Glioblastoma Multiforme: PARADIGM pathway analysis of mRNA expression and copy number data<BR>(primary solid tumor cohort)

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	124
FOXM1 transcription factor network	102
Angiopoietin receptor Tie2-mediated signaling	87
Endothelins	83
TCGA08_p53	76
TCGA08_rtk_signaling	76
HIF-2-alpha transcription factor network	75
Thromboxane A2 receptor signaling	73
Ceramide signaling pathway	73
PDGFR-alpha signaling pathway	72

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	124	9473	76	-0.07	0.11	1000	-1000	-0.014	-1000
FOXM1 transcription factor network	102	5219	51	-0.3	0.056	1000	-1000	-0.043	-1000
Angiopoietin receptor Tie2-mediated signaling	87	7697	88	-0.29	0.053	1000	-1000	-0.049	-1000
Endothelins	83	7982	96	-0.12	0.037	1000	-1000	-0.023	-1000
TCGA08_p53	76	534	7	-0.002	0.033	1000	-1000	-0.011	-1000
TCGA08_rtk_signaling	76	1998	26	-0.033	0.1	1000	-1000	-0.018	-1000
HIF-2-alpha transcription factor network	75	3261	43	-0.081	0.048	1000	-1000	-0.041	-1000
Thromboxane A2 receptor signaling	73	7669	105	-0.07	0.045	1000	-1000	-0.021	-1000
Ceramide signaling pathway	73	5589	76	-0.087	0.072	1000	-1000	-0.019	-1000
PDGFR-alpha signaling pathway	72	3182	44	-0.096	0.037	1000	-1000	-0.025	-1000
Effects of Botulinum toxin	70	1836	26	-0.008	0.053	1000	-1000	-0.011	-1000
Syndecan-3-mediated signaling events	69	2441	35	-0.063	0.08	1000	-1000	-0.012	-1000
Canonical Wnt signaling pathway	66	3403	51	-0.1	0.068	1000	-1000	-0.021	-1000
Wnt signaling	66	468	7	-0.005	0.038	1000	-1000	0	-1000
PLK2 and PLK4 events	65	197	3	-0.019	0.036	1000	-1000	-0.02	-1000
Ras signaling in the CD4+ TCR pathway	65	1117	17	0	0.042	1000	-1000	0	-1000
Arf6 signaling events	64	4020	62	-0.004	0.094	1000	-1000	-0.002	-1000
TCGA08_retinoblastoma	63	505	8	-0.049	0.059	1000	-1000	-0.004	-1000
LPA receptor mediated events	62	6324	102	-0.12	0.037	1000	-1000	-0.033	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	62	2073	33	-0.048	0.069	1000	-1000	-0.008	-1000
Syndecan-1-mediated signaling events	61	2090	34	-0.009	0.036	1000	-1000	-0.014	-1000
EGFR-dependent Endothelin signaling events	61	1289	21	-0.017	0.036	1000	-1000	-0.024	-1000
Syndecan-4-mediated signaling events	59	4013	67	-0.15	0.037	1000	-1000	-0.031	-1000
S1P4 pathway	59	1478	25	-0.016	0.037	1000	-1000	-0.009	-1000
S1P5 pathway	58	996	17	-0.012	0.037	1000	-1000	-0.012	-1000
Nongenotropic Androgen signaling	57	2986	52	-0.087	0.06	1000	-1000	-0.024	-1000
Signaling events mediated by VEGFR1 and VEGFR2	53	6738	125	-0.058	0.05	1000	-1000	-0.04	-1000
amb2 Integrin signaling	52	4289	82	-0.017	0.076	1000	-1000	-0.021	-1000
Glypican 2 network	52	210	4	0	0.008	1000	-1000	0	-1000
IL2 signaling events mediated by STAT5	52	1147	22	-0.072	0.039	1000	-1000	-0.017	-1000
IL23-mediated signaling events	52	3137	60	-0.061	0.15	1000	-1000	-0.042	-1000
IL2 signaling events mediated by PI3K	51	2967	58	-0.19	0.047	1000	-1000	-0.029	-1000
Fc-epsilon receptor I signaling in mast cells	50	4915	97	-0.1	0.05	1000	-1000	-0.042	-1000
Syndecan-2-mediated signaling events	48	3329	69	-0.025	0.038	1000	-1000	-0.033	-1000
Osteopontin-mediated events	47	1821	38	-0.068	0.051	1000	-1000	-0.015	-1000
FoxO family signaling	47	3062	64	-0.17	0.053	1000	-1000	-0.018	-1000
Arf6 downstream pathway	46	1988	43	-0.026	0.05	1000	-1000	-0.03	-1000
Ephrin B reverse signaling	46	2212	48	-0.065	0.067	1000	-1000	-0.047	-1000
S1P1 pathway	46	1673	36	-0.026	0.038	1000	-1000	-0.019	-1000
BCR signaling pathway	46	4651	99	-0.049	0.052	1000	-1000	-0.025	-1000
JNK signaling in the CD4+ TCR pathway	44	753	17	-0.12	0.064	1000	-1000	-0.012	-1000
Presenilin action in Notch and Wnt signaling	44	2708	61	-0.081	0.08	1000	-1000	-0.039	-1000
Glypican 1 network	44	2144	48	-0.033	0.054	1000	-1000	-0.034	-1000
ErbB2/ErbB3 signaling events	43	2811	65	-0.042	0.037	1000	-1000	-0.046	-1000
Regulation of nuclear SMAD2/3 signaling	43	5873	136	-0.21	0.2	1000	-1000	-0.04	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	43	2956	68	-0.099	0.048	1000	-1000	-0.027	-1000
Signaling events mediated by PTP1B	42	3260	76	-0.034	0.061	1000	-1000	-0.023	-1000
mTOR signaling pathway	42	2264	53	-0.038	0.047	1000	-1000	-0.026	-1000
EPHB forward signaling	42	3620	85	-0.053	0.082	1000	-1000	-0.042	-1000
IL12-mediated signaling events	41	3595	87	-0.11	0.1	1000	-1000	-0.014	-1000
Noncanonical Wnt signaling pathway	41	1086	26	-0.031	0.038	1000	-1000	-0.02	-1000
E-cadherin signaling in keratinocytes	41	1791	43	-0.041	0.064	1000	-1000	-0.019	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	40	2204	54	-0.035	0.078	1000	-1000	-0.025	-1000
Reelin signaling pathway	40	2279	56	-0.015	0.073	1000	-1000	-0.014	-1000
FAS signaling pathway (CD95)	40	1909	47	-0.14	0.049	1000	-1000	-0.023	-1000
Stabilization and expansion of the E-cadherin adherens junction	40	2968	74	-0.11	0.078	1000	-1000	-0.05	-1000
Class I PI3K signaling events	40	2938	73	-0.046	0.066	1000	-1000	-0.02	-1000
BMP receptor signaling	39	3204	81	-0.029	0.059	1000	-1000	-0.007	-1000
Class I PI3K signaling events mediated by Akt	39	2703	68	-0.033	0.066	1000	-1000	-0.019	-1000
Paxillin-dependent events mediated by a4b1	39	1432	36	-0.055	0.057	1000	-1000	-0.043	-1000
Signaling events mediated by PRL	39	1341	34	-0.029	0.048	1000	-1000	-0.024	-1000
Paxillin-independent events mediated by a4b1 and a4b7	38	1411	37	-0.034	0.085	1000	-1000	-0.016	-1000
Sphingosine 1-phosphate (S1P) pathway	37	1039	28	-0.02	0.037	1000	-1000	-0.02	-1000
PLK1 signaling events	37	3221	85	-0.037	0.062	1000	-1000	-0.021	-1000
Integrins in angiogenesis	37	3121	84	-0.042	0.071	1000	-1000	-0.019	-1000
Plasma membrane estrogen receptor signaling	37	3203	86	-0.069	0.053	1000	-1000	-0.038	-1000
p38 MAPK signaling pathway	37	1651	44	-0.003	0.043	1000	-1000	-0.008	-1000
IL1-mediated signaling events	36	2263	62	-0.039	0.075	1000	-1000	-0.037	-1000
Regulation of p38-alpha and p38-beta	36	1986	54	-0.035	0.048	1000	-1000	-0.034	-1000
IL6-mediated signaling events	36	2729	75	-0.081	0.098	1000	-1000	-0.028	-1000
Neurotrophic factor-mediated Trk receptor signaling	36	4320	120	-0.04	0.091	1000	-1000	-0.025	-1000
PDGFR-beta signaling pathway	36	3507	97	-0.053	0.066	1000	-1000	-0.043	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	35	2984	85	-0.13	0.12	1000	-1000	-0.035	-1000
IFN-gamma pathway	35	2394	68	-0.04	0.066	1000	-1000	-0.037	-1000
IGF1 pathway	35	2025	57	-0.049	0.067	1000	-1000	-0.027	-1000
EPO signaling pathway	34	1880	55	-0.006	0.069	1000	-1000	-0.021	-1000
Aurora B signaling	34	2297	67	-0.031	0.062	1000	-1000	-0.022	-1000
Caspase cascade in apoptosis	33	2512	74	-0.068	0.064	1000	-1000	-0.024	-1000
Signaling events regulated by Ret tyrosine kinase	33	2724	82	-0.051	0.069	1000	-1000	-0.025	-1000
E-cadherin signaling in the nascent adherens junction	33	2514	76	-0.044	0.091	1000	-1000	-0.038	-1000
Hedgehog signaling events mediated by Gli proteins	32	2104	65	-0.016	0.074	1000	-1000	-0.021	-1000
p75(NTR)-mediated signaling	32	4010	125	-0.025	0.084	1000	-1000	-0.04	-1000
Signaling events mediated by HDAC Class III	32	1284	40	-0.051	0.052	1000	-1000	-0.046	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	31	714	23	-0.022	0.057	1000	-1000	-0.005	-1000
Signaling mediated by p38-gamma and p38-delta	31	470	15	-0.026	0.037	1000	-1000	-0.019	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	31	1406	45	-0.027	0.077	1000	-1000	-0.018	-1000
S1P3 pathway	31	1322	42	-0.029	0.037	1000	-1000	-0.017	-1000
ErbB4 signaling events	30	2104	69	-0.071	0.064	1000	-1000	-0.02	-1000
IL4-mediated signaling events	30	2753	91	-0.31	0.058	1000	-1000	-0.059	-1000
Retinoic acid receptors-mediated signaling	30	1752	58	-0.047	0.06	1000	-1000	-0.013	-1000
Alternative NF-kappaB pathway	30	398	13	0	0.069	1000	-1000	0	-1000
TCR signaling in naïve CD8+ T cells	29	2773	93	-0.33	0.38	1000	-1000	-0.025	-1000
Insulin Pathway	29	2167	74	-0.053	0.085	1000	-1000	-0.031	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	29	2272	78	-0.023	0.076	1000	-1000	-0.034	-1000
Visual signal transduction: Cones	28	1067	38	-0.013	0.06	1000	-1000	-0.014	-1000
a4b1 and a4b7 Integrin signaling	28	144	5	0.029	0.053	1000	-1000	0.034	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	28	2356	83	-0.031	0.07	1000	-1000	-0.016	-1000
LPA4-mediated signaling events	27	331	12	-0.018	0.016	1000	-1000	-0.015	-1000
BARD1 signaling events	27	1543	57	-0.065	0.084	1000	-1000	-0.055	-1000
Aurora A signaling	27	1633	60	-0.017	0.059	1000	-1000	-0.019	-1000
Regulation of Telomerase	27	2834	102	-0.026	0.079	1000	-1000	-0.031	-1000
Nectin adhesion pathway	26	1700	63	-0.011	0.085	1000	-1000	-0.022	-1000
VEGFR1 specific signals	26	1471	56	-0.034	0.043	1000	-1000	-0.026	-1000
Insulin-mediated glucose transport	25	823	32	-0.019	0.044	1000	-1000	-0.019	-1000
Circadian rhythm pathway	24	545	22	-0.01	0.056	1000	-1000	-0.019	-1000
Glucocorticoid receptor regulatory network	24	2825	114	-0.13	0.065	1000	-1000	-0.048	-1000
Signaling events mediated by HDAC Class I	24	2523	104	-0.048	0.066	1000	-1000	-0.036	-1000
TRAIL signaling pathway	23	1141	48	-0.022	0.088	1000	-1000	-0.019	-1000
Regulation of Androgen receptor activity	23	1628	70	-0.032	0.068	1000	-1000	-0.027	-1000
RXR and RAR heterodimerization with other nuclear receptor	22	1175	52	-0.046	0.11	1000	-1000	-0.021	-1000
Calcium signaling in the CD4+ TCR pathway	22	701	31	-0.022	0.074	1000	-1000	-0.025	-1000
E-cadherin signaling events	22	114	5	0.034	0.064	1000	-1000	0.034	-1000
Arf6 trafficking events	21	1510	71	-0.037	0.049	1000	-1000	-0.032	-1000
Coregulation of Androgen receptor activity	20	1529	76	-0.028	0.068	1000	-1000	-0.018	-1000
Signaling events mediated by HDAC Class II	20	1572	75	-0.03	0.094	1000	-1000	-0.026	-1000
Canonical NF-kappaB pathway	19	763	39	-0.033	0.066	1000	-1000	-0.017	-1000
Atypical NF-kappaB pathway	19	606	31	-0.023	0.038	1000	-1000	-0.019	-1000
ceramide signaling pathway	18	905	49	-0.016	0.055	1000	-1000	-0.015	-1000
Signaling mediated by p38-alpha and p38-beta	18	819	44	-0.014	0.074	1000	-1000	-0.013	-1000
Arf1 pathway	18	1016	54	-0.054	0.045	1000	-1000	-0.012	-1000
Sumoylation by RanBP2 regulates transcriptional repression	17	459	27	-0.033	0.075	1000	-1000	-0.026	-1000
Cellular roles of Anthrax toxin	16	630	39	-0.074	0.037	1000	-1000	-0.01	-1000
Rapid glucocorticoid signaling	16	329	20	-0.011	0.037	1000	-1000	-0.011	-1000
Nephrin/Neph1 signaling in the kidney podocyte	15	535	34	-0.056	0.098	1000	-1000	-0.041	-1000
Signaling events mediated by the Hedgehog family	15	813	52	-0.016	0.089	1000	-1000	-0.02	-1000
Aurora C signaling	15	110	7	0	0.061	1000	-1000	-0.006	-1000
FOXA2 and FOXA3 transcription factor networks	11	519	46	0	0.11	1000	-1000	-0.036	-1000
IL27-mediated signaling events	11	570	51	-0.023	0.069	1000	-1000	-0.036	-1000
Class IB PI3K non-lipid kinase events	11	33	3	-0.037	0.037	1000	-1000	-0.034	-1000
Visual signal transduction: Rods	8	463	52	-0.035	0.087	1000	-1000	-0.009	-1000
Ephrin A reverse signaling	2	20	7	-0.019	0.049	1000	-1000	-0.013	-1000
Total	5247	294883	7203	-7.1	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	0.04	0.45	0.6	99	-0.73	83	182
HDAC7	-0.003	0.009	-10000	0	-0.043	14	14
HIF1A/ARNT/Cbp/p300/Src-1	-0.031	0.38	0.58	32	-0.71	73	105
SMAD4	0.034	0.014	0.081	12	0	58	70
ID2	0.061	0.46	0.64	96	-0.72	83	179
AP1	0.014	0.081	-10000	0	-0.17	73	73
ABCG2	0.027	0.46	0.62	97	-0.73	85	182
HIF1A	0.045	0.13	0.24	74	-0.16	60	134
TFF3	0.057	0.46	0.65	89	-0.72	81	170
GATA2	0.04	0.014	0.077	22	-0.091	2	24
AKT1	0.056	0.14	0.26	84	-0.2	36	120
response to hypoxia	0.017	0.096	0.18	87	-0.12	40	127
MCL1	0.068	0.46	0.64	97	-0.72	83	180
NDRG1	0.011	0.44	0.6	81	-0.73	87	168
SERPINE1	-0.053	0.38	0.56	41	-0.75	76	117
FECH	0.053	0.46	0.64	90	-0.72	83	173
FURIN	0.065	0.46	0.64	98	-0.72	83	181
NCOA2	0.038	0.006	-10000	0	-10000	0	0
EP300	0.079	0.2	0.39	92	-0.3	31	123
HMOX1	-0.003	0.45	0.64	70	-0.75	86	156
BHLHE40	-0.049	0.39	0.54	74	-0.69	89	163
BHLHE41	-0.049	0.39	0.54	74	-0.69	89	163
HIF1A/ARNT/SMAD3/SMAD4/SP1	0.069	0.18	0.36	35	-0.23	37	72
ENG	0.034	0.16	0.32	50	-0.26	18	68
JUN	0.036	0.013	0.066	2	-0.001	45	47
RORA	0.037	0.45	0.63	83	-0.72	84	167
ABCB1	-0.049	0.2	-10000	0	-0.84	25	25
TFRC	0.045	0.46	0.64	89	-0.73	83	172
CXCR4	0.029	0.46	0.64	81	-0.74	86	167
TF	-0.065	0.4	0.65	38	-0.72	88	126
CITED2	0.027	0.45	0.61	92	-0.72	86	178
HIF1A/ARNT	-0.061	0.43	0.66	21	-0.84	73	94
LDHA	-0.065	0.28	-10000	0	-0.98	40	40
ETS1	0.072	0.47	0.64	101	-0.72	83	184
PGK1	0.062	0.47	0.64	98	-0.73	84	182
NOS2	-0.049	0.39	0.54	74	-0.69	89	163
ITGB2	0.02	0.45	0.63	78	-0.74	86	164
ALDOA	0.071	0.47	0.64	101	-0.73	82	183
Cbp/p300/CITED2	-0.025	0.44	0.62	59	-0.78	84	143
FOS	0.026	0.019	-10000	0	0	167	167
HK2	0.073	0.47	0.64	102	-0.73	82	184
SP1	0.033	0.059	0.11	28	-0.15	39	67
GCK	0.11	0.26	0.63	48	-0.53	6	54
HK1	0.017	0.44	0.64	74	-0.72	83	157
NPM1	0.067	0.46	0.64	98	-0.72	82	180
EGLN1	0.065	0.46	0.62	109	-0.72	83	192
CREB1	0.033	0.034	-10000	0	-0.099	30	30
PGM1	0.066	0.47	0.63	111	-0.73	82	193
SMAD3	0.038	0.009	0.081	12	-10000	0	12
EDN1	0.059	0.22	0.48	34	-0.54	18	52
IGFBP1	0.007	0.41	0.61	68	-0.74	71	139
VEGFA	-0.017	0.38	0.57	56	-0.65	84	140
HIF1A/JAB1	0.046	0.1	0.2	44	-0.19	17	61
CP	-0.02	0.43	0.63	62	-0.74	88	150
CXCL12	-0.019	0.41	0.61	53	-0.72	80	133
COPS5	0.038	0.006	-10000	0	-10000	0	0
SMAD3/SMAD4	0.041	0.052	0.14	6	-0.14	34	40
BNIP3	0.005	0.44	0.65	68	-0.73	82	150
EGLN3	0.017	0.44	0.61	85	-0.72	82	167
CA9	-0.006	0.42	0.61	57	-0.73	79	136
TERT	0.065	0.46	0.65	98	-0.72	83	181
ENO1	0.06	0.47	0.63	111	-0.73	82	193
PFKL	0.069	0.47	0.65	99	-0.72	83	182
NCOA1	0.034	0.011	-10000	0	0	49	49
ADM	-0.006	0.44	0.64	67	-0.74	89	156
ARNT	0.048	0.12	0.23	78	-0.14	67	145
HNF4A	0.038	0.012	-10000	0	-10000	0	0
ADFP	-0.049	0.39	0.54	74	-0.69	89	163
SLC2A1	0.016	0.39	0.59	73	-0.63	81	154
LEP	0.024	0.42	0.61	81	-0.74	70	151
HIF1A/ARNT/Cbp/p300	-0.045	0.38	0.58	29	-0.72	73	102
EPO	0.029	0.31	0.56	49	-0.6	38	87
CREBBP	0.084	0.19	0.39	95	-0.27	28	123
HIF1A/ARNT/Cbp/p300/HDAC7	-0.07	0.37	0.56	20	-0.73	78	98
PFKFB3	0.023	0.45	0.65	77	-0.73	82	159
NT5E	-0.014	0.43	0.64	58	-0.72	89	147

×

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	-0.093	0.63	0.96	28	-1.2	101	129
PLK1	0.055	0.14	0.62	10	-0.77	5	15
BIRC5	-0.073	0.43	0.62	10	-1.2	59	69
HSPA1B	-0.093	0.63	0.9	33	-1.2	103	136
MAP2K1	0.042	0.095	0.25	44	-10000	0	44
BRCA2	-0.09	0.63	1	26	-1.2	98	124
FOXM1	-0.22	0.9	1.1	26	-1.8	102	128
XRCC1	-0.087	0.64	1	27	-1.2	100	127
FOXM1B/p19	-0.3	0.55	-10000	0	-1.3	101	101
Cyclin D1/CDK4	-0.11	0.56	0.87	20	-1.1	104	124
CDC2	-0.1	0.68	1	34	-1.3	102	136
TGFA	-0.069	0.56	0.84	35	-1	103	138
SKP2	-0.091	0.63	0.98	28	-1.2	100	128
CCNE1	0.024	0.037	0.1	15	-0.035	110	125
CKS1B	-0.1	0.66	1	28	-1.2	105	133
RB1	-0.08	0.36	0.46	13	-0.99	51	64
FOXM1C/SP1	-0.19	0.71	0.85	18	-1.4	103	121
AURKB	0.056	0.13	0.67	9	-0.88	2	11
CENPF	-0.12	0.69	1	30	-1.2	113	143
CDK4	0.024	0.049	0.15	23	-10000	0	23
MYC	-0.11	0.54	0.78	26	-1	105	131
CHEK2	0.031	0.082	0.21	34	-10000	0	34
ONECUT1	-0.092	0.61	0.87	35	-1.1	104	139
CDKN2A	0.004	0.018	0.078	1	-0.16	3	4
LAMA4	-0.095	0.64	0.94	31	-1.2	103	134
FOXM1B/HNF6	-0.17	0.74	0.91	28	-1.4	104	132
FOS	-0.15	0.68	0.95	30	-1.2	129	159
SP1	0.034	0.019	-10000	0	-0.044	24	24
CDC25B	-0.09	0.65	1	29	-1.2	103	132
response to radiation	0.021	0.063	0.14	67	-10000	0	67
CENPB	-0.083	0.65	0.97	33	-1.2	104	137
CENPA	-0.095	0.64	1	28	-1.2	101	129
NEK2	-0.086	0.64	1.1	28	-1.2	101	129
HIST1H2BA	-0.093	0.63	0.9	33	-1.2	103	136
CCNA2	0.023	0.031	0.09	5	-0.035	76	81
EP300	0.034	0.011	-10000	0	-10000	0	0
CCNB1/CDK1	-0.18	0.8	1.1	26	-1.5	109	135
CCNB2	-0.11	0.67	1	30	-1.3	101	131
CCNB1	-0.13	0.72	1.1	28	-1.3	109	137
ETV5	-0.12	0.67	0.98	27	-1.2	123	150
ESR1	-0.094	0.63	0.96	28	-1.2	101	129
CCND1	-0.12	0.58	0.89	28	-1.1	105	133
GSK3A	0.034	0.08	0.2	42	-10000	0	42
Cyclin A-E1/CDK1-2	0.043	0.098	0.24	18	-0.16	42	60
CDK2	0.024	0.037	0.1	12	-0.035	117	129
G2/M transition of mitotic cell cycle	0.023	0.075	0.17	63	-10000	0	63
FOXM1B/Cbp/p300	-0.16	0.66	0.78	17	-1.3	103	120
GAS1	-0.096	0.65	0.97	30	-1.2	104	134
MMP2	-0.12	0.67	0.94	31	-1.2	117	148
RB1/FOXM1C	-0.16	0.58	0.85	17	-1.2	104	121
CREBBP	0.037	0.004	-10000	0	-10000	0	0

×

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	-0.83	138	138
NCK1/PAK1/Dok-R	-0.12	0.17	-10000	0	-0.38	129	129
NCK1/Dok-R	-0.14	0.35	-10000	0	-0.85	96	96
PIK3CA	0.032	0.013	-10000	0	0	74	74
mol:beta2-estradiol	0.031	0.097	0.23	96	-10000	0	96
RELA	0.037	0.005	-10000	0	0	10	10
SHC1	0.033	0.011	-10000	0	0	53	53
Rac/GDP	0.018	0.019	-10000	0	-0.13	5	5
F2	0.053	0.11	0.28	87	-0.11	8	95
TNIP2	0.037	0.005	-10000	0	0	11	11
NF kappa B/RelA	-0.11	0.36	-10000	0	-0.83	96	96
FN1	0.035	0.009	-10000	0	0	31	31
PLD2	-0.15	0.36	-10000	0	-0.88	96	96
PTPN11	0.037	0.006	-10000	0	0	12	12
GRB14	0.032	0.013	-10000	0	0	71	71
ELK1	-0.14	0.33	-10000	0	-0.82	96	96
GRB7	0.037	0.007	-10000	0	0	16	16
PAK1	0.036	0.007	-10000	0	0	18	18
Tie2/Ang1/alpha5/beta1 Integrin	-0.13	0.36	-10000	0	-0.86	95	95
CDKN1A	-0.19	0.35	-10000	0	-0.66	167	167
ITGA5	0.033	0.012	-10000	0	0	62	62
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.14	0.35	-10000	0	-0.86	96	96
CRK	0.036	0.008	-10000	0	0	25	25
mol:NO	-0.12	0.32	0.42	2	-0.59	134	136
PLG	-0.15	0.36	-10000	0	-0.88	96	96
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.17	0.36	-10000	0	-0.74	124	124
GRB2	0.036	0.007	-10000	0	0	19	19
PIK3R1	0.032	0.013	-10000	0	0	67	67
ANGPT2	-0.22	0.45	-10000	0	-1	112	112
BMX	-0.15	0.36	-10000	0	-0.88	96	96
ANGPT1	-0.16	0.42	-10000	0	-1	95	95
tube development	-0.21	0.36	-10000	0	-0.7	164	164
ANGPT4	0.023	0.029	-10000	0	-0.026	126	126
response to hypoxia	-0.013	0.026	-10000	0	-0.063	96	96
Tie2/Ang1/GRB14	-0.14	0.37	-10000	0	-0.89	96	96
alpha5/beta1 Integrin	0.032	0.043	-10000	0	-0.14	21	21
FGF2	0.036	0.017	-10000	0	-0.013	44	44
STAT5A (dimer)	-0.23	0.44	-10000	0	-0.81	172	172
mol:L-citrulline	-0.12	0.32	0.42	2	-0.59	134	136
AGTR1	0.022	0.034	-10000	0	-0.039	114	114
MAPK14	-0.16	0.37	-10000	0	-0.89	97	97
Tie2/SHP2	-0.078	0.24	-10000	0	-0.85	33	33
TEK	-0.088	0.25	-10000	0	-0.96	31	31
RPS6KB1	-0.2	0.37	-10000	0	-0.77	134	134
Angiotensin II/AT1	0.015	0.036	-10000	0	-0.057	88	88
Tie2/Ang1/GRB2	-0.14	0.37	-10000	0	-0.9	96	96
MAPK3	-0.15	0.34	-10000	0	-0.84	96	96
MAPK1	-0.15	0.33	-10000	0	-0.84	96	96
Tie2/Ang1/GRB7	-0.14	0.37	-10000	0	-0.9	96	96
NFKB1	0.036	0.007	-10000	0	0	18	18
MAPK8	-0.15	0.36	-10000	0	-0.88	96	96
PI3K	-0.24	0.44	-10000	0	-0.92	130	130
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	0.37	-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	-0.74	140	140
STAT5A	0.037	0.005	-10000	0	0	8	8
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.2	0.37	-10000	0	-0.77	132	132
Tie2/Ang2	-0.29	0.5	-10000	0	-0.97	163	163
Tie2/Ang1	-0.15	0.38	-10000	0	-0.93	96	96
FOXO1	-0.22	0.39	-10000	0	-0.76	166	166
ELF1	0.028	0.036	0.1	3	-0.046	80	83
ELF2	-0.14	0.35	-10000	0	-0.86	96	96
mol:Choline	-0.15	0.35	-10000	0	-0.86	96	96
cell migration	-0.066	0.097	-10000	0	-0.22	130	130
FYN	-0.24	0.41	-10000	0	-0.8	164	164
DOK2	0	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.17	0.32	0.39	2	-0.59	171	173
ETS1	0	0.12	-10000	0	-0.25	91	91
PXN	-0.17	0.31	-10000	0	-0.65	133	133
ITGB1	0.029	0.016	-10000	0	0	117	117
NOS3	-0.15	0.35	0.47	1	-0.67	133	134
RAC1	0.026	0.017	-10000	0	0	156	156
TNF	-0.003	0.12	-10000	0	-0.25	93	93
MAPKKK cascade	-0.15	0.35	-10000	0	-0.86	96	96
RASA1	0.035	0.01	-10000	0	0	35	35
Tie2/Ang1/Shc	-0.15	0.37	-10000	0	-0.9	96	96
NCK1	0.036	0.009	-10000	0	0	28	28
vasculogenesis	-0.11	0.29	0.4	3	-0.53	134	137
mol:Phosphatidic acid	-0.15	0.35	-10000	0	-0.86	96	96
mol:Angiotensin II	-0.004	0.013	-10000	0	-0.032	75	75
mol:NADP	-0.12	0.32	0.42	2	-0.59	134	136
Rac1/GTP	-0.18	0.34	-10000	0	-0.7	129	129
MMP2	-0.15	0.36	-10000	0	-0.89	96	96

×

Endothelins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.022	0.14	0.21	74	-0.26	87	161
PTK2B	0.037	0.006	-10000	0	0	15	15
mol:Ca2+	-0.084	0.24	0.39	1	-0.54	67	68
EDN1	0.003	0.091	0.16	4	-0.16	103	107
EDN3	0.034	0.012	-10000	0	0	56	56
EDN2	0.037	0.006	-10000	0	0	15	15
HRAS/GDP	-0.015	0.18	0.3	20	-0.36	64	84
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	-0.001	0.12	0.18	19	-0.25	60	79
ADCY4	-0.037	0.095	0.14	34	-0.2	96	130
ADCY5	-0.037	0.095	0.14	34	-0.2	96	130
ADCY6	-0.008	0.13	0.22	48	-0.24	62	110
ADCY7	-0.011	0.13	0.22	50	-0.24	65	115
ADCY1	0	0.11	0.22	35	-0.25	40	75
ADCY2	-0.006	0.13	0.22	47	-0.24	63	110
ADCY3	-0.037	0.095	0.14	34	-0.2	96	130
ADCY8	-0.009	0.13	0.22	45	-0.24	54	99
ADCY9	-0.008	0.13	0.22	51	-0.24	64	115
arachidonic acid secretion	-0.078	0.26	0.34	23	-0.51	103	126
ETB receptor/Endothelin-1/Gq/GTP	-0.007	0.11	0.17	13	-0.22	70	83
GNAO1	0.031	0.014	-10000	0	0	87	87
HRAS	0.035	0.01	-10000	0	0	37	37
ETA receptor/Endothelin-1/G12/GTP	0.005	0.12	-10000	0	-0.23	69	69
ETA receptor/Endothelin-1/Gs/GTP	0.002	0.12	-10000	0	-0.21	98	98
mol:GTP	0	0.007	0.026	3	-0.025	4	7
COL3A1	-0.076	0.15	0.19	9	-0.36	103	112
EDNRB	0.024	0.045	0.098	62	-0.084	45	107
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.02	0.14	0.21	69	-0.28	64	133
CYSLTR1	-0.041	0.12	0.18	35	-0.24	96	131
SLC9A1	-0.016	0.087	0.13	4	-0.19	67	71
mol:GDP	-0.024	0.17	0.3	21	-0.38	62	83
SLC9A3	-0.12	0.29	-10000	0	-0.65	85	85
RAF1	-0.035	0.21	0.3	31	-0.41	88	119
JUN	-0.12	0.32	0.47	1	-0.76	74	75
JAK2	-0.023	0.14	0.21	64	-0.25	87	151
mol:IP3	-0.005	0.12	0.21	16	-0.27	52	68
ETA receptor/Endothelin-1	-0.028	0.14	-10000	0	-0.28	109	109
PLCB1	0.033	0.014	-10000	0	-0.003	59	59
PLCB2	0.03	0.023	-10000	0	-0.024	73	73
ETA receptor/Endothelin-3	0.007	0.087	-10000	0	-0.15	99	99
FOS	-0.097	0.35	0.4	20	-0.84	83	103
Gai/GDP	-0.073	0.28	-10000	0	-0.72	71	71
CRK	0.036	0.008	-10000	0	0	25	25
mol:Ca ++	-0.021	0.17	0.26	54	-0.33	83	137
BCAR1	0	0	-10000	0	-10000	0	0
PRKCB1	-0.007	0.12	0.21	19	-0.28	55	74
GNAQ	0.028	0.027	-10000	0	-0.035	67	67
GNAZ	0.032	0.014	-10000	0	0	81	81
GNAL	0.036	0.007	-10000	0	0	17	17
Gs family/GDP	-0.014	0.16	0.29	18	-0.35	62	80
ETA receptor/Endothelin-1/Gq/GTP	-0.009	0.12	0.19	11	-0.26	67	78
MAPK14	-0.012	0.098	0.18	6	-0.25	45	51
TRPC6	-0.089	0.25	-10000	0	-0.57	66	66
GNAI2	0.034	0.011	-10000	0	0	46	46
GNAI3	0.037	0.007	-10000	0	0	16	16
GNAI1	0.019	0.019	-10000	0	0	255	255
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	-0.003	0.1	0.17	18	-0.24	50	68
ETB receptor/Endothelin-2	0.019	0.07	-10000	0	-0.11	98	98
ETB receptor/Endothelin-3	0.016	0.069	-10000	0	-0.11	93	93
ETB receptor/Endothelin-1	0	0.1	0.17	28	-0.16	115	143
MAPK3	-0.078	0.32	0.39	21	-0.73	84	105
MAPK1	-0.093	0.34	0.38	23	-0.77	89	112
Rac1/GDP	-0.015	0.15	0.31	13	-0.37	45	58
cAMP biosynthetic process	0.019	0.12	0.23	50	-0.22	39	89
MAPK8	-0.12	0.3	0.35	4	-0.57	125	129
SRC	0.036	0.009	-10000	0	0	31	31
ETB receptor/Endothelin-1/Gi/GTP	-0.032	0.14	0.15	4	-0.34	60	64
p130Cas/CRK/Src/PYK2	-0.021	0.19	0.37	15	-0.47	47	62
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	-0.018	0.15	0.31	11	-0.38	47	58
COL1A2	-0.055	0.17	0.22	1	-0.47	60	61
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	0.006	0.091	-10000	0	-0.15	108	108
mol:DAG	-0.005	0.12	0.21	16	-0.27	53	69
MAP2K2	-0.056	0.26	0.37	29	-0.56	85	114
MAP2K1	-0.062	0.26	0.33	25	-0.57	87	112
EDNRA	-0.007	0.1	0.16	1	-0.19	98	99
positive regulation of muscle contraction	0.019	0.14	0.22	126	-0.26	46	172
Gq family/GDP	0.001	0.16	0.31	4	-0.34	63	67
HRAS/GTP	-0.015	0.17	0.29	25	-0.35	64	89
PRKCH	-0.007	0.12	0.24	16	-0.29	48	64
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCA	-0.012	0.13	0.21	18	-0.28	54	72
PRKCB	-0.007	0.12	0.21	20	-0.27	56	76
PRKCE	-0.013	0.12	0.21	15	-0.29	51	66
PRKCD	-0.007	0.13	0.25	22	-0.28	52	74
PRKCG	-0.013	0.13	0.22	17	-0.28	55	72
regulation of vascular smooth muscle contraction	-0.12	0.42	0.45	14	-1	83	97
PRKCQ	-0.005	0.12	0.24	19	-0.28	42	61
PLA2G4A	-0.088	0.28	0.35	23	-0.56	103	126
GNA14	0.028	0.027	-10000	0	-0.035	67	67
GNA15	0.031	0.02	-10000	0	-0.035	27	27
GNA12	0.024	0.018	-10000	0	0	180	180
GNA11	0.033	0.017	-10000	0	-0.037	17	17
Rac1/GTP	0.007	0.11	-10000	0	-0.23	65	65
MMP1	0.021	0.073	0.22	13	-10000	0	13

×

TCGA08_p53

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2A	-0.002	0.004	0	444	-10000	0	444
TP53	0.005	0.034	-10000	0	-0.26	6	6
Senescence	0.004	0.036	-10000	0	-0.24	8	8
Apoptosis	0.004	0.036	-10000	0	-0.24	8	8
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.002	0.035	0.3	7	-10000	0	7
MDM4	0.033	0.012	-10000	0	0	61	61

×

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	0.018	-10000	0	0	165	165
HRAS	0.035	0.01	-10000	0	0	37	37
EGFR	0.01	0.017	-10000	0	0	373	373
AKT	0.087	0.12	0.25	113	-0.18	10	123
FOXO3	0.033	0.012	-10000	0	0	61	61
AKT1	0.033	0.012	-10000	0	0	58	58
FOXO1	0.031	0.015	-10000	0	0	95	95
AKT3	0.036	0.008	-10000	0	0	22	22
FOXO4	0.038	0.002	-10000	0	0	2	2
MET	0.024	0.018	-10000	0	0	184	184
PIK3CA	0.032	0.013	-10000	0	0	74	74
PIK3CB	0.036	0.007	-10000	0	0	18	18
NRAS	0.033	0.013	-10000	0	0	66	66
PIK3CG	0.026	0.017	-10000	0	0	157	157
PIK3R3	0.036	0.007	-10000	0	0	17	17
PIK3R2	0.036	0.007	-10000	0	0	20	20
NF1	0.037	0.003	-10000	0	0	4	4
RAS	-0.003	0.056	-10000	0	-0.26	11	11
ERBB2	0.037	0.004	-10000	0	0	7	7
proliferation/survival/translation	-0.033	0.096	0.34	18	-0.26	7	25
PI3K	0.036	0.087	0.21	65	-0.15	11	76
PIK3R1	0.033	0.013	-10000	0	0	67	67
KRAS	0.035	0.009	-10000	0	0	34	34
FOXO	0.1	0.1	0.24	122	-0.1	4	126
AKT2	0.036	0.007	-10000	0	0	18	18
PTEN	0.026	0.017	-10000	0	0	158	158

×

HIF-2-alpha transcription factor network

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
MMP14	-0.017	0.16	-10000	0	-0.63	30	30
oxygen homeostasis	0.006	0.027	0.06	65	-0.027	17	82
TCEB2	0.037	0.004	-10000	0	0	6	6
TCEB1	0.036	0.008	-10000	0	0	22	22
VHL/Elongin B/Elongin C/HIF2A	0.012	0.15	0.32	34	-0.26	40	74
EPO	-0.044	0.23	0.42	29	-0.46	62	91
FIH (dimer)	0.017	0.044	0.12	24	-0.042	60	84
APEX1	0.014	0.045	0.13	6	-0.054	38	44
SERPINE1	-0.078	0.22	0.38	14	-0.49	85	99
FLT1	-0.014	0.17	-10000	0	-0.71	23	23
ADORA2A	-0.038	0.26	0.46	44	-0.47	71	115
germ cell development	-0.046	0.24	0.4	44	-0.44	83	127
SLC11A2	-0.038	0.27	0.48	42	-0.46	82	124
BHLHE40	-0.05	0.25	0.39	43	-0.45	84	127
HIF1AN	0.017	0.044	0.12	24	-0.042	60	84
HIF2A/ARNT/SIRT1	-0.018	0.17	0.33	32	-0.32	56	88
ETS1	0.048	0.032	0.12	41	-0.11	11	52
CITED2	-0.06	0.26	-10000	0	-0.79	52	52
KDR	-0.005	0.16	-10000	0	-0.86	16	16
PGK1	-0.042	0.28	0.45	50	-0.48	87	137
SIRT1	0.027	0.017	-10000	0	0	149	149
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF2A/ARNT	-0.042	0.28	0.49	10	-0.51	83	93
EPAS1	0.005	0.15	0.32	48	-0.27	39	87
SP1	0.042	0.011	0.11	8	-10000	0	8
ABCG2	-0.048	0.28	0.48	40	-0.47	94	134
EFNA1	-0.044	0.27	0.46	38	-0.47	85	123
FXN	-0.038	0.26	0.46	44	-0.47	70	114
POU5F1	-0.05	0.25	0.39	43	-0.45	84	127
neuron apoptosis	0.042	0.28	0.5	83	-0.48	9	92
EP300	0.034	0.011	-10000	0	0	49	49
EGLN3	0.019	0.044	0.12	21	-0.042	66	87
EGLN2	0.024	0.047	0.12	29	-0.042	66	95
EGLN1	0.024	0.046	0.12	28	-0.043	45	73
VHL/Elongin B/Elongin C	0.046	0.023	-10000	0	-0.11	9	9
VHL	0	0	-10000	0	-10000	0	0
ARNT	0.014	0.045	0.12	6	-0.053	38	44
SLC2A1	-0.063	0.24	0.41	30	-0.46	87	117
TWIST1	-0.07	0.22	0.42	17	-0.45	92	109
ELK1	0.039	0.035	0.11	29	-0.095	25	54
HIF2A/ARNT/Cbp/p300	-0.002	0.2	0.36	37	-0.33	56	93
VEGFA	-0.081	0.25	0.42	18	-0.48	102	120
CREBBP	0.037	0.004	-10000	0	0	7	7

×

Thromboxane A2 receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGM2	0.035	0.011	-10000	0	0	43	43
GNB1/GNG2	-0.045	0.077	-10000	0	-0.17	130	130
AKT1	-0.007	0.16	0.28	35	-0.3	44	79
EGF	0.036	0.008	-10000	0	0	25	25
mol:TXA2	0	0.001	0.003	2	-10000	0	2
FGR	-0.021	0.063	0.31	12	-0.16	3	15
mol:Ca2+	-0.003	0.18	0.35	23	-0.27	132	155
LYN	-0.02	0.068	0.31	14	-0.16	8	22
RhoA/GTP	0	0.082	0.16	20	-0.13	93	113
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	-0.018	0.2	0.38	23	-0.32	127	150
GNG2	0	0	-10000	0	-10000	0	0
ARRB2	0.036	0.008	-10000	0	0	27	27
TP alpha/Gq family/GDP/G beta5/gamma2	0.004	0.077	-10000	0	-0.25	32	32
G beta5/gamma2	-0.053	0.1	-10000	0	-0.23	129	129
PRKCH	-0.017	0.2	0.36	23	-0.32	129	152
DNM1	0.036	0.008	-10000	0	0	26	26
TXA2/TP beta/beta Arrestin3	0.015	0.019	-10000	0	-10000	0	0
mol:GTP	0.001	0.002	0.005	55	-0.002	5	60
PTGDR	0.036	0.009	-10000	0	0	29	29
G12 family/GTP	-0.044	0.14	-10000	0	-0.29	102	102
ADRBK1	0.037	0.006	-10000	0	0	13	13
ADRBK2	0.035	0.009	-10000	0	0	32	32
RhoA/GTP/ROCK1	0.045	0.027	-10000	0	-0.12	10	10
mol:GDP	-0.005	0.13	0.41	16	-0.26	20	36
mol:NADP	0.026	0.018	-10000	0	0	160	160
RAB11A	0.036	0.007	-10000	0	0	17	17
PRKG1	0.028	0.016	-10000	0	0	127	127
mol:IP3	-0.015	0.22	0.38	22	-0.33	132	154
cell morphogenesis	0.045	0.026	-10000	0	-0.12	10	10
PLCB2	-0.039	0.27	0.45	12	-0.44	132	144
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.018	0.067	0.3	16	-10000	0	16
mol:PDG2	0	0	0.003	1	-10000	0	1
HCK	-0.024	0.051	0.29	6	-0.17	10	16
RHOA	0.036	0.007	-10000	0	0	20	20
PTGIR	0.036	0.008	-10000	0	0	27	27
PRKCB1	-0.021	0.21	0.36	22	-0.34	132	154
GNAQ	0.035	0.01	-10000	0	0	35	35
mol:L-citrulline	0.026	0.018	-10000	0	0	160	160
TXA2/TXA2-R family	-0.05	0.28	0.42	19	-0.48	130	149
LCK	-0.019	0.066	0.3	15	-10000	0	15
TXA2/TP beta/beta Arrestin3/RAB11/GDP	0.033	0.039	0.2	2	-0.13	3	5
TXA2-R family/G12 family/GDP/G beta/gamma	-0.033	0.16	-10000	0	-0.46	61	61
TXA2/TP beta/beta Arrestin2/RAB11/GDP	0.03	0.041	0.2	2	-0.13	3	5
MAPK14	-0.006	0.15	0.29	31	-0.22	125	156
TGM2/GTP	-0.019	0.23	0.4	18	-0.37	122	140
MAPK11	-0.008	0.15	0.29	29	-0.22	125	154
ARHGEF1	0.007	0.12	0.22	40	-0.18	94	134
GNAI2	0.034	0.011	-10000	0	0	46	46
JNK cascade	-0.024	0.22	0.38	22	-0.35	130	152
RAB11/GDP	0.035	0.01	-10000	0	-0.009	23	23
ICAM1	-0.006	0.18	0.32	32	-0.27	126	158
cAMP biosynthetic process	-0.016	0.2	0.35	22	-0.31	126	148
Gq family/GTP/EBP50	0.014	0.055	0.25	8	-0.16	32	40
actin cytoskeleton reorganization	0.045	0.026	-10000	0	-0.12	10	10
SRC	-0.025	0.049	0.27	7	-10000	0	7
GNB5	0.036	0.007	-10000	0	0	18	18
GNB1	0.034	0.011	-10000	0	0	47	47
EGF/EGFR	-0.013	0.11	0.31	17	-0.22	47	64
VCAM1	-0.024	0.2	0.32	33	-0.33	135	168
TP beta/Gq family/GDP/G beta5/gamma2	0.004	0.077	-10000	0	-0.25	32	32
platelet activation	-0.011	0.19	0.37	23	-0.28	127	150
PGI2/IP	0.026	0.006	-10000	0	-10000	0	0
PRKACA	0.014	0.024	-10000	0	-10000	0	0
Gq family/GDP/G beta5/gamma2	0.008	0.067	-10000	0	-0.22	30	30
TXA2/TP beta/beta Arrestin2	0.005	0.048	-10000	0	-0.3	7	7
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.007	0.02	-10000	0	-10000	0	0
mol:DAG	-0.024	0.23	0.39	22	-0.38	129	151
EGFR	0.01	0.017	-10000	0	0	373	373
TXA2/TP alpha	-0.032	0.25	0.45	13	-0.42	126	139
Gq family/GTP	0.008	0.041	0.21	6	-0.12	28	34
YES1	-0.02	0.065	0.29	14	-0.16	3	17
GNAI2/GTP	0.008	0.049	-10000	0	-0.14	4	4
PGD2/DP	0.026	0.007	-10000	0	-10000	0	0
SLC9A3R1	0.035	0.01	-10000	0	0	35	35
FYN	-0.019	0.067	0.29	14	-0.16	7	21
mol:NO	0.026	0.018	-10000	0	0	160	160
GNA15	0.034	0.011	-10000	0	0	45	45
PGK/cGMP	0.03	0.025	-10000	0	-10000	0	0
RhoA/GDP	0.035	0.011	-10000	0	-0.008	26	26
TP alpha/TGM2/GDP/G beta/gamma	0.029	0.043	0.18	1	-0.13	3	4
NOS3	0.026	0.018	-10000	0	0	160	160
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCA	-0.017	0.2	0.36	22	-0.32	127	149
PRKCB	-0.018	0.2	0.35	23	-0.32	132	155
PRKCE	-0.019	0.2	0.36	23	-0.33	132	155
PRKCD	-0.022	0.22	0.36	24	-0.35	129	153
PRKCG	-0.023	0.22	0.37	22	-0.35	132	154
muscle contraction	-0.044	0.26	0.41	19	-0.44	130	149
PRKCZ	-0.018	0.2	0.35	24	-0.32	130	154
ARR3	0.038	0.002	-10000	0	0	2	2
TXA2/TP beta	0.037	0.039	0.19	1	-0.13	4	5
PRKCQ	-0.026	0.2	0.35	24	-0.32	127	151
MAPKKK cascade	-0.034	0.24	0.39	21	-0.4	130	151
SELE	-0.012	0.18	0.33	25	-0.27	134	159
TP beta/GNAI2/GDP/G beta/gamma	0.026	0.054	0.19	2	-0.16	16	18
ROCK1	0.037	0.007	-10000	0	0	16	16
GNA14	0.035	0.009	-10000	0	0	34	34
chemotaxis	-0.07	0.31	0.49	10	-0.56	135	145
GNA12	0.024	0.018	-10000	0	0	180	180
GNA13	0.036	0.008	-10000	0	0	21	21
GNA11	0.034	0.011	-10000	0	0	46	46
Rac1/GTP	0.018	0.02	-10000	0	-0.13	5	5

×

Ceramide signaling pathway

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
SPHK2	-0.012	0.012	0	247	-10000	0	247
MAP4K4	0.002	0.057	-10000	0	-0.23	13	13
BAG4	0.037	0.005	-10000	0	0	10	10
PKC zeta/ceramide	-0.054	0.12	-10000	0	-0.2	158	158
NFKBIA	0.034	0.012	-10000	0	0	54	54
BIRC3	0.031	0.014	-10000	0	0	84	84
BAX	-0.024	0.094	-10000	0	-0.36	29	29
RIPK1	0.036	0.007	-10000	0	0	19	19
AKT1	-0.001	0.078	0.63	6	-10000	0	6
BAD	-0.06	0.12	0.22	2	-0.21	157	159
SMPD1	-0.003	0.054	0.18	2	-0.21	16	18
RB1	-0.061	0.12	0.21	1	-0.21	158	159
FADD/Caspase 8	0.013	0.054	-10000	0	-0.26	5	5
MAP2K4	-0.06	0.12	0.19	5	-0.21	149	154
NSMAF	0.036	0.008	-10000	0	0	27	27
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.064	0.12	0.2	5	-0.21	155	160
EGF	0.036	0.008	-10000	0	0	25	25
mol:ceramide	-0.056	0.13	-10000	0	-0.22	158	158
MADD	0.036	0.007	-10000	0	0	19	19
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	-0.012	0.012	0	244	-10000	0	244
ASAH1	0.037	0.007	-10000	0	0	16	16
negative regulation of cell cycle	-0.06	0.12	0.21	1	-0.21	158	159
cell proliferation	-0.036	0.11	-10000	0	-0.19	140	140
BID	-0.042	0.21	-10000	0	-0.65	49	49
MAP3K1	-0.058	0.12	0.17	2	-0.21	149	151
EIF2A	-0.062	0.11	0.2	2	-0.2	155	157
TRADD	0.037	0.005	-10000	0	0	8	8
CRADD	0.037	0.007	-10000	0	0	16	16
MAPK3	-0.059	0.1	0.19	4	-0.2	147	151
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.068	0.11	0.19	4	-0.21	154	158
Cathepsin D/ceramide	-0.043	0.13	-10000	0	-0.21	156	156
FADD	0.008	0.049	-10000	0	-0.22	6	6
KSR1	-0.06	0.12	0.2	1	-0.21	158	159
MAPK8	-0.087	0.15	0.16	2	-0.25	190	192
PRKRA	-0.063	0.12	-10000	0	-0.21	157	157
PDGFA	0.02	0.019	-10000	0	0	241	241
TRAF2	0.036	0.007	-10000	0	0	19	19
IGF1	0.036	0.008	-10000	0	0	25	25
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.056	0.12	-10000	0	-0.21	158	158
CTSD	0.033	0.012	-10000	0	0	58	58
regulation of nitric oxide biosynthetic process	0.051	0.025	-10000	0	-0.14	7	7
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.038	0.12	-10000	0	-0.2	140	140
PRKCD	0.035	0.01	-10000	0	0	42	42
PRKCZ	0	0	-10000	0	-10000	0	0
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	-0.012	0.012	0	244	-10000	0	244
RelA/NF kappa B1	0.051	0.025	-10000	0	-0.14	7	7
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.036	0.007	-10000	0	0	18	18
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	0.016	0.058	-10000	0	-0.25	9	9
TNFR1A/BAG4/TNF-alpha	0.055	0.056	-10000	0	-0.12	41	41
mol:Sphingosine-1-phosphate	-0.012	0.012	0	247	-10000	0	247
MAP2K1	-0.068	0.11	0.18	5	-0.21	154	159
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.037	0.005	-10000	0	0	10	10
CYCS	-0.014	0.07	-10000	0	-0.27	22	22
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
NFKB1	0.036	0.007	-10000	0	0	18	18
TNFR1A/BAG4	0.036	0.054	-10000	0	-0.14	42	42
EIF2AK2	-0.065	0.12	0.21	2	-0.21	155	157
TNF-alpha/TNFR1A/FAN	0.049	0.066	-10000	0	-0.13	54	54
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	0.032	0.058	-10000	0	-0.31	7	7
MAP2K2	-0.063	0.1	0.18	8	-0.2	150	158
SMPD3	0.005	0.057	0.16	1	-0.27	8	9
TNF	0.037	0.004	-10000	0	0	6	6
PKC zeta/PAR4	0.027	0.005	-10000	0	-10000	0	0
mol:PHOSPHOCHOLINE	-0.03	0.074	0.13	6	-0.13	134	140
NF kappa B1/RelA/I kappa B alpha	0.072	0.048	-10000	0	-0.12	19	19
AIFM1	-0.039	0.087	-10000	0	-0.29	26	26
BCL2	0.036	0.007	-10000	0	0	17	17

×

PDGFR-alpha signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	0.018	0.033	0.092	4	-0.056	53	57
PDGF/PDGFRA/CRKL	0.009	0.068	-10000	0	-0.14	67	67
positive regulation of JUN kinase activity	0.026	0.062	-10000	0	-0.11	65	65
CRKL	0.036	0.009	-10000	0	0	29	29
PDGF/PDGFRA/Caveolin-3	0.01	0.068	-10000	0	-0.14	68	68
AP1	-0.096	0.22	0.29	2	-0.6	75	77
mol:IP3	-0.017	0.04	0.052	46	-0.095	59	105
PLCG1	-0.017	0.04	0.052	46	-0.096	59	105
PDGF/PDGFRA/alphaV Integrin	0.006	0.075	-10000	0	-0.15	77	77
RAPGEF1	0.036	0.008	-10000	0	0	21	21
CRK	0.036	0.008	-10000	0	0	25	25
mol:Ca2+	-0.017	0.04	0.052	45	-0.095	59	104
CAV3	0.037	0.005	-10000	0	0	11	11
CAV1	0.016	0.019	-10000	0	0	287	287
SHC/Grb2/SOS1	0.028	0.063	-10000	0	-0.11	65	65
PDGF/PDGFRA/Shf	-0.003	0.053	0.082	1	-0.088	117	118
FOS	-0.091	0.22	0.22	1	-0.62	69	70
JUN	-0.025	0.056	0.22	9	-0.2	16	25
oligodendrocyte development	0.005	0.075	-10000	0	-0.15	77	77
GRB2	0.036	0.007	-10000	0	0	19	19
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:DAG	-0.017	0.04	0.052	46	-0.095	59	105
PDGF/PDGFRA	0.018	0.033	0.092	4	-0.056	53	57
actin cytoskeleton reorganization	0.008	0.066	-10000	0	-0.14	66	66
SRF	-0.015	0.021	0.034	67	-10000	0	67
SHC1	0.034	0.012	-10000	0	0	53	53
PI3K	0.009	0.091	-10000	0	-0.15	110	110
PDGF/PDGFRA/Crk/C3G	0.028	0.073	-10000	0	-0.13	76	76
JAK1	-0.011	0.02	0.025	70	-10000	0	70
ELK1/SRF	-0.017	0.083	0.14	72	-0.16	55	127
SHB	0.034	0.011	-10000	0	0	52	52
SHF	0	0	-10000	0	-10000	0	0
CSNK2A1	0.026	0.035	-10000	0	-0.032	108	108
GO:0007205	-0.028	0.067	0.1	18	-0.2	53	71
SOS1	0	0	-10000	0	-10000	0	0
Ras protein signal transduction	0.026	0.062	-10000	0	-0.11	65	65
PDGF/PDGFRA/SHB	0.008	0.066	-10000	0	-0.14	66	66
PDGF/PDGFRA/Caveolin-1	-0.013	0.075	-10000	0	-0.16	85	85
ITGAV	0.035	0.009	-10000	0	0	34	34
ELK1	-0.032	0.068	0.14	7	-0.15	85	92
PIK3CA	0.032	0.013	-10000	0	0	74	74
PDGF/PDGFRA/Crk	0.007	0.073	-10000	0	-0.14	77	77
JAK-STAT cascade	-0.011	0.02	0.025	70	-10000	0	70
cell proliferation	-0.003	0.053	0.082	1	-0.088	117	118

×

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	-0.008	0.006	0	166	-10000	0	166
UniProt:P19321	0	0	-10000	0	-10000	0	0
RIMS1/UNC13B	0.041	0.04	-10000	0	-0.14	19	19
STXBP1	0.03	0.015	-10000	0	0	106	106
ACh/CHRNA1	0.027	0.054	0.097	54	-0.075	93	147
RAB3GAP2/RIMS1/UNC13B	0.053	0.051	-10000	0	-0.13	26	26
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	0.036	0.008	-10000	0	0	24	24
mol:ACh	0.016	0.065	0.098	140	-0.088	92	232
RAB3GAP2	0.036	0.008	-10000	0	0	27	27
STX1A/SNAP25/VAMP2	0.022	0.1	0.18	16	-0.15	83	99
UniProt:P10844	0	0	-10000	0	-10000	0	0
muscle contraction	0.027	0.054	0.097	54	-0.075	93	147
UNC13B	0.032	0.013	-10000	0	0	73	73
CHRNA1	0.036	0.007	-10000	0	0	18	18
UniProt:P10845	0	0	-10000	0	-10000	0	0
ACh/Synaptotagmin 1	0.013	0.042	0.1	20	-0.084	41	61
SNAP25	0.002	0.003	-10000	0	0	275	275
VAMP2	0.004	0.001	-10000	0	0	50	50
SYT1	0.018	0.019	-10000	0	0	266	266
UniProt:Q00496	0	0	-10000	0	-10000	0	0
STXIA/STXBP1	0.019	0.016	0.086	1	-10000	0	1
STX1A/SNAP25 fragment 1/VAMP2	0.022	0.1	0.18	16	-0.15	83	99

×

Syndecan-3-mediated signaling events

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
CTTN	0.037	0.006	-10000	0	0	13	13
Syndecan-3/Src/Cortactin	-0.022	0.18	-10000	0	-0.45	71	71
Syndecan-3/Neurocan	-0.057	0.2	-10000	0	-0.53	74	74
POMC	0.037	0.006	-10000	0	0	13	13
EGFR	0.01	0.017	-10000	0	0	373	373
Syndecan-3/EGFR	-0.053	0.16	-10000	0	-0.42	72	72
AGRP	0.037	0.005	-10000	0	0	8	8
NCSTN	0.036	0.009	-10000	0	0	29	29
PSENEN	0.035	0.009	-10000	0	0	33	33
RP11-540L11.1	0	0	-10000	0	-10000	0	0
APH1B	0.037	0.006	-10000	0	0	14	14
APH1A	0.036	0.007	-10000	0	0	17	17
NCAN	0.024	0.018	-10000	0	0	189	189
long-term memory	-0.029	0.2	-10000	0	-0.49	76	76
Syndecan-3/IL8	-0.052	0.18	-10000	0	-0.47	74	74
PSEN1	0.034	0.011	-10000	0	0	48	48
Src/Cortactin	0.051	0.018	-10000	0	-0.14	1	1
FYN	0.031	0.015	-10000	0	0	93	93
limb bud formation	-0.061	0.18	-10000	0	-0.49	74	74
MC4R	0.036	0.007	-10000	0	0	19	19
SRC	0.035	0.009	-10000	0	0	31	31
PTN	0.023	0.018	-10000	0	0	197	197
FGFR/FGF/Syndecan-3	-0.062	0.18	-10000	0	-0.5	74	74
neuron projection morphogenesis	-0.033	0.2	0.33	6	-0.49	71	77
Syndecan-3/AgRP	-0.04	0.19	-10000	0	-0.48	74	74
Syndecan-3/AgRP/MC4R	-0.021	0.19	-10000	0	-0.48	74	74
Fyn/Cortactin	0.03	0.061	-10000	0	-0.14	53	53
SDC3	-0.063	0.18	-10000	0	-0.5	74	74
GO:0007205	0	0	-10000	0	-10000	0	0
positive regulation of leukocyte migration	-0.052	0.18	-10000	0	-0.46	74	74
IL8	0.02	0.019	-10000	0	0	244	244
Syndecan-3/Fyn/Cortactin	-0.03	0.2	-10000	0	-0.5	76	76
Syndecan-3/CASK	-0.062	0.17	-10000	0	-0.48	74	74
alpha-MSH/MC4R	0.053	0.013	-10000	0	-10000	0	0
Gamma Secretase	0.08	0.073	-10000	0	-0.15	28	28

×

Canonical Wnt signaling pathway

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
HDAC1	0.034	0.046	0.12	68	-0.039	84	152
AES	0.032	0.043	0.11	66	-0.036	85	151
FBXW11	0.036	0.008	-10000	0	0	24	24
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.027	-10000	0	-10000	0	0
SMAD4	0.033	0.012	-10000	0	0	58	58
DKK2	0.035	0.009	-10000	0	0	31	31
TLE1	0.032	0.042	0.11	66	-0.036	84	150
MACF1	0.034	0.012	-10000	0	0	52	52
CTNNB1	0.043	0.11	0.28	28	-0.35	15	43
WIF1	0.029	0.015	-10000	0	0	110	110
beta catenin/RanBP3	0.068	0.16	0.42	64	-0.35	9	73
KREMEN2	0.037	0.004	-10000	0	0	6	6
DKK1	0.019	0.019	-10000	0	0	258	258
beta catenin/beta TrCP1	0.059	0.12	0.29	27	-0.34	16	43
FZD1	0.026	0.018	-10000	0	0	162	162
AXIN2	-0.025	0.094	0.12	2	-0.24	69	71
AXIN1	0.038	0.004	-10000	0	0	6	6
RAN	0.037	0.006	-10000	0	0	13	13
Axin1/APC/GSK3/beta catenin	0.013	0.16	-10000	0	-0.6	30	30
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.025	0.13	0.25	10	-0.41	20	30
Axin1/APC/GSK3	0.004	0.096	0.26	8	-0.36	20	28
Axin1/APC/GSK3/beta catenin/Macf1	0.026	0.13	0.29	9	-0.38	30	39
HNF1A	0.034	0.044	0.11	71	-0.036	89	160
CTBP1	0.032	0.042	0.11	62	-0.037	84	146
MYC	-0.1	0.41	0.74	14	-1.2	51	65
RANBP3	0.037	0.007	-10000	0	0	16	16
DKK2/LRP6/Kremen 2	0.066	0.028	-10000	0	-0.12	1	1
NKD1	0	0.001	-10000	0	-10000	0	0
TCF4	0.031	0.04	0.11	62	-0.037	68	130
TCF3	0.033	0.043	0.11	67	-0.036	87	154
WNT1/LRP6/FZD1/Axin1	0.063	0.046	-10000	0	-10000	0	0
Ran/GTP	0.026	0.016	-10000	0	-0.13	5	5
CtBP/CBP/TCF/TLE1/AES	0.038	0.19	0.46	67	-0.35	19	86
LEF1	0.035	0.045	0.12	73	-0.037	85	158
DVL1	0.006	0.1	-10000	0	-0.41	19	19
CSNK2A1	0.034	0.011	-10000	0	0	50	50
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.011	0.16	0.25	10	-0.5	30	40
DKK1/LRP6/Kremen 2	0.035	0.038	-10000	0	-10000	0	0
LRP6	0.035	0.011	-10000	0	0	44	44
CSNK1A1	0.035	0.047	0.12	70	-0.039	86	156
NLK	0.027	0.024	-10000	0	-0.033	58	58
CCND1	-0.083	0.35	0.8	3	-1.2	39	42
WNT1	0.037	0.007	-10000	0	0	18	18
GSK3A	0.036	0.008	0.058	1	0	25	26
GSK3B	0.035	0.01	-10000	0	0	37	37
FRAT1	0.027	0.017	-10000	0	0	138	138
PPP2R5D	0.018	0.057	-10000	0	-0.26	14	14
APC	0.035	0.11	0.19	146	-10000	0	146
WNT1/LRP6/FZD1	0.003	0.045	-10000	0	-0.26	9	9
CREBBP	0.034	0.043	0.11	67	-0.036	88	155

×

Wnt signaling

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
Noncanonical Wnts/FZD	-0.005	0.087	-9999	-0.17	88	88
FZD6	0.028	0.017	-9999	0	132	132
WNT6	0.038	0.002	-9999	0	2	2
WNT4	0.036	0.008	-9999	0	21	21
FZD3	0.03	0.015	-9999	0	108	108
WNT5A	0.03	0.015	-9999	0	101	101
WNT11	0.037	0.007	-9999	0	16	16

×

PLK2 and PLK4 events

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
PLK2	0.031	0.014	-9999	0	0	84	84
PLK4	0.036	0.007	-9999	0	0	18	18
regulation of centriole replication	-0.019	0.009	0	95	-9999	0	95

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.003	0.13	0.32	1	-0.27	63	64
MAP3K8	0.024	0.018	-10000	0	0	176	176
FOS	0.02	0.11	0.23	6	-0.28	28	34
PRKCA	0.029	0.026	-10000	0	-0.03	79	79
PTPN7	0.029	0.03	0.068	53	-0.03	92	145
HRAS	0.035	0.01	-10000	0	0	37	37
PRKCB	0	0.008	0.017	61	-0.012	78	139
NRAS	0.033	0.013	-10000	0	0	66	66
RAS family/GTP	0.042	0.067	-10000	0	-0.13	54	54
MAPK3	0.036	0.051	-10000	0	-0.33	2	2
MAP2K1	0.008	0.056	0.18	1	-0.22	12	13
ELK1	0.027	0.029	-10000	0	-0.04	82	82
BRAF	0.007	0.022	-10000	0	-10000	0	0
mol:GTP	0	0.002	0.003	61	-0.004	80	141
MAPK1	0.009	0.13	-10000	0	-0.42	34	34
RAF1	0	0.067	-10000	0	-0.34	17	17
KRAS	0.035	0.01	-10000	0	0	34	34

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	0.014	0.034	-10000	0	-0.1	38	38
ARNO/beta Arrestin1-2	0.042	0.026	-10000	0	-0.094	7	7
EGFR	0.01	0.017	-10000	0	0	373	373
EPHA2	0.034	0.012	-10000	0	0	56	56
USP6	0.036	0.007	-10000	0	0	20	20
IQSEC1	0.037	0.007	-10000	0	0	17	17
EGFR/EGFR/EGF/EGF	-0.004	0.057	-10000	0	-0.14	65	65
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
mol:GTP	0.002	0.014	0.12	2	-0.067	3	5
ARRB1	0.037	0.005	-10000	0	0	11	11
FBXO8	0	0	-10000	0	-10000	0	0
TSHR	0.034	0.011	-10000	0	0	51	51
EGF	0.036	0.008	-10000	0	0	25	25
somatostatin receptor activity	0	0	0.001	136	0	10	146
ARAP2	0	0	0	115	0	6	121
mol:GDP	0.063	0.07	0.16	125	-0.16	7	132
mol:PI-3-4-5-P3	0	0	0	128	0	9	137
ITGA2B	0.037	0.003	-10000	0	0	4	4
ARF6	0.036	0.009	-10000	0	0	31	31
Ephrin A1/EPHA2/NCK1/GIT1	0.075	0.055	-10000	0	-0.13	25	25
ADAP1	0	0	0	59	0	4	63
KIF13B	0.033	0.012	-10000	0	0	62	62
HGF/MET	0.034	0.027	-10000	0	-10000	0	0
PXN	0.037	0.005	-10000	0	0	9	9
ARF6/GTP	0.078	0.094	0.2	127	-0.21	9	136
EGFR/EGFR/EGF/EGF/ARFGEP100	0.002	0.057	-10000	0	-0.12	64	64
ADRB2	0.035	0.01	-10000	0	0	41	41
receptor agonist activity	0	0	0	129	0	10	139
actin filament binding	0	0	0	129	0	10	139
SRC	0.036	0.009	-10000	0	0	31	31
ITGB3	0.037	0.004	-10000	0	0	6	6
GNAQ	0.035	0.01	-10000	0	0	35	35
EFA6/PI-4-5-P2	0.001	0.001	0.001	149	-0.001	7	156
ARF6/GDP	0.033	0.073	0.17	15	-0.21	25	40
ARF6/GDP/GULP/ACAP1	0.053	0.075	0.2	27	-0.18	5	32
alphaIIb/beta3 Integrin/paxillin/GIT1	0.094	0.016	-10000	0	-10000	0	0
ACAP1	0	0	0	58	-10000	0	58
ACAP2	0	0	0	99	0	5	104
LHCGR/beta Arrestin2	0.031	0.025	-10000	0	-0.14	7	7
EFNA1	0.034	0.012	-10000	0	0	53	53
HGF	0.026	0.018	-10000	0	0	163	163
CYTH3	0	0	0.001	132	-0.001	9	141
CYTH2	0	0.001	0.003	3	-0.004	10	13
NCK1	0.036	0.009	-10000	0	0	28	28
fibronectin binding	0	0	0	129	0	10	139
endosomal lumen acidification	0	0	0	125	0	11	136
microtubule-based process	0	0	-10000	0	0	4	4
GULP1	0.025	0.018	-10000	0	0	169	169
GNAQ/ARNO	0.027	0.008	0.042	7	0	35	42
mol:Phosphatidic acid	0	0	0	99	0	5	104
PIP3-E	0	0	0	59	0	20	79
MET	0.024	0.018	-10000	0	0	184	184
GNA14	0.035	0.009	-10000	0	0	34	34
GNA15	0.034	0.011	-10000	0	0	45	45
GIT1	0.037	0.004	-10000	0	0	7	7
mol:PI-4-5-P2	0	0	0.001	137	-0.001	8	145
GNA11	0.034	0.011	-10000	0	0	46	46
LHCGR	0.038	0.002	-10000	0	0	1	1
AGTR1	0.036	0.008	-10000	0	0	22	22
desensitization of G-protein coupled receptor protein signaling pathway	0.031	0.025	-10000	0	-0.14	7	7
IPCEF1/ARNO	0.001	0.038	-10000	0	-0.084	65	65
alphaIIb/beta3 Integrin	0.055	0.006	-10000	0	-10000	0	0

×

TCGA08_retinoblastoma

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
CDKN2B	0.004	0.027	-10000	0	-0.054	53	53
CDKN2C	-0.007	0.023	-10000	0	-0.034	122	122
CDKN2A	0.006	0.016	0.087	1	-10000	0	1
CCND2	-0.002	0.019	0.11	6	-10000	0	6
RB1	-0.049	0.091	0.17	1	-0.19	143	144
CDK4	-0.002	0.021	0.13	6	-10000	0	6
CDK6	-0.001	0.02	0.13	6	-10000	0	6
G1/S progression	0.059	0.099	0.19	165	-0.16	2	167

×

LPA receptor mediated events

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
GNB1/GNG2	0.005	0.057	-10000	0	-0.14	61	61
NF kappa B1 p50/RelA/I kappa B alpha	0.009	0.097	0.22	11	-0.2	45	56
AP1	-0.01	0.073	0.09	3	-0.14	94	97
mol:PIP3	-0.024	0.05	-10000	0	-0.13	77	77
AKT1	0.002	0.096	0.21	21	-0.25	24	45
PTK2B	-0.002	0.058	0.12	6	-0.15	58	64
RHOA	0.019	0.08	0.17	18	-0.36	12	30
PIK3CB	0.036	0.008	-10000	0	-0.003	20	20
mol:Ca2+	-0.009	0.04	0.17	5	-0.14	19	24
MAGI3	0	0	-10000	0	-0.005	2	2
RELA	0.037	0.005	-10000	0	0	10	10
apoptosis	0.002	0.062	0.1	36	-0.16	54	90
HRAS/GDP	0.022	0.028	-10000	0	-0.13	16	16
positive regulation of microtubule depolymerization	-0.021	0.073	0.18	9	-0.21	37	46
NF kappa B1 p50/RelA	-0.021	0.067	0.078	64	-0.16	56	120
endothelial cell migration	-0.016	0.097	-10000	0	-0.3	54	54
ADCY4	-0.007	0.09	0.16	13	-0.25	39	52
ADCY5	-0.007	0.09	0.16	13	-0.25	39	52
ADCY6	-0.004	0.09	0.17	12	-0.25	37	49
ADCY7	-0.007	0.094	0.17	12	-0.24	43	55
ADCY1	-0.013	0.082	0.16	5	-0.25	37	42
ADCY2	-0.006	0.092	0.17	12	-0.24	40	52
ADCY3	-0.007	0.09	0.16	13	-0.25	39	52
ADCY8	-0.006	0.088	0.16	13	-0.24	39	52
ADCY9	-0.005	0.091	0.17	13	-0.24	40	53
GSK3B	-0.01	0.064	0.18	6	-0.16	57	63
arachidonic acid secretion	-0.022	0.11	0.15	9	-0.24	69	78
GNG2	0	0.001	0.002	1	-0.004	16	17
TRIP6	-0.013	0.081	-10000	0	-0.25	52	52
GNAO1	0.004	0.058	0.13	25	-0.16	48	73
HRAS	0.035	0.01	-10000	0	0	37	37
NFKBIA	-0.017	0.084	0.18	14	-0.22	38	52
GAB1	0.034	0.012	-10000	0	0	55	55
mol:GTP	0	0	-10000	0	-10000	0	0
lamellipodium assembly	-0.002	0.2	-10000	0	-0.82	29	29
JUN	0.034	0.011	-10000	0	0	44	44
LPA/LPA2/NHERF2	0.02	0.029	-10000	0	-0.061	54	54
TIAM1	-0.01	0.24	-10000	0	-1	29	29
PIK3R1	0.033	0.013	-10000	0	0	68	68
mol:IP3	-0.009	0.038	0.2	3	-0.14	19	22
PLCB3	0.007	0.035	0.2	4	-10000	0	4
FOS	0.025	0.018	-10000	0	0	166	166
positive regulation of mitosis	-0.022	0.11	0.15	9	-0.24	69	78
LPA/LPA1-2-3	-0.008	0.04	-10000	0	-0.12	54	54
mol:Ca ++	0	0	-10000	0	-10000	0	0
JNK cascade	0	0.001	-10000	0	-0.002	2	2
BCAR1	0	0	-10000	0	-10000	0	0
stress fiber formation	0.01	0.066	0.15	1	-0.27	10	11
GNAZ	0.003	0.063	0.13	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	54	54
LPA/LPA2/MAGI-3	-0.004	0.017	-10000	0	-0.05	56	56
ARHGEF1	0.034	0.12	0.2	143	-0.16	37	180
GNAI2	0.004	0.069	0.13	39	-0.17	54	93
GNAI3	0.007	0.063	0.13	39	-0.15	54	93
GNAI1	0.001	0.049	0.13	17	-0.16	32	49
LPA/LPA3	-0.006	0.021	-10000	0	-0.066	54	54
LPA/LPA2	-0.005	0.021	-10000	0	-0.065	54	54
LPA/LPA1	-0.012	0.054	-10000	0	-0.17	54	54
HB-EGF/EGFR	-0.005	0.052	0.1	11	-0.14	51	62
HBEGF	-0.01	0.012	0	291	-10000	0	291
mol:DAG	-0.009	0.038	0.2	3	-0.14	19	22
cAMP biosynthetic process	-0.001	0.11	0.19	34	-0.26	47	81
NFKB1	0.036	0.007	-10000	0	0	18	18
SRC	0.035	0.009	-10000	0	0	31	31
GNB1	0.034	0.011	-10000	0	0	47	47
LYN	-0.024	0.095	0.18	18	-0.22	65	83
GNAQ	0.009	0.026	0.058	38	-0.057	57	95
LPAR2	0	0.001	0.002	1	-0.005	4	5
LPAR3	0	0.001	-10000	0	-0.002	5	5
LPAR1	-0.009	0.033	-10000	0	-0.1	54	54
IL8	-0.12	0.2	0.29	14	-0.39	161	175
PTK2	0.014	0.058	0.13	38	-0.13	53	91
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
CASP3	0.002	0.063	0.1	36	-0.16	54	90
EGFR	0.01	0.017	-10000	0	0	373	373
PLCG1	0.005	0.038	0.062	25	-0.082	57	82
PLD2	0.016	0.054	0.13	38	-0.12	55	93
G12/G13	0.016	0.062	-10000	0	-0.15	48	48
PI3K-beta	-0.013	0.068	-10000	0	-0.25	24	24
cell migration	0.001	0.072	-10000	0	-0.25	29	29
SLC9A3R2	0.037	0.004	-10000	0	0	7	7
PXN	0.01	0.067	-10000	0	-0.28	10	10
HRAS/GTP	-0.022	0.11	0.16	9	-0.26	65	74
RAC1	0.026	0.017	-10000	0	0	156	156
MMP9	0.017	0.019	-10000	0	0	281	281
PRKCE	0.037	0.004	-10000	0	-0.011	3	3
PRKCD	-0.005	0.055	0.2	13	-0.2	3	16
Gi(beta/gamma)	-0.013	0.11	0.15	14	-0.26	61	75
mol:LPA	-0.009	0.033	-10000	0	-0.1	54	54
TRIP6/p130 Cas/FAK1/Paxillin	-0.006	0.08	0.13	1	-0.21	45	46
MAPKKK cascade	-0.022	0.11	0.15	9	-0.24	69	78
contractile ring contraction involved in cytokinesis	0.019	0.081	0.18	17	-0.35	12	29
mol:GDP	0	0	-10000	0	-10000	0	0
GNA14	0.009	0.026	0.058	37	-0.057	57	94
GNA15	0.008	0.026	0.058	35	-0.056	55	90
GNA12	0.024	0.018	-10000	0	0	180	180
GNA13	0.036	0.007	-10000	0	0	21	21
MAPT	-0.021	0.074	0.18	9	-0.21	38	47
GNA11	0.011	0.023	0.058	39	-0.056	38	77
Rac1/GTP	-0.003	0.22	-10000	0	-0.86	29	29
MMP2	-0.016	0.097	-10000	0	-0.3	54	54

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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
HIF3A	0.035	0.009	-10000	0	0	34	34
oxygen homeostasis	0	0	-10000	0	-10000	0	0
TCEB2	0.037	0.004	-10000	0	0	6	6
TCEB1	0.036	0.008	-10000	0	0	22	22
HIF1A/p53	-0.04	0.13	0.2	2	-0.28	98	100
HIF1A	-0.033	0.11	-10000	0	-0.28	78	78
COPS5	0.037	0.006	-10000	0	0	13	13
VHL/Elongin B/Elongin C/RBX1/CUL2	0.052	0.061	-10000	0	-0.12	23	23
FIH (dimer)	0.028	0.016	-10000	0	0	131	131
CDKN2A	0.005	0.013	-10000	0	0	444	444
ARNT/IPAS	0.051	0.016	-10000	0	-10000	0	0
HIF1AN	0.028	0.016	-10000	0	0	131	131
GNB2L1	0.037	0.005	-10000	0	0	10	10
HIF1A/ARNT	-0.039	0.13	-10000	0	-0.28	97	97
CUL2	0.028	0.017	-10000	0	0	133	133
OS9	0.031	0.015	-10000	0	0	93	93
RACK1/Elongin B/Elongin C	0.069	0.032	-10000	0	-0.13	9	9
response to hypoxia	0	0	-10000	0	-10000	0	0
HIF1A/Hsp90	-0.038	0.13	0.2	2	-0.28	101	103
PHD1-3/OS9	0.056	0.065	-10000	0	-0.14	30	30
HIF1A/RACK1/Elongin B/Elongin C	-0.02	0.15	-10000	0	-0.28	101	101
VHL	0	0	-10000	0	-10000	0	0
HSP90AA1	0.035	0.01	-10000	0	0	35	35
HIF1A/JAB1	-0.04	0.13	0.23	1	-0.28	101	102
EGLN3	0.031	0.015	-10000	0	0	96	96
EGLN2	0.036	0.008	-10000	0	0	21	21
EGLN1	0.035	0.009	-10000	0	0	32	32
TP53	0.032	0.013	-10000	0	0	71	71
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	0.006	0.1	-10000	0	-0.62	12	12
ARNT	0.037	0.005	-10000	0	0	11	11
ARD1A	0	0	-10000	0	-10000	0	0
RBX1	0.034	0.011	-10000	0	0	45	45
HIF1A/p19ARF	-0.048	0.11	-10000	0	-0.27	90	90

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.033	0.012	-10000	0	0	57	57
CCL5	0.034	0.012	-10000	0	0	55	55
SDCBP	0.036	0.007	-10000	0	0	20	20
FGFR/FGF2/Syndecan-1	0.011	0.096	0.17	40	-0.23	11	51
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	0.016	0.1	0.21	21	-0.24	16	37
Syndecan-1/Syntenin	0.026	0.11	0.22	33	-0.24	18	51
MAPK3	0.003	0.1	0.19	25	-0.22	22	47
HGF/MET	0.034	0.027	-10000	0	-10000	0	0
TGFB1/TGF beta receptor Type II	0.033	0.012	-10000	0	0	57	57
BSG	0.033	0.012	-10000	0	0	57	57
keratinocyte migration	0.015	0.1	0.21	21	-0.23	16	37
Syndecan-1/RANTES	0.02	0.1	0.22	24	-0.24	14	38
Syndecan-1/CD147	0.024	0.12	0.23	15	-0.23	22	37
Syndecan-1/Syntenin/PIP2	0.023	0.11	0.2	33	-0.23	18	51
LAMA5	0.032	0.013	-10000	0	0	72	72
positive regulation of cell-cell adhesion	0.022	0.1	0.2	33	-0.23	18	51
MMP7	0.027	0.017	-10000	0	0	140	140
HGF	0.026	0.018	-10000	0	0	163	163
Syndecan-1/CASK	-0.009	0.081	0.16	4	-0.23	15	19
Syndecan-1/HGF/MET	0.023	0.093	0.24	10	-0.24	10	20
regulation of cell adhesion	-0.005	0.11	0.23	30	-0.23	22	52
HPSE	0.033	0.012	-10000	0	0	59	59
positive regulation of cell migration	0.011	0.096	0.17	40	-0.23	11	51
SDC1	0.008	0.089	0.15	33	-0.15	86	119
Syndecan-1/Collagen	0.011	0.096	0.17	40	-0.23	11	51
PPIB	0.035	0.01	-10000	0	0	35	35
MET	0.024	0.018	-10000	0	0	184	184
PRKACA	0.036	0.007	-10000	0	0	17	17
MMP9	0.017	0.019	-10000	0	0	281	281
MAPK1	0.002	0.1	0.18	23	-0.22	22	45
homophilic cell adhesion	0.015	0.1	0.19	49	-0.23	13	62
MMP1	0.032	0.013	-10000	0	0	74	74

×

EGFR-dependent Endothelin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.035	0.01	-10000	0	0	37	37
EGFR	0.01	0.017	-10000	0	0	373	373
EGF/EGFR	0.001	0.053	-10000	0	-0.11	66	66
EGF/EGFR dimer/SHC/GRB2/SOS1	0.007	0.059	-10000	0	-0.11	63	63
mol:GTP	0	0	-10000	0	-10000	0	0
EDNRA	0.029	0.016	-10000	0	0	123	123
response to oxidative stress	0	0	-10000	0	-10000	0	0
EGF	0.036	0.008	-10000	0	0	25	25
EGF/EGFR dimer/SHC	0.001	0.057	-10000	0	-0.12	63	63
mol:GDP	0.005	0.056	-10000	0	-0.11	63	63
mol:Ca2+	0	0	-10000	0	-10000	0	0
EDN1	0.034	0.012	-10000	0	0	54	54
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
HRAS/GTP	-0.004	0.052	-10000	0	-0.11	71	71
SHC1	0.034	0.012	-10000	0	0	53	53
HRAS/GDP	0	0.059	-10000	0	-0.12	71	71
FRAP1	-0.017	0.039	0.055	20	-0.11	63	83
EGF/EGFR dimer	-0.004	0.057	-10000	0	-0.14	65	65
SOS1	0	0	-10000	0	-10000	0	0
GRB2	0.036	0.007	-10000	0	0	19	19
ETA receptor/Endothelin-1	0.024	0.06	-10000	0	-0.14	52	52

×

Syndecan-4-mediated signaling events

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	-0.032	0.16	-10000	0	-0.46	43	43
Syndecan-4/Syndesmos	-0.14	0.29	-10000	0	-0.76	66	66
positive regulation of JNK cascade	-0.13	0.26	-10000	0	-0.64	78	78
Syndecan-4/ADAM12	-0.14	0.29	-10000	0	-0.76	66	66
CCL5	0.034	0.012	-10000	0	0	55	55
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
DNM2	0.036	0.007	-10000	0	0	20	20
ITGA5	0.033	0.012	-10000	0	0	62	62
SDCBP	0.036	0.007	-10000	0	0	20	20
PLG	0.028	0.025	-10000	0	-0.044	41	41
ADAM12	0.026	0.017	-10000	0	0	154	154
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	-0.024	0.023	-10000	0	-10000	0	0
Syndecan-4/Laminin alpha1	-0.14	0.29	-10000	0	-0.76	66	66
Syndecan-4/CXCL12/CXCR4	-0.14	0.29	-10000	0	-0.69	78	78
Syndecan-4/Laminin alpha3	-0.13	0.3	-10000	0	-0.75	66	66
MDK	0.031	0.015	-10000	0	0	96	96
Syndecan-4/FZD7	-0.14	0.3	-10000	0	-0.67	90	90
Syndecan-4/Midkine	-0.14	0.3	-10000	0	-0.69	83	83
FZD7	0.027	0.017	-10000	0	0	144	144
Syndecan-4/FGFR1/FGF	-0.1	0.29	-10000	0	-0.72	63	63
THBS1	0.031	0.014	-10000	0	0	90	90
integrin-mediated signaling pathway	-0.13	0.29	-10000	0	-0.64	86	86
positive regulation of MAPKKK cascade	-0.13	0.26	-10000	0	-0.64	78	78
Syndecan-4/TACI	-0.13	0.3	-10000	0	-0.76	66	66
CXCR4	0.03	0.015	-10000	0	0	104	104
cell adhesion	-0.009	0.056	0.21	3	-0.24	20	23
Syndecan-4/Dynamin	-0.13	0.3	-10000	0	-0.76	66	66
Syndecan-4/TSP1	-0.14	0.29	-10000	0	-0.76	65	65
Syndecan-4/GIPC	-0.13	0.3	-10000	0	-0.76	66	66
Syndecan-4/RANTES	-0.13	0.29	-10000	0	-0.76	66	66
ITGB1	0.029	0.016	-10000	0	0	117	117
LAMA1	0	0	-10000	0	-10000	0	0
LAMA3	0.034	0.011	-10000	0	0	48	48
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCA	0	0.11	1.1	5	-10000	0	5
Syndecan-4/alpha-Actinin	-0.14	0.3	-10000	0	-0.68	84	84
TFPI	0.03	0.015	-10000	0	0	105	105
F2	0.01	0.043	-10000	0	-0.046	171	171
alpha5/beta1 Integrin	0.032	0.043	-10000	0	-0.14	21	21
positive regulation of cell adhesion	-0.13	0.28	-10000	0	-0.72	66	66
ACTN1	0.029	0.016	-10000	0	0	124	124
TNC	0.028	0.016	-10000	0	0	125	125
Syndecan-4/CXCL12	-0.14	0.29	-10000	0	-0.76	65	65
FGF6	0.036	0.009	-10000	0	0	28	28
RHOA	0.036	0.007	-10000	0	0	20	20
CXCL12	0.024	0.018	-10000	0	0	186	186
TNFRSF13B	0.037	0.005	-10000	0	0	10	10
FGF2	0.036	0.008	-10000	0	0	25	25
FGFR1	0.037	0.004	-10000	0	0	7	7
Syndecan-4/PI-4-5-P2	-0.14	0.29	-10000	0	-0.76	66	66
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.029	0.025	-10000	0	-0.044	41	41
cell migration	-0.01	0.016	-10000	0	-10000	0	0
PRKCD	0.029	0.025	-10000	0	-0.044	38	38
vasculogenesis	-0.13	0.28	-10000	0	-0.72	65	65
SDC4	-0.15	0.31	-10000	0	-0.82	65	65
Syndecan-4/Tenascin C	-0.14	0.3	-10000	0	-0.68	86	86
Syndecan-4/PI-4-5-P2/PKC alpha	-0.019	0.018	-10000	0	-10000	0	0
Syndecan-4/Syntenin	-0.13	0.3	-10000	0	-0.76	67	67
MMP9	0.012	0.024	-10000	0	-0.044	36	36
Rac1/GTP	-0.009	0.057	0.21	3	-0.25	20	23
cytoskeleton organization	-0.14	0.27	-10000	0	-0.71	66	66
GIPC1	0.036	0.007	-10000	0	0	18	18
Syndecan-4/TFPI	-0.14	0.3	-10000	0	-0.72	73	73

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-10000	0	-10000	0	0
GNAO1	0.031	0.014	-10000	0	0	87	87
CDC42/GTP	0.004	0.1	-10000	0	-0.24	51	51
PLCG1	-0.016	0.094	0.11	1	-0.2	85	86
mol:GTP	0	0	-10000	0	-10000	0	0
GNAI2	0.034	0.011	-10000	0	0	46	46
GNAI3	0.037	0.007	-10000	0	0	16	16
G12/G13	0.027	0.048	-10000	0	-0.14	29	29
cell migration	0.003	0.1	-10000	0	-0.23	51	51
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
MAPK3	-0.016	0.097	0.11	1	-0.2	91	92
MAPK1	-0.01	0.091	-10000	0	-0.19	82	82
S1P/S1P5/Gi	-0.012	0.098	-10000	0	-0.2	84	84
GNAI1	0.019	0.019	-10000	0	0	255	255
CDC42/GDP	0.026	0.006	-10000	0	-10000	0	0
S1P/S1P5/G12	0.01	0.031	-10000	0	-0.1	29	29
RHOA	0.037	0.1	0.19	146	-0.18	3	149
S1P/S1P4/Gi	-0.012	0.098	-10000	0	-0.2	84	84
mol:GDP	0	0	-10000	0	-10000	0	0
GNAZ	0.032	0.014	-10000	0	0	81	81
S1P/S1P4/G12/G13	0.025	0.038	-10000	0	-0.1	29	29
GNA12	0.024	0.018	-10000	0	0	180	180
GNA13	0.036	0.008	-10000	0	0	21	21
CDC42	0.036	0.008	-10000	0	0	26	26

×

S1P5 pathway

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
mol:S1P	0	0	-10000	0	-10000	0	0
telencephalon oligodendrocyte cell migration	-0.004	0.1	0.24	53	-10000	0	53
GNAI2	0.034	0.011	-10000	0	0	46	46
S1P/S1P5/G12	0.01	0.031	-10000	0	-0.1	29	29
mol:GDP	0	0	-10000	0	-10000	0	0
GNAO1	0.031	0.014	-10000	0	0	87	87
RhoA/GTP	0.004	0.11	-10000	0	-0.24	53	53
negative regulation of cAMP metabolic process	-0.012	0.098	-10000	0	-0.2	85	85
GNAZ	0.032	0.014	-10000	0	0	81	81
GNAI3	0.037	0.007	-10000	0	0	16	16
GNA12	0.024	0.018	-10000	0	0	180	180
S1PR5	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
S1P/S1P5/Gi	-0.012	0.098	-10000	0	-0.2	84	84
RhoA/GDP	0.025	0.019	-10000	0	-0.13	7	7
RHOA	0.036	0.007	-10000	0	0	20	20
GNAI1	0.019	0.019	-10000	0	0	255	255

×

Nongenotropic Androgen signaling

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
PTK2	-0.011	0.003	0	33	-10000	0	33
GNB1/GNG2	0.038	0.032	-10000	0	-0.1	20	20
regulation of S phase of mitotic cell cycle	-0.005	0.08	-10000	0	-0.18	72	72
GNAO1	0.031	0.014	-10000	0	0	87	87
HRAS	0.035	0.01	-10000	0	0	37	37
SHBG/T-DHT	0.025	0.005	-10000	0	-10000	0	0
PELP1	0.036	0.007	-10000	0	0	19	19
AKT1	-0.011	0.004	0	58	-10000	0	58
MAP2K1	-0.031	0.081	0.17	28	-0.18	66	94
T-DHT/AR	0.026	0.008	-10000	0	-10000	0	0
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.003	0.003	9	-0.006	77	86
GNAI2	0.034	0.011	-10000	0	0	46	46
GNAI3	0.036	0.007	-10000	0	0	16	16
GNAI1	0.019	0.019	-10000	0	0	255	255
mol:GDP	-0.021	0.034	-10000	0	-0.15	12	12
cell proliferation	-0.057	0.18	0.26	15	-0.42	85	100
PIK3CA	0.032	0.013	-10000	0	0	74	74
FOS	-0.087	0.28	0.36	3	-0.69	84	87
mol:Ca2+	-0.004	0.02	0.027	2	-0.053	58	60
MAPK3	-0.04	0.13	0.24	17	-0.31	77	94
MAPK1	-0.038	0.16	0.24	3	-0.4	55	58
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:IP3	0	0.002	0.003	59	-0.004	75	134
cAMP biosynthetic process	-0.003	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	75	134
HRAS/GTP	0.042	0.066	-10000	0	-0.096	69	69
actin cytoskeleton reorganization	0.02	0.055	-10000	0	-0.12	47	47
SRC	0.035	0.009	-10000	0	0	31	31
voltage-gated calcium channel activity	0	0.002	0.003	59	-0.004	75	134
PI3K	0.02	0.063	-10000	0	-0.13	75	75
apoptosis	0.046	0.19	0.42	85	-0.24	12	97
T-DHT/AR/PELP1	0.044	0.025	-10000	0	-0.12	7	7
HRAS/GDP	0.01	0.06	-10000	0	-0.18	16	16
CREB1	-0.066	0.19	0.24	12	-0.46	85	97
RAC1-CDC42/GTP	0.029	0.061	-10000	0	-0.12	47	47
AR	0.036	0.008	-10000	0	0	23	23
GNB1	0.034	0.011	-10000	0	0	47	47
RAF1	-0.021	0.076	0.19	27	-0.22	13	40
RAC1-CDC42/GDP	0.022	0.054	-10000	0	-0.16	13	13
T-DHT/AR/PELP1/Src	0.06	0.033	-10000	0	-0.12	7	7
MAP2K2	-0.034	0.075	0.17	20	-0.17	65	85
T-DHT/AR/PELP1/Src/PI3K	-0.004	0.08	-10000	0	-0.18	71	71
GNAZ	0.032	0.014	-10000	0	0	81	81
SHBG	0.036	0.007	-10000	0	0	17	17
Gi family/GNB1/GNG2/GDP	-0.044	0.17	-10000	0	-0.44	60	60
mol:T-DHT	0	0.001	0.002	1	-0.004	23	24
RAC1	0.026	0.017	-10000	0	0	156	156
GNRH1	-0.012	0.002	0	11	-10000	0	11
Gi family/GTP	-0.008	0.081	0.12	1	-0.19	61	62
CDC42	0.036	0.008	-10000	0	0	26	26

×

Signaling events mediated by VEGFR1 and VEGFR2

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
alphaV beta3 Integrin	0.045	0.042	-10000	0	-0.14	24	24
AKT1	-0.058	0.21	0.31	15	-0.38	107	122
PTK2B	-0.013	0.12	0.22	53	-0.35	16	69
VEGFR2 homodimer/Frs2	0.023	0.072	0.16	3	-0.3	16	19
CAV1	0.016	0.019	-10000	0	0	287	287
CALM1	0.033	0.012	-10000	0	0	60	60
VEGFR2 homodimer/VEGFA homodimer/Frs2	0.009	0.1	-10000	0	-0.26	33	33
endothelial cell proliferation	-0.016	0.17	0.31	27	-0.35	53	80
mol:Ca2+	-0.005	0.13	0.24	69	-0.27	31	100
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	0.012	0.11	-10000	0	-0.24	40	40
RP11-342D11.1	-0.026	0.098	0.17	40	-0.25	37	77
CDH5	0.031	0.014	-10000	0	0	91	91
VEGFA homodimer	0.018	0.077	-10000	0	-0.12	107	107
SHC1	0.034	0.012	-10000	0	0	53	53
SHC2	0.033	0.012	-10000	0	0	57	57
HRAS/GDP	-0.006	0.097	-10000	0	-0.24	45	45
SH2D2A	0.037	0.006	-10000	0	0	12	12
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	0.003	0.13	0.29	2	-0.36	22	24
VEGFR2 homodimer/VEGFA homodimer/TsAd	0.009	0.1	-10000	0	-0.27	30	30
VEGFR1 homodimer	0.035	0.01	-10000	0	0	37	37
SHC/GRB2/SOS1	0.021	0.11	-10000	0	-0.25	40	40
GRB10	-0.025	0.1	0.2	23	-0.31	37	60
PTPN11	0.037	0.006	-10000	0	0	12	12
GRB2	0.036	0.007	-10000	0	0	19	19
PAK1	0.036	0.007	-10000	0	0	18	18
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	0.016	0.14	0.27	1	-0.27	50	51
HRAS	0.035	0.01	-10000	0	0	37	37
VEGF/Rho/ROCK1/Integrin Complex	-0.014	0.13	0.2	4	-0.35	42	46
HIF1A	0.034	0.011	-10000	0	0	47	47
FRS2	0.036	0.008	-10000	0	0	24	24
oxygen and reactive oxygen species metabolic process	0.011	0.1	-10000	0	-0.24	40	40
mol:GTP	0	0	-10000	0	-10000	0	0
FLT4	0.037	0.005	-10000	0	0	10	10
Nck/Pak	0.05	0.025	-10000	0	-0.14	6	6
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.004	0.12	-10000	0	-0.26	44	44
mol:GDP	0.01	0.1	-10000	0	-0.24	43	43
mol:NADP	0.015	0.14	0.34	19	-0.34	17	36
eNOS/Hsp90	0.026	0.14	0.34	17	-0.33	17	34
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:IP3	-0.005	0.13	0.24	69	-0.28	31	100
HIF1A/ARNT	0.047	0.032	-10000	0	-0.14	11	11
SHB	0.034	0.011	-10000	0	0	52	52
VEGFA	0.024	0.024	0.08	11	-0.053	14	25
VEGFC	0.034	0.011	-10000	0	0	51	51
FAK1/Vinculin	-0.025	0.16	0.26	16	-0.4	44	60
mol:Ca ++	0	0	-10000	0	-10000	0	0
RHOA	0.036	0.007	-10000	0	0	20	20
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.025	0.12	0.23	1	-0.26	37	38
PTPN6	0.034	0.012	-10000	0	0	55	55
EPAS1	0.03	0.057	0.13	2	-0.19	20	22
mol:L-citrulline	0.015	0.14	0.34	19	-0.34	17	36
ITGAV	0.035	0.009	-10000	0	0	34	34
PIK3CA	0.032	0.013	-10000	0	0	74	74
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	0.029	0.12	0.23	1	-0.26	34	35
VEGFR2 homodimer/VEGFA homodimer	0.01	0.12	-10000	0	-0.26	42	42
VEGFR2/3 heterodimer	0.022	0.073	0.16	3	-0.29	17	20
VEGFB	0.037	0.005	-10000	0	0	9	9
MAPK11	-0.009	0.14	0.28	45	-0.3	35	80
VEGFR2 homodimer	0.001	0.072	0.16	14	-0.38	11	25
FLT1	0.035	0.01	-10000	0	0	37	37
NEDD4	0.032	0.028	0.082	28	-0.05	38	66
MAPK3	0.008	0.14	0.28	51	-0.26	25	76
MAPK1	0.006	0.14	0.28	53	-0.26	30	83
VEGFA145/NRP2	0.004	0.08	-10000	0	-0.14	107	107
VEGFR1/2 heterodimer	0.02	0.072	0.16	3	-0.29	17	20
KDR	0.001	0.072	0.16	14	-0.38	11	25
VEGFA165/NRP1/VEGFR2 homodimer	0.015	0.11	0.23	5	-0.24	40	45
SRC	0.035	0.009	-10000	0	0	31	31
platelet activating factor biosynthetic process	0.007	0.14	0.28	53	-0.26	30	83
PI3K	-0.036	0.17	0.26	9	-0.3	104	113
VEGFR2 homodimer/VEGFA homodimer/NCK1	0.008	0.11	-10000	0	-0.2	57	57
FES	-0.006	0.14	0.24	72	-0.26	37	109
GAB1	-0.025	0.16	0.25	11	-0.29	102	113
VEGFR2 homodimer/VEGFA homodimer/Src	0.008	0.1	-10000	0	-0.26	31	31
CTNNB1	0.036	0.007	-10000	0	0	17	17
SOS1	0	0	-10000	0	-10000	0	0
ARNT	0.037	0.005	-10000	0	0	11	11
eNOS/Caveolin-1	-0.007	0.11	0.33	4	-0.36	15	19
VEGFR2 homodimer/VEGFA homodimer/Yes	0.004	0.11	-10000	0	-0.25	41	41
PI3K/GAB1	-0.045	0.2	0.3	11	-0.37	100	111
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	0.041	0.12	0.26	3	-0.24	30	33
PRKACA	0.036	0.007	-10000	0	0	17	17
VEGFR2/3 heterodimer/VEGFC homodimer	0.045	0.074	0.2	1	-0.27	15	16
HSP90AA1	0.035	0.01	-10000	0	0	35	35
CDC42	-0.006	0.13	0.24	70	-0.26	37	107
actin cytoskeleton reorganization	0.009	0.1	-10000	0	-0.26	30	30
PTK2	-0.024	0.17	0.25	29	-0.42	42	71
EDG1	-0.026	0.098	0.17	40	-0.25	37	77
mol:DAG	-0.005	0.13	0.24	69	-0.28	31	100
CaM/Ca2+	-0.013	0.12	0.21	61	-0.28	31	92
MAP2K3	-0.013	0.13	0.24	60	-0.27	31	91
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	0.028	0.14	0.25	68	-0.31	38	106
PLCG1	-0.006	0.13	0.24	69	-0.28	31	100
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	0.025	0.11	0.23	1	-0.25	30	31
IQGAP1	0.034	0.011	-10000	0	0	47	47
YES1	0.035	0.01	-10000	0	0	43	43
VEGFR2 homodimer/VEGFA homodimer/SHP2	0.008	0.11	-10000	0	-0.26	35	35
VEGFR2 homodimer/VEGFA homodimer/SHP1	0.006	0.1	-10000	0	-0.26	33	33
cell migration	-0.029	0.17	0.28	18	-0.39	54	72
mol:PI-3-4-5-P3	-0.032	0.16	0.26	10	-0.29	104	114
FYN	0.031	0.015	-10000	0	0	93	93
VEGFB/NRP1	-0.01	0.12	0.2	65	-0.26	31	96
mol:NO	0.015	0.14	0.34	19	-0.34	17	36
PXN	0.037	0.005	-10000	0	0	9	9
HRAS/GTP	-0.052	0.073	-10000	0	-0.25	42	42
VEGFR2 homodimer/VEGFA homodimer/GRB10	0.011	0.12	-10000	0	-0.31	38	38
VHL	0	0	-10000	0	-10000	0	0
ITGB3	0.037	0.004	-10000	0	0	6	6
NOS3	0.012	0.14	0.35	17	-0.38	17	34
VEGFR2 homodimer/VEGFA homodimer/Sck	0.002	0.11	-10000	0	-0.27	38	38
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCA	-0.011	0.13	0.24	59	-0.27	31	90
PRKCB	-0.007	0.12	0.24	59	-0.26	31	90
VCL	0.028	0.016	-10000	0	0	128	128
VEGFA165/NRP1	-0.009	0.1	0.19	28	-0.26	37	65
VEGFR1/2 heterodimer/VEGFA homodimer	0.006	0.1	-10000	0	-0.26	32	32
VEGFA165/NRP2	0.004	0.08	-10000	0	-0.14	107	107
MAPKKK cascade	-0.018	0.11	0.25	13	-0.32	30	43
NRP2	0.037	0.005	-10000	0	0	8	8
VEGFC homodimer	0.034	0.011	-10000	0	0	51	51
NCK1	0.036	0.009	-10000	0	0	28	28
ROCK1	0.037	0.007	-10000	0	0	16	16
FAK1/Paxillin	-0.01	0.17	0.27	19	-0.4	43	62
MAP3K13	-0.007	0.13	0.24	68	-0.26	37	105
PDPK1	-0.044	0.15	0.24	27	-0.27	103	130

×

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	0.03	0.087	-10000	0	-0.14	92	92
alphaM/beta2 Integrin/GPIbA	0.05	0.071	-10000	0	-0.12	62	62
alphaM/beta2 Integrin/proMMP-9	-0.008	0.089	-10000	0	-0.13	144	144
PLAUR	0.031	0.014	-10000	0	0	90	90
HMGB1	0.04	0.014	0.087	1	-10000	0	1
alphaM/beta2 Integrin/Talin	0.039	0.073	-10000	0	-0.13	58	58
AGER	0.042	0.01	0.085	2	-10000	0	2
RAP1A	0.037	0.005	-10000	0	0	10	10
SELPLG	0.037	0.006	-10000	0	0	12	12
mol:LDL	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	0.075	0.087	-10000	0	-0.13	5	5
mol:GTP	0	0	-10000	0	-10000	0	0
MMP9	0.017	0.019	-10000	0	0	281	281
CYR61	0.025	0.018	-10000	0	0	167	167
TLN1	0.03	0.015	-10000	0	0	104	104
Rap1/GTP	0.025	0.071	-10000	0	-0.21	20	20
RHOA	0.036	0.007	-10000	0	0	20	20
P-selectin oligomer	0.037	0.006	-10000	0	0	14	14
MYH2	0.019	0.066	-10000	0	-0.23	13	13
MST1R	0.036	0.008	-10000	0	0	22	22
leukocyte activation during inflammatory response	0.053	0.067	-10000	0	-0.1	59	59
APOB	0.037	0.006	-10000	0	0	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
complement component iC3b receptor activity	0	0	-10000	0	-10000	0	0
MMP2	0.03	0.015	-10000	0	0	104	104
JAM3	0.034	0.012	-10000	0	0	55	55
GP1BA	0.037	0.006	-10000	0	0	12	12
alphaM/beta2 Integrin/CTGF	0.021	0.087	-10000	0	-0.13	105	105
alphaM/beta2 Integrin	0.021	0.075	-10000	0	-0.24	19	19
JAM3 homodimer	0.034	0.012	-10000	0	0	55	55
ICAM2	0.035	0.009	-10000	0	0	30	30
ICAM1	0.032	0.014	-10000	0	0	78	78
phagocytosis triggered by activation of immune response cell surface activating receptor	0.021	0.075	0.14	2	-0.23	19	21
cell adhesion	0.049	0.07	-10000	0	-0.12	62	62
NFKB1	-0.003	0.081	0.21	22	-10000	0	22
THY1	0.032	0.014	-10000	0	0	83	83
RhoA/GDP	0.025	0.019	-10000	0	-0.13	7	7
Lipoprotein(a)	0.046	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/LRP/tPA	0.036	0.1	-10000	0	-0.14	103	103
IL6	-0.017	0.037	-10000	0	-10000	0	0
ITGB2	0.033	0.02	0.083	1	-10000	0	1
elevation of cytosolic calcium ion concentration	0.026	0.087	-10000	0	-0.14	72	72
alphaM/beta2 Integrin/JAM2/JAM3	0.05	0.1	-10000	0	-0.15	88	88
JAM2	0.034	0.012	-10000	0	0	55	55
alphaM/beta2 Integrin/ICAM1	0.076	0.078	-10000	0	-0.12	49	49
alphaM/beta2 Integrin/uPA/Plg	0.039	0.084	-10000	0	-0.13	66	66
RhoA/GTP	0.024	0.068	-10000	0	-0.24	13	13
positive regulation of phagocytosis	0.012	0.1	0.17	1	-0.23	56	57
Ron/MSP	0.052	0.014	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPAR/uPA	0.031	0.09	-10000	0	-0.14	72	72
alphaM/beta2 Integrin/uPAR	0.038	0.079	-10000	0	-0.14	69	69
PLAU	0.022	0.019	-10000	0	0	215	215
PLAT	0.028	0.016	-10000	0	0	131	131
actin filament polymerization	0.02	0.066	0.19	2	-0.22	13	15
MST1	0.036	0.008	-10000	0	0	27	27
alphaM/beta2 Integrin/lipoprotein(a)	0.062	0.07	-10000	0	-0.11	59	59
TNF	0.003	0.089	0.22	20	-10000	0	20
RAP1B	0	0	-10000	0	-10000	0	0
alphaM/beta2 Integrin/uPA	0.021	0.075	-10000	0	-0.14	68	68
fibrinolysis	0.034	0.081	-10000	0	-0.13	66	66
HCK	0.027	0.017	-10000	0	0	145	145
dendritic cell antigen processing and presentation	0.021	0.075	0.14	2	-0.23	19	21
VTN	0.037	0.004	-10000	0	0	7	7
alphaM/beta2 Integrin/CYR61	0.012	0.094	-10000	0	-0.14	123	123
LPA	0.035	0.01	-10000	0	0	35	35
LRP1	0.032	0.013	-10000	0	0	73	73
cell migration	-0.001	0.1	0.15	4	-0.14	146	150
FN1	0.035	0.009	-10000	0	0	31	31
alphaM/beta2 Integrin/Thy1	0.032	0.085	-10000	0	-0.13	87	87
MPO	0.037	0.004	-10000	0	0	6	6
KNG1	0.037	0.007	-10000	0	0	16	16
RAP1/GDP	0.025	0.007	-10000	0	-0.1	1	1
ROCK1	0.019	0.068	0.21	2	-0.24	14	16
ELA2	0	0	-10000	0	-10000	0	0
PLG	0.035	0.01	-10000	0	0	37	37
CTGF	0.027	0.017	-10000	0	0	143	143
alphaM/beta2 Integrin/Hck	0.03	0.091	-10000	0	-0.17	70	70
ITGAM	0.043	0.01	0.085	2	-10000	0	2
alphaM/beta2 Integrin/P-Selectin/PSGL1	0.071	0.074	-10000	0	-0.12	57	57
HP	0.028	0.017	-10000	0	0	136	136
leukocyte adhesion	0.02	0.12	-10000	0	-0.26	32	32
SELP	0.037	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	0.031	0.015	-9999	0	96	96
GPC2	0	0	-9999	-10000	0	0
GPC2/Midkine	0.008	0.049	-9999	-0.13	57	57
neuron projection morphogenesis	0.008	0.049	-9999	-0.13	57	57

×

IL2 signaling events mediated by STAT5

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
GAB2	0.033	0.014	-10000	0	-0.004	59	59
ELF1	0.039	0.017	-10000	0	-10000	0	0
CCNA2	0.029	0.016	-10000	0	0	119	119
PIK3CA	0.032	0.015	-10000	0	-0.003	81	81
JAK3	0.036	0.01	-10000	0	-0.007	26	26
PIK3R1	0.033	0.014	-10000	0	-0.001	70	70
JAK1	0.034	0.012	-10000	0	-0.003	48	48
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.02	0.18	0.24	1	-0.48	45	46
SHC1	0.033	0.014	-10000	0	-0.004	60	60
SP1	-0.014	0.12	-10000	0	-0.27	89	89
IL2RA	0.012	0.011	-10000	0	-10000	0	0
IL2RB	0.034	0.013	-10000	0	-0.003	55	55
SOS1	0	0.002	-10000	0	-10000	0	0
IL2RG	0.036	0.01	-10000	0	-0.004	29	29
G1/S transition of mitotic cell cycle	-0.07	0.27	0.31	9	-0.6	91	100
PTPN11	0.037	0.009	-10000	0	-0.009	17	17
CCND2	-0.072	0.19	-10000	0	-0.49	88	88
LCK	0.036	0.01	-10000	0	-0.006	26	26
GRB2	0.036	0.01	-10000	0	-0.006	24	24
IL2	0.037	0.009	-10000	0	-0.011	14	14
CDK6	0.025	0.018	-10000	0	0	165	165
CCND3	-0.025	0.2	0.34	3	-0.72	28	31

×

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	-0.061	0.6	0.72	42	-1	129	171
IL23A	0.089	0.37	0.77	20	-0.97	22	42
NF kappa B1 p50/RelA/I kappa B alpha	0.088	0.35	0.61	31	-0.84	27	58
positive regulation of T cell mediated cytotoxicity	0.095	0.4	0.75	40	-0.95	26	66
ITGA3	0.091	0.36	0.72	26	-0.92	20	46
IL17F	0.037	0.27	0.49	41	-0.6	28	69
IL12B	0.061	0.08	0.2	71	-10000	0	71
STAT1 (dimer)	0.072	0.37	0.64	36	-0.92	26	62
CD4	0.074	0.42	0.72	36	-1.1	33	69
IL23	0.095	0.36	0.72	18	-0.95	21	39
IL23R	0.068	0.14	0.27	103	-0.15	10	113
IL1B	0.084	0.4	0.75	30	-1.2	22	52
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	0.09	0.36	0.68	34	-0.91	19	53
TYK2	0.043	0.06	0.15	49	-10000	0	49
STAT4	0.035	0.009	-10000	0	0	31	31
STAT3	0.035	0.01	-10000	0	0	40	40
IL18RAP	0.036	0.008	-10000	0	-0.032	3	3
IL12RB1	0.045	0.06	0.15	52	-10000	0	52
PIK3CA	0.032	0.013	-10000	0	0	74	74
IL12Rbeta1/TYK2	0.055	0.076	0.19	37	-0.13	12	49
IL23R/JAK2	0.1	0.16	0.35	97	-0.2	11	108
positive regulation of chronic inflammatory response	0.095	0.4	0.75	40	-0.95	26	66
natural killer cell activation	-0.005	0.011	-10000	0	-0.03	42	42
JAK2	0.057	0.08	0.2	69	-10000	0	69
PIK3R1	0.033	0.013	-10000	0	0	67	67
NFKB1	0.04	0.01	0.067	3	0	18	21
RELA	0.04	0.008	0.067	3	0	10	13
positive regulation of dendritic cell antigen processing and presentation	0.097	0.35	0.71	19	-0.91	21	40
ALOX12B	0.087	0.36	0.68	37	-0.86	24	61
CXCL1	0.096	0.37	0.73	39	-0.91	20	59
T cell proliferation	0.095	0.4	0.75	40	-0.95	26	66
NFKBIA	0.037	0.014	0.068	2	0	54	56
IL17A	0.069	0.25	0.46	54	-0.48	26	80
PI3K	0.051	0.35	0.62	28	-0.9	26	54
IFNG	0.019	0.033	0.097	26	-0.087	3	29
STAT3 (dimer)	0.054	0.35	0.62	28	-0.86	27	55
IL18R1	0.036	0.008	-10000	0	-0.033	4	4
IL23/IL23R/JAK2/TYK2/SOCS3	0.096	0.27	0.55	52	-0.51	21	73
IL18/IL18R	0.062	0.037	-10000	0	-0.12	7	7
macrophage activation	-0.002	0.016	0.038	1	-0.043	15	16
TNF	0.091	0.37	0.76	20	-0.98	18	38
STAT3/STAT4	0.071	0.36	0.61	28	-0.88	27	55
STAT4 (dimer)	0.073	0.36	0.63	31	-0.92	26	57
IL18	0.032	0.013	-10000	0	-10000	0	0
IL19	0.091	0.36	0.67	37	-0.89	21	58
STAT5A (dimer)	0.085	0.37	0.64	36	-0.9	27	63
STAT1	0.035	0.01	-10000	0	0	41	41
SOCS3	0.037	0.004	-10000	0	0	6	6
CXCL9	0.1	0.37	0.76	26	-0.91	20	46
MPO	0.088	0.36	0.69	31	-0.91	19	50
positive regulation of humoral immune response	0.095	0.4	0.75	40	-0.95	26	66
IL23/IL23R/JAK2/TYK2	0.078	0.39	0.73	33	-0.98	26	59
IL6	0.15	0.37	0.73	48	-0.91	18	66
STAT5A	0.037	0.005	-10000	0	0	8	8
IL2	0.023	0.03	-10000	0	-0.037	98	98
positive regulation of tyrosine phosphorylation of STAT protein	-0.005	0.011	-10000	0	-0.03	42	42
CD3E	0.088	0.36	0.68	34	-0.9	20	54
keratinocyte proliferation	0.095	0.4	0.75	40	-0.95	26	66
NOS2	0.089	0.36	0.66	41	-0.83	28	69

×

IL2 signaling events mediated by PI3K

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
BCL2L1	0.007	0.095	0.32	3	-0.39	3	6
UGCG	-0.025	0.19	-10000	0	-0.73	30	30
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.006	0.15	0.27	6	-0.34	44	50
mol:GTP	0	0.001	-10000	0	-10000	0	0
mol:glucosylceramide	-0.023	0.18	-10000	0	-0.72	30	30
mol:DAG	-0.19	0.36	-10000	0	-0.82	125	125
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.016	0.18	0.28	5	-0.42	58	63
FRAP1	-0.027	0.2	0.3	6	-0.47	59	65
FOXO3	-0.037	0.2	0.28	8	-0.47	66	74
AKT1	-0.037	0.21	0.3	4	-0.5	64	68
GAB2	0.03	0.02	-10000	0	-0.012	84	84
SMPD1	0.002	0.1	-10000	0	-0.52	15	15
SGMS1	-0.13	0.27	-10000	0	-0.6	122	122
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	-0.03	0.043	-10000	0	-0.12	75	75
CALM1	0.033	0.012	-10000	0	0	60	60
cell proliferation	-0.093	0.24	0.29	7	-0.42	122	129
EIF3A	0.026	0.017	-10000	0	0	153	153
PI3K	0.018	0.078	-10000	0	-0.15	75	75
RPS6KB1	0.029	0.042	-10000	0	-0.7	1	1
mol:sphingomyelin	-0.19	0.36	-10000	0	-0.82	125	125
natural killer cell activation	0	0.004	0.007	26	-0.01	47	73
JAK3	0.035	0.017	-10000	0	-0.029	25	25
PIK3R1	0.032	0.02	-10000	0	-0.031	24	24
JAK1	0.033	0.019	-10000	0	-0.029	25	25
NFKB1	0.036	0.007	-10000	0	0	18	18
MYC	-0.065	0.29	0.42	7	-0.83	57	64
MYB	0.034	0.042	-10000	0	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.024	0.16	0.25	6	-0.39	50	56
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.047	0.055	-10000	0	-0.64	1	1
mol:PI-3-4-5-P3	-0.022	0.16	0.24	6	-0.38	50	56
Rac1/GDP	0.004	0.05	0.11	4	-0.13	48	52
T cell proliferation	-0.02	0.15	0.24	7	-0.35	50	57
SHC1	0.03	0.02	-10000	0	-0.011	86	86
RAC1	0.026	0.017	-10000	0	0	156	156
positive regulation of cyclin-dependent protein kinase activity	0.005	0.011	0.056	24	-10000	0	24
PRKCZ	-0.023	0.15	0.23	6	-0.36	50	56
NF kappa B1 p50/RelA	-0.001	0.19	0.31	5	-0.42	59	64
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	0.007	0.092	0.2	3	-0.29	21	24
HSP90AA1	0.035	0.01	-10000	0	0	35	35
RELA	0.037	0.005	-10000	0	0	10	10
IL2RA	0.023	0.022	-10000	0	-0.005	180	180
IL2RB	0.033	0.019	-10000	0	-0.029	24	24
TERT	0.036	0.007	-10000	0	0	17	17
E2F1	0.031	0.02	-10000	0	-10000	0	0
SOS1	0	0.003	0.008	30	-0.009	46	76
RPS6	0.032	0.013	-10000	0	0	71	71
mol:cAMP	-0.003	0.007	-10000	0	-0.031	25	25
PTPN11	0.034	0.017	-10000	0	-0.022	42	42
IL2RG	0.035	0.017	-10000	0	-0.031	23	23
actin cytoskeleton organization	-0.02	0.15	0.24	7	-0.35	50	57
GRB2	0.034	0.016	-10000	0	-0.017	44	44
IL2	0.036	0.016	-10000	0	-0.031	23	23
PIK3CA	0.031	0.021	-10000	0	-0.03	28	28
Rac1/GTP	0.027	0.065	0.16	5	-0.12	48	53
LCK	0.035	0.017	-10000	0	-0.031	22	22
BCL2	-0.015	0.16	0.42	1	-0.46	25	26

×

Fc-epsilon receptor I signaling in mast cells

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
PPAP2A	0.033	0.013	-10000	0	0	65	65
LAT2	-0.017	0.093	-10000	0	-0.28	46	46
AP1	-0.051	0.18	-10000	0	-0.4	66	66
mol:PIP3	0.016	0.14	0.27	35	-0.31	37	72
IKBKB	0.008	0.096	0.21	33	-0.19	37	70
AKT1	-0.055	0.1	0.29	9	-0.28	40	49
IKBKG	0.008	0.095	0.21	32	-0.19	37	69
MS4A2	0.04	0.008	0.068	5	0	7	12
mol:Sphingosine-1-phosphate	0	0	-10000	0	-10000	0	0
PIK3CA	0.032	0.013	-10000	0	0	74	74
MAP3K1	-0.022	0.12	0.25	15	-0.32	49	64
mol:Ca2+	0.018	0.12	0.24	36	-0.24	35	71
LYN	0.031	0.016	0.09	1	-0.034	7	8
CBLB	-0.023	0.11	0.18	1	-0.28	65	66
SHC1	0.034	0.012	-10000	0	0	53	53
RasGAP/p62DOK	0.05	0.052	-10000	0	-0.12	36	36
positive regulation of cell migration	0	0	-10000	0	-10000	0	0
INPP5D	0	0	-10000	0	-10000	0	0
PLD2	-0.032	0.072	0.29	12	-0.17	10	22
PTPN13	-0.035	0.19	0.34	1	-0.59	38	39
PTPN11	0.031	0.023	-10000	0	-0.036	48	48
GO:0007205	0	0	-10000	0	-10000	0	0
regulation of mast cell degranulation	-0.035	0.12	0.34	7	-0.31	40	47
SYK	0.031	0.015	-10000	0	-0.034	7	7
GRB2	0.037	0.007	-10000	0	0	19	19
LAT/PLCgamma1/GRB2/SLP76/GADs	0.011	0.12	0.21	7	-0.28	55	62
LAT	-0.023	0.11	0.18	1	-0.28	64	65
PAK2	-0.022	0.13	0.25	14	-0.34	52	66
NFATC2	-0.013	0.013	-10000	0	-0.043	69	69
HRAS	-0.023	0.14	0.24	8	-0.35	54	62
GAB2	0.034	0.011	-10000	0	0	51	51
PLA2G1B	-0.007	0.19	-10000	0	-0.9	20	20
Fc epsilon R1	0.042	0.067	-10000	0	-0.11	70	70
Antigen/IgE/Fc epsilon R1	0.043	0.06	-10000	0	-0.094	69	69
mol:GDP	-0.016	0.14	0.23	5	-0.36	50	55
JUN	0.034	0.011	-10000	0	0	44	44
mol:Ca++	0	0	-10000	0	-10000	0	0
PIK3R1	0.033	0.013	-10000	0	0	67	67
FOS	0.025	0.018	-10000	0	0	166	166
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.017	0.12	-10000	0	-0.28	67	67
CHUK	0.008	0.094	0.21	31	-0.19	38	69
KLRG1	-0.02	0.095	0.12	2	-0.27	48	50
VAV1	-0.025	0.11	0.15	3	-0.29	61	64
calcium-dependent protein kinase C activity	0	0	-10000	0	-10000	0	0
CBL	-0.023	0.11	0.18	1	-0.28	64	65
negative regulation of mast cell degranulation	-0.024	0.089	-10000	0	-0.25	50	50
BTK	-0.014	0.13	-10000	0	-0.37	46	46
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.026	0.11	-10000	0	-0.19	121	121
GAB2/PI3K/SHP2	-0.07	0.072	-10000	0	-0.21	71	71
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.004	0.079	-10000	0	-0.21	53	53
RAF1	-0.006	0.2	-10000	0	-0.97	20	20
Fc epsilon R1/FcgammaRIIB/SHIP	0.024	0.095	-10000	0	-0.13	128	128
FCER1G	0.03	0.016	-10000	0	0	111	111
FCER1A	0.034	0.013	-10000	0	-0.032	9	9
Antigen/IgE/Fc epsilon R1/Fyn	0.041	0.082	-10000	0	-0.11	97	97
MAPK3	-0.006	0.18	-10000	0	-0.89	20	20
MAPK1	-0.015	0.2	-10000	0	-0.94	20	20
NFKB1	0.036	0.007	-10000	0	0	18	18
MAPK8	-0.1	0.28	-10000	0	-0.56	128	128
DUSP1	0.032	0.014	-10000	0	0	78	78
NF-kappa-B/RelA	0.017	0.068	0.16	23	-0.13	38	61
actin cytoskeleton reorganization	-0.026	0.19	0.36	1	-0.59	37	38
mol:Glucocorticoid Dexamethasone	0	0	-10000	0	-10000	0	0
PI3K	-0.014	0.15	0.26	3	-0.35	57	60
FER	-0.023	0.11	0.18	1	-0.28	67	68
RELA	0.037	0.005	-10000	0	0	10	10
ITK	0.002	0.037	-10000	0	-0.23	4	4
SOS1	0	0	-10000	0	-10000	0	0
PLCG1	-0.005	0.14	0.27	15	-0.35	46	61
cytokine secretion	0.008	0.045	0.088	22	-0.094	40	62
SPHK1	-0.019	0.11	0.16	2	-0.28	64	66
PTK2	-0.028	0.2	0.36	1	-0.63	36	37
NTAL/PLCgamma1/GRB2/SLP76/GADs	0.027	0.13	0.24	17	-0.29	46	63
EDG1	0	0	-10000	0	-10000	0	0
mol:DAG	-0.001	0.15	0.27	27	-0.34	43	70
MAP2K2	-0.009	0.19	-10000	0	-0.9	20	20
MAP2K1	-0.016	0.18	-10000	0	-0.92	20	20
MAP2K7	0.036	0.007	-10000	0	0	18	18
KLRG1/SHP2	0.001	0.096	0.2	7	-0.25	46	53
MAP2K4	0.026	0.14	-10000	0	-0.88	12	12
Fc epsilon R1/FcgammaRIIB	0.026	0.1	-10000	0	-0.14	128	128
mol:Choline	-0.032	0.072	0.29	12	-0.17	10	22
SHC/Grb2/SOS1	0.013	0.13	0.2	1	-0.27	67	68
FYN	0.031	0.015	-10000	0	0	93	93
DOK1	0.038	0.002	-10000	0	0	2	2
PXN	-0.029	0.19	0.42	3	-0.58	36	39
HCLS1	-0.026	0.12	0.16	6	-0.31	66	72
PRKCB	0.01	0.12	0.23	32	-0.25	41	73
FCGR2B	0.021	0.019	-10000	0	0	223	223
IGHE	-0.001	0.005	0.029	5	-10000	0	5
KLRG1/SHIP	-0.024	0.091	-10000	0	-0.26	50	50
LCP2	0.032	0.014	-10000	0	0	77	77
PLA2G4A	-0.016	0.12	0.16	6	-0.3	59	65
RASA1	0.035	0.01	-10000	0	0	35	35
mol:Phosphatidic acid	-0.032	0.072	0.29	12	-0.17	10	22
IKK complex	0.005	0.084	0.23	21	-0.16	24	45
WIPF1	0.036	0.007	-10000	0	0	19	19

×

Syndecan-2-mediated signaling 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
Syndecan-2/Fibronectin	0.015	0.06	-10000	0	-0.13	67	67
EPHB2	0.035	0.01	-10000	0	0	39	39
Syndecan-2/TACI	0.018	0.054	-10000	0	-0.12	64	64
LAMA1	0	0	-10000	0	-10000	0	0
Syndecan-2/alpha2 ITGB1	0.022	0.073	-10000	0	-0.12	64	64
HRAS	0.035	0.01	-10000	0	0	37	37
Syndecan-2/CASK	-0.008	0.04	-10000	0	-0.11	68	68
ITGA5	0.033	0.012	-10000	0	0	62	62
BAX	-0.01	0.071	-10000	0	-0.89	3	3
EPB41	0.037	0.006	-10000	0	0	13	13
positive regulation of cell-cell adhesion	0.014	0.053	-10000	0	-0.11	72	72
LAMA3	0.034	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	0.02	0.019	-10000	0	0	237	237
Syndecan-2/MMP2	0.01	0.061	-10000	0	-0.14	65	65
RP11-540L11.1	0	0	-10000	0	-10000	0	0
alpha2 ITGB1	0.022	0.054	-10000	0	-0.14	41	41
dendrite morphogenesis	0.017	0.052	-10000	0	-0.12	60	60
Syndecan-2/GM-CSF	0.018	0.054	-10000	0	-0.12	64	64
determination of left/right symmetry	0.007	0.023	-10000	0	-0.23	4	4
Syndecan-2/PKC delta	0.017	0.053	-10000	0	-0.12	61	61
GNB2L1	0.037	0.005	-10000	0	0	10	10
MAPK3	-0.023	0.051	0.18	10	-0.19	4	14
MAPK1	-0.02	0.049	0.12	31	-0.21	4	35
Syndecan-2/RACK1	0.031	0.063	-10000	0	-0.11	75	75
NF1	0.037	0.003	-10000	0	0	4	4
FGFR/FGF/Syndecan-2	0.007	0.023	-10000	0	-0.23	4	4
ITGA2	0.029	0.016	-10000	0	0	114	114
MAPK8	-0.005	0.038	-10000	0	-0.39	3	3
Syndecan-2/alpha2/beta1 Integrin	0.01	0.063	-10000	0	-0.11	90	90
Syndecan-2/Kininogen	0.018	0.054	-10000	0	-0.12	63	63
ITGB1	0.029	0.016	-10000	0	0	117	117
SRC	-0.025	0.052	0.17	12	-0.19	8	20
Syndecan-2/CASK/Protein 4.1	0.016	0.049	-10000	0	-0.1	66	66
extracellular matrix organization	0.015	0.053	-10000	0	-0.12	61	61
actin cytoskeleton reorganization	0.015	0.059	-10000	0	-0.13	67	67
Syndecan-2/Caveolin-2/Ras	0.008	0.067	-10000	0	-0.13	77	77
Syndecan-2/Laminin alpha3	0.016	0.052	-10000	0	-0.12	61	61
Syndecan-2/RasGAP	0.038	0.078	-10000	0	-0.12	80	80
alpha5/beta1 Integrin	0.032	0.043	-10000	0	-0.14	21	21
PRKCD	0.035	0.01	-10000	0	0	42	42
Syndecan-2 dimer	0.017	0.052	-10000	0	-0.12	60	60
GO:0007205	0.001	0.01	-10000	0	-0.11	4	4
DNA mediated transformation	0	0	-10000	0	-10000	0	0
Syndecan-2/RasGAP/Src	0.015	0.066	0.19	3	-0.19	17	20
RHOA	0.036	0.007	-10000	0	0	20	20
SDCBP	0.036	0.007	-10000	0	0	20	20
TNFRSF13B	0.037	0.005	-10000	0	0	10	10
RASA1	0.035	0.01	-10000	0	0	35	35
alpha2/beta1 Integrin	0.022	0.054	-10000	0	-0.14	41	41
Syndecan-2/Synbindin	0.017	0.058	-10000	0	-0.12	64	64
TGFB1	0.033	0.012	-10000	0	0	57	57
CASP3	-0.017	0.05	0.18	7	-0.19	4	11
FN1	0.035	0.009	-10000	0	0	31	31
Syndecan-2/IL8	-0.003	0.068	-10000	0	-0.17	61	61
SDC2	0.007	0.023	-10000	0	-0.23	4	4
KNG1	0.037	0.007	-10000	0	0	16	16
Syndecan-2/Neurofibromin	0.018	0.055	-10000	0	-0.12	67	67
TRAPPC4	0.036	0.007	-10000	0	0	17	17
CSF2	0.037	0.005	-10000	0	0	8	8
Syndecan-2/TGFB1	0.015	0.053	-10000	0	-0.12	61	61
Syndecan-2/Syntenin/PI-4-5-P2	0.014	0.054	-10000	0	-0.11	72	72
Syndecan-2/Ezrin	0.015	0.052	-10000	0	-0.11	69	69
PRKACA	-0.022	0.052	0.18	11	-0.19	4	15
angiogenesis	-0.003	0.068	-10000	0	-0.17	61	61
MMP2	0.03	0.015	-10000	0	0	104	104
IL8	0.02	0.019	-10000	0	0	244	244
calcineurin-NFAT signaling pathway	0.018	0.054	-10000	0	-0.12	64	64

×

Osteopontin-mediated events

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
IKK alpha homodimer	0.005	0.079	0.19	3	-0.19	38	41
NF kappa B1 p50/RelA/I kappa B alpha	-0.015	0.13	0.28	3	-0.32	44	47
alphaV/beta3 Integrin/Osteopontin/Src	0.028	0.08	-10000	0	-0.15	76	76
AP1	-0.012	0.14	0.28	4	-0.28	79	83
ILK	-0.031	0.072	0.19	3	-0.23	33	36
bone resorption	-0.04	0.082	0.18	6	-0.25	25	31
PTK2B	0.037	0.006	-10000	0	0	15	15
PYK2/p130Cas	0.046	0.09	-10000	0	-0.18	41	41
ITGAV	0.031	0.027	-10000	0	-0.056	36	36
mol:GTP	0	0	-10000	0	-10000	0	0
CD44/Rho Family GTPase/ROCK2	0.022	0.068	-10000	0	-0.14	73	73
alphaV/beta3 Integrin/Osteopontin	0.051	0.093	-10000	0	-0.16	71	71
MAP3K1	-0.029	0.065	0.19	3	-0.2	27	30
JUN	0.035	0.011	-10000	0	0	44	44
MAPK3	-0.032	0.085	0.18	7	-0.24	41	48
MAPK1	-0.029	0.086	0.17	12	-0.25	39	51
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
NFKB1	0.036	0.007	-10000	0	0	18	18
MAPK8	-0.028	0.061	0.2	2	-0.21	23	25
ITGB3	0.033	0.027	-10000	0	-0.055	40	40
NFKBIA	-0.036	0.11	0.19	7	-0.32	46	53
FOS	0.026	0.018	-10000	0	0	166	166
CD44	0.029	0.016	-10000	0	0	113	113
CHUK	0.027	0.017	-10000	0	0	139	139
PLAU	-0.068	0.26	-10000	0	-0.99	32	32
NF kappa B1 p50/RelA	0.005	0.13	0.25	1	-0.33	40	41
BCAR1	0	0	-10000	0	-10000	0	0
RELA	0.037	0.005	-10000	0	0	10	10
alphaV beta3 Integrin	0.041	0.058	-10000	0	-0.11	55	55
mol:GDP	0	0	-10000	0	-10000	0	0
SYK	-0.031	0.065	0.18	3	-0.23	29	32
VAV3	-0.034	0.063	0.18	2	-0.23	31	33
MAP3K14	-0.028	0.075	0.18	6	-0.22	29	35
ROCK2	0.036	0.007	-10000	0	0	19	19
SPP1	0.031	0.026	-10000	0	-0.058	30	30
RAC1	0.026	0.017	-10000	0	0	156	156
Rac1/GTP	-0.022	0.07	0.15	4	-0.22	28	32
MMP2	-0.061	0.12	0.24	2	-0.32	62	64

×

FoxO family 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
G6PC	-0.013	0.076	-10000	0	-0.38	6	6
PLK1	-0.067	0.21	-10000	0	-0.68	23	23
CDKN1B	-0.11	0.22	0.41	4	-0.37	137	141
FOXO3	-0.07	0.23	0.32	3	-0.49	89	92
KAT2B	-0.001	0.021	0.048	15	-0.041	82	97
FOXO1/SIRT1	0.004	0.081	-10000	0	-0.27	27	27
CAT	-0.08	0.26	-10000	0	-0.82	33	33
CTNNB1	0.036	0.007	-10000	0	0	17	17
AKT1	0.021	0.044	0.11	1	-0.061	72	73
FOXO1	-0.012	0.085	0.27	2	-0.3	23	25
MAPK10	0.044	0.092	0.19	125	-0.15	19	144
mol:GTP	-0.001	0.005	-10000	0	-10000	0	0
FOXO4	-0.028	0.21	0.33	9	-0.5	54	63
response to oxidative stress	0	0.023	0.053	13	-0.043	61	74
FOXO3A/SIRT1	-0.068	0.23	-10000	0	-0.48	89	89
XPO1	0.037	0.004	-10000	0	0	4	4
EP300	0.035	0.012	-10000	0	-10000	0	0
BCL2L11	0.024	0.034	-10000	0	-10000	0	0
FOXO1/SKP2	0.007	0.086	0.24	2	-0.28	22	24
mol:GDP	0	0.023	0.053	13	-0.043	61	74
RAN	0.035	0.012	-10000	0	-0.014	24	24
GADD45A	-0.14	0.33	0.42	1	-0.88	68	69
YWHAQ	0.037	0.005	-10000	0	0	8	8
FOXO1/14-3-3 family	0.003	0.15	-10000	0	-0.5	25	25
MST1	0.022	0.043	0.11	2	-0.059	87	89
CSNK1D	0.036	0.007	-10000	0	0	20	20
CSNK1E	0.033	0.013	-10000	0	0	65	65
FOXO4/14-3-3 family	-0.003	0.15	-10000	0	-0.5	26	26
YWHAB	0.034	0.011	-10000	0	0	44	44
MAPK8	0.023	0.077	0.18	70	-0.14	16	86
MAPK9	0.053	0.097	0.19	146	-0.15	15	161
YWHAG	0	0	-10000	0	-10000	0	0
YWHAE	0.036	0.009	-10000	0	0	29	29
YWHAZ	0.036	0.008	-10000	0	0	21	21
SIRT1	0.022	0.023	-10000	0	-0.035	31	31
SOD2	-0.14	0.36	0.43	7	-0.76	106	113
RBL2	-0.073	0.29	-10000	0	-0.92	37	37
RAL/GDP	0.02	0.05	-10000	0	-0.14	20	20
CHUK	0.013	0.04	0.1	1	-0.059	79	80
Ran/GTP	0.02	0.026	-10000	0	-0.12	6	6
CSNK1G2	0.036	0.007	-10000	0	0	20	20
RAL/GTP	0.023	0.051	0.15	3	-0.12	23	26
CSNK1G1	0.037	0.005	-10000	0	0	10	10
FASLG	0.021	0.042	-10000	0	-0.59	1	1
SKP2	0.036	0.007	-10000	0	0	20	20
USP7	0.036	0.011	-10000	0	-0.011	21	21
IKBKB	0.024	0.044	0.11	2	-0.059	92	94
CCNB1	-0.17	0.42	0.53	2	-1	89	91
FOXO1-3a-4/beta catenin	-0.042	0.22	0.42	7	-0.39	85	92
proteasomal ubiquitin-dependent protein catabolic process	0.007	0.085	0.24	2	-0.28	22	24
CSNK1A1	0.037	0.006	-10000	0	0	13	13
SGK1	-0.001	0.021	0.048	15	-0.041	82	97
CSNK1G3	0.037	0.006	-10000	0	0	12	12
Ran/GTP/Exportin 1	0.041	0.037	-10000	0	-0.12	8	8
ZFAND5	-0.016	0.18	0.42	6	-0.54	31	37
SFN	0.032	0.014	-10000	0	0	80	80
CDK2	0.037	0.012	-10000	0	-10000	0	0
FOXO3A/14-3-3	-0.014	0.16	-10000	0	-0.43	36	36
CREBBP	0.039	0.006	-10000	0	-0.032	1	1
FBXO32	-0.066	0.21	0.35	1	-0.45	89	90
BCL6	-0.093	0.33	-10000	0	-1	46	46
RALB	0.034	0.014	-10000	0	-0.016	33	33
RALA	0.025	0.019	-10000	0	-0.001	177	177
YWHAH	0.032	0.013	-10000	0	0	73	73

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	-0.017	0.2	-10000	0	-0.82	26	26
regulation of axonogenesis	0.005	0.069	0.22	41	-10000	0	41
myoblast fusion	-0.015	0.098	0.36	28	-0.17	2	30
mol:GTP	0.013	0.07	-10000	0	-0.18	54	54
regulation of calcium-dependent cell-cell adhesion	-0.026	0.075	0.15	68	-10000	0	68
ARF1/GTP	0.033	0.065	-10000	0	-0.14	56	56
mol:GM1	0.001	0.05	-10000	0	-0.14	54	54
mol:Choline	-0.017	0.042	0.063	1	-0.13	48	49
lamellipodium assembly	-0.012	0.11	-10000	0	-0.38	39	39
MAPK3	0.01	0.085	0.14	38	-0.21	51	89
ARF6/GTP/NME1/Tiam1	0.027	0.076	0.15	1	-0.15	68	69
ARF1	0.036	0.008	-10000	0	0	23	23
ARF6/GDP	0.015	0.098	0.17	2	-0.36	28	30
ARF1/GDP	0.012	0.11	-10000	0	-0.28	52	52
ARF6	0.04	0.042	-10000	0	-0.13	25	25
RAB11A	0.036	0.007	-10000	0	0	17	17
TIAM1	0.03	0.022	-10000	0	-0.046	31	31
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.012	0.083	0.14	37	-0.23	40	77
actin filament bundle formation	-0.017	0.11	0.29	54	-10000	0	54
KALRN	0.002	0.08	0.12	3	-0.26	37	40
RAB11FIP3/RAB11A	0.049	0.034	-10000	0	-0.16	12	12
RhoA/GDP	0.018	0.11	-10000	0	-0.29	54	54
NME1	-0.001	0.008	-10000	0	-0.03	26	26
Rac1/GDP	0.012	0.097	-10000	0	-0.29	39	39
substrate adhesion-dependent cell spreading	0.013	0.07	-10000	0	-0.18	54	54
cortical actin cytoskeleton organization	-0.013	0.11	-10000	0	-0.38	39	39
RAC1	0.026	0.017	-10000	0	0	156	156
liver development	0.013	0.07	-10000	0	-0.18	54	54
ARF6/GTP	0.013	0.07	-10000	0	-0.18	54	54
RhoA/GTP	0.033	0.067	-10000	0	-0.15	57	57
mol:GDP	-0.008	0.11	0.17	2	-0.3	51	53
ARF6/GTP/RAB11FIP3/RAB11A	0.05	0.072	-10000	0	-0.13	61	61
RHOA	0.036	0.007	-10000	0	0	20	20
PLD1	0.011	0.055	-10000	0	-0.14	53	53
RAB11FIP3	0.036	0.007	-10000	0	0	19	19
tube morphogenesis	-0.012	0.11	-10000	0	-0.38	39	39
ruffle organization	-0.005	0.069	-10000	0	-0.22	41	41
regulation of epithelial cell migration	0.013	0.07	-10000	0	-0.18	54	54
PLD2	0.012	0.055	-10000	0	-0.14	50	50
PIP5K1A	-0.005	0.069	-10000	0	-0.22	41	41
mol:Phosphatidic acid	-0.017	0.042	0.063	1	-0.13	48	49
Rac1/GTP	-0.013	0.11	-10000	0	-0.38	39	39

×

Ephrin B reverse 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
EFNB2	0.029	0.016	-10000	0	0	115	115
EPHB2	0.035	0.011	0.062	1	0	39	40
EFNB1	-0.018	0.016	0.024	58	-10000	0	58
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.051	0.053	-10000	0	-0.14	9	9
Ephrin B2/EPHB1-2	0.034	0.056	-10000	0	-0.1	50	50
neuron projection morphogenesis	0.035	0.041	-10000	0	-0.12	14	14
Ephrin B1/EPHB1-2/Tiam1	0.058	0.048	0.18	1	-0.1	27	28
DNM1	0.036	0.009	-10000	0	0	26	26
cell-cell signaling	0	0.004	0.023	2	-10000	0	2
MAP2K4	-0.052	0.16	0.2	1	-0.51	51	52
YES1	-0.052	0.23	-10000	0	-0.74	51	51
Ephrin B1/EPHB1-2/NCK2	0.062	0.044	0.18	1	-0.1	19	20
PI3K	-0.017	0.19	-10000	0	-0.55	52	52
mol:GDP	0.056	0.047	0.18	1	-0.1	27	28
ITGA2B	0.037	0.003	-10000	0	0	4	4
endothelial cell proliferation	0.018	0.046	-10000	0	-0.11	42	42
FYN	-0.063	0.24	-10000	0	-0.76	51	51
MAP3K7	-0.048	0.16	-10000	0	-0.54	49	49
FGR	-0.049	0.22	-10000	0	-0.72	51	51
TIAM1	0.034	0.011	-10000	0	0	44	44
PIK3R1	0.033	0.013	-10000	0	0	67	67
RGS3	0.036	0.008	-10000	0	0	24	24
cell adhesion	-0.031	0.17	-10000	0	-0.52	52	52
LYN	-0.058	0.23	-10000	0	-0.73	51	51
Ephrin B1/EPHB1-2/Src Family Kinases	-0.054	0.21	-10000	0	-0.67	51	51
Ephrin B1/EPHB1-2	-0.045	0.17	-10000	0	-0.57	49	49
SRC	-0.048	0.22	-10000	0	-0.71	51	51
ITGB3	0.037	0.004	-10000	0	0	6	6
EPHB1	0.031	0.015	-10000	0	0	95	95
EPHB4	0.026	0.017	-10000	0	0	157	157
RAC1	0.026	0.017	-10000	0	0	156	156
Ephrin B2/EPHB4	0.018	0.046	-10000	0	-0.11	42	42
alphaIIb/beta3 Integrin	0.055	0.006	-10000	0	-10000	0	0
BLK	-0.051	0.22	-10000	0	-0.71	52	52
HCK	-0.063	0.23	-10000	0	-0.73	51	51
regulation of stress fiber formation	-0.06	0.043	0.1	19	-10000	0	19
MAPK8	-0.055	0.15	0.22	1	-0.49	51	52
Ephrin B1/EPHB1-2/RGS3	0.067	0.034	-10000	0	-0.11	5	5
endothelial cell migration	0.004	0.16	0.19	112	-0.44	43	155
NCK2	0.036	0.007	-10000	0	0	19	19
PTPN13	0.035	0.014	-10000	0	0	63	63
regulation of focal adhesion formation	-0.06	0.043	0.1	19	-10000	0	19
chemotaxis	-0.065	0.033	0.11	5	-10000	0	5
PIK3CA	0.032	0.013	-10000	0	0	74	74
Rac1/GTP	0.043	0.047	-10000	0	-0.13	10	10
angiogenesis	-0.045	0.17	-10000	0	-0.56	50	50
LCK	-0.047	0.22	-10000	0	-0.71	51	51

×

S1P1 pathway

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
VEGFR2 homodimer/VEGFA homodimer	0.001	0.078	-10000	0	-0.14	105	105
PDGFRB	0.037	0.009	0.059	1	0	25	26
SPHK1	0.018	0.021	-10000	0	-10000	0	0
mol:S1P	0.019	0.028	-10000	0	-10000	0	0
S1P1/S1P/Gi	-0.004	0.12	0.21	24	-0.38	27	51
GNAO1	0.033	0.016	-10000	0	0	87	87
PDGFB-D/PDGFRB/PLCgamma1	0.026	0.13	0.24	35	-0.34	27	62
PLCG1	-0.009	0.12	0.22	16	-0.36	27	43
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.037	0.009	0.059	1	0	25	26
GNAI2	0.037	0.012	-10000	0	0	46	46
GNAI3	0.038	0.008	-10000	0	0	16	16
GNAI1	0.02	0.02	-10000	0	0	255	255
mol:GDP	0	0	-10000	0	-10000	0	0
EDG1	-0.026	0.051	0.078	25	-0.12	105	130
S1P1/S1P	0	0.052	0.22	2	-0.22	1	3
negative regulation of cAMP metabolic process	-0.003	0.12	0.21	24	-0.37	27	51
MAPK3	-0.004	0.13	0.27	17	-0.39	23	40
calcium-dependent phospholipase C activity	0	0.003	-10000	0	-10000	0	0
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
RhoA/GDP	0.025	0.019	-10000	0	-0.13	7	7
KDR	0.032	0.015	-10000	0	0	90	90
PLCB2	0.029	0.081	0.21	30	-0.21	1	31
RAC1	0.026	0.017	-10000	0	0	156	156
RhoA/GTP	-0.001	0.049	0.15	1	-0.2	3	4
receptor internalization	-0.001	0.049	0.21	2	-0.21	1	3
PTGS2	0.027	0.14	0.34	11	-0.47	11	22
Rac1/GTP	-0.003	0.041	-10000	0	-0.19	2	2
RHOA	0.036	0.007	-10000	0	0	20	20
VEGFA	0.025	0.019	-10000	0	0	181	181
negative regulation of T cell proliferation	-0.003	0.12	0.21	24	-0.37	27	51
GO:0007205	0	0	-10000	0	-10000	0	0
GNAZ	0.033	0.015	-10000	0	0	81	81
MAPK1	-0.001	0.13	0.28	16	-0.4	21	37
S1P1/S1P/PDGFB-D/PDGFRB	0.03	0.087	0.24	19	-0.22	4	23
ABCC1	0.038	0.008	-10000	0	0	19	19

×

BCR signaling pathway

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
JUN	-0.006	0.12	0.34	4	-0.31	34	38
IKBKB	0.018	0.081	0.3	7	-0.28	8	15
AKT1	0.006	0.093	0.23	36	-0.18	13	49
IKBKG	0.011	0.077	0.31	4	-0.24	13	17
CALM1	-0.024	0.12	0.21	6	-0.37	41	47
PIK3CA	0.032	0.013	-10000	0	0	74	74
MAP3K1	0.023	0.14	0.29	16	-0.34	37	53
MAP3K7	0.034	0.011	-10000	0	0	45	45
mol:Ca2+	-0.022	0.13	0.22	5	-0.38	41	46
DOK1	0.038	0.002	-10000	0	0	2	2
AP-1	-0.013	0.098	0.22	13	-0.22	45	58
LYN	0.032	0.013	-10000	0	0	72	72
BLNK	0.021	0.019	-10000	0	0	226	226
SHC1	0.034	0.012	-10000	0	0	53	53
BCR complex	0.052	0.015	-10000	0	-10000	0	0
CD22	-0.015	0.091	-10000	0	-0.29	36	36
CAMK2G	-0.017	0.12	0.22	8	-0.35	42	50
CSNK2A1	0.034	0.011	-10000	0	0	50	50
INPP5D	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	-0.036	0.056	-10000	0	-0.19	24	24
GO:0007205	-0.023	0.14	0.23	6	-0.39	42	48
SYK	0.032	0.013	-10000	0	0	76	76
ELK1	-0.028	0.13	0.22	5	-0.37	42	47
NFATC1	-0.02	0.098	0.3	6	-0.26	37	43
B-cell antigen/BCR complex	0.052	0.015	-10000	0	-10000	0	0
PAG1/CSK	0.024	0.022	-10000	0	-0.13	10	10
NFKBIB	0.022	0.045	0.18	3	-0.13	20	23
HRAS	-0.024	0.12	0.2	12	-0.33	43	55
NFKBIA	0.023	0.041	0.18	3	-0.12	15	18
NF-kappa-B/RelA/I kappa B beta	0.027	0.04	0.17	4	-0.1	20	24
RasGAP/Csk	0.044	0.096	-10000	0	-0.12	118	118
mol:GDP	-0.021	0.13	0.22	6	-0.37	42	48
PTEN	0.026	0.017	-10000	0	0	158	158
CD79B	0.037	0.005	-10000	0	0	10	10
NF-kappa-B/RelA/I kappa B alpha	0.028	0.038	0.17	4	-0.1	13	17
GRB2	0.036	0.007	-10000	0	0	19	19
PI3K/BCAP/CD19	-0.033	0.16	0.38	4	-0.42	49	53
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:IP3	-0.022	0.13	0.23	4	-0.4	40	44
CSK	0.036	0.007	-10000	0	0	20	20
FOS	-0.026	0.13	0.2	10	-0.36	44	54
CHUK	-0.049	0.14	0.3	4	-0.26	119	123
IBTK	0.035	0.009	-10000	0	0	31	31
CARD11/BCL10/MALT1/TAK1	0.003	0.13	0.25	2	-0.34	40	42
PTPN6	-0.024	0.09	0.16	12	-0.3	35	47
RELA	0.037	0.005	-10000	0	0	10	10
BCL2A1	0.018	0.035	0.099	14	-0.091	23	37
VAV2	-0.019	0.1	-10000	0	-0.3	44	44
ubiquitin-dependent protein catabolic process	0.024	0.045	0.18	3	-0.13	20	23
BTK	0.019	0.012	-10000	0	-10000	0	0
CD19	-0.015	0.094	-10000	0	-0.29	38	38
MAP4K1	0.036	0.008	-10000	0	0	21	21
CD72	0.033	0.012	-10000	0	0	58	58
PAG1	0	0	-10000	0	-10000	0	0
MAPK14	0.019	0.12	0.28	14	-0.3	37	51
SH3BP5	0.034	0.011	-10000	0	0	52	52
PIK3AP1	-0.021	0.14	0.24	4	-0.41	39	43
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.032	0.18	-10000	0	-0.5	52	52
RAF1	-0.03	0.11	0.19	8	-0.31	45	53
RasGAP/p62DOK/SHIP	0.036	0.084	-10000	0	-0.11	115	115
CD79A	0.035	0.009	-10000	0	0	31	31
re-entry into mitotic cell cycle	-0.014	0.097	0.21	13	-0.22	44	57
RASA1	0.035	0.01	-10000	0	0	35	35
MAPK3	-0.036	0.098	0.22	6	-0.28	44	50
MAPK1	-0.034	0.1	0.2	6	-0.29	42	48
CD72/SHP1	0.001	0.11	0.25	16	-0.28	37	53
NFKB1	0.036	0.007	-10000	0	0	18	18
MAPK8	0.019	0.12	0.28	17	-0.3	37	54
actin cytoskeleton organization	0.028	0.12	0.24	27	-0.28	29	56
NF-kappa-B/RelA	0.046	0.092	0.32	3	-0.25	24	27
Calcineurin	-0.002	0.13	0.23	3	-0.33	42	45
PI3K	-0.032	0.088	-10000	0	-0.25	43	43
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.018	0.14	0.22	8	-0.38	49	57
SOS1	0	0	-10000	0	-10000	0	0
Bam32/HPK1	0.017	0.15	-10000	0	-0.56	13	13
DAPP1	-0.004	0.15	-10000	0	-0.65	11	11
cytokine secretion	-0.018	0.094	0.3	6	-0.25	37	43
mol:DAG	-0.022	0.13	0.23	4	-0.4	40	44
PLCG2	0.033	0.013	-10000	0	0	65	65
MAP2K1	-0.033	0.1	0.2	5	-0.3	45	50
B-cell antigen/BCR complex/FcgammaRIIB	0.017	0.075	-10000	0	-0.12	99	99
mol:PI-3-4-5-P3	-0.02	0.072	0.2	19	-0.22	17	36
ETS1	-0.026	0.12	0.21	7	-0.33	41	48
B-cell antigen/BCR complex/LYN/SYK/BLNK	0.039	0.092	-10000	0	-0.15	63	63
B-cell antigen/BCR complex/LYN	-0.009	0.097	-10000	0	-0.3	38	38
MALT1	0.035	0.009	-10000	0	0	30	30
TRAF6	0.037	0.006	-10000	0	0	14	14
RAC1	0.025	0.12	0.24	23	-0.29	28	51
B-cell antigen/BCR complex/LYN/SYK	0.032	0.1	0.24	9	-0.25	44	53
CARD11	-0.022	0.13	0.21	7	-0.37	42	49
FCGR2B	0.021	0.019	-10000	0	0	223	223
PPP3CA	0.035	0.01	-10000	0	0	37	37
BCL10	0.036	0.007	-10000	0	0	20	20
IKK complex	0.006	0.048	0.18	9	-0.12	15	24
PTPRC	0.03	0.016	-10000	0	0	110	110
PDPK1	-0.015	0.063	0.18	23	-0.17	12	35
PPP3CB	0.028	0.017	-10000	0	0	133	133
PPP3CC	0.037	0.006	-10000	0	0	12	12
POU2F2	0.017	0.032	0.11	7	-0.084	22	29

×

JNK signaling in the CD4+ TCR 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
LAT/GRAP2/SLP76/HPK1	0.069	0.06	-10000	0	-0.12	32	32
MAP4K1	0.036	0.008	-10000	0	0	21	21
MAP3K8	0.025	0.018	-10000	0	0	176	176
PRKCB	0	0	-10000	0	-10000	0	0
DBNL	0	0	-10000	0	-10000	0	0
CRKL	0.036	0.009	-10000	0	0	29	29
MAP3K1	-0.001	0.054	-10000	0	-0.24	7	7
JUN	-0.12	0.23	0.24	2	-0.52	121	123
MAP3K7	-0.001	0.054	-10000	0	-0.24	9	9
GRAP2	0.035	0.01	-10000	0	0	36	36
CRK	0.036	0.008	-10000	0	0	25	25
MAP2K4	-0.01	0.07	0.16	4	-0.25	19	23
LAT	0.037	0.005	-10000	0	0	9	9
LCP2	0.032	0.014	-10000	0	0	77	77
MAPK8	-0.11	0.24	-10000	0	-0.54	121	121
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	0.011	0.057	-10000	0	-0.16	33	33
LAT/GRAP2/SLP76/HPK1/HIP-55	0.064	0.055	-10000	0	-0.11	32	32

×

Presenilin action in Notch and Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Delta 1/NOTCH/NOTCH(cleaved)	-0.03	0.17	-10000	0	-0.47	62	62
HDAC1	0.028	0.034	0.098	14	-0.039	84	98
AES	0.036	0.013	0.072	12	-0.003	35	47
FBXW11	0.036	0.008	-10000	0	0	24	24
DTX1	0	0	-10000	0	-10000	0	0
LRP6/FZD1	0.035	0.027	-10000	0	-10000	0	0
TLE1	0.035	0.013	0.072	9	-0.006	35	44
AP1	-0.012	0.076	-10000	0	-0.21	58	58
NCSTN	0.036	0.009	-10000	0	0	29	29
ADAM10	0.034	0.012	-10000	0	0	56	56
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.011	0.13	-10000	0	-0.48	15	15
NICD/RBPSUH	-0.011	0.18	-10000	0	-0.48	61	61
WIF1	0.03	0.016	-10000	0	0	110	110
NOTCH1	-0.031	0.17	-10000	0	-0.49	61	61
PSENEN	0.035	0.009	-10000	0	0	33	33
KREMEN2	0.037	0.004	-10000	0	0	6	6
DKK1	0.019	0.019	-10000	0	0	258	258
beta catenin/beta TrCP1	0.054	0.097	0.24	23	-0.28	12	35
APH1B	0.037	0.006	-10000	0	0	14	14
APH1A	0.036	0.007	-10000	0	0	17	17
AXIN1	0.012	0.068	0.26	3	-0.47	1	4
CtBP/CBP/TCF1/TLE1/AES	0.016	0.075	0.18	47	-0.21	9	56
PSEN1	0.034	0.011	-10000	0	0	48	48
FOS	0.025	0.018	-10000	0	0	166	166
JUN	0.034	0.011	-10000	0	0	44	44
MAP3K7	0.033	0.018	0.064	7	-0.009	62	69
CTNNB1	0.039	0.094	0.22	33	-0.28	9	42
MAPK3	0.037	0.003	-10000	0	0	4	4
DKK2/LRP6/Kremen 2	0.065	0.028	-10000	0	-0.12	1	1
HNF1A	0.037	0.01	0.072	10	-0.018	11	21
CTBP1	0.035	0.013	0.074	9	-0.006	33	42
MYC	-0.081	0.37	-10000	0	-1.2	52	52
NKD1	0	0.003	-10000	0	-10000	0	0
FZD1	0.026	0.018	-10000	0	0	162	162
NOTCH1 precursor/Deltex homolog 1	-0.035	0.16	-10000	0	-0.47	62	62
apoptosis	-0.012	0.076	-10000	0	-0.21	59	59
Delta 1/NOTCHprecursor	-0.035	0.16	-10000	0	-0.47	62	62
DLL1	0	0	-10000	0	-10000	0	0
PPARD	0.021	0.068	-10000	0	-0.72	3	3
Gamma Secretase	0.08	0.073	-10000	0	-0.15	29	29
APC	-0.023	0.17	0.28	1	-0.65	29	30
DVL1	0.012	0.1	-10000	0	-0.34	28	28
CSNK2A1	0.034	0.012	-10000	0	-0.001	51	51
MAP3K7IP1	0	0.008	0.026	9	-10000	0	9
DKK1/LRP6/Kremen 2	0.034	0.038	-10000	0	-10000	0	0
LRP6	0.034	0.011	-10000	0	0	44	44
CSNK1A1	0.037	0.007	-10000	0	-0.002	14	14
NLK	0.006	0.041	-10000	0	-0.21	14	14
CCND1	-0.052	0.34	-10000	0	-1.1	44	44
WNT1	0.036	0.007	-10000	0	0	18	18
Axin1/APC/beta catenin	0.009	0.14	0.27	5	-0.42	30	35
DKK2	0.035	0.009	-10000	0	0	31	31
NOTCH1 precursor/DVL1	-0.015	0.19	0.31	1	-0.49	57	58
GSK3B	0.035	0.01	-10000	0	0	37	37
FRAT1	0.028	0.017	-10000	0	0	138	138
NOTCH/Deltex homolog 1	-0.03	0.17	-10000	0	-0.47	62	62
PPP2R5D	0.021	0.047	-10000	0	-0.28	7	7
MAPK1	0.034	0.011	-10000	0	0	47	47
WNT1/LRP6/FZD1	0.06	0.045	-10000	0	-10000	0	0
RBPJ	0.036	0.008	-10000	0	0	21	21
CREBBP	0.033	0.022	0.072	4	-0.019	62	66

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	0.054	0.056	-10000	0	-0.13	35	35
fibroblast growth factor receptor signaling pathway	0.054	0.055	-10000	0	-0.13	35	35
LAMA1	0	0	-10000	0	-10000	0	0
PRNP	0.032	0.013	-10000	0	0	74	74
GPC1/SLIT2	0.033	0.045	-10000	0	-0.14	24	24
SMAD2	-0.023	0.054	0.21	12	-0.2	3	15
GPC1/PrPc/Cu2+	0.026	0.057	-10000	0	-0.13	49	49
GPC1/Laminin alpha1	0.015	0.04	-10000	0	-0.13	35	35
TDGF1	0.036	0.007	-10000	0	0	20	20
CRIPTO/GPC1	0.039	0.047	-10000	0	-0.14	29	29
APP/GPC1	0.037	0.056	-10000	0	-0.15	36	36
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.024	0.033	0.09	21	-0.12	23	44
FLT1	0.035	0.01	-10000	0	0	37	37
GPC1/TGFB/TGFBR1/TGFBR2	0.054	0.053	-10000	0	-0.12	34	34
SERPINC1	0.037	0.005	-10000	0	0	11	11
FYN	-0.018	0.029	0.09	24	-0.12	8	32
FGR	-0.022	0.033	0.09	22	-0.12	21	43
positive regulation of MAPKKK cascade	-0.029	0.12	0.2	22	-0.28	58	80
SLIT2	0.03	0.015	-10000	0	0	100	100
GPC1/NRG	0.039	0.05	-10000	0	-0.14	34	34
NRG1	0.037	0.005	-10000	0	0	9	9
GPC1/VEGF165 homodimer/VEGFR1 homodimer	0.008	0.087	-10000	0	-0.13	122	122
LYN	-0.022	0.034	0.09	23	-0.12	23	46
mol:Spermine	-0.01	0.004	-10000	0	-10000	0	0
cell growth	0.054	0.055	-10000	0	-0.13	35	35
BMP signaling pathway	-0.033	0.012	0	64	-10000	0	64
SRC	-0.025	0.035	0.09	23	-0.12	28	51
TGFBR1	0.036	0.007	-10000	0	0	17	17
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	0.018	0.019	-10000	0	0	266	266
GPC1	0.033	0.013	-10000	0	0	64	64
TGFBR1 (dimer)	0.036	0.007	-10000	0	0	17	17
VEGFA	0.024	0.018	-10000	0	0	181	181
BLK	-0.025	0.035	0.09	25	-0.12	26	51
HCK	-0.018	0.031	0.09	19	-0.12	16	35
FGF2	0.036	0.008	-10000	0	0	25	25
FGFR1	0.037	0.004	-10000	0	0	7	7
VEGFR1 homodimer	0.035	0.01	-10000	0	0	37	37
TGFBR2	0.035	0.009	-10000	0	0	30	30
cell death	0.037	0.055	-10000	0	-0.15	36	36
ATIII/GPC1	0.039	0.049	-10000	0	-0.14	32	32
PLA2G2A/GPC1	-0.003	0.073	-10000	0	-0.15	92	92
LCK	-0.025	0.034	0.09	23	-0.12	25	48
neuron differentiation	0.039	0.05	-10000	0	-0.14	34	34
PrPc/Cu2+	0.016	0.037	-10000	0	-0.13	29	29
APP	0.036	0.007	-10000	0	0	19	19
TGFBR2 (dimer)	0.035	0.009	-10000	0	0	30	30

×

ErbB2/ErbB3 signaling events

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
USP8	-0.016	0.01	0.014	17	-10000	0	17
RAS family/GTP	0.013	0.11	0.22	1	-0.2	38	39
NFATC4	-0.027	0.065	0.2	12	-0.2	5	17
ERBB2IP	0.035	0.011	-10000	0	-0.001	40	40
HSP90 (dimer)	0.035	0.01	-10000	0	0	35	35
mammary gland morphogenesis	-0.037	0.071	0.16	5	-0.18	15	20
JUN	-0.003	0.088	0.23	9	-0.35	7	16
HRAS	0.035	0.01	-10000	0	0	37	37
DOCK7	-0.039	0.065	0.15	7	-0.18	17	24
ErbB2/ErbB3/neuregulin 1 beta/SHC	0.024	0.079	0.21	15	-0.13	84	99
AKT1	-0.01	0.009	0.015	35	-10000	0	35
BAD	-0.017	0.007	0.015	3	-10000	0	3
MAPK10	0.003	0.074	0.16	43	-0.15	12	55
mol:GTP	0	0.002	0.003	2	-0.006	24	26
ErbB2/ErbB3/neuregulin 1 beta	-0.037	0.077	0.19	7	-0.2	14	21
RAF1	-0.016	0.11	0.32	11	-0.24	30	41
ErbB2/ErbB3/neuregulin 2	0.001	0.073	0.21	15	-0.13	91	106
STAT3	-0.028	0.25	-10000	0	-0.9	38	38
cell migration	-0.008	0.072	0.18	28	-0.16	22	50
mol:PI-3-4-5-P3	-0.001	0.002	0.004	17	-0.004	76	93
cell proliferation	-0.039	0.24	0.49	3	-0.62	49	52
FOS	-0.03	0.2	0.36	11	-0.42	90	101
NRAS	0.033	0.013	-10000	0	0	66	66
mol:Ca2+	-0.037	0.071	0.16	5	-0.18	15	20
MAPK3	-0.016	0.18	0.42	5	-0.48	38	43
MAPK1	-0.042	0.22	0.42	5	-0.58	51	56
JAK2	-0.03	0.076	0.17	18	-0.18	16	34
NF2	0.012	0.014	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	-0.007	0.078	0.14	11	-0.16	89	100
NRG1	0.037	0.005	-10000	0	0	9	9
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
MAPK8	-0.017	0.085	0.18	2	-0.22	49	51
MAPK9	0.009	0.078	0.17	55	-0.14	5	60
ERBB2	-0.016	0.07	0.26	31	-10000	0	31
ERBB3	0.018	0.019	-10000	0	0	260	260
SHC1	0.034	0.012	-10000	0	0	53	53
RAC1	0.026	0.017	-10000	0	0	156	156
apoptosis	0.013	0.03	0.19	11	-0.069	2	13
STAT3 (dimer)	-0.025	0.24	-10000	0	-0.88	38	38
RNF41	-0.021	0.016	0.077	5	-0.12	2	7
FRAP1	-0.008	0.005	0.002	78	-10000	0	78
RAC1-CDC42/GTP	-0.024	0.045	-10000	0	-0.13	52	52
ErbB2/ErbB2/HSP90 (dimer)	-0.018	0.058	0.2	31	-0.14	1	32
CHRNA1	-0.006	0.15	0.37	7	-0.37	39	46
myelination	-0.028	0.084	0.26	18	-0.2	5	23
PPP3CB	-0.026	0.067	0.17	12	-0.18	14	26
KRAS	0.035	0.009	-10000	0	0	34	34
RAC1-CDC42/GDP	0.022	0.074	0.22	1	-0.16	49	50
NRG2	0.037	0.005	-10000	0	0	8	8
mol:GDP	-0.007	0.078	0.14	11	-0.16	89	100
SOS1	0	0.001	-10000	0	-0.004	8	8
MAP2K2	-0.026	0.11	0.28	12	-0.24	35	47
SRC	0.035	0.009	-10000	0	0	31	31
mol:cAMP	-0.001	0.001	0.003	7	-0.004	1	8
PTPN11	-0.034	0.08	0.17	16	-0.23	5	21
MAP2K1	-0.034	0.2	0.46	3	-0.59	32	35
heart morphogenesis	-0.037	0.071	0.16	5	-0.18	15	20
RAS family/GDP	0.019	0.11	0.24	1	-0.18	73	74
GRB2	0.036	0.007	-10000	0	0	19	19
PRKACA	0.019	0.009	-10000	0	-10000	0	0
CHRNE	0.002	0.026	0.086	6	-0.12	7	13
HSP90AA1	0.035	0.01	-10000	0	0	35	35
activation of caspase activity	0.01	0.009	-10000	0	-0.015	35	35
nervous system development	-0.037	0.071	0.16	5	-0.18	15	20
CDC42	0.036	0.008	-10000	0	0	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	0.039	-10000	0	-0.056	96	96
HSPA8	0.037	0.009	-10000	0	0	27	27
SMAD3/SMAD4/ER alpha	0.046	0.087	0.23	9	-0.16	18	27
AKT1	0.031	0.019	-10000	0	-0.034	24	24
GSC	0.004	0.033	0.11	20	-0.063	3	23
NKX2-5	0.034	0.017	0.074	7	-0.056	12	19
muscle cell differentiation	-0.017	0.13	0.31	52	-10000	0	52
SMAD2-3/SMAD4/SP1	0.052	0.14	0.33	5	-0.25	48	53
SMAD4	0.023	0.056	0.14	1	-0.13	31	32
CBFB	0.037	0.006	-10000	0	0	13	13
SAP18	0.035	0.011	-10000	0	0	46	46
Cbp/p300/MSG1	0.009	0.087	-10000	0	-0.11	149	149
SMAD3/SMAD4/VDR	0.046	0.12	-10000	0	-0.2	32	32
MYC	0.029	0.015	-10000	0	-10000	0	0
CDKN2B	-0.21	0.2	-10000	0	-0.53	50	50
AP1	-0.003	0.099	0.22	2	-0.26	40	42
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	-0.015	0.13	-10000	0	-0.37	41	41
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	-0.042	0.15	0.21	2	-0.41	53	55
SP3	0.036	0.016	0.081	14	-0.053	10	24
CREB1	0.037	0.005	-10000	0	0	8	8
FOXH1	0.036	0.015	0.076	10	-0.053	9	19
SMAD3/SMAD4/GR	0.042	0.093	0.24	2	-0.18	22	24
GATA3	0.029	0.018	-10000	0	-10000	0	0
SKI/SIN3/HDAC complex/NCoR1	-0.008	0.098	-10000	0	-0.3	32	32
MEF2C/TIF2	-0.02	0.075	0.26	10	-0.22	17	27
endothelial cell migration	0.2	0.49	1.1	106	-10000	0	106
MAX	0.027	0.043	0.085	87	-0.053	88	175
RBBP7	0.037	0.005	-10000	0	0	10	10
RBBP4	0.034	0.012	-10000	0	0	61	61
RUNX2	0.037	0.004	-10000	0	0	7	7
RUNX3	0.035	0.009	-10000	0	0	34	34
RUNX1	0.037	0.006	-10000	0	0	13	13
CTBP1	0.036	0.008	-10000	0	0	27	27
NR3C1	0.028	0.043	0.086	89	-0.053	89	178
VDR	0.036	0.008	-10000	0	0	23	23
CDKN1A	-0.097	0.35	0.38	2	-1.1	58	60
KAT2B	-0.003	0.008	-10000	0	-0.027	9	9
SMAD2/SMAD2/SMAD4/FOXH1	0.049	0.078	0.2	3	-0.16	36	39
DCP1A	0.036	0.008	-10000	0	0	26	26
SKI	0.036	0.009	-10000	0	0	27	27
SERPINE1	-0.2	0.5	-10000	0	-1.2	106	106
SMAD3/SMAD4/ATF2	0.042	0.087	0.22	1	-0.16	29	30
SMAD3/SMAD4/ATF3	0.018	0.1	-10000	0	-0.19	56	56
SAP30	0.037	0.007	-10000	0	0	19	19
Cbp/p300/PIAS3	0.042	0.075	-10000	0	-0.095	96	96
JUN	-0.015	0.097	0.2	8	-0.26	38	46
SMAD3/SMAD4/IRF7	0.045	0.09	-10000	0	-0.17	31	31
TFE3	0.017	0.061	0.11	8	-0.096	103	111
COL1A2	-0.06	0.2	-10000	0	-0.63	56	56
mesenchymal cell differentiation	-0.042	0.087	0.16	33	-0.22	1	34
DLX1	0	0	-10000	0	-10000	0	0
TCF3	0.036	0.007	-10000	0	0	18	18
FOS	0.02	0.03	0.13	1	-0.049	29	30
SMAD3/SMAD4/Max	0.042	0.088	0.24	2	-0.17	16	18
Cbp/p300/SNIP1	0.044	0.058	-10000	0	-0.082	29	29
ZBTB17	0.036	0.006	-10000	0	-10000	0	0
LAMC1	-0.034	0.099	0.17	7	-0.31	39	46
TGIF2/HDAC complex/SMAD3/SMAD4	0.039	0.085	0.22	1	-0.16	30	31
IRF7	0.035	0.01	-10000	0	-10000	0	0
ESR1	0.043	0.033	0.12	67	-0.002	34	101
HNF4A	0.035	0.01	-10000	0	0	37	37
MEF2C	-0.026	0.071	0.24	14	-0.22	19	33
SMAD2-3/SMAD4	0.043	0.096	0.24	1	-0.2	31	32
Cbp/p300/Src-1	0.032	0.076	-10000	0	-0.1	90	90
IGHV3OR16-13	0.005	0.055	-10000	0	-0.48	6	6
TGIF2/HDAC complex	0.034	0.011	-10000	0	0	45	45
CREBBP	0.022	0.035	-10000	0	-0.046	103	103
SKIL	0.037	0.006	-10000	0	0	12	12
HDAC1	0.036	0.008	-10000	0	0	24	24
HDAC2	0.033	0.012	-10000	0	0	61	61
SNIP1	0.037	0.007	-10000	0	0	14	14
GCN5L2	-0.003	0.013	-10000	0	-0.027	92	92
SMAD3/SMAD4/TFE3	0.032	0.12	0.27	3	-0.23	47	50
MSG1/HSC70	0.01	0.079	-10000	0	-0.14	102	102
SMAD2	0.036	0.018	0.092	4	-0.051	13	17
SMAD3	0.02	0.059	0.14	2	-0.13	38	40
SMAD3/E2F4-5/DP1/p107/SMAD4	0.002	0.075	-10000	0	-0.2	36	36
SMAD2/SMAD2/SMAD4	-0.015	0.067	0.17	5	-0.19	45	50
NCOR1	0.036	0.009	-10000	0	0	27	27
NCOA2	0.037	0.005	-10000	0	0	11	11
NCOA1	0.034	0.011	-10000	0	0	49	49
MYOD/E2A	0.053	0.013	-10000	0	-10000	0	0
SMAD2-3/SMAD4/SP1/MIZ-1	0.061	0.15	0.34	4	-0.25	40	44
IFNB1	-0.006	0.06	0.17	8	-0.18	7	15
SMAD3/SMAD4/MEF2C	0.028	0.093	0.24	1	-0.23	20	21
CITED1	0.026	0.017	-10000	0	0	153	153
SMAD2-3/SMAD4/ARC105	0.057	0.098	0.26	1	-0.18	27	28
RBL1	0	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	-0.022	0.14	-10000	0	-0.43	38	38
RUNX1-3/PEBPB2	0.068	0.024	-10000	0	-10000	0	0
SMAD7	-0.043	0.18	0.28	1	-0.44	61	62
MYC/MIZ-1	0.029	0.058	-10000	0	-0.14	49	49
SMAD3/SMAD4	-0.08	0.23	0.2	2	-0.46	115	117
IL10	-0.012	0.063	0.18	9	-0.19	4	13
PIASy/HDAC complex	0.03	0.031	0.073	16	-0.031	87	103
PIAS3	0.024	0.029	-10000	0	-0.031	108	108
CDK2	0.022	0.033	-10000	0	-0.043	92	92
IL5	-0.011	0.065	0.19	10	-0.19	2	12
CDK4	0.021	0.031	-10000	0	-0.046	69	69
PIAS4	0.03	0.031	0.074	14	-0.031	87	101
ATF3	0.028	0.016	-10000	0	0	129	129
SMAD3/SMAD4/SP1	0.03	0.14	0.31	1	-0.25	53	54
FOXG1	0.027	0.021	0.068	3	-0.004	146	149
FOXO3	-0.017	0.013	-10000	0	-0.065	1	1
FOXO1	-0.016	0.012	-10000	0	-10000	0	0
FOXO4	-0.019	0.011	-10000	0	-10000	0	0
heart looping	-0.026	0.07	0.24	14	-0.22	19	33
CEBPB	0.032	0.014	-10000	0	-10000	0	0
SMAD3/SMAD4/DLX1	0.025	0.073	0.19	1	-0.14	48	49
MYOD1	0.037	0.005	-10000	0	0	10	10
SMAD3/SMAD4/HNF4	0.04	0.086	0.22	1	-0.16	28	29
SMAD3/SMAD4/GATA3	0.036	0.087	-10000	0	-0.17	24	24
SnoN/SIN3/HDAC complex/NCoR1	0.037	0.006	-10000	0	0	12	12
SMAD3/SMAD4/RUNX1-3/PEBPB2	0.069	0.095	-10000	0	-0.16	13	13
SMAD3/SMAD4/SP1-3	0.047	0.14	0.32	1	-0.25	48	49
MED15	0.035	0.009	-10000	0	0	31	31
SP1	0.016	0.075	0.12	20	-0.12	107	127
SIN3B	0.036	0.009	-10000	0	0	27	27
SIN3A	0	0.001	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	0.069	0.085	0.25	1	-0.16	38	39
ITGB5	-0.031	0.11	0.26	11	-0.28	32	43
TGIF/SIN3/HDAC complex/CtBP	-0.015	0.12	-10000	0	-0.35	34	34
SMAD3/SMAD4/AR	0.041	0.086	0.22	1	-0.16	29	30
AR	0.036	0.008	-10000	0	0	23	23
negative regulation of cell growth	-0.015	0.12	0.18	1	-0.29	59	60
SMAD3/SMAD4/MYOD	0.043	0.087	0.22	1	-0.16	37	38
E2F5	0.037	0.005	-10000	0	0	9	9
E2F4	0.037	0.005	-10000	0	0	8	8
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	0.061	0.099	0.24	1	-0.17	34	35
SMAD2-3/SMAD4/FOXO1-3a-4	-0.025	0.13	0.22	2	-0.41	38	40
TFDP1	0.034	0.012	-10000	0	0	56	56
SMAD3/SMAD4/AP1	0.019	0.12	0.25	2	-0.26	39	41
SMAD3/SMAD4/RUNX2	0.043	0.087	0.22	1	-0.16	32	33
TGIF2	0.034	0.011	-10000	0	0	45	45
TGIF1	0.033	0.013	-10000	0	0	67	67
ATF2	0.037	0.005	-10000	0	0	11	11

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	0.043	0.011	-10000	0	-10000	0	0
NFATC2	0.024	0.16	0.29	5	-0.37	37	42
NFATC3	0.017	0.13	0.28	20	-0.24	73	93
CD40LG	-0.011	0.34	0.5	44	-0.69	71	115
ITCH	0.034	0.048	0.19	8	-10000	0	8
CBLB	0.036	0.049	0.2	11	-0.12	1	12
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.045	0.26	0.38	15	-0.63	53	68
JUNB	0.032	0.014	-10000	0	0	77	77
CaM/Ca2+/Calcineurin A alpha-beta B1	0.034	0.029	-10000	0	-0.13	7	7
T cell anergy	0.016	0.067	0.21	23	-0.21	2	25
TLE4	0.014	0.11	-10000	0	-0.32	19	19
Jun/NFAT1-c-4/p21SNFT	-0.014	0.33	0.45	3	-0.73	71	74
AP-1/NFAT1-c-4	-0.041	0.34	-10000	0	-0.78	67	67
IKZF1	0.023	0.094	0.39	5	-0.31	12	17
T-helper 2 cell differentiation	-0.069	0.23	-10000	0	-0.61	43	43
AP-1/NFAT1	0.02	0.15	0.29	18	-0.29	43	61
CALM1	0.046	0.024	0.13	1	-10000	0	1
EGR2	-0.069	0.42	0.5	13	-0.97	75	88
EGR3	-0.053	0.42	0.47	28	-0.96	74	102
NFAT1/FOXP3	0.048	0.13	0.26	3	-0.29	24	27
EGR1	0.03	0.016	0.073	1	-10000	0	1
JUN	0.033	0.043	0.12	34	-0.05	13	47
EGR4	0.038	0.004	0.073	1	-10000	0	1
mol:Ca2+	0.005	0.004	-10000	0	-10000	0	0
GBP3	0.011	0.1	0.18	3	-0.24	37	40
FOSL1	0.034	0.012	-10000	0	0	56	56
NFAT1-c-4/MAF/IRF4	0.014	0.34	0.43	6	-0.72	74	80
DGKA	0.016	0.1	-10000	0	-0.31	18	18
CREM	0.028	0.016	-10000	0	0	120	120
NFAT1-c-4/PPARG	-0.001	0.33	0.43	5	-0.73	74	79
CTLA4	0.012	0.093	-10000	0	-0.27	19	19
NFAT1-c-4 (dimer)/EGR1	-0.023	0.34	0.43	2	-0.76	76	78
NFAT1-c-4 (dimer)/EGR4	0.007	0.34	0.43	6	-0.74	74	80
FOS	0.024	0.039	0.11	20	-0.052	10	30
IFNG	-0.001	0.13	-10000	0	-0.44	11	11
T cell activation	-0.01	0.22	0.43	5	-0.54	33	38
MAF	0.035	0.01	-10000	0	0	36	36
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.006	0.28	0.6	73	-0.44	28	101
TNF	-0.036	0.31	0.39	18	-0.7	75	93
FASLG	-0.093	0.46	0.55	3	-1.1	76	79
TBX21	0.041	0.007	0.11	3	-10000	0	3
BATF3	0	0	-10000	0	-10000	0	0
PRKCQ	0.028	0.018	-10000	0	-10000	0	0
PTPN1	0.014	0.12	0.43	2	-0.36	22	24
NFAT1-c-4/ICER1	-0.023	0.32	0.42	6	-0.74	74	80
GATA3	0.029	0.017	-10000	0	-10000	0	0
T-helper 1 cell differentiation	0.012	0.14	-10000	0	-0.43	11	11
IL2RA	-0.054	0.25	0.33	11	-0.6	59	70
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	0.012	0.11	-10000	0	-0.36	21	21
E2F1	0.036	0.05	-10000	0	-0.25	12	12
PPARG	0.036	0.008	-10000	0	0	25	25
SLC3A2	0.012	0.12	0.24	1	-0.38	26	27
IRF4	0.037	0.005	-10000	0	0	10	10
PTGS2	-0.07	0.28	0.44	3	-0.69	68	71
CSF2	-0.01	0.34	0.5	44	-0.69	70	114
JunB/Fra1/NFAT1-c-4	-0.013	0.32	-10000	0	-0.72	72	72
IL4	-0.072	0.23	-10000	0	-0.64	42	42
IL5	-0.011	0.34	0.5	44	-0.69	70	114
IL2	-0.01	0.22	0.43	5	-0.56	31	36
IL3	0.007	0.087	-10000	0	-0.53	8	8
RNF128	0.013	0.023	0.18	1	-10000	0	1
NFATC1	-0.006	0.28	0.44	28	-0.6	73	101
CDK4	-0.014	0.27	0.56	38	-1	14	52
PTPRK	0.002	0.14	-10000	0	-0.43	36	36
IL8	-0.099	0.29	0.46	7	-0.74	66	73
POU2F1	0.04	0.009	-10000	0	-10000	0	0

×

Signaling events mediated by PTP1B

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
PDGFRB	0.036	0.008	-10000	0	0	25	25
Jak2/Leptin Receptor	0.001	0.13	-10000	0	-0.35	40	40
PTP1B/AKT1	0.002	0.12	0.21	3	-0.25	56	59
FYN	0.031	0.015	-10000	0	0	93	93
p210 bcr-abl/PTP1B	-0.01	0.11	0.22	3	-0.27	48	51
EGFR	0.01	0.017	-10000	0	-0.031	4	4
EGF/EGFR	-0.034	0.095	-10000	0	-0.29	41	41
CSF1	0.037	0.005	-10000	0	0	9	9
AKT1	0.034	0.012	-10000	0	0	58	58
INSR	0.036	0.007	-10000	0	-0.002	16	16
PTP1B/N-cadherin	-0.005	0.12	0.21	2	-0.27	58	60
Insulin Receptor/Insulin	0.02	0.12	-10000	0	-0.26	38	38
HCK	0.027	0.017	-10000	0	0	145	145
CRK	0.036	0.008	-10000	0	0	25	25
TYK2	-0.012	0.12	0.28	20	-0.29	44	64
EGF	0.028	0.025	-10000	0	-0.023	93	93
YES1	0.035	0.01	-10000	0	0	43	43
CAV1	0.004	0.15	0.24	29	-0.29	57	86
TXN	0.035	0.011	-10000	0	-0.001	42	42
PTP1B/IRS1/GRB2	0.007	0.13	0.22	1	-0.27	51	52
cell migration	0.01	0.11	0.27	48	-0.22	3	51
STAT3	0.035	0.01	-10000	0	0	40	40
PRLR	0.039	0.006	-10000	0	-10000	0	0
ITGA2B	0.037	0.003	-10000	0	0	4	4
CSF1R	0.028	0.017	-10000	0	0	132	132
Prolactin Receptor/Prolactin	0.058	0.013	-10000	0	-10000	0	0
FGR	0.033	0.012	-10000	0	0	58	58
PTP1B/p130 Cas	-0.012	0.11	0.19	3	-0.26	50	53
Crk/p130 Cas	-0.001	0.12	0.2	3	-0.26	52	55
DOK1	-0.009	0.11	0.2	5	-0.3	35	40
JAK2	-0.01	0.13	0.26	1	-0.36	42	43
Jak2/Leptin Receptor/Leptin	-0.012	0.12	-10000	0	-0.32	32	32
PIK3R1	0.033	0.013	-10000	0	0	67	67
PTPN1	-0.01	0.11	0.22	3	-0.27	48	51
LYN	0.032	0.013	-10000	0	0	72	72
CDH2	0.033	0.012	-10000	0	0	57	57
SRC	0.015	0.1	-10000	0	-0.48	17	17
ITGB3	0.037	0.004	-10000	0	0	6	6
CAT1/PTP1B	-0.007	0.18	0.28	31	-0.37	63	94
CAPN1	0.036	0.006	-10000	0	-0.003	9	9
CSK	0.036	0.007	-10000	0	0	20	20
PI3K	0.009	0.13	-10000	0	-0.3	44	44
mol:H2O2	0.003	0.005	0.027	3	-10000	0	3
STAT3 (dimer)	-0.01	0.11	-10000	0	-0.29	32	32
negative regulation of transcription	-0.01	0.13	0.26	1	-0.35	42	43
FCGR2A	0.029	0.016	-10000	0	0	114	114
FER	0.037	0.009	-10000	0	-0.003	19	19
alphaIIb/beta3 Integrin	0.054	0.006	-10000	0	-10000	0	0
BLK	0.037	0.007	-10000	0	0	16	16
Insulin Receptor/Insulin/Shc	0.061	0.036	-10000	0	-0.13	8	8
RHOA	0.036	0.007	-10000	0	0	20	20
LEPR	0.036	0.008	-10000	0	0	22	22
BCAR1	0	0	-10000	0	-10000	0	0
p210 bcr-abl/Grb2	0.036	0.007	-10000	0	0	19	19
mol:NADPH	0	0.003	-10000	0	-10000	0	0
TRPV6	-0.004	0.16	0.22	19	-0.36	60	79
PRL	0.039	0.007	-10000	0	-10000	0	0
SOCS3	0.024	0.016	-10000	0	-10000	0	0
SPRY2	0.03	0.019	-10000	0	0	140	140
Insulin Receptor/Insulin/IRS1	0.058	0.046	-10000	0	-0.12	22	22
CSF1/CSF1R	-0.003	0.13	0.22	1	-0.28	54	55
Ras protein signal transduction	-0.005	0.091	0.58	10	-10000	0	10
IRS1	0.034	0.011	-10000	0	0	52	52
INS	0.036	0.008	-10000	0	-0.001	21	21
LEP	0.026	0.017	-10000	0	0	158	158
STAT5B	-0.003	0.11	0.25	2	-0.3	30	32
STAT5A	-0.003	0.11	0.25	2	-0.29	33	35
GRB2	0.036	0.007	-10000	0	0	19	19
PDGFB-D/PDGFRB	0.002	0.12	0.22	3	-0.27	47	50
CSN2	0.013	0.04	-10000	0	-10000	0	0
PIK3CA	0.032	0.013	-10000	0	0	74	74
LAT	-0.027	0.18	-10000	0	-0.46	64	64
YBX1	0.041	0.04	-10000	0	-0.29	7	7
LCK	0.036	0.008	-10000	0	0	21	21
SHC1	0.034	0.012	-10000	0	0	53	53
NOX4	0.035	0.016	-10000	0	0	83	83

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.035	0.01	-10000	0	0	39	39
mol:PIP3	-0.021	0.054	0.091	3	-0.22	22	25
FRAP1	0.025	0.1	0.24	3	-0.48	13	16
AKT1	0.009	0.1	0.17	104	-0.24	31	135
INSR	0.037	0.006	-10000	0	0	15	15
Insulin Receptor/Insulin	0.047	0.013	-10000	0	-10000	0	0
mol:GTP	0.036	0.11	0.2	69	-0.25	31	100
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	-0.005	0.054	-10000	0	-0.19	25	25
TSC2	0.036	0.008	-10000	0	0	26	26
RHEB/GDP	-0.02	0.072	0.11	35	-0.24	26	61
TSC1	0.035	0.01	-10000	0	0	41	41
Insulin Receptor/IRS1	0.023	0.06	-10000	0	-0.25	22	22
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0.026	0.075	0.17	3	-0.2	21	24
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.026	0.017	-10000	0	0	153	153
RPS6KB1	0.035	0.088	0.25	12	-0.29	7	19
MAP3K5	-0.025	0.084	0.16	1	-0.22	73	74
PIK3R1	0.033	0.013	-10000	0	0	67	67
apoptosis	-0.025	0.083	0.16	1	-0.22	73	74
mol:LY294002	0	0	0.001	13	-0.001	21	34
EIF4B	0.03	0.087	0.24	17	-0.29	7	24
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	0.022	0.071	0.27	2	-0.24	9	11
eIF4E/eIF4G1/eIF4A1	0.01	0.073	-10000	0	-0.3	16	16
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	0.024	0.083	0.18	1	-0.23	32	33
mTOR/RHEB/GTP/Raptor/GBL	0.001	0.06	0.18	20	-0.16	18	38
FKBP1A	0.033	0.013	-10000	0	0	63	63
RHEB/GTP	0.017	0.087	0.24	6	-0.23	28	34
mol:Amino Acids	0	0	0.001	13	-0.001	21	34
FKBP12/Rapamycin	0.022	0.024	-10000	0	-0.13	10	10
PDPK1	-0.024	0.056	0.16	9	-0.21	21	30
EIF4E	0.035	0.01	-10000	0	0	37	37
ASK1/PP5C	-0.038	0.23	-10000	0	-0.56	81	81
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.005	0.08	-10000	0	-0.3	29	29
TSC1/TSC2	0.04	0.12	0.22	70	-0.27	31	101
tumor necrosis factor receptor activity	0	0	0.001	21	-0.001	13	34
RPS6	0.032	0.013	-10000	0	0	71	71
PPP5C	0.035	0.009	-10000	0	0	32	32
EIF4G1	0.034	0.011	-10000	0	0	46	46
IRS1	0.001	0.058	-10000	0	-0.26	23	23
INS	0.036	0.007	-10000	0	0	20	20
PTEN	0.026	0.017	-10000	0	0	158	158
PDK2	-0.024	0.056	0.16	9	-0.22	20	29
EIF4EBP1	-0.024	0.25	-10000	0	-1.1	26	26
PIK3CA	0.033	0.014	-10000	0	0	74	74
PPP2R5D	0.019	0.092	0.26	3	-0.43	13	16
peptide biosynthetic process	-0.022	0.017	0.18	3	-10000	0	3
RHEB	0.026	0.018	-10000	0	0	159	159
EIF4A1	0.036	0.007	-10000	0	0	20	20
mol:Rapamycin	0	0.001	0.004	20	-0.003	13	33
EEF2	-0.022	0.017	0.18	3	-10000	0	3
eIF4E/4E-BP1	-0.007	0.25	-10000	0	-1.1	26	26

×

EPHB forward signaling

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
Ephrin A5/EPHB2	0.046	0.015	-10000	0	-10000	0	0
cell-cell adhesion	0.031	0.04	0.19	13	-10000	0	13
Ephrin B/EPHB2/RasGAP	0.062	0.089	-10000	0	-0.13	73	73
ITSN1	0.036	0.007	-10000	0	0	17	17
PIK3CA	0.032	0.013	-10000	0	0	74	74
SHC1	0.034	0.012	-10000	0	0	53	53
Ephrin B1/EPHB3	0.046	0.015	-10000	0	-10000	0	0
Ephrin B1/EPHB1	0.04	0.026	-10000	0	-0.11	6	6
HRAS/GDP	0.004	0.081	-10000	0	-0.21	41	41
Ephrin B/EPHB1/GRB7	0.069	0.074	-10000	0	-0.12	45	45
Endophilin/SYNJ1	-0.026	0.058	0.19	15	-0.18	2	17
KRAS	0.035	0.009	-10000	0	0	34	34
Ephrin B/EPHB1/Src	0.064	0.076	-10000	0	-0.12	50	50
endothelial cell migration	0.022	0.072	-10000	0	-0.14	63	63
GRB2	0.036	0.007	-10000	0	0	19	19
GRB7	0.037	0.007	-10000	0	0	16	16
PAK1	-0.029	0.064	0.2	18	-10000	0	18
HRAS	0.035	0.01	-10000	0	0	37	37
RRAS	-0.025	0.061	0.21	13	-0.18	10	23
DNM1	0.036	0.008	-10000	0	0	26	26
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	-0.019	0.066	0.19	18	-0.18	11	29
lamellipodium assembly	-0.031	0.04	-10000	0	-0.19	13	13
Ephrin B/EPHB1/Src/p52 SHC/GRB2	0.012	0.071	-10000	0	-0.28	14	14
PIK3R1	0.033	0.013	-10000	0	0	67	67
EPHB2	0.035	0.01	-10000	0	0	39	39
EPHB3	0.034	0.011	-10000	0	0	47	47
EPHB1	0.031	0.015	-10000	0	0	95	95
EPHB4	0.026	0.017	-10000	0	0	157	157
mol:GDP	0.018	0.11	0.2	99	-0.23	33	132
Ephrin B/EPHB2	0.053	0.068	-10000	0	-0.11	63	63
Ephrin B/EPHB3	0.053	0.067	-10000	0	-0.11	62	62
JNK cascade	-0.006	0.072	0.23	23	-0.19	4	27
Ephrin B/EPHB1	0.053	0.065	-10000	0	-0.11	52	52
RAP1/GDP	0.024	0.12	0.2	106	-0.22	33	139
EFNB2	0.029	0.016	-10000	0	0	115	115
EFNB3	0.036	0.008	-10000	0	0	25	25
EFNB1	0.038	0.002	-10000	0	0	2	2
Ephrin B2/EPHB1-2	0.034	0.058	-10000	0	-0.11	50	50
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.037	0.005	-10000	0	0	10	10
CDC42/GTP	0.046	0.082	-10000	0	-0.19	31	31
Rap1/GTP	-0.045	0.051	0.053	7	-0.2	21	28
axon guidance	0.046	0.014	-10000	0	-10000	0	0
MAPK3	-0.004	0.07	0.16	5	-0.28	14	19
MAPK1	-0.004	0.072	0.18	1	-0.28	17	18
Rac1/GDP	-0.009	0.091	0.23	22	-0.24	31	53
actin cytoskeleton reorganization	-0.042	0.06	-10000	0	-0.2	37	37
CDC42/GDP	0.029	0.13	0.22	107	-0.23	33	140
PI3K	0.026	0.076	-10000	0	-0.14	63	63
EFNA5	0.037	0.005	-10000	0	0	9	9
Ephrin B2/EPHB4	0.018	0.046	-10000	0	-0.11	42	42
Ephrin B/EPHB2/Intersectin/N-WASP	0.004	0.06	-10000	0	-0.17	42	42
CDC42	0.036	0.008	-10000	0	0	26	26
RAS family/GTP	-0.053	0.06	-10000	0	-0.24	24	24
PTK2	-0.013	0.087	0.54	11	-0.2	15	26
MAP4K4	-0.006	0.073	0.23	23	-0.19	4	27
SRC	0.035	0.009	-10000	0	0	31	31
KALRN	0.036	0.008	-10000	0	0	22	22
Intersectin/N-WASP	0.035	0.033	-10000	0	-0.14	7	7
neuron projection morphogenesis	0.055	0.17	0.34	112	-0.22	12	124
MAP2K1	0.001	0.07	0.2	1	-0.28	15	16
WASL	0.026	0.017	-10000	0	0	157	157
Ephrin B1/EPHB1-2/NCK1	0.082	0.039	-10000	0	-0.12	10	10
cell migration	-0.01	0.086	0.2	5	-0.28	19	24
NRAS	0.033	0.013	-10000	0	0	66	66
SYNJ1	-0.027	0.058	0.19	15	-0.18	2	17
PXN	0.037	0.005	-10000	0	0	9	9
TF	-0.022	0.051	0.18	7	-0.18	20	27
HRAS/GTP	0.036	0.079	-10000	0	-0.14	59	59
Ephrin B1/EPHB1-2	0.054	0.035	-10000	0	-0.11	6	6
cell adhesion mediated by integrin	0.019	0.049	0.15	5	-0.23	7	12
RAC1	0.026	0.017	-10000	0	0	156	156
mol:GTP	0.044	0.076	-10000	0	-0.13	60	60
RAC1-CDC42/GTP	-0.032	0.046	-10000	0	-0.2	14	14
RASA1	0.035	0.01	-10000	0	0	35	35
RAC1-CDC42/GDP	0.012	0.094	0.24	20	-0.24	31	51
ruffle organization	0.066	0.17	0.32	130	-0.25	7	137
NCK1	0.036	0.009	-10000	0	0	28	28
receptor internalization	-0.032	0.054	0.18	14	-0.18	2	16
Ephrin B/EPHB2/KALRN	0.068	0.079	-10000	0	-0.12	60	60
ROCK1	-0.009	0.048	0.18	21	-10000	0	21
RAS family/GDP	-0.044	0.063	-10000	0	-0.21	42	42
Rac1/GTP	-0.029	0.045	-10000	0	-0.2	13	13
Ephrin B/EPHB1/Src/Paxillin	0.01	0.062	-10000	0	-0.15	52	52

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	0.044	0.091	0.23	35	-0.2	8	43
TBX21	0.076	0.2	0.55	10	-0.57	8	18
B2M	0.036	0.007	-10000	0	0	20	20
TYK2	0.039	0.041	0.12	18	-0.056	10	28
IL12RB1	0.039	0.042	0.12	18	-0.056	12	30
GADD45B	0.067	0.3	0.53	20	-0.98	26	46
IL12RB2	0.041	0.042	0.12	22	-0.053	23	45
GADD45G	0.1	0.2	0.52	16	-0.54	6	22
natural killer cell activation	0.013	0.025	0.058	78	-0.037	12	90
RELB	0.035	0.009	-10000	0	0	30	30
RELA	0.037	0.005	-10000	0	0	10	10
IL18	0.034	0.025	0.091	2	-0.039	27	29
IL2RA	0.026	0.017	-10000	0	0	152	152
IFNG	0.035	0.01	-10000	0	0	35	35
STAT3 (dimer)	0.07	0.23	0.44	38	-0.51	32	70
HLA-DRB5	-0.001	0.009	-10000	0	-0.023	41	41
FASLG	0.08	0.2	0.53	13	-0.57	8	21
NF kappa B2 p52/RelB	0.062	0.19	0.44	14	-0.47	18	32
CD4	0.025	0.027	-10000	0	-0.017	132	132
SOCS1	0.037	0.004	-10000	0	0	7	7
EntrezGene:6955	-0.001	0.01	-10000	0	-0.026	56	56
CD3D	0.025	0.029	-10000	0	-0.025	113	113
CD3E	0.028	0.028	-10000	0	-0.035	78	78
CD3G	0.027	0.03	-10000	0	-0.043	70	70
IL12Rbeta2/JAK2	0.057	0.062	0.19	19	-10000	0	19
CCL3	0.079	0.2	0.46	37	-0.48	18	55
CCL4	0.047	0.33	0.54	28	-1	32	60
HLA-A	0.037	0.006	-10000	0	0	15	15
IL18/IL18R	0.097	0.074	0.24	18	-0.13	6	24
NOS2	0.082	0.2	0.45	40	-0.44	17	57
IL12/IL12R/TYK2/JAK2/SPHK2	0.041	0.091	0.22	32	-0.22	10	42
IL1R1	0.079	0.21	0.58	11	-0.59	7	18
IL4	0.002	0.05	-10000	0	-0.08	76	76
JAK2	0.035	0.04	0.12	16	-0.057	10	26
EntrezGene:6957	-0.001	0.009	-10000	0	-0.023	41	41
TCR/CD3/MHC I/CD8	0.012	0.048	-10000	0	-0.25	7	7
RAB7A	0.083	0.27	0.55	13	-0.78	26	39
lysosomal transport	0.085	0.26	0.54	15	-0.73	26	41
FOS	-0.11	0.48	0.49	17	-1	100	117
STAT4 (dimer)	0.096	0.22	0.48	36	-0.52	17	53
STAT5A (dimer)	0.081	0.2	0.43	17	-0.48	17	34
GZMA	0.075	0.21	0.52	24	-0.57	8	32
GZMB	0.073	0.2	0.58	12	-0.58	7	19
HLX	0.035	0.009	-10000	0	0	30	30
LCK	0.069	0.21	0.46	34	-0.51	17	51
TCR/CD3/MHC II/CD4	-0.02	0.12	0.16	19	-0.24	83	102
IL2/IL2R	0.064	0.049	-10000	0	-10000	0	0
MAPK14	0.098	0.25	0.53	20	-0.71	22	42
CCR5	0.091	0.21	0.55	17	-0.78	5	22
IL1B	0.03	0.039	0.12	8	-0.051	29	37
STAT6	0.051	0.1	0.3	17	-0.41	4	21
STAT4	0.035	0.009	-10000	0	0	31	31
STAT3	0.035	0.01	-10000	0	0	40	40
STAT1	0.035	0.01	-10000	0	0	41	41
NFKB1	0.036	0.007	-10000	0	0	18	18
NFKB2	0.028	0.017	-10000	0	0	132	132
IL12B	0.042	0.042	0.12	23	-0.056	15	38
CD8A	0	0	-10000	0	-10000	0	0
CD8B	0.037	0.004	-10000	0	0	7	7
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	-0.043	0.091	0.2	8	-0.23	35	43
IL2RB	0.034	0.011	-10000	0	0	49	49
proteasomal ubiquitin-dependent protein catabolic process	0.097	0.21	0.47	38	-0.49	17	55
IL2RG	0.036	0.008	-10000	0	0	25	25
IL12	0.064	0.063	0.19	23	-10000	0	23
STAT5A	0.037	0.005	-10000	0	0	8	8
CD247	0.028	0.028	-10000	0	-0.041	66	66
IL2	0.037	0.005	-10000	0	0	9	9
SPHK2	0.036	0.009	-10000	0	0	29	29
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.04	0.042	0.12	17	-0.057	12	29
IL12/IL12R/TYK2/JAK2	0.074	0.22	0.5	35	-0.52	18	53
MAP2K3	0.094	0.24	0.52	20	-0.67	22	42
RIPK2	0.037	0.006	-10000	0	0	14	14
MAP2K6	0.098	0.24	0.5	25	-0.62	22	47
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.021	0.028	-10000	0	-0.012	186	186
IL18RAP	0.04	0.023	0.091	3	-0.038	33	36
IL12Rbeta1/TYK2	0.052	0.065	0.18	10	-0.15	15	25
EOMES	-0.019	0.04	0.1	1	-0.11	46	47
STAT1 (dimer)	0.085	0.2	0.46	30	-0.47	15	45
T cell proliferation	0.085	0.19	0.43	38	-0.43	20	58
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.04	0.023	0.091	3	-0.038	33	36
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	0.053	0.18	0.41	3	-0.49	21	24
ATF2	0.09	0.24	0.51	19	-0.67	22	41

×

Noncanonical Wnt signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0.004	0.097	-10000	0	-0.25	28	28
mol:DAG	-0.011	0.086	0.2	4	-0.24	27	31
PLCG1	-0.012	0.088	0.2	4	-0.25	27	31
YES1	-0.015	0.082	0.13	1	-0.17	82	83
FZD3	0.03	0.015	-10000	0	0	108	108
FZD6	0.028	0.017	-10000	0	0	132	132
G protein	0.004	0.1	0.2	26	-0.27	27	53
MAP3K7	-0.031	0.078	0.2	9	-0.23	31	40
mol:Ca2+	-0.011	0.084	0.18	5	-0.24	27	32
mol:IP3	-0.011	0.086	0.2	4	-0.24	27	31
NLK	-0.011	0.16	-10000	0	-0.83	18	18
GNB1	0.034	0.011	-10000	0	0	47	47
CAMK2A	-0.027	0.08	0.22	9	-0.23	26	35
MAP3K7IP1	0	0	-10000	0	-10000	0	0
Noncanonical Wnts/FZD	-0.005	0.087	-10000	0	-0.17	88	88
CSNK1A1	0.037	0.006	-10000	0	0	13	13
GNAS	-0.015	0.079	-10000	0	-0.17	83	83
GO:0007205	-0.016	0.087	0.24	8	-0.25	26	34
WNT6	0.038	0.002	-10000	0	0	2	2
WNT4	0.036	0.008	-10000	0	0	21	21
NFAT1/CK1 alpha	-0.004	0.097	0.22	3	-0.26	29	32
GNG2	0	0	-10000	0	-10000	0	0
WNT5A	0.03	0.015	-10000	0	0	101	101
WNT11	0.037	0.007	-10000	0	0	16	16
CDC42	-0.025	0.08	0.17	4	-0.26	23	27

×

E-cadherin signaling in keratinocytes

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
keratinocyte differentiation	-0.02	0.11	0.2	3	-0.37	29	32
adherens junction organization	-0.001	0.077	-10000	0	-0.3	21	21
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	0.026	0.11	0.19	48	-0.29	23	71
FMN1	0.008	0.064	0.14	4	-0.25	17	21
mol:IP3	-0.009	0.078	0.14	2	-0.25	32	34
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.013	0.068	0.15	3	-0.27	17	20
CTNNB1	0.036	0.007	-10000	0	0	17	17
AKT1	-0.004	0.091	0.15	2	-0.34	24	26
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	0.024	0.071	-10000	0	-0.41	6	6
CTNND1	0.036	0.01	-10000	0	0	36	36
mol:PI-4-5-P2	0.003	0.066	0.14	3	-0.26	19	22
VASP	0.001	0.065	0.14	4	-0.26	18	22
ZYX	0.006	0.059	0.15	3	-0.33	9	12
JUB	0.008	0.064	0.14	4	-0.25	17	21
EGFR(dimer)	0	0.066	-10000	0	-0.31	14	14
E-cadherin/beta catenin-gamma catenin	0.064	0.031	-10000	0	-0.11	3	3
mol:PI-3-4-5-P3	0.025	0.097	0.22	1	-0.29	24	25
PIK3CA	0.032	0.015	-10000	0	-0.002	78	78
PI3K	0.025	0.099	0.22	1	-0.3	24	25
FYN	-0.041	0.13	0.17	5	-0.32	71	76
mol:Ca2+	-0.009	0.077	0.14	2	-0.25	32	34
JUP	0.034	0.012	-10000	0	0	52	52
PIK3R1	0.033	0.016	-10000	0	-0.004	75	75
mol:DAG	-0.009	0.078	0.14	2	-0.25	32	34
CDH1	0.035	0.01	-10000	0	0	39	39
RhoA/GDP	0.052	0.12	0.19	86	-0.28	24	110
establishment of polarity of embryonic epithelium	0.001	0.064	0.14	4	-0.26	18	22
SRC	0.035	0.009	-10000	0	0	31	31
RAC1	0.026	0.017	-10000	0	0	156	156
RHOA	0.036	0.007	-10000	0	0	20	20
EGFR	0.01	0.017	-10000	0	0	373	373
CASR	-0.025	0.074	0.15	14	-0.28	24	38
RhoA/GTP	0.007	0.085	-10000	0	-0.27	25	25
AKT2	-0.003	0.082	0.17	1	-0.29	24	25
actin cable formation	-0.002	0.064	0.13	4	-0.26	19	23
apoptosis	0.008	0.1	0.34	28	-0.17	12	40
CTNNA1	0.037	0.008	-10000	0	-0.002	20	20
mol:GDP	-0.022	0.073	0.17	2	-0.29	23	25
PIP5K1A	0.002	0.067	-10000	0	-0.26	19	19
PLCG1	-0.009	0.08	0.14	2	-0.26	32	34
Rac1/GTP	-0.004	0.071	-10000	0	-0.31	14	14
homophilic cell adhesion	-0.001	0.003	-10000	0	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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
DYNC1H1	0.034	0.011	-10000	0	0	50	50
VLDLR	0.028	0.016	-10000	0	0	129	129
LRPAP1	0.037	0.007	-10000	0	0	16	16
NUDC	0.035	0.009	-10000	0	0	30	30
RELN/LRP8	0.042	0.045	-10000	0	-0.13	11	11
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	14	14
KATNA1	0.034	0.011	-10000	0	0	46	46
GO:0030286	0	0	-10000	0	-10000	0	0
ABL1	0.033	0.1	0.19	128	-0.21	6	134
IQGAP1/CaM	0.032	0.059	-10000	0	-0.14	46	46
DAB1	0.037	0.006	-10000	0	0	12	12
IQGAP1	0.034	0.011	-10000	0	0	47	47
PLA2G7	0.034	0.012	-10000	0	0	56	56
CALM1	0.033	0.012	-10000	0	0	60	60
DYNLT1	0.035	0.01	-10000	0	0	42	42
mol:Ca2+	0	0	-10000	0	-10000	0	0
LRPAP1/LRP8	0.046	0.036	-10000	0	-0.15	14	14
UniProt:Q4QZ09	0	0	-10000	0	-10000	0	0
CLIP1	0.036	0.008	-10000	0	0	26	26
CDK5R1	0.036	0.008	-10000	0	0	25	25
LIS1/Poliovirus Protein 3A	-0.023	0.028	-10000	0	-0.14	24	24
CDK5R2	0.036	0.007	-10000	0	0	17	17
mol:PP1	0	0	-10000	0	-10000	0	0
RELN/VLDLR/DAB1	0.034	0.049	-10000	0	-0.12	20	20
YWHAE	0.036	0.009	-10000	0	0	29	29
NDEL1/14-3-3 E	0.058	0.17	0.32	127	-0.27	17	144
MAP1B	-0.013	0.066	-10000	0	-0.2	50	50
RAC1	-0.003	0.051	-10000	0	-0.25	13	13
p35/CDK5	-0.026	0.055	0.18	6	-0.21	12	18
RELN	0.024	0.018	-10000	0	0	181	181
PAFAH/LIS1	0.022	0.039	-10000	0	-0.15	21	21
LIS1/CLIP170	0.022	0.042	-10000	0	-0.15	24	24
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.035	0.08	0.14	10	-0.28	25	35
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.012	0.086	-10000	0	-0.23	51	51
GO:0005869	0	0	-10000	0	-10000	0	0
NDEL1	0.05	0.16	0.3	121	-0.27	15	136
LIS1/IQGAP1	0.02	0.048	-10000	0	-0.18	24	24
RHOA	-0.006	0.064	-10000	0	-0.32	13	13
PAFAH1B1	-0.02	0.008	-10000	0	-10000	0	0
PAFAH1B3	0.032	0.013	-10000	0	0	75	75
PAFAH1B2	0.037	0.005	-10000	0	0	8	8
MAP1B/LIS1/Dynein heavy chain	0.006	0.079	-10000	0	-0.2	53	53
NDEL1/Katanin 60/Dynein heavy chain	0.078	0.15	0.34	100	-0.26	22	122
LRP8	0.035	0.01	-10000	0	0	37	37
NDEL1/Katanin 60	0.05	0.16	0.32	116	-0.27	18	134
P39/CDK5	-0.025	0.056	0.18	7	-0.21	12	19
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0.021	0.051	-10000	0	-0.19	24	24
CDK5	-0.014	0.043	0.17	7	-0.22	6	13
PPP2R5D	0.037	0.005	-10000	0	0	10	10
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0.019	0.036	-10000	0	-0.12	26	26
CSNK2A1	0.034	0.011	-10000	0	0	50	50
RELN/VLDLR/DAB1/LIS1	0.033	0.06	-10000	0	-0.13	33	33
RELN/VLDLR	0.046	0.06	-10000	0	-0.12	26	26
CDC42	-0.002	0.042	-10000	0	-0.18	16	16

×

Reelin signaling pathway

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
CDK5R1/CDK5	0.03	0.042	-10000	0	-0.14	18	18
VLDLR	0.028	0.016	-10000	0	0	129	129
CRKL	0.036	0.009	-10000	0	0	29	29
LRPAP1	0.037	0.007	-10000	0	0	16	16
FYN	0.031	0.015	-10000	0	0	93	93
ITGA3	0.033	0.012	-10000	0	0	59	59
RELN/VLDLR/Fyn	0.02	0.062	-10000	0	-0.13	52	52
MAPK8IP1/MKK7/MAP3K11/JNK1	0.073	0.062	-10000	0	-0.11	5	5
AKT1	-0.015	0.071	-10000	0	-0.2	53	53
MAP2K7	0.036	0.007	-10000	0	0	18	18
RAPGEF1	0.036	0.008	-10000	0	0	21	21
DAB1	0.037	0.006	-10000	0	0	12	12
RELN/LRP8/DAB1	0.043	0.037	-10000	0	-0.11	3	3
LRPAP1/LRP8	0.046	0.036	-10000	0	-0.15	14	14
RELN/LRP8/DAB1/Fyn	0.043	0.06	-10000	0	-0.12	33	33
DAB1/alpha3/beta1 Integrin	0.033	0.059	-10000	0	-0.12	23	23
long-term memory	0.042	0.064	-10000	0	-0.12	33	33
DAB1/LIS1	0.05	0.073	-10000	0	-0.13	31	31
DAB1/CRLK/C3G	0.04	0.06	-10000	0	-0.19	1	1
PIK3CA	0.032	0.013	-10000	0	0	74	74
DAB1/NCK2	0.052	0.073	-10000	0	-0.13	29	29
ARHGEF2	0.036	0.007	-10000	0	0	20	20
mol:Src family inhibitors PP1 and PP2	0	0	-10000	0	-10000	0	0
GRIN2A	0.037	0.006	-10000	0	0	14	14
CDK5R1	0.036	0.008	-10000	0	0	25	25
RELN	0.024	0.018	-10000	0	0	181	181
PIK3R1	0.033	0.013	-10000	0	0	67	67
RELN/LRP8/Fyn	0.031	0.057	-10000	0	-0.13	34	34
GRIN2A/RELN/LRP8/DAB1/Fyn	0.054	0.072	-10000	0	-0.12	33	33
MAPK8	0.029	0.016	-10000	0	0	122	122
RELN/VLDLR/DAB1	0.032	0.046	-10000	0	-0.11	20	20
ITGB1	0.029	0.016	-10000	0	0	117	117
MAP1B	0.019	0.081	0.16	95	-0.2	3	98
RELN/LRP8	0.042	0.045	-10000	0	-0.13	11	11
GRIN2B/RELN/LRP8/DAB1/Fyn	0.053	0.072	-10000	0	-0.12	33	33
PI3K	0.02	0.075	-10000	0	-0.15	75	75
mol:PP2	0	0	-10000	0	-10000	0	0
alpha3/beta1 Integrin	0.037	0.027	-10000	0	-0.14	1	1
RAP1A	0.029	0.11	0.27	42	-10000	0	42
PAFAH1B1	0.036	0.008	-10000	0	0	27	27
MAPK8IP1	0.036	0.009	-10000	0	0	28	28
CRLK/C3G	0.051	0.016	-10000	0	-10000	0	0
GRIN2B	0.036	0.008	-10000	0	0	24	24
NCK2	0.036	0.007	-10000	0	0	19	19
neuron differentiation	0.009	0.066	-10000	0	-0.24	15	15
neuron adhesion	0.03	0.12	0.27	43	-10000	0	43
LRP8	0.035	0.01	-10000	0	0	37	37
GSK3B	-0.013	0.078	-10000	0	-0.3	19	19
RELN/VLDLR/DAB1/Fyn	0.032	0.065	-10000	0	-0.11	52	52
MAP3K11	0.037	0.005	-10000	0	0	11	11
RELN/VLDLR/DAB1/P13K	-0.007	0.073	-10000	0	-0.19	57	57
CDK5	0.025	0.018	-10000	0	0	178	178
MAPT	-0.012	0.067	0.7	1	-10000	0	1
neuron migration	-0.004	0.11	0.2	61	-0.29	27	88
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	0.009	0.067	-10000	0	-0.24	15	15
RELN/VLDLR	0.046	0.06	-10000	0	-0.12	26	26

×

FAS signaling pathway (CD95)

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
SPTAN1	-0.019	0.057	0.22	7	-0.22	22	29
RFC1	-0.021	0.05	0.19	2	-0.22	24	26
PRKDC	-0.018	0.053	0.18	3	-0.22	22	25
RIPK1	0.034	0.012	-10000	0	-0.012	30	30
CASP7	-0.14	0.27	-10000	0	-0.58	138	138
FASLG/FAS/FADD/FAF1	-0.007	0.084	0.16	31	-0.18	42	73
MAP2K4	-0.034	0.14	0.28	4	-0.32	48	52
mol:ceramide	0.009	0.091	0.18	4	-0.24	20	24
GSN	-0.009	0.061	0.19	12	-0.23	19	31
FASLG/FAS/FADD/FAF1/Caspase 8	-0.007	0.096	0.18	13	-0.25	27	40
FAS	0.023	0.02	-10000	0	0	219	219
BID	-0.031	0.032	-10000	0	-0.13	13	13
MAP3K1	-0.082	0.19	0.42	1	-0.37	142	143
MAP3K7	0.035	0.011	-10000	0	0	45	45
RB1	-0.017	0.045	0.23	1	-0.22	22	23
CFLAR	0.035	0.011	-10000	0	-0.018	19	19
HGF/MET	0.036	0.051	-10000	0	-0.12	24	24
ARHGDIB	-0.016	0.058	0.22	7	-0.23	20	27
FADD	0.039	0.008	-10000	0	0	13	13
actin filament polymerization	0.008	0.061	0.23	19	-0.19	12	31
NFKB1	0.03	0.11	-10000	0	-0.64	11	11
MAPK8	-0.026	0.14	0.45	2	-0.32	37	39
DFFA	-0.018	0.05	0.22	3	-0.22	23	26
DNA fragmentation during apoptosis	-0.016	0.047	0.22	2	-0.21	22	24
FAS/FADD/MET	0.026	0.053	-10000	0	-0.12	27	27
CFLAR/RIP1	0.049	0.02	-10000	0	-0.13	2	2
FAIM3	0.036	0.007	-10000	0	0	17	17
FAF1	0.039	0.011	-10000	0	0	31	31
PARP1	-0.02	0.05	0.22	2	-0.22	25	27
DFFB	-0.017	0.047	0.22	2	-0.22	22	24
CHUK	0.017	0.098	-10000	0	-0.61	10	10
FASLG	0.04	0.008	-10000	0	0	11	11
FAS/FADD	0.025	0.054	-10000	0	-0.14	35	35
HGF	0.026	0.018	-10000	0	0	163	163
LMNA	-0.022	0.048	0.2	3	-0.2	22	25
CASP6	-0.018	0.048	0.18	3	-0.21	23	26
CASP10	0.04	0.005	-10000	0	0	1	1
CASP3	-0.012	0.051	-10000	0	-0.23	24	24
PTPN13	0.033	0.012	-10000	0	0	60	60
CASP8	-0.032	0.008	-10000	0	-10000	0	0
IL6	0.022	0.14	-10000	0	-0.58	8	8
MET	0.024	0.018	-10000	0	0	184	184
ICAD/CAD	-0.022	0.05	0.25	4	-0.21	22	26
FASLG/FAS/FADD/FAF1/Caspase 10	0.009	0.092	0.18	4	-0.25	20	24
activation of caspase activity by cytochrome c	-0.031	0.032	-10000	0	-0.13	13	13
PAK2	-0.012	0.054	0.21	7	-0.21	22	29
BCL2	0.036	0.007	-10000	0	0	17	17

×

Stabilization and expansion of the E-cadherin adherens junction

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
adherens junction organization	-0.001	0.085	-10000	0	-0.21	55	55
epithelial cell differentiation	0.063	0.053	-10000	0	-0.13	26	26
CYFIP2	0.032	0.013	-10000	0	0	76	76
ENAH	-0.042	0.072	0.26	11	-0.27	6	17
EGFR	0.01	0.017	-10000	0	0	373	373
EPHA2	0.034	0.012	-10000	0	0	56	56
MYO6	-0.03	0.049	0.18	9	-0.21	12	21
CTNNB1	0.036	0.007	-10000	0	0	17	17
ABI1/Sra1/Nap1	0.033	0.066	-10000	0	-0.13	57	57
AQP5	-0.018	0.079	0.25	1	-0.36	20	21
CTNND1	0.035	0.01	-10000	0	0	36	36
mol:PI-4-5-P2	-0.032	0.045	0.17	7	-0.2	14	21
regulation of calcium-dependent cell-cell adhesion	-0.028	0.045	0.18	9	-0.19	8	17
EGF	0.036	0.008	-10000	0	0	25	25
NCKAP1	0.038	0.003	-10000	0	0	3	3
AQP3	-0.033	0.093	-10000	0	-0.33	39	39
cortical microtubule organization	0.063	0.053	-10000	0	-0.13	26	26
GO:0000145	-0.031	0.041	0.16	7	-0.19	14	21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.07	0.055	-10000	0	-0.13	26	26
MLLT4	0.035	0.01	-10000	0	0	36	36
ARF6/GDP	-0.053	0.039	-10000	0	-0.22	12	12
ARF6	0.035	0.009	-10000	0	0	31	31
Ephrin A1/EPHA2/NCK1/GIT1	0.075	0.055	-10000	0	-0.13	25	25
mol:Ca2+	0	0	-10000	0	-10000	0	0
VASP	-0.03	0.083	0.16	1	-0.31	32	33
PVRL2	0.035	0.009	-10000	0	0	31	31
ZYX	-0.024	0.045	0.18	4	-0.21	17	21
ARF6/GTP	0.078	0.062	-10000	0	-0.13	24	24
CDH1	0.035	0.01	-10000	0	0	39	39
EGFR/EGFR/EGF/EGF	0	0.061	-10000	0	-0.13	67	67
RhoA/GDP	0.064	0.058	-10000	0	-0.14	30	30
actin cytoskeleton organization	-0.027	0.046	0.17	6	-0.22	13	19
IGF-1R heterotetramer	0.034	0.011	-10000	0	0	51	51
GIT1	0.037	0.004	-10000	0	0	7	7
IGF1R	0.034	0.011	-10000	0	0	51	51
IGF1	0.036	0.008	-10000	0	0	25	25
DIAPH1	-0.11	0.27	-10000	0	-0.51	142	142
Wnt receptor signaling pathway	-0.063	0.053	0.13	26	-10000	0	26
RHOA	0.036	0.007	-10000	0	0	20	20
RhoA/GTP	-0.054	0.041	-10000	0	-0.23	13	13
CTNNA1	0.036	0.007	-10000	0	0	19	19
VCL	-0.027	0.047	0.17	6	-0.22	13	19
EFNA1	0.034	0.012	-10000	0	0	53	53
LPP	-0.031	0.049	0.18	5	-0.22	16	21
Ephrin A1/EPHA2	0.046	0.063	-10000	0	-0.14	41	41
SEC6/SEC8	-0.045	0.028	-10000	0	-0.14	24	24
MGAT3	-0.029	0.046	0.18	9	-0.19	8	17
HGF/MET	0.036	0.052	-10000	0	-0.14	19	19
HGF	0.026	0.018	-10000	0	0	163	163
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.001	0.085	-10000	0	-0.21	55	55
actin cable formation	-0.039	0.11	0.35	11	-0.31	33	44
KIAA1543	-0.026	0.035	0.16	6	-0.18	8	14
KIFC3	-0.032	0.042	0.19	5	-0.19	8	13
NCK1	0.036	0.009	-10000	0	0	28	28
EXOC3	0.036	0.007	-10000	0	0	20	20
ACTN1	-0.027	0.051	0.19	7	-0.21	18	25
NCK1/GIT1	0.051	0.024	-10000	0	-0.14	6	6
mol:GDP	0.063	0.053	-10000	0	-0.13	26	26
EXOC4	0	0	-10000	0	-10000	0	0
STX4	-0.032	0.047	0.19	7	-0.22	11	18
PIP5K1C	-0.032	0.046	0.18	7	-0.2	14	21
LIMA1	0.032	0.013	-10000	0	0	72	72
ABI1	0.028	0.017	-10000	0	0	136	136
ROCK1	-0.034	0.091	0.33	16	-0.29	5	21
adherens junction assembly	-0.024	0.067	0.23	6	-0.3	14	20
IGF-1R heterotetramer/IGF1	0.049	0.063	-10000	0	-0.14	39	39
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.049	0.023	-10000	0	-0.14	3	3
MET	0.024	0.018	-10000	0	0	184	184
PLEKHA7	-0.029	0.03	0.055	20	-0.13	26	46
mol:GTP	0.072	0.054	-10000	0	-0.13	25	25
establishment of epithelial cell apical/basal polarity	-0.039	0.058	0.19	4	-0.24	7	11
cortical actin cytoskeleton stabilization	-0.001	0.085	-10000	0	-0.21	55	55
regulation of cell-cell adhesion	-0.027	0.046	0.17	6	-0.22	13	19
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.001	0.085	-10000	0	-0.21	55	55

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	-0.027	0.048	0.17	7	-0.22	10	17
DAPP1	-0.022	0.13	0.2	4	-0.29	65	69
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.043	0.19	0.29	3	-0.47	59	62
mol:DAG	-0.007	0.092	0.2	25	-0.2	45	70
HRAS	0.036	0.02	0.089	3	-0.032	24	27
RAP1A	0.039	0.014	0.064	7	-0.019	20	27
ARF5/GDP	-0.001	0.098	-10000	0	-0.34	30	30
PLCG2	0.033	0.013	-10000	0	0	65	65
PLCG1	0.035	0.01	-10000	0	0	43	43
ARF5	0.026	0.018	-10000	0	0	164	164
mol:GTP	-0.026	0.053	0.18	13	-0.19	10	23
ARF1/GTP	-0.018	0.049	0.15	14	-0.2	12	26
RHOA	0.036	0.007	-10000	0	0	20	20
YES1	0.035	0.01	-10000	0	0	43	43
RAP1A/GTP	-0.026	0.048	0.16	13	-0.19	10	23
ADAP1	-0.025	0.05	0.17	13	-0.18	10	23
ARAP3	-0.025	0.052	0.18	13	-0.19	10	23
INPPL1	0.037	0.006	-10000	0	0	13	13
PREX1	0	0	-10000	0	-10000	0	0
ARHGEF6	0.034	0.011	-10000	0	0	51	51
ARHGEF7	0.033	0.012	-10000	0	0	58	58
ARF1	0.036	0.008	-10000	0	0	23	23
NRAS	0.035	0.019	-10000	0	-0.033	11	11
FYN	0.031	0.015	-10000	0	0	93	93
ARF6	0.035	0.009	-10000	0	0	31	31
FGR	0.033	0.012	-10000	0	0	58	58
mol:Ca2+	0.005	0.062	0.15	44	-0.12	17	61
mol:IP4	0	0	-10000	0	-10000	0	0
TIAM1	0.034	0.011	-10000	0	0	44	44
ZAP70	0.037	0.003	-10000	0	0	4	4
mol:IP3	-0.008	0.066	0.18	26	-0.16	22	48
LYN	0.032	0.013	-10000	0	0	72	72
ARF1/GDP	0.01	0.11	0.24	1	-0.35	34	35
RhoA/GDP	0.028	0.091	0.2	16	-0.21	32	48
PDK1/Src/Hsp90	0.066	0.028	-10000	0	-0.12	2	2
BLNK	0.021	0.019	-10000	0	0	226	226
actin cytoskeleton reorganization	0.009	0.11	0.22	29	-0.29	27	56
SRC	0.035	0.009	-10000	0	0	31	31
PLEKHA2	-0.017	0.006	-10000	0	-10000	0	0
RAC1	0.026	0.017	-10000	0	0	156	156
PTEN	0.027	0.022	-10000	0	-0.037	13	13
HSP90AA1	0.035	0.01	-10000	0	0	35	35
ARF6/GTP	-0.027	0.056	0.18	15	-0.2	10	25
RhoA/GTP	-0.028	0.058	0.19	15	-0.2	11	26
Src family/SYK family/BLNK-LAT	-0.046	0.15	-10000	0	-0.34	81	81
BLK	0.037	0.007	-10000	0	0	16	16
PDPK1	0.037	0.004	-10000	0	0	6	6
CYTH1	-0.025	0.05	0.17	13	-0.18	10	23
HCK	0.027	0.017	-10000	0	0	145	145
CYTH3	-0.025	0.05	0.17	13	-0.18	10	23
CYTH2	-0.025	0.05	0.17	13	-0.18	10	23
KRAS	0.035	0.021	0.086	1	-0.033	30	31
GO:0030676	0	0	-10000	0	-10000	0	0
FOXO3	-0.005	0.043	0.24	2	-0.2	12	14
SGK1	0	0.04	-10000	0	-0.19	13	13
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	-0.007	0.11	0.22	3	-0.35	35	38
SOS1	0	0	-10000	0	-10000	0	0
SYK	0.032	0.013	-10000	0	0	76	76
ARF6/GDP	-0.027	0.067	0.2	12	-0.22	24	36
mol:PI-3-4-5-P3	-0.026	0.051	0.17	12	-0.19	10	22
ARAP3/RAP1A/GTP	-0.026	0.049	0.16	13	-0.19	10	23
VAV1	0.036	0.008	-10000	0	0	26	26
mol:PI-3-4-P2	-0.012	0.002	-10000	0	-10000	0	0
RAS family/GTP/PI3K Class I	0.063	0.093	0.21	108	-0.14	41	149
PLEKHA1	-0.012	0.009	-10000	0	-10000	0	0
Rac1/GDP	0	0.1	0.24	1	-0.32	33	34
LAT	0.037	0.005	-10000	0	0	9	9
Rac1/GTP	-0.006	0.15	0.16	1	-0.44	39	40
ITK	-0.028	0.051	0.16	14	-0.19	10	24
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.02	0.11	0.24	13	-0.27	51	64
LCK	0.036	0.008	-10000	0	0	21	21
BTK	-0.027	0.054	0.16	16	-0.19	10	26

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	0.067	0.065	-10000	0	-0.12	12	12
SMAD6-7/SMURF1	0.047	0.039	-10000	0	-0.12	3	3
NOG	0	0	-10000	0	-10000	0	0
SMAD9	-0.024	0.16	-10000	0	-0.47	52	52
SMAD4	0.033	0.012	-10000	0	0	58	58
SMAD5	-0.024	0.097	-10000	0	-0.31	42	42
BMP7/USAG1	0.034	0.027	-10000	0	-10000	0	0
SMAD5/SKI	-0.019	0.11	-10000	0	-0.31	47	47
SMAD1	-0.029	0.15	-10000	0	-0.42	44	44
BMP2	0.028	0.016	-10000	0	0	128	128
SMAD1/SMAD1/SMAD4	-0.01	0.13	-10000	0	-0.4	36	36
BMPR1A	0.027	0.017	-10000	0	0	149	149
BMPR1B	0.037	0.006	-10000	0	0	12	12
BMPR1A-1B/BAMBI	0.022	0.063	-10000	0	-0.12	56	56
AHSG	0.036	0.007	-10000	0	0	19	19
CER1	0.033	0.012	-10000	0	0	60	60
BMP2-4/CER1	0.04	0.056	-10000	0	-0.12	35	35
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.01	0.079	-10000	0	-0.24	32	32
BMP2-4 (homodimer)	0.029	0.051	-10000	0	-0.14	35	35
RGMB	0	0	-10000	0	-10000	0	0
BMP6/BMPR2/BMPR1A-1B	0.059	0.058	-10000	0	-0.12	12	12
RGMA	0	0	-10000	0	-10000	0	0
SMURF1	0.026	0.017	-10000	0	0	157	157
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.017	0.067	-10000	0	-0.17	60	60
BMP2-4/USAG1	0.033	0.047	-10000	0	-0.12	17	17
SMAD6/SMURF1/SMAD5	-0.012	0.098	-10000	0	-0.3	40	40
SOSTDC1	0.025	0.018	-10000	0	0	177	177
BMP7/BMPR2/BMPR1A-1B	0.059	0.058	-10000	0	-0.12	14	14
SKI	0.036	0.008	-10000	0	0	27	27
BMP6 (homodimer)	0.036	0.009	-10000	0	0	28	28
HFE2	0	0	-10000	0	-10000	0	0
ZFYVE16	0.035	0.01	-10000	0	0	38	38
MAP3K7	0.034	0.011	-10000	0	0	45	45
BMP2-4/CHRD	0.042	0.055	-10000	0	-0.12	34	34
SMAD5/SMAD5/SMAD4	-0.022	0.11	-10000	0	-0.31	51	51
MAPK1	0.034	0.011	-10000	0	0	47	47
TAK1/TAB family	0.008	0.065	-10000	0	-0.18	26	26
BMP7 (homodimer)	0.034	0.011	-10000	0	0	47	47
NUP214	0.036	0.008	-10000	0	0	22	22
BMP6/FETUA	0.051	0.016	-10000	0	-10000	0	0
SMAD1/SKI	-0.013	0.15	-10000	0	-0.41	44	44
SMAD6	0.037	0.005	-10000	0	0	10	10
CTDSP2	0.032	0.014	-10000	0	0	81	81
BMP2-4/FETUA	0.042	0.056	-10000	0	-0.12	35	35
MAP3K7IP1	0	0	-10000	0	-10000	0	0
GREM1	0.033	0.013	-10000	0	0	66	66
BMPR2 (homodimer)	0.037	0.005	-10000	0	0	11	11
GADD34/PP1CA	0.053	0.053	-10000	0	-0.13	31	31
BMPR1A-1B (homodimer)	0.037	0.032	-10000	0	-0.14	6	6
CHRDL1	0	0	-10000	0	-10000	0	0
ENDOFIN/SMAD1	-0.015	0.16	0.3	1	-0.41	47	48
SMAD6-7/SMURF1/SMAD1	0.004	0.14	-10000	0	-0.46	27	27
SMAD6/SMURF1	0.026	0.017	-10000	0	0	157	157
BAMBI	0.02	0.019	-10000	0	0	242	242
SMURF2	0.036	0.007	-10000	0	0	19	19
BMP2-4/CHRDL1	0.027	0.044	-10000	0	-0.11	35	35
BMP2-4/GREM1	0.037	0.055	-10000	0	-0.12	34	34
SMAD7	0.035	0.01	-10000	0	0	43	43
SMAD8A/SMAD8A/SMAD4	-0.014	0.16	-10000	0	-0.44	61	61
SMAD1/SMAD6	-0.014	0.14	-10000	0	-0.42	37	37
TAK1/SMAD6	0.034	0.036	-10000	0	-0.14	10	10
BMP7	0.034	0.011	-10000	0	0	47	47
BMP6	0.036	0.009	-10000	0	0	28	28
MAP3K7IP2	0	0	-10000	0	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.001	0.055	-10000	0	-0.22	17	17
PPM1A	0.035	0.01	-10000	0	0	35	35
SMAD1/SMURF2	-0.013	0.16	0.3	1	-0.41	46	47
SMAD7/SMURF1	0.034	0.03	-10000	0	-0.14	3	3
CTDSPL	0.037	0.006	-10000	0	0	14	14
PPP1CA	0.036	0.008	-10000	0	0	22	22
XIAP	0	0	-10000	0	-10000	0	0
CTDSP1	0.037	0.007	-10000	0	0	16	16
PPP1R15A	0.034	0.011	-10000	0	0	51	51
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.011	0.069	-10000	0	-0.21	30	30
CHRD	0.036	0.007	-10000	0	0	19	19
BMPR2	0.037	0.005	-10000	0	0	11	11
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.016	0.069	-10000	0	-0.17	56	56
BMP4	0.034	0.012	-10000	0	0	54	54
FST	0.034	0.011	-10000	0	0	50	50
BMP2-4/NOG	0.027	0.044	-10000	0	-0.11	35	35
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	0.057	0.063	-10000	0	-0.11	10	10

×

Class I PI3K signaling events mediated by Akt

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
BCL2L1	-0.021	0.007	-10000	0	-10000	0	0
BAD/BCL-XL/YWHAZ	0.049	0.033	-10000	0	-0.12	10	10
CDKN1B	-0.026	0.13	0.2	6	-0.34	62	68
CDKN1A	-0.026	0.13	-10000	0	-0.34	63	63
FRAP1	0	0	-10000	0	-10000	0	0
PRKDC	0.035	0.01	-10000	0	0	42	42
FOXO3	-0.021	0.12	0.2	4	-0.36	54	58
AKT1	-0.02	0.13	-10000	0	-0.34	63	63
BAD	0.037	0.007	-10000	0	0	16	16
AKT3	0.015	0.004	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
FOXO4	-0.028	0.12	-10000	0	-0.33	66	66
AKT1/ASK1	-0.011	0.13	-10000	0	-0.33	67	67
BAD/YWHAZ	0.066	0.037	-10000	0	-0.13	12	12
RICTOR	0	0	-10000	0	-10000	0	0
RAF1	0.036	0.008	-10000	0	0	27	27
JNK cascade	0.011	0.13	0.32	67	-10000	0	67
TSC1	-0.029	0.13	0.2	1	-0.35	64	65
YWHAZ	0.036	0.008	-10000	0	0	21	21
AKT1/RAF1	-0.004	0.14	-10000	0	-0.35	68	68
EP300	0.034	0.011	-10000	0	0	49	49
mol:GDP	-0.02	0.13	-10000	0	-0.34	63	63
mol:PI-3-4-5-P3	0	0	-10000	0	-10000	0	0
TSC2	-0.03	0.13	-10000	0	-0.34	67	67
YWHAQ	0.037	0.005	-10000	0	0	8	8
TBC1D4	-0.001	0.025	0.14	14	-10000	0	14
MAP3K5	0.031	0.014	-10000	0	0	91	91
MAPKAP1	0.035	0.009	-10000	0	0	32	32
negative regulation of cell cycle	0.006	0.11	0.34	28	-0.17	1	29
YWHAH	0.032	0.013	-10000	0	0	73	73
AKT1S1	-0.023	0.12	-10000	0	-0.32	68	68
CASP9	-0.023	0.12	-10000	0	-0.34	62	62
YWHAB	0.034	0.011	-10000	0	0	44	44
p27Kip1/KPNA1	-0.009	0.14	0.29	4	-0.33	66	70
GBL	0	0	-10000	0	-10000	0	0
PDK1/Src/Hsp90	0.066	0.028	-10000	0	-0.12	2	2
YWHAE	0.036	0.009	-10000	0	0	29	29
SRC	0.035	0.009	-10000	0	0	31	31
AKT2/p21CIP1	-0.027	0.12	0.24	1	-0.3	64	65
KIAA1303	0	0	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0	0.039	-10000	0	-10000	0	0
CHUK	-0.021	0.11	-10000	0	-0.34	48	48
BAD/BCL-XL	-0.002	0.13	-10000	0	-0.33	65	65
mTORC2	0.022	0.014	-10000	0	-0.093	6	6
AKT2	0.015	0.003	-10000	0	-10000	0	0
FOXO1-3a-4/14-3-3 family	-0.017	0.14	-10000	0	-0.44	32	32
PDPK1	0.037	0.004	-10000	0	0	6	6
MDM2	-0.011	0.13	0.2	35	-0.33	59	94
MAPKKK cascade	0.004	0.14	0.34	68	-10000	0	68
MDM2/Cbp/p300	0.021	0.14	0.27	4	-0.32	60	64
TSC1/TSC2	-0.033	0.13	0.24	10	-0.35	66	76
proteasomal ubiquitin-dependent protein catabolic process	0.02	0.14	0.26	4	-0.31	60	64
glucose import	-0.008	0.024	0.2	4	-10000	0	4
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.001	0.076	-10000	0	-0.19	63	63
response to stress	0	0	-10000	0	-10000	0	0
SLC2A4	-0.008	0.024	0.2	4	-10000	0	4
GSK3A	-0.024	0.12	0.2	4	-0.33	60	64
FOXO1	-0.023	0.13	-10000	0	-0.35	57	57
GSK3B	-0.029	0.13	0.2	3	-0.35	66	69
SFN	0.032	0.014	-10000	0	0	80	80
G1/S transition of mitotic cell cycle	-0.031	0.14	0.26	9	-0.35	65	74
p27Kip1/14-3-3 family	0.008	0.11	-10000	0	-0.51	14	14
PRKACA	0.036	0.007	-10000	0	0	17	17
KPNA1	0.036	0.008	-10000	0	0	23	23
HSP90AA1	0.035	0.01	-10000	0	0	35	35
YWHAG	0	0	-10000	0	-10000	0	0
RHEB	0.026	0.017	-10000	0	0	159	159
CREBBP	0.037	0.004	-10000	0	0	7	7

×

Paxillin-dependent events mediated by a4b1

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.036	0.009	-9999	0	29	29
Rac1/GDP	0.027	0.02	-9999	-0.025	7	7
DOCK1	0.026	0.017	-9999	0	159	159
ITGA4	0.037	0.006	-9999	0	13	13
RAC1	0.026	0.017	-9999	0	156	156
alpha4/beta7 Integrin	0.053	0.012	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.036	0.008	-9999	0	25	25
alpha4/beta1 Integrin	0.057	0.033	-9999	-10000	0	0
alpha4/beta7 Integrin/Paxillin	0.054	0.016	-9999	-10000	0	0
lamellipodium assembly	-0.044	0.14	-9999	-0.36	74	74
PIK3CA	0.032	0.013	-9999	0	74	74
PI3K	0.02	0.075	-9999	-0.15	75	75
ARF6	0.035	0.009	-9999	0	31	31
TLN1	0.03	0.015	-9999	0	104	104
PXN	-0.022	0.005	-9999	-10000	0	0
PIK3R1	0.033	0.013	-9999	0	67	67
ARF6/GTP	0.053	0.048	-9999	-0.11	1	1
cell adhesion	0.046	0.05	-9999	-0.12	12	12
CRKL/CBL	0.052	0.014	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	0.043	0.026	-9999	-10000	0	0
ITGB1	0.029	0.016	-9999	0	117	117
ITGB7	0.037	0.006	-9999	0	14	14
ARF6/GDP	0.036	0.015	-9999	-0.026	10	10
alpha4/beta1 Integrin/Paxillin/VCAM1	0.012	0.08	-9999	-0.11	119	119
p130Cas/Crk/Dock1	0.03	0.036	-9999	-0.11	18	18
VCAM1	0.023	0.018	-9999	0	196	196
alpha4/beta1 Integrin/Paxillin/Talin	0.048	0.051	-9999	-0.12	12	12
alpha4/beta1 Integrin/Paxillin/GIT1	0.057	0.046	-9999	-10000	0	0
BCAR1	0	0	-9999	-10000	0	0
mol:GDP	-0.055	0.045	-9999	-10000	0	0
CBL	0.037	0.005	-9999	0	9	9
PRKACA	0.036	0.007	-9999	0	17	17
GIT1	0.037	0.004	-9999	0	7	7
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	0.048	0.051	-9999	-0.12	12	12
Rac1/GTP	-0.05	0.16	-9999	-0.4	74	74

×

Signaling events mediated by PRL

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
CCNE1	0.033	0.012	-10000	0	0	60	60
mol:Halofuginone	-0.002	0.03	-10000	0	-0.17	15	15
ITGA1	0	0	-10000	0	-10000	0	0
CDKN1A	-0.025	0.15	-10000	0	-0.4	59	59
PRL-3/alpha Tubulin	0.041	0.042	-10000	0	-0.14	22	22
mol:Ca2+	-0.018	0.044	0.26	11	-10000	0	11
AGT	0.03	0.015	-10000	0	0	106	106
CCNA2	-0.026	0.11	0.18	22	-0.58	14	36
TUBA1B	0.037	0.007	-10000	0	0	16	16
EGR1	0.002	0.058	0.11	4	-0.34	14	18
CDK2/Cyclin E1	-0.003	0.15	-10000	0	-0.36	59	59
MAPK3	-0.02	0.009	0	78	-10000	0	78
PRL-2 /Rab GGTase beta	0.048	0.035	-10000	0	-0.16	12	12
MAPK1	-0.018	0.01	0	116	-10000	0	116
PTP4A1	-0.023	0.1	-10000	0	-0.6	14	14
PTP4A3	0.032	0.013	-10000	0	0	74	74
PTP4A2	0.036	0.007	-10000	0	0	20	20
ITGB1	-0.015	0.011	0	175	-10000	0	175
SRC	0.035	0.009	-10000	0	0	31	31
RAC1	0	0.085	-10000	0	-0.38	20	20
Rab GGTase beta/Rab GGTase alpha	0.046	0.032	-10000	0	-0.14	11	11
PRL-1/ATF-5	-0.029	0.11	0.33	1	-0.54	15	16
RABGGTA	0.035	0.01	-10000	0	0	40	40
BCAR1	-0.009	0.054	0.25	21	-10000	0	21
RHOC	-0.003	0.11	-10000	0	-0.39	34	34
RHOA	-0.006	0.13	-10000	0	-0.43	34	34
cell motility	-0.002	0.12	0.26	1	-0.4	30	31
PRL-1/alpha Tubulin	-0.028	0.11	0.2	24	-0.55	15	39
PRL-3/alpha1 Integrin	0.018	0.032	-10000	0	-0.13	21	21
ROCK1	-0.001	0.12	0.26	1	-0.36	38	39
RABGGTB	0.036	0.008	-10000	0	0	25	25
CDK2	0.035	0.01	-10000	0	0	43	43
mitosis	-0.023	0.099	-10000	0	-0.59	14	14
ATF5	0.035	0.009	-10000	0	0	31	31

×

Paxillin-independent events mediated by a4b1 and a4b7

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
PTK2	0.005	0.038	-10000	0	-10000	0	0
CRKL	0.036	0.009	-10000	0	0	29	29
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
DOCK1	0.026	0.017	-10000	0	0	159	159
ITGA4	0.037	0.006	-10000	0	0	13	13
alpha4/beta7 Integrin/MAdCAM1	0.085	0.037	-10000	0	-0.12	6	6
EPO	0.026	0.017	-10000	0	0	157	157
alpha4/beta7 Integrin	0.053	0.012	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.036	0.008	-10000	0	0	25	25
alpha4/beta1 Integrin	0.042	0.024	-10000	0	-10000	0	0
EPO/EPOR (dimer)	0.038	0.026	-10000	0	-10000	0	0
lamellipodium assembly	-0.018	0.11	-10000	0	-0.39	23	23
PIK3CA	0.032	0.013	-10000	0	0	74	74
PI3K	0.02	0.075	-10000	0	-0.15	75	75
ARF6	0.035	0.009	-10000	0	0	31	31
JAK2	0.012	0.027	-10000	0	-10000	0	0
PXN	0.037	0.005	-10000	0	0	9	9
PIK3R1	0.033	0.013	-10000	0	0	67	67
MADCAM1	0.036	0.008	-10000	0	0	25	25
cell adhesion	0.082	0.036	-10000	0	-0.12	6	6
CRKL/CBL	0.052	0.014	-10000	0	-10000	0	0
ITGB1	0.029	0.016	-10000	0	0	117	117
SRC	-0.034	0.059	0.2	4	-10000	0	4
ITGB7	0.037	0.006	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
alpha4/beta1 Integrin/VCAM1	0.006	0.079	-10000	0	-0.12	125	125
p130Cas/Crk/Dock1	-0.033	0.064	0.21	4	-0.19	8	12
VCAM1	0.023	0.018	-10000	0	0	196	196
RHOA	0.036	0.007	-10000	0	0	20	20
alpha4/beta1 Integrin/Paxillin/GIT1	0.069	0.049	-10000	0	-10000	0	0
BCAR1	-0.031	0.059	0.27	5	-10000	0	5
EPOR	0.036	0.007	-10000	0	0	19	19
mol:GDP	0	0	-10000	0	-10000	0	0
CBL	0.037	0.005	-10000	0	0	9	9
GIT1	0.037	0.004	-10000	0	0	7	7
Rac1/GTP	-0.018	0.11	-10000	0	-0.4	23	23

×

Sphingosine 1-phosphate (S1P) pathway

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
SPHK2	0.036	0.009	-10000	0	0	29	29
SPHK1	0.034	0.011	-10000	0	0	49	49
GNAI2	0.034	0.011	-10000	0	0	46	46
mol:S1P	0.018	0.014	-10000	0	-10000	0	0
GNAO1	0.031	0.014	-10000	0	0	87	87
mol:Sphinganine-1-P	-0.02	0.008	-10000	0	-10000	0	0
growth factor activity	0	0	-10000	0	-10000	0	0
S1P/S1P2/G12/G13	0.03	0.045	-10000	0	-0.17	2	2
GNAI3	0.037	0.007	-10000	0	0	16	16
G12/G13	0.027	0.048	-10000	0	-0.14	29	29
S1PR3	0	0	-10000	0	-10000	0	0
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
S1P1/S1P	0.005	0.02	-10000	0	-10000	0	0
S1PR5	0	0	-10000	0	-10000	0	0
S1PR4	0	0	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	0	255	255
S1P/S1P5/G12	0.018	0.036	-10000	0	-0.18	2	2
S1P/S1P3/Gq	0.027	0.043	0.17	9	-0.24	8	17
S1P/S1P4/Gi	-0.007	0.1	0.15	2	-0.28	44	46
GNAQ	0.035	0.01	-10000	0	0	35	35
GNAZ	0.032	0.014	-10000	0	0	81	81
GNA14	0.035	0.009	-10000	0	0	34	34
GNA15	0.034	0.011	-10000	0	0	45	45
GNA12	0.024	0.018	-10000	0	0	180	180
GNA13	0.036	0.008	-10000	0	0	21	21
GNA11	0.034	0.011	-10000	0	0	46	46
ABCC1	0.036	0.007	-10000	0	0	19	19

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	-0.002	0.01	-10000	0	-0.035	23	23
BUB1B	-0.012	0.082	0.11	22	-0.21	59	81
PLK1	0.009	0.028	0.093	21	-0.07	4	25
PLK1S1	0.004	0.016	0.055	22	-0.039	3	25
KIF2A	-0.005	0.044	0.17	10	-0.12	16	26
regulation of mitotic centrosome separation	0.009	0.028	0.093	21	-0.07	4	25
GOLGA2	0.036	0.009	-10000	0	0	28	28
Hec1/SPC24	0.015	0.042	0.11	4	-0.099	43	47
WEE1	-0.017	0.13	-10000	0	-0.43	39	39
cytokinesis	-0.018	0.12	0.16	13	-0.3	61	74
PP2A-alpha B56	0.062	0.08	-10000	0	-0.5	7	7
AURKA	0.006	0.037	0.11	2	-0.2	13	15
PICH/PLK1	-0.028	0.068	0.12	12	-0.15	89	101
CENPE	0.007	0.05	0.15	33	-0.13	4	37
RhoA/GTP	0.025	0.019	-10000	0	-0.13	7	7
positive regulation of microtubule depolymerization	-0.005	0.044	0.17	10	-0.12	16	26
PPP2CA	0.036	0.008	-10000	0	0	22	22
FZR1	0.036	0.007	-10000	0	0	18	18
TPX2	-0.022	0.09	0.11	4	-0.22	84	88
PAK1	0.037	0.007	-10000	0	0	18	18
SPC24	0	0	-10000	0	-10000	0	0
FBXW11	0.036	0.008	-10000	0	0	24	24
CLSPN	0.012	0.031	0.12	1	-0.21	7	8
GORASP1	0.035	0.009	-10000	0	0	34	34
metaphase	0.001	0.003	0.016	8	-0.011	3	11
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	0.004	0.016	0.055	22	-0.039	3	25
G2 phase of mitotic cell cycle	-0.001	0.003	0.014	2	-0.011	1	3
STAG2	0.036	0.008	-10000	0	0	23	23
GRASP65/GM130/RAB1/GTP	-0.015	0.15	-10000	0	-0.6	27	27
spindle elongation	0.009	0.028	0.093	21	-0.07	4	25
ODF2	0.036	0.009	-10000	0	0	29	29
BUB1	0.029	0.067	-10000	0	-0.55	6	6
TPT1	-0.001	0.053	0.097	1	-0.18	38	39
CDC25C	0.015	0.03	-10000	0	-0.22	6	6
CDC25B	0.025	0.026	-10000	0	-0.03	72	72
SGOL1	0.002	0.01	0.035	23	-10000	0	23
RHOA	0.036	0.007	-10000	0	0	20	20
CCNB1/CDK1	0	0.1	-10000	0	-0.21	90	90
CDC14B	-0.011	0.005	0.01	17	-10000	0	17
CDC20	0.028	0.016	-10000	0	0	129	129
PLK1/PBIP1	-0.008	0.039	0.084	8	-0.09	75	83
mitosis	-0.002	0.006	0.029	15	-10000	0	15
FBXO5	-0.009	0.06	0.11	24	-0.16	48	72
CDC2	0	0.005	-10000	0	-0.012	69	69
NDC80	0.03	0.015	-10000	0	0	98	98
metaphase plate congression	0.005	0.06	-10000	0	-0.26	23	23
ERCC6L	-0.019	0.091	0.15	1	-0.2	90	91
NLP/gamma Tubulin	0.003	0.028	0.074	14	-0.099	21	35
microtubule cytoskeleton organization	-0.001	0.052	0.097	1	-0.18	38	39
G2/M transition DNA damage checkpoint	-0.001	0.002	0.012	4	-10000	0	4
PPP1R12A	0.036	0.008	-10000	0	0	26	26
interphase	-0.001	0.002	0.012	4	-10000	0	4
PLK1/PRC1-2	0.012	0.078	0.15	2	-0.14	90	92
GRASP65/GM130/RAB1/GTP/PLK1	0.05	0.054	-10000	0	-0.12	29	29
RAB1A	0.036	0.007	-10000	0	0	18	18
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.007	0.027	0.075	40	-0.064	10	50
mitotic prometaphase	0	0.005	0.021	23	-10000	0	23
proteasomal ubiquitin-dependent protein catabolic process	-0.037	0.097	0.17	2	-0.22	76	78
microtubule-based process	0.024	0.027	0.11	7	-0.066	2	9
Golgi organization	0.009	0.028	0.093	21	-0.07	4	25
Cohesin/SA2	0.024	0.033	0.1	5	-0.095	18	23
PPP1CB/MYPT1	0.048	0.036	-10000	0	-0.15	15	15
KIF20A	0.029	0.016	-10000	0	0	111	111
APC/C/CDC20	0.024	0.026	0.11	5	-0.066	1	6
PPP2R1A	0.034	0.012	-10000	0	0	56	56
chromosome segregation	-0.008	0.039	0.083	8	-0.089	75	83
PRC1	0.029	0.016	-10000	0	0	124	124
ECT2	0.004	0.06	0.15	41	-0.12	17	58
C13orf34	0.007	0.024	0.07	36	-0.058	3	39
NUDC	0.005	0.06	-10000	0	-0.26	23	23
regulation of attachment of spindle microtubules to kinetochore	-0.012	0.082	0.11	22	-0.21	59	81
spindle assembly	0.005	0.028	0.086	22	-0.076	14	36
spindle stabilization	0.004	0.016	0.055	22	-0.039	3	25
APC/C/HCDH1	0.025	0.027	0.084	1	-0.12	16	17
MKLP2/PLK1	0.024	0.027	0.11	7	-0.066	2	9
CCNB1	0.028	0.02	-10000	0	-0.031	15	15
PPP1CB	0.037	0.006	-10000	0	0	13	13
BTRC	0.028	0.016	-10000	0	0	130	130
ROCK2	0.019	0.031	-10000	0	-0.21	3	3
TUBG1	0.004	0.051	-10000	0	-0.22	23	23
G2/M transition of mitotic cell cycle	-0.027	0.087	0.1	1	-0.2	90	91
MLF1IP	-0.008	0.006	0.011	6	-10000	0	6
INCENP	0.037	0.005	-10000	0	0	8	8

×

Integrins in angiogenesis

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
VEGFR2 homodimer/VEGFA homodimer	-0.001	0.078	-10000	0	-0.14	105	105
alphaV beta3 Integrin	0.061	0.048	-10000	0	-0.13	26	26
PTK2	-0.028	0.13	0.26	7	-0.35	33	40
IGF1R	0.034	0.011	-10000	0	0	51	51
PI4KB	0.037	0.006	-10000	0	0	13	13
MFGE8	0.037	0.006	-10000	0	0	15	15
SRC	0.035	0.009	-10000	0	0	31	31
CDKN1B	0	0.094	-10000	0	-0.31	40	40
VEGFA	0.024	0.018	-10000	0	0	181	181
ILK	0.013	0.07	-10000	0	-0.3	22	22
ROCK1	0.037	0.007	-10000	0	0	16	16
AKT1	-0.003	0.068	0.2	1	-0.31	21	22
PTK2B	-0.015	0.092	0.18	45	-0.2	15	60
alphaV/beta3 Integrin/JAM-A	0.071	0.047	-10000	0	-0.11	20	20
CBL	0.037	0.005	-10000	0	0	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	0.063	0.044	-10000	0	-0.12	24	24
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.071	0.067	-10000	0	-0.13	44	44
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.013	0.1	-10000	0	-0.31	28	28
alphaV/beta3 Integrin/Syndecan-1	0.056	0.044	-10000	0	-0.12	16	16
PI4KA	0.033	0.013	-10000	0	0	68	68
IGF-1R heterotetramer/IGF1/IRS1	0.05	0.083	-10000	0	-0.14	67	67
PI4 Kinase	0.038	0.051	-10000	0	-0.14	34	34
PIK3CA	0.032	0.013	-10000	0	0	74	74
alphaV/beta3 Integrin/Osteopontin	0.049	0.07	-10000	0	-0.14	56	56
RPS6KB1	-0.042	0.075	0.32	6	-0.21	18	24
TLN1	0.03	0.015	-10000	0	0	104	104
MAPK3	0.002	0.086	-10000	0	-0.33	27	27
GPR124	0.036	0.008	-10000	0	0	22	22
MAPK1	-0.001	0.085	-10000	0	-0.34	24	24
PXN	0.037	0.005	-10000	0	0	9	9
PIK3R1	0.033	0.013	-10000	0	0	67	67
alphaV/beta3 Integrin/Tumstatin	0.065	0.044	-10000	0	-0.12	24	24
cell adhesion	0.048	0.054	-10000	0	-0.16	26	26
ANGPTL3	0.037	0.006	-10000	0	0	12	12
VEGFR2 homodimer/VEGFA homodimer/Src	0.012	0.077	-10000	0	-0.13	101	101
IGF-1R heterotetramer	0.034	0.011	-10000	0	0	51	51
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
TGFBR2	0.035	0.009	-10000	0	0	30	30
ITGB3	0.037	0.004	-10000	0	0	6	6
IGF1	0.036	0.008	-10000	0	0	25	25
RAC1	0.026	0.017	-10000	0	0	156	156
regulation of cell-matrix adhesion	0.061	0.045	-10000	0	-0.12	24	24
apoptosis	0.035	0.009	-10000	0	0	34	34
CD47	0.036	0.008	-10000	0	0	26	26
alphaV/beta3 Integrin/CD47	0.061	0.048	-10000	0	-0.13	26	26
VCL	0.028	0.016	-10000	0	0	128	128
alphaV/beta3 Integrin/Del1	0.064	0.043	-10000	0	-0.12	23	23
CSF1	0.037	0.005	-10000	0	0	9	9
PIK3C2A	0.01	0.018	-10000	0	-10000	0	0
PI4 Kinase/Pyk2	0.006	0.093	-10000	0	-0.22	25	25
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	0.031	0.092	-10000	0	-0.13	113	113
FAK1/Vinculin	-0.02	0.12	0.27	5	-0.32	26	31
alphaV beta3/Integrin/ppsTEM5	0.062	0.045	-10000	0	-0.12	24	24
RHOA	0.036	0.007	-10000	0	0	20	20
VTN	0.037	0.004	-10000	0	0	7	7
BCAR1	0	0	-10000	0	-10000	0	0
FGF2	0.036	0.008	-10000	0	0	25	25
F11R	-0.02	0.008	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Lactadherin	0.063	0.046	-10000	0	-0.13	24	24
alphaV/beta3 Integrin/TGFBR2	0.06	0.048	-10000	0	-0.12	27	27
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	0.061	0.041	-10000	0	-0.11	24	24
HSP90AA1	0.035	0.01	-10000	0	0	35	35
alphaV/beta3 Integrin/Talin	0.047	0.051	-10000	0	-0.12	32	32
mol:GDP	0	0	-10000	0	-10000	0	0
FN1	0.035	0.009	-10000	0	0	31	31
alphaV/beta3 Integrin/Pyk2	0.035	0.098	0.2	37	-0.13	112	149
SDC1	0.032	0.014	-10000	0	0	82	82
VAV3	-0.027	0.028	0.18	1	-0.18	5	6
PTPN11	0.037	0.006	-10000	0	0	12	12
IRS1	0.034	0.011	-10000	0	0	52	52
FAK1/Paxillin	-0.009	0.12	0.25	7	-0.32	26	33
cell migration	-0.027	0.1	0.25	5	-0.29	26	31
ITGAV	0.035	0.009	-10000	0	0	34	34
PI3K	0.056	0.085	-10000	0	-0.2	14	14
SPP1	0.034	0.012	-10000	0	0	54	54
KDR	0.031	0.014	-10000	0	0	90	90
mol:PI-4-5-P2	0	0	-10000	0	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.035	0.009	-10000	0	0	34	34
COL4A3	0.038	0.002	-10000	0	0	1	1
angiogenesis	-0.001	0.094	-10000	0	-0.37	25	25
Rac1/GTP	-0.027	0.033	-10000	0	-0.18	6	6
EDIL3	0.037	0.005	-10000	0	0	8	8
cell proliferation	0.06	0.047	-10000	0	-0.12	27	27

×

Plasma membrane estrogen receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	0.05	0.04	-10000	0	-0.098	20	20
ER alpha/Gai/GDP/Gbeta gamma	-0.047	0.18	-10000	0	-0.47	54	54
AKT1	-0.053	0.23	-10000	0	-0.63	60	60
PIK3CA	0.032	0.013	-10000	0	0	74	74
E2/ER alpha (dimer)/PELP1/Src/PI3K	-0.047	0.24	-10000	0	-0.65	59	59
mol:Ca2+	0.007	0.051	0.17	19	-0.21	3	22
IGF1R	0.034	0.011	-10000	0	0	51	51
E2/ER alpha (dimer)/Striatin	0.048	0.013	-10000	0	-10000	0	0
SHC1	0.034	0.012	-10000	0	0	53	53
apoptosis	0.053	0.22	0.6	61	-10000	0	61
RhoA/GTP	-0.044	0.036	-10000	0	-0.13	51	51
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.02	0.15	-10000	0	-0.39	51	51
regulation of stress fiber formation	0.039	0.059	0.18	22	-0.14	27	49
E2/ERA-ERB (dimer)	0.046	0.016	-10000	0	-10000	0	0
KRAS	0.035	0.009	-10000	0	0	34	34
G13/GTP	0.044	0.014	-10000	0	-10000	0	0
pseudopodium formation	-0.039	0.059	0.14	27	-0.18	22	49
E2/ER alpha (dimer)/PELP1	0.045	0.023	-10000	0	-0.11	7	7
GRB2	0.036	0.007	-10000	0	0	19	19
GNG2	0	0	-10000	0	-10000	0	0
GNAO1	0.031	0.014	-10000	0	0	87	87
HRAS	0.035	0.01	-10000	0	0	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	-0.019	0.17	0.28	2	-0.44	49	51
E2/ER beta (dimer)	0.026	0.007	-10000	0	-10000	0	0
mol:GDP	0.004	0.059	-10000	0	-0.19	24	24
mol:NADP	-0.019	0.17	0.28	2	-0.44	49	51
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:IP3	0.007	0.051	0.18	19	-0.22	3	22
IGF-1R heterotetramer	0.034	0.011	-10000	0	0	51	51
PLCB1	0.01	0.037	-10000	0	-0.2	1	1
PLCB2	0.009	0.037	-10000	0	-0.2	1	1
IGF1	0.036	0.008	-10000	0	0	25	25
mol:L-citrulline	-0.019	0.17	0.28	2	-0.44	49	51
RHOA	0.036	0.007	-10000	0	0	20	20
Gai/GDP	-0.069	0.24	-10000	0	-0.64	71	71
JNK cascade	0.026	0.007	-10000	0	-10000	0	0
BCAR1	0	0	-10000	0	-10000	0	0
ESR2	0.035	0.009	-10000	0	0	34	34
GNAQ	0.035	0.01	-10000	0	0	35	35
ESR1	0.035	0.009	-10000	0	0	32	32
Gq family/GDP/Gbeta gamma	-0.01	0.15	-10000	0	-0.46	39	39
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.016	0.14	-10000	0	-0.69	15	15
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.003	0.16	0.26	9	-0.39	49	58
GNAZ	0.032	0.014	-10000	0	0	81	81
E2/ER alpha (dimer)	0.026	0.007	-10000	0	-10000	0	0
STRN	0.038	0.002	-10000	0	0	2	2
GNAL	0.036	0.007	-10000	0	0	17	17
PELP1	0.036	0.007	-10000	0	0	19	19
MAPK11	-0.016	0.006	-10000	0	-10000	0	0
GNAI2	0.034	0.011	-10000	0	0	46	46
GNAI3	0.037	0.007	-10000	0	0	16	16
GNAI1	0.019	0.019	-10000	0	0	255	255
HBEGF	-0.02	0.19	0.34	25	-0.44	52	77
cAMP biosynthetic process	0.038	0.017	-10000	0	-10000	0	0
SRC	-0.049	0.17	0.21	6	-0.44	56	62
PI3K	0.02	0.075	-10000	0	-0.15	75	75
GNB1	0.034	0.011	-10000	0	0	47	47
G13/GDP/Gbeta gamma	0.02	0.068	-10000	0	-0.18	29	29
SOS1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.031	0.12	-10000	0	-0.33	48	48
Gs family/GTP	0.048	0.021	-10000	0	-10000	0	0
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0.042	0.065	-10000	0	-0.13	54	54
vasodilation	-0.017	0.16	0.28	2	-0.42	49	51
mol:DAG	0.007	0.051	0.18	19	-0.22	3	22
Gs family/GDP/Gbeta gamma	0.002	0.061	-10000	0	-0.18	29	29
MSN	-0.039	0.061	0.14	27	-0.19	22	49
Gq family/GTP	0.024	0.04	-10000	0	-0.21	1	1
mol:PI-3-4-5-P3	-0.045	0.23	-10000	0	-0.62	59	59
NRAS	0.033	0.013	-10000	0	0	66	66
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	0.017	0.16	0.42	49	-0.28	2	51
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
RhoA/GDP	0.019	0.069	-10000	0	-0.19	26	26
NOS3	-0.022	0.18	0.29	2	-0.47	49	51
GNA11	0.034	0.011	-10000	0	0	46	46
MAPKKK cascade	-0.001	0.16	0.31	1	-0.48	38	39
E2/ER alpha (dimer)/PELP1/Src	-0.007	0.17	0.25	15	-0.4	51	66
ruffle organization	-0.039	0.059	0.14	27	-0.18	22	49
ROCK2	-0.034	0.065	0.17	30	-0.19	13	43
GNA14	0.035	0.009	-10000	0	0	34	34
GNA15	0.034	0.011	-10000	0	0	45	45
GNA13	0.036	0.008	-10000	0	0	21	21
MMP9	-0.034	0.18	0.35	6	-0.41	61	67
MMP2	-0.032	0.18	0.25	12	-0.44	54	66

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0.016	0.035	-10000	0	-0.095	41	41
TRAF2/ASK1	0.032	0.044	-10000	0	-0.11	36	36
ATM	0.035	0.01	-10000	0	0	38	38
MAP2K3	0.018	0.083	0.22	4	-0.28	17	21
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.014	0.086	0.23	6	-0.26	22	28
hyperosmotic response	0	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
GADD45G	0.033	0.013	-10000	0	0	68	68
TXN	0.007	0.002	-10000	0	0	41	41
CALM1	0.033	0.012	-10000	0	0	60	60
GADD45A	0.032	0.014	-10000	0	0	79	79
GADD45B	0.032	0.014	-10000	0	0	79	79
MAP3K1	0.036	0.008	-10000	0	0	23	23
MAP3K6	0.036	0.008	-10000	0	0	24	24
MAP3K7	0.034	0.011	-10000	0	0	45	45
MAP3K4	0.033	0.013	-10000	0	0	66	66
mol:Ca2+	0	0	-10000	0	-10000	0	0
ASK1/ASK2	0.034	0.052	-10000	0	-0.14	37	37
TAK1/TAB family	-0.003	0.029	0.067	36	-0.14	13	49
RAC1/OSM/MEKK3	0.032	0.026	-10000	0	-0.1	5	5
TRAF2	0.036	0.007	-10000	0	0	19	19
RAC1/OSM/MEKK3/MKK3	0.012	0.066	-10000	0	-0.23	17	17
TRAF6	0.008	0.001	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
mol:LPS	0	0	-10000	0	-10000	0	0
CAMK2B	0.018	0.019	-10000	0	0	262	262
CCM2	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKIIB	0.009	0.056	-10000	0	-0.13	57	57
MAPK11	0.034	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	0.069	-10000	0	-0.13	70	70
OSM/MEKK3	0.028	0.003	-10000	0	-10000	0	0
TAOK1	0.007	0.002	-10000	0	0	38	38
TAOK2	0.012	0.023	-10000	0	-0.2	6	6
TAOK3	0.007	0.041	-10000	0	-0.2	19	19
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.037	0.005	-10000	0	0	8	8
MAP3K7IP2	0	0	-10000	0	-10000	0	0
MAP3K5	0.031	0.014	-10000	0	0	91	91
MAP3K10	0.036	0.007	-10000	0	0	19	19
MAP3K3	0.037	0.004	-10000	0	0	6	6
TRX/ASK1	0.023	0.034	-10000	0	-0.17	12	12
GADD45/MTK1/MTK1	0.043	0.076	-10000	0	-0.13	68	68

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	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	0	-10000	0	-10000	0	0
ERC1	0.033	0.012	-10000	0	0	58	58
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.008	0.11	-10000	0	-0.28	58	58
IRAK/TOLLIP	0.03	0.036	0.18	4	-0.12	22	26
IKBKB	0.037	0.003	-10000	0	0	4	4
IKBKG	0.037	0.003	-10000	0	0	4	4
IL1 alpha/IL1R2	0.044	0.023	-10000	0	-10000	0	0
IL1A	0.036	0.008	-10000	0	0	23	23
IL1B	-0.015	0.011	-10000	0	-10000	0	0
IRAK/TRAF6/p62/Atypical PKCs	0.055	0.052	0.19	4	-0.13	29	33
IL1R2	0.031	0.014	-10000	0	0	89	89
IL1R1	0.037	0.006	-10000	0	0	13	13
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.014	0.1	-10000	0	-0.3	36	36
TOLLIP	0.035	0.009	-10000	0	0	34	34
TICAM2	0	0	-10000	0	-10000	0	0
MAP3K3	0.037	0.004	-10000	0	0	6	6
TAK1/TAB1/TAB2	0.02	0.022	-10000	0	-0.1	14	14
IKK complex/ELKS	-0.038	0.12	-10000	0	-0.3	38	38
JUN	-0.032	0.034	0.14	4	-0.18	5	9
MAP3K7	0.034	0.011	-10000	0	0	45	45
IL1 beta fragment/IL1R1/IL1RAP/PI3K	0.029	0.11	-10000	0	-0.14	107	107
IL1 alpha/IL1R1/IL1RAP/MYD88	0.066	0.069	-10000	0	-0.12	50	50
PIK3R1	0.033	0.013	-10000	0	0	67	67
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	0.075	0.075	-10000	0	-0.12	49	49
IL1 beta fragment/IL1R1/IL1RAP	0.024	0.08	-10000	0	-0.14	84	84
NFKB1	0.036	0.007	-10000	0	0	18	18
MAPK8	-0.025	0.029	0.16	5	-0.17	3	8
IRAK1	-0.019	0.01	-10000	0	-0.11	5	5
IL1RN/IL1R1	0.054	0.01	-10000	0	-10000	0	0
IRAK4	0.036	0.008	-10000	0	0	22	22
PRKCI	0.036	0.008	-10000	0	0	25	25
TRAF6	0.037	0.006	-10000	0	0	14	14
PI3K	0.02	0.075	-10000	0	-0.15	75	75
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.007	0.11	-10000	0	-0.26	66	66
CHUK	0.027	0.017	-10000	0	0	139	139
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	0.024	0.08	-10000	0	-0.14	84	84
IL1 beta/IL1R2	0.019	0.071	-10000	0	-0.13	69	69
IRAK/TRAF6/TAK1/TAB1/TAB2	0.036	0.045	0.16	4	-0.11	32	36
NF kappa B1 p50/RelA	0.014	0.098	-10000	0	-0.2	40	40
IRAK3	0.036	0.009	-10000	0	0	29	29
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	0.039	0.082	-10000	0	-0.13	81	81
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	0.009	0.073	-10000	0	-0.28	14	14
IL1 alpha/IL1R1/IL1RAP	0.051	0.054	-10000	0	-0.12	34	34
RELA	0.037	0.005	-10000	0	0	10	10
MAP3K7IP1	0	0	-10000	0	-10000	0	0
SQSTM1	0.035	0.01	-10000	0	0	36	36
MYD88	0.035	0.01	-10000	0	0	37	37
IRAK/TRAF6/MEKK3	0.052	0.04	0.19	4	-0.12	22	26
IL1RAP	0.031	0.014	-10000	0	0	86	86
UBE2N	0.037	0.006	-10000	0	0	15	15
IRAK/TRAF6	-0.039	0.062	0.063	70	-0.19	24	94
CASP1	0.03	0.015	-10000	0	0	109	109
IL1RN/IL1R2	0.046	0.021	-10000	0	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88	0.038	0.095	-10000	0	-0.14	92	92
TMEM189-UBE2V1	0	0	-10000	0	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	0.002	0.097	-10000	0	-0.31	35	35
PIK3CA	0.032	0.013	-10000	0	0	74	74
IL1RN	0.037	0.004	-10000	0	0	6	6
TRAF6/TAK1/TAB1/TAB2	0.044	0.035	-10000	0	-0.11	19	19
MAP2K6	-0.025	0.032	0.18	8	-0.17	3	11

×

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	0.048	0.011	-10000	0	-10000	0	0
response to insulin stimulus	0	0	-10000	0	-10000	0	0
RIPK1	0.036	0.007	-10000	0	0	19	19
response to stress	0	0	-10000	0	-10000	0	0
MAP2K6	0.037	0.004	-10000	0	0	7	7
mol:GTP	0	0	-10000	0	-10000	0	0
MAP2K4	0.036	0.007	-10000	0	0	20	20
RAC1-CDC42/GTP/PAK family	0.001	0.046	-10000	0	-0.14	44	44
response to UV	0	0	-10000	0	-10000	0	0
YES1	0.035	0.01	-10000	0	0	43	43
interleukin-1 receptor activity	0	0	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
MAP3K3	0.037	0.004	-10000	0	0	6	6
FYN	0.031	0.015	-10000	0	0	93	93
MAP3K12	0.037	0.005	-10000	0	0	11	11
FGR	0.033	0.012	-10000	0	0	58	58
p38 alpha/TAB1	-0.035	0.078	-10000	0	-0.24	48	48
PRKG1	0.028	0.016	-10000	0	0	127	127
DUSP8	0.035	0.01	-10000	0	0	42	42
PGK/cGMP/p38 alpha	0.004	0.1	0.18	2	-0.25	42	44
apoptosis	-0.034	0.075	-10000	0	-0.24	48	48
RAL/GTP	0.028	0.038	-10000	0	-0.12	20	20
LYN	0.032	0.013	-10000	0	0	72	72
DUSP1	0.032	0.014	-10000	0	0	78	78
PAK1	0.036	0.007	-10000	0	0	18	18
SRC	0.035	0.009	-10000	0	0	31	31
RAC1/OSM/MEKK3/MKK3	0.048	0.037	-10000	0	-0.11	5	5
TRAF6	0.037	0.006	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
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	0.033	0.028	-10000	0	-0.11	5	5
MAPK11	0	0.13	0.23	13	-0.31	45	58
BLK	0.037	0.007	-10000	0	0	16	16
HCK	0.027	0.017	-10000	0	0	145	145
MAP2K3	0.037	0.005	-10000	0	0	11	11
DUSP16	0	0	-10000	0	-10000	0	0
DUSP10	0.034	0.011	-10000	0	0	48	48
TRAF6/MEKK3	0.046	0.011	-10000	0	-0.1	1	1
MAP3K7IP1	0	0	-10000	0	-10000	0	0
MAPK14	0.009	0.11	0.19	15	-0.28	42	57
positive regulation of innate immune response	0.002	0.14	0.24	12	-0.34	47	59
LCK	0.036	0.008	-10000	0	0	21	21
p38alpha-beta/MKP7	0	0.14	0.23	12	-0.33	47	59
p38alpha-beta/MKP5	0.015	0.14	0.25	11	-0.34	42	53
PGK/cGMP	0.021	0.012	-10000	0	-10000	0	0
PAK2	0.035	0.009	-10000	0	0	33	33
p38alpha-beta/MKP1	0.006	0.15	0.26	12	-0.34	49	61
CDC42	0.036	0.008	-10000	0	0	26	26
RALB	0.036	0.007	-10000	0	0	17	17
RALA	0.025	0.018	-10000	0	0	173	173
PAK3	0.027	0.017	-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	0.066	0.28	0.6	14	-0.74	23	37
CRP	0.056	0.27	0.59	10	-0.74	22	32
cell cycle arrest	0.049	0.3	0.54	17	-0.77	33	50
TIMP1	0.003	0.37	0.57	14	-0.79	73	87
IL6ST	0.029	0.034	-10000	0	-0.051	29	29
Rac1/GDP	0.04	0.11	0.3	14	-0.32	11	25
AP1	0.013	0.2	-10000	0	-0.55	38	38
GAB2	0.035	0.013	-10000	0	-0.042	1	1
TNFSF11	0.054	0.26	0.57	9	-0.74	23	32
HSP90B1	-0.002	0.28	-10000	0	-0.95	37	37
GAB1	0.034	0.013	-10000	0	-0.042	1	1
MAPK14	0.026	0.065	-10000	0	-0.27	4	4
AKT1	-0.013	0.17	-10000	0	-0.58	29	29
FOXO1	-0.019	0.17	0.32	1	-0.55	33	34
MAP2K6	0.029	0.071	0.21	2	-0.27	7	9
mol:GTP	0	0.004	-10000	0	-0.022	1	1
MAP2K4	0.034	0.14	0.36	24	-0.37	18	42
MITF	0.031	0.084	0.23	11	-0.28	11	22
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TYK2	0.035	0.01	-10000	0	0	42	42
A2M	-0.081	0.35	-10000	0	-1.2	46	46
CEBPB	0.033	0.023	0.12	1	-0.11	7	8
GRB2/SOS1/GAB family/SHP2	0.02	0.13	0.27	2	-0.45	27	29
STAT3	0.031	0.31	0.55	14	-0.83	33	47
STAT1	0.021	0.064	-10000	0	-0.7	3	3
CEBPD	0.022	0.34	0.57	10	-0.88	45	55
PIK3CA	0.033	0.014	-10000	0	-0.042	1	1
PI3K	0.021	0.076	-10000	0	-0.15	75	75
JUN	0.035	0.011	-10000	0	0	44	44
PIAS3/MITF	0.075	0.11	0.27	21	-0.28	12	33
MAPK11	0.023	0.063	-10000	0	-0.28	3	3
STAT3 (dimer)/FOXO1	-0.023	0.27	0.45	11	-0.63	54	65
GRB2/SOS1/GAB family	0.042	0.12	0.23	2	-0.31	30	32
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	0.005	0.1	0.18	9	-0.28	37	46
GRB2	0.037	0.009	-10000	0	-0.042	1	1
JAK2	0.032	0.013	-10000	0	0	74	74
LBP	0.064	0.27	0.51	21	-0.61	36	57
PIK3R1	0.033	0.013	-10000	0	-0.042	1	1
JAK1	0.03	0.026	-10000	0	-0.041	47	47
MYC	0.011	0.37	0.61	11	-0.87	60	71
FGG	0.055	0.26	0.57	9	-0.74	22	31
macrophage differentiation	0.049	0.3	0.54	17	-0.77	33	50
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	0.057	0.075	-10000	0	-0.17	7	7
JUNB	0.048	0.3	0.55	17	-0.85	29	46
FOS	0.025	0.018	-10000	0	0	166	166
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	0.031	0.085	0.22	16	-0.28	11	27
STAT1/PIAS1	0.073	0.13	0.3	14	-0.32	11	25
GRB2/SOS1/GAB family/SHP2/PI3K	0	0.17	-10000	0	-0.51	34	34
STAT3 (dimer)	0.036	0.3	0.55	15	-0.82	33	48
PRKCD	0.098	0.22	0.41	88	-0.45	24	112
IL6R	0.031	0.028	-10000	0	-0.041	62	62
SOCS3	0.057	0.092	0.49	5	-10000	0	5
gp130 (dimer)/JAK1/JAK1/LMO4	0.045	0.088	0.19	1	-0.17	43	44
Rac1/GTP	0.038	0.12	0.31	15	-0.34	12	27
HCK	0.027	0.017	-10000	0	0	145	145
MAPKKK cascade	0.014	0.19	0.33	3	-0.59	35	38
bone resorption	0.057	0.26	0.54	12	-0.69	23	35
IRF1	0.048	0.3	0.57	14	-0.83	29	43
mol:GDP	0.03	0.093	0.25	16	-0.27	13	29
SOS1	0.001	0.005	0.025	12	-0.022	1	13
VAV1	0.028	0.091	0.24	14	-0.28	13	27
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.012	0.075	-10000	0	-0.32	15	15
PTPN11	0.02	0.085	-10000	0	-0.7	6	6
IL6/IL6RA	0.025	0.039	-10000	0	-10000	0	0
gp130 (dimer)/TYK2/TYK2/LMO4	0.05	0.075	-10000	0	-0.15	43	43
gp130 (dimer)/JAK2/JAK2/LMO4	0.05	0.064	-10000	0	-0.12	33	33
IL6	0.016	0.028	-10000	0	-0.048	9	9
PIAS3	0.036	0.007	-10000	0	0	17	17
PTPRE	0.01	0.031	-10000	0	-0.06	28	28
PIAS1	0.036	0.008	-10000	0	0	26	26
RAC1	0.027	0.018	-10000	0	0	157	157
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	0.026	0.058	0.17	8	-0.24	5	13
LMO4	0.03	0.034	-10000	0	-0.051	26	26
STAT3 (dimer)/PIAS3	0.027	0.28	0.49	3	-0.76	33	36
MCL1	-0.01	0.17	0.4	1	-0.74	15	16

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.036	0.009	-10000	0	0	29	29
RAS family/GTP/Tiam1	-0.005	0.084	-10000	0	-0.2	64	64
NT3 (dimer)/TRKC	0.048	0.026	-10000	0	-0.14	6	6
NT3 (dimer)/TRKB	0.027	0.07	-10000	0	-0.12	75	75
SHC/Grb2/SOS1/GAB1/PI3K	-0.007	0.093	-10000	0	-0.2	75	75
RAPGEF1	0.036	0.008	-10000	0	0	21	21
BDNF	0.033	0.013	-10000	0	0	69	69
PIK3CA	0.032	0.013	-10000	0	0	74	74
DYNLT1	0.035	0.01	-10000	0	0	42	42
NTRK1	0.037	0.006	-10000	0	0	13	13
NTRK2	0.027	0.017	-10000	0	0	139	139
NTRK3	0.035	0.01	-10000	0	0	35	35
NT-4/5 (dimer)/TRKB	0.013	0.059	-10000	0	-0.11	80	80
neuron apoptosis	-0.003	0.12	0.31	45	-0.26	1	46
SHC 2-3/Grb2	0.002	0.13	0.27	1	-0.33	45	46
SHC1	0.034	0.012	-10000	0	0	53	53
SHC2	-0.012	0.12	-10000	0	-0.44	28	28
SHC3	-0.013	0.12	-10000	0	-0.42	30	30
STAT3 (dimer)	0.013	0.085	-10000	0	-0.28	37	37
NT3 (dimer)/TRKA	0.061	0.031	-10000	0	-10000	0	0
RIN/GDP	0.003	0.074	0.19	7	-0.22	25	32
GIPC1	0.036	0.007	-10000	0	0	18	18
KRAS	0.035	0.009	-10000	0	0	34	34
DNAJA3	-0.007	0.038	0.14	3	-0.16	3	6
RIN/GTP	0.012	0.036	-10000	0	-0.13	27	27
CCND1	-0.011	0.11	-10000	0	-0.49	26	26
MAGED1	0.036	0.008	-10000	0	0	27	27
PTPN11	0.037	0.006	-10000	0	0	12	12
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1	0.041	0.032	-10000	0	-0.12	14	14
GRB2	0.036	0.007	-10000	0	0	19	19
NGF (dimer)/TRKA/MATK	0.048	0.013	-10000	0	-10000	0	0
TRKA/NEDD4-2	0.05	0.019	-10000	0	-0.14	1	1
ELMO1	0.019	0.019	-10000	0	0	251	251
RhoG/GTP/ELMO1/DOCK1	0.011	0.047	-10000	0	-0.12	46	46
NGF	0	0	-10000	0	-10000	0	0
HRAS	0.035	0.01	-10000	0	0	37	37
DOCK1	0.026	0.017	-10000	0	0	159	159
GAB2	0.034	0.011	-10000	0	0	51	51
RIT2	0.025	0.018	-10000	0	0	168	168
RIT1	0.033	0.012	-10000	0	0	60	60
FRS2	0.036	0.008	-10000	0	0	24	24
DNM1	0.036	0.008	-10000	0	0	26	26
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.036	0.008	-10000	0	0	25	25
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	0.01	0.047	0.16	2	-0.17	11	13
mol:GDP	0.003	0.11	0.27	13	-0.3	28	41
NGF (dimer)	0	0	-10000	0	-10000	0	0
RhoG/GDP	0.003	0.043	-10000	0	-0.13	45	45
RIT1/GDP	0.011	0.083	0.21	11	-0.22	25	36
TIAM1	0.034	0.011	-10000	0	0	44	44
PIK3R1	0.033	0.013	-10000	0	0	67	67
BDNF (dimer)/TRKB	0.028	0.071	-10000	0	-0.12	74	74
KIDINS220/CRKL/C3G	0.051	0.016	-10000	0	-10000	0	0
SHC/RasGAP	0.038	0.051	-10000	0	-0.15	31	31
FRS2 family/SHP2	0.07	0.027	-10000	0	-0.12	6	6
SHC/GRB2/SOS1/GAB1	0.05	0.046	-10000	0	-0.11	25	25
RIT1/GTP	0.015	0.04	-10000	0	-0.13	36	36
NT3 (dimer)	0.036	0.008	-10000	0	0	26	26
RAP1/GDP	0	0.059	-10000	0	-0.17	28	28
KIDINS220/CRKL	0.036	0.009	-10000	0	0	29	29
BDNF (dimer)	0.033	0.013	-10000	0	0	69	69
ubiquitin-dependent protein catabolic process	0.045	0.017	-10000	0	-0.11	1	1
Schwann cell development	-0.011	0.016	-10000	0	-0.055	37	37
EHD4	0.035	0.01	-10000	0	0	36	36
FRS2 family/GRB2/SOS1	0.065	0.029	-10000	0	-0.11	8	8
FRS2 family/SHP2/CRK family/C3G/GAB2	0.01	0.069	-10000	0	-0.24	22	22
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.037	0.005	-10000	0	0	10	10
CDC42/GTP	0.018	0.08	-10000	0	-0.15	73	73
ABL1	0.032	0.013	-10000	0	0	71	71
SH2B family/GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
Rap1/GTP	0.005	0.07	-10000	0	-0.24	11	11
STAT3	0.013	0.085	-10000	0	-0.28	37	37
axon guidance	0.005	0.07	-10000	0	-0.14	80	80
MAPK3	-0.013	0.046	0.18	25	-10000	0	25
MAPK1	-0.013	0.042	0.18	20	-10000	0	20
CDC42/GDP	0.011	0.078	0.18	11	-0.21	24	35
NTF3	0.036	0.008	-10000	0	0	26	26
NTF4	0	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/FAIM	0.045	0.025	-10000	0	-0.11	9	9
PI3K	0.02	0.075	-10000	0	-0.15	75	75
FRS3	0.037	0.003	-10000	0	0	4	4
FAIM	0.035	0.009	-10000	0	0	30	30
GAB1	0.034	0.012	-10000	0	0	55	55
RASGRF1	-0.007	0.038	0.14	2	-0.13	4	6
SOS1	0	0	-10000	0	-10000	0	0
MCF2L	-0.019	0.021	0.09	10	-0.12	2	12
RGS19	0.034	0.012	-10000	0	0	55	55
CDC42	0.036	0.008	-10000	0	0	26	26
RAS family/GTP	0.011	0.099	0.23	2	-0.38	19	21
Rac1/GDP	0.01	0.071	0.22	7	-0.23	18	25
NGF (dimer)/TRKA/GRIT	0.025	0.004	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.04	0.24	-10000	0	-0.85	38	38
NGF (dimer)/TRKA/NEDD4-2	0.045	0.017	-10000	0	-0.11	1	1
MAP2K1	-0.009	0.063	0.19	24	-0.18	6	30
NGFR	0.032	0.013	-10000	0	0	72	72
NGF (dimer)/TRKA/GIPC/GAIP	0.013	0.046	-10000	0	-0.2	14	14
RAS family/GTP/PI3K	-0.025	0.11	-10000	0	-0.2	105	105
FRS2 family/SHP2/GRB2/SOS1	0.079	0.039	-10000	0	-0.14	10	10
NRAS	0.033	0.013	-10000	0	0	66	66
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
PRKCI	0.036	0.008	-10000	0	0	25	25
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCZ	0	0	-10000	0	-10000	0	0
MAPKKK cascade	0.011	0.088	-10000	0	-0.48	13	13
RASA1	0.035	0.01	-10000	0	0	35	35
TRKA/c-Abl	0.033	0.059	-10000	0	-0.14	50	50
SQSTM1	0.035	0.01	-10000	0	0	36	36
BDNF (dimer)/TRKB/GIPC	0.049	0.076	-10000	0	-0.12	69	69
NGF (dimer)/TRKA/p62/Atypical PKCs	0.055	0.034	-10000	0	-0.1	15	15
MATK	0.036	0.007	-10000	0	0	20	20
NEDD4L	0.034	0.011	-10000	0	0	45	45
RAS family/GDP	-0.019	0.056	-10000	0	-0.16	48	48
NGF (dimer)/TRKA	0.009	0.039	0.15	4	-0.13	4	8
Rac1/GTP	-0.013	0.057	-10000	0	-0.2	26	26
FRS2 family/SHP2/CRK family	0.091	0.056	-10000	0	-0.12	17	17

×

PDGFR-beta signaling pathway

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
S1P1/Sphingosine-1-phosphate	0.022	0.1	0.27	26	-0.3	20	46
PDGFB-D/PDGFRB/SLAP	0.02	0.072	-10000	0	-0.15	71	71
PDGFB-D/PDGFRB/APS/CBL	0.046	0.022	-10000	0	-0.11	7	7
AKT1	-0.027	0.094	0.29	14	-0.24	16	30
mol:PI-4-5-P2	0	0.001	-10000	0	-10000	0	0
mol:Sphingosine-1-phosphate	0.025	0.11	0.28	20	-0.33	19	39
PIK3CA	0.032	0.013	-10000	0	0	74	74
FGR	0.008	0.092	0.26	5	-0.44	12	17
mol:Ca2+	0.017	0.11	0.27	17	-0.37	19	36
MYC	0.008	0.26	0.39	35	-0.67	52	87
SHC1	0.034	0.012	-10000	0	0	53	53
HRAS/GDP	0.016	0.068	0.18	33	-0.16	17	50
LRP1/PDGFRB/PDGFB	0.051	0.055	-10000	0	-0.13	32	32
GRB10	0.022	0.019	-10000	0	0	213	213
PTPN11	0.037	0.006	-10000	0	0	12	12
GO:0007205	0.017	0.11	0.28	16	-0.37	19	35
PTEN	0.026	0.017	-10000	0	0	158	158
GRB2	0.036	0.007	-10000	0	0	19	19
GRB7	0.037	0.007	-10000	0	0	16	16
PDGFB-D/PDGFRB/SHP2	0.049	0.033	-10000	0	-0.14	13	13
PDGFB-D/PDGFRB/GRB10	0.022	0.051	-10000	0	-0.14	34	34
cell cycle arrest	0.019	0.072	-10000	0	-0.15	71	71
HRAS	0.035	0.01	-10000	0	0	37	37
HIF1A	-0.032	0.087	0.26	14	-0.25	15	29
GAB1	0.012	0.13	0.31	16	-0.37	28	44
mol:GTP	0	0	-10000	0	-10000	0	0
DNM2	0.012	0.13	0.32	24	-0.33	26	50
PDGFB-D/PDGFRB	0.054	0.053	-10000	0	-0.14	12	12
mol:GDP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0.045	0.04	-10000	0	-0.14	20	20
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	0.005	0.1	0.23	4	-0.28	34	38
positive regulation of MAPKKK cascade	0.049	0.033	-10000	0	-0.14	13	13
PIK3R1	0.033	0.013	-10000	0	0	67	67
mol:IP3	0.017	0.11	0.28	16	-0.38	19	35
E5	-0.001	0.001	-10000	0	-10000	0	0
CSK	0.034	0.013	-10000	0	-0.013	32	32
PDGFB-D/PDGFRB/GRB7	0.051	0.022	-10000	0	-0.14	4	4
SHB	0.034	0.011	-10000	0	0	52	52
BLK	0.015	0.076	0.26	5	-0.39	7	12
PTPN2	0.035	0.016	0.065	1	-0.015	42	43
PDGFB-D/PDGFRB/SNX15	0.051	0.025	-10000	0	-0.14	7	7
BCAR1	0	0	-10000	0	-10000	0	0
VAV2	0	0.16	0.32	19	-0.4	44	63
CBL	0.037	0.005	-10000	0	0	9	9
PDGFB-D/PDGFRB/DEP1	0.05	0.026	-10000	0	-0.14	7	7
LCK	0.018	0.065	0.31	2	-0.34	4	6
PDGFRB	0.032	0.022	0.069	2	-0.02	71	73
ACP1	0.036	0.009	-10000	0	0	29	29
HCK	-0.046	0.17	-10000	0	-0.48	60	60
ABL1	0.008	0.12	0.25	24	-0.34	27	51
PDGFB-D/PDGFRB/CBL	0.012	0.13	0.32	10	-0.41	28	38
PTPN1	0.033	0.017	-10000	0	-0.009	64	64
SNX15	0.037	0.004	-10000	0	0	7	7
STAT3	0.035	0.01	-10000	0	0	40	40
STAT1	0.035	0.01	-10000	0	0	41	41
cell proliferation	0.016	0.24	0.37	41	-0.6	52	93
SLA	0.028	0.016	-10000	0	0	131	131
actin cytoskeleton reorganization	-0.015	0.075	0.2	40	-0.19	7	47
SRC	0.014	0.057	0.36	1	-0.44	2	3
PI3K	-0.05	0.044	-10000	0	-0.17	33	33
PDGFB-D/PDGFRB/GRB7/SHC	0.062	0.038	-10000	0	-0.12	10	10
SH2B2	0	0	-10000	0	-10000	0	0
PLCgamma1/SPHK1	0.026	0.11	0.28	20	-0.34	19	39
LYN	-0.033	0.16	0.22	1	-0.46	52	53
LRP1	0.032	0.013	-10000	0	0	73	73
SOS1	0	0	-10000	0	-10000	0	0
STAT5B	0.037	0.005	-10000	0	0	8	8
STAT5A	0.037	0.005	-10000	0	0	8	8
NCK1-2/p130 Cas	0.065	0.065	-10000	0	-0.14	23	23
SPHK1	0.035	0.012	0.06	4	0	49	53
EDG1	0	0.004	0.024	4	-10000	0	4
mol:DAG	0.017	0.11	0.28	16	-0.38	19	35
PLCG1	0.017	0.11	0.28	16	-0.38	19	35
NHERF/PDGFRB	0.065	0.036	-10000	0	-0.12	11	11
YES1	-0.009	0.14	0.24	1	-0.56	26	27
cell migration	0.064	0.036	-10000	0	-0.12	11	11
SHC/Grb2/SOS1	0.066	0.061	-10000	0	-0.13	19	19
SLC9A3R2	0.037	0.004	-10000	0	0	7	7
SLC9A3R1	0.035	0.01	-10000	0	0	35	35
NHERF1-2/PDGFRB/PTEN	0.057	0.058	-10000	0	-0.11	14	14
FYN	-0.053	0.18	-10000	0	-0.45	80	80
DOK1	-0.014	0.059	0.18	36	-10000	0	36
HRAS/GTP	0.022	0.028	-10000	0	-0.13	16	16
PDGFB	0.035	0.01	-10000	0	0	35	35
RAC1	0.03	0.19	0.36	43	-0.42	48	91
PRKCD	-0.011	0.062	0.18	37	-0.14	1	38
FER	-0.012	0.062	0.18	36	-0.14	1	37
MAPKKK cascade	-0.006	0.075	0.17	57	-0.17	5	62
RASA1	-0.012	0.063	0.18	36	-0.18	5	41
NCK1	0.036	0.009	-10000	0	0	28	28
NCK2	0.036	0.007	-10000	0	0	19	19
p62DOK/Csk	-0.013	0.063	0.17	34	-0.19	3	37
PDGFB-D/PDGFRB/SHB	0.047	0.027	-10000	0	-0.14	5	5
chemotaxis	0.008	0.12	0.24	27	-0.33	27	54
STAT1-3-5/STAT1-3-5	0.063	0.071	-10000	0	-0.14	36	36
Bovine Papilomavirus E5/PDGFRB	0.021	0.024	-10000	0	-0.11	9	9
PTPRJ	0.037	0.006	-10000	0	0	15	15

×

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

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
MET/RANBP9	0.032	0.035	-10000	0	-0.14	9	9
CRKL	0.043	0.11	0.28	6	-0.4	16	22
mol:PIP3	0.002	0.053	0.29	1	-0.54	2	3
AKT1	-0.011	0.051	-10000	0	-0.54	1	1
PTK2B	0.037	0.006	-10000	0	0	15	15
RAPGEF1	0.04	0.11	0.3	15	-0.37	16	31
RANBP10	0.037	0.005	-10000	0	0	9	9
PIK3CA	0.032	0.013	-10000	0	0	74	74
HGF/MET/SHIP2	0.045	0.039	-10000	0	-0.12	2	2
MAP3K5	0.042	0.1	0.26	5	-0.37	15	20
HGF/MET/CIN85/CBL/ENDOPHILINS	0.043	0.036	-10000	0	-10000	0	0
AP1	0.034	0.079	0.15	90	-0.15	42	132
mol:SU11274	0	0	-10000	0	-10000	0	0
SHC1	0.034	0.012	-10000	0	0	53	53
apoptosis	-0.13	0.36	-10000	0	-0.77	115	115
STAT3 (dimer)	0.01	0.061	-10000	0	-0.27	13	13
GAB1/CRKL/SHP2/PI3K	0.061	0.12	0.3	2	-0.42	14	16
INPP5D	0	0	-10000	0	-10000	0	0
CBL/CRK	0.059	0.11	0.29	4	-0.39	16	20
PTPN11	0.037	0.006	-10000	0	0	12	12
GO:0007205	0	0	-10000	0	-10000	0	0
PLCG1	0.035	0.01	-10000	0	0	43	43
PTEN	0.026	0.017	-10000	0	0	158	158
ELK1	0.11	0.18	0.35	176	-10000	0	176
mol:SU5416	0	0	-10000	0	-10000	0	0
SHP2/GRB2/SOS1GAB1	0.011	0.034	0.16	1	-0.14	14	15
PAK1	-0.014	0.053	-10000	0	-0.52	1	1
HGF/MET/RANBP10	0.046	0.038	-10000	0	-10000	0	0
HRAS	0.008	0.084	-10000	0	-0.47	11	11
DOCK1	0.031	0.1	0.29	7	-0.39	15	22
GAB1	0.041	0.1	0.22	2	-0.42	15	17
CRK	0.042	0.11	0.28	4	-0.4	16	20
mol:PHA665752	0	0	-10000	0	-10000	0	0
mol:GDP	0.018	0.068	-10000	0	-0.42	10	10
JUN	0.034	0.011	-10000	0	0	44	44
EntrezGene:200958	0	0	-10000	0	-10000	0	0
HGF/MET	0.009	0.017	-10000	0	-0.12	1	1
PIK3R1	0.033	0.013	-10000	0	0	67	67
cell morphogenesis	0.025	0.11	0.28	27	-0.32	14	41
GRB2/SHC	0.071	0.064	0.17	91	-0.12	2	93
FOS	0.025	0.018	-10000	0	0	166	166
GLMN	0.004	0.004	0.068	2	-10000	0	2
cell motility	0.11	0.18	0.35	176	-10000	0	176
HGF/MET/MUC20	0.031	0.025	-10000	0	-10000	0	0
cell migration	0.069	0.063	0.16	91	-0.12	2	93
GRB2	0.036	0.007	-10000	0	0	19	19
CBL	0.037	0.005	-10000	0	0	9	9
MET/RANBP10	0.035	0.027	-10000	0	-10000	0	0
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	0.013	0.048	-10000	0	-0.26	7	7
MET/MUC20	0.018	0.013	-10000	0	-10000	0	0
RAP1B	0.04	0.1	0.28	15	-0.35	16	31
RAP1A	0.035	0.1	0.31	16	-0.36	15	31
HGF/MET/RANBP9	0.043	0.043	-10000	0	-0.12	9	9
RAF1	0.028	0.1	0.3	1	-0.45	13	14
STAT3	0.008	0.058	-10000	0	-0.29	12	12
cell proliferation	0.03	0.078	0.26	8	-0.28	10	18
RPS6KB1	0.014	0.019	-10000	0	-10000	0	0
MAPK3	0.079	0.16	0.33	119	-10000	0	119
MAPK1	0.12	0.22	0.41	142	-10000	0	142
RANBP9	0.036	0.007	-10000	0	0	18	18
MAPK8	-0.035	0.15	0.26	4	-0.35	53	57
SRC	0.006	0.047	-10000	0	-0.25	7	7
PI3K	0.056	0.073	0.17	78	-0.15	8	86
MET/Glomulin	0.016	0.028	-10000	0	-0.088	21	21
SOS1	0	0	-10000	0	-10000	0	0
MAP2K1	0.022	0.1	0.27	2	-0.43	14	16
MET	0.024	0.018	-10000	0	0	184	184
MAP4K1	0.051	0.11	0.29	5	-0.39	15	20
PTK2	0.035	0.009	-10000	0	0	33	33
MAP2K2	0.028	0.1	0.31	8	-0.44	11	19
BAD	-0.017	0.052	-10000	0	-0.41	2	2
MAP2K4	0.036	0.1	0.26	8	-0.35	14	22
SHP2/GRB2/SOS1/GAB1	0.02	0.079	-10000	0	-0.34	16	16
INPPL1	0.037	0.006	-10000	0	0	13	13
PXN	0.037	0.005	-10000	0	0	9	9
SH3KBP1	0	0	-10000	0	-10000	0	0
HGS	-0.001	0.017	0.09	1	-0.12	1	2
PLCgamma1/PKC	0.025	0.014	-10000	0	-0.13	3	3
HGF	0.026	0.018	-10000	0	0	163	163
RASA1	0.035	0.01	-10000	0	0	35	35
NCK1	0.036	0.009	-10000	0	0	28	28
PTPRJ	0.037	0.006	-10000	0	0	15	15
NCK/PLCgamma1	0.074	0.058	0.17	97	-0.12	1	98
PDPK1	-0.002	0.048	0.27	2	-0.56	1	3
HGF/MET/SHIP	0.031	0.025	-10000	0	-10000	0	0

×

IFN-gamma 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	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.052	0.075	-10000	0	-0.12	39	39
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
CRKL	0.036	0.009	-10000	0	0	29	29
STAT1 (dimer)/Cbp/p300	0.025	0.089	0.29	8	-0.22	20	28
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	0.045	0.063	0.17	1	-0.14	39	40
antigen processing and presentation of peptide antigen via MHC class I	-0.026	0.079	-10000	0	-0.19	59	59
CaM/Ca2+	0.048	0.08	-10000	0	-0.14	41	41
RAP1A	0.037	0.005	-10000	0	0	10	10
STAT1 (dimer)/SHP2	-0.023	0.062	0.17	19	-0.19	9	28
AKT1	-0.032	0.092	0.31	10	-0.23	31	41
MAP2K1	-0.027	0.063	0.17	24	-0.2	8	32
MAP3K11	-0.02	0.071	0.23	17	-0.18	6	23
IFNGR1	0.032	0.02	0.095	3	-0.037	19	22
mol:GTP	0	0	-10000	0	-10000	0	0
CaM/Ca2+/CAMKII	-0.025	0.12	-10000	0	-0.3	61	61
Rap1/GTP	-0.04	0.036	-10000	0	-0.16	6	6
CRKL/C3G	0.051	0.016	-10000	0	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	0.066	0.078	-10000	0	-0.13	35	35
CEBPB	-0.002	0.13	0.37	9	-0.43	22	31
STAT3	0.035	0.01	-10000	0	0	40	40
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	0.063	0.096	-10000	0	-0.74	4	4
STAT1	-0.023	0.069	0.27	11	-0.19	9	20
CALM1	0.033	0.012	-10000	0	0	60	60
IFN-gamma (dimer)	0.03	0.022	-10000	0	-0.037	39	39
PIK3CA	0.032	0.013	-10000	0	0	74	74
STAT1 (dimer)/PIAS1	-0.024	0.078	0.21	23	-0.21	15	38
CEBPB/PTGES2/Cbp/p300	0.007	0.11	-10000	0	-0.32	28	28
mol:Ca2+	0.048	0.072	-10000	0	-0.12	39	39
MAPK3	0.011	0.084	0.42	3	-0.59	2	5
STAT1 (dimer)	-0.026	0.11	0.18	5	-0.26	57	62
MAPK1	-0.038	0.21	0.45	3	-0.74	37	40
JAK2	0.028	0.023	0.087	2	-0.038	36	38
PIK3R1	0.033	0.013	-10000	0	0	67	67
JAK1	0.034	0.018	0.076	1	-0.037	17	18
CAMK2D	0	0	-10000	0	-10000	0	0
DAPK1	0.006	0.11	0.36	8	-0.42	10	18
SMAD7	-0.009	0.065	0.17	24	-0.14	17	41
CBL/CRKL/C3G	0.022	0.078	0.29	9	-0.19	3	12
PI3K	0.029	0.096	-10000	0	-0.19	34	34
IFNG	0.03	0.022	-10000	0	-0.037	39	39
apoptosis	0.018	0.099	0.37	6	-0.44	8	14
CAMK2G	0.026	0.018	-10000	0	0	159	159
STAT3 (dimer)	0.035	0.01	-10000	0	0	40	40
CAMK2A	0.037	0.005	-10000	0	0	8	8
CAMK2B	0.018	0.019	-10000	0	0	262	262
FRAP1	-0.033	0.084	0.29	10	-0.21	32	42
PRKCD	-0.031	0.09	0.32	11	-0.22	20	31
RAP1B	0	0	-10000	0	-10000	0	0
negative regulation of cell growth	-0.026	0.079	-10000	0	-0.19	59	59
PTPN2	0.036	0.008	-10000	0	0	22	22
EP300	0.035	0.011	-10000	0	0	49	49
IRF1	-0.034	0.072	0.32	7	-0.28	13	20
STAT1 (dimer)/PIASy	-0.025	0.07	0.26	10	-0.19	5	15
SOCS1	0.018	0.095	-10000	0	-1	4	4
mol:GDP	-0.019	0.074	0.2	22	-0.18	3	25
CASP1	-0.018	0.079	0.23	14	-0.17	60	74
PTGES2	0.036	0.008	-10000	0	0	21	21
IRF9	0.004	0.064	0.21	11	-0.17	27	38
mol:PI-3-4-5-P3	0.015	0.084	-10000	0	-0.16	50	50
RAP1/GDP	-0.031	0.053	0.11	18	-0.18	4	22
CBL	-0.019	0.071	0.25	14	-0.19	4	18
MAP3K1	-0.021	0.064	0.23	11	-0.18	6	17
PIAS1	0.036	0.008	-10000	0	0	26	26
PIAS4	0.036	0.007	-10000	0	0	16	16
antigen processing and presentation of peptide antigen via MHC class II	-0.026	0.079	-10000	0	-0.19	59	59
PTPN11	-0.016	0.065	0.18	28	-0.18	6	34
CREBBP	0.038	0.005	-10000	0	0	7	7
RAPGEF1	0.036	0.008	-10000	0	0	21	21

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.036	0.007	-10000	0	0	19	19
PTK2	0.035	0.009	-10000	0	0	33	33
CRKL	-0.018	0.044	0.1	27	-0.15	24	51
GRB2/SOS1/SHC	0.041	0.032	-10000	0	-0.12	14	14
HRAS	0.035	0.01	-10000	0	0	37	37
IRS1/Crk	0.017	0.046	-10000	0	-0.13	39	39
IGF-1R heterotetramer/IGF1/PTP1B	0.052	0.056	-10000	0	-0.14	28	28
AKT1	-0.036	0.073	0.16	22	-0.22	30	52
BAD	-0.041	0.07	0.15	21	-0.22	28	49
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	-0.017	0.043	0.1	27	-0.15	22	49
IGF-1R heterotetramer/IGF1/IRS1/Shp2	0.026	0.048	-10000	0	-0.14	29	29
RAF1	-0.036	0.14	0.26	3	-0.54	30	33
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	0.046	0.054	-10000	0	-0.13	29	29
YWHAZ	0.036	0.008	-10000	0	0	21	21
IGF-1R heterotetramer/IGF1/IRS1	0.035	0.048	-10000	0	-0.15	24	24
PIK3CA	0.032	0.013	-10000	0	0	74	74
RPS6KB1	-0.034	0.071	0.16	28	-0.2	23	51
GNB2L1	0.037	0.005	-10000	0	0	10	10
positive regulation of MAPKKK cascade	-0.034	0.12	0.25	6	-0.42	30	36
PXN	0.037	0.005	-10000	0	0	9	9
PIK3R1	0.033	0.013	-10000	0	0	67	67
cell adhesion	0	0	-10000	0	-10000	0	0
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
HRAS/GTP	0.017	0.052	-10000	0	-0.13	42	42
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	0.067	0.056	-10000	0	-0.12	33	33
IGF-1R heterotetramer	0.038	0.014	0.1	1	-0.035	1	2
IGF-1R heterotetramer/IGF1/IRS/Nck	0.048	0.06	-10000	0	-0.14	35	35
Crk/p130 Cas/Paxillin	0.038	0.055	0.22	1	-0.13	36	37
IGF1R	0.038	0.014	0.1	1	-0.036	1	2
IGF1	0.034	0.025	-10000	0	-0.059	28	28
IRS2/Crk	-0.029	0.055	0.1	20	-0.18	30	50
PI3K	0.041	0.087	-10000	0	-0.14	78	78
apoptosis	0.039	0.078	0.21	30	-0.18	20	50
HRAS/GDP	0.022	0.028	-10000	0	-0.13	16	16
PRKCD	0.005	0.06	0.2	5	-0.21	23	28
RAF1/14-3-3 E	-0.012	0.13	0.29	4	-0.47	30	34
BAD/14-3-3	-0.04	0.081	0.19	20	-0.22	30	50
PRKCZ	-0.029	0.069	0.16	29	-0.19	23	52
Crk/p130 Cas/Paxillin/FAK1	-0.049	0.07	0.13	20	-0.22	31	51
PTPN1	0.034	0.011	-10000	0	0	45	45
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.007	0.058	-10000	0	-0.22	25	25
BCAR1	0	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1/SHC/GRB10	0.04	0.071	-10000	0	-0.14	43	43
mol:GDP	0	0	-10000	0	-10000	0	0
SOS1	0	0	-10000	0	-10000	0	0
IRS1/NCK2	0.028	0.05	0.13	4	-0.14	34	38
GRB10	0.022	0.019	-10000	0	0	213	213
PTPN11	-0.018	0.044	0.1	27	-0.15	23	50
IRS1	0.011	0.041	0.12	4	-0.15	24	28
IRS2	-0.014	0.039	0.1	22	-0.17	12	34
IGF-1R heterotetramer/IGF1	0.041	0.051	-10000	0	-0.17	24	24
GRB2	0.036	0.007	-10000	0	0	19	19
PDPK1	-0.028	0.075	0.18	29	-0.2	22	51
YWHAE	0.036	0.009	-10000	0	0	29	29
PRKD1	0.002	0.058	0.2	1	-0.23	22	23
SHC1	0.034	0.012	-10000	0	0	53	53

×

EPO signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.035	0.089	0.36	3	-10000	0	3
CRKL	0.032	0.1	0.26	37	-0.17	1	38
mol:DAG	0.011	0.07	0.24	3	-0.21	31	34
HRAS	0.032	0.11	0.25	54	-0.2	12	66
MAPK8	0.008	0.078	0.17	78	-10000	0	78
RAP1A	0.033	0.1	0.24	39	-0.18	2	41
GAB1	0.028	0.097	0.26	31	-0.18	2	33
MAPK14	0.026	0.1	0.18	138	-10000	0	138
EPO	0.025	0.024	-10000	0	-0.036	26	26
PLCG1	0.011	0.071	0.24	3	-0.21	31	34
EPOR/TRPC2/IP3 Receptors	0.039	0.022	0.1	3	-0.036	27	30
RAPGEF1	0.036	0.008	-10000	0	0	21	21
EPO/EPOR (dimer)/SOCS3	0.054	0.038	-10000	0	-10000	0	0
GAB1/SHC/GRB2/SOS1	0.049	0.082	0.25	19	-0.19	11	30
EPO/EPOR (dimer)	0.037	0.035	-10000	0	-10000	0	0
IRS2	0.024	0.097	0.25	30	-0.18	11	41
STAT1	0.012	0.075	0.26	3	-0.24	18	21
STAT5B	0.012	0.075	0.24	4	-0.22	22	26
cell proliferation	0.004	0.077	0.16	79	-10000	0	79
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.006	0.078	0.14	5	-0.19	19	24
TEC	0.034	0.1	0.26	39	-0.17	1	40
SOCS3	0.037	0.004	-10000	0	0	6	6
STAT1 (dimer)	0.013	0.074	0.26	3	-0.23	18	21
JAK2	0.034	0.023	0.094	3	-0.036	23	26
PIK3R1	0.033	0.013	-10000	0	0	67	67
EPO/EPOR (dimer)/JAK2	0.053	0.072	0.25	5	-0.17	1	6
EPO/EPOR	0.037	0.035	-10000	0	-10000	0	0
LYN	0.034	0.014	-10000	0	-10000	0	0
TEC/VAV2	0.016	0.09	0.21	35	-0.17	1	36
elevation of cytosolic calcium ion concentration	0.039	0.022	0.1	3	-0.036	27	30
SHC1	0.034	0.012	-10000	0	0	53	53
EPO/EPOR (dimer)/LYN	0.042	0.06	-10000	0	-0.13	30	30
mol:IP3	0.011	0.07	0.24	3	-0.21	31	34
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	0.011	0.1	0.24	27	-0.19	21	48
SH2B3	0.039	0.017	-10000	0	-0.034	2	2
NFKB1	0.026	0.1	0.17	139	-0.21	1	140
EPO/EPOR (dimer)/JAK2/SOCS3	0.021	0.035	0.17	22	-10000	0	22
PTPN6	0.031	0.094	0.18	113	-0.17	1	114
TEC/VAV2/GRB2	0.069	0.085	0.26	25	-0.2	4	29
EPOR	0.039	0.022	0.1	3	-0.036	27	30
INPP5D	0	0	-10000	0	-10000	0	0
mol:GDP	0.015	0.094	0.23	24	-0.19	11	35
SOS1	0	0	-10000	0	-10000	0	0
PLCG2	0.033	0.013	-10000	0	0	65	65
CRKL/CBL/C3G	0.068	0.082	0.25	25	-0.17	1	26
VAV2	0.03	0.098	0.25	34	-0.17	1	35
CBL	0.035	0.1	0.26	39	-0.17	1	40
SHC/Grb2/SOS1	0.024	0.053	-10000	0	-0.19	10	10
STAT5A	0.012	0.074	0.26	3	-0.21	33	36
GRB2	0.036	0.007	-10000	0	0	19	19
STAT5 (dimer)	0.029	0.083	0.28	6	-0.23	9	15
LYN/PLCgamma2	0.028	0.071	-10000	0	-0.17	53	53
PTPN11	0.037	0.006	-10000	0	0	12	12
BTK	0.032	0.1	0.26	35	-0.17	1	36
BCL2	0.036	0.091	0.36	1	-10000	0	1

×

Aurora B signaling

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
Condensin I complex	-0.011	0.1	-10000	0	-0.23	72	72
STMN1	-0.021	0.009	0.019	1	-10000	0	1
Aurora B/RasGAP/Survivin	0.035	0.075	-10000	0	-0.14	73	73
Chromosomal passenger complex/Cul3 protein complex	-0.031	0.076	-10000	0	-0.19	66	66
BIRC5	0.03	0.016	0.067	2	0	109	111
DES	0.025	0.092	-10000	0	-0.6	10	10
Aurora C/Aurora B/INCENP	0.059	0.027	-10000	0	-10000	0	0
Aurora B/TACC1	0.043	0.026	-10000	0	-0.11	9	9
Aurora B/PP2A	0.05	0.017	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
CBX5	-0.003	0.051	-10000	0	-0.19	31	31
mitotic metaphase/anaphase transition	-0.001	0.003	0.022	1	-10000	0	1
NDC80	-0.019	0.01	0.027	1	-10000	0	1
Cul3 protein complex	0.029	0.033	-10000	0	-0.14	8	8
KIF2C	-0.019	0.12	-10000	0	-0.43	36	36
PEBP1	0.036	0.008	-10000	0	0	20	20
KIF20A	0.029	0.016	-10000	0	0	111	111
mol:GDP	0	0	-10000	0	-10000	0	0
Aurora B/RasGAP	0.041	0.045	-10000	0	-0.14	25	25
SEPT1	0	0	-10000	0	-10000	0	0
SMC2	0.033	0.013	-10000	0	0	64	64
SMC4	0.033	0.013	-10000	0	0	67	67
NSUN2/NPM1/Nucleolin	-0.004	0.084	-10000	0	-0.5	10	10
PSMA3	0.035	0.01	-10000	0	0	40	40
G2/M transition of mitotic cell cycle	-0.001	0.003	-10000	0	-10000	0	0
H3F3B	0.01	0.031	-10000	0	-0.2	11	11
AURKB	0.033	0.014	-10000	0	-0.007	52	52
AURKC	0.034	0.011	-10000	0	0	48	48
CDCA8	0.033	0.015	-10000	0	-0.004	63	63
cytokinesis	-0.027	0.14	0.17	1	-0.43	49	50
Aurora B/Septin1	-0.014	0.14	0.2	2	-0.41	47	49
AURKA	0.033	0.013	-10000	0	0	65	65
INCENP	0.035	0.016	0.064	4	-0.024	30	34
KLHL13	0	0	-10000	0	-10000	0	0
BUB1	0.037	0.006	0.062	1	0	12	13
hSgo1/Aurora B/Survivin	0.023	0.05	-10000	0	-0.11	57	57
EVI5	0.037	0.007	-10000	0	0	18	18
RhoA/GTP	0.01	0.13	-10000	0	-0.32	54	54
SGOL1	0	0	-10000	0	-10000	0	0
CENPA	-0.003	0.1	-10000	0	-0.34	33	33
NCAPG	0.031	0.014	-10000	0	0	88	88
Aurora B/HC8 Proteasome	0.045	0.031	-10000	0	-0.14	9	9
NCAPD2	0.032	0.014	-10000	0	0	78	78
Aurora B/PP1-gamma	0.048	0.027	-10000	0	-0.14	6	6
RHOA	0.036	0.007	-10000	0	0	20	20
NCAPH	0.036	0.009	-10000	0	0	29	29
NPM1	0.003	0.083	-10000	0	-0.38	17	17
RASA1	0.035	0.01	-10000	0	0	35	35
KLHL9	0.023	0.018	-10000	0	0	199	199
mitotic prometaphase	-0.001	0.003	-10000	0	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.045	0.031	-10000	0	-0.14	9	9
PPP1CC	0.037	0.006	-10000	0	0	14	14
Centraspindlin	0.003	0.13	-10000	0	-0.35	52	52
RhoA/GDP	0.025	0.019	-10000	0	-0.13	7	7
NSUN2	0.002	0.041	-10000	0	-0.28	9	9
MYLK	-0.014	0.069	-10000	0	-0.2	62	62
KIF23	0.029	0.018	-10000	0	-0.006	102	102
VIM	-0.016	0.012	0.023	2	-10000	0	2
RACGAP1	0.032	0.016	-10000	0	-0.003	84	84
mitosis	0	0	-10000	0	-10000	0	0
NCL	0.003	0.063	-10000	0	-0.28	22	22
Chromosomal passenger complex	-0.014	0.1	0.14	4	-0.27	55	59
Chromosomal passenger complex/EVI5	0.062	0.086	-10000	0	-0.15	56	56
TACC1	0.036	0.008	-10000	0	0	22	22
PPP2R5D	0.037	0.005	-10000	0	0	10	10
CUL3	0.038	0.003	-10000	0	0	3	3
response to DNA damage stimulus	0	0	-10000	0	-10000	0	0

×

Caspase cascade in apoptosis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TOP1	-0.008	0.1	0.3	1	-0.3	34	35
ACTA1	-0.032	0.092	0.24	3	-0.29	32	35
NUMA1	0	0.092	0.3	1	-0.32	25	26
SPTAN1	-0.041	0.094	0.22	9	-0.29	36	45
LIMK1	0.01	0.11	0.19	76	-0.34	16	92
BIRC3	0.032	0.014	-10000	0	0	84	84
BIRC2	0.037	0.006	-10000	0	0	14	14
BAX	0.035	0.01	-10000	0	0	41	41
CASP10	-0.01	0.032	0.084	47	-10000	0	47
CRMA	0	0	-10000	0	-0.001	4	4
XIAP	0	0	0.001	3	-0.001	11	14
PTK2	-0.007	0.096	0.3	1	-0.29	37	38
DIABLO	0.037	0.005	-10000	0	0	10	10
apoptotic nuclear changes	-0.04	0.093	0.22	9	-0.29	36	45
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.037	0.007	-10000	0	0	16	16
GSN	-0.032	0.098	0.22	9	-0.32	29	38
MADD	0.036	0.007	-10000	0	0	19	19
TFAP2A	0.041	0.089	-10000	0	-0.64	7	7
BID	-0.002	0.04	-10000	0	-0.18	20	20
MAP3K1	-0.002	0.055	-10000	0	-0.39	6	6
TRADD	0.037	0.005	-10000	0	0	8	8
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0.051	0.018	-10000	0	-0.14	2	2
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.037	0.098	0.21	12	-0.3	35	47
CASP9	0.035	0.009	-10000	0	0	30	30
DNA repair	0.028	0.067	0.19	39	-10000	0	39
neuron apoptosis	0.02	0.11	-10000	0	-0.62	13	13
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.021	0.094	0.32	2	-0.32	28	30
APAF1	0.037	0.005	-10000	0	0	8	8
CASP6	0.026	0.12	0.37	1	-0.86	7	8
TRAF2	0.036	0.007	-10000	0	0	19	19
ICAD/CAD	-0.042	0.09	0.39	3	-0.31	27	30
CASP7	-0.068	0.1	-10000	0	-0.22	133	133
KRT18	0.025	0.057	-10000	0	-0.47	5	5
apoptosis	-0.033	0.098	0.6	1	-0.34	26	27
DFFA	-0.039	0.088	0.26	3	-0.31	29	32
DFFB	-0.037	0.087	0.3	2	-0.32	27	29
PARP1	-0.028	0.068	-10000	0	-0.2	39	39
actin filament polymerization	-0.016	0.1	0.32	16	-0.18	76	92
TNF	0.037	0.004	-10000	0	0	6	6
CYCS	0.011	0.04	0.2	3	-0.24	3	6
SATB1	0.018	0.11	0.35	1	-0.75	7	8
SLK	-0.025	0.086	0.29	2	-0.3	29	31
p15 BID/BAX	0	0.074	0.18	3	-0.18	52	55
CASP2	0.052	0.096	0.21	113	-0.24	5	118
JNK cascade	0.002	0.055	0.39	6	-10000	0	6
CASP3	-0.036	0.09	0.24	1	-0.31	32	33
LMNB2	0.061	0.089	0.26	13	-0.31	3	16
RIPK1	0.036	0.007	-10000	0	0	19	19
CASP4	0.031	0.015	-10000	0	0	93	93
Mammalian IAPs/DIABLO	0.057	0.036	-10000	0	-0.15	6	6
negative regulation of DNA binding	0.041	0.088	-10000	0	-0.63	7	7
stress fiber formation	-0.035	0.086	0.29	2	-0.3	29	31
GZMB	-0.015	0.012	0	193	-10000	0	193
CASP1	-0.01	0.066	-10000	0	-0.2	55	55
LMNB1	0.041	0.13	0.27	13	-0.35	16	29
APP	0.02	0.11	-10000	0	-0.63	13	13
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
response to stress	0	0	0.001	8	-0.001	27	35
CASP8	-0.011	0.002	0	14	-10000	0	14
VIM	-0.031	0.099	0.43	1	-0.34	27	28
LMNA	0.064	0.089	0.27	13	-0.3	4	17
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	0.016	0.053	-10000	0	-0.22	10	10
LRDD	0	0	-10000	0	-10000	0	0
SREBF1	-0.038	0.087	0.2	2	-0.31	29	31
APAF-1/Caspase 9	0.018	0.084	-10000	0	-0.61	8	8
nuclear fragmentation during apoptosis	0	0.09	0.3	1	-0.31	25	26
CFL2	0.016	0.11	0.18	76	-0.32	17	93
GAS2	-0.03	0.09	0.18	5	-0.3	29	34
positive regulation of apoptosis	0.06	0.1	0.24	23	-0.34	6	29
PRF1	0.025	0.018	-10000	0	0	169	169

×

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	0.098	-10000	0	-0.39	29	29
Crk/p130 Cas/Paxillin	-0.051	0.093	-10000	0	-0.2	109	109
JUN	-0.017	0.049	-10000	0	-0.24	13	13
HRAS	0.035	0.01	-10000	0	0	37	37
RET51/GFRalpha1/GDNF/GRB10	0.043	0.062	-10000	0	-0.11	31	31
RAP1A	0.037	0.005	-10000	0	0	10	10
FRS2	0.036	0.008	-10000	0	0	24	24
RAP1A/GDP	0.027	0.008	-10000	0	-0.13	1	1
RET51/GFRalpha1/GDNF/DOK1	0.069	0.045	-10000	0	-10000	0	0
EntrezGene:5979	0	0	-10000	0	-10000	0	0
PTPN11	0.037	0.006	-10000	0	0	12	12
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.036	0.008	-10000	0	0	25	25
RET9/GFRalpha1/GDNF/Enigma	0.052	0.033	-10000	0	-10000	0	0
RHOA	0.036	0.007	-10000	0	0	20	20
RAP1A/GTP	0.061	0.049	-10000	0	-0.11	1	1
GRB7	0.037	0.007	-10000	0	0	16	16
RET51/GFRalpha1/GDNF	0.068	0.045	-10000	0	-10000	0	0
MAPKKK cascade	0	0.074	-10000	0	-0.12	97	97
BCAR1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/IRS1	0.043	0.046	-10000	0	-0.1	23	23
lamellipodium assembly	-0.02	0.082	-10000	0	-0.21	52	52
RET51/GFRalpha1/GDNF/SHC	0.063	0.05	-10000	0	-0.12	8	8
PIK3CA	0.032	0.013	-10000	0	0	74	74
RET9/GFRalpha1/GDNF/SHC	0.045	0.039	-10000	0	-0.11	8	8
RET9/GFRalpha1/GDNF/Shank3	0.035	0.022	-10000	0	-10000	0	0
MAPK3	-0.028	0.039	0.2	9	-10000	0	9
DOK1	0.038	0.002	-10000	0	0	2	2
DOK6	0	0	-10000	0	-10000	0	0
PXN	0.037	0.005	-10000	0	0	9	9
neurite development	-0.022	0.04	0.2	7	-0.21	8	15
DOK5	0.029	0.016	-10000	0	0	111	111
GFRA1	0.027	0.017	-10000	0	0	138	138
MAPK8	0	0.046	-10000	0	-0.17	24	24
HRAS/GTP	0.031	0.093	-10000	0	-0.12	106	106
tube development	0.029	0.031	0.21	6	-0.1	8	14
MAPK1	-0.024	0.051	0.25	10	-10000	0	10
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.007	0.06	-10000	0	-0.21	13	13
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
SRC	0.035	0.009	-10000	0	0	31	31
PDLIM7	0.037	0.005	-10000	0	0	9	9
RET51/GFRalpha1/GDNF/Dok6	0.062	0.044	-10000	0	-10000	0	0
SHC1	0.034	0.012	-10000	0	0	53	53
RET51/GFRalpha1/GDNF/Dok4	0.068	0.046	-10000	0	-10000	0	0
RET51/GFRalpha1/GDNF/Dok5	0.044	0.074	-10000	0	-0.11	66	66
PRKCA	0.037	0.004	-10000	0	0	6	6
HRAS/GDP	0.022	0.028	-10000	0	-0.13	16	16
CREB1	-0.024	0.095	-10000	0	-0.19	108	108
PIK3R1	0.033	0.013	-10000	0	0	67	67
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.005	0.063	-10000	0	-0.17	27	27
RET51/GFRalpha1/GDNF/Grb7	0.068	0.045	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
RET	0.029	0.016	-10000	0	0	121	121
DOK4	0.037	0.006	-10000	0	0	12	12
JNK cascade	-0.018	0.049	-10000	0	-0.23	15	15
RET9/GFRalpha1/GDNF/FRS2	0.051	0.033	-10000	0	-10000	0	0
SHANK3	0	0	-10000	0	-10000	0	0
RASA1	0.035	0.01	-10000	0	0	35	35
NCK1	0.036	0.009	-10000	0	0	28	28
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.008	0.056	-10000	0	-0.17	16	16
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.019	0.091	-10000	0	-0.19	103	103
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.026	0.097	-10000	0	-0.19	119	119
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	0.012	0.044	-10000	0	-0.18	16	16
PI3K	-0.049	0.13	0.18	1	-0.26	98	99
SOS1	0	0	-10000	0	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	0.042	0.039	-10000	0	-0.1	8	8
GRB10	0.022	0.019	-10000	0	0	213	213
activation of MAPKK activity	0.014	0.046	-10000	0	-0.25	12	12
RET51/GFRalpha1/GDNF/FRS2	0.067	0.046	-10000	0	-10000	0	0
GAB1	0.034	0.012	-10000	0	0	55	55
IRS1	0.034	0.011	-10000	0	0	52	52
IRS2	0.031	0.015	-10000	0	0	94	94
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	0.014	0.051	-10000	0	-0.17	23	23
RET51/GFRalpha1/GDNF/PKC alpha	0.068	0.045	-10000	0	-10000	0	0
GRB2	0.036	0.007	-10000	0	0	19	19
PRKACA	0.036	0.007	-10000	0	0	17	17
GDNF	0.037	0.005	-10000	0	0	8	8
RAC1	0.026	0.017	-10000	0	0	156	156
RET51/GFRalpha1/GDNF/IRS1	0.06	0.057	-10000	0	-0.11	22	22
Rac1/GTP	-0.022	0.096	-10000	0	-0.24	52	52
RET9/GFRalpha1/GDNF	0.037	0.023	-10000	0	-10000	0	0
GFRalpha1/GDNF	0.04	0.025	-10000	0	-10000	0	0

×

E-cadherin signaling in the nascent adherens junction

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
CTTN	0.005	0.076	-10000	0	-0.29	26	26
KLHL20	0.045	0.097	0.22	66	-0.19	23	89
CYFIP2	0.032	0.013	-10000	0	0	76	76
Rac1/GDP	0.007	0.065	0.22	4	-0.28	11	15
ENAH	0.005	0.078	-10000	0	-0.31	23	23
AP1M1	0	0	-10000	0	-10000	0	0
RAP1B	0	0	0	56	0	5	61
RAP1A	0.037	0.005	-10000	0	0	10	10
CTNNB1	0.037	0.007	-10000	0	0	17	17
CDC42/GTP	-0.026	0.056	0.12	22	-0.22	16	38
ABI1/Sra1/Nap1	-0.017	0.036	-10000	0	-0.14	32	32
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	0.084	0.04	-10000	0	-0.13	8	8
RAPGEF1	-0.004	0.08	0.23	2	-0.28	22	24
CTNND1	0.035	0.01	-10000	0	0	36	36
regulation of calcium-dependent cell-cell adhesion	0.018	0.08	-10000	0	-0.29	26	26
CRK	0.003	0.082	0.18	22	-0.29	23	45
E-cadherin/gamma catenin/alpha catenin	0.063	0.036	-10000	0	-0.12	9	9
alphaE/beta7 Integrin	0.051	0.024	-10000	0	-0.14	6	6
IQGAP1	0.034	0.011	-10000	0	0	47	47
NCKAP1	0.038	0.003	-10000	0	0	3	3
Rap1/GTP/I-afadin	0.044	0.015	-10000	0	-0.099	1	1
DLG1	0.004	0.079	-10000	0	-0.3	26	26
ChemicalAbstracts:7440-70-2	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.036	0.044	-10000	0	-0.18	31	31
MLLT4	0.035	0.01	-10000	0	0	36	36
ARF6/GTP/NME1/Tiam1	0.038	0.032	-10000	0	-0.1	22	22
PI3K	-0.044	0.058	0.063	2	-0.23	31	33
ARF6	0.035	0.009	-10000	0	0	31	31
mol:Ca2+	0	0	0.001	67	0	29	96
E-cadherin/gamma catenin	0.049	0.019	-10000	0	-10000	0	0
TIAM1	0.035	0.011	-10000	0	0	44	44
E-cadherin(dimer)/Ca2+	0.071	0.055	-10000	0	-0.13	26	26
AKT1	-0.022	0.058	0.15	16	-0.19	21	37
PIK3R1	0.033	0.013	-10000	0	0	67	67
CDH1	0.035	0.01	-10000	0	0	39	39
RhoA/GDP	0.013	0.079	0.24	9	-0.26	12	21
actin cytoskeleton organization	0.038	0.079	0.18	66	-0.14	23	89
CDC42/GDP	0.011	0.075	0.22	9	-0.26	12	21
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	0.009	0.052	-10000	0	-0.19	25	25
ITGB7	0.037	0.006	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
E-cadherin/beta catenin/alpha catenin/p120 catenin	0.077	0.06	-10000	0	-0.14	26	26
E-cadherin/Ca2+/beta catenin/alpha catenin	0.056	0.033	-10000	0	-0.11	11	11
mol:GDP	-0.004	0.082	0.24	10	-0.29	13	23
CDC42/GTP/IQGAP1	0.037	0.042	-10000	0	-0.11	34	34
JUP	0.034	0.011	-10000	0	0	52	52
p120 catenin/RhoA/GDP	0.027	0.085	0.24	9	-0.25	17	26
RAC1/GTP/IQGAP1	0.025	0.043	-10000	0	-0.12	32	32
PIP5K1C/AP1M1	0.021	0.03	-10000	0	-0.13	19	19
RHOA	0.036	0.007	-10000	0	0	20	20
CDC42	0.036	0.008	-10000	0	0	26	26
CTNNA1	0.036	0.007	-10000	0	0	19	19
positive regulation of S phase of mitotic cell cycle	0.013	0.048	0.13	16	-0.12	32	48
NME1	0	0	-10000	0	0	31	31
clathrin coat assembly	0	0	-10000	0	-10000	0	0
TJP1	0.007	0.076	-10000	0	-0.3	23	23
regulation of cell-cell adhesion	-0.029	0.04	-10000	0	-0.17	25	25
WASF2	-0.009	0.019	-10000	0	-0.074	33	33
Rap1/GTP	-0.022	0.066	0.16	29	-0.25	15	44
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	0.091	0.053	-10000	0	-0.13	13	13
CCND1	0.015	0.057	0.14	16	-0.15	32	48
VAV2	0.016	0.13	-10000	0	-0.56	14	14
RAP1/GDP	-0.01	0.071	0.17	28	-0.25	15	43
adherens junction assembly	0.007	0.074	-10000	0	-0.29	23	23
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
ABI1	0.028	0.017	-10000	0	0	136	136
PIP5K1C	0.035	0.01	-10000	0	0	42	42
regulation of heterotypic cell-cell adhesion	0.063	0.049	0.2	2	-0.13	15	17
E-cadherin/beta catenin	0.008	0.02	-10000	0	-0.097	5	5
mol:GTP	0	0	0.001	63	0	31	94
SRC	0.004	0.073	-10000	0	-0.29	24	24
PIK3CA	0.032	0.013	-10000	0	0	74	74
Rac1/GTP	-0.008	0.077	0.18	2	-0.29	24	26
E-cadherin/beta catenin/alpha catenin	0.064	0.038	-10000	0	-0.13	11	11
ITGAE	0.036	0.007	-10000	0	0	20	20
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.018	0.082	-10000	0	-0.3	26	26

×

Hedgehog signaling events mediated by Gli proteins

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
HDAC1	0.036	0.008	-10000	0	0	24	24
HDAC2	0.033	0.012	-10000	0	0	61	61
GNB1/GNG2	0.029	0.035	-10000	0	-0.11	15	15
forebrain development	0.051	0.084	0.35	14	-0.4	3	17
GNAO1	0.032	0.015	-10000	0	0	87	87
SMO/beta Arrestin2	0.037	0.032	-10000	0	-0.14	4	4
SMO	0.027	0.018	-10000	0	-10000	0	0
ARRB2	0.036	0.009	-10000	0	0	27	27
GLI3/SPOP	-0.001	0.11	-10000	0	-0.31	37	37
mol:GTP	0.001	0.002	-10000	0	-10000	0	0
GSK3B	0.035	0.01	-10000	0	0	37	37
GNAI2	0.035	0.011	-10000	0	0	46	46
SIN3/HDAC complex	0.056	0.042	-10000	0	-0.12	18	18
GNAI1	0.019	0.019	-10000	0	0	255	255
XPO1	0.04	0.008	0.089	4	-10000	0	4
GLI1/Su(fu)	0.021	0.059	0.3	7	-0.39	2	9
SAP30	0.036	0.007	-10000	0	0	19	19
mol:GDP	0.027	0.018	-10000	0	-10000	0	0
MIM/GLI2A	0.042	0.013	0.12	11	-10000	0	11
IFT88	0.035	0.01	-10000	0	0	35	35
GNAI3	0.037	0.007	-10000	0	0	16	16
GLI2	0.001	0.088	0.16	1	-0.32	23	24
GLI3	-0.016	0.099	-10000	0	-0.3	35	35
CSNK1D	0.036	0.007	-10000	0	0	20	20
CSNK1E	0.033	0.013	-10000	0	0	65	65
SAP18	0.034	0.011	-10000	0	0	46	46
embryonic digit morphogenesis	0.035	0.01	-10000	0	0	35	35
GNG2	0	0	-10000	0	-10000	0	0
Gi family/GTP	-0.008	0.089	0.14	1	-0.26	36	37
SIN3B	0.035	0.008	-10000	0	0	27	27
SIN3A	0	0.001	-10000	0	-10000	0	0
GLI3/Su(fu)	-0.014	0.075	-10000	0	-0.26	29	29
GLI2/Su(fu)	-0.003	0.073	-10000	0	-0.3	20	20
FOXA2	0.048	0.044	-10000	0	-0.5	2	2
neural tube patterning	0.051	0.084	0.35	14	-0.4	3	17
SPOP	0.036	0.008	-10000	0	0	25	25
Su(fu)/PIAS1	0.047	0.038	0.099	141	-0.078	11	152
GNB1	0.034	0.011	-10000	0	0	47	47
CSNK1G2	0.036	0.007	-10000	0	0	20	20
CSNK1G3	0.037	0.006	-10000	0	0	12	12
MTSS1	0.042	0.013	0.12	11	-10000	0	11
embryonic limb morphogenesis	0.051	0.084	0.35	14	-0.4	3	17
SUFU	0.003	0.011	0.048	2	-0.1	4	6
LGALS3	0.029	0.016	-10000	0	0	118	118
catabolic process	0.01	0.14	-10000	0	-0.4	38	38
GLI3A/CBP	0.045	0.01	-10000	0	-10000	0	0
KIF3A	0.034	0.012	-10000	0	0	53	53
GLI1	0.049	0.084	0.37	12	-0.41	3	15
RAB23	0.035	0.009	-10000	0	0	33	33
CSNK1A1	0.037	0.006	-10000	0	0	13	13
IFT172	0	0	-10000	0	-10000	0	0
RBBP7	0.037	0.005	-10000	0	0	10	10
Su(fu)/Galectin3	0.038	0.041	0.099	117	-0.11	9	126
GNAZ	0.032	0.014	-10000	0	0	81	81
RBBP4	0.033	0.012	-10000	0	0	61	61
CSNK1G1	0.037	0.005	-10000	0	0	10	10
PIAS1	0.036	0.008	-10000	0	0	26	26
PRKACA	0.036	0.007	-10000	0	0	17	17
GLI2/SPOP	0.017	0.096	-10000	0	-0.31	27	27
STK36	0.003	0.007	0.033	19	-10000	0	19
Gi family/GNB1/GNG2/GDP	-0.016	0.1	-10000	0	-0.35	31	31
PTCH1	0.052	0.095	0.48	10	-0.54	1	11
MIM/GLI1	0.074	0.086	0.38	11	-0.43	2	13
CREBBP	0.045	0.01	-10000	0	-10000	0	0
Su(fu)/SIN3/HDAC complex	-0.002	0.097	0.17	2	-0.3	31	33

×

p75(NTR)-mediated signaling

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
Sortilin/TRAF6	0.051	0.024	-10000	0	-0.14	6	6
Necdin/E2F1	-0.015	0.082	-10000	0	-0.14	146	146
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	0.073	0.048	-10000	0	-0.12	23	23
NGF (dimer)/p75(NTR)/BEX1	0.012	0.063	-10000	0	-0.11	95	95
NT-4/5 (dimer)/p75(NTR)	0.024	0.01	-10000	0	-10000	0	0
IKBKB	0.037	0.003	-10000	0	0	4	4
AKT1	-0.018	0.078	0.2	24	-0.2	24	48
IKBKG	0.037	0.003	-10000	0	0	4	4
BDNF	0.033	0.013	-10000	0	0	69	69
MGDIs/NGR/p75(NTR)/LINGO1	0.022	0.009	-10000	0	-10000	0	0
FURIN	0.037	0.005	-10000	0	0	11	11
proBDNF (dimer)/p75(NTR)/Sortilin	0.056	0.035	-10000	0	-0.12	2	2
LINGO1	0	0	-10000	0	-10000	0	0
Sortilin/TRAF6/NRIF	0.022	0.068	-10000	0	-0.16	47	47
proBDNF (dimer)	0.033	0.013	-10000	0	0	69	69
NTRK1	0.037	0.006	-10000	0	0	13	13
RTN4R	0	0	-10000	0	-10000	0	0
neuron apoptosis	-0.002	0.13	0.27	3	-0.36	42	45
IRAK1	0.036	0.008	-10000	0	0	22	22
SHC1	-0.003	0.036	0.093	60	-10000	0	60
ARHGDIA	0.036	0.007	-10000	0	0	20	20
RhoA/GTP	0.025	0.019	-10000	0	-0.13	7	7
Gamma Secretase	0.08	0.073	-10000	0	-0.15	28	28
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	0.041	0.058	-10000	0	-0.11	52	52
MAGEH1	0.032	0.013	-10000	0	0	71	71
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.001	0.074	-10000	0	-0.11	143	143
Mammalian IAPs/DIABLO	0.057	0.036	-10000	0	-0.15	6	6
proNGF (dimer)	0	0	-10000	0	-10000	0	0
MAGED1	0.036	0.008	-10000	0	0	27	27
APP	0.036	0.007	-10000	0	0	19	19
NT-4/5 (dimer)	0	0	-10000	0	-10000	0	0
ZNF274	0.032	0.013	-10000	0	0	73	73
RhoA/GDP/RHOGDI	0.051	0.03	0.18	1	-0.1	6	7
NGF	0	0	-10000	0	-10000	0	0
cell cycle arrest	0.004	0.055	0.22	8	-10000	0	8
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	0.016	0.057	-10000	0	-0.18	33	33
NT-4/5 (dimer)/p75(NTR)/TRAF6	0.042	0.02	-10000	0	-0.11	1	1
NCSTN	0.036	0.009	-10000	0	0	29	29
mol:GTP	0.032	0.04	-10000	0	-0.11	29	29
PSENEN	0.035	0.009	-10000	0	0	33	33
mol:ceramide	-0.007	0.045	0.1	65	-10000	0	65
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	0.013	0.052	-10000	0	-0.26	10	10
p75(NTR)/beta APP	0.044	0.031	-10000	0	-0.14	8	8
BEX1	0.029	0.016	-10000	0	0	116	116
mol:GDP	-0.008	0.003	-10000	0	-10000	0	0
NGF (dimer)	0.047	0.035	-10000	0	-10000	0	0
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	0.041	0.018	-10000	0	-10000	0	0
PIK3R1	0.033	0.013	-10000	0	0	67	67
RAC1/GTP	0.026	0.025	-10000	0	-0.094	5	5
MYD88	0.035	0.01	-10000	0	0	37	37
CHUK	0.027	0.017	-10000	0	0	139	139
NGF (dimer)/p75(NTR)/PKA	0.033	0.041	-10000	0	-0.11	29	29
RHOB	0.032	0.013	-10000	0	0	75	75
RHOA	0.036	0.007	-10000	0	0	20	20
MAGE-G1/E2F1	0.026	0.007	-10000	0	-10000	0	0
NT3 (dimer)	0.036	0.008	-10000	0	0	26	26
TP53	-0.007	0.077	0.2	40	-0.2	6	46
PRDM4	-0.007	0.047	0.1	71	-10000	0	71
BDNF (dimer)	0.076	0.036	-10000	0	-10000	0	0
PIK3CA	0.032	0.013	-10000	0	0	74	74
SORT1	0.037	0.006	-10000	0	0	15	15
activation of caspase activity	0.066	0.046	-10000	0	-0.12	23	23
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	0.058	0.032	-10000	0	-0.11	5	5
RHOC	0.036	0.007	-10000	0	0	20	20
XIAP	0	0	-10000	0	-10000	0	0
MAPK10	0.016	0.11	0.24	44	-0.3	18	62
DIABLO	0.037	0.005	-10000	0	0	10	10
SMPD2	-0.007	0.045	0.1	65	-10000	0	65
APH1B	0.037	0.006	-10000	0	0	14	14
APH1A	0.036	0.007	-10000	0	0	17	17
proNGF (dimer)/p75(NTR)/Sortilin	0.042	0.023	-10000	0	-0.11	4	4
PSEN1	0.034	0.011	-10000	0	0	48	48
APAF-1/Pro-Caspase 9	0.051	0.018	-10000	0	-0.14	2	2
NT3 (dimer)/p75(NTR)	0.046	0.022	-10000	0	-10000	0	0
MAPK8	0.001	0.076	0.23	18	-0.26	7	25
MAPK9	0.029	0.1	0.24	49	-0.26	10	59
APAF1	0.037	0.005	-10000	0	0	8	8
NTF3	0.036	0.008	-10000	0	0	26	26
NTF4	0	0	-10000	0	-10000	0	0
NDN	0.018	0.019	-10000	0	0	264	264
RAC1/GDP	0.018	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	0.072	0.059	-10000	0	-0.12	31	31
RhoA-B-C/GTP	0.032	0.04	-10000	0	-0.11	29	29
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.08	0.062	-10000	0	-0.12	24	24
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	0.084	0.031	-10000	0	-0.12	2	2
PRKACB	0.034	0.011	-10000	0	0	50	50
proBDNF (dimer)/p75 ECD	0.047	0.02	-10000	0	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-10000	0	-10000	0	0
BIRC3	0.031	0.014	-10000	0	0	84	84
BIRC2	0.037	0.006	-10000	0	0	14	14
neuron projection morphogenesis	-0.016	0.066	0.13	26	-0.16	27	53
BAD	0.014	0.1	0.25	34	-0.28	14	48
RIPK2	0.037	0.006	-10000	0	0	14	14
NGFR	0.032	0.013	-10000	0	0	72	72
CYCS	-0.012	0.043	0.19	5	-0.18	3	8
ADAM17	0.037	0.006	-10000	0	0	13	13
NGF (dimer)/p75(NTR)/TRAF6/RIP2	0.058	0.031	-10000	0	-0.11	3	3
BCL2L11	0.014	0.1	0.25	34	-0.29	13	47
BDNF (dimer)/p75(NTR)	0.042	0.024	-10000	0	-10000	0	0
PI3K	0.029	0.069	-10000	0	-0.12	73	73
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	0.04	0.022	-10000	0	-0.1	4	4
NDNL2	0	0	-10000	0	-10000	0	0
YWHAE	0.036	0.009	-10000	0	0	29	29
PRKCI	0.036	0.008	-10000	0	0	25	25
NGF (dimer)/p75(NTR)	0.024	0.01	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	0.051	0.047	-10000	0	-0.11	27	27
TRAF6	0.037	0.006	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
PRKCZ	0	0	-10000	0	-10000	0	0
PLG	0.035	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	15	-0.15	2	17
SQSTM1	0.035	0.01	-10000	0	0	36	36
NGFRAP1	0.037	0.006	-10000	0	0	14	14
CASP3	0.014	0.1	0.24	34	-0.28	15	49
E2F1	0.035	0.01	-10000	0	0	36	36
CASP9	0.035	0.009	-10000	0	0	30	30
IKK complex	0.04	0.069	-10000	0	-0.26	8	8
NGF (dimer)/TRKA	0.027	0.004	-10000	0	-10000	0	0
MMP7	0.027	0.017	-10000	0	0	140	140
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	0.065	0.054	-10000	0	-0.11	30	30
MMP3	0.036	0.008	-10000	0	0	23	23
APAF-1/Caspase 9	-0.025	0.041	-10000	0	-0.2	7	7

×

Signaling events mediated by HDAC Class III

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
EP300	0.034	0.011	-10000	0	0	49	49
HDAC4	0.035	0.009	-10000	0	0	31	31
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.001	0.037	-10000	0	-0.12	39	39
CDKN1A	-0.032	0.11	-10000	0	-0.47	28	28
KAT2B	0	0	-10000	0	-10000	0	0
BAX	0.035	0.01	-10000	0	0	41	41
FOXO3	-0.004	0.022	0.25	2	-0.1	1	3
FOXO1	0.031	0.015	-10000	0	0	95	95
FOXO4	0.011	0.024	-10000	0	-0.18	8	8
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.035	0.01	-10000	0	0	41	41
TAT	0.037	0.006	-10000	0	0	12	12
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.012	0.002	-10000	0	-10000	0	0
PPARGC1A	0.032	0.014	-10000	0	0	78	78
FHL2	0.028	0.016	-10000	0	0	127	127
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.042	0.046	0.16	30	-0.16	6	36
HIST2H4A	0.001	0.037	0.12	39	-10000	0	39
SIRT1/FOXO3a	0.023	0.043	0.15	32	-0.096	13	45
SIRT1	0.035	0.046	0.18	39	-10000	0	39
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.05	0.055	0.17	25	-0.12	17	42
SIRT1/Histone H1b	0.03	0.044	0.15	29	-0.16	7	36
apoptosis	-0.051	0.052	0.13	10	-0.17	25	35
SIRT1/PGC1A	0.032	0.043	0.14	31	-0.11	14	45
p53/SIRT1	0.041	0.083	0.34	28	-0.15	20	48
SIRT1/FOXO4	0.03	0.044	0.16	2	-0.17	7	9
FOXO1/FHL2/SIRT1	0.027	0.055	0.16	13	-0.11	34	47
HIST1H1E	0.013	0.024	-10000	0	-0.18	7	7
SIRT1/p300	0.041	0.05	0.16	31	-0.15	12	43
muscle cell differentiation	0.005	0.037	0.12	5	-0.11	39	44
TP53	0.042	0.046	0.18	43	-10000	0	43
KU70/SIRT1/BAX	0.052	0.052	0.17	25	-0.13	10	35
CREBBP	0.037	0.004	-10000	0	0	7	7
MEF2D	0.037	0.006	-10000	0	0	13	13
HIV-1 Tat/SIRT1	0.043	0.044	0.16	31	-0.14	5	36
ACSS2	0.001	0.037	0.12	39	-10000	0	39
SIRT1/PCAF/MYOD	-0.005	0.038	0.12	39	-0.12	5	44

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SMAD4	0.033	0.012	-10000	0	0	58	58
SMAD2	-0.022	0.068	0.17	2	-0.22	34	36
SMAD3	0.011	0.064	0.27	1	-0.33	7	8
SMAD3/SMAD4	-0.008	0.17	-10000	0	-0.48	47	47
SMAD4/Ubc9/PIASy	0.057	0.052	-10000	0	-0.12	34	34
SMAD2/SMAD2/SMAD4	0.021	0.11	-10000	0	-0.26	28	28
PPM1A	0.035	0.01	-10000	0	0	35	35
CALM1	0.033	0.012	-10000	0	0	60	60
SMAD2/SMAD4	-0.004	0.07	-10000	0	-0.2	37	37
MAP3K1	0.036	0.008	-10000	0	0	23	23
TRAP-1/SMAD4	0.039	0.052	-10000	0	-0.14	38	38
MAPK3	0.037	0.003	-10000	0	0	4	4
MAPK1	0.034	0.011	-10000	0	0	47	47
NUP214	0.036	0.008	-10000	0	0	22	22
CTDSP1	0.037	0.007	-10000	0	0	16	16
CTDSP2	0.032	0.014	-10000	0	0	81	81
CTDSPL	0.037	0.006	-10000	0	0	14	14
KPNB1	0.036	0.008	-10000	0	0	23	23
TGFBRAP1	0.037	0.005	-10000	0	0	11	11
UBE2I	0.037	0.004	-10000	0	0	5	5
NUP153	0.035	0.009	-10000	0	0	32	32
KPNA2	0.035	0.01	-10000	0	0	39	39
PIAS4	0.037	0.007	-10000	0	0	16	16

×

Signaling mediated by p38-gamma and p38-delta

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
EEF2K	-0.017	0.005	0	47	-10000	0	47
SNTA1	0.032	0.014	-10000	0	0	78	78
response to hypoxia	0	0	-10000	0	-10000	0	0
STMN1	-0.015	0.034	0.084	51	-10000	0	51
MAPK12	-0.011	0.03	0.2	3	-0.17	10	13
CCND1	-0.023	0.11	-10000	0	-0.37	43	43
p38 gamma/SNTA1	-0.012	0.036	0.2	4	-0.16	11	15
MAP2K3	0.037	0.005	-10000	0	0	11	11
PKN1	0.034	0.011	-10000	0	0	45	45
G2/M transition checkpoint	-0.011	0.03	0.2	3	-0.16	10	13
MAP2K6	-0.006	0.035	0.22	6	-0.18	11	17
MAPT	-0.026	0.078	0.17	4	-0.2	75	79
MAPK13	-0.021	0.007	0	47	-10000	0	47
hyperosmotic response	0	0	-10000	0	-10000	0	0
ZAK	0.01	0.031	-10000	0	-0.2	11	11

×

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

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
BAG4	0.037	0.005	-10000	0	0	10	10
Caspase 8 (4 units)	-0.004	0.095	-10000	0	-0.24	22	22
NEF	0.002	0.001	-10000	0	-10000	0	0
NFKBIA	0.04	0.019	0.079	64	-10000	0	64
BIRC3	-0.025	0.03	0.18	3	-0.2	2	5
CYCS	-0.002	0.08	0.18	47	-0.26	12	59
RIPK1	0.036	0.007	-10000	0	0	19	19
CD247	0.039	0.007	-10000	0	-10000	0	0
MAP2K7	-0.009	0.11	-10000	0	-0.38	13	13
protein ubiquitination	0.012	0.069	0.2	4	-0.26	9	13
CRADD	0.037	0.007	-10000	0	0	16	16
DAXX	0.037	0.005	-10000	0	0	8	8
FAS	0.021	0.019	-10000	0	0	219	219
BID	-0.014	0.061	-10000	0	-0.27	8	8
NF-kappa-B/RelA/I kappa B alpha	0.077	0.053	-10000	0	-0.13	16	16
TRADD	0.037	0.005	-10000	0	0	8	8
MAP3K5	0.031	0.014	-10000	0	0	91	91
CFLAR	0.037	0.005	-10000	0	0	9	9
FADD	0.037	0.006	-10000	0	0	13	13
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	0.077	0.054	-10000	0	-0.13	16	16
MAPK8	-0.006	0.1	0.55	1	-0.36	13	14
APAF1	0.037	0.005	-10000	0	0	8	8
TRAF1	0.036	0.009	-10000	0	0	28	28
TRAF2	0.036	0.007	-10000	0	0	19	19
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	0.002	0.059	0.18	1	-0.28	8	9
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.028	0.078	-10000	0	-0.29	11	11
CHUK	0.013	0.07	0.21	4	-0.28	8	12
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0.045	0.084	-10000	0	-0.12	59	59
TCRz/NEF	0.034	0.006	-10000	0	-10000	0	0
TNF	0.037	0.004	-10000	0	0	6	6
FASLG	0.019	0.01	-10000	0	-10000	0	0
NFKB1	0.043	0.017	0.08	72	-10000	0	72
TNFR1A/BAG4/TNF-alpha	0.055	0.056	-10000	0	-0.12	41	41
CASP6	0.01	0.11	-10000	0	-0.57	6	6
CASP7	-0.027	0.14	0.27	5	-0.3	48	53
RELA	0.044	0.016	0.081	74	-10000	0	74
CASP2	0.026	0.018	-10000	0	0	160	160
CASP3	0.002	0.11	0.28	6	-0.34	17	23
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
TNFR1A/BAG4	0.036	0.054	-10000	0	-0.14	42	42
CASP8	0.037	0.006	-10000	0	0	14	14
CASP9	0.035	0.009	-10000	0	0	30	30
MAP3K14	0.024	0.079	0.2	3	-0.27	12	15
APAF-1/Caspase 9	-0.01	0.082	0.17	5	-0.23	13	18
BCL2	-0.014	0.098	0.39	2	-0.34	15	17

×

S1P3 pathway

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
PDGFRB	0.036	0.008	-10000	0	0	25	25
mol:S1P	0.001	0.002	0.019	4	-10000	0	4
S1P1/S1P/Gi	-0.015	0.09	-10000	0	-0.2	75	75
GNAO1	0.032	0.015	-10000	0	-10000	0	0
S1P/S1P3/G12/G13	0.026	0.039	-10000	0	-0.1	29	29
AKT1	-0.018	0.16	-10000	0	-0.46	53	53
AKT3	-0.029	0.13	-10000	0	-0.5	13	13
mol:GTP	0	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	0.036	0.008	-10000	0	0	25	25
GNAI2	0.035	0.011	-10000	0	-10000	0	0
GNAI3	0.037	0.007	-10000	0	-10000	0	0
GNAI1	0.019	0.019	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
S1PR3	0.001	0.002	0.02	4	-10000	0	4
S1PR2	0	0	-10000	0	-10000	0	0
EDG1	0	0	-10000	0	-10000	0	0
mol:Ca2+	-0.006	0.099	0.2	1	-0.29	35	36
MAPK3	-0.012	0.098	0.19	1	-0.28	38	39
MAPK1	-0.006	0.092	0.19	1	-0.27	32	33
JAK2	-0.012	0.11	0.2	8	-0.31	40	48
CXCR4	-0.009	0.099	0.19	1	-0.28	40	41
FLT1	0.036	0.01	-10000	0	-10000	0	0
RhoA/GDP	0.025	0.019	-10000	0	-0.13	7	7
Rac1/GDP	0.018	0.019	-10000	0	-0.13	5	5
SRC	-0.013	0.095	-10000	0	-0.28	36	36
S1P/S1P3/Gi	-0.007	0.099	0.2	1	-0.29	35	36
RAC1	0.026	0.017	-10000	0	0	156	156
RhoA/GTP	0.009	0.11	0.19	1	-0.27	40	41
VEGFA	0.025	0.019	-10000	0	-10000	0	0
S1P/S1P2/Gi	-0.009	0.098	0.16	1	-0.26	47	48
VEGFR1 homodimer/VEGFA homodimer	0.007	0.079	-10000	0	-0.14	107	107
RHOA	0.036	0.007	-10000	0	0	20	20
S1P/S1P3/Gq	0.016	0.039	-10000	0	-0.15	26	26
GNAQ	0.035	0.01	-10000	0	0	35	35
GNAZ	0.032	0.014	-10000	0	-10000	0	0
G12/G13	0.027	0.048	-10000	0	-0.14	29	29
GNA14	0.035	0.009	-10000	0	0	34	34
GNA15	0.034	0.011	-10000	0	0	45	45
GNA12	0.024	0.018	-10000	0	0	180	180
GNA13	0.036	0.008	-10000	0	0	21	21
GNA11	0.034	0.011	-10000	0	0	46	46
Rac1/GTP	0	0.092	-10000	0	-0.3	25	25

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	0.023	0.13	-10000	0	-0.63	18	18
epithelial cell differentiation	-0.004	0.14	-10000	0	-0.65	18	18
ITCH	0.03	0.032	0.11	1	-0.1	23	24
WWP1	-0.023	0.22	-10000	0	-1.1	18	18
FYN	0.031	0.015	-10000	0	0	93	93
EGFR	0.01	0.017	-10000	0	0	373	373
PRL	0.036	0.007	-10000	0	0	17	17
neuron projection morphogenesis	-0.028	0.11	0.28	6	-0.49	19	25
PTPRZ1	0.024	0.018	-10000	0	0	186	186
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	0.054	0.12	-10000	0	-0.53	18	18
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	0.005	0.11	-10000	0	-0.57	18	18
ADAM17	0.031	0.031	-10000	0	-0.099	23	23
ErbB4/ErbB4	-0.003	0.13	-10000	0	-0.68	18	18
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.01	0.12	-10000	0	-0.62	18	18
NCOR1	0.036	0.008	-10000	0	0	27	27
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	0.017	0.12	-10000	0	-0.58	18	18
GRIN2B	-0.01	0.11	0.21	2	-0.55	18	20
ErbB4/ErbB2/betacellulin	0.027	0.11	0.22	1	-0.55	18	19
STAT1	0.035	0.01	-10000	0	0	41	41
HBEGF	0.036	0.008	-10000	0	0	22	22
PRLR	0.037	0.005	-10000	0	0	10	10
E4ICDs/ETO2	0.022	0.13	-10000	0	-0.63	18	18
axon guidance	-0.025	0.16	0.33	1	-0.79	18	19
NEDD4	0.03	0.031	0.11	1	-0.11	21	22
Prolactin receptor/Prolactin receptor/Prolactin	0.053	0.012	-10000	0	-10000	0	0
CBFA2T3	0.036	0.009	-10000	0	0	28	28
ErbB4/ErbB2/HBEGF	0.026	0.11	0.22	1	-0.55	18	19
MAPK3	-0.018	0.11	0.29	6	-0.51	18	24
STAT1 (dimer)	0.021	0.13	-10000	0	-0.63	18	18
MAPK1	-0.02	0.11	0.33	5	-0.5	19	24
JAK2	0.032	0.013	-10000	0	0	74	74
ErbB4/ErbB2/neuregulin 1 beta	0.004	0.11	0.21	1	-0.55	18	19
NRG1	-0.023	0.017	-10000	0	-0.084	18	18
NRG3	0	0	-10000	0	-10000	0	0
NRG2	0.037	0.005	-10000	0	0	8	8
NRG4	0	0	-10000	0	-10000	0	0
heart development	-0.025	0.16	0.33	1	-0.79	18	19
neural crest cell migration	0.005	0.11	0.21	1	-0.54	18	19
ERBB2	-0.023	0.019	0.047	11	-0.084	18	29
WWOX/E4ICDs	0.024	0.13	-10000	0	-0.63	18	18
SHC1	0.034	0.012	-10000	0	0	53	53
ErbB4/EGFR/neuregulin 4	-0.013	0.099	-10000	0	-0.47	18	18
apoptosis	-0.006	0.12	0.58	18	-10000	0	18
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	0.025	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB2/epiregulin	0.026	0.11	-10000	0	-0.55	18	18
ErbB4/ErbB4/betacellulin/betacellulin	0.024	0.13	-10000	0	-0.63	18	18
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	0.064	0.13	-10000	0	-0.57	18	18
MDM2	0.009	0.14	0.27	41	-0.6	18	59
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	0.02	0.1	-10000	0	-0.51	18	18
STAT5A	-0.033	0.15	0.29	1	-0.77	18	19
ErbB4/EGFR/neuregulin 1 beta	-0.003	0.089	-10000	0	-0.43	18	18
DLG4	0.037	0.006	-10000	0	0	14	14
GRB2/SHC	0.044	0.037	-10000	0	-0.15	14	14
E4ICDs/TAB2/NCoR1	0.017	0.12	-10000	0	-0.61	18	18
STAT5A (dimer)	0.004	0.16	-10000	0	-0.72	18	18
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.012	0.16	0.29	2	-0.77	18	20
LRIG1	0.031	0.014	-10000	0	0	87	87
EREG	0.036	0.008	-10000	0	0	22	22
BTC	0.037	0.005	-10000	0	0	8	8
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.026	0.16	0.33	1	-0.8	18	19
ERBB4	-0.003	0.13	-10000	0	-0.69	18	18
STAT5B	0.037	0.005	-10000	0	0	8	8
YAP1	-0.071	0.2	-10000	0	-0.48	93	93
GRB2	0.036	0.007	-10000	0	0	19	19
ErbB4/ErbB2/neuregulin 4	0.002	0.11	-10000	0	-0.54	18	18
glial cell differentiation	-0.017	0.12	0.6	18	-10000	0	18
WWOX	0.036	0.007	-10000	0	0	17	17
cell proliferation	-0.011	0.11	-10000	0	-0.57	18	18

×

IL4-mediated signaling events

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
BCL2L1	-0.042	0.38	0.83	1	-1	22	23
STAT6 (cleaved dimer)	-0.067	0.35	-10000	0	-0.95	29	29
IGHG1	-0.01	0.26	0.43	21	-0.78	23	44
IGHG3	-0.058	0.36	0.63	1	-0.94	29	30
AKT1	-0.018	0.27	0.52	6	-0.72	29	35
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	0.018	0.19	0.46	5	-0.55	8	13
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.004	0.26	0.51	3	-0.74	19	22
THY1	-0.12	0.5	0.78	2	-1.2	61	63
MYB	0.033	0.012	-10000	0	0	60	60
HMGA1	0.037	0.006	-10000	0	0	13	13
IL4/IL4R/JAK1/IL2R gamma/JAK3	0.001	0.26	0.55	7	-0.59	17	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.004	0.25	0.5	3	-0.77	16	19
SP1	0.028	0.077	0.12	88	-0.14	73	161
INPP5D	0	0	-10000	0	-10000	0	0
SOCS5	0.007	0.046	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.047	0.36	-10000	0	-0.97	26	26
SOCS1	-0.035	0.3	0.52	3	-0.67	30	33
SOCS3	-0.001	0.22	-10000	0	-0.69	2	2
FCER2	-0.024	0.32	0.66	2	-0.79	17	19
PARP14	0.001	0.001	-10000	0	-10000	0	0
CCL17	-0.056	0.38	0.79	2	-1	22	24
GRB2	0.036	0.007	-10000	0	0	19	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	0.006	0.22	0.44	10	-0.57	19	29
T cell proliferation	-0.064	0.37	0.66	1	-1	26	27
IL4R/JAK1	-0.066	0.38	0.66	1	-1	27	28
EGR2	-0.11	0.5	0.8	2	-1.3	53	55
JAK2	0.019	0.067	0.15	18	-10000	0	18
JAK3	0.035	0.018	-10000	0	-0.039	17	17
PIK3R1	0.033	0.013	-10000	0	0	67	67
JAK1	0.027	0.04	0.11	6	-10000	0	6
COL1A2	-0.11	0.47	0.54	3	-1.2	76	79
CCL26	-0.055	0.38	0.72	1	-0.97	29	30
IL4R	-0.052	0.41	0.81	3	-1.1	23	26
PTPN6	0.016	0.037	-10000	0	-0.06	4	4
IL13RA2	-0.31	0.65	0.76	3	-1.1	175	178
IL13RA1	0.024	0.068	0.16	18	-10000	0	18
IRF4	0.044	0.12	-10000	0	-0.52	2	2
ARG1	0.006	0.21	0.52	2	-0.79	9	11
CBL	-0.007	0.24	0.49	4	-0.56	17	21
GTF3A	0.049	0.035	0.12	70	-0.15	3	73
PIK3CA	0.032	0.013	-10000	0	0	74	74
IL13RA1/JAK2	0.024	0.1	0.23	10	-0.17	10	20
IRF4/BCL6	0.04	0.12	-10000	0	-0.45	2	2
CD40LG	0.042	0.005	0.14	1	-10000	0	1
MAPK14	-0.004	0.24	0.53	1	-0.58	12	13
mitosis	-0.015	0.26	0.51	6	-0.68	29	35
STAT6	-0.06	0.42	0.82	4	-1.1	27	31
SPI1	0.038	0.013	-10000	0	-10000	0	0
RPS6KB1	-0.018	0.25	0.49	6	-0.66	29	35
STAT6 (dimer)	-0.06	0.42	0.82	4	-1.1	27	31
STAT6 (dimer)/PARP14	-0.077	0.37	-10000	0	-1	27	27
mast cell activation	-0.002	0.016	-10000	0	-0.041	19	19
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	0.009	0.21	0.49	3	-0.6	5	8
FRAP1	-0.018	0.27	0.52	6	-0.72	29	35
LTA	-0.057	0.38	0.72	1	-1	23	24
FES	0.037	0.007	-10000	0	0	16	16
T-helper 1 cell differentiation	0.058	0.42	1.1	27	-0.82	4	31
CCL11	-0.059	0.36	-10000	0	-0.99	24	24
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	0.013	0.21	0.51	4	-0.6	6	10
IL2RG	0.035	0.018	-10000	0	-0.039	13	13
IL10	-0.052	0.38	0.75	4	-1	22	26
IRS1	0.034	0.011	-10000	0	0	52	52
IRS2	0.031	0.015	-10000	0	0	94	94
IL4	0.027	0.17	0.57	1	-0.9	5	6
IL5	-0.057	0.38	-10000	0	-1.1	20	20
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.053	0.38	0.7	6	-0.92	35	41
COL1A1	0.019	0.26	0.56	13	-0.89	12	25
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.071	0.38	-10000	0	-1.1	23	23
IL2R gamma/JAK3	0.055	0.02	-10000	0	-0.08	1	1
TFF3	-0.051	0.38	0.79	2	-1	21	23
ALOX15	-0.057	0.38	0.72	1	-1.1	21	22
MYBL1	0.031	0.015	-10000	0	0	97	97
T-helper 2 cell differentiation	-0.04	0.34	0.63	4	-0.81	30	34
SHC1	0.034	0.012	-10000	0	0	53	53
CEBPB	0.035	0.016	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.013	0.26	0.51	5	-0.78	19	24
mol:PI-3-4-5-P3	-0.018	0.27	0.52	6	-0.72	29	35
PI3K	-0.023	0.28	0.53	5	-0.77	29	34
DOK2	0	0	-10000	0	-10000	0	0
ETS1	0.004	0.047	-10000	0	-0.091	6	6
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	0.007	0.21	0.43	10	-0.56	22	32
ITGB3	-0.056	0.38	0.72	1	-1	22	23
PIGR	-0.052	0.38	0.77	3	-1	23	26
IGHE	-0.004	0.08	0.17	41	-0.18	16	57
MAPKKK cascade	0.009	0.21	0.44	11	-0.55	22	33
BCL6	0.032	0.013	-10000	0	0	70	70
OPRM1	-0.056	0.38	0.72	1	-1.1	21	22
RETNLB	-0.055	0.38	0.72	1	-0.97	29	30
SELP	-0.054	0.38	0.79	2	-1	22	24
AICDA	-0.056	0.36	0.7	2	-1	21	23

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.036	0.008	-10000	0	0	24	24
HDAC3	0.037	0.005	-10000	0	0	8	8
VDR	0.036	0.008	-10000	0	0	23	23
Cbp/p300/PCAF	0.044	0.025	-10000	0	-0.11	8	8
EP300	0.034	0.011	-10000	0	0	49	49
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.001	0.058	-10000	0	-0.23	14	14
KAT2B	0	0	-10000	0	-10000	0	0
MAPK14	0.037	0.005	-10000	0	0	8	8
AKT1	0.007	0.08	0.16	58	-0.22	13	71
RAR alpha/9cRA/Cyclin H	0.001	0.11	0.38	1	-0.24	48	49
mol:9cRA	0	0	-10000	0	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	-0.003	0.06	-10000	0	-0.21	25	25
CDC2	-0.001	0.004	-10000	0	-10000	0	0
response to UV	-0.001	0.007	0.03	1	-0.025	33	34
RAR alpha/Jnk1	0.019	0.041	0.16	1	-0.35	2	3
NCOR2	0.037	0.004	-10000	0	0	6	6
VDR/VDR/Vit D3	0.027	0.006	-10000	0	-10000	0	0
RXRs/RARs/NRIP1/9cRA	-0.022	0.15	0.41	3	-0.5	37	40
NCOA2	0.037	0.005	-10000	0	0	11	11
NCOA3	0.034	0.011	-10000	0	0	45	45
NCOA1	0.034	0.011	-10000	0	0	49	49
VDR/VDR/DNA	0.036	0.008	-10000	0	0	23	23
RARG	0.033	0.018	-10000	0	-0.024	44	44
RAR gamma1/9cRA	0.048	0.012	-10000	0	-10000	0	0
MAPK3	0.033	0.019	-10000	0	-0.033	37	37
MAPK1	0.034	0.011	-10000	0	0	47	47
MAPK8	0.025	0.023	-10000	0	-0.007	146	146
mol:Vit D3	0	0	-10000	0	-10000	0	0
RXRs/VDR/DNA/Vit D3	0	0.11	-10000	0	-0.3	49	49
RARA	0.007	0.036	-10000	0	-0.2	9	9
negative regulation of phosphoinositide 3-kinase cascade	0	0	-10000	0	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.005	0.048	0.23	1	-0.19	15	16
PRKCA	0.032	0.029	0.084	5	-0.074	33	38
RXRs/RARs/NRIP1/9cRA/HDAC1	-0.023	0.16	0.48	2	-0.55	38	40
RXRG	0.017	0.029	-10000	0	-10000	0	0
RXRA	-0.017	0.064	-10000	0	-0.19	33	33
RXRB	0.018	0.028	0.13	1	-10000	0	1
VDR/Vit D3/DNA	0.027	0.006	-10000	0	-10000	0	0
RBP1	0.027	0.017	-10000	0	0	143	143
CRBP1/9-cic-RA	-0.003	0.059	-10000	0	-0.13	91	91
RARB	0.033	0.022	0.077	1	-0.035	44	45
PRKCG	0.03	0.029	0.084	5	-0.073	33	38
MNAT1	0.034	0.011	-10000	0	0	44	44
RAR alpha/RXRs	-0.006	0.12	0.25	1	-0.37	34	35
RXRs/RARs/SMRT(N-CoR2)/9cRA	-0.001	0.095	0.35	2	-0.28	31	33
proteasomal ubiquitin-dependent protein catabolic process	-0.006	0.067	0.23	2	-0.2	24	26
RXRs/RARs/NRIP1/9cRA/HDAC3	-0.023	0.16	0.45	2	-0.55	38	40
positive regulation of DNA binding	-0.006	0.1	-10000	0	-0.23	48	48
NRIP1	-0.047	0.27	0.53	2	-1	33	35
RXRs/RARs	-0.008	0.12	-10000	0	-0.38	41	41
RXRs/RXRs/DNA/9cRA	-0.016	0.1	-10000	0	-0.3	50	50
PRKACA	0.036	0.007	-10000	0	0	17	17
CDK7	0.036	0.008	-10000	0	0	26	26
TFIIH	0.06	0.051	-10000	0	-0.16	19	19
RAR alpha/9cRA	0.024	0.092	-10000	0	-0.19	25	25
CCNH	0.036	0.008	-10000	0	0	21	21
CREBBP	0.037	0.004	-10000	0	0	7	7
RAR gamma2/9cRA	0.057	0.052	-10000	0	-0.15	18	18

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	0.04	0.027	-9999	-0.14	2	2
FBXW11	0.036	0.008	-9999	0	24	24
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.008	-9999	0	24	24
CHUK	0.027	0.017	-9999	0	139	139
NF kappa B2 p100/RelB	0.069	0.064	-9999	-0.12	12	12
NFKB1	0.036	0.007	-9999	0	18	18
MAP3K14	0.037	0.006	-9999	0	13	13
NF kappa B1 p50/RelB	0.05	0.023	-9999	-0.14	4	4
RELB	0.035	0.009	-9999	0	30	30
NFKB2	0.028	0.017	-9999	0	132	132
NF kappa B2 p52/RelB	0.036	0.023	-9999	-10000	0	0
regulation of B cell activation	0.036	0.023	-9999	-10000	0	0

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	0.035	0.077	0.22	16	-0.28	10	26
FYN	-0.003	0.11	0.26	9	-0.32	26	35
LAT/GRAP2/SLP76	0.028	0.077	0.27	4	-0.3	10	14
IKBKB	0.037	0.003	-10000	0	0	4	4
AKT1	0.009	0.091	0.24	16	-0.26	20	36
B2M	0.038	0.009	-10000	0	0	20	20
IKBKG	-0.001	0.035	0.1	14	-0.1	8	22
MAP3K8	0.025	0.018	-10000	0	0	176	176
mol:Ca2+	-0.01	0.01	-10000	0	-0.04	4	4
integrin-mediated signaling pathway	0.024	0.007	-10000	0	-0.1	1	1
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	0.014	0.11	0.28	15	-0.33	19	34
TRPV6	0.38	0.59	1.3	155	-10000	0	155
CD28	0.038	0.002	-10000	0	0	1	1
SHC1	0.026	0.083	0.24	19	-0.33	9	28
receptor internalization	0.027	0.066	0.21	4	-0.44	5	9
PRF1	-0.1	0.29	-10000	0	-0.6	123	123
KRAS	0.035	0.009	-10000	0	0	34	34
GRB2	0.036	0.007	-10000	0	0	19	19
COT/AKT1	0.009	0.069	0.24	3	-0.22	19	22
LAT	0.02	0.076	0.25	7	-0.32	10	17
EntrezGene:6955	0.001	0.004	-10000	0	-10000	0	0
CD3D	0.036	0.012	-10000	0	0	46	46
CD3E	0.039	0.007	-10000	0	0	10	10
CD3G	0.038	0.008	-10000	0	-10000	0	0
RASGRP2	0.006	0.02	-10000	0	-0.15	5	5
RASGRP1	-0.015	0.13	0.24	26	-0.24	83	109
HLA-A	0.038	0.008	-10000	0	0	15	15
RASSF5	0	0	-10000	0	-10000	0	0
RAP1A/GTP/RAPL	0.025	0.007	-10000	0	-0.1	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	0.014	0.058	0.15	36	-0.11	15	51
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.005	0.038	-10000	0	-0.14	21	21
PRKCA	0.006	0.063	0.18	27	-0.19	5	32
GRAP2	0.035	0.01	-10000	0	0	36	36
mol:IP3	0.007	0.056	-10000	0	-0.23	11	11
EntrezGene:6957	0.002	0.004	0.022	1	-10000	0	1
TCR/CD3/MHC I/CD8	0.024	0.051	0.16	7	-0.32	4	11
ORAI1	-0.33	0.5	-10000	0	-1.1	155	155
CSK	0.02	0.073	0.23	6	-0.32	10	16
B7 family/CD28	0.066	0.096	0.28	16	-0.3	9	25
CHUK	0.027	0.017	-10000	0	0	139	139
TCR/CD3/MHC I/CD8/LCK/ZAP-70	0.024	0.078	0.22	7	-0.34	10	17
PTPN6	0.02	0.083	0.22	23	-0.33	10	33
VAV1	0.026	0.083	0.24	21	-0.32	10	31
Monovalent TCR/CD3	0.027	0.018	0.12	1	-10000	0	1
CBL	0.037	0.005	-10000	0	0	9	9
LCK	0.011	0.092	0.24	12	-0.35	12	24
PAG1	0.023	0.073	0.21	9	-0.31	10	19
RAP1A	0.037	0.005	-10000	0	0	10	10
TCR/CD3/MHC I/CD8/LCK	0.024	0.079	0.22	9	-0.34	10	19
CD80	0.037	0.006	-10000	0	0	13	13
CD86	0.034	0.013	-10000	0	0	63	63
PDK1/CARD11/BCL10/MALT1	0.004	0.048	-10000	0	-0.16	21	21
HRAS	0.035	0.01	-10000	0	0	37	37
GO:0035030	0.014	0.073	0.2	21	-0.27	9	30
CD8A	0.002	0.004	0.024	1	-10000	0	1
CD8B	0.039	0.006	-10000	0	-10000	0	0
PTPRC	0.03	0.016	-10000	0	0	110	110
PDK1/PKC theta	0.012	0.099	0.29	16	-0.32	13	29
CSK/PAG1	0.018	0.072	0.23	6	-0.3	10	16
SOS1	0	0	-10000	0	-10000	0	0
peptide-MHC class I	0.051	0.036	-10000	0	-0.14	14	14
GRAP2/SLP76	0.038	0.086	0.26	4	-0.34	10	14
STIM1	-0.065	0.12	1.1	2	-10000	0	2
RAS family/GTP	0.009	0.076	0.19	19	-0.18	27	46
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	0.027	0.068	0.21	4	-0.46	5	9
mol:DAG	-0.005	0.043	-10000	0	-0.21	11	11
RAP1A/GDP	0.011	0.028	0.075	28	-0.056	10	38
PLCG1	0.034	0.01	-10000	0	0	43	43
CD247	0.038	0.008	-10000	0	-10000	0	0
cytotoxic T cell degranulation	-0.098	0.28	0.37	1	-0.58	123	124
RAP1A/GTP	0.004	0.008	-10000	0	-0.056	5	5
mol:PI-3-4-5-P3	0.015	0.096	0.26	16	-0.3	17	33
LAT/GRAP2/SLP76/VAV1/PLCgamma1	0.015	0.07	-10000	0	-0.29	10	10
NRAS	0.033	0.013	-10000	0	0	66	66
ZAP70	0.038	0.003	-10000	0	0	4	4
GRB2/SOS1	0.025	0.02	-10000	0	-0.13	8	8
LAT/GRAP2/SLP76/VAV1	0.018	0.07	0.2	1	-0.3	9	10
MALT1	0.035	0.009	-10000	0	0	30	30
TRAF6	0.037	0.006	-10000	0	0	14	14
CD8 heterodimer	0.03	0.009	-10000	0	-10000	0	0
CARD11	0	0	-10000	0	-10000	0	0
PRKCB	-0.014	0.029	-10000	0	-0.16	11	11
PRKCE	0.005	0.063	0.18	27	-0.18	7	34
PRKCQ	0.015	0.1	0.28	19	-0.34	13	32
LCP2	0.032	0.013	-10000	0	0	77	77
BCL10	0.036	0.007	-10000	0	0	20	20
regulation of survival gene product expression	0.009	0.083	0.23	16	-0.23	20	36
IKK complex	0.004	0.044	0.14	21	-0.098	2	23
RAS family/GDP	-0.003	0.015	-10000	0	-0.041	33	33
MAP3K14	0.009	0.066	0.19	20	-0.18	19	39
PDPK1	0.011	0.086	0.25	16	-0.26	16	32
TCR/CD3/MHC I/CD8/Fyn	0.019	0.069	0.27	1	-0.38	7	8

×

Insulin Pathway

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
CBL/APS/CAP	0.036	0.049	-10000	0	-0.11	22	22
TC10/GTP	0.03	0.048	-10000	0	-0.12	21	21
Insulin Receptor/Insulin/IRS1/Shp2	0.077	0.06	-10000	0	-0.13	28	28
HRAS	0.035	0.01	-10000	0	0	37	37
APS homodimer	0	0	-10000	0	-10000	0	0
GRB14	0.032	0.013	-10000	0	0	71	71
FOXO3	-0.053	0.21	-10000	0	-0.65	52	52
AKT1	-0.027	0.088	0.25	13	-0.21	26	39
INSR	0.034	0.022	-10000	0	-0.039	34	34
Insulin Receptor/Insulin	0.057	0.063	0.23	4	-0.14	34	38
mol:GTP	0	0	-10000	0	-10000	0	0
GRB10	0.022	0.019	-10000	0	0	213	213
SORBS1	0.028	0.017	-10000	0	0	133	133
CRK	0.036	0.008	-10000	0	0	25	25
PTPN1	-0.027	0.039	0.14	7	-0.25	7	14
CAV1	-0.012	0.038	0.2	5	-0.19	8	13
CBL/APS/CAP/Crk-II/C3G	0.054	0.055	-10000	0	-0.1	14	14
Insulin Receptor/Insulin/IRS1/NCK2	0.075	0.064	-10000	0	-0.14	31	31
mol:GDP	0	0	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0.036	0.08	-10000	0	-0.13	81	81
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	0.024	0.069	-10000	0	-0.32	11	11
RPS6KB1	-0.033	0.081	0.22	14	-0.2	26	40
PARD6A	0.036	0.007	-10000	0	0	19	19
CBL	0.037	0.005	-10000	0	0	9	9
tumor necrosis factor-mediated signaling pathway	0	0	-10000	0	-10000	0	0
DOK1	0.023	0.019	-10000	0	-10000	0	0
PIK3R1	0.033	0.013	-10000	0	0	67	67
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.036	0.085	0.17	19	-0.22	26	45
HRAS/GTP	-0.035	0.033	0.035	18	-0.12	41	59
Insulin Receptor	0.034	0.022	-10000	0	-0.039	34	34
Insulin Receptor/Insuli/IRS1/GRB2/SHC	0.085	0.069	-10000	0	-0.13	32	32
PRKCI	0.028	0.087	-10000	0	-0.43	16	16
Insulin Receptor/Insulin/GRB14/PDK1	0.015	0.068	-10000	0	-0.13	77	77
SHC1	0.034	0.012	-10000	0	0	53	53
negative regulation of MAPKKK cascade	0.035	0.055	-10000	0	-10000	0	0
PI3K	0.048	0.088	-10000	0	-0.13	81	81
NCK2	0.036	0.007	-10000	0	0	19	19
RHOQ	0.037	0.006	-10000	0	0	15	15
mol:H2O2	-0.005	0.005	-10000	0	-0.033	7	7
HRAS/GDP	0.022	0.028	-10000	0	-0.13	16	16
AKT2	-0.028	0.082	0.25	13	-0.2	8	21
PRKCZ	0.006	0.075	-10000	0	-0.4	15	15
SH2B2	0	0	-10000	0	-10000	0	0
SHC/SHIP	-0.016	0.049	0.17	16	-0.15	4	20
F2RL2	0.037	0.005	-10000	0	0	10	10
TRIP10	0.036	0.008	-10000	0	0	26	26
Insulin Receptor/Insulin/Shc	0.059	0.039	-10000	0	-0.12	8	8
TC10/GTP/CIP4/Exocyst	0.044	0.029	-10000	0	-0.11	14	14
Insulin Receptor/Insulin/SHC/GRB2/Sos1	0.074	0.048	-10000	0	-0.12	14	14
RAPGEF1	0.036	0.008	-10000	0	0	21	21
RASA1	0.035	0.01	-10000	0	0	35	35
NCK1	0.036	0.009	-10000	0	0	28	28
CBL/APS/CAP/Crk-II	0.048	0.041	-10000	0	-0.11	14	14
TC10/GDP	0.024	0.024	-10000	0	-0.13	12	12
Insulin Receptor/Insulin/SHC/GRB10	0.045	0.067	-10000	0	-0.13	34	34
INPP5D	-0.022	0.025	0.047	22	-0.11	22	44
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	0.037	0.006	-10000	0	0	12	12
IRS1	0.034	0.011	-10000	0	0	52	52
p62DOK/RasGAP	0.035	0.055	-10000	0	-10000	0	0
INS	0.036	0.024	0.098	11	-0.039	33	44
mol:PI-3-4-P2	-0.022	0.024	0.046	22	-0.11	22	44
GRB2	0.036	0.007	-10000	0	0	19	19
EIF4EBP1	-0.037	0.081	0.23	13	-0.21	25	38
PTPRA	0.033	0.016	-10000	0	-0.052	6	6
PIK3CA	0.032	0.013	-10000	0	0	74	74
TC10/GTP/CIP4	0.044	0.029	-10000	0	-0.11	14	14
PDPK1	0.037	0.004	-10000	0	0	6	6
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	0.015	0.052	-10000	0	-0.16	32	32
Insulin Receptor/Insulin/IRS1	0.057	0.047	-10000	0	-0.12	22	22
Insulin Receptor/Insulin/IRS3	0.05	0.033	-10000	0	-0.069	6	6
Par3/Par6	0.077	0.041	-10000	0	-0.11	16	16

×

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

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
MAP4K1	0.018	0.11	0.28	14	-0.39	20	34
CRKL	0.017	0.1	0.24	7	-0.41	21	28
HRAS	0.031	0.099	0.25	3	-0.33	20	23
mol:PIP3	0.061	0.13	0.31	36	-0.38	16	52
SPRED1	0	0	-10000	0	-10000	0	0
SPRED2	0.037	0.004	-10000	0	0	5	5
GAB1	0.024	0.11	0.24	8	-0.42	21	29
FOXO3	0.042	0.17	0.32	27	-0.39	40	67
AKT1	0.049	0.17	0.32	26	-0.39	40	66
BAD	0.042	0.16	0.31	28	-0.37	40	68
megakaryocyte differentiation	0.025	0.1	0.23	8	-0.41	19	27
GSK3B	0.041	0.17	0.32	26	-0.38	43	69
RAF1	0.02	0.087	0.25	5	-0.28	21	26
SHC1	0.034	0.012	-10000	0	0	53	53
STAT3	0.017	0.1	0.24	2	-0.42	21	23
STAT1	0.016	0.19	-10000	0	-0.86	20	20
HRAS/SPRED1	0.023	0.086	0.21	3	-0.27	21	24
cell proliferation	0.012	0.095	0.24	2	-0.4	21	23
PIK3CA	0.033	0.013	-10000	0	0	74	74
TEC	0.037	0.006	-10000	0	0	13	13
RPS6KB1	0.052	0.12	0.27	15	-0.38	21	36
HRAS/SPRED2	0.043	0.096	0.26	5	-0.27	20	25
LYN/TEC/p62DOK	0.063	0.12	-10000	0	-0.41	21	21
MAPK3	0.016	0.079	0.24	11	-0.21	22	33
STAP1	0.021	0.1	0.28	3	-0.41	21	24
GRAP2	0.035	0.01	-10000	0	0	36	36
JAK2	0.017	0.17	-10000	0	-0.72	21	21
STAT1 (dimer)	0.022	0.19	-10000	0	-0.84	20	20
mol:Gleevec	-0.002	0.006	-10000	0	-0.022	1	1
GRB2/SOCS1/VAV1	0.076	0.11	0.29	1	-0.39	21	22
actin filament polymerization	0.026	0.1	0.25	2	-0.4	21	23
LYN	0.032	0.013	-10000	0	0	72	72
STAP1/STAT5A (dimer)	0.022	0.13	0.34	1	-0.54	21	22
PIK3R1	0.033	0.013	-10000	0	0	67	67
CBL/CRKL/GRB2	0.052	0.11	0.28	6	-0.38	21	27
PI3K	0.063	0.13	0.31	11	-0.4	19	30
PTEN	0.026	0.017	-10000	0	0	158	158
SCF/KIT/EPO/EPOR	0.029	0.22	-10000	0	-0.98	20	20
MAPK8	0.011	0.096	0.24	2	-0.4	21	23
STAT3 (dimer)	0.019	0.1	0.27	3	-0.41	21	24
positive regulation of transcription	0.017	0.069	0.21	12	-0.18	18	30
mol:GDP	0.041	0.097	0.22	1	-0.33	21	22
PIK3C2B	0.018	0.1	0.28	5	-0.41	21	26
CBL/CRKL	0.04	0.11	0.27	7	-0.39	21	28
FER	0.023	0.1	0.25	4	-0.42	20	24
SH2B3	0.019	0.1	0.26	1	-0.42	20	21
PDPK1	0.055	0.12	0.29	34	-0.33	19	53
SNAI2	0.026	0.11	0.24	8	-0.42	20	28
positive regulation of cell proliferation	0.027	0.16	-10000	0	-0.66	21	21
KITLG	0.039	0.021	-10000	0	-0.051	20	20
cell motility	0.027	0.16	-10000	0	-0.66	21	21
PTPN6	0.024	0.025	-10000	0	-0.033	64	64
EPOR	0.05	0.084	-10000	0	-0.5	2	2
STAT5A (dimer)	0.033	0.14	0.3	1	-0.54	21	22
SOCS1	0.037	0.004	-10000	0	0	7	7
cell migration	-0.023	0.1	0.4	20	-0.24	2	22
SOS1	0	0	-10000	0	-10000	0	0
EPO	0.027	0.022	-10000	0	-0.036	13	13
VAV1	0.036	0.008	-10000	0	0	26	26
GRB10	0.013	0.089	0.27	5	-0.43	13	18
PTPN11	0.029	0.021	-10000	0	-0.032	51	51
SCF/KIT	0.029	0.11	0.26	2	-0.43	21	23
GO:0007205	-0.002	0.006	0.021	16	-10000	0	16
MAP2K1	0.011	0.077	0.21	5	-0.23	22	27
CBL	0.037	0.005	-10000	0	0	9	9
KIT	0.009	0.24	-10000	0	-1.1	22	22
MAP2K2	0.015	0.082	0.29	10	-0.23	20	30
SHC/Grb2/SOS1	0.053	0.11	-10000	0	-0.38	21	21
STAT5A	0.033	0.14	-10000	0	-0.55	21	21
GRB2	0.036	0.007	-10000	0	0	19	19
response to radiation	0.028	0.11	0.24	8	-0.41	20	28
SHC/GRAP2	0.044	0.031	-10000	0	-0.14	8	8
PTPRO	0.024	0.1	0.23	8	-0.42	19	27
SH2B2	0.025	0.1	0.25	2	-0.41	21	23
DOK1	0.038	0.002	-10000	0	0	2	2
MATK	0.021	0.1	0.24	2	-0.41	20	22
CREBBP	0.053	0.044	0.15	1	-0.12	20	21
BCL2	0.041	0.13	-10000	0	-0.85	5	5

×

Visual signal transduction: Cones

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
Cone Metarhodopsin II/Cone Transducin	0.042	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 +	0.011	0.06	-10000	0	-0.11	87	87
mol:ADP	0	0	-10000	0	-10000	0	0
GNAT2	0.037	0.005	-10000	0	0	9	9
RGS9-1/Gbeta5/R9AP	0.047	0.015	-10000	0	-0.11	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
PDE6H/GNAT2/GTP	0.048	0.013	-10000	0	-10000	0	0
GRK7	0	0	-10000	0	-10000	0	0
CNGB3	0.037	0.005	-10000	0	0	9	9
Cone Metarhodopsin II/X-Arrestin	0.028	0.002	-10000	0	-10000	0	0
mol:Ca2+	-0.012	0.058	0.096	82	-10000	0	82
Cone PDE6	0.058	0.048	-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	86	86
GNAT2/GDP	0.06	0.021	-10000	0	-0.1	1	1
GNB5	0.036	0.007	-10000	0	0	18	18
mol:GMP (4 units)	-0.013	0.036	0.2	12	-10000	0	12
Cone Transducin	0.046	0.011	-10000	0	-10000	0	0
SLC24A2	0.031	0.015	-10000	0	0	95	95
GNB3/GNGT2	0.027	0.006	-10000	0	-10000	0	0
GNB3	0.036	0.008	-10000	0	0	22	22
GNAT2/GTP	0.027	0.004	-10000	0	-10000	0	0
CNGA3	0.023	0.018	-10000	0	0	200	200
ARR3	0.038	0.002	-10000	0	0	2	2
absorption of light	0	0	-10000	0	-10000	0	0
cGMP/Cone CNG Channel	0.011	0.06	-10000	0	-0.11	87	87
mol:Pi	0.047	0.015	-10000	0	-0.11	1	1
Cone CNG Channel	0.031	0.076	-10000	0	-0.11	82	82
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
mol:K +	0.031	0.015	-10000	0	0	95	95
RGS9	0.036	0.007	-10000	0	0	18	18
PDE6C	0.028	0.017	-10000	0	0	132	132
GNGT2	0	0	-10000	0	-10000	0	0
mol:cGMP (4 units)	0	0	-10000	0	-10000	0	0
PDE6H	0.036	0.008	-10000	0	0	27	27

×

a4b1 and a4b7 Integrin signaling

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.029	0.016	-9999	0	117	117
ITGB7	0.037	0.006	-9999	0	14	14
ITGA4	0.037	0.006	-9999	0	13	13
alpha4/beta7 Integrin	0.053	0.012	-9999	-9999	0	0
alpha4/beta1 Integrin	0.042	0.024	-9999	-9999	0	0

×

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	0.011	-10000	0	0	50	50
NFATC1	0.001	0.11	0.24	1	-0.39	25	26
NFATC2	-0.031	0.084	0.16	2	-0.17	102	104
NFATC3	0.009	0.019	-10000	0	-0.1	14	14
YWHAE	0.036	0.009	-10000	0	0	29	29
Calcineurin A alpha-beta B1/CABIN1	-0.013	0.073	0.16	3	-0.21	39	42
Exportin 1/Ran/NUP214	0.07	0.03	-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	-0.21	27	27
BCL2/BAX	0.049	0.024	-10000	0	-0.14	4	4
CaM/Ca2+/Calcineurin A alpha-beta B1	0.021	0.026	-10000	0	-0.13	14	14
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	14	14
BAX	0.035	0.01	-10000	0	0	41	41
MAPK14	0.037	0.005	-10000	0	0	8	8
BAD	0.037	0.007	-10000	0	0	16	16
CABIN1/MEF2D	0.004	0.079	-10000	0	-0.21	37	37
Calcineurin A alpha-beta B1/BCL2	0.036	0.007	-10000	0	0	17	17
FKBP8	0.036	0.008	-10000	0	0	24	24
activation-induced cell death of T cells	-0.004	0.079	0.2	37	-10000	0	37
KPNB1	0.036	0.008	-10000	0	0	23	23
KPNA2	0.035	0.01	-10000	0	0	39	39
XPO1	0.037	0.003	-10000	0	0	4	4
SFN	0.032	0.014	-10000	0	0	80	80
MAP3K8	0.025	0.018	-10000	0	0	176	176
NFAT4/CK1 alpha	0.024	0.044	-10000	0	-0.17	16	16
MEF2D/NFAT1/Cbp/p300	0.018	0.11	0.23	1	-0.22	37	38
CABIN1	-0.013	0.073	0.16	3	-0.21	39	42
CALM1	0.033	0.012	-10000	0	0	60	60
RAN	0.037	0.006	-10000	0	0	13	13
MAP3K1	0.036	0.008	-10000	0	0	23	23
CAMK4	0.037	0.005	-10000	0	0	10	10
mol:Ca2+	0	0.001	-10000	0	-10000	0	0
MAPK3	0.037	0.003	-10000	0	0	4	4
YWHAH	0.032	0.013	-10000	0	0	73	73
Calcineurin A alpha-beta B1/AKAP79/PKA	0.05	0.017	-10000	0	-10000	0	0
YWHAB	0.034	0.011	-10000	0	0	44	44
MAPK8	0.029	0.016	-10000	0	0	122	122
MAPK9	0.037	0.006	-10000	0	0	14	14
YWHAG	0	0	-10000	0	-10000	0	0
FKBP1A	0.033	0.012	-10000	0	0	63	63
NFAT1-c-4/YWHAQ	0.002	0.11	-10000	0	-0.36	24	24
PRKCH	0.034	0.011	-10000	0	0	46	46
CABIN1/Cbp/p300	0.048	0.029	-10000	0	-0.14	8	8
CASP3	0.035	0.009	-10000	0	0	31	31
PIM1	0.037	0.005	-10000	0	0	11	11
Calcineurin A alpha-beta B1/FKBP12/FK506	0.02	0.019	-10000	0	-0.1	10	10
apoptosis	0.02	0.035	-10000	0	-0.16	13	13
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.001	0.097	-10000	0	-0.3	29	29
PRKCB	0	0	-10000	0	-10000	0	0
PRKCE	0.038	0.002	-10000	0	0	2	2
JNK2/NFAT4	0.026	0.037	-10000	0	-0.12	20	20
BAD/BCL-XL	0.048	0.026	-10000	0	-0.14	5	5
PRKCD	0.035	0.01	-10000	0	0	42	42
NUP214	0.036	0.008	-10000	0	0	22	22
PRKCZ	0	0	-10000	0	-10000	0	0
PRKCA	0.037	0.004	-10000	0	0	6	6
PRKCG	0.035	0.009	-10000	0	0	31	31
PRKCQ	0.027	0.017	-10000	0	0	143	143
FKBP38/BCL2	0.052	0.015	-10000	0	-10000	0	0
EP300	0.034	0.011	-10000	0	0	49	49
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.034	0.011	-10000	0	0	50	50
NFATc/JNK1	0.01	0.1	-10000	0	-0.37	25	25
CaM/Ca2+/FKBP38	0.04	0.031	-10000	0	-0.11	14	14
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSNK1A1	-0.016	0.021	0.088	12	-0.11	9	21
CaM/Ca2+/CAMK IV	0.041	0.03	-10000	0	-0.11	14	14
NFATc/ERK1	0.02	0.11	-10000	0	-0.37	25	25
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	0.02	0.09	-10000	0	-0.21	27	27
NR4A1	-0.022	0.079	0.17	5	-0.21	34	39
GSK3B	0.035	0.01	-10000	0	0	37	37
positive T cell selection	0.009	0.019	-10000	0	-0.1	14	14
NFAT1/CK1 alpha	-0.018	0.072	0.14	1	-0.18	46	47
RCH1/ KPNB1	0.037	0.058	-10000	0	-0.15	44	44
YWHAQ	0.037	0.005	-10000	0	0	8	8
PRKACA	0.036	0.007	-10000	0	0	17	17
AKAP5	0.035	0.009	-10000	0	0	34	34
MEF2D	0.037	0.006	-10000	0	0	13	13
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.036	0.008	-10000	0	0	21	21
NFATc/p38 alpha	0.02	0.11	0.25	1	-0.37	25	26
CREBBP	0.037	0.004	-10000	0	0	7	7
BCL2	0.036	0.007	-10000	0	0	17	17

×

LPA4-mediated signaling events

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.Total.Perturbations
ADCY4	-0.009	0.001	0	2	-9999	2
ADCY5	-0.009	0.001	0	2	-9999	2
ADCY6	-0.018	0.003	0	18	-9999	18
ADCY7	-0.017	0.005	0	37	-9999	37
ADCY1	-0.013	0.009	0	152	-9999	152
ADCY2	-0.018	0.003	0	18	-9999	18
ADCY3	-0.009	0.001	0	2	-9999	2
ADCY8	-0.016	0.007	0	72	-9999	72
PRKCE	-0.012	0.001	0	2	-9999	2
ADCY9	-0.018	0.003	0	13	-9999	13
mol:DAG	0	0	-10000	0	-9999	0
cAMP biosynthetic process	0.016	0.047	0.18	13	-9999	13

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	0.044	0.039	-10000	0	-0.14	19	19
ATM	0.035	0.01	-10000	0	0	38	38
UBE2D3	0.037	0.006	-10000	0	0	12	12
PRKDC	0.035	0.01	-10000	0	0	42	42
ATR	0.036	0.008	-10000	0	0	27	27
UBE2L3	0.035	0.009	-10000	0	0	33	33
FANCD2	0.009	0.035	-10000	0	-0.2	14	14
protein ubiquitination	0.077	0.057	-10000	0	-0.12	21	21
XRCC5	0.037	0.005	-10000	0	0	10	10
XRCC6	0.035	0.01	-10000	0	0	41	41
M/R/N Complex	0.071	0.025	-10000	0	-0.12	4	4
MRE11A	0.037	0.005	-10000	0	0	10	10
DNA-PK	0.059	0.05	-10000	0	-0.14	22	22
FA complex/FANCD2/Ubiquitin	0.003	0.085	-10000	0	-0.29	27	27
FANCF	0.036	0.008	-10000	0	0	25	25
BRCA1	0.037	0.006	-10000	0	0	14	14
CCNE1	0.033	0.012	-10000	0	0	60	60
CDK2/Cyclin E1	0.046	0.024	-10000	0	-0.14	2	2
FANCG	0.031	0.014	-10000	0	0	86	86
BRCA1/BACH1/BARD1	0.047	0.038	-10000	0	-0.14	19	19
FANCE	0.037	0.004	-10000	0	0	7	7
FANCC	0.036	0.007	-10000	0	0	19	19
NBN	0.037	0.006	-10000	0	0	13	13
FANCA	0.036	0.007	-10000	0	0	20	20
DNA repair	-0.014	0.084	0.24	9	-0.29	15	24
BRCA1/BARD1/ubiquitin	0.047	0.038	-10000	0	-0.14	19	19
BARD1/DNA-PK	0.07	0.067	-10000	0	-0.14	35	35
FANCL	0	0	-10000	0	-10000	0	0
mRNA polyadenylation	-0.044	0.039	0.14	19	-10000	0	19
BRCA1/BARD1/CTIP/M/R/N Complex	0.01	0.065	-10000	0	-0.22	27	27
BRCA1/BACH1/BARD1/TopBP1	0.053	0.062	-10000	0	-0.13	47	47
BRCA1/BARD1/P53	0.068	0.068	-10000	0	-0.13	46	46
BARD1/CSTF1/BRCA1	0.061	0.043	-10000	0	-0.12	19	19
BRCA1/BACH1	0.037	0.006	-10000	0	0	14	14
BARD1	0.036	0.008	-10000	0	0	23	23
PCNA	0.033	0.012	-10000	0	0	63	63
BRCA1/BARD1/UbcH5C	0.065	0.043	-10000	0	-0.13	20	20
BRCA1/BARD1/UbcH7	0.061	0.047	-10000	0	-0.13	23	23
BRCA1/BARD1/RAD51/PCNA	0.071	0.062	-10000	0	-0.13	33	33
BARD1/DNA-PK/P53	0.069	0.084	-10000	0	-0.13	57	57
BRCA1/BARD1/Ubiquitin	0.047	0.038	-10000	0	-0.14	19	19
BRCA1/BARD1/CTIP	0.041	0.058	-10000	0	-0.13	44	44
FA complex	0.012	0.058	-10000	0	-0.18	35	35
BARD1/EWS	0.044	0.039	-10000	0	-0.14	19	19
RBBP8	-0.02	0.009	-10000	0	-10000	0	0
TP53	0.032	0.013	-10000	0	0	71	71
TOPBP1	0.034	0.011	-10000	0	0	50	50
G1/S transition of mitotic cell cycle	-0.065	0.067	0.13	46	-10000	0	46
BRCA1/BARD1	0.084	0.06	-10000	0	-0.13	21	21
CSTF1	0.035	0.01	-10000	0	0	39	39
BARD1/EWS-Fli1	0.022	0.03	-10000	0	-0.13	19	19
CDK2	0.035	0.01	-10000	0	0	43	43
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	0.036	0.007	-10000	0	0	17	17
RAD50	0.037	0.006	-10000	0	0	13	13
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	0.047	0.038	-10000	0	-0.14	19	19
EWSR1	0.035	0.009	-10000	0	0	34	34

×

Aurora A signaling

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
Aurora A/GADD45A	0.024	0.067	0.16	1	-0.22	26	27
BIRC5	0.03	0.015	-10000	0	0	109	109
NFKBIA	-0.009	0.045	0.23	4	-0.18	18	22
CPEB1	0.034	0.012	-10000	0	0	56	56
AKT1	-0.006	0.036	0.25	2	-0.18	9	11
NDEL1	0.036	0.008	-10000	0	0	21	21
Aurora A/BRCA1	0.028	0.052	-10000	0	-0.17	23	23
NDEL1/TACC3	0.038	0.068	-10000	0	-0.18	29	29
GADD45A	0.032	0.014	-10000	0	0	79	79
GSK3B	0.036	0.015	0.089	26	0	37	63
PAK1/Aurora A	0.032	0.057	0.16	1	-0.18	23	24
MDM2	0.034	0.012	-10000	0	0	54	54
JUB	0	0	-10000	0	-10000	0	0
TPX2	-0.017	0.011	-10000	0	-10000	0	0
TP53	0.006	0.064	-10000	0	-0.24	25	25
DLG7	0.002	0.04	0.1	17	-0.17	21	38
AURKAIP1	0.036	0.009	-10000	0	0	29	29
ARHGEF7	0.033	0.012	-10000	0	0	58	58
G2 phase of mitotic cell cycle	0	0	-10000	0	-10000	0	0
Aurora A/NDEL1/TACC3	0.04	0.072	-10000	0	-0.2	29	29
G2/M transition of mitotic cell cycle	0.028	0.051	-10000	0	-0.17	23	23
AURKA	0.011	0.051	0.14	15	-0.21	21	36
AURKB	0.009	0.032	-10000	0	-0.13	21	21
CDC25B	0.003	0.073	-10000	0	-0.27	28	28
G2/M transition checkpoint	0.002	0.041	-10000	0	-0.16	23	23
mRNA polyadenylation	0.021	0.056	-10000	0	-0.17	23	23
Aurora A/CPEB	0.022	0.056	-10000	0	-0.17	23	23
Aurora A/TACC1/TRAP/chTOG	0.051	0.086	-10000	0	-0.22	25	25
BRCA1	0.037	0.006	-10000	0	0	14	14
centrosome duplication	0.031	0.057	0.16	1	-0.18	23	24
regulation of centrosome cycle	0.037	0.067	-10000	0	-0.18	29	29
spindle assembly	0.049	0.084	-10000	0	-0.22	25	25
TDRD7	0.034	0.011	-10000	0	0	44	44
Aurora A/RasGAP/Survivin	0.037	0.083	-10000	0	-0.2	30	30
CENPA	0	0.079	-10000	0	-0.32	26	26
Aurora A/PP2A	0.033	0.057	-10000	0	-0.19	23	23
meiosis	0	0	-10000	0	-10000	0	0
protein catabolic process	0.001	0.056	0.15	2	-0.21	21	23
negative regulation of DNA binding	0.004	0.073	0.16	1	-0.26	27	28
prophase	0	0	-10000	0	-10000	0	0
GIT1/beta-PIX	0.042	0.045	-10000	0	-0.14	27	27
RASA1	0.035	0.01	-10000	0	0	35	35
Ajuba/Aurora A	0.002	0.041	-10000	0	-0.16	23	23
mitotic prometaphase	-0.004	0.011	0.069	11	-10000	0	11
proteasomal ubiquitin-dependent protein catabolic process	0.011	0.051	0.14	15	-0.21	21	36
TACC1	0.036	0.008	-10000	0	0	22	22
TACC3	0.033	0.012	-10000	0	0	57	57
Aurora A/Antizyme1	0.047	0.062	-10000	0	-0.18	23	23
Aurora A/RasGAP	0.029	0.067	-10000	0	-0.24	23	23
OAZ1	0.036	0.008	-10000	0	0	23	23
RAN	0.037	0.006	-10000	0	0	13	13
mitosis	0	0	-10000	0	-10000	0	0
PRKACA	0.037	0.014	0.089	26	0	17	43
GIT1	0.037	0.004	-10000	0	0	7	7
GIT1/beta-PIX/PAK1	0.059	0.048	-10000	0	-0.12	26	26
Importin alpha/Importin beta/TPX2	-0.017	0.011	-10000	0	-10000	0	0
PPP2R5D	0.037	0.005	-10000	0	0	10	10
Aurora A/TPX2	-0.006	0.069	-10000	0	-0.22	31	31
PAK1	0.036	0.007	-10000	0	0	18	18
CKAP5	0.035	0.01	-10000	0	0	40	40

×

Regulation of Telomerase

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
Telomerase catalytic core complex	0.024	0.16	-10000	0	-0.56	11	11
RAD9A	0.037	0.006	-10000	0	0	12	12
AP1	0.01	0.081	-10000	0	-0.17	73	73
IFNAR2	0.034	0.021	-10000	0	-0.036	37	37
AKT1	0.012	0.056	-10000	0	-0.25	19	19
ER alpha/Oestrogen	0.024	0.015	-10000	0	-10000	0	0
NFX1/SIN3/HDAC complex	-0.007	0.086	-10000	0	-0.26	36	36
EGF	0.034	0.015	-10000	0	-0.033	18	18
SMG5	0.037	0.006	-10000	0	0	13	13
SMG6	0.036	0.008	-10000	0	0	21	21
SP3/HDAC2	0.039	0.053	-10000	0	-0.16	22	22
TERT/c-Abl	0.03	0.17	-10000	0	-0.54	16	16
SAP18	0.035	0.011	-10000	0	0	46	46
MRN complex	0.071	0.025	-10000	0	-0.12	4	4
WT1	0.033	0.021	-10000	0	-0.035	37	37
WRN	0.036	0.008	-10000	0	0	27	27
SP1	0.034	0.024	-10000	0	-0.043	39	39
SP3	0.034	0.016	-10000	0	-0.031	25	25
TERF2IP	0.035	0.01	-10000	0	0	38	38
Telomerase/Nucleolin	0.046	0.16	-10000	0	-0.54	14	14
Mad/Max	0.048	0.028	-10000	0	-10000	0	0
TERT	0.02	0.16	-10000	0	-0.57	11	11
CCND1	-0.018	0.29	-10000	0	-0.95	40	40
MAX	0.032	0.018	-10000	0	-0.031	29	29
RBBP7	0.037	0.005	-10000	0	0	10	10
RBBP4	0.033	0.012	-10000	0	0	61	61
TERF2	0.029	0.011	0.085	6	0	51	57
PTGES3	0.036	0.008	-10000	0	0	27	27
SIN3A	0	0.001	-10000	0	-10000	0	0
Telomerase/911	0.044	0.11	-10000	0	-0.47	13	13
CDKN1B	-0.026	0.082	0.14	4	-0.34	26	30
RAD1	0.036	0.008	-10000	0	0	23	23
XRCC5	0.037	0.005	-10000	0	0	10	10
XRCC6	0.035	0.01	-10000	0	0	41	41
SAP30	0.037	0.007	-10000	0	0	19	19
TRF2/PARP2	0.031	0.057	-10000	0	-0.14	46	46
UBE3A	0.036	0.011	-10000	0	-0.03	9	9
JUN	0.033	0.017	-10000	0	-0.031	19	19
E6	0	0.003	-10000	0	-10000	0	0
HPV-16 E6/E6AP	0.025	0.021	-10000	0	-0.044	24	24
FOS	0.024	0.021	-10000	0	-0.031	17	17
IFN-gamma/IRF1	0.035	0.069	-10000	0	-0.18	38	38
PARP2	0.034	0.011	-10000	0	0	52	52
BLM	0.03	0.015	-10000	0	0	107	107
Telomerase	0.007	0.09	-10000	0	-0.26	35	35
IRF1	0.027	0.039	-10000	0	-0.12	29	29
ESR1	0.036	0.009	-10000	0	0	32	32
KU/TER	0.048	0.029	-10000	0	-0.14	9	9
ATM/TRF2	0.045	0.028	-10000	0	-0.1	9	9
ubiquitin-dependent protein catabolic process	0.001	0.084	-10000	0	-0.26	29	29
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	0	0.086	-10000	0	-0.27	29	29
HDAC1	0.036	0.008	-10000	0	0	24	24
HDAC2	0.031	0.024	-10000	0	-0.042	34	34
ATM	0.022	0.037	0.13	37	-0.18	5	42
SMAD3	-0.019	0.013	0.022	24	-10000	0	24
ABL1	0.032	0.013	-10000	0	0	71	71
MXD1	0.035	0.016	-10000	0	-0.031	29	29
MRE11A	0.037	0.005	-10000	0	0	10	10
HUS1	0.026	0.017	-10000	0	0	154	154
RPS6KB1	0.037	0.005	-10000	0	0	9	9
TERT/NF kappa B1/14-3-3	0.041	0.18	-10000	0	-0.56	15	15
NR2F2	0.023	0.023	-10000	0	-0.03	49	49
MAPK3	-0.018	0.016	0.021	61	-10000	0	61
MAPK1	-0.016	0.016	0.021	58	-10000	0	58
TGFB1/TGF beta receptor Type II	0.033	0.012	-10000	0	0	57	57
NFKB1	0.036	0.007	-10000	0	0	18	18
HNRNPC	0.035	0.009	-10000	0	0	31	31
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0.022	0.037	0.13	37	-0.18	5	42
NBN	0.037	0.006	-10000	0	0	13	13
EGFR	0.01	0.017	-10000	0	-0.031	1	1
mol:Oestrogen	0	0.002	-10000	0	-10000	0	0
EGF/EGFR	-0.003	0.057	-10000	0	-0.14	65	65
MYC	0.029	0.02	-10000	0	-0.03	21	21
IL2	0.035	0.023	-10000	0	-0.043	37	37
KU	0.048	0.029	-10000	0	-0.14	9	9
RAD50	0.037	0.006	-10000	0	0	13	13
HSP90AA1	0.035	0.01	-10000	0	0	35	35
TGFB1	0.033	0.012	-10000	0	0	57	57
TRF2/BLM	0.013	0.077	-10000	0	-0.14	92	92
FRAP1	0	0	-10000	0	-10000	0	0
KU/TERT	0.047	0.17	-10000	0	-0.56	11	11
SP1/HDAC2	0.043	0.047	-10000	0	-0.14	14	14
PINX1	0	0	-10000	0	-10000	0	0
Telomerase/EST1A	0.043	0.16	-10000	0	-0.51	14	14
Smad3/Myc	0.014	0.049	-10000	0	-0.12	41	41
911 complex	0.049	0.04	-10000	0	-0.12	5	5
IFNG	0.028	0.04	-10000	0	-0.12	31	31
Telomerase/PinX1	0.035	0.15	-10000	0	-0.51	13	13
Telomerase/AKT1/mTOR/p70S6K	0.013	0.12	-10000	0	-0.38	26	26
SIN3B	0.036	0.009	-10000	0	0	27	27
YWHAE	0.036	0.009	-10000	0	0	29	29
Telomerase/EST1B	0.047	0.16	-10000	0	-0.52	12	12
response to DNA damage stimulus	0.008	0.019	-10000	0	-0.086	12	12
MRN complex/TRF2/Rap1	0.079	0.072	-10000	0	-0.14	39	39
TRF2/WRN	0.036	0.045	-10000	0	-0.11	39	39
Telomerase/hnRNP C1/C2	0.045	0.16	-10000	0	-0.52	14	14
E2F1	0.032	0.021	-10000	0	-0.035	34	34
ZNFX1	0	0.001	-10000	0	-10000	0	0
PIF1	0	0	-10000	0	-10000	0	0
NCL	0.036	0.007	-10000	0	0	18	18
DKC1	0.036	0.008	-10000	0	0	21	21
telomeric DNA binding	0	0	-10000	0	-10000	0	0

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.036	0.008	-10000	0	0	25	25
alphaV beta3 Integrin	0.045	0.042	-10000	0	-0.14	24	24
PTK2	0.011	0.11	-10000	0	-0.28	49	49
positive regulation of JNK cascade	0.023	0.09	-10000	0	-0.26	33	33
CDC42/GDP	0.038	0.13	0.31	1	-0.35	35	36
Rac1/GDP	0.027	0.11	0.3	1	-0.35	21	22
RAP1B	0	0	-10000	0	-10000	0	0
RAP1A	0.037	0.005	-10000	0	0	10	10
CTNNB1	0.036	0.007	-10000	0	0	17	17
CDC42/GTP	0.031	0.11	-10000	0	-0.32	33	33
nectin-3/I-afadin	0.045	0.027	-10000	0	-0.14	5	5
RAPGEF1	0.006	0.12	0.28	4	-0.36	39	43
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.005	0.13	-10000	0	-0.39	39	39
PDGFB-D/PDGFRB	0.036	0.008	-10000	0	0	25	25
TLN1	-0.009	0.056	0.16	15	-0.22	16	31
Rap1/GTP	0	0.086	-10000	0	-0.27	39	39
IQGAP1	0.034	0.011	-10000	0	0	47	47
Rap1/GTP/I-afadin	0.044	0.015	-10000	0	-0.1	1	1
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0.045	0.027	-10000	0	-0.14	5	5
PVR	0.036	0.009	-10000	0	0	28	28
Necl-5(dimer)	0.036	0.009	-10000	0	0	28	28
mol:GDP	0.024	0.14	0.31	1	-0.42	36	37
MLLT4	0.035	0.01	-10000	0	0	36	36
PIK3CA	0.032	0.013	-10000	0	0	74	74
PI3K	0.059	0.089	-10000	0	-0.13	73	73
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0.051	0.016	-10000	0	-10000	0	0
positive regulation of lamellipodium assembly	0.018	0.085	-10000	0	-0.3	19	19
PVRL1	0.037	0.005	-10000	0	0	9	9
PVRL3	0.033	0.012	-10000	0	0	60	60
PVRL2	0.035	0.009	-10000	0	0	31	31
PIK3R1	0.033	0.013	-10000	0	0	67	67
CDH1	0.035	0.01	-10000	0	0	39	39
CLDN1	0.036	0.008	-10000	0	0	27	27
JAM-A/CLDN1	0.076	0.045	-10000	0	-0.11	8	8
SRC	0.01	0.14	-10000	0	-0.42	39	39
ITGB3	0.037	0.004	-10000	0	0	6	6
nectin-1(dimer)/I-afadin/I-afadin	0.051	0.016	-10000	0	-10000	0	0
FARP2	0.029	0.14	-10000	0	-0.43	24	24
RAC1	0.026	0.017	-10000	0	0	156	156
CTNNA1	0.036	0.007	-10000	0	0	19	19
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0.06	0.035	-10000	0	-0.12	5	5
nectin-1/I-afadin	0.051	0.016	-10000	0	-10000	0	0
nectin-2/I-afadin	0.049	0.023	-10000	0	-0.14	3	3
RAC1/GTP/IQGAP1/filamentous actin	0.025	0.043	-10000	0	-0.12	32	32
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0.061	0.034	-10000	0	-0.12	5	5
CDC42/GTP/IQGAP1/filamentous actin	0.036	0.042	-10000	0	-0.11	34	34
F11R	0.034	0.011	-10000	0	0	52	52
positive regulation of filopodium formation	0.023	0.09	-10000	0	-0.26	33	33
alphaV/beta3 Integrin/Talin	0.029	0.089	0.22	29	-0.2	34	63
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0.049	0.023	-10000	0	-0.14	3	3
nectin-2(dimer)/I-afadin/I-afadin	0.049	0.023	-10000	0	-0.14	3	3
PIP5K1C	-0.011	0.039	0.093	4	-0.2	15	19
VAV2	0.025	0.15	-10000	0	-0.49	25	25
RAP1/GDP	0.027	0.11	0.27	1	-0.32	37	38
ITGAV	0.035	0.009	-10000	0	0	34	34
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0.058	0.038	-10000	0	-0.13	7	7
nectin-3(dimer)/I-afadin/I-afadin	0.045	0.027	-10000	0	-0.14	5	5
Rac1/GTP	0.024	0.1	-10000	0	-0.36	19	19
PTPRM	0.008	0.043	-10000	0	-0.22	16	16
E-cadherin/beta catenin/alpha catenin	0.085	0.06	-10000	0	-0.12	14	14
adherens junction assembly	0	0	-10000	0	-10000	0	0
CDC42	0.036	0.008	-10000	0	0	26	26

×

VEGFR1 specific signals

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
VEGFR1 homodimer/VEGFB homodimer	0.033	0.027	-10000	0	-10000	0	0
VEGFR1 homodimer/NRP1	-0.014	0.015	-10000	0	-10000	0	0
mol:DAG	-0.018	0.033	0.19	2	-10000	0	2
VEGFR1 homodimer/NRP1/VEGFR 121	-0.003	0.06	-10000	0	-0.19	8	8
CaM/Ca2+	-0.022	0.043	0.17	4	-0.19	2	6
HIF1A	0.041	0.013	-10000	0	-10000	0	0
GAB1	0.034	0.012	-10000	0	0	55	55
AKT1	-0.034	0.086	0.2	4	-0.31	24	28
PLCG1	-0.018	0.034	0.19	2	-10000	0	2
NOS3	0.003	0.071	-10000	0	-0.33	7	7
CBL	0.037	0.005	-10000	0	0	9	9
mol:NO	0.011	0.076	-10000	0	-0.32	7	7
FLT1	0.016	0.007	-10000	0	-10000	0	0
PGF	0.032	0.013	-10000	0	0	73	73
VEGFR1 homodimer/NRP2/VEGFR121	0.009	0.073	-10000	0	-0.2	8	8
CALM1	0.033	0.012	-10000	0	0	60	60
PIK3CA	0.032	0.013	-10000	0	0	74	74
eNOS/Hsp90	0.031	0.089	-10000	0	-0.32	7	7
endothelial cell proliferation	-0.002	0.052	0.2	1	-0.25	3	4
mol:Ca2+	-0.018	0.033	0.19	2	-10000	0	2
MAPK3	-0.027	0.033	0.15	2	-10000	0	2
MAPK1	-0.026	0.035	0.15	2	-0.19	1	3
PIK3R1	0.033	0.013	-10000	0	0	67	67
PLGF homodimer	0.032	0.013	-10000	0	0	73	73
PRKACA	0.036	0.007	-10000	0	0	17	17
RP11-342D11.1	0	0	-10000	0	-10000	0	0
CAV1	0.016	0.019	-10000	0	0	287	287
VEGFA homodimer	0.024	0.018	-10000	0	0	181	181
VEGFR1 homodimer/VEGFA homodimer	0.02	0.038	-10000	0	-0.21	8	8
platelet activating factor biosynthetic process	-0.023	0.051	-10000	0	-10000	0	0
PI3K	0.038	0.079	-10000	0	-0.2	16	16
PRKCA	-0.023	0.033	0.17	2	-10000	0	2
PRKCB	-0.016	0.031	0.17	2	-10000	0	2
VEGFR1 homodimer/PLGF homodimer	0.03	0.028	-10000	0	-10000	0	0
VEGFA	0.024	0.018	-10000	0	0	181	181
VEGFB	0.037	0.005	-10000	0	0	9	9
mol:IP3	-0.018	0.033	0.19	2	-10000	0	2
RASA1	-0.026	0.029	0.16	4	-0.2	6	10
NRP2	0.037	0.005	-10000	0	0	8	8
VEGFR1 homodimer	0.016	0.007	-10000	0	-10000	0	0
VEGFB homodimer	0.037	0.005	-10000	0	0	9	9
NCK1	0.036	0.009	-10000	0	0	28	28
eNOS/Caveolin-1	0	0.073	-10000	0	-0.33	8	8
PTPN11	0.037	0.006	-10000	0	0	12	12
mol:PI-3-4-5-P3	0.036	0.078	-10000	0	-0.2	16	16
mol:L-citrulline	0.011	0.076	-10000	0	-0.32	7	7
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	0.024	0.085	-10000	0	-0.2	10	10
VEGFR1 homodimer/VEGFA homodimer/NCK1	0.009	0.073	-10000	0	-0.21	9	9
CD2AP	0.034	0.011	-10000	0	0	47	47
PI3K/GAB1	0.043	0.089	-10000	0	-0.2	23	23
PDPK1	-0.033	0.063	0.17	16	-0.26	3	19
VEGFR1 homodimer/VEGFA homodimer/SHP2	0.008	0.075	-10000	0	-0.21	11	11
mol:NADP	0.011	0.076	-10000	0	-0.32	7	7
HSP90AA1	0.035	0.01	-10000	0	0	35	35
ubiquitin-dependent protein catabolic process	0.023	0.083	-10000	0	-0.2	10	10
VEGFR1 homodimer/NRP2	0.033	0.027	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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
Insulin responsive Vesicles	0.016	0.1	-10000	0	-0.25	42	42
CaM/Ca2+	0.021	0.026	-10000	0	-0.13	14	14
AKT1	0.033	0.012	-10000	0	0	58	58
AKT2	0.036	0.007	-10000	0	0	18	18
STXBP4	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	-0.005	0.095	0.18	2	-0.26	45	47
YWHAZ	0.036	0.008	-10000	0	0	21	21
CALM1	0.033	0.012	-10000	0	0	60	60
YWHAQ	0.037	0.005	-10000	0	0	8	8
TBC1D4	-0.019	0.009	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.032	0.013	-10000	0	0	73	73
YWHAB	0.034	0.011	-10000	0	0	44	44
SNARE/Synip	0.04	0.036	-10000	0	-0.12	19	19
YWHAG	0	0	-10000	0	-10000	0	0
ASIP	0.035	0.01	-10000	0	0	35	35
PRKCI	0.036	0.008	-10000	0	0	25	25
AS160/CaM/Ca2+	0.021	0.026	-10000	0	-0.13	14	14
RHOQ	0.037	0.006	-10000	0	0	15	15
GYS1	0	0.035	-10000	0	-0.2	7	7
PRKCZ	0	0	-10000	0	-10000	0	0
TRIP10	0.036	0.008	-10000	0	0	26	26
TC10/GTP/CIP4/Exocyst	0.044	0.029	-10000	0	-0.11	14	14
AS160/14-3-3	-0.006	0.098	-10000	0	-0.38	21	21
VAMP2	0.034	0.011	-10000	0	0	50	50
SLC2A4	-0.007	0.1	0.19	2	-0.28	46	48
STX4	0.037	0.007	-10000	0	0	16	16
GSK3B	0.003	0.078	-10000	0	-0.3	29	29
SFN	0.032	0.014	-10000	0	0	80	80
LNPEP	0.037	0.005	-10000	0	0	10	10
YWHAE	0.036	0.009	-10000	0	0	29	29

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	0.032	0.15	-10000	0	-0.98	10	10
CLOCK	0.035	0.019	-10000	0	-0.067	10	10
TIMELESS/CRY2	0.025	0.16	-10000	0	-1	10	10
DEC1/BMAL1	0.035	0.056	-10000	0	-0.14	42	42
ATR	0.036	0.008	-10000	0	0	27	27
NR1D1	0.01	0.058	-10000	0	-0.38	2	2
ARNTL	0.033	0.02	-10000	0	-0.07	8	8
TIMELESS	-0.007	0.15	-10000	0	-1.1	10	10
NPAS2	0.038	0.017	-10000	0	-0.067	10	10
CRY2	0.036	0.008	-10000	0	0	25	25
mol:CO	-0.01	0.027	0.13	10	-0.069	47	57
CHEK1	0.034	0.011	-10000	0	0	52	52
mol:HEME	0.01	0.027	0.069	47	-0.13	10	57
PER1	0.034	0.012	-10000	0	0	53	53
BMAL/CLOCK/NPAS2	0.056	0.076	0.23	1	-0.14	50	51
BMAL1/CLOCK	0.009	0.12	-10000	0	-0.51	18	18
S phase of mitotic cell cycle	0.032	0.15	-10000	0	-0.98	10	10
TIMELESS/CHEK1/ATR	0.032	0.16	-10000	0	-1	10	10
mol:NADPH	0.01	0.027	0.069	47	-0.13	10	57
PER1/TIMELESS	0.024	0.16	-10000	0	-1	10	10
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.037	0.007	-10000	0	0	16	16

×

Glucocorticoid receptor regulatory network

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
PCK2	-0.024	0.1	-10000	0	-0.59	10	10
SMARCC2	0.034	0.011	-10000	0	0	52	52
SMARCC1	0.035	0.01	-10000	0	0	35	35
TBX21	0.03	0.055	0.34	1	-10000	0	1
SUMO2	0.035	0.018	-10000	0	-0.031	31	31
STAT1 (dimer)	0.037	0.038	0.1	5	-0.17	13	18
FKBP4	0.035	0.01	-10000	0	0	36	36
FKBP5	0.029	0.016	-10000	0	0	121	121
GR alpha/HSP90/FKBP51/HSP90	-0.008	0.078	-10000	0	-0.21	8	8
PRL	0.038	0.05	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	-0.04	0.12	-10000	0	-0.32	1	1
RELA	0.016	0.11	0.17	32	-0.16	125	157
FGG	-0.048	0.1	-10000	0	-0.32	2	2
GR beta/TIF2	-0.023	0.076	-10000	0	-0.24	1	1
IFNG	0.034	0.078	-10000	0	-10000	0	0
apoptosis	-0.018	0.2	0.45	20	-0.52	29	49
CREB1	0.044	0.009	-10000	0	-10000	0	0
histone acetylation	0.021	0.052	-10000	0	-10000	0	0
BGLAP	0.039	0.06	-10000	0	-10000	0	0
GR/PKAc	0.023	0.091	-10000	0	-0.18	19	19
NF kappa B1 p50/RelA	0.027	0.18	0.29	27	-0.26	121	148
SMARCD1	0.036	0.007	-10000	0	0	18	18
MDM2	-0.008	0.035	-10000	0	-10000	0	0
GATA3	0.034	0.021	-10000	0	-10000	0	0
AKT1	0.029	0.029	0.16	8	-0.086	17	25
CSF2	0.004	0.032	-10000	0	-10000	0	0
GSK3B	0.033	0.019	-10000	0	-0.031	27	27
NR1I3	-0.013	0.18	0.45	16	-0.5	17	33
CSN2	-0.045	0.087	-10000	0	-0.29	2	2
BRG1/BAF155/BAF170/BAF60A	0.065	0.075	-10000	0	-0.16	40	40
NFATC1	0.042	0.008	-10000	0	-10000	0	0
POU2F1	0.041	0.012	-10000	0	-10000	0	0
CDKN1A	-0.12	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	0.028	25	-10000	0	25
SFN	0.032	0.014	-10000	0	0	80	80
GR alpha/HSP90/FKBP51/HSP90/14-3-3	0.024	0.08	-10000	0	-0.2	4	4
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.068	0.27	0.42	15	-0.66	70	85
JUN	0.025	0.054	0.35	3	-10000	0	3
IL4	0.035	0.051	-10000	0	-10000	0	0
CDK5R1	0.036	0.009	-10000	0	0	25	25
PRKACA	0.036	0.007	-10000	0	0	17	17
cortisol/GR alpha (monomer)/AP-1	-0.048	0.053	-10000	0	-0.25	7	7
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.02	0.087	-10000	0	-0.18	13	13
cortisol/GR alpha (monomer)	-0.054	0.12	-10000	0	-0.37	2	2
NCOA2	0.037	0.005	-10000	0	0	11	11
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	0.039	0.032	0.17	5	-10000	0	5
AP-1/NFAT1-c-4	0.051	0.073	0.42	2	-10000	0	2
AFP	0.025	0.069	-10000	0	-10000	0	0
SUV420H1	0.034	0.012	-10000	0	0	56	56
IRF1	-0.029	0.12	-10000	0	-0.63	15	15
TP53	-0.014	0.17	-10000	0	-0.48	58	58
PPP5C	0.035	0.009	-10000	0	0	32	32
KRT17	0.039	0.078	0.43	1	-10000	0	1
KRT14	0.03	0.066	0.35	1	-10000	0	1
TBP	0.043	0.017	-10000	0	-10000	0	0
CREBBP	0.03	0.018	-10000	0	-0.092	10	10
HDAC1	0.033	0.007	-10000	0	-10000	0	0
HDAC2	0.032	0.012	-10000	0	-10000	0	0
AP-1	0.051	0.073	0.43	2	-10000	0	2
MAPK14	0.035	0.018	-10000	0	-0.031	29	29
MAPK10	0.03	0.021	-10000	0	-0.031	27	27
MAPK11	0.032	0.02	-10000	0	-0.031	28	28
KRT5	0.038	0.076	0.43	1	-10000	0	1
interleukin-1 receptor activity	-0.001	0	-10000	0	-10000	0	0
NCOA1	0.033	0.019	0.097	2	-0.067	10	12
STAT1	0.037	0.038	0.1	4	-0.17	13	17
CGA	0.036	0.054	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	-0.035	0.071	-10000	0	-0.36	9	9
MAPK3	0.034	0.02	0.078	1	-0.031	38	39
MAPK1	0.032	0.02	-10000	0	-0.031	28	28
ICAM1	0.017	0.12	-10000	0	-10000	0	0
NFKB1	0.016	0.11	0.17	30	-0.16	123	153
MAPK8	0.034	0.058	0.33	1	-10000	0	1
MAPK9	0.035	0.018	-10000	0	-0.031	27	27
cortisol/GR alpha (dimer)	-0.022	0.2	0.45	20	-0.54	29	49
BAX	-0.032	0.17	-10000	0	-0.93	8	8
POMC	0.03	0.072	0.47	1	-10000	0	1
EP300	0.027	0.019	-10000	0	-0.092	10	10
cortisol/GR alpha (dimer)/p53	-0.069	0.13	-10000	0	-0.42	17	17
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.069	0.24	32	-10000	0	32
SGK1	-0.017	0.061	-10000	0	-0.25	14	14
IL13	0.029	0.064	-10000	0	-10000	0	0
IL6	0.019	0.11	0.3	4	-10000	0	4
PRKACG	0.036	0.007	-10000	0	0	20	20
IL5	0.014	0.079	-10000	0	-10000	0	0
IL2	0.039	0.074	-10000	0	-10000	0	0
CDK5	0.025	0.019	-10000	0	0	178	178
PRKACB	0.034	0.011	-10000	0	0	50	50
HSP90AA1	0.035	0.01	-10000	0	0	35	35
IL8	-0.13	0.39	0.32	2	-0.78	127	129
CDK5R1/CDK5	0.031	0.043	-10000	0	-0.14	18	18
NF kappa B1 p50/RelA/PKAc	0.055	0.16	0.3	22	-0.21	111	133
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	-0.04	0.11	-10000	0	-0.45	1	1
SMARCA4	0.033	0.012	-10000	0	0	61	61
chromatin remodeling	-0.036	0.11	-10000	0	-0.37	25	25
NF kappa B1 p50/RelA/Cbp	0.044	0.16	-10000	0	-0.22	115	115
JUN (dimer)	0.025	0.054	0.35	3	-10000	0	3
YWHAH	0.032	0.013	-10000	0	0	73	73
VIPR1	0.033	0.061	0.36	4	-10000	0	4
NR3C1	-0.038	0.085	-10000	0	-0.34	1	1
NR4A1	0.04	0.009	-10000	0	-10000	0	0
TIF2/SUV420H1	0.037	0.054	-10000	0	-0.14	42	42
MAPKKK cascade	-0.018	0.2	0.45	20	-0.52	29	49
cortisol/GR alpha (dimer)/Src-1	-0.046	0.12	-10000	0	-0.39	2	2
PBX1	0.041	0.011	-10000	0	-10000	0	0
POU1F1	0.042	0.011	-10000	0	-10000	0	0
SELE	0.022	0.13	-10000	0	-10000	0	0
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	-0.036	0.11	-10000	0	-0.37	25	25
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	-0.04	0.11	-10000	0	-0.45	1	1
mol:cortisol	-0.034	0.059	-10000	0	-0.2	1	1
MMP1	0.034	0.076	0.34	1	-0.46	5	6

×

Signaling events mediated by HDAC Class I

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
NF kappa B/RelA	0.053	0.097	-10000	0	-0.21	46	46
Ran/GTP/Exportin 1/HDAC1	-0.029	0.022	-10000	0	-0.11	25	25
NF kappa B1 p50/RelA/I kappa B alpha	0.006	0.11	-10000	0	-0.27	47	47
SUMO1	0.037	0.004	-10000	0	0	5	5
ZFPM1	0	0	-10000	0	-10000	0	0
NPC/RanGAP1/SUMO1/Ubc9	0.001	0.041	-10000	0	-0.14	21	21
FKBP3	0.035	0.01	-10000	0	0	39	39
Histones	0.035	0.075	-10000	0	-0.23	22	22
YY1/LSF	0.014	0.066	-10000	0	-0.22	21	21
SMG5	0.037	0.006	-10000	0	0	13	13
RAN	0.037	0.006	-10000	0	0	13	13
I kappa B alpha/HDAC3	0.002	0.076	-10000	0	-0.2	51	51
I kappa B alpha/HDAC1	0.01	0.095	-10000	0	-0.23	54	54
SAP18	0.034	0.011	-10000	0	0	46	46
RELA	-0.003	0.083	0.19	1	-0.28	20	21
HDAC1/Smad7	0.045	0.042	-10000	0	-0.12	7	7
RANGAP1	0.034	0.011	-10000	0	0	44	44
HDAC3/TR2	0.026	0.071	-10000	0	-0.25	21	21
NuRD/MBD3 Complex	-0.011	0.12	-10000	0	-0.32	43	43
NF kappa B1 p50/RelA	0.011	0.092	-10000	0	-0.31	19	19
EntrezGene:23225	0	0	-10000	0	-10000	0	0
GATA2	0.037	0.007	-10000	0	0	16	16
GATA1	0.038	0.002	-10000	0	0	2	2
Mad/Max	0.052	0.015	-10000	0	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.01	0.11	-10000	0	-0.32	41	41
RBBP7	0.037	0.005	-10000	0	0	10	10
NPC	0.018	0.02	-10000	0	-0.086	18	18
RBBP4	0.033	0.012	-10000	0	0	61	61
MAX	0.035	0.01	-10000	0	0	36	36
EntrezGene:9972	0	0	-10000	0	-10000	0	0
FBXW11	0.036	0.008	-10000	0	0	24	24
NFKBIA	0	0.08	-10000	0	-0.32	26	26
KAT2B	0	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
SIN3/HDAC complex	-0.007	0.089	-10000	0	-0.28	31	31
SIN3 complex	0.057	0.042	-10000	0	-0.12	18	18
SMURF1	0.026	0.017	-10000	0	0	157	157
CHD3	0.037	0.006	-10000	0	0	13	13
SAP30	0.036	0.007	-10000	0	0	19	19
EntrezGene:23636	0	0	-10000	0	-10000	0	0
NCOR1	0.036	0.008	-10000	0	0	27	27
YY1/HDAC3	-0.002	0.078	-10000	0	-0.24	31	31
YY1/HDAC2	0.014	0.063	-10000	0	-0.22	21	21
YY1/HDAC1	0.016	0.065	-10000	0	-0.22	21	21
NuRD/MBD2 Complex (MeCP1)	-0.006	0.097	-10000	0	-0.27	40	40
PPARG	0.001	0.078	-10000	0	-0.21	54	54
HDAC8/hEST1B	0.048	0.012	-10000	0	-10000	0	0
UBE2I	0.037	0.004	-10000	0	0	5	5
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.008	-10000	0	0	24	24
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
HDAC3/SMRT (N-CoR2)	0.026	0.071	-10000	0	-0.25	21	21
MBD3L2	0	0	-10000	0	-10000	0	0
ubiquitin-dependent protein catabolic process	0.044	0.041	-10000	0	-0.12	7	7
CREBBP	0.037	0.004	-10000	0	0	7	7
NuRD/MBD3/MBD3L2 Complex	-0.006	0.11	-10000	0	-0.29	44	44
HDAC1	0.036	0.008	-10000	0	0	24	24
HDAC3	0.007	0.062	-10000	0	-0.29	15	15
HDAC2	0.033	0.012	-10000	0	0	61	61
YY1	0.01	0.033	-10000	0	-0.23	8	8
HDAC8	0	0	-10000	0	-10000	0	0
SMAD7	0.035	0.01	-10000	0	0	43	43
NCOR2	0.037	0.004	-10000	0	0	6	6
MXD1	0.038	0.002	-10000	0	0	2	2
STAT3	0.006	0.062	-10000	0	-0.22	34	34
NFKB1	0.036	0.007	-10000	0	0	18	18
EntrezGene:8021	0	0	-10000	0	-10000	0	0
RANBP2	0.036	0.008	-10000	0	0	24	24
YY1/LSF/HDAC1	0.03	0.073	-10000	0	-0.21	21	21
YY1/SAP30/HDAC1	0.031	0.072	-10000	0	-0.21	21	21
EP300	0.034	0.011	-10000	0	0	49	49
STAT3 (dimer non-phopshorylated)	0.006	0.062	-10000	0	-0.22	34	34
proteasomal ubiquitin-dependent protein catabolic process	0	0.08	-10000	0	-0.32	26	26
histone deacetylation	-0.006	0.096	-10000	0	-0.27	41	41
STAT3 (dimer non-phopshorylated)/HDAC3	0.001	0.094	-10000	0	-0.31	28	28
nuclear export	-0.048	0.011	-10000	0	-10000	0	0
PRKACA	0.036	0.007	-10000	0	0	17	17
GATAD2B	0	0	-10000	0	-10000	0	0
GATAD2A	0.034	0.011	-10000	0	0	50	50
GATA2/HDAC3	0.026	0.071	-10000	0	-0.25	20	20
GATA1/HDAC1	0.051	0.024	-10000	0	-0.14	6	6
GATA1/HDAC3	0.027	0.071	-10000	0	-0.25	21	21
CHD4	0.035	0.01	-10000	0	0	41	41
TNF-alpha/TNFR1A	0.036	0.055	-10000	0	-0.14	43	43
SIN3/HDAC complex/Mad/Max	-0.007	0.088	-10000	0	-0.28	31	31
NuRD Complex	-0.005	0.11	0.16	2	-0.3	42	44
positive regulation of chromatin silencing	0.033	0.074	-10000	0	-0.23	22	22
SIN3B	0.036	0.008	-10000	0	0	27	27
MTA2	0.037	0.005	-10000	0	0	9	9
SIN3A	0	0	-10000	0	-10000	0	0
XPO1	0.037	0.003	-10000	0	0	4	4
SUMO1/HDAC1	0.037	0.055	-10000	0	-0.22	5	5
HDAC complex	0.066	0.073	-10000	0	-0.15	42	42
GATA1/Fog1	0.028	0.002	-10000	0	-10000	0	0
FKBP25/HDAC1/HDAC2	0.055	0.05	-10000	0	-0.14	22	22
TNF	0.037	0.004	-10000	0	0	6	6
negative regulation of cell growth	-0.007	0.088	-10000	0	-0.28	32	32
NuRD/MBD2/PRMT5 Complex	-0.006	0.097	-10000	0	-0.27	40	40
Ran/GTP/Exportin 1	0.037	0.059	-10000	0	-0.16	21	21
NF kappa B/RelA/I kappa B alpha	-0.007	0.097	-10000	0	-0.26	52	52
SIN3/HDAC complex/NCoR1	-0.005	0.094	-10000	0	-0.3	30	30
TFCP2	0.036	0.008	-10000	0	0	26	26
NR2C1	0.037	0.005	-10000	0	0	8	8
MBD3	0.035	0.01	-10000	0	0	35	35
MBD2	0.037	0.007	-10000	0	0	16	16

×

TRAIL signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TNFSF10	0.03	0.015	-10000	0	0	103	103
positive regulation of NF-kappaB transcription factor activity	0.037	0.045	-10000	0	-0.14	25	25
MAP2K4	0.015	0.053	0.21	2	-0.22	7	9
IKBKB	0.037	0.003	-10000	0	0	4	4
TNFRSF10B	0.036	0.008	-10000	0	0	23	23
TNFRSF10A	0	0	-10000	0	-10000	0	0
SMPD1	0.014	0.028	-10000	0	-0.1	21	21
IKBKG	0.037	0.003	-10000	0	0	4	4
mol:GTP	0	0	-10000	0	-10000	0	0
TNFRSF10D	0.037	0.005	-10000	0	0	10	10
TRAIL/TRAILR2	0.037	0.045	-10000	0	-0.14	24	24
TRAIL/TRAILR3	0.037	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1	0.016	0.035	-10000	0	-0.13	26	26
TRAIL/TRAILR4	0.037	0.045	-10000	0	-0.14	25	25
TRAIL/TRAILR1/DAP3/GTP	0.03	0.04	-10000	0	-0.1	33	33
IKK complex	-0.022	0.11	-10000	0	-0.22	111	111
RIPK1	0.036	0.007	-10000	0	0	19	19
response to oxidative stress	0	0	-10000	0	-10000	0	0
DAP3/GTP	0.024	0.024	-10000	0	-0.13	12	12
MAPK3	-0.019	0.01	-10000	0	-10000	0	0
MAP3K1	0.022	0.05	-10000	0	-0.21	6	6
TRAILR4 (trimer)	0.037	0.005	-10000	0	0	10	10
TRADD	0.037	0.005	-10000	0	0	8	8
TRAILR1 (trimer)	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	0.018	0.047	-10000	0	-0.16	24	24
CFLAR	0.037	0.005	-10000	0	0	9	9
MAPK1	-0.017	0.011	-10000	0	-10000	0	0
TRAIL/TRAILR1/FADD/TRADD/RIP	0.071	0.048	-10000	0	-0.11	26	26
mol:ceramide	0.014	0.028	-10000	0	-0.1	21	21
FADD	0.037	0.006	-10000	0	0	13	13
MAPK8	0.007	0.042	0.19	1	-0.23	5	6
TRAF2	0.036	0.007	-10000	0	0	19	19
TRAILR3 (trimer)	0.037	0.006	-10000	0	0	12	12
CHUK	0.027	0.017	-10000	0	0	139	139
TRAIL/TRAILR1/FADD	0.034	0.039	-10000	0	-0.11	26	26
DAP3	0.036	0.008	-10000	0	0	23	23
CASP10	-0.006	0.051	0.14	14	-0.16	23	37
JNK cascade	0.037	0.045	-10000	0	-0.14	25	25
TRAIL (trimer)	0.03	0.015	-10000	0	0	103	103
TNFRSF10C	0.037	0.006	-10000	0	0	12	12
TRAIL/TRAILR1/DAP3/GTP/FADD	0.044	0.047	-10000	0	-0.1	33	33
TRAIL/TRAILR2/FADD	0.052	0.049	-10000	0	-0.12	24	24
cell death	0.014	0.028	-10000	0	-0.1	21	21
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	0.024	0.049	-10000	0	-0.16	23	23
TRAILR2 (trimer)	0.036	0.008	-10000	0	0	23	23
CASP8	0.016	0.027	-10000	0	-10000	0	0
negative regulation of caspase activity	0	0	-10000	0	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	0.088	0.057	-10000	0	-0.11	24	24

×

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	0.003	0	25	-10000	0	25
SMARCC1	-0.005	0.12	-10000	0	-1.2	4	4
REL	0.037	0.004	-10000	0	-0.01	3	3
HDAC7	-0.032	0.054	0.18	2	-0.24	9	11
JUN	0.035	0.011	-10000	0	0	44	44
EP300	0.034	0.011	-10000	0	0	49	49
KAT2B	0	0	-10000	0	-10000	0	0
KAT5	0	0	-10000	0	-10000	0	0
MAPK14	-0.018	0.018	0.038	22	-10000	0	22
FOXO1	0.031	0.015	-10000	0	0	95	95
T-DHT/AR	0.02	0.076	0.25	1	-0.23	16	17
MAP2K6	0.036	0.012	-10000	0	-0.035	10	10
BRM/BAF57	0.049	0.024	-10000	0	-0.14	3	3
MAP2K4	0.036	0.013	0.075	1	-0.035	11	12
SMARCA2	0.034	0.012	-10000	0	-10000	0	0
PDE9A	-0.013	0.2	-10000	0	-0.8	28	28
NCOA2	0.037	0.006	-10000	0	0	11	11
CEBPA	0.029	0.016	-10000	0	0	121	121
EHMT2	0.038	0.003	-10000	0	0	4	4
cell proliferation	-0.011	0.095	0.34	7	-0.33	10	17
NR0B1	0.031	0.014	-10000	0	0	90	90
EGR1	0.03	0.016	-10000	0	0	107	107
RXRs/9cRA	0.068	0.021	-10000	0	-0.11	1	1
AR/RACK1/Src	-0.015	0.062	0.2	11	-0.22	2	13
AR/GR	0.004	0.062	0.19	1	-0.21	25	26
GNB2L1	0.037	0.005	-10000	0	0	10	10
PKN1	0.034	0.011	-10000	0	0	45	45
RCHY1	0.037	0.006	-10000	0	0	15	15
epidermal growth factor receptor activity	0	0	-10000	0	-10000	0	0
MAPK8	-0.014	0.017	0.032	14	-10000	0	14
T-DHT/AR/TIF2/CARM1	0.017	0.057	0.23	6	-0.2	4	10
SRC	-0.022	0.038	0.19	10	-10000	0	10
NR3C1	0.036	0.008	-10000	0	0	23	23
KLK3	-0.028	0.084	0.4	1	-0.62	1	2
APPBP2	0.035	0.015	-10000	0	-0.034	16	16
TRIM24	0.025	0.018	-10000	0	-10000	0	0
T-DHT/AR/TIP60	-0.024	0.028	0.09	3	-0.16	7	10
TMPRSS2	0.014	0.089	-10000	0	-0.58	9	9
RXRG	0.037	0.006	-10000	0	0	13	13
mol:9cRA	0	0	0.003	1	-10000	0	1
RXRA	0.036	0.008	-10000	0	0	25	25
RXRB	0.038	0.003	-10000	0	0	3	3
CARM1	0.036	0.008	-10000	0	0	21	21
NR2C2	0.037	0.005	-10000	0	0	8	8
KLK2	-0.006	0.049	0.23	2	-10000	0	2
AR	-0.005	0.046	0.16	6	-0.19	21	27
SENP1	0	0	-10000	0	-10000	0	0
HSP90AA1	0.035	0.01	-10000	0	0	35	35
MDM2	0.033	0.012	-10000	0	-0.001	55	55
SRY	-0.001	0.001	-10000	0	-0.017	1	1
GATA2	0.037	0.007	-10000	0	0	16	16
MYST2	0	0	-10000	0	-0.003	1	1
HOXB13	0.038	0.004	-10000	0	-10000	0	0
T-DHT/AR/RACK1/Src	-0.017	0.064	0.2	17	-0.23	2	19
positive regulation of transcription	0.036	0.007	-10000	0	0	16	16
DNAJA1	0.032	0.017	-10000	0	-0.034	16	16
proteasomal ubiquitin-dependent protein catabolic process	0.013	0.036	-10000	0	-0.26	8	8
NCOA1	0.04	0.024	0.13	5	-0.18	2	7
SPDEF	0.038	0.004	-10000	0	0	4	4
T-DHT/AR/TIF2	-0.028	0.085	0.25	2	-0.24	44	46
T-DHT/AR/Hsp90	-0.022	0.045	0.2	6	-0.21	3	9
GSK3B	0.035	0.01	-10000	0	0	37	37
NR2C1	0.037	0.005	-10000	0	0	8	8
mol:T-DHT	-0.02	0.036	0.14	13	-0.12	4	17
SIRT1	0.027	0.017	-10000	0	0	149	149
ZMIZ2	0.026	0.017	-10000	0	0	152	152
POU2F1	0.038	0.035	0.12	13	-0.11	21	34
T-DHT/AR/DAX-1	-0.021	0.04	0.22	3	-0.19	2	5
CREBBP	0.037	0.004	-10000	0	0	7	7
SMARCE1	0.037	0.005	-10000	0	0	9	9

×

RXR and RAR heterodimerization with other nuclear receptor

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
TGFB1	-0.018	0.14	0.32	14	-1	8	22
VDR	0.036	0.008	-10000	0	0	23	23
FAM120B	0	0	-10000	0	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.011	0.1	0.25	2	-0.28	42	44
RXRs/LXRs/DNA/Oxysterols	0.004	0.14	0.3	2	-0.41	45	47
MED1	0.035	0.01	-10000	0	0	40	40
mol:9cRA	0	0.016	0.043	4	-0.048	43	47
RARs/THRs/DNA/Src-1	0.016	0.056	-10000	0	-0.16	44	44
RXRs/NUR77	0.078	0.068	0.22	1	-0.14	6	7
RXRs/PPAR	0.018	0.049	-10000	0	-0.18	4	4
NCOR2	0.037	0.004	-10000	0	0	6	6
VDR/VDR/Vit D3	0.027	0.006	-10000	0	-10000	0	0
RARs/VDR/DNA/Vit D3	0.082	0.026	-10000	0	-10000	0	0
RARA	0.037	0.004	-10000	0	0	6	6
NCOA1	0.034	0.011	-10000	0	0	49	49
VDR/VDR/DNA	0.036	0.008	-10000	0	0	23	23
RARs/RARs/DNA/9cRA	0.057	0.033	-10000	0	-10000	0	0
RARG	0.037	0.005	-10000	0	0	11	11
RPS6KB1	-0.006	0.08	0.5	6	-0.4	8	14
RARs/THRs/DNA/SMRT	0.029	0.031	-10000	0	-0.18	9	9
THRA	0.037	0.006	-10000	0	0	14	14
mol:Bile acids	0	0	-10000	0	-10000	0	0
VDR/Vit D3/DNA	0.027	0.006	-10000	0	-10000	0	0
RXRs/PPAR/9cRA/PGJ2/DNA	0.058	0.075	0.29	3	-0.16	41	44
NR1H4	0.037	0.005	-10000	0	0	8	8
RXRs/LXRs/DNA	0.084	0.11	0.31	2	-0.22	40	42
NR1H2	0.03	0.032	0.09	2	-0.062	48	50
NR1H3	0.031	0.033	-10000	0	-0.069	43	43
RXRs/VDR/DNA/Vit D3	0.071	0.064	0.21	1	-0.11	32	33
NR4A1	0.036	0.007	-10000	0	0	17	17
mol:ATRA	0	0	-10000	0	-10000	0	0
RXRs/FXR/9cRA/MED1	0.008	0.063	-10000	0	-0.21	18	18
RXRG	0.031	0.03	0.09	1	-0.059	46	47
RXR alpha/CCPG	0.023	0.022	-10000	0	-0.059	8	8
RXRA	0.03	0.031	0.09	1	-0.061	46	47
RXRB	0.032	0.033	-10000	0	-0.067	48	48
THRB	0.037	0.005	-10000	0	0	8	8
PPARG	0.036	0.008	-10000	0	0	25	25
PPARD	0.038	0.003	-10000	0	0	3	3
TNF	-0.001	0.13	-10000	0	-0.52	13	13
mol:Oxysterols	0	0.015	0.043	4	-0.041	48	52
cholesterol transport	0.004	0.14	0.3	2	-0.41	45	47
PPARA	0.034	0.011	-10000	0	0	44	44
mol:Vit D3	0	0	-10000	0	-10000	0	0
RARB	0.037	0.005	-10000	0	0	11	11
RXRs/NUR77/BCL2	0.02	0.032	-10000	0	-0.17	2	2
SREBF1	-0.012	0.17	-10000	0	-0.49	42	42
RXRs/RXRs/DNA/9cRA	0.058	0.075	0.28	3	-0.16	41	44
ABCA1	-0.046	0.26	-10000	0	-0.85	45	45
RARs/THRs	0.11	0.029	-10000	0	-0.12	1	1
RXRs/FXR	0.079	0.068	0.22	1	-0.15	5	6
BCL2	0.036	0.007	-10000	0	0	17	17

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.002	0.039	0.098	27	-0.12	6	33
NFATC2	-0.001	0.028	0.084	17	-0.095	11	28
NFATC3	-0.003	0.039	0.098	27	-0.12	7	34
CD40LG	0.013	0.12	0.29	39	-10000	0	39
PTGS2	-0.022	0.07	0.27	4	-10000	0	4
JUNB	0.032	0.014	-10000	0	0	77	77
CaM/Ca2+/Calcineurin A alpha-beta B1	0.026	0.027	-10000	0	-0.12	13	13
CaM/Ca2+	0.026	0.027	-10000	0	-0.12	13	13
CALM1	0.036	0.014	-10000	0	-10000	0	0
JUN	0.037	0.013	-10000	0	-10000	0	0
mol:Ca2+	0	0.002	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0.022	0.02	-10000	0	-0.1	10	10
FOSL1	0.034	0.012	-10000	0	0	56	56
CREM	0.029	0.016	-10000	0	0	120	120
Jun/NFAT1-c-4/p21SNFT	0.056	0.072	0.27	13	-0.18	4	17
FOS	0.028	0.02	-10000	0	-10000	0	0
IFNG	0.008	0.11	0.3	29	-10000	0	29
AP-1/NFAT1-c-4	0.074	0.11	-10000	0	-0.26	3	3
FASLG	0.011	0.12	0.29	36	-10000	0	36
NFAT1-c-4/ICER1	0.041	0.054	0.22	10	-10000	0	10
IL2RA	0.001	0.09	0.25	17	-10000	0	17
FKBP12/FK506	0.022	0.023	-10000	0	-0.13	10	10
CSF2	0.013	0.12	0.3	33	-10000	0	33
JunB/Fra1/NFAT1-c-4	0.046	0.059	0.22	5	-0.18	1	6
IL4	0.013	0.12	0.29	38	-10000	0	38
IL2	0.014	0.084	-10000	0	-0.81	5	5
IL3	0.031	0.081	-10000	0	-0.61	7	7
FKBP1A	0.033	0.012	-10000	0	0	63	63
BATF3	0	0	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
POU2F1	0.04	0.009	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	0.064	0.031	-9999	-0.12	3	3
E-cadherin/beta catenin	0.049	0.022	-9999	-0.14	3	3
CTNNB1	0.036	0.007	-9999	0	17	17
JUP	0.034	0.011	-9999	0	52	52
CDH1	0.035	0.01	-9999	0	39	39

×

Arf6 trafficking events

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
SLC2A4	0.037	0.006	-10000	0	0	14	14
CLTC	0.007	0.097	-10000	0	-0.34	31	31
calcium ion-dependent exocytosis	0.015	0.067	0.13	1	-0.22	19	20
Dynamin 2/GTP	0.027	0.011	-10000	0	-0.1	1	1
EXOC4	0	0	-10000	0	-10000	0	0
CD59	0.002	0.084	-10000	0	-0.29	30	30
CPE	-0.015	0.009	-10000	0	-0.11	1	1
CTNNB1	0.036	0.007	-10000	0	0	17	17
membrane fusion	0.019	0.065	-10000	0	-0.22	15	15
CTNND1	-0.02	0.011	0.089	1	-0.18	1	2
DNM2	0.036	0.007	-10000	0	0	20	20
mol:PI-4-5-P2	0.007	0.069	0.15	4	-0.23	23	27
TSHR	-0.017	0.009	0.093	1	-0.11	1	2
INS	0.006	0.095	-10000	0	-0.46	19	19
BIN1	0.032	0.013	-10000	0	0	76	76
mol:Choline	0.019	0.065	-10000	0	-0.22	15	15
growth hormone secretagogue receptor activity	0	0	-10000	0	-10000	0	0
mol:GDP	-0.009	0.005	-10000	0	-0.1	1	1
membrane depolarization	0	0	-10000	0	-10000	0	0
ARF6	0.035	0.009	-10000	0	0	31	31
mol:Ca2+	0.026	0.01	-10000	0	-0.1	1	1
JUP	0.01	0.075	-10000	0	-0.28	25	25
ASAP2/amphiphysin II	0.029	0.045	-10000	0	-0.1	48	48
ARF6/GTP	0.026	0.01	-10000	0	-0.13	1	1
CDH1	0.007	0.076	-10000	0	-0.28	27	27
clathrin-independent pinocytosis	0.026	0.009	-10000	0	-0.13	1	1
MAPK8IP3	0.037	0.004	-10000	0	0	6	6
positive regulation of endocytosis	0.026	0.009	-10000	0	-0.13	1	1
EXOC2	0.036	0.008	-10000	0	0	23	23
substrate adhesion-dependent cell spreading	0	0.056	-10000	0	-0.27	10	10
insulin receptor binding	0	0	-10000	0	-10000	0	0
SPAG9	0.035	0.01	-10000	0	0	36	36
regulation of calcium-dependent cell-cell adhesion	-0.037	0.084	0.28	26	-10000	0	26
positive regulation of phagocytosis	-0.015	0.007	-10000	0	-10000	0	0
ARF6/GTP/JIP3	0.047	0.015	-10000	0	-0.11	1	1
ACAP1	0.02	0.061	-10000	0	-0.22	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
CHRM2	-0.001	0.071	-10000	0	-0.29	22	22
clathrin heavy chain/ACAP1	0.011	0.09	0.2	7	-0.25	35	42
JIP4/KLC1	0.049	0.061	-10000	0	-0.15	38	38
EXOC1	0.034	0.011	-10000	0	0	47	47
exocyst	0	0.056	-10000	0	-0.27	10	10
RALA/GTP	0.014	0.029	-10000	0	-0.13	17	17
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0.039	0.039	-10000	0	-0.12	26	26
receptor recycling	0.026	0.009	-10000	0	-0.13	1	1
CTNNA1	-0.02	0.011	0.089	1	-0.18	1	2
NME1	-0.009	0.005	-10000	0	-0.1	1	1
clathrin coat assembly	0.008	0.096	-10000	0	-0.33	31	31
IL2RA	0.004	0.072	-10000	0	-0.34	17	17
VAMP3	-0.015	0.007	-10000	0	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	0.029	0.09	-10000	0	-0.24	35	35
EXOC6	0	0	-10000	0	-10000	0	0
PLD1	-0.001	0.042	-10000	0	-0.21	14	14
PLD2	0	0.042	-10000	0	-0.21	14	14
EXOC5	0.031	0.014	-10000	0	0	91	91
PIP5K1C	0.006	0.066	-10000	0	-0.24	20	20
SDC1	0.011	0.078	-10000	0	-0.28	27	27
ARF6/GDP	0.026	0.007	-10000	0	0	31	31
EXOC7	0.037	0.004	-10000	0	0	7	7
E-cadherin/beta catenin	0.039	0.087	-10000	0	-0.29	26	26
mol:Phosphatidic acid	0.019	0.065	-10000	0	-0.22	15	15
endocytosis	-0.028	0.044	0.1	48	-10000	0	48
SCAMP2	0.036	0.009	-10000	0	0	29	29
ADRB2	0.006	0.095	0.27	1	-0.33	30	31
EXOC3	0.036	0.007	-10000	0	0	20	20
ASAP2	0	0	-10000	0	-10000	0	0
Dynamin 2/GDP	0.024	0.01	0.09	1	-0.1	1	2
KLC1	0.033	0.013	-10000	0	0	64	64
AVPR2	0.001	0.093	0.21	3	-0.32	31	34
RALA	0.025	0.018	-10000	0	0	173	173
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	0.019	0.09	0.22	1	-0.27	31	32

×

Coregulation of Androgen receptor activity

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
NRIP1	0.035	0.012	-10000	0	-10000	0	0
SVIL	0.026	0.018	-10000	0	-10000	0	0
ZNF318	0.035	0.006	-10000	0	-0.046	1	1
JMJD2C	0.004	0	-10000	0	-10000	0	0
T-DHT/AR/Ubc9	0.052	0.04	-10000	0	-0.094	3	3
CARM1	0.036	0.008	-10000	0	0	21	21
PRDX1	0.036	0.008	-10000	0	0	24	24
PELP1	0.036	0.007	-10000	0	0	19	19
CTNNB1	0.037	0.007	-10000	0	-10000	0	0
AKT1	0.033	0.012	-10000	0	-0.001	59	59
PTK2B	0.037	0.006	-10000	0	-10000	0	0
MED1	0.034	0.01	-10000	0	0	40	40
MAK	0.034	0.009	-10000	0	-0.046	1	1
response to oxidative stress	0	0	-10000	0	-10000	0	0
HIP1	0.023	0.019	-10000	0	-10000	0	0
GSN	0.033	0.014	-10000	0	-10000	0	0
NCOA2	0.037	0.006	-10000	0	0	11	11
NCOA6	0.034	0.013	-10000	0	-10000	0	0
DNA-PK	0.057	0.05	-10000	0	-0.14	22	22
NCOA4	0.029	0.016	-10000	0	0	125	125
PIAS3	0.037	0.007	-10000	0	-10000	0	0
cell proliferation	0.013	0.049	-10000	0	-0.43	5	5
XRCC5	0.037	0.005	-10000	0	0	10	10
UBE3A	0.038	0.007	-10000	0	-10000	0	0
T-DHT/AR/SNURF	0.031	0.031	-10000	0	-0.073	18	18
FHL2	-0.028	0.17	-10000	0	-0.66	33	33
RANBP9	0.037	0.007	-10000	0	-10000	0	0
JMJD1A	0.01	0.005	-10000	0	-10000	0	0
CDK6	0.025	0.018	-10000	0	0	165	165
TGFB1I1	0.034	0.012	-10000	0	-10000	0	0
T-DHT/AR/CyclinD1	0.034	0.056	-10000	0	-0.11	32	32
XRCC6	0.034	0.01	-10000	0	0	41	41
T-DHT/AR	0.044	0.073	-10000	0	-0.14	15	15
CTDSP1	0.037	0.007	-10000	0	-10000	0	0
CTDSP2	0.031	0.014	-10000	0	-0.04	1	1
BRCA1	0.037	0.006	-10000	0	-10000	0	0
TCF4	0.032	0.012	-10000	0	-0.034	1	1
CDKN2A	0.005	0.012	-10000	0	0	444	444
SRF	0.04	0.055	0.1	73	-0.15	33	106
NKX3-1	0.013	0.034	-10000	0	-0.3	1	1
KLK3	0.018	0.046	-10000	0	-10000	0	0
TMF1	0.036	0.007	-10000	0	0	19	19
HNRNPA1	0.036	0.007	-10000	0	-10000	0	0
AOF2	0.001	0.001	-10000	0	-10000	0	0
APPL1	-0.021	0.009	-10000	0	-10000	0	0
T-DHT/AR/Caspase 8	0.05	0.04	-10000	0	-0.094	3	3
AR	0.036	0.03	-10000	0	-0.065	33	33
UBA3	0	0	-10000	0	-10000	0	0
PATZ1	0.035	0.009	-10000	0	-10000	0	0
PAWR	0.037	0.007	-10000	0	0	18	18
PRKDC	0.034	0.01	-10000	0	0	42	42
PA2G4	0.035	0.009	-10000	0	-0.034	1	1
UBE2I	0.037	0.004	-10000	0	0	5	5
T-DHT/AR/Cyclin D3/CDK11 p58	0.045	0.043	-10000	0	-0.083	28	28
RPS6KA3	0.037	0.007	-10000	0	-10000	0	0
T-DHT/AR/ARA70	0.041	0.046	-10000	0	-0.1	7	7
LATS2	-0.001	0	-10000	0	-10000	0	0
T-DHT/AR/PRX1	0.046	0.042	-10000	0	-0.11	10	10
Cyclin D3/CDK11 p58	0.022	0.028	-10000	0	-0.13	16	16
VAV3	0.03	0.016	-10000	0	-10000	0	0
KLK2	0.009	0.039	-10000	0	-0.32	3	3
CASP8	0.036	0.006	-10000	0	0	14	14
T-DHT/AR/TIF2/CARM1	0.068	0.048	-10000	0	-0.11	1	1
TMPRSS2	0.012	0.033	-10000	0	-0.32	1	1
CCND1	0.03	0.016	-10000	0	-10000	0	0
PIAS1	0.037	0.009	-10000	0	-10000	0	0
mol:T-DHT	0.003	0.016	0.045	1	-0.05	18	19
CDC2L1	0	0	-10000	0	-10000	0	0
PIAS4	0.038	0.007	-10000	0	-10000	0	0
T-DHT/AR/CDK6	0.038	0.04	-10000	0	-0.1	1	1
CMTM2	0	0	-10000	0	-10000	0	0
SNURF	0	0	-10000	0	-10000	0	0
ZMIZ1	0.027	0.029	-10000	0	-0.069	15	15
CCND3	0.036	0.009	-10000	0	0	28	28
TGIF1	0.032	0.013	-10000	0	0	67	67
FKBP4	0.036	0.01	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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
G beta1gamma2/HDAC5	0.059	0.041	-10000	0	-0.11	20	20
HDAC3	0.037	0.005	-10000	0	0	8	8
Ran/GTP/Exportin 1/HDAC4	-0.03	0.022	-10000	0	-0.1	35	35
GATA1/HDAC4	0.048	0.034	-10000	0	-0.14	15	15
GATA1/HDAC5	0.054	0.013	-10000	0	-0.14	1	1
GATA2/HDAC5	0.052	0.016	-10000	0	-0.14	1	1
HDAC5/BCL6/BCoR	0.054	0.051	-10000	0	-0.12	28	28
HDAC9	0.023	0.018	-10000	0	0	202	202
Glucocorticoid receptor/Hsp90/HDAC6	0.064	0.04	-10000	0	-0.13	16	16
HDAC4/ANKRA2	0.046	0.04	-10000	0	-0.14	19	19
HDAC5/YWHAB	0.047	0.029	-10000	0	-0.16	7	7
NPC/RanGAP1/SUMO1/Ubc9	0.001	0.041	-10000	0	-0.14	21	21
GATA2	0.037	0.007	-10000	0	0	16	16
HDAC4/RFXANK	0.04	0.049	-10000	0	-0.15	30	30
BCOR	0.035	0.01	-10000	0	0	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
HDAC10	0	0	-10000	0	-10000	0	0
HDAC5	0.037	0.007	-10000	0	0	16	16
GNB1/GNG2	0.02	0.031	-10000	0	-0.13	20	20
Histones	0.022	0.066	-10000	0	-0.16	39	39
ADRBK1	0.037	0.006	-10000	0	0	13	13
HDAC4	0.035	0.009	-10000	0	0	31	31
XPO1	0.037	0.003	-10000	0	0	4	4
HDAC5/ANKRA2	0.051	0.025	-10000	0	-0.14	7	7
HDAC4/Ubc9	0.048	0.034	-10000	0	-0.14	15	15
HDAC7	0	0	-10000	0	-10000	0	0
HDAC5/14-3-3 E	0.049	0.031	-10000	0	-0.14	11	11
TUBA1B	0.037	0.007	-10000	0	0	16	16
HDAC6	0.038	0.002	-10000	0	0	2	2
HDAC5/RFXANK	0.045	0.038	-10000	0	-0.14	18	18
CAMK4	0.037	0.005	-10000	0	0	10	10
Tubulin/HDAC6	0.059	0.053	-10000	0	-0.12	36	36
SUMO1	0.037	0.004	-10000	0	0	5	5
EntrezGene:9972	0	0	-10000	0	-10000	0	0
YWHAB	0.034	0.011	-10000	0	0	44	44
GATA1	0.038	0.002	-10000	0	0	2	2
EntrezGene:8021	0	0	-10000	0	-10000	0	0
YWHAE	0.036	0.009	-10000	0	0	29	29
NR3C1	0.036	0.008	-10000	0	0	23	23
SUMO1/HDAC4	0.035	0.057	-10000	0	-0.24	5	5
SRF	0.037	0.004	-10000	0	0	6	6
HDAC4/YWHAB	0.042	0.043	-10000	0	-0.15	20	20
Tubulin	0.039	0.052	-10000	0	-0.14	36	36
HDAC4/14-3-3 E	0.043	0.044	-10000	0	-0.14	24	24
GNB1	0.034	0.011	-10000	0	0	47	47
RANGAP1	0.034	0.011	-10000	0	0	44	44
BCL6/BCoR	0.038	0.047	-10000	0	-0.14	28	28
HDAC4/HDAC3/SMRT (N-CoR2)	0.067	0.037	-10000	0	-0.12	15	15
HDAC4/SRF	0.067	0.035	-10000	0	-0.12	13	13
HDAC4/ER alpha	0.046	0.035	-10000	0	-0.14	15	15
EntrezGene:23225	0	0	-10000	0	-10000	0	0
positive regulation of chromatin silencing	0.022	0.065	-10000	0	-0.16	39	39
cell motility	0.058	0.053	-10000	0	-0.12	36	36
EntrezGene:23636	0	0	-10000	0	-10000	0	0
UBE2I	0.037	0.004	-10000	0	0	5	5
HDAC7/HDAC3	0.027	0.008	-10000	0	-0.13	1	1
BCL6	0.033	0.013	-10000	0	0	70	70
HDAC4/CaMK II delta B	0.035	0.009	-10000	0	0	31	31
Hsp90/HDAC6	0.051	0.019	-10000	0	-0.14	2	2
ESR1	0.035	0.009	-10000	0	0	32	32
HDAC6/HDAC11	0.055	0.008	-10000	0	-10000	0	0
Ran/GTP/Exportin 1	0.037	0.059	-10000	0	-0.16	21	21
NPC	0.018	0.02	-10000	0	-0.086	18	18
MEF2C	0.035	0.009	-10000	0	0	31	31
RAN	0.037	0.006	-10000	0	0	13	13
HDAC4/MEF2C	0.094	0.055	-10000	0	-0.12	25	25
GNG2	0	0	-10000	0	-10000	0	0
NCOR2	0.037	0.004	-10000	0	0	6	6
TUBB2A	0.034	0.011	-10000	0	0	47	47
HDAC11	0.037	0.005	-10000	0	0	8	8
HSP90AA1	0.035	0.01	-10000	0	0	35	35
RANBP2	0.036	0.008	-10000	0	0	24	24
ANKRA2	0.037	0.007	-10000	0	0	16	16
RFXANK	0.035	0.01	-10000	0	0	36	36
nuclear import	-0.028	0.058	0.21	26	-10000	0	26

×

Canonical NF-kappaB 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
FBXW11	0.035	0.019	0.082	8	-0.073	11	19
mol:GTP	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.009	0.085	0.23	4	-0.26	22	26
ERC1	0.033	0.012	-10000	0	0	58	58
RIP2/NOD2	0.052	0.018	-10000	0	-0.14	2	2
NFKBIA	-0.033	0.045	0.2	2	-0.27	13	15
BIRC2	0.037	0.006	-10000	0	0	14	14
IKBKB	0.037	0.003	-10000	0	0	4	4
RIPK2	0.037	0.006	-10000	0	0	14	14
IKBKG	0.023	0.055	-10000	0	-0.34	8	8
IKK complex/A20	0.063	0.079	-10000	0	-0.33	8	8
NEMO/A20/RIP2	0.037	0.006	-10000	0	0	14	14
XPO1	0.037	0.003	-10000	0	0	4	4
NEMO/ATM	0.043	0.063	-10000	0	-0.34	9	9
tumor necrosis factor receptor activity	0	0	-10000	0	-10000	0	0
RAN	0.037	0.006	-10000	0	0	13	13
Exportin 1/RanGTP	0.048	0.022	-10000	0	-0.14	6	6
IKK complex/ELKS	0.038	0.07	-10000	0	-0.31	9	9
BCL10/MALT1/TRAF6	0.065	0.035	-10000	0	-0.12	10	10
NOD2	0.036	0.007	-10000	0	0	20	20
NFKB1	0.035	0.019	0.082	9	-0.072	12	21
RELA	0.035	0.019	0.082	9	-0.07	12	21
MALT1	0.035	0.009	-10000	0	0	30	30
cIAP1/UbcH5C	0.051	0.027	-10000	0	-0.18	6	6
ATM	0.035	0.01	-10000	0	0	38	38
TNF/TNFR1A	0.036	0.055	-10000	0	-0.14	43	43
TRAF6	0.037	0.006	-10000	0	0	14	14
PRKCA	0.037	0.004	-10000	0	0	6	6
CHUK	0.027	0.017	-10000	0	0	139	139
UBE2D3	0.037	0.006	-10000	0	0	12	12
TNF	0.037	0.004	-10000	0	0	6	6
NF kappa B1 p50/RelA	0.066	0.059	-10000	0	-0.16	26	26
BCL10	0.036	0.007	-10000	0	0	20	20
proteasomal ubiquitin-dependent protein catabolic process	-0.033	0.044	0.2	2	-0.27	13	15
beta TrCP1/SCF ubiquitin ligase complex	0.034	0.019	0.082	8	-0.073	11	19
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
IKK complex	0.047	0.067	-10000	0	-0.32	8	8
CYLD	0.037	0.006	-10000	0	0	12	12
IKK complex/PKC alpha	0.057	0.074	-10000	0	-0.32	8	8

×

Atypical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	0.051	0.019	-10000	0	-0.14	2	2
FBXW11	0.036	0.008	-10000	0	0	24	24
NF kappa B1 p50/c-Rel	0.034	0.017	-10000	0	-0.12	5	5
NF kappa B1 p50/RelA/I kappa B alpha	0.026	0.072	0.2	2	-0.26	16	18
NFKBIA	0.005	0.056	-10000	0	-0.19	24	24
MAPK14	0.037	0.005	-10000	0	0	8	8
NF kappa B1 p105/p50	0.032	0.02	-10000	0	-0.14	5	5
ARRB2	0.012	0.025	-10000	0	-0.2	7	7
REL	0.038	0.002	-10000	0	0	2	2
response to oxidative stress	0	0	-10000	0	-10000	0	0
BCL3/NF kappa B1 p50	0.033	0.017	-10000	0	-0.12	4	4
response to UV	0	0	-10000	0	-10000	0	0
NF kappa B1 p105/RelA	0.033	0.018	-10000	0	-0.12	5	5
PIK3CA	0.032	0.013	-10000	0	0	74	74
NF kappa B1 p50 dimer	-0.021	0.026	0.18	6	-0.14	5	11
PIK3R1	0.033	0.013	-10000	0	0	67	67
NFKB1	-0.023	0.005	-10000	0	-10000	0	0
RELA	0.037	0.005	-10000	0	0	10	10
positive regulation of anti-apoptosis	0.014	0.041	0.14	1	-0.21	5	6
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	0.027	0.075	0.19	2	-0.26	16	18
SRC	0.035	0.009	-10000	0	0	31	31
PI3K	0.02	0.075	-10000	0	-0.15	75	75
NF kappa B1 p50/RelA	0.013	0.041	-10000	0	-0.21	5	5
IKBKB	0.037	0.003	-10000	0	0	4	4
beta TrCP1/SCF ubiquitin ligase complex	0.036	0.008	-10000	0	0	24	24
SYK	0.032	0.013	-10000	0	0	76	76
I kappa B alpha/PIK3R1	0.018	0.074	0.19	4	-0.24	25	29
cell death	0.027	0.072	0.18	2	-0.25	17	19
NF kappa B1 p105/c-Rel	0.034	0.017	-10000	0	-0.12	5	5
LCK	0.036	0.008	-10000	0	0	21	21
BCL3	0.036	0.008	-10000	0	0	27	27

×

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	0.003	0.086	-10000	0	-0.3	21	21
BAG4	0.037	0.005	-10000	0	0	10	10
BAD	-0.004	0.034	0.12	4	-0.14	10	14
NFKBIA	0.034	0.012	-10000	0	0	54	54
BIRC3	0.031	0.014	-10000	0	0	84	84
BAX	0	0.045	0.19	13	-0.15	9	22
EnzymeConsortium:3.1.4.12	0.003	0.023	0.081	2	-0.084	10	12
IKBKB	-0.007	0.086	0.24	1	-0.31	17	18
MAP2K2	-0.011	0.05	0.18	19	-0.16	8	27
MAP2K1	-0.015	0.041	0.17	6	-0.16	10	16
SMPD1	0.002	0.03	0.12	3	-0.12	14	17
GO:0005551	0	0	-10000	0	-10000	0	0
FADD/Caspase 8	0.01	0.083	-10000	0	-0.35	10	10
MAP2K4	-0.007	0.038	0.18	4	-0.15	6	10
protein ubiquitination	-0.007	0.089	0.52	1	-0.33	15	16
EnzymeConsortium:2.7.1.37	-0.016	0.047	0.18	6	-0.17	7	13
response to UV	0	0	0.002	8	-0.002	1	9
RAF1	-0.011	0.039	0.17	6	-0.15	11	17
CRADD	0.036	0.007	-10000	0	0	16	16
mol:ceramide	0.002	0.034	0.12	3	-0.13	12	15
I-kappa-B-alpha/RELA/p50/ubiquitin	0.042	0.031	-10000	0	-0.11	16	16
MADD	0.036	0.007	-10000	0	0	19	19
MAP3K1	-0.002	0.036	0.17	5	-0.15	7	12
TRADD	0.037	0.005	-10000	0	0	8	8
RELA/p50	0.037	0.005	-10000	0	0	10	10
MAPK3	-0.008	0.045	0.18	7	-0.16	5	12
MAPK1	-0.015	0.056	0.18	6	-0.2	16	22
p50/RELA/I-kappa-B-alpha	0.045	0.036	-10000	0	-0.14	16	16
FADD	0.007	0.079	-10000	0	-0.32	11	11
KSR1	-0.004	0.034	0.13	4	-0.15	8	12
MAPK8	-0.01	0.035	0.19	5	-0.15	4	9
TRAF2	0.036	0.007	-10000	0	0	19	19
response to radiation	0	0	0.002	1	-10000	0	1
CHUK	-0.01	0.081	0.21	1	-0.32	15	16
TNF R/SODD	0.036	0.054	-10000	0	-0.14	42	42
TNF	0.037	0.004	-10000	0	0	6	6
CYCS	0.015	0.052	0.15	20	-0.15	5	25
IKBKG	-0.007	0.085	0.21	2	-0.31	17	19
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.012	0.088	-10000	0	-0.34	13	13
RELA	0.037	0.005	-10000	0	0	10	10
RIPK1	0.036	0.007	-10000	0	0	19	19
AIFM1	-0.005	0.042	0.14	14	-0.15	8	22
TNF/TNF R/SODD	0.055	0.056	-10000	0	-0.12	41	41
TNFRSF1A	0.033	0.013	-10000	0	0	66	66
response to heat	0	0	0.002	1	-10000	0	1
CASP8	0.035	0.089	-10000	0	-0.64	8	8
NSMAF	0.005	0.086	0.22	4	-0.3	19	23
response to hydrogen peroxide	0	0	0.002	8	-0.002	1	9
BCL2	0.036	0.007	-10000	0	0	17	17

×

Signaling mediated by p38-alpha and p38-beta

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
PTGS2	0.045	0.063	0.31	1	-10000	0	1
MKNK1	0.035	0.01	-10000	0	0	39	39
MAPK14	0.047	0.036	0.17	3	-0.082	22	25
ATF2/c-Jun	0.001	0.091	-10000	0	-0.31	31	31
MAPK11	0.044	0.038	0.17	3	-0.082	22	25
MITF	0.032	0.048	0.18	3	-0.2	7	10
MAPKAPK5	0.034	0.038	0.18	3	-10000	0	3
KRT8	0.035	0.038	0.21	2	-10000	0	2
MAPKAPK3	0.036	0.008	-10000	0	0	21	21
MAPKAPK2	0.036	0.007	-10000	0	0	17	17
p38alpha-beta/CK2	0.063	0.056	0.24	3	-10000	0	3
CEBPB	0.024	0.067	0.2	3	-0.2	26	29
SLC9A1	0.032	0.04	0.16	1	-0.25	2	3
mol:GDP	0	0	-10000	0	-10000	0	0
ATF2	0.033	0.054	0.27	4	-0.26	1	5
p38alpha-beta/MNK1	0.065	0.068	-10000	0	-0.14	17	17
JUN	-0.003	0.088	-10000	0	-0.32	29	29
PPARGC1A	0.033	0.055	0.19	5	-0.2	13	18
USF1	0.028	0.037	0.18	3	-10000	0	3
RAB5/GDP/GDI1	0.014	0.076	-10000	0	-0.21	26	26
NOS2	0.028	0.036	0.18	3	-10000	0	3
DDIT3	0.024	0.057	0.23	1	-0.2	17	18
RAB5A	0.035	0.009	-10000	0	0	33	33
HSPB1	0.074	0.13	0.28	123	-0.15	5	128
p38alpha-beta/HBP1	0.056	0.058	0.24	2	-10000	0	2
CREB1	0.025	0.067	0.23	1	-0.18	32	33
RAB5/GDP	0.02	0.033	-10000	0	-0.13	24	24
EIF4E	-0.014	0.06	0.22	10	-0.19	7	17
RPS6KA4	0.034	0.038	0.18	3	-10000	0	3
PLA2G4A	-0.014	0.055	0.23	6	-0.19	11	17
GDI1	0.024	0.06	0.2	2	-0.23	18	20
TP53	0.009	0.049	0.17	9	-10000	0	9
RPS6KA5	0.035	0.041	0.18	3	-0.19	1	4
ESR1	0.033	0.037	0.23	1	-10000	0	1
HBP1	0.026	0.017	-10000	0	0	157	157
MEF2C	0.032	0.048	0.18	3	-0.22	7	10
MEF2A	0.031	0.048	0.2	2	-0.22	7	9
EIF4EBP1	0.021	0.073	0.23	1	-0.26	6	7
KRT19	0.036	0.039	0.19	3	-10000	0	3
ELK4	0.033	0.038	0.18	3	-10000	0	3
ATF6	0.034	0.038	0.23	1	-10000	0	1
ATF1	0.019	0.071	0.23	1	-0.31	3	4
p38alpha-beta/MAPKAPK2	0.074	0.056	0.27	1	-10000	0	1
p38alpha-beta/MAPKAPK3	0.074	0.057	0.23	3	-0.13	2	5

×

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	0.008	0.035	0.13	30	-0.18	3	33
EntrezGene:79658	0	0	-10000	0	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	-0.002	0.046	0.14	4	-0.17	11	15
AP2	0.022	0.027	-10000	0	-0.13	15	15
mol:DAG	0	0	-10000	0	-10000	0	0
Arfaptin 2/Rac/GTP	0.03	0.036	-10000	0	-0.12	16	16
CLTB	0.037	0.005	-10000	0	0	9	9
coatomer protein complex/ARF1/GTP/ER cargo protein	0.011	0.037	-10000	0	-0.18	10	10
CD4	0.032	0.013	-10000	0	0	76	76
CLTA	0.034	0.011	-10000	0	0	44	44
mol:GTP	-0.003	0.002	0.007	1	-0.019	6	7
ARFGAP1	-0.011	0.003	0	45	-10000	0	45
mol:PI-4-5-P2	0.008	0.018	0.096	15	-0.064	4	19
ARF1/GTP	0.019	0.017	-10000	0	-0.11	6	6
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.031	-10000	0	-0.18	9	9
mol:Choline	0.007	0.018	0.099	15	-10000	0	15
mol:GDP	0	0	-10000	0	-10000	0	0
ARF1	0.036	0.008	-10000	0	0	23	23
DDEF1	0.006	0.018	0.098	15	-10000	0	15
ARF1/GDP	0.006	0.013	-10000	0	-0.082	7	7
AP2M1	0.035	0.009	-10000	0	0	32	32
EntrezGene:1313	0	0	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.017	0.066	1	-0.11	9	10
Rac/GTP	0.018	0.02	-10000	0	-0.14	5	5
ARF1/GTP/GGA3/ARF-GAP1	0.042	0.025	-10000	0	-0.1	8	8
ARFIP2	0.032	0.016	-10000	0	-0.037	17	17
COPA	0.037	0.006	-10000	0	0	14	14
RAC1	0.026	0.017	-10000	0	0	156	156
ARF1/GTP/coatomer protein complex	0.006	0.044	-10000	0	-0.18	11	11
ARF1/GTP/ARHGAP10	0.022	0.015	-10000	0	-0.11	6	6
GGA3	0.037	0.005	-10000	0	0	9	9
ARF1/GTP/Membrin	0.028	0.026	-10000	0	-0.25	3	3
AP2A1	0	0	-10000	0	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	0.005	0.037	-10000	0	-0.19	12	12
ARF1/GDP/Membrin	0.032	0.029	-10000	0	-0.28	3	3
Arfaptin 2/Rac/GDP	0.029	0.036	-10000	0	-0.12	16	16
CYTH2	-0.003	0.002	0.007	1	-0.019	6	7
ARF1/GTP/GGA3	0.045	0.021	-10000	0	-0.12	6	6
mol:ATP	0	0	-10000	0	-10000	0	0
Rac/GDP	0.018	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	0.005	0.058	-10000	0	-0.26	14	14
PLD2	0.007	0.018	0.099	15	-10000	0	15
ARF-GAP1/v-SNARE	-0.011	0.003	0	45	-10000	0	45
PIP5K1A	0.008	0.018	0.097	15	-0.064	4	19
ARF1/GTP/Membrin/GBF1/p115	0.006	0.036	-10000	0	-0.1	12	12
mol:Phosphatic acid	0	0	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.007	0.018	0.099	15	-10000	0	15
KDEL Receptor/Ligand/ARF-GAP1	-0.011	0.003	0	45	-10000	0	45
GOSR2	0.016	0.018	-10000	0	-0.32	1	1
USO1	0.013	0.034	-10000	0	-0.29	6	6
GBF1	-0.054	0.14	-10000	0	-0.31	108	108
ARF1/GTP/Arfaptin 2	0.043	0.033	-10000	0	-0.12	17	17
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	0.032	0.046	-10000	0	-0.12	35	35

×

Sumoylation by RanBP2 regulates transcriptional repression

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.036	0.008	-9999	0	24	24
Ran/GTP/Exportin 1/HDAC4	-0.033	0.03	-9999	-0.12	35	35
MDM2/SUMO1	0.035	0.053	-9999	-0.21	5	5
HDAC4	0.035	0.009	-9999	0	31	31
Ran/GTP/Exportin 1/HDAC1	-0.032	0.029	-9999	-0.14	25	25
SUMO1	0.037	0.004	-9999	0	5	5
NPC/RanGAP1/SUMO1	0.005	0.033	-9999	-0.15	21	21
mol:GTP	0	0	-9999	-10000	0	0
XPO1	-0.008	0.04	-9999	-0.15	21	21
EntrezGene:23636	0	0	-9999	-10000	0	0
RAN	0.037	0.006	-9999	0	13	13
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.036	0.008	-9999	0	24	24
SUMO1/HDAC4	0.035	0.057	-9999	-0.24	5	5
SUMO1/HDAC1	0.037	0.055	-9999	-0.22	5	5
RANGAP1	0.034	0.011	-9999	0	44	44
MDM2/SUMO1/SUMO1	0.075	0.051	-9999	-0.12	16	16
NPC/RanGAP1/SUMO1/RanBP2/Ubc9	0.001	0.041	-9999	-0.14	21	21
Ran/GTP	0.02	0.049	-9999	-0.14	21	21
EntrezGene:23225	0	0	-9999	-10000	0	0
MDM2	0.034	0.012	-9999	0	54	54
UBE2I	0.037	0.004	-9999	0	5	5
Ran/GTP/Exportin 1	0.013	0.05	-9999	-0.16	21	21
NPC	0.018	0.02	-9999	-0.086	18	18
PIAS2	0.036	0.007	-9999	0	19	19
PIAS1	0.036	0.008	-9999	0	26	26
EntrezGene:9972	0	0	-9999	-10000	0	0

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.036	0.007	-10000	0	0	17	17
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	-0.074	0.16	-10000	0	-0.34	138	138
MAP2K2	0.019	0.038	-10000	0	-0.59	2	2
MAP2K1	-0.009	0.002	-10000	0	-10000	0	0
MAP2K7	-0.009	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	-0.009	0.002	-10000	0	-10000	0	0
IL1B	-0.004	0.044	0.084	71	-0.086	9	80
Channel	0.023	0.004	-10000	0	-10000	0	0
NLRP1	-0.009	0.002	-10000	0	-10000	0	0
CALM1	0.033	0.012	-10000	0	0	60	60
negative regulation of phagocytosis	-0.022	0.12	-10000	0	-0.41	46	46
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	0.025	0.005	-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)	0.023	0.004	-10000	0	-10000	0	0
macrophage activation	-0.012	0.013	0.071	9	-10000	0	9
TNF	0.037	0.004	-10000	0	0	6	6
VCAM1	-0.074	0.16	-10000	0	-0.34	136	136
platelet activation	-0.022	0.12	-10000	0	-0.41	46	46
MAPKKK cascade	0.004	0.018	0.064	3	-0.067	24	27
IL18	-0.009	0.036	0.1	5	-10000	0	5
negative regulation of macrophage activation	-0.002	0	-10000	0	-10000	0	0
LEF	-0.002	0	-10000	0	-10000	0	0
CASP1	-0.001	0.004	0.022	12	-10000	0	12
mol:cAMP	-0.022	0.12	-10000	0	-0.41	46	46
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)	0.023	0.004	-10000	0	-10000	0	0
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

Rapid glucocorticoid signaling

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
Gs family/GDP/Gbeta gamma	0.036	0.029	-9999	0	-0.094	20	20
MAPK9	0.008	0.001	-9999	0	0	14	14
adrenocorticotropin secretion	-0.011	0.002	0	16	-10000	0	16
GNB1/GNG2	0.019	0.026	-9999	0	-0.1	20	20
GNB1	0.034	0.011	-9999	0	0	47	47
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	8	8
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	0.007	-9999	0	0	17	17
GNG2	0	0	-9999	0	-10000	0	0
CRH	0.037	0.007	-9999	0	0	16	16
mol:cortisol	0	0	-9999	0	-10000	0	0
MAPK8	0.006	0.003	-9999	0	0	122	122
MAPK11	0.007	0.002	-9999	0	0	49	49

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	-0.056	0.019	-10000	0	-10000	0	0
KIRREL	0.04	0.01	0.083	2	-0.042	1	3
Nephrin/NEPH1Par3/Par6/Atypical PKCs	0.056	0.019	-10000	0	-10000	0	0
PLCG1	0.035	0.01	-10000	0	0	43	43
ARRB2	0.036	0.008	-10000	0	0	27	27
WASL	0.026	0.017	-10000	0	0	157	157
Nephrin/NEPH1/podocin/CD2AP	0.084	0.051	0.21	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	0.039	-10000	0	-0.21	8	8
FYN	-0.009	0.043	0.17	24	-10000	0	24
mol:Ca2+	0.084	0.041	0.2	1	-0.12	3	4
mol:DAG	0.086	0.042	0.2	1	-0.12	3	4
NPHS2	0.041	0.009	0.09	1	-0.042	1	2
mol:IP3	0.086	0.042	0.2	1	-0.12	3	4
regulation of endocytosis	0.053	0.05	-10000	0	-0.13	4	4
Nephrin/NEPH1/podocin/Cholesterol	0.072	0.028	0.18	1	-10000	0	1
establishment of cell polarity	0.056	0.019	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2	0.098	0.059	-10000	0	-0.14	16	16
Nephrin/NEPH1/beta Arrestin2	0.056	0.052	-10000	0	-0.13	4	4
NPHS1	0.039	0.011	0.078	6	-10000	0	6
Nephrin/NEPH1/podocin	0.055	0.044	0.21	1	-0.11	1	2
TJP1	0.035	0.009	-10000	0	0	33	33
NCK1	0.036	0.009	-10000	0	0	28	28
NCK2	0.036	0.007	-10000	0	0	19	19
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	0.088	0.042	0.21	1	-0.12	3	4
CD2AP	0.034	0.011	-10000	0	0	47	47
Nephrin/NEPH1/podocin/GRB2	0.089	0.043	0.21	1	-0.12	7	8
GRB2	0.036	0.007	-10000	0	0	19	19
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.013	0.053	0.18	30	-10000	0	30
cytoskeleton organization	-0.01	0.04	0.22	7	-0.2	4	11
Nephrin/NEPH1	0.047	0.016	-10000	0	-10000	0	0
Nephrin/NEPH1/ZO-1	0.066	0.038	-10000	0	-0.14	9	9

×

Signaling events mediated by the Hedgehog family

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
TGFB2	0.039	0.044	0.31	2	-10000	0	2
IHH	0.054	0.023	0.18	5	-10000	0	5
SHH Np/Cholesterol/GAS1	0.015	0.027	-10000	0	-0.11	15	15
LRPAP1	0.037	0.007	-10000	0	0	16	16
dorsoventral neural tube patterning	-0.015	0.027	0.11	15	-10000	0	15
SMO/beta Arrestin2	0.089	0.066	0.27	15	-10000	0	15
SMO	0.03	0.041	0.25	3	-10000	0	3
AKT1	-0.009	0.14	-10000	0	-0.46	30	30
ARRB2	0.036	0.008	-10000	0	0	27	27
BOC	0	0	-10000	0	-10000	0	0
ADRBK1	0.037	0.006	-10000	0	0	13	13
heart looping	0.031	0.042	0.25	4	-10000	0	4
STIL	0.044	0.095	0.19	132	-10000	0	132
DHH N/PTCH2	0.027	0.004	-10000	0	-10000	0	0
DHH N/PTCH1	0.029	0.022	-10000	0	-10000	0	0
PIK3CA	0.032	0.013	-10000	0	0	74	74
DHH	0	0	-10000	0	-10000	0	0
PTHLH	0.035	0.045	-10000	0	-10000	0	0
determination of left/right symmetry	0.031	0.042	0.25	4	-10000	0	4
PIK3R1	0.033	0.013	-10000	0	0	67	67
skeletal system development	0.035	0.045	0.3	2	-10000	0	2
IHH N/Hhip	0.035	0.014	0.12	4	-10000	0	4
DHH N/Hhip	0	0	-10000	0	-10000	0	0
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	0.031	0.042	0.25	4	-10000	0	4
pancreas development	0	0	-10000	0	-10000	0	0
HHAT	0.036	0.007	-10000	0	0	18	18
PI3K	0.02	0.075	-10000	0	-0.15	75	75
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	0.031	0.014	-10000	0	0	89	89
somite specification	0.031	0.042	0.25	4	-10000	0	4
SHH Np/Cholesterol/PTCH1	0.026	0.028	0.18	1	-10000	0	1
SHH Np/Cholesterol/PTCH2	0.022	0.016	-10000	0	-10000	0	0
SHH Np/Cholesterol/Megalin	0.021	0.016	-10000	0	-10000	0	0
SHH	-0.016	0.011	-10000	0	-10000	0	0
catabolic process	0.041	0.034	0.19	2	-10000	0	2
SMO/Vitamin D3	0.029	0.04	0.27	3	-10000	0	3
SHH Np/Cholesterol/Hhip	-0.011	0.008	-10000	0	-10000	0	0
LRP2	0.037	0.006	-10000	0	0	13	13
receptor-mediated endocytosis	0.028	0.04	0.23	4	-10000	0	4
SHH Np/Cholesterol/BOC	-0.011	0.008	-10000	0	-10000	0	0
SHH Np/Cholesterol/CDO	0.022	0.016	-10000	0	-10000	0	0
mesenchymal cell differentiation	0.011	0.008	-10000	0	-10000	0	0
mol:Vitamin D3	0.08	0.086	0.21	140	-10000	0	140
IHH N/PTCH2	0.063	0.017	0.16	3	-10000	0	3
CDON	0.037	0.004	-10000	0	0	7	7
IHH N/PTCH1	0.055	0.032	-10000	0	-10000	0	0
Megalin/LRPAP1	0.05	0.029	-10000	0	-0.14	10	10
PTCH2	0.037	0.005	-10000	0	0	10	10
SHH Np/Cholesterol	0.012	0.009	-10000	0	-10000	0	0
PTCH1	0.041	0.034	0.19	2	-10000	0	2
HHIP	0	0	-10000	0	-10000	0	0

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.037	0.005	-9999	0	8	8
Aurora C/Aurora B/INCENP	0.061	0.027	-9999	-10000	0	0
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	0.005	0.062	-9999	-0.39	12	12
AURKB	0.035	0.01	-9999	0	42	42
AURKC	0.034	0.011	-9999	0	48	48

×

FOXA2 and FOXA3 transcription factor networks

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ACADVL	0.047	0.2	0.6	1	-0.68	19	20
PCK1	0.048	0.12	0.43	2	-0.62	3	5
HNF4A	0.069	0.18	0.74	2	-0.69	8	10
KCNJ11	0.074	0.19	0.47	3	-0.6	16	19
AKT1	0.064	0.14	0.42	1	-0.42	16	17
response to starvation	0.003	0.002	-10000	0	-10000	0	0
DLK1	0.085	0.2	0.58	3	-0.67	11	14
NKX2-1	0.042	0.11	-10000	0	-0.72	1	1
ACADM	0.056	0.18	0.52	3	-0.72	11	14
TAT	0.052	0.14	0.62	1	-0.66	5	6
CEBPB	0.034	0.016	0.12	1	-10000	0	1
CEBPA	0.032	0.018	0.093	1	-10000	0	1
TTR	0.035	0.19	0.6	4	-0.64	13	17
PKLR	0.061	0.17	0.56	2	-0.67	9	11
APOA1	0.087	0.22	0.77	2	-0.82	9	11
CPT1C	0.06	0.17	0.47	3	-0.58	14	17
ALAS1	0.036	0.25	0.44	1	-1.2	15	16
TFRC	0.026	0.29	0.51	6	-0.96	34	40
FOXF1	0.029	0.013	-10000	0	-0.089	1	1
NF1	0.035	0.036	-10000	0	-0.17	15	15
HNF1A (dimer)	0.048	0.007	0.15	1	-10000	0	1
CPT1A	0.058	0.17	0.6	1	-0.68	8	9
HMGCS1	0.061	0.17	0.5	5	-0.69	8	13
NR3C1	0.048	0.019	-10000	0	-10000	0	0
CPT1B	0.048	0.16	0.6	1	-0.67	9	10
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.04	0.006	-10000	0	-10000	0	0
GCK	0.1	0.2	0.53	24	-0.67	8	32
CREB1	0.045	0.013	0.15	1	-10000	0	1
IGFBP1	0.055	0.13	-10000	0	-0.58	7	7
PDX1	0.063	0.12	-10000	0	-10000	0	0
UCP2	0.03	0.24	0.53	3	-0.68	41	44
ALDOB	0.075	0.19	0.57	2	-0.7	10	12
AFP	0.013	0.029	-10000	0	-10000	0	0
BDH1	0.051	0.2	0.56	2	-0.68	18	20
HADH	0.067	0.21	0.55	1	-0.7	17	18
F2	0.085	0.22	0.97	1	-0.86	8	9
HNF1A	0.048	0.007	0.15	1	-10000	0	1
G6PC	0.012	0.082	0.42	1	-0.34	1	2
SLC2A2	0.079	0.13	-10000	0	-10000	0	0
INS	0.026	0.042	0.19	14	-0.094	34	48
FOXA1	0.01	0.015	0.16	1	-10000	0	1
FOXA3	0.019	0.057	0.21	3	-0.19	24	27
FOXA2	0.11	0.23	0.64	2	-0.72	14	16
ABCC8	0.073	0.19	0.57	2	-0.7	10	12
ALB	0.014	0.03	-10000	0	-10000	0	0

×

IL27-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.037	0.013	-10000	0	-10000	0	0
CD4-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
cytokine production during immune response	-0.001	0.06	0.38	3	-10000	0	3
IL27/IL27R/JAK1	0.039	0.063	-10000	0	-10000	0	0
TBX21	-0.021	0.086	0.34	13	-10000	0	13
IL12B	0.038	0.005	-10000	0	0	8	8
IL12A	-0.011	0.002	0.013	2	-10000	0	2
IL6ST	0.035	0.011	-10000	0	-0.033	1	1
IL27RA/JAK1	0.025	0.043	-10000	0	-10000	0	0
IL27	-0.001	0.003	-10000	0	-10000	0	0
TYK2	0.035	0.011	-10000	0	-0.033	1	1
T-helper cell lineage commitment	0.069	0.079	-10000	0	-10000	0	0
T-helper 2 cell differentiation	-0.001	0.06	0.38	3	-10000	0	3
T cell proliferation during immune response	-0.001	0.06	0.38	3	-10000	0	3
MAPKKK cascade	0.001	0.06	-10000	0	-0.38	3	3
STAT3	0.035	0.01	-10000	0	0	40	40
STAT2	0.036	0.008	-10000	0	0	21	21
STAT1	0.034	0.01	-10000	0	0	41	41
IL12RB1	0.036	0.008	-10000	0	0	22	22
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.023	0.082	0.34	11	-10000	0	11
IL27/IL27R/JAK2/TYK2	0.001	0.06	-10000	0	-0.38	3	3
positive regulation of T cell mediated cytotoxicity	0.001	0.06	-10000	0	-0.38	3	3
STAT1 (dimer)	0.044	0.081	-10000	0	-10000	0	0
JAK2	0.032	0.014	-10000	0	-0.032	1	1
JAK1	0.034	0.011	-10000	0	0	44	44
STAT2 (dimer)	0.014	0.093	-10000	0	-0.32	12	12
T cell proliferation	0.009	0.054	-10000	0	-0.3	1	1
IL12/IL12R/TYK2/JAK2	0.009	0.18	-10000	0	-0.76	26	26
IL17A	0.067	0.079	-10000	0	-10000	0	0
mast cell activation	-0.001	0.06	0.38	3	-10000	0	3
IFNG	0.003	0.028	-10000	0	-0.089	21	21
T cell differentiation	-0.002	0.003	-10000	0	-0.017	10	10
STAT3 (dimer)	0.011	0.1	-10000	0	-0.36	13	13
STAT5A (dimer)	0.015	0.095	-10000	0	-0.32	12	12
STAT4 (dimer)	0.014	0.092	-10000	0	-0.34	8	8
STAT4	0.035	0.009	-10000	0	0	31	31
T cell activation	-0.005	0.005	-10000	0	-0.084	1	1
IL27R/JAK2/TYK2	0.038	0.064	-10000	0	-10000	0	0
GATA3	0.003	0.07	0.62	6	-10000	0	6
IL18	-0.01	0.004	0	74	-10000	0	74
positive regulation of mast cell cytokine production	0.011	0.1	-10000	0	-0.36	13	13
IL27/EBI3	0.025	0.011	-10000	0	-10000	0	0
IL27RA	0.002	0.029	-10000	0	-10000	0	0
IL6	0.023	0.021	-10000	0	-10000	0	0
STAT5A	0.037	0.005	-10000	0	0	8	8
monocyte differentiation	0	0	-10000	0	-10000	0	0
IL2	-0.008	0.028	-10000	0	-10000	0	0
IL1B	-0.009	0.005	0	101	-10000	0	101
EBI3	0.036	0.011	-10000	0	-0.033	1	1
TNF	-0.012	0.001	0	6	-10000	0	6

×

Class IB PI3K non-lipid kinase 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.Down.Perturbations	Number.of.Total.Perturbations
cAMP biosynthetic process	-0.037	0.005	0	11	-9999	0	11
PI3K Class IB/PDE3B	0.037	0.005	-9999	0	0	11	11
PDE3B	0.037	0.005	-9999	0	0	11	11

×

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 +	0.037	0.005	-10000	0	0	10	10
GNAT1/GTP	0.027	0.005	-10000	0	-10000	0	0
Metarhodopsin II/Arrestin	0.049	0.011	-10000	0	-10000	0	0
PDE6G/GNAT1/GTP	0.049	0.009	-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	0.037	0.006	-10000	0	0	14	14
GRK1	0	0	-10000	0	-10000	0	0
CNG Channel	0.07	0.025	-10000	0	-10000	0	0
mol:Na +	0.044	0.017	-10000	0	-10000	0	0
mol:ADP	0	0	-10000	0	-10000	0	0
RGS9-1/Gbeta5/R9AP	0.047	0.015	-10000	0	-0.11	1	1
mol:GDP	0	0	-10000	0	-10000	0	0
cGMP/CNG Channel	0.055	0.02	-10000	0	-10000	0	0
CNGB1	0.037	0.005	-10000	0	0	11	11
RDH5	0.036	0.008	-10000	0	0	25	25
SAG	0.037	0.005	-10000	0	0	11	11
mol:Ca2+	-0.035	0.026	0.16	8	-10000	0	8
Na + (4 Units)	0.042	0.019	-10000	0	-10000	0	0
RGS9	0.036	0.007	-10000	0	0	18	18
GNB1/GNGT1	0.032	0.038	-10000	0	-0.14	13	13
GNAT1/GDP	0.06	0.022	-10000	0	-0.1	1	1
GUCY2D	0.037	0.006	-10000	0	0	12	12
GNGT1	0.026	0.017	-10000	0	0	158	158
GUCY2F	0.038	0.002	-10000	0	0	1	1
GNB5	0.036	0.007	-10000	0	0	18	18
mol:GMP (4 units)	0.029	0.009	-10000	0	-10000	0	0
mol:11-cis-retinal	0.036	0.008	-10000	0	0	25	25
mol:cGMP	0.029	0.007	-10000	0	-10000	0	0
GNB1	0.034	0.011	-10000	0	0	47	47
Rhodopsin	0.052	0.015	-10000	0	-10000	0	0
SLC24A1	0.037	0.005	-10000	0	0	10	10
CNGA1	0.037	0.005	-10000	0	0	9	9
Metarhodopsin II	0.024	0.004	-10000	0	-10000	0	0
mol:Ca ++	0	0	-10000	0	-10000	0	0
GC1/GCAP Family	0.047	0.009	-10000	0	-10000	0	0
RGS9BP	0	0	-10000	0	-10000	0	0
Metarhodopsin II/Transducin	0.006	0.037	-10000	0	-0.16	15	15
GCAP Family/Ca ++	0.024	0.003	-10000	0	-10000	0	0
PDE6A/B	0.054	0.01	-10000	0	-10000	0	0
mol:Pi	0.047	0.015	-10000	0	-0.11	1	1
mol:all-trans-retinal	0	0	-10000	0	-10000	0	0
Transducin	0.042	0.042	-10000	0	-0.11	13	13
PDE6B	0.037	0.005	-10000	0	0	11	11
PDE6A	0.037	0.004	-10000	0	0	7	7
PDE6G	0.037	0.003	-10000	0	0	4	4
RHO	0.037	0.006	-10000	0	0	13	13
PDE6	0.087	0.027	-10000	0	-0.11	1	1
GUCA1A	0	0	-10000	0	-10000	0	0
GC2/GCAP Family	0.048	0.006	-10000	0	-10000	0	0
GUCA1C	0	0	-10000	0	-10000	0	0
GUCA1B	0.037	0.004	-10000	0	0	6	6

×

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	0.049	0.009	-10000	0	-9999	0	0
EFNA5	0.037	0.005	-10000	0	0	9	9
FYN	-0.019	0.016	0.18	2	-9999	0	2
neuron projection morphogenesis	0.049	0.009	-10000	0	-9999	0	0
cell-cell signaling	0	0	-10000	0	-9999	0	0
Ephrin A5/EPHA5	0.049	0.009	-10000	0	-9999	0	0
EPHA5	0.037	0.005	-10000	0	0	9	9

pid_entity	TCGA.87.5896	TCGA.81.5910	TCGA.76.6285	TCGA.76.6282
109_MAP3K5	0.34	0.025	-0.28	0.039
47_PPARGC1A	0.038	0.038	0.038	0
105_BMP4	0.038	0.038	0	0.038
105_BMP6	0.038	0.038	0	0.038
105_BMP7	0.038	0.038	0	0.038
105_BMP2	0.038	0.038	0	0.038
131_RELN/VLDLR	0	0.077	0.097	0.097
30_TGFB1/TGF beta receptor Type II	0	0.037	0	0
84_STAT5B	0.17	0.14	-0.28	0.062
84_STAT5A	0.17	0.14	-0.28	0.056