (dimer)/JAK2/SOCS3	0.015	0.015	-10000	0	-10000	0	0
PTPN6	0.049	0.094	0.17	167	-10000	0	167
TEC/VAV2/GRB2	0.082	0.071	0.23	33	-10000	0	33
EPOR	0.041	0.013	-10000	0	-0.032	2	2
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.06	0.072	0.21	28	-10000	0	28
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.032	0.012	-10000	0	0	63	63
CRKL/CBL/C3G	0.08	0.067	0.22	28	-10000	0	28
VAV2	0.047	0.091	0.16	154	-10000	0	154
CBL	0.049	0.093	0.16	186	-10000	0	186
SHC/Grb2/SOS1	0.021	0.035	-10000	0	-0.1	4	4
STAT5A	0.019	0.065	0.25	2	-0.19	28	30
GRB2	0.035	0.007	-10000	0	0	17	17
STAT5 (dimer)	0.034	0.073	0.27	5	-0.22	2	7
LYN/PLCgamma2	0.026	0.07	-10000	0	-0.17	53	53
PTPN11	0.036	0.005	-10000	0	0	11	11
BTK	0.046	0.093	0.16	182	-10000	0	182
BCL2	0.047	0.082	0.31	1	-10000	0	1

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	0.029	0.085	-10000	0	-0.14	87	87
alphaM/beta2 Integrin/GPIbA	0.049	0.069	-10000	0	-0.12	59	59
alphaM/beta2 Integrin/proMMP-9	-0.008	0.09	-10000	0	-0.13	145	145
PLAUR	0.03	0.014	-10000	0	0	89	89
HMGB1	0.038	0.015	0.082	1	-10000	0	1
alphaM/beta2 Integrin/Talin	0.038	0.071	-10000	0	-0.13	56	56
AGER	0.041	0.01	0.08	2	-10000	0	2
RAP1A	0.036	0.005	-10000	0	0	11	11
SELPLG	0.036	0.004	-10000	0	0	6	6
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.074	0.084	-10000	0	-0.12	50	50
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.017	0.018	-10000	0	0	267	267
CYR61	0.025	0.017	-10000	0	0	166	166
TLN1	0.029	0.015	-10000	0	0	102	102
Rap1/GTP	0.028	0.072	-10000	0	-0.22	17	17
RHOA	0.035	0.007	-10000	0	0	18	18
P-selectin oligomer	0.036	0.006	-10000	0	0	14	14
MYH2	0.025	0.071	0.18	3	-0.28	8	11
MST1R	0.035	0.007	-10000	0	0	21	21
leukocyte activation during inflammatory response	0.056	0.064	-10000	0	-0.1	54	54
APOB	0.036	0.006	-10000	0	0	14	14
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.029	0.015	-10000	0	0	108	108
JAM3	0.033	0.011	-10000	0	0	51	51
GP1BA	0.036	0.005	-10000	0	0	10	10
alphaM/beta2 Integrin/CTGF	0.021	0.085	-10000	0	-0.13	101	101
alphaM/beta2 Integrin	0.024	0.072	0.17	1	-0.24	15	16
JAM3 homodimer	0.033	0.011	-10000	0	0	51	51
ICAM2	0.034	0.009	-10000	0	0	31	31
ICAM1	0.031	0.014	-10000	0	0	84	84
phagocytosis triggered by activation of immune response cell surface activating receptor	0.025	0.075	0.17	1	-0.24	16	17
cell adhesion	0.048	0.068	-10000	0	-0.12	59	59
NFKB1	-0.002	0.078	0.21	20	-10000	0	20
THY1	0.031	0.013	-10000	0	0	79	79
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
Lipoprotein(a)	0.045	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.038	0.1	-10000	0	-0.14	100	100
IL6	-0.015	0.039	-10000	0	-10000	0	0
ITGB2	0.033	0.019	0.077	1	-10000	0	1
elevation of cytosolic calcium ion concentration	0.03	0.085	-10000	0	-0.14	67	67
alphaM/beta2 Integrin/JAM2/JAM3	0.049	0.1	-10000	0	-0.15	91	91
JAM2	0.033	0.012	-10000	0	0	57	57
alphaM/beta2 Integrin/ICAM1	0.077	0.076	-10000	0	-0.12	45	45
alphaM/beta2 Integrin/uPA/Plg	0.041	0.08	-10000	0	-0.12	62	62
RhoA/GTP	0.029	0.073	0.17	11	-0.24	14	25
positive regulation of phagocytosis	0.017	0.1	0.21	1	-0.23	56	57
Ron/MSP	0.051	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.032	0.087	-10000	0	-0.14	67	67
alphaM/beta2 Integrin/uPAR	0.038	0.076	-10000	0	-0.13	63	63
PLAU	0.019	0.018	-10000	0	0	237	237
PLAT	0.027	0.016	-10000	0	0	128	128
actin filament polymerization	0.027	0.073	0.21	6	-0.27	8	14
MST1	0.035	0.008	-10000	0	0	25	25
alphaM/beta2 Integrin/lipoprotein(a)	0.062	0.068	-10000	0	-0.1	54	54
TNF	0.006	0.088	0.21	17	-10000	0	17
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.019	0.073	-10000	0	-0.14	65	65
fibrinolysis	0.039	0.079	-10000	0	-0.12	62	62
HCK	0.027	0.016	-10000	0	0	128	128
dendritic cell antigen processing and presentation	0.025	0.075	0.17	1	-0.24	16	17
VTN	0.036	0.004	-10000	0	0	6	6
alphaM/beta2 Integrin/CYR61	0.011	0.092	-10000	0	-0.14	120	120
LPA	0.034	0.009	-10000	0	0	33	33
LRP1	0.031	0.013	-10000	0	0	71	71
cell migration	0.001	0.11	0.15	36	-0.14	149	185
FN1	0.035	0.009	-10000	0	0	29	29
alphaM/beta2 Integrin/Thy1	0.031	0.084	-10000	0	-0.13	90	90
MPO	0.036	0.004	-10000	0	0	5	5
KNG1	0.035	0.008	-10000	0	0	28	28
RAP1/GDP	0.024	0.007	-10000	0	-0.11	1	1
ROCK1	0.025	0.073	0.19	2	-0.27	11	13
ELA2	0.034	0.009	-10000	0	0	32	32
PLG	0.034	0.01	-10000	0	0	37	37
CTGF	0.026	0.016	-10000	0	0	141	141
alphaM/beta2 Integrin/Hck	0.031	0.092	-10000	0	-0.18	72	72
ITGAM	0.042	0.01	0.08	2	-10000	0	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.071	0.072	-10000	0	-0.12	54	54
HP	0.027	0.016	-10000	0	0	136	136
leukocyte adhesion	0.023	0.12	-10000	0	-0.21	65	65
SELP	0.036	0.006	-10000	0	0	14	14

×

Glypican 2 network

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
MDK	0.03	0.014	-9999	0	92	92
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.007	0.05	-9999	-0.13	57	57
neuron projection morphogenesis	0.007	0.05	-9999	-0.13	57	57

×

JNK signaling in the CD4+ TCR pathway

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
LAT/GRAP2/SLP76/HPK1	0.069	0.057	-10000	0	-0.12	32	32
MAP4K1	0.035	0.008	-10000	0	0	26	26
MAP3K8	0.022	0.018	-10000	0	0	196	196
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
MAP3K1	0	0.054	0.13	1	-0.16	32	33
JUN	-0.14	0.24	-10000	0	-0.51	138	138
MAP3K7	0	0.052	-10000	0	-0.17	30	30
GRAP2	0.034	0.009	-10000	0	0	35	35
CRK	0.035	0.008	-10000	0	0	23	23
MAP2K4	-0.016	0.071	-10000	0	-0.25	20	20
LAT	0.036	0.005	-10000	0	0	10	10
LCP2	0.031	0.013	-10000	0	0	77	77
MAPK8	-0.13	0.25	-10000	0	-0.54	138	138
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.01	0.056	-10000	0	-0.16	33	33
LAT/GRAP2/SLP76/HPK1/HIP-55	0.063	0.054	-10000	0	-0.11	32	32

×

IL23-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCL2	-0.064	0.6	0.74	36	-1	127	163
IL23A	0.089	0.37	0.78	20	-0.95	23	43
NF kappa B1 p50/RelA/I kappa B alpha	0.08	0.34	0.62	22	-0.84	25	47
positive regulation of T cell mediated cytotoxicity	0.088	0.4	0.77	36	-0.94	25	61
ITGA3	0.088	0.36	0.74	23	-0.91	21	44
IL17F	0.034	0.27	0.51	33	-0.59	28	61
IL12B	0.061	0.079	0.2	70	-0.075	2	72
STAT1 (dimer)	0.07	0.36	0.65	32	-0.91	25	57
CD4	0.071	0.42	0.75	29	-1.1	31	60
IL23	0.096	0.36	0.73	18	-0.93	22	40
IL23R	0.067	0.14	0.28	93	-0.15	11	104
IL1B	0.083	0.4	0.75	30	-1.1	26	56
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.097	0.36	0.7	30	-0.88	19	49
TYK2	0.043	0.059	0.15	49	-10000	0	49
STAT4	0.035	0.009	-10000	0	0	29	29
STAT3	0.034	0.01	-10000	0	0	37	37
IL18RAP	0.035	0.008	-10000	0	-0.031	4	4
IL12RB1	0.045	0.059	0.15	53	-10000	0	53
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL12Rbeta1/TYK2	0.055	0.074	0.19	38	-0.13	11	49
IL23R/JAK2	0.1	0.16	0.38	75	-0.19	16	91
positive regulation of chronic inflammatory response	0.088	0.4	0.77	36	-0.94	25	61
natural killer cell activation	-0.005	0.011	-10000	0	-0.031	39	39
JAK2	0.056	0.079	0.2	68	-10000	0	68
PIK3R1	0.032	0.012	-10000	0	0	63	63
NFKB1	0.039	0.009	0.066	2	0	18	20
RELA	0.039	0.008	0.066	2	0	9	11
positive regulation of dendritic cell antigen processing and presentation	0.098	0.35	0.71	20	-0.89	22	42
ALOX12B	0.085	0.36	0.69	30	-0.87	21	51
CXCL1	0.095	0.37	0.73	39	-0.85	24	63
T cell proliferation	0.088	0.4	0.77	36	-0.94	25	61
NFKBIA	0.036	0.014	0.066	2	0	57	59
IL17A	0.058	0.24	0.46	51	-0.46	29	80
PI3K	0.046	0.35	0.64	22	-0.86	27	49
IFNG	0.019	0.033	0.098	28	-0.081	6	34
STAT3 (dimer)	0.048	0.35	0.61	27	-0.84	27	54
IL18R1	0.035	0.008	-10000	0	-0.032	5	5
IL23/IL23R/JAK2/TYK2/SOCS3	0.094	0.27	0.55	51	-0.51	22	73
IL18/IL18R	0.062	0.035	-10000	0	-0.12	7	7
macrophage activation	-0.002	0.016	0.038	1	-0.043	15	16
TNF	0.091	0.36	0.76	20	-0.95	18	38
STAT3/STAT4	0.068	0.36	0.62	25	-0.88	27	52
STAT4 (dimer)	0.07	0.36	0.63	30	-0.89	27	57
IL18	0.031	0.013	-10000	0	-0.03	1	1
IL19	0.098	0.36	0.75	19	-0.88	19	38
STAT5A (dimer)	0.083	0.37	0.64	35	-0.88	27	62
STAT1	0.034	0.01	-10000	0	0	40	40
SOCS3	0.036	0.004	-10000	0	0	7	7
CXCL9	0.099	0.37	0.73	33	-0.87	21	54
MPO	0.086	0.36	0.69	30	-0.86	22	52
positive regulation of humoral immune response	0.088	0.4	0.77	36	-0.94	25	61
IL23/IL23R/JAK2/TYK2	0.086	0.4	0.77	36	-0.98	24	60
IL6	0.15	0.37	0.74	44	-0.89	18	62
STAT5A	0.036	0.004	-10000	0	0	5	5
IL2	0.022	0.03	-10000	0	-0.036	102	102
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.011	-10000	0	-0.031	39	39
CD3E	0.086	0.36	0.7	26	-0.89	19	45
keratinocyte proliferation	0.088	0.4	0.77	36	-0.94	25	61
NOS2	0.087	0.36	0.68	37	-0.82	27	64

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.032	0.012	-10000	0	0	63	63
LAT2	-0.016	0.094	0.16	1	-0.28	46	47
AP1	-0.058	0.18	-10000	0	-0.39	68	68
mol:PIP3	0.021	0.14	0.28	30	-0.3	34	64
IKBKB	0.011	0.094	0.2	31	-0.19	35	66
AKT1	-0.055	0.1	0.26	9	-0.29	33	42
IKBKG	0.01	0.093	0.2	31	-0.19	35	66
MS4A2	0.039	0.008	0.066	4	0	5	9
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
MAP3K1	-0.023	0.12	0.25	6	-0.31	49	55
mol:Ca2+	0.023	0.12	0.24	34	-0.24	34	68
LYN	0.03	0.015	-10000	0	-0.034	6	6
CBLB	-0.023	0.11	0.16	2	-0.28	66	68
SHC1	0.033	0.011	-10000	0	0	52	52
RasGAP/p62DOK	0.048	0.052	-10000	0	-0.12	36	36
positive regulation of cell migration	-0.011	0.003	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.032	0.071	0.26	13	-0.17	11	24
PTPN13	-0.036	0.19	-10000	0	-0.6	38	38
PTPN11	0.031	0.022	-10000	0	-0.035	47	47
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.036	0.11	0.24	6	-0.32	34	40
SYK	0.03	0.015	-10000	0	-0.034	6	6
GRB2	0.036	0.007	-10000	0	0	17	17
LAT/PLCgamma1/GRB2/SLP76/GADs	0.009	0.11	0.21	3	-0.28	50	53
LAT	-0.021	0.11	0.18	3	-0.28	65	68
PAK2	-0.022	0.13	0.23	6	-0.33	50	56
NFATC2	-0.013	0.013	-10000	0	-0.043	69	69
HRAS	-0.02	0.14	0.22	4	-0.35	52	56
GAB2	0.033	0.011	-10000	0	0	47	47
PLA2G1B	-0.005	0.19	-10000	0	-0.92	20	20
Fc epsilon R1	0.042	0.067	-10000	0	-0.11	72	72
Antigen/IgE/Fc epsilon R1	0.044	0.06	-10000	0	-0.093	72	72
mol:GDP	-0.013	0.14	0.22	2	-0.36	48	50
JUN	0.034	0.01	-10000	0	0	40	40
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
FOS	0.025	0.017	-10000	0	0	158	158
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.015	0.12	-10000	0	-0.29	68	68
CHUK	0.012	0.091	0.2	33	-0.19	32	65
KLRG1	-0.018	0.099	0.14	2	-0.28	47	49
VAV1	-0.021	0.11	0.16	4	-0.28	59	63
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.024	0.11	0.16	2	-0.28	68	70
negative regulation of mast cell degranulation	-0.021	0.092	0.12	1	-0.25	51	52
BTK	-0.012	0.13	-10000	0	-0.38	44	44
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.027	0.11	-10000	0	-0.18	134	134
GAB2/PI3K/SHP2	-0.068	0.073	-10000	0	-0.2	80	80
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.003	0.072	-10000	0	-0.19	57	57
RAF1	-0.007	0.2	-10000	0	-0.97	20	20
Fc epsilon R1/FcgammaRIIB/SHIP	0.024	0.095	-10000	0	-0.13	129	129
FCER1G	0.029	0.016	-10000	0	0	113	113
FCER1A	0.033	0.013	-10000	0	-0.032	9	9
Antigen/IgE/Fc epsilon R1/Fyn	0.041	0.082	-10000	0	-0.11	99	99
MAPK3	-0.004	0.19	-10000	0	-0.9	20	20
MAPK1	-0.013	0.2	-10000	0	-0.95	20	20
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.12	0.28	-10000	0	-0.56	143	143
DUSP1	0.031	0.013	-10000	0	0	77	77
NF-kappa-B/RelA	0.018	0.066	0.14	27	-0.13	35	62
actin cytoskeleton reorganization	-0.027	0.19	-10000	0	-0.6	36	36
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.01	0.15	0.23	8	-0.35	53	61
FER	-0.022	0.12	0.16	3	-0.28	68	71
RELA	0.036	0.005	-10000	0	0	9	9
ITK	0.001	0.04	-10000	0	-0.26	4	4
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.007	0.14	0.25	8	-0.35	43	51
cytokine secretion	0.01	0.045	0.091	21	-0.094	37	58
SPHK1	-0.02	0.12	0.15	4	-0.28	66	70
PTK2	-0.03	0.2	-10000	0	-0.64	36	36
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.025	0.12	0.28	3	-0.28	48	51
EDG1	-0.011	0.003	-10000	0	-10000	0	0
mol:DAG	0.003	0.15	0.26	30	-0.33	42	72
MAP2K2	-0.005	0.2	-10000	0	-0.92	20	20
MAP2K1	-0.017	0.19	-10000	0	-0.92	20	20
MAP2K7	0.035	0.008	-10000	0	0	24	24
KLRG1/SHP2	0.001	0.097	0.2	8	-0.25	46	54
MAP2K4	0.025	0.14	-10000	0	-0.9	11	11
Fc epsilon R1/FcgammaRIIB	0.026	0.1	-10000	0	-0.14	129	129
mol:Choline	-0.031	0.07	0.26	13	-0.17	11	24
SHC/Grb2/SOS1	0.011	0.13	0.2	1	-0.28	62	63
FYN	0.03	0.014	-10000	0	0	90	90
DOK1	0.036	0.002	-10000	0	0	2	2
PXN	-0.03	0.19	-10000	0	-0.59	36	36
HCLS1	-0.025	0.13	0.16	6	-0.32	65	71
PRKCB	0.013	0.12	0.23	32	-0.24	38	70
FCGR2B	0.021	0.018	-10000	0	0	222	222
IGHE	-0.001	0.004	0.023	1	-10000	0	1
KLRG1/SHIP	-0.022	0.094	0.12	1	-0.26	51	52
LCP2	0.031	0.013	-10000	0	0	77	77
PLA2G4A	-0.016	0.12	0.16	10	-0.3	59	69
RASA1	0.034	0.009	-10000	0	0	32	32
mol:Phosphatidic acid	-0.031	0.07	0.26	13	-0.17	11	24
IKK complex	0.008	0.079	0.19	27	-0.16	20	47
WIPF1	0	0	-10000	0	-10000	0	0

×

PLK2 and PLK4 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	0.031	0.014	-10000	0	0	83	83
PLK4	0.035	0.007	-10000	0	0	20	20
regulation of centriole replication	-0.011	0.032	0.092	43	-9999	0	43

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.002	0.077	0.2	2	-0.19	36	38
NF kappa B1 p50/RelA/I kappa B alpha	-0.019	0.12	0.25	1	-0.32	43	44
alphaV/beta3 Integrin/Osteopontin/Src	0.026	0.081	-10000	0	-0.16	74	74
AP1	-0.011	0.14	0.28	6	-0.28	75	81
ILK	-0.031	0.072	0.2	2	-0.23	33	35
bone resorption	-0.039	0.083	0.18	7	-0.24	35	42
PTK2B	0.035	0.006	-10000	0	0	16	16
PYK2/p130Cas	0.045	0.09	-10000	0	-0.16	59	59
ITGAV	0.031	0.026	-10000	0	-0.056	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.02	0.068	-10000	0	-0.14	73	73
alphaV/beta3 Integrin/Osteopontin	0.05	0.092	-10000	0	-0.16	72	72
MAP3K1	-0.03	0.063	0.22	1	-0.2	27	28
JUN	0.034	0.01	-10000	0	0	40	40
MAPK3	-0.031	0.085	0.18	6	-0.24	40	46
MAPK1	-0.029	0.086	0.17	12	-0.25	38	50
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.027	0.059	0.23	1	-0.2	26	27
ITGB3	0.032	0.026	-10000	0	-0.055	39	39
NFKBIA	-0.038	0.11	0.18	5	-0.32	44	49
FOS	0.026	0.017	-10000	0	0	158	158
CD44	0.029	0.015	-10000	0	0	110	110
CHUK	0.025	0.017	-10000	0	0	163	163
PLAU	-0.071	0.25	-10000	0	-0.97	32	32
NF kappa B1 p50/RelA	-0.001	0.12	-10000	0	-0.34	36	36
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
alphaV beta3 Integrin	0.04	0.058	-10000	0	-0.13	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.032	0.065	0.19	2	-0.23	29	31
VAV3	-0.024	0.072	0.18	3	-0.22	33	36
MAP3K14	-0.028	0.074	0.17	5	-0.23	24	29
ROCK2	0.035	0.007	-10000	0	0	21	21
SPP1	0.03	0.026	-10000	0	-0.058	29	29
RAC1	0.024	0.017	-10000	0	0	173	173
Rac1/GTP	-0.021	0.07	0.17	1	-0.22	28	29
MMP2	-0.061	0.12	-10000	0	-0.32	61	61

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	0.044	0.042	-10000	0	-0.14	24	24
AKT1	-0.017	0.17	0.27	20	-0.41	48	68
PTK2B	-0.001	0.11	0.2	57	-0.3	19	76
VEGFR2 homodimer/Frs2	0.026	0.082	0.18	5	-0.31	17	22
CAV1	0.016	0.018	-10000	0	0	290	290
CALM1	0.033	0.011	-10000	0	0	54	54
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.022	0.085	0.18	2	-0.27	22	24
endothelial cell proliferation	0.011	0.14	0.28	30	-0.38	29	59
mol:Ca2+	0.006	0.13	0.21	88	-0.24	47	135
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.017	0.087	0.2	2	-0.27	23	25
RP11-342D11.1	-0.005	0.1	0.17	69	-0.23	46	115
CDH5	0.03	0.014	-10000	0	0	92	92
VEGFA homodimer	0.036	0.034	-10000	0	-0.098	13	13
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	0.032	0.012	-10000	0	0	64	64
HRAS/GDP	0.005	0.09	-10000	0	-0.24	46	46
SH2D2A	0.036	0.006	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.021	0.11	0.28	3	-0.37	16	19
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.022	0.086	0.18	2	-0.28	22	24
VEGFR1 homodimer	0.034	0.009	-10000	0	0	33	33
SHC/GRB2/SOS1	0.036	0.1	-10000	0	-0.23	47	47
GRB10	-0.011	0.11	0.2	39	-0.32	34	73
PTPN11	0.036	0.005	-10000	0	0	11	11
GRB2	0.035	0.007	-10000	0	0	17	17
PAK1	0.036	0.006	-10000	0	0	15	15
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.037	0.12	0.22	2	-0.27	38	40
HRAS	0.034	0.009	-10000	0	0	32	32
VEGF/Rho/ROCK1/Integrin Complex	0.012	0.1	0.18	5	-0.32	30	35
HIF1A	0.033	0.01	-10000	0	0	44	44
FRS2	0.034	0.009	-10000	0	0	30	30
oxygen and reactive oxygen species metabolic process	0.016	0.085	0.19	2	-0.27	23	25
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.036	0.006	-10000	0	0	12	12
Nck/Pak	0.049	0.023	-10000	0	-0.14	5	5
VEGFR2 homodimer/VEGFA homodimer/Fyn	0.01	0.1	0.18	2	-0.28	33	35
mol:GDP	0.017	0.093	-10000	0	-0.23	47	47
mol:NADP	0.032	0.12	0.32	19	-0.34	14	33
eNOS/Hsp90	0.029	0.12	0.3	19	-0.32	15	34
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.006	0.13	0.22	88	-0.24	47	135
HIF1A/ARNT	0.046	0.031	-10000	0	-0.14	11	11
SHB	0.033	0.011	-10000	0	0	51	51
VEGFA	-0.003	0.013	-10000	0	-0.039	52	52
VEGFC	0.033	0.011	-10000	0	0	51	51
FAK1/Vinculin	0.012	0.12	0.26	13	-0.44	19	32
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.035	0.007	-10000	0	0	18	18
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.037	0.1	0.2	5	-0.27	27	32
PTPN6	0.033	0.011	-10000	0	0	51	51
EPAS1	0.032	0.062	-10000	0	-0.22	17	17
mol:L-citrulline	0.032	0.12	0.32	19	-0.34	14	33
ITGAV	0.034	0.009	-10000	0	0	31	31
PIK3CA	0.031	0.013	-10000	0	0	80	80
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.039	0.094	0.2	5	-0.26	25	30
VEGFR2 homodimer/VEGFA homodimer	0.012	0.097	-10000	0	-0.23	56	56
VEGFR2/3 heterodimer	0.026	0.084	0.18	5	-0.31	18	23
VEGFB	0.036	0.005	-10000	0	0	8	8
MAPK11	0.009	0.13	0.27	42	-0.33	21	63
VEGFR2 homodimer	-0.006	0.081	0.17	4	-0.38	15	19
FLT1	0.034	0.009	-10000	0	0	33	33
NEDD4	0.029	0.033	0.088	9	-0.056	54	63
MAPK3	0.012	0.12	0.27	44	-0.3	20	64
MAPK1	0.01	0.13	0.27	45	-0.28	23	68
VEGFA145/NRP2	0.023	0.022	-10000	0	-0.045	7	7
VEGFR1/2 heterodimer	0.024	0.083	0.18	4	-0.31	18	22
KDR	-0.006	0.082	0.17	4	-0.38	15	19
VEGFA165/NRP1/VEGFR2 homodimer	0.024	0.098	0.2	12	-0.23	47	59
SRC	0.036	0.006	-10000	0	0	14	14
platelet activating factor biosynthetic process	0.012	0.13	0.26	47	-0.3	21	68
PI3K	-0.001	0.14	0.24	28	-0.34	44	72
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.021	0.086	0.18	2	-0.27	22	24
FES	0.007	0.13	0.22	89	-0.31	21	110
GAB1	0.012	0.12	0.24	17	-0.36	26	43
VEGFR2 homodimer/VEGFA homodimer/Src	0.021	0.086	0.17	1	-0.28	22	23
CTNNB1	0.036	0.006	-10000	0	0	15	15
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0.036	0.004	-10000	0	0	5	5
eNOS/Caveolin-1	0.009	0.095	0.29	4	-0.37	12	16
VEGFR2 homodimer/VEGFA homodimer/Yes	0.018	0.09	0.18	1	-0.3	22	23
PI3K/GAB1	-0.003	0.16	0.26	25	-0.39	48	73
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.06	0.097	0.23	3	-0.25	21	24
PRKACA	0.035	0.008	-10000	0	0	25	25
VEGFR2/3 heterodimer/VEGFC homodimer	0.038	0.08	0.2	1	-0.28	16	17
HSP90AA1	0	0	-10000	0	-10000	0	0
CDC42	0.007	0.13	0.22	86	-0.32	20	106
actin cytoskeleton reorganization	0.022	0.086	0.18	2	-0.27	22	24
PTK2	0.009	0.13	0.25	22	-0.44	21	43
EDG1	0	0.14	0.22	78	-0.34	30	108
mol:DAG	0.006	0.13	0.22	88	-0.24	47	135
CaM/Ca2+	0.02	0.12	0.22	50	-0.23	49	99
MAP2K3	0	0.12	0.22	65	-0.31	19	84
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.046	0.14	0.23	102	-0.3	43	145
PLCG1	0.006	0.13	0.22	88	-0.24	47	135
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.035	0.091	0.2	4	-0.27	21	25
IQGAP1	0.033	0.011	-10000	0	0	51	51
YES1	0.034	0.01	-10000	0	0	41	41
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.021	0.089	0.18	2	-0.28	24	26
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.019	0.086	0.18	2	-0.27	22	24
cell migration	0.007	0.14	0.26	22	-0.38	34	56
mol:PI-3-4-5-P3	0.001	0.14	0.24	28	-0.32	44	72
FYN	0.03	0.014	-10000	0	0	90	90
VEGFB/NRP1	0.006	0.12	0.2	88	-0.31	19	107
mol:NO	0.032	0.12	0.32	19	-0.34	14	33
PXN	0.036	0.004	-10000	0	0	7	7
HRAS/GTP	-0.045	0.069	-10000	0	-0.24	46	46
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.006	0.097	-10000	0	-0.3	43	43
VHL	0	0	-10000	0	-10000	0	0
ITGB3	0.036	0.003	-10000	0	0	4	4
NOS3	0.031	0.13	0.33	17	-0.38	14	31
VEGFR2 homodimer/VEGFA homodimer/Sck	0.015	0.093	-10000	0	-0.27	29	29
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCA	0	0.12	0.22	69	-0.29	23	92
PRKCB	0.004	0.12	0.22	67	-0.22	47	114
VCL	0.025	0.017	-10000	0	0	154	154
VEGFA165/NRP1	-0.025	0.082	0.12	39	-0.23	47	86
VEGFR1/2 heterodimer/VEGFA homodimer	0.02	0.086	0.18	2	-0.28	21	23
VEGFA165/NRP2	0.023	0.022	-10000	0	-0.045	7	7
MAPKKK cascade	-0.031	0.091	0.17	8	-0.32	33	41
NRP2	0.036	0.005	-10000	0	0	8	8
VEGFC homodimer	0.033	0.011	-10000	0	0	51	51
NCK1	0.035	0.008	-10000	0	0	27	27
ROCK1	0.036	0.006	-10000	0	0	15	15
FAK1/Paxillin	0.027	0.13	0.26	17	-0.42	21	38
MAP3K13	0.007	0.13	0.22	87	-0.31	21	108
PDPK1	-0.017	0.13	0.22	38	-0.33	34	72

×

Ephrin B reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EFNB2	0.028	0.015	-10000	0	0	116	116
EPHB2	0.034	0.011	-10000	0	0	42	42
EFNB1	-0.017	0.02	0.084	8	-10000	0	8
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.047	0.053	-10000	0	-0.14	8	8
Ephrin B2/EPHB1-2	0.031	0.056	-10000	0	-0.1	52	52
neuron projection morphogenesis	0.032	0.041	-10000	0	-0.14	8	8
Ephrin B1/EPHB1-2/Tiam1	0.057	0.049	-10000	0	-0.11	16	16
DNM1	0.035	0.008	-10000	0	0	26	26
cell-cell signaling	0	0.003	0.023	1	-10000	0	1
MAP2K4	-0.054	0.16	-10000	0	-0.52	52	52
YES1	-0.055	0.24	-10000	0	-0.75	52	52
Ephrin B1/EPHB1-2/NCK2	0.061	0.044	-10000	0	-0.1	19	19
PI3K	-0.02	0.19	-10000	0	-0.56	51	51
mol:GDP	0.055	0.048	-10000	0	-0.11	20	20
ITGA2B	0.036	0.004	-10000	0	0	5	5
endothelial cell proliferation	0.015	0.047	-10000	0	-0.11	46	46
FYN	-0.067	0.24	-10000	0	-0.77	52	52
MAP3K7	-0.051	0.16	0.22	1	-0.54	51	52
FGR	-0.051	0.23	-10000	0	-0.73	51	51
TIAM1	0.033	0.011	-10000	0	0	46	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
RGS3	0.035	0.008	-10000	0	0	23	23
cell adhesion	-0.032	0.17	-10000	0	-0.53	51	51
LYN	-0.062	0.23	-10000	0	-0.74	52	52
Ephrin B1/EPHB1-2/Src Family Kinases	-0.057	0.21	-10000	0	-0.68	52	52
Ephrin B1/EPHB1-2	-0.048	0.18	-10000	0	-0.57	51	51
SRC	-0.05	0.23	-10000	0	-0.72	52	52
ITGB3	0.036	0.003	-10000	0	0	4	4
EPHB1	0.03	0.015	-10000	0	0	95	95
EPHB4	0.025	0.017	-10000	0	0	166	166
RAC1	0.024	0.017	-10000	0	0	173	173
Ephrin B2/EPHB4	0.016	0.047	-10000	0	-0.11	46	46
alphaIIb/beta3 Integrin	0.054	0.006	-10000	0	-10000	0	0
BLK	-0.052	0.23	-10000	0	-0.72	52	52
HCK	-0.065	0.23	-10000	0	-0.74	52	52
regulation of stress fiber formation	-0.059	0.043	0.1	20	-10000	0	20
MAPK8	-0.056	0.15	-10000	0	-0.49	52	52
Ephrin B1/EPHB1-2/RGS3	0.066	0.035	-10000	0	-0.11	6	6
endothelial cell migration	0.01	0.17	0.19	127	-0.45	43	170
NCK2	0.035	0.007	-10000	0	0	17	17
PTPN13	0.034	0.013	-10000	0	0	60	60
regulation of focal adhesion formation	-0.059	0.043	0.1	20	-10000	0	20
chemotaxis	-0.064	0.034	0.11	6	-10000	0	6
PIK3CA	0.031	0.013	-10000	0	0	80	80
Rac1/GTP	0.04	0.047	-10000	0	-0.14	8	8
angiogenesis	-0.047	0.18	-10000	0	-0.57	51	51
LCK	-0.049	0.23	-10000	0	-0.72	51	51

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	0.001	0.047	-10000	0	-10000	0	0
PLK1	-0.059	0.2	-10000	0	-0.68	19	19
CDKN1B	-0.11	0.21	0.4	4	-0.37	136	140
FOXO3	-0.065	0.22	0.33	5	-0.49	81	86
KAT2B	-0.001	0.021	0.047	17	-0.041	76	93
FOXO1/SIRT1	0.014	0.048	-10000	0	-0.22	8	8
CAT	-0.075	0.26	-10000	0	-1.1	19	19
CTNNB1	0.036	0.006	-10000	0	0	15	15
AKT1	0.021	0.042	-10000	0	-0.062	62	62
FOXO1	0.004	0.051	0.22	1	-0.24	8	9
MAPK10	0.044	0.093	0.19	129	-0.15	19	148
mol:GTP	-0.001	0.004	-10000	0	-10000	0	0
FOXO4	-0.031	0.2	0.26	15	-0.44	62	77
response to oxidative stress	0	0.023	0.052	13	-0.047	42	55
FOXO3A/SIRT1	-0.06	0.21	-10000	0	-0.47	85	85
XPO1	0.036	0.004	-10000	0	0	5	5
EP300	0.034	0.011	-10000	0	-10000	0	0
BCL2L11	0.024	0.031	-10000	0	-10000	0	0
FOXO1/SKP2	0.02	0.054	0.2	1	-0.23	8	9
mol:GDP	0	0.023	0.052	13	-0.047	42	55
RAN	0.034	0.011	-10000	0	-0.015	20	20
GADD45A	-0.15	0.33	0.47	1	-0.86	69	70
YWHAQ	0.036	0.005	-10000	0	0	9	9
FOXO1/14-3-3 family	0.005	0.15	-10000	0	-0.52	21	21
MST1	0.022	0.043	0.11	1	-0.06	86	87
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.012	-10000	0	0	67	67
FOXO4/14-3-3 family	-0.003	0.15	-10000	0	-0.55	21	21
YWHAB	0.035	0.008	-10000	0	0	24	24
MAPK8	0.024	0.076	0.18	76	-0.14	12	88
MAPK9	0.052	0.097	0.19	151	-0.14	17	168
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
YWHAZ	0.035	0.007	-10000	0	0	21	21
SIRT1	0.019	0.023	-10000	0	-0.035	38	38
SOD2	-0.14	0.35	0.39	6	-0.75	101	107
RBL2	-0.072	0.28	-10000	0	-0.93	36	36
RAL/GDP	0.018	0.049	-10000	0	-0.14	20	20
CHUK	0.012	0.038	-10000	0	-0.059	73	73
Ran/GTP	0.019	0.025	-10000	0	-0.12	6	6
CSNK1G2	0.034	0.009	-10000	0	0	30	30
RAL/GTP	0.017	0.051	0.14	2	-0.12	22	24
CSNK1G1	0.036	0.006	-10000	0	0	14	14
FASLG	0.022	0.041	-10000	0	-0.59	1	1
SKP2	0.035	0.006	-10000	0	0	16	16
USP7	0.034	0.011	-10000	0	-0.012	23	23
IKBKB	0.023	0.044	0.11	1	-0.059	93	94
CCNB1	-0.16	0.42	0.49	1	-1.1	83	84
FOXO1-3a-4/beta catenin	-0.039	0.21	0.37	10	-0.4	78	88
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.054	0.2	1	-0.23	8	9
CSNK1A1	0.036	0.006	-10000	0	0	14	14
SGK1	-0.001	0.021	0.047	17	-0.041	76	93
CSNK1G3	0.036	0.006	-10000	0	0	13	13
Ran/GTP/Exportin 1	0.039	0.036	-10000	0	-0.14	7	7
ZFAND5	-0.019	0.16	0.24	15	-0.36	60	75
SFN	0.031	0.013	-10000	0	0	78	78
CDK2	0.036	0.012	-10000	0	-0.031	3	3
FOXO3A/14-3-3	-0.012	0.16	-10000	0	-0.48	29	29
CREBBP	0.038	0.008	-10000	0	-0.031	3	3
FBXO32	-0.059	0.2	0.32	1	-0.44	81	82
BCL6	-0.093	0.32	-10000	0	-1	46	46
RALB	0.033	0.013	-10000	0	-0.015	32	32
RALA	0.023	0.018	-10000	0	-0.001	184	184
YWHAH	0.031	0.013	-10000	0	0	73	73

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.032	0.17	-10000	0	-0.46	66	66
HDAC1	0.027	0.034	0.093	16	-0.039	84	100
AES	0.033	0.013	0.069	9	-0.004	46	55
FBXW11	0.035	0.008	-10000	0	0	25	25
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.033	0.027	-10000	0	-10000	0	0
TLE1	0.034	0.013	0.068	8	-0.007	36	44
AP1	-0.01	0.073	-10000	0	-0.2	55	55
NCSTN	0.035	0.008	-10000	0	0	28	28
ADAM10	0.033	0.012	-10000	0	0	56	56
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.011	0.12	-10000	0	-0.45	14	14
NICD/RBPSUH	-0.035	0.17	-10000	0	-0.46	66	66
WIF1	0.028	0.015	-10000	0	0	112	112
NOTCH1	-0.031	0.18	-10000	0	-0.49	64	64
PSENEN	0.035	0.008	-10000	0	0	28	28
KREMEN2	0.036	0.004	-10000	0	0	7	7
DKK1	0.017	0.018	-10000	0	0	271	271
beta catenin/beta TrCP1	0.062	0.091	0.23	18	-0.32	7	25
APH1B	0.035	0.006	-10000	0	0	16	16
APH1A	0.036	0.005	-10000	0	0	11	11
AXIN1	0.013	0.065	0.25	1	-10000	0	1
CtBP/CBP/TCF1/TLE1/AES	0.012	0.072	0.17	49	-0.18	19	68
PSEN1	0.033	0.011	-10000	0	0	46	46
FOS	0.025	0.017	-10000	0	0	158	158
JUN	0.034	0.01	-10000	0	0	40	40
MAP3K7	0.032	0.018	0.063	7	-0.011	61	68
CTNNB1	0.048	0.088	0.22	24	-0.32	5	29
MAPK3	0.036	0.004	-10000	0	0	6	6
DKK2/LRP6/Kremen 2	0.064	0.027	-10000	0	-0.12	1	1
HNF1A	0	0.006	0.031	10	-10000	0	10
CTBP1	0.034	0.013	0.07	7	-0.007	34	41
MYC	-0.079	0.37	-10000	0	-1.2	50	50
NKD1	0	0.003	-10000	0	-10000	0	0
FZD1	0.024	0.017	-10000	0	0	173	173
NOTCH1 precursor/Deltex homolog 1	-0.035	0.17	-10000	0	-0.46	66	66
apoptosis	-0.01	0.073	-10000	0	-0.2	56	56
Delta 1/NOTCHprecursor	-0.035	0.17	-10000	0	-0.46	66	66
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.025	0.036	-10000	0	-10000	0	0
Gamma Secretase	0.08	0.07	-10000	0	-0.15	28	28
APC	-0.023	0.17	0.23	4	-0.58	34	38
DVL1	0.019	0.096	-10000	0	-0.42	17	17
CSNK2A1	0.034	0.009	-10000	0	0	31	31
MAP3K7IP1	0.032	0.018	0.063	8	-0.012	55	63
DKK1/LRP6/Kremen 2	0.031	0.037	-10000	0	-10000	0	0
LRP6	0.034	0.01	-10000	0	0	40	40
CSNK1A1	0.036	0.006	-10000	0	0	14	14
NLK	0.011	0.051	0.13	1	-0.21	20	21
CCND1	-0.047	0.34	-10000	0	-1.2	41	41
WNT1	0.035	0.006	-10000	0	0	16	16
Axin1/APC/beta catenin	0.012	0.13	0.24	1	-0.42	30	31
DKK2	0.034	0.009	-10000	0	0	31	31
NOTCH1 precursor/DVL1	-0.009	0.19	-10000	0	-0.47	63	63
GSK3B	0.034	0.01	-10000	0	0	40	40
FRAT1	0.025	0.017	-10000	0	0	161	161
NOTCH/Deltex homolog 1	-0.032	0.17	-10000	0	-0.46	66	66
PPP2R5D	0.027	0.037	-10000	0	-0.25	4	4
MAPK1	0.033	0.01	-10000	0	0	45	45
WNT1/LRP6/FZD1	0.057	0.046	-10000	0	-10000	0	0
RBPJ	0	0	-10000	0	-10000	0	0
CREBBP	0.032	0.021	0.07	5	-0.019	62	67

×

IL2 signaling events mediated by PI3K

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.004	0.093	-10000	0	-0.53	1	1
UGCG	-0.027	0.19	-10000	0	-0.74	31	31
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.006	0.13	0.26	9	-0.31	55	64
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.026	0.19	-10000	0	-0.72	31	31
mol:DAG	-0.007	0.032	0.17	15	-10000	0	15
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.024	0.18	0.3	5	-0.42	62	67
FRAP1	-0.034	0.2	0.3	9	-0.47	62	71
FOXO3	-0.033	0.2	0.3	8	-0.46	64	72
AKT1	-0.039	0.21	0.31	7	-0.5	64	71
GAB2	0.03	0.019	-10000	0	-0.012	80	80
SMPD1	0.003	0.09	-10000	0	-0.49	14	14
SGMS1	-0.003	0.034	0.076	11	-0.072	65	76
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	-0.028	0.045	0.083	6	-0.13	73	79
CALM1	0.033	0.011	-10000	0	0	54	54
cell proliferation	-0.032	0.19	0.27	12	-0.39	69	81
EIF3A	0	0	-10000	0	-10000	0	0
PI3K	0.018	0.077	-10000	0	-0.16	73	73
RPS6KB1	0.029	0.027	-10000	0	-10000	0	0
mol:sphingomyelin	-0.007	0.032	0.17	15	-10000	0	15
natural killer cell activation	0	0.003	0.007	25	-0.01	44	69
JAK3	0.034	0.016	-10000	0	-0.028	22	22
PIK3R1	0.031	0.019	-10000	0	-0.029	24	24
JAK1	0.032	0.019	-10000	0	-0.028	29	29
NFKB1	0.035	0.007	-10000	0	0	18	18
MYC	-0.065	0.29	0.45	7	-0.83	56	63
MYB	0.034	0.041	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.025	0.16	0.26	7	-0.38	54	61
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.038	0.032	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.023	0.16	0.27	8	-0.37	54	62
Rac1/GDP	0.004	0.05	0.1	14	-0.13	46	60
T cell proliferation	-0.023	0.15	0.26	8	-0.35	53	61
SHC1	0.029	0.019	-10000	0	-0.011	85	85
RAC1	0.024	0.017	-10000	0	0	173	173
positive regulation of cyclin-dependent protein kinase activity	0.005	0.012	0.057	24	-10000	0	24
PRKCZ	-0.025	0.15	0.26	8	-0.36	54	62
NF kappa B1 p50/RelA	-0.011	0.19	0.31	8	-0.42	62	70
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.006	0.094	-10000	0	-0.32	18	18
HSP90AA1	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
IL2RA	0.021	0.021	-10000	0	-0.004	198	198
IL2RB	0.032	0.018	-10000	0	-0.028	22	22
TERT	0.036	0.006	-10000	0	0	14	14
E2F1	0.036	0.031	-10000	0	-10000	0	0
SOS1	0	0.003	0.008	27	-0.009	44	71
RPS6	0.031	0.013	-10000	0	0	81	81
mol:cAMP	-0.003	0.007	-10000	0	-0.031	25	25
PTPN11	0.032	0.018	-10000	0	-0.023	47	47
IL2RG	0.034	0.017	-10000	0	-0.03	24	24
actin cytoskeleton organization	-0.023	0.15	0.26	8	-0.35	53	61
GRB2	0.033	0.016	-10000	0	-0.017	42	42
IL2	0.035	0.016	-10000	0	-0.03	24	24
PIK3CA	0.03	0.02	-10000	0	-0.029	26	26
Rac1/GTP	0.026	0.064	0.16	5	-0.12	46	51
LCK	0.034	0.017	-10000	0	-0.03	25	25
BCL2	-0.02	0.16	0.31	2	-0.43	37	39

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.017	0.056	0.22	8	-0.21	21	29
RFC1	-0.02	0.048	0.18	2	-0.21	25	27
PRKDC	-0.016	0.055	0.19	7	-0.21	23	30
RIPK1	0.027	0.021	-10000	0	-0.023	73	73
CASP7	-0.16	0.28	-10000	0	-0.57	162	162
FASLG/FAS/FADD/FAF1	-0.012	0.083	0.16	27	-0.17	48	75
MAP2K4	-0.043	0.14	0.21	2	-0.31	42	44
mol:ceramide	0.004	0.089	0.18	5	-0.23	19	24
GSN	-0.008	0.058	0.19	11	-0.22	19	30
FASLG/FAS/FADD/FAF1/Caspase 8	-0.011	0.093	0.18	12	-0.23	28	40
FAS	0.021	0.02	-10000	0	0	238	238
BID	-0.031	0.033	-10000	0	-0.13	21	21
MAP3K1	-0.1	0.19	-10000	0	-0.36	166	166
MAP3K7	0.035	0.01	-10000	0	0	41	41
RB1	-0.017	0.045	0.23	1	-0.21	23	24
CFLAR	0.029	0.021	-10000	0	-0.027	59	59
HGF/MET	0.034	0.049	-10000	0	-0.12	22	22
ARHGDIB	-0.016	0.055	0.22	6	-0.22	21	27
FADD	0.038	0.007	-10000	0	0	12	12
actin filament polymerization	0.008	0.058	0.21	19	-0.19	11	30
NFKB1	0.029	0.1	-10000	0	-0.63	10	10
MAPK8	-0.033	0.13	0.24	1	-0.34	22	23
DFFA	-0.017	0.048	0.22	3	-0.21	24	27
DNA fragmentation during apoptosis	-0.016	0.046	0.22	2	-0.2	24	26
FAS/FADD/MET	0.025	0.052	-10000	0	-0.12	27	27
CFLAR/RIP1	0.048	0.02	-10000	0	-0.064	9	9
FAIM3	0.033	0.009	-10000	0	0	36	36
FAF1	0.038	0.012	-10000	0	-10000	0	0
PARP1	-0.019	0.048	0.22	1	-0.21	26	27
DFFB	-0.016	0.046	0.22	2	-0.21	23	25
CHUK	0.015	0.096	-10000	0	-0.6	10	10
FASLG	0.039	0.008	-10000	0	-10000	0	0
FAS/FADD	0.021	0.053	-10000	0	-0.14	34	34
HGF	0.024	0.017	-10000	0	0	177	177
LMNA	-0.02	0.049	0.2	5	-0.19	25	30
CASP6	-0.017	0.047	0.17	3	-0.2	24	27
CASP10	0.039	0.004	-10000	0	-10000	0	0
CASP3	-0.011	0.05	-10000	0	-0.22	25	25
PTPN13	0.032	0.012	-10000	0	0	60	60
CASP8	-0.029	0.013	0.084	3	-10000	0	3
IL6	0.02	0.13	-10000	0	-0.61	6	6
MET	0.023	0.018	-10000	0	0	191	191
ICAD/CAD	-0.021	0.049	0.25	4	-0.2	23	27
FASLG/FAS/FADD/FAF1/Caspase 10	0.004	0.09	0.18	5	-0.24	19	24
activation of caspase activity by cytochrome c	-0.031	0.033	-10000	0	-0.13	16	16
PAK2	-0.015	0.049	0.14	2	-0.2	25	27
BCL2	0.035	0.007	-10000	0	0	20	20

×

BCR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
JUN	0.003	0.12	0.26	3	-0.32	29	32
IKBKB	0.017	0.078	0.26	4	-0.25	10	14
AKT1	0.001	0.083	0.22	27	-0.18	13	40
IKBKG	0.009	0.07	0.23	1	-0.24	11	12
CALM1	-0.029	0.12	0.21	3	-0.35	46	49
PIK3CA	0.031	0.013	-10000	0	0	80	80
MAP3K1	0.027	0.13	0.29	7	-0.36	23	30
MAP3K7	0.034	0.01	-10000	0	0	41	41
mol:Ca2+	-0.027	0.13	0.22	4	-0.37	45	49
DOK1	0.036	0.002	-10000	0	0	2	2
AP-1	-0.009	0.092	0.19	11	-0.22	38	49
LYN	0.031	0.013	-10000	0	0	74	74
BLNK	0.019	0.018	-10000	0	0	243	243
SHC1	0.033	0.011	-10000	0	0	52	52
BCR complex	0.05	0.015	-10000	0	-10000	0	0
CD22	-0.016	0.092	-10000	0	-0.29	35	35
CAMK2G	-0.018	0.12	0.21	4	-0.34	43	47
CSNK2A1	0.034	0.009	-10000	0	0	31	31
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.036	0.054	-10000	0	-0.2	24	24
GO:0007205	-0.028	0.14	0.22	4	-0.38	45	49
SYK	0.031	0.013	-10000	0	0	76	76
ELK1	-0.033	0.13	0.21	4	-0.36	45	49
NFATC1	-0.017	0.092	0.25	4	-0.27	28	32
B-cell antigen/BCR complex	0.05	0.015	-10000	0	-10000	0	0
PAG1/CSK	0.023	0.022	-10000	0	-0.13	10	10
NFKBIB	0.02	0.042	0.14	1	-0.13	19	20
HRAS	-0.028	0.12	0.18	7	-0.32	47	54
NFKBIA	0.02	0.039	0.14	1	-0.12	16	17
NF-kappa-B/RelA/I kappa B beta	0.025	0.038	0.14	1	-0.1	19	20
RasGAP/Csk	0.045	0.096	-10000	0	-0.12	113	113
mol:GDP	-0.026	0.13	0.22	4	-0.36	45	49
PTEN	0.026	0.017	-10000	0	0	148	148
CD79B	0.036	0.005	-10000	0	0	10	10
NF-kappa-B/RelA/I kappa B alpha	0.025	0.036	0.14	1	-0.099	14	15
GRB2	0.035	0.007	-10000	0	0	17	17
PI3K/BCAP/CD19	-0.038	0.16	0.38	1	-0.43	45	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	-0.026	0.13	0.23	4	-0.38	44	48
CSK	0.035	0.007	-10000	0	0	21	21
FOS	-0.031	0.13	0.2	7	-0.35	46	53
CHUK	-0.061	0.14	0.23	1	-0.26	124	125
IBTK	0.034	0.009	-10000	0	0	30	30
CARD11/BCL10/MALT1/TAK1	-0.003	0.13	0.23	1	-0.34	39	40
PTPN6	-0.021	0.094	0.18	7	-0.31	32	39
RELA	0.036	0.005	-10000	0	0	9	9
BCL2A1	0.017	0.034	0.095	12	-0.089	21	33
VAV2	-0.014	0.1	-10000	0	-0.32	31	31
ubiquitin-dependent protein catabolic process	0.021	0.042	0.14	1	-0.13	19	20
BTK	0.019	0.012	-10000	0	-10000	0	0
CD19	-0.016	0.093	-10000	0	-0.29	36	36
MAP4K1	0.035	0.008	-10000	0	0	26	26
CD72	0.033	0.011	-10000	0	0	55	55
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	0.023	0.12	0.26	8	-0.31	23	31
SH3BP5	0.033	0.011	-10000	0	0	51	51
PIK3AP1	-0.023	0.14	0.23	4	-0.4	42	46
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.036	0.18	-10000	0	-0.49	55	55
RAF1	-0.033	0.11	0.19	5	-0.32	42	47
RasGAP/p62DOK/SHIP	0.037	0.084	-10000	0	-0.11	112	112
CD79A	0.034	0.009	-10000	0	0	34	34
re-entry into mitotic cell cycle	-0.01	0.092	0.18	11	-0.22	38	49
RASA1	0.034	0.009	-10000	0	0	32	32
MAPK3	-0.038	0.096	0.18	3	-0.3	37	40
MAPK1	-0.037	0.099	0.19	4	-0.3	39	43
CD72/SHP1	-0.002	0.1	0.26	7	-0.29	36	43
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	0.022	0.12	0.28	7	-0.32	22	29
actin cytoskeleton organization	0.034	0.11	0.26	15	-0.3	18	33
NF-kappa-B/RelA	0.042	0.087	0.26	1	-0.24	23	24
Calcineurin	-0.009	0.13	0.24	2	-0.32	43	45
PI3K	-0.031	0.085	-10000	0	-0.27	34	34
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.018	0.14	0.24	4	-0.41	40	44
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	0.015	0.15	-10000	0	-0.62	8	8
DAPP1	-0.004	0.15	-10000	0	-0.7	8	8
cytokine secretion	-0.015	0.088	0.25	4	-0.25	28	32
mol:DAG	-0.026	0.13	0.23	4	-0.38	44	48
PLCG2	0.032	0.012	-10000	0	0	63	63
MAP2K1	-0.036	0.1	0.18	4	-0.32	39	43
B-cell antigen/BCR complex/FcgammaRIIB	0.016	0.074	-10000	0	-0.12	96	96
mol:PI-3-4-5-P3	-0.018	0.07	0.18	18	-0.22	15	33
ETS1	-0.029	0.11	0.21	5	-0.33	38	43
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.034	0.091	-10000	0	-0.15	60	60
B-cell antigen/BCR complex/LYN	-0.011	0.098	-10000	0	-0.3	38	38
MALT1	0.034	0.009	-10000	0	0	32	32
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.031	0.12	0.27	13	-0.31	18	31
B-cell antigen/BCR complex/LYN/SYK	0.023	0.11	-10000	0	-0.28	33	33
CARD11	-0.027	0.13	0.22	4	-0.36	45	49
FCGR2B	0.021	0.018	-10000	0	0	222	222
PPP3CA	0.034	0.01	-10000	0	0	38	38
BCL10	0.035	0.007	-10000	0	0	20	20
IKK complex	0.003	0.043	0.12	5	-0.12	9	14
PTPRC	0.029	0.015	-10000	0	0	110	110
PDPK1	-0.015	0.056	0.16	17	-0.17	9	26
PPP3CB	0.025	0.017	-10000	0	0	157	157
PPP3CC	0.036	0.006	-10000	0	0	13	13
POU2F2	0.015	0.03	0.09	2	-0.08	23	25

×

S1P3 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
PDGFRB	0.035	0.008	-10000	0	0	27	27
mol:S1P	0.001	0.001	0.017	4	-10000	0	4
S1P1/S1P/Gi	-0.018	0.11	-10000	0	-0.23	78	78
GNAO1	0.031	0.014	-10000	0	0	87	87
S1P/S1P3/G12/G13	0.024	0.038	-10000	0	-0.1	28	28
AKT1	-0.012	0.16	-10000	0	-0.5	44	44
AKT3	0.01	0.077	-10000	0	-0.37	2	2
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	27	27
GNAI2	0.034	0.011	-10000	0	-10000	0	0
GNAI3	0.036	0.007	-10000	0	0	15	15
GNAI1	0.018	0.019	-10000	0	0	263	263
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.002	0.018	4	-10000	0	4
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.033	0.01	-10000	0	0	45	45
mol:Ca2+	-0.001	0.1	0.19	1	-0.26	47	48
MAPK3	-0.008	0.098	0.17	1	-0.24	52	53
MAPK1	-0.003	0.094	0.17	1	-0.24	42	43
JAK2	-0.011	0.11	0.19	5	-0.31	43	48
CXCR4	-0.006	0.099	0.14	4	-0.25	49	53
FLT1	0.036	0.01	0.069	1	-10000	0	1
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
SRC	-0.007	0.098	0.17	1	-0.25	48	49
S1P/S1P3/Gi	0	0.1	0.19	1	-0.26	46	47
RAC1	0.024	0.017	-10000	0	0	173	173
RhoA/GTP	0.012	0.11	0.18	1	-0.27	40	41
VEGFA	0.002	0.002	0.032	3	-10000	0	3
S1P/S1P2/Gi	-0.004	0.099	0.16	1	-0.2	78	79
VEGFR1 homodimer/VEGFA homodimer	0.029	0.01	0.11	3	-10000	0	3
RHOA	0.035	0.007	-10000	0	0	18	18
S1P/S1P3/Gq	0.015	0.04	-10000	0	-0.15	26	26
GNAQ	0.034	0.009	-10000	0	0	31	31
GNAZ	0.031	0.014	-10000	0	0	81	81
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
Rac1/GTP	0.001	0.092	-10000	0	-0.29	27	27

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.034	0.009	-10000	0	0	34	34
SPHK1	0.033	0.011	-10000	0	0	50	50
GNAI2	0.034	0.01	-10000	0	0	43	43
mol:S1P	0.018	0.015	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
mol:Sphinganine-1-P	-0.012	0.032	0.092	42	-10000	0	42
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.028	0.046	-10000	0	-0.16	4	4
GNAI3	0.036	0.006	-10000	0	0	15	15
G12/G13	0.025	0.047	-10000	0	-0.14	28	28
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0.033	0.01	-10000	0	0	45	45
S1P1/S1P	0.035	0.033	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.018	0.018	-10000	0	0	263	263
S1P/S1P5/G12	0.016	0.037	-10000	0	-0.16	4	4
S1P/S1P3/Gq	0.025	0.042	-10000	0	-0.25	8	8
S1P/S1P4/Gi	-0.003	0.11	0.13	7	-0.22	74	81
GNAQ	0.034	0.009	-10000	0	0	31	31
GNAZ	0.031	0.013	-10000	0	0	81	81
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA12	0.023	0.018	-10000	0	0	193	193
GNA13	0.035	0.007	-10000	0	0	19	19
GNA11	0.033	0.011	-10000	0	0	54	54
ABCC1	0.035	0.007	-10000	0	0	19	19

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0.028	0.041	-10000	0	-0.14	18	18
VLDLR	0.027	0.016	-10000	0	0	135	135
CRKL	0.035	0.009	-10000	0	0	29	29
LRPAP1	0.035	0.007	-10000	0	0	18	18
FYN	0.03	0.014	-10000	0	0	90	90
ITGA3	0.033	0.011	-10000	0	0	56	56
RELN/VLDLR/Fyn	0.018	0.06	-10000	0	-0.13	51	51
MAPK8IP1/MKK7/MAP3K11/JNK1	0.068	0.06	-10000	0	-0.11	4	4
AKT1	-0.014	0.069	-10000	0	-0.2	49	49
MAP2K7	0.035	0.008	-10000	0	0	24	24
RAPGEF1	0.035	0.007	-10000	0	0	19	19
DAB1	0.036	0.005	-10000	0	0	9	9
RELN/LRP8/DAB1	0.041	0.036	-10000	0	-0.11	3	3
LRPAP1/LRP8	0.045	0.036	-10000	0	-0.15	14	14
RELN/LRP8/DAB1/Fyn	0.041	0.059	-10000	0	-0.12	33	33
DAB1/alpha3/beta1 Integrin	0.029	0.058	-10000	0	-0.12	21	21
long-term memory	0.042	0.064	-10000	0	-0.12	31	31
DAB1/LIS1	0.048	0.072	-10000	0	-0.13	30	30
DAB1/CRLK/C3G	0.038	0.058	-10000	0	-0.12	23	23
PIK3CA	0.031	0.013	-10000	0	0	80	80
DAB1/NCK2	0.049	0.072	-10000	0	-0.13	28	28
ARHGEF2	0.035	0.007	-10000	0	0	20	20
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.035	0.006	-10000	0	0	16	16
CDK5R1	0.035	0.008	-10000	0	0	24	24
RELN	0.023	0.018	-10000	0	0	188	188
PIK3R1	0.032	0.012	-10000	0	0	63	63
RELN/LRP8/Fyn	0.029	0.056	-10000	0	-0.13	34	34
GRIN2A/RELN/LRP8/DAB1/Fyn	0.051	0.071	-10000	0	-0.12	33	33
MAPK8	0.027	0.016	-10000	0	0	138	138
RELN/VLDLR/DAB1	0.03	0.044	-10000	0	-0.11	19	19
ITGB1	0.027	0.016	-10000	0	0	138	138
MAP1B	0.023	0.083	0.16	107	-0.21	3	110
RELN/LRP8	0.039	0.044	-10000	0	-0.13	11	11
GRIN2B/RELN/LRP8/DAB1/Fyn	0.051	0.07	-10000	0	-0.12	31	31
PI3K	0.019	0.075	-10000	0	-0.16	73	73
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.034	0.027	-10000	0	-0.14	1	1
RAP1A	0.032	0.11	0.25	41	-0.19	1	42
PAFAH1B1	0.035	0.008	-10000	0	0	25	25
MAPK8IP1	0.035	0.008	-10000	0	0	24	24
CRLK/C3G	0.05	0.015	-10000	0	-10000	0	0
GRIN2B	0.035	0.007	-10000	0	0	22	22
NCK2	0.035	0.007	-10000	0	0	17	17
neuron differentiation	0.009	0.064	-10000	0	-0.22	14	14
neuron adhesion	0.033	0.11	0.24	47	-10000	0	47
LRP8	0.034	0.009	-10000	0	0	35	35
GSK3B	-0.009	0.079	0.18	1	-0.21	45	46
RELN/VLDLR/DAB1/Fyn	0.031	0.064	-10000	0	-0.11	51	51
MAP3K11	0.036	0.005	-10000	0	0	10	10
RELN/VLDLR/DAB1/P13K	-0.008	0.074	-10000	0	-0.19	55	55
CDK5	0.023	0.018	-10000	0	0	192	192
MAPT	-0.013	0.067	0.72	1	-10000	0	1
neuron migration	0	0.12	0.21	70	-0.28	33	103
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.009	0.064	-10000	0	-0.22	14	14
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	26	26

×

Regulation of nuclear SMAD2/3 signaling

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
EP300	0.019	0.038	-10000	0	-0.055	93	93
HSPA8	0.036	0.009	-10000	0	0	24	24
SMAD3/SMAD4/ER alpha	0.044	0.087	0.23	9	-0.14	34	43
AKT1	0.029	0.021	-10000	0	-0.029	39	39
GSC	0.002	0.028	0.11	11	-0.064	3	14
NKX2-5	0.033	0.017	0.07	8	-0.06	12	20
muscle cell differentiation	-0.017	0.13	0.31	49	-10000	0	49
SMAD2-3/SMAD4/SP1	0.051	0.14	0.33	5	-0.23	57	62
SMAD4	0.022	0.054	0.14	1	-0.12	33	34
CBFB	0.035	0.006	-10000	0	0	16	16
SAP18	0.034	0.01	-10000	0	0	41	41
Cbp/p300/MSG1	0.011	0.086	-10000	0	-0.12	121	121
SMAD3/SMAD4/VDR	0.045	0.12	-10000	0	-0.2	33	33
MYC	0.029	0.014	-10000	0	-10000	0	0
CDKN2B	-0.21	0.19	-10000	0	-0.49	51	51
AP1	-0.001	0.099	0.24	1	-0.23	48	49
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.011	0.13	-10000	0	-0.36	39	39
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.002	0.081	-10000	0	-0.27	31	31
SP3	0.035	0.016	0.08	11	-0.054	10	21
CREB1	0.036	0.004	-10000	0	0	7	7
FOXH1	0.035	0.016	0.073	9	-0.06	12	21
SMAD3/SMAD4/GR	0.04	0.091	0.26	1	-0.16	29	30
GATA3	0.027	0.018	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	-0.003	0.091	-10000	0	-0.28	31	31
MEF2C/TIF2	-0.019	0.074	0.3	7	-0.23	15	22
endothelial cell migration	0.19	0.5	1.2	104	-10000	0	104
MAX	0.026	0.043	0.084	87	-0.053	89	176
RBBP7	0.036	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	56	56
RUNX2	0.037	0.002	-10000	0	0	1	1
RUNX3	0.034	0.009	-10000	0	0	34	34
RUNX1	0.036	0.005	-10000	0	0	10	10
CTBP1	0.035	0.008	-10000	0	0	26	26
NR3C1	0.027	0.043	0.085	86	-0.053	90	176
VDR	0.035	0.007	-10000	0	0	18	18
CDKN1A	-0.11	0.36	0.39	1	-1.1	59	60
KAT2B	-0.003	0.008	-10000	0	-0.024	11	11
SMAD2/SMAD2/SMAD4/FOXH1	0.049	0.077	0.2	2	-0.16	37	39
DCP1A	0.035	0.008	-10000	0	0	24	24
SKI	0.037	0.001	-10000	0	-10000	0	0
SERPINE1	-0.2	0.5	-10000	0	-1.2	104	104
SMAD3/SMAD4/ATF2	0.041	0.086	0.21	1	-0.15	45	46
SMAD3/SMAD4/ATF3	0.021	0.1	-10000	0	-0.17	75	75
SAP30	0.035	0.007	-10000	0	0	20	20
Cbp/p300/PIAS3	0.041	0.073	-10000	0	-0.094	92	92
JUN	-0.014	0.097	0.19	7	-0.25	42	49
SMAD3/SMAD4/IRF7	0.044	0.09	-10000	0	-0.16	35	35
TFE3	0.016	0.059	0.11	8	-0.095	101	109
COL1A2	-0.045	0.21	-10000	0	-0.64	53	53
mesenchymal cell differentiation	-0.041	0.086	0.16	34	-10000	0	34
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.035	0.008	-10000	0	0	28	28
FOS	0.02	0.03	0.12	2	-0.047	39	41
SMAD3/SMAD4/Max	0.041	0.087	0.26	1	-0.15	30	31
Cbp/p300/SNIP1	0.044	0.056	-10000	0	-0.12	9	9
ZBTB17	0.035	0.006	-10000	0	-10000	0	0
LAMC1	-0.033	0.098	0.16	6	-0.3	38	44
TGIF2/HDAC complex/SMAD3/SMAD4	0.04	0.084	0.21	1	-0.15	47	48
IRF7	0.034	0.01	-10000	0	-10000	0	0
ESR1	0.037	0.039	0.12	67	-0.026	59	126
HNF4A	0.035	0.007	-10000	0	0	20	20
MEF2C	-0.028	0.068	0.3	7	-0.23	19	26
SMAD2-3/SMAD4	0.043	0.095	0.24	1	-0.19	31	32
Cbp/p300/Src-1	0.031	0.075	-10000	0	-0.14	43	43
IGHV3OR16-13	0.005	0.056	-10000	0	-0.48	6	6
TGIF2/HDAC complex	0.035	0.008	-10000	0	0	28	28
CREBBP	0.022	0.034	-10000	0	-0.045	101	101
SKIL	0.036	0.006	-10000	0	0	13	13
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.032	0.013	-10000	0	0	67	67
SNIP1	0.037	0.007	-10000	0	0	12	12
GCN5L2	0.022	0.034	-10000	0	-0.04	114	114
SMAD3/SMAD4/TFE3	0.031	0.12	0.28	4	-0.22	52	56
MSG1/HSC70	0.009	0.079	-10000	0	-0.14	100	100
SMAD2	0.035	0.017	0.089	2	-0.048	11	13
SMAD3	0.019	0.058	0.14	1	-0.12	43	44
SMAD3/E2F4-5/DP1/p107/SMAD4	0.002	0.073	-10000	0	-0.18	43	43
SMAD2/SMAD2/SMAD4	-0.012	0.07	0.18	8	-0.2	40	48
NCOR1	0.035	0.008	-10000	0	0	26	26
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA1	0.033	0.011	-10000	0	0	50	50
MYOD/E2A	0.051	0.014	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.059	0.14	0.34	5	-0.23	48	53
IFNB1	-0.005	0.057	0.2	2	-0.19	4	6
SMAD3/SMAD4/MEF2C	0.027	0.092	0.27	3	-0.24	18	21
CITED1	0.026	0.017	-10000	0	0	151	151
SMAD2-3/SMAD4/ARC105	0.042	0.085	0.22	2	-0.17	31	33
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.007	0.1	-10000	0	-0.33	29	29
RUNX1-3/PEBPB2	0.066	0.023	-10000	0	-10000	0	0
SMAD7	-0.04	0.18	0.28	2	-0.44	55	57
MYC/MIZ-1	0.028	0.057	-10000	0	-0.14	47	47
SMAD3/SMAD4	-0.08	0.23	-10000	0	-0.47	110	110
IL10	-0.007	0.061	0.19	8	-0.18	3	11
PIASy/HDAC complex	0.028	0.031	0.068	28	-0.031	89	117
PIAS3	0.023	0.029	-10000	0	-0.031	107	107
CDK2	0.021	0.032	-10000	0	-0.03	129	129
IL5	-0.008	0.063	0.2	5	-0.2	2	7
CDK4	0.021	0.031	-10000	0	-0.046	73	73
PIAS4	0.028	0.031	0.068	28	-0.031	89	117
ATF3	0.028	0.016	-10000	0	0	125	125
SMAD3/SMAD4/SP1	0.03	0.14	0.27	9	-0.24	62	71
FOXG1	0.001	0.007	0.023	22	-10000	0	22
FOXO3	-0.009	0.008	-10000	0	-10000	0	0
FOXO1	-0.008	0.007	-10000	0	-10000	0	0
FOXO4	-0.008	0.007	-10000	0	-10000	0	0
heart looping	-0.028	0.068	0.3	7	-0.22	19	26
CEBPB	0.032	0.013	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.025	0.073	0.18	2	-0.14	50	52
MYOD1	0.036	0.004	-10000	0	0	7	7
SMAD3/SMAD4/HNF4	0.04	0.085	0.21	1	-0.15	46	47
SMAD3/SMAD4/GATA3	0.033	0.085	-10000	0	-0.17	22	22
SnoN/SIN3/HDAC complex/NCoR1	0.036	0.006	-10000	0	0	13	13
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.069	0.093	-10000	0	-0.15	16	16
SMAD3/SMAD4/SP1-3	0.047	0.14	0.34	3	-0.24	54	57
MED15	0	0	-10000	0	-10000	0	0
SP1	0.014	0.075	0.12	18	-0.12	107	125
SIN3B	0.035	0.009	-10000	0	0	29	29
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.07	0.084	0.24	2	-0.16	37	39
ITGB5	-0.031	0.1	0.23	3	-0.27	32	35
TGIF/SIN3/HDAC complex/CtBP	-0.009	0.096	-10000	0	-0.3	32	32
SMAD3/SMAD4/AR	0.041	0.085	0.21	1	-0.15	49	50
AR	0.035	0.007	-10000	0	0	22	22
negative regulation of cell growth	-0.016	0.12	0.18	1	-0.29	63	64
SMAD3/SMAD4/MYOD	0.042	0.086	0.21	1	-0.15	50	51
E2F5	0.036	0.005	-10000	0	0	8	8
E2F4	0.036	0.006	-10000	0	0	12	12
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.062	0.097	0.24	1	-0.18	30	31
SMAD2-3/SMAD4/FOXO1-3a-4	-0.006	0.097	-10000	0	-0.3	32	32
TFDP1	0.033	0.011	-10000	0	0	53	53
SMAD3/SMAD4/AP1	0.024	0.12	0.26	1	-0.24	44	45
SMAD3/SMAD4/RUNX2	0.041	0.086	-10000	0	-0.16	34	34
TGIF2	0.035	0.008	-10000	0	0	28	28
TGIF1	0	0	-10000	0	-10000	0	0
ATF2	0.036	0.005	-10000	0	0	11	11

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.033	0.01	-10000	0	0	45	45
VLDLR	0.027	0.016	-10000	0	0	135	135
LRPAP1	0.035	0.007	-10000	0	0	18	18
NUDC	0.035	0.008	-10000	0	0	27	27
RELN/LRP8	0.039	0.044	-10000	0	-0.13	11	11
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
KATNA1	0.033	0.01	-10000	0	0	44	44
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.037	0.1	0.19	139	-0.21	6	145
IQGAP1/CaM	0.031	0.058	-10000	0	-0.15	44	44
DAB1	0.036	0.005	-10000	0	0	9	9
IQGAP1	0.033	0.011	-10000	0	0	51	51
PLA2G7	0.033	0.011	-10000	0	0	53	53
CALM1	0.033	0.011	-10000	0	0	54	54
DYNLT1	0.033	0.01	-10000	0	0	44	44
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.045	0.036	-10000	0	-0.15	14	14
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0	0	-10000	0	-10000	0	0
CDK5R1	0.035	0.008	-10000	0	0	24	24
LIS1/Poliovirus Protein 3A	-0.023	0.028	-10000	0	-0.14	24	24
CDK5R2	0.035	0.006	-10000	0	0	16	16
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.031	0.048	-10000	0	-0.12	19	19
YWHAE	0.035	0.008	-10000	0	0	27	27
NDEL1/14-3-3 E	0.064	0.17	0.32	136	-0.27	17	153
MAP1B	-0.014	0.067	-10000	0	-0.2	51	51
RAC1	-0.003	0.051	-10000	0	-0.26	12	12
p35/CDK5	-0.025	0.056	0.2	7	-0.21	12	19
RELN	0.023	0.018	-10000	0	0	188	188
PAFAH/LIS1	0.022	0.039	-10000	0	-0.15	21	21
LIS1/CLIP170	-0.023	0.028	-10000	0	-0.14	24	24
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.034	0.078	0.14	8	-0.27	26	34
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.014	0.087	0.17	1	-0.23	52	53
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.056	0.16	0.3	135	-0.27	15	150
LIS1/IQGAP1	0.014	0.058	-10000	0	-0.15	50	50
RHOA	-0.005	0.065	-10000	0	-0.27	19	19
PAFAH1B1	-0.021	0.007	-10000	0	-10000	0	0
PAFAH1B3	0.031	0.013	-10000	0	0	76	76
PAFAH1B2	0.036	0.004	-10000	0	0	7	7
MAP1B/LIS1/Dynein heavy chain	0.007	0.078	-10000	0	-0.2	54	54
NDEL1/Katanin 60/Dynein heavy chain	0.082	0.15	0.33	109	-0.26	22	131
LRP8	0.034	0.009	-10000	0	0	35	35
NDEL1/Katanin 60	0.056	0.16	0.31	126	-0.27	18	144
P39/CDK5	-0.025	0.056	0.2	7	-0.21	12	19
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0.052	-10000	0	-0.19	26	26
CDK5	-0.014	0.045	0.19	8	-0.22	6	14
PPP2R5D	0.036	0.004	-10000	0	0	5	5
LIS1/CLIP170/Dynein Complex/Dynactin Complex	-0.019	0.023	-10000	0	-0.12	24	24
CSNK2A1	0.034	0.009	-10000	0	0	31	31
RELN/VLDLR/DAB1/LIS1	0.033	0.059	-10000	0	-0.13	33	33
RELN/VLDLR	0.044	0.06	-10000	0	-0.12	26	26
CDC42	-0.002	0.045	-10000	0	-0.2	15	15

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.035	0.009	-10000	0	0	29	29
Rac1/GDP	0.024	0.021	-10000	0	-0.025	10	10
DOCK1	0.024	0.017	-10000	0	0	175	175
ITGA4	0.036	0.006	-10000	0	0	13	13
RAC1	0.024	0.017	-10000	0	0	173	173
alpha4/beta7 Integrin	0.052	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
alpha4/beta1 Integrin	0.051	0.034	-10000	0	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.052	0.017	-10000	0	-10000	0	0
lamellipodium assembly	-0.046	0.14	-10000	0	-0.36	73	73
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.019	0.075	-10000	0	-0.16	73	73
ARF6	0.035	0.008	-10000	0	0	27	27
TLN1	0.029	0.015	-10000	0	0	102	102
PXN	-0.021	0.01	0.092	3	-10000	0	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
ARF6/GTP	0.049	0.048	-10000	0	-0.11	1	1
cell adhesion	0.049	0.047	-10000	0	-0.11	13	13
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.039	0.026	-10000	0	-10000	0	0
ITGB1	0.027	0.016	-10000	0	0	138	138
ITGB7	0.036	0.005	-10000	0	0	11	11
ARF6/GDP	0.035	0.015	-10000	0	-0.025	14	14
alpha4/beta1 Integrin/Paxillin/VCAM1	0.016	0.079	-10000	0	-0.11	116	116
p130Cas/Crk/Dock1	0.028	0.035	-10000	0	-0.11	17	17
VCAM1	0.022	0.018	-10000	0	0	196	196
alpha4/beta1 Integrin/Paxillin/Talin	0.051	0.048	-10000	0	-0.12	13	13
alpha4/beta1 Integrin/Paxillin/GIT1	0.059	0.04	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.057	0.039	-10000	0	-10000	0	0
CBL	0.036	0.004	-10000	0	0	7	7
PRKACA	0.035	0.008	-10000	0	0	25	25
GIT1	0.036	0.003	-10000	0	0	4	4
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.051	0.048	-10000	0	-0.12	13	13
Rac1/GTP	-0.052	0.16	-10000	0	-0.4	73	73

×

EPHB forward signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Ephrin A5/EPHB2	0.045	0.014	-10000	0	-10000	0	0
cell-cell adhesion	0.03	0.04	0.19	13	-10000	0	13
Ephrin B/EPHB2/RasGAP	0.058	0.09	-10000	0	-0.13	73	73
ITSN1	0.035	0.007	-10000	0	0	21	21
PIK3CA	0.031	0.013	-10000	0	0	80	80
SHC1	0.033	0.011	-10000	0	0	52	52
Ephrin B1/EPHB3	0.044	0.015	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.039	0.025	-10000	0	-0.12	6	6
HRAS/GDP	0.004	0.081	0.17	1	-0.22	37	38
Ephrin B/EPHB1/GRB7	0.067	0.075	-10000	0	-0.12	46	46
Endophilin/SYNJ1	-0.027	0.056	0.19	14	-0.18	2	16
KRAS	0.034	0.009	-10000	0	0	35	35
Ephrin B/EPHB1/Src	0.065	0.077	-10000	0	-0.12	53	53
endothelial cell migration	0.02	0.073	-10000	0	-0.14	63	63
GRB2	0.035	0.007	-10000	0	0	17	17
GRB7	0.036	0.006	-10000	0	0	14	14
PAK1	-0.028	0.061	0.18	19	-10000	0	19
HRAS	0.034	0.009	-10000	0	0	32	32
RRAS	-0.026	0.056	0.2	10	-0.18	9	19
DNM1	0.035	0.008	-10000	0	0	26	26
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.019	0.065	0.18	20	-0.18	11	31
lamellipodium assembly	-0.03	0.04	-10000	0	-0.19	13	13
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.008	0.072	-10000	0	-0.29	14	14
PIK3R1	0.032	0.012	-10000	0	0	63	63
EPHB2	0.034	0.01	-10000	0	0	42	42
EPHB3	0.033	0.011	-10000	0	0	52	52
EPHB1	0.03	0.014	-10000	0	0	95	95
EPHB4	0.025	0.017	-10000	0	0	166	166
mol:GDP	0.019	0.12	0.2	96	-0.24	34	130
Ephrin B/EPHB2	0.051	0.068	-10000	0	-0.11	65	65
Ephrin B/EPHB3	0.05	0.068	-10000	0	-0.11	64	64
JNK cascade	-0.005	0.07	0.23	23	-0.19	4	27
Ephrin B/EPHB1	0.051	0.066	-10000	0	-0.11	54	54
RAP1/GDP	0.028	0.12	0.2	101	-0.22	35	136
EFNB2	0.028	0.015	-10000	0	0	116	116
EFNB3	0.035	0.009	-10000	0	0	29	29
EFNB1	0.037	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	0.03	0.058	-10000	0	-0.11	52	52
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CDC42/GTP	0.043	0.083	-10000	0	-0.19	33	33
Rap1/GTP	-0.044	0.052	0.052	8	-0.2	22	30
axon guidance	0.044	0.014	-10000	0	-10000	0	0
MAPK3	-0.009	0.071	0.18	3	-0.27	16	19
MAPK1	-0.009	0.074	0.18	2	-0.27	20	22
Rac1/GDP	-0.008	0.093	0.25	19	-0.24	31	50
actin cytoskeleton reorganization	-0.039	0.06	-10000	0	-0.2	39	39
CDC42/GDP	0.036	0.13	0.22	109	-0.23	35	144
PI3K	0.024	0.076	-10000	0	-0.14	63	63
EFNA5	0.036	0.004	-10000	0	0	6	6
Ephrin B2/EPHB4	0.016	0.047	-10000	0	-0.11	46	46
Ephrin B/EPHB2/Intersectin/N-WASP	0.001	0.06	-10000	0	-0.3	6	6
CDC42	0.035	0.008	-10000	0	0	24	24
RAS family/GTP	-0.052	0.06	-10000	0	-0.24	24	24
PTK2	-0.015	0.08	0.53	9	-0.2	15	24
MAP4K4	-0.005	0.071	0.23	23	-0.19	4	27
SRC	0.036	0.006	-10000	0	0	14	14
KALRN	0.035	0.008	-10000	0	0	23	23
Intersectin/N-WASP	0.032	0.033	-10000	0	-0.14	7	7
neuron projection morphogenesis	0.064	0.17	0.33	124	-0.22	13	137
MAP2K1	-0.001	0.071	0.2	1	-0.27	17	18
WASL	0.024	0.017	-10000	0	0	172	172
Ephrin B1/EPHB1-2/NCK1	0.082	0.038	-10000	0	-0.12	9	9
cell migration	-0.015	0.087	0.2	2	-0.29	19	21
NRAS	0.032	0.012	-10000	0	0	63	63
SYNJ1	-0.027	0.057	0.19	14	-0.18	2	16
PXN	0.036	0.004	-10000	0	0	7	7
TF	-0.022	0.051	0.19	6	-0.18	21	27
HRAS/GTP	0.034	0.079	-10000	0	-0.2	21	21
Ephrin B1/EPHB1-2	0.052	0.035	-10000	0	-0.11	6	6
cell adhesion mediated by integrin	0.019	0.046	0.15	4	-0.27	4	8
RAC1	0.024	0.017	-10000	0	0	173	173
mol:GTP	0.042	0.077	-10000	0	-0.13	59	59
RAC1-CDC42/GTP	-0.03	0.046	-10000	0	-0.2	14	14
RASA1	0.034	0.009	-10000	0	0	32	32
RAC1-CDC42/GDP	0.011	0.095	0.25	17	-0.24	32	49
ruffle organization	0.074	0.17	0.31	141	-0.25	6	147
NCK1	0.035	0.008	-10000	0	0	27	27
receptor internalization	-0.031	0.053	0.18	14	-0.18	2	16
Ephrin B/EPHB2/KALRN	0.064	0.079	-10000	0	-0.12	62	62
ROCK1	-0.01	0.045	0.18	17	-10000	0	17
RAS family/GDP	-0.042	0.063	-10000	0	-0.21	41	41
Rac1/GTP	-0.028	0.045	-10000	0	-0.2	13	13
Ephrin B/EPHB1/Src/Paxillin	0.009	0.065	-10000	0	-0.22	6	6

×

ErbB2/ErbB3 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
USP8	-0.015	0.013	0.085	5	-10000	0	5
RAS family/GTP	0.013	0.11	0.22	1	-0.18	73	74
NFATC4	-0.021	0.067	0.17	20	-0.18	5	25
ERBB2IP	0.034	0.011	-10000	0	-0.001	42	42
HSP90 (dimer)	0	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.029	0.077	0.17	9	-0.18	19	28
JUN	-0.004	0.087	0.21	6	-0.36	7	13
HRAS	0.034	0.009	-10000	0	0	32	32
DOCK7	-0.036	0.068	0.15	11	-0.16	71	82
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.027	0.08	0.21	14	-0.13	85	99
AKT1	-0.01	0.008	0.013	30	-10000	0	30
BAD	-0.015	0.014	0.085	7	-10000	0	7
MAPK10	0.007	0.072	0.16	42	-0.15	13	55
mol:GTP	0	0.001	-10000	0	-0.005	24	24
ErbB2/ErbB3/neuregulin 1 beta	-0.03	0.083	0.2	7	-0.19	19	26
RAF1	-0.019	0.1	0.25	10	-0.24	33	43
ErbB2/ErbB3/neuregulin 2	0.002	0.073	0.2	17	-0.13	91	108
STAT3	-0.023	0.24	-10000	0	-0.9	35	35
cell migration	-0.005	0.071	0.19	20	-0.18	15	35
mol:PI-3-4-5-P3	-0.001	0.002	0.004	14	-0.005	4	18
cell proliferation	-0.041	0.24	0.44	3	-0.58	58	61
FOS	-0.032	0.2	0.37	6	-0.42	90	96
NRAS	0.032	0.012	-10000	0	0	63	63
mol:Ca2+	-0.029	0.077	0.17	9	-0.18	19	28
MAPK3	-0.019	0.18	0.4	3	-0.48	38	41
MAPK1	-0.044	0.22	0.4	3	-0.57	50	53
JAK2	-0.027	0.078	0.17	19	-0.18	19	38
NF2	0.01	0.008	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.005	0.08	0.15	13	-0.16	88	101
NRG1	0.036	0.005	-10000	0	0	9	9
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
MAPK8	-0.014	0.087	0.19	4	-0.22	49	53
MAPK9	0.014	0.076	0.16	57	-0.14	5	62
ERBB2	-0.016	0.068	0.26	29	-10000	0	29
ERBB3	0.018	0.018	-10000	0	0	256	256
SHC1	0.033	0.011	-10000	0	0	52	52
RAC1	0.024	0.017	-10000	0	0	173	173
apoptosis	0.012	0.03	0.2	10	-0.07	4	14
STAT3 (dimer)	-0.021	0.24	-10000	0	-0.88	35	35
RNF41	-0.02	0.019	0.076	10	-0.12	2	12
FRAP1	-0.015	0.012	0.084	5	-10000	0	5
RAC1-CDC42/GTP	-0.022	0.044	-10000	0	-0.13	48	48
ErbB2/ErbB2/HSP90 (dimer)	-0.025	0.008	-10000	0	-10000	0	0
CHRNA1	-0.007	0.15	0.35	5	-0.36	42	47
myelination	-0.033	0.072	0.22	9	-0.2	4	13
PPP3CB	-0.02	0.067	0.16	18	-0.18	14	32
KRAS	0.034	0.009	-10000	0	0	35	35
RAC1-CDC42/GDP	0.021	0.074	0.22	1	-0.16	45	46
NRG2	0.036	0.005	-10000	0	0	10	10
mol:GDP	-0.005	0.08	0.15	13	-0.16	88	101
SOS1	0	0.001	-10000	0	-0.004	5	5
MAP2K2	-0.028	0.1	0.22	11	-0.24	38	49
SRC	0.036	0.006	-10000	0	0	14	14
mol:cAMP	-0.001	0.001	0.003	2	-0.004	1	3
PTPN11	-0.031	0.083	0.17	21	-0.18	19	40
MAP2K1	-0.038	0.2	0.38	2	-0.57	35	37
heart morphogenesis	-0.029	0.077	0.17	9	-0.18	19	28
RAS family/GDP	0.021	0.11	0.24	1	-0.18	76	77
GRB2	0.035	0.007	-10000	0	0	17	17
PRKACA	0.018	0.009	-10000	0	-10000	0	0
CHRNE	0.001	0.025	0.075	2	-0.12	7	9
HSP90AA1	0	0	-10000	0	-10000	0	0
activation of caspase activity	0.01	0.008	-10000	0	-0.013	30	30
nervous system development	-0.029	0.077	0.17	9	-0.18	19	28
CDC42	0.035	0.008	-10000	0	0	24	24

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0	0	-10000	0	-10000	0	0
GNB1/GNG2	0.003	0.099	-10000	0	-0.25	27	27
mol:DAG	-0.012	0.09	0.18	4	-0.25	27	31
PLCG1	-0.013	0.092	0.18	4	-0.25	27	31
YES1	-0.016	0.084	0.14	1	-0.28	20	21
FZD3	0.029	0.015	-10000	0	0	110	110
FZD6	0.027	0.016	-10000	0	0	130	130
G protein	0.003	0.1	0.2	23	-0.27	25	48
MAP3K7	-0.036	0.074	0.15	4	-0.23	31	35
mol:Ca2+	-0.012	0.088	0.18	4	-0.24	27	31
mol:IP3	-0.012	0.09	0.18	4	-0.25	27	31
NLK	-0.039	0.25	-10000	0	-0.78	52	52
GNB1	0.035	0.007	-10000	0	0	20	20
CAMK2A	-0.031	0.078	0.17	4	-0.24	27	31
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
Noncanonical Wnts/FZD	-0.006	0.089	-10000	0	-0.17	89	89
CSNK1A1	0.036	0.006	-10000	0	0	14	14
GNAS	-0.014	0.08	0.14	2	-0.17	83	85
GO:0007205	-0.02	0.085	0.18	4	-0.25	27	31
WNT6	0.037	0.002	-10000	0	0	1	1
WNT4	0.035	0.007	-10000	0	0	18	18
NFAT1/CK1 alpha	-0.005	0.098	0.22	5	-0.26	27	32
GNG2	0	0	-10000	0	-10000	0	0
WNT5A	0.029	0.015	-10000	0	0	99	99
WNT11	0.036	0.006	-10000	0	0	14	14
CDC42	-0.025	0.082	0.17	5	-0.27	21	26

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.063	0.064	-9999	-0.12	12	12
SMAD6-7/SMURF1	0.044	0.038	-9999	-0.12	2	2
NOG	0	0	-9999	-10000	0	0
SMAD9	-0.024	0.15	-9999	-0.44	54	54
SMAD4	0.032	0.012	-9999	0	58	58
SMAD5	-0.029	0.098	-9999	-0.3	45	45
BMP7/USAG1	0.033	0.027	-9999	-10000	0	0
SMAD5/SKI	-0.021	0.11	-9999	-0.31	43	43
SMAD1	-0.031	0.15	-9999	-0.4	50	50
BMP2	0.029	0.015	-9999	0	107	107
SMAD1/SMAD1/SMAD4	-0.01	0.13	-9999	-0.36	42	42
BMPR1A	0.025	0.017	-9999	0	167	167
BMPR1B	0.036	0.006	-9999	0	14	14
BMPR1A-1B/BAMBI	0.02	0.06	-9999	-0.13	50	50
AHSG	0.035	0.009	-9999	0	29	29
CER1	0.031	0.013	-9999	0	71	71
BMP2-4/CER1	0.039	0.055	-9999	-0.12	35	35
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.01	0.078	-9999	-0.24	31	31
BMP2-4 (homodimer)	0.029	0.051	-9999	-0.14	35	35
RGMB	0	0	-9999	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.058	0.052	-9999	-0.12	12	12
RGMA	0	0	-9999	-10000	0	0
SMURF1	0.025	0.017	-9999	0	167	167
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.021	0.07	-9999	-0.17	58	58
BMP2-4/USAG1	0.033	0.046	-9999	-0.12	16	16
SMAD6/SMURF1/SMAD5	-0.012	0.09	-9999	-0.29	33	33
SOSTDC1	0.023	0.018	-9999	0	184	184
BMP7/BMPR2/BMPR1A-1B	0.058	0.053	-9999	-0.12	14	14
SKI	0.037	0	-9999	-10000	0	0
BMP6 (homodimer)	0.035	0.008	-9999	0	24	24
HFE2	0	0	-9999	-10000	0	0
ZFYVE16	0.034	0.009	-9999	0	35	35
MAP3K7	0.034	0.01	-9999	0	41	41
BMP2-4/CHRD	0.043	0.054	-9999	-0.12	34	34
SMAD5/SMAD5/SMAD4	-0.022	0.11	-9999	-0.31	43	43
MAPK1	0.033	0.01	-9999	0	45	45
TAK1/TAB family	0.019	0.083	-9999	-0.21	18	18
BMP7 (homodimer)	0.034	0.01	-9999	0	39	39
NUP214	0.035	0.007	-9999	0	18	18
BMP6/FETUA	0.049	0.016	-9999	-10000	0	0
SMAD1/SKI	-0.015	0.15	-9999	-0.38	52	52
SMAD6	0.036	0.005	-9999	0	11	11
CTDSP2	0.033	0.012	-9999	0	57	57
BMP2-4/FETUA	0.042	0.055	-9999	-0.12	35	35
MAP3K7IP1	0.034	0.009	-9999	0	35	35
GREM1	0.032	0.012	-9999	0	64	64
BMPR2 (homodimer)	0.036	0.006	-9999	0	12	12
GADD34/PP1CA	0.052	0.053	-9999	-0.13	31	31
BMPR1A-1B (homodimer)	0.034	0.032	-9999	-0.14	6	6
CHRDL1	0	0	-9999	-10000	0	0
ENDOFIN/SMAD1	-0.018	0.15	-9999	-0.39	53	53
SMAD6-7/SMURF1/SMAD1	0.004	0.14	-9999	-0.38	42	42
SMAD6/SMURF1	0.025	0.017	-9999	0	167	167
BAMBI	0.018	0.018	-9999	0	255	255
SMURF2	0.035	0.007	-9999	0	20	20
BMP2-4/CHRDL1	0.028	0.043	-9999	-0.11	35	35
BMP2-4/GREM1	0.039	0.054	-9999	-0.12	33	33
SMAD7	0.033	0.01	-9999	0	44	44
SMAD8A/SMAD8A/SMAD4	-0.012	0.15	-9999	-0.41	58	58
SMAD1/SMAD6	-0.015	0.14	-9999	-0.38	43	43
TAK1/SMAD6	0.032	0.034	-9999	-0.14	8	8
BMP7	0.034	0.01	-9999	0	39	39
BMP6	0.035	0.008	-9999	0	24	24
MAP3K7IP2	0.033	0.011	-9999	0	46	46
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.003	0.055	-9999	-0.22	16	16
PPM1A	0.034	0.009	-9999	0	30	30
SMAD1/SMURF2	-0.017	0.15	-9999	-0.39	51	51
SMAD7/SMURF1	0.033	0.029	-9999	-0.14	2	2
CTDSPL	0.036	0.006	-9999	0	12	12
PPP1CA	0.035	0.007	-9999	0	20	20
XIAP	0	0	-9999	-10000	0	0
CTDSP1	0.035	0.006	-9999	0	16	16
PPP1R15A	0.033	0.011	-9999	0	55	55
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.016	0.072	-9999	-0.21	32	32
CHRD	0.035	0.007	-9999	0	22	22
BMPR2	0.036	0.006	-9999	0	12	12
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.02	0.071	-9999	-0.18	53	53
BMP4	0.033	0.011	-9999	0	49	49
FST	0.033	0.011	-9999	0	48	48
BMP2-4/NOG	0.028	0.043	-9999	-0.11	35	35
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.05	0.061	-9999	-0.12	9	9

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0.025	0.019	-10000	0	-0.13	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
MAP3K7IP2	0.033	0.011	-10000	0	0	46	46
ERC1	0	0	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.01	0.12	-10000	0	-0.27	67	67
IRAK/TOLLIP	0.028	0.033	-10000	0	-0.12	22	22
IKBKB	0.036	0.003	-10000	0	0	4	4
IKBKG	0.037	0	-10000	0	-10000	0	0
IL1 alpha/IL1R2	0.043	0.022	-10000	0	-10000	0	0
IL1A	0.035	0.007	-10000	0	0	22	22
IL1B	0.003	0.044	0.092	94	-10000	0	94
IRAK/TRAF6/p62/Atypical PKCs	0.053	0.05	-10000	0	-0.13	28	28
IL1R2	0.03	0.014	-10000	0	0	90	90
IL1R1	0.036	0.006	-10000	0	0	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.015	0.1	-10000	0	-0.31	34	34
TOLLIP	0.034	0.009	-10000	0	0	30	30
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.036	0.004	-10000	0	0	7	7
TAK1/TAB1/TAB2	0.056	0.047	-10000	0	-0.14	19	19
IKK complex/ELKS	-0.045	0.096	-10000	0	-0.26	16	16
JUN	-0.039	0.041	0.19	1	-0.21	9	10
MAP3K7	0.034	0.01	-10000	0	0	41	41
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.032	0.11	-10000	0	-0.14	111	111
IL1 alpha/IL1R1/IL1RAP/MYD88	0.065	0.069	-10000	0	-0.13	50	50
PIK3R1	0.032	0.012	-10000	0	0	63	63
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.074	0.075	-10000	0	-0.12	49	49
IL1 beta fragment/IL1R1/IL1RAP	0.026	0.081	0.16	8	-0.14	83	91
NFKB1	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.033	0.036	0.16	3	-0.2	7	10
IRAK1	-0.018	0.01	-10000	0	-0.11	5	5
IL1RN/IL1R1	0.053	0.01	-10000	0	-10000	0	0
IRAK4	0.035	0.007	-10000	0	0	18	18
PRKCI	0.035	0.008	-10000	0	0	26	26
TRAF6	0.036	0.005	-10000	0	0	10	10
PI3K	0.019	0.075	-10000	0	-0.16	73	73
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.12	-10000	0	-0.27	64	64
CHUK	0.025	0.017	-10000	0	0	163	163
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.026	0.081	0.16	8	-0.14	83	91
IL1 beta/IL1R2	0.017	0.071	-10000	0	-0.14	71	71
IRAK/TRAF6/TAK1/TAB1/TAB2	0.059	0.067	-10000	0	-0.14	34	34
NF kappa B1 p50/RelA	0.016	0.098	-10000	0	-0.15	106	106
IRAK3	0.035	0.008	-10000	0	0	27	27
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.038	0.082	-10000	0	-0.13	81	81
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.008	0.076	-10000	0	-0.19	51	51
IL1 alpha/IL1R1/IL1RAP	0.049	0.053	-10000	0	-0.12	33	33
RELA	0.036	0.005	-10000	0	0	9	9
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
SQSTM1	0.034	0.009	-10000	0	0	35	35
MYD88	0.034	0.009	-10000	0	0	36	36
IRAK/TRAF6/MEKK3	0.049	0.038	-10000	0	-0.12	22	22
IL1RAP	0.03	0.014	-10000	0	0	94	94
UBE2N	0.036	0.006	-10000	0	0	13	13
IRAK/TRAF6	-0.039	0.062	0.062	69	-0.19	24	93
CASP1	0.029	0.015	-10000	0	0	108	108
IL1RN/IL1R2	0.045	0.021	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.038	0.096	-10000	0	-0.15	91	91
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.1	-10000	0	-0.3	38	38
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL1RN	0.036	0.004	-10000	0	0	6	6
TRAF6/TAK1/TAB1/TAB2	0.065	0.059	-10000	0	-0.14	22	22
MAP2K6	-0.038	0.035	0.18	3	-0.2	7	10

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.041	0.087	0.23	22	-0.2	8	30
TBX21	0.067	0.2	0.51	12	-0.52	9	21
B2M	0.035	0.008	-10000	0	0	27	27
TYK2	0.036	0.039	0.12	14	-0.05	28	42
IL12RB1	0.037	0.04	0.11	19	-0.051	31	50
GADD45B	0.058	0.29	0.51	18	-0.99	24	42
IL12RB2	0.04	0.04	0.12	20	-0.051	23	43
GADD45G	0.089	0.18	0.48	19	-0.49	5	24
natural killer cell activation	0.012	0.024	0.055	73	-0.032	22	95
RELB	0.034	0.009	-10000	0	0	32	32
RELA	0.036	0.005	-10000	0	0	9	9
IL18	0.034	0.022	0.088	2	-0.043	17	19
IL2RA	0.024	0.017	-10000	0	0	172	172
IFNG	0.034	0.009	-10000	0	0	30	30
STAT3 (dimer)	0.072	0.22	0.43	34	-0.5	28	62
HLA-DRB5	-0.001	0.009	-10000	0	-0.023	45	45
FASLG	0.071	0.2	0.52	12	-0.52	9	21
NF kappa B2 p52/RelB	0.05	0.18	0.41	15	-0.45	18	33
CD4	0.025	0.026	-10000	0	-0.04	55	55
SOCS1	0.036	0.005	-10000	0	0	8	8
EntrezGene:6955	-0.001	0.01	-10000	0	-0.025	59	59
CD3D	0.025	0.028	-10000	0	-0.042	64	64
CD3E	0.028	0.027	-10000	0	-0.04	67	67
CD3G	0.027	0.028	-10000	0	-0.042	67	67
IL12Rbeta2/JAK2	0.055	0.059	0.18	19	-10000	0	19
CCL3	0.07	0.2	0.44	30	-0.45	20	50
CCL4	0.039	0.33	0.56	16	-1	31	47
HLA-A	0.036	0.006	-10000	0	0	13	13
IL18/IL18R	0.094	0.061	0.21	36	-0.097	22	58
NOS2	0.072	0.19	0.42	37	-0.4	23	60
IL12/IL12R/TYK2/JAK2/SPHK2	0.038	0.086	0.22	26	-0.19	13	39
IL1R1	0.069	0.2	0.55	11	-0.52	8	19
IL4	0.004	0.048	-10000	0	-0.073	82	82
JAK2	0.033	0.038	0.11	13	-0.051	23	36
EntrezGene:6957	-0.001	0.009	-10000	0	-0.023	45	45
TCR/CD3/MHC I/CD8	0.006	0.044	0.11	1	-0.17	15	16
RAB7A	0.09	0.2	0.44	30	-0.51	24	54
lysosomal transport	0.09	0.2	0.42	35	-0.49	24	59
FOS	-0.11	0.48	0.5	10	-1.1	94	104
STAT4 (dimer)	0.084	0.2	0.43	37	-0.45	24	61
STAT5A (dimer)	0.077	0.19	0.42	13	-0.45	19	32
GZMA	0.067	0.2	0.55	12	-0.52	9	21
GZMB	0.066	0.2	0.57	11	-0.52	9	20
HLX	0	0	-10000	0	-10000	0	0
LCK	0.061	0.2	0.45	27	-0.46	20	47
TCR/CD3/MHC II/CD4	-0.023	0.12	0.16	22	-0.25	81	103
IL2/IL2R	0.063	0.044	-10000	0	-10000	0	0
MAPK14	0.092	0.23	0.47	29	-0.6	23	52
CCR5	0.075	0.17	0.39	40	-0.37	22	62
IL1B	0.029	0.037	0.11	9	-0.05	26	35
STAT6	0.052	0.098	0.28	22	-0.4	3	25
STAT4	0.035	0.009	-10000	0	0	29	29
STAT3	0.034	0.01	-10000	0	0	37	37
STAT1	0.034	0.01	-10000	0	0	40	40
NFKB1	0.035	0.007	-10000	0	0	18	18
NFKB2	0.025	0.017	-10000	0	0	158	158
IL12B	0.04	0.04	0.12	20	-0.051	25	45
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0	0	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.04	0.087	0.2	8	-0.23	22	30
IL2RB	0.033	0.011	-10000	0	0	53	53
proteasomal ubiquitin-dependent protein catabolic process	0.085	0.2	0.43	37	-0.42	24	61
IL2RG	0.035	0.008	-10000	0	0	24	24
IL12	0.061	0.06	0.18	20	-10000	0	20
STAT5A	0.036	0.004	-10000	0	0	5	5
CD247	-0.001	0.009	-10000	0	-0.023	45	45
IL2	0.036	0.005	-10000	0	0	10	10
SPHK2	0.034	0.009	-10000	0	0	34	34
FRAP1	0.035	0.007	-10000	0	0	17	17
IL12A	0.038	0.04	0.12	16	-0.051	32	48
IL12/IL12R/TYK2/JAK2	0.062	0.21	0.48	30	-0.48	20	50
MAP2K3	0.086	0.23	0.46	30	-0.59	25	55
RIPK2	0.036	0.006	-10000	0	0	14	14
MAP2K6	0.089	0.22	0.46	30	-0.55	25	55
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.021	0.027	-10000	0	-0.044	48	48
IL18RAP	0.038	0.02	0.083	3	-0.041	22	25
IL12Rbeta1/TYK2	0.049	0.062	0.18	7	-0.15	14	21
EOMES	-0.018	0.038	0.075	2	-0.098	49	51
STAT1 (dimer)	0.086	0.19	0.43	25	-0.43	11	36
T cell proliferation	0.074	0.18	0.39	37	-0.38	26	63
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.039	0.02	0.083	3	-0.041	22	25
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.043	0.17	0.33	2	-0.45	28	30
ATF2	0.084	0.21	0.44	28	-0.57	23	51

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.002	0.038	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
DOCK1	0.024	0.017	-10000	0	0	175	175
ITGA4	0.036	0.006	-10000	0	0	13	13
alpha4/beta7 Integrin/MAdCAM1	0.083	0.035	-10000	0	-0.12	5	5
EPO	0.025	0.017	-10000	0	0	166	166
alpha4/beta7 Integrin	0.052	0.011	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
alpha4/beta1 Integrin	0.039	0.025	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.035	0.026	-10000	0	-10000	0	0
lamellipodium assembly	-0.015	0.1	-10000	0	-0.37	20	20
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.019	0.075	-10000	0	-0.16	73	73
ARF6	0.035	0.008	-10000	0	0	27	27
JAK2	0.01	0.03	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
MADCAM1	0.034	0.009	-10000	0	0	32	32
cell adhesion	0.08	0.034	-10000	0	-0.12	5	5
CRKL/CBL	0.051	0.014	-10000	0	-10000	0	0
ITGB1	0.027	0.016	-10000	0	0	138	138
SRC	-0.034	0.058	0.19	4	-10000	0	4
ITGB7	0.036	0.005	-10000	0	0	11	11
RAC1	0.024	0.017	-10000	0	0	173	173
alpha4/beta1 Integrin/VCAM1	0.003	0.077	-10000	0	-0.12	126	126
p130Cas/Crk/Dock1	-0.031	0.063	0.2	4	-0.2	7	11
VCAM1	0.022	0.018	-10000	0	0	196	196
RHOA	0.035	0.007	-10000	0	0	18	18
alpha4/beta1 Integrin/Paxillin/GIT1	0.067	0.043	-10000	0	-10000	0	0
BCAR1	-0.033	0.051	0.18	4	-10000	0	4
EPOR	0.035	0.008	-10000	0	0	28	28
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.036	0.004	-10000	0	0	7	7
GIT1	0.036	0.003	-10000	0	0	4	4
Rac1/GTP	-0.016	0.1	-10000	0	-0.4	19	19

×

Class I PI3K 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.023	0.053	0.17	14	-0.22	9	23
DAPP1	-0.027	0.12	-10000	0	-0.3	66	66
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.048	0.19	0.25	2	-0.48	59	61
mol:DAG	-0.015	0.087	0.2	13	-0.21	43	56
HRAS	0.034	0.02	0.068	1	-0.032	27	28
RAP1A	0.038	0.013	0.063	4	-0.017	20	24
ARF5/GDP	-0.002	0.095	-10000	0	-0.31	32	32
PLCG2	0.032	0.012	-10000	0	0	63	63
PLCG1	0.035	0.007	-10000	0	0	19	19
ARF5	0.024	0.017	-10000	0	0	175	175
mol:GTP	-0.025	0.052	0.16	16	-0.2	9	25
ARF1/GTP	-0.02	0.045	0.12	14	-0.2	11	25
RHOA	0.035	0.007	-10000	0	0	18	18
YES1	0.034	0.01	-10000	0	0	41	41
RAP1A/GTP	-0.025	0.051	0.16	15	-0.19	9	24
ADAP1	-0.026	0.046	0.14	13	-0.19	9	22
ARAP3	-0.025	0.051	0.16	16	-0.19	9	25
INPPL1	0.036	0.006	-10000	0	0	12	12
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0.033	0.011	-10000	0	0	48	48
ARHGEF7	0.032	0.012	-10000	0	0	59	59
ARF1	0.035	0.008	-10000	0	0	24	24
NRAS	0.034	0.018	0.068	1	-0.033	12	13
FYN	0.03	0.014	-10000	0	0	90	90
ARF6	0.035	0.008	-10000	0	0	27	27
FGR	0.033	0.011	-10000	0	0	54	54
mol:Ca2+	0.003	0.058	0.14	35	-0.12	18	53
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.033	0.011	-10000	0	0	46	46
ZAP70	0.036	0.002	-10000	0	0	2	2
mol:IP3	-0.009	0.068	0.18	29	-0.16	21	50
LYN	0.031	0.013	-10000	0	0	74	74
ARF1/GDP	0.007	0.11	-10000	0	-0.33	36	36
RhoA/GDP	0.023	0.089	0.19	11	-0.21	30	41
PDK1/Src/Hsp90	0.047	0.01	-10000	0	-10000	0	0
BLNK	0.019	0.018	-10000	0	0	243	243
actin cytoskeleton reorganization	0.007	0.1	0.2	24	-0.29	25	49
SRC	0.036	0.006	-10000	0	0	14	14
PLEKHA2	-0.012	0.024	0.085	29	-10000	0	29
RAC1	0.024	0.017	-10000	0	0	173	173
PTEN	0.026	0.022	-10000	0	-0.035	16	16
HSP90AA1	0	0	-10000	0	-10000	0	0
ARF6/GTP	-0.028	0.052	0.16	15	-0.2	9	24
RhoA/GTP	-0.028	0.058	0.18	17	-0.21	10	27
Src family/SYK family/BLNK-LAT	-0.053	0.16	-10000	0	-0.35	85	85
BLK	0.035	0.007	-10000	0	0	17	17
PDPK1	0.036	0.004	-10000	0	0	7	7
CYTH1	-0.026	0.046	0.14	13	-0.19	9	22
HCK	0.027	0.016	-10000	0	0	128	128
CYTH3	-0.026	0.046	0.14	13	-0.19	9	22
CYTH2	-0.026	0.046	0.14	13	-0.19	9	22
KRAS	0.034	0.021	0.075	2	-0.032	31	33
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.003	0.031	0.21	3	-0.16	1	4
SGK1	0	0.03	0.21	2	-0.15	2	4
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.008	0.11	-10000	0	-0.33	37	37
SOS1	0	0	-10000	0	-10000	0	0
SYK	0.031	0.013	-10000	0	0	76	76
ARF6/GDP	-0.028	0.066	0.18	13	-0.22	26	39
mol:PI-3-4-5-P3	-0.026	0.049	0.15	13	-0.2	9	22
ARAP3/RAP1A/GTP	-0.025	0.051	0.16	15	-0.2	9	24
VAV1	0.034	0.009	-10000	0	0	35	35
mol:PI-3-4-P2	-0.011	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.062	0.092	0.21	102	-0.14	42	144
PLEKHA1	-0.008	0.022	0.085	23	-10000	0	23
Rac1/GDP	-0.002	0.098	-10000	0	-0.31	33	33
LAT	0.036	0.005	-10000	0	0	10	10
Rac1/GTP	-0.005	0.15	-10000	0	-0.46	35	35
ITK	-0.029	0.049	0.15	14	-0.19	9	23
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.026	0.11	0.23	11	-0.28	50	61
LCK	0.035	0.007	-10000	0	0	17	17
BTK	-0.027	0.052	0.15	17	-0.19	9	26

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	27	27
Jak2/Leptin Receptor	-0.003	0.14	-10000	0	-0.32	55	55
PTP1B/AKT1	0	0.11	-10000	0	-0.27	43	43
FYN	0.03	0.014	-10000	0	0	90	90
p210 bcr-abl/PTP1B	-0.01	0.11	0.17	3	-0.27	44	47
EGFR	0.009	0.016	-10000	0	-0.031	3	3
EGF/EGFR	-0.033	0.09	-10000	0	-0.28	38	38
CSF1	0.036	0.005	-10000	0	0	8	8
AKT1	0.033	0.011	-10000	0	0	53	53
INSR	0.035	0.009	-10000	0	-0.001	26	26
PTP1B/N-cadherin	-0.005	0.12	0.18	1	-0.28	52	53
Insulin Receptor/Insulin	0.02	0.11	-10000	0	-0.26	32	32
HCK	0.027	0.016	-10000	0	0	128	128
CRK	0.035	0.008	-10000	0	0	23	23
TYK2	-0.009	0.12	0.3	19	-0.29	41	60
EGF	0.027	0.024	-10000	0	-0.031	66	66
YES1	0.034	0.01	-10000	0	0	41	41
CAV1	0.007	0.14	0.21	33	-0.3	48	81
TXN	0.035	0.011	-10000	0	0	40	40
PTP1B/IRS1/GRB2	0.006	0.12	0.2	1	-0.28	45	46
cell migration	0.01	0.11	0.27	44	-0.17	3	47
STAT3	0.034	0.01	-10000	0	0	37	37
PRLR	0.038	0.004	-10000	0	-10000	0	0
ITGA2B	0.036	0.004	-10000	0	0	5	5
CSF1R	0.027	0.016	-10000	0	0	131	131
Prolactin Receptor/Prolactin	0.057	0.012	-10000	0	-10000	0	0
FGR	0.033	0.011	-10000	0	0	54	54
PTP1B/p130 Cas	-0.012	0.1	0.16	1	-0.26	45	46
Crk/p130 Cas	-0.001	0.11	0.17	1	-0.26	48	49
DOK1	-0.008	0.1	0.18	4	-0.29	33	37
JAK2	-0.014	0.13	-10000	0	-0.34	55	55
Jak2/Leptin Receptor/Leptin	-0.014	0.12	-10000	0	-0.31	34	34
PIK3R1	0.032	0.012	-10000	0	0	63	63
PTPN1	-0.01	0.11	0.17	3	-0.27	44	47
LYN	0.031	0.013	-10000	0	0	74	74
CDH2	0.033	0.011	-10000	0	0	55	55
SRC	0.014	0.099	-10000	0	-0.45	18	18
ITGB3	0.036	0.003	-10000	0	0	4	4
CAT1/PTP1B	-0.01	0.17	0.23	19	-0.36	65	84
CAPN1	0.036	0.006	-10000	0	-0.004	8	8
CSK	0.035	0.007	-10000	0	0	21	21
PI3K	0.011	0.13	-10000	0	-0.29	43	43
mol:H2O2	0.004	0.005	0.029	6	-10000	0	6
STAT3 (dimer)	-0.012	0.11	-10000	0	-0.28	35	35
negative regulation of transcription	-0.014	0.13	-10000	0	-0.33	55	55
FCGR2A	0.028	0.015	-10000	0	0	114	114
FER	0.036	0.008	-10000	0	-0.002	15	15
alphaIIb/beta3 Integrin	0.053	0.006	-10000	0	-10000	0	0
BLK	0.035	0.007	-10000	0	0	17	17
Insulin Receptor/Insulin/Shc	0.059	0.036	-10000	0	-0.13	8	8
RHOA	0.035	0.007	-10000	0	0	18	18
LEPR	0.035	0.007	-10000	0	0	20	20
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.035	0.007	-10000	0	0	17	17
mol:NADPH	0.001	0.003	-10000	0	-10000	0	0
TRPV6	-0.006	0.15	0.2	5	-0.35	58	63
PRL	0.038	0.007	-10000	0	-10000	0	0
SOCS3	0.022	0.051	-10000	0	-1.1	1	1
SPRY2	0.029	0.018	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	0.056	0.046	-10000	0	-0.12	23	23
CSF1/CSF1R	-0.002	0.13	-10000	0	-0.28	50	50
Ras protein signal transduction	-0.01	0.069	0.57	5	-10000	0	5
IRS1	0.033	0.011	-10000	0	0	52	52
INS	0.036	0.007	-10000	0	-0.002	15	15
LEP	0.024	0.017	-10000	0	0	173	173
STAT5B	-0.004	0.11	0.17	2	-0.28	32	34
STAT5A	-0.004	0.11	0.17	4	-0.28	33	37
GRB2	0.035	0.007	-10000	0	0	17	17
PDGFB-D/PDGFRB	0.001	0.12	0.18	1	-0.27	44	45
CSN2	0.013	0.041	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
LAT	-0.028	0.18	-10000	0	-0.47	64	64
YBX1	0.038	0.042	-10000	0	-0.29	8	8
LCK	0.035	0.007	-10000	0	0	17	17
SHC1	0.033	0.011	-10000	0	0	52	52
NOX4	0.034	0.015	-10000	0	-10000	0	0

×

Glypican 1 network

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
GPC1/FGF2 dimer/FGFR1 dimer	0.052	0.056	-10000	0	-0.13	36	36
fibroblast growth factor receptor signaling pathway	0.051	0.055	-10000	0	-0.13	36	36
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.033	0.011	-10000	0	0	52	52
GPC1/SLIT2	0.032	0.044	-10000	0	-0.14	23	23
SMAD2	-0.023	0.048	0.18	11	-0.2	3	14
GPC1/PrPc/Cu2+	0.026	0.058	-10000	0	-0.14	52	52
GPC1/Laminin alpha1	0.015	0.04	-10000	0	-0.13	35	35
TDGF1	0.035	0.007	-10000	0	0	18	18
CRIPTO/GPC1	0.038	0.047	-10000	0	-0.14	29	29
APP/GPC1	0.034	0.058	-10000	0	-0.16	38	38
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.023	0.033	0.089	22	-0.12	22	44
FLT1	0.034	0.009	-10000	0	0	33	33
GPC1/TGFB/TGFBR1/TGFBR2	0.051	0.053	-10000	0	-0.12	34	34
SERPINC1	0.036	0.005	-10000	0	0	11	11
FYN	-0.018	0.029	0.089	23	-0.12	8	31
FGR	-0.022	0.033	0.089	23	-0.12	21	44
positive regulation of MAPKKK cascade	-0.038	0.12	0.2	10	-0.3	62	72
SLIT2	0.029	0.015	-10000	0	0	103	103
GPC1/NRG	0.037	0.05	-10000	0	-0.14	35	35
NRG1	0.036	0.005	-10000	0	0	9	9
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.032	0.043	-10000	0	-0.12	35	35
LYN	-0.022	0.033	0.089	22	-0.12	23	45
mol:Spermine	-0.01	0.004	-10000	0	-10000	0	0
cell growth	0.051	0.055	-10000	0	-0.13	36	36
BMP signaling pathway	-0.032	0.012	0	64	-10000	0	64
SRC	-0.025	0.034	0.089	23	-0.12	28	51
TGFBR1	0.035	0.007	-10000	0	0	17	17
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.018	0.018	-10000	0	0	262	262
GPC1	0.032	0.012	-10000	0	0	64	64
TGFBR1 (dimer)	0.035	0.007	-10000	0	0	17	17
VEGFA	0	0	-10000	0	-10000	0	0
BLK	-0.025	0.034	0.089	24	-0.12	27	51
HCK	-0.018	0.03	0.089	19	-0.12	16	35
FGF2	0.035	0.008	-10000	0	0	25	25
FGFR1	0.036	0.005	-10000	0	0	9	9
VEGFR1 homodimer	0.034	0.009	-10000	0	0	33	33
TGFBR2	0.035	0.009	-10000	0	0	29	29
cell death	0.034	0.057	-10000	0	-0.16	38	38
ATIII/GPC1	0.037	0.049	-10000	0	-0.14	33	33
PLA2G2A/GPC1	-0.005	0.074	-10000	0	-0.15	93	93
LCK	-0.024	0.034	0.089	24	-0.12	25	49
neuron differentiation	0.037	0.05	-10000	0	-0.14	35	35
PrPc/Cu2+	0.016	0.038	-10000	0	-0.13	31	31
APP	0.035	0.007	-10000	0	0	21	21
TGFBR2 (dimer)	0.034	0.009	-10000	0	0	29	29

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	0.017	0.051	-10000	0	-0.18	28	28
PDGFRB	0.036	0.009	-10000	0	-0.001	28	28
SPHK1	0.017	0.04	-10000	0	-0.76	1	1
mol:S1P	0.019	0.042	-10000	0	-0.68	1	1
S1P1/S1P/Gi	-0.001	0.14	0.23	19	-0.42	33	52
GNAO1	0.032	0.015	0.063	1	0	87	88
PDGFB-D/PDGFRB/PLCgamma1	0.027	0.14	0.25	22	-0.37	31	53
PLCG1	-0.005	0.13	0.22	21	-0.42	29	50
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.036	0.009	-10000	0	-0.001	28	28
GNAI2	0.036	0.012	-10000	0	0	43	43
GNAI3	0.037	0.007	-10000	0	0	15	15
GNAI1	0.018	0.019	-10000	0	0	263	263
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	0.007	0.073	0.12	5	-0.27	27	32
S1P1/S1P	0.024	0.077	0.22	3	-0.28	17	20
negative regulation of cAMP metabolic process	0	0.14	0.23	20	-0.41	33	53
MAPK3	0.002	0.14	0.27	22	-0.44	26	48
calcium-dependent phospholipase C activity	0	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
KDR	0.027	0.034	0.093	1	-0.13	18	19
PLCB2	0.036	0.089	0.22	19	-0.26	17	36
RAC1	0.024	0.017	-10000	0	0	173	173
RhoA/GTP	0.018	0.066	-10000	0	-0.24	18	18
receptor internalization	0.023	0.073	0.21	3	-0.26	17	20
PTGS2	0.032	0.15	0.34	10	-0.44	20	30
Rac1/GTP	0.009	0.057	-10000	0	-0.27	12	12
RHOA	0.035	0.007	-10000	0	0	18	18
VEGFA	-0.001	0.021	-10000	0	-0.098	23	23
negative regulation of T cell proliferation	0	0.14	0.23	20	-0.41	33	53
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.032	0.015	-10000	0	0	81	81
MAPK1	0.003	0.14	0.26	22	-0.46	24	46
S1P1/S1P/PDGFB-D/PDGFRB	0.052	0.1	0.25	12	-0.29	20	32
ABCC1	0.036	0.008	-10000	0	0	19	19

×

E-cadherin signaling in keratinocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
keratinocyte differentiation	-0.019	0.11	0.22	2	-0.37	28	30
adherens junction organization	-0.001	0.076	0.18	1	-0.31	19	20
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.11	0.22	15	-0.31	20	35
FMN1	0.008	0.063	0.18	1	-0.27	15	16
mol:IP3	-0.008	0.079	0.14	5	-0.25	32	37
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.013	0.067	0.19	1	-0.28	15	16
CTNNB1	0.035	0.006	-10000	0	0	15	15
AKT1	-0.006	0.088	0.14	2	-0.31	26	28
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.027	0.067	-10000	0	-0.48	4	4
CTNND1	0.035	0.009	-10000	0	0	32	32
mol:PI-4-5-P2	0.003	0.067	0.17	3	-0.27	17	20
VASP	0.002	0.062	0.18	1	-0.27	15	16
ZYX	0.006	0.057	0.16	1	-0.32	9	10
JUB	0.008	0.063	0.18	1	-0.27	15	16
EGFR(dimer)	0.001	0.065	-10000	0	-0.32	13	13
E-cadherin/beta catenin-gamma catenin	0.064	0.029	-10000	0	-0.12	3	3
mol:PI-3-4-5-P3	0.02	0.093	-10000	0	-0.29	25	25
PIK3CA	0.03	0.015	-10000	0	-0.002	84	84
PI3K	0.02	0.095	-10000	0	-0.29	25	25
FYN	-0.042	0.13	0.25	1	-0.33	64	65
mol:Ca2+	-0.008	0.078	0.14	5	-0.24	32	37
JUP	0.033	0.011	-10000	0	0	51	51
PIK3R1	0.031	0.015	-10000	0	-0.004	72	72
mol:DAG	-0.008	0.079	0.14	5	-0.25	32	37
CDH1	0.034	0.01	-10000	0	0	38	38
RhoA/GDP	0.062	0.13	0.24	28	-0.3	20	48
establishment of polarity of embryonic epithelium	0.002	0.062	0.18	1	-0.27	15	16
SRC	0.036	0.006	-10000	0	0	14	14
RAC1	0.024	0.017	-10000	0	0	173	173
RHOA	0.035	0.007	-10000	0	0	18	18
EGFR	0.009	0.016	-10000	0	0	381	381
CASR	-0.024	0.075	0.14	17	-0.27	25	42
RhoA/GTP	0.009	0.086	-10000	0	-0.26	27	27
AKT2	-0.005	0.08	0.15	1	-0.28	25	26
actin cable formation	-0.002	0.061	0.17	1	-0.26	16	17
apoptosis	0.01	0.098	0.33	29	-0.21	4	33
CTNNA1	0.035	0.008	-10000	0	-0.001	21	21
mol:GDP	-0.021	0.074	0.19	4	-0.31	20	24
PIP5K1A	0.003	0.067	0.17	3	-0.27	17	20
PLCG1	-0.008	0.081	0.14	5	-0.26	32	37
Rac1/GTP	-0.004	0.069	-10000	0	-0.32	13	13
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.012	0.05	-10000	0	-0.12	46	46
TRAF2/ASK1	0.032	0.043	-10000	0	-0.12	35	35
ATM	0.034	0.009	-10000	0	0	35	35
MAP2K3	0.014	0.099	0.24	1	-0.31	24	25
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.011	0.09	0.27	1	-0.28	23	24
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.032	0.012	-10000	0	0	67	67
TXN	0.007	0.002	-10000	0	0	40	40
CALM1	0.033	0.011	-10000	0	0	54	54
GADD45A	0.031	0.013	-10000	0	0	75	75
GADD45B	0.03	0.014	-10000	0	0	89	89
MAP3K1	0.035	0.007	-10000	0	0	20	20
MAP3K6	0.035	0.007	-10000	0	0	20	20
MAP3K7	0.034	0.01	-10000	0	0	41	41
MAP3K4	0.032	0.012	-10000	0	0	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.032	0.053	-10000	0	-0.14	38	38
TAK1/TAB family	0.009	0.054	-10000	0	-0.31	11	11
RAC1/OSM/MEKK3	0.03	0.026	-10000	0	-0.1	5	5
TRAF2	0.036	0.006	-10000	0	0	15	15
RAC1/OSM/MEKK3/MKK3	0.012	0.075	-10000	0	-0.27	21	21
TRAF6	0.009	0.033	-10000	0	-0.2	12	12
RAC1	0.024	0.017	-10000	0	0	173	173
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.017	0.018	-10000	0	0	272	272
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.009	0.054	-10000	0	-0.13	53	53
MAPK11	0.033	0.011	-10000	0	0	49	49
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	0.011	0.066	-10000	0	-0.13	66	66
OSM/MEKK3	0.027	0.003	-10000	0	-10000	0	0
TAOK1	0.007	0.002	-10000	0	0	35	35
TAOK2	0.012	0.024	-10000	0	-0.2	6	6
TAOK3	0.006	0.041	-10000	0	-0.2	19	19
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
MAPK14	0.036	0.004	-10000	0	0	6	6
MAP3K7IP2	0.033	0.011	-10000	0	0	46	46
MAP3K5	0.03	0.014	-10000	0	0	90	90
MAP3K10	0.035	0.008	-10000	0	0	28	28
MAP3K3	0.036	0.004	-10000	0	0	7	7
TRX/ASK1	0.022	0.037	-10000	0	-0.16	16	16
GADD45/MTK1/MTK1	0.043	0.075	-10000	0	-0.13	64	64

×

PLK1 signaling events

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
regulation of centriole-centriole cohesion	-0.001	0.009	0.026	1	-0.034	16	17
BUB1B	-0.023	0.084	0.12	22	-0.22	64	86
PLK1	0.004	0.023	0.083	17	-0.071	3	20
PLK1S1	0.002	0.014	0.049	21	-0.039	2	23
KIF2A	0.004	0.021	0.076	15	-0.064	3	18
regulation of mitotic centrosome separation	0.005	0.023	0.083	17	-0.071	3	20
GOLGA2	0.035	0.008	-10000	0	0	28	28
Hec1/SPC24	-0.004	0.01	-10000	0	-0.055	5	5
WEE1	-0.032	0.13	-10000	0	-0.46	36	36
cytokinesis	-0.021	0.11	0.16	9	-0.3	57	66
PP2A-alpha B56	0.051	0.087	-10000	0	-0.51	9	9
AURKA	0.002	0.016	0.056	21	-0.04	2	23
PICH/PLK1	-0.034	0.073	0.071	9	-0.18	87	96
CENPE	0.003	0.047	0.12	50	-0.1	12	62
RhoA/GTP	0.024	0.019	-10000	0	-0.13	7	7
positive regulation of microtubule depolymerization	0.004	0.02	0.074	16	-0.063	3	19
PPP2CA	0.035	0.007	-10000	0	0	21	21
FZR1	0.035	0.008	-10000	0	0	28	28
TPX2	-0.025	0.089	0.11	2	-0.22	84	86
PAK1	0.036	0.006	-10000	0	0	15	15
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.008	-10000	0	0	25	25
CLSPN	0.01	0.025	-10000	0	-0.2	5	5
GORASP1	0.034	0.009	-10000	0	0	33	33
metaphase	0.001	0.003	0.015	11	-0.011	1	12
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.002	0.014	0.049	21	-0.039	2	23
G2 phase of mitotic cell cycle	-0.001	0.002	0.01	7	-10000	0	7
STAG2	0.035	0.007	-10000	0	0	22	22
GRASP65/GM130/RAB1/GTP	-0.02	0.14	-10000	0	-0.6	26	26
spindle elongation	0.005	0.023	0.083	17	-0.071	3	20
ODF2	0.035	0.009	-10000	0	0	29	29
BUB1	0.02	0.074	-10000	0	-0.57	7	7
TPT1	-0.002	0.05	-10000	0	-0.18	34	34
CDC25C	0.011	0.03	-10000	0	-0.22	7	7
CDC25B	0.012	0.032	-10000	0	-0.029	175	175
SGOL1	0.001	0.009	0.034	16	-0.026	1	17
RHOA	0.035	0.007	-10000	0	0	18	18
CCNB1/CDK1	-0.02	0.12	-10000	0	-0.23	98	98
CDC14B	-0.011	0.004	0.01	6	-10000	0	6
CDC20	0.028	0.016	-10000	0	0	125	125
PLK1/PBIP1	-0.015	0.036	0.069	6	-0.089	77	83
mitosis	-0.001	0.003	0.011	11	-10000	0	11
FBXO5	-0.017	0.061	0.12	17	-0.16	54	71
CDC2	0.015	0.023	-10000	0	-0.03	42	42
NDC80	0	0	-10000	0	-10000	0	0
metaphase plate congression	0.002	0.059	-10000	0	-0.26	23	23
ERCC6L	-0.045	0.1	-10000	0	-0.22	93	93
NLP/gamma Tubulin	0.001	0.027	0.075	11	-0.1	21	32
microtubule cytoskeleton organization	-0.002	0.05	-10000	0	-0.18	34	34
G2/M transition DNA damage checkpoint	-0.001	0.002	0.01	5	-10000	0	5
PPP1R12A	0.035	0.008	-10000	0	0	24	24
interphase	-0.001	0.002	0.01	5	-10000	0	5
PLK1/PRC1-2	0.007	0.075	0.13	1	-0.14	87	88
GRASP65/GM130/RAB1/GTP/PLK1	0.046	0.053	-10000	0	-0.12	29	29
RAB1A	0.035	0.007	-10000	0	0	18	18
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.002	0.018	0.066	18	-0.051	1	19
mitotic prometaphase	-0.001	0.005	0.02	23	-10000	0	23
proteasomal ubiquitin-dependent protein catabolic process	-0.048	0.1	0.18	1	-0.27	42	43
microtubule-based process	0.019	0.024	0.099	5	-0.064	3	8
Golgi organization	0.005	0.023	0.083	17	-0.071	3	20
Cohesin/SA2	0.02	0.033	0.096	6	-0.094	21	27
PPP1CB/MYPT1	0.046	0.036	-10000	0	-0.15	14	14
KIF20A	0.029	0.015	-10000	0	0	109	109
APC/C/CDC20	0.019	0.024	0.11	5	-0.061	1	6
PPP2R1A	0.032	0.012	-10000	0	0	61	61
chromosome segregation	-0.015	0.035	0.068	6	-0.088	77	83
PRC1	0.028	0.016	-10000	0	0	123	123
ECT2	0.001	0.059	0.15	46	-0.11	24	70
C13orf34	0.003	0.019	0.07	17	-0.056	2	19
NUDC	0.001	0.059	-10000	0	-0.26	23	23
regulation of attachment of spindle microtubules to kinetochore	-0.023	0.083	0.11	24	-0.21	64	88
spindle assembly	0.002	0.025	0.085	15	-0.078	13	28
spindle stabilization	0.002	0.014	0.048	21	-0.044	1	22
APC/C/HCDH1	0.024	0.026	0.089	1	-0.12	15	16
MKLP2/PLK1	0.019	0.024	0.099	5	-0.064	3	8
CCNB1	0.014	0.028	-10000	0	-0.028	116	116
PPP1CB	0.036	0.006	-10000	0	0	15	15
BTRC	0.025	0.017	-10000	0	0	155	155
ROCK2	0.016	0.029	-10000	0	-0.21	3	3
TUBG1	0.002	0.05	-10000	0	-0.22	22	22
G2/M transition of mitotic cell cycle	-0.047	0.1	0.14	18	-0.23	92	110
MLF1IP	-0.009	0.006	0.01	1	-10000	0	1
INCENP	0.036	0.005	-10000	0	0	8	8

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0.036	0.006	-10000	0	0	15	15
MKNK1	0.034	0.009	-10000	0	0	34	34
mol:PIP3	-0.018	0.057	0.094	7	-0.23	22	29
FRAP1	0.03	0.1	0.28	2	-0.48	12	14
AKT1	0.007	0.1	0.17	95	-0.26	30	125
INSR	0.035	0.008	-10000	0	0	25	25
Insulin Receptor/Insulin	0.046	0.013	-10000	0	-10000	0	0
mol:GTP	0.032	0.11	0.2	58	-0.26	30	88
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.047	-10000	0	-0.19	15	15
TSC2	0.035	0.008	-10000	0	0	28	28
RHEB/GDP	0.002	0.076	0.14	1	-0.22	35	36
TSC1	0.034	0.01	-10000	0	0	40	40
Insulin Receptor/IRS1	0.022	0.061	-10000	0	-0.25	23	23
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.023	0.071	0.16	1	-0.22	14	15
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0	0	-10000	0	-10000	0	0
RPS6KB1	0.036	0.085	0.26	10	-0.32	4	14
MAP3K5	-0.026	0.084	0.16	1	-0.22	73	74
PIK3R1	0.033	0.012	-10000	0	0	63	63
apoptosis	-0.026	0.084	0.16	1	-0.22	73	74
mol:LY294002	0	0	0.001	4	-0.001	18	22
EIF4B	0.029	0.082	0.24	11	-0.31	5	16
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.03	0.072	0.24	7	-0.28	4	11
eIF4E/eIF4G1/eIF4A1	0.009	0.075	-10000	0	-0.3	15	15
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.022	0.082	-10000	0	-0.22	34	34
mTOR/RHEB/GTP/Raptor/GBL	0.006	0.06	0.2	8	-0.21	10	18
FKBP1A	0.034	0.01	-10000	0	0	44	44
RHEB/GTP	0.014	0.086	0.23	5	-0.23	29	34
mol:Amino Acids	0	0	0.001	4	-0.001	18	22
FKBP12/Rapamycin	0.022	0.023	-10000	0	-0.13	10	10
PDPK1	-0.021	0.061	0.16	15	-0.23	20	35
EIF4E	0.034	0.01	-10000	0	0	38	38
ASK1/PP5C	-0.034	0.24	-10000	0	-0.56	79	79
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.02	0.11	-10000	0	-0.33	32	32
TSC1/TSC2	0.035	0.12	0.21	58	-0.28	30	88
tumor necrosis factor receptor activity	0	0	0.001	18	-0.001	4	22
RPS6	0.031	0.013	-10000	0	0	81	81
PPP5C	0.034	0.01	-10000	0	0	39	39
EIF4G1	0.033	0.011	-10000	0	0	49	49
IRS1	0.001	0.058	-10000	0	-0.26	23	23
INS	0.036	0.006	-10000	0	0	14	14
PTEN	0.026	0.017	-10000	0	0	148	148
PDK2	-0.021	0.061	0.16	15	-0.23	19	34
EIF4EBP1	-0.02	0.25	-10000	0	-1.1	24	24
PIK3CA	0.031	0.014	-10000	0	0	80	80
PPP2R5D	0.025	0.097	0.27	3	-0.44	12	15
peptide biosynthetic process	-0.02	0.017	0.18	3	-10000	0	3
RHEB	0.024	0.017	-10000	0	0	173	173
EIF4A1	0.035	0.007	-10000	0	0	17	17
mol:Rapamycin	0	0.001	0.004	16	-0.003	14	30
EEF2	-0.021	0.017	0.18	3	-10000	0	3
eIF4E/4E-BP1	-0.004	0.24	-10000	0	-1.1	24	24

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	0.01	0.057	-10000	0	-0.2	28	28
epithelial cell differentiation	0.063	0.051	-10000	0	-0.14	25	25
CYFIP2	0.031	0.013	-10000	0	0	78	78
ENAH	-0.041	0.07	0.24	12	-0.25	9	21
EGFR	0.009	0.016	-10000	0	0	381	381
EPHA2	0.033	0.011	-10000	0	0	54	54
MYO6	-0.029	0.049	0.18	9	-0.21	13	22
CTNNB1	0.036	0.006	-10000	0	0	15	15
ABI1/Sra1/Nap1	0.031	0.063	-10000	0	-0.12	58	58
AQP5	-0.02	0.051	0.21	2	-0.28	9	11
CTNND1	0.034	0.009	-10000	0	0	32	32
mol:PI-4-5-P2	-0.031	0.044	0.18	6	-0.2	13	19
regulation of calcium-dependent cell-cell adhesion	-0.028	0.044	0.18	8	-0.19	8	16
EGF	0.035	0.008	-10000	0	0	25	25
NCKAP1	0.036	0.002	-10000	0	0	2	2
AQP3	-0.035	0.075	-10000	0	-0.3	32	32
cortical microtubule organization	0.063	0.051	-10000	0	-0.14	25	25
GO:0000145	-0.03	0.04	0.16	6	-0.19	13	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.07	0.054	-10000	0	-0.14	25	25
MLLT4	0.034	0.009	-10000	0	0	36	36
ARF6/GDP	-0.052	0.039	-10000	0	-0.22	12	12
ARF6	0.035	0.008	-10000	0	0	27	27
Ephrin A1/EPHA2/NCK1/GIT1	0.076	0.052	-10000	0	-0.12	24	24
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.029	0.079	0.16	1	-0.28	33	34
PVRL2	0.034	0.009	-10000	0	0	35	35
ZYX	-0.021	0.046	0.18	6	-0.21	15	21
ARF6/GTP	0.079	0.059	-10000	0	-0.12	23	23
CDH1	0.034	0.01	-10000	0	0	38	38
EGFR/EGFR/EGF/EGF	-0.001	0.059	-10000	0	-0.13	66	66
RhoA/GDP	0.063	0.056	-10000	0	-0.14	29	29
actin cytoskeleton organization	-0.024	0.045	0.17	6	-0.22	12	18
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
GIT1	0.036	0.003	-10000	0	0	4	4
IGF1R	0.033	0.012	-10000	0	0	57	57
IGF1	0.035	0.008	-10000	0	0	23	23
DIAPH1	-0.12	0.27	-10000	0	-0.52	130	130
Wnt receptor signaling pathway	-0.063	0.051	0.14	25	-10000	0	25
RHOA	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	-0.053	0.041	-10000	0	-0.21	16	16
CTNNA1	0.035	0.007	-10000	0	0	20	20
VCL	-0.024	0.046	0.17	6	-0.23	12	18
EFNA1	0.033	0.011	-10000	0	0	50	50
LPP	-0.03	0.045	0.18	4	-0.22	13	17
Ephrin A1/EPHA2	0.046	0.062	-10000	0	-0.14	40	40
SEC6/SEC8	-0.044	0.028	-10000	0	-0.14	25	25
MGAT3	-0.028	0.044	0.19	8	-0.19	8	16
HGF/MET	0.036	0.05	-10000	0	-0.14	16	16
HGF	0.024	0.017	-10000	0	0	177	177
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	0.01	0.057	-10000	0	-0.21	28	28
actin cable formation	-0.039	0.1	0.32	9	-0.3	33	42
KIAA1543	-0.025	0.036	0.16	7	-0.18	8	15
KIFC3	-0.031	0.042	0.19	5	-0.19	8	13
NCK1	0.035	0.008	-10000	0	0	27	27
EXOC3	0.036	0.003	-10000	0	0	4	4
ACTN1	-0.026	0.049	0.19	7	-0.21	16	23
NCK1/GIT1	0.05	0.022	-10000	0	-0.14	5	5
mol:GDP	0.063	0.051	-10000	0	-0.14	25	25
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.028	0.03	0.053	22	-0.13	25	47
PIP5K1C	-0.031	0.045	0.18	6	-0.21	13	19
LIMA1	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.017	-10000	0	0	152	152
ROCK1	-0.034	0.085	0.28	17	-0.29	5	22
adherens junction assembly	-0.023	0.073	0.23	6	-0.33	14	20
IGF-1R heterotetramer/IGF1	0.048	0.062	-10000	0	-0.14	37	37
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
MET	0.023	0.018	-10000	0	0	191	191
PLEKHA7	-0.028	0.03	0.053	22	-0.13	25	47
mol:GTP	0.073	0.051	-10000	0	-0.12	24	24
establishment of epithelial cell apical/basal polarity	-0.038	0.039	0.12	13	-0.18	10	23
cortical actin cytoskeleton stabilization	0.01	0.057	-10000	0	-0.2	28	28
regulation of cell-cell adhesion	-0.024	0.045	0.17	6	-0.22	12	18
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	0.01	0.057	-10000	0	-0.21	28	28

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.013	0.19	-10000	0	-0.83	23	23
regulation of axonogenesis	0.003	0.064	0.25	22	-10000	0	22
myoblast fusion	-0.015	0.093	0.35	27	-10000	0	27
mol:GTP	0.015	0.065	-10000	0	-0.18	44	44
regulation of calcium-dependent cell-cell adhesion	-0.026	0.073	0.17	41	-10000	0	41
ARF1/GTP	0.035	0.061	-10000	0	-0.14	46	46
mol:GM1	0.003	0.047	-10000	0	-0.13	45	45
mol:Choline	-0.015	0.041	0.085	3	-0.13	40	43
lamellipodium assembly	-0.009	0.1	-10000	0	-0.37	33	33
MAPK3	0.012	0.081	-10000	0	-0.29	25	25
ARF6/GTP/NME1/Tiam1	0.027	0.074	-10000	0	-0.18	41	41
ARF1	0.035	0.008	-10000	0	0	24	24
ARF6/GDP	0.015	0.093	-10000	0	-0.35	27	27
ARF1/GDP	0.013	0.1	-10000	0	-0.29	43	43
ARF6	0.039	0.042	-10000	0	-0.13	25	25
RAB11A	0.035	0.007	-10000	0	0	18	18
TIAM1	0.029	0.022	-10000	0	-0.044	32	32
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.082	-10000	0	-0.31	24	24
actin filament bundle formation	-0.019	0.11	0.29	47	-10000	0	47
KALRN	0.006	0.069	0.13	2	-0.26	28	30
RAB11FIP3/RAB11A	0.047	0.034	-10000	0	-0.16	12	12
RhoA/GDP	0.02	0.11	-10000	0	-0.29	47	47
NME1	-0.001	0.008	-10000	0	-0.03	24	24
Rac1/GDP	0.013	0.089	-10000	0	-0.3	29	29
substrate adhesion-dependent cell spreading	0.015	0.065	-10000	0	-0.18	44	44
cortical actin cytoskeleton organization	-0.009	0.1	-10000	0	-0.37	33	33
RAC1	0.024	0.017	-10000	0	0	173	173
liver development	0.015	0.065	-10000	0	-0.18	44	44
ARF6/GTP	0.015	0.065	-10000	0	-0.18	44	44
RhoA/GTP	0.034	0.063	-10000	0	-0.15	50	50
mol:GDP	-0.005	0.1	0.17	2	-0.3	44	46
ARF6/GTP/RAB11FIP3/RAB11A	0.051	0.068	-10000	0	-0.14	45	45
RHOA	0.035	0.007	-10000	0	0	18	18
PLD1	0.012	0.051	-10000	0	-0.14	44	44
RAB11FIP3	0.036	0.006	-10000	0	0	15	15
tube morphogenesis	-0.009	0.1	-10000	0	-0.37	33	33
ruffle organization	-0.003	0.064	-10000	0	-0.25	22	22
regulation of epithelial cell migration	0.015	0.065	-10000	0	-0.18	44	44
PLD2	0.012	0.052	-10000	0	-0.14	46	46
PIP5K1A	-0.003	0.064	-10000	0	-0.25	22	22
mol:Phosphatidic acid	-0.015	0.041	0.085	3	-0.13	40	43
Rac1/GTP	-0.009	0.1	-10000	0	-0.37	33	33

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.018	0.021	0.092	16	-10000	0	16
BAD/BCL-XL/YWHAZ	0.048	0.034	-10000	0	-0.12	12	12
CDKN1B	-0.024	0.12	-10000	0	-0.33	57	57
CDKN1A	-0.024	0.12	-10000	0	-0.33	58	58
FRAP1	0.035	0.007	-10000	0	0	17	17
PRKDC	0.033	0.01	-10000	0	0	44	44
FOXO3	-0.019	0.11	-10000	0	-0.31	59	59
AKT1	-0.019	0.12	-10000	0	-0.33	58	58
BAD	0.036	0.006	-10000	0	0	14	14
AKT3	0.014	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.019	0.11	-10000	0	-0.31	59	59
AKT1/ASK1	-0.009	0.12	-10000	0	-0.32	58	58
BAD/YWHAZ	0.063	0.037	-10000	0	-0.13	12	12
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.035	0.008	-10000	0	0	28	28
JNK cascade	0.009	0.12	0.31	58	-10000	0	58
TSC1	-0.025	0.12	0.2	1	-0.33	57	58
YWHAZ	0.035	0.007	-10000	0	0	21	21
AKT1/RAF1	-0.002	0.13	-10000	0	-0.34	60	60
EP300	0.033	0.011	-10000	0	0	49	49
mol:GDP	-0.019	0.12	-10000	0	-0.32	58	58
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.027	0.12	-10000	0	-0.33	60	60
YWHAQ	0.036	0.005	-10000	0	0	9	9
TBC1D4	-0.001	0.022	0.12	14	-10000	0	14
MAP3K5	0.03	0.014	-10000	0	0	90	90
MAPKAP1	0.034	0.009	-10000	0	0	31	31
negative regulation of cell cycle	0.005	0.11	0.4	20	-10000	0	20
YWHAH	0.031	0.013	-10000	0	0	73	73
AKT1S1	-0.019	0.11	-10000	0	-0.31	59	59
CASP9	-0.021	0.11	0.2	3	-0.32	57	60
YWHAB	0.035	0.008	-10000	0	0	24	24
p27Kip1/KPNA1	-0.008	0.13	0.27	3	-0.32	58	61
GBL	0.036	0.006	-10000	0	0	15	15
PDK1/Src/Hsp90	0.047	0.01	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
SRC	0.036	0.006	-10000	0	0	14	14
AKT2/p21CIP1	-0.025	0.11	0.23	1	-0.29	57	58
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.015	0.067	-10000	0	-0.44	7	7
CHUK	-0.021	0.1	-10000	0	-0.33	46	46
BAD/BCL-XL	0.004	0.12	-10000	0	-0.32	56	56
mTORC2	0.06	0.031	-10000	0	-0.12	8	8
AKT2	0.014	0.004	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.007	0.13	-10000	0	-0.46	24	24
PDPK1	0.036	0.004	-10000	0	0	7	7
MDM2	-0.017	0.12	0.2	11	-0.32	57	68
MAPKKK cascade	0.002	0.13	0.33	60	-10000	0	60
MDM2/Cbp/p300	0.015	0.13	0.27	1	-0.31	58	59
TSC1/TSC2	-0.03	0.13	0.26	8	-0.34	60	68
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.12	0.26	1	-0.3	58	59
glucose import	-0.008	0.022	0.2	3	-10000	0	3
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.012	0.082	-10000	0	-0.33	9	9
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.008	0.022	0.2	3	-10000	0	3
GSK3A	-0.019	0.11	0.23	9	-0.32	54	63
FOXO1	-0.019	0.11	-10000	0	-0.31	59	59
GSK3B	-0.024	0.12	0.2	1	-0.34	58	59
SFN	0.031	0.013	-10000	0	0	78	78
G1/S transition of mitotic cell cycle	-0.028	0.12	0.25	8	-0.33	59	67
p27Kip1/14-3-3 family	0.008	0.11	-10000	0	-0.53	13	13
PRKACA	0.035	0.008	-10000	0	0	25	25
KPNA1	0.035	0.008	-10000	0	0	27	27
HSP90AA1	0	0	-10000	0	-10000	0	0
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.024	0.017	-10000	0	0	173	173
CREBBP	0.036	0.005	-10000	0	0	8	8

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FOXP3	0.042	0.01	-10000	0	-0.042	1	1
NFATC2	0.014	0.15	0.27	5	-0.37	38	43
NFATC3	0.017	0.13	0.28	21	-0.24	68	89
CD40LG	-0.016	0.33	0.49	41	-0.72	63	104
ITCH	0.035	0.046	0.19	8	-10000	0	8
CBLB	0.036	0.048	0.19	11	-10000	0	11
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.051	0.26	0.38	13	-0.64	52	65
JUNB	0.031	0.014	-10000	0	0	83	83
CaM/Ca2+/Calcineurin A alpha-beta B1	0.033	0.027	-10000	0	-0.13	6	6
T cell anergy	0.016	0.067	0.26	10	-0.25	1	11
TLE4	0.01	0.11	-10000	0	-0.32	21	21
Jun/NFAT1-c-4/p21SNFT	-0.017	0.33	-10000	0	-0.74	68	68
AP-1/NFAT1-c-4	-0.033	0.35	-10000	0	-0.81	59	59
IKZF1	0.006	0.099	0.17	6	-0.24	37	43
T-helper 2 cell differentiation	-0.085	0.23	-10000	0	-0.67	35	35
AP-1/NFAT1	0.017	0.14	0.28	17	-0.29	44	61
CALM1	0.046	0.024	0.13	2	-10000	0	2
EGR2	-0.08	0.41	0.51	10	-1	65	75
EGR3	-0.059	0.42	0.51	10	-1.1	58	68
NFAT1/FOXP3	0.038	0.12	0.26	3	-0.28	27	30
EGR1	0.029	0.015	0.07	1	-10000	0	1
JUN	0.032	0.041	0.11	35	-0.052	11	46
EGR4	0.037	0.004	0.07	1	-10000	0	1
mol:Ca2+	0.005	0.003	-10000	0	-10000	0	0
GBP3	0.006	0.099	0.17	6	-0.24	37	43
FOSL1	0.033	0.011	-10000	0	0	55	55
NFAT1-c-4/MAF/IRF4	0.009	0.33	-10000	0	-0.74	69	69
DGKA	0.011	0.1	-10000	0	-0.31	20	20
CREM	0.026	0.016	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.009	0.33	-10000	0	-0.74	70	70
CTLA4	0.009	0.092	0.18	1	-0.26	21	22
NFAT1-c-4 (dimer)/EGR1	-0.03	0.34	-10000	0	-0.79	70	70
NFAT1-c-4 (dimer)/EGR4	-0.001	0.33	-10000	0	-0.75	69	69
FOS	0.023	0.038	0.11	19	-0.049	9	28
IFNG	-0.009	0.13	-10000	0	-0.45	10	10
T cell activation	-0.013	0.21	-10000	0	-0.56	26	26
MAF	0.034	0.009	-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	0.008	0.28	0.61	68	-0.46	16	84
TNF	-0.04	0.31	0.42	6	-0.72	69	75
FASLG	-0.1	0.46	-10000	0	-1.1	73	73
TBX21	0.04	0.006	0.11	3	-10000	0	3
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.026	0.018	-10000	0	-10000	0	0
PTPN1	0.008	0.12	0.42	1	-0.37	23	24
NFAT1-c-4/ICER1	-0.033	0.32	-10000	0	-0.74	70	70
GATA3	0.027	0.018	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.004	0.14	-10000	0	-0.44	10	10
IL2RA	-0.06	0.25	0.36	4	-0.63	55	59
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.007	0.11	-10000	0	-0.36	24	24
E2F1	0.037	0.051	-10000	0	-0.25	13	13
PPARG	0.035	0.008	-10000	0	-10000	0	0
SLC3A2	0.008	0.12	0.24	2	-0.38	26	28
IRF4	0.037	0.002	-10000	0	-10000	0	0
PTGS2	-0.071	0.28	0.45	1	-0.71	62	63
CSF2	-0.016	0.33	0.49	40	-0.72	62	102
JunB/Fra1/NFAT1-c-4	-0.014	0.31	-10000	0	-0.72	68	68
IL4	-0.089	0.24	-10000	0	-0.7	34	34
IL5	-0.016	0.33	0.49	41	-0.72	62	103
IL2	-0.013	0.22	-10000	0	-0.57	25	25
IL3	0.007	0.088	-10000	0	-0.58	7	7
RNF128	0.014	0.022	0.17	1	-10000	0	1
NFATC1	-0.008	0.28	0.46	15	-0.61	68	83
CDK4	-0.011	0.27	0.55	28	-1	14	42
PTPRK	-0.001	0.14	-10000	0	-0.43	34	34
IL8	-0.1	0.29	0.48	5	-0.76	60	65
POU2F1	0.039	0.008	-10000	0	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.035	0.009	-10000	0	0	29	29
RAS family/GTP/Tiam1	-0.006	0.085	-10000	0	-0.2	62	62
NT3 (dimer)/TRKC	0.046	0.026	-10000	0	-0.14	6	6
NT3 (dimer)/TRKB	0.026	0.069	-10000	0	-0.12	73	73
SHC/Grb2/SOS1/GAB1/PI3K	-0.008	0.095	-10000	0	-0.21	75	75
RAPGEF1	0.035	0.007	-10000	0	0	19	19
BDNF	0.032	0.012	-10000	0	0	67	67
PIK3CA	0.031	0.013	-10000	0	0	80	80
DYNLT1	0.033	0.01	-10000	0	0	44	44
NTRK1	0.035	0.006	-10000	0	0	16	16
NTRK2	0.026	0.016	-10000	0	0	142	142
NTRK3	0.034	0.01	-10000	0	0	38	38
NT-4/5 (dimer)/TRKB	0.013	0.058	-10000	0	-0.12	77	77
neuron apoptosis	-0.007	0.12	0.32	42	-0.23	1	43
SHC 2-3/Grb2	0.007	0.13	0.24	1	-0.34	42	43
SHC1	0.033	0.011	-10000	0	0	52	52
SHC2	-0.012	0.12	-10000	0	-0.43	29	29
SHC3	-0.012	0.12	-10000	0	-0.41	31	31
STAT3 (dimer)	0.022	0.087	-10000	0	-0.28	36	36
NT3 (dimer)/TRKA	0.059	0.03	-10000	0	-10000	0	0
RIN/GDP	0.001	0.074	0.18	5	-0.22	25	30
GIPC1	0.035	0.008	-10000	0	0	24	24
KRAS	0.034	0.009	-10000	0	0	35	35
DNAJA3	-0.005	0.04	0.14	3	-0.16	3	6
RIN/GTP	0.011	0.035	-10000	0	-0.13	26	26
CCND1	-0.011	0.11	-10000	0	-0.49	25	25
MAGED1	0.035	0.008	-10000	0	0	26	26
PTPN11	0.036	0.005	-10000	0	0	11	11
RICS	0.033	0.011	-10000	0	0	46	46
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.04	0.031	-10000	0	-0.12	14	14
GRB2	0.035	0.007	-10000	0	0	17	17
NGF (dimer)/TRKA/MATK	0.045	0.014	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.048	0.019	-10000	0	-0.14	1	1
ELMO1	0.018	0.018	-10000	0	0	257	257
RhoG/GTP/ELMO1/DOCK1	0.008	0.046	-10000	0	-0.12	46	46
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.034	0.009	-10000	0	0	32	32
DOCK1	0.024	0.017	-10000	0	0	175	175
GAB2	0.033	0.011	-10000	0	0	47	47
RIT2	0.024	0.017	-10000	0	0	170	170
RIT1	0.032	0.012	-10000	0	0	60	60
FRS2	0.034	0.009	-10000	0	0	30	30
DNM1	0.035	0.008	-10000	0	0	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.009	0.048	0.16	2	-0.17	12	14
mol:GDP	-0.001	0.1	0.22	6	-0.32	24	30
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.002	0.043	-10000	0	-0.13	45	45
RIT1/GDP	0.008	0.081	0.19	6	-0.23	22	28
TIAM1	0.033	0.011	-10000	0	0	46	46
PIK3R1	0.032	0.012	-10000	0	0	63	63
BDNF (dimer)/TRKB	0.027	0.069	-10000	0	-0.12	70	70
KIDINS220/CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
SHC/RasGAP	0.037	0.051	-10000	0	-0.15	31	31
FRS2 family/SHP2	0.067	0.028	-10000	0	-0.12	6	6
SHC/GRB2/SOS1/GAB1	0.048	0.046	-10000	0	-0.11	25	25
RIT1/GTP	0.015	0.04	-10000	0	-0.13	35	35
NT3 (dimer)	0.035	0.008	-10000	0	0	23	23
RAP1/GDP	-0.002	0.06	-10000	0	-0.18	27	27
KIDINS220/CRKL	0.034	0.009	-10000	0	0	29	29
BDNF (dimer)	0.032	0.012	-10000	0	0	67	67
ubiquitin-dependent protein catabolic process	0.043	0.017	-10000	0	-0.11	1	1
Schwann cell development	-0.01	0.016	-10000	0	-0.056	33	33
EHD4	0.034	0.01	-10000	0	0	41	41
FRS2 family/GRB2/SOS1	0.062	0.029	-10000	0	-0.11	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.008	0.07	-10000	0	-0.25	20	20
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CDC42/GTP	0.019	0.081	-10000	0	-0.14	73	73
ABL1	0.032	0.013	-10000	0	0	70	70
SH2B family/GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
Rap1/GTP	0.003	0.068	-10000	0	-0.24	12	12
STAT3	0.022	0.087	-10000	0	-0.28	36	36
axon guidance	0.005	0.07	-10000	0	-0.14	79	79
MAPK3	-0.007	0.055	0.17	43	-10000	0	43
MAPK1	-0.008	0.05	0.17	35	-10000	0	35
CDC42/GDP	0.011	0.08	0.18	10	-0.22	22	32
NTF3	0.035	0.008	-10000	0	0	23	23
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.043	0.025	-10000	0	-0.12	9	9
PI3K	0.019	0.075	-10000	0	-0.16	73	73
FRS3	0.036	0.002	-10000	0	0	2	2
FAIM	0.034	0.009	-10000	0	0	30	30
GAB1	0.032	0.012	-10000	0	0	59	59
RASGRF1	-0.006	0.039	0.14	2	-0.13	4	6
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.018	0.02	0.089	10	-0.12	2	12
RGS19	0.033	0.011	-10000	0	0	51	51
CDC42	0.035	0.008	-10000	0	0	24	24
RAS family/GTP	0.009	0.1	0.23	1	-0.38	22	23
Rac1/GDP	0.009	0.068	0.18	7	-0.23	17	24
NGF (dimer)/TRKA/GRIT	0.039	0.035	-10000	0	-0.12	21	21
neuron projection morphogenesis	-0.035	0.24	-10000	0	-0.87	36	36
NGF (dimer)/TRKA/NEDD4-2	0.043	0.017	-10000	0	-0.12	1	1
MAP2K1	-0.011	0.058	0.18	17	-0.19	6	23
NGFR	0.031	0.013	-10000	0	0	71	71
NGF (dimer)/TRKA/GIPC/GAIP	0.014	0.043	-10000	0	-0.22	9	9
RAS family/GTP/PI3K	-0.023	0.1	-10000	0	-0.21	99	99
FRS2 family/SHP2/GRB2/SOS1	0.076	0.039	-10000	0	-0.14	10	10
NRAS	0.032	0.012	-10000	0	0	63	63
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
PRKCI	0.035	0.008	-10000	0	0	26	26
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.086	-10000	0	-0.48	12	12
RASA1	0.034	0.009	-10000	0	0	32	32
TRKA/c-Abl	0.032	0.058	-10000	0	-0.14	48	48
SQSTM1	0.034	0.009	-10000	0	0	35	35
BDNF (dimer)/TRKB/GIPC	0.049	0.074	-10000	0	-0.12	66	66
NGF (dimer)/TRKA/p62/Atypical PKCs	0.053	0.033	-10000	0	-0.1	14	14
MATK	0.034	0.009	-10000	0	0	30	30
NEDD4L	0.033	0.01	-10000	0	0	44	44
RAS family/GDP	-0.02	0.056	-10000	0	-0.16	48	48
NGF (dimer)/TRKA	0.009	0.04	0.15	4	-0.13	4	8
Rac1/GTP	-0.014	0.055	-10000	0	-0.21	23	23
FRS2 family/SHP2/CRK family	0.087	0.056	-10000	0	-0.12	17	17

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	0.03	0.035	-10000	0	-0.14	9	9
CRKL	0.042	0.11	0.28	6	-0.4	21	27
mol:PIP3	-0.009	0.1	-10000	0	-0.79	7	7
AKT1	-0.02	0.092	0.25	1	-0.7	7	8
PTK2B	0.035	0.006	-10000	0	0	16	16
RAPGEF1	0.04	0.11	0.29	10	-0.38	21	31
RANBP10	0.036	0.005	-10000	0	0	10	10
PIK3CA	0.031	0.013	-10000	0	0	80	80
HGF/MET/SHIP2	0.042	0.038	-10000	0	-0.12	2	2
MAP3K5	0.04	0.11	0.27	8	-0.36	23	31
HGF/MET/CIN85/CBL/ENDOPHILINS	0.04	0.035	-10000	0	-10000	0	0
AP1	0.035	0.079	0.14	105	-0.14	46	151
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
apoptosis	-0.12	0.36	-10000	0	-0.79	109	109
STAT3 (dimer)	0.011	0.059	-10000	0	-0.28	11	11
GAB1/CRKL/SHP2/PI3K	0.058	0.13	0.31	2	-0.39	22	24
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.059	0.12	0.29	3	-0.39	21	24
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.035	0.007	-10000	0	0	19	19
PTEN	0.026	0.017	-10000	0	0	148	148
ELK1	0.12	0.18	0.35	181	-10000	0	181
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.012	0.034	0.16	1	-0.16	7	8
PAK1	-0.024	0.088	-10000	0	-0.68	7	7
HGF/MET/RANBP10	0.042	0.037	-10000	0	-10000	0	0
HRAS	0.011	0.083	-10000	0	-0.47	11	11
DOCK1	0.031	0.11	0.26	8	-0.39	20	28
GAB1	0.045	0.12	-10000	0	-0.41	21	21
CRK	0.043	0.11	0.29	3	-0.4	21	24
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.069	-10000	0	-0.42	10	10
JUN	0.034	0.01	-10000	0	0	40	40
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.01	0.017	-10000	0	-0.12	1	1
PIK3R1	0.032	0.012	-10000	0	0	63	63
cell morphogenesis	0.024	0.11	0.28	22	-0.32	14	36
GRB2/SHC	0.077	0.065	0.17	115	-0.12	2	117
FOS	0.025	0.017	-10000	0	0	158	158
GLMN	0.004	0.004	0.068	2	-10000	0	2
cell motility	0.12	0.18	0.35	181	-10000	0	181
HGF/MET/MUC20	0.029	0.024	-10000	0	-10000	0	0
cell migration	0.075	0.063	0.17	115	-0.12	2	117
GRB2	0.035	0.007	-10000	0	0	17	17
CBL	0.036	0.004	-10000	0	0	7	7
MET/RANBP10	0.033	0.026	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.013	0.048	-10000	0	-0.19	20	20
MET/MUC20	0.017	0.013	-10000	0	-10000	0	0
RAP1B	0.039	0.11	0.28	10	-0.36	21	31
RAP1A	0.034	0.11	0.29	9	-0.35	21	30
HGF/MET/RANBP9	0.04	0.042	-10000	0	-0.12	8	8
RAF1	0.038	0.1	0.28	2	-0.45	13	15
STAT3	0.009	0.058	-10000	0	-0.29	11	11
cell proliferation	0.039	0.081	0.23	16	-0.28	9	25
RPS6KB1	0.014	0.018	-10000	0	-10000	0	0
MAPK3	0.084	0.17	0.38	38	-10000	0	38
MAPK1	0.12	0.22	0.52	68	-10000	0	68
RANBP9	0.035	0.007	-10000	0	0	18	18
MAPK8	-0.048	0.16	0.26	2	-0.34	74	76
SRC	0.007	0.046	-10000	0	-0.18	19	19
PI3K	0.061	0.074	0.17	97	-0.15	10	107
MET/Glomulin	0.016	0.026	-10000	0	-0.087	17	17
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.029	0.1	0.27	2	-0.43	14	16
MET	0.023	0.018	-10000	0	0	191	191
MAP4K1	0.048	0.11	0.3	4	-0.37	22	26
PTK2	0.034	0.009	-10000	0	0	32	32
MAP2K2	0.038	0.11	0.3	14	-0.42	12	26
BAD	-0.027	0.088	-10000	0	-0.63	8	8
MAP2K4	0.033	0.11	0.27	10	-0.34	23	33
SHP2/GRB2/SOS1/GAB1	0.016	0.085	-10000	0	-0.33	22	22
INPPL1	0.036	0.006	-10000	0	0	12	12
PXN	0.036	0.004	-10000	0	0	7	7
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	0.001	0.018	0.081	3	-0.12	1	4
PLCgamma1/PKC	0.025	0.013	-10000	0	-0.13	3	3
HGF	0.024	0.017	-10000	0	0	177	177
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
PTPRJ	0.036	0.005	-10000	0	0	11	11
NCK/PLCgamma1	0.083	0.059	0.17	120	-0.12	1	121
PDPK1	-0.012	0.096	0.29	1	-0.74	7	8
HGF/MET/SHIP	0.029	0.024	-10000	0	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0.047	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.035	0.007	-10000	0	0	20	20
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.036	0.004	-10000	0	0	6	6
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.035	0.007	-10000	0	0	19	19
RAC1-CDC42/GTP/PAK family	0.002	0.048	-10000	0	-0.14	41	41
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.034	0.01	-10000	0	0	41	41
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.036	0.004	-10000	0	0	7	7
FYN	0.03	0.014	-10000	0	0	90	90
MAP3K12	0.036	0.005	-10000	0	0	9	9
FGR	0.033	0.011	-10000	0	0	54	54
p38 alpha/TAB1	0.018	0.11	0.19	3	-0.26	38	41
PRKG1	0.026	0.016	-10000	0	0	141	141
DUSP8	0.034	0.01	-10000	0	0	39	39
PGK/cGMP/p38 alpha	0.004	0.098	0.17	1	-0.25	38	39
apoptosis	0.017	0.1	0.18	3	-0.25	38	41
RAL/GTP	0.026	0.038	-10000	0	-0.12	20	20
LYN	0.031	0.013	-10000	0	0	74	74
DUSP1	0.031	0.013	-10000	0	0	77	77
PAK1	0.036	0.006	-10000	0	0	15	15
SRC	0.036	0.006	-10000	0	0	14	14
RAC1/OSM/MEKK3/MKK3	0.044	0.037	-10000	0	-0.11	5	5
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.024	0.017	-10000	0	0	173	173
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
mol:LPS	0	0	-10000	0	-10000	0	0
mol:cGMP	0	0	-10000	0	-10000	0	0
CCM2	0	0	-10000	0	-10000	0	0
RAC1-CDC42/GTP	0.03	0.028	-10000	0	-0.12	5	5
MAPK11	-0.002	0.13	0.21	3	-0.32	44	47
BLK	0.035	0.007	-10000	0	0	17	17
HCK	0.027	0.016	-10000	0	0	128	128
MAP2K3	0.036	0.005	-10000	0	0	10	10
DUSP16	0	0	-10000	0	-10000	0	0
DUSP10	0.033	0.011	-10000	0	0	48	48
TRAF6/MEKK3	0.045	0.01	-10000	0	-0.1	1	1
MAP3K7IP1	0.034	0.009	-10000	0	0	35	35
MAPK14	0.009	0.11	0.18	4	-0.27	40	44
positive regulation of innate immune response	0.001	0.14	0.23	3	-0.34	47	50
LCK	0.035	0.007	-10000	0	0	17	17
p38alpha-beta/MKP7	-0.001	0.14	0.21	4	-0.33	47	51
p38alpha-beta/MKP5	0.014	0.14	0.24	3	-0.34	40	43
PGK/cGMP	0.02	0.012	-10000	0	-10000	0	0
PAK2	0.035	0.007	-10000	0	0	20	20
p38alpha-beta/MKP1	0.005	0.14	0.24	3	-0.34	47	50
CDC42	0.035	0.008	-10000	0	0	24	24
RALB	0.035	0.007	-10000	0	0	17	17
RALA	0.024	0.018	-10000	0	0	180	180
PAK3	0.027	0.016	-10000	0	0	139	139

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.064	0.26	0.62	9	-0.77	17	26
CRP	0.06	0.26	0.61	9	-0.76	17	26
cell cycle arrest	0.052	0.29	0.53	17	-0.75	30	47
TIMP1	0.005	0.36	0.55	15	-0.8	68	83
IL6ST	0.028	0.033	0.09	1	-0.048	36	37
Rac1/GDP	0.039	0.11	0.3	16	-0.3	11	27
AP1	0.012	0.2	0.31	2	-0.55	39	41
GAB2	0.034	0.012	-10000	0	-0.041	1	1
TNFSF11	0.058	0.26	0.57	8	-0.77	17	25
HSP90B1	0.001	0.22	0.3	3	-0.84	30	33
GAB1	0.033	0.013	-10000	0	-0.042	1	1
MAPK14	0.029	0.065	-10000	0	-0.3	3	3
AKT1	-0.013	0.17	-10000	0	-0.58	29	29
FOXO1	-0.014	0.16	-10000	0	-0.52	33	33
MAP2K6	0.028	0.07	-10000	0	-0.28	6	6
mol:GTP	0	0.004	-10000	0	-0.022	1	1
MAP2K4	0.033	0.14	0.34	24	-0.37	14	38
MITF	0.032	0.083	0.22	11	-0.29	9	20
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.033	0.011	-10000	0	0	46	46
A2M	-0.076	0.34	-10000	0	-1.2	44	44
CEBPB	0.032	0.013	-10000	0	0	71	71
GRB2/SOS1/GAB family/SHP2	0.021	0.13	0.26	3	-0.48	24	27
STAT3	0.042	0.3	0.54	16	-0.8	30	46
STAT1	0.021	0.065	-10000	0	-0.72	3	3
CEBPD	0.024	0.33	0.54	11	-0.9	42	53
PIK3CA	0.031	0.014	-10000	0	-0.041	1	1
PI3K	0.019	0.075	-10000	0	-0.15	74	74
JUN	0.034	0.01	-10000	0	0	40	40
PIAS3/MITF	0.077	0.11	0.27	22	-0.3	9	31
MAPK11	0.026	0.064	-10000	0	-0.3	3	3
STAT3 (dimer)/FOXO1	-0.021	0.26	0.44	9	-0.63	49	58
GRB2/SOS1/GAB family	0.043	0.12	0.23	2	-0.31	30	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.004	0.1	0.18	10	-0.29	35	45
GRB2	0.036	0.008	-10000	0	-0.042	1	1
JAK2	0.031	0.014	-10000	0	0	83	83
LBP	0.064	0.25	0.52	18	-0.64	24	42
PIK3R1	0.032	0.013	-10000	0	-0.042	1	1
JAK1	0.03	0.026	-10000	0	-0.042	45	45
MYC	0.014	0.36	0.6	10	-0.88	56	66
FGG	0.058	0.26	0.57	8	-0.77	17	25
macrophage differentiation	0.052	0.29	0.53	17	-0.75	30	47
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.054	0.074	-10000	0	-0.19	5	5
JUNB	0.053	0.29	0.52	23	-0.87	25	48
FOS	0.025	0.017	-10000	0	0	158	158
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.028	0.083	0.22	13	-0.29	10	23
STAT1/PIAS1	0.071	0.12	0.28	20	-0.37	6	26
GRB2/SOS1/GAB family/SHP2/PI3K	-0.001	0.17	-10000	0	-0.5	35	35
STAT3 (dimer)	0.044	0.29	0.54	16	-0.79	30	46
PRKCD	0.11	0.22	0.41	95	-0.44	20	115
IL6R	0.03	0.027	-10000	0	-0.041	57	57
SOCS3	0.059	0.086	0.42	3	-10000	0	3
gp130 (dimer)/JAK1/JAK1/LMO4	0.045	0.087	0.18	1	-0.17	43	44
Rac1/GTP	0.033	0.11	0.31	10	-0.33	11	21
HCK	0.027	0.016	-10000	0	0	128	128
MAPKKK cascade	0.011	0.19	0.34	2	-0.59	35	37
bone resorption	0.06	0.25	0.56	9	-0.72	17	26
IRF1	0.053	0.29	0.55	16	-0.88	23	39
mol:GDP	0.031	0.09	0.24	14	-0.29	9	23
SOS1	0.001	0.004	0.025	10	-0.022	1	11
VAV1	0.03	0.09	0.24	15	-0.29	9	24
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.02	0.075	-10000	0	-0.33	12	12
PTPN11	0.015	0.099	-10000	0	-0.73	8	8
IL6/IL6RA	0.023	0.038	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.047	0.074	-10000	0	-0.15	40	40
gp130 (dimer)/JAK2/JAK2/LMO4	0.048	0.063	-10000	0	-0.12	33	33
IL6	0.015	0.027	-10000	0	-0.045	13	13
PIAS3	0.036	0.006	-10000	0	0	14	14
PTPRE	0.01	0.03	-10000	0	-0.058	31	31
PIAS1	0.035	0.008	-10000	0	0	27	27
RAC1	0.024	0.018	-10000	0	0	174	174
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.018	0.052	0.17	6	-0.22	6	12
LMO4	0.029	0.033	0.09	1	-0.047	44	45
STAT3 (dimer)/PIAS3	0.015	0.26	0.47	5	-0.73	31	36
MCL1	-0.014	0.16	-10000	0	-0.85	11	11

×

IGF1 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.035	0.007	-10000	0	0	17	17
PTK2	0.034	0.009	-10000	0	0	32	32
CRKL	-0.017	0.044	0.097	27	-0.15	24	51
GRB2/SOS1/SHC	0.04	0.031	-10000	0	-0.12	14	14
HRAS	0.034	0.009	-10000	0	0	32	32
IRS1/Crk	0.018	0.047	-10000	0	-0.14	35	35
IGF-1R heterotetramer/IGF1/PTP1B	0.052	0.055	-10000	0	-0.14	29	29
AKT1	-0.034	0.075	0.15	28	-0.22	30	58
BAD	-0.038	0.072	0.15	25	-0.22	29	54
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.018	0.045	0.1	28	-0.16	24	52
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.025	0.048	0.16	1	-0.14	29	30
RAF1	-0.032	0.14	-10000	0	-0.56	27	27
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.046	0.054	0.17	1	-0.14	30	31
YWHAZ	0.035	0.007	-10000	0	0	21	21
IGF-1R heterotetramer/IGF1/IRS1	0.033	0.049	0.17	1	-0.16	24	25
PIK3CA	0.031	0.013	-10000	0	0	80	80
RPS6KB1	-0.033	0.071	0.16	31	-0.2	22	53
GNB2L1	0.036	0.002	-10000	0	0	2	2
positive regulation of MAPKKK cascade	-0.033	0.12	0.23	3	-0.43	27	30
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
HRAS/GTP	0.015	0.054	-10000	0	-0.14	43	43
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.066	0.057	-10000	0	-0.12	34	34
IGF-1R heterotetramer	0.036	0.014	0.092	1	-0.034	1	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.048	0.06	0.18	1	-0.14	35	36
Crk/p130 Cas/Paxillin	0.038	0.056	0.2	3	-0.13	35	38
IGF1R	0.036	0.014	0.092	1	-0.034	1	2
IGF1	0.033	0.026	0.092	1	-0.055	33	34
IRS2/Crk	-0.03	0.057	0.1	18	-0.18	32	50
PI3K	0.039	0.087	0.2	1	-0.14	78	79
apoptosis	0.037	0.076	0.23	23	-0.18	12	35
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
PRKCD	0.004	0.064	0.17	8	-0.21	24	32
RAF1/14-3-3 E	-0.012	0.13	-10000	0	-0.48	27	27
BAD/14-3-3	-0.039	0.08	0.19	12	-0.24	23	35
PRKCZ	-0.027	0.07	0.15	32	-0.2	22	54
Crk/p130 Cas/Paxillin/FAK1	-0.046	0.072	0.13	26	-0.22	29	55
PTPN1	0.034	0.009	-10000	0	0	30	30
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.006	0.06	-10000	0	-0.22	25	25
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.038	0.07	-10000	0	-0.14	40	40
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.027	0.051	0.13	5	-0.14	35	40
GRB10	0.021	0.018	-10000	0	0	220	220
PTPN11	-0.018	0.045	0.1	28	-0.15	24	52
IRS1	0.01	0.042	0.12	5	-0.16	24	29
IRS2	-0.019	0.049	0.1	20	-0.19	24	44
IGF-1R heterotetramer/IGF1	0.039	0.051	0.15	1	-0.17	24	25
GRB2	0.035	0.007	-10000	0	0	17	17
PDPK1	-0.026	0.076	0.17	31	-0.2	22	53
YWHAE	0.035	0.008	-10000	0	0	27	27
PRKD1	-0.002	0.064	0.2	1	-0.24	25	26
SHC1	0.033	0.011	-10000	0	0	52	52

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	0.053	0.036	-10000	0	-0.097	20	20
ER alpha/Gai/GDP/Gbeta gamma	-0.038	0.17	-10000	0	-0.5	44	44
AKT1	-0.053	0.23	-10000	0	-0.62	61	61
PIK3CA	0.031	0.013	-10000	0	0	80	80
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.046	0.24	-10000	0	-0.64	59	59
mol:Ca2+	0.001	0.044	0.17	4	-0.25	3	7
IGF1R	0.033	0.012	-10000	0	0	57	57
E2/ER alpha (dimer)/Striatin	0.046	0.012	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
apoptosis	0.052	0.22	0.58	63	-10000	0	63
RhoA/GTP	-0.041	0.038	-10000	0	-0.13	48	48
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.012	0.15	0.18	4	-0.36	54	58
regulation of stress fiber formation	0.038	0.058	0.18	20	-0.14	23	43
E2/ERA-ERB (dimer)	0.045	0.015	-10000	0	-10000	0	0
KRAS	0.034	0.009	-10000	0	0	35	35
G13/GTP	0.043	0.013	-10000	0	-10000	0	0
pseudopodium formation	-0.038	0.058	0.14	23	-0.18	20	43
E2/ER alpha (dimer)/PELP1	0.044	0.023	-10000	0	-0.11	7	7
GRB2	0.035	0.007	-10000	0	0	17	17
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	0.03	0.014	-10000	0	0	87	87
HRAS	0.034	0.009	-10000	0	0	32	32
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.012	0.16	-10000	0	-0.4	54	54
E2/ER beta (dimer)	0.025	0.006	-10000	0	-10000	0	0
mol:GDP	0.004	0.057	0.13	2	-0.19	27	29
mol:NADP	-0.012	0.16	-10000	0	-0.4	54	54
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.002	0.042	0.17	4	-0.33	1	5
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
PLCB1	0.01	0.04	-10000	0	-0.33	1	1
PLCB2	0.008	0.04	-10000	0	-0.33	1	1
IGF1	0.035	0.008	-10000	0	0	23	23
mol:L-citrulline	-0.012	0.16	-10000	0	-0.4	54	54
RHOA	0.035	0.007	-10000	0	0	18	18
Gai/GDP	-0.066	0.24	-10000	0	-0.64	69	69
JNK cascade	0.025	0.006	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.034	0.009	-10000	0	0	31	31
GNAQ	0.034	0.009	-10000	0	0	31	31
ESR1	0.035	0.009	-10000	0	0	29	29
Gq family/GDP/Gbeta gamma	-0.003	0.15	-10000	0	-0.51	32	32
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.015	0.14	-10000	0	-0.68	17	17
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	0.001	0.16	0.25	2	-0.38	49	51
GNAZ	0.031	0.013	-10000	0	0	81	81
E2/ER alpha (dimer)	0.026	0.006	-10000	0	-10000	0	0
STRN	0.036	0.003	-10000	0	0	3	3
GNAL	0.036	0.006	-10000	0	0	13	13
PELP1	0.035	0.007	-10000	0	0	17	17
MAPK11	-0.016	0.006	-10000	0	-10000	0	0
GNAI2	0.034	0.01	-10000	0	0	43	43
GNAI3	0.036	0.006	-10000	0	0	15	15
GNAI1	0.018	0.018	-10000	0	0	263	263
HBEGF	-0.02	0.18	0.31	10	-0.44	48	58
cAMP biosynthetic process	0.037	0.015	-10000	0	-10000	0	0
SRC	-0.041	0.16	0.2	5	-0.47	45	50
PI3K	0.019	0.075	-10000	0	-0.16	73	73
GNB1	0.035	0.007	-10000	0	0	20	20
G13/GDP/Gbeta gamma	0.022	0.068	-10000	0	-0.17	34	34
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.025	0.12	-10000	0	-0.3	57	57
Gs family/GTP	0.047	0.019	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.063	-10000	0	-0.13	52	52
vasodilation	-0.01	0.16	-10000	0	-0.38	54	54
mol:DAG	0.002	0.042	0.17	4	-0.33	1	5
Gs family/GDP/Gbeta gamma	0.004	0.062	-10000	0	-0.18	34	34
MSN	-0.039	0.057	0.14	20	-0.19	21	41
Gq family/GTP	0.022	0.043	-10000	0	-0.34	1	1
mol:PI-3-4-5-P3	-0.045	0.23	-10000	0	-0.6	63	63
NRAS	0.032	0.012	-10000	0	0	63	63
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.01	0.16	0.38	54	-10000	0	54
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
RhoA/GDP	0.018	0.067	-10000	0	-0.19	29	29
NOS3	-0.014	0.17	-10000	0	-0.44	49	49
GNA11	0.033	0.011	-10000	0	0	54	54
MAPKKK cascade	0	0.15	-10000	0	-0.47	37	37
E2/ER alpha (dimer)/PELP1/Src	-0.003	0.16	0.23	6	-0.38	54	60
ruffle organization	-0.038	0.058	0.14	23	-0.18	20	43
ROCK2	-0.034	0.061	0.16	25	-0.19	12	37
GNA14	0.034	0.009	-10000	0	0	30	30
GNA15	0.033	0.012	-10000	0	0	57	57
GNA13	0.035	0.007	-10000	0	0	19	19
MMP9	-0.025	0.17	0.37	4	-0.43	51	55
MMP2	-0.025	0.17	0.22	12	-0.46	47	59

×

IFN-gamma 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
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.05	0.073	-10000	0	-0.12	39	39
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.035	0.009	-10000	0	0	29	29
STAT1 (dimer)/Cbp/p300	0.022	0.083	0.27	5	-0.22	17	22
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.042	0.062	-10000	0	-0.14	39	39
antigen processing and presentation of peptide antigen via MHC class I	-0.025	0.079	0.12	5	-0.19	55	60
CaM/Ca2+	0.046	0.078	-10000	0	-0.14	33	33
RAP1A	0.036	0.005	-10000	0	0	11	11
STAT1 (dimer)/SHP2	-0.022	0.059	0.16	17	-0.18	9	26
AKT1	-0.033	0.084	0.27	5	-0.23	32	37
MAP2K1	-0.028	0.056	0.15	17	-0.2	8	25
MAP3K11	-0.022	0.059	0.16	23	-0.18	7	30
IFNGR1	0.031	0.019	-10000	0	-0.036	19	19
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.028	0.12	-10000	0	-0.35	43	43
Rap1/GTP	-0.039	0.036	-10000	0	-0.16	7	7
CRKL/C3G	0.05	0.015	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.064	0.076	-10000	0	-0.13	35	35
CEBPB	-0.009	0.12	0.35	3	-0.42	22	25
STAT3	0.034	0.01	-10000	0	0	37	37
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.061	0.089	-10000	0	-0.74	3	3
STAT1	-0.024	0.06	0.17	19	-0.18	9	28
CALM1	0.033	0.011	-10000	0	0	54	54
IFN-gamma (dimer)	0.03	0.021	-10000	0	-0.037	38	38
PIK3CA	0.031	0.013	-10000	0	0	80	80
STAT1 (dimer)/PIAS1	-0.025	0.07	0.18	20	-0.21	15	35
CEBPB/PTGES2/Cbp/p300	0.008	0.09	-10000	0	-0.29	23	23
mol:Ca2+	0.046	0.07	-10000	0	-0.12	39	39
MAPK3	0.006	0.079	0.34	1	-0.68	2	3
STAT1 (dimer)	-0.027	0.11	0.19	7	-0.26	54	61
MAPK1	-0.041	0.2	0.34	1	-0.75	35	36
JAK2	0.027	0.022	-10000	0	-0.037	34	34
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.033	0.017	-10000	0	-0.036	17	17
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	-0.001	0.096	0.3	4	-0.4	12	16
SMAD7	-0.009	0.06	0.16	22	-0.15	14	36
CBL/CRKL/C3G	0.018	0.071	0.27	4	-0.19	4	8
PI3K	0.026	0.094	-10000	0	-0.18	39	39
IFNG	0.03	0.021	-10000	0	-0.037	38	38
apoptosis	0.012	0.086	0.31	3	-0.41	8	11
CAMK2G	0.024	0.018	-10000	0	0	179	179
STAT3 (dimer)	0.034	0.01	-10000	0	0	37	37
CAMK2A	0.036	0.005	-10000	0	0	10	10
CAMK2B	0.017	0.018	-10000	0	0	272	272
FRAP1	-0.039	0.077	0.23	5	-0.22	32	37
PRKCD	-0.032	0.08	0.29	5	-0.21	25	30
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.025	0.079	0.12	5	-0.19	55	60
PTPN2	0.035	0.007	-10000	0	0	18	18
EP300	0.034	0.011	-10000	0	0	49	49
IRF1	-0.035	0.058	0.21	3	-0.28	12	15
STAT1 (dimer)/PIASy	-0.025	0.065	0.24	6	-0.19	7	13
SOCS1	0.019	0.083	-10000	0	-1	3	3
mol:GDP	-0.021	0.066	0.17	21	-0.18	4	25
CASP1	-0.019	0.073	0.18	15	-0.16	62	77
PTGES2	0.035	0.007	-10000	0	0	20	20
IRF9	-0.002	0.044	0.12	16	-0.13	19	35
mol:PI-3-4-5-P3	0.013	0.082	-10000	0	-0.15	72	72
RAP1/GDP	-0.031	0.052	0.11	15	-0.18	5	20
CBL	-0.022	0.058	0.16	21	-0.18	6	27
MAP3K1	-0.023	0.056	0.15	19	-0.18	6	25
PIAS1	0.035	0.008	-10000	0	0	27	27
PIAS4	0.035	0.008	-10000	0	0	27	27
antigen processing and presentation of peptide antigen via MHC class II	-0.025	0.079	0.12	5	-0.19	55	60
PTPN11	-0.016	0.059	0.16	25	-0.18	6	31
CREBBP	0.037	0.005	-10000	0	0	8	8
RAPGEF1	0.035	0.007	-10000	0	0	19	19

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.036	0.028	-9999	-0.14	2	2
FBXW11	0.035	0.008	-9999	0	25	25
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.008	-9999	0	25	25
CHUK	0.025	0.017	-9999	0	163	163
NF kappa B2 p100/RelB	0.066	0.059	-9999	-0.12	10	10
NFKB1	0.035	0.007	-9999	0	18	18
MAP3K14	0.036	0.006	-9999	0	13	13
NF kappa B1 p50/RelB	0.048	0.024	-9999	-0.14	5	5
RELB	0.034	0.009	-9999	0	32	32
NFKB2	0.025	0.017	-9999	0	158	158
NF kappa B2 p52/RelB	0.033	0.023	-9999	-10000	0	0
regulation of B cell activation	0.032	0.023	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GRB2/SOS1/SHC	0.027	0.073	0.2	18	-0.27	9	27
FYN	-0.011	0.1	0.23	10	-0.31	31	41
LAT/GRAP2/SLP76	0.02	0.072	0.22	4	-0.29	10	14
IKBKB	0.036	0.003	-10000	0	0	4	4
AKT1	0.005	0.083	0.21	16	-0.24	21	37
B2M	0.036	0.01	-10000	0	-10000	0	0
IKBKG	-0.003	0.034	0.094	13	-0.097	10	23
MAP3K8	0.022	0.018	-10000	0	0	196	196
mol:Ca2+	-0.01	0.01	0.088	1	-0.038	2	3
integrin-mediated signaling pathway	0.024	0.007	-10000	0	-0.11	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.007	0.1	0.25	16	-0.28	25	41
TRPV6	0.4	0.59	1.2	168	-10000	0	168
CD28	0.037	0.001	-10000	0	-10000	0	0
SHC1	0.018	0.077	0.2	27	-0.32	9	36
receptor internalization	0.018	0.06	0.17	8	-0.29	8	16
PRF1	-0.14	0.31	-10000	0	-0.61	145	145
KRAS	0.034	0.009	-10000	0	0	35	35
GRB2	0.035	0.007	-10000	0	0	17	17
COT/AKT1	0.006	0.063	0.19	5	-0.21	18	23
LAT	0.012	0.072	0.21	13	-0.31	10	23
EntrezGene:6955	0.001	0.004	0.014	41	-10000	0	41
CD3D	0.035	0.011	-10000	0	-10000	0	0
CD3E	0.038	0.007	-10000	0	-10000	0	0
CD3G	0.037	0.008	-10000	0	-10000	0	0
RASGRP2	0.006	0.02	0.074	3	-0.14	6	9
RASGRP1	-0.024	0.13	0.23	25	-0.24	93	118
HLA-A	0.037	0.007	-10000	0	-10000	0	0
RASSF5	0	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.024	0.007	-10000	0	-0.11	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.009	0.053	0.13	36	-0.1	18	54
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.005	0.037	-10000	0	-0.12	26	26
PRKCA	-0.001	0.057	0.18	19	-0.19	5	24
GRAP2	0.034	0.009	-10000	0	0	35	35
mol:IP3	0.002	0.053	-10000	0	-0.24	8	8
EntrezGene:6957	0.001	0.004	0.014	41	-10000	0	41
TCR/CD3/MHC I/CD8	0.018	0.048	0.15	11	-0.22	5	16
ORAI1	-0.35	0.5	0.38	5	-1.1	168	173
CSK	0.013	0.072	0.21	14	-0.3	11	25
B7 family/CD28	0.062	0.096	0.27	19	-0.32	7	26
CHUK	0.025	0.017	-10000	0	0	163	163
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.015	0.074	0.2	9	-0.32	11	20
PTPN6	0.008	0.076	0.22	12	-0.31	12	24
VAV1	0.018	0.076	0.21	25	-0.31	9	34
Monovalent TCR/CD3	0.022	0.017	0.11	1	-10000	0	1
CBL	0.036	0.004	-10000	0	0	7	7
LCK	0.006	0.09	0.24	12	-0.31	15	27
PAG1	0.015	0.071	0.21	10	-0.3	11	21
RAP1A	0.036	0.005	-10000	0	0	11	11
TCR/CD3/MHC I/CD8/LCK	0.014	0.075	0.21	9	-0.31	12	21
CD80	0.036	0.007	-10000	0	0	16	16
CD86	0.032	0.012	-10000	0	0	64	64
PDK1/CARD11/BCL10/MALT1	0.002	0.046	-10000	0	-0.14	25	25
HRAS	0.034	0.009	-10000	0	0	32	32
GO:0035030	0.011	0.073	0.2	21	-0.26	8	29
CD8A	0.001	0.004	0.015	41	-10000	0	41
CD8B	0.001	0.004	0.015	43	-10000	0	43
PTPRC	0.029	0.015	-10000	0	0	110	110
PDK1/PKC theta	0.006	0.09	0.23	22	-0.28	15	37
CSK/PAG1	0.011	0.071	0.21	13	-0.29	11	24
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0.049	0.035	-10000	0	-0.14	13	13
GRAP2/SLP76	0.029	0.083	0.24	5	-0.32	11	16
STIM1	-0.06	0.18	1.2	7	-10000	0	7
RAS family/GTP	0.004	0.072	0.16	21	-0.18	29	50
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.019	0.062	0.18	8	-0.3	8	16
mol:DAG	-0.02	0.036	-10000	0	-0.22	8	8
RAP1A/GDP	0.009	0.027	0.071	26	-0.051	15	41
PLCG1	0.035	0.007	-10000	0	0	19	19
CD247	0.001	0.004	0.014	41	-10000	0	41
cytotoxic T cell degranulation	-0.14	0.3	-10000	0	-0.59	145	145
RAP1A/GTP	0.003	0.008	-10000	0	-0.053	6	6
mol:PI-3-4-5-P3	0.009	0.09	0.24	17	-0.26	20	37
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.011	0.067	0.2	2	-0.29	8	10
NRAS	0.032	0.012	-10000	0	0	63	63
ZAP70	0.037	0.002	-10000	0	0	2	2
GRB2/SOS1	0.024	0.02	-10000	0	-0.13	8	8
LAT/GRAP2/SLP76/VAV1	0.01	0.066	0.21	4	-0.3	7	11
MALT1	0.034	0.009	-10000	0	0	32	32
TRAF6	0.036	0.005	-10000	0	0	10	10
CD8 heterodimer	0.003	0.008	0.027	43	-10000	0	43
CARD11	0	0	-10000	0	-10000	0	0
PRKCB	-0.016	0.026	-10000	0	-0.16	8	8
PRKCE	-0.001	0.057	0.18	19	-0.19	5	24
PRKCQ	0.008	0.094	0.25	20	-0.3	15	35
LCP2	0.031	0.013	-10000	0	0	77	77
BCL10	0.035	0.007	-10000	0	0	20	20
regulation of survival gene product expression	0.005	0.076	0.2	17	-0.22	18	35
IKK complex	-0.002	0.038	0.13	13	-0.098	2	15
RAS family/GDP	-0.004	0.015	-10000	0	-0.04	37	37
MAP3K14	0.009	0.063	0.18	24	-0.17	18	42
PDPK1	0.005	0.079	0.21	18	-0.23	19	37
TCR/CD3/MHC I/CD8/Fyn	0.01	0.068	0.18	1	-0.36	7	8

×

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

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
BAG4	0.036	0.005	-10000	0	0	11	11
Caspase 8 (4 units)	-0.009	0.096	-10000	0	-0.24	24	24
NEF	0.002	0	-10000	0	-10000	0	0
NFKBIA	0.038	0.019	0.077	64	-10000	0	64
BIRC3	-0.025	0.029	0.18	2	-0.2	2	4
CYCS	-0.003	0.083	0.18	51	-0.26	10	61
RIPK1	0.035	0.007	-10000	0	0	20	20
CD247	0.002	0	-10000	0	-10000	0	0
MAP2K7	-0.01	0.1	-10000	0	-0.36	11	11
protein ubiquitination	0.013	0.065	0.21	3	-0.27	6	9
CRADD	0.036	0.006	-10000	0	0	12	12
DAXX	0.036	0.004	-10000	0	0	6	6
FAS	0.019	0.018	-10000	0	0	238	238
BID	-0.002	0.056	0.12	1	-0.17	42	43
NF-kappa-B/RelA/I kappa B alpha	0.075	0.054	-10000	0	-0.13	17	17
TRADD	0.036	0.005	-10000	0	0	11	11
MAP3K5	0.03	0.014	-10000	0	0	90	90
CFLAR	0.036	0.005	-10000	0	0	8	8
FADD	0.036	0.006	-10000	0	0	12	12
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.075	0.055	-10000	0	-0.13	17	17
MAPK8	-0.007	0.093	-10000	0	-0.35	10	10
APAF1	0.036	0.003	-10000	0	0	4	4
TRAF1	0.035	0.008	-10000	0	0	23	23
TRAF2	0.036	0.006	-10000	0	0	15	15
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.003	0.06	-10000	0	-0.17	45	45
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.031	0.075	-10000	0	-0.27	12	12
CHUK	0.013	0.066	0.21	3	-0.29	6	9
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.041	0.082	-10000	0	-0.12	58	58
TCRz/NEF	0.007	0.001	-10000	0	-10000	0	0
TNF	0.036	0.003	-10000	0	0	4	4
FASLG	0.018	0.003	-10000	0	-10000	0	0
NFKB1	0.042	0.016	0.078	72	-10000	0	72
TNFR1A/BAG4/TNF-alpha	0.053	0.056	-10000	0	-0.12	41	41
CASP6	0.006	0.11	-10000	0	-0.57	7	7
CASP7	-0.032	0.14	0.27	11	-0.31	30	41
RELA	0.043	0.016	0.078	74	-10000	0	74
CASP2	0.024	0.017	-10000	0	0	169	169
CASP3	0	0.11	0.26	10	-0.33	15	25
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
TNFR1A/BAG4	0.035	0.054	-10000	0	-0.14	42	42
CASP8	0.036	0.006	-10000	0	0	13	13
CASP9	0.034	0.009	-10000	0	0	33	33
MAP3K14	0.026	0.076	0.19	2	-0.27	10	12
APAF-1/Caspase 9	-0.009	0.085	0.14	53	-0.23	15	68
BCL2	-0.015	0.09	0.27	1	-0.32	9	10

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	0.028	0.11	0.32	9	-0.3	22	31
PDGFB-D/PDGFRB/SLAP	0.018	0.072	-10000	0	-0.15	71	71
PDGFB-D/PDGFRB/APS/CBL	0.045	0.022	-10000	0	-0.12	7	7
AKT1	-0.026	0.089	0.27	12	-0.24	15	27
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.019	0.1	0.29	9	-0.32	22	31
PIK3CA	0.031	0.013	-10000	0	0	80	80
FGR	0.006	0.1	0.26	4	-0.5	13	17
mol:Ca2+	0.011	0.1	0.25	9	-0.37	20	29
MYC	0.01	0.26	0.4	21	-0.68	50	71
SHC1	0.033	0.011	-10000	0	0	52	52
HRAS/GDP	0.012	0.066	0.17	26	-0.18	12	38
LRP1/PDGFRB/PDGFB	0.048	0.055	-10000	0	-0.13	32	32
GRB10	0.021	0.018	-10000	0	0	220	220
PTPN11	0.036	0.005	-10000	0	0	11	11
GO:0007205	0.011	0.1	0.25	9	-0.37	20	29
PTEN	0.026	0.017	-10000	0	0	148	148
GRB2	0.035	0.007	-10000	0	0	17	17
GRB7	0.036	0.006	-10000	0	0	14	14
PDGFB-D/PDGFRB/SHP2	0.047	0.033	-10000	0	-0.14	13	13
PDGFB-D/PDGFRB/GRB10	0.021	0.049	-10000	0	-0.14	30	30
cell cycle arrest	0.017	0.072	-10000	0	-0.15	71	71
HRAS	0.034	0.009	-10000	0	0	32	32
HIF1A	-0.03	0.081	0.24	13	-0.25	12	25
GAB1	0.006	0.12	0.27	10	-0.36	31	41
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.005	0.12	0.3	14	-0.32	30	44
PDGFB-D/PDGFRB	0.056	0.053	0.19	1	-0.14	14	15
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.044	0.04	-10000	0	-0.14	20	20
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.025	0.12	0.29	8	-0.28	38	46
positive regulation of MAPKKK cascade	0.047	0.033	-10000	0	-0.14	13	13
PIK3R1	0.032	0.012	-10000	0	0	63	63
mol:IP3	0.011	0.1	0.25	9	-0.38	20	29
E5	-0.001	0.002	-10000	0	-10000	0	0
CSK	0.034	0.011	-10000	0	-0.009	29	29
PDGFB-D/PDGFRB/GRB7	0.05	0.022	-10000	0	-0.14	4	4
SHB	0.033	0.011	-10000	0	0	51	51
BLK	0.012	0.077	0.36	1	-0.46	6	7
PTPN2	0.032	0.018	-10000	0	-0.019	49	49
PDGFB-D/PDGFRB/SNX15	0.049	0.025	-10000	0	-0.14	7	7
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	-0.006	0.15	0.29	13	-0.41	43	56
CBL	0.036	0.004	-10000	0	0	7	7
PDGFB-D/PDGFRB/DEP1	0.049	0.026	-10000	0	-0.14	7	7
LCK	0.017	0.06	0.26	4	-0.35	2	6
PDGFRB	0.031	0.021	0.064	2	-0.019	71	73
ACP1	0.035	0.007	-10000	0	0	18	18
HCK	-0.043	0.18	0.22	1	-0.5	61	62
ABL1	0.002	0.11	0.25	10	-0.34	29	39
PDGFB-D/PDGFRB/CBL	0.006	0.13	0.28	7	-0.43	27	34
PTPN1	0.032	0.018	-10000	0	-0.015	60	60
SNX15	0.036	0.004	-10000	0	0	6	6
STAT3	0.034	0.01	-10000	0	0	37	37
STAT1	0.034	0.01	-10000	0	0	40	40
cell proliferation	0.018	0.24	0.38	24	-0.6	51	75
SLA	0.027	0.016	-10000	0	0	134	134
actin cytoskeleton reorganization	-0.018	0.067	0.2	30	-0.19	7	37
SRC	0.017	0.052	0.29	2	-10000	0	2
PI3K	-0.047	0.044	-10000	0	-0.17	35	35
PDGFB-D/PDGFRB/GRB7/SHC	0.061	0.037	-10000	0	-0.12	10	10
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.019	0.1	0.29	9	-0.33	22	31
LYN	-0.035	0.16	0.22	2	-0.47	53	55
LRP1	0.031	0.013	-10000	0	0	71	71
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0.036	0.004	-10000	0	0	5	5
STAT5A	0.036	0.004	-10000	0	0	5	5
NCK1-2/p130 Cas	0.066	0.065	-10000	0	-0.14	25	25
SPHK1	0.033	0.011	0.058	1	0	50	51
EDG1	0.034	0.011	0.058	1	0	45	46
mol:DAG	0.011	0.1	0.25	9	-0.38	20	29
PLCG1	0.011	0.1	0.26	9	-0.38	20	29
NHERF/PDGFRB	0.062	0.036	-10000	0	-0.12	11	11
YES1	-0.009	0.13	0.23	2	-0.52	25	27
cell migration	0.061	0.036	-10000	0	-0.12	11	11
SHC/Grb2/SOS1	0.068	0.061	-10000	0	-0.13	20	20
SLC9A3R2	0.036	0.005	-10000	0	0	9	9
SLC9A3R1	0.034	0.01	-10000	0	0	37	37
NHERF1-2/PDGFRB/PTEN	0.06	0.052	-10000	0	-0.11	13	13
FYN	-0.055	0.19	0.22	1	-0.45	81	82
DOK1	-0.017	0.053	0.17	27	-10000	0	27
HRAS/GTP	0.021	0.027	-10000	0	-0.13	15	15
PDGFB	0.034	0.01	-10000	0	0	37	37
RAC1	0.031	0.19	0.32	39	-0.43	48	87
PRKCD	-0.015	0.053	0.17	27	-0.13	3	30
FER	-0.016	0.054	0.17	26	-0.13	2	28
MAPKKK cascade	-0.014	0.061	0.15	44	-0.18	5	49
RASA1	-0.015	0.055	0.17	27	-0.19	4	31
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.035	0.007	-10000	0	0	17	17
p62DOK/Csk	-0.014	0.063	0.18	31	-0.2	3	34
PDGFB-D/PDGFRB/SHB	0.045	0.027	-10000	0	-0.14	5	5
chemotaxis	0.002	0.11	0.25	11	-0.33	29	40
STAT1-3-5/STAT1-3-5	0.062	0.072	-10000	0	-0.15	21	21
Bovine Papilomavirus E5/PDGFRB	0.02	0.024	-10000	0	-0.14	7	7
PTPRJ	0.036	0.005	-10000	0	0	11	11

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.027	0.016	-9999	0	138	138
ITGB7	0.036	0.005	-9999	0	11	11
ITGA4	0.036	0.006	-9999	0	13	13
alpha4/beta7 Integrin	0.052	0.011	-9999	-9999	0	0
alpha4/beta1 Integrin	0.039	0.025	-9999	-9999	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.006	0.096	-10000	0	-0.39	27	27
Crk/p130 Cas/Paxillin	-0.056	0.092	-10000	0	-0.19	118	118
JUN	-0.016	0.047	-10000	0	-0.25	11	11
HRAS	0.034	0.009	-10000	0	0	32	32
RET51/GFRalpha1/GDNF/GRB10	0.037	0.058	-10000	0	-0.12	27	27
RAP1A	0.036	0.005	-10000	0	0	11	11
FRS2	0.034	0.009	-10000	0	0	30	30
RAP1A/GDP	0.026	0.008	-10000	0	-0.13	1	1
RET51/GFRalpha1/GDNF/DOK1	0.063	0.044	-10000	0	-10000	0	0
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.005	-10000	0	0	11	11
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.035	0.008	-10000	0	0	23	23
RET9/GFRalpha1/GDNF/Enigma	0.047	0.033	-10000	0	-10000	0	0
RHOA	0.035	0.007	-10000	0	0	18	18
RAP1A/GTP	0.055	0.047	-10000	0	-0.11	1	1
GRB7	0.036	0.006	-10000	0	0	14	14
RET51/GFRalpha1/GDNF	0.063	0.044	-10000	0	-10000	0	0
MAPKKK cascade	-0.004	0.073	-10000	0	-0.18	14	14
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.038	0.045	-10000	0	-0.1	23	23
lamellipodium assembly	-0.027	0.082	-10000	0	-0.2	59	59
RET51/GFRalpha1/GDNF/SHC	0.059	0.049	-10000	0	-0.12	8	8
PIK3CA	0.031	0.013	-10000	0	0	80	80
RET9/GFRalpha1/GDNF/SHC	0.04	0.039	-10000	0	-0.11	8	8
RET9/GFRalpha1/GDNF/Shank3	0.032	0.022	-10000	0	-10000	0	0
MAPK3	-0.025	0.037	0.2	9	-10000	0	9
DOK1	0.036	0.002	-10000	0	0	2	2
DOK6	0	0	-10000	0	-10000	0	0
PXN	0.036	0.004	-10000	0	0	7	7
neurite development	-0.021	0.041	0.2	7	-0.21	9	16
DOK5	0.029	0.015	-10000	0	0	100	100
GFRA1	0.025	0.017	-10000	0	0	161	161
MAPK8	0	0.045	-10000	0	-0.18	19	19
HRAS/GTP	0.023	0.091	-10000	0	-0.12	109	109
tube development	0.025	0.025	0.2	1	-0.096	8	9
MAPK1	-0.023	0.038	0.19	10	-10000	0	10
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.013	0.063	-10000	0	-0.22	14	14
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
SRC	0.036	0.006	-10000	0	0	14	14
PDLIM7	0.036	0.005	-10000	0	0	11	11
RET51/GFRalpha1/GDNF/Dok6	0.057	0.043	-10000	0	-10000	0	0
SHC1	0.033	0.011	-10000	0	0	52	52
RET51/GFRalpha1/GDNF/Dok4	0.063	0.044	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.039	0.071	-10000	0	-0.11	65	65
PRKCA	0.036	0.004	-10000	0	0	6	6
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
CREB1	-0.031	0.095	-10000	0	-0.19	115	115
PIK3R1	0.032	0.012	-10000	0	0	63	63
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.011	0.064	-10000	0	-0.17	28	28
RET51/GFRalpha1/GDNF/Grb7	0.063	0.044	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.028	0.016	-10000	0	0	126	126
DOK4	0.035	0.006	-10000	0	0	16	16
JNK cascade	-0.016	0.047	-10000	0	-0.23	13	13
RET9/GFRalpha1/GDNF/FRS2	0.045	0.034	-10000	0	-10000	0	0
SHANK3	0	0	-10000	0	-10000	0	0
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.011	0.038	-10000	0	-0.17	17	17
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.024	0.091	-10000	0	-0.19	105	105
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.032	0.096	-10000	0	-0.19	121	121
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.008	0.048	-10000	0	-0.18	17	17
PI3K	-0.057	0.13	-10000	0	-0.26	105	105
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.042	0.035	-10000	0	-0.096	8	8
GRB10	0.021	0.018	-10000	0	0	220	220
activation of MAPKK activity	0.01	0.049	-10000	0	-0.28	11	11
RET51/GFRalpha1/GDNF/FRS2	0.06	0.045	-10000	0	-10000	0	0
GAB1	0.032	0.012	-10000	0	0	59	59
IRS1	0.033	0.011	-10000	0	0	52	52
IRS2	0.03	0.014	-10000	0	0	96	96
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.008	0.056	-10000	0	-0.17	26	26
RET51/GFRalpha1/GDNF/PKC alpha	0.063	0.044	-10000	0	-10000	0	0
GRB2	0.035	0.007	-10000	0	0	17	17
PRKACA	0.035	0.008	-10000	0	0	25	25
GDNF	0.036	0.004	-10000	0	0	6	6
RAC1	0.024	0.017	-10000	0	0	173	173
RET51/GFRalpha1/GDNF/IRS1	0.056	0.056	-10000	0	-0.11	22	22
Rac1/GTP	-0.029	0.097	-10000	0	-0.23	59	59
RET9/GFRalpha1/GDNF	0.033	0.023	-10000	0	-10000	0	0
GFRalpha1/GDNF	0.037	0.025	-10000	0	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.032	0.012	-10000	0	0	67	67
GNB1/GNG2	0.028	0.034	-10000	0	-0.11	14	14
forebrain development	0.034	0.063	0.25	4	-0.42	3	7
GNAO1	0.03	0.014	-10000	0	0	87	87
SMO/beta Arrestin2	0.033	0.031	-10000	0	-0.14	4	4
SMO	0.024	0.018	-10000	0	-10000	0	0
ARRB2	0.035	0.008	-10000	0	0	26	26
GLI3/SPOP	0.002	0.11	0.27	1	-0.32	32	33
mol:GTP	0	0.001	-10000	0	-10000	0	0
GSK3B	0.034	0.01	-10000	0	0	40	40
GNAI2	0.034	0.01	-10000	0	0	43	43
SIN3/HDAC complex	0.055	0.041	-10000	0	-0.12	17	17
GNAI1	0.018	0.018	-10000	0	0	263	263
XPO1	0.037	0.005	-10000	0	-10000	0	0
GLI1/Su(fu)	0.012	0.047	-10000	0	-0.3	5	5
SAP30	0.035	0.007	-10000	0	0	20	20
mol:GDP	0.024	0.018	-10000	0	-10000	0	0
MIM/GLI2A	0.041	0.013	0.12	11	-10000	0	11
IFT88	0.035	0.008	-10000	0	0	28	28
GNAI3	0.036	0.006	-10000	0	0	15	15
GLI2	0.001	0.089	-10000	0	-0.34	21	21
GLI3	-0.013	0.1	0.27	1	-0.32	30	31
CSNK1D	0.035	0.007	-10000	0	0	20	20
CSNK1E	0.032	0.012	-10000	0	0	67	67
SAP18	0.034	0.01	-10000	0	0	41	41
embryonic digit morphogenesis	0.035	0.008	-10000	0	0	28	28
GNG2	0	0	-10000	0	-10000	0	0
Gi family/GTP	-0.01	0.088	-10000	0	-0.2	69	69
SIN3B	0.034	0.009	-10000	0	0	29	29
SIN3A	0	0	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.012	0.072	-10000	0	-0.26	26	26
GLI2/Su(fu)	-0.003	0.072	-10000	0	-0.31	17	17
FOXA2	0.05	0.041	-10000	0	-0.49	1	1
neural tube patterning	0.034	0.063	0.25	4	-0.42	3	7
SPOP	0.035	0.008	-10000	0	0	23	23
Su(fu)/PIAS1	0.047	0.038	0.098	151	-0.083	9	160
GNB1	0.035	0.007	-10000	0	0	20	20
CSNK1G2	0.034	0.009	-10000	0	0	30	30
CSNK1G3	0.036	0.006	-10000	0	0	13	13
MTSS1	0.041	0.013	0.12	11	-10000	0	11
embryonic limb morphogenesis	0.034	0.063	0.25	4	-0.42	3	7
SUFU	0.002	0.01	-10000	0	-0.11	4	4
LGALS3	0.028	0.015	-10000	0	0	114	114
catabolic process	0.012	0.14	0.31	2	-0.44	31	33
GLI3A/CBP	0.044	0.008	-10000	0	-10000	0	0
KIF3A	0.033	0.011	-10000	0	0	55	55
GLI1	0.034	0.064	0.25	4	-0.43	3	7
RAB23	0.034	0.009	-10000	0	0	31	31
CSNK1A1	0.036	0.006	-10000	0	0	14	14
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0.036	0.005	-10000	0	0	8	8
Su(fu)/Galectin3	0.038	0.04	0.098	123	-0.11	8	131
GNAZ	0.031	0.013	-10000	0	0	81	81
RBBP4	0.033	0.011	-10000	0	0	56	56
CSNK1G1	0.036	0.006	-10000	0	0	14	14
PIAS1	0.035	0.008	-10000	0	0	27	27
PRKACA	0.035	0.008	-10000	0	0	25	25
GLI2/SPOP	0.016	0.097	-10000	0	-0.32	25	25
STK36	0.001	0.003	0.022	4	-10000	0	4
Gi family/GNB1/GNG2/GDP	-0.015	0.1	-10000	0	-0.36	30	30
PTCH1	0.033	0.059	0.23	4	-0.38	3	7
MIM/GLI1	0.057	0.069	0.35	2	-0.39	3	5
CREBBP	0.044	0.008	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	0.002	0.091	0.16	2	-0.24	44	46

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.007	0.071	-10000	0	-0.29	22	22
KLHL20	0.048	0.09	0.2	58	-0.19	16	74
CYFIP2	0.031	0.013	-10000	0	0	78	78
Rac1/GDP	0.007	0.061	0.2	1	-0.29	10	11
ENAH	0.007	0.074	-10000	0	-0.31	21	21
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	0	62	0	12	74
RAP1A	0.036	0.005	-10000	0	0	11	11
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	-0.026	0.052	0.12	13	-0.21	18	31
ABI1/Sra1/Nap1	-0.014	0.033	-10000	0	-0.14	27	27
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.084	0.036	-10000	0	-0.13	8	8
RAPGEF1	-0.006	0.074	-10000	0	-0.29	18	18
CTNND1	0.034	0.009	-10000	0	0	32	32
regulation of calcium-dependent cell-cell adhesion	0.02	0.076	-10000	0	-0.29	23	23
CRK	0	0.076	0.2	1	-0.29	22	23
E-cadherin/gamma catenin/alpha catenin	0.061	0.035	-10000	0	-0.12	8	8
alphaE/beta7 Integrin	0.049	0.025	-10000	0	-0.14	7	7
IQGAP1	0.033	0.011	-10000	0	0	51	51
NCKAP1	0.036	0.002	-10000	0	0	2	2
Rap1/GTP/I-afadin	0.043	0.015	-10000	0	-0.1	1	1
DLG1	0.007	0.075	-10000	0	-0.3	23	23
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.035	0.044	-10000	0	-0.18	30	30
MLLT4	0.034	0.009	-10000	0	0	36	36
ARF6/GTP/NME1/Tiam1	0.036	0.033	-10000	0	-0.1	23	23
PI3K	-0.043	0.058	0.059	2	-0.23	30	32
ARF6	0.035	0.008	-10000	0	0	27	27
mol:Ca2+	0	0	0.001	69	0	28	97
E-cadherin/gamma catenin	0.048	0.018	-10000	0	-10000	0	0
TIAM1	0.033	0.011	-10000	0	0	46	46
E-cadherin(dimer)/Ca2+	0.07	0.054	-10000	0	-0.14	25	25
AKT1	-0.023	0.052	0.13	7	-0.18	24	31
PIK3R1	0.032	0.012	-10000	0	0	63	63
CDH1	0.034	0.01	-10000	0	0	38	38
RhoA/GDP	0.011	0.07	0.19	2	-0.27	12	14
actin cytoskeleton organization	0.04	0.072	0.17	62	-0.14	16	78
CDC42/GDP	0.011	0.068	0.19	2	-0.26	11	13
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.012	0.049	-10000	0	-0.2	23	23
ITGB7	0.036	0.005	-10000	0	0	11	11
RAC1	0.024	0.017	-10000	0	0	173	173
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.077	0.057	-10000	0	-0.15	25	25
E-cadherin/Ca2+/beta catenin/alpha catenin	0.056	0.031	-10000	0	-0.11	10	10
mol:GDP	-0.006	0.071	0.19	2	-0.3	12	14
CDC42/GTP/IQGAP1	0.035	0.042	-10000	0	-0.12	33	33
JUP	0.033	0.011	-10000	0	0	51	51
p120 catenin/RhoA/GDP	0.026	0.077	0.21	1	-0.26	15	16
RAC1/GTP/IQGAP1	0.023	0.042	-10000	0	-0.12	30	30
PIP5K1C/AP1M1	0.02	0.03	-10000	0	-0.13	18	18
RHOA	0.035	0.007	-10000	0	0	18	18
CDC42	0.035	0.008	-10000	0	0	24	24
CTNNA1	0.035	0.007	-10000	0	0	20	20
positive regulation of S phase of mitotic cell cycle	0.014	0.045	0.11	8	-0.13	26	34
NME1	0	0	-10000	0	0	32	32
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.008	0.072	-10000	0	-0.3	20	20
regulation of cell-cell adhesion	-0.028	0.04	-10000	0	-0.17	25	25
WASF2	-0.008	0.018	-10000	0	-0.074	27	27
Rap1/GTP	-0.023	0.061	0.15	19	-0.25	16	35
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.09	0.051	-10000	0	-0.13	13	13
CCND1	0.016	0.054	0.13	8	-0.16	26	34
VAV2	0.019	0.1	-10000	0	-0.54	8	8
RAP1/GDP	-0.011	0.064	0.16	17	-0.25	15	32
adherens junction assembly	0.009	0.071	-10000	0	-0.29	20	20
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.026	0.017	-10000	0	0	152	152
PIP5K1C	0.033	0.011	-10000	0	0	50	50
regulation of heterotypic cell-cell adhesion	0.068	0.047	0.2	3	-0.13	14	17
E-cadherin/beta catenin	0.006	0.02	-10000	0	-0.097	5	5
mol:GTP	0	0	0.001	64	0	32	96
SRC	0.006	0.073	-10000	0	-0.29	23	23
PIK3CA	0.031	0.013	-10000	0	0	80	80
Rac1/GTP	-0.007	0.07	0.18	1	-0.28	21	22
E-cadherin/beta catenin/alpha catenin	0.064	0.036	-10000	0	-0.13	10	10
ITGAE	0.035	0.007	-10000	0	0	19	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.02	0.077	-10000	0	-0.3	23	23

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K1	0.016	0.11	0.27	11	-0.38	21	32
CRKL	0.019	0.1	0.23	9	-0.4	21	30
HRAS	0.034	0.1	0.25	9	-0.33	21	30
mol:PIP3	0.052	0.12	0.29	27	-0.35	20	47
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.036	0.004	-10000	0	0	6	6
GAB1	0.025	0.11	0.24	11	-0.4	22	33
FOXO3	0.053	0.16	0.32	28	-0.36	38	66
AKT1	0.054	0.17	0.33	27	-0.39	38	65
BAD	0.047	0.16	0.32	27	-0.37	39	66
megakaryocyte differentiation	0.025	0.1	0.24	10	-0.39	19	29
GSK3B	0.047	0.17	0.33	29	-0.39	39	68
RAF1	0.023	0.091	0.24	13	-0.28	22	35
SHC1	0.033	0.011	-10000	0	0	52	52
STAT3	0.018	0.1	0.22	5	-0.4	22	27
STAT1	0.015	0.2	-10000	0	-0.87	21	21
HRAS/SPRED1	0.025	0.09	0.22	9	-0.27	22	31
cell proliferation	0.01	0.095	0.23	4	-0.38	22	26
PIK3CA	0.031	0.013	-10000	0	0	80	80
TEC	0.036	0.005	-10000	0	0	8	8
RPS6KB1	0.055	0.12	0.27	19	-0.37	21	40
HRAS/SPRED2	0.044	0.1	0.25	12	-0.28	21	33
LYN/TEC/p62DOK	0.065	0.12	-10000	0	-0.4	21	21
MAPK3	0.02	0.088	0.24	25	-0.22	18	43
STAP1	0.026	0.1	0.23	5	-0.39	22	27
GRAP2	0.034	0.009	-10000	0	0	35	35
JAK2	0.015	0.17	-10000	0	-0.74	21	21
STAT1 (dimer)	0.02	0.2	-10000	0	-0.85	21	21
mol:Gleevec	-0.002	0.006	-10000	0	-0.023	1	1
GRB2/SOCS1/VAV1	0.072	0.11	-10000	0	-0.39	21	21
actin filament polymerization	0.027	0.1	0.23	5	-0.38	22	27
LYN	0.031	0.013	-10000	0	0	74	74
STAP1/STAT5A (dimer)	0.024	0.14	0.29	1	-0.54	21	22
PIK3R1	0.032	0.012	-10000	0	0	63	63
CBL/CRKL/GRB2	0.053	0.11	0.28	3	-0.38	21	24
PI3K	0.061	0.13	0.3	15	-0.37	21	36
PTEN	0.026	0.017	-10000	0	0	148	148
SCF/KIT/EPO/EPOR	0.022	0.22	-10000	0	-1	21	21
MAPK8	0.009	0.095	0.23	3	-0.39	22	25
STAT3 (dimer)	0.02	0.1	0.24	7	-0.39	22	29
positive regulation of transcription	0.021	0.078	0.22	27	-0.18	18	45
mol:GDP	0.041	0.098	0.24	1	-0.34	21	22
PIK3C2B	0.025	0.1	0.24	11	-0.39	22	33
CBL/CRKL	0.041	0.11	0.27	4	-0.38	21	25
FER	0.023	0.1	0.24	6	-0.39	22	28
SH2B3	0.026	0.1	0.23	5	-0.39	22	27
PDPK1	0.046	0.12	0.28	28	-0.33	21	49
SNAI2	0.026	0.11	0.23	11	-0.4	21	32
positive regulation of cell proliferation	0.027	0.17	-10000	0	-0.66	21	21
KITLG	0.038	0.021	-10000	0	-0.051	20	20
cell motility	0.027	0.17	-10000	0	-0.66	21	21
PTPN6	0.023	0.025	-10000	0	-0.033	67	67
EPOR	0.048	0.083	-10000	0	-10000	0	0
STAT5A (dimer)	0.032	0.14	-10000	0	-0.54	21	21
SOCS1	0.036	0.005	-10000	0	0	8	8
cell migration	-0.022	0.1	0.38	22	-0.25	7	29
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.025	0.022	-10000	0	-0.036	15	15
VAV1	0.034	0.009	-10000	0	0	35	35
GRB10	0.011	0.087	0.3	4	-0.4	13	17
PTPN11	0.027	0.022	-10000	0	-0.032	56	56
SCF/KIT	0.03	0.11	0.24	5	-0.41	22	27
GO:0007205	-0.002	0.007	0.021	19	-0.022	2	21
MAP2K1	0.013	0.081	0.22	12	-0.23	22	34
CBL	0.036	0.004	-10000	0	0	7	7
KIT	0.006	0.24	-10000	0	-1.1	21	21
MAP2K2	0.018	0.093	0.28	24	-0.23	20	44
SHC/Grb2/SOS1	0.052	0.11	-10000	0	-0.36	21	21
STAT5A	0.032	0.14	-10000	0	-0.56	21	21
GRB2	0.035	0.007	-10000	0	0	17	17
response to radiation	0.027	0.11	0.23	12	-0.39	21	33
SHC/GRAP2	0.043	0.03	-10000	0	-0.14	8	8
PTPRO	0.024	0.1	0.24	10	-0.4	19	29
SH2B2	0.026	0.1	0.23	5	-0.39	22	27
DOK1	0.036	0.002	-10000	0	0	2	2
MATK	0.019	0.1	0.23	4	-0.39	22	26
CREBBP	0.051	0.045	0.14	3	-0.12	21	24
BCL2	0.04	0.13	-10000	0	-0.87	6	6

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.007	0.088	-10000	0	-0.34	12	12
ACTA1	-0.037	0.092	-10000	0	-0.31	32	32
NUMA1	-0.002	0.085	-10000	0	-0.31	20	20
SPTAN1	-0.044	0.092	0.2	5	-0.29	37	42
LIMK1	0.011	0.11	0.19	79	-0.34	16	95
BIRC3	0.031	0.013	-10000	0	0	81	81
BIRC2	0.036	0.005	-10000	0	0	11	11
BAX	0.033	0.01	-10000	0	0	44	44
CASP10	-0.008	0.031	0.082	47	-10000	0	47
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0	0	-10000	0	-10000	0	0
PTK2	-0.01	0.092	-10000	0	-0.29	30	30
DIABLO	0.036	0.004	-10000	0	0	6	6
apoptotic nuclear changes	-0.044	0.092	0.2	5	-0.29	37	42
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.036	0.006	-10000	0	0	12	12
GSN	-0.038	0.098	0.2	5	-0.32	33	38
MADD	0.036	0.006	-10000	0	0	15	15
TFAP2A	0.045	0.055	-10000	0	-0.44	5	5
BID	0	0.039	0.11	5	-0.19	16	21
MAP3K1	-0.003	0.051	-10000	0	-0.39	5	5
TRADD	0.036	0.005	-10000	0	0	11	11
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.05	0.018	-10000	0	-0.14	2	2
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.042	0.099	0.2	12	-0.31	35	47
CASP9	0.034	0.009	-10000	0	0	33	33
DNA repair	0.034	0.071	0.28	18	-10000	0	18
neuron apoptosis	0.017	0.12	-10000	0	-0.62	15	15
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.025	0.088	-10000	0	-0.31	28	28
APAF1	0.036	0.003	-10000	0	0	4	4
CASP6	0.027	0.11	-10000	0	-0.84	6	6
TRAF2	0.036	0.006	-10000	0	0	15	15
ICAD/CAD	-0.047	0.084	0.22	1	-0.3	32	33
CASP7	-0.079	0.11	-10000	0	-0.24	141	141
KRT18	0.027	0.051	-10000	0	-0.46	4	4
apoptosis	-0.033	0.092	-10000	0	-0.34	19	19
DFFA	-0.043	0.087	0.17	1	-0.3	33	34
DFFB	-0.042	0.085	-10000	0	-0.3	31	31
PARP1	-0.035	0.071	-10000	0	-0.28	18	18
actin filament polymerization	-0.017	0.11	0.32	16	-0.18	79	95
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.016	0.039	0.18	3	-0.24	3	6
SATB1	0.018	0.11	-10000	0	-0.73	6	6
SLK	-0.026	0.085	-10000	0	-0.29	33	33
p15 BID/BAX	0.002	0.06	0.15	2	-0.16	44	46
CASP2	0.062	0.1	0.22	131	-0.26	5	136
JNK cascade	0.003	0.051	0.38	5	-10000	0	5
CASP3	-0.04	0.092	-10000	0	-0.31	34	34
LMNB2	0.062	0.092	0.22	14	-0.36	4	18
RIPK1	0.035	0.007	-10000	0	0	20	20
CASP4	0.03	0.014	-10000	0	0	92	92
Mammalian IAPs/DIABLO	0.058	0.034	-10000	0	-0.15	6	6
negative regulation of DNA binding	0.045	0.054	-10000	0	-0.43	5	5
stress fiber formation	-0.036	0.085	-10000	0	-0.29	33	33
GZMB	-0.005	0.033	0.092	47	-10000	0	47
CASP1	-0.011	0.066	-10000	0	-0.2	55	55
LMNB1	0.044	0.13	0.24	8	-0.39	15	23
APP	0.017	0.12	-10000	0	-0.63	15	15
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
response to stress	0	0	-10000	0	-10000	0	0
CASP8	-0.011	0.002	0	13	-10000	0	13
VIM	-0.033	0.095	0.22	1	-0.34	23	24
LMNA	0.067	0.088	0.23	13	-0.36	2	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.018	0.056	0.16	1	-0.23	11	12
LRDD	0.035	0.007	-10000	0	0	20	20
SREBF1	-0.043	0.088	0.18	1	-0.3	34	35
APAF-1/Caspase 9	0.014	0.1	-10000	0	-0.61	12	12
nuclear fragmentation during apoptosis	-0.002	0.084	-10000	0	-0.3	20	20
CFL2	0.017	0.11	0.18	78	-0.32	16	94
GAS2	-0.033	0.092	0.2	2	-0.3	32	34
positive regulation of apoptosis	0.062	0.1	0.23	21	-0.4	6	27
PRF1	0.023	0.018	-10000	0	0	192	192

×

ErbB4 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ErbB4/ErbB4/HBEGF/HBEGF	0.02	0.13	-10000	0	-0.63	18	18
epithelial cell differentiation	-0.008	0.14	-10000	0	-0.65	18	18
ITCH	0.031	0.031	0.11	1	-0.1	22	23
WWP1	-0.021	0.22	-10000	0	-1.1	18	18
FYN	0.03	0.014	-10000	0	0	90	90
EGFR	0.009	0.016	-10000	0	0	381	381
PRL	0.036	0.006	-10000	0	0	15	15
neuron projection morphogenesis	-0.028	0.11	0.24	6	-0.5	19	25
PTPRZ1	0.022	0.018	-10000	0	0	201	201
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.054	0.12	-10000	0	-0.54	18	18
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.003	0.11	-10000	0	-0.57	18	18
ADAM17	0.031	0.031	-10000	0	-0.096	24	24
ErbB4/ErbB4	0.001	0.14	-10000	0	-0.69	18	18
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.009	0.12	-10000	0	-0.62	18	18
NCOR1	0.035	0.008	-10000	0	0	26	26
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.016	0.12	-10000	0	-0.58	18	18
GRIN2B	-0.028	0.11	0.21	3	-0.55	18	21
ErbB4/ErbB2/betacellulin	0.024	0.12	-10000	0	-0.55	18	18
STAT1	0.034	0.01	-10000	0	0	40	40
HBEGF	0.035	0.008	-10000	0	0	23	23
PRLR	0.036	0.004	-10000	0	0	6	6
E4ICDs/ETO2	0.02	0.13	-10000	0	-0.63	18	18
axon guidance	-0.032	0.16	-10000	0	-0.78	18	18
NEDD4	0.029	0.031	0.11	1	-0.11	21	22
Prolactin receptor/Prolactin receptor/Prolactin	0.052	0.011	-10000	0	-10000	0	0
CBFA2T3	0.034	0.009	-10000	0	0	30	30
ErbB4/ErbB2/HBEGF	0.023	0.11	-10000	0	-0.55	18	18
MAPK3	-0.021	0.11	0.26	5	-0.52	18	23
STAT1 (dimer)	0.019	0.13	-10000	0	-0.63	18	18
MAPK1	-0.023	0.11	0.26	5	-0.52	19	24
JAK2	0.031	0.014	-10000	0	0	83	83
ErbB4/ErbB2/neuregulin 1 beta	0.003	0.11	0.21	1	-0.55	18	19
NRG1	-0.022	0.021	0.089	5	-0.083	18	23
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.036	0.005	-10000	0	0	10	10
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.032	0.16	-10000	0	-0.78	18	18
neural crest cell migration	0.003	0.11	0.21	1	-0.54	18	19
ERBB2	-0.021	0.023	0.098	8	-0.083	18	26
WWOX/E4ICDs	0.022	0.13	-10000	0	-0.62	18	18
SHC1	0.033	0.011	-10000	0	0	52	52
ErbB4/EGFR/neuregulin 4	-0.015	0.099	-10000	0	-0.48	18	18
apoptosis	-0.004	0.12	0.58	18	-10000	0	18
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.021	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB2/epiregulin	0.023	0.11	-10000	0	-0.55	18	18
ErbB4/ErbB4/betacellulin/betacellulin	0.022	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.062	0.13	-10000	0	-0.57	18	18
MDM2	0	0.13	0.27	13	-0.6	18	31
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.02	0.1	-10000	0	-0.51	18	18
STAT5A	-0.037	0.15	-10000	0	-0.76	18	18
ErbB4/EGFR/neuregulin 1 beta	-0.005	0.089	-10000	0	-0.43	18	18
DLG4	0.036	0.005	-10000	0	0	11	11
GRB2/SHC	0.043	0.037	-10000	0	-0.15	14	14
E4ICDs/TAB2/NCoR1	0.029	0.13	-10000	0	-0.62	18	18
STAT5A (dimer)	-0.001	0.16	-10000	0	-0.72	18	18
MAP3K7IP2	0.033	0.011	-10000	0	0	46	46
STAT5B (dimer)	-0.017	0.16	0.28	1	-0.76	18	19
LRIG1	0.03	0.014	-10000	0	0	85	85
EREG	0.035	0.008	-10000	0	0	23	23
BTC	0.036	0.005	-10000	0	0	9	9
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.032	0.16	-10000	0	-0.79	18	18
ERBB4	0.001	0.14	-10000	0	-0.69	18	18
STAT5B	0.036	0.004	-10000	0	0	5	5
YAP1	-0.071	0.2	-10000	0	-0.49	93	93
GRB2	0.035	0.007	-10000	0	0	17	17
ErbB4/ErbB2/neuregulin 4	0.001	0.11	-10000	0	-0.55	18	18
glial cell differentiation	-0.029	0.13	0.62	18	-10000	0	18
WWOX	0.035	0.007	-10000	0	0	17	17
cell proliferation	-0.014	0.11	-10000	0	-0.57	18	18

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	0.041	0.01	-10000	0	-10000	0	0
RGS9BP	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
GRK1	0	0	-10000	0	-10000	0	0
mol:Na +	0.01	0.06	-10000	0	-0.11	88	88
mol:ADP	0	0	-10000	0	-10000	0	0
GNAT2	0.036	0.005	-10000	0	0	8	8
RGS9-1/Gbeta5/R9AP	0.045	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.046	0.012	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.036	0.005	-10000	0	0	9	9
Cone Metarhodopsin II/X-Arrestin	0.027	0	-10000	0	-10000	0	0
mol:Ca2+	-0.014	0.056	0.092	75	-0.11	71	146
Cone PDE6	0.053	0.047	-10000	0	-0.11	1	1
Cone Metarhodopsin II	0	0	-10000	0	-10000	0	0
Na + (4 Units)	0.017	0.064	-10000	0	-0.11	87	87
GNAT2/GDP	0.058	0.02	-10000	0	-0.1	1	1
GNB5	0.035	0.008	-10000	0	0	24	24
mol:GMP (4 units)	-0.011	0.032	0.18	12	-10000	0	12
Cone Transducin	0.045	0.01	-10000	0	-10000	0	0
SLC24A2	0.029	0.015	-10000	0	0	100	100
GNB3/GNGT2	0.026	0.005	-10000	0	-10000	0	0
GNB3	0.035	0.007	-10000	0	0	18	18
GNAT2/GTP	0.027	0.003	-10000	0	-10000	0	0
CNGA3	0.022	0.018	-10000	0	0	197	197
ARR3	0.037	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.01	0.061	-10000	0	-0.12	88	88
mol:Pi	0.045	0.015	-10000	0	-0.11	1	1
Cone CNG Channel	0.026	0.075	-10000	0	-0.11	81	81
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.029	0.015	-10000	0	0	100	100
RGS9	0.035	0.007	-10000	0	0	17	17
PDE6C	0.025	0.017	-10000	0	0	155	155
GNGT2	0	0	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.035	0.008	-10000	0	0	23	23

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.028	0.15	-10000	0	-0.46	26	26
RAD9A	0.036	0.005	-10000	0	0	11	11
AP1	0.011	0.079	-10000	0	-0.17	70	70
IFNAR2	0.033	0.02	-10000	0	-0.035	36	36
AKT1	0.013	0.056	-10000	0	-0.25	19	19
ER alpha/Oestrogen	0.024	0.014	-10000	0	-0.023	13	13
NFX1/SIN3/HDAC complex	-0.005	0.082	-10000	0	-0.26	32	32
EGF	0.033	0.016	-10000	0	-0.014	45	45
SMG5	0	0	-10000	0	-10000	0	0
SMG6	0	0	-10000	0	-10000	0	0
SP3/HDAC2	0.038	0.052	-10000	0	-0.16	20	20
TERT/c-Abl	0.035	0.16	-10000	0	-0.46	28	28
SAP18	0.034	0.01	-10000	0	0	41	41
MRN complex	0.069	0.024	-10000	0	-0.12	4	4
WT1	0.033	0.02	-10000	0	-0.035	36	36
WRN	0.035	0.009	-10000	0	0	29	29
SP1	0.033	0.023	-10000	0	-0.043	38	38
SP3	0.033	0.016	-10000	0	-0.03	25	25
TERF2IP	0.034	0.01	-10000	0	0	37	37
Telomerase/Nucleolin	0.04	0.16	-10000	0	-0.44	30	30
Mad/Max	0.047	0.028	-10000	0	-10000	0	0
TERT	0.024	0.16	-10000	0	-0.47	26	26
CCND1	-0.013	0.29	-10000	0	-0.95	39	39
MAX	0.032	0.018	-10000	0	-0.03	29	29
RBBP7	0.036	0.005	-10000	0	0	8	8
RBBP4	0.033	0.012	-10000	0	0	56	56
TERF2	0.027	0.011	0.085	4	-10000	0	4
PTGES3	0.036	0.006	-10000	0	0	14	14
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.048	0.1	-10000	0	-0.4	14	14
CDKN1B	-0.027	0.082	0.099	35	-0.34	26	61
RAD1	0.035	0.007	-10000	0	0	18	18
XRCC5	0.036	0.005	-10000	0	0	9	9
XRCC6	0.034	0.01	-10000	0	0	39	39
SAP30	0.035	0.007	-10000	0	0	20	20
TRF2/PARP2	0.033	0.056	-10000	0	-0.14	45	45
UBE3A	0.035	0.011	-10000	0	-0.023	17	17
JUN	0.032	0.016	-10000	0	-0.03	17	17
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.025	0.02	-10000	0	-0.13	4	4
FOS	0.024	0.02	-10000	0	-0.03	15	15
IFN-gamma/IRF1	0.034	0.069	-10000	0	-0.18	38	38
PARP2	0.035	0.007	-10000	0	0	21	21
BLM	0.029	0.015	-10000	0	0	107	107
Telomerase	0.016	0.055	-10000	0	-0.32	9	9
IRF1	0.025	0.039	-10000	0	-0.11	31	31
ESR1	0.035	0.009	-10000	0	0	29	29
KU/TER	0.047	0.029	-10000	0	-0.14	9	9
ATM/TRF2	0.044	0.027	-10000	0	-0.11	7	7
ubiquitin-dependent protein catabolic process	0.003	0.079	0.14	1	-0.26	27	28
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0.003	0.081	-10000	0	-0.27	27	27
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC2	0.029	0.023	-10000	0	-0.041	33	33
ATM	0.022	0.038	0.13	38	-0.18	5	43
SMAD3	-0.014	0.028	0.09	28	-10000	0	28
ABL1	0.032	0.013	-10000	0	0	70	70
MXD1	0.034	0.016	-10000	0	-0.03	29	29
MRE11A	0.036	0.004	-10000	0	0	7	7
HUS1	0.025	0.017	-10000	0	0	166	166
RPS6KB1	0.036	0.005	-10000	0	0	9	9
TERT/NF kappa B1/14-3-3	0.043	0.17	-10000	0	-0.49	23	23
NR2F2	0.022	0.023	-10000	0	-0.03	52	52
MAPK3	-0.017	0.017	0.093	2	-10000	0	2
MAPK1	-0.014	0.022	0.095	10	-10000	0	10
TGFB1/TGF beta receptor Type II	0.032	0.012	-10000	0	0	66	66
NFKB1	0.035	0.007	-10000	0	0	18	18
HNRNPC	0	0	-10000	0	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.022	0.038	0.13	38	-0.18	5	43
NBN	0.036	0.006	-10000	0	0	14	14
EGFR	0.009	0.016	-10000	0	0	382	382
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.005	0.056	-10000	0	-0.14	64	64
MYC	0.028	0.019	-10000	0	-0.029	21	21
IL2	0.034	0.023	-10000	0	-0.043	36	36
KU	0.047	0.029	-10000	0	-0.14	9	9
RAD50	0.036	0.006	-10000	0	0	13	13
HSP90AA1	0	0	-10000	0	-10000	0	0
TGFB1	0.032	0.012	-10000	0	0	66	66
TRF2/BLM	0.01	0.077	-10000	0	-0.15	92	92
FRAP1	0.035	0.007	-10000	0	0	17	17
KU/TERT	0.05	0.16	-10000	0	-0.44	29	29
SP1/HDAC2	0.042	0.045	-10000	0	-0.085	38	38
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.025	0.14	-10000	0	-0.42	30	30
Smad3/Myc	0.013	0.048	-10000	0	-0.12	39	39
911 complex	0.046	0.039	-10000	0	-0.12	5	5
IFNG	0.027	0.04	-10000	0	-0.1	38	38
Telomerase/PinX1	0.025	0.14	-10000	0	-0.42	30	30
Telomerase/AKT1/mTOR/p70S6K	0.022	0.093	0.22	1	-0.43	11	12
SIN3B	0.035	0.009	-10000	0	0	29	29
YWHAE	0.035	0.008	-10000	0	0	27	27
Telomerase/EST1B	0.025	0.14	-10000	0	-0.42	30	30
response to DNA damage stimulus	0.009	0.017	-10000	0	-0.08	9	9
MRN complex/TRF2/Rap1	0.077	0.071	-10000	0	-0.14	39	39
TRF2/WRN	0.034	0.045	-10000	0	-0.11	40	40
Telomerase/hnRNP C1/C2	0.025	0.14	-10000	0	-0.42	30	30
E2F1	0.033	0.02	-10000	0	-0.035	35	35
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.035	0.007	-10000	0	0	17	17
DKC1	0.035	0.007	-10000	0	0	18	18
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	0.05	0.023	-10000	0	-0.14	6	6
Necdin/E2F1	-0.018	0.085	-10000	0	-0.14	156	156
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.073	0.047	-10000	0	-0.12	23	23
NGF (dimer)/p75(NTR)/BEX1	0.011	0.063	-10000	0	-0.12	95	95
NT-4/5 (dimer)/p75(NTR)	0.023	0.009	-10000	0	-10000	0	0
IKBKB	0.036	0.003	-10000	0	0	4	4
AKT1	-0.016	0.078	0.2	25	-0.2	23	48
IKBKG	0.037	0	-10000	0	-10000	0	0
BDNF	0.032	0.012	-10000	0	0	67	67
MGDIs/NGR/p75(NTR)/LINGO1	0.021	0.009	-10000	0	-10000	0	0
FURIN	0.036	0.006	-10000	0	0	12	12
proBDNF (dimer)/p75(NTR)/Sortilin	0.055	0.034	-10000	0	-0.12	2	2
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.023	0.067	-10000	0	-0.15	50	50
proBDNF (dimer)	0.032	0.012	-10000	0	0	67	67
NTRK1	0.035	0.006	-10000	0	0	16	16
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	0.004	0.11	0.26	2	-0.36	29	31
IRAK1	0.035	0.007	-10000	0	0	19	19
SHC1	-0.003	0.035	0.091	61	-10000	0	61
ARHGDIA	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	0.024	0.019	-10000	0	-0.13	7	7
Gamma Secretase	0.08	0.069	-10000	0	-0.15	28	28
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.039	0.058	-10000	0	-0.11	54	54
MAGEH1	0.032	0.013	-10000	0	0	70	70
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.003	0.075	-10000	0	-0.11	146	146
Mammalian IAPs/DIABLO	0.057	0.035	-10000	0	-0.15	6	6
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.035	0.008	-10000	0	0	26	26
APP	0.035	0.007	-10000	0	0	21	21
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.034	0.009	-10000	0	0	36	36
RhoA/GDP/RHOGDI	0.05	0.029	0.18	1	-0.1	6	7
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.004	0.054	0.22	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.016	0.056	-10000	0	-0.18	32	32
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.041	0.019	-10000	0	-0.12	1	1
NCSTN	0.035	0.008	-10000	0	0	28	28
mol:GTP	0.031	0.04	-10000	0	-0.11	29	29
PSENEN	0.035	0.008	-10000	0	0	28	28
mol:ceramide	-0.007	0.044	0.19	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.014	0.052	-10000	0	-0.18	26	26
p75(NTR)/beta APP	0.042	0.032	-10000	0	-0.14	9	9
BEX1	0.028	0.015	-10000	0	0	115	115
mol:GDP	-0.008	0.003	-10000	0	-10000	0	0
NGF (dimer)	0.046	0.034	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.039	0.017	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
RAC1/GTP	0.024	0.024	-10000	0	-0.095	5	5
MYD88	0.034	0.009	-10000	0	0	36	36
CHUK	0.025	0.017	-10000	0	0	163	163
NGF (dimer)/p75(NTR)/PKA	0.031	0.041	-10000	0	-0.12	29	29
RHOB	0.031	0.013	-10000	0	0	74	74
RHOA	0.035	0.007	-10000	0	0	18	18
MAGE-G1/E2F1	0.026	0.005	-10000	0	-10000	0	0
NT3 (dimer)	0.035	0.008	-10000	0	0	23	23
TP53	-0.014	0.064	0.22	8	-0.2	6	14
PRDM4	-0.006	0.046	0.19	8	-10000	0	8
BDNF (dimer)	0.08	0.032	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
SORT1	0.036	0.006	-10000	0	0	15	15
activation of caspase activity	0.066	0.045	-10000	0	-0.12	23	23
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.057	0.031	-10000	0	-0.11	5	5
RHOC	0.035	0.007	-10000	0	0	20	20
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0.016	0.1	0.2	32	-0.31	16	48
DIABLO	0.036	0.004	-10000	0	0	6	6
SMPD2	-0.007	0.044	0.19	8	-10000	0	8
APH1B	0.035	0.006	-10000	0	0	16	16
APH1A	0.036	0.005	-10000	0	0	11	11
proNGF (dimer)/p75(NTR)/Sortilin	0.041	0.023	-10000	0	-0.12	4	4
PSEN1	0.033	0.011	-10000	0	0	46	46
APAF-1/Pro-Caspase 9	0.05	0.018	-10000	0	-0.14	2	2
NT3 (dimer)/p75(NTR)	0.044	0.021	-10000	0	-10000	0	0
MAPK8	0.004	0.077	0.2	18	-0.26	9	27
MAPK9	0.028	0.088	0.2	37	-0.27	8	45
APAF1	0.036	0.003	-10000	0	0	4	4
NTF3	0.035	0.008	-10000	0	0	23	23
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.018	0.018	-10000	0	0	258	258
RAC1/GDP	0.017	0.019	-10000	0	-0.13	5	5
RhoA-B-C/GDP	0.049	0.073	-10000	0	-0.14	53	53
p75 CTF/Sortilin/TRAF6/NRIF	0.076	0.055	-10000	0	-0.12	32	32
RhoA-B-C/GTP	0.031	0.04	-10000	0	-0.11	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.087	0.058	-10000	0	-0.12	25	25
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.085	0.029	-10000	0	-0.12	2	2
PRKACB	0.033	0.011	-10000	0	0	50	50
proBDNF (dimer)/p75 ECD	0.046	0.019	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.031	0.013	-10000	0	0	81	81
BIRC2	0.036	0.005	-10000	0	0	11	11
neuron projection morphogenesis	-0.016	0.07	0.14	27	-0.16	29	56
BAD	0.012	0.091	0.2	22	-0.28	15	37
RIPK2	0.036	0.006	-10000	0	0	14	14
NGFR	0.031	0.013	-10000	0	0	71	71
CYCS	-0.012	0.042	0.19	5	-0.19	3	8
ADAM17	0.036	0.006	-10000	0	0	13	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.057	0.03	-10000	0	-0.11	3	3
BCL2L11	0.012	0.091	0.2	22	-0.28	14	36
BDNF (dimer)/p75(NTR)	0.041	0.023	-10000	0	-10000	0	0
PI3K	0.028	0.068	-10000	0	-0.12	71	71
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.039	0.021	-10000	0	-0.1	4	4
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
PRKCI	0.035	0.008	-10000	0	0	26	26
NGF (dimer)/p75(NTR)	0.023	0.009	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.05	0.047	-10000	0	-0.12	27	27
TRAF6	0.036	0.005	-10000	0	0	10	10
RAC1	0.024	0.017	-10000	0	0	173	173
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.034	0.01	-10000	0	0	37	37
oligodendrocyte cell fate commitment	0	0	-10000	0	-10000	0	0
CASP6	0.031	0.035	0.14	16	-0.15	2	18
SQSTM1	0.034	0.009	-10000	0	0	35	35
NGFRAP1	0.036	0.006	-10000	0	0	13	13
CASP3	0.012	0.09	0.19	22	-0.27	16	38
E2F1	0.035	0.007	-10000	0	0	17	17
CASP9	0.034	0.009	-10000	0	0	33	33
IKK complex	0.037	0.067	-10000	0	-0.25	9	9
NGF (dimer)/TRKA	0.026	0.005	-10000	0	-10000	0	0
MMP7	0.027	0.016	-10000	0	0	137	137
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.07	0.051	-10000	0	-0.11	31	31
MMP3	0.035	0.007	-10000	0	0	20	20
APAF-1/Caspase 9	-0.022	0.041	-10000	0	-0.2	7	7

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.033	0.011	-10000	0	0	49	49
HDAC4	0.035	0.009	-10000	0	0	29	29
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.003	0.041	-10000	0	-0.13	45	45
CDKN1A	-0.039	0.12	-10000	0	-0.46	37	37
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.033	0.01	-10000	0	0	44	44
FOXO3	0	0.031	0.25	6	-10000	0	6
FOXO1	0	0	-10000	0	-10000	0	0
FOXO4	0.006	0.022	-10000	0	-0.18	7	7
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.034	0.01	-10000	0	0	39	39
TAT	0.036	0.005	-10000	0	0	11	11
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.011	0.001	-10000	0	-10000	0	0
PPARGC1A	0.031	0.013	-10000	0	0	79	79
FHL2	0.028	0.016	-10000	0	0	126	126
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.04	0.044	0.16	32	-0.14	3	35
HIST2H4A	0.003	0.041	0.13	45	-10000	0	45
SIRT1/FOXO3a	0.026	0.039	0.15	38	-10000	0	38
SIRT1	0.032	0.046	0.18	39	-10000	0	39
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.048	0.055	0.17	25	-0.12	14	39
SIRT1/Histone H1b	0.029	0.044	0.18	2	-0.16	5	7
apoptosis	-0.049	0.05	0.12	7	-0.17	27	34
SIRT1/PGC1A	0.031	0.042	0.14	27	-0.11	11	38
p53/SIRT1	0.043	0.089	0.33	36	-0.15	18	54
SIRT1/FOXO4	0.026	0.042	0.15	30	-0.14	9	39
FOXO1/FHL2/SIRT1	0.023	0.04	0.13	25	-0.091	20	45
HIST1H1E	0.013	0.023	-10000	0	-0.18	6	6
SIRT1/p300	0.038	0.048	0.16	32	-0.14	8	40
muscle cell differentiation	0.003	0.036	0.12	2	-0.11	39	41
TP53	0.041	0.046	0.18	43	-10000	0	43
KU70/SIRT1/BAX	0.05	0.05	0.17	27	-0.12	7	34
CREBBP	0.036	0.005	-10000	0	0	8	8
MEF2D	0.036	0.005	-10000	0	0	11	11
HIV-1 Tat/SIRT1	0.039	0.043	0.15	37	-0.14	2	39
ACSS2	0.003	0.041	0.13	45	-10000	0	45
SIRT1/PCAF/MYOD	-0.003	0.036	0.12	39	-0.12	2	41

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	0.019	0.024	-10000	0	-0.13	10	10
alphaV beta3 Integrin	0.059	0.048	-10000	0	-0.13	27	27
PTK2	0.006	0.088	0.24	7	-0.29	21	28
IGF1R	0.033	0.012	-10000	0	0	57	57
PI4KB	0	0	-10000	0	-10000	0	0
MFGE8	0.035	0.007	-10000	0	0	19	19
SRC	0.036	0.006	-10000	0	0	14	14
CDKN1B	0	0.094	-10000	0	-0.31	39	39
VEGFA	0	0	-10000	0	-10000	0	0
ILK	0.01	0.072	-10000	0	-0.29	25	25
ROCK1	0.036	0.006	-10000	0	0	15	15
AKT1	-0.004	0.07	0.2	1	-0.3	23	24
PTK2B	-0.004	0.072	0.18	48	-0.19	4	52
alphaV/beta3 Integrin/JAM-A	0.071	0.048	-10000	0	-0.12	21	21
CBL	0.036	0.004	-10000	0	0	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.062	0.044	-10000	0	-0.12	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.068	0.067	-10000	0	-0.13	44	44
VEGF/Rho/ROCK/alphaV/beta3 Integrin	0.007	0.057	-10000	0	-0.28	11	11
alphaV/beta3 Integrin/Syndecan-1	0.055	0.043	-10000	0	-0.12	16	16
PI4KA	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	0.049	0.083	-10000	0	-0.15	66	66
PI4 Kinase	0	0	-10000	0	-10000	0	0
PIK3CA	0.031	0.013	-10000	0	0	80	80
alphaV/beta3 Integrin/Osteopontin	0.047	0.07	-10000	0	-0.14	57	57
RPS6KB1	-0.044	0.066	0.23	4	-0.28	4	8
TLN1	0.029	0.015	-10000	0	0	102	102
MAPK3	0.002	0.086	-10000	0	-0.33	26	26
GPR124	0.035	0.008	-10000	0	0	24	24
MAPK1	-0.002	0.087	-10000	0	-0.34	25	25
PXN	0.036	0.004	-10000	0	0	7	7
PIK3R1	0.032	0.012	-10000	0	0	63	63
alphaV/beta3 Integrin/Tumstatin	0.063	0.043	-10000	0	-0.12	24	24
cell adhesion	0.048	0.052	-10000	0	-0.16	25	25
ANGPTL3	0.036	0.005	-10000	0	0	10	10
VEGFR2 homodimer/VEGFA homodimer/Src	0.036	0.029	-10000	0	-0.12	10	10
IGF-1R heterotetramer	0.032	0.012	-10000	0	0	57	57
Rac1/GDP	0.017	0.019	-10000	0	-0.13	5	5
TGFBR2	0.035	0.009	-10000	0	0	29	29
ITGB3	0.036	0.003	-10000	0	0	4	4
IGF1	0.035	0.008	-10000	0	0	23	23
RAC1	0.024	0.017	-10000	0	0	173	173
regulation of cell-matrix adhesion	0.059	0.045	-10000	0	-0.12	24	24
apoptosis	0.034	0.009	-10000	0	0	31	31
CD47	0.035	0.008	-10000	0	0	23	23
alphaV/beta3 Integrin/CD47	0.06	0.047	-10000	0	-0.13	25	25
VCL	0.025	0.017	-10000	0	0	154	154
alphaV/beta3 Integrin/Del1	0.063	0.043	-10000	0	-0.12	24	24
CSF1	0.036	0.005	-10000	0	0	8	8
PIK3C2A	0.01	0.018	-10000	0	-10000	0	0
PI4 Kinase/Pyk2	0.026	0.041	-10000	0	-0.12	29	29
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.046	0.05	-10000	0	-0.12	28	28
FAK1/Vinculin	0.013	0.076	0.25	6	-0.26	16	22
alphaV beta3/Integrin/ppsTEM5	0.06	0.045	-10000	0	-0.12	24	24
RHOA	0.035	0.007	-10000	0	0	18	18
VTN	0.036	0.004	-10000	0	0	6	6
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	0.035	0.008	-10000	0	0	25	25
F11R	-0.012	0.032	0.092	44	-10000	0	44
alphaV/beta3 Integrin/Lactadherin	0.061	0.045	-10000	0	-0.13	24	24
alphaV/beta3 Integrin/TGFBR2	0.059	0.047	-10000	0	-0.12	27	27
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.059	0.04	-10000	0	-0.11	24	24
HSP90AA1	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Talin	0.046	0.049	-10000	0	-0.11	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.035	0.009	-10000	0	0	29	29
alphaV/beta3 Integrin/Pyk2	0.063	0.061	0.19	43	-0.12	28	71
SDC1	0.031	0.014	-10000	0	0	83	83
VAV3	-0.026	0.029	0.18	2	-0.19	5	7
PTPN11	0.036	0.005	-10000	0	0	11	11
IRS1	0.033	0.011	-10000	0	0	52	52
FAK1/Paxillin	0.024	0.081	0.24	7	-0.24	21	28
cell migration	-0.004	0.07	0.23	6	-0.25	16	22
ITGAV	0.034	0.009	-10000	0	0	31	31
PI3K	0.054	0.086	-10000	0	-0.14	54	54
SPP1	0.033	0.011	-10000	0	0	54	54
KDR	0.029	0.015	-10000	0	0	101	101
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.034	0.009	-10000	0	0	31	31
COL4A3	0.037	0	-10000	0	-10000	0	0
angiogenesis	0	0.094	-10000	0	-0.37	25	25
Rac1/GTP	-0.025	0.035	0.18	2	-0.18	6	8
EDIL3	0.036	0.004	-10000	0	0	5	5
cell proliferation	0.058	0.046	-10000	0	-0.12	27	27

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	0.031	0.049	-10000	0	-0.11	23	23
TC10/GTP	0.027	0.047	-10000	0	-0.12	20	20
Insulin Receptor/Insulin/IRS1/Shp2	0.074	0.059	-10000	0	-0.13	29	29
HRAS	0.034	0.009	-10000	0	0	32	32
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.032	0.013	-10000	0	0	70	70
FOXO3	-0.01	0.016	0.021	2	-0.055	33	35
AKT1	-0.025	0.087	0.22	16	-0.21	24	40
INSR	0.032	0.021	-10000	0	-0.039	34	34
Insulin Receptor/Insulin	0.058	0.063	0.22	7	-0.14	34	41
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.021	0.018	-10000	0	0	220	220
SORBS1	0.025	0.017	-10000	0	0	154	154
CRK	0.035	0.008	-10000	0	0	23	23
PTPN1	-0.024	0.047	0.14	17	-0.25	8	25
CAV1	-0.012	0.037	0.16	6	-0.19	8	14
CBL/APS/CAP/Crk-II/C3G	0.05	0.053	-10000	0	-0.11	13	13
Insulin Receptor/Insulin/IRS1/NCK2	0.072	0.063	-10000	0	-0.14	32	32
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.033	0.079	-10000	0	-0.13	82	82
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.021	0.068	-10000	0	-0.36	8	8
RPS6KB1	-0.032	0.081	0.2	16	-0.2	25	41
PARD6A	0.035	0.007	-10000	0	0	20	20
CBL	0.036	0.004	-10000	0	0	7	7
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.021	0.018	-10000	0	-10000	0	0
PIK3R1	0.032	0.012	-10000	0	0	63	63
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.035	0.085	0.17	22	-0.22	27	49
HRAS/GTP	-0.036	0.033	-10000	0	-0.12	43	43
Insulin Receptor	0.031	0.021	-10000	0	-0.039	34	34
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.082	0.068	-10000	0	-0.13	34	34
PRKCI	0.023	0.091	-10000	0	-0.4	19	19
Insulin Receptor/Insulin/GRB14/PDK1	0.014	0.068	-10000	0	-0.13	77	77
SHC1	0.033	0.011	-10000	0	0	52	52
negative regulation of MAPKKK cascade	0.029	0.055	-10000	0	-0.21	1	1
PI3K	0.045	0.086	-10000	0	-0.13	82	82
NCK2	0.035	0.007	-10000	0	0	17	17
RHOQ	0.035	0.007	-10000	0	0	17	17
mol:H2O2	-0.004	0.006	-10000	0	-0.034	8	8
HRAS/GDP	0.021	0.027	-10000	0	-0.13	15	15
AKT2	-0.028	0.078	0.21	14	-0.19	14	28
PRKCZ	0.002	0.079	-10000	0	-0.39	18	18
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.016	0.051	0.16	24	-0.14	5	29
F2RL2	0.036	0.004	-10000	0	0	7	7
TRIP10	0.034	0.009	-10000	0	0	36	36
Insulin Receptor/Insulin/Shc	0.057	0.037	-10000	0	-0.12	8	8
TC10/GTP/CIP4/Exocyst	0.041	0.029	-10000	0	-0.12	14	14
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.072	0.046	-10000	0	-0.13	14	14
RAPGEF1	0.035	0.007	-10000	0	0	19	19
RASA1	0.034	0.009	-10000	0	0	32	32
NCK1	0.035	0.008	-10000	0	0	27	27
CBL/APS/CAP/Crk-II	0.044	0.041	-10000	0	-0.11	13	13
TC10/GDP	0.023	0.024	-10000	0	-0.13	12	12
Insulin Receptor/Insulin/SHC/GRB10	0.043	0.065	-10000	0	-0.13	30	30
INPP5D	-0.02	0.027	0.061	23	-0.11	23	46
SOS1	0	0	-10000	0	-10000	0	0
SGK1	-0.006	0.005	-10000	0	-10000	0	0
mol:cAMP	0	0	-10000	0	-10000	0	0
PTPN11	0.036	0.005	-10000	0	0	11	11
IRS1	0.033	0.011	-10000	0	0	52	52
p62DOK/RasGAP	0.029	0.056	-10000	0	-0.21	1	1
INS	0.034	0.022	0.097	7	-0.039	34	41
mol:PI-3-4-P2	-0.02	0.027	0.061	23	-0.11	23	46
GRB2	0.035	0.007	-10000	0	0	17	17
EIF4EBP1	-0.034	0.079	0.2	13	-0.21	24	37
PTPRA	0.034	0.016	-10000	0	-0.052	7	7
PIK3CA	0.031	0.013	-10000	0	0	80	80
TC10/GTP/CIP4	0.041	0.029	-10000	0	-0.12	14	14
PDPK1	0.036	0.004	-10000	0	0	7	7
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.014	0.052	-10000	0	-0.16	34	34
Insulin Receptor/Insulin/IRS1	0.053	0.046	-10000	0	-0.12	23	23
Insulin Receptor/Insulin/IRS3	0.046	0.031	-10000	0	-0.069	8	8
Par3/Par6	0.073	0.041	-10000	0	-0.11	16	16

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.032	0.012	-10000	0	0	58	58
mol:Halofuginone	-0.001	0.029	-10000	0	-0.17	14	14
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.028	0.15	-10000	0	-0.41	59	59
PRL-3/alpha Tubulin	0.018	0.032	-10000	0	-0.13	21	21
mol:Ca2+	-0.017	0.044	0.26	11	-10000	0	11
AGT	0.029	0.015	-10000	0	0	108	108
CCNA2	-0.03	0.1	-10000	0	-0.58	13	13
TUBA1B	0	0	-10000	0	-10000	0	0
EGR1	0.002	0.056	0.11	4	-0.32	14	18
CDK2/Cyclin E1	-0.005	0.15	-10000	0	-0.37	59	59
MAPK3	-0.013	0.03	0.092	37	-10000	0	37
PRL-2 /Rab GGTase beta	0.047	0.035	-10000	0	-0.16	12	12
MAPK1	-0.01	0.032	0.092	42	-10000	0	42
PTP4A1	-0.022	0.099	-10000	0	-0.6	13	13
PTP4A3	0.031	0.013	-10000	0	0	73	73
PTP4A2	0.035	0.006	-10000	0	0	16	16
ITGB1	-0.009	0.026	0.092	27	-10000	0	27
SRC	0.036	0.006	-10000	0	0	14	14
RAC1	-0.001	0.085	-10000	0	-0.39	20	20
Rab GGTase beta/Rab GGTase alpha	0.045	0.032	-10000	0	-0.14	11	11
PRL-1/ATF-5	-0.033	0.1	-10000	0	-0.54	14	14
RABGGTA	0.034	0.01	-10000	0	0	41	41
BCAR1	-0.009	0.055	0.25	21	-10000	0	21
RHOC	-0.007	0.12	-10000	0	-0.36	44	44
RHOA	-0.008	0.13	-10000	0	-0.44	34	34
cell motility	-0.005	0.12	-10000	0	-0.37	39	39
PRL-1/alpha Tubulin	-0.034	0.095	-10000	0	-0.55	14	14
PRL-3/alpha1 Integrin	0.018	0.032	-10000	0	-0.13	21	21
ROCK1	-0.004	0.12	-10000	0	-0.37	39	39
RABGGTB	0.035	0.008	-10000	0	0	26	26
CDK2	0.034	0.01	-10000	0	0	40	40
mitosis	-0.021	0.098	-10000	0	-0.59	13	13
ATF5	0.034	0.009	-10000	0	0	36	36

×

Regulation of cytoplasmic and nuclear SMAD2/3 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
SMAD4	0.032	0.012	-10000	0	0	58	58
SMAD2	-0.016	0.06	0.17	2	-0.24	19	21
SMAD3	0.005	0.054	-10000	0	-0.32	6	6
SMAD3/SMAD4	-0.01	0.17	-10000	0	-0.49	45	45
SMAD4/Ubc9/PIASy	0.054	0.052	-10000	0	-0.12	34	34
SMAD2/SMAD2/SMAD4	0.027	0.1	-10000	0	-0.25	28	28
PPM1A	0.034	0.009	-10000	0	0	30	30
CALM1	0.033	0.011	-10000	0	0	54	54
SMAD2/SMAD4	0	0.066	-10000	0	-0.21	29	29
MAP3K1	0.035	0.007	-10000	0	0	20	20
TRAP-1/SMAD4	0.036	0.053	-10000	0	-0.14	40	40
MAPK3	0.036	0.004	-10000	0	0	6	6
MAPK1	0.033	0.01	-10000	0	0	45	45
NUP214	0.035	0.007	-10000	0	0	18	18
CTDSP1	0.035	0.006	-10000	0	0	16	16
CTDSP2	0.033	0.012	-10000	0	0	57	57
CTDSPL	0.036	0.006	-10000	0	0	12	12
KPNB1	0.035	0.007	-10000	0	0	22	22
TGFBRAP1	0.036	0.005	-10000	0	0	10	10
UBE2I	0.036	0.004	-10000	0	0	6	6
NUP153	0.034	0.009	-10000	0	0	31	31
KPNA2	0.034	0.01	-10000	0	0	39	39
PIAS4	0.035	0.008	-10000	0	0	27	27

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.058	0.38	0.83	1	-1.1	21	22
STAT6 (cleaved dimer)	-0.07	0.35	-10000	0	-0.94	31	31
IGHG1	-0.015	0.26	0.43	20	-0.8	22	42
IGHG3	-0.068	0.36	0.63	1	-0.95	29	30
AKT1	-0.026	0.27	0.52	4	-0.74	29	33
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.014	0.19	0.47	4	-0.57	7	11
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.01	0.26	0.53	2	-0.78	18	20
THY1	-0.13	0.5	0.78	2	-1.2	62	64
MYB	0.032	0.012	-10000	0	0	58	58
HMGA1	0.036	0.005	-10000	0	0	11	11
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.003	0.26	0.54	8	-0.61	13	21
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.009	0.25	0.51	2	-0.81	15	17
SP1	0.029	0.076	0.12	95	-0.14	71	166
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.007	0.045	-10000	0	-0.078	1	1
STAT6 (dimer)/ETS1	-0.056	0.37	-10000	0	-0.96	28	28
SOCS1	-0.041	0.3	0.52	2	-0.68	29	31
SOCS3	-0.006	0.22	-10000	0	-0.65	3	3
FCER2	-0.03	0.32	0.65	1	-0.79	16	17
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.065	0.38	0.72	1	-1.1	21	22
GRB2	0.035	0.007	-10000	0	0	17	17
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.002	0.22	0.49	4	-0.61	15	19
T cell proliferation	-0.073	0.38	0.66	1	-1	26	27
IL4R/JAK1	-0.073	0.38	0.66	1	-1	28	29
EGR2	-0.12	0.5	0.72	1	-1.3	51	52
JAK2	0.019	0.066	0.15	18	-10000	0	18
JAK3	0.035	0.016	-10000	0	-0.037	10	10
PIK3R1	0.032	0.012	-10000	0	0	63	63
JAK1	0.026	0.039	0.11	7	-10000	0	7
COL1A2	-0.11	0.48	0.49	6	-1.2	76	82
CCL26	-0.064	0.38	0.72	1	-0.98	29	30
IL4R	-0.061	0.41	0.8	3	-1.1	22	25
PTPN6	0.015	0.037	-10000	0	-0.06	4	4
IL13RA2	-0.32	0.66	0.76	3	-1.1	174	177
IL13RA1	0.023	0.067	0.15	18	-10000	0	18
IRF4	0.046	0.11	-10000	0	-10000	0	0
ARG1	-0.003	0.22	0.49	6	-0.89	10	16
CBL	-0.01	0.24	0.49	4	-0.58	14	18
GTF3A	0.048	0.034	0.12	70	-0.15	3	73
PIK3CA	0.031	0.013	-10000	0	0	80	80
IL13RA1/JAK2	0.025	0.1	0.23	13	-0.17	10	23
IRF4/BCL6	0.042	0.11	-10000	0	-10000	0	0
CD40LG	0.041	0.004	0.14	1	-10000	0	1
MAPK14	-0.007	0.24	0.5	3	-0.59	11	14
mitosis	-0.021	0.26	0.51	5	-0.69	29	34
STAT6	-0.07	0.43	0.82	4	-1.1	27	31
SPI1	0.037	0.013	0.1	2	-10000	0	2
RPS6KB1	-0.025	0.26	0.48	6	-0.67	29	35
STAT6 (dimer)	-0.07	0.43	0.82	4	-1.1	27	31
STAT6 (dimer)/PARP14	-0.084	0.38	-10000	0	-1	28	28
mast cell activation	-0.002	0.016	-10000	0	-0.041	20	20
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.005	0.22	0.5	2	-0.61	5	7
FRAP1	-0.026	0.27	0.52	4	-0.73	29	33
LTA	-0.068	0.38	0.72	1	-1.1	21	22
FES	0.035	0.007	-10000	0	0	17	17
T-helper 1 cell differentiation	0.067	0.42	1.1	27	-0.82	4	31
CCL11	-0.069	0.36	-10000	0	-1	22	22
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.009	0.22	0.51	4	-0.61	5	9
IL2RG	0.034	0.016	-10000	0	-0.035	7	7
IL10	-0.052	0.39	0.71	3	-1	22	25
IRS1	0.033	0.011	-10000	0	0	52	52
IRS2	0.03	0.014	-10000	0	0	96	96
IL4	0.022	0.18	0.57	1	-0.88	7	8
IL5	-0.067	0.38	0.72	1	-1.1	21	22
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.06	0.39	0.69	7	-0.92	37	44
COL1A1	0.017	0.26	0.6	6	-1.1	7	13
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.077	0.38	-10000	0	-1.1	22	22
IL2R gamma/JAK3	0.054	0.019	-10000	0	-10000	0	0
TFF3	-0.062	0.38	0.72	1	-1	21	22
ALOX15	-0.067	0.38	0.72	1	-1.1	21	22
MYBL1	0.03	0.014	-10000	0	0	97	97
T-helper 2 cell differentiation	-0.048	0.34	0.63	4	-0.83	29	33
SHC1	0.033	0.011	-10000	0	0	52	52
CEBPB	0.035	0.015	0.1	4	-10000	0	4
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.019	0.26	0.53	4	-0.82	17	21
mol:PI-3-4-5-P3	-0.025	0.27	0.52	4	-0.73	29	33
PI3K	-0.03	0.29	0.52	4	-0.79	28	32
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.004	0.047	-10000	0	-0.088	8	8
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.002	0.22	0.44	9	-0.58	21	30
ITGB3	-0.067	0.38	0.72	1	-1.1	21	22
PIGR	-0.055	0.38	0.71	2	-1.1	21	23
IGHE	-0.007	0.079	0.18	37	-0.18	16	53
MAPKKK cascade	0.003	0.21	0.44	9	-0.57	21	30
BCL6	0.031	0.012	-10000	0	-10000	0	0
OPRM1	-0.067	0.38	0.72	1	-1.1	21	22
RETNLB	-0.064	0.38	0.72	1	-0.98	29	30
SELP	-0.063	0.38	0.79	2	-1.1	21	23
AICDA	-0.066	0.36	-10000	0	-1	20	20

×

Aurora B 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
Condensin I complex	0.001	0.011	-10000	0	-0.09	7	7
STMN1	-0.015	0.027	0.091	30	-10000	0	30
Aurora B/RasGAP/Survivin	0.034	0.074	-10000	0	-0.14	71	71
Chromosomal passenger complex/Cul3 protein complex	-0.032	0.076	-10000	0	-0.19	64	64
BIRC5	0.029	0.015	-10000	0	0	108	108
DES	0.028	0.078	-10000	0	-0.6	7	7
Aurora C/Aurora B/INCENP	0.062	0.022	-10000	0	-10000	0	0
Aurora B/TACC1	0.042	0.026	-10000	0	-0.11	9	9
Aurora B/PP2A	0.05	0.015	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.001	0.05	-10000	0	-0.19	28	28
mitotic metaphase/anaphase transition	-0.001	0.003	0.009	20	-0.009	1	21
NDC80	-0.01	0.007	0.014	3	-10000	0	3
Cul3 protein complex	0.026	0.032	-10000	0	-0.14	8	8
KIF2C	-0.018	0.12	-10000	0	-0.43	35	35
PEBP1	-0.001	0.003	0.009	18	-0.008	11	29
KIF20A	0.028	0.015	-10000	0	0	109	109
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.04	0.044	-10000	0	-0.14	25	25
SEPT1	0	0	-10000	0	-10000	0	0
SMC2	0	0	-10000	0	-10000	0	0
SMC4	0	0	-10000	0	-10000	0	0
NSUN2/NPM1/Nucleolin	0	0.072	-10000	0	-0.46	7	7
PSMA3	0.034	0.009	-10000	0	0	35	35
G2/M transition of mitotic cell cycle	-0.001	0.002	0.008	10	-0.006	3	13
H3F3B	0.009	0.032	-10000	0	-0.2	11	11
AURKB	0.032	0.015	-10000	0	-0.009	54	54
AURKC	0.036	0.006	-10000	0	0	15	15
CDCA8	0.032	0.013	-10000	0	-0.003	58	58
cytokinesis	-0.024	0.14	0.18	7	-0.42	49	56
Aurora B/Septin1	-0.013	0.14	0.19	4	-0.39	49	53
AURKA	-0.001	0.002	0.008	10	-0.006	3	13
INCENP	0.034	0.014	0.058	1	-0.022	28	29
KLHL13	0	0	-10000	0	-10000	0	0
BUB1	0.036	0.006	0.058	1	0	11	12
hSgo1/Aurora B/Survivin	0.022	0.05	-10000	0	-0.11	56	56
EVI5	0.035	0.007	-10000	0	0	18	18
RhoA/GTP	0.012	0.13	-10000	0	-0.32	52	52
SGOL1	0	0	-10000	0	-10000	0	0
CENPA	-0.004	0.075	0.12	2	-0.27	31	33
NCAPG	0	0	-10000	0	-10000	0	0
Aurora B/HC8 Proteasome	0.045	0.029	-10000	0	-0.14	8	8
NCAPD2	0	0	-10000	0	-10000	0	0
Aurora B/PP1-gamma	0.048	0.026	-10000	0	-0.15	6	6
RHOA	0.035	0.007	-10000	0	0	18	18
NCAPH	0	0	-10000	0	-10000	0	0
NPM1	0.006	0.065	-10000	0	-0.3	18	18
RASA1	0.034	0.009	-10000	0	0	32	32
KLHL9	0.021	0.018	-10000	0	0	213	213
mitotic prometaphase	-0.001	0.003	0.009	18	-0.008	11	29
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.029	-10000	0	-0.14	8	8
PPP1CC	0.036	0.005	-10000	0	0	9	9
Centraspindlin	0.002	0.13	-10000	0	-0.34	51	51
RhoA/GDP	0.024	0.019	-10000	0	-0.13	7	7
NSUN2	0.003	0.037	-10000	0	-0.28	7	7
MYLK	-0.015	0.07	-10000	0	-0.2	64	64
KIF23	0.028	0.018	-10000	0	-0.006	103	103
VIM	-0.013	0.019	0.088	12	-10000	0	12
RACGAP1	0.03	0.016	-10000	0	-0.003	86	86
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.004	0.062	-10000	0	-0.28	21	21
Chromosomal passenger complex	-0.015	0.096	0.13	4	-0.25	59	63
Chromosomal passenger complex/EVI5	0.062	0.085	-10000	0	-0.15	55	55
TACC1	0.035	0.008	-10000	0	0	23	23
PPP2R5D	0.036	0.004	-10000	0	0	5	5
CUL3	0.036	0.002	-10000	0	0	2	2
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Aurora A signaling

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
Aurora A/GADD45A	0.023	0.057	0.16	1	-0.2	26	27
BIRC5	0.029	0.015	-10000	0	0	108	108
NFKBIA	-0.008	0.042	0.14	8	-0.18	16	24
CPEB1	0.033	0.012	-10000	0	0	57	57
AKT1	-0.006	0.033	0.17	2	-0.18	7	9
NDEL1	0.035	0.007	-10000	0	0	18	18
Aurora A/BRCA1	0.023	0.043	0.14	1	-0.15	23	24
NDEL1/TACC3	0.036	0.057	0.16	1	-0.18	21	22
GADD45A	0.031	0.013	-10000	0	0	75	75
GSK3B	0.035	0.016	0.089	25	0	40	65
PAK1/Aurora A	0.029	0.05	0.16	1	-0.16	24	25
MDM2	0.033	0.011	-10000	0	0	46	46
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.012	0.026	0.092	26	-10000	0	26
TP53	0.004	0.07	-10000	0	-0.23	33	33
DLG7	-0.004	0.043	0.19	2	-0.18	13	15
AURKAIP1	0	0	-10000	0	-10000	0	0
ARHGEF7	0.032	0.012	-10000	0	0	59	59
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.038	0.061	0.17	1	-0.18	24	25
G2/M transition of mitotic cell cycle	0.023	0.042	-10000	0	-0.15	23	23
AURKA	0.006	0.05	0.13	24	-0.21	19	43
AURKB	0.008	0.034	-10000	0	-0.14	26	26
CDC25B	0	0.074	0.12	1	-0.28	28	29
G2/M transition checkpoint	0.001	0.036	0.088	1	-0.14	23	24
mRNA polyadenylation	0.015	0.051	-10000	0	-0.13	46	46
Aurora A/CPEB	0.015	0.051	0.14	1	-0.13	46	47
Aurora A/TACC1/TRAP/chTOG	0.051	0.081	-10000	0	-0.21	29	29
BRCA1	0.036	0.006	-10000	0	0	12	12
centrosome duplication	0.029	0.049	0.16	1	-0.16	24	25
regulation of centrosome cycle	0.035	0.056	0.15	1	-0.18	21	22
spindle assembly	0.049	0.08	-10000	0	-0.2	29	29
TDRD7	0.034	0.01	-10000	0	0	40	40
Aurora A/RasGAP/Survivin	0.04	0.073	-10000	0	-0.18	25	25
CENPA	0.002	0.064	-10000	0	-0.26	25	25
Aurora A/PP2A	0.029	0.05	0.16	1	-0.16	24	25
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	-0.007	0.052	-10000	0	-0.21	18	18
negative regulation of DNA binding	0.002	0.073	-10000	0	-0.24	36	36
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.04	0.045	-10000	0	-0.14	27	27
RASA1	0.034	0.009	-10000	0	0	32	32
Ajuba/Aurora A	0.001	0.036	0.089	1	-0.14	23	24
mitotic prometaphase	-0.004	0.009	0.068	8	-10000	0	8
proteasomal ubiquitin-dependent protein catabolic process	0.006	0.049	0.13	24	-0.21	19	43
TACC1	0.035	0.008	-10000	0	0	23	23
TACC3	0.032	0.012	-10000	0	0	59	59
Aurora A/Antizyme1	0.023	0.044	0.14	1	-0.15	24	25
Aurora A/RasGAP	0.027	0.06	0.16	1	-0.22	23	24
OAZ1	0.034	0.009	-10000	0	0	34	34
RAN	0.036	0.005	-10000	0	0	10	10
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.036	0.015	0.088	27	-10000	0	27
GIT1	0.036	0.003	-10000	0	0	4	4
GIT1/beta-PIX/PAK1	0.058	0.047	-10000	0	-0.12	26	26
Importin alpha/Importin beta/TPX2	-0.012	0.026	0.092	26	-10000	0	26
PPP2R5D	0.036	0.004	-10000	0	0	5	5
Aurora A/TPX2	-0.028	0.055	0.096	4	-0.22	21	25
PAK1	0.036	0.006	-10000	0	0	15	15
CKAP5	0.034	0.01	-10000	0	0	37	37

×

TRAIL signaling pathway

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
TNFSF10	0.029	0.015	-10000	0	0	109	109
positive regulation of NF-kappaB transcription factor activity	0.035	0.045	-10000	0	-0.14	25	25
MAP2K4	0.015	0.059	0.21	2	-0.27	8	10
IKBKB	0.036	0.003	-10000	0	0	4	4
TNFRSF10B	0.035	0.008	-10000	0	0	26	26
TNFRSF10A	0	0	-10000	0	-10000	0	0
SMPD1	0.014	0.028	-10000	0	-0.1	20	20
IKBKG	0.037	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.036	0.006	-10000	0	0	12	12
TRAIL/TRAILR2	0.034	0.044	-10000	0	-0.14	24	24
TRAIL/TRAILR3	0.035	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1	0.015	0.035	-10000	0	-0.13	26	26
TRAIL/TRAILR4	0.035	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1/DAP3/GTP	0.028	0.04	-10000	0	-0.1	34	34
IKK complex	-0.033	0.12	-10000	0	-0.22	132	132
RIPK1	0.035	0.007	-10000	0	0	20	20
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.023	0.024	-10000	0	-0.13	12	12
MAPK3	-0.005	0.039	0.092	68	-10000	0	68
MAP3K1	0.022	0.055	-10000	0	-0.28	7	7
TRAILR4 (trimer)	0.036	0.006	-10000	0	0	12	12
TRADD	0.036	0.005	-10000	0	0	11	11
TRAILR1 (trimer)	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.018	0.049	-10000	0	-0.17	23	23
CFLAR	0.036	0.005	-10000	0	0	8	8
MAPK1	-0.004	0.039	0.092	68	-10000	0	68
TRAIL/TRAILR1/FADD/TRADD/RIP	0.07	0.047	-10000	0	-0.1	25	25
mol:ceramide	0.014	0.028	-10000	0	-0.1	20	20
FADD	0.036	0.006	-10000	0	0	12	12
MAPK8	0.008	0.04	0.19	1	-0.24	4	5
TRAF2	0.036	0.006	-10000	0	0	15	15
TRAILR3 (trimer)	0.036	0.006	-10000	0	0	14	14
CHUK	0.025	0.017	-10000	0	0	163	163
TRAIL/TRAILR1/FADD	0.033	0.038	-10000	0	-0.11	25	25
DAP3	0.035	0.007	-10000	0	0	22	22
CASP10	-0.004	0.051	0.14	15	-0.16	22	37
JNK cascade	0.035	0.045	-10000	0	-0.14	25	25
TRAIL (trimer)	0.029	0.015	-10000	0	0	109	109
TNFRSF10C	0.036	0.006	-10000	0	0	14	14
TRAIL/TRAILR1/DAP3/GTP/FADD	0.042	0.047	-10000	0	-0.11	33	33
TRAIL/TRAILR2/FADD	0.05	0.048	-10000	0	-0.12	23	23
cell death	0.014	0.028	-10000	0	-0.1	20	20
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.024	0.05	-10000	0	-0.17	20	20
TRAILR2 (trimer)	0.035	0.008	-10000	0	0	26	26
CASP8	0.016	0.023	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.086	0.057	-10000	0	-0.11	23	23

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.034	0.009	-10000	0	0	32	32
NFATC1	0.004	0.1	0.23	1	-0.4	22	23
NFATC2	-0.034	0.082	-10000	0	-0.16	115	115
NFATC3	0.01	0.019	-10000	0	-0.1	13	13
YWHAE	0.035	0.008	-10000	0	0	27	27
Calcineurin A alpha-beta B1/CABIN1	-0.007	0.075	0.16	2	-0.23	22	24
Exportin 1/Ran/NUP214	0.068	0.029	-10000	0	-0.15	6	6
mol:DAG	0	0	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	0.02	0.089	-10000	0	-0.24	12	12
BCL2/BAX	0.047	0.023	-10000	0	-0.14	3	3
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.026	-10000	0	-0.13	13	13
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
BAX	0.033	0.01	-10000	0	0	44	44
MAPK14	0.036	0.004	-10000	0	0	6	6
BAD	0.036	0.006	-10000	0	0	14	14
CABIN1/MEF2D	0.007	0.081	-10000	0	-0.22	21	21
Calcineurin A alpha-beta B1/BCL2	0.035	0.007	-10000	0	0	20	20
FKBP8	0.035	0.009	-10000	0	0	29	29
activation-induced cell death of T cells	-0.007	0.08	0.22	21	-10000	0	21
KPNB1	0.035	0.007	-10000	0	0	22	22
KPNA2	0.034	0.01	-10000	0	0	39	39
XPO1	0.036	0.004	-10000	0	0	5	5
SFN	0.031	0.013	-10000	0	0	78	78
MAP3K8	0.022	0.018	-10000	0	0	196	196
NFAT4/CK1 alpha	0.025	0.042	0.17	1	-0.16	16	17
MEF2D/NFAT1/Cbp/p300	0.011	0.11	0.23	1	-0.21	36	37
CABIN1	-0.007	0.075	0.16	2	-0.24	22	24
CALM1	0.033	0.011	-10000	0	0	54	54
RAN	0.036	0.005	-10000	0	0	10	10
MAP3K1	0.035	0.007	-10000	0	0	20	20
CAMK4	0.036	0.005	-10000	0	0	9	9
mol:Ca2+	0	0.001	-10000	0	-10000	0	0
MAPK3	0.036	0.004	-10000	0	0	6	6
YWHAH	0.031	0.013	-10000	0	0	73	73
Calcineurin A alpha-beta B1/AKAP79/PKA	0.049	0.016	-10000	0	-10000	0	0
YWHAB	0.035	0.008	-10000	0	0	24	24
MAPK8	0.027	0.016	-10000	0	0	138	138
MAPK9	0.036	0.006	-10000	0	0	15	15
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.033	0.01	-10000	0	0	44	44
NFAT1-c-4/YWHAQ	0.001	0.1	-10000	0	-0.37	20	20
PRKCH	0.034	0.01	-10000	0	0	43	43
CABIN1/Cbp/p300	0.047	0.028	-10000	0	-0.14	7	7
CASP3	0.034	0.009	-10000	0	0	31	31
PIM1	0.036	0.005	-10000	0	0	8	8
Calcineurin A alpha-beta B1/FKBP12/FK506	0.02	0.019	-10000	0	-0.11	10	10
apoptosis	0.02	0.035	-10000	0	-0.21	6	6
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.095	-10000	0	-0.32	24	24
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.036	0.003	-10000	0	0	4	4
JNK2/NFAT4	0.026	0.036	-10000	0	-0.12	20	20
BAD/BCL-XL	0.048	0.025	-10000	0	-0.14	6	6
PRKCD	0.034	0.01	-10000	0	0	40	40
NUP214	0.035	0.007	-10000	0	0	18	18
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.036	0.004	-10000	0	0	6	6
PRKCG	0.037	0	-10000	0	-10000	0	0
PRKCQ	0.025	0.017	-10000	0	0	158	158
FKBP38/BCL2	0.049	0.016	-10000	0	-10000	0	0
EP300	0.033	0.011	-10000	0	0	49	49
PRKCB1	0.031	0.013	-10000	0	0	82	82
CSNK2A1	0.034	0.009	-10000	0	0	31	31
NFATc/JNK1	0.013	0.099	0.24	1	-0.39	21	22
CaM/Ca2+/FKBP38	0.04	0.03	-10000	0	-0.11	13	13
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSNK1A1	-0.016	0.021	0.087	12	-0.11	9	21
CaM/Ca2+/CAMK IV	0.041	0.029	-10000	0	-0.11	13	13
NFATc/ERK1	0.022	0.1	0.24	1	-0.38	22	23
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.019	0.091	-10000	0	-0.24	15	15
NR4A1	-0.024	0.079	0.18	2	-0.2	27	29
GSK3B	0.034	0.01	-10000	0	0	40	40
positive T cell selection	0.01	0.019	-10000	0	-0.1	13	13
NFAT1/CK1 alpha	-0.019	0.069	-10000	0	-0.18	42	42
RCH1/ KPNB1	0.036	0.057	-10000	0	-0.15	43	43
YWHAQ	0.036	0.005	-10000	0	0	9	9
PRKACA	0.035	0.008	-10000	0	0	25	25
AKAP5	0.034	0.009	-10000	0	0	31	31
MEF2D	0.036	0.005	-10000	0	0	11	11
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.035	0.007	-10000	0	0	21	21
NFATc/p38 alpha	0.022	0.1	0.24	1	-0.38	22	23
CREBBP	0.036	0.005	-10000	0	0	8	8
BCL2	0.035	0.007	-10000	0	0	20	20

×

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	-0.011	0.026	0.084	36	-10000	0	36
SNTA1	0.033	0.011	-10000	0	0	55	55
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.014	0.033	0.082	52	-10000	0	52
MAPK12	-0.011	0.029	0.2	3	-0.17	9	12
CCND1	-0.019	0.1	-10000	0	-0.37	39	39
p38 gamma/SNTA1	-0.01	0.038	0.2	3	-0.16	10	13
MAP2K3	0.036	0.005	-10000	0	0	10	10
PKN1	0.033	0.011	-10000	0	0	48	48
G2/M transition checkpoint	-0.011	0.029	0.2	3	-0.17	9	12
MAP2K6	-0.005	0.034	0.21	5	-0.18	10	15
MAPT	-0.025	0.077	0.16	5	-0.2	73	78
MAPK13	-0.014	0.03	0.092	36	-10000	0	36
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.01	0.031	-10000	0	-0.2	11	11

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.036	0.005	-10000	0	0	8	8
VDR	0.035	0.007	-10000	0	0	18	18
Cbp/p300/PCAF	0.042	0.024	-10000	0	-0.12	7	7
EP300	0.033	0.011	-10000	0	0	49	49
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.002	0.05	-10000	0	-0.2	5	5
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.036	0.004	-10000	0	0	6	6
AKT1	0.008	0.078	0.21	1	-0.22	10	11
RAR alpha/9cRA/Cyclin H	-0.024	0.12	-10000	0	-0.3	35	35
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.055	-10000	0	-0.2	20	20
CDC2	0.019	0.02	-10000	0	-0.001	241	241
response to UV	-0.001	0.007	-10000	0	-0.026	33	33
RAR alpha/Jnk1	0.023	0.028	0.16	1	-10000	0	1
NCOR2	0.036	0.002	-10000	0	0	2	2
VDR/VDR/Vit D3	0.026	0.005	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.028	0.15	-10000	0	-0.54	33	33
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA3	0.035	0.008	-10000	0	0	27	27
NCOA1	0.033	0.011	-10000	0	0	50	50
VDR/VDR/DNA	0.035	0.007	-10000	0	0	18	18
RARG	0.032	0.017	-10000	0	-0.025	41	41
RAR gamma1/9cRA	0.046	0.012	-10000	0	-10000	0	0
MAPK3	0.032	0.018	-10000	0	-0.03	39	39
MAPK1	0.033	0.01	-10000	0	0	45	45
MAPK8	0.024	0.022	-10000	0	-0.045	21	21
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.02	0.12	-10000	0	-0.36	33	33
RARA	0.006	0.037	-10000	0	-0.2	11	11
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.006	0.038	-10000	0	-0.16	8	8
PRKCA	0.031	0.027	0.075	4	-0.072	32	36
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.029	0.16	-10000	0	-0.61	33	33
RXRG	0.019	0.028	-10000	0	-10000	0	0
RXRA	-0.011	0.082	0.15	4	-0.3	24	28
RXRB	0.019	0.026	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.026	0.005	-10000	0	-10000	0	0
RBP1	0.026	0.016	-10000	0	0	141	141
CRBP1/9-cic-RA	-0.004	0.06	-10000	0	-0.13	90	90
RARB	0.032	0.021	-10000	0	-0.046	32	32
PRKCG	0.031	0.027	-10000	0	-0.071	33	33
MNAT1	0.034	0.01	-10000	0	0	38	38
RAR alpha/RXRs	-0.013	0.13	-10000	0	-0.42	24	24
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.006	0.089	-10000	0	-0.32	18	18
proteasomal ubiquitin-dependent protein catabolic process	-0.007	0.056	-10000	0	-0.18	11	11
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.029	0.16	-10000	0	-0.61	33	33
positive regulation of DNA binding	-0.028	0.12	-10000	0	-0.28	36	36
NRIP1	-0.053	0.27	-10000	0	-1.1	33	33
RXRs/RARs	-0.007	0.12	-10000	0	-0.41	33	33
RXRs/RXRs/DNA/9cRA	-0.032	0.11	-10000	0	-0.36	33	33
PRKACA	0.035	0.008	-10000	0	0	25	25
CDK7	0.035	0.008	-10000	0	0	24	24
TFIIH	0.059	0.049	-10000	0	-0.16	19	19
RAR alpha/9cRA	0.022	0.087	-10000	0	-0.17	22	22
CCNH	0.035	0.007	-10000	0	0	18	18
CREBBP	0.036	0.005	-10000	0	0	8	8
RAR gamma2/9cRA	0.056	0.049	-10000	0	-0.14	18	18

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.044	0.037	-10000	0	-0.14	17	17
ATM	0.034	0.009	-10000	0	0	35	35
UBE2D3	0.036	0.006	-10000	0	0	12	12
PRKDC	0.033	0.01	-10000	0	0	44	44
ATR	0.035	0.008	-10000	0	0	25	25
UBE2L3	0.034	0.009	-10000	0	0	33	33
FANCD2	0.008	0.035	-10000	0	-0.2	14	14
protein ubiquitination	0.077	0.055	-10000	0	-0.13	21	21
XRCC5	0.036	0.005	-10000	0	0	9	9
XRCC6	0.034	0.01	-10000	0	0	39	39
M/R/N Complex	0.069	0.024	-10000	0	-0.12	4	4
MRE11A	0.036	0.004	-10000	0	0	7	7
DNA-PK	0.057	0.049	-10000	0	-0.14	22	22
FA complex/FANCD2/Ubiquitin	0.002	0.087	-10000	0	-0.29	27	27
FANCF	0.035	0.008	-10000	0	0	27	27
BRCA1	0.036	0.006	-10000	0	0	12	12
CCNE1	0.032	0.012	-10000	0	0	58	58
CDK2/Cyclin E1	0.045	0.023	-10000	0	-0.14	2	2
FANCG	0.03	0.014	-10000	0	0	85	85
BRCA1/BACH1/BARD1	0.046	0.037	-10000	0	-0.14	18	18
FANCE	0.036	0.003	-10000	0	0	4	4
FANCC	0.035	0.007	-10000	0	0	17	17
NBN	0.036	0.006	-10000	0	0	14	14
FANCA	0.035	0.007	-10000	0	0	17	17
DNA repair	-0.018	0.081	0.22	7	-0.29	17	24
BRCA1/BARD1/ubiquitin	0.046	0.037	-10000	0	-0.14	18	18
BARD1/DNA-PK	0.07	0.064	-10000	0	-0.14	34	34
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.037	0.14	17	-10000	0	17
BRCA1/BARD1/CTIP/M/R/N Complex	0.011	0.063	-10000	0	-0.22	26	26
BRCA1/BACH1/BARD1/TopBP1	0.051	0.061	-10000	0	-0.13	45	45
BRCA1/BARD1/P53	0.067	0.067	-10000	0	-0.13	46	46
BARD1/CSTF1/BRCA1	0.062	0.04	-10000	0	-0.12	17	17
BRCA1/BACH1	0.036	0.006	-10000	0	0	12	12
BARD1	0.035	0.007	-10000	0	0	20	20
PCNA	0.034	0.01	-10000	0	0	41	41
BRCA1/BARD1/UbcH5C	0.064	0.042	-10000	0	-0.13	19	19
BRCA1/BARD1/UbcH7	0.059	0.046	-10000	0	-0.13	23	23
BRCA1/BARD1/RAD51/PCNA	0.072	0.06	-10000	0	-0.13	34	34
BARD1/DNA-PK/P53	0.068	0.083	-10000	0	-0.13	57	57
BRCA1/BARD1/Ubiquitin	0.046	0.037	-10000	0	-0.14	18	18
BRCA1/BARD1/CTIP	0.04	0.058	-10000	0	-0.13	44	44
FA complex	0.012	0.059	-10000	0	-0.18	34	34
BARD1/EWS	0.044	0.038	-10000	0	-0.14	18	18
RBBP8	-0.013	0.029	0.092	34	-10000	0	34
TP53	0.031	0.013	-10000	0	0	73	73
TOPBP1	0.033	0.011	-10000	0	0	52	52
G1/S transition of mitotic cell cycle	-0.064	0.066	0.13	46	-10000	0	46
BRCA1/BARD1	0.085	0.058	-10000	0	-0.13	21	21
CSTF1	0.034	0.009	-10000	0	0	30	30
BARD1/EWS-Fli1	0.021	0.029	-10000	0	-0.13	18	18
CDK2	0.034	0.01	-10000	0	0	40	40
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.035	0.008	-10000	0	0	25	25
RAD50	0.036	0.006	-10000	0	0	13	13
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.046	0.037	-10000	0	-0.14	18	18
EWSR1	0.034	0.009	-10000	0	0	33	33

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.035	0.008	-10000	0	0	27	27
alphaV beta3 Integrin	0.044	0.042	-10000	0	-0.14	24	24
PTK2	0.012	0.11	-10000	0	-0.32	28	28
positive regulation of JNK cascade	0.021	0.09	-10000	0	-0.26	35	35
CDC42/GDP	0.036	0.12	-10000	0	-0.34	37	37
Rac1/GDP	0.028	0.099	-10000	0	-0.33	17	17
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.036	0.005	-10000	0	0	11	11
CTNNB1	0.036	0.006	-10000	0	0	15	15
CDC42/GTP	0.029	0.11	-10000	0	-0.31	33	33
nectin-3/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
RAPGEF1	0.005	0.12	-10000	0	-0.35	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.13	-10000	0	-0.38	41	41
PDGFB-D/PDGFRB	0.035	0.008	-10000	0	0	27	27
TLN1	-0.006	0.058	0.16	21	-0.23	13	34
Rap1/GTP	-0.002	0.085	-10000	0	-0.27	40	40
IQGAP1	0.033	0.011	-10000	0	0	51	51
Rap1/GTP/I-afadin	0.042	0.015	-10000	0	-0.1	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
PVR	0.034	0.009	-10000	0	0	32	32
Necl-5(dimer)	0.034	0.009	-10000	0	0	32	32
mol:GDP	0.021	0.14	-10000	0	-0.4	38	38
MLLT4	0.034	0.009	-10000	0	0	36	36
PIK3CA	0.031	0.013	-10000	0	0	80	80
PI3K	0.057	0.088	-10000	0	-0.13	71	71
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.05	0.015	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.019	0.078	-10000	0	-0.28	16	16
PVRL1	0.036	0.004	-10000	0	0	7	7
PVRL3	0.032	0.012	-10000	0	0	60	60
PVRL2	0.034	0.009	-10000	0	0	35	35
PIK3R1	0.032	0.012	-10000	0	0	63	63
CDH1	0.034	0.01	-10000	0	0	38	38
CLDN1	0.034	0.009	-10000	0	0	36	36
JAM-A/CLDN1	0.074	0.045	-10000	0	-0.11	9	9
SRC	0.012	0.14	-10000	0	-0.41	41	41
ITGB3	0.036	0.003	-10000	0	0	4	4
nectin-1(dimer)/I-afadin/I-afadin	0.05	0.015	-10000	0	-10000	0	0
FARP2	0.027	0.13	-10000	0	-0.43	21	21
RAC1	0.024	0.017	-10000	0	0	173	173
CTNNA1	0.035	0.007	-10000	0	0	20	20
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.057	0.035	-10000	0	-0.12	5	5
nectin-1/I-afadin	0.05	0.015	-10000	0	-10000	0	0
nectin-2/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.023	0.042	-10000	0	-0.12	30	30
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.059	0.034	-10000	0	-0.12	5	5
CDC42/GTP/IQGAP1/filamentous actin	0.035	0.042	-10000	0	-0.12	33	33
F11R	0.033	0.011	-10000	0	0	52	52
positive regulation of filopodium formation	0.021	0.09	-10000	0	-0.26	35	35
alphaV/beta3 Integrin/Talin	0.031	0.087	0.21	32	-0.21	25	57
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.047	0.023	-10000	0	-0.14	3	3
PIP5K1C	-0.01	0.04	0.089	4	-0.22	14	18
VAV2	0.025	0.14	-10000	0	-0.45	22	22
RAP1/GDP	0.026	0.11	-10000	0	-0.31	38	38
ITGAV	0.034	0.009	-10000	0	0	31	31
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.056	0.038	-10000	0	-0.13	7	7
nectin-3(dimer)/I-afadin/I-afadin	0.043	0.027	-10000	0	-0.14	5	5
Rac1/GTP	0.024	0.094	-10000	0	-0.33	16	16
PTPRM	0.008	0.045	-10000	0	-0.22	16	16
E-cadherin/beta catenin/alpha catenin	0.084	0.057	-10000	0	-0.12	12	12
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.035	0.008	-10000	0	0	24	24

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	-0.023	0.1	0.23	2	-0.47	16	18
SMARCC2	0.033	0.01	-10000	0	0	44	44
SMARCC1	0.034	0.009	-10000	0	0	32	32
TBX21	0.031	0.055	0.34	1	-10000	0	1
SUMO2	0.034	0.019	0.071	1	-0.03	33	34
STAT1 (dimer)	0.036	0.038	0.11	19	-0.17	13	32
FKBP4	0.034	0.009	-10000	0	0	34	34
FKBP5	0.028	0.015	-10000	0	0	117	117
GR alpha/HSP90/FKBP51/HSP90	-0.024	0.064	-10000	0	-0.18	10	10
PRL	0.04	0.058	0.54	1	-10000	0	1
cortisol/GR alpha (dimer)/TIF2	-0.042	0.12	-10000	0	-0.32	1	1
RELA	0.015	0.11	0.18	32	-0.16	125	157
FGG	-0.049	0.1	-10000	0	-0.32	2	2
GR beta/TIF2	-0.025	0.075	-10000	0	-0.22	2	2
IFNG	0.037	0.081	-10000	0	-10000	0	0
apoptosis	-0.017	0.2	0.44	26	-0.5	36	62
CREB1	0.043	0.01	-10000	0	-10000	0	0
histone acetylation	0.022	0.054	0.22	1	-0.24	1	2
BGLAP	0.04	0.061	-10000	0	-10000	0	0
GR/PKAc	0.021	0.091	-10000	0	-0.2	11	11
NF kappa B1 p50/RelA	0.03	0.18	0.3	30	-0.26	118	148
SMARCD1	0.035	0.007	-10000	0	0	20	20
MDM2	-0.008	0.036	-10000	0	-10000	0	0
GATA3	0.031	0.021	-10000	0	-10000	0	0
AKT1	0.029	0.029	0.16	7	-0.09	17	24
CSF2	0.006	0.032	-10000	0	-10000	0	0
GSK3B	0.032	0.02	0.071	1	-0.03	30	31
NR1I3	-0.012	0.18	0.45	18	-0.5	19	37
CSN2	-0.046	0.089	0.26	2	-0.29	2	4
BRG1/BAF155/BAF170/BAF60A	0.064	0.073	-10000	0	-0.16	38	38
NFATC1	0.04	0.01	-10000	0	-10000	0	0
POU2F1	0.04	0.012	-10000	0	-10000	0	0
CDKN1A	-0.13	0.41	-10000	0	-1.2	59	59
response to stress	0	0	-10000	0	-10000	0	0
response to UV	0.001	0.008	0.029	27	-10000	0	27
SFN	0.031	0.013	-10000	0	0	78	78
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.011	0.068	-10000	0	-0.15	7	7
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.066	0.27	0.43	18	-0.66	71	89
JUN	0.024	0.053	0.35	3	-10000	0	3
IL4	0.035	0.053	-10000	0	-10000	0	0
CDK5R1	0.035	0.009	-10000	0	0	24	24
PRKACA	0.035	0.008	-10000	0	0	25	25
cortisol/GR alpha (monomer)/AP-1	-0.047	0.051	-10000	0	-0.22	10	10
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.005	0.073	-10000	0	-0.16	17	17
cortisol/GR alpha (monomer)	-0.057	0.12	-10000	0	-0.37	2	2
NCOA2	0.036	0.006	-10000	0	0	12	12
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.039	0.031	0.17	7	-10000	0	7
AP-1/NFAT1-c-4	0.048	0.075	0.44	2	-10000	0	2
AFP	0.025	0.066	-10000	0	-10000	0	0
SUV420H1	0.033	0.011	-10000	0	0	51	51
IRF1	-0.027	0.12	-10000	0	-0.64	14	14
TP53	-0.016	0.17	-10000	0	-0.49	57	57
PPP5C	0.034	0.01	-10000	0	0	39	39
KRT17	0.041	0.08	0.45	1	-10000	0	1
KRT14	0.031	0.067	-10000	0	-10000	0	0
TBP	0.042	0.018	-10000	0	-10000	0	0
CREBBP	0.029	0.018	-10000	0	-0.093	10	10
HDAC1	0.032	0.007	-10000	0	-10000	0	0
HDAC2	0.031	0.012	-10000	0	-10000	0	0
AP-1	0.048	0.075	0.44	2	-10000	0	2
MAPK14	0.034	0.019	-10000	0	-0.03	32	32
MAPK10	0.029	0.02	0.073	1	-0.031	25	26
MAPK11	0.031	0.02	0.071	1	-0.03	31	32
KRT5	0.041	0.078	0.45	1	-10000	0	1
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.033	0.018	0.092	2	-0.066	9	11
STAT1	0.036	0.038	0.11	19	-0.17	13	32
CGA	0.036	0.056	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.033	0.067	-10000	0	-0.35	6	6
MAPK3	0.034	0.019	0.075	2	-0.03	35	37
MAPK1	0.031	0.02	-10000	0	-0.03	30	30
ICAM1	0.029	0.14	0.34	15	-10000	0	15
NFKB1	0.016	0.11	0.17	30	-0.16	121	151
MAPK8	0.034	0.058	0.28	2	-10000	0	2
MAPK9	0.033	0.019	-10000	0	-0.03	30	30
cortisol/GR alpha (dimer)	-0.021	0.2	0.44	25	-0.52	36	61
BAX	-0.033	0.18	-10000	0	-0.86	10	10
POMC	0.032	0.074	0.48	1	-10000	0	1
EP300	0.026	0.019	-10000	0	-0.093	10	10
cortisol/GR alpha (dimer)/p53	-0.071	0.13	-10000	0	-0.42	19	19
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.069	0.24	31	-10000	0	31
SGK1	-0.016	0.06	-10000	0	-0.25	12	12
IL13	0.029	0.063	-10000	0	-10000	0	0
IL6	0.03	0.13	0.34	17	-10000	0	17
PRKACG	0.036	0.005	-10000	0	0	11	11
IL5	0.021	0.071	0.43	1	-10000	0	1
IL2	0.042	0.075	-10000	0	-10000	0	0
CDK5	0.023	0.018	-10000	0	0	192	192
PRKACB	0.033	0.011	-10000	0	0	50	50
HSP90AA1	0	0	-10000	0	-10000	0	0
IL8	-0.11	0.4	0.34	16	-0.79	125	141
CDK5R1/CDK5	0.028	0.042	-10000	0	-0.14	18	18
NF kappa B1 p50/RelA/PKAc	0.055	0.16	0.3	28	-0.21	108	136
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.038	0.1	-10000	0	-0.37	1	1
SMARCA4	0.032	0.012	-10000	0	0	63	63
chromatin remodeling	-0.037	0.11	-10000	0	-0.37	28	28
NF kappa B1 p50/RelA/Cbp	0.046	0.16	0.3	21	-0.22	112	133
JUN (dimer)	0.024	0.053	0.35	3	-10000	0	3
YWHAH	0.031	0.013	-10000	0	0	73	73
VIPR1	0.034	0.065	0.38	5	-10000	0	5
NR3C1	-0.04	0.085	-10000	0	-0.34	1	1
NR4A1	0.039	0.008	-10000	0	-10000	0	0
TIF2/SUV420H1	0.036	0.054	-10000	0	-0.14	42	42
MAPKKK cascade	-0.017	0.2	0.44	26	-0.5	36	62
cortisol/GR alpha (dimer)/Src-1	-0.05	0.12	-10000	0	-0.36	3	3
PBX1	0.04	0.011	-10000	0	-10000	0	0
POU1F1	0.041	0.011	-10000	0	-10000	0	0
SELE	0.026	0.13	0.34	2	-10000	0	2
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.037	0.11	-10000	0	-0.37	28	28
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.038	0.1	-10000	0	-0.37	1	1
mol:cortisol	-0.034	0.061	-10000	0	-10000	0	0
MMP1	0.038	0.072	0.35	1	-0.49	3	4

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.003	0.036	0.096	25	-0.1	9	34
NFATC2	-0.001	0.027	0.078	19	-0.096	10	29
NFATC3	-0.003	0.038	0.093	30	-0.1	10	40
CD40LG	0.015	0.12	0.29	41	-0.24	1	42
PTGS2	-0.017	0.073	0.28	7	-0.24	1	8
JUNB	0.031	0.014	-10000	0	0	83	83
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.026	0.083	1	-0.12	12	13
CaM/Ca2+	0.026	0.026	0.083	1	-0.12	12	13
CALM1	0.035	0.013	0.07	1	-10000	0	1
JUN	0.036	0.012	0.07	1	-10000	0	1
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.022	0.02	-10000	0	-0.11	10	10
FOSL1	0.033	0.011	-10000	0	0	55	55
CREM	0.026	0.016	-10000	0	0	142	142
Jun/NFAT1-c-4/p21SNFT	0.057	0.069	0.26	12	-0.18	3	15
FOS	0.027	0.019	0.07	1	-10000	0	1
IFNG	0.014	0.11	0.3	36	-10000	0	36
AP-1/NFAT1-c-4	0.093	0.11	0.35	10	-0.26	1	11
FASLG	0.014	0.12	0.29	39	-0.24	1	40
NFAT1-c-4/ICER1	0.041	0.052	0.21	10	-10000	0	10
IL2RA	0.005	0.088	0.26	19	-0.24	1	20
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSF2	0.015	0.12	0.29	40	-0.24	1	41
JunB/Fra1/NFAT1-c-4	0.057	0.061	0.22	9	-0.18	1	10
IL4	0.015	0.12	0.29	39	-10000	0	39
IL2	0.012	0.087	-10000	0	-0.84	5	5
IL3	0.03	0.085	-10000	0	-0.58	9	9
FKBP1A	0.033	0.01	-10000	0	0	44	44
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.039	0.008	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.053	0.093	-10000	0	-0.19	54	54
Ran/GTP/Exportin 1/HDAC1	-0.029	0.022	-10000	0	-0.11	26	26
NF kappa B1 p50/RelA/I kappa B alpha	0.006	0.11	-10000	0	-0.25	53	53
SUMO1	0.036	0.003	-10000	0	0	4	4
ZFPM1	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
FKBP3	0.034	0.009	-10000	0	0	33	33
Histones	0.034	0.072	-10000	0	-0.22	23	23
YY1/LSF	0.016	0.062	-10000	0	-0.22	18	18
SMG5	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
I kappa B alpha/HDAC3	0.001	0.076	-10000	0	-0.2	51	51
I kappa B alpha/HDAC1	0.008	0.097	-10000	0	-0.22	63	63
SAP18	0.034	0.01	-10000	0	0	41	41
RELA	-0.002	0.076	0.19	1	-0.26	16	17
HDAC1/Smad7	0.042	0.041	-10000	0	-0.12	6	6
RANGAP1	0.033	0.01	-10000	0	0	45	45
HDAC3/TR2	0.027	0.07	-10000	0	-0.25	21	21
NuRD/MBD3 Complex	-0.009	0.11	-10000	0	-0.34	36	36
NF kappa B1 p50/RelA	0.011	0.088	-10000	0	-0.29	18	18
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.035	0.007	-10000	0	0	18	18
GATA1	0.037	0	-10000	0	-10000	0	0
Mad/Max	0.051	0.013	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.007	0.11	-10000	0	-0.33	35	35
RBBP7	0.036	0.005	-10000	0	0	8	8
NPC	0.017	0.02	-10000	0	-0.087	18	18
RBBP4	0.033	0.011	-10000	0	0	56	56
MAX	0.034	0.009	-10000	0	0	32	32
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.035	0.008	-10000	0	0	25	25
NFKBIA	0.002	0.078	-10000	0	-0.32	23	23
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.006	0.087	-10000	0	-0.29	29	29
SIN3 complex	0.056	0.041	-10000	0	-0.12	17	17
SMURF1	0.025	0.017	-10000	0	0	167	167
CHD3	0.036	0.005	-10000	0	0	11	11
SAP30	0.035	0.007	-10000	0	0	20	20
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.035	0.008	-10000	0	0	26	26
YY1/HDAC3	0	0.074	-10000	0	-0.24	29	29
YY1/HDAC2	0.016	0.056	-10000	0	-0.2	17	17
YY1/HDAC1	0.017	0.061	-10000	0	-0.22	18	18
NuRD/MBD2 Complex (MeCP1)	-0.002	0.091	-10000	0	-0.28	33	33
PPARG	0.002	0.077	-10000	0	-0.21	52	52
HDAC8/hEST1B	0.023	0.005	-10000	0	-10000	0	0
UBE2I	0.036	0.004	-10000	0	0	6	6
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.008	-10000	0	0	25	25
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
HDAC3/SMRT (N-CoR2)	0.026	0.07	-10000	0	-0.25	21	21
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.042	0.04	-10000	0	-0.12	6	6
CREBBP	0.036	0.005	-10000	0	0	8	8
NuRD/MBD3/MBD3L2 Complex	-0.003	0.1	-10000	0	-0.32	34	34
HDAC1	0.035	0.007	-10000	0	0	21	21
HDAC3	0.009	0.057	-10000	0	-0.15	45	45
HDAC2	0.032	0.012	-10000	0	0	67	67
YY1	0.01	0.028	-10000	0	-0.21	7	7
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	0.033	0.01	-10000	0	0	44	44
NCOR2	0.036	0.002	-10000	0	0	2	2
MXD1	0.036	0.003	-10000	0	0	3	3
STAT3	0.006	0.06	-10000	0	-0.21	33	33
NFKB1	0.035	0.007	-10000	0	0	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
YY1/LSF/HDAC1	0.03	0.07	-10000	0	-0.21	18	18
YY1/SAP30/HDAC1	0.032	0.068	-10000	0	-0.2	18	18
EP300	0.033	0.011	-10000	0	0	49	49
STAT3 (dimer non-phopshorylated)	0.006	0.06	-10000	0	-0.21	33	33
proteasomal ubiquitin-dependent protein catabolic process	0.002	0.077	-10000	0	-0.32	23	23
histone deacetylation	-0.003	0.092	-10000	0	-0.27	35	35
STAT3 (dimer non-phopshorylated)/HDAC3	0	0.092	-10000	0	-0.31	27	27
nuclear export	-0.023	0.005	-10000	0	-10000	0	0
PRKACA	0.035	0.008	-10000	0	0	25	25
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0.033	0.011	-10000	0	0	53	53
GATA2/HDAC3	0.026	0.069	-10000	0	-0.24	21	21
GATA1/HDAC1	0.05	0.024	-10000	0	-0.14	7	7
GATA1/HDAC3	0.027	0.07	-10000	0	-0.25	21	21
CHD4	0.034	0.01	-10000	0	0	37	37
TNF-alpha/TNFR1A	0.035	0.055	-10000	0	-0.14	43	43
SIN3/HDAC complex/Mad/Max	-0.004	0.085	-10000	0	-0.26	33	33
NuRD Complex	-0.002	0.1	0.16	1	-0.33	33	34
positive regulation of chromatin silencing	0.032	0.071	-10000	0	-0.21	23	23
SIN3B	0.035	0.009	-10000	0	0	29	29
MTA2	0.036	0.004	-10000	0	0	6	6
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0.036	0.004	-10000	0	0	5	5
SUMO1/HDAC1	0.036	0.055	-10000	0	-0.22	6	6
HDAC complex	0.066	0.069	-10000	0	-0.14	40	40
GATA1/Fog1	0.027	0	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.054	0.046	-10000	0	-0.13	20	20
TNF	0.036	0.003	-10000	0	0	4	4
negative regulation of cell growth	-0.004	0.085	-10000	0	-0.26	34	34
NuRD/MBD2/PRMT5 Complex	-0.002	0.091	-10000	0	-0.28	33	33
Ran/GTP/Exportin 1	0.036	0.059	-10000	0	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	-0.006	0.093	-10000	0	-0.25	53	53
SIN3/HDAC complex/NCoR1	-0.003	0.088	-10000	0	-0.31	25	25
TFCP2	0.035	0.008	-10000	0	0	25	25
NR2C1	0.036	0.004	-10000	0	0	5	5
MBD3	0.034	0.01	-10000	0	0	43	43
MBD2	0.035	0.007	-10000	0	0	17	17

×

Coregulation of Androgen receptor activity

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
NRIP1	0.035	0.01	-10000	0	-10000	0	0
SVIL	0.024	0.018	-10000	0	-10000	0	0
ZNF318	0.035	0.005	-10000	0	-0.044	1	1
JMJD2C	0.036	0.014	-10000	0	-10000	0	0
T-DHT/AR/Ubc9	0.052	0.041	-10000	0	-0.079	32	32
CARM1	0.035	0.009	-10000	0	0	29	29
PRDX1	0.035	0.007	-10000	0	0	20	20
PELP1	0.035	0.007	-10000	0	0	17	17
CTNNB1	0.036	0.006	-10000	0	-10000	0	0
AKT1	0.032	0.011	-10000	0	-0.001	54	54
PTK2B	0.036	0.007	-10000	0	-10000	0	0
MED1	0	0	-10000	0	-10000	0	0
MAK	0.033	0.008	-10000	0	-0.044	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	0.022	0.018	-10000	0	-10000	0	0
GSN	0.032	0.013	-10000	0	-10000	0	0
NCOA2	0.036	0.006	-10000	0	0	12	12
NCOA6	0.034	0.01	-10000	0	-10000	0	0
DNA-PK	0.055	0.049	-10000	0	-0.14	22	22
NCOA4	0.027	0.016	-10000	0	0	139	139
PIAS3	0.036	0.006	-10000	0	-10000	0	0
cell proliferation	0.022	0.049	-10000	0	-0.43	5	5
XRCC5	0.036	0.005	-10000	0	0	9	9
UBE3A	0.037	0.003	-10000	0	-10000	0	0
T-DHT/AR/SNURF	0.031	0.033	0.12	1	-0.071	33	34
FHL2	0.018	0.2	-10000	0	-0.68	33	33
RANBP9	0.036	0.007	-10000	0	-10000	0	0
JMJD1A	0.044	0.012	-10000	0	-10000	0	0
CDK6	0.024	0.017	-10000	0	0	176	176
TGFB1I1	0.033	0.012	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.034	0.056	-10000	0	-0.1	53	53
XRCC6	0.033	0.01	-10000	0	0	39	39
T-DHT/AR	0.048	0.059	0.22	1	-0.13	33	34
CTDSP1	0.036	0.006	-10000	0	0	16	16
CTDSP2	0.031	0.012	-10000	0	-0.042	1	1
BRCA1	0.036	0.006	-10000	0	-10000	0	0
TCF4	0.031	0.012	-10000	0	-0.038	1	1
CDKN2A	0.004	0.012	-10000	0	0	444	444
SRF	0.04	0.055	0.11	90	-0.15	33	123
NKX3-1	0.025	0.07	-10000	0	-0.3	15	15
KLK3	0.016	0.046	-10000	0	-10000	0	0
TMF1	0.035	0.007	-10000	0	0	18	18
HNRNPA1	-0.001	0	-10000	0	-10000	0	0
AOF2	0.034	0.011	-10000	0	-10000	0	0
APPL1	-0.011	0.004	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	0.05	0.041	-10000	0	-0.08	33	33
AR	0.035	0.03	-10000	0	-0.068	33	33
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	-0.001	0	-10000	0	-10000	0	0
PAWR	0.036	0.006	-10000	0	0	15	15
PRKDC	0.033	0.01	-10000	0	0	44	44
PA2G4	0.034	0.007	-10000	0	-0.034	1	1
UBE2I	0.036	0.004	-10000	0	0	6	6
T-DHT/AR/Cyclin D3/CDK11 p58	0.045	0.044	0.13	1	-0.078	42	43
RPS6KA3	0.036	0.007	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.039	0.046	-10000	0	-0.086	21	21
LATS2	-0.001	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.046	0.043	-10000	0	-0.079	39	39
Cyclin D3/CDK11 p58	0.021	0.028	-10000	0	-0.13	16	16
VAV3	0.029	0.015	-10000	0	-10000	0	0
KLK2	0.026	0.051	-10000	0	-0.32	8	8
CASP8	0.035	0.006	-10000	0	0	13	13
T-DHT/AR/TIF2/CARM1	0.07	0.046	-10000	0	-0.11	1	1
TMPRSS2	0.025	0.071	-10000	0	-0.3	15	15
CCND1	0.029	0.015	-10000	0	-10000	0	0
PIAS1	0.036	0.008	-10000	0	-10000	0	0
mol:T-DHT	0.004	0.017	0.051	1	-0.049	33	34
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.036	0.009	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.036	0.04	-10000	0	-0.08	17	17
CMTM2	0	0	-10000	0	-10000	0	0
SNURF	0	0	-10000	0	-10000	0	0
ZMIZ1	0.004	0.017	0.051	1	-0.049	33	34
CCND3	0.035	0.008	-10000	0	0	26	26
TGIF1	-0.001	0	-10000	0	-10000	0	0
FKBP4	0.035	0.009	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	0.027	0.078	-10000	0	-0.24	22	22
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
AKT1	0.033	0.011	-10000	0	0	53	53
AKT2	0.035	0.008	-10000	0	0	28	28
STXBP4	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.006	0.075	0.17	2	-0.26	22	24
YWHAZ	0.035	0.007	-10000	0	0	21	21
CALM1	0.033	0.011	-10000	0	0	54	54
YWHAQ	0.036	0.005	-10000	0	0	9	9
TBC1D4	-0.016	0.021	0.092	16	-10000	0	16
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.031	0.013	-10000	0	0	73	73
YWHAB	0.035	0.008	-10000	0	0	24	24
SNARE/Synip	0.021	0.017	-10000	0	-0.11	8	8
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0.036	0.006	-10000	0	0	15	15
PRKCI	0.035	0.008	-10000	0	0	26	26
AS160/CaM/Ca2+	0.021	0.026	-10000	0	-0.13	13	13
RHOQ	0.035	0.007	-10000	0	0	17	17
GYS1	0.002	0.041	0.24	4	-0.21	6	10
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.034	0.009	-10000	0	0	36	36
TC10/GTP/CIP4/Exocyst	0.041	0.029	-10000	0	-0.12	14	14
AS160/14-3-3	-0.005	0.098	-10000	0	-0.4	19	19
VAMP2	0.033	0.011	-10000	0	0	48	48
SLC2A4	0.005	0.081	0.18	1	-0.29	22	23
STX4	0	0	-10000	0	-10000	0	0
GSK3B	0.004	0.076	-10000	0	-0.3	27	27
SFN	0.031	0.013	-10000	0	0	78	78
LNPEP	0.036	0.005	-10000	0	0	8	8
YWHAE	0.035	0.008	-10000	0	0	27	27

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.032	0.012	-10000	0	0	66	66
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	0.001	0.067	0.5	2	-10000	0	2
IL27/IL27R/JAK1	0.04	0.062	-10000	0	-10000	0	0
TBX21	-0.014	0.093	0.34	19	-10000	0	19
IL12B	0.037	0.005	-10000	0	0	9	9
IL12A	-0.011	0.002	0.002	14	-10000	0	14
IL6ST	0.034	0.011	-10000	0	-0.033	1	1
IL27RA/JAK1	0.027	0.048	-10000	0	-10000	0	0
IL27	-0.001	0.004	-10000	0	-10000	0	0
TYK2	0.034	0.011	-10000	0	-0.033	1	1
T-helper cell lineage commitment	0.064	0.083	0.18	153	-0.18	2	155
T-helper 2 cell differentiation	0.001	0.067	0.5	2	-10000	0	2
T cell proliferation during immune response	0.001	0.067	0.5	2	-10000	0	2
MAPKKK cascade	-0.001	0.067	-10000	0	-0.5	2	2
STAT3	0.034	0.01	-10000	0	0	37	37
STAT2	0.036	0.006	-10000	0	0	13	13
STAT1	0.034	0.01	-10000	0	0	40	40
IL12RB1	0.035	0.008	-10000	0	0	23	23
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.015	0.091	0.34	18	-10000	0	18
IL27/IL27R/JAK2/TYK2	-0.002	0.067	-10000	0	-0.51	2	2
positive regulation of T cell mediated cytotoxicity	-0.001	0.067	-10000	0	-0.5	2	2
STAT1 (dimer)	0.048	0.08	-10000	0	-10000	0	0
JAK2	0.03	0.014	-10000	0	-0.032	1	1
JAK1	0.033	0.01	-10000	0	0	41	41
STAT2 (dimer)	0.015	0.099	-10000	0	-0.37	6	6
T cell proliferation	0.003	0.061	-10000	0	-0.32	3	3
IL12/IL12R/TYK2/JAK2	0.006	0.18	-10000	0	-0.76	26	26
IL17A	0.062	0.082	0.18	146	-0.18	2	148
mast cell activation	0.001	0.067	0.5	2	-10000	0	2
IFNG	0.003	0.029	-10000	0	-0.093	12	12
T cell differentiation	-0.001	0.003	-10000	0	-0.017	9	9
STAT3 (dimer)	0.011	0.11	-10000	0	-0.39	11	11
STAT5A (dimer)	0.016	0.1	-10000	0	-0.36	7	7
STAT4 (dimer)	0.015	0.098	-10000	0	-0.37	6	6
STAT4	0.035	0.009	-10000	0	0	29	29
T cell activation	-0.005	0.005	-10000	0	-0.085	1	1
IL27R/JAK2/TYK2	0.039	0.062	-10000	0	-10000	0	0
GATA3	0.007	0.092	0.67	9	-10000	0	9
IL18	-0.01	0.004	0	72	-10000	0	72
positive regulation of mast cell cytokine production	0.011	0.11	-10000	0	-0.38	11	11
IL27/EBI3	0.025	0.011	-10000	0	-10000	0	0
IL27RA	0.001	0.025	-10000	0	-10000	0	0
IL6	0.019	0.018	-10000	0	0	238	238
STAT5A	0.036	0.004	-10000	0	0	5	5
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.007	0.031	0.35	1	-10000	0	1
IL1B	-0.009	0.005	0	101	-10000	0	101
EBI3	0.034	0.012	-10000	0	-0.033	1	1
TNF	-0.011	0.001	0	4	-10000	0	4

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.062	0.03	-9999	-0.12	3	3
E-cadherin/beta catenin	0.048	0.022	-9999	-0.14	3	3
CTNNB1	0.036	0.006	-9999	0	15	15
JUP	0.033	0.011	-9999	0	51	51
CDH1	0.034	0.01	-9999	0	38	38

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	-0.011	0.002	0.012	1	-10000	0	1
SMARCC1	-0.005	0.12	-10000	0	-1.2	4	4
REL	0.036	0.004	-10000	0	-0.007	4	4
HDAC7	-0.029	0.057	0.17	5	-0.21	19	24
JUN	0.034	0.01	-10000	0	0	40	40
EP300	0.033	0.011	-10000	0	0	49	49
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.017	0.019	0.089	4	-10000	0	4
FOXO1	0	0	-10000	0	-10000	0	0
T-DHT/AR	0.02	0.078	0.25	2	-0.22	19	21
MAP2K6	0.035	0.013	-10000	0	-0.034	14	14
BRM/BAF57	0.047	0.024	-10000	0	-0.14	3	3
MAP2K4	0.034	0.014	-10000	0	-0.033	16	16
SMARCA2	0.032	0.013	-10000	0	0	67	67
PDE9A	-0.013	0.2	-10000	0	-0.79	29	29
NCOA2	0.036	0.006	-10000	0	0	12	12
CEBPA	0.028	0.016	-10000	0	0	121	121
EHMT2	0.037	0.002	-10000	0	0	1	1
cell proliferation	-0.022	0.086	0.31	2	-0.31	14	16
NR0B1	0.03	0.014	-10000	0	0	88	88
EGR1	0.029	0.015	-10000	0	0	107	107
RXRs/9cRA	0.067	0.019	-10000	0	-0.11	1	1
AR/RACK1/Src	-0.02	0.052	0.19	1	-0.22	2	3
AR/GR	0.003	0.06	0.16	1	-0.2	25	26
GNB2L1	0.037	0.002	-10000	0	0	2	2
PKN1	0.033	0.011	-10000	0	0	48	48
RCHY1	0.035	0.006	-10000	0	0	16	16
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.012	0.02	0.087	7	-10000	0	7
T-DHT/AR/TIF2/CARM1	0.016	0.055	0.21	3	-0.2	3	6
SRC	-0.021	0.034	0.17	7	-10000	0	7
NR3C1	0.035	0.008	-10000	0	0	24	24
KLK3	-0.003	0.073	0.32	1	-0.36	3	4
APPBP2	0.034	0.015	-10000	0	-0.033	16	16
TRIM24	0.023	0.018	-10000	0	0	186	186
T-DHT/AR/TIP60	-0.023	0.028	0.081	2	-0.15	8	10
TMPRSS2	0.016	0.085	-10000	0	-0.55	8	8
RXRG	0.036	0.006	-10000	0	0	13	13
mol:9cRA	0	0	0.002	1	-10000	0	1
RXRA	0.035	0.007	-10000	0	0	19	19
RXRB	0.037	0.002	-10000	0	0	1	1
CARM1	0.035	0.009	-10000	0	0	29	29
NR2C2	0.036	0.005	-10000	0	0	8	8
KLK2	-0.006	0.041	-10000	0	-0.25	1	1
AR	-0.004	0.043	0.14	4	-0.2	17	21
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0	0	-10000	0	-10000	0	0
MDM2	0.032	0.011	-10000	0	-0.001	47	47
SRY	0.036	0.004	-10000	0	-0.009	4	4
GATA2	0.035	0.007	-10000	0	0	18	18
MYST2	0.034	0.01	-10000	0	0	37	37
HOXB13	0.037	0.003	-10000	0	0	4	4
T-DHT/AR/RACK1/Src	-0.022	0.053	0.18	8	-0.23	2	10
positive regulation of transcription	0.035	0.007	-10000	0	0	18	18
DNAJA1	0.031	0.017	-10000	0	-0.033	16	16
proteasomal ubiquitin-dependent protein catabolic process	0.014	0.037	-10000	0	-0.26	8	8
NCOA1	0.038	0.023	0.13	4	-0.18	2	6
SPDEF	0.037	0.004	-10000	0	0	5	5
T-DHT/AR/TIF2	-0.031	0.084	0.18	2	-0.25	40	42
T-DHT/AR/Hsp90	-0.023	0.028	0.081	2	-0.15	9	11
GSK3B	0.034	0.01	-10000	0	0	40	40
NR2C1	0.036	0.004	-10000	0	0	5	5
mol:T-DHT	-0.019	0.031	0.15	7	-0.12	3	10
SIRT1	0.024	0.017	-10000	0	0	171	171
ZMIZ2	-0.001	0.001	-10000	0	-0.016	1	1
POU2F1	0.037	0.035	0.12	13	-0.11	22	35
T-DHT/AR/DAX-1	-0.021	0.036	0.17	1	-0.19	2	3
CREBBP	0.036	0.005	-10000	0	0	8	8
SMARCE1	0.037	0.004	-10000	0	0	6	6

×

Ceramide signaling pathway

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
SPHK2	-0.008	0.033	0.092	47	-10000	0	47
MAP4K4	0.004	0.051	-10000	0	-0.21	9	9
BAG4	0.036	0.005	-10000	0	0	11	11
PKC zeta/ceramide	0.003	0.05	-10000	0	-0.23	14	14
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.013	-10000	0	0	81	81
BAX	0.001	0.078	-10000	0	-0.33	23	23
RIPK1	0.035	0.007	-10000	0	0	20	20
AKT1	-0.012	0.04	0.47	2	-10000	0	2
BAD	-0.004	0.05	-10000	0	-0.24	13	13
SMPD1	-0.003	0.052	0.13	3	-0.2	17	20
RB1	-0.004	0.051	0.21	1	-0.24	14	15
FADD/Caspase 8	0.014	0.05	-10000	0	-0.24	5	5
MAP2K4	-0.007	0.054	0.18	4	-0.23	14	18
NSMAF	0.035	0.009	-10000	0	0	29	29
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.01	0.054	0.2	7	-0.24	13	20
EGF	0.035	0.008	-10000	0	0	25	25
mol:ceramide	0.004	0.054	-10000	0	-0.25	14	14
MADD	0.036	0.006	-10000	0	0	15	15
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.007	0.034	0.092	51	-10000	0	51
ASAH1	0.035	0.007	-10000	0	0	17	17
negative regulation of cell cycle	-0.003	0.051	0.2	1	-0.24	14	15
cell proliferation	0.019	0.056	0.2	2	-0.22	6	8
BID	0.004	0.15	-10000	0	-0.59	26	26
MAP3K1	-0.001	0.053	0.14	2	-0.24	14	16
EIF2A	-0.01	0.052	0.2	5	-0.22	14	19
TRADD	0.036	0.005	-10000	0	0	11	11
CRADD	0.036	0.006	-10000	0	0	12	12
MAPK3	-0.006	0.051	0.18	11	-0.23	6	17
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.014	0.064	0.18	10	-0.22	22	32
Cathepsin D/ceramide	0.019	0.059	-10000	0	-0.24	14	14
FADD	0.009	0.045	-10000	0	-0.23	3	3
KSR1	-0.004	0.051	-10000	0	-0.24	14	14
MAPK8	-0.04	0.095	0.18	1	-0.19	111	112
PRKRA	-0.006	0.054	0.23	2	-0.23	15	17
PDGFA	0.027	0.016	-10000	0	0	134	134
TRAF2	0.036	0.006	-10000	0	0	15	15
IGF1	0.035	0.008	-10000	0	0	23	23
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	0.004	0.054	-10000	0	-0.24	14	14
CTSD	0.033	0.011	-10000	0	0	55	55
regulation of nitric oxide biosynthetic process	0.049	0.025	-10000	0	-0.14	7	7
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	0.021	0.06	0.21	2	-0.24	6	8
PRKCD	0.034	0.01	-10000	0	0	40	40
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.007	0.034	0.092	51	-10000	0	51
RelA/NF kappa B1	0.049	0.025	-10000	0	-0.14	7	7
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.036	0.006	-10000	0	0	15	15
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.018	0.054	-10000	0	-0.24	6	6
TNFR1A/BAG4/TNF-alpha	0.053	0.056	-10000	0	-0.12	41	41
mol:Sphingosine-1-phosphate	-0.008	0.033	0.092	47	-10000	0	47
MAP2K1	-0.016	0.053	0.18	8	-0.23	13	21
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.036	0.005	-10000	0	0	9	9
CYCS	0.024	0.064	0.14	12	-0.21	9	21
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
NFKB1	0.035	0.007	-10000	0	0	18	18
TNFR1A/BAG4	0.035	0.054	-10000	0	-0.14	42	42
EIF2AK2	-0.011	0.055	0.21	5	-0.23	14	19
TNF-alpha/TNFR1A/FAN	0.047	0.066	-10000	0	-0.13	54	54
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.033	0.051	-10000	0	-0.26	5	5
MAP2K2	-0.008	0.053	0.18	20	-0.22	5	25
SMPD3	0.006	0.056	0.16	1	-0.28	9	10
TNF	0.036	0.003	-10000	0	0	4	4
PKC zeta/PAR4	0.026	0.005	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	0.005	0.045	0.13	7	-0.15	16	23
NF kappa B1/RelA/I kappa B alpha	0.07	0.047	-10000	0	-0.12	20	20
AIFM1	-0.004	0.052	0.14	2	-0.2	18	20
BCL2	0.035	0.007	-10000	0	0	20	20

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.047	0.064	-10000	0	-10000	0	0
MKNK1	0.034	0.009	-10000	0	0	34	34
MAPK14	0.047	0.036	0.16	3	-0.082	20	23
ATF2/c-Jun	0.002	0.091	-10000	0	-0.32	30	30
MAPK11	0.044	0.038	0.16	3	-0.082	20	23
MITF	0.032	0.048	0.17	7	-0.2	7	14
MAPKAPK5	0.034	0.038	0.18	3	-10000	0	3
KRT8	0.036	0.039	0.17	9	-10000	0	9
MAPKAPK3	0.035	0.007	-10000	0	0	19	19
MAPKAPK2	0.034	0.01	-10000	0	0	43	43
p38alpha-beta/CK2	0.063	0.055	0.23	3	-10000	0	3
CEBPB	0.024	0.069	0.17	17	-0.21	27	44
SLC9A1	0.032	0.04	0.16	1	-0.26	2	3
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.032	0.054	0.26	4	-0.26	2	6
p38alpha-beta/MNK1	0.066	0.067	0.21	1	-0.14	17	18
JUN	-0.002	0.088	-10000	0	-0.32	29	29
PPARGC1A	0.032	0.056	0.2	4	-0.21	13	17
USF1	0.028	0.037	0.18	3	-10000	0	3
RAB5/GDP/GDI1	0.014	0.076	-10000	0	-0.22	26	26
NOS2	0.028	0.037	0.18	3	-10000	0	3
DDIT3	0.029	0.061	0.17	8	-0.19	20	28
RAB5A	0.034	0.009	-10000	0	0	32	32
HSPB1	0.086	0.13	0.28	144	-0.15	3	147
p38alpha-beta/HBP1	0.053	0.057	0.22	2	-10000	0	2
CREB1	0.024	0.069	0.22	1	-0.18	34	35
RAB5/GDP	0.019	0.034	-10000	0	-0.13	24	24
EIF4E	-0.015	0.056	0.2	8	-0.2	6	14
RPS6KA4	0.034	0.038	0.18	3	-10000	0	3
PLA2G4A	-0.014	0.052	0.2	4	-0.19	11	15
GDI1	0.025	0.059	0.18	3	-0.23	17	20
TP53	0.01	0.05	0.17	10	-10000	0	10
RPS6KA5	0.035	0.04	0.18	5	-0.19	1	6
ESR1	0.032	0.037	0.19	2	-10000	0	2
HBP1	0.025	0.017	-10000	0	0	163	163
MEF2C	0.032	0.048	0.22	1	-0.22	7	8
MEF2A	0.031	0.046	0.18	4	-0.21	6	10
EIF4EBP1	0.021	0.073	0.22	1	-0.34	3	4
KRT19	0.036	0.039	0.18	7	-10000	0	7
ELK4	0.031	0.036	0.16	2	-10000	0	2
ATF6	0.033	0.037	-10000	0	-10000	0	0
ATF1	0.019	0.072	0.22	1	-0.26	3	4
p38alpha-beta/MAPKAPK2	0.07	0.055	0.21	2	-10000	0	2
p38alpha-beta/MAPKAPK3	0.073	0.056	0.22	3	-0.13	2	5

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	0.06	0.038	-10000	0	-0.11	20	20
HDAC3	0.036	0.005	-10000	0	0	8	8
Ran/GTP/Exportin 1/HDAC4	-0.03	0.022	-10000	0	-0.1	35	35
GATA1/HDAC4	0.047	0.034	-10000	0	-0.14	15	15
GATA1/HDAC5	0.053	0.012	-10000	0	-0.14	1	1
GATA2/HDAC5	0.051	0.016	-10000	0	-0.14	1	1
HDAC5/BCL6/BCoR	0.052	0.051	-10000	0	-0.13	28	28
HDAC9	0.021	0.018	-10000	0	0	210	210
Glucocorticoid receptor/Hsp90/HDAC6	0.044	0.028	-10000	0	-0.12	14	14
HDAC4/ANKRA2	0.044	0.04	-10000	0	-0.14	20	20
HDAC5/YWHAB	0.048	0.028	-10000	0	-0.16	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
GATA2	0.035	0.007	-10000	0	0	18	18
HDAC4/RFXANK	0.038	0.049	-10000	0	-0.15	30	30
BCOR	0.034	0.009	-10000	0	0	35	35
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0.036	0.006	-10000	0	0	14	14
GNB1/GNG2	0.021	0.031	-10000	0	-0.13	20	20
Histones	0.023	0.066	-10000	0	-0.16	39	39
ADRBK1	0.036	0.006	-10000	0	0	13	13
HDAC4	0.035	0.009	-10000	0	0	29	29
XPO1	0.036	0.004	-10000	0	0	5	5
HDAC5/ANKRA2	0.049	0.025	-10000	0	-0.14	7	7
HDAC4/Ubc9	0.046	0.034	-10000	0	-0.14	15	15
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.047	0.031	-10000	0	-0.14	11	11
TUBA1B	0	0	-10000	0	-10000	0	0
HDAC6	0.037	0	-10000	0	-10000	0	0
HDAC5/RFXANK	0.044	0.038	-10000	0	-0.14	18	18
CAMK4	0.036	0.005	-10000	0	0	9	9
Tubulin/HDAC6	0.036	0.043	-10000	0	-0.12	38	38
SUMO1	0.036	0.003	-10000	0	0	4	4
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.035	0.008	-10000	0	0	24	24
GATA1	0.037	0	-10000	0	-10000	0	0
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.035	0.008	-10000	0	0	27	27
NR3C1	0.035	0.008	-10000	0	0	24	24
SUMO1/HDAC4	0.033	0.058	-10000	0	-0.23	6	6
SRF	0.037	0.002	-10000	0	0	1	1
HDAC4/YWHAB	0.043	0.042	-10000	0	-0.15	20	20
Tubulin	0.015	0.042	-10000	0	-0.13	38	38
HDAC4/14-3-3 E	0.042	0.044	-10000	0	-0.14	24	24
GNB1	0.035	0.007	-10000	0	0	20	20
RANGAP1	0.033	0.01	-10000	0	0	45	45
BCL6/BCoR	0.036	0.047	-10000	0	-0.14	28	28
HDAC4/HDAC3/SMRT (N-CoR2)	0.065	0.036	-10000	0	-0.12	15	15
HDAC4/SRF	0.065	0.035	-10000	0	-0.12	14	14
HDAC4/ER alpha	0.044	0.035	-10000	0	-0.14	15	15
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.023	0.066	-10000	0	-0.16	39	39
cell motility	0.036	0.043	-10000	0	-0.11	38	38
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.036	0.004	-10000	0	0	6	6
HDAC7/HDAC3	0.027	0.003	-10000	0	-10000	0	0
BCL6	0.032	0.013	-10000	0	0	69	69
HDAC4/CaMK II delta B	0.034	0.009	-10000	0	0	29	29
Hsp90/HDAC6	0.027	0	-10000	0	-10000	0	0
ESR1	0.035	0.009	-10000	0	0	29	29
HDAC6/HDAC11	0.054	0.006	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.036	0.059	-10000	0	-0.16	21	21
NPC	0.017	0.02	-10000	0	-0.087	18	18
MEF2C	0.035	0.008	-10000	0	0	28	28
RAN	0.036	0.005	-10000	0	0	10	10
HDAC4/MEF2C	0.093	0.054	-10000	0	-0.12	25	25
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.036	0.002	-10000	0	0	2	2
TUBB2A	0.033	0.011	-10000	0	0	47	47
HDAC11	0.036	0.004	-10000	0	0	7	7
HSP90AA1	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
ANKRA2	0.036	0.006	-10000	0	0	14	14
RFXANK	0.034	0.01	-10000	0	0	42	42
nuclear import	-0.029	0.058	0.21	26	-10000	0	26

×

Cellular roles of Anthrax toxin

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ANTXR1	0.035	0.006	-10000	0	0	16	16
ANTXR2	0	0	-10000	0	-10000	0	0
negative regulation of myeloid dendritic cell antigen processing and presentation	-0.002	0	-10000	0	-10000	0	0
monocyte activation	-0.069	0.16	-10000	0	-0.34	135	135
MAP2K2	0.018	0.039	-10000	0	-0.59	2	2
MAP2K1	-0.008	0.002	-10000	0	-10000	0	0
MAP2K7	-0.008	0.002	-10000	0	-10000	0	0
MAP2K6	-0.009	0.002	-10000	0	-10000	0	0
CYAA	-0.007	0.001	-10000	0	-10000	0	0
MAP2K4	-0.008	0.002	-10000	0	-10000	0	0
IL1B	0	0.041	0.082	71	-0.076	57	128
Channel	0.023	0.004	-10000	0	-10000	0	0
NLRP1	-0.001	0	-10000	0	-10000	0	0
CALM1	0.033	0.011	-10000	0	0	54	54
negative regulation of phagocytosis	-0.018	0.12	-10000	0	-0.41	41	41
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0.002	0	-10000	0	-10000	0	0
MAPK3	-0.009	0.002	-10000	0	-10000	0	0
MAPK1	-0.008	0.003	-10000	0	-10000	0	0
PGR	-0.009	0.002	-10000	0	-10000	0	0
PA/Cellular Receptors	0.024	0.004	-10000	0	-10000	0	0
apoptosis	-0.002	0	-10000	0	-10000	0	0
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	0.022	0.004	-10000	0	-10000	0	0
macrophage activation	-0.012	0.011	0.067	7	-10000	0	7
TNF	0.036	0.003	-10000	0	0	4	4
VCAM1	-0.069	0.16	-10000	0	-0.34	134	134
platelet activation	-0.018	0.12	-10000	0	-0.41	41	41
MAPKKK cascade	0.003	0.02	0.064	3	-0.07	30	33
IL18	-0.005	0.035	0.084	39	-0.076	60	99
negative regulation of macrophage activation	-0.002	0	-10000	0	-10000	0	0
LEF	-0.002	0	-10000	0	-10000	0	0
CASP1	0.003	0.004	0.025	12	-10000	0	12
mol:cAMP	-0.018	0.12	-10000	0	-0.41	41	41
necrosis	-0.002	0	-10000	0	-10000	0	0
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	0.022	0.004	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.008	0.14	0.32	19	-1	8	27
VDR	0.035	0.007	-10000	0	0	18	18
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.013	0.098	0.25	2	-0.28	38	40
RXRs/LXRs/DNA/Oxysterols	0.005	0.14	0.3	2	-0.4	45	47
MED1	0	0	-10000	0	-10000	0	0
mol:9cRA	0	0.016	0.046	3	-0.049	43	46
RARs/THRs/DNA/Src-1	0.016	0.053	-10000	0	-0.21	5	5
RXRs/NUR77	0.079	0.064	-10000	0	-0.13	10	10
RXRs/PPAR	0.02	0.047	-10000	0	-0.19	5	5
NCOR2	0.036	0.002	-10000	0	0	2	2
VDR/VDR/Vit D3	0.026	0.005	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.082	0.022	-10000	0	-10000	0	0
RARA	0.036	0.003	-10000	0	0	3	3
NCOA1	0.033	0.011	-10000	0	0	50	50
VDR/VDR/DNA	0.035	0.007	-10000	0	0	18	18
RARs/RARs/DNA/9cRA	0.056	0.032	-10000	0	-10000	0	0
RARG	0.036	0.005	-10000	0	0	8	8
RPS6KB1	-0.004	0.087	0.51	8	-0.4	8	16
RARs/THRs/DNA/SMRT	0.03	0.024	-10000	0	-0.17	5	5
THRA	0.036	0.005	-10000	0	0	11	11
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.026	0.005	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.058	0.074	0.29	3	-0.16	39	42
NR1H4	0.036	0.004	-10000	0	0	6	6
RXRs/LXRs/DNA	0.084	0.1	0.31	2	-0.22	36	38
NR1H2	0.029	0.031	0.09	2	-0.062	45	47
NR1H3	0.03	0.033	0.091	1	-0.069	44	45
RXRs/VDR/DNA/Vit D3	0.072	0.061	-10000	0	-0.13	8	8
NR4A1	0.036	0.006	-10000	0	0	12	12
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.016	0.039	-10000	0	-0.14	6	6
RXRG	0.03	0.03	0.089	1	-0.06	46	47
RXR alpha/CCPG	0.023	0.021	-10000	0	-0.055	10	10
RXRA	0.03	0.03	0.089	1	-0.061	44	45
RXRB	0.031	0.033	-10000	0	-0.067	48	48
THRB	0.036	0.004	-10000	0	0	7	7
PPARG	0.035	0.008	-10000	0	0	26	26
PPARD	0.037	0.002	-10000	0	0	1	1
TNF	-0.001	0.13	-10000	0	-0.53	12	12
mol:Oxysterols	0	0.015	0.046	3	-0.042	49	52
cholesterol transport	0.005	0.14	0.3	2	-0.4	45	47
PPARA	0.033	0.01	-10000	0	0	44	44
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.036	0.005	-10000	0	0	10	10
RXRs/NUR77/BCL2	0.02	0.029	-10000	0	-0.16	1	1
SREBF1	-0.01	0.17	0.34	2	-0.75	16	18
RXRs/RXRs/DNA/9cRA	0.058	0.074	0.28	3	-0.16	39	42
ABCA1	-0.043	0.26	0.34	2	-0.84	45	47
RARs/THRs	0.1	0.024	-10000	0	-0.12	1	1
RXRs/FXR	0.08	0.065	-10000	0	-0.12	32	32
BCL2	0.035	0.007	-10000	0	0	20	20

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.049	0.019	-10000	0	-0.14	2	2
FBXW11	0.035	0.008	-10000	0	0	25	25
NF kappa B1 p50/c-Rel	0.033	0.018	-10000	0	-0.12	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.022	0.067	-10000	0	-0.26	13	13
NFKBIA	0.002	0.056	-10000	0	-0.3	8	8
MAPK14	0.036	0.004	-10000	0	0	6	6
NF kappa B1 p105/p50	0.028	0.03	-10000	0	-0.13	16	16
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
REL	0.036	0.003	-10000	0	0	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.031	0.019	-10000	0	-0.12	5	5
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.032	0.02	-10000	0	-0.12	7	7
PIK3CA	0.031	0.013	-10000	0	0	80	80
NF kappa B1 p50 dimer	-0.02	0.029	0.18	7	-0.14	5	12
PIK3R1	0.032	0.012	-10000	0	0	63	63
NFKB1	-0.021	0.011	0.092	4	-10000	0	4
RELA	0.036	0.005	-10000	0	0	9	9
positive regulation of anti-apoptosis	0.013	0.038	0.14	2	-0.16	4	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.023	0.071	-10000	0	-0.25	15	15
SRC	0.036	0.006	-10000	0	0	14	14
PI3K	0.019	0.075	-10000	0	-0.16	73	73
NF kappa B1 p50/RelA	0.013	0.038	0.14	2	-0.13	22	24
IKBKB	0.036	0.003	-10000	0	0	4	4
beta TrCP1/SCF ubiquitin ligase complex	0.035	0.008	-10000	0	0	25	25
SYK	0.031	0.013	-10000	0	0	76	76
I kappa B alpha/PIK3R1	0.014	0.07	-10000	0	-0.24	23	23
cell death	0.022	0.069	-10000	0	-0.24	15	15
NF kappa B1 p105/c-Rel	0.033	0.018	-10000	0	-0.12	5	5
LCK	0.035	0.007	-10000	0	0	17	17
BCL3	0.034	0.009	-10000	0	0	34	34

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.03	0.15	-10000	0	-0.99	10	10
CLOCK	0.033	0.019	-10000	0	-0.067	10	10
TIMELESS/CRY2	0.024	0.16	-10000	0	-1	10	10
DEC1/BMAL1	0.033	0.056	-10000	0	-0.13	49	49
ATR	0.035	0.008	-10000	0	0	25	25
NR1D1	0.014	0.065	-10000	0	-10000	0	0
ARNTL	0.032	0.02	-10000	0	-0.069	8	8
TIMELESS	0	0.16	-10000	0	-1.1	10	10
NPAS2	0.037	0.017	-10000	0	-0.067	10	10
CRY2	0.035	0.007	-10000	0	0	21	21
mol:CO	-0.01	0.027	0.13	10	-0.13	1	11
CHEK1	0.033	0.011	-10000	0	0	49	49
mol:HEME	0.01	0.027	0.13	1	-0.13	10	11
PER1	0.033	0.011	-10000	0	0	51	51
BMAL/CLOCK/NPAS2	0.056	0.075	0.23	1	-0.14	50	51
BMAL1/CLOCK	0.01	0.12	-10000	0	-0.53	16	16
S phase of mitotic cell cycle	0.03	0.15	-10000	0	-0.99	10	10
TIMELESS/CHEK1/ATR	0.03	0.16	-10000	0	-1	10	10
mol:NADPH	0.01	0.027	0.13	1	-0.13	10	11
PER1/TIMELESS	0.022	0.16	-10000	0	-1	10	10
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.035	0.007	-10000	0	0	19	19

×

Signaling events mediated by the Hedgehog family

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB2	0.034	0.032	-10000	0	-10000	0	0
IHH	0.051	0.012	-10000	0	-10000	0	0
SHH Np/Cholesterol/GAS1	0.014	0.027	-10000	0	-0.11	15	15
LRPAP1	0.035	0.007	-10000	0	0	18	18
dorsoventral neural tube patterning	-0.014	0.026	0.11	15	-10000	0	15
SMO/beta Arrestin2	0.09	0.065	0.26	14	-10000	0	14
SMO	0.025	0.031	0.19	1	-10000	0	1
AKT1	-0.009	0.13	-10000	0	-0.44	29	29
ARRB2	0.035	0.008	-10000	0	0	26	26
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.036	0.006	-10000	0	0	13	13
heart looping	0.026	0.033	0.22	3	-10000	0	3
STIL	0.053	0.094	0.19	154	-10000	0	154
DHH N/PTCH2	0.027	0.003	-10000	0	-10000	0	0
DHH N/PTCH1	0.016	0.02	0.11	21	-10000	0	21
PIK3CA	0.031	0.013	-10000	0	0	80	80
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.038	0.048	-10000	0	-10000	0	0
determination of left/right symmetry	0.026	0.033	0.22	3	-10000	0	3
PIK3R1	0.032	0.012	-10000	0	0	63	63
skeletal system development	0.038	0.047	-10000	0	-10000	0	0
IHH N/Hhip	0.033	0.008	-10000	0	-10000	0	0
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.026	0.033	0.22	3	-10000	0	3
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.035	0.007	-10000	0	0	20	20
PI3K	0.019	0.075	-10000	0	-0.16	73	73
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.03	0.014	-10000	0	0	87	87
somite specification	0.026	0.033	0.22	3	-10000	0	3
SHH Np/Cholesterol/PTCH1	0.017	0.023	0.16	1	-10000	0	1
SHH Np/Cholesterol/PTCH2	0.02	0.016	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.02	0.016	-10000	0	-10000	0	0
SHH	-0.014	0.012	0.092	1	-10000	0	1
catabolic process	0.02	0.025	0.14	22	-10000	0	22
SMO/Vitamin D3	0.023	0.04	0.19	19	-10000	0	19
SHH Np/Cholesterol/Hhip	-0.01	0.008	-10000	0	-10000	0	0
LRP2	0.036	0.006	-10000	0	0	13	13
receptor-mediated endocytosis	0.022	0.038	0.17	19	-10000	0	19
SHH Np/Cholesterol/BOC	-0.01	0.008	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.02	0.016	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.01	0.008	-10000	0	-10000	0	0
mol:Vitamin D3	0.079	0.089	0.2	173	-10000	0	173
IHH N/PTCH2	0.061	0.011	-10000	0	-10000	0	0
CDON	0.036	0.005	-10000	0	0	8	8
IHH N/PTCH1	0.046	0.028	0.17	21	-10000	0	21
Megalin/LRPAP1	0.048	0.029	-10000	0	-0.14	10	10
PTCH2	0.036	0.005	-10000	0	0	8	8
SHH Np/Cholesterol	0.011	0.009	-10000	0	-10000	0	0
PTCH1	0.02	0.025	0.14	22	-10000	0	22
HHIP	0	0	-10000	0	-10000	0	0

×

ceramide signaling 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.005	0.081	-10000	0	-0.29	17	17
BAG4	0.036	0.005	-10000	0	0	11	11
BAD	-0.004	0.033	0.11	1	-0.14	10	11
NFKBIA	0.033	0.012	-10000	0	0	57	57
BIRC3	0.031	0.013	-10000	0	0	81	81
BAX	0.002	0.045	0.18	17	-0.13	10	27
EnzymeConsortium:3.1.4.12	0.004	0.021	0.061	2	-0.078	9	11
IKBKB	-0.005	0.08	-10000	0	-0.29	15	15
MAP2K2	-0.007	0.054	0.17	28	-0.16	7	35
MAP2K1	-0.014	0.04	0.17	6	-0.16	9	15
SMPD1	0.003	0.029	0.1	1	-0.12	13	14
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.012	0.076	-10000	0	-0.32	8	8
MAP2K4	-0.007	0.034	0.15	3	-0.14	5	8
protein ubiquitination	-0.006	0.08	-10000	0	-0.31	13	13
EnzymeConsortium:2.7.1.37	-0.013	0.048	0.17	9	-0.17	7	16
response to UV	0	0	0.002	12	-0.002	1	13
RAF1	-0.01	0.038	0.17	6	-0.14	10	16
CRADD	0.036	0.006	-10000	0	0	12	12
mol:ceramide	0.003	0.032	0.11	1	-0.13	10	11
I-kappa-B-alpha/RELA/p50/ubiquitin	0.039	0.033	-10000	0	-0.11	18	18
MADD	0.035	0.006	-10000	0	0	15	15
MAP3K1	-0.002	0.033	0.15	2	-0.14	7	9
TRADD	0.036	0.005	-10000	0	0	11	11
RELA/p50	0.036	0.005	-10000	0	0	9	9
MAPK3	-0.006	0.048	0.16	14	-0.16	5	19
MAPK1	-0.012	0.057	0.17	9	-0.2	14	23
p50/RELA/I-kappa-B-alpha	0.043	0.038	-10000	0	-0.14	18	18
FADD	0.009	0.073	-10000	0	-0.29	8	8
KSR1	-0.004	0.031	0.11	1	-0.15	6	7
MAPK8	-0.01	0.029	0.16	2	-0.15	3	5
TRAF2	0.036	0.006	-10000	0	0	15	15
response to radiation	0	0	0.002	1	-10000	0	1
CHUK	-0.008	0.074	-10000	0	-0.3	13	13
TNF R/SODD	0.035	0.054	-10000	0	-0.14	42	42
TNF	0.036	0.003	-10000	0	0	4	4
CYCS	0.017	0.052	0.15	22	-0.14	9	31
IKBKG	-0.006	0.078	-10000	0	-0.29	16	16
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.015	0.083	-10000	0	-0.34	10	10
RELA	0.036	0.005	-10000	0	0	9	9
RIPK1	0.035	0.007	-10000	0	0	20	20
AIFM1	-0.004	0.039	0.12	14	-0.14	11	25
TNF/TNF R/SODD	0.053	0.055	-10000	0	-0.12	41	41
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
response to heat	0	0	0.002	1	-10000	0	1
CASP8	0.036	0.079	-10000	0	-0.55	8	8
NSMAF	0.008	0.082	0.21	5	-0.3	15	20
response to hydrogen peroxide	0	0	0.002	12	-0.002	1	13
BCL2	0.035	0.007	-10000	0	0	20	20

×

Arf6 trafficking events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	0.036	0.005	-10000	0	0	11	11
CLTC	0.013	0.087	-10000	0	-0.32	24	24
calcium ion-dependent exocytosis	0.017	0.067	0.13	1	-0.22	18	19
Dynamin 2/GTP	0.026	0.011	-10000	0	-0.1	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.004	0.079	-10000	0	-0.28	27	27
CPE	-0.015	0.009	-10000	0	-0.11	1	1
CTNNB1	0.036	0.006	-10000	0	0	15	15
membrane fusion	0.019	0.066	-10000	0	-0.17	31	31
CTNND1	-0.019	0.011	0.086	1	-0.18	1	2
DNM2	0.035	0.009	-10000	0	0	29	29
mol:PI-4-5-P2	0.011	0.066	0.16	2	-0.22	18	20
TSHR	-0.016	0.009	0.091	1	-0.11	1	2
INS	0.012	0.081	-10000	0	-0.44	14	14
BIN1	0.031	0.013	-10000	0	0	77	77
mol:Choline	0.019	0.066	-10000	0	-0.17	31	31
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.005	-10000	0	-0.11	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.035	0.008	-10000	0	0	27	27
mol:Ca2+	0.025	0.011	-10000	0	-0.1	1	1
JUP	0.012	0.069	-10000	0	-0.27	21	21
ASAP2/amphiphysin II	0.028	0.045	-10000	0	-0.1	48	48
ARF6/GTP	0.025	0.009	-10000	0	-0.13	1	1
CDH1	0.009	0.071	-10000	0	-0.26	24	24
clathrin-independent pinocytosis	0.025	0.009	-10000	0	-0.13	1	1
MAPK8IP3	0.036	0.004	-10000	0	0	7	7
positive regulation of endocytosis	0.025	0.009	-10000	0	-0.13	1	1
EXOC2	0.036	0.006	-10000	0	0	15	15
substrate adhesion-dependent cell spreading	0.005	0.052	-10000	0	-0.3	5	5
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.034	0.01	-10000	0	0	37	37
regulation of calcium-dependent cell-cell adhesion	-0.038	0.076	0.27	21	-10000	0	21
positive regulation of phagocytosis	-0.015	0.007	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.046	0.014	-10000	0	-0.12	1	1
ACAP1	0.02	0.063	-10000	0	-0.22	16	16
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	0.004	0.062	-10000	0	-0.3	14	14
clathrin heavy chain/ACAP1	0.017	0.084	0.2	9	-0.32	10	19
JIP4/KLC1	0.036	0.035	-10000	0	-0.1	26	26
EXOC1	0.033	0.011	-10000	0	0	50	50
exocyst	0.003	0.051	-10000	0	-0.31	5	5
RALA/GTP	0.013	0.03	-10000	0	-0.13	17	17
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.038	0.038	-10000	0	-0.12	26	26
receptor recycling	0.025	0.009	-10000	0	-0.13	1	1
CTNNA1	-0.019	0.011	0.086	1	-0.18	1	2
NME1	-0.009	0.005	-10000	0	-0.11	1	1
clathrin coat assembly	0.012	0.087	-10000	0	-0.32	24	24
IL2RA	0.007	0.067	-10000	0	-0.32	14	14
VAMP3	-0.015	0.007	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.032	0.082	-10000	0	-0.3	10	10
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.001	0.043	-10000	0	-0.21	15	15
PLD2	-0.001	0.043	-10000	0	-0.21	15	15
EXOC5	0.03	0.014	-10000	0	0	85	85
PIP5K1C	0.009	0.062	-10000	0	-0.23	15	15
SDC1	0.014	0.073	-10000	0	-0.26	24	24
ARF6/GDP	0.026	0.006	-10000	0	0	27	27
EXOC7	0.036	0.005	-10000	0	0	10	10
E-cadherin/beta catenin	0.041	0.079	-10000	0	-0.28	21	21
mol:Phosphatidic acid	0.019	0.066	-10000	0	-0.17	31	31
endocytosis	-0.027	0.044	0.1	48	-10000	0	48
SCAMP2	0.034	0.009	-10000	0	0	31	31
ADRB2	0.011	0.086	0.23	1	-0.32	21	22
EXOC3	0.036	0.003	-10000	0	0	4	4
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.023	0.01	0.089	1	-0.1	1	2
KLC1	0	0	-10000	0	-10000	0	0
AVPR2	0.005	0.083	-10000	0	-0.32	21	21
RALA	0.024	0.018	-10000	0	0	180	180
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.021	0.084	0.22	1	-0.28	23	24

×

Arf1 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
coatomer protein complex	0.009	0.034	0.14	28	-0.22	2	30
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.009	0.046	0.12	2	-0.19	7	9
AP2	0.021	0.027	-10000	0	-0.13	15	15
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.027	0.036	-10000	0	-0.12	15	15
CLTB	0.036	0.005	-10000	0	0	11	11
coatomer protein complex/ARF1/GTP/ER cargo protein	0.014	0.031	-10000	0	-0.18	10	10
CD4	0.031	0.013	-10000	0	0	72	72
CLTA	0.034	0.01	-10000	0	0	42	42
mol:GTP	-0.003	0.002	-10000	0	-0.019	6	6
ARFGAP1	-0.011	0.003	0	41	-10000	0	41
mol:PI-4-5-P2	0.008	0.019	0.1	11	-10000	0	11
ARF1/GTP	0.019	0.017	-10000	0	-0.1	8	8
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.031	-10000	0	-0.18	9	9
mol:Choline	0.008	0.019	0.11	11	-10000	0	11
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.035	0.008	-10000	0	0	24	24
DDEF1	0.006	0.018	0.11	8	-10000	0	8
ARF1/GDP	0.007	0.011	-10000	0	-0.086	3	3
AP2M1	0.034	0.01	-10000	0	0	37	37
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.012	0.017	0.066	1	-0.11	9	10
Rac/GTP	0.016	0.02	-10000	0	-0.14	5	5
ARF1/GTP/GGA3/ARF-GAP1	0.041	0.025	-10000	0	-0.1	8	8
ARFIP2	0.032	0.014	-10000	0	-0.038	13	13
COPA	0.036	0.006	-10000	0	0	13	13
RAC1	0.024	0.017	-10000	0	0	173	173
ARF1/GTP/coatomer protein complex	0.005	0.044	-10000	0	-0.19	10	10
ARF1/GTP/ARHGAP10	0.021	0.015	-10000	0	-0.11	6	6
GGA3	0.036	0.004	-10000	0	0	7	7
ARF1/GTP/Membrin	0.028	0.025	-10000	0	-0.24	3	3
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.005	0.036	-10000	0	-0.18	12	12
ARF1/GDP/Membrin	0.031	0.028	-10000	0	-0.27	3	3
Arfaptin 2/Rac/GDP	0.027	0.035	-10000	0	-0.12	15	15
CYTH2	-0.003	0.002	-10000	0	-0.019	6	6
ARF1/GTP/GGA3	0.044	0.021	-10000	0	-0.12	6	6
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.017	0.019	-10000	0	-0.13	5	5
mol:Brefeldin A	0	0	-10000	0	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	0.004	0.058	-10000	0	-0.19	31	31
PLD2	0.008	0.019	0.11	11	-10000	0	11
ARF-GAP1/v-SNARE	-0.011	0.003	0	41	-10000	0	41
PIP5K1A	0.008	0.019	0.1	11	-10000	0	11
ARF1/GTP/Membrin/GBF1/p115	0.002	0.036	-10000	0	-0.11	8	8
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.008	0.019	0.11	11	-10000	0	11
KDEL Receptor/Ligand/ARF-GAP1	-0.011	0.003	0	41	-10000	0	41
GOSR2	0.015	0.023	-10000	0	-0.31	2	2
USO1	0.002	0.006	0.036	10	-0.03	4	14
GBF1	-0.075	0.15	-10000	0	-0.31	140	140
ARF1/GTP/Arfaptin 2	0.041	0.033	-10000	0	-0.12	17	17
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.031	0.046	-10000	0	-0.12	35	35

×

Canonical NF-kappaB 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
FBXW11	0.033	0.02	0.077	8	-0.076	13	21
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.003	0.079	-10000	0	-0.25	18	18
ERC1	0	0	-10000	0	-10000	0	0
RIP2/NOD2	0.026	0.011	-10000	0	-0.13	2	2
NFKBIA	-0.033	0.046	0.2	1	-0.28	14	15
BIRC2	0.036	0.005	-10000	0	0	11	11
IKBKB	0.036	0.003	-10000	0	0	4	4
RIPK2	0.036	0.006	-10000	0	0	14	14
IKBKG	0.021	0.046	-10000	0	-0.25	9	9
IKK complex/A20	0.06	0.072	-10000	0	-0.26	8	8
NEMO/A20/RIP2	0.036	0.006	-10000	0	0	14	14
XPO1	0.036	0.004	-10000	0	0	5	5
NEMO/ATM	0.04	0.054	-10000	0	-0.29	7	7
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
Exportin 1/RanGTP	0.047	0.022	-10000	0	-0.14	6	6
IKK complex/ELKS	0.029	0.052	-10000	0	-0.25	7	7
BCL10/MALT1/TRAF6	0.063	0.034	-10000	0	-0.12	10	10
NOD2	0	0	-10000	0	-10000	0	0
NFKB1	0.034	0.02	0.077	9	-0.073	13	22
RELA	0.034	0.02	0.077	9	-0.072	15	24
MALT1	0.034	0.009	-10000	0	0	32	32
cIAP1/UbcH5C	0.05	0.027	-10000	0	-0.18	6	6
ATM	0.034	0.009	-10000	0	0	35	35
TNF/TNFR1A	0.035	0.055	-10000	0	-0.14	43	43
TRAF6	0.036	0.005	-10000	0	0	10	10
PRKCA	0.036	0.004	-10000	0	0	6	6
CHUK	0.025	0.017	-10000	0	0	163	163
UBE2D3	0.036	0.006	-10000	0	0	12	12
TNF	0.036	0.003	-10000	0	0	4	4
NF kappa B1 p50/RelA	0.065	0.06	-10000	0	-0.17	27	27
BCL10	0.035	0.007	-10000	0	0	20	20
proteasomal ubiquitin-dependent protein catabolic process	-0.033	0.046	0.2	1	-0.27	14	15
beta TrCP1/SCF ubiquitin ligase complex	0.033	0.021	0.077	8	-0.076	13	21
TNFRSF1A	0.032	0.012	-10000	0	0	64	64
IKK complex	0.041	0.06	-10000	0	-0.26	7	7
CYLD	0.036	0.006	-10000	0	0	15	15
IKK complex/PKC alpha	0.051	0.066	-10000	0	-0.26	7	7

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	0.033	0.027	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.014	0.016	-10000	0	-10000	0	0
mol:DAG	-0.019	0.032	0.19	1	-10000	0	1
VEGFR1 homodimer/NRP1/VEGFR 121	0.008	0.017	-10000	0	-10000	0	0
CaM/Ca2+	-0.023	0.04	0.19	1	-10000	0	1
HIF1A	0.04	0.013	-10000	0	-10000	0	0
GAB1	0.032	0.012	-10000	0	0	59	59
AKT1	-0.032	0.087	0.2	7	-0.3	24	31
PLCG1	-0.019	0.032	0.19	1	-10000	0	1
NOS3	0.008	0.066	-10000	0	-0.32	6	6
CBL	0.036	0.004	-10000	0	0	7	7
mol:NO	0.013	0.072	-10000	0	-0.31	6	6
FLT1	0.016	0.008	-10000	0	-10000	0	0
PGF	0.031	0.013	-10000	0	0	71	71
VEGFR1 homodimer/NRP2/VEGFR121	0.03	0.025	-10000	0	-10000	0	0
CALM1	0.033	0.011	-10000	0	0	54	54
PIK3CA	0.031	0.013	-10000	0	0	80	80
eNOS/Hsp90	0.001	0.068	-10000	0	-0.3	6	6
endothelial cell proliferation	-0.006	0.048	-10000	0	-0.31	3	3
mol:Ca2+	-0.019	0.032	0.19	1	-10000	0	1
MAPK3	-0.027	0.033	-10000	0	-10000	0	0
MAPK1	-0.027	0.035	0.15	2	-10000	0	2
PIK3R1	0.032	0.012	-10000	0	0	63	63
PLGF homodimer	0.031	0.013	-10000	0	0	71	71
PRKACA	0.035	0.008	-10000	0	0	25	25
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.016	0.018	-10000	0	0	290	290
VEGFA homodimer	0	0	-10000	0	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.014	0.016	-10000	0	-10000	0	0
platelet activating factor biosynthetic process	-0.028	0.045	0.21	1	-10000	0	1
PI3K	0.037	0.077	-10000	0	-0.2	15	15
PRKCA	-0.024	0.031	0.17	1	-10000	0	1
PRKCB	-0.017	0.029	0.17	1	-10000	0	1
VEGFR1 homodimer/PLGF homodimer	0.03	0.029	-10000	0	-10000	0	0
VEGFA	0	0	-10000	0	-10000	0	0
VEGFB	0.036	0.005	-10000	0	0	8	8
mol:IP3	-0.019	0.032	0.19	1	-10000	0	1
RASA1	-0.026	0.026	0.19	1	-10000	0	1
NRP2	0.036	0.005	-10000	0	0	8	8
VEGFR1 homodimer	0.016	0.008	-10000	0	-10000	0	0
VEGFB homodimer	0.036	0.005	-10000	0	0	8	8
NCK1	0.035	0.008	-10000	0	0	27	27
eNOS/Caveolin-1	0.002	0.069	-10000	0	-0.32	7	7
PTPN11	0.036	0.005	-10000	0	0	11	11
mol:PI-3-4-5-P3	0.035	0.076	-10000	0	-0.2	15	15
mol:L-citrulline	0.013	0.072	-10000	0	-0.31	6	6
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.041	0.043	-10000	0	-0.19	3	3
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.028	0.028	-10000	0	-0.19	1	1
CD2AP	0.034	0.01	-10000	0	0	41	41
PI3K/GAB1	0.041	0.087	-10000	0	-0.19	22	22
PDPK1	-0.03	0.066	0.24	4	-0.26	2	6
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.029	0.029	-10000	0	-0.19	1	1
mol:NADP	0.013	0.072	-10000	0	-0.31	6	6
HSP90AA1	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.042	-10000	0	-0.18	3	3
VEGFR1 homodimer/NRP2	0.032	0.028	-10000	0	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.035	0.007	-10000	0	0	21	21
Ran/GTP/Exportin 1/HDAC4	-0.032	0.03	-10000	0	-0.15	20	20
MDM2/SUMO1	0.034	0.053	-10000	0	-0.21	6	6
HDAC4	0.035	0.009	-10000	0	0	29	29
Ran/GTP/Exportin 1/HDAC1	-0.031	0.03	-10000	0	-0.14	26	26
SUMO1	0.036	0.003	-10000	0	0	4	4
NPC/RanGAP1/SUMO1	0.005	0.034	-10000	0	-0.15	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
XPO1	-0.008	0.041	-10000	0	-0.16	21	21
EntrezGene:23636	0	0	-10000	0	-10000	0	0
RAN	0.036	0.005	-10000	0	0	10	10
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.035	0.008	-10000	0	0	25	25
SUMO1/HDAC4	0.033	0.058	-10000	0	-0.23	6	6
SUMO1/HDAC1	0.036	0.055	-10000	0	-0.22	6	6
RANGAP1	0.033	0.01	-10000	0	0	45	45
MDM2/SUMO1/SUMO1	0.077	0.047	-10000	0	-0.12	17	17
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.007	0.034	-10000	0	-0.15	21	21
Ran/GTP	0.019	0.05	-10000	0	-0.15	21	21
EntrezGene:23225	0	0	-10000	0	-10000	0	0
MDM2	0.033	0.011	-10000	0	0	46	46
UBE2I	0.036	0.004	-10000	0	0	6	6
Ran/GTP/Exportin 1	0.013	0.051	0.2	1	-0.26	5	6
NPC	0.017	0.02	-10000	0	-0.087	18	18
PIAS2	0.035	0.007	-10000	0	0	18	18
PIAS1	0.035	0.008	-10000	0	0	27	27
EntrezGene:9972	0	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0.037	0.028	-9999	0	-0.095	20	20
MAPK9	0.007	0.001	-9999	0	0	15	15
adrenocorticotropin secretion	-0.011	0.002	0	17	-10000	0	17
GNB1/GNG2	0.02	0.025	-9999	0	-0.11	20	20
GNB1	0.035	0.007	-9999	0	0	20	20
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	0	-10000	0	0
mol:GDP	0	0	-9999	0	-10000	0	0
MAPK14	0.008	0.001	-9999	0	0	6	6
Gs family/GTP	0.023	0.004	-9999	0	-10000	0	0
EntrezGene:2778	0	0	-9999	0	-10000	0	0
vasopressin secretion	0	0	-9999	0	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	0	-10000	0	0
glutamate secretion	0.003	0	-9999	0	-10000	0	0
GNAL	0.036	0.006	-9999	0	0	13	13
GNG2	0	0	-9999	0	-10000	0	0
CRH	0.035	0.007	-9999	0	0	17	17
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.006	0.003	-9999	0	0	138	138
MAPK11	0.007	0.002	-9999	0	0	49	49

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.054	0.018	-10000	0	-10000	0	0
KIRREL	0.038	0.01	-10000	0	-0.041	1	1
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.054	0.018	-10000	0	-10000	0	0
PLCG1	0.035	0.007	-10000	0	0	19	19
ARRB2	0.035	0.008	-10000	0	0	26	26
WASL	0.024	0.017	-10000	0	0	172	172
Nephrin/NEPH1/podocin/CD2AP	0.084	0.05	0.2	1	-0.12	17	18
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	0.015	0.036	-10000	0	-0.23	5	5
FYN	-0.008	0.046	0.18	24	-10000	0	24
mol:Ca2+	0.086	0.037	0.19	1	-0.12	3	4
mol:DAG	0.087	0.037	0.2	1	-0.12	3	4
NPHS2	0.039	0.008	-10000	0	-0.041	1	1
mol:IP3	0.087	0.037	0.2	1	-0.12	3	4
regulation of endocytosis	0.052	0.05	-10000	0	-0.13	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.07	0.028	0.18	1	-10000	0	1
establishment of cell polarity	0.054	0.018	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.096	0.058	-10000	0	-0.14	16	16
Nephrin/NEPH1/beta Arrestin2	0.055	0.051	-10000	0	-0.13	4	4
NPHS1	0.039	0.01	0.077	6	-10000	0	6
Nephrin/NEPH1/podocin	0.053	0.044	0.21	1	-0.1	1	2
TJP1	0.034	0.01	-10000	0	0	38	38
NCK1	0.035	0.008	-10000	0	0	27	27
NCK2	0.035	0.007	-10000	0	0	17	17
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.089	0.038	0.2	1	-0.12	3	4
CD2AP	0.034	0.01	-10000	0	0	41	41
Nephrin/NEPH1/podocin/GRB2	0.087	0.043	0.2	1	-0.12	7	8
GRB2	0.035	0.007	-10000	0	0	17	17
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.014	0.049	0.18	25	-10000	0	25
cytoskeleton organization	-0.009	0.036	0.21	5	-0.22	3	8
Nephrin/NEPH1	0.046	0.016	-10000	0	-10000	0	0
Nephrin/NEPH1/ZO-1	0.064	0.038	-10000	0	-0.14	9	9

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.032	0.19	0.53	1	-0.66	20	21
PCK1	0.048	0.12	0.52	3	-0.53	4	7
HNF4A	0.048	0.16	0.69	1	-0.71	6	7
KCNJ11	0.057	0.18	0.47	4	-0.57	18	22
AKT1	0.057	0.13	0.37	1	-0.35	20	21
response to starvation	0.003	0.002	-10000	0	-10000	0	0
DLK1	0.07	0.19	0.56	3	-0.57	17	20
NKX2-1	0.025	0.11	0.28	3	-0.32	16	19
ACADM	0.041	0.18	0.49	2	-0.66	14	16
TAT	0.045	0.13	0.5	2	-0.6	6	8
CEBPB	0.034	0.015	0.12	1	-10000	0	1
CEBPA	0.031	0.018	-10000	0	-10000	0	0
TTR	0.02	0.18	0.64	2	-0.64	12	14
PKLR	0.046	0.17	0.47	4	-0.63	9	13
APOA1	0.064	0.2	0.63	3	-0.84	7	10
CPT1C	0.045	0.16	0.44	4	-0.53	17	21
ALAS1	0.025	0.24	-10000	0	-1.2	15	15
TFRC	0.014	0.29	0.52	5	-0.96	35	40
FOXF1	0.031	0.013	-10000	0	-10000	0	0
NF1	0.034	0.036	-10000	0	-0.17	15	15
HNF1A (dimer)	0.006	0.005	0.11	1	-10000	0	1
CPT1A	0.043	0.16	0.53	1	-0.63	9	10
HMGCS1	0.047	0.17	0.56	2	-0.58	12	14
NR3C1	0.046	0.02	-10000	0	-10000	0	0
CPT1B	0.043	0.16	0.49	2	-0.58	12	14
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.036	0.005	-10000	0	-10000	0	0
GCK	0.094	0.19	0.5	14	-0.56	11	25
CREB1	0.043	0.013	0.11	14	-10000	0	14
IGFBP1	0.058	0.13	0.62	1	-0.63	5	6
PDX1	0.047	0.11	0.33	4	-0.31	12	16
UCP2	0.012	0.24	0.5	3	-0.68	43	46
ALDOB	0.057	0.18	0.49	3	-0.61	14	17
AFP	0.015	0.032	0.27	2	-10000	0	2
BDH1	0.033	0.19	0.53	1	-0.68	19	20
HADH	0.057	0.18	0.47	4	-0.57	18	22
F2	0.063	0.2	0.78	1	-0.84	7	8
HNF1A	0.006	0.005	0.11	1	-10000	0	1
G6PC	0.006	0.083	0.42	1	-10000	0	1
SLC2A2	0.055	0.13	0.44	1	-0.43	5	6
INS	0.025	0.042	0.19	14	-0.095	34	48
FOXA1	0.014	0.013	0.15	2	-10000	0	2
FOXA3	0.019	0.056	0.2	5	-0.18	24	29
FOXA2	0.091	0.22	0.65	3	-0.65	18	21
ABCC8	0.056	0.18	0.51	2	-0.62	13	15
ALB	0.016	0.032	0.3	1	-10000	0	1

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.036	0.005	-9999	0	8	8
Aurora C/Aurora B/INCENP	0.063	0.022	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.005	0.064	-9999	-0.39	13	13
AURKB	0.034	0.01	-9999	0	39	39
AURKC	0.036	0.006	-9999	0	15	15

×

Class IB PI3K non-lipid kinase events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.036	0.005	0	9	-9999	0	9
PI3K Class IB/PDE3B	0.036	0.005	-9999	0	0	9	9
PDE3B	0.036	0.005	-9999	0	0	9	9

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	-0.009	0.001	0	4	-9999	4
ADCY5	-0.009	0.001	0	4	-9999	4
ADCY6	-0.017	0.006	0.085	1	-9999	1
ADCY7	-0.014	0.018	0.085	15	-9999	15
ADCY1	-0.012	0.009	-10000	0	-9999	0
ADCY2	-0.017	0.007	0.085	2	-9999	2
ADCY3	-0.009	0.001	0	4	-9999	4
ADCY8	-0.007	0.032	0.085	54	-9999	54
PRKCE	-0.011	0.001	0	4	-9999	4
ADCY9	-0.017	0.009	0.085	4	-9999	4
mol:DAG	0	0	-10000	0	-9999	0
cAMP biosynthetic process	0.018	0.043	0.17	12	-9999	12

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.036	0.006	-10000	0	0	12	12
GNAT1/GTP	0.026	0.004	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.047	0.01	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.048	0.008	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
absorption of light	0	0	-10000	0	-10000	0	0
GNAT1	0.036	0.006	-10000	0	0	12	12
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.068	0.024	-10000	0	-10000	0	0
mol:Na +	0.043	0.016	-10000	0	-10000	0	0
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.045	0.015	-10000	0	-0.12	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.054	0.018	-10000	0	-10000	0	0
CNGB1	0.035	0.007	-10000	0	0	17	17
RDH5	0.035	0.007	-10000	0	0	19	19
SAG	0.036	0.005	-10000	0	0	8	8
mol:Ca2+	-0.033	0.031	0.18	9	-10000	0	9
Na + (4 Units)	0.04	0.018	-10000	0	-10000	0	0
RGS9	0.035	0.007	-10000	0	0	17	17
GNB1/GNGT1	0.031	0.038	-10000	0	-0.14	13	13
GNAT1/GDP	0.058	0.02	-10000	0	-0.1	1	1
GUCY2D	0.036	0.006	-10000	0	0	12	12
GNGT1	0.024	0.017	-10000	0	0	172	172
GUCY2F	0.037	0	-10000	0	-10000	0	0
GNB5	0.035	0.008	-10000	0	0	24	24
mol:GMP (4 units)	0.029	0.007	-10000	0	-10000	0	0
mol:11-cis-retinal	0.035	0.007	-10000	0	0	19	19
mol:cGMP	0.029	0.006	-10000	0	-10000	0	0
GNB1	0.035	0.007	-10000	0	0	20	20
Rhodopsin	0.051	0.013	-10000	0	-10000	0	0
SLC24A1	0.036	0.006	-10000	0	0	12	12
CNGA1	0.036	0.005	-10000	0	0	11	11
Metarhodopsin II	0.023	0.004	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.046	0.007	-10000	0	-10000	0	0
RGS9BP	0	0	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.009	0.029	-10000	0	-0.15	14	14
GCAP Family/Ca ++	0.023	0.001	-10000	0	-10000	0	0
PDE6A/B	0.053	0.009	-10000	0	-10000	0	0
mol:Pi	0.045	0.015	-10000	0	-0.11	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.041	0.041	-10000	0	-0.11	13	13
PDE6B	0.036	0.004	-10000	0	0	5	5
PDE6A	0.036	0.005	-10000	0	0	9	9
PDE6G	0.036	0.003	-10000	0	0	3	3
RHO	0.036	0.006	-10000	0	0	14	14
PDE6	0.084	0.027	-10000	0	-0.11	1	1
GUCA1A	0	0	-10000	0	-10000	0	0
GC2/GCAP Family	0.047	0.002	-10000	0	-10000	0	0
GUCA1C	0	0	-10000	0	-10000	0	0
GUCA1B	0.037	0.002	-10000	0	0	1	1

×

Ephrin A reverse signaling

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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	0.048	0.008	-10000	0	-9999	0	0
EFNA5	0.036	0.004	-10000	0	0	6	6
FYN	-0.019	0.016	0.18	2	-9999	0	2
neuron projection morphogenesis	0.048	0.008	-10000	0	-9999	0	0
cell-cell signaling	0	0	-10000	0	-9999	0	0
Ephrin A5/EPHA5	0.048	0.008	-10000	0	-9999	0	0
EPHA5	0.036	0.005	-10000	0	0	10	10