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

Pathway.Name	Avg.Num.Perturbations
HIF-1-alpha transcription factor network	194
Nephrin/Neph1 signaling in the kidney podocyte	187
TCR signaling in naïve CD8+ T cells	136
TCGA08_p53	132
FOXA2 and FOXA3 transcription factor networks	114
Syndecan-4-mediated signaling events	110
Aurora B signaling	110
IL12-mediated signaling events	106
FOXM1 transcription factor network	100
PDGFR-alpha signaling pathway	90

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	194	14818	76	-1.3	0.026	1000	-1000	-0.16	-1000
Nephrin/Neph1 signaling in the kidney podocyte	187	6365	34	-0.62	0.016	1000	-1000	-0.082	-1000
TCR signaling in naïve CD8+ T cells	136	12666	93	-0.67	0.33	1000	-1000	-0.12	-1000
TCGA08_p53	132	927	7	-0.66	0.31	1000	-1000	-0.022	-1000
FOXA2 and FOXA3 transcription factor networks	114	5248	46	-1.3	0.025	1000	-1000	-0.085	-1000
Syndecan-4-mediated signaling events	110	7420	67	-0.65	0.11	1000	-1000	-0.13	-1000
Aurora B signaling	110	7416	67	-0.42	0.016	1000	-1000	-0.098	-1000
IL12-mediated signaling events	106	9274	87	-0.72	0.17	1000	-1000	-0.15	-1000
FOXM1 transcription factor network	100	5141	51	-0.83	0.04	1000	-1000	-0.2	-1000
PDGFR-alpha signaling pathway	90	3963	44	-0.28	0.034	1000	-1000	-0.084	-1000
JNK signaling in the CD4+ TCR pathway	79	1347	17	-0.43	0.016	1000	-1000	-0.091	-1000
amb2 Integrin signaling	75	6164	82	-0.57	0.016	1000	-1000	-0.14	-1000
IL4-mediated signaling events	72	6604	91	-0.84	0.54	1000	-1000	-0.16	-1000
Glypican 1 network	67	3227	48	-0.57	0.045	1000	-1000	-0.078	-1000
EGFR-dependent Endothelin signaling events	67	1420	21	-0.68	0.016	1000	-1000	-0.098	-1000
Aurora C signaling	65	460	7	-0.4	0.014	1000	-1000	-0.072	-1000
IL23-mediated signaling events	63	3796	60	-0.41	0.021	1000	-1000	-0.17	-1000
Caspase cascade in apoptosis	62	4654	74	-0.33	0.16	1000	-1000	-0.084	-1000
Glypican 2 network	62	251	4	-0.12	-1000	1000	-1000	-0.048	-1000
TCGA08_retinoblastoma	61	494	8	-0.85	0.22	1000	-1000	-0.043	-1000
Syndecan-1-mediated signaling events	59	2028	34	-0.41	0.016	1000	-1000	-0.097	-1000
HIF-2-alpha transcription factor network	55	2386	43	-0.76	0.33	1000	-1000	-0.12	-1000
Hypoxic and oxygen homeostasis regulation of HIF-1-alpha	54	1807	33	-0.83	0.016	1000	-1000	-0.098	-1000
BMP receptor signaling	53	4339	81	-0.7	0.016	1000	-1000	-0.14	-1000
Signaling events mediated by the Hedgehog family	45	2372	52	-0.45	0.12	1000	-1000	-0.12	-1000
Fc-epsilon receptor I signaling in mast cells	44	4345	97	-0.35	0.042	1000	-1000	-0.14	-1000
IL27-mediated signaling events	40	2052	51	-0.61	0.074	1000	-1000	-0.12	-1000
Calcineurin-regulated NFAT-dependent transcription in lymphocytes	39	2697	68	-0.55	0.067	1000	-1000	-0.15	-1000
Effects of Botulinum toxin	38	999	26	-0.37	0.016	1000	-1000	-0.095	-1000
Ephrin A reverse signaling	36	257	7	-0.058	0	1000	-1000	-0.048	-1000
Calcium signaling in the CD4+ TCR pathway	36	1125	31	-0.48	0.016	1000	-1000	-0.16	-1000
Arf6 signaling events	35	2201	62	-0.68	0.016	1000	-1000	-0.094	-1000
p75(NTR)-mediated signaling	35	4498	125	-0.43	0.016	1000	-1000	-0.15	-1000
IL2 signaling events mediated by STAT5	33	747	22	-0.47	0.038	1000	-1000	-0.064	-1000
VEGFR1 specific signals	33	1866	56	-0.48	0.049	1000	-1000	-0.12	-1000
S1P1 pathway	31	1142	36	-0.38	0.018	1000	-1000	-0.11	-1000
LPA4-mediated signaling events	30	360	12	-0.17	0.028	1000	-1000	-0.033	-1000
IL2 signaling events mediated by PI3K	30	1797	58	-0.46	0.033	1000	-1000	-0.11	-1000
BCR signaling pathway	30	3014	99	-0.35	0.034	1000	-1000	-0.13	-1000
PLK1 signaling events	29	2513	85	-0.4	0.016	1000	-1000	-0.089	-1000
Integrins in angiogenesis	29	2447	84	-0.38	0.04	1000	-1000	-0.14	-1000
Coregulation of Androgen receptor activity	27	2103	76	-0.94	0.033	1000	-1000	-0.076	-1000
Glucocorticoid receptor regulatory network	27	3123	114	-0.41	0.15	1000	-1000	-0.092	-1000
Regulation of Telomerase	27	2788	102	-0.68	0.045	1000	-1000	-0.14	-1000
Lissencephaly gene (LIS1) in neuronal migration and development	25	1398	54	-0.66	0.031	1000	-1000	-0.14	-1000
Reelin signaling pathway	25	1401	56	-0.24	0.016	1000	-1000	-0.13	-1000
Signaling events mediated by Stem cell factor receptor (c-Kit)	25	2004	78	-0.32	0.046	1000	-1000	-0.097	-1000
IL6-mediated signaling events	24	1855	75	-0.28	0.078	1000	-1000	-0.13	-1000
Aurora A signaling	22	1354	60	-0.24	0.054	1000	-1000	-0.091	-1000
Visual signal transduction: Rods	21	1111	52	-0.28	0.016	1000	-1000	-0.13	-1000
Signaling events mediated by PTP1B	20	1591	76	-0.68	0.048	1000	-1000	-0.12	-1000
HIV-1 Nef: Negative effector of Fas and TNF-alpha	20	932	45	-0.59	0.061	1000	-1000	-0.13	-1000
Angiopoietin receptor Tie2-mediated signaling	20	1824	88	-0.32	0.079	1000	-1000	-0.16	-1000
EPO signaling pathway	19	1090	55	-0.29	0.018	1000	-1000	-0.14	-1000
Neurotrophic factor-mediated Trk receptor signaling	19	2315	120	-0.17	0.15	1000	-1000	-0.11	-1000
Syndecan-2-mediated signaling events	18	1298	69	-0.57	0.056	1000	-1000	-0.1	-1000
Regulation of nuclear SMAD2/3 signaling	15	2145	136	-0.46	0.091	1000	-1000	-0.12	-1000
Paxillin-independent events mediated by a4b1 and a4b7	15	562	37	-0.3	0.022	1000	-1000	-0.14	-1000
Endothelins	15	1533	96	-0.35	0.089	1000	-1000	-0.11	-1000
Wnt signaling	15	111	7	-0.073	0.016	1000	-1000	-0.077	-1000
S1P3 pathway	15	649	42	-0.38	0.062	1000	-1000	-0.084	-1000
Presenilin action in Notch and Wnt signaling	14	908	61	-0.19	0.092	1000	-1000	-0.099	-1000
FoxO family signaling	14	913	64	-0.57	0.12	1000	-1000	-0.11	-1000
LPA receptor mediated events	14	1444	102	-0.39	0.062	1000	-1000	-0.13	-1000
Sphingosine 1-phosphate (S1P) pathway	13	365	28	-0.14	0.024	1000	-1000	-0.088	-1000
Thromboxane A2 receptor signaling	13	1400	105	-0.68	0.069	1000	-1000	-0.1	-1000
Ceramide signaling pathway	13	1032	76	-0.68	0.23	1000	-1000	-0.098	-1000
Class I PI3K signaling events	13	964	73	-0.48	0.036	1000	-1000	-0.11	-1000
PLK2 and PLK4 events	12	38	3	-0.014	0.01	1000	-1000	-0.034	-1000
IFN-gamma pathway	12	818	68	-0.38	0.017	1000	-1000	-0.14	-1000
FAS signaling pathway (CD95)	12	604	47	-0.45	0.031	1000	-1000	-0.06	-1000
Canonical Wnt signaling pathway	12	630	51	-0.19	0.096	1000	-1000	-0.078	-1000
E-cadherin signaling events	12	62	5	-0.023	0.016	1000	-1000	-0.066	-1000
ErbB4 signaling events	11	777	69	-0.18	0.11	1000	-1000	-0.12	-1000
Regulation of Androgen receptor activity	11	801	70	-0.97	0.04	1000	-1000	-0.093	-1000
Noncanonical Wnt signaling pathway	10	270	26	-0.12	0.016	1000	-1000	-0.12	-1000
S1P5 pathway	10	174	17	-0.14	0.045	1000	-1000	-0.081	-1000
Nongenotropic Androgen signaling	10	551	52	-0.17	0.074	1000	-1000	-0.094	-1000
Signaling events mediated by VEGFR1 and VEGFR2	10	1340	125	-0.4	0.044	1000	-1000	-0.15	-1000
Stabilization and expansion of the E-cadherin adherens junction	10	762	74	-0.68	0.1	1000	-1000	-0.14	-1000
a4b1 and a4b7 Integrin signaling	9	48	5	-0.022	0.016	1000	-1000	-0.061	-1000
S1P4 pathway	9	249	25	-0.14	0.035	1000	-1000	-0.085	-1000
Signaling events regulated by Ret tyrosine kinase	8	692	82	-0.059	0.032	1000	-1000	-0.12	-1000
TCGA08_rtk_signaling	8	213	26	-0.28	0.041	1000	-1000	-0.029	-1000
Visual signal transduction: Cones	7	296	38	-0.036	0.016	1000	-1000	-0.1	-1000
Canonical NF-kappaB pathway	6	256	39	-0.2	0.074	1000	-1000	-0.12	-1000
Signaling events mediated by PRL	6	219	34	-0.056	0.049	1000	-1000	-0.089	-1000
ErbB2/ErbB3 signaling events	5	368	65	-0.13	0.061	1000	-1000	-0.1	-1000
Insulin-mediated glucose transport	5	166	32	-0.079	0.067	1000	-1000	-0.099	-1000
Signaling events mediated by HDAC Class III	5	208	40	-0.065	0.032	1000	-1000	-0.069	-1000
IL1-mediated signaling events	5	355	62	-0.096	0.062	1000	-1000	-0.14	-1000
Signaling mediated by p38-gamma and p38-delta	5	76	15	0	0.037	1000	-1000	-0.056	-1000
Syndecan-3-mediated signaling events	5	187	35	-0.04	0.016	1000	-1000	-0.099	-1000
Arf6 trafficking events	5	366	71	-0.13	0.05	1000	-1000	-0.11	-1000
Class IB PI3K non-lipid kinase events	5	15	3	-0.007	0.007	1000	-1000	-0.02	-1000
Arf6 downstream pathway	4	198	43	-0.034	0.034	1000	-1000	-0.065	-1000
Ephrin B reverse signaling	4	215	48	-0.022	0.034	1000	-1000	-0.11	-1000
E-cadherin signaling in the nascent adherens junction	4	357	76	-0.026	0.068	1000	-1000	-0.14	-1000
p38 MAPK signaling pathway	4	182	44	-0.11	0.051	1000	-1000	-0.091	-1000
Ras signaling in the CD4+ TCR pathway	4	71	17	-0.037	0.055	1000	-1000	-0.068	-1000
BARD1 signaling events	3	188	57	-0.18	0.044	1000	-1000	-0.11	-1000
Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met)	3	314	85	-0.037	0.081	1000	-1000	-0.11	-1000
EPHB forward signaling	3	298	85	-0.073	0.075	1000	-1000	-0.15	-1000
Osteopontin-mediated events	2	87	38	-0.029	0.1	1000	-1000	-0.15	-1000
Cellular roles of Anthrax toxin	2	108	39	-0.023	0.028	1000	-1000	-0.046	-1000
ceramide signaling pathway	2	129	49	-0.12	0.054	1000	-1000	-0.081	-1000
RXR and RAR heterodimerization with other nuclear receptor	2	125	52	-0.029	0.092	1000	-1000	-0.092	-1000
Paxillin-dependent events mediated by a4b1	2	98	36	-0.031	0.031	1000	-1000	-0.1	-1000
Regulation of p38-alpha and p38-beta	2	136	54	-0.04	0.074	1000	-1000	-0.081	-1000
Insulin Pathway	2	168	74	-0.034	0.057	1000	-1000	-0.14	-1000
Plasma membrane estrogen receptor signaling	2	255	86	-0.16	0.076	1000	-1000	-0.13	-1000
PDGFR-beta signaling pathway	2	236	97	-0.057	0.09	1000	-1000	-0.13	-1000
E-cadherin signaling in keratinocytes	2	124	43	-0.3	0.056	1000	-1000	-0.11	-1000
Signaling events mediated by HDAC Class II	1	101	75	-0.026	0.051	1000	-1000	-0.099	-1000
Hedgehog signaling events mediated by Gli proteins	1	110	65	-0.062	0.093	1000	-1000	-0.097	-1000
Class I PI3K signaling events mediated by Akt	1	81	68	-0.079	0.061	1000	-1000	-0.1	-1000
Role of Calcineurin-dependent NFAT signaling in lymphocytes	1	154	83	-0.079	0.081	1000	-1000	-0.12	-1000
Signaling events mediated by HDAC Class I	1	146	104	-0.029	0.064	1000	-1000	-0.11	-1000
Retinoic acid receptors-mediated signaling	1	93	58	-0.022	0.065	1000	-1000	-0.1	-1000
Atypical NF-kappaB pathway	1	37	31	-0.024	0.036	1000	-1000	-0.1	-1000
IGF1 pathway	1	57	57	-0.068	0.073	1000	-1000	-0.15	-1000
Regulation of cytoplasmic and nuclear SMAD2/3 signaling	0	0	23	0	0.063	1000	-1000	-0.12	-1000
Circadian rhythm pathway	0	16	22	-0.019	0.066	1000	-1000	-0.087	-1000
mTOR signaling pathway	0	52	53	-0.005	0.046	1000	-1000	-0.088	-1000
Nectin adhesion pathway	0	27	63	-0.015	0.082	1000	-1000	-0.1	-1000
TRAIL signaling pathway	0	21	48	-0.002	0.072	1000	-1000	-0.093	-1000
Signaling mediated by p38-alpha and p38-beta	0	42	44	-0.043	0.052	1000	-1000	-0.077	-1000
Sumoylation by RanBP2 regulates transcriptional repression	0	0	27	0	0.039	1000	-1000	-0.08	-1000
Rapid glucocorticoid signaling	0	10	20	-0.005	0.016	1000	-1000	-0.053	-1000
Arf1 pathway	0	25	54	-0.011	0.035	1000	-1000	-0.064	-1000
Alternative NF-kappaB pathway	0	8	13	-0.006	0.016	1000	-1000	-0.099	-1000
Total	3556	199670	7203	-41	-990	131000	-131000	-14	-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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PKM2	-0.98	0.53	-9999	-1.3	293	293
HDAC7	0.014	0.005	-9999	-10000	0	0
HIF1A/ARNT/Cbp/p300/Src-1	-0.68	0.33	-9999	-0.9	286	286
SMAD4	0.017	0	-9999	-10000	0	0
ID2	-0.98	0.53	-9999	-1.3	304	304
AP1	-0.012	0.081	-9999	-0.57	10	10
ABCG2	-0.98	0.53	-9999	-1.3	302	302
HIF1A	-0.1	0.048	-9999	-10000	0	0
TFF3	-0.99	0.53	-9999	-1.3	304	304
GATA2	0.003	0.1	-9999	-0.76	9	9
AKT1	-0.094	0.052	-9999	-10000	0	0
response to hypoxia	-0.13	0.058	-9999	-10000	0	0
MCL1	-0.98	0.53	-9999	-1.3	303	303
NDRG1	-0.98	0.53	-9999	-1.3	302	302
SERPINE1	-1	0.56	-9999	-1.4	304	304
FECH	-0.98	0.53	-9999	-1.3	304	304
FURIN	-0.98	0.53	-9999	-1.3	304	304
NCOA2	0.005	0.07	-9999	-0.76	4	4
EP300	-0.1	0.074	-9999	-0.36	2	2
HMOX1	-0.99	0.55	-9999	-1.3	305	305
BHLHE40	-0.98	0.53	-9999	-1.3	304	304
BHLHE41	-1.1	0.58	-9999	-1.4	309	309
HIF1A/ARNT/SMAD3/SMAD4/SP1	-0.077	0.046	-9999	-10000	0	0
ENG	-0.056	0.055	-9999	-10000	0	0
JUN	0.016	0.003	-9999	-10000	0	0
RORA	-0.98	0.53	-9999	-1.3	293	293
ABCB1	-0.3	0.42	-9999	-1.3	63	63
TFRC	-0.98	0.53	-9999	-1.3	293	293
CXCR4	-1.1	0.6	-9999	-1.5	312	312
TF	-1	0.58	-9999	-1.4	300	300
CITED2	-0.98	0.53	-9999	-1.3	304	304
HIF1A/ARNT	-1.3	0.85	-9999	-1.7	319	319
LDHA	-0.085	0.064	-9999	-0.86	2	2
ETS1	-0.98	0.53	-9999	-1.3	303	303
PGK1	-0.98	0.53	-9999	-1.3	302	302
NOS2	-0.98	0.53	-9999	-1.3	306	306
ITGB2	-1	0.57	-9999	-1.4	302	302
ALDOA	-0.98	0.53	-9999	-1.3	302	302
Cbp/p300/CITED2	-0.98	0.53	-9999	-1.4	276	276
FOS	0	0.11	-9999	-0.76	10	10
HK2	-1.2	0.58	-9999	-1.5	358	358
SP1	0.021	0.029	-9999	-10000	0	0
GCK	-0.18	0.18	-9999	-1.1	10	10
HK1	-0.98	0.53	-9999	-1.3	304	304
NPM1	-0.98	0.53	-9999	-1.3	293	293
EGLN1	-0.98	0.53	-9999	-1.3	291	291
CREB1	0.026	0.002	-9999	-10000	0	0
PGM1	-0.98	0.53	-9999	-1.3	303	303
SMAD3	0.017	0	-9999	-10000	0	0
EDN1	-0.092	0.17	-9999	-0.8	19	19
IGFBP1	-1	0.57	-9999	-1.4	308	308
VEGFA	-0.77	0.41	-9999	-1.1	217	217
HIF1A/JAB1	-0.052	0.026	-9999	-10000	0	0
CP	-1.2	0.59	-9999	-1.5	350	350
CXCL12	-0.98	0.53	-9999	-1.3	297	297
COPS5	0.011	0.008	-9999	-10000	0	0
SMAD3/SMAD4	0	0	-9999	-10000	0	0
BNIP3	-0.98	0.53	-9999	-1.3	300	300
EGLN3	-1.3	0.51	-9999	-1.5	380	380
CA9	-1.3	0.47	-9999	-1.5	390	390
TERT	-1	0.55	-9999	-1.4	310	310
ENO1	-0.98	0.53	-9999	-1.3	293	293
PFKL	-0.98	0.53	-9999	-1.3	291	291
NCOA1	0.014	0.004	-9999	-10000	0	0
ADM	-1	0.57	-9999	-1.4	316	316
ARNT	-0.1	0.046	-9999	-10000	0	0
HNF4A	-0.046	0.22	-9999	-0.76	41	41
ADFP	-0.99	0.53	-9999	-1.3	307	307
SLC2A1	-0.63	0.33	-9999	-0.98	150	150
LEP	-1	0.55	-9999	-1.4	309	309
HIF1A/ARNT/Cbp/p300	-0.7	0.33	-9999	-0.92	289	289
EPO	-0.61	0.39	-9999	-1.1	170	170
CREBBP	-0.1	0.074	-9999	-0.34	6	6
HIF1A/ARNT/Cbp/p300/HDAC7	-0.75	0.38	-9999	-1	274	274
PFKFB3	-0.98	0.53	-9999	-1.3	304	304
NT5E	-0.98	0.53	-9999	-1.3	302	302

×

Nephrin/Neph1 signaling in the kidney podocyte

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
positive regulation of NF-kappaB transcription factor activity	0.49	0.26	0.63	374	-10000	0	374
KIRREL	-0.049	0.078	-10000	0	-0.84	4	4
Nephrin/NEPH1Par3/Par6/Atypical PKCs	-0.5	0.26	-10000	0	-0.63	374	374
PLCG1	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
WASL	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/CD2AP	-0.54	0.31	-10000	0	-0.86	209	209
ChemicalAbstracts:57-88-5	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/NCK1-2/N-WASP	-0.42	0.25	-10000	0	-0.67	209	209
FYN	-0.51	0.3	-10000	0	-0.62	398	398
mol:Ca2+	-0.53	0.31	-10000	0	-0.84	209	209
mol:DAG	-0.54	0.31	-10000	0	-0.85	209	209
NPHS2	-0.42	0.39	-10000	0	-0.82	231	231
mol:IP3	-0.54	0.31	-10000	0	-0.85	209	209
regulation of endocytosis	-0.48	0.28	-10000	0	-0.76	209	209
Nephrin/NEPH1/podocin/Cholesterol	-0.55	0.32	-10000	0	-0.66	398	398
establishment of cell polarity	-0.49	0.26	-10000	0	-0.63	374	374
Nephrin/NEPH1/podocin/NCK1-2	-0.5	0.3	-10000	0	-0.8	209	209
Nephrin/NEPH1/beta Arrestin2	-0.49	0.29	-10000	0	-0.78	209	209
NPHS1	-0.62	0.33	-10000	0	-0.8	374	374
Nephrin/NEPH1/podocin	-0.52	0.3	-10000	0	-0.62	398	398
TJP1	0.016	0	-10000	0	-10000	0	0
NCK1	0.016	0	-10000	0	-10000	0	0
NCK2	0.016	0	-10000	0	-10000	0	0
heterophilic cell adhesion	0	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/PLCgamma1	-0.54	0.31	-10000	0	-0.86	209	209
CD2AP	0.016	0	-10000	0	-10000	0	0
Nephrin/NEPH1/podocin/GRB2	-0.54	0.31	-10000	0	-0.66	392	392
GRB2	0.016	0	-10000	0	-10000	0	0
homophilic cell adhesion	0	0	-10000	0	-10000	0	0
TRPC6	-0.5	0.3	-10000	0	-0.8	209	209
cytoskeleton organization	-0.54	0.32	-10000	0	-0.86	209	209
Nephrin/NEPH1	-0.37	0.2	-10000	0	-0.47	374	374
Nephrin/NEPH1/ZO-1	-0.4	0.22	-10000	0	-0.51	374	374

×

TCR signaling in naïve CD8+ T cells

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
GRB2/SOS1/SHC	-0.34	0.33	-10000	0	-0.69	220	220
FYN	-0.42	0.5	-10000	0	-0.94	220	220
LAT/GRAP2/SLP76	-0.37	0.39	-10000	0	-0.76	221	221
IKBKB	0.016	0	-10000	0	-10000	0	0
AKT1	-0.26	0.29	-10000	0	-0.54	223	223
B2M	0.009	0.009	-10000	0	-10000	0	0
IKBKG	-0.081	0.071	-10000	0	-0.19	73	73
MAP3K8	0.012	0.057	-10000	0	-0.86	2	2
mol:Ca2+	-0.12	0.045	-10000	0	-0.14	319	319
integrin-mediated signaling pathway	-0.018	0.1	-10000	0	-0.58	15	15
LAT/GRAP2/SLP76/VAV1/PI3K Class IA	-0.42	0.45	-10000	0	-0.86	230	230
TRPV6	-0.67	0.26	-10000	0	-0.77	417	417
CD28	-0.06	0.24	-10000	0	-0.87	37	37
SHC1	-0.45	0.49	-10000	0	-0.94	227	227
receptor internalization	-0.53	0.57	-10000	0	-1.1	231	231
PRF1	-0.5	0.6	-10000	0	-1.1	209	209
KRAS	0.016	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
COT/AKT1	-0.19	0.22	-10000	0	-0.42	209	209
LAT	-0.52	0.54	-10000	0	-1	243	243
EntrezGene:6955	-0.003	0.005	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	216	216
CD3E	-0.37	0.44	-10000	0	-0.88	205	205
CD3G	-0.33	0.43	-10000	0	-0.87	186	186
RASGRP2	-0.023	0.029	-10000	0	-0.14	2	2
RASGRP1	-0.24	0.28	-10000	0	-0.51	218	218
HLA-A	0.006	0.041	-10000	0	-0.88	1	1
RASSF5	-0.012	0.15	-10000	0	-0.86	15	15
RAP1A/GTP/RAPL	-0.018	0.1	-10000	0	-0.59	15	15
mol:GTP	0	0	-10000	0	-10000	0	0
mol:GDP	-0.038	0.082	-10000	0	-0.14	3	3
PDK1/CARD11/BCL10/MALT1/TRAF6	-0.15	0.13	-10000	0	-0.34	93	93
PRKCA	-0.14	0.17	-10000	0	-0.31	189	189
GRAP2	-0.046	0.22	-10000	0	-0.86	34	34
mol:IP3	-0.16	0.34	0.26	154	-0.5	211	365
EntrezGene:6957	-0.003	0.006	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.54	0.64	-10000	0	-1.1	230	230
ORAI1	0.33	0.13	0.38	416	-10000	0	416
CSK	-0.47	0.51	-10000	0	-0.98	226	226
B7 family/CD28	-0.53	0.52	-10000	0	-1	227	227
CHUK	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70	-0.58	0.63	-10000	0	-1.2	231	231
PTPN6	-0.45	0.53	-10000	0	-1	214	214
VAV1	-0.5	0.54	-10000	0	-1	235	235
Monovalent TCR/CD3	-0.46	0.54	-10000	0	-1	221	221
CBL	0.016	0	-10000	0	-10000	0	0
LCK	-0.45	0.53	-10000	0	-1	220	220
PAG1	-0.47	0.51	-10000	0	-0.98	227	227
RAP1A	0.016	0	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK	-0.55	0.64	-10000	0	-1.2	225	225
CD80	-0.19	0.37	-10000	0	-0.87	108	108
CD86	-0.13	0.32	-10000	0	-0.87	76	76
PDK1/CARD11/BCL10/MALT1	-0.18	0.16	-10000	0	-0.35	187	187
HRAS	0.016	0	-10000	0	-10000	0	0
GO:0035030	-0.36	0.42	-10000	0	-0.78	227	227
CD8A	-0.4	0.44	-10000	0	-0.87	225	225
CD8B	-0.31	0.43	-10000	0	-0.88	174	174
PTPRC	-0.091	0.28	-10000	0	-0.87	54	54
PDK1/PKC theta	-0.33	0.36	-10000	0	-0.69	224	224
CSK/PAG1	-0.45	0.5	-10000	0	-0.96	223	223
SOS1	0.016	0	-10000	0	-10000	0	0
peptide-MHC class I	-0.001	0.031	-10000	0	-0.68	1	1
GRAP2/SLP76	-0.44	0.44	-10000	0	-0.9	223	223
STIM1	0.18	0.064	-10000	0	-10000	0	0
RAS family/GTP	-0.065	0.11	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8/LCK/ZAP-70/CBL/ubiquitin	-0.6	0.66	-10000	0	-1.2	231	231
mol:DAG	-0.21	0.26	-10000	0	-0.46	219	219
RAP1A/GDP	-0.014	0.035	-10000	0	-10000	0	0
PLCG1	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	159	159
cytotoxic T cell degranulation	-0.46	0.56	-10000	0	-1	212	212
RAP1A/GTP	-0.008	0.008	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	-0.32	0.35	-10000	0	-0.67	228	228
LAT/GRAP2/SLP76/VAV1/PLCgamma1	-0.27	0.44	0.3	102	-0.71	218	320
NRAS	0.016	0	-10000	0	-10000	0	0
ZAP70	-0.48	0.44	-10000	0	-0.87	272	272
GRB2/SOS1	0	0	-10000	0	-10000	0	0
LAT/GRAP2/SLP76/VAV1	-0.39	0.35	-10000	0	-0.74	224	224
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
CD8 heterodimer	-0.52	0.56	-10000	0	-1.1	230	230
CARD11	-0.17	0.36	-10000	0	-0.86	101	101
PRKCB	-0.14	0.17	-10000	0	-0.31	201	201
PRKCE	-0.14	0.17	-10000	0	-0.31	198	198
PRKCQ	-0.4	0.43	-10000	0	-0.82	230	230
LCP2	-0.043	0.22	-10000	0	-0.86	32	32
BCL10	0.016	0	-10000	0	-10000	0	0
regulation of survival gene product expression	-0.21	0.24	-10000	0	-0.45	223	223
IKK complex	-0.029	0.084	-10000	0	-10000	0	0
RAS family/GDP	-0.012	0.011	-10000	0	-10000	0	0
MAP3K14	-0.13	0.18	-10000	0	-0.32	112	112
PDPK1	-0.24	0.27	-10000	0	-0.51	220	220
TCR/CD3/MHC I/CD8/Fyn	-0.57	0.66	-10000	0	-1.2	222	222

×

TCGA08_p53

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
CDKN2A	-0.66	0.13	-10000	0	-0.68	463	463
TP53	-0.17	0.037	-10000	0	-10000	0	0
Senescence	-0.17	0.036	-10000	0	-10000	0	0
Apoptosis	-0.17	0.036	-10000	0	-10000	0	0
Activated_Oncogenes	0	0	-10000	0	-10000	0	0
MDM2	0.31	0.06	0.33	463	-10000	0	463
MDM4	0.014	0.04	-10000	0	-0.86	1	1

×

FOXA2 and FOXA3 transcription factor networks

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
ACADVL	-0.45	0.48	-10000	0	-1.1	121	121
PCK1	-0.94	0.72	-10000	0	-1.5	264	264
HNF4A	-0.59	0.58	-10000	0	-1.3	136	136
KCNJ11	-0.45	0.51	-10000	0	-1.2	101	101
AKT1	-0.17	0.18	-10000	0	-10000	0	0
response to starvation	-0.02	0.039	-10000	0	-10000	0	0
DLK1	-0.56	0.58	-10000	0	-1.3	153	153
NKX2-1	-0.048	0.21	0.58	1	-0.82	3	4
ACADM	-0.45	0.48	-10000	0	-1.1	118	118
TAT	-0.52	0.35	-10000	0	-0.85	201	201
CEBPB	-0.026	0.14	-10000	0	-0.92	12	12
CEBPA	-0.019	0.12	-10000	0	-0.9	9	9
TTR	-0.91	0.48	-10000	0	-1.2	321	321
PKLR	-0.51	0.56	-10000	0	-1.3	118	118
APOA1	-0.56	0.57	-10000	0	-1.3	131	131
CPT1C	-0.45	0.48	-10000	0	-1.1	121	121
ALAS1	-0.17	0.2	-10000	0	-10000	0	0
TFRC	-0.63	0.42	-10000	0	-1	206	206
FOXF1	-0.004	0.12	-10000	0	-0.84	10	10
NF1	0.025	0.001	-10000	0	-10000	0	0
HNF1A (dimer)	-0.001	0.083	-10000	0	-0.81	4	4
CPT1A	-0.45	0.48	-10000	0	-1.1	114	114
HMGCS1	-0.45	0.48	-10000	0	-1.1	113	113
NR3C1	0.003	0.067	-10000	0	-0.97	1	1
CPT1B	-0.47	0.5	-10000	0	-1.2	112	112
chromatin remodeling	0	0	-10000	0	-10000	0	0
SP1	0.017	0.005	-10000	0	-10000	0	0
GCK	-0.46	0.49	-10000	0	-1.1	123	123
CREB1	-0.027	0.065	-10000	0	-10000	0	0
IGFBP1	-0.32	0.42	-10000	0	-1	112	112
PDX1	-0.19	0.22	-10000	0	-1.1	5	5
UCP2	-0.45	0.48	-10000	0	-1.1	121	121
ALDOB	-0.95	0.63	-10000	0	-1.2	368	368
AFP	-0.74	0.51	-10000	0	-0.99	312	312
BDH1	-0.6	0.57	-10000	0	-1.2	186	186
HADH	-0.44	0.49	-10000	0	-1.2	96	96
F2	-0.66	0.62	-10000	0	-1.3	193	193
HNF1A	-0.001	0.083	-10000	0	-0.81	4	4
G6PC	-0.81	0.66	-10000	0	-1.5	227	227
SLC2A2	-0.32	0.47	-10000	0	-1.7	41	41
INS	0.01	0.055	-10000	0	-10000	0	0
FOXA1	-0.4	0.41	-10000	0	-0.95	146	146
FOXA3	-0.62	0.38	-10000	0	-0.88	291	291
FOXA2	-0.52	0.57	-10000	0	-1.3	129	129
ABCC8	-0.45	0.49	-10000	0	-1.2	102	102
ALB	-1.3	0.49	-10000	0	-1.4	422	422

×

Syndecan-4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.056	0.14	-9999	-0.54	37	37
Syndecan-4/Syndesmos	-0.47	0.4	-9999	-0.85	218	218
positive regulation of JNK cascade	-0.54	0.38	-9999	-0.85	263	263
Syndecan-4/ADAM12	-0.58	0.5	-9999	-1	241	241
CCL5	-0.36	0.44	-9999	-0.86	206	206
Rac1/GDP	0	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
ITGA5	-0.052	0.24	-9999	-0.86	37	37
SDCBP	0.016	0	-9999	-10000	0	0
PLG	-0.38	0.37	-9999	-0.73	256	256
ADAM12	-0.23	0.4	-9999	-0.86	135	135
mol:GTP	0	0	-9999	-10000	0	0
NUDT16L1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-4/PKC alpha	-0.1	0.071	-9999	-10000	0	0
Syndecan-4/Laminin alpha1	-0.48	0.4	-9999	-0.86	221	221
Syndecan-4/CXCL12/CXCR4	-0.6	0.43	-9999	-0.94	263	263
Syndecan-4/Laminin alpha3	-0.47	0.4	-9999	-0.85	221	221
MDK	-0.052	0.24	-9999	-0.86	37	37
Syndecan-4/FZD7	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/Midkine	-0.5	0.42	-9999	-0.89	229	229
FZD7	0.014	0.035	-9999	-0.76	1	1
Syndecan-4/FGFR1/FGF	-0.44	0.34	-9999	-0.77	220	220
THBS1	0.014	0.035	-9999	-0.76	1	1
integrin-mediated signaling pathway	-0.45	0.36	-9999	-0.8	222	222
positive regulation of MAPKKK cascade	-0.54	0.38	-9999	-0.85	263	263
Syndecan-4/TACI	-0.51	0.43	-9999	-0.9	229	229
CXCR4	-0.3	0.42	-9999	-0.86	170	170
cell adhesion	-0.009	0.12	-9999	-0.51	14	14
Syndecan-4/Dynamin	-0.47	0.4	-9999	-0.85	218	218
Syndecan-4/TSP1	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/GIPC	-0.47	0.4	-9999	-0.85	219	219
Syndecan-4/RANTES	-0.65	0.46	-9999	-1	272	272
ITGB1	0.016	0	-9999	-10000	0	0
LAMA1	-0.007	0.13	-9999	-0.77	14	14
LAMA3	0.007	0.089	-9999	-0.86	5	5
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	0.11	0.067	-9999	-10000	0	0
Syndecan-4/alpha-Actinin	-0.47	0.4	-9999	-0.85	218	218
TFPI	0	0.11	-9999	-0.82	9	9
F2	-0.32	0.43	-9999	-0.87	182	182
alpha5/beta1 Integrin	-0.051	0.18	-9999	-0.67	37	37
positive regulation of cell adhesion	-0.46	0.39	-9999	-0.82	224	224
ACTN1	0.014	0.04	-9999	-0.86	1	1
TNC	0	0.11	-9999	-0.76	10	10
Syndecan-4/CXCL12	-0.47	0.4	-9999	-0.85	222	222
FGF6	0	0.002	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CXCL12	0.003	0.099	-9999	-0.76	8	8
TNFRSF13B	-0.065	0.25	-9999	-0.86	43	43
FGF2	0.009	0.073	-9999	-0.78	4	4
FGFR1	0.016	0	-9999	-10000	0	0
Syndecan-4/PI-4-5-P2	-0.48	0.39	-9999	-0.86	218	218
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.043	0.23	-9999	-0.83	37	37
cell migration	-0.03	0.022	-9999	-10000	0	0
PRKCD	0.024	0.047	-9999	-0.85	1	1
vasculogenesis	-0.44	0.37	-9999	-0.8	219	219
SDC4	-0.52	0.44	-9999	-0.94	218	218
Syndecan-4/Tenascin C	-0.48	0.39	-9999	-0.85	222	222
Syndecan-4/PI-4-5-P2/PKC alpha	-0.08	0.055	-9999	-10000	0	0
Syndecan-4/Syntenin	-0.47	0.4	-9999	-0.85	218	218
MMP9	-0.39	0.44	-9999	-0.86	223	223
Rac1/GTP	-0.018	0.12	-9999	-0.53	14	14
cytoskeleton organization	-0.44	0.37	-9999	-0.8	218	218
GIPC1	0.014	0.035	-9999	-0.76	1	1
Syndecan-4/TFPI	-0.48	0.4	-9999	-0.85	223	223

×

Aurora B signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Condensin I complex	-0.25	0.32	-9999	-0.68	154	154
STMN1	-0.3	0.35	-9999	-0.66	229	229
Aurora B/RasGAP/Survivin	-0.41	0.48	-9999	-0.87	233	233
Chromosomal passenger complex/Cul3 protein complex	-0.17	0.23	-9999	-0.49	138	138
BIRC5	-0.25	0.41	-9999	-0.89	140	140
DES	-0.38	0.34	-9999	-0.62	258	258
Aurora C/Aurora B/INCENP	-0.24	0.28	-9999	-0.53	230	230
Aurora B/TACC1	-0.27	0.3	-9999	-0.58	229	229
Aurora B/PP2A	-0.3	0.34	-9999	-0.66	229	229
mol:GTP	0	0	-9999	-10000	0	0
CBX5	-0.074	0.091	-9999	-10000	0	0
mitotic metaphase/anaphase transition	0.001	0.008	-9999	-10000	0	0
NDC80	-0.42	0.5	-9999	-0.9	233	233
Cul3 protein complex	-0.015	0.084	-9999	-0.48	15	15
KIF2C	-0.16	0.18	-9999	-0.34	187	187
PEBP1	0.007	0.008	-9999	-10000	0	0
KIF20A	-0.4	0.44	-9999	-0.87	228	228
mol:GDP	0	0	-9999	-10000	0	0
Aurora B/RasGAP	-0.3	0.34	-9999	-0.66	229	229
SEPT1	-0.1	0.3	-9999	-0.86	63	63
SMC2	0.016	0	-9999	-10000	0	0
SMC4	0.016	0	-9999	-10000	0	0
NSUN2/NPM1/Nucleolin	-0.19	0.24	-9999	-0.46	168	168
PSMA3	0.016	0	-9999	-10000	0	0
G2/M transition of mitotic cell cycle	-0.003	0.004	-9999	-10000	0	0
H3F3B	-0.17	0.21	-9999	-0.39	229	229
AURKB	-0.41	0.44	-9999	-0.87	229	229
AURKC	0.014	0.04	-9999	-0.86	1	1
CDCA8	-0.026	0.17	-9999	-0.9	18	18
cytokinesis	-0.35	0.37	-9999	-0.74	203	203
Aurora B/Septin1	-0.37	0.42	-9999	-0.83	197	197
AURKA	0.001	0.099	-9999	-0.87	6	6
INCENP	0.007	0.009	-9999	-10000	0	0
KLHL13	-0.008	0.14	-9999	-0.76	15	15
BUB1	-0.4	0.44	-9999	-0.87	223	223
hSgo1/Aurora B/Survivin	-0.4	0.49	-9999	-0.85	234	234
EVI5	0.009	0.008	-9999	-10000	0	0
RhoA/GTP	-0.32	0.34	-9999	-0.71	185	185
SGOL1	-0.015	0.16	-9999	-0.86	17	17
CENPA	-0.3	0.35	-9999	-0.63	236	236
NCAPG	-0.29	0.42	-9999	-0.86	167	167
Aurora B/HC8 Proteasome	-0.3	0.34	-9999	-0.66	229	229
NCAPD2	0.016	0	-9999	-10000	0	0
Aurora B/PP1-gamma	-0.3	0.34	-9999	-0.66	229	229
RHOA	0.016	0	-9999	-10000	0	0
NCAPH	-0.14	0.34	-9999	-0.86	84	84
NPM1	-0.22	0.24	-9999	-0.47	229	229
RASA1	0.016	0	-9999	-10000	0	0
KLHL9	0.016	0	-9999	-10000	0	0
mitotic prometaphase	-0.01	0.011	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.3	0.34	-9999	-0.66	229	229
PPP1CC	0.016	0	-9999	-10000	0	0
Centraspindlin	-0.35	0.38	-9999	-0.78	191	191
RhoA/GDP	0	0	-9999	-10000	0	0
NSUN2	-0.22	0.24	-9999	-0.47	229	229
MYLK	-0.17	0.21	-9999	-0.39	229	229
KIF23	-0.008	0.11	-9999	-0.88	8	8
VIM	-0.35	0.41	-9999	-0.74	241	241
RACGAP1	0.003	0.058	-9999	-0.88	2	2
mitosis	0	0	-9999	-10000	0	0
NCL	-0.22	0.24	-9999	-0.47	229	229
Chromosomal passenger complex	-0.36	0.41	-9999	-0.76	225	225
Chromosomal passenger complex/EVI5	-0.37	0.48	-9999	-1	139	139
TACC1	0.016	0	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
CUL3	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0

×

IL12-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IL12/IL12R/TYK2/JAK2/SOCS1	-0.17	0.26	-10000	0	-0.55	108	108
TBX21	-0.56	0.68	-10000	0	-1.2	214	214
B2M	0.01	0.009	-10000	0	-10000	0	0
TYK2	0.012	0.021	-10000	0	-10000	0	0
IL12RB1	-0.28	0.43	-10000	0	-0.91	152	152
GADD45B	-0.31	0.43	-10000	0	-0.82	153	153
IL12RB2	-0.11	0.31	-10000	0	-0.88	67	67
GADD45G	-0.32	0.44	-10000	0	-0.82	159	159
natural killer cell activation	-0.01	0.03	-10000	0	-10000	0	0
RELB	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL18	0.002	0.099	-10000	0	-0.87	6	6
IL2RA	-0.16	0.35	-10000	0	-0.86	96	96
IFNG	-0.39	0.44	-10000	0	-0.86	220	220
STAT3 (dimer)	-0.39	0.47	-10000	0	-0.86	210	210
HLA-DRB5	-0.04	0.22	-10000	0	-0.86	31	31
FASLG	-0.62	0.7	-10000	0	-1.3	237	237
NF kappa B2 p52/RelB	-0.53	0.54	-10000	0	-1.1	207	207
CD4	0	0.12	-10000	0	-0.86	9	9
SOCS1	0.007	0.089	-10000	0	-0.86	5	5
EntrezGene:6955	-0.002	0.01	-10000	0	-10000	0	0
CD3D	-0.38	0.44	-10000	0	-0.87	216	216
CD3E	-0.36	0.44	-10000	0	-0.87	205	205
CD3G	-0.33	0.43	-10000	0	-0.87	186	186
IL12Rbeta2/JAK2	-0.083	0.25	-10000	0	-0.69	67	67
CCL3	-0.5	0.63	-10000	0	-1.2	186	186
CCL4	-0.52	0.67	-10000	0	-1.2	199	199
HLA-A	0.008	0.041	-10000	0	-0.87	1	1
IL18/IL18R	-0.15	0.31	-10000	0	-0.6	153	153
NOS2	-0.38	0.5	-10000	0	-0.93	176	176
IL12/IL12R/TYK2/JAK2/SPHK2	-0.17	0.26	-10000	0	-0.57	93	93
IL1R1	-0.46	0.6	-10000	0	-1.1	199	199
IL4	0.014	0.031	-10000	0	-10000	0	0
JAK2	0.012	0.021	-10000	0	-10000	0	0
EntrezGene:6957	-0.002	0.01	-10000	0	-10000	0	0
TCR/CD3/MHC I/CD8	-0.72	0.83	-10000	0	-1.5	237	237
RAB7A	-0.25	0.37	-10000	0	-0.74	81	81
lysosomal transport	-0.24	0.36	-10000	0	-0.69	89	89
FOS	-0.38	0.5	-10000	0	-0.94	191	191
STAT4 (dimer)	-0.42	0.53	-10000	0	-0.98	196	196
STAT5A (dimer)	-0.66	0.62	-10000	0	-1.2	239	239
GZMA	-0.58	0.71	-10000	0	-1.3	217	217
GZMB	-0.54	0.68	-10000	0	-1.2	214	214
HLX	-0.083	0.28	-10000	0	-0.86	54	54
LCK	-0.53	0.7	-10000	0	-1.2	207	207
TCR/CD3/MHC II/CD4	-0.38	0.47	-10000	0	-0.88	212	212
IL2/IL2R	-0.44	0.42	-10000	0	-0.71	292	292
MAPK14	-0.32	0.44	-10000	0	-0.82	160	160
CCR5	-0.49	0.6	-10000	0	-1.1	206	206
IL1B	0.005	0.082	-10000	0	-0.86	4	4
STAT6	-0.086	0.15	-10000	0	-10000	0	0
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0	-10000	0	-10000	0	0
STAT1	0.014	0.04	-10000	0	-0.86	1	1
NFKB1	0.016	0	-10000	0	-10000	0	0
NFKB2	0.016	0	-10000	0	-10000	0	0
IL12B	-0.095	0.3	-10000	0	-0.9	57	57
CD8A	-0.4	0.44	-10000	0	-0.87	225	225
CD8B	-0.31	0.43	-10000	0	-0.87	174	174
T-helper 1 cell differentiation	0	0	-10000	0	-10000	0	0
natural killer cell mediated cytotoxicity	0.17	0.26	0.54	108	-10000	0	108
IL2RB	-0.47	0.44	-10000	0	-0.86	263	263
proteasomal ubiquitin-dependent protein catabolic process	-0.38	0.48	-10000	0	-0.87	193	193
IL2RG	-0.045	0.22	-10000	0	-0.86	33	33
IL12	-0.072	0.24	-10000	0	-0.72	58	58
STAT5A	0.016	0	-10000	0	-10000	0	0
CD247	-0.28	0.42	-10000	0	-0.87	159	159
IL2	-0.008	0.12	-10000	0	-0.86	10	10
SPHK2	0.012	0.05	-10000	0	-0.76	2	2
FRAP1	0	0	-10000	0	-10000	0	0
IL12A	0.01	0.047	-10000	0	-0.92	1	1
IL12/IL12R/TYK2/JAK2	-0.6	0.79	-10000	0	-1.4	207	207
MAP2K3	-0.32	0.44	-10000	0	-0.8	181	181
RIPK2	0.014	0.04	-10000	0	-0.86	1	1
MAP2K6	-0.32	0.44	-10000	0	-0.8	181	181
regulation of dendritic cell antigen processing and presentation	0	0	-10000	0	-10000	0	0
HLA-DRA	0.011	0.069	-10000	0	-0.86	3	3
IL18RAP	-0.25	0.41	-10000	0	-0.87	143	143
IL12Rbeta1/TYK2	-0.21	0.35	-10000	0	-0.72	152	152
EOMES	-0.31	0.38	-10000	0	-0.74	205	205
STAT1 (dimer)	-0.46	0.51	-10000	0	-0.95	224	224
T cell proliferation	-0.28	0.37	-10000	0	-0.67	175	175
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
IL18R1	0.001	0.1	-10000	0	-0.82	7	7
CD8-positive alpha-beta T cell lineage commitment	0	0	-10000	0	-10000	0	0
NF kappa B1 p50/RelA	-0.38	0.33	-10000	0	-0.75	184	184
ATF2	-0.28	0.41	-10000	0	-0.77	143	143

×

FOXM1 transcription factor network

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
NFATC3	-0.2	0.68	-10000	0	-1.2	114	114
PLK1	-0.11	0.41	-10000	0	-0.8	124	124
BIRC5	-0.14	0.43	-10000	0	-0.79	140	140
HSPA1B	-0.2	0.68	-10000	0	-1.2	116	116
MAP2K1	0.04	0.047	-10000	0	-10000	0	0
BRCA2	-0.21	0.69	-10000	0	-1.2	121	121
FOXM1	-0.39	1	-10000	0	-1.9	128	128
XRCC1	-0.2	0.68	-10000	0	-1.2	113	113
FOXM1B/p19	-0.5	0.5	0.51	1	-1.2	127	128
Cyclin D1/CDK4	-0.2	0.61	-10000	0	-1.1	103	103
CDC2	-0.23	0.73	-10000	0	-1.3	128	128
TGFA	-0.17	0.61	-10000	0	-1.1	103	103
SKP2	-0.2	0.68	-10000	0	-1.2	116	116
CCNE1	0.004	0.1	-10000	0	-0.88	6	6
CKS1B	-0.2	0.68	-10000	0	-1.2	113	113
RB1	-0.2	0.26	-10000	0	-0.69	90	90
FOXM1C/SP1	-0.3	0.78	-10000	0	-1.5	124	124
AURKB	-0.26	0.47	-10000	0	-0.77	204	204
CENPF	-0.22	0.72	-10000	0	-1.3	118	118
CDK4	0.02	0.022	-10000	0	-10000	0	0
MYC	-0.16	0.61	-10000	0	-1	115	115
CHEK2	0.038	0.064	-10000	0	-0.91	1	1
ONECUT1	-0.2	0.66	-10000	0	-1.2	115	115
CDKN2A	-0.83	0.16	-10000	0	-0.86	463	463
LAMA4	-0.29	0.7	-10000	0	-1.2	131	131
FOXM1B/HNF6	-0.29	0.8	-10000	0	-1.5	116	116
FOS	-0.21	0.69	-10000	0	-1.2	120	120
SP1	0.017	0.005	-10000	0	-10000	0	0
CDC25B	-0.2	0.69	-10000	0	-1.2	118	118
response to radiation	0.013	0.05	-10000	0	-10000	0	0
CENPB	-0.2	0.68	-10000	0	-1.2	114	114
CENPA	-0.3	0.78	-10000	0	-1.4	137	137
NEK2	-0.26	0.76	-10000	0	-1.4	128	128
HIST1H2BA	-0.21	0.68	-10000	0	-1.2	119	119
CCNA2	-0.16	0.36	-10000	0	-0.88	96	96
EP300	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.29	0.82	-10000	0	-1.5	119	119
CCNB2	-0.26	0.76	-10000	0	-1.4	122	122
CCNB1	-0.23	0.73	-10000	0	-1.3	119	119
ETV5	-0.2	0.68	-10000	0	-1.2	114	114
ESR1	-0.2	0.68	-10000	0	-1.2	115	115
CCND1	-0.19	0.64	-10000	0	-1.1	104	104
GSK3A	0.036	0.042	-10000	0	-10000	0	0
Cyclin A-E1/CDK1-2	-0.084	0.29	-10000	0	-0.64	96	96
CDK2	0.015	0.016	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	0.014	0.059	-10000	0	-10000	0	0
FOXM1B/Cbp/p300	-0.44	0.59	-10000	0	-1.4	128	128
GAS1	-0.24	0.71	-10000	0	-1.2	133	133
MMP2	-0.2	0.68	-10000	0	-1.2	114	114
RB1/FOXM1C	-0.22	0.68	-10000	0	-1.2	115	115
CREBBP	0.016	0	-10000	0	-10000	0	0

×

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.38	-9999	-0.76	184	184
PDGF/PDGFRA/CRKL	-0.21	0.27	-9999	-0.55	184	184
positive regulation of JUN kinase activity	-0.16	0.2	-9999	-0.52	1	1
CRKL	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Caveolin-3	-0.22	0.27	-9999	-0.56	185	185
AP1	-0.16	0.24	-9999	-1.3	10	10
mol:IP3	-0.2	0.29	-9999	-0.57	184	184
PLCG1	-0.2	0.29	-9999	-0.57	184	184
PDGF/PDGFRA/alphaV Integrin	-0.21	0.27	-9999	-0.55	184	184
RAPGEF1	0.016	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
mol:Ca2+	-0.19	0.29	-9999	-0.56	184	184
CAV3	0.003	0.04	-9999	-0.86	1	1
CAV1	-0.05	0.23	-9999	-0.86	36	36
SHC/Grb2/SOS1	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/Shf	-0.21	0.27	-9999	-0.55	185	185
FOS	-0.12	0.26	-9999	-1.2	10	10
JUN	-0.013	0.017	-9999	-10000	0	0
oligodendrocyte development	-0.21	0.27	-9999	-0.55	184	184
GRB2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
mol:DAG	-0.2	0.29	-9999	-0.57	184	184
PDGF/PDGFRA	-0.28	0.38	-9999	-0.76	184	184
actin cytoskeleton reorganization	-0.21	0.27	-9999	-0.55	184	184
SRF	0.034	0.009	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
PI3K	-0.18	0.23	-9999	-0.46	184	184
PDGF/PDGFRA/Crk/C3G	-0.18	0.23	-9999	-0.5	6	6
JAK1	-0.19	0.28	-9999	-0.55	184	184
ELK1/SRF	-0.15	0.2	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
SHF	0.014	0.035	-9999	-0.76	1	1
CSNK2A1	0.017	0.022	-9999	-10000	0	0
GO:0007205	-0.2	0.3	-9999	-0.58	184	184
SOS1	0.016	0	-9999	-10000	0	0
Ras protein signal transduction	-0.16	0.2	-9999	-0.52	1	1
PDGF/PDGFRA/SHB	-0.21	0.27	-9999	-0.55	184	184
PDGF/PDGFRA/Caveolin-1	-0.26	0.3	-9999	-0.59	212	212
ITGAV	0.016	0	-9999	-10000	0	0
ELK1	-0.16	0.27	-9999	-0.5	184	184
PIK3CA	0.016	0	-9999	-10000	0	0
PDGF/PDGFRA/Crk	-0.21	0.27	-9999	-0.55	184	184
JAK-STAT cascade	-0.19	0.28	-9999	-0.55	184	184
cell proliferation	-0.21	0.27	-9999	-0.55	185	185

×

JNK signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
LAT/GRAP2/SLP76/HPK1	-0.43	0.55	-9999	-0.93	221	221
MAP4K1	-0.35	0.43	-9999	-0.86	197	197
MAP3K8	0.012	0.057	-9999	-0.86	2	2
PRKCB	0.007	0.085	-9999	-0.82	5	5
DBNL	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
MAP3K1	-0.16	0.3	-9999	-0.62	121	121
JUN	0.001	0.076	-9999	-0.53	4	4
MAP3K7	-0.16	0.3	-9999	-0.62	121	121
GRAP2	-0.046	0.22	-9999	-0.86	34	34
CRK	0.016	0	-9999	-10000	0	0
MAP2K4	-0.14	0.29	-9999	-0.59	121	121
LAT	-0.25	0.4	-9999	-0.86	143	143
LCP2	-0.043	0.22	-9999	-0.86	32	32
MAPK8	-0.011	0.081	-9999	-0.57	4	4
LAT/GRAP2/SLP76/HPK1/HIP-55/CRK family	-0.21	0.3	-9999	-0.67	121	121
LAT/GRAP2/SLP76/HPK1/HIP-55	-0.41	0.52	-9999	-0.88	221	221

×

amb2 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaM/beta2 Integrin/proMMP-2	-0.15	0.29	-9999	-0.67	105	105
alphaM/beta2 Integrin/GPIbA	-0.14	0.28	-9999	-0.67	101	101
alphaM/beta2 Integrin/proMMP-9	-0.4	0.43	-9999	-0.76	254	254
PLAUR	-0.028	0.19	-9999	-0.86	24	24
HMGB1	0.015	0.013	-9999	-10000	0	0
alphaM/beta2 Integrin/Talin	-0.14	0.28	-9999	-0.67	101	101
AGER	-0.13	0.33	-9999	-0.86	79	79
RAP1A	0.016	0	-9999	-10000	0	0
SELPLG	-0.048	0.23	-9999	-0.86	35	35
mol:LDL	0	0	-9999	-10000	0	0
alphaM/beta2 Integrin/RAGE/HMGB1	-0.23	0.34	-9999	-0.95	56	56
mol:GTP	0	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
CYR61	0.008	0.079	-9999	-0.76	5	5
TLN1	0.016	0	-9999	-10000	0	0
Rap1/GTP	-0.26	0.21	-9999	-0.57	112	112
RHOA	0.016	0	-9999	-10000	0	0
P-selectin oligomer	-0.02	0.16	-9999	-0.76	22	22
MYH2	-0.35	0.26	-9999	-0.65	172	172
MST1R	0.006	0.088	-9999	-0.78	6	6
leukocyte activation during inflammatory response	-0.28	0.35	-9999	-0.64	210	210
APOB	-0.27	0.41	-9999	-0.86	158	158
mol:GDP	0	0	-9999	-10000	0	0
complement component iC3b receptor activity	0	0	-9999	-10000	0	0
MMP2	0.007	0.089	-9999	-0.86	5	5
JAM3	0.016	0	-9999	-10000	0	0
GP1BA	0.014	0.035	-9999	-0.76	1	1
alphaM/beta2 Integrin/CTGF	-0.15	0.29	-9999	-0.67	105	105
alphaM/beta2 Integrin	-0.31	0.25	-9999	-0.54	216	216
JAM3 homodimer	0.016	0	-9999	-10000	0	0
ICAM2	0.016	0	-9999	-10000	0	0
ICAM1	-0.003	0.13	-9999	-0.86	10	10
phagocytosis triggered by activation of immune response cell surface activating receptor	-0.31	0.25	-9999	-0.53	216	216
cell adhesion	-0.14	0.28	-9999	-0.66	101	101
NFKB1	-0.18	0.37	-9999	-0.95	58	58
THY1	0.014	0.035	-9999	-0.76	1	1
RhoA/GDP	0	0	-9999	-10000	0	0
Lipoprotein(a)	-0.2	0.28	-9999	-0.6	159	159
alphaM/beta2 Integrin/LRP/tPA	-0.14	0.27	-9999	-0.74	48	48
IL6	-0.2	0.41	-9999	-0.91	91	91
ITGB2	-0.17	0.36	-9999	-0.86	99	99
elevation of cytosolic calcium ion concentration	-0.16	0.3	-9999	-0.87	39	39
alphaM/beta2 Integrin/JAM2/JAM3	-0.13	0.26	-9999	-0.61	101	101
JAM2	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/ICAM1	-0.14	0.28	-9999	-0.89	34	34
alphaM/beta2 Integrin/uPA/Plg	-0.37	0.34	-9999	-0.95	84	84
RhoA/GTP	-0.38	0.27	-9999	-0.68	179	179
positive regulation of phagocytosis	-0.26	0.27	-9999	-0.79	73	73
Ron/MSP	-0.016	0.098	-9999	-0.63	12	12
alphaM/beta2 Integrin/uPAR/uPA	-0.16	0.3	-9999	-0.89	39	39
alphaM/beta2 Integrin/uPAR	-0.17	0.32	-9999	-0.7	116	116
PLAU	0.004	0.093	-9999	-0.76	7	7
PLAT	-0.004	0.12	-9999	-0.76	12	12
actin filament polymerization	-0.34	0.24	-9999	-0.62	172	172
MST1	0.005	0.098	-9999	-0.86	6	6
alphaM/beta2 Integrin/lipoprotein(a)	-0.29	0.36	-9999	-0.65	210	210
TNF	-0.15	0.34	-9999	-0.85	62	62
RAP1B	0.016	0	-9999	-10000	0	0
alphaM/beta2 Integrin/uPA	-0.15	0.29	-9999	-0.66	105	105
fibrinolysis	-0.36	0.34	-9999	-0.92	88	88
HCK	-0.034	0.2	-9999	-0.86	27	27
dendritic cell antigen processing and presentation	-0.31	0.25	-9999	-0.53	216	216
VTN	-0.11	0.29	-9999	-0.77	76	76
alphaM/beta2 Integrin/CYR61	-0.15	0.29	-9999	-0.66	104	104
LPA	0.002	0.069	-9999	-0.86	3	3
LRP1	0.016	0	-9999	-10000	0	0
cell migration	-0.37	0.41	-9999	-0.7	255	255
FN1	-0.052	0.24	-9999	-0.86	37	37
alphaM/beta2 Integrin/Thy1	-0.14	0.29	-9999	-0.67	101	101
MPO	-0.013	0.15	-9999	-0.86	15	15
KNG1	-0.57	0.33	-9999	-0.76	363	363
RAP1/GDP	0	0	-9999	-10000	0	0
ROCK1	-0.34	0.26	-9999	-0.64	168	168
ELA2	0	0	-9999	-10000	0	0
PLG	-0.4	0.38	-9999	-0.76	256	256
CTGF	0.006	0.086	-9999	-0.76	6	6
alphaM/beta2 Integrin/Hck	-0.17	0.35	-9999	-0.77	105	105
ITGAM	-0.02	0.17	-9999	-0.87	19	19
alphaM/beta2 Integrin/P-Selectin/PSGL1	-0.19	0.35	-9999	-0.75	108	108
HP	-0.21	0.38	-9999	-0.86	121	121
leukocyte adhesion	-0.18	0.27	-9999	-0.81	50	50
SELP	-0.02	0.16	-9999	-0.76	22	22

×

IL4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.48	0.48	-10000	0	-1.2	107	107
STAT6 (cleaved dimer)	-0.59	0.5	-10000	0	-1.1	178	178
IGHG1	-0.17	0.19	-10000	0	-0.66	12	12
IGHG3	-0.48	0.46	-10000	0	-1.1	127	127
AKT1	-0.28	0.34	-10000	0	-0.83	80	80
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHP1	-0.25	0.32	-10000	0	-0.81	84	84
IL4/IL4R/JAK1/IL2R gamma/JAK3/IRS1	-0.27	0.3	-10000	0	-0.8	59	59
THY1	-0.48	0.49	-10000	0	-1.2	104	104
MYB	-0.22	0.39	-10000	0	-0.86	130	130
HMGA1	0.014	0.04	-10000	0	-0.86	1	1
IL4/IL4R/JAK1/IL2R gamma/JAK3	-0.4	0.43	-10000	0	-0.98	118	118
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHIP	-0.27	0.3	-10000	0	-0.81	59	59
SP1	0.022	0.015	-10000	0	-10000	0	0
INPP5D	0.008	0.08	-10000	0	-0.86	4	4
SOCS5	0.026	0.017	-10000	0	-10000	0	0
STAT6 (dimer)/ETS1	-0.56	0.48	-10000	0	-1.2	154	154
SOCS1	-0.33	0.34	-10000	0	-0.81	69	69
SOCS3	-0.3	0.35	-10000	0	-0.88	76	76
FCER2	-0.42	0.44	-10000	0	-1.1	74	74
PARP14	0.016	0.004	-10000	0	-10000	0	0
CCL17	-0.51	0.51	-10000	0	-1.2	112	112
GRB2	0.016	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP	-0.23	0.28	-10000	0	-0.8	49	49
T cell proliferation	-0.51	0.52	-10000	0	-1.2	120	120
IL4R/JAK1	-0.48	0.48	-10000	0	-1.2	107	107
EGR2	-0.49	0.5	-10000	0	-1.2	105	105
JAK2	0.008	0.023	-10000	0	-10000	0	0
JAK3	-0.17	0.36	-10000	0	-0.87	102	102
PIK3R1	0.016	0	-10000	0	-10000	0	0
JAK1	0.007	0.016	-10000	0	-10000	0	0
COL1A2	-0.22	0.31	-10000	0	-0.9	64	64
CCL26	-0.49	0.49	-10000	0	-1.2	104	104
IL4R	-0.51	0.52	-10000	0	-1.2	108	108
PTPN6	0.027	0.012	-10000	0	-10000	0	0
IL13RA2	-0.55	0.56	-10000	0	-1.3	123	123
IL13RA1	0.008	0.023	-10000	0	-10000	0	0
IRF4	-0.28	0.44	-10000	0	-0.98	121	121
ARG1	-0.17	0.27	-10000	0	-0.81	38	38
CBL	-0.36	0.4	-10000	0	-0.93	112	112
GTF3A	0.011	0.03	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
IL13RA1/JAK2	-0.006	0.044	-10000	0	-10000	0	0
IRF4/BCL6	-0.28	0.39	-10000	0	-0.94	112	112
CD40LG	-0.09	0.31	-10000	0	-0.92	57	57
MAPK14	-0.36	0.4	-10000	0	-0.95	105	105
mitosis	-0.27	0.32	-10000	0	-0.78	80	80
STAT6	-0.55	0.56	-10000	0	-1.3	117	117
SPI1	-0.097	0.3	-10000	0	-0.86	64	64
RPS6KB1	-0.25	0.31	-10000	0	-0.77	68	68
STAT6 (dimer)	-0.56	0.56	-10000	0	-1.3	117	117
STAT6 (dimer)/PARP14	-0.51	0.52	-10000	0	-1.2	116	116
mast cell activation	0.012	0.014	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/DOK2	-0.31	0.37	-10000	0	-0.89	94	94
FRAP1	-0.28	0.34	-10000	0	-0.83	80	80
LTA	-0.61	0.56	-10000	0	-1.3	146	146
FES	0.012	0.05	-10000	0	-0.76	2	2
T-helper 1 cell differentiation	0.54	0.54	1.3	118	-10000	0	118
CCL11	-0.7	0.61	-10000	0	-1.3	212	212
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES	-0.3	0.35	-10000	0	-0.87	86	86
IL2RG	-0.04	0.22	-10000	0	-0.86	33	33
IL10	-0.5	0.51	-10000	0	-1.2	111	111
IRS1	0.012	0.05	-10000	0	-0.76	2	2
IRS2	0.001	0.11	-10000	0	-0.86	8	8
IL4	-0.11	0.13	-10000	0	-10000	0	0
IL5	-0.49	0.48	-10000	0	-1.2	107	107
IL4/IL4R/JAK1/IL13RA1/JAK2	-0.39	0.38	-10000	0	-0.9	88	88
COL1A1	-0.41	0.44	-10000	0	-0.92	185	185
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
IL4/IL4R/JAK1	-0.48	0.49	-10000	0	-1.2	88	88
IL2R gamma/JAK3	-0.17	0.37	-10000	0	-0.84	105	105
TFF3	-0.5	0.51	-10000	0	-1.2	113	113
ALOX15	-0.49	0.49	-10000	0	-1.2	103	103
MYBL1	-0.052	0.24	-10000	0	-0.86	37	37
T-helper 2 cell differentiation	-0.43	0.42	-10000	0	-0.97	122	122
SHC1	0.014	0.04	-10000	0	-0.86	1	1
CEBPB	-0.002	0.14	-10000	0	-0.87	12	12
IL4/IL4R/JAK1/IL2R gamma/JAK3/FES/IRS2	-0.26	0.3	-10000	0	-0.8	57	57
mol:PI-3-4-5-P3	-0.28	0.34	-10000	0	-0.83	80	80
PI3K	-0.3	0.36	-10000	0	-0.9	80	80
DOK2	-0.035	0.21	-10000	0	-0.86	28	28
ETS1	0.028	0.015	-10000	0	-10000	0	0
IL4/IL4R/JAK1/IL2R gamma/JAK3/SHC/SHIP/GRB2	-0.21	0.28	-10000	0	-0.78	50	50
ITGB3	-0.48	0.49	-10000	0	-1.2	108	108
PIGR	-0.84	0.71	-10000	0	-1.5	248	248
IGHE	0.028	0.093	0.29	10	-0.41	2	12
MAPKKK cascade	-0.21	0.27	-10000	0	-0.76	50	50
BCL6	0.012	0.006	-10000	0	-10000	0	0
OPRM1	-0.49	0.48	-10000	0	-1.2	105	105
RETNLB	-0.49	0.48	-10000	0	-1.2	110	110
SELP	-0.51	0.53	-10000	0	-1.3	111	111
AICDA	-0.62	0.55	-10000	0	-1.2	175	175

×

Glypican 1 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GPC1/FGF2 dimer/FGFR1 dimer	-0.005	0.051	-10000	0	-0.5	5	5
fibroblast growth factor receptor signaling pathway	-0.005	0.051	-10000	0	-0.5	5	5
LAMA1	-0.007	0.13	-10000	0	-0.77	14	14
PRNP	0.016	0	-10000	0	-10000	0	0
GPC1/SLIT2	-0.12	0.23	-10000	0	-0.57	99	99
SMAD2	0.045	0.022	-10000	0	-10000	0	0
GPC1/PrPc/Cu2+	-0.001	0.023	-10000	0	-0.5	1	1
GPC1/Laminin alpha1	-0.018	0.1	-10000	0	-0.58	15	15
TDGF1	-0.57	0.33	-10000	0	-0.76	364	364
CRIPTO/GPC1	-0.43	0.25	-10000	0	-0.57	364	364
APP/GPC1	-0.002	0.037	-10000	0	-0.57	2	2
mol:NO	0	0	-10000	0	-10000	0	0
YES1	-0.36	0.22	-10000	0	-0.48	364	364
FLT1	0.008	0.08	-10000	0	-0.86	4	4
GPC1/TGFB/TGFBR1/TGFBR2	-0.001	0.022	-10000	0	-0.48	1	1
SERPINC1	-0.066	0.24	-10000	0	-0.77	49	49
FYN	-0.36	0.22	-10000	0	-0.48	364	364
FGR	-0.36	0.23	-10000	0	-0.91	5	5
positive regulation of MAPKKK cascade	-0.37	0.25	-10000	0	-0.74	49	49
SLIT2	-0.14	0.31	-10000	0	-0.76	98	98
GPC1/NRG	-0.014	0.089	-10000	0	-0.57	12	12
NRG1	-0.002	0.12	-10000	0	-0.76	11	11
GPC1/VEGF165 homodimer/VEGFR1 homodimer	-0.26	0.3	-10000	0	-0.59	216	216
LYN	-0.36	0.22	-10000	0	-0.48	364	364
mol:Spermine	0.014	0.027	-10000	0	-0.58	1	1
cell growth	-0.005	0.051	-10000	0	-0.5	5	5
BMP signaling pathway	-0.014	0.035	0.76	1	-10000	0	1
SRC	-0.36	0.22	-10000	0	-0.75	2	2
TGFBR1	0.016	0	-10000	0	-10000	0	0
mol:Cu2+	0	0	-10000	0	-10000	0	0
PLA2G2A	-0.075	0.26	-10000	0	-0.86	47	47
GPC1	0.014	0.035	-10000	0	-0.76	1	1
TGFBR1 (dimer)	0.016	0	-10000	0	-10000	0	0
VEGFA	-0.38	0.44	-10000	0	-0.86	215	215
BLK	-0.4	0.26	-10000	0	-0.93	32	32
HCK	-0.39	0.25	-10000	0	-0.51	373	373
FGF2	0.009	0.073	-10000	0	-0.78	4	4
FGFR1	0.016	0	-10000	0	-10000	0	0
VEGFR1 homodimer	0.008	0.08	-10000	0	-0.86	4	4
TGFBR2	0.016	0	-10000	0	-10000	0	0
cell death	-0.002	0.037	-10000	0	-0.57	2	2
ATIII/GPC1	-0.061	0.18	-10000	0	-0.58	50	50
PLA2G2A/GPC1	-0.067	0.2	-10000	0	-0.66	48	48
LCK	-0.39	0.24	-10000	0	-0.86	23	23
neuron differentiation	-0.014	0.089	-10000	0	-0.57	12	12
PrPc/Cu2+	0	0	-10000	0	-10000	0	0
APP	0.014	0.035	-10000	0	-0.76	1	1
TGFBR2 (dimer)	0.016	0	-10000	0	-10000	0	0

×

EGFR-dependent Endothelin signaling 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EGF/EGFR	-0.39	0.17	-9999	-0.87	27	27
EGF/EGFR dimer/SHC/GRB2/SOS1	-0.37	0.14	-9999	-0.91	9	9
mol:GTP	0	0	-9999	-10000	0	0
EDNRA	0.012	0.057	-9999	-0.86	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
EGF	-0.68	0.23	-9999	-0.76	432	432
EGF/EGFR dimer/SHC	-0.45	0.16	-9999	-0.5	433	433
mol:GDP	-0.37	0.14	-9999	-0.89	9	9
mol:Ca2+	0	0	-9999	-10000	0	0
EDN1	-0.017	0.17	-9999	-0.86	18	18
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.34	0.13	-9999	-0.82	9	9
SHC1	0.014	0.04	-9999	-0.86	1	1
HRAS/GDP	-0.34	0.13	-9999	-0.83	9	9
FRAP1	-0.35	0.13	-9999	-0.86	9	9
EGF/EGFR dimer	-0.52	0.19	-9999	-0.58	433	433
SOS1	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
ETA receptor/Endothelin-1	-0.028	0.13	-9999	-0.66	20	20

×

Aurora C signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
INCENP	0.016	0	-9999	-10000	0	0
Aurora C/Aurora B/INCENP	-0.26	0.27	-9999	-0.53	230	230
metaphase	0	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
H3F3B	-0.065	0.068	-9999	-10000	0	0
AURKB	-0.4	0.44	-9999	-0.86	229	229
AURKC	0.014	0.04	-9999	-0.86	1	1

×

IL23-mediated 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
CCL2	-0.26	0.48	-10000	0	-1	81	81
IL23A	-0.24	0.48	-10000	0	-1.1	63	63
NF kappa B1 p50/RelA/I kappa B alpha	-0.33	0.39	-10000	0	-1	88	88
positive regulation of T cell mediated cytotoxicity	-0.29	0.53	-10000	0	-1.1	91	91
ITGA3	-0.25	0.47	-10000	0	-1	66	66
IL17F	-0.15	0.35	-10000	0	-0.73	40	40
IL12B	-0.088	0.3	-10000	0	-0.89	57	57
STAT1 (dimer)	-0.29	0.5	-10000	0	-1.1	91	91
CD4	-0.26	0.48	-10000	0	-1	80	80
IL23	-0.28	0.49	-10000	0	-1.1	79	79
IL23R	-0.012	0.15	-10000	0	-0.8	9	9
IL1B	-0.26	0.49	-10000	0	-1.1	66	66
T-helper cell lineage commitment	0	0	-10000	0	-10000	0	0
IL24	-0.25	0.48	-10000	0	-1	74	74
TYK2	0.016	0.025	-10000	0	-10000	0	0
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
STAT3	0.016	0.001	-10000	0	-10000	0	0
IL18RAP	-0.26	0.41	-10000	0	-0.88	143	143
IL12RB1	-0.27	0.43	-10000	0	-0.89	152	152
PIK3CA	0.016	0.001	-10000	0	-10000	0	0
IL12Rbeta1/TYK2	-0.21	0.34	-10000	0	-0.7	152	152
IL23R/JAK2	-0.011	0.16	-10000	0	-0.79	8	8
positive regulation of chronic inflammatory response	-0.29	0.53	-10000	0	-1.1	91	91
natural killer cell activation	0.002	0.012	0.063	9	-10000	0	9
JAK2	0.021	0.035	-10000	0	-10000	0	0
PIK3R1	0.016	0.001	-10000	0	-10000	0	0
NFKB1	0.01	0.009	-10000	0	-10000	0	0
RELA	0.01	0.009	-10000	0	-10000	0	0
positive regulation of dendritic cell antigen processing and presentation	-0.27	0.47	-10000	0	-1	79	79
ALOX12B	-0.31	0.51	-10000	0	-1.1	92	92
CXCL1	-0.3	0.53	-10000	0	-1.1	95	95
T cell proliferation	-0.29	0.53	-10000	0	-1.1	91	91
NFKBIA	0.01	0.009	-10000	0	-10000	0	0
IL17A	-0.1	0.29	-10000	0	-0.59	11	11
PI3K	-0.34	0.4	-10000	0	-1	91	91
IFNG	-0.054	0.069	0.14	3	-0.12	195	198
STAT3 (dimer)	-0.32	0.38	-10000	0	-0.97	88	88
IL18R1	-0.003	0.1	-10000	0	-0.82	7	7
IL23/IL23R/JAK2/TYK2/SOCS3	-0.19	0.38	-10000	0	-0.8	81	81
IL18/IL18R	-0.2	0.29	-10000	0	-0.62	153	153
macrophage activation	-0.017	0.018	-10000	0	-0.044	24	24
TNF	-0.26	0.49	-10000	0	-1.1	66	66
STAT3/STAT4	-0.37	0.44	-10000	0	-1.1	99	99
STAT4 (dimer)	-0.32	0.54	-10000	0	-1.1	99	99
IL18	-0.002	0.097	-10000	0	-0.86	6	6
IL19	-0.26	0.47	-10000	0	-1	74	74
STAT5A (dimer)	-0.29	0.5	-10000	0	-1.1	91	91
STAT1	0.014	0.04	-10000	0	-0.86	1	1
SOCS3	0.012	0.057	-10000	0	-0.86	2	2
CXCL9	-0.41	0.6	-10000	0	-1.1	162	162
MPO	-0.26	0.48	-10000	0	-1	88	88
positive regulation of humoral immune response	-0.29	0.53	-10000	0	-1.1	91	91
IL23/IL23R/JAK2/TYK2	-0.31	0.55	-10000	0	-1.2	91	91
IL6	-0.3	0.53	-10000	0	-1.1	85	85
STAT5A	0.016	0	-10000	0	-10000	0	0
IL2	-0.017	0.12	-10000	0	-0.86	10	10
positive regulation of tyrosine phosphorylation of STAT protein	0.002	0.012	0.063	9	-10000	0	9
CD3E	-0.4	0.6	-10000	0	-1.1	172	172
keratinocyte proliferation	-0.29	0.53	-10000	0	-1.1	91	91
NOS2	-0.26	0.48	-10000	0	-1	79	79

×

Caspase cascade in apoptosis

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
TOP1	-0.13	0.27	-10000	0	-0.5	154	154
ACTA1	-0.19	0.36	-10000	0	-0.68	155	155
NUMA1	-0.13	0.27	-10000	0	-0.58	102	102
SPTAN1	-0.19	0.36	-10000	0	-0.68	154	154
LIMK1	-0.19	0.36	-10000	0	-0.68	155	155
BIRC3	-0.12	0.32	-10000	0	-0.86	74	74
BIRC2	0.011	0.007	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
CASP10	-0.28	0.47	-10000	0	-0.88	168	168
CRMA	0	0	-10000	0	-10000	0	0
XIAP	0.012	0.007	-10000	0	-10000	0	0
PTK2	-0.13	0.27	-10000	0	-0.53	130	130
DIABLO	0.016	0	-10000	0	-10000	0	0
apoptotic nuclear changes	-0.18	0.35	-10000	0	-0.66	154	154
response to UV	0	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
GSN	-0.19	0.36	-10000	0	-0.68	154	154
MADD	0.016	0	-10000	0	-10000	0	0
TFAP2A	-0.3	0.28	-10000	0	-0.54	263	263
BID	-0.09	0.17	-10000	0	-0.37	100	100
MAP3K1	-0.043	0.11	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-10000	0	-10000	0	0
mol:Activated DNA	0	0	-10000	0	-10000	0	0
ARHGDIB	-0.19	0.36	-10000	0	-0.68	154	154
CASP9	0.016	0.001	-10000	0	-10000	0	0
DNA repair	0.012	0.095	-10000	0	-0.21	33	33
neuron apoptosis	0.011	0.046	-10000	0	-0.62	1	1
mol:NAD	0	0	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	-0.17	0.35	-10000	0	-0.77	100	100
APAF1	0.016	0.001	-10000	0	-10000	0	0
CASP6	-0.05	0.16	-10000	0	-0.39	27	27
TRAF2	0.016	0	-10000	0	-10000	0	0
ICAD/CAD	-0.17	0.35	-10000	0	-0.77	100	100
CASP7	0.051	0.13	0.34	74	-10000	0	74
KRT18	-0.002	0.047	-10000	0	-0.3	2	2
apoptosis	-0.17	0.33	-10000	0	-0.7	104	104
DFFA	-0.19	0.36	-10000	0	-0.68	154	154
DFFB	-0.19	0.36	-10000	0	-0.68	154	154
PARP1	-0.013	0.095	0.21	33	-10000	0	33
actin filament polymerization	0.16	0.33	0.72	100	-10000	0	100
TNF	0.002	0.11	-10000	0	-0.81	8	8
CYCS	-0.068	0.13	-10000	0	-0.28	100	100
SATB1	-0.037	0.15	-10000	0	-0.48	3	3
SLK	-0.19	0.36	-10000	0	-0.68	154	154
p15 BID/BAX	-0.073	0.16	-10000	0	-10000	0	0
CASP2	0.031	0.09	-10000	0	-0.43	1	1
JNK cascade	0.043	0.11	-10000	0	-10000	0	0
CASP3	-0.21	0.38	-10000	0	-0.72	154	154
LMNB2	0.011	0.086	-10000	0	-0.39	4	4
RIPK1	0.016	0	-10000	0	-10000	0	0
CASP4	0.016	0	-10000	0	-10000	0	0
Mammalian IAPs/DIABLO	-0.081	0.19	-10000	0	-0.52	74	74
negative regulation of DNA binding	-0.29	0.28	-10000	0	-0.54	263	263
stress fiber formation	-0.18	0.35	-10000	0	-0.66	154	154
GZMB	-0.33	0.51	-10000	0	-0.99	168	168
CASP1	0.023	0	-10000	0	-10000	0	0
LMNB1	0.008	0.091	-10000	0	-0.37	6	6
APP	0.011	0.046	-10000	0	-0.62	1	1
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
response to stress	0	0	-10000	0	-10000	0	0
CASP8	0.015	0	-10000	0	-10000	0	0
VIM	-0.17	0.31	-10000	0	-0.67	104	104
LMNA	0.011	0.086	-10000	0	-0.39	4	4
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD/PIDD	-0.03	0.074	-10000	0	-0.41	7	7
LRDD	0.003	0.1	-10000	0	-0.85	7	7
SREBF1	-0.19	0.36	-10000	0	-0.68	155	155
APAF-1/Caspase 9	-0.009	0.063	-10000	0	-10000	0	0
nuclear fragmentation during apoptosis	-0.13	0.26	-10000	0	-0.57	102	102
CFL2	-0.17	0.34	-10000	0	-0.75	100	100
GAS2	-0.2	0.36	-10000	0	-0.68	157	157
positive regulation of apoptosis	0.015	0.087	-10000	0	-0.4	3	3
PRF1	-0.22	0.39	-10000	0	-0.86	126	126

×

Glypican 2 network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MDK	-0.052	0.24	-9999	-0.86	37	37
GPC2	-0.083	0.28	-9999	-0.86	54	54
GPC2/Midkine	-0.12	0.29	-9999	-0.74	80	80
neuron projection morphogenesis	-0.12	0.29	-9999	-0.74	80	80

×

TCGA08_retinoblastoma

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDKN2B	-0.009	0.089	-10000	0	-0.88	5	5
CDKN2C	0.079	0.017	-10000	0	-10000	0	0
CDKN2A	-0.85	0.16	-10000	0	-0.88	463	463
CCND2	0.18	0.046	0.46	5	-10000	0	5
RB1	-0.2	0.048	-10000	0	-0.48	5	5
CDK4	0.22	0.05	0.48	5	-10000	0	5
CDK6	0.2	0.052	0.51	5	-0.18	1	6
G1/S progression	0.2	0.052	0.47	5	-10000	0	5

×

Syndecan-1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	0.007	0.089	-9999	-0.86	5	5
CCL5	-0.36	0.44	-9999	-0.86	206	206
SDCBP	0.016	0	-9999	-10000	0	0
FGFR/FGF2/Syndecan-1	-0.21	0.23	-9999	-0.59	79	79
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
Syndecan-1/Laminin-5	-0.2	0.22	-9999	-0.56	79	79
Syndecan-1/Syntenin	-0.19	0.22	-9999	-0.56	79	79
MAPK3	-0.16	0.2	-9999	-0.54	46	46
HGF/MET	-0.034	0.15	-9999	-0.67	24	24
TGFB1/TGF beta receptor Type II	0.007	0.089	-9999	-0.86	5	5
BSG	0.016	0	-9999	-10000	0	0
keratinocyte migration	-0.19	0.21	-9999	-0.55	79	79
Syndecan-1/RANTES	-0.41	0.34	-9999	-0.69	250	250
Syndecan-1/CD147	-0.2	0.18	-9999	-0.53	79	79
Syndecan-1/Syntenin/PIP2	-0.21	0.19	-9999	-0.54	79	79
LAMA5	0.014	0.035	-9999	-0.76	1	1
positive regulation of cell-cell adhesion	-0.2	0.18	-9999	-0.53	79	79
MMP7	-0.12	0.3	-9999	-0.77	83	83
HGF	-0.021	0.17	-9999	-0.81	21	21
Syndecan-1/CASK	-0.2	0.22	-9999	-0.57	79	79
Syndecan-1/HGF/MET	-0.22	0.22	-9999	-0.59	88	88
regulation of cell adhesion	-0.14	0.19	-9999	-0.67	13	13
HPSE	0.012	0.05	-9999	-0.76	2	2
positive regulation of cell migration	-0.21	0.23	-9999	-0.59	79	79
SDC1	-0.22	0.23	-9999	-0.6	79	79
Syndecan-1/Collagen	-0.21	0.23	-9999	-0.59	79	79
PPIB	0.016	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PRKACA	0.016	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
MAPK1	-0.16	0.2	-9999	-0.7	13	13
homophilic cell adhesion	-0.21	0.22	-9999	-0.59	79	79
MMP1	-0.15	0.34	-9999	-0.83	95	95

×

HIF-2-alpha transcription factor network

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
MMP14	-0.027	0.083	-10000	0	-0.73	6	6
oxygen homeostasis	-0.001	0.015	-10000	0	-10000	0	0
TCEB2	0.014	0.035	-10000	0	-0.76	1	1
TCEB1	0.016	0	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C/HIF2A	-0.23	0.14	-10000	0	-0.72	1	1
EPO	-0.4	0.41	-10000	0	-0.9	132	132
FIH (dimer)	0.014	0.02	-10000	0	-10000	0	0
APEX1	0.013	0.014	-10000	0	-10000	0	0
SERPINE1	-0.34	0.4	-10000	0	-0.92	102	102
FLT1	-0.017	0.073	-10000	0	-0.76	4	4
ADORA2A	-0.3	0.34	-10000	0	-0.82	68	68
germ cell development	-0.4	0.44	-10000	0	-0.89	183	183
SLC11A2	-0.28	0.34	-10000	0	-0.81	68	68
BHLHE40	-0.28	0.34	-10000	0	-0.81	68	68
HIF1AN	0.014	0.02	-10000	0	-10000	0	0
HIF2A/ARNT/SIRT1	-0.3	0.22	-10000	0	-0.52	200	200
ETS1	0.037	0.004	-10000	0	-10000	0	0
CITED2	-0.02	0.024	-10000	0	-10000	0	0
KDR	-0.014	0.068	-10000	0	-1.4	1	1
PGK1	-0.28	0.34	-10000	0	-0.81	68	68
SIRT1	0.012	0.007	-10000	0	-10000	0	0
response to hypoxia	-0.002	0.005	-10000	0	-10000	0	0
HIF2A/ARNT	-0.34	0.41	-10000	0	-1	68	68
EPAS1	-0.27	0.19	-10000	0	-0.46	144	144
SP1	0.026	0.005	-10000	0	-10000	0	0
ABCG2	-0.29	0.34	-10000	0	-0.81	69	69
EFNA1	-0.29	0.34	-10000	0	-0.81	69	69
FXN	-0.3	0.34	-10000	0	-0.82	68	68
POU5F1	-0.42	0.47	-10000	0	-0.95	183	183
neuron apoptosis	0.33	0.39	0.96	68	-10000	0	68
EP300	0.016	0	-10000	0	-10000	0	0
EGLN3	-0.76	0.29	-10000	0	-0.87	424	424
EGLN2	0.011	0.016	-10000	0	-10000	0	0
EGLN1	0.014	0.02	-10000	0	-10000	0	0
VHL/Elongin B/Elongin C	-0.001	0.022	-10000	0	-0.48	1	1
VHL	0.016	0	-10000	0	-10000	0	0
ARNT	0.013	0.014	-10000	0	-10000	0	0
SLC2A1	-0.31	0.36	-10000	0	-0.9	71	71
TWIST1	-0.3	0.34	-10000	0	-0.83	71	71
ELK1	0.026	0	-10000	0	-10000	0	0
HIF2A/ARNT/Cbp/p300	-0.26	0.2	-10000	0	-0.55	68	68
VEGFA	-0.46	0.48	-10000	0	-0.98	180	180
CREBBP	0.016	0	-10000	0	-10000	0	0

×

Hypoxic and oxygen homeostasis regulation of HIF-1-alpha

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HIF3A	-0.008	0.14	-9999	-0.79	14	14
oxygen homeostasis	0	0	-9999	-10000	0	0
TCEB2	0.014	0.035	-9999	-0.76	1	1
TCEB1	0.016	0	-9999	-10000	0	0
HIF1A/p53	-0.08	0.045	-9999	-10000	0	0
HIF1A	-0.098	0.036	-9999	-10000	0	0
COPS5	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2	-0.001	0.018	-9999	-10000	0	0
FIH (dimer)	0.016	0	-9999	-10000	0	0
CDKN2A	-0.83	0.16	-9999	-0.86	463	463
ARNT/IPAS	-0.017	0.1	-9999	-0.6	14	14
HIF1AN	0.016	0	-9999	-10000	0	0
GNB2L1	0.014	0.04	-9999	-0.86	1	1
HIF1A/ARNT	-0.08	0.045	-9999	-10000	0	0
CUL2	0.016	0	-9999	-10000	0	0
OS9	0.016	0	-9999	-10000	0	0
RACK1/Elongin B/Elongin C	-0.002	0.034	-9999	-0.53	2	2
response to hypoxia	0	0	-9999	-10000	0	0
HIF1A/Hsp90	-0.08	0.045	-9999	-10000	0	0
PHD1-3/OS9	-0.46	0.17	-9999	-0.52	423	423
HIF1A/RACK1/Elongin B/Elongin C	-0.065	0.036	-9999	-0.5	2	2
VHL	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
HIF1A/JAB1	-0.08	0.045	-9999	-10000	0	0
EGLN3	-0.76	0.28	-9999	-0.86	424	424
EGLN2	0.016	0	-9999	-10000	0	0
EGLN1	0.016	0	-9999	-10000	0	0
TP53	0.016	0	-9999	-10000	0	0
VHL/Elongin B/Elongin C/RBX1/CUL2/HIF1A	-0.001	0.013	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
ARD1A	0	0	-9999	-10000	0	0
RBX1	0.016	0	-9999	-10000	0	0
HIF1A/p19ARF	-0.56	0.11	-9999	-0.57	463	463

×

BMP receptor signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BMP7/BMPR2/BMPR1A-1B/FS	-0.6	0.32	-9999	-0.87	253	253
SMAD6-7/SMURF1	0	0	-9999	-10000	0	0
NOG	-0.12	0.32	-9999	-0.85	78	78
SMAD9	-0.064	0.084	-9999	-0.58	9	9
SMAD4	0.016	0	-9999	-10000	0	0
SMAD5	-0.18	0.17	-9999	-0.52	17	17
BMP7/USAG1	-0.7	0.35	-9999	-0.81	416	416
SMAD5/SKI	-0.17	0.16	-9999	-0.5	13	13
SMAD1	0.002	0.042	-9999	-10000	0	0
BMP2	0.009	0.073	-9999	-0.78	4	4
SMAD1/SMAD1/SMAD4	0	0	-9999	-10000	0	0
BMPR1A	0.016	0	-9999	-10000	0	0
BMPR1B	-0.51	0.36	-9999	-0.76	328	328
BMPR1A-1B/BAMBI	-0.34	0.23	-9999	-0.85	4	4
AHSG	-0.009	0.12	-9999	-0.86	9	9
CER1	0.004	0.007	-9999	-10000	0	0
BMP2-4/CER1	-0.005	0.052	-9999	-0.52	5	5
BMP2-4/BMPR2/BMPR1A-1B/RGM/ENDOFIN/GADD34/PP1CA	-0.14	0.11	-9999	-0.5	17	17
BMP2-4 (homodimer)	-0.006	0.06	-9999	-0.59	5	5
RGMB	0.012	0.057	-9999	-0.86	2	2
BMP6/BMPR2/BMPR1A-1B	-0.3	0.2	-9999	-0.52	1	1
RGMA	0.008	0.079	-9999	-0.76	5	5
SMURF1	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/XIAP	-0.17	0.14	-9999	-0.57	17	17
BMP2-4/USAG1	-0.31	0.24	-9999	-0.49	306	306
SMAD6/SMURF1/SMAD5	-0.17	0.16	-9999	-0.5	13	13
SOSTDC1	-0.48	0.37	-9999	-0.76	305	305
BMP7/BMPR2/BMPR1A-1B	-0.59	0.31	-9999	-0.87	235	235
SKI	0.016	0	-9999	-10000	0	0
BMP6 (homodimer)	0.009	0.07	-9999	-0.76	4	4
HFE2	-0.017	0.16	-9999	-0.86	16	16
ZFYVE16	0.016	0	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
BMP2-4/CHRD	-0.016	0.094	-9999	-0.54	14	14
SMAD5/SMAD5/SMAD4	-0.17	0.16	-9999	-0.5	13	13
MAPK1	0.016	0	-9999	-10000	0	0
TAK1/TAB family	-0.13	0.1	-9999	-0.51	13	13
BMP7 (homodimer)	-0.51	0.36	-9999	-0.76	323	323
NUP214	0.016	0	-9999	-10000	0	0
BMP6/FETUA	-0.017	0.1	-9999	-0.64	13	13
SMAD1/SKI	0.012	0.039	-9999	-10000	0	0
SMAD6	0.016	0	-9999	-10000	0	0
CTDSP2	0.016	0	-9999	-10000	0	0
BMP2-4/FETUA	-0.016	0.093	-9999	-0.55	14	14
MAP3K7IP1	0	0	-9999	-10000	0	0
GREM1	-0.18	0.34	-9999	-0.77	118	118
BMPR2 (homodimer)	0.016	0	-9999	-10000	0	0
GADD34/PP1CA	0	0	-9999	-10000	0	0
BMPR1A-1B (homodimer)	-0.39	0.26	-9999	-0.57	328	328
CHRDL1	-0.39	0.38	-9999	-0.76	253	253
ENDOFIN/SMAD1	0.012	0.039	-9999	-10000	0	0
SMAD6-7/SMURF1/SMAD1	0.005	0.003	-9999	-10000	0	0
SMAD6/SMURF1	0.016	0	-9999	-10000	0	0
BAMBI	0.008	0.079	-9999	-0.76	5	5
SMURF2	0.016	0	-9999	-10000	0	0
BMP2-4/CHRDL1	-0.26	0.25	-9999	-0.49	255	255
BMP2-4/GREM1	-0.13	0.22	-9999	-0.5	121	121
SMAD7	0.016	0	-9999	-10000	0	0
SMAD8A/SMAD8A/SMAD4	-0.037	0.089	-9999	-0.54	9	9
SMAD1/SMAD6	0.012	0.039	-9999	-10000	0	0
TAK1/SMAD6	0	0	-9999	-10000	0	0
BMP7	-0.51	0.36	-9999	-0.76	323	323
BMP6	0.009	0.07	-9999	-0.76	4	4
MAP3K7IP2	0	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/SMAD7/SMURF1	-0.12	0.13	-9999	-0.46	17	17
PPM1A	0.016	0	-9999	-10000	0	0
SMAD1/SMURF2	0.012	0.039	-9999	-10000	0	0
SMAD7/SMURF1	0	0	-9999	-10000	0	0
CTDSPL	0.016	0	-9999	-10000	0	0
PPP1CA	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
CTDSP1	0.016	0	-9999	-10000	0	0
PPP1R15A	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM/FS	-0.21	0.18	-9999	-0.6	56	56
CHRD	-0.001	0.12	-9999	-0.79	10	10
BMPR2	0.016	0	-9999	-10000	0	0
BMP2-4/BMPR2/BMPR1A-1B/RGM	-0.17	0.13	-9999	-0.58	17	17
BMP4	0.014	0.035	-9999	-0.76	1	1
FST	-0.072	0.25	-9999	-0.78	53	53
BMP2-4/NOG	-0.096	0.21	-9999	-0.56	82	82
BMP7/BMPR2/BMPR1A-1B/SMAD6/SMURF1	-0.56	0.29	-9999	-0.83	235	235

×

Signaling events mediated by the Hedgehog family

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
TGFB2	-0.25	0.26	-10000	0	-0.75	31	31
IHH	-0.1	0.24	-10000	0	-0.83	45	45
SHH Np/Cholesterol/GAS1	-0.038	0.13	-10000	0	-0.46	39	39
LRPAP1	0.016	0	-10000	0	-10000	0	0
dorsoventral neural tube patterning	0.037	0.13	0.46	39	-10000	0	39
SMO/beta Arrestin2	-0.15	0.16	-10000	0	-0.61	32	32
SMO	-0.14	0.19	-10000	0	-0.64	32	32
AKT1	-0.042	0.091	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
BOC	0.016	0	-10000	0	-10000	0	0
ADRBK1	0.016	0	-10000	0	-10000	0	0
heart looping	-0.14	0.19	-10000	0	-0.63	32	32
STIL	-0.098	0.17	-10000	0	-0.74	7	7
DHH N/PTCH2	-0.045	0.16	-10000	0	-0.64	34	34
DHH N/PTCH1	-0.16	0.16	-10000	0	-0.63	35	35
PIK3CA	0.016	0	-10000	0	-10000	0	0
DHH	-0.001	0.11	-10000	0	-0.76	10	10
PTHLH	-0.45	0.41	-10000	0	-0.74	301	301
determination of left/right symmetry	-0.14	0.19	-10000	0	-0.63	32	32
PIK3R1	0.016	0	-10000	0	-10000	0	0
skeletal system development	-0.44	0.4	-10000	0	-0.74	301	301
IHH N/Hhip	-0.21	0.32	-10000	0	-0.66	149	149
DHH N/Hhip	-0.16	0.26	-10000	0	-0.59	127	127
mol:Cholesterol	0	0	-10000	0	-10000	0	0
heart development	-0.14	0.19	-10000	0	-0.63	32	32
pancreas development	-0.18	0.34	-10000	0	-0.77	119	119
HHAT	0.016	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EntrezGene:84976	0	0	-10000	0	-10000	0	0
GAS1	-0.033	0.19	-10000	0	-0.76	30	30
somite specification	-0.14	0.19	-10000	0	-0.63	32	32
SHH Np/Cholesterol/PTCH1	-0.14	0.15	-10000	0	-0.68	10	10
SHH Np/Cholesterol/PTCH2	-0.036	0.13	-10000	0	-0.51	34	34
SHH Np/Cholesterol/Megalin	-0.048	0.15	-10000	0	-0.5	46	46
SHH	0.018	0.087	-10000	0	-0.58	10	10
catabolic process	-0.16	0.2	-10000	0	-0.66	31	31
SMO/Vitamin D3	-0.14	0.15	-10000	0	-0.73	7	7
SHH Np/Cholesterol/Hhip	-0.12	0.21	-10000	0	-0.47	125	125
LRP2	-0.05	0.22	-10000	0	-0.76	41	41
receptor-mediated endocytosis	-0.16	0.18	-10000	0	-0.78	19	19
SHH Np/Cholesterol/BOC	-0.009	0.065	-10000	0	-0.46	10	10
SHH Np/Cholesterol/CDO	-0.072	0.18	-10000	0	-0.53	65	65
mesenchymal cell differentiation	0.12	0.21	0.46	125	-10000	0	125
mol:Vitamin D3	-0.11	0.18	-10000	0	-0.68	10	10
IHH N/PTCH2	-0.087	0.22	-10000	0	-0.62	67	67
CDON	-0.087	0.28	-10000	0	-0.86	56	56
IHH N/PTCH1	-0.16	0.2	-10000	0	-0.67	31	31
Megalin/LRPAP1	-0.049	0.16	-10000	0	-0.57	41	41
PTCH2	-0.028	0.19	-10000	0	-0.86	24	24
SHH Np/Cholesterol	-0.01	0.067	-10000	0	-0.47	10	10
PTCH1	-0.16	0.2	-10000	0	-0.66	31	31
HHIP	-0.18	0.34	-10000	0	-0.77	119	119

×

Fc-epsilon receptor I signaling in mast cells

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PPAP2A	0.016	0	-9999	-10000	0	0
LAT2	-0.17	0.24	-9999	-0.71	62	62
AP1	-0.16	0.21	-9999	-0.57	80	80
mol:PIP3	-0.24	0.34	-9999	-0.71	141	141
IKBKB	-0.093	0.17	-9999	-0.34	77	77
AKT1	-0.18	0.22	-9999	-0.73	23	23
IKBKG	-0.093	0.17	-9999	-0.34	86	86
MS4A2	-0.18	0.36	-9999	-0.86	102	102
mol:Sphingosine-1-phosphate	0	0	-9999	-10000	0	0
PIK3CA	0.009	0.008	-9999	-10000	0	0
MAP3K1	-0.13	0.27	-9999	-0.58	93	93
mol:Ca2+	-0.17	0.24	-9999	-0.48	141	141
LYN	0.011	0.009	-9999	-10000	0	0
CBLB	-0.12	0.16	-9999	-0.54	24	24
SHC1	0.014	0.04	-9999	-0.86	1	1
RasGAP/p62DOK	-0.001	0.024	-9999	-0.53	1	1
positive regulation of cell migration	0	0	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
PLD2	-0.19	0.29	-9999	-0.92	23	23
PTPN13	-0.076	0.16	-9999	-0.48	22	22
PTPN11	0.014	0.007	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
regulation of mast cell degranulation	-0.051	0.17	-9999	-0.41	6	6
SYK	0.007	0.051	-9999	-0.77	2	2
GRB2	0.015	0.001	-9999	-10000	0	0
LAT/PLCgamma1/GRB2/SLP76/GADs	-0.31	0.32	-9999	-0.77	137	137
LAT	-0.27	0.3	-9999	-0.66	155	155
PAK2	-0.16	0.3	-9999	-0.64	110	110
NFATC2	-0.07	0.085	-9999	-0.64	1	1
HRAS	-0.19	0.33	-9999	-0.7	121	121
GAB2	0.016	0	-9999	-10000	0	0
PLA2G1B	0.042	0.027	-9999	-10000	0	0
Fc epsilon R1	-0.27	0.33	-9999	-0.63	207	207
Antigen/IgE/Fc epsilon R1	-0.26	0.31	-9999	-0.59	207	207
mol:GDP	-0.22	0.36	-9999	-0.78	125	125
JUN	0.016	0	-9999	-10000	0	0
mol:Ca++	0	0	-9999	-10000	0	0
PIK3R1	0.009	0.008	-9999	-10000	0	0
FOS	0	0.11	-9999	-0.76	10	10
Antigen/IgE/Fc epsilon R1/LYN/SYK	-0.14	0.17	-9999	-0.58	24	24
CHUK	-0.093	0.17	-9999	-0.34	77	77
KLRG1	-0.13	0.16	-9999	-0.55	24	24
VAV1	-0.24	0.31	-9999	-0.71	131	131
calcium-dependent protein kinase C activity	0	0	-9999	-10000	0	0
CBL	-0.12	0.16	-9999	-0.54	24	24
negative regulation of mast cell degranulation	-0.12	0.16	-9999	-0.55	26	26
BTK	-0.19	0.24	-9999	-0.63	92	92
Fc epsilon R1/FcgammaRIIB/SHIP/RasGAP/p62DOK	-0.18	0.22	-9999	-0.58	86	86
GAB2/PI3K/SHP2	-0.2	0.24	-9999	-0.83	23	23
Antigen/IgE/Fc epsilon R1/LYN/SYK/WIP	-0.13	0.16	-9999	-0.56	24	24
RAF1	0.028	0.028	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB/SHIP	-0.33	0.4	-9999	-0.96	104	104
FCER1G	-0.19	0.37	-9999	-0.87	107	107
FCER1A	-0.025	0.16	-9999	-0.78	21	21
Antigen/IgE/Fc epsilon R1/Fyn	-0.24	0.29	-9999	-0.56	196	196
MAPK3	0.041	0.026	-9999	-10000	0	0
MAPK1	0.041	0.026	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	-0.012	0.072	-9999	-10000	0	0
DUSP1	0.014	0.04	-9999	-0.86	1	1
NF-kappa-B/RelA	-0.072	0.075	-9999	-10000	0	0
actin cytoskeleton reorganization	-0.082	0.16	-9999	-0.48	24	24
mol:Glucocorticoid Dexamethasone	0	0	-9999	-10000	0	0
PI3K	-0.23	0.3	-9999	-0.74	110	110
FER	-0.12	0.16	-9999	-0.55	25	25
RELA	0.016	0	-9999	-10000	0	0
ITK	-0.16	0.2	-9999	-0.43	159	159
SOS1	0.016	0	-9999	-10000	0	0
PLCG1	-0.21	0.37	-9999	-0.76	127	127
cytokine secretion	-0.053	0.054	-9999	-10000	0	0
SPHK1	-0.16	0.22	-9999	-0.66	57	57
PTK2	-0.086	0.17	-9999	-0.5	24	24
NTAL/PLCgamma1/GRB2/SLP76/GADs	-0.26	0.32	-9999	-0.77	112	112
EDG1	0	0	-9999	-10000	0	0
mol:DAG	-0.2	0.32	-9999	-0.68	114	114
MAP2K2	0.036	0.032	-9999	-0.43	1	1
MAP2K1	0.037	0.024	-9999	-10000	0	0
MAP2K7	0.016	0	-9999	-10000	0	0
KLRG1/SHP2	-0.12	0.15	-9999	-0.53	24	24
MAP2K4	0.017	0.016	-9999	-10000	0	0
Fc epsilon R1/FcgammaRIIB	-0.35	0.42	-9999	-0.74	221	221
mol:Choline	-0.19	0.29	-9999	-0.89	23	23
SHC/Grb2/SOS1	-0.11	0.14	-9999	-0.5	23	23
FYN	0.016	0	-9999	-10000	0	0
DOK1	0.016	0	-9999	-10000	0	0
PXN	-0.07	0.16	-9999	-0.47	17	17
HCLS1	-0.14	0.19	-9999	-0.66	32	32
PRKCB	-0.15	0.23	-9999	-0.47	123	123
FCGR2B	-0.16	0.35	-9999	-0.86	97	97
IGHE	-0.006	0.011	-9999	-10000	0	0
KLRG1/SHIP	-0.12	0.16	-9999	-0.57	26	26
LCP2	-0.044	0.22	-9999	-0.87	32	32
PLA2G4A	-0.13	0.16	-9999	-0.54	28	28
RASA1	0.016	0	-9999	-10000	0	0
mol:Phosphatidic acid	-0.19	0.29	-9999	-0.89	23	23
IKK complex	-0.051	0.13	-9999	-0.28	2	2
WIPF1	0.016	0	-9999	-10000	0	0

×

IL27-mediated signaling events

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
TGFB1	0.008	0.09	-10000	0	-0.86	5	5
CD4-positive alpha-beta T cell lineage commitment	0	0.001	-10000	0	-10000	0	0
cytokine production during immune response	0.074	0.2	0.63	26	-0.44	3	29
IL27/IL27R/JAK1	-0.079	0.35	0.58	1	-0.87	48	49
TBX21	-0.21	0.41	0.5	1	-0.76	142	143
IL12B	-0.096	0.28	-10000	0	-0.87	57	57
IL12A	0.008	0.033	-10000	0	-0.69	1	1
IL6ST	-0.005	0.11	-10000	0	-0.77	10	10
IL27RA/JAK1	0.009	0.063	-10000	0	-0.7	1	1
IL27	-0.044	0.21	-10000	0	-0.88	29	29
TYK2	0.011	0.012	-10000	0	-10000	0	0
T-helper cell lineage commitment	-0.024	0.13	-10000	0	-0.74	2	2
T-helper 2 cell differentiation	0.074	0.2	0.63	26	-0.44	3	29
T cell proliferation during immune response	0.074	0.2	0.63	26	-0.44	3	29
MAPKKK cascade	-0.074	0.2	0.44	3	-0.63	26	29
STAT3	0.016	0	-10000	0	-10000	0	0
STAT2	0.016	0	-10000	0	-10000	0	0
STAT1	0.015	0.041	-10000	0	-0.87	1	1
IL12RB1	-0.27	0.41	-10000	0	-0.87	152	152
positive regulation of tyrosine phosphorylation of STAT protein	0	0	-10000	0	-10000	0	0
IL12RB2	-0.16	0.35	0.5	1	-0.71	87	88
IL27/IL27R/JAK2/TYK2	-0.076	0.2	0.44	3	-0.66	23	26
positive regulation of T cell mediated cytotoxicity	-0.074	0.2	0.44	3	-0.63	26	29
STAT1 (dimer)	-0.062	0.5	0.54	108	-1	61	169
JAK2	0.011	0.012	-10000	0	-10000	0	0
JAK1	0.017	0.006	-10000	0	-10000	0	0
STAT2 (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
T cell proliferation	-0.12	0.25	0.4	1	-0.71	46	47
IL12/IL12R/TYK2/JAK2	-0.18	0.27	-10000	0	-0.59	101	101
IL17A	-0.024	0.13	-10000	0	-0.74	2	2
mast cell activation	0.074	0.2	0.63	26	-0.44	3	29
IFNG	-0.041	0.066	0.13	3	-0.11	220	223
T cell differentiation	-0.011	0.011	0.03	3	-0.026	129	132
STAT3 (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
STAT5A (dimer)	-0.079	0.18	0.39	3	-0.63	21	24
STAT4 (dimer)	-0.11	0.24	0.39	2	-0.76	41	43
STAT4	-0.039	0.21	-10000	0	-0.86	30	30
T cell activation	-0.012	0.007	0.1	1	-10000	0	1
IL27R/JAK2/TYK2	-0.037	0.094	-10000	0	-0.71	1	1
GATA3	-0.61	0.69	-10000	0	-1.3	230	230
IL18	0.005	0.077	-10000	0	-0.68	6	6
positive regulation of mast cell cytokine production	-0.078	0.17	0.38	3	-0.62	21	24
IL27/EBI3	-0.13	0.33	-10000	0	-0.83	80	80
IL27RA	-0.003	0.065	-10000	0	-0.76	1	1
IL6	-0.087	0.28	-10000	0	-0.83	59	59
STAT5A	0.016	0	-10000	0	-10000	0	0
monocyte differentiation	-0.002	0.003	-10000	0	-10000	0	0
IL2	0	0.091	-10000	0	-0.6	10	10
IL1B	0.009	0.061	-10000	0	-0.66	4	4
EBI3	-0.12	0.32	-10000	0	-0.88	71	71
TNF	0.003	0.083	-10000	0	-0.63	8	8

×

Calcineurin-regulated NFAT-dependent transcription in lymphocytes

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
FOXP3	-0.19	0.36	-10000	0	-1.1	67	67
NFATC2	-0.081	0.23	-10000	0	-0.66	26	26
NFATC3	-0.023	0.064	-10000	0	-10000	0	0
CD40LG	-0.25	0.46	-10000	0	-1.1	62	62
ITCH	0.054	0.059	-10000	0	-10000	0	0
CBLB	0.054	0.059	-10000	0	-10000	0	0
CD4-positive CD25-positive alpha-beta regulatory T cell lineage commitment	-0.55	0.57	-10000	0	-1.1	200	200
JUNB	0.013	0.05	-10000	0	-0.76	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.012	0.059	-10000	0	-10000	0	0
T cell anergy	0.024	0.094	-10000	0	-0.45	2	2
TLE4	-0.031	0.17	-10000	0	-0.76	4	4
Jun/NFAT1-c-4/p21SNFT	-0.24	0.28	-10000	0	-0.96	29	29
AP-1/NFAT1-c-4	-0.31	0.37	-10000	0	-1.1	46	46
IKZF1	-0.14	0.37	-10000	0	-0.89	89	89
T-helper 2 cell differentiation	-0.35	0.28	-10000	0	-0.74	93	93
AP-1/NFAT1	-0.094	0.16	-10000	0	-0.64	12	12
CALM1	0.028	0.037	-10000	0	-10000	0	0
EGR2	-0.11	0.28	-10000	0	-1.4	7	7
EGR3	-0.11	0.28	-10000	0	-1.5	6	6
NFAT1/FOXP3	-0.29	0.41	-10000	0	-1	96	96
EGR1	0.006	0.093	-10000	0	-0.76	7	7
JUN	0.005	0.022	-10000	0	-10000	0	0
EGR4	0.007	0.069	-10000	0	-0.86	3	3
mol:Ca2+	0.007	0.041	-10000	0	-10000	0	0
GBP3	-0.034	0.18	-10000	0	-0.79	6	6
FOSL1	-0.026	0.19	-10000	0	-0.86	23	23
NFAT1-c-4/MAF/IRF4	-0.28	0.36	-10000	0	-0.9	101	101
DGKA	-0.034	0.18	-10000	0	-1.1	4	4
CREM	0.014	0.005	-10000	0	-10000	0	0
NFAT1-c-4/PPARG	-0.17	0.21	-10000	0	-1	6	6
CTLA4	-0.43	0.59	-10000	0	-1	215	215
NFAT1-c-4 (dimer)/EGR1	-0.17	0.23	-10000	0	-1.1	9	9
NFAT1-c-4 (dimer)/EGR4	-0.17	0.22	-10000	0	-0.98	10	10
FOS	-0.011	0.11	-10000	0	-0.77	10	10
IFNG	-0.5	0.52	-10000	0	-1	215	215
T cell activation	-0.052	0.22	-10000	0	-0.83	15	15
MAF	0.016	0	-10000	0	-10000	0	0
T-helper 2 cell lineage commitment	0	0	-10000	0	-10000	0	0
activation-induced cell death of T cells	0.067	0.2	0.82	4	-10000	0	4
TNF	-0.097	0.27	-10000	0	-1.1	11	11
FASLG	-0.35	0.47	-10000	0	-0.93	80	80
TBX21	-0.3	0.44	-10000	0	-0.93	156	156
BATF3	-0.058	0.24	-10000	0	-0.86	40	40
PRKCQ	-0.032	0.12	-10000	0	-0.76	12	12
PTPN1	-0.031	0.17	-10000	0	-0.76	4	4
NFAT1-c-4/ICER1	-0.17	0.21	-10000	0	-1	6	6
GATA3	-0.35	0.39	-10000	0	-0.76	230	230
T-helper 1 cell differentiation	-0.49	0.5	-10000	0	-1	215	215
IL2RA	-0.39	0.46	-10000	0	-1.1	120	120
T-helper 1 cell lineage commitment	0	0	-10000	0	-10000	0	0
CASP3	-0.031	0.17	-10000	0	-0.76	4	4
E2F1	-0.074	0.28	-10000	0	-0.86	54	54
PPARG	0.016	0.001	-10000	0	-10000	0	0
SLC3A2	-0.031	0.17	-10000	0	-0.76	4	4
IRF4	-0.19	0.37	-10000	0	-0.86	114	114
PTGS2	-0.22	0.4	-10000	0	-1.1	36	36
CSF2	-0.22	0.4	-10000	0	-1.1	35	35
JunB/Fra1/NFAT1-c-4	-0.18	0.22	-10000	0	-0.91	12	12
IL4	-0.36	0.29	-10000	0	-0.79	85	85
IL5	-0.21	0.38	-10000	0	-1	29	29
IL2	-0.053	0.22	-10000	0	-0.85	15	15
IL3	-0.051	0.049	-10000	0	-10000	0	0
RNF128	0.032	0.16	-10000	0	-0.8	18	18
NFATC1	-0.067	0.2	-10000	0	-0.82	4	4
CDK4	0.038	0.18	-10000	0	-10000	0	0
PTPRK	-0.031	0.17	-10000	0	-0.76	4	4
IL8	-0.23	0.42	-10000	0	-1.1	40	40
POU2F1	0.016	0.003	-10000	0	-10000	0	0

×

Effects of Botulinum toxin

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
STX1A	0.008	0.069	-9999	-0.66	5	5
UniProt:P19321	0	0	-9999	-10000	0	0
RIMS1/UNC13B	-0.019	0.11	-9999	-0.67	14	14
STXBP1	0.014	0.035	-9999	-0.76	1	1
ACh/CHRNA1	-0.28	0.32	-9999	-0.63	212	212
RAB3GAP2/RIMS1/UNC13B	-0.017	0.097	-9999	-0.58	14	14
mol:Ca2+	0	0	-9999	-10000	0	0
UniProt:P30996	0	0	-9999	-10000	0	0
UniProt:Q60393	0	0	-9999	-10000	0	0
CST086	0	0	-9999	-10000	0	0
RIMS1	-0.014	0.15	-9999	-0.86	14	14
mol:ACh	-0.008	0.053	-9999	-0.13	71	71
RAB3GAP2	0.016	0	-9999	-10000	0	0
STX1A/SNAP25/VAMP2	-0.037	0.099	-9999	-0.62	4	4
UniProt:P10844	0	0	-9999	-10000	0	0
muscle contraction	-0.28	0.31	-9999	-0.63	212	212
UNC13B	0.016	0	-9999	-10000	0	0
CHRNA1	-0.37	0.44	-9999	-0.86	212	212
UniProt:P10845	0	0	-9999	-10000	0	0
ACh/Synaptotagmin 1	-0.088	0.21	-9999	-0.54	81	81
SNAP25	-0.038	0.12	-9999	-0.33	68	68
VAMP2	0.009	0	-9999	-10000	0	0
SYT1	-0.12	0.29	-9999	-0.76	81	81
UniProt:Q00496	0	0	-9999	-10000	0	0
STXIA/STXBP1	-0.007	0.062	-9999	-0.56	6	6
STX1A/SNAP25 fragment 1/VAMP2	-0.037	0.099	-9999	-0.62	4	4

×

Ephrin A reverse signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAPKKK cascade	-0.057	0.17	-9999	-0.54	51	51
EFNA5	-0.057	0.23	-9999	-0.76	45	45
FYN	-0.027	0.16	-9999	-0.49	51	51
neuron projection morphogenesis	-0.057	0.17	-9999	-0.54	51	51
cell-cell signaling	0	0	-9999	-10000	0	0
Ephrin A5/EPHA5	-0.058	0.17	-9999	-0.54	51	51
EPHA5	-0.009	0.11	-9999	-0.86	8	8

×

Calcium signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC1	-0.015	0.047	-9999	-10000	0	0
NFATC2	-0.016	0.055	-9999	-0.63	1	1
NFATC3	-0.015	0.047	-9999	-10000	0	0
CD40LG	-0.32	0.43	-9999	-0.95	100	100
PTGS2	-0.3	0.39	-9999	-0.86	93	93
JUNB	0.012	0.05	-9999	-0.76	2	2
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.021	0.018	-9999	-10000	0	0
CaM/Ca2+	-0.021	0.018	-9999	-10000	0	0
CALM1	0.005	0.013	-9999	-10000	0	0
JUN	0.006	0.013	-9999	-10000	0	0
mol:Ca2+	-0.021	0.019	-9999	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	-0.002	0.003	-9999	-10000	0	0
FOSL1	-0.026	0.19	-9999	-0.86	23	23
CREM	0.015	0.001	-9999	-10000	0	0
Jun/NFAT1-c-4/p21SNFT	-0.19	0.2	-9999	-0.75	32	32
FOS	-0.011	0.11	-9999	-0.77	10	10
IFNG	-0.45	0.52	-9999	-0.99	211	211
AP-1/NFAT1-c-4	-0.42	0.41	-9999	-1.1	94	94
FASLG	-0.48	0.52	-9999	-0.99	216	216
NFAT1-c-4/ICER1	-0.081	0.075	-9999	-0.56	1	1
IL2RA	-0.35	0.45	-9999	-1	104	104
FKBP12/FK506	0	0	-9999	-10000	0	0
CSF2	-0.3	0.39	-9999	-0.86	91	91
JunB/Fra1/NFAT1-c-4	-0.095	0.12	-9999	-0.63	8	8
IL4	-0.29	0.37	-9999	-0.83	89	89
IL2	-0.013	0.11	-9999	-0.77	10	10
IL3	-0.029	0.026	-9999	-10000	0	0
FKBP1A	0.016	0	-9999	-10000	0	0
BATF3	-0.058	0.24	-9999	-0.86	40	40
mol:FK506	0	0	-9999	-10000	0	0
POU2F1	0.016	0.003	-9999	-10000	0	0

×

Arf6 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CENTA1/KIF3B	-0.004	0.045	-9999	-0.5	4	4
ARNO/beta Arrestin1-2	-0.017	0.061	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EPHA2	0.014	0.035	-9999	-0.76	1	1
USP6	0.014	0.04	-9999	-0.86	1	1
IQSEC1	0.015	0	-9999	-10000	0	0
EGFR/EGFR/EGF/EGF	-0.52	0.19	-9999	-0.58	433	433
ARRB2	-0.012	0.1	-9999	-0.39	33	33
mol:GTP	-0.011	0.048	-9999	-0.24	2	2
ARRB1	0.016	0	-9999	-10000	0	0
FBXO8	0.016	0	-9999	-10000	0	0
TSHR	-0.089	0.28	-9999	-0.86	57	57
EGF	-0.68	0.23	-9999	-0.76	432	432
somatostatin receptor activity	0	0	-9999	-0.001	16	16
ARAP2	0.014	0.035	-9999	-0.76	1	1
mol:GDP	-0.056	0.094	-9999	-0.34	21	21
mol:PI-3-4-5-P3	0	0	-9999	-0.001	9	9
ITGA2B	-0.012	0.15	-9999	-0.86	15	15
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.002	0.031	-9999	-0.52	1	1
ADAP1	0.009	0.07	-9999	-0.76	4	4
KIF13B	0.016	0	-9999	-10000	0	0
HGF/MET	-0.034	0.15	-9999	-0.67	24	24
PXN	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.086	0.09	-9999	-0.34	19	19
EGFR/EGFR/EGF/EGF/ARFGEP100	-0.45	0.16	-9999	-0.5	433	433
ADRB2	0.012	0.05	-9999	-0.76	2	2
receptor agonist activity	0	0	-9999	0	13	13
actin filament binding	0	0	-9999	-0.001	17	17
SRC	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
GNAQ	0.015	0.003	-9999	-10000	0	0
EFA6/PI-4-5-P2	0	0	-9999	-0.001	11	11
ARF6/GDP	-0.068	0.14	-9999	-0.39	5	5
ARF6/GDP/GULP/ACAP1	-0.23	0.26	-9999	-0.54	183	183
alphaIIb/beta3 Integrin/paxillin/GIT1	-0.017	0.092	-9999	-0.52	14	14
ACAP1	-0.32	0.43	-9999	-0.86	184	184
ACAP2	0.016	0	-9999	-10000	0	0
LHCGR/beta Arrestin2	-0.041	0.15	-9999	-0.59	33	33
EFNA1	0.014	0.04	-9999	-0.86	1	1
HGF	-0.021	0.17	-9999	-0.81	21	21
CYTH3	0.015	0	-9999	-10000	0	0
CYTH2	0.01	0.001	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
fibronectin binding	0	0	-9999	-0.001	12	12
endosomal lumen acidification	0	0	-9999	-0.001	19	19
microtubule-based process	0	0	-9999	-10000	0	0
GULP1	-0.012	0.14	-9999	-0.76	17	17
GNAQ/ARNO	0.004	0.009	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
PIP3-E	0	0	-9999	0	1	1
MET	0.006	0.089	-9999	-0.86	5	5
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GIT1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-0.001	11	11
GNA11	0.012	0.05	-9999	-0.76	2	2
LHCGR	-0.052	0.22	-9999	-0.86	32	32
AGTR1	-0.026	0.18	-9999	-0.76	26	26
desensitization of G-protein coupled receptor protein signaling pathway	-0.04	0.15	-9999	-0.59	33	33
IPCEF1/ARNO	-0.35	0.13	-9999	-0.82	8	8
alphaIIb/beta3 Integrin	-0.022	0.12	-9999	-0.66	16	16

×

p75(NTR)-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Sortilin/TRAF6	-0.001	0.026	-9999	-0.57	1	1
Necdin/E2F1	-0.078	0.22	-9999	-0.68	55	55
proNGF (dimer)/p75(NTR)/Sortilin/NADE/14-3-3 E	-0.088	0.22	-9999	-0.98	11	11
NGF (dimer)/p75(NTR)/BEX1	-0.28	0.32	-9999	-0.58	233	233
NT-4/5 (dimer)/p75(NTR)	-0.06	0.19	-9999	-0.67	43	43
IKBKB	0.016	0	-9999	-10000	0	0
AKT1	-0.04	0.23	-9999	-0.96	11	11
IKBKG	0.016	0	-9999	-10000	0	0
BDNF	-0.11	0.31	-9999	-0.86	68	68
MGDIs/NGR/p75(NTR)/LINGO1	-0.077	0.21	-9999	-0.62	60	60
FURIN	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75(NTR)/Sortilin	-0.13	0.26	-9999	-0.63	96	96
LINGO1	-0.021	0.18	-9999	-0.86	20	20
Sortilin/TRAF6/NRIF	-0.001	0.015	-9999	-10000	0	0
proBDNF (dimer)	-0.11	0.3	-9999	-0.86	68	68
NTRK1	-0.047	0.21	-9999	-0.76	38	38
RTN4R	0.003	0.1	-9999	-0.85	7	7
neuron apoptosis	-0.073	0.24	-9999	-0.7	33	33
IRAK1	0.016	0	-9999	-10000	0	0
SHC1	-0.071	0.26	-9999	-0.65	76	76
ARHGDIA	0.014	0.035	-9999	-0.76	1	1
RhoA/GTP	0	0	-9999	-10000	0	0
Gamma Secretase	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-H1	-0.094	0.23	-9999	-0.6	74	74
MAGEH1	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/Necdin	-0.097	0.23	-9999	-0.6	75	75
Mammalian IAPs/DIABLO	-0.081	0.19	-9999	-0.52	74	74
proNGF (dimer)	-0.072	0.26	-9999	-0.86	48	48
MAGED1	0.014	0.04	-9999	-0.86	1	1
APP	0.014	0.035	-9999	-0.76	1	1
NT-4/5 (dimer)	-0.004	0.089	-9999	-0.86	5	5
ZNF274	0.016	0	-9999	-10000	0	0
RhoA/GDP/RHOGDI	-0.089	0.22	-9999	-0.56	74	74
NGF	-0.072	0.26	-9999	-0.86	48	48
cell cycle arrest	-0.022	0.27	-9999	-0.58	74	74
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK	-0.05	0.12	-9999	-0.57	11	11
NT-4/5 (dimer)/p75(NTR)/TRAF6	-0.052	0.17	-9999	-0.58	43	43
NCSTN	0.016	0	-9999	-10000	0	0
mol:GTP	-0.1	0.25	-9999	-0.65	75	75
PSENEN	0.016	0	-9999	-10000	0	0
mol:ceramide	-0.054	0.24	-9999	-0.59	74	74
NGF (dimer)/p75(NTR)/TRAF6/RIP2/IRAK/p62/Atypical PKCs	-0.039	0.094	-9999	-0.44	11	11
p75(NTR)/beta APP	-0.054	0.18	-9999	-0.66	39	39
BEX1	-0.27	0.37	-9999	-0.76	177	177
mol:GDP	-0.082	0.26	-9999	-0.66	75	75
NGF (dimer)	-0.36	0.31	-9999	-0.85	84	84
MGDIs/NGR/p75(NTR)/LINGO1/RHOGDI	-0.071	0.2	-9999	-0.57	60	60
PIK3R1	0.016	0	-9999	-10000	0	0
RAC1/GTP	-0.09	0.22	-9999	-0.58	75	75
MYD88	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/PKA	-0.1	0.25	-9999	-0.65	75	75
RHOB	0.016	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
MAGE-G1/E2F1	-0.075	0.21	-9999	-0.67	54	54
NT3 (dimer)	0.006	0.09	-9999	-0.79	6	6
TP53	-0.051	0.24	-9999	-0.91	11	11
PRDM4	-0.055	0.24	-9999	-0.6	74	74
BDNF (dimer)	-0.43	0.37	-9999	-0.89	134	134
PIK3CA	0.016	0	-9999	-10000	0	0
SORT1	0.014	0.035	-9999	-0.76	1	1
activation of caspase activity	-0.087	0.21	-9999	-0.96	11	11
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.094	0.23	-9999	-0.6	74	74
RHOC	0.016	0	-9999	-10000	0	0
XIAP	0.016	0	-9999	-10000	0	0
MAPK10	-0.032	0.22	-9999	-0.64	28	28
DIABLO	0.016	0	-9999	-10000	0	0
SMPD2	-0.055	0.24	-9999	-0.6	74	74
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin	-0.1	0.25	-9999	-0.65	76	76
PSEN1	0.016	0	-9999	-10000	0	0
APAF-1/Pro-Caspase 9	0	0	-9999	-10000	0	0
NT3 (dimer)/p75(NTR)	-0.06	0.19	-9999	-0.66	44	44
MAPK8	-0.029	0.22	-9999	-0.64	27	27
MAPK9	-0.029	0.22	-9999	-0.64	27	27
APAF1	0.016	0	-9999	-10000	0	0
NTF3	0.006	0.09	-9999	-0.79	6	6
NTF4	-0.004	0.089	-9999	-0.86	5	5
NDN	0.011	0.061	-9999	-0.76	3	3
RAC1/GDP	0	0	-9999	-10000	0	0
RhoA-B-C/GDP	-0.08	0.2	-9999	-0.91	11	11
p75 CTF/Sortilin/TRAF6/NRIF	-0.001	0.02	-9999	-10000	0	0
RhoA-B-C/GTP	-0.1	0.24	-9999	-0.64	75	75
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.11	0.23	-9999	-0.54	94	94
proBDNF (dimer)/p75(NTR)/Sortilin/TRAF6	-0.12	0.24	-9999	-0.58	94	94
PRKACB	0.016	0	-9999	-10000	0	0
proBDNF (dimer)/p75 ECD	-0.094	0.23	-9999	-0.66	68	68
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	74	74
BIRC2	0.016	0	-9999	-10000	0	0
neuron projection morphogenesis	-0.001	0.26	-9999	-0.56	58	58
BAD	-0.018	0.21	-9999	-0.6	27	27
RIPK2	0.014	0.04	-9999	-0.86	1	1
NGFR	-0.054	0.24	-9999	-0.86	38	38
CYCS	-0.043	0.23	-9999	-0.97	11	11
ADAM17	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)/TRAF6/RIP2	-0.094	0.23	-9999	-0.6	75	75
BCL2L11	-0.017	0.21	-9999	-0.6	27	27
BDNF (dimer)/p75(NTR)	-0.14	0.3	-9999	-0.72	96	96
PI3K	-0.093	0.23	-9999	-0.6	74	74
proNGF (dimer)/p75(NTR)/Sortilin/MAGE-G1	-0.094	0.23	-9999	-0.6	74	74
NDNL2	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
NGF (dimer)/p75(NTR)	-0.12	0.28	-9999	-0.75	75	75
ChemicalAbstracts:146-91-8	0	0	-9999	-10000	0	0
proNGF (dimer)/p75(NTR)/Sortilin/NRAGE	-0.095	0.23	-9999	-0.6	75	75
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
PRKCZ	0.011	0.061	-9999	-0.76	3	3
PLG	-0.4	0.38	-9999	-0.76	256	256
oligodendrocyte cell fate commitment	0	0	-9999	-10000	0	0
CASP6	-0.14	0.25	-9999	-0.72	46	46
SQSTM1	0.016	0	-9999	-10000	0	0
NGFRAP1	0.016	0	-9999	-10000	0	0
CASP3	-0.011	0.19	-9999	-0.54	27	27
E2F1	-0.083	0.28	-9999	-0.86	54	54
CASP9	0.016	0	-9999	-10000	0	0
IKK complex	-0.076	0.15	-9999	-0.59	16	16
NGF (dimer)/TRKA	-0.11	0.24	-9999	-0.64	84	84
MMP7	-0.12	0.3	-9999	-0.77	83	83
proNGF (dimer)/p75(NTR)/Sortilin/TRAF6/NRIF	-0.088	0.22	-9999	-0.56	74	74
MMP3	-0.075	0.26	-9999	-0.86	46	46
APAF-1/Caspase 9	-0.12	0.18	-9999	-0.69	13	13

×

IL2 signaling events mediated by STAT5

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GAB2	0.017	0	-9999	-10000	0	0
ELF1	-0.044	0.14	-9999	-10000	0	0
CCNA2	-0.16	0.35	-9999	-0.86	96	96
PIK3CA	0.017	0	-9999	-10000	0	0
JAK3	-0.17	0.36	-9999	-0.86	102	102
PIK3R1	0.017	0	-9999	-10000	0	0
JAK1	0.017	0	-9999	-10000	0	0
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.11	0.25	-9999	-0.66	56	56
SHC1	0.015	0.04	-9999	-0.86	1	1
SP1	0.024	0.023	-9999	-10000	0	0
IL2RA	-0.12	0.33	-9999	-0.78	96	96
IL2RB	-0.47	0.44	-9999	-0.86	263	263
SOS1	0.017	0	-9999	-10000	0	0
IL2RG	-0.044	0.22	-9999	-0.86	33	33
G1/S transition of mitotic cell cycle	-0.049	0.2	-9999	-0.49	38	38
PTPN11	0.017	0	-9999	-10000	0	0
CCND2	0.038	0.053	-9999	-0.78	2	2
LCK	-0.023	0.18	-9999	-0.85	22	22
GRB2	0.017	0	-9999	-10000	0	0
IL2	-0.008	0.12	-9999	-0.86	10	10
CDK6	0.014	0.035	-9999	-0.76	1	1
CCND3	-0.084	0.21	-9999	-0.67	27	27

×

VEGFR1 specific signals

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR1 homodimer/VEGFB homodimer	-0.006	0.062	-9999	-0.68	4	4
VEGFR1 homodimer/NRP1	-0.006	0.063	-9999	-0.69	4	4
mol:DAG	-0.26	0.29	-9999	-0.97	4	4
VEGFR1 homodimer/NRP1/VEGFR 121	-0.24	0.27	-9999	-0.54	216	216
CaM/Ca2+	-0.27	0.24	-9999	-1	3	3
HIF1A	0.023	0.032	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
AKT1	-0.22	0.2	-9999	-0.89	3	3
PLCG1	-0.27	0.29	-9999	-0.99	4	4
NOS3	-0.18	0.24	-9999	-0.87	3	3
CBL	0.016	0	-9999	-10000	0	0
mol:NO	-0.17	0.23	-9999	-0.81	3	3
FLT1	0.034	0.074	-9999	-0.78	4	4
PGF	-0.48	0.44	-9999	-0.86	268	268
VEGFR1 homodimer/NRP2/VEGFR121	-0.24	0.27	-9999	-1	6	6
CALM1	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
eNOS/Hsp90	-0.16	0.23	-9999	-0.78	3	3
endothelial cell proliferation	-0.2	0.25	-9999	-0.86	5	5
mol:Ca2+	-0.26	0.28	-9999	-0.95	4	4
MAPK3	-0.21	0.26	-9999	-0.94	3	3
MAPK1	-0.21	0.26	-9999	-0.94	3	3
PIK3R1	0.016	0	-9999	-10000	0	0
PLGF homodimer	-0.48	0.44	-9999	-0.86	268	268
PRKACA	0.016	0	-9999	-10000	0	0
RP11-342D11.1	0	0	-9999	-10000	0	0
CAV1	-0.05	0.23	-9999	-0.86	36	36
VEGFA homodimer	-0.38	0.44	-9999	-0.86	215	215
VEGFR1 homodimer/VEGFA homodimer	-0.26	0.29	-9999	-0.58	216	216
platelet activating factor biosynthetic process	-0.2	0.25	-9999	-0.9	3	3
PI3K	-0.27	0.24	-9999	-0.94	4	4
PRKCA	-0.24	0.27	-9999	-0.89	4	4
PRKCB	-0.24	0.27	-9999	-0.92	6	6
VEGFR1 homodimer/PLGF homodimer	-0.32	0.29	-9999	-0.58	269	269
VEGFA	-0.38	0.44	-9999	-0.86	215	215
VEGFB	0.016	0	-9999	-10000	0	0
mol:IP3	-0.26	0.29	-9999	-0.97	4	4
RASA1	0.049	0.061	-9999	-0.62	4	4
NRP2	0.003	0.11	-9999	-0.86	7	7
VEGFR1 homodimer	0.034	0.074	-9999	-0.77	4	4
VEGFB homodimer	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.19	0.26	-9999	-0.81	28	28
PTPN11	0.016	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.27	0.24	-9999	-0.92	4	4
mol:L-citrulline	-0.17	0.23	-9999	-0.81	3	3
VEGFR1 homodimer/VEGFA homodimer/CBL/CD2AP	-0.22	0.25	-9999	-0.95	4	4
VEGFR1 homodimer/VEGFA homodimer/NCK1	-0.24	0.27	-9999	-1	4	4
CD2AP	0.016	0	-9999	-10000	0	0
PI3K/GAB1	-0.25	0.23	-9999	-0.99	3	3
PDPK1	-0.22	0.26	-9999	-0.96	3	3
VEGFR1 homodimer/VEGFA homodimer/SHP2	-0.24	0.27	-9999	-1	4	4
mol:NADP	-0.17	0.23	-9999	-0.81	3	3
HSP90AA1	0.016	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	-0.22	0.24	-9999	-0.92	4	4
VEGFR1 homodimer/NRP2	-0.014	0.091	-9999	-0.61	11	11

×

S1P1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	215	215
PDGFRB	0.016	0.004	-9999	-10000	0	0
SPHK1	-0.031	0.1	-9999	-0.36	40	40
mol:S1P	-0.024	0.095	-9999	-0.4	6	6
S1P1/S1P/Gi	-0.047	0.14	-9999	-0.53	9	9
GNAO1	0.011	0.078	-9999	-0.84	4	4
PDGFB-D/PDGFRB/PLCgamma1	-0.055	0.088	-9999	-0.67	1	1
PLCG1	-0.028	0.13	-9999	-0.69	1	1
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0.004	-9999	-10000	0	0
GNAI2	0.018	0.005	-9999	-10000	0	0
GNAI3	0.015	0.006	-9999	-10000	0	0
GNAI1	0.01	0.062	-9999	-0.76	3	3
mol:GDP	0	0	-9999	-10000	0	0
EDG1	-0.25	0.3	-9999	-0.58	215	215
S1P1/S1P	-0.21	0.21	-9999	-0.61	23	23
negative regulation of cAMP metabolic process	-0.045	0.14	-9999	-0.51	9	9
MAPK3	-0.038	0.17	-9999	-0.64	13	13
calcium-dependent phospholipase C activity	0	0.003	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
KDR	0.013	0.035	-9999	-0.76	1	1
PLCB2	-0.2	0.26	-9999	-0.67	56	56
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.17	0.17	-9999	-0.51	21	21
receptor internalization	-0.2	0.2	-9999	-0.4	217	217
PTGS2	-0.049	0.24	-9999	-0.99	25	25
Rac1/GTP	-0.17	0.17	-9999	-0.51	21	21
RHOA	0.016	0	-9999	-10000	0	0
VEGFA	-0.38	0.44	-9999	-0.86	215	215
negative regulation of T cell proliferation	-0.045	0.14	-9999	-0.51	9	9
GO:0007205	0	0	-9999	-10000	0	0
GNAZ	0.01	0.062	-9999	-0.76	3	3
MAPK1	-0.038	0.17	-9999	-0.64	13	13
S1P1/S1P/PDGFB-D/PDGFRB	-0.17	0.24	-9999	-0.62	22	22
ABCC1	0.015	0.005	-9999	-10000	0	0

×

LPA4-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ADCY4	0.028	0	-9999	-10000	0	0
ADCY5	0.007	0.1	-9999	-0.5	19	19
ADCY6	0.028	0	-9999	-10000	0	0
ADCY7	0.008	0.11	-9999	-0.59	15	15
ADCY1	0.017	0.074	-9999	-0.52	9	9
ADCY2	-0.13	0.26	-9999	-0.58	122	122
ADCY3	0.028	0	-9999	-10000	0	0
ADCY8	-0.17	0.28	-9999	-0.59	149	149
PRKCE	0.015	0	-9999	-10000	0	0
ADCY9	0.028	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
cAMP biosynthetic process	-0.089	0.17	-9999	-0.51	46	46

×

IL2 signaling events mediated by PI3K

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
BCL2L1	-0.13	0.24	-10000	0	-0.78	34	34
UGCG	-0.022	0.031	-10000	0	-10000	0	0
AKT1/mTOR/p70S6K/Hsp90/TERT	-0.086	0.2	-10000	0	-0.51	45	45
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucosylceramide	-0.008	0.045	-10000	0	-10000	0	0
mol:DAG	-0.004	0.006	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	-0.11	0.17	-10000	0	-0.57	32	32
FRAP1	-0.09	0.23	-10000	0	-0.62	45	45
FOXO3	-0.081	0.22	-10000	0	-0.64	36	36
AKT1	-0.098	0.24	-10000	0	-0.65	48	48
GAB2	0.015	0.005	-10000	0	-10000	0	0
SMPD1	-0.022	0.031	-10000	0	-10000	0	0
SGMS1	-0.022	0.031	-10000	0	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
mol:GDP	0.029	0.006	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
cell proliferation	-0.023	0.096	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
RPS6KB1	-0.029	0.088	-10000	0	-10000	0	0
mol:sphingomyelin	-0.004	0.006	-10000	0	-10000	0	0
natural killer cell activation	0	0.002	-10000	0	-10000	0	0
JAK3	-0.17	0.36	-10000	0	-0.86	102	102
PIK3R1	0.019	0.004	-10000	0	-10000	0	0
JAK1	0.019	0.004	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
MYC	-0.08	0.23	-10000	0	-0.66	32	32
MYB	-0.19	0.34	-10000	0	-0.73	130	130
IL2/IL2R alpha/beta/gamma/JAK1/LCK/JAK3/SHC/GAB2/GRB2/SOS1/SHP2/PI3K	-0.13	0.26	-10000	0	-0.68	61	61
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.037	0.064	-10000	0	-0.45	1	1
mol:PI-3-4-5-P3	-0.12	0.25	-10000	0	-0.65	61	61
Rac1/GDP	0	0	-10000	0	-10000	0	0
T cell proliferation	-0.1	0.24	-10000	0	-0.65	46	46
SHC1	0.013	0.04	-10000	0	-0.86	1	1
RAC1	0.015	0.003	-10000	0	-10000	0	0
positive regulation of cyclin-dependent protein kinase activity	-0.008	0.026	-10000	0	-0.051	130	130
PRKCZ	-0.11	0.25	-10000	0	-0.69	46	46
NF kappa B1 p50/RelA	-0.1	0.16	-10000	0	-0.59	26	26
IL2/IL2R beta/gamma/JAK1/LCK/JAK3/PI3K	-0.16	0.27	-10000	0	-0.58	102	102
HSP90AA1	0.016	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
IL2RA	-0.16	0.35	-10000	0	-0.86	96	96
IL2RB	-0.46	0.44	-10000	0	-0.86	263	263
TERT	-0.12	0.31	-10000	0	-0.86	70	70
E2F1	-0.1	0.2	-10000	0	-0.39	130	130
SOS1	0.014	0.006	-10000	0	-10000	0	0
RPS6	0.014	0.04	-10000	0	-0.86	1	1
mol:cAMP	0.004	0.013	0.025	130	-10000	0	130
PTPN11	0.015	0.005	-10000	0	-10000	0	0
IL2RG	-0.042	0.22	-10000	0	-0.86	33	33
actin cytoskeleton organization	-0.1	0.24	-10000	0	-0.65	46	46
GRB2	0.014	0.006	-10000	0	-10000	0	0
IL2	-0.006	0.12	-10000	0	-0.86	10	10
PIK3CA	0.018	0.004	-10000	0	-10000	0	0
Rac1/GTP	0.033	0.021	-10000	0	-10000	0	0
LCK	-0.021	0.18	-10000	0	-0.85	22	22
BCL2	-0.056	0.18	-10000	0	-0.55	18	18

×

BCR signaling 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
JUN	-0.057	0.17	-10000	0	-0.41	40	40
IKBKB	-0.025	0.1	-10000	0	-10000	0	0
AKT1	-0.026	0.12	-10000	0	-0.3	3	3
IKBKG	-0.025	0.11	-10000	0	-0.3	2	2
CALM1	-0.044	0.1	-10000	0	-0.5	3	3
PIK3CA	0.016	0	-10000	0	-10000	0	0
MAP3K1	-0.12	0.25	-10000	0	-0.64	66	66
MAP3K7	0.016	0	-10000	0	-10000	0	0
mol:Ca2+	-0.057	0.11	0.27	1	-0.5	4	5
DOK1	0.016	0	-10000	0	-10000	0	0
AP-1	-0.012	0.09	-10000	0	-0.26	2	2
LYN	0.016	0	-10000	0	-10000	0	0
BLNK	0.014	0.035	-10000	0	-0.76	1	1
SHC1	0.014	0.04	-10000	0	-0.86	1	1
BCR complex	-0.17	0.3	-10000	0	-0.68	123	123
CD22	-0.16	0.24	-10000	0	-0.68	51	51
CAMK2G	-0.031	0.1	-10000	0	-0.5	2	2
CSNK2A1	0.016	0	-10000	0	-10000	0	0
INPP5D	0.008	0.08	-10000	0	-0.86	4	4
SHC/GRB2/SOS1	-0.11	0.19	-10000	0	-0.85	4	4
GO:0007205	-0.057	0.11	0.27	1	-0.51	4	5
SYK	0.013	0.05	-10000	0	-0.76	2	2
ELK1	-0.044	0.11	-10000	0	-0.51	3	3
NFATC1	-0.075	0.2	-10000	0	-0.5	62	62
B-cell antigen/BCR complex	-0.17	0.3	-10000	0	-0.68	123	123
PAG1/CSK	-0.003	0.043	-10000	0	-0.67	2	2
NFKBIB	0.004	0.038	-10000	0	-10000	0	0
HRAS	-0.039	0.12	-10000	0	-0.49	4	4
NFKBIA	0.005	0.038	-10000	0	-10000	0	0
NF-kappa-B/RelA/I kappa B beta	0.013	0.031	-10000	0	-10000	0	0
RasGAP/Csk	-0.22	0.33	-10000	0	-1	47	47
mol:GDP	-0.052	0.1	0.29	1	-0.48	4	5
PTEN	0.016	0	-10000	0	-10000	0	0
CD79B	0.01	0.069	-10000	0	-0.86	3	3
NF-kappa-B/RelA/I kappa B alpha	0.013	0.031	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
PI3K/BCAP/CD19	-0.083	0.22	-10000	0	-0.57	59	59
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.068	0.11	0.27	1	-0.52	4	5
CSK	0.016	0	-10000	0	-10000	0	0
FOS	-0.04	0.11	-10000	0	-0.5	5	5
CHUK	-0.025	0.11	-10000	0	-0.3	1	1
IBTK	0.016	0	-10000	0	-10000	0	0
CARD11/BCL10/MALT1/TAK1	-0.13	0.2	-10000	0	-0.54	75	75
PTPN6	-0.14	0.22	-10000	0	-0.68	39	39
RELA	0.016	0	-10000	0	-10000	0	0
BCL2A1	-0.012	0.069	-10000	0	-0.14	103	103
VAV2	-0.17	0.29	-10000	0	-0.8	69	69
ubiquitin-dependent protein catabolic process	0.01	0.037	-10000	0	-10000	0	0
BTK	-0.086	0.17	0.46	1	-10000	0	1
CD19	-0.2	0.33	-10000	0	-0.9	73	73
MAP4K1	-0.35	0.43	-10000	0	-0.86	197	197
CD72	-0.2	0.38	-10000	0	-0.86	116	116
PAG1	0.012	0.057	-10000	0	-0.86	2	2
MAPK14	-0.089	0.22	-10000	0	-0.53	63	63
SH3BP5	0.014	0.035	-10000	0	-0.76	1	1
PIK3AP1	-0.04	0.11	-10000	0	-0.55	6	6
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2/CD72	-0.12	0.24	-10000	0	-0.57	77	77
RAF1	-0.026	0.12	-10000	0	-0.54	2	2
RasGAP/p62DOK/SHIP	-0.22	0.32	-10000	0	-0.97	48	48
CD79A	-0.21	0.38	-10000	0	-0.86	123	123
re-entry into mitotic cell cycle	-0.012	0.09	-10000	0	-0.26	2	2
RASA1	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.002	0.1	-10000	0	-0.43	2	2
MAPK1	-0.002	0.1	-10000	0	-0.43	1	1
CD72/SHP1	-0.24	0.33	-10000	0	-0.83	96	96
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	-0.089	0.22	-10000	0	-0.53	63	63
actin cytoskeleton organization	-0.1	0.26	-10000	0	-0.67	63	63
NF-kappa-B/RelA	0.034	0.058	-10000	0	-10000	0	0
Calcineurin	-0.044	0.071	-10000	0	-10000	0	0
PI3K	-0.14	0.22	-10000	0	-0.61	60	60
B-cell antigen/BCR complex/Btk/LYN/SYK/BLNK/PLCgamma2	-0.064	0.1	-10000	0	-0.55	4	4
SOS1	0.016	0	-10000	0	-10000	0	0
Bam32/HPK1	-0.28	0.32	-10000	0	-0.74	129	129
DAPP1	-0.11	0.19	-10000	0	-0.61	36	36
cytokine secretion	-0.069	0.19	-10000	0	-0.47	62	62
mol:DAG	-0.068	0.11	0.27	1	-0.52	4	5
PLCG2	0.002	0.11	-10000	0	-0.82	8	8
MAP2K1	-0.014	0.11	-10000	0	-0.48	2	2
B-cell antigen/BCR complex/FcgammaRIIB	-0.26	0.38	-10000	0	-0.73	173	173
mol:PI-3-4-5-P3	-0.1	0.15	-10000	0	-0.41	60	60
ETS1	-0.019	0.093	-10000	0	-0.44	2	2
B-cell antigen/BCR complex/LYN/SYK/BLNK	-0.13	0.22	-10000	0	-0.5	122	122
B-cell antigen/BCR complex/LYN	-0.14	0.22	-10000	0	-0.58	69	69
MALT1	0.016	0	-10000	0	-10000	0	0
TRAF6	0.016	0	-10000	0	-10000	0	0
RAC1	-0.11	0.28	-10000	0	-0.73	63	63
B-cell antigen/BCR complex/LYN/SYK	-0.17	0.25	-10000	0	-0.75	39	39
CARD11	-0.15	0.26	-10000	0	-0.61	102	102
FCGR2B	-0.16	0.35	-10000	0	-0.86	97	97
PPP3CA	0.016	0	-10000	0	-10000	0	0
BCL10	0.016	0	-10000	0	-10000	0	0
IKK complex	0.004	0.047	-10000	0	-10000	0	0
PTPRC	-0.083	0.28	-10000	0	-0.86	54	54
PDPK1	-0.062	0.1	-10000	0	-0.3	8	8
PPP3CB	0.016	0	-10000	0	-10000	0	0
PPP3CC	0.016	0	-10000	0	-10000	0	0
POU2F2	-0.001	0.059	-10000	0	-0.14	64	64

×

PLK1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
regulation of centriole-centriole cohesion	0	0.058	0.29	17	-10000	0	17
BUB1B	-0.025	0.13	-10000	0	-0.51	24	24
PLK1	-0.014	0.06	-10000	0	-0.2	10	10
PLK1S1	0	0.031	-10000	0	-10000	0	0
KIF2A	-0.004	0.072	-10000	0	-0.6	3	3
regulation of mitotic centrosome separation	-0.014	0.059	-10000	0	-0.2	10	10
GOLGA2	0.016	0	-10000	0	-10000	0	0
Hec1/SPC24	-0.19	0.34	-10000	0	-0.72	121	121
WEE1	-0.003	0.057	-10000	0	-0.28	7	7
cytokinesis	-0.22	0.27	-10000	0	-0.5	228	228
PP2A-alpha B56	-0.15	0.16	-10000	0	-10000	0	0
AURKA	-0.003	0.046	-10000	0	-0.3	6	6
PICH/PLK1	-0.047	0.17	-10000	0	-0.84	18	18
CENPE	-0.068	0.21	-10000	0	-0.63	59	59
RhoA/GTP	0	0	-10000	0	-10000	0	0
positive regulation of microtubule depolymerization	-0.004	0.071	-10000	0	-0.6	3	3
PPP2CA	0.016	0	-10000	0	-10000	0	0
FZR1	0.014	0.035	-10000	0	-0.76	1	1
TPX2	-0.053	0.12	-10000	0	-0.26	120	120
PAK1	0.016	0.002	-10000	0	-10000	0	0
SPC24	-0.082	0.28	-10000	0	-0.86	53	53
FBXW11	0.016	0	-10000	0	-10000	0	0
CLSPN	-0.027	0.097	-10000	0	-0.28	56	56
GORASP1	0.016	0	-10000	0	-10000	0	0
metaphase	-0.004	0.01	-10000	0	-0.02	124	124
mol:GTP	0	0	-10000	0	-10000	0	0
NLP	-0.007	0.031	-10000	0	-0.098	10	10
G2 phase of mitotic cell cycle	0.001	0.002	-10000	0	-0.014	6	6
STAG2	0.016	0	-10000	0	-10000	0	0
GRASP65/GM130/RAB1/GTP	0.009	0.013	-10000	0	-10000	0	0
spindle elongation	-0.014	0.059	-10000	0	-0.2	10	10
ODF2	0.016	0.002	-10000	0	-10000	0	0
BUB1	-0.18	0.19	-10000	0	-0.46	7	7
TPT1	0	0.031	-10000	0	-10000	0	0
CDC25C	-0.13	0.17	-10000	0	-0.31	224	224
CDC25B	0.006	0.091	-10000	0	-0.88	5	5
SGOL1	0	0.058	-10000	0	-0.29	17	17
RHOA	0.016	0	-10000	0	-10000	0	0
CCNB1/CDK1	-0.025	0.11	-10000	0	-0.74	9	9
CDC14B	0.016	0.002	-10000	0	-10000	0	0
CDC20	-0.058	0.24	-10000	0	-0.86	40	40
PLK1/PBIP1	-0.04	0.11	-10000	0	-0.61	15	15
mitosis	-0.001	0.004	0.03	6	-10000	0	6
FBXO5	0.001	0.045	-10000	0	-0.21	2	2
CDC2	-0.001	0.004	-10000	0	-0.023	9	9
NDC80	-0.18	0.36	-10000	0	-0.86	104	104
metaphase plate congression	-0.006	0.042	-10000	0	-10000	0	0
ERCC6L	-0.039	0.17	-10000	0	-0.82	18	18
NLP/gamma Tubulin	-0.004	0.035	-10000	0	-0.12	5	5
microtubule cytoskeleton organization	0	0.031	-10000	0	-10000	0	0
G2/M transition DNA damage checkpoint	0.001	0.001	-10000	0	-10000	0	0
PPP1R12A	0.016	0.002	-10000	0	-10000	0	0
interphase	0.001	0.001	-10000	0	-10000	0	0
PLK1/PRC1-2	-0.27	0.29	-10000	0	-0.57	228	228
GRASP65/GM130/RAB1/GTP/PLK1	-0.014	0.027	-10000	0	-10000	0	0
RAB1A	0.016	0	-10000	0	-10000	0	0
prophase	0	0	-10000	0	-10000	0	0
Aurora A/BORA	0.006	0.039	-10000	0	-10000	0	0
mitotic prometaphase	-0.003	0.005	-10000	0	-0.012	117	117
proteasomal ubiquitin-dependent protein catabolic process	-0.012	0.043	-10000	0	-10000	0	0
microtubule-based process	-0.26	0.31	-10000	0	-0.58	228	228
Golgi organization	-0.014	0.059	-10000	0	-0.2	10	10
Cohesin/SA2	-0.025	0.046	-10000	0	-10000	0	0
PPP1CB/MYPT1	0	0	-10000	0	-10000	0	0
KIF20A	-0.4	0.44	-10000	0	-0.86	228	228
APC/C/CDC20	-0.048	0.18	-10000	0	-0.64	40	40
PPP2R1A	0.016	0	-10000	0	-10000	0	0
chromosome segregation	-0.04	0.11	-10000	0	-0.6	15	15
PRC1	0.005	0.098	-10000	0	-0.86	6	6
ECT2	-0.001	0.054	-10000	0	-10000	0	0
C13orf34	0.002	0.043	-10000	0	-10000	0	0
NUDC	-0.006	0.042	-10000	0	-10000	0	0
regulation of attachment of spindle microtubules to kinetochore	-0.025	0.12	-10000	0	-0.51	24	24
spindle assembly	-0.008	0.048	-10000	0	-0.16	8	8
spindle stabilization	0	0.031	-10000	0	-10000	0	0
APC/C/HCDH1	-0.001	0.023	-10000	0	-0.5	1	1
MKLP2/PLK1	-0.26	0.31	-10000	0	-0.59	228	228
CCNB1	0.001	0.11	-10000	0	-0.88	8	8
PPP1CB	0.016	0.002	-10000	0	-10000	0	0
BTRC	0.016	0	-10000	0	-10000	0	0
ROCK2	0.005	0.046	-10000	0	-0.47	1	1
TUBG1	0	0.031	-10000	0	-10000	0	0
G2/M transition of mitotic cell cycle	-0.027	0.1	-10000	0	-0.71	9	9
MLF1IP	-0.009	0.12	-10000	0	-0.69	15	15
INCENP	0.008	0.008	-10000	0	-10000	0	0

×

Integrins in angiogenesis

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
VEGFR2 homodimer/VEGFA homodimer	-0.3	0.33	-9999	-0.67	215	215
alphaV beta3 Integrin	-0.005	0.051	-9999	-0.5	5	5
PTK2	-0.14	0.23	-9999	-0.69	3	3
IGF1R	0.016	0	-9999	-10000	0	0
PI4KB	0.016	0	-9999	-10000	0	0
MFGE8	0.014	0.04	-9999	-0.86	1	1
SRC	0.016	0	-9999	-10000	0	0
CDKN1B	-0.086	0.2	-9999	-0.53	76	76
VEGFA	-0.38	0.44	-9999	-0.86	215	215
ILK	-0.086	0.2	-9999	-0.53	76	76
ROCK1	0.016	0	-9999	-10000	0	0
AKT1	-0.079	0.18	-9999	-0.5	68	68
PTK2B	-0.19	0.27	-9999	-0.48	215	215
alphaV/beta3 Integrin/JAM-A	-0.069	0.16	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
alphaV beta3 Integrin/ANGPTL3	-0.22	0.24	-9999	-0.48	220	220
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.009	0.068	-9999	-0.52	7	7
VEGF/Rho/ROCK/alphaV/beta3 Integrin	-0.13	0.15	-9999	-0.48	45	45
alphaV/beta3 Integrin/Syndecan-1	-0.006	0.054	-9999	-0.48	6	6
PI4KA	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.046	0.14	-9999	-0.88	3	3
PI4 Kinase	0	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin	-0.004	0.044	-9999	-0.48	4	4
RPS6KB1	-0.042	0.13	-9999	-0.8	3	3
TLN1	0.016	0	-9999	-10000	0	0
MAPK3	-0.04	0.085	-9999	-0.62	3	3
GPR124	0.012	0.057	-9999	-0.86	2	2
MAPK1	-0.04	0.085	-9999	-0.62	3	3
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Tumstatin	-0.055	0.15	-9999	-0.48	54	54
cell adhesion	-0.17	0.18	-9999	-0.84	1	1
ANGPTL3	-0.34	0.38	-9999	-0.76	219	219
VEGFR2 homodimer/VEGFA homodimer/Src	-0.26	0.29	-9999	-0.58	215	215
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
TGFBR2	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
IGF1	0.003	0.11	-9999	-0.86	7	7
RAC1	0.016	0	-9999	-10000	0	0
regulation of cell-matrix adhesion	-0.003	0.043	-9999	-0.54	3	3
apoptosis	0.016	0	-9999	-10000	0	0
CD47	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/CD47	-0.001	0.022	-9999	-0.48	1	1
VCL	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Del1	-0.014	0.085	-9999	-0.52	13	13
CSF1	0.016	0	-9999	-10000	0	0
PIK3C2A	-0.086	0.2	-9999	-0.53	76	76
PI4 Kinase/Pyk2	-0.24	0.25	-9999	-0.76	45	45
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.24	0.26	-9999	-0.52	215	215
FAK1/Vinculin	-0.11	0.19	-9999	-0.55	2	2
alphaV beta3/Integrin/ppsTEM5	-0.003	0.043	-9999	-0.55	3	3
RHOA	0.016	0	-9999	-10000	0	0
VTN	-0.11	0.29	-9999	-0.77	76	76
BCAR1	0.014	0.035	-9999	-0.76	1	1
FGF2	0.009	0.073	-9999	-0.78	4	4
F11R	0.026	0.057	-9999	-0.59	4	4
alphaV/beta3 Integrin/Lactadherin	-0.002	0.034	-9999	-0.53	2	2
alphaV/beta3 Integrin/TGFBR2	-0.001	0.022	-9999	-0.48	1	1
alphaV/beta3 Integrin/c-FMS/Cbl/Cas	-0.001	0.02	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.001	0.02	-9999	-0.45	1	1
mol:GDP	0	0	-9999	-10000	0	0
FN1	-0.052	0.24	-9999	-0.86	37	37
alphaV/beta3 Integrin/Pyk2	-0.22	0.24	-9999	-0.48	215	215
SDC1	0.008	0.079	-9999	-0.76	5	5
VAV3	0.04	0.08	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
FAK1/Paxillin	-0.11	0.19	-9999	-0.55	2	2
cell migration	-0.088	0.18	-9999	-0.53	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PI3K	-0.061	0.14	-9999	-10000	0	0
SPP1	0.011	0.061	-9999	-0.76	3	3
KDR	0.014	0.035	-9999	-0.76	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
alphaV/beta3 Integrin/Caspase 8	0.016	0	-9999	-10000	0	0
COL4A3	-0.07	0.24	-9999	-0.76	53	53
angiogenesis	0.005	0.14	-9999	-0.8	1	1
Rac1/GTP	-0.011	0.063	-9999	-10000	0	0
EDIL3	-0.005	0.13	-9999	-0.8	12	12
cell proliferation	-0.001	0.022	-9999	-0.48	1	1

×

Coregulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NRIP1	0.013	0.038	-9999	-0.8	1	1
SVIL	0.015	0.007	-9999	-10000	0	0
ZNF318	0.016	0.022	-9999	-10000	0	0
JMJD2C	0	0.02	-9999	-0.11	15	15
T-DHT/AR/Ubc9	-0.077	0.11	-9999	-0.56	22	22
CARM1	0.015	0.003	-9999	-10000	0	0
PRDX1	0.016	0.001	-9999	-10000	0	0
PELP1	0.016	0.003	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
AKT1	0.017	0.006	-9999	-10000	0	0
PTK2B	0.015	0.003	-9999	-10000	0	0
MED1	0.013	0.009	-9999	-10000	0	0
MAK	0.016	0.022	-9999	-10000	0	0
response to oxidative stress	0	0.001	-9999	-10000	0	0
HIP1	0.013	0.038	-9999	-0.8	1	1
GSN	0.015	0.007	-9999	-10000	0	0
NCOA2	0.009	0.07	-9999	-0.76	4	4
NCOA6	0.016	0.003	-9999	-10000	0	0
DNA-PK	0.005	0.026	-9999	-10000	0	0
NCOA4	0.015	0.002	-9999	-10000	0	0
PIAS3	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.027	0.026	-9999	-10000	0	0
XRCC5	0.016	0.005	-9999	-10000	0	0
UBE3A	0.014	0.012	-9999	-10000	0	0
T-DHT/AR/SNURF	-0.094	0.15	-9999	-0.6	35	35
FHL2	-0.037	0.098	-9999	-1.2	3	3
RANBP9	0.016	0.003	-9999	-10000	0	0
JMJD1A	-0.12	0.054	-9999	-0.14	419	419
CDK6	0.014	0.035	-9999	-0.76	1	1
TGFB1I1	0.013	0.041	-9999	-0.86	1	1
T-DHT/AR/CyclinD1	-0.1	0.16	-9999	-0.6	42	42
XRCC6	0.016	0.005	-9999	-10000	0	0
T-DHT/AR	-0.15	0.12	-9999	-0.6	22	22
CTDSP1	0.015	0.003	-9999	-10000	0	0
CTDSP2	0.015	0.017	-9999	-10000	0	0
BRCA1	0.015	0.007	-9999	-10000	0	0
TCF4	0.014	0.013	-9999	-10000	0	0
CDKN2A	-0.83	0.16	-9999	-0.86	463	463
SRF	0.027	0.01	-9999	-10000	0	0
NKX3-1	-0.19	0.068	-9999	-10000	0	0
KLK3	0.025	0.14	-9999	-0.7	18	18
TMF1	0.015	0.003	-9999	-10000	0	0
HNRNPA1	0.014	0.012	-9999	-10000	0	0
AOF2	-0.001	0.01	-9999	-10000	0	0
APPL1	0.033	0.013	-9999	-10000	0	0
T-DHT/AR/Caspase 8	-0.076	0.11	-9999	-0.55	22	22
AR	-0.068	0.16	-9999	-0.8	22	22
UBA3	0.015	0.003	-9999	-10000	0	0
PATZ1	0.014	0.012	-9999	-10000	0	0
PAWR	0.014	0.035	-9999	-0.76	1	1
PRKDC	0.016	0.005	-9999	-10000	0	0
PA2G4	0.014	0.012	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
T-DHT/AR/Cyclin D3/CDK11 p58	-0.069	0.1	-9999	-0.51	22	22
RPS6KA3	0.015	0.007	-9999	-10000	0	0
T-DHT/AR/ARA70	-0.078	0.11	-9999	-0.56	22	22
LATS2	0.014	0.011	-9999	-10000	0	0
T-DHT/AR/PRX1	-0.068	0.1	-9999	-0.51	22	22
Cyclin D3/CDK11 p58	0	0	-9999	-10000	0	0
VAV3	-0.007	0.13	-9999	-0.76	14	14
KLK2	-0.082	0.14	-9999	-0.81	15	15
CASP8	0.016	0.003	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.063	0.12	-9999	-0.56	21	21
TMPRSS2	-0.94	0.35	-9999	-1.1	419	419
CCND1	-0.021	0.18	-9999	-0.86	20	20
PIAS1	0.014	0.012	-9999	-10000	0	0
mol:T-DHT	-0.062	0.026	-9999	-0.072	409	409
CDC2L1	0	0.001	-9999	-10000	0	0
PIAS4	0.013	0.018	-9999	-10000	0	0
T-DHT/AR/CDK6	-0.078	0.11	-9999	-0.57	22	22
CMTM2	-0.001	0.12	-9999	-0.86	9	9
SNURF	-0.011	0.14	-9999	-0.76	16	16
ZMIZ1	-0.032	0.021	-9999	-10000	0	0
CCND3	0.016	0.001	-9999	-10000	0	0
TGIF1	0.014	0.012	-9999	-10000	0	0
FKBP4	0.016	0.003	-9999	-10000	0	0

×

Glucocorticoid receptor regulatory network

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PCK2	0.018	0.11	-10000	0	-1.4	1	1
SMARCC2	0.018	0	-10000	0	-10000	0	0
SMARCC1	0.018	0	-10000	0	-10000	0	0
TBX21	-0.25	0.41	-10000	0	-0.82	159	159
SUMO2	0.01	0.008	-10000	0	-10000	0	0
STAT1 (dimer)	0.024	0.056	-10000	0	-1.2	1	1
FKBP4	0.016	0	-10000	0	-10000	0	0
FKBP5	0.003	0.1	-10000	0	-0.85	7	7
GR alpha/HSP90/FKBP51/HSP90	0.05	0.13	0.39	5	-0.59	7	12
PRL	-0.01	0.11	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/TIF2	0.13	0.29	0.57	77	-0.61	2	79
RELA	0.006	0.075	-10000	0	-10000	0	0
FGG	-0.16	0.43	0.59	11	-0.74	133	144
GR beta/TIF2	0.054	0.14	0.39	9	-0.56	5	14
IFNG	-0.41	0.44	-10000	0	-0.84	208	208
apoptosis	-0.098	0.22	-10000	0	-0.62	10	10
CREB1	-0.017	0.11	-10000	0	-0.4	7	7
histone acetylation	0.018	0.13	0.39	7	-0.4	6	13
BGLAP	-0.004	0.12	-10000	0	-0.57	2	2
GR/PKAc	0.061	0.1	0.37	5	-0.6	1	6
NF kappa B1 p50/RelA	0.015	0.14	-10000	0	-0.56	4	4
SMARCD1	0.018	0	-10000	0	-10000	0	0
MDM2	0.044	0.093	0.32	9	-10000	0	9
GATA3	-0.35	0.39	-10000	0	-0.75	230	230
AKT1	0	0.005	-10000	0	-10000	0	0
CSF2	-0.026	0.16	-10000	0	-0.71	15	15
GSK3B	0.01	0.008	-10000	0	-10000	0	0
NR1I3	-0.06	0.22	-10000	0	-0.83	10	10
CSN2	0.038	0.19	0.5	4	-0.66	1	5
BRG1/BAF155/BAF170/BAF60A	0	0.004	-10000	0	-10000	0	0
NFATC1	0.018	0.005	-10000	0	-10000	0	0
POU2F1	0.02	0.005	-10000	0	-10000	0	0
CDKN1A	0.05	0.055	-10000	0	-0.72	2	2
response to stress	0	0	-10000	0	-10000	0	0
response to UV	-0.003	0.006	-10000	0	-10000	0	0
SFN	-0.079	0.27	-10000	0	-0.84	53	53
GR alpha/HSP90/FKBP51/HSP90/14-3-3	-0.005	0.21	0.38	2	-0.61	19	21
prolactin receptor activity	0	0	-10000	0	-10000	0	0
EGR1	-0.057	0.22	-10000	0	-0.85	8	8
JUN	-0.22	0.25	-10000	0	-0.58	98	98
IL4	-0.02	0.12	-10000	0	-0.58	2	2
CDK5R1	0.012	0.007	-10000	0	-10000	0	0
PRKACA	0.016	0	-10000	0	-10000	0	0
cortisol/GR alpha (monomer)/AP-1	-0.25	0.26	0.31	2	-0.65	93	95
GR alpha/HSP90/FKBP51/HSP90/PP5C	0.056	0.12	0.38	5	-0.6	4	9
cortisol/GR alpha (monomer)	0.14	0.34	0.66	87	-0.81	1	88
NCOA2	0.009	0.07	-10000	0	-0.76	4	4
response to hypoxia	0	0	-10000	0	-10000	0	0
FOS	-0.05	0.13	-10000	0	-0.82	10	10
AP-1/NFAT1-c-4	-0.32	0.34	-10000	0	-0.78	111	111
AFP	-0.37	0.57	-10000	0	-1.4	108	108
SUV420H1	0.016	0	-10000	0	-10000	0	0
IRF1	0.079	0.15	0.5	8	-0.62	1	9
TP53	0.044	0.022	-10000	0	-10000	0	0
PPP5C	0.016	0	-10000	0	-10000	0	0
KRT17	-0.24	0.41	-10000	0	-1.2	60	60
KRT14	-0.13	0.29	-10000	0	-0.85	60	60
TBP	0.029	0.001	-10000	0	-10000	0	0
CREBBP	0.042	0.076	-10000	0	-10000	0	0
HDAC1	0.01	0.008	-10000	0	-10000	0	0
HDAC2	0.011	0.014	-10000	0	-10000	0	0
AP-1	-0.32	0.34	-10000	0	-0.78	113	113
MAPK14	0.009	0.008	-10000	0	-10000	0	0
MAPK10	0	0.079	-10000	0	-0.77	5	5
MAPK11	0.01	0.008	-10000	0	-10000	0	0
KRT5	-0.25	0.38	-10000	0	-0.88	100	100
interleukin-1 receptor activity	0	0.011	-10000	0	-10000	0	0
NCOA1	0.019	0.002	-10000	0	-10000	0	0
STAT1	0.025	0.056	-10000	0	-1.2	1	1
CGA	-0.13	0.38	-10000	0	-1.2	50	50
NF kappa B1 p50/RelA/Cbp/cortisol/GR alpha (monomer)/HDAC2	0.086	0.15	0.46	31	-10000	0	31
MAPK3	0.008	0.008	-10000	0	-10000	0	0
MAPK1	0.009	0.008	-10000	0	-10000	0	0
ICAM1	-0.042	0.22	-10000	0	-0.8	20	20
NFKB1	0.006	0.075	-10000	0	-10000	0	0
MAPK8	-0.14	0.19	-10000	0	-0.48	58	58
MAPK9	0.009	0.008	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)	-0.1	0.23	-10000	0	-0.65	11	11
BAX	0.052	0.029	-10000	0	-10000	0	0
POMC	-0.033	0.17	-10000	0	-0.92	4	4
EP300	0.042	0.077	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/p53	0.15	0.29	0.59	79	-0.7	1	80
proteasomal ubiquitin-dependent protein catabolic process	0.023	0.071	0.28	2	-10000	0	2
SGK1	0.099	0.094	-10000	0	-10000	0	0
IL13	-0.35	0.28	-10000	0	-0.74	116	116
IL6	-0.11	0.37	-10000	0	-0.98	63	63
PRKACG	0.003	0.006	-10000	0	-10000	0	0
IL5	-0.28	0.21	-10000	0	-0.66	54	54
IL2	-0.17	0.25	-10000	0	-0.81	29	29
CDK5	0.012	0.007	-10000	0	-10000	0	0
PRKACB	0.016	0	-10000	0	-10000	0	0
HSP90AA1	0.016	0	-10000	0	-10000	0	0
IL8	-0.071	0.29	-10000	0	-0.89	41	41
CDK5R1/CDK5	0	0.003	-10000	0	-10000	0	0
NF kappa B1 p50/RelA/PKAc	0.027	0.099	-10000	0	-10000	0	0
cortisol/GR alpha (dimer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.55	72	-0.65	1	73
SMARCA4	0.018	0	-10000	0	-10000	0	0
chromatin remodeling	0.097	0.15	0.42	29	-10000	0	29
NF kappa B1 p50/RelA/Cbp	0.062	0.13	-10000	0	-10000	0	0
JUN (dimer)	-0.21	0.25	-10000	0	-0.58	98	98
YWHAH	0.016	0	-10000	0	-10000	0	0
VIPR1	-0.055	0.22	-10000	0	-0.84	21	21
NR3C1	0.075	0.19	0.51	30	-0.95	1	31
NR4A1	-0.002	0.14	-10000	0	-0.74	17	17
TIF2/SUV420H1	-0.005	0.052	-10000	0	-0.57	4	4
MAPKKK cascade	-0.098	0.22	-10000	0	-0.62	10	10
cortisol/GR alpha (dimer)/Src-1	0.14	0.29	0.57	79	-0.8	1	80
PBX1	0	0.12	-10000	0	-0.76	12	12
POU1F1	0.009	0.009	-10000	0	-10000	0	0
SELE	-0.086	0.35	-10000	0	-1.3	33	33
cortisol/GR alpha/BRG1/BAF155/BAF170/BAF60A	0.097	0.15	0.42	29	-10000	0	29
cortisol/GR alpha (monomer)/Hsp90/FKBP52/HSP90	0.14	0.26	0.55	72	-0.65	1	73
mol:cortisol	0.057	0.2	0.4	66	-10000	0	66
MMP1	-0.23	0.4	-10000	0	-0.99	95	95

×

Regulation of Telomerase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Telomerase catalytic core complex	-0.24	0.28	-9999	-0.85	71	71
RAD9A	0.016	0	-9999	-10000	0	0
AP1	-0.012	0.082	-9999	-0.57	10	10
IFNAR2	0.014	0.007	-9999	-10000	0	0
AKT1	0.014	0.069	-9999	-0.43	10	10
ER alpha/Oestrogen	-0.002	0.038	-9999	-0.59	2	2
NFX1/SIN3/HDAC complex	0.045	0.052	-9999	-10000	0	0
EGF	-0.68	0.23	-9999	-0.76	432	432
SMG5	0.016	0	-9999	-10000	0	0
SMG6	0.016	0	-9999	-10000	0	0
SP3/HDAC2	0	0	-9999	-10000	0	0
TERT/c-Abl	-0.22	0.26	-9999	-0.79	69	69
SAP18	0.013	0.006	-9999	-10000	0	0
MRN complex	0	0	-9999	-10000	0	0
WT1	-0.36	0.39	-9999	-0.76	229	229
WRN	0.016	0	-9999	-10000	0	0
SP1	0.015	0.007	-9999	-10000	0	0
SP3	0.014	0.006	-9999	-10000	0	0
TERF2IP	0.016	0	-9999	-10000	0	0
Telomerase/Nucleolin	-0.19	0.23	-9999	-0.72	59	59
Mad/Max	0	0	-9999	-10000	0	0
TERT	-0.25	0.29	-9999	-0.88	71	71
CCND1	-0.22	0.27	-9999	-0.79	74	74
MAX	0.014	0.006	-9999	-10000	0	0
RBBP7	0.013	0.006	-9999	-10000	0	0
RBBP4	0.013	0.006	-9999	-10000	0	0
TERF2	0	0	-9999	-10000	0	0
PTGES3	0.016	0	-9999	-10000	0	0
SIN3A	0.013	0.006	-9999	-10000	0	0
Telomerase/911	0	0.025	-9999	-10000	0	0
CDKN1B	-0.23	0.3	-9999	-0.55	220	220
RAD1	0.016	0	-9999	-10000	0	0
XRCC5	0.016	0	-9999	-10000	0	0
XRCC6	0.016	0	-9999	-10000	0	0
SAP30	-0.016	0.16	-9999	-0.86	16	16
TRF2/PARP2	0	0	-9999	-10000	0	0
UBE3A	0.014	0.006	-9999	-10000	0	0
JUN	0.014	0.006	-9999	-10000	0	0
E6	-0.001	0.004	-9999	-10000	0	0
HPV-16 E6/E6AP	0	0	-9999	-10000	0	0
FOS	-0.002	0.11	-9999	-0.76	10	10
IFN-gamma/IRF1	-0.3	0.32	-9999	-0.65	220	220
PARP2	0.016	0	-9999	-10000	0	0
BLM	-0.004	0.13	-9999	-0.86	11	11
Telomerase	-0.016	0.16	-9999	-0.41	29	29
IRF1	0.016	0.041	-9999	-0.86	1	1
ESR1	0.01	0.05	-9999	-0.76	2	2
KU/TER	0	0	-9999	-10000	0	0
ATM/TRF2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0.039	0.051	-9999	-10000	0	0
HPV-16 E6/E6AP/NFX1/SIN3/HDAC complex	-0.006	0.031	-9999	-10000	0	0
HDAC1	0.013	0.006	-9999	-10000	0	0
HDAC2	0.015	0.007	-9999	-10000	0	0
ATM	0	0	-9999	-10000	0	0
SMAD3	0.024	0.07	-9999	-0.66	5	5
ABL1	0.016	0	-9999	-10000	0	0
MXD1	0.014	0.006	-9999	-10000	0	0
MRE11A	0.016	0	-9999	-10000	0	0
HUS1	0.016	0	-9999	-10000	0	0
RPS6KB1	0.016	0	-9999	-10000	0	0
TERT/NF kappa B1/14-3-3	-0.18	0.25	-9999	-0.75	59	59
NR2F2	0.006	0.013	-9999	-10000	0	0
MAPK3	0.008	0.099	-9999	-0.67	10	10
MAPK1	0.008	0.099	-9999	-0.67	10	10
TGFB1/TGF beta receptor Type II	0.007	0.089	-9999	-0.86	5	5
NFKB1	0.016	0	-9999	-10000	0	0
HNRNPC	0.016	0	-9999	-10000	0	0
DNA damage response signal transduction by p53 class mediator resulting in induction of apoptosis	0	0	-9999	-10000	0	0
NBN	0.016	0	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
mol:Oestrogen	-0.001	0.002	-9999	-10000	0	0
EGF/EGFR	-0.52	0.19	-9999	-0.58	433	433
MYC	-0.015	0.16	-9999	-0.87	16	16
IL2	-0.009	0.13	-9999	-0.87	10	10
KU	0	0	-9999	-10000	0	0
RAD50	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
TGFB1	0.007	0.089	-9999	-0.86	5	5
TRF2/BLM	-0.014	0.094	-9999	-0.63	11	11
FRAP1	0	0	-9999	-10000	0	0
KU/TERT	-0.22	0.26	-9999	-0.78	68	68
SP1/HDAC2	0.006	0.013	-9999	-10000	0	0
PINX1	0.016	0	-9999	-10000	0	0
Telomerase/EST1A	-0.19	0.23	-9999	-0.72	59	59
Smad3/Myc	-0.018	0.12	-9999	-0.6	20	20
911 complex	0	0	-9999	-10000	0	0
IFNG	-0.38	0.43	-9999	-0.85	220	220
Telomerase/PinX1	-0.19	0.23	-9999	-0.72	59	59
Telomerase/AKT1/mTOR/p70S6K	-0.014	0.08	-9999	-0.53	2	2
SIN3B	0.013	0.006	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
Telomerase/EST1B	-0.19	0.23	-9999	-0.72	59	59
response to DNA damage stimulus	0.004	0	-9999	-10000	0	0
MRN complex/TRF2/Rap1	0	0	-9999	-10000	0	0
TRF2/WRN	0	0	-9999	-10000	0	0
Telomerase/hnRNP C1/C2	-0.19	0.23	-9999	-0.72	59	59
E2F1	-0.085	0.28	-9999	-0.87	54	54
ZNFX1	0.013	0.006	-9999	-10000	0	0
PIF1	-0.13	0.33	-9999	-0.86	79	79
NCL	0.016	0	-9999	-10000	0	0
DKC1	0.016	0	-9999	-10000	0	0
telomeric DNA binding	0	0	-9999	-10000	0	0

×

Lissencephaly gene (LIS1) in neuronal migration and development

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
DYNC1H1	0.016	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
NUDC	0.016	0	-9999	-10000	0	0
RELN/LRP8	-0.16	0.23	-9999	-0.49	160	160
CaM/Ca2+	0	0	-9999	-10000	0	0
KATNA1	0.016	0	-9999	-10000	0	0
GO:0030286	0	0	-9999	-10000	0	0
ABL1	-0.12	0.23	-9999	-0.52	5	5
IQGAP1/CaM	0	0	-9999	-10000	0	0
DAB1	-0.009	0.13	-9999	-0.86	11	11
IQGAP1	0.016	0	-9999	-10000	0	0
PLA2G7	-0.66	0.38	-9999	-0.86	366	366
CALM1	0.016	0	-9999	-10000	0	0
DYNLT1	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
LRPAP1/LRP8	-0.001	0.03	-9999	-0.67	1	1
UniProt:Q4QZ09	0	0	-9999	-10000	0	0
CLIP1	0.016	0	-9999	-10000	0	0
CDK5R1	0.016	0	-9999	-10000	0	0
LIS1/Poliovirus Protein 3A	0	0	-9999	-10000	0	0
CDK5R2	-0.1	0.29	-9999	-0.86	61	61
mol:PP1	0	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.18	0.24	-9999	-0.5	169	169
YWHAE	0.016	0	-9999	-10000	0	0
NDEL1/14-3-3 E	-0.14	0.17	-9999	-0.6	15	15
MAP1B	-0.001	0.021	-9999	-0.33	2	2
RAC1	0	0	-9999	-10000	0	0
p35/CDK5	-0.12	0.18	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.76	159	159
PAFAH/LIS1	-0.44	0.24	-9999	-0.58	366	366
LIS1/CLIP170	0	0	-9999	-10000	0	0
LIS1/NDEL1/Katanin 60/Dynein Light chain/Dynein heavy chain	-0.1	0.12	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1/PAFAH1B2/PAFAH1B3	-0.1	0.14	-9999	-0.7	1	1
GO:0005869	0	0	-9999	-10000	0	0
NDEL1	-0.14	0.19	-9999	-0.65	15	15
LIS1/IQGAP1	0	0	-9999	-10000	0	0
RHOA	0	0	-9999	-10000	0	0
PAFAH1B1	0.031	0	-9999	-10000	0	0
PAFAH1B3	0.014	0.035	-9999	-0.76	1	1
PAFAH1B2	0.016	0	-9999	-10000	0	0
MAP1B/LIS1/Dynein heavy chain	-0.001	0.013	-9999	-10000	0	0
NDEL1/Katanin 60/Dynein heavy chain	-0.13	0.16	-9999	-0.56	15	15
LRP8	0.014	0.04	-9999	-0.86	1	1
NDEL1/Katanin 60	-0.14	0.17	-9999	-0.6	15	15
P39/CDK5	-0.18	0.23	-9999	-0.87	15	15
LIS1/NudC/Dynein intermediate chain/microtubule organizing center	0	0	-9999	-10000	0	0
CDK5	-0.096	0.22	-9999	-10000	0	0
PPP2R5D	0.016	0	-9999	-10000	0	0
LIS1/CLIP170/Dynein Complex/Dynactin Complex	0	0	-9999	-10000	0	0
CSNK2A1	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1/LIS1	-0.15	0.2	-9999	-0.52	15	15
RELN/VLDLR	-0.15	0.21	-9999	-0.52	5	5
CDC42	0	0	-9999	-10000	0	0

×

Reelin signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CDK5R1/CDK5	0	0	-9999	-10000	0	0
VLDLR	0.016	0	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
LRPAP1	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ITGA3	0.014	0.04	-9999	-0.86	1	1
RELN/VLDLR/Fyn	-0.16	0.23	-9999	-0.49	159	159
MAPK8IP1/MKK7/MAP3K11/JNK1	-0.003	0.042	-9999	-0.83	1	1
AKT1	-0.066	0.16	-9999	-0.56	1	1
MAP2K7	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
DAB1	-0.009	0.13	-9999	-0.86	11	11
RELN/LRP8/DAB1	-0.16	0.22	-9999	-0.46	170	170
LRPAP1/LRP8	-0.001	0.03	-9999	-0.67	1	1
RELN/LRP8/DAB1/Fyn	-0.15	0.21	-9999	-0.43	170	170
DAB1/alpha3/beta1 Integrin	-0.13	0.18	-9999	-0.83	1	1
long-term memory	-0.21	0.25	-9999	-0.89	22	22
DAB1/LIS1	-0.14	0.19	-9999	-0.86	1	1
DAB1/CRLK/C3G	-0.13	0.18	-9999	-0.83	1	1
PIK3CA	0.016	0	-9999	-10000	0	0
DAB1/NCK2	-0.14	0.19	-9999	-0.87	1	1
ARHGEF2	0.016	0	-9999	-10000	0	0
mol:Src family inhibitors PP1 and PP2	0	0	-9999	-10000	0	0
GRIN2A	-0.11	0.3	-9999	-0.84	68	68
CDK5R1	0.016	0	-9999	-10000	0	0
RELN	-0.24	0.36	-9999	-0.76	159	159
PIK3R1	0.016	0	-9999	-10000	0	0
RELN/LRP8/Fyn	-0.16	0.23	-9999	-0.49	160	160
GRIN2A/RELN/LRP8/DAB1/Fyn	-0.22	0.26	-9999	-0.62	69	69
MAPK8	0.016	0	-9999	-10000	0	0
RELN/VLDLR/DAB1	-0.16	0.22	-9999	-0.46	169	169
ITGB1	0.016	0	-9999	-10000	0	0
MAP1B	-0.15	0.2	-9999	-0.52	16	16
RELN/LRP8	-0.16	0.23	-9999	-0.49	160	160
GRIN2B/RELN/LRP8/DAB1/Fyn	-0.15	0.21	-9999	-0.54	18	18
PI3K	0	0	-9999	-10000	0	0
mol:PP2	0	0	-9999	-10000	0	0
alpha3/beta1 Integrin	-0.001	0.03	-9999	-0.67	1	1
RAP1A	-0.12	0.16	-9999	-0.76	1	1
PAFAH1B1	0.016	0	-9999	-10000	0	0
MAPK8IP1	0.012	0.05	-9999	-0.76	2	2
CRLK/C3G	0	0	-9999	-10000	0	0
GRIN2B	0.008	0.057	-9999	-0.86	2	2
NCK2	0.016	0	-9999	-10000	0	0
neuron differentiation	-0.028	0.12	-9999	-0.54	2	2
neuron adhesion	-0.05	0.2	-9999	-0.71	1	1
LRP8	0.014	0.04	-9999	-0.86	1	1
GSK3B	-0.052	0.15	-9999	-0.53	1	1
RELN/VLDLR/DAB1/Fyn	-0.15	0.21	-9999	-0.53	15	15
MAP3K11	0.014	0.035	-9999	-0.76	1	1
RELN/VLDLR/DAB1/P13K	-0.11	0.15	-9999	-0.6	1	1
CDK5	0.016	0	-9999	-10000	0	0
MAPT	0.015	0.087	-9999	-0.71	6	6
neuron migration	-0.059	0.21	-9999	-0.61	1	1
RELN/LRP8/DAB1/Fyn/MAPK8IP1/MKK7/MAP3K11/JNK1	-0.058	0.1	-9999	-0.55	2	2
RELN/VLDLR	-0.15	0.21	-9999	-0.52	5	5

×

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

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
MAP4K1	-0.17	0.27	-10000	0	-0.53	89	89
CRKL	0.019	0.11	-10000	0	-0.46	18	18
HRAS	-0.045	0.18	-10000	0	-0.51	41	41
mol:PIP3	-0.002	0.1	-10000	0	-0.45	18	18
SPRED1	0.016	0	-10000	0	-10000	0	0
SPRED2	0.016	0	-10000	0	-10000	0	0
GAB1	0.007	0.12	-10000	0	-0.5	18	18
FOXO3	0.025	0.1	-10000	0	-0.41	18	18
AKT1	0.015	0.11	-10000	0	-0.45	18	18
BAD	0.024	0.1	-10000	0	-0.6	4	4
megakaryocyte differentiation	-0.066	0.21	-10000	0	-0.45	98	98
GSK3B	0.025	0.1	-10000	0	-0.6	4	4
RAF1	-0.012	0.16	-10000	0	-0.45	10	10
SHC1	0.014	0.04	-10000	0	-0.86	1	1
STAT3	0.008	0.12	-10000	0	-0.5	18	18
STAT1	-0.014	0.23	-10000	0	-1	18	18
HRAS/SPRED1	-0.068	0.12	-10000	0	-0.4	41	41
cell proliferation	0.008	0.12	-10000	0	-0.48	18	18
PIK3CA	0.016	0	-10000	0	-10000	0	0
TEC	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.009	0.12	-10000	0	-0.48	20	20
HRAS/SPRED2	-0.068	0.12	-10000	0	-0.4	41	41
LYN/TEC/p62DOK	-0.017	0.099	-10000	0	-0.67	4	4
MAPK3	0.011	0.12	-10000	0	-0.37	2	2
STAP1	-0.32	0.22	-10000	0	-0.43	365	365
GRAP2	-0.046	0.22	-10000	0	-0.86	34	34
JAK2	-0.066	0.18	-10000	0	-0.91	18	18
STAT1 (dimer)	-0.012	0.23	-10000	0	-1	18	18
mol:Gleevec	-0.002	0.005	-10000	0	-10000	0	0
GRB2/SOCS1/VAV1	-0.13	0.22	-10000	0	-0.56	46	46
actin filament polymerization	0.003	0.13	-10000	0	-0.48	23	23
LYN	0.016	0	-10000	0	-10000	0	0
STAP1/STAT5A (dimer)	-0.3	0.23	-10000	0	-0.86	27	27
PIK3R1	0.016	0	-10000	0	-10000	0	0
CBL/CRKL/GRB2	-0.012	0.09	-10000	0	-0.59	4	4
PI3K	-0.017	0.1	-10000	0	-0.56	7	7
PTEN	0.016	0	-10000	0	-10000	0	0
SCF/KIT/EPO/EPOR	-0.13	0.33	-10000	0	-1.3	20	20
MAPK8	0.008	0.12	-10000	0	-0.5	18	18
STAT3 (dimer)	0.008	0.12	-10000	0	-0.48	18	18
positive regulation of transcription	0.014	0.1	-10000	0	-0.31	1	1
mol:GDP	-0.12	0.2	-10000	0	-0.62	44	44
PIK3C2B	0.008	0.12	-10000	0	-0.5	18	18
CBL/CRKL	0.027	0.11	-10000	0	-0.62	4	4
FER	0.007	0.12	-10000	0	-0.51	19	19
SH2B3	0.008	0.12	-10000	0	-0.5	18	18
PDPK1	0.009	0.098	-10000	0	-0.4	18	18
SNAI2	0.007	0.12	-10000	0	-0.52	18	18
positive regulation of cell proliferation	0.001	0.18	-10000	0	-0.79	18	18
KITLG	0	0.11	-10000	0	-0.78	9	9
cell motility	0.001	0.18	-10000	0	-0.79	18	18
PTPN6	0.008	0.011	-10000	0	-10000	0	0
EPOR	0.041	0.07	-10000	0	-10000	0	0
STAT5A (dimer)	0.005	0.16	-10000	0	-0.65	19	19
SOCS1	0.007	0.089	-10000	0	-0.86	5	5
cell migration	0.046	0.19	0.5	66	-10000	0	66
SOS1	0.016	0	-10000	0	-10000	0	0
EPO	-0.3	0.42	-10000	0	-0.86	172	172
VAV1	-0.2	0.38	-10000	0	-0.86	119	119
GRB10	0.007	0.12	-10000	0	-0.5	18	18
PTPN11	0.008	0.01	-10000	0	-10000	0	0
SCF/KIT	-0.034	0.11	-10000	0	-0.45	30	30
GO:0007205	-0.001	0.006	-10000	0	-10000	0	0
MAP2K1	0.005	0.13	-10000	0	-0.42	2	2
CBL	0.016	0	-10000	0	-10000	0	0
KIT	-0.007	0.27	-10000	0	-1.1	25	25
MAP2K2	0.004	0.13	-10000	0	-0.42	2	2
SHC/Grb2/SOS1	-0.018	0.1	-10000	0	-0.62	5	5
STAT5A	0.004	0.16	-10000	0	-0.67	19	19
GRB2	0.016	0	-10000	0	-10000	0	0
response to radiation	0.007	0.12	-10000	0	-0.5	18	18
SHC/GRAP2	-0.048	0.17	-10000	0	-0.66	35	35
PTPRO	-0.068	0.21	-10000	0	-0.46	98	98
SH2B2	0.002	0.13	-10000	0	-0.49	23	23
DOK1	0.016	0	-10000	0	-10000	0	0
MATK	-0.047	0.2	-10000	0	-0.51	66	66
CREBBP	0.045	0.012	-10000	0	-10000	0	0
BCL2	0.043	0.067	-10000	0	-10000	0	0

×

IL6-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.14	0.31	-9999	-0.76	40	40
CRP	-0.2	0.4	-9999	-0.92	87	87
cell cycle arrest	-0.18	0.36	-9999	-0.82	70	70
TIMP1	-0.15	0.34	-9999	-0.77	71	71
IL6ST	-0.004	0.11	-9999	-0.75	10	10
Rac1/GDP	-0.14	0.26	-9999	-0.6	84	84
AP1	0.026	0.1	-9999	-0.48	1	1
GAB2	0.012	0.008	-9999	-10000	0	0
TNFSF11	-0.19	0.38	-9999	-0.93	55	55
HSP90B1	0.005	0.092	-9999	-10000	0	0
GAB1	0.013	0.007	-9999	-10000	0	0
MAPK14	0.023	0.13	-9999	-0.71	3	3
AKT1	0.061	0.032	-9999	-10000	0	0
FOXO1	0.078	0.016	-9999	-10000	0	0
MAP2K6	-0.011	0.13	-9999	-0.66	4	4
mol:GTP	-0.001	0.003	-9999	-10000	0	0
MAP2K4	-0.14	0.28	-9999	-0.67	62	62
MITF	-0.02	0.14	-9999	-0.72	2	2
positive regulation of NF-kappaB transcription factor activity	0	0	-9999	-10000	0	0
TYK2	0.016	0	-9999	-10000	0	0
A2M	0.028	0.005	-9999	-10000	0	0
CEBPB	0.001	0.14	-9999	-0.86	12	12
GRB2/SOS1/GAB family/SHP2	0.003	0.07	-9999	-10000	0	0
STAT3	-0.19	0.38	-9999	-0.89	63	63
STAT1	-0.006	0.025	-9999	-0.49	1	1
CEBPD	-0.14	0.32	-9999	-0.78	35	35
PIK3CA	0.018	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
JUN	0.01	0.008	-9999	-10000	0	0
PIAS3/MITF	-0.013	0.13	-9999	-0.68	2	2
MAPK11	0.023	0.13	-9999	-0.71	3	3
STAT3 (dimer)/FOXO1	-0.068	0.28	-9999	-0.64	19	19
GRB2/SOS1/GAB family	-0.044	0.1	-9999	-0.64	2	2
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/HCK	-0.033	0.15	-9999	-0.63	10	10
GRB2	0.013	0.007	-9999	-10000	0	0
JAK2	0.016	0	-9999	-10000	0	0
LBP	-0.27	0.45	-9999	-0.89	140	140
PIK3R1	0.017	0	-9999	-10000	0	0
JAK1	0.015	0.006	-9999	-10000	0	0
MYC	-0.15	0.33	-9999	-0.81	43	43
FGG	-0.28	0.44	-9999	-0.91	109	109
macrophage differentiation	-0.18	0.36	-9999	-0.82	70	70
IL6/IL6RA/gp130 (dimer)/JAK2/JAK2/LMO4	-0.066	0.17	-9999	-0.54	33	33
JUNB	-0.14	0.31	-9999	-0.77	35	35
FOS	-0.006	0.11	-9999	-0.76	10	10
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4	-0.03	0.15	-9999	-0.44	21	21
STAT1/PIAS1	-0.043	0.16	-9999	-0.48	20	20
GRB2/SOS1/GAB family/SHP2/PI3K	0.023	0.035	-9999	-10000	0	0
STAT3 (dimer)	-0.19	0.38	-9999	-0.89	63	63
PRKCD	-0.15	0.31	-9999	-0.75	48	48
IL6R	0.015	0.006	-9999	-10000	0	0
SOCS3	0.038	0.12	-9999	-0.68	4	4
gp130 (dimer)/JAK1/JAK1/LMO4	-0.008	0.07	-9999	-0.5	5	5
Rac1/GTP	-0.18	0.24	-9999	-0.61	90	90
HCK	-0.036	0.2	-9999	-0.87	27	27
MAPKKK cascade	0.028	0.061	-9999	-10000	0	0
bone resorption	-0.18	0.36	-9999	-0.86	55	55
IRF1	-0.14	0.32	-9999	-0.76	40	40
mol:GDP	-0.15	0.27	-9999	-0.6	96	96
SOS1	0.01	0.008	-9999	-10000	0	0
VAV1	-0.15	0.28	-9999	-0.62	96	96
IL6/IL6RA/gp130 (dimer)/JAK1/JAK1/LMO4/SOCS3	0.003	0.12	-9999	-0.66	2	2
PTPN11	-0.004	0.012	-9999	-10000	0	0
IL6/IL6RA	-0.079	0.21	-9999	-0.64	59	59
gp130 (dimer)/TYK2/TYK2/LMO4	-0.008	0.069	-9999	-0.48	10	10
gp130 (dimer)/JAK2/JAK2/LMO4	-0.008	0.069	-9999	-0.48	10	10
IL6	-0.092	0.28	-9999	-0.84	59	59
PIAS3	0.016	0	-9999	-10000	0	0
PTPRE	0.017	0.017	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
RAC1	0.015	0.002	-9999	-10000	0	0
IL6/IL6RA/gp130 (dimer)/TYK2/TYK2/LMO4	-0.03	0.13	-9999	-0.4	12	12
LMO4	0.012	0.014	-9999	-10000	0	0
STAT3 (dimer)/PIAS3	-0.22	0.3	-9999	-0.81	62	62
MCL1	0.077	0.015	-9999	-10000	0	0

×

Aurora A 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Aurora A/GADD45A	0.02	0.046	-9999	-10000	0	0
BIRC5	-0.24	0.4	-9999	-0.86	140	140
NFKBIA	0.048	0.041	-9999	-10000	0	0
CPEB1	-0.14	0.31	-9999	-0.77	94	94
AKT1	0.048	0.041	-9999	-10000	0	0
NDEL1	0.016	0	-9999	-10000	0	0
Aurora A/BRCA1	0.018	0.042	-9999	-10000	0	0
NDEL1/TACC3	0.016	0.078	-9999	-0.74	4	4
GADD45A	0.016	0	-9999	-10000	0	0
GSK3B	0.014	0.019	-9999	-10000	0	0
PAK1/Aurora A	0.02	0.046	-9999	-10000	0	0
MDM2	0.016	0	-9999	-10000	0	0
JUB	0.012	0.05	-9999	-0.76	2	2
TPX2	-0.14	0.3	-9999	-0.67	120	120
TP53	0.025	0.037	-9999	-10000	0	0
DLG7	0.02	0.045	-9999	-0.29	6	6
AURKAIP1	0.012	0.05	-9999	-0.76	2	2
ARHGEF7	0.016	0	-9999	-10000	0	0
G2 phase of mitotic cell cycle	0	0	-9999	-10000	0	0
Aurora A/NDEL1/TACC3	0.017	0.082	-9999	-0.77	4	4
G2/M transition of mitotic cell cycle	0.018	0.041	-9999	-10000	0	0
AURKA	0.027	0.056	-9999	-0.34	6	6
AURKB	-0.14	0.15	-9999	-0.29	229	229
CDC25B	0.018	0.064	-9999	-0.58	2	2
G2/M transition checkpoint	0.016	0.051	-9999	-0.45	2	2
mRNA polyadenylation	-0.073	0.19	-9999	-0.45	94	94
Aurora A/CPEB	-0.074	0.19	-9999	-0.46	94	94
Aurora A/TACC1/TRAP/chTOG	-0.003	0.024	-9999	-10000	0	0
BRCA1	0.016	0	-9999	-10000	0	0
centrosome duplication	0.02	0.046	-9999	-10000	0	0
regulation of centrosome cycle	-0.007	0.068	-9999	-0.73	4	4
spindle assembly	-0.003	0.024	-9999	-10000	0	0
TDRD7	0.016	0	-9999	-10000	0	0
Aurora A/RasGAP/Survivin	-0.14	0.21	-9999	-0.47	137	137
CENPA	-0.12	0.14	-9999	-0.3	160	160
Aurora A/PP2A	0.02	0.046	-9999	-10000	0	0
meiosis	0	0	-9999	-10000	0	0
protein catabolic process	0.054	0.036	-9999	-10000	0	0
negative regulation of DNA binding	0.025	0.037	-9999	-10000	0	0
prophase	0	0	-9999	-10000	0	0
GIT1/beta-PIX	0	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
Ajuba/Aurora A	0.016	0.051	-9999	-0.45	2	2
mitotic prometaphase	0.038	0.04	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.027	0.056	-9999	-0.34	6	6
TACC1	0.016	0	-9999	-10000	0	0
TACC3	0.008	0.08	-9999	-0.86	4	4
Aurora A/Antizyme1	0.02	0.053	-9999	-0.42	2	2
Aurora A/RasGAP	0.02	0.046	-9999	-10000	0	0
OAZ1	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
mitosis	0	0	-9999	-10000	0	0
PRKACA	0.014	0.019	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
GIT1/beta-PIX/PAK1	0	0	-9999	-10000	0	0
Importin alpha/Importin beta/TPX2	-0.14	0.3	-9999	-0.67	120	120
PPP2R5D	0.016	0	-9999	-10000	0	0
Aurora A/TPX2	-0.092	0.25	-9999	-0.52	120	120
PAK1	0.016	0	-9999	-10000	0	0
CKAP5	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Rods

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:K +	0.016	0	-9999	-10000	0	0
GNAT1/GTP	-0.007	0.069	-9999	-0.68	5	5
Metarhodopsin II/Arrestin	-0.019	0.1	-9999	-0.6	15	15
PDE6G/GNAT1/GTP	-0.012	0.079	-9999	-0.56	10	10
mol:GTP	0	0	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
GNAT1	-0.002	0.089	-9999	-0.86	5	5
GRK1	0.003	0.006	-9999	-10000	0	0
CNG Channel	-0.11	0.21	-9999	-0.92	11	11
mol:Na +	-0.11	0.21	-9999	-0.82	18	18
mol:ADP	0.003	0.006	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	33	33
mol:GDP	0	0	-9999	-10000	0	0
cGMP/CNG Channel	-0.12	0.22	-9999	-0.86	18	18
CNGB1	-0.005	0.11	-9999	-0.86	8	8
RDH5	0	0.12	-9999	-0.83	9	9
SAG	0.002	0.006	-9999	-10000	0	0
mol:Ca2+	-0.074	0.22	-9999	-0.78	18	18
Na + (4 Units)	-0.1	0.19	-9999	-0.75	18	18
RGS9	-0.005	0.13	-9999	-0.82	12	12
GNB1/GNGT1	-0.22	0.32	-9999	-0.67	161	161
GNAT1/GDP	-0.035	0.12	-9999	-0.54	11	11
GUCY2D	-0.028	0.18	-9999	-0.86	22	22
GNGT1	-0.28	0.41	-9999	-0.86	161	161
GUCY2F	0.002	0.005	-9999	-10000	0	0
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	-0.036	0.14	-9999	-0.59	25	25
mol:11-cis-retinal	0	0.12	-9999	-0.83	9	9
mol:cGMP	-0.039	0.14	-9999	-0.52	33	33
GNB1	0.016	0	-9999	-10000	0	0
Rhodopsin	-0.033	0.14	-9999	-0.66	24	24
SLC24A1	0.016	0	-9999	-10000	0	0
CNGA1	-0.13	0.3	-9999	-0.76	91	91
Metarhodopsin II	-0.017	0.096	-9999	-0.55	15	15
mol:Ca ++	0	0	-9999	-10000	0	0
GC1/GCAP Family	-0.041	0.14	-9999	-0.55	34	34
RGS9BP	-0.019	0.16	-9999	-0.76	21	21
Metarhodopsin II/Transducin	-0.11	0.16	-9999	-0.62	9	9
GCAP Family/Ca ++	-0.016	0.098	-9999	-0.56	14	14
PDE6A/B	-0.035	0.15	-9999	-0.67	25	25
mol:Pi	-0.035	0.13	-9999	-0.5	33	33
mol:all-trans-retinal	0	0	-9999	-10000	0	0
Transducin	-0.19	0.26	-9999	-0.55	162	162
PDE6B	0.008	0.079	-9999	-0.76	5	5
PDE6A	-0.025	0.18	-9999	-0.86	21	21
PDE6G	0.007	0.081	-9999	-0.78	5	5
RHO	-0.017	0.15	-9999	-0.86	15	15
PDE6	-0.056	0.16	-9999	-0.84	8	8
GUCA1A	-0.01	0.12	-9999	-0.86	9	9
GC2/GCAP Family	-0.016	0.098	-9999	-0.58	12	12
GUCA1C	0.001	0.05	-9999	-0.76	2	2
GUCA1B	0.008	0.08	-9999	-0.86	4	4

×

Signaling events mediated by PTP1B

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-10000	0	-10000	0	0
Jak2/Leptin Receptor	-0.045	0.099	-10000	0	-0.56	4	4
PTP1B/AKT1	-0.031	0.045	-10000	0	-0.42	2	2
FYN	0.016	0	-10000	0	-10000	0	0
p210 bcr-abl/PTP1B	-0.048	0.051	-10000	0	-0.37	5	5
EGFR	-0.015	0.12	-10000	0	-0.87	9	9
EGF/EGFR	-0.38	0.14	-10000	0	-0.42	433	433
CSF1	0.016	0	-10000	0	-10000	0	0
AKT1	0.016	0.001	-10000	0	-10000	0	0
INSR	0.016	0.001	-10000	0	-10000	0	0
PTP1B/N-cadherin	-0.048	0.086	-10000	0	-0.46	15	15
Insulin Receptor/Insulin	-0.011	0.031	-10000	0	-10000	0	0
HCK	-0.034	0.2	-10000	0	-0.86	27	27
CRK	0.016	0	-10000	0	-10000	0	0
TYK2	-0.034	0.049	-10000	0	-0.45	2	2
EGF	-0.68	0.23	-10000	0	-0.76	432	432
YES1	0.016	0	-10000	0	-10000	0	0
CAV1	-0.15	0.1	-10000	0	-0.42	39	39
TXN	0.002	0.005	-10000	0	-10000	0	0
PTP1B/IRS1/GRB2	-0.031	0.046	-10000	0	-0.44	4	4
cell migration	0.048	0.051	0.37	5	-10000	0	5
STAT3	0.015	0.003	-10000	0	-10000	0	0
PRLR	-0.09	0.24	-10000	0	-0.76	57	57
ITGA2B	-0.025	0.15	-10000	0	-0.86	15	15
CSF1R	0.003	0.11	-10000	0	-0.86	7	7
Prolactin Receptor/Prolactin	-0.068	0.19	-10000	0	-0.58	57	57
FGR	0.01	0.069	-10000	0	-0.86	3	3
PTP1B/p130 Cas	-0.036	0.05	-10000	0	-0.43	3	3
Crk/p130 Cas	-0.03	0.04	-10000	0	-0.42	2	2
DOK1	-0.018	0.044	-10000	0	-0.38	2	2
JAK2	-0.05	0.11	-10000	0	-0.42	14	14
Jak2/Leptin Receptor/Leptin	-0.051	0.13	-10000	0	-0.54	9	9
PIK3R1	0.016	0	-10000	0	-10000	0	0
PTPN1	-0.048	0.051	-10000	0	-0.37	5	5
LYN	0.016	0	-10000	0	-10000	0	0
CDH2	-0.007	0.13	-10000	0	-0.76	14	14
SRC	0	0.02	-10000	0	-10000	0	0
ITGB3	0	0.035	-10000	0	-0.76	1	1
CAT1/PTP1B	-0.24	0.14	-10000	0	-0.56	39	39
CAPN1	0.002	0.005	-10000	0	-10000	0	0
CSK	0.016	0	-10000	0	-10000	0	0
PI3K	0.011	0.029	-10000	0	-10000	0	0
mol:H2O2	-0.007	0.002	-10000	0	-10000	0	0
STAT3 (dimer)	-0.033	0.12	-10000	0	-0.66	3	3
negative regulation of transcription	-0.049	0.11	-10000	0	-0.41	14	14
FCGR2A	-0.025	0.18	-10000	0	-0.86	22	22
FER	0	0.035	-10000	0	-0.77	1	1
alphaIIb/beta3 Integrin	-0.022	0.12	-10000	0	-0.66	16	16
BLK	-0.04	0.21	-10000	0	-0.86	30	30
Insulin Receptor/Insulin/Shc	-0.001	0.027	-10000	0	-0.59	1	1
RHOA	0.002	0.005	-10000	0	-10000	0	0
LEPR	0.014	0.004	-10000	0	-10000	0	0
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
p210 bcr-abl/Grb2	0.016	0	-10000	0	-10000	0	0
mol:NADPH	-0.007	0.003	-10000	0	-10000	0	0
TRPV6	-0.23	0.16	-10000	0	-0.56	55	55
PRL	0	0.002	-10000	0	-10000	0	0
SOCS3	0.028	0.051	-10000	0	-0.74	2	2
SPRY2	0.001	0.005	-10000	0	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.032	-10000	0	-0.5	2	2
CSF1/CSF1R	-0.037	0.071	-10000	0	-0.51	9	9
Ras protein signal transduction	0.039	0.016	-10000	0	-10000	0	0
IRS1	0.012	0.05	-10000	0	-0.76	2	2
INS	0.001	0.001	-10000	0	-10000	0	0
LEP	-0.073	0.26	-10000	0	-0.86	46	46
STAT5B	-0.043	0.065	-10000	0	-0.46	4	4
STAT5A	-0.043	0.065	-10000	0	-0.46	4	4
GRB2	0.016	0	-10000	0	-10000	0	0
PDGFB-D/PDGFRB	-0.035	0.048	-10000	0	-0.45	2	2
CSN2	-0.006	0.067	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
LAT	-0.11	0.17	-10000	0	-0.35	144	144
YBX1	0.003	0.008	-10000	0	-10000	0	0
LCK	-0.024	0.18	-10000	0	-0.85	22	22
SHC1	0.014	0.04	-10000	0	-0.86	1	1
NOX4	-0.007	0.078	-10000	0	-0.77	5	5

×

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

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BAG4	0.016	0	-9999	-10000	0	0
Caspase 8 (4 units)	-0.1	0.092	-9999	-10000	0	0
NEF	-0.06	0.085	-9999	-10000	0	0
NFKBIA	0.001	0.045	-9999	-10000	0	0
BIRC3	-0.07	0.31	-9999	-0.79	74	74
CYCS	-0.082	0.14	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
CD247	-0.38	0.48	-9999	-1.1	159	159
MAP2K7	-0.044	0.11	-9999	-10000	0	0
protein ubiquitination	0.06	0.072	-9999	-0.45	1	1
CRADD	0.016	0	-9999	-10000	0	0
DAXX	0.016	0	-9999	-10000	0	0
FAS	0.016	0	-9999	-10000	0	0
BID	-0.097	0.15	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha	-0.05	0.12	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
FADD	0.016	0	-9999	-10000	0	0
NF-kappa-B/RelA/I kappa B alpha/ubiquitin	-0.05	0.12	-9999	-10000	0	0
MAPK8	-0.031	0.1	-9999	-10000	0	0
APAF1	0.016	0	-9999	-10000	0	0
TRAF1	0.014	0.04	-9999	-0.86	1	1
TRAF2	0.016	0	-9999	-10000	0	0
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8/FASLG	-0.14	0.13	-9999	-10000	0	0
TNFR1A/Caspase 2/TNF-alpha/FADD/TRADD/RIP1/cIAP2/TRAF1/TRAF2/Ask1/RAIDD	0.012	0.059	-9999	-10000	0	0
CHUK	0.061	0.076	-9999	-0.49	1	1
FAS/FADD/DAXX/Ask1/Caspase 8/Caspase 8	0	0	-9999	-10000	0	0
TCRz/NEF	-0.41	0.45	-9999	-0.75	264	264
TNF	0.002	0.11	-9999	-0.81	8	8
FASLG	-0.59	0.61	-9999	-1.1	264	264
NFKB1	0.001	0.045	-9999	-10000	0	0
TNFR1A/BAG4/TNF-alpha	-0.009	0.068	-9999	-0.53	8	8
CASP6	-0.05	0.052	-9999	-10000	0	0
CASP7	-0.063	0.21	-9999	-0.55	47	47
RELA	0.001	0.045	-9999	-10000	0	0
CASP2	0.016	0	-9999	-10000	0	0
CASP3	-0.063	0.21	-9999	-0.55	51	51
TNFRSF1A	0.016	0	-9999	-10000	0	0
TNFR1A/BAG4	0	0	-9999	-10000	0	0
CASP8	0.016	0	-9999	-10000	0	0
CASP9	0.016	0	-9999	-10000	0	0
MAP3K14	0.053	0.082	-9999	-0.53	3	3
APAF-1/Caspase 9	-0.13	0.18	-9999	-0.56	51	51
BCL2	-0.019	0.097	-9999	-10000	0	0

×

Angiopoietin receptor Tie2-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
AKT1	-0.081	0.31	-10000	0	-0.91	26	26
NCK1/PAK1/Dok-R	-0.081	0.1	-10000	0	-0.42	24	24
NCK1/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
PIK3CA	0.002	0.005	-10000	0	-10000	0	0
mol:beta2-estradiol	-0.007	0.034	0.32	3	-10000	0	3
RELA	0.016	0	-10000	0	-10000	0	0
SHC1	0.006	0.041	-10000	0	-0.87	1	1
Rac/GDP	0	0	-10000	0	-10000	0	0
F2	-0.32	0.42	-10000	0	-0.86	182	182
TNIP2	0.016	0	-10000	0	-10000	0	0
NF kappa B/RelA	-0.053	0.22	-10000	0	-0.97	26	26
FN1	-0.052	0.24	-10000	0	-0.86	37	37
PLD2	0.038	0.29	-10000	0	-1.1	26	26
PTPN11	0.016	0	-10000	0	-10000	0	0
GRB14	-0.029	0.18	-10000	0	-0.76	28	28
ELK1	0.066	0.26	-10000	0	-0.98	26	26
GRB7	0.004	0.093	-10000	0	-0.76	7	7
PAK1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/alpha5/beta1 Integrin	-0.11	0.29	-10000	0	-1	38	38
CDKN1A	-0.11	0.31	-10000	0	-0.69	17	17
ITGA5	-0.052	0.24	-10000	0	-0.86	37	37
mol:GTP	0	0	-10000	0	-10000	0	0
RasGAP/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
CRK	0.016	0	-10000	0	-10000	0	0
mol:NO	-0.046	0.26	-10000	0	-0.66	26	26
PLG	-0.19	0.35	-10000	0	-1.3	26	26
mol:GDP	0	0	-10000	0	-10000	0	0
chemokinesis	-0.12	0.2	-10000	0	-0.85	26	26
GRB2	0.016	0	-10000	0	-10000	0	0
PIK3R1	0.008	0.009	-10000	0	-10000	0	0
ANGPT2	-0.21	0.38	-10000	0	-0.65	154	154
BMX	-0.04	0.34	-10000	0	-1.1	26	26
ANGPT1	0.079	0.19	-10000	0	-1.3	6	6
tube development	-0.13	0.34	-10000	0	-0.74	22	22
ANGPT4	-0.021	0.16	-10000	0	-0.87	16	16
response to hypoxia	-0.002	0.016	-10000	0	-10000	0	0
Tie2/Ang1/GRB14	-0.049	0.31	-10000	0	-1.2	26	26
alpha5/beta1 Integrin	-0.051	0.18	-10000	0	-0.67	37	37
FGF2	0.011	0.075	-10000	0	-0.78	4	4
STAT5A (dimer)	-0.15	0.36	-10000	0	-0.85	23	23
mol:L-citrulline	-0.046	0.26	-10000	0	-0.66	26	26
AGTR1	-0.037	0.17	-10000	0	-0.76	26	26
MAPK14	0.002	0.3	-10000	0	-1.2	26	26
Tie2/SHP2	-0.058	0.25	-10000	0	-1.1	25	25
TEK	-0.049	0.28	-10000	0	-1.2	25	25
RPS6KB1	-0.043	0.28	-10000	0	-0.87	26	26
Angiotensin II/AT1	-0.044	0.13	-10000	0	-0.59	26	26
Tie2/Ang1/GRB2	-0.027	0.29	-10000	0	-1.1	26	26
MAPK3	0.05	0.27	-10000	0	-1	26	26
MAPK1	0.05	0.27	-10000	0	-1	26	26
Tie2/Ang1/GRB7	-0.032	0.3	-10000	0	-1.2	26	26
NFKB1	0.016	0	-10000	0	-10000	0	0
MAPK8	0.038	0.29	-10000	0	-1.1	26	26
PI3K	-0.066	0.32	-10000	0	-1.1	26	26
FES	-0.004	0.31	-10000	0	-1.1	27	27
Crk/Dok-R	-0.079	0.26	-10000	0	-1.1	26	26
Tie2/Ang1/ABIN2	-0.027	0.29	-10000	0	-1.1	26	26
blood circulation	0	0	-10000	0	-10000	0	0
negative regulation of caspase activity	-0.07	0.29	-10000	0	-0.8	26	26
STAT5A	0.016	0.001	-10000	0	-10000	0	0
mol:ROS	0	0	-10000	0	-10000	0	0
PTK2	-0.043	0.28	-10000	0	-0.87	26	26
Tie2/Ang2	-0.19	0.4	-10000	0	-1.1	22	22
Tie2/Ang1	0.03	0.32	-10000	0	-1.2	26	26
FOXO1	-0.1	0.31	-10000	0	-0.81	26	26
ELF1	0.025	0.013	-10000	0	-10000	0	0
ELF2	0.034	0.3	-10000	0	-1.1	26	26
mol:Choline	0.041	0.28	-10000	0	-1	26	26
cell migration	-0.055	0.071	-10000	0	-10000	0	0
FYN	-0.15	0.36	-10000	0	-0.86	22	22
DOK2	-0.035	0.21	-10000	0	-0.86	28	28
negative regulation of cell cycle	-0.094	0.3	-10000	0	-0.62	17	17
ETS1	0.029	0.033	-10000	0	-10000	0	0
PXN	-0.022	0.25	-10000	0	-0.7	26	26
ITGB1	0.016	0	-10000	0	-10000	0	0
NOS3	-0.057	0.28	-10000	0	-0.75	26	26
RAC1	0.016	0	-10000	0	-10000	0	0
TNF	0.009	0.11	-10000	0	-0.8	8	8
MAPKKK cascade	0.041	0.28	-10000	0	-1	26	26
RASA1	0.016	0	-10000	0	-10000	0	0
Tie2/Ang1/Shc	0.001	0.3	-10000	0	-1.1	26	26
NCK1	0.016	0	-10000	0	-10000	0	0
vasculogenesis	-0.038	0.24	-10000	0	-0.58	26	26
mol:Phosphatidic acid	0.041	0.28	-10000	0	-1	26	26
mol:Angiotensin II	-0.017	0.022	-10000	0	-10000	0	0
mol:NADP	-0.046	0.26	-10000	0	-0.66	26	26
Rac1/GTP	-0.13	0.19	-10000	0	-0.8	26	26
MMP2	0.033	0.3	-10000	0	-1.1	26	26

×

EPO 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	-0.022	0.18	-9999	-10000	0	0
CRKL	-0.097	0.22	-9999	-10000	0	0
mol:DAG	-0.13	0.17	-9999	-10000	0	0
HRAS	-0.11	0.15	-9999	-10000	0	0
MAPK8	-0.14	0.26	-9999	-0.48	172	172
RAP1A	-0.097	0.22	-9999	-10000	0	0
GAB1	-0.097	0.22	-9999	-10000	0	0
MAPK14	-0.14	0.26	-9999	-10000	0	0
EPO	-0.29	0.42	-9999	-0.85	172	172
PLCG1	-0.13	0.17	-9999	-10000	0	0
EPOR/TRPC2/IP3 Receptors	0.007	0.019	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/SOCS3	-0.2	0.27	-9999	-0.55	172	172
GAB1/SHC/GRB2/SOS1	-0.12	0.16	-9999	-10000	0	0
EPO/EPOR (dimer)	-0.23	0.32	-9999	-0.65	172	172
IRS2	-0.11	0.23	-9999	-0.88	2	2
STAT1	-0.068	0.21	-9999	-10000	0	0
STAT5B	-0.073	0.21	-9999	-10000	0	0
cell proliferation	-0.12	0.24	-9999	-10000	0	0
GAB1/SHIP/PIK3R1/SHP2/SHC	-0.12	0.15	-9999	-0.71	1	1
TEC	-0.097	0.22	-9999	-10000	0	0
SOCS3	0.012	0.057	-9999	-0.86	2	2
STAT1 (dimer)	-0.066	0.21	-9999	-10000	0	0
JAK2	0.006	0.018	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2	-0.1	0.24	-9999	-10000	0	0
EPO/EPOR	-0.23	0.32	-9999	-0.65	172	172
LYN	0.018	0.001	-9999	-10000	0	0
TEC/VAV2	-0.084	0.22	-9999	-10000	0	0
elevation of cytosolic calcium ion concentration	0.007	0.019	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
EPO/EPOR (dimer)/LYN	-0.16	0.28	-9999	-0.54	172	172
mol:IP3	-0.13	0.17	-9999	-10000	0	0
PI3K regualtory subunit polypeptide 1/IRS2/SHIP	-0.14	0.18	-9999	-0.79	3	3
SH2B3	0.006	0.018	-9999	-10000	0	0
NFKB1	-0.14	0.26	-9999	-10000	0	0
EPO/EPOR (dimer)/JAK2/SOCS3	-0.11	0.15	-9999	-0.53	2	2
PTPN6	-0.11	0.23	-9999	-10000	0	0
TEC/VAV2/GRB2	-0.13	0.17	-9999	-10000	0	0
EPOR	0.007	0.019	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
mol:GDP	-0.12	0.16	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
PLCG2	0.002	0.11	-9999	-0.82	8	8
CRKL/CBL/C3G	-0.13	0.17	-9999	-10000	0	0
VAV2	-0.097	0.22	-9999	-10000	0	0
CBL	-0.097	0.22	-9999	-10000	0	0
SHC/Grb2/SOS1	-0.13	0.17	-9999	-10000	0	0
STAT5A	-0.073	0.21	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
STAT5 (dimer)	-0.048	0.21	-9999	-10000	0	0
LYN/PLCgamma2	-0.01	0.081	-9999	-0.63	8	8
PTPN11	0.016	0	-9999	-10000	0	0
BTK	-0.2	0.29	-9999	-0.88	27	27
BCL2	-0.022	0.18	-9999	-10000	0	0

×

Neurotrophic factor-mediated Trk receptor signaling

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
CRKL	0.016	0	-10000	0	-10000	0	0
RAS family/GTP/Tiam1	-0.014	0.057	-10000	0	-0.62	1	1
NT3 (dimer)/TRKC	-0.039	0.15	-10000	0	-0.61	31	31
NT3 (dimer)/TRKB	-0.14	0.25	-10000	0	-0.55	125	125
SHC/Grb2/SOS1/GAB1/PI3K	-0.001	0.012	-10000	0	-10000	0	0
RAPGEF1	0.016	0	-10000	0	-10000	0	0
BDNF	-0.11	0.31	-10000	0	-0.86	68	68
PIK3CA	0.016	0	-10000	0	-10000	0	0
DYNLT1	0.016	0	-10000	0	-10000	0	0
NTRK1	-0.047	0.21	-10000	0	-0.76	38	38
NTRK2	-0.13	0.3	-10000	0	-0.76	91	91
NTRK3	-0.028	0.18	-10000	0	-0.76	27	27
NT-4/5 (dimer)/TRKB	-0.14	0.26	-10000	0	-0.56	123	123
neuron apoptosis	0.15	0.19	0.58	46	-10000	0	46
SHC 2-3/Grb2	-0.16	0.21	-10000	0	-0.65	46	46
SHC1	0.014	0.04	-10000	0	-0.86	1	1
SHC2	-0.1	0.15	-10000	0	-0.5	34	34
SHC3	-0.17	0.25	-10000	0	-0.64	86	86
STAT3 (dimer)	0.011	0.07	-10000	0	-10000	0	0
NT3 (dimer)/TRKA	-0.09	0.21	-10000	0	-0.56	78	78
RIN/GDP	0.048	0.063	-10000	0	-0.32	1	1
GIPC1	0.014	0.035	-10000	0	-0.76	1	1
KRAS	0.016	0	-10000	0	-10000	0	0
DNAJA3	-0.075	0.15	-10000	0	-0.63	15	15
RIN/GTP	-0.001	0.031	-10000	0	-0.68	1	1
CCND1	0.007	0.16	-10000	0	-0.78	20	20
MAGED1	0.014	0.04	-10000	0	-0.86	1	1
PTPN11	0.016	0	-10000	0	-10000	0	0
RICS	0	0	-10000	0	-10000	0	0
NT-4/5 (dimer)	-0.004	0.089	-10000	0	-0.86	5	5
SHC/GRB2/SOS1	-0.001	0.026	-10000	0	-0.58	1	1
GRB2	0.016	0	-10000	0	-10000	0	0
NGF (dimer)/TRKA/MATK	-0.16	0.28	-10000	0	-0.6	124	124
TRKA/NEDD4-2	-0.046	0.16	-10000	0	-0.58	38	38
ELMO1	0.012	0.057	-10000	0	-0.86	2	2
RhoG/GTP/ELMO1/DOCK1	-0.002	0.038	-10000	0	-0.59	2	2
NGF	-0.072	0.26	-10000	0	-0.86	48	48
HRAS	0.016	0	-10000	0	-10000	0	0
DOCK1	0.016	0	-10000	0	-10000	0	0
GAB2	0.016	0	-10000	0	-10000	0	0
RIT2	0.002	0.04	-10000	0	-0.86	1	1
RIT1	0.016	0	-10000	0	-10000	0	0
FRS2	0.016	0	-10000	0	-10000	0	0
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
CRK	0.016	0	-10000	0	-10000	0	0
SH2B1 (homopentamer)	0	0	-10000	0	-10000	0	0
RhoG/GTP	-0.075	0.15	-10000	0	-0.6	17	17
mol:GDP	0.062	0.085	-10000	0	-0.52	1	1
NGF (dimer)	-0.072	0.26	-10000	0	-0.86	48	48
RhoG/GDP	-0.003	0.044	-10000	0	-0.68	2	2
RIT1/GDP	0.055	0.062	-10000	0	-0.32	1	1
TIAM1	0.014	0.035	-10000	0	-0.76	1	1
PIK3R1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB	-0.17	0.27	-10000	0	-0.56	147	147
KIDINS220/CRKL/C3G	0	0	-10000	0	-10000	0	0
SHC/RasGAP	-0.001	0.03	-10000	0	-0.67	1	1
FRS2 family/SHP2	0	0	-10000	0	-10000	0	0
SHC/GRB2/SOS1/GAB1	-0.001	0.024	-10000	0	-0.52	1	1
RIT1/GTP	0	0	-10000	0	-10000	0	0
NT3 (dimer)	0.006	0.09	-10000	0	-0.79	6	6
RAP1/GDP	-0.008	0.03	-10000	0	-10000	0	0
KIDINS220/CRKL	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)	-0.11	0.3	-10000	0	-0.86	68	68
ubiquitin-dependent protein catabolic process	-0.096	0.21	-10000	0	-0.55	84	84
Schwann cell development	-0.027	0.033	-10000	0	-10000	0	0
EHD4	0.016	0	-10000	0	-10000	0	0
FRS2 family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/CRK family/C3G/GAB2	0	0	-10000	0	-10000	0	0
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.15	0.24	-10000	0	-0.83	28	28
ABL1	0.016	0	-10000	0	-10000	0	0
SH2B family/GRB2/SOS1	0	0	-10000	0	-10000	0	0
Rap1/GTP	-0.052	0.08	-10000	0	-10000	0	0
STAT3	0.011	0.07	-10000	0	-10000	0	0
axon guidance	-0.14	0.22	-10000	0	-0.77	28	28
MAPK3	-0.11	0.27	-10000	0	-0.59	90	90
MAPK1	-0.11	0.27	-10000	0	-0.59	90	90
CDC42/GDP	0.055	0.062	-10000	0	-0.32	1	1
NTF3	0.006	0.09	-10000	0	-0.79	6	6
NTF4	-0.004	0.089	-10000	0	-0.86	5	5
NGF (dimer)/TRKA/FAIM	-0.096	0.21	-10000	0	-0.55	84	84
PI3K	0	0	-10000	0	-10000	0	0
FRS3	0.016	0	-10000	0	-10000	0	0
FAIM	0.016	0	-10000	0	-10000	0	0
GAB1	0.016	0	-10000	0	-10000	0	0
RASGRF1	-0.086	0.17	-10000	0	-0.61	25	25
SOS1	0.016	0	-10000	0	-10000	0	0
MCF2L	0.001	0.14	-10000	0	-0.52	31	31
RGS19	0.016	0	-10000	0	-10000	0	0
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	0.048	0.068	-10000	0	-10000	0	0
Rac1/GDP	0.055	0.062	-10000	0	-0.32	1	1
NGF (dimer)/TRKA/GRIT	-0.098	0.22	-10000	0	-0.56	84	84
neuron projection morphogenesis	-0.027	0.15	-10000	0	-0.54	15	15
NGF (dimer)/TRKA/NEDD4-2	-0.097	0.21	-10000	0	-0.55	84	84
MAP2K1	0.053	0.024	-10000	0	-0.48	1	1
NGFR	-0.054	0.24	-10000	0	-0.86	38	38
NGF (dimer)/TRKA/GIPC/GAIP	-0.056	0.12	-10000	0	-0.6	2	2
RAS family/GTP/PI3K	0	0	-10000	0	-10000	0	0
FRS2 family/SHP2/GRB2/SOS1	0	0	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
GRB2/SOS1	0	0	-10000	0	-10000	0	0
PRKCI	0.016	0	-10000	0	-10000	0	0
ChemicalAbstracts:146-91-8	0	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
MAPKKK cascade	-0.1	0.19	-10000	0	-0.57	53	53
RASA1	0.016	0	-10000	0	-10000	0	0
TRKA/c-Abl	-0.045	0.16	-10000	0	-0.57	38	38
SQSTM1	0.016	0	-10000	0	-10000	0	0
BDNF (dimer)/TRKB/GIPC	-0.16	0.25	-10000	0	-0.6	67	67
NGF (dimer)/TRKA/p62/Atypical PKCs	-0.083	0.18	-10000	0	-0.88	3	3
MATK	-0.078	0.27	-10000	0	-0.86	51	51
NEDD4L	0.014	0.035	-10000	0	-0.76	1	1
RAS family/GDP	-0.007	0.029	-10000	0	-10000	0	0
NGF (dimer)/TRKA	-0.081	0.16	-10000	0	-0.48	40	40
Rac1/GTP	-0.047	0.086	-10000	0	-0.42	5	5
FRS2 family/SHP2/CRK family	0	0	-10000	0	-10000	0	0

×

Syndecan-2-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Syndecan-2/Fibronectin	-0.045	0.15	-9999	-0.58	37	37
EPHB2	0.001	0.11	-9999	-0.78	9	9
Syndecan-2/TACI	-0.052	0.16	-9999	-0.58	43	43
LAMA1	-0.007	0.13	-9999	-0.77	14	14
Syndecan-2/alpha2 ITGB1	-0.007	0.056	-9999	-0.49	5	5
HRAS	0.016	0	-9999	-10000	0	0
Syndecan-2/CASK	0	0	-9999	-10000	0	0
ITGA5	-0.052	0.24	-9999	-0.86	37	37
BAX	0.056	0	-9999	-10000	0	0
EPB41	0.016	0	-9999	-10000	0	0
positive regulation of cell-cell adhesion	0	0	-9999	-10000	0	0
LAMA3	0.007	0.089	-9999	-0.86	5	5
EZR	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
CAV2	0.003	0.11	-9999	-0.86	7	7
Syndecan-2/MMP2	-0.006	0.059	-9999	-0.58	5	5
RP11-540L11.1	0	0	-9999	-10000	0	0
alpha2 ITGB1	-0.002	0.037	-9999	-0.57	2	2
dendrite morphogenesis	-0.009	0.069	-9999	-0.51	9	9
Syndecan-2/GM-CSF	-0.017	0.097	-9999	-0.58	14	14
determination of left/right symmetry	0.027	0	-9999	-10000	0	0
Syndecan-2/PKC delta	-0.001	0.026	-9999	-0.58	1	1
GNB2L1	0.014	0.04	-9999	-0.86	1	1
MAPK3	0.022	0.095	-9999	-0.52	14	14
MAPK1	0.022	0.095	-9999	-0.52	14	14
Syndecan-2/RACK1	-0.001	0.023	-9999	-0.5	1	1
NF1	0.016	0	-9999	-10000	0	0
FGFR/FGF/Syndecan-2	0.027	0	-9999	-10000	0	0
ITGA2	0.012	0.05	-9999	-0.76	2	2
MAPK8	0.048	0	-9999	-10000	0	0
Syndecan-2/alpha2/beta1 Integrin	-0.014	0.079	-9999	-0.83	1	1
Syndecan-2/Kininogen	-0.37	0.21	-9999	-0.49	363	363
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.049	0.024	-9999	-0.47	1	1
Syndecan-2/CASK/Protein 4.1	0	0	-9999	-10000	0	0
extracellular matrix organization	-0.006	0.058	-9999	-0.58	5	5
actin cytoskeleton reorganization	-0.044	0.15	-9999	-0.58	37	37
Syndecan-2/Caveolin-2/Ras	-0.008	0.063	-9999	-0.53	7	7
Syndecan-2/Laminin alpha3	-0.006	0.059	-9999	-0.58	5	5
Syndecan-2/RasGAP	-0.001	0.021	-9999	-0.47	1	1
alpha5/beta1 Integrin	-0.051	0.18	-9999	-0.67	37	37
PRKCD	0.014	0.04	-9999	-0.86	1	1
Syndecan-2 dimer	-0.01	0.069	-9999	-0.51	9	9
GO:0007205	0.005	0	-9999	-10000	0	0
DNA mediated transformation	0	0	-9999	-10000	0	0
Syndecan-2/RasGAP/Src	-0.001	0.02	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
SDCBP	0.016	0	-9999	-10000	0	0
TNFRSF13B	-0.065	0.25	-9999	-0.86	43	43
RASA1	0.016	0	-9999	-10000	0	0
alpha2/beta1 Integrin	-0.002	0.037	-9999	-0.57	2	2
Syndecan-2/Synbindin	0	0	-9999	-10000	0	0
TGFB1	0.007	0.089	-9999	-0.86	5	5
CASP3	0.043	0.026	-9999	-0.52	1	1
FN1	-0.052	0.24	-9999	-0.86	37	37
Syndecan-2/IL8	-0.036	0.14	-9999	-0.56	31	31
SDC2	0.027	0	-9999	-10000	0	0
KNG1	-0.57	0.33	-9999	-0.76	363	363
Syndecan-2/Neurofibromin	0	0	-9999	-10000	0	0
TRAPPC4	0.016	0	-9999	-10000	0	0
CSF2	-0.018	0.15	-9999	-0.86	14	14
Syndecan-2/TGFB1	-0.006	0.059	-9999	-0.58	5	5
Syndecan-2/Syntenin/PI-4-5-P2	0	0	-9999	-10000	0	0
Syndecan-2/Ezrin	0	0	-9999	-10000	0	0
PRKACA	0.045	0	-9999	-10000	0	0
angiogenesis	-0.036	0.14	-9999	-0.56	31	31
MMP2	0.007	0.089	-9999	-0.86	5	5
IL8	-0.04	0.21	-9999	-0.85	31	31
calcineurin-NFAT signaling pathway	-0.052	0.16	-9999	-0.58	43	43

×

Regulation of nuclear SMAD2/3 signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.015	0.01	-10000	0	-10000	0	0
HSPA8	0.016	0.005	-10000	0	-10000	0	0
SMAD3/SMAD4/ER alpha	0.025	0.083	-10000	0	-0.51	2	2
AKT1	0.02	0.006	-10000	0	-10000	0	0
GSC	-0.024	0.22	-10000	0	-0.76	39	39
NKX2-5	-0.048	0.22	-10000	0	-0.86	32	32
muscle cell differentiation	0.033	0.11	0.58	9	-10000	0	9
SMAD2-3/SMAD4/SP1	0.035	0.079	-10000	0	-10000	0	0
SMAD4	0.032	0.03	-10000	0	-10000	0	0
CBFB	0.016	0	-10000	0	-10000	0	0
SAP18	0.015	0.005	-10000	0	-10000	0	0
Cbp/p300/MSG1	0.005	0.034	-10000	0	-0.56	1	1
SMAD3/SMAD4/VDR	0.012	0.05	-10000	0	-10000	0	0
MYC	-0.028	0.16	-10000	0	-0.86	16	16
CDKN2B	0.056	0.086	-10000	0	-0.67	5	5
AP1	0.061	0.071	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/SnoN/SIN3/HDAC complex/NCoR1	0.011	0.046	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/FOXG1	0.039	0.069	-10000	0	-0.45	4	4
SP3	0.02	0	-10000	0	-10000	0	0
CREB1	0.016	0	-10000	0	-10000	0	0
FOXH1	-0.051	0.24	-10000	0	-0.88	36	36
SMAD3/SMAD4/GR	0.009	0.045	-10000	0	-0.6	1	1
GATA3	-0.35	0.38	-10000	0	-0.75	230	230
SKI/SIN3/HDAC complex/NCoR1	0.056	0.042	-10000	0	-10000	0	0
MEF2C/TIF2	-0.068	0.18	-10000	0	-0.86	13	13
endothelial cell migration	0.091	0.26	0.74	65	-10000	0	65
MAX	0.008	0.02	-10000	0	-10000	0	0
RBBP7	0.015	0.005	-10000	0	-10000	0	0
RBBP4	0.015	0.005	-10000	0	-10000	0	0
RUNX2	-0.008	0.14	-10000	0	-0.86	13	13
RUNX3	-0.37	0.44	-10000	0	-0.86	210	210
RUNX1	-0.048	0.23	-10000	0	-0.86	35	35
CTBP1	0.016	0	-10000	0	-10000	0	0
NR3C1	0.006	0.045	-10000	0	-0.87	1	1
VDR	0.011	0.061	-10000	0	-0.76	3	3
CDKN1A	0.083	0.077	-10000	0	-0.64	2	2
KAT2B	0.014	0.006	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1	-0.048	0.17	-10000	0	-0.61	36	36
DCP1A	0.016	0	-10000	0	-10000	0	0
SKI	0.015	0.005	-10000	0	-10000	0	0
SERPINE1	-0.093	0.26	-10000	0	-0.74	65	65
SMAD3/SMAD4/ATF2	0.009	0.031	-10000	0	-10000	0	0
SMAD3/SMAD4/ATF3	0.003	0.06	-10000	0	-0.5	5	5
SAP30	-0.014	0.16	-10000	0	-0.86	16	16
Cbp/p300/PIAS3	0.008	0.029	-10000	0	-10000	0	0
JUN	0.077	0.067	-10000	0	-10000	0	0
SMAD3/SMAD4/IRF7	-0.01	0.11	-10000	0	-0.56	15	15
TFE3	0.022	0.011	-10000	0	-10000	0	0
COL1A2	-0.098	0.26	-10000	0	-0.75	64	64
mesenchymal cell differentiation	0.007	0.1	0.59	13	-10000	0	13
DLX1	-0.46	0.44	-10000	0	-0.86	260	260
TCF3	0.016	0	-10000	0	-10000	0	0
FOS	0.009	0.11	-10000	0	-0.74	10	10
SMAD3/SMAD4/Max	0.01	0.035	-10000	0	-10000	0	0
Cbp/p300/SNIP1	0	0	-10000	0	-10000	0	0
ZBTB17	-0.002	0.047	-10000	0	-0.73	2	2
LAMC1	0.072	0.042	-10000	0	-10000	0	0
TGIF2/HDAC complex/SMAD3/SMAD4	0.009	0.031	-10000	0	-10000	0	0
IRF7	-0.011	0.16	-10000	0	-0.85	16	16
ESR1	0.005	0.054	-10000	0	-0.76	2	2
HNF4A	-0.05	0.22	-10000	0	-0.76	41	41
MEF2C	-0.002	0.22	-10000	0	-0.82	17	17
SMAD2-3/SMAD4	0.006	0.032	-10000	0	-10000	0	0
Cbp/p300/Src-1	0.006	0.021	-10000	0	-10000	0	0
IGHV3OR16-13	-0.051	0.054	-10000	0	-10000	0	0
TGIF2/HDAC complex	0.016	0	-10000	0	-10000	0	0
CREBBP	0.015	0.008	-10000	0	-10000	0	0
SKIL	0.016	0	-10000	0	-10000	0	0
HDAC1	0.015	0.005	-10000	0	-10000	0	0
HDAC2	0.015	0.005	-10000	0	-10000	0	0
SNIP1	0.015	0.005	-10000	0	-10000	0	0
GCN5L2	-0.002	0.011	-10000	0	-10000	0	0
SMAD3/SMAD4/TFE3	0.011	0.037	-10000	0	-10000	0	0
MSG1/HSC70	0.003	0.033	-10000	0	-0.67	1	1
SMAD2	0.022	0.019	-10000	0	-10000	0	0
SMAD3	0.033	0.027	-10000	0	-10000	0	0
SMAD3/E2F4-5/DP1/p107/SMAD4	0.064	0.03	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4	0.025	0.02	-10000	0	-10000	0	0
NCOR1	0.015	0.005	-10000	0	-10000	0	0
NCOA2	0.009	0.07	-10000	0	-0.76	4	4
NCOA1	0.016	0	-10000	0	-10000	0	0
MYOD/E2A	-0.038	0.15	-10000	0	-0.67	27	27
SMAD2-3/SMAD4/SP1/MIZ-1	0.077	0.086	-10000	0	-10000	0	0
IFNB1	0.047	0.1	-10000	0	-10000	0	0
SMAD3/SMAD4/MEF2C	-0.02	0.2	-10000	0	-0.9	10	10
CITED1	0.012	0.04	-10000	0	-0.86	1	1
SMAD2-3/SMAD4/ARC105	0.008	0.031	-10000	0	-10000	0	0
RBL1	0.016	0	-10000	0	-10000	0	0
SMAD2-3/SMAD4/FOXO1-3a-4/CEBPB	0.078	0.064	-10000	0	-0.58	1	1
RUNX1-3/PEBPB2	-0.29	0.32	-10000	0	-0.61	231	231
SMAD7	0.052	0.08	-10000	0	-10000	0	0
MYC/MIZ-1	-0.024	0.12	-10000	0	-0.65	18	18
SMAD3/SMAD4	-0.018	0.12	-10000	0	-10000	0	0
IL10	-0.2	0.32	-10000	0	-1	31	31
PIASy/HDAC complex	0.018	0.01	-10000	0	-10000	0	0
PIAS3	0.014	0.006	-10000	0	-10000	0	0
CDK2	0.015	0.008	-10000	0	-10000	0	0
IL5	-0.17	0.26	-10000	0	-0.76	15	15
CDK4	0.015	0.009	-10000	0	-10000	0	0
PIAS4	0.018	0.01	-10000	0	-10000	0	0
ATF3	0.008	0.079	-10000	0	-0.76	5	5
SMAD3/SMAD4/SP1	-0.012	0.054	-10000	0	-10000	0	0
FOXG1	-0.026	0.17	-10000	0	-0.87	19	19
FOXO3	0.037	0.008	-10000	0	-10000	0	0
FOXO1	0.037	0.008	-10000	0	-10000	0	0
FOXO4	0.037	0.008	-10000	0	-10000	0	0
heart looping	-0.001	0.22	-10000	0	-0.8	17	17
CEBPB	-0.004	0.14	-10000	0	-0.87	12	12
SMAD3/SMAD4/DLX1	-0.32	0.29	-10000	0	-0.58	260	260
MYOD1	-0.043	0.2	-10000	0	-0.86	27	27
SMAD3/SMAD4/HNF4	-0.034	0.14	-10000	0	-0.5	38	38
SMAD3/SMAD4/GATA3	-0.24	0.26	-10000	0	-0.77	20	20
SnoN/SIN3/HDAC complex/NCoR1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX1-3/PEBPB2	-0.24	0.28	-10000	0	-0.87	21	21
SMAD3/SMAD4/SP1-3	-0.006	0.044	-10000	0	-10000	0	0
MED15	0.016	0	-10000	0	-10000	0	0
SP1	0.012	0.051	-10000	0	-10000	0	0
SIN3B	0.015	0.005	-10000	0	-10000	0	0
SIN3A	0.015	0.005	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/NKX2-5	-0.073	0.22	-10000	0	-0.83	22	22
ITGB5	0.085	0.066	-10000	0	-10000	0	0
TGIF/SIN3/HDAC complex/CtBP	0.054	0.041	-10000	0	-10000	0	0
SMAD3/SMAD4/AR	-0.014	0.11	-10000	0	-0.52	13	13
AR	-0.02	0.16	-10000	0	-0.76	22	22
negative regulation of cell growth	0.063	0.069	-10000	0	-10000	0	0
SMAD3/SMAD4/MYOD	-0.025	0.14	-10000	0	-0.6	27	27
E2F5	0.016	0	-10000	0	-10000	0	0
E2F4	0.016	0	-10000	0	-10000	0	0
SMAD2/SMAD2/SMAD4/FOXH1/SMIF	-0.036	0.14	-10000	0	-0.64	11	11
SMAD2-3/SMAD4/FOXO1-3a-4	0.074	0.044	-10000	0	-10000	0	0
TFDP1	0.016	0	-10000	0	-10000	0	0
SMAD3/SMAD4/AP1	0.01	0.066	-10000	0	-10000	0	0
SMAD3/SMAD4/RUNX2	-0.007	0.1	-10000	0	-0.59	13	13
TGIF2	0.016	0	-10000	0	-10000	0	0
TGIF1	0.016	0	-10000	0	-10000	0	0
ATF2	0.016	0	-10000	0	-10000	0	0

×

Paxillin-independent events mediated by a4b1 and a4b7

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.017	0.093	-9999	-0.52	16	16
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
alpha4/beta7 Integrin/MAdCAM1	-0.026	0.11	-9999	-0.52	24	24
EPO	-0.3	0.42	-9999	-0.86	172	172
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.67	16	16
EPO/EPOR (dimer)	-0.24	0.32	-9999	-0.67	172	172
lamellipodium assembly	0.003	0.013	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
JAK2	-0.13	0.17	-9999	-0.66	7	7
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
MADCAM1	-0.002	0.11	-9999	-0.86	8	8
cell adhesion	-0.026	0.11	-9999	-0.52	24	24
CRKL/CBL	0	0	-9999	-10000	0	0
ITGB1	0.016	0	-9999	-10000	0	0
SRC	0.01	0.14	-9999	-0.54	26	26
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/VCAM1	-0.036	0.14	-9999	-0.58	30	30
p130Cas/Crk/Dock1	-0.028	0.11	-9999	-0.84	2	2
VCAM1	-0.011	0.15	-9999	-0.84	15	15
RHOA	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.017	0.094	-9999	-0.52	16	16
BCAR1	0.022	0.14	-9999	-0.93	2	2
EPOR	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
Rac1/GTP	0.003	0.013	-9999	-10000	0	0

×

Endothelins

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
AKT1	0.002	0.22	-10000	0	-0.88	3	3
PTK2B	0.016	0.001	-10000	0	-10000	0	0
mol:Ca2+	0.086	0.12	-10000	0	-0.76	2	2
EDN1	-0.04	0.2	-10000	0	-0.78	18	18
EDN3	-0.02	0.16	-10000	0	-0.86	16	16
EDN2	-0.088	0.28	-10000	0	-0.82	59	59
HRAS/GDP	0.055	0.16	-10000	0	-0.73	6	6
ETA receptor/Endothelin-1/Gq/GTP/PLC beta	0.022	0.15	-10000	0	-0.49	13	13
ADCY4	0.005	0.17	-10000	0	-0.74	3	3
ADCY5	-0.012	0.2	-10000	0	-0.7	12	12
ADCY6	0.005	0.17	-10000	0	-0.74	3	3
ADCY7	-0.011	0.2	-10000	0	-0.73	7	7
ADCY1	-0.003	0.18	-10000	0	-0.74	4	4
ADCY2	-0.13	0.27	-10000	0	-0.71	28	28
ADCY3	0.005	0.17	-10000	0	-0.74	3	3
ADCY8	-0.16	0.28	-10000	0	-0.74	34	34
ADCY9	0.005	0.17	-10000	0	-0.74	3	3
arachidonic acid secretion	0.081	0.15	-10000	0	-0.54	8	8
ETB receptor/Endothelin-1/Gq/GTP	0.034	0.11	-10000	0	-0.48	11	11
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0.002	-10000	0	-10000	0	0
ETA receptor/Endothelin-1/G12/GTP	-0.019	0.22	0.38	65	-0.83	3	68
ETA receptor/Endothelin-1/Gs/GTP	-0.018	0.21	0.36	65	-0.79	3	68
mol:GTP	0.004	0.002	-10000	0	-10000	0	0
COL3A1	-0.051	0.35	-10000	0	-0.95	51	51
EDNRB	0.006	0.071	-10000	0	-0.79	3	3
response to oxidative stress	0	0	-10000	0	-10000	0	0
CYSLTR2	-0.049	0.31	-10000	0	-0.78	41	41
CYSLTR1	0.002	0.22	-10000	0	-0.84	4	4
SLC9A1	-0.016	0.12	-10000	0	-0.39	2	2
mol:GDP	0.048	0.18	-10000	0	-0.7	9	9
SLC9A3	-0.35	0.3	-10000	0	-0.66	144	144
RAF1	0.051	0.16	-10000	0	-0.7	8	8
JUN	0.089	0.12	-10000	0	-0.57	1	1
JAK2	0.002	0.22	-10000	0	-0.88	3	3
mol:IP3	0.019	0.17	-10000	0	-0.57	15	15
ETA receptor/Endothelin-1	-0.034	0.28	0.45	65	-0.66	18	83
PLCB1	0.005	0.093	-10000	0	-0.76	7	7
PLCB2	-0.078	0.27	-10000	0	-0.86	52	52
ETA receptor/Endothelin-3	-0.024	0.16	-10000	0	-0.68	18	18
FOS	0.065	0.2	-10000	0	-0.88	12	12
Gai/GDP	0.039	0.071	-10000	0	-0.63	1	1
CRK	0.016	0.001	-10000	0	-10000	0	0
mol:Ca ++	0.001	0.24	-10000	0	-0.8	13	13
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
PRKCB1	0.021	0.16	-10000	0	-0.54	15	15
GNAQ	0.02	0.003	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
GNAL	0.016	0	-10000	0	-10000	0	0
Gs family/GDP	-0.042	0.1	-10000	0	-0.61	9	9
ETA receptor/Endothelin-1/Gq/GTP	0.044	0.14	-10000	0	-0.5	9	9
MAPK14	0.026	0.13	-10000	0	-0.6	7	7
TRPC6	0.086	0.13	-10000	0	-0.81	2	2
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
ETB receptor/Endothelin-1/Gq/GTP/PLC beta	0.016	0.14	-10000	0	-0.53	12	12
ETB receptor/Endothelin-2	-0.085	0.21	-10000	0	-0.63	62	62
ETB receptor/Endothelin-3	-0.03	0.13	-10000	0	-0.66	19	19
ETB receptor/Endothelin-1	-0.037	0.17	-10000	0	-0.63	19	19
MAPK3	0.065	0.19	-10000	0	-0.72	14	14
MAPK1	0.065	0.19	-10000	0	-0.72	14	14
Rac1/GDP	0.055	0.16	-10000	0	-0.73	6	6
cAMP biosynthetic process	-0.063	0.19	-10000	0	-0.62	13	13
MAPK8	0.081	0.13	-10000	0	-0.59	2	2
SRC	0.016	0	-10000	0	-10000	0	0
ETB receptor/Endothelin-1/Gi/GTP	-0.005	0.085	-10000	0	-0.58	3	3
p130Cas/CRK/Src/PYK2	0.076	0.17	-10000	0	-0.72	6	6
mol:K +	0	0	-10000	0	-10000	0	0
G12/GDP	0.055	0.16	-10000	0	-0.73	6	6
COL1A2	-0.11	0.34	-10000	0	-0.89	65	65
EntrezGene:2778	0	0	-10000	0	-10000	0	0
ETA receptor/Endothelin-2	-0.08	0.23	-10000	0	-0.63	61	61
mol:DAG	0.019	0.17	-10000	0	-0.57	15	15
MAP2K2	0.061	0.17	-10000	0	-0.69	9	9
MAP2K1	0.062	0.17	-10000	0	-0.69	8	8
EDNRA	-0.011	0.14	-10000	0	-0.98	2	2
positive regulation of muscle contraction	0.014	0.19	-10000	0	-0.78	3	3
Gq family/GDP	-0.031	0.14	-10000	0	-0.7	13	13
HRAS/GTP	0.039	0.17	-10000	0	-0.7	9	9
PRKCH	0.031	0.16	-10000	0	-0.6	10	10
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.031	0.16	-10000	0	-0.68	7	7
PRKCB	0.025	0.18	-10000	0	-0.69	13	13
PRKCE	0.03	0.16	-10000	0	-0.6	10	10
PRKCD	0.03	0.16	-10000	0	-0.6	10	10
PRKCG	0.006	0.19	-10000	0	-0.71	16	16
regulation of vascular smooth muscle contraction	0.065	0.22	-10000	0	-1	12	12
PRKCQ	0.019	0.18	-10000	0	-0.64	13	13
PLA2G4A	0.081	0.16	-10000	0	-0.59	8	8
GNA14	0.009	0.093	-10000	0	-0.76	7	7
GNA15	-0.003	0.14	-10000	0	-0.86	12	12
GNA12	0.016	0	-10000	0	-10000	0	0
GNA11	0.016	0.05	-10000	0	-0.76	2	2
Rac1/GTP	-0.019	0.22	0.38	65	-0.83	3	68
MMP1	-0.14	0.37	-10000	0	-0.86	95	95

×

Wnt signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Noncanonical Wnts/FZD	-0.063	0.13	-9999	-0.61	7	7
FZD6	0.016	0	-9999	-10000	0	0
WNT6	-0.01	0.15	-9999	-0.86	14	14
WNT4	-0.073	0.25	-9999	-0.76	55	55
FZD3	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.061	-9999	-0.76	3	3
WNT11	-0.037	0.2	-9999	-0.77	32	32

×

S1P3 pathway

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
mol:S1P	0.002	0	-9999	-10000	0	0
S1P1/S1P/Gi	0.04	0.045	-9999	-10000	0	0
GNAO1	0.011	0.078	-9999	-0.84	4	4
S1P/S1P3/G12/G13	-0.001	0.02	-9999	-0.44	1	1
AKT1	-0.002	0.013	-9999	-10000	0	0
AKT3	-0.024	0.1	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
GNAI2	0.018	0	-9999	-10000	0	0
GNAI3	0.018	0	-9999	-10000	0	0
GNAI1	0.013	0.061	-9999	-0.76	3	3
mol:GDP	0	0	-9999	-10000	0	0
S1PR3	0.017	0.035	-9999	-0.76	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
mol:Ca2+	0.054	0.049	-9999	-0.54	1	1
MAPK3	0.062	0.047	-9999	-0.51	1	1
MAPK1	0.062	0.047	-9999	-0.51	1	1
JAK2	-0.025	0.13	-9999	-0.48	2	2
CXCR4	-0.13	0.26	-9999	-0.47	171	171
FLT1	0.012	0.08	-9999	-0.86	4	4
RhoA/GDP	0	0	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.062	0.047	-9999	-0.51	1	1
S1P/S1P3/Gi	0.054	0.05	-9999	-0.55	1	1
RAC1	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.005	0.036	-9999	-0.49	1	1
VEGFA	-0.38	0.44	-9999	-0.86	215	215
S1P/S1P2/Gi	0.049	0.043	-9999	-10000	0	0
VEGFR1 homodimer/VEGFA homodimer	-0.28	0.35	-9999	-0.67	216	216
RHOA	0.016	0	-9999	-10000	0	0
S1P/S1P3/Gq	0.009	0.072	-9999	-0.6	1	1
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.013	0.061	-9999	-0.76	3	3
G12/G13	0	0	-9999	-10000	0	0
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.012	0.05	-9999	-0.76	2	2
Rac1/GTP	-0.005	0.036	-9999	-0.49	1	1

×

Presenilin action in Notch and Wnt signaling

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
Delta 1/NOTCH/NOTCH(cleaved)	0	0	-10000	0	-10000	0	0
HDAC1	0.003	0.011	-10000	0	-10000	0	0
AES	0.003	0.007	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
DTX1	-0.054	0.22	-10000	0	-0.76	43	43
LRP6/FZD1	0	0	-10000	0	-10000	0	0
TLE1	0.015	0.002	-10000	0	-10000	0	0
AP1	-0.097	0.16	-10000	0	-0.35	134	134
NCSTN	0.016	0	-10000	0	-10000	0	0
ADAM10	0.016	0	-10000	0	-10000	0	0
Beta Catenin/TCF1/CtBP/CBP/TLE1/AES/SMAD4	0.012	0.067	-10000	0	-0.45	1	1
NICD/RBPSUH	0	0	-10000	0	-10000	0	0
WIF1	-0.003	0.094	-10000	0	-0.77	7	7
NOTCH1	0	0	-10000	0	-10000	0	0
PSENEN	0.016	0	-10000	0	-10000	0	0
KREMEN2	-0.081	0.27	-10000	0	-0.86	52	52
DKK1	-0.016	0.16	-10000	0	-0.84	18	18
beta catenin/beta TrCP1	0.084	0.085	-10000	0	-10000	0	0
APH1B	0.016	0	-10000	0	-10000	0	0
APH1A	0.016	0	-10000	0	-10000	0	0
AXIN1	-0.011	0.035	-10000	0	-10000	0	0
CtBP/CBP/TCF1/TLE1/AES	0.008	0.047	-10000	0	-10000	0	0
PSEN1	0.016	0	-10000	0	-10000	0	0
FOS	0	0.11	-10000	0	-0.76	10	10
JUN	0.016	0	-10000	0	-10000	0	0
MAP3K7	0.002	0.008	-10000	0	-10000	0	0
CTNNB1	0.08	0.092	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.091	0.21	-10000	0	-0.57	76	76
HNF1A	-0.003	0.069	-10000	0	-0.76	4	4
CTBP1	0.003	0.007	-10000	0	-10000	0	0
MYC	-0.016	0.14	-10000	0	-0.73	16	16
NKD1	-0.19	0.34	-10000	0	-0.76	127	127
FZD1	0.016	0	-10000	0	-10000	0	0
NOTCH1 precursor/Deltex homolog 1	-0.036	0.11	-10000	0	-10000	0	0
apoptosis	-0.096	0.16	-10000	0	-0.34	134	134
Delta 1/NOTCHprecursor	0	0	-10000	0	-10000	0	0
DLL1	0.016	0	-10000	0	-10000	0	0
PPARD	0.007	0.024	-10000	0	-10000	0	0
Gamma Secretase	0	0	-10000	0	-10000	0	0
APC	-0.011	0.035	-10000	0	-10000	0	0
DVL1	-0.006	0.034	-10000	0	-0.48	2	2
CSNK2A1	0.015	0.004	-10000	0	-10000	0	0
MAP3K7IP1	-0.002	0.004	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.083	0.22	-10000	0	-0.62	64	64
LRP6	0.016	0	-10000	0	-10000	0	0
CSNK1A1	0.015	0.004	-10000	0	-10000	0	0
NLK	0.004	0.014	-10000	0	-10000	0	0
CCND1	-0.021	0.15	-10000	0	-0.73	20	20
WNT1	-0.029	0.19	-10000	0	-0.86	24	24
Axin1/APC/beta catenin	0.081	0.051	-10000	0	-10000	0	0
DKK2	-0.029	0.19	-10000	0	-0.83	25	25
NOTCH1 precursor/DVL1	-0.003	0.024	-10000	0	-10000	0	0
GSK3B	0.012	0.007	-10000	0	-10000	0	0
FRAT1	0.002	0.006	-10000	0	-10000	0	0
NOTCH/Deltex homolog 1	-0.036	0.11	-10000	0	-10000	0	0
PPP2R5D	0.092	0.16	0.36	126	-10000	0	126
MAPK1	0.016	0	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	-0.033	0.12	-10000	0	-0.52	25	25
RBPJ	0.016	0	-10000	0	-10000	0	0
CREBBP	0.02	0.005	-10000	0	-10000	0	0

×

FoxO family signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G6PC	-0.57	0.68	-9999	-1.3	224	224
PLK1	-0.13	0.37	-9999	-0.79	89	89
CDKN1B	0.062	0.16	-9999	-10000	0	0
FOXO3	-0.042	0.23	-9999	-0.66	12	12
KAT2B	0.013	0.02	-9999	-10000	0	0
FOXO1/SIRT1	-0.14	0.21	-9999	-0.41	1	1
CAT	-0.028	0.21	-9999	-0.69	5	5
CTNNB1	0.016	0	-9999	-10000	0	0
AKT1	-0.008	0.038	-9999	-10000	0	0
FOXO1	-0.16	0.23	-9999	-0.41	224	224
MAPK10	0.032	0.052	-9999	-0.44	5	5
mol:GTP	0.003	0.001	-9999	-10000	0	0
FOXO4	0.11	0.045	-9999	-10000	0	0
response to oxidative stress	-0.029	0.045	-9999	-10000	0	0
FOXO3A/SIRT1	0.028	0.2	-9999	-0.56	11	11
XPO1	0.017	0	-9999	-10000	0	0
EP300	-0.004	0.027	-9999	-10000	0	0
BCL2L11	0.011	0.043	-9999	-10000	0	0
FOXO1/SKP2	-0.14	0.21	-9999	-0.4	3	3
mol:GDP	-0.029	0.045	-9999	-10000	0	0
RAN	0.018	0.001	-9999	-10000	0	0
GADD45A	0.12	0.097	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
FOXO1/14-3-3 family	0.034	0.084	-9999	-10000	0	0
MST1	0.002	0.1	-9999	-0.88	6	6
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
FOXO4/14-3-3 family	0.046	0.093	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
MAPK8	0.038	0.019	-9999	-10000	0	0
MAPK9	0.037	0.019	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
SIRT1	0.037	0.028	-9999	-10000	0	0
SOD2	0.013	0.21	-9999	-0.68	7	7
RBL2	0.022	0.16	-9999	-10000	0	0
RAL/GDP	0.008	0.023	-9999	-10000	0	0
CHUK	0.013	0.02	-9999	-10000	0	0
Ran/GTP	0.015	0.006	-9999	-10000	0	0
CSNK1G2	0.014	0.035	-9999	-0.76	1	1
RAL/GTP	0.024	0.026	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
FASLG	-0.36	0.39	-9999	-0.73	252	252
SKP2	0.016	0	-9999	-10000	0	0
USP7	0.018	0.001	-9999	-10000	0	0
IKBKB	0.013	0.02	-9999	-10000	0	0
CCNB1	-0.034	0.23	-9999	-0.94	9	9
FOXO1-3a-4/beta catenin	-0.071	0.1	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.14	0.21	-9999	-0.39	4	4
CSNK1A1	0.016	0	-9999	-10000	0	0
SGK1	0.013	0.02	-9999	-10000	0	0
CSNK1G3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0.019	0.016	-9999	-10000	0	0
ZFAND5	0.11	0.042	-9999	-10000	0	0
SFN	-0.079	0.27	-9999	-0.84	53	53
CDK2	-0.018	0.041	-9999	-10000	0	0
FOXO3A/14-3-3	0.013	0.097	-9999	-10000	0	0
CREBBP	-0.018	0.041	-9999	-10000	0	0
FBXO32	-0.03	0.22	-9999	-0.8	7	7
BCL6	0.022	0.16	-9999	-10000	0	0
RALB	0.018	0	-9999	-10000	0	0
RALA	0.018	0	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0

×

LPA receptor mediated 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GNB1/GNG2	-0.02	0.089	-9999	-0.43	20	20
NF kappa B1 p50/RelA/I kappa B alpha	-0.007	0.035	-9999	-10000	0	0
AP1	-0.029	0.098	-9999	-10000	0	0
mol:PIP3	-0.026	0.091	-9999	-10000	0	0
AKT1	-0.013	0.055	-9999	-10000	0	0
PTK2B	0.034	0.058	-9999	-10000	0	0
RHOA	0.036	0.037	-9999	-10000	0	0
PIK3CB	0.015	0	-9999	-10000	0	0
mol:Ca2+	0.051	0.054	-9999	-0.48	1	1
MAGI3	0.011	0.061	-9999	-0.76	3	3
RELA	0.016	0	-9999	-10000	0	0
apoptosis	-0.021	0.085	-9999	-0.38	24	24
HRAS/GDP	0	0	-9999	-10000	0	0
positive regulation of microtubule depolymerization	0.046	0.071	-9999	-0.42	1	1
NF kappa B1 p50/RelA	-0.018	0.072	-9999	-10000	0	0
endothelial cell migration	0.008	0.13	-9999	-0.54	25	25
ADCY4	0.033	0.12	-9999	-0.48	22	22
ADCY5	0.024	0.13	-9999	-0.5	23	23
ADCY6	0.033	0.12	-9999	-0.49	20	20
ADCY7	0.027	0.12	-9999	-0.48	22	22
ADCY1	0.029	0.12	-9999	-0.49	20	20
ADCY2	-0.015	0.14	-9999	-0.52	22	22
ADCY3	0.033	0.12	-9999	-0.48	22	22
ADCY8	-0.026	0.14	-9999	-0.49	22	22
ADCY9	0.033	0.12	-9999	-0.48	22	22
GSK3B	0.043	0.055	-9999	-10000	0	0
arachidonic acid secretion	0.04	0.11	-9999	-0.44	20	20
GNG2	0.015	0	-9999	-10000	0	0
TRIP6	0	0.003	-9999	-10000	0	0
GNAO1	0.009	0.12	-9999	-0.49	24	24
HRAS	0.016	0	-9999	-10000	0	0
NFKBIA	0.062	0.063	-9999	-10000	0	0
GAB1	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
lamellipodium assembly	0	0.04	-9999	-0.86	1	1
JUN	0.016	0	-9999	-10000	0	0
LPA/LPA2/NHERF2	-0.002	0.024	-9999	-0.49	1	1
TIAM1	-0.001	0.047	-9999	-1	1	1
PIK3R1	0.015	0	-9999	-10000	0	0
mol:IP3	0.052	0.055	-9999	-0.5	1	1
PLCB3	0.037	0.024	-9999	-0.44	1	1
FOS	0	0.11	-9999	-0.76	10	10
positive regulation of mitosis	0.04	0.11	-9999	-0.44	20	20
LPA/LPA1-2-3	-0.025	0.1	-9999	-0.45	24	24
mol:Ca ++	0	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
stress fiber formation	0.04	0.076	-9999	-10000	0	0
GNAZ	0.01	0.12	-9999	-0.49	23	23
EGFR/PI3K-beta/Gab1	-0.027	0.094	-9999	-10000	0	0
positive regulation of dendritic cell cytokine production	-0.025	0.1	-9999	-0.45	24	24
LPA/LPA2/MAGI-3	-0.004	0.04	-9999	-0.49	3	3
ARHGEF1	0.031	0.096	-9999	-0.49	1	1
GNAI2	0.014	0.11	-9999	-0.48	20	20
GNAI3	0.014	0.11	-9999	-0.48	20	20
GNAI1	0.01	0.12	-9999	-0.49	23	23
LPA/LPA3	-0.007	0.062	-9999	-0.67	4	4
LPA/LPA2	-0.001	0.012	-9999	-10000	0	0
LPA/LPA1	-0.027	0.12	-9999	-0.52	25	25
HB-EGF/EGFR	-0.28	0.29	-9999	-0.58	229	229
HBEGF	-0.29	0.35	-9999	-0.67	223	223
mol:DAG	0.052	0.055	-9999	-0.5	1	1
cAMP biosynthetic process	0.021	0.12	-9999	-0.46	21	21
NFKB1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
GNB1	0.015	0	-9999	-10000	0	0
LYN	0.062	0.063	-9999	-10000	0	0
GNAQ	-0.004	0.037	-9999	-0.4	4	4
LPAR2	0.016	0	-9999	-10000	0	0
LPAR3	0.002	0.08	-9999	-0.86	4	4
LPAR1	-0.012	0.15	-9999	-0.74	20	20
IL8	-0.074	0.2	-9999	-0.49	36	36
PTK2	0.025	0.1	-9999	-0.48	4	4
Rac1/GDP	0	0	-9999	-10000	0	0
CASP3	-0.021	0.086	-9999	-0.38	24	24
EGFR	-0.001	0.12	-9999	-0.85	9	9
PLCG1	0.019	0.056	-9999	-0.41	4	4
PLD2	0.025	0.1	-9999	-0.48	4	4
G12/G13	-0.02	0.089	-9999	-10000	0	0
PI3K-beta	-0.015	0.064	-9999	-10000	0	0
cell migration	-0.008	0.033	-9999	-10000	0	0
SLC9A3R2	0.014	0.035	-9999	-0.76	1	1
PXN	0.04	0.077	-9999	-10000	0	0
HRAS/GTP	-0.025	0.098	-9999	-0.46	20	20
RAC1	0.016	0	-9999	-10000	0	0
MMP9	-0.39	0.44	-9999	-0.86	223	223
PRKCE	0.015	0.004	-9999	-10000	0	0
PRKCD	0.059	0.057	-9999	-10000	0	0
Gi(beta/gamma)	-0.025	0.097	-9999	-0.45	22	22
mol:LPA	0.004	0.022	-9999	-10000	0	0
TRIP6/p130 Cas/FAK1/Paxillin	-0.018	0.081	-9999	-10000	0	0
MAPKKK cascade	0.04	0.11	-9999	-0.44	20	20
contractile ring contraction involved in cytokinesis	0.036	0.037	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNA14	-0.01	0.062	-9999	-0.41	11	11
GNA15	-0.014	0.076	-9999	-0.43	15	15
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
MAPT	0.047	0.072	-9999	-0.43	1	1
GNA11	-0.006	0.044	-9999	-0.39	6	6
Rac1/GTP	0	0.042	-9999	-0.92	1	1
MMP2	0.008	0.13	-9999	-0.54	25	25

×

Sphingosine 1-phosphate (S1P) pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.012	0.05	-9999	-0.76	2	2
SPHK1	-0.058	0.24	-9999	-0.86	40	40
GNAI2	0.016	0	-9999	-10000	0	0
mol:S1P	0.001	0.095	-9999	-0.31	42	42
GNAO1	0.009	0.078	-9999	-0.84	4	4
mol:Sphinganine-1-P	-0.03	0.2	-9999	-0.66	42	42
growth factor activity	0	0	-9999	-10000	0	0
S1P/S1P2/G12/G13	-0.017	0.056	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
S1PR3	0.014	0.035	-9999	-0.76	1	1
S1PR2	0.016	0	-9999	-10000	0	0
EDG1	0	0	-9999	-10000	0	0
S1P1/S1P	-0.023	0.075	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	82	82
S1PR4	-0.03	0.2	-9999	-0.86	25	25
GNAI1	0.011	0.061	-9999	-0.76	3	3
S1P/S1P5/G12	-0.11	0.21	-9999	-0.54	82	82
S1P/S1P3/Gq	-0.023	0.085	-9999	-0.45	14	14
S1P/S1P4/Gi	0.024	0.097	-9999	-0.4	4	4
GNAQ	0.016	0	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
GNA14	0.004	0.093	-9999	-0.76	7	7
GNA15	-0.006	0.14	-9999	-0.86	12	12
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
GNA11	0.012	0.05	-9999	-0.76	2	2
ABCC1	0.016	0	-9999	-10000	0	0

×

Thromboxane A2 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
TGM2	-0.003	0.12	-10000	0	-0.86	9	9
GNB1/GNG2	-0.034	0.062	-10000	0	-0.22	11	11
AKT1	0.056	0.1	-10000	0	-0.25	1	1
EGF	-0.68	0.23	-10000	0	-0.76	432	432
mol:TXA2	0	0.001	-10000	0	-10000	0	0
FGR	-0.034	0.082	-10000	0	-0.61	2	2
mol:Ca2+	0.043	0.14	-10000	0	-0.34	17	17
LYN	-0.032	0.073	-10000	0	-10000	0	0
RhoA/GTP	-0.017	0.037	-10000	0	-0.19	1	1
mol:PGI2	0	0	-10000	0	-10000	0	0
SYK	0.052	0.15	-10000	0	-0.38	16	16
GNG2	0.016	0	-10000	0	-10000	0	0
ARRB2	0.014	0.04	-10000	0	-0.86	1	1
TP alpha/Gq family/GDP/G beta5/gamma2	0.03	0.077	-10000	0	-0.43	7	7
G beta5/gamma2	-0.045	0.081	-10000	0	-0.3	12	12
PRKCH	0.044	0.15	-10000	0	-0.4	13	13
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
TXA2/TP beta/beta Arrestin3	-0.013	0.042	-10000	0	-0.28	8	8
mol:GTP	0.001	0.001	-10000	0	-10000	0	0
PTGDR	-0.12	0.32	-10000	0	-0.86	76	76
G12 family/GTP	-0.042	0.089	-10000	0	-0.33	13	13
ADRBK1	0.016	0	-10000	0	-10000	0	0
ADRBK2	0.016	0	-10000	0	-10000	0	0
RhoA/GTP/ROCK1	0	0	-10000	0	-10000	0	0
mol:GDP	-0.031	0.1	0.31	9	-10000	0	9
mol:NADP	0.016	0	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
PRKG1	0	0.11	-10000	0	-0.76	10	10
mol:IP3	0.04	0.17	-10000	0	-0.42	21	21
cell morphogenesis	0	0	-10000	0	-10000	0	0
PLCB2	0.031	0.21	-10000	0	-0.59	21	21
mol:cGMP	0	0.001	-10000	0	-10000	0	0
BLK	-0.056	0.13	-10000	0	-0.61	15	15
mol:PDG2	0	0	-10000	0	-10000	0	0
HCK	-0.054	0.12	-10000	0	-0.6	9	9
RHOA	0.016	0	-10000	0	-10000	0	0
PTGIR	0.014	0.04	-10000	0	-0.86	1	1
PRKCB1	0.039	0.16	-10000	0	-0.41	21	21
GNAQ	0.016	0	-10000	0	-10000	0	0
mol:L-citrulline	0.016	0	-10000	0	-10000	0	0
TXA2/TXA2-R family	0.038	0.21	-10000	0	-0.53	36	36
LCK	-0.049	0.12	-10000	0	-0.6	12	12
TXA2/TP beta/beta Arrestin3/RAB11/GDP	-0.043	0.099	-10000	0	-10000	0	0
TXA2-R family/G12 family/GDP/G beta/gamma	0.027	0.037	-10000	0	-10000	0	0
TXA2/TP beta/beta Arrestin2/RAB11/GDP	-0.043	0.098	-10000	0	-10000	0	0
MAPK14	0.055	0.11	-10000	0	-0.31	1	1
TGM2/GTP	0.039	0.19	-10000	0	-0.49	19	19
MAPK11	0.055	0.11	-10000	0	-0.31	1	1
ARHGEF1	0.043	0.087	-10000	0	-0.33	1	1
GNAI2	0.016	0	-10000	0	-10000	0	0
JNK cascade	0.046	0.16	-10000	0	-0.41	21	21
RAB11/GDP	0.015	0.002	-10000	0	-10000	0	0
ICAM1	0.046	0.13	-10000	0	-0.38	11	11
cAMP biosynthetic process	0.037	0.16	-10000	0	-0.4	20	20
Gq family/GTP/EBP50	0.027	0.059	-10000	0	-0.34	3	3
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	-0.032	0.073	-10000	0	-10000	0	0
GNB5	0.016	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
EGF/EGFR	-0.089	0.11	-10000	0	-0.41	15	15
VCAM1	0.044	0.14	-10000	0	-0.35	20	20
TP beta/Gq family/GDP/G beta5/gamma2	0.03	0.077	-10000	0	-0.43	7	7
platelet activation	0.069	0.15	-10000	0	-0.34	11	11
PGI2/IP	-0.001	0.031	-10000	0	-0.68	1	1
PRKACA	-0.055	0.13	-10000	0	-0.34	77	77
Gq family/GDP/G beta5/gamma2	0.025	0.078	-10000	0	-0.43	7	7
TXA2/TP beta/beta Arrestin2	-0.013	0.059	-10000	0	-0.41	10	10
positive regulation of NF-kappaB transcription factor activity	0	0	-10000	0	-10000	0	0
TBXA2R	-0.02	0.13	-10000	0	-10000	0	0
mol:DAG	0.039	0.18	-10000	0	-0.47	21	21
EGFR	-0.001	0.12	-10000	0	-0.85	9	9
TXA2/TP alpha	0.036	0.2	-10000	0	-0.55	21	21
Gq family/GTP	-0.004	0.054	-10000	0	-0.28	9	9
YES1	-0.032	0.073	-10000	0	-10000	0	0
GNAI2/GTP	-0.037	0.085	-10000	0	-10000	0	0
PGD2/DP	-0.11	0.25	-10000	0	-0.68	76	76
SLC9A3R1	0.016	0	-10000	0	-10000	0	0
FYN	-0.032	0.073	-10000	0	-10000	0	0
mol:NO	0.016	0	-10000	0	-10000	0	0
GNA15	-0.006	0.14	-10000	0	-0.86	12	12
PGK/cGMP	-0.01	0.071	-10000	0	-0.5	10	10
RhoA/GDP	0.015	0.002	-10000	0	-10000	0	0
TP alpha/TGM2/GDP/G beta/gamma	-0.049	0.11	-10000	0	-0.71	1	1
NOS3	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
PRKCA	0.044	0.15	-10000	0	-0.4	13	13
PRKCB	0.042	0.16	-10000	0	-0.44	17	17
PRKCE	0.046	0.15	-10000	0	-0.4	14	14
PRKCD	0.043	0.16	-10000	0	-0.41	17	17
PRKCG	0.032	0.18	-10000	0	-0.51	23	23
muscle contraction	0.045	0.2	-10000	0	-0.53	21	21
PRKCZ	0.051	0.15	-10000	0	-0.39	12	12
ARR3	0.004	0.007	-10000	0	-10000	0	0
TXA2/TP beta	-0.042	0.096	-10000	0	-10000	0	0
PRKCQ	0.038	0.16	-10000	0	-0.43	18	18
MAPKKK cascade	0.038	0.19	-10000	0	-0.49	23	23
SELE	0.039	0.15	-10000	0	-0.42	31	31
TP beta/GNAI2/GDP/G beta/gamma	-0.04	0.093	-10000	0	-10000	0	0
ROCK1	0.016	0	-10000	0	-10000	0	0
GNA14	0.004	0.093	-10000	0	-0.76	7	7
chemotaxis	0.039	0.23	-10000	0	-0.61	35	35
GNA12	0.016	0	-10000	0	-10000	0	0
GNA13	0.016	0	-10000	0	-10000	0	0
GNA11	0.012	0.05	-10000	0	-0.76	2	2
Rac1/GTP	0	0	-10000	0	-10000	0	0

×

Ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SPHK2	0.028	0.039	-10000	0	-0.57	2	2
MAP4K4	0.025	0.094	-10000	0	-0.48	1	1
BAG4	0.016	0	-10000	0	-10000	0	0
PKC zeta/ceramide	-0.1	0.047	-10000	0	-0.49	3	3
NFKBIA	0.016	0	-10000	0	-10000	0	0
BIRC3	-0.12	0.32	-10000	0	-0.86	74	74
BAX	-0.043	0.018	-10000	0	-10000	0	0
RIPK1	0.016	0	-10000	0	-10000	0	0
AKT1	0.047	0.008	-10000	0	-10000	0	0
BAD	-0.099	0.035	-10000	0	-0.27	1	1
SMPD1	0.026	0.043	-10000	0	-0.28	1	1
RB1	-0.098	0.036	-10000	0	-10000	0	0
FADD/Caspase 8	0.04	0.088	-10000	0	-10000	0	0
MAP2K4	-0.082	0.034	-10000	0	-10000	0	0
NSMAF	0.016	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
RAF1	-0.086	0.058	-10000	0	-0.59	4	4
EGF	-0.68	0.23	-10000	0	-0.76	432	432
mol:ceramide	-0.12	0.038	0.2	1	-10000	0	1
MADD	0.016	0	-10000	0	-10000	0	0
response to oxidative stress	0	0	-10000	0	-10000	0	0
mol:Free Fatty acid	0.031	0	-10000	0	-10000	0	0
ASAH1	0.016	0	-10000	0	-10000	0	0
negative regulation of cell cycle	-0.097	0.036	-10000	0	-10000	0	0
cell proliferation	-0.055	0.064	-10000	0	-0.52	5	5
BID	-0.012	0.066	-10000	0	-10000	0	0
MAP3K1	-0.098	0.036	-10000	0	-10000	0	0
EIF2A	-0.068	0.033	-10000	0	-10000	0	0
TRADD	0.016	0	-10000	0	-10000	0	0
CRADD	0.016	0	-10000	0	-10000	0	0
MAPK3	-0.066	0.053	-10000	0	-0.54	4	4
response to heat	0	0	-10000	0	-10000	0	0
MAPK1	-0.066	0.053	-10000	0	-0.54	4	4
Cathepsin D/ceramide	-0.099	0.034	-10000	0	-0.27	1	1
FADD	0.025	0.094	-10000	0	-0.48	1	1
KSR1	-0.1	0.061	-10000	0	-0.63	4	4
MAPK8	-0.077	0.037	-10000	0	-0.35	2	2
PRKRA	-0.098	0.036	-10000	0	-10000	0	0
PDGFA	0.016	0	-10000	0	-10000	0	0
TRAF2	0.016	0	-10000	0	-10000	0	0
IGF1	0.003	0.11	-10000	0	-0.86	7	7
mol:GD3	0	0	-10000	0	-10000	0	0
ganglioside biosynthetic process	-0.12	0.038	0.2	1	-10000	0	1
CTSD	0.014	0.035	-10000	0	-0.76	1	1
regulation of nitric oxide biosynthetic process	0	0	-10000	0	-10000	0	0
response to radiation	0	0	-10000	0	-10000	0	0
ERK1/PKC delta	-0.058	0.07	-10000	0	-0.57	5	5
PRKCD	0.014	0.04	-10000	0	-0.86	1	1
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
mol:GW4869	0	0	-10000	0	-10000	0	0
mol:sphingosine	0.031	0	-10000	0	-10000	0	0
RelA/NF kappa B1	0	0	-10000	0	-10000	0	0
mol:glutathione	0	0	-10000	0	-10000	0	0
PAWR	0.014	0.035	-10000	0	-0.76	1	1
TNF-alpha/TNFR1A/TRADD/MADD/cIAP2/RIP1/TRAF2/RAIDD	-0.035	0.078	-10000	0	-0.51	1	1
TNFR1A/BAG4/TNF-alpha	-0.009	0.068	-10000	0	-0.53	8	8
mol:Sphingosine-1-phosphate	0.028	0.039	-10000	0	-0.57	2	2
MAP2K1	-0.072	0.055	-10000	0	-0.55	4	4
mol:C11AG	0	0	-10000	0	-10000	0	0
RELA	0.016	0	-10000	0	-10000	0	0
CYCS	-0.064	0.023	-10000	0	-10000	0	0
TNFRSF1A	0.016	0	-10000	0	-10000	0	0
NFKB1	0.016	0	-10000	0	-10000	0	0
TNFR1A/BAG4	0	0	-10000	0	-10000	0	0
EIF2AK2	-0.082	0.034	-10000	0	-10000	0	0
TNF-alpha/TNFR1A/FAN	-0.009	0.068	-10000	0	-0.53	8	8
response to hydrogen peroxide	0	0	-10000	0	-10000	0	0
CASP8	-0.016	0.036	-10000	0	-10000	0	0
MAP2K2	-0.073	0.054	-10000	0	-0.55	4	4
SMPD3	0.026	0.053	-10000	0	-0.33	2	2
TNF	0.002	0.11	-10000	0	-0.81	8	8
PKC zeta/PAR4	-0.005	0.052	-10000	0	-0.57	4	4
mol:PHOSPHOCHOLINE	0.23	0.085	0.26	432	-10000	0	432
NF kappa B1/RelA/I kappa B alpha	-0.003	0.036	-10000	0	-10000	0	0
AIFM1	-0.064	0.023	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Class I PI3K signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ARF5/GTP	0	0	-9999	-10000	0	0
DAPP1	0.029	0.12	-9999	-0.54	9	9
Src family/SYK family/BLNK-LAT/BTK-ITK	-0.15	0.26	-9999	-0.72	54	54
mol:DAG	-0.076	0.15	-9999	-0.32	56	56
HRAS	0.017	0	-9999	-10000	0	0
RAP1A	0.017	0	-9999	-10000	0	0
ARF5/GDP	0.017	0.075	-9999	-10000	0	0
PLCG2	0.002	0.11	-9999	-0.82	8	8
PLCG1	0.016	0	-9999	-10000	0	0
ARF5	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
RAP1A/GTP	0	0	-9999	-10000	0	0
ADAP1	-0.003	0.034	-9999	-10000	0	0
ARAP3	0	0	-9999	-10000	0	0
INPPL1	0.016	0	-9999	-10000	0	0
PREX1	0.016	0	-9999	-10000	0	0
ARHGEF6	0.016	0	-9999	-10000	0	0
ARHGEF7	0.016	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
NRAS	0.017	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
FGR	0.01	0.069	-9999	-0.86	3	3
mol:Ca2+	-0.025	0.078	-9999	-10000	0	0
mol:IP4	0	0	-9999	-10000	0	0
TIAM1	0.014	0.035	-9999	-0.76	1	1
ZAP70	-0.48	0.44	-9999	-0.86	272	272
mol:IP3	-0.041	0.11	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
ARF1/GDP	0.017	0.075	-9999	-10000	0	0
RhoA/GDP	-0.003	0.006	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
BLNK	0.014	0.035	-9999	-0.76	1	1
actin cytoskeleton reorganization	0.044	0.082	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PLEKHA2	0.036	0.056	-9999	-0.57	4	4
RAC1	0.016	0	-9999	-10000	0	0
PTEN	0	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
RhoA/GTP	0	0	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT	-0.21	0.24	-9999	-0.56	129	129
BLK	-0.04	0.21	-9999	-0.86	30	30
PDPK1	0.016	0	-9999	-10000	0	0
CYTH1	0	0	-9999	-10000	0	0
HCK	-0.034	0.2	-9999	-0.86	27	27
CYTH3	0	0	-9999	-10000	0	0
CYTH2	0	0	-9999	-10000	0	0
KRAS	0.017	0	-9999	-10000	0	0
GO:0030676	0	0	-9999	-10000	0	0
FOXO3	0	0	-9999	-10000	0	0
SGK1	0	0	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
mol:GDP	0.009	0.079	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
SYK	0.012	0.05	-9999	-0.76	2	2
ARF6/GDP	-0.003	0.006	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
ARAP3/RAP1A/GTP	0	0	-9999	-10000	0	0
VAV1	-0.2	0.38	-9999	-0.86	119	119
mol:PI-3-4-P2	0.025	0.063	-9999	-0.67	4	4
RAS family/GTP/PI3K Class I	0	0	-9999	-10000	0	0
PLEKHA1	0.036	0.056	-9999	-0.57	4	4
Rac1/GDP	0.017	0.075	-9999	-10000	0	0
LAT	-0.25	0.4	-9999	-0.86	143	143
Rac1/GTP	-0.003	0.1	-9999	-10000	0	0
ITK	-0.15	0.22	-9999	-10000	0	0
Src family/SYK family/BLNK-LAT/BTK-ITK/PLC-gamma	-0.12	0.21	-9999	-0.46	72	72
LCK	-0.024	0.18	-9999	-0.85	22	22
BTK	-0.094	0.18	-9999	-10000	0	0

×

PLK2 and PLK4 events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLK2	-0.014	0.16	-9999	-0.86	16	16
PLK4	0.01	0.069	-9999	-0.86	3	3
regulation of centriole replication	0.003	0.14	-9999	-0.67	19	19

×

IFN-gamma pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.2	0.22	-9999	-10000	0	0
positive regulation of NF-kappaB transcription factor activity	0	0.001	-9999	-10000	0	0
CRKL	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/Cbp/p300	-0.16	0.17	-9999	-1.2	1	1
IFN-gammaR/JAK1/JAK1/JAK2/JAK2	-0.026	0.028	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class I	-0.11	0.091	-9999	-0.37	1	1
CaM/Ca2+	-0.18	0.2	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/SHP2	-0.18	0.2	-9999	-1	1	1
AKT1	-0.16	0.17	-9999	-10000	0	0
MAP2K1	-0.13	0.22	-9999	-10000	0	0
MAP3K11	-0.15	0.23	-9999	-0.81	1	1
IFNGR1	0.001	0.019	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKII	-0.28	0.29	-9999	-0.75	108	108
Rap1/GTP	-0.13	0.14	-9999	-10000	0	0
CRKL/C3G	0	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2 /TC-PTP	-0.21	0.23	-9999	-10000	0	0
CEBPB	-0.07	0.2	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
IFN-gamma/IFN-gammaR/JAK1/JAK1/JAK2/JAK2/SOCS1	-0.2	0.22	-9999	-1	2	2
STAT1	-0.15	0.24	-9999	-1	1	1
CALM1	0.016	0	-9999	-10000	0	0
IFN-gamma (dimer)	-0.38	0.43	-9999	-0.85	220	220
PIK3CA	0.016	0	-9999	-10000	0	0
STAT1 (dimer)/PIAS1	-0.17	0.19	-9999	-0.95	1	1
CEBPB/PTGES2/Cbp/p300	-0.076	0.085	-9999	-0.47	1	1
mol:Ca2+	-0.2	0.21	-9999	-10000	0	0
MAPK3	-0.091	0.2	-9999	-10000	0	0
STAT1 (dimer)	-0.14	0.12	-9999	-0.54	1	1
MAPK1	-0.091	0.2	-9999	-10000	0	0
JAK2	0.001	0.019	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
JAK1	0.001	0.019	-9999	-10000	0	0
CAMK2D	0.016	0	-9999	-10000	0	0
DAPK1	-0.025	0.15	-9999	-0.63	2	2
SMAD7	-0.023	0.082	-9999	-10000	0	0
CBL/CRKL/C3G	-0.16	0.18	-9999	-10000	0	0
PI3K	-0.17	0.19	-9999	-10000	0	0
IFNG	-0.38	0.44	-9999	-0.86	220	220
apoptosis	-0.038	0.12	-9999	-0.44	2	2
CAMK2G	0.016	0	-9999	-10000	0	0
STAT3 (dimer)	0.016	0	-9999	-10000	0	0
CAMK2A	-0.26	0.37	-9999	-0.76	168	168
CAMK2B	-0.11	0.28	-9999	-0.76	75	75
FRAP1	-0.11	0.2	-9999	-10000	0	0
PRKCD	-0.14	0.2	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
negative regulation of cell growth	-0.11	0.091	-9999	-0.37	1	1
PTPN2	0.016	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
IRF1	-0.059	0.19	-9999	-0.66	3	3
STAT1 (dimer)/PIASy	-0.17	0.19	-9999	-0.95	1	1
SOCS1	0.012	0.079	-9999	-0.73	5	5
mol:GDP	-0.16	0.17	-9999	-10000	0	0
CASP1	-0.023	0.082	-9999	-10000	0	0
PTGES2	0.013	0.05	-9999	-0.76	2	2
IRF9	0.017	0.076	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.17	0.18	-9999	-10000	0	0
RAP1/GDP	-0.13	0.14	-9999	-10000	0	0
CBL	-0.15	0.23	-9999	-10000	0	0
MAP3K1	-0.15	0.23	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PIAS4	0.015	0.001	-9999	-10000	0	0
antigen processing and presentation of peptide antigen via MHC class II	-0.11	0.091	-9999	-0.37	1	1
PTPN11	-0.17	0.24	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAPGEF1	0.016	0	-9999	-10000	0	0

×

FAS signaling pathway (CD95)

Figure 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
SPTAN1	0.013	0.045	-10000	0	-10000	0	0
RFC1	0.013	0.045	-10000	0	-10000	0	0
PRKDC	0.013	0.045	-10000	0	-10000	0	0
RIPK1	0.013	0.005	-10000	0	-10000	0	0
CASP7	-0.023	0.068	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1	-0.14	0.16	0.26	6	-0.35	21	27
MAP2K4	-0.089	0.16	-10000	0	-0.42	21	21
mol:ceramide	-0.16	0.2	-10000	0	-0.48	30	30
GSN	0.013	0.045	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 8	-0.18	0.18	-10000	0	-0.44	21	21
FAS	0.015	0.006	-10000	0	-10000	0	0
BID	0.02	0.07	-10000	0	-10000	0	0
MAP3K1	-0.037	0.1	-10000	0	-10000	0	0
MAP3K7	0.014	0.005	-10000	0	-10000	0	0
RB1	0.013	0.045	-10000	0	-10000	0	0
CFLAR	0.013	0.005	-10000	0	-10000	0	0
HGF/MET	-0.036	0.15	-10000	0	-0.58	30	30
ARHGDIB	0.013	0.045	-10000	0	-10000	0	0
FADD	0.015	0.006	-10000	0	-10000	0	0
actin filament polymerization	-0.013	0.045	-10000	0	-10000	0	0
NFKB1	-0.065	0.071	-10000	0	-10000	0	0
MAPK8	-0.086	0.18	-10000	0	-0.51	21	21
DFFA	0.013	0.045	-10000	0	-10000	0	0
DNA fragmentation during apoptosis	0.013	0.045	-10000	0	-10000	0	0
FAS/FADD/MET	-0.006	0.058	-10000	0	-0.57	5	5
CFLAR/RIP1	0	0	-10000	0	-10000	0	0
FAIM3	-0.052	0.24	-10000	0	-0.86	37	37
FAF1	0.015	0.006	-10000	0	-10000	0	0
PARP1	0.013	0.045	-10000	0	-10000	0	0
DFFB	0.013	0.045	-10000	0	-10000	0	0
CHUK	-0.052	0.06	-10000	0	-10000	0	0
FASLG	-0.45	0.44	-10000	0	-0.87	252	252
FAS/FADD	0	0	-10000	0	-10000	0	0
HGF	-0.021	0.17	-10000	0	-0.81	21	21
LMNA	0.011	0.049	-10000	0	-0.52	1	1
CASP6	0.013	0.045	-10000	0	-10000	0	0
CASP10	0.015	0.006	-10000	0	-10000	0	0
CASP3	0.015	0.052	-10000	0	-10000	0	0
PTPN13	0.004	0.093	-10000	0	-0.76	7	7
CASP8	0.031	0.11	0.4	37	-10000	0	37
IL6	-0.12	0.32	-10000	0	-0.92	59	59
MET	0.007	0.089	-10000	0	-0.86	5	5
ICAD/CAD	0.013	0.045	-10000	0	-10000	0	0
FASLG/FAS/FADD/FAF1/Caspase 10	-0.16	0.2	-10000	0	-0.49	30	30
activation of caspase activity by cytochrome c	0.02	0.07	-10000	0	-10000	0	0
PAK2	0.013	0.045	-10000	0	-10000	0	0
BCL2	0.016	0.001	-10000	0	-10000	0	0

×

Canonical Wnt 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
HDAC1	0.005	0.018	-10000	0	-10000	0	0
AES	0.004	0.016	-10000	0	-10000	0	0
FBXW11	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-10000	0	0
LRP6/FZD1	0	0	-10000	0	-10000	0	0
SMAD4	0.016	0	-10000	0	-10000	0	0
DKK2	-0.029	0.19	-10000	0	-0.83	25	25
TLE1	0.004	0.016	-10000	0	-10000	0	0
MACF1	0.016	0.003	-10000	0	-10000	0	0
CTNNB1	0.051	0.1	-10000	0	-0.45	1	1
WIF1	-0.009	0.093	-10000	0	-0.77	7	7
beta catenin/RanBP3	0.004	0.11	0.36	19	-10000	0	19
KREMEN2	-0.081	0.27	-10000	0	-0.86	52	52
DKK1	-0.016	0.16	-10000	0	-0.84	18	18
beta catenin/beta TrCP1	0.057	0.094	-10000	0	-10000	0	0
FZD1	0.015	0.005	-10000	0	-10000	0	0
AXIN2	0.012	0.081	-10000	0	-1.4	1	1
AXIN1	0.016	0.004	-10000	0	-10000	0	0
RAN	0.016	0.001	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin	0.002	0.018	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES/SMAD4	0.074	0.065	-10000	0	-10000	0	0
Axin1/APC/GSK3	0.04	0.084	-10000	0	-10000	0	0
Axin1/APC/GSK3/beta catenin/Macf1	0.059	0.1	-10000	0	-10000	0	0
HNF1A	-0.002	0.071	-10000	0	-0.75	4	4
CTBP1	0.005	0.017	-10000	0	-10000	0	0
MYC	-0.005	0.14	-10000	0	-0.75	16	16
RANBP3	0.016	0.001	-10000	0	-10000	0	0
DKK2/LRP6/Kremen 2	-0.091	0.21	-10000	0	-0.57	76	76
NKD1	-0.19	0.34	-10000	0	-0.76	127	127
TCF4	0.005	0.017	-10000	0	-10000	0	0
TCF3	0.005	0.016	-10000	0	-10000	0	0
WNT1/LRP6/FZD1/Axin1	-0.026	0.11	-10000	0	-0.52	24	24
Ran/GTP	0	0.001	-10000	0	-10000	0	0
CtBP/CBP/TCF/TLE1/AES	0.018	0.1	0.57	2	-10000	0	2
LEF1	-0.023	0.15	-10000	0	-0.87	15	15
DVL1	0.004	0.036	-10000	0	-0.33	2	2
CSNK2A1	0.015	0.003	-10000	0	-10000	0	0
beta catenin/TCF/CtBP/CBP/TLE1/AES	0.083	0.071	-10000	0	-10000	0	0
DKK1/LRP6/Kremen 2	-0.083	0.22	-10000	0	-0.62	64	64
LRP6	0.016	0.003	-10000	0	-10000	0	0
CSNK1A1	0.005	0.018	-10000	0	-10000	0	0
NLK	0.016	0.005	-10000	0	-10000	0	0
CCND1	-0.01	0.16	-10000	0	-0.75	20	20
WNT1	-0.03	0.19	-10000	0	-0.86	24	24
GSK3A	0.016	0.004	-10000	0	-10000	0	0
GSK3B	0.015	0.005	-10000	0	-10000	0	0
FRAT1	0.014	0.005	-10000	0	-10000	0	0
PPP2R5D	0.096	0.16	0.36	126	-10000	0	126
APC	-0.019	0.11	-10000	0	-10000	0	0
WNT1/LRP6/FZD1	0.013	0.067	0.28	7	-10000	0	7
CREBBP	0.005	0.016	-10000	0	-10000	0	0

×

E-cadherin signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
E-cadherin/beta catenin-gamma catenin	-0.022	0.11	-9999	-0.51	21	21
E-cadherin/beta catenin	-0.023	0.11	-9999	-0.57	19	19
CTNNB1	0.016	0	-9999	-10000	0	0
JUP	0.011	0.061	-9999	-0.76	3	3
CDH1	-0.015	0.15	-9999	-0.76	19	19

×

ErbB4 signaling events

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
ErbB4/ErbB4/HBEGF/HBEGF	-0.11	0.07	-10000	0	-10000	0	0
epithelial cell differentiation	-0.047	0.11	-10000	0	-10000	0	0
ITCH	0.056	0.018	-10000	0	-10000	0	0
WWP1	-0.098	0.066	-10000	0	-10000	0	0
FYN	0.016	0	-10000	0	-10000	0	0
EGFR	-0.001	0.12	-10000	0	-0.85	9	9
PRL	0.006	0.008	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.016	0.074	-10000	0	-10000	0	0
PTPRZ1	-0.088	0.26	-10000	0	-0.77	61	61
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/GRB2/SHC	-0.051	0.065	-10000	0	-0.55	1	1
ErbB4 CYT2/ErbB4 CYT2/neuregulin 1 beta/neuregulin 1 beta	-0.081	0.086	-10000	0	-0.52	11	11
ADAM17	0.056	0.018	-10000	0	-10000	0	0
ErbB4/ErbB4	-0.14	0.084	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 3/neuregulin 3	-0.12	0.1	-10000	0	-0.64	10	10
NCOR1	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta/Fyn	-0.073	0.068	-10000	0	-0.52	7	7
GRIN2B	-0.054	0.085	-10000	0	-0.51	9	9
ErbB4/ErbB2/betacellulin	-0.14	0.17	-10000	0	-0.52	69	69
STAT1	0.014	0.04	-10000	0	-0.86	1	1
HBEGF	0.016	0	-10000	0	-10000	0	0
PRLR	-0.076	0.25	-10000	0	-0.76	57	57
E4ICDs/ETO2	-0.11	0.079	-10000	0	-0.7	2	2
axon guidance	-0.015	0.071	-10000	0	-10000	0	0
NEDD4	0.056	0.018	-10000	0	-10000	0	0
Prolactin receptor/Prolactin receptor/Prolactin	-0.069	0.19	-10000	0	-0.58	57	57
CBFA2T3	0.012	0.057	-10000	0	-0.86	2	2
ErbB4/ErbB2/HBEGF	-0.065	0.038	-10000	0	-0.52	1	1
MAPK3	-0.027	0.076	-10000	0	-10000	0	0
STAT1 (dimer)	-0.11	0.072	-10000	0	-0.54	1	1
MAPK1	-0.027	0.076	-10000	0	-10000	0	0
JAK2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 1 beta	-0.075	0.073	-10000	0	-0.52	8	8
NRG1	0.041	0.094	-10000	0	-0.57	11	11
NRG3	-0.003	0.13	-10000	0	-0.86	10	10
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
NRG4	-0.059	0.23	-10000	0	-0.78	44	44
heart development	-0.015	0.071	-10000	0	-10000	0	0
neural crest cell migration	-0.074	0.072	-10000	0	-0.52	8	8
ERBB2	0.052	0.042	-10000	0	-0.57	2	2
WWOX/E4ICDs	-0.11	0.075	-10000	0	-0.7	1	1
SHC1	0.014	0.04	-10000	0	-0.86	1	1
ErbB4/EGFR/neuregulin 4	-0.15	0.15	-10000	0	-0.56	53	53
apoptosis	0.11	0.062	0.39	7	-10000	0	7
ErbB4/ErbB4/neuregulin 2 beta/neuregulin 2 beta	-0.12	0.089	-10000	0	-0.53	10	10
ErbB4/ErbB2/epiregulin	-0.098	0.13	-10000	0	-0.57	31	31
ErbB4/ErbB4/betacellulin/betacellulin	-0.18	0.19	-10000	0	-0.6	76	76
ErbB4/ErbB4/HBEGF/HBEGF/Prolactin receptor/Prolactin receptor/Prolactin/JAK2	-0.12	0.14	-10000	0	-0.52	24	24
MDM2	-0.11	0.073	-10000	0	-10000	0	0
ErbB4 JM-B/ErbB4 JM-B/neuregulin 1 beta/neuregulin 1 beta	-0.051	0.068	-10000	0	-0.51	7	7
STAT5A	-0.003	0.066	-10000	0	-10000	0	0
ErbB4/EGFR/neuregulin 1 beta	-0.083	0.096	-10000	0	-0.56	15	15
DLG4	0.016	0	-10000	0	-10000	0	0
GRB2/SHC	-0.001	0.03	-10000	0	-0.67	1	1
E4ICDs/TAB2/NCoR1	-0.11	0.047	-10000	0	-10000	0	0
STAT5A (dimer)	-0.05	0.12	-10000	0	-10000	0	0
MAP3K7IP2	0	0	-10000	0	-10000	0	0
STAT5B (dimer)	-0.005	0.063	-10000	0	-10000	0	0
LRIG1	0.016	0	-10000	0	-10000	0	0
EREG	-0.04	0.21	-10000	0	-0.86	30	30
BTC	-0.11	0.28	-10000	0	-0.76	76	76
ErbB4/ErbB4/neuregulin 1 beta/neuregulin 1 beta	-0.015	0.071	-10000	0	-10000	0	0
ERBB4	-0.14	0.085	-10000	0	-10000	0	0
STAT5B	0.016	0	-10000	0	-10000	0	0
YAP1	-0.034	0.016	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
ErbB4/ErbB2/neuregulin 4	-0.11	0.14	-10000	0	-0.52	42	42
glial cell differentiation	0.1	0.047	-10000	0	-10000	0	0
WWOX	0.014	0.04	-10000	0	-0.86	1	1
cell proliferation	-0.076	0.16	-10000	0	-0.6	11	11

×

Regulation of Androgen receptor activity

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.031	0.002	-9999	-10000	0	0
SMARCC1	0.027	0.009	-9999	-10000	0	0
REL	0.01	0.05	-9999	-0.76	2	2
HDAC7	-0.097	0.08	-9999	-0.67	2	2
JUN	0.015	0.003	-9999	-10000	0	0
EP300	0.015	0.003	-9999	-10000	0	0
KAT2B	0.015	0.003	-9999	-10000	0	0
KAT5	0.016	0	-9999	-10000	0	0
MAPK14	0.001	0.041	-9999	-0.61	2	2
FOXO1	0.016	0.001	-9999	-10000	0	0
T-DHT/AR	-0.11	0.082	-9999	-0.72	2	2
MAP2K6	-0.001	0.051	-9999	-0.78	2	2
BRM/BAF57	0	0	-9999	-10000	0	0
MAP2K4	0.002	0.006	-9999	-10000	0	0
SMARCA2	0.015	0.003	-9999	-10000	0	0
PDE9A	-0.12	0.13	-9999	-1.2	5	5
NCOA2	0.009	0.07	-9999	-0.76	4	4
CEBPA	-0.001	0.12	-9999	-0.86	9	9
EHMT2	0.015	0.003	-9999	-10000	0	0
cell proliferation	-0.089	0.089	-9999	-0.53	1	1
NR0B1	-0.05	0.21	-9999	-0.86	30	30
EGR1	0.004	0.093	-9999	-0.76	7	7
RXRs/9cRA	-0.005	0.049	-9999	-0.54	4	4
AR/RACK1/Src	-0.013	0.054	-9999	-0.59	1	1
AR/GR	0.003	0.081	-9999	-0.77	2	2
GNB2L1	0.014	0.04	-9999	-0.86	1	1
PKN1	0.015	0.003	-9999	-10000	0	0
RCHY1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0.002	-9999	-10000	0	0
MAPK8	0.004	0.011	-9999	-10000	0	0
T-DHT/AR/TIF2/CARM1	-0.014	0.065	-9999	-0.57	3	3
SRC	0.005	0.038	-9999	-10000	0	0
NR3C1	0.014	0.04	-9999	-0.86	1	1
KLK3	-0.05	0.18	-9999	-0.72	21	21
APPBP2	0.002	0.006	-9999	-10000	0	0
TRIM24	0.015	0.003	-9999	-10000	0	0
T-DHT/AR/TIP60	-0.024	0.044	-9999	-0.59	2	2
TMPRSS2	-0.97	0.37	-9999	-1.1	419	419
RXRG	0.006	0.08	-9999	-0.87	4	4
mol:9cRA	0	0.001	-9999	-10000	0	0
RXRA	0.016	0.001	-9999	-10000	0	0
RXRB	0.016	0.001	-9999	-10000	0	0
CARM1	0.015	0.003	-9999	-10000	0	0
NR2C2	0.016	0.001	-9999	-10000	0	0
KLK2	-0.018	0.12	-9999	-0.62	15	15
AR	-0.008	0.08	-9999	-0.4	11	11
SENP1	0.016	0.001	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
MDM2	0.013	0.009	-9999	-10000	0	0
SRY	0.002	0.007	-9999	-10000	0	0
GATA2	0.001	0.1	-9999	-0.76	9	9
MYST2	0.016	0.001	-9999	-10000	0	0
HOXB13	-0.17	0.35	-9999	-0.86	96	96
T-DHT/AR/RACK1/Src	-0.013	0.052	-9999	-0.6	1	1
positive regulation of transcription	0.001	0.1	-9999	-0.76	9	9
DNAJA1	0.002	0.006	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.04	0.002	-9999	-10000	0	0
NCOA1	0.024	0.005	-9999	-10000	0	0
SPDEF	-0.18	0.37	-9999	-0.87	108	108
T-DHT/AR/TIF2	0.024	0.044	-9999	-10000	0	0
T-DHT/AR/Hsp90	-0.025	0.043	-9999	-0.58	2	2
GSK3B	0.002	0.005	-9999	-10000	0	0
NR2C1	0.016	0.001	-9999	-10000	0	0
mol:T-DHT	-0.009	0.042	-9999	-0.51	2	2
SIRT1	0.015	0.003	-9999	-10000	0	0
ZMIZ2	0.013	0.009	-9999	-10000	0	0
POU2F1	0.004	0.014	-9999	-10000	0	0
T-DHT/AR/DAX-1	-0.063	0.14	-9999	-0.59	24	24
CREBBP	0.015	0.003	-9999	-10000	0	0
SMARCE1	0.015	0.003	-9999	-10000	0	0

×

Noncanonical Wnt 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NFATC2	0.014	0.04	-9999	-0.86	1	1
GNB1/GNG2	-0.054	0.11	-9999	-0.54	7	7
mol:DAG	0.011	0.13	-9999	-0.49	7	7
PLCG1	0.011	0.13	-9999	-0.51	7	7
YES1	-0.01	0.14	-9999	-0.57	7	7
FZD3	0.016	0	-9999	-10000	0	0
FZD6	0.016	0	-9999	-10000	0	0
G protein	-0.049	0.1	-9999	-0.51	7	7
MAP3K7	-0.1	0.22	-9999	-0.56	44	44
mol:Ca2+	0.011	0.13	-9999	-0.47	7	7
mol:IP3	0.011	0.13	-9999	-0.49	7	7
NLK	-0.008	0.01	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CAMK2A	-0.12	0.24	-9999	-0.62	44	44
MAP3K7IP1	0	0	-9999	-10000	0	0
Noncanonical Wnts/FZD	-0.063	0.13	-9999	-0.61	7	7
CSNK1A1	0.016	0	-9999	-10000	0	0
GNAS	-0.01	0.14	-9999	-0.57	7	7
GO:0007205	0.012	0.13	-9999	-0.48	7	7
WNT6	-0.01	0.15	-9999	-0.86	14	14
WNT4	-0.073	0.25	-9999	-0.76	55	55
NFAT1/CK1 alpha	-0.048	0.1	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
WNT5A	0.011	0.061	-9999	-0.76	3	3
WNT11	-0.037	0.2	-9999	-0.77	32	32
CDC42	0.002	0.14	-9999	-0.54	7	7

×

S1P5 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
telencephalon oligodendrocyte cell migration	0.045	0.092	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	82	82
mol:GDP	0	0	-9999	-10000	0	0
GNAO1	0.009	0.078	-9999	-0.84	4	4
RhoA/GTP	-0.046	0.094	-9999	-10000	0	0
negative regulation of cAMP metabolic process	-0.052	0.11	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
GNAI3	0.016	0	-9999	-10000	0	0
GNA12	0.016	0	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	82	82
mol:GTP	0	0	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
RhoA/GDP	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
GNAI1	0.011	0.061	-9999	-0.76	3	3

×

Nongenotropic Androgen signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	0.015	0	-10000	0	-10000	0	0
GNB1/GNG2	-0.02	0.093	-10000	0	-0.45	22	22
regulation of S phase of mitotic cell cycle	-0.013	0.063	-10000	0	-10000	0	0
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0.001	-10000	0	-10000	0	0
SHBG/T-DHT	-0.05	0.15	-10000	0	-0.51	47	47
PELP1	0.016	0.001	-10000	0	-10000	0	0
AKT1	0.015	0	-10000	0	-10000	0	0
MAP2K1	0.049	0.088	-10000	0	-10000	0	0
T-DHT/AR	-0.027	0.12	-10000	0	-0.58	22	22
G-protein coupled receptor activity	0	0	-10000	0	-10000	0	0
mol:GTP	0	0.001	-10000	0	-0.007	10	10
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
mol:GDP	-0.025	0.11	-10000	0	-0.55	22	22
cell proliferation	0.074	0.1	-10000	0	-0.66	2	2
PIK3CA	0.016	0	-10000	0	-10000	0	0
FOS	0.06	0.14	-10000	0	-0.83	10	10
mol:Ca2+	-0.003	0.014	-10000	0	-0.11	4	4
MAPK3	0.066	0.096	-10000	0	-0.58	2	2
MAPK1	0.046	0.051	-10000	0	-0.3	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	0	0.001	-10000	0	-0.005	10	10
cAMP biosynthetic process	-0.045	0.15	-10000	0	-0.49	47	47
GNG2	0.016	0	-10000	0	-10000	0	0
potassium channel inhibitor activity	0	0.001	-10000	0	-0.005	10	10
HRAS/GTP	-0.018	0.083	-10000	0	-0.45	1	1
actin cytoskeleton reorganization	0	0	-10000	0	-10000	0	0
SRC	0.016	0.001	-10000	0	-10000	0	0
voltage-gated calcium channel activity	0	0.001	-10000	0	-0.005	10	10
PI3K	0	0	-10000	0	-10000	0	0
apoptosis	-0.064	0.087	0.4	10	-10000	0	10
T-DHT/AR/PELP1	-0.023	0.1	-10000	0	-0.5	22	22
HRAS/GDP	-0.023	0.11	-10000	0	-0.51	22	22
CREB1	0.064	0.092	-10000	0	-0.43	10	10
RAC1-CDC42/GTP	0	0	-10000	0	-10000	0	0
AR	-0.02	0.16	-10000	0	-0.76	22	22
GNB1	0.016	0	-10000	0	-10000	0	0
RAF1	0.037	0.09	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.022	0.1	-10000	0	-0.48	22	22
T-DHT/AR/PELP1/Src	-0.02	0.094	-10000	0	-0.45	22	22
MAP2K2	0.048	0.09	-10000	0	-10000	0	0
T-DHT/AR/PELP1/Src/PI3K	-0.013	0.063	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
SHBG	-0.061	0.23	-10000	0	-0.76	47	47
Gi family/GNB1/GNG2/GDP	-0.008	0.045	-10000	0	-0.45	2	2
mol:T-DHT	0	0	-10000	0	-0.004	8	8
RAC1	0.016	0	-10000	0	-10000	0	0
GNRH1	-0.17	0.31	-10000	0	-0.68	129	129
Gi family/GTP	-0.013	0.06	-10000	0	-0.48	4	4
CDC42	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by VEGFR1 and VEGFR2

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.57	1	1
AKT1	-0.051	0.19	-9999	-0.69	2	2
PTK2B	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/Frs2	-0.003	0.044	-9999	-0.84	1	1
CAV1	-0.05	0.23	-9999	-0.86	36	36
CALM1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2	-0.23	0.25	-9999	-1.3	1	1
endothelial cell proliferation	-0.037	0.19	-9999	-0.69	1	1
mol:Ca2+	-0.16	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Rac	-0.21	0.24	-9999	-1.2	1	1
RP11-342D11.1	-0.17	0.26	-9999	-1.1	1	1
CDH5	0.014	0.04	-9999	-0.86	1	1
VEGFA homodimer	-0.23	0.26	-9999	-0.52	215	215
SHC1	0.014	0.04	-9999	-0.86	1	1
SHC2	0.009	0.075	-9999	-0.81	4	4
HRAS/GDP	-0.17	0.18	-9999	-0.91	1	1
SH2D2A	-0.28	0.42	-9999	-0.86	164	164
VEGFR2 homodimer/VEGFA homodimer/SHP1/eNOS	-0.14	0.15	-9999	-0.79	1	1
VEGFR2 homodimer/VEGFA homodimer/TsAd	-0.4	0.34	-9999	-1	65	65
VEGFR1 homodimer	0.008	0.08	-9999	-0.86	4	4
SHC/GRB2/SOS1	-0.18	0.21	-9999	-1.1	1	1
GRB10	-0.16	0.26	-9999	-1.1	1	1
PTPN11	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
PAK1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/IQGAP1/Cadherin/beta catenin	-0.2	0.22	-9999	-1	2	2
HRAS	0.016	0	-9999	-10000	0	0
VEGF/Rho/ROCK1/Integrin Complex	-0.084	0.094	-9999	-0.58	1	1
HIF1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
oxygen and reactive oxygen species metabolic process	-0.21	0.23	-9999	-1.2	1	1
mol:GTP	0	0	-9999	-10000	0	0
FLT4	0.016	0	-9999	-10000	0	0
Nck/Pak	0	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Fyn	-0.23	0.25	-9999	-1.3	1	1
mol:GDP	-0.18	0.2	-9999	-1	1	1
mol:NADP	-0.061	0.19	-9999	-0.62	1	1
eNOS/Hsp90	-0.05	0.18	-9999	-0.57	1	1
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	-0.16	0.27	-9999	-1.1	1	1
HIF1A/ARNT	0	0	-9999	-10000	0	0
SHB	0.016	0	-9999	-10000	0	0
VEGFA	-0.37	0.44	-9999	-0.86	215	215
VEGFC	0.014	0.04	-9999	-0.86	1	1
FAK1/Vinculin	-0.1	0.22	-9999	-1	1	1
mol:Ca ++	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/alphaV beta3 Integrin	-0.21	0.24	-9999	-1.2	1	1
PTPN6	0.016	0	-9999	-10000	0	0
EPAS1	0.026	0.039	-9999	-0.73	1	1
mol:L-citrulline	-0.061	0.19	-9999	-0.62	1	1
ITGAV	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/Frs2/GRB2	-0.21	0.24	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer	-0.22	0.25	-9999	-1.3	1	1
VEGFR2/3 heterodimer	-0.003	0.044	-9999	-0.84	1	1
VEGFB	0.016	0	-9999	-10000	0	0
MAPK11	-0.15	0.26	-9999	-1.1	1	1
VEGFR2 homodimer	0.043	0.052	-9999	-0.74	2	2
FLT1	0.008	0.08	-9999	-0.86	4	4
NEDD4	0.018	0.001	-9999	-10000	0	0
MAPK3	-0.14	0.25	-9999	-0.76	2	2
MAPK1	-0.14	0.25	-9999	-0.76	2	2
VEGFA145/NRP2	-0.3	0.33	-9999	-0.67	220	220
VEGFR1/2 heterodimer	-0.007	0.067	-9999	-0.62	5	5
KDR	0.044	0.053	-9999	-0.74	2	2
VEGFA165/NRP1/VEGFR2 homodimer	-0.21	0.23	-9999	-1.2	2	2
SRC	0.016	0	-9999	-10000	0	0
platelet activating factor biosynthetic process	-0.14	0.25	-9999	-0.78	2	2
PI3K	-0.16	0.18	-9999	-0.82	4	4
VEGFR2 homodimer/VEGFA homodimer/NCK1	-0.23	0.25	-9999	-1.3	1	1
FES	-0.16	0.27	-9999	-1	2	2
GAB1	-0.16	0.19	-9999	-0.82	4	4
VEGFR2 homodimer/VEGFA homodimer/Src	-0.23	0.25	-9999	-1.3	1	1
CTNNB1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
ARNT	0.016	0	-9999	-10000	0	0
eNOS/Caveolin-1	-0.081	0.2	-9999	-0.61	12	12
VEGFR2 homodimer/VEGFA homodimer/Yes	-0.23	0.25	-9999	-1.3	1	1
PI3K/GAB1	-0.051	0.19	-9999	-0.69	2	2
VEGFR2 homodimer/VEGFA homodimer/Frs2/Nck/Pak	-0.2	0.22	-9999	-1.2	1	1
PRKACA	0.016	0	-9999	-10000	0	0
VEGFR2/3 heterodimer/VEGFC homodimer	-0.004	0.046	-9999	-0.78	1	1
HSP90AA1	0.016	0	-9999	-10000	0	0
CDC42	-0.16	0.27	-9999	-1.2	1	1
actin cytoskeleton reorganization	-0.4	0.33	-9999	-1	65	65
PTK2	-0.12	0.24	-9999	-1.1	1	1
EDG1	-0.17	0.26	-9999	-1.1	1	1
mol:DAG	-0.16	0.27	-9999	-1.1	1	1
CaM/Ca2+	-0.18	0.21	-9999	-1	1	1
MAP2K3	-0.14	0.26	-9999	-1.1	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10/NEDD4	-0.21	0.23	-9999	-1.2	1	1
PLCG1	-0.16	0.27	-9999	-1.2	1	1
VEGFR2 homodimer/VEGFA homodimer/Src/Shb	-0.21	0.24	-9999	-1.2	1	1
IQGAP1	0.016	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
VEGFR2 homodimer/VEGFA homodimer/SHP2	-0.23	0.25	-9999	-1.3	1	1
VEGFR2 homodimer/VEGFA homodimer/SHP1	-0.23	0.25	-9999	-1.3	1	1
cell migration	-0.05	0.2	-9999	-0.77	1	1
mol:PI-3-4-5-P3	-0.15	0.17	-9999	-0.74	4	4
FYN	0.016	0	-9999	-10000	0	0
VEGFB/NRP1	-0.19	0.21	-9999	-1	1	1
mol:NO	-0.061	0.19	-9999	-0.62	1	1
PXN	0.016	0	-9999	-10000	0	0
HRAS/GTP	-0.17	0.18	-9999	-0.92	1	1
VEGFR2 homodimer/VEGFA homodimer/GRB10	-0.21	0.23	-9999	-1.2	1	1
VHL	0.016	0	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
NOS3	-0.071	0.2	-9999	-0.73	1	1
VEGFR2 homodimer/VEGFA homodimer/Sck	-0.23	0.26	-9999	-1.1	3	3
RAC1	0.016	0	-9999	-10000	0	0
PRKCA	-0.14	0.25	-9999	-1	1	1
PRKCB	-0.14	0.26	-9999	-0.96	2	2
VCL	0.016	0	-9999	-10000	0	0
VEGFA165/NRP1	-0.21	0.24	-9999	-1.2	1	1
VEGFR1/2 heterodimer/VEGFA homodimer	-0.23	0.26	-9999	-1.1	4	4
VEGFA165/NRP2	-0.3	0.33	-9999	-0.67	220	220
MAPKKK cascade	-0.16	0.18	-9999	-0.92	1	1
NRP2	0.003	0.11	-9999	-0.86	7	7
VEGFC homodimer	0.014	0.04	-9999	-0.86	1	1
NCK1	0.016	0	-9999	-10000	0	0
ROCK1	0.016	0	-9999	-10000	0	0
FAK1/Paxillin	-0.1	0.22	-9999	-1	1	1
MAP3K13	-0.16	0.27	-9999	-1.2	1	1
PDPK1	-0.068	0.2	-9999	-0.63	4	4

×

Stabilization and expansion of the E-cadherin 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
adherens junction organization	-0.012	0.058	-9999	-10000	0	0
epithelial cell differentiation	-0.016	0.08	-9999	-10000	0	0
CYFIP2	0.003	0.099	-9999	-0.76	8	8
ENAH	0.08	0.064	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
EPHA2	0.014	0.035	-9999	-0.76	1	1
MYO6	0.033	0.099	-9999	-0.8	2	2
CTNNB1	0.016	0	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.008	0.062	-9999	-0.48	8	8
AQP5	-0.17	0.24	-9999	-0.53	147	147
CTNND1	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.035	0.084	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.019	0.12	-9999	-0.85	1	1
EGF	-0.68	0.23	-9999	-0.76	432	432
NCKAP1	0.016	0	-9999	-10000	0	0
AQP3	-0.051	0.16	-9999	-0.58	35	35
cortical microtubule organization	-0.016	0.08	-9999	-10000	0	0
GO:0000145	0.035	0.08	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.016	0.081	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GDP	-0.013	0.062	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
Ephrin A1/EPHA2/NCK1/GIT1	-0.002	0.031	-9999	-0.52	1	1
mol:Ca2+	0	0	-9999	-10000	0	0
VASP	0.052	0.084	-9999	-0.59	1	1
PVRL2	0.016	0	-9999	-10000	0	0
ZYX	0.035	0.085	-9999	-10000	0	0
ARF6/GTP	-0.002	0.028	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
EGFR/EGFR/EGF/EGF	-0.35	0.15	-9999	-0.79	26	26
RhoA/GDP	-0.015	0.074	-9999	-10000	0	0
actin cytoskeleton organization	0.042	0.094	-9999	-0.73	2	2
IGF-1R heterotetramer	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
IGF1R	0.016	0	-9999	-10000	0	0
IGF1	0.003	0.11	-9999	-0.86	7	7
DIAPH1	-0.011	0.09	-9999	-0.7	8	8
Wnt receptor signaling pathway	0.016	0.08	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
RhoA/GTP	-0.013	0.063	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
VCL	0.042	0.096	-9999	-0.76	2	2
EFNA1	0.014	0.04	-9999	-0.86	1	1
LPP	0.045	0.089	-9999	-0.81	1	1
Ephrin A1/EPHA2	-0.016	0.075	-9999	-10000	0	0
SEC6/SEC8	-0.013	0.063	-9999	-10000	0	0
MGAT3	0.019	0.12	-9999	-0.88	1	1
HGF/MET	-0.037	0.13	-9999	-0.96	4	4
HGF	-0.021	0.17	-9999	-0.81	21	21
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN	-0.012	0.059	-9999	-10000	0	0
actin cable formation	0.1	0.07	-9999	-10000	0	0
KIAA1543	0.037	0.13	-9999	-0.87	6	6
KIFC3	0.034	0.087	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
EXOC3	0.016	0	-9999	-10000	0	0
ACTN1	0.034	0.093	-9999	-0.88	1	1
NCK1/GIT1	0	0	-9999	-10000	0	0
mol:GDP	-0.016	0.08	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
STX4	0.035	0.085	-9999	-10000	0	0
PIP5K1C	0.035	0.085	-9999	-10000	0	0
LIMA1	0.016	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
ROCK1	-0.012	0.054	-9999	-10000	0	0
adherens junction assembly	0.059	0.13	-9999	-0.8	7	7
IGF-1R heterotetramer/IGF1	-0.021	0.087	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PLEKHA7	0.032	0.1	-9999	-0.8	3	3
mol:GTP	-0.002	0.031	-9999	-0.52	1	1
establishment of epithelial cell apical/basal polarity	0.072	0.076	-9999	-10000	0	0
cortical actin cytoskeleton stabilization	-0.012	0.058	-9999	-10000	0	0
regulation of cell-cell adhesion	0.042	0.094	-9999	-0.73	2	2
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin/EPLIN/cortical actin cytoskeleton	-0.012	0.059	-9999	-10000	0	0

×

a4b1 and a4b7 Integrin signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
alpha4/beta1 Integrin	-0.022	0.12	-9999	-0.67	16	16

×

S1P4 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
mol:S1P	0	0	-9999	-10000	0	0
GNAO1	0.009	0.078	-9999	-0.84	4	4
CDC42/GTP	-0.017	0.061	-9999	-10000	0	0
PLCG1	0.035	0.078	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GNAI2	0.016	0	-9999	-10000	0	0
GNAI3	0.016	0	-9999	-10000	0	0
G12/G13	0	0	-9999	-10000	0	0
cell migration	-0.017	0.06	-9999	-10000	0	0
S1PR5	-0.14	0.33	-9999	-0.86	82	82
S1PR4	-0.03	0.2	-9999	-0.86	25	25
MAPK3	0.035	0.078	-9999	-10000	0	0
MAPK1	0.035	0.078	-9999	-10000	0	0
S1P/S1P5/Gi	-0.052	0.11	-9999	-10000	0	0
GNAI1	0.011	0.061	-9999	-0.76	3	3
CDC42/GDP	0	0	-9999	-10000	0	0
S1P/S1P5/G12	-0.1	0.22	-9999	-0.59	82	82
RHOA	0.016	0.12	-9999	-0.49	25	25
S1P/S1P4/Gi	-0.02	0.07	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
GNAZ	0.011	0.061	-9999	-0.76	3	3
S1P/S1P4/G12/G13	-0.028	0.12	-9999	-0.53	25	25
GNA12	0.016	0	-9999	-10000	0	0
GNA13	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

Signaling events regulated by Ret tyrosine kinase

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTK2	-0.011	0.035	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.032	0.091	-9999	-0.49	4	4
JUN	0.032	0.1	-9999	-0.53	4	4
HRAS	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/GRB10	-0.048	0.15	-9999	-0.69	10	10
RAP1A	0.016	0	-9999	-10000	0	0
FRS2	0.016	0	-9999	-10000	0	0
RAP1A/GDP	0	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/DOK1	-0.048	0.15	-9999	-0.71	9	9
EntrezGene:5979	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Enigma	-0.038	0.13	-9999	-0.48	38	38
RHOA	0.016	0	-9999	-10000	0	0
RAP1A/GTP	-0.042	0.14	-9999	-0.85	4	4
GRB7	0.004	0.093	-9999	-0.76	7	7
RET51/GFRalpha1/GDNF	-0.048	0.15	-9999	-0.51	37	37
MAPKKK cascade	-0.037	0.12	-9999	-0.72	4	4
BCAR1	0.014	0.035	-9999	-0.76	1	1
RET9/GFRalpha1/GDNF/IRS1	-0.035	0.12	-9999	-0.47	36	36
lamellipodium assembly	-0.03	0.085	-9999	-0.44	4	4
RET51/GFRalpha1/GDNF/SHC	-0.049	0.15	-9999	-0.67	11	11
PIK3CA	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC	-0.034	0.12	-9999	-0.47	35	35
RET9/GFRalpha1/GDNF/Shank3	-0.033	0.12	-9999	-0.47	34	34
MAPK3	0.011	0.14	-9999	-0.79	4	4
DOK1	0.016	0	-9999	-10000	0	0
DOK6	0	0.11	-9999	-0.76	10	10
PXN	0.016	0	-9999	-10000	0	0
neurite development	-0.039	0.12	-9999	-0.75	4	4
DOK5	-0.005	0.13	-9999	-0.77	13	13
GFRA1	-0.035	0.19	-9999	-0.77	31	31
MAPK8	0.021	0.11	-9999	-0.56	4	4
HRAS/GTP	-0.042	0.14	-9999	-0.85	4	4
tube development	-0.031	0.11	-9999	-0.44	34	34
MAPK1	0.011	0.14	-9999	-0.79	4	4
RET9/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.022	0.078	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PDLIM7	0.008	0.08	-9999	-0.86	4	4
RET51/GFRalpha1/GDNF/Dok6	-0.053	0.17	-9999	-0.9	10	10
SHC1	0.014	0.04	-9999	-0.86	1	1
RET51/GFRalpha1/GDNF/Dok4	-0.048	0.15	-9999	-0.71	9	9
RET51/GFRalpha1/GDNF/Dok5	-0.059	0.19	-9999	-0.59	41	41
PRKCA	0.016	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
CREB1	-0.028	0.093	-9999	-0.37	23	23
PIK3R1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.022	0.079	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/Grb7	-0.054	0.17	-9999	-0.82	12	12
mol:GDP	0	0	-9999	-10000	0	0
RET	-0.011	0.14	-9999	-0.77	16	16
DOK4	0.016	0	-9999	-10000	0	0
JNK cascade	0.032	0.1	-9999	-0.52	4	4
RET9/GFRalpha1/GDNF/FRS2	-0.033	0.12	-9999	-0.47	34	34
SHANK3	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.022	0.079	-9999	-0.31	22	22
RET51/GFRalpha1/GDNF/FRS2/SHP2/Grb2	-0.031	0.099	-9999	-0.61	4	4
RET51/GFRalpha1/GDNF/DOK/RasGAP/NCK	-0.031	0.099	-9999	-0.61	4	4
RET51/GFRalpha1/GDNF/SHC/Grb2/SOS1	-0.033	0.11	-9999	-0.76	4	4
PI3K	-0.045	0.13	-9999	-0.74	4	4
SOS1	0.016	0	-9999	-10000	0	0
RET9/GFRalpha1/GDNF/Shank3/Grb2	-0.031	0.11	-9999	-0.44	34	34
GRB10	0.016	0	-9999	-10000	0	0
activation of MAPKK activity	-0.028	0.089	-9999	-0.53	4	4
RET51/GFRalpha1/GDNF/FRS2	-0.048	0.15	-9999	-0.71	9	9
GAB1	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
IRS2	0.001	0.11	-9999	-0.86	8	8
RET51/GFRalpha1/GDNF/SHC/GAB1/Grb2	-0.033	0.11	-9999	-0.76	4	4
RET51/GFRalpha1/GDNF/PKC alpha	-0.048	0.15	-9999	-0.71	9	9
GRB2	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GDNF	0.001	0.069	-9999	-0.86	3	3
RAC1	0.016	0	-9999	-10000	0	0
RET51/GFRalpha1/GDNF/IRS1	-0.049	0.16	-9999	-0.71	9	9
Rac1/GTP	-0.036	0.1	-9999	-0.54	4	4
RET9/GFRalpha1/GDNF	-0.037	0.13	-9999	-0.52	34	34
GFRalpha1/GDNF	-0.042	0.15	-9999	-0.6	34	34

×

TCGA08_rtk_signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRA	-0.28	0.38	-9999	-0.76	184	184
HRAS	0.016	0	-9999	-10000	0	0
EGFR	-0.001	0.12	-9999	-0.85	9	9
AKT	0.036	0.03	-9999	-10000	0	0
FOXO3	0.016	0	-9999	-10000	0	0
AKT1	0.016	0	-9999	-10000	0	0
FOXO1	0.016	0	-9999	-10000	0	0
AKT3	0.016	0	-9999	-10000	0	0
FOXO4	0.016	0	-9999	-10000	0	0
MET	0.007	0.089	-9999	-0.86	5	5
PIK3CA	0.016	0	-9999	-10000	0	0
PIK3CB	0.016	0	-9999	-10000	0	0
NRAS	0.016	0	-9999	-10000	0	0
PIK3CG	0.01	0.069	-9999	-0.86	3	3
PIK3R3	0.016	0	-9999	-10000	0	0
PIK3R2	0.016	0	-9999	-10000	0	0
NF1	0.016	0	-9999	-10000	0	0
RAS	-0.041	0.099	-9999	-0.38	5	5
ERBB2	0.012	0.05	-9999	-0.76	2	2
proliferation/survival/translation	-0.041	0.013	-9999	-10000	0	0
PI3K	-0.022	0.092	-9999	-0.3	5	5
PIK3R1	0.016	0	-9999	-10000	0	0
KRAS	0.016	0	-9999	-10000	0	0
FOXO	0.041	0.034	-9999	-10000	0	0
AKT2	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0

×

Visual signal transduction: Cones

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Cone Metarhodopsin II/Cone Transducin	-0.028	0.12	-9999	-0.51	26	26
RGS9BP	-0.019	0.16	-9999	-0.76	21	21
mol:GTP	0	0	-9999	-10000	0	0
GRK1	0.003	0.006	-9999	-10000	0	0
mol:Na +	-0.012	0.085	-9999	-0.59	10	10
mol:ADP	0.013	0.033	-9999	-0.68	1	1
GNAT2	0.014	0.005	-9999	-10000	0	0
RGS9-1/Gbeta5/R9AP	-0.035	0.13	-9999	-0.5	33	33
mol:GDP	0	0	-9999	-10000	0	0
PDE6H/GNAT2/GTP	-0.001	0.027	-9999	-0.59	1	1
GRK7	0.01	0.041	-9999	-0.86	1	1
CNGB3	-0.008	0.11	-9999	-0.86	8	8
Cone Metarhodopsin II/X-Arrestin	0	0	-9999	-10000	0	0
mol:Ca2+	-0.009	0.12	-9999	-0.65	14	14
Cone PDE6	-0.033	0.12	-9999	-0.91	1	1
Cone Metarhodopsin II	-0.001	0.025	-9999	-0.56	1	1
Na + (4 Units)	-0.019	0.12	-9999	-0.65	14	14
GNAT2/GDP	-0.03	0.11	-9999	-0.5	7	7
GNB5	0.016	0	-9999	-10000	0	0
mol:GMP (4 units)	0.015	0.045	-9999	-0.54	3	3
Cone Transducin	-0.029	0.12	-9999	-0.54	26	26
SLC24A2	-0.01	0.1	-9999	-0.86	7	7
GNB3/GNGT2	-0.036	0.15	-9999	-0.67	26	26
GNB3	-0.033	0.2	-9999	-0.86	26	26
GNAT2/GTP	0	0	-9999	-10000	0	0
CNGA3	0.001	0.057	-9999	-0.86	2	2
ARR3	0.004	0.007	-9999	-10000	0	0
absorption of light	0	0	-9999	-10000	0	0
cGMP/Cone CNG Channel	-0.012	0.085	-9999	-0.6	10	10
mol:Pi	-0.035	0.13	-9999	-0.5	33	33
Cone CNG Channel	-0.013	0.085	-9999	-0.66	3	3
mol:all-trans-retinal	0	0	-9999	-10000	0	0
mol:K +	-0.01	0.1	-9999	-0.86	7	7
RGS9	-0.005	0.13	-9999	-0.82	12	12
PDE6C	0.003	0.057	-9999	-0.86	2	2
GNGT2	0.016	0	-9999	-10000	0	0
mol:cGMP (4 units)	0	0	-9999	-10000	0	0
PDE6H	0.003	0.04	-9999	-0.86	1	1

×

Canonical NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
FBXW11	0.02	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	0.074	0.074	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
RIP2/NOD2	-0.16	0.29	-9999	-0.67	118	118
NFKBIA	0.065	0	-9999	-10000	0	0
BIRC2	0.016	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
RIPK2	0.014	0.04	-9999	-0.86	1	1
IKBKG	-0.049	0.086	-9999	-10000	0	0
IKK complex/A20	-0.043	0.082	-9999	-0.59	2	2
NEMO/A20/RIP2	0.014	0.04	-9999	-0.86	1	1
XPO1	0.016	0	-9999	-10000	0	0
NEMO/ATM	-0.044	0.077	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
Exportin 1/RanGTP	0	0	-9999	-10000	0	0
IKK complex/ELKS	-0.036	0.063	-9999	-10000	0	0
BCL10/MALT1/TRAF6	0	0	-9999	-10000	0	0
NOD2	-0.2	0.38	-9999	-0.86	118	118
NFKB1	0.02	0	-9999	-10000	0	0
RELA	0.02	0	-9999	-10000	0	0
MALT1	0.016	0	-9999	-10000	0	0
cIAP1/UbcH5C	0	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
TNF/TNFR1A	-0.01	0.079	-9999	-0.62	8	8
TRAF6	0.016	0	-9999	-10000	0	0
PRKCA	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
UBE2D3	0.016	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
NF kappa B1 p50/RelA	0	0	-9999	-10000	0	0
BCL10	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.065	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.02	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
IKK complex	-0.04	0.071	-9999	-10000	0	0
CYLD	0.016	0	-9999	-10000	0	0
IKK complex/PKC alpha	-0.037	0.065	-9999	-10000	0	0

×

Signaling events mediated by PRL

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CCNE1	0.005	0.098	-10000	0	-0.86	6	6
mol:Halofuginone	0.007	0.001	-10000	0	-10000	0	0
ITGA1	0.016	0	-10000	0	-10000	0	0
CDKN1A	0.041	0.031	-10000	0	-10000	0	0
PRL-3/alpha Tubulin	-0.024	0.12	-10000	0	-0.67	17	17
mol:Ca2+	-0.021	0.17	0.41	17	-0.66	26	43
AGT	-0.03	0.19	-10000	0	-0.83	26	26
CCNA2	-0.056	0.23	-10000	0	-0.89	4	4
TUBA1B	0.016	0	-10000	0	-10000	0	0
EGR1	0.024	0.071	-10000	0	-0.56	7	7
CDK2/Cyclin E1	-0.008	0.055	-10000	0	-0.47	6	6
MAPK3	0.006	0.13	-10000	0	-0.67	17	17
PRL-2 /Rab GGTase beta	0	0	-10000	0	-10000	0	0
MAPK1	0.006	0.13	-10000	0	-0.67	17	17
PTP4A1	0.045	0.057	-10000	0	-10000	0	0
PTP4A3	-0.015	0.16	-10000	0	-0.86	17	17
PTP4A2	0.016	0	-10000	0	-10000	0	0
ITGB1	0.006	0.13	-10000	0	-0.67	17	17
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.032	0.06	-10000	0	-10000	0	0
Rab GGTase beta/Rab GGTase alpha	-0.002	0.037	-10000	0	-0.57	2	2
PRL-1/ATF-5	0.045	0.068	-10000	0	-10000	0	0
RABGGTA	0.012	0.05	-10000	0	-0.76	2	2
BCAR1	0.013	0.08	0.41	17	-0.59	1	18
RHOC	0.032	0.06	-10000	0	-10000	0	0
RHOA	0.032	0.06	-10000	0	-10000	0	0
cell motility	0.038	0.062	-10000	0	-10000	0	0
PRL-1/alpha Tubulin	0.049	0.053	-10000	0	-10000	0	0
PRL-3/alpha1 Integrin	-0.024	0.12	-10000	0	-0.67	17	17
ROCK1	0.038	0.062	-10000	0	-10000	0	0
RABGGTB	0.016	0	-10000	0	-10000	0	0
CDK2	0.016	0	-10000	0	-10000	0	0
mitosis	0.045	0.057	-10000	0	-10000	0	0
ATF5	0.01	0.069	-10000	0	-0.86	3	3

×

ErbB2/ErbB3 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
USP8	0.029	0.003	-10000	0	-10000	0	0
RAS family/GTP	-0.012	0.065	-10000	0	-0.71	2	2
NFATC4	0.027	0.072	-10000	0	-0.46	1	1
ERBB2IP	0.008	0.008	-10000	0	-10000	0	0
HSP90 (dimer)	0.016	0	-10000	0	-10000	0	0
mammary gland morphogenesis	-0.016	0.074	-10000	0	-0.65	1	1
JUN	0.038	0.077	-10000	0	-0.41	1	1
HRAS	0.015	0.001	-10000	0	-10000	0	0
DOCK7	0.022	0.085	-10000	0	-0.61	1	1
ErbB2/ErbB3/neuregulin 1 beta/SHC	-0.02	0.099	-10000	0	-0.89	2	2
AKT1	0.016	0.002	-10000	0	-10000	0	0
BAD	0.027	0.024	-10000	0	-0.5	1	1
MAPK10	-0.01	0.043	-10000	0	-0.4	1	1
mol:GTP	-0.002	0.003	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta	-0.017	0.08	-10000	0	-0.73	1	1
RAF1	0.042	0.087	-10000	0	-0.66	2	2
ErbB2/ErbB3/neuregulin 2	-0.022	0.1	-10000	0	-0.49	21	21
STAT3	0	0.002	-10000	0	-10000	0	0
cell migration	0.061	0.052	-10000	0	-10000	0	0
mol:PI-3-4-5-P3	0	0.001	-10000	0	-10000	0	0
cell proliferation	-0.088	0.26	-10000	0	-0.6	6	6
FOS	-0.036	0.19	-10000	0	-0.5	11	11
NRAS	0.015	0.001	-10000	0	-10000	0	0
mol:Ca2+	-0.016	0.074	-10000	0	-0.65	1	1
MAPK3	-0.057	0.21	-10000	0	-0.55	5	5
MAPK1	-0.057	0.21	-10000	0	-0.55	5	5
JAK2	0.022	0.085	-10000	0	-0.61	1	1
NF2	0	0.002	-10000	0	-10000	0	0
ErbB2/ErbB3/neuregulin 1 beta/SHC/GRB2/SOS1	0.008	0.088	-10000	0	-0.38	19	19
NRG1	-0.009	0.12	-10000	0	-0.76	11	11
GRB2/SOS1	0	0	-10000	0	-10000	0	0
MAPK8	0.027	0.078	-10000	0	-0.45	1	1
MAPK9	-0.007	0.034	-10000	0	-10000	0	0
ERBB2	-0.002	0.038	-10000	0	-0.59	2	2
ERBB3	-0.005	0.1	-10000	0	-0.76	9	9
SHC1	0.007	0.041	-10000	0	-0.86	1	1
RAC1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.002	0.016	0.34	1	-10000	0	1
STAT3 (dimer)	0	0.002	-10000	0	-10000	0	0
RNF41	0.038	0.005	-10000	0	-10000	0	0
FRAP1	0.015	0.002	-10000	0	-10000	0	0
RAC1-CDC42/GTP	-0.01	0.048	-10000	0	-0.4	1	1
ErbB2/ErbB2/HSP90 (dimer)	-0.002	0.032	-10000	0	-0.5	2	2
CHRNA1	-0.13	0.28	-10000	0	-0.45	212	212
myelination	0.054	0.068	-10000	0	-0.45	1	1
PPP3CB	0.022	0.08	-10000	0	-0.56	1	1
KRAS	0.015	0.001	-10000	0	-10000	0	0
RAC1-CDC42/GDP	-0.013	0.068	-10000	0	-0.73	2	2
NRG2	-0.002	0.12	-10000	0	-0.85	10	10
mol:GDP	0.008	0.087	-10000	0	-0.37	19	19
SOS1	0.009	0.008	-10000	0	-10000	0	0
MAP2K2	0.048	0.09	-10000	0	-0.6	2	2
SRC	0.016	0	-10000	0	-10000	0	0
mol:cAMP	0	0.001	-10000	0	-10000	0	0
PTPN11	0.021	0.084	-10000	0	-0.61	1	1
MAP2K1	-0.039	0.18	-10000	0	-0.56	5	5
heart morphogenesis	-0.016	0.074	-10000	0	-0.65	1	1
RAS family/GDP	-0.012	0.065	-10000	0	-0.71	2	2
GRB2	0.009	0.008	-10000	0	-10000	0	0
PRKACA	-0.001	0.005	-10000	0	-10000	0	0
CHRNE	0.021	0.024	-10000	0	-0.24	1	1
HSP90AA1	0.016	0	-10000	0	-10000	0	0
activation of caspase activity	-0.016	0.002	-10000	0	-10000	0	0
nervous system development	-0.016	0.074	-10000	0	-0.65	1	1
CDC42	0.016	0	-10000	0	-10000	0	0

×

Insulin-mediated glucose transport

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Insulin responsive Vesicles	-0.006	0.036	-10000	0	-10000	0	0
CaM/Ca2+	0	0	-10000	0	-10000	0	0
AKT1	0.016	0	-10000	0	-10000	0	0
AKT2	0.016	0	-10000	0	-10000	0	0
STXBP4	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:glucose	0.065	0.091	0.32	32	-0.37	1	33
YWHAZ	0.016	0	-10000	0	-10000	0	0
CALM1	0.016	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
TBC1D4	0.031	0	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
YWHAB	0.016	0	-10000	0	-10000	0	0
SNARE/Synip	0	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
ASIP	-0.066	0.25	-10000	0	-0.86	43	43
PRKCI	0.016	0	-10000	0	-10000	0	0
AS160/CaM/Ca2+	0	0	-10000	0	-10000	0	0
RHOQ	0.016	0	-10000	0	-10000	0	0
GYS1	0.044	0	-10000	0	-10000	0	0
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
TRIP10	0.016	0	-10000	0	-10000	0	0
TC10/GTP/CIP4/Exocyst	0	0	-10000	0	-10000	0	0
AS160/14-3-3	-0.022	0.062	-10000	0	-10000	0	0
VAMP2	0.016	0	-10000	0	-10000	0	0
SLC2A4	0.067	0.094	0.33	32	-0.41	1	33
STX4	0.016	0	-10000	0	-10000	0	0
GSK3B	0.035	0	-10000	0	-10000	0	0
SFN	-0.079	0.27	-10000	0	-0.84	53	53
LNPEP	0.014	0.035	-10000	0	-0.76	1	1
YWHAE	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class III

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EP300	0.016	0	-10000	0	-10000	0	0
HDAC4	0.016	0	-10000	0	-10000	0	0
induction of apoptosis	0	0	-10000	0	-10000	0	0
regulation of S phase of mitotic cell cycle	-0.026	0.032	0.67	1	-10000	0	1
CDKN1A	-0.003	0.042	-10000	0	-0.65	2	2
KAT2B	0.016	0	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
FOXO3	0	0	-10000	0	-10000	0	0
FOXO1	0.016	0	-10000	0	-10000	0	0
FOXO4	0.031	0	-10000	0	-10000	0	0
response to UV	0	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
TAT	0	0.1	-10000	0	-0.86	7	7
mol:Lysophosphatidic acid	0	0	-10000	0	-10000	0	0
MYOD1	-0.018	0.16	-10000	0	-0.67	27	27
PPARGC1A	-0.065	0.24	-10000	0	-0.76	50	50
FHL2	0.011	0.061	-10000	0	-0.76	3	3
response to nutrient levels	0	0	-10000	0	-10000	0	0
KU70/SIRT1	0.001	0.008	-10000	0	-10000	0	0
HIST2H4A	0.026	0.032	-10000	0	-0.67	1	1
SIRT1/FOXO3a	0	0.007	-10000	0	-10000	0	0
SIRT1	0.001	0.011	-10000	0	-10000	0	0
response to hypoxia	0	0	-10000	0	-10000	0	0
SIRT1/MEF2D/HDAC4	0.001	0.008	-10000	0	-10000	0	0
SIRT1/Histone H1b	0	0.015	-10000	0	-10000	0	0
apoptosis	-0.001	0.008	-10000	0	-10000	0	0
SIRT1/PGC1A	-0.052	0.15	-10000	0	-0.5	50	50
p53/SIRT1	0.002	0.024	0.38	2	-10000	0	2
SIRT1/FOXO4	0.001	0.009	-10000	0	-10000	0	0
FOXO1/FHL2/SIRT1	-0.002	0.036	-10000	0	-0.45	3	3
HIST1H1E	0.029	0.015	-10000	0	-0.3	1	1
SIRT1/p300	0.001	0.008	-10000	0	-10000	0	0
muscle cell differentiation	0.032	0.13	0.57	27	-10000	0	27
TP53	0.001	0.011	-10000	0	-10000	0	0
KU70/SIRT1/BAX	0.001	0.008	-10000	0	-10000	0	0
CREBBP	0.016	0	-10000	0	-10000	0	0
MEF2D	0.016	0	-10000	0	-10000	0	0
HIV-1 Tat/SIRT1	-0.009	0.081	-10000	0	-0.67	7	7
ACSS2	0.028	0.005	-10000	0	-10000	0	0
SIRT1/PCAF/MYOD	-0.032	0.13	-10000	0	-0.58	27	27

×

IL1-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
UBC13/UEV1A	0	0	-9999	-10000	0	0
PRKCZ	0.011	0.061	-9999	-0.76	3	3
MAP3K7IP2	0	0	-9999	-10000	0	0
ERC1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4	-0.003	0.023	-9999	-10000	0	0
IRAK/TOLLIP	0	0	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
IKBKG	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R2	-0.09	0.22	-9999	-0.62	69	69
IL1A	-0.008	0.14	-9999	-0.86	12	12
IL1B	0.025	0.062	-9999	-0.64	4	4
IRAK/TRAF6/p62/Atypical PKCs	-0.002	0.029	-9999	-10000	0	0
IL1R2	-0.082	0.26	-9999	-0.8	58	58
IL1R1	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.002	0.019	-9999	-10000	0	0
TOLLIP	0.016	0	-9999	-10000	0	0
TICAM2	0.016	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
IKK complex/ELKS	0.042	0.047	-9999	-10000	0	0
JUN	0.062	0.025	-9999	-10000	0	0
MAP3K7	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/PI3K	-0.006	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88	-0.015	0.088	-9999	-0.52	14	14
PIK3R1	0.016	0	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4	-0.014	0.082	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP	-0.006	0.057	-9999	-0.52	5	5
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.053	0.027	-9999	-10000	0	0
IRAK1	0.031	0.006	-9999	-10000	0	0
IL1RN/IL1R1	-0.024	0.12	-9999	-0.67	17	17
IRAK4	0.016	0	-9999	-10000	0	0
PRKCI	0.016	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.003	0.025	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/MYD88s	-0.006	0.057	-9999	-0.52	5	5
IL1 beta/IL1R2	-0.067	0.18	-9999	-0.52	62	62
IRAK/TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.005	0.044	-9999	-10000	0	0
IRAK3	0.016	0	-9999	-10000	0	0
IL1 beta fragment/IL1R1/IL1RAP/TICAM2/IRAK4	-0.006	0.05	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/TOLLIP	-0.008	0.046	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP	-0.017	0.097	-9999	-0.58	14	14
RELA	0.016	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
SQSTM1	0.016	0	-9999	-10000	0	0
MYD88	0.016	0	-9999	-10000	0	0
IRAK/TRAF6/MEKK3	0	0	-9999	-10000	0	0
IL1RAP	0.012	0.057	-9999	-0.86	2	2
UBE2N	0.016	0	-9999	-10000	0	0
IRAK/TRAF6	-0.004	0.04	-9999	-10000	0	0
CASP1	0.016	0	-9999	-10000	0	0
IL1RN/IL1R2	-0.096	0.23	-9999	-0.63	73	73
IL1 beta fragment/IL1R1/IL1RAP/MYD88	-0.006	0.053	-9999	-10000	0	0
TMEM189-UBE2V1	0.007	0.008	-9999	-10000	0	0
IL1 alpha/IL1R1/IL1RAP/MYD88/IRAK4/IRAK/TOLLIP	-0.005	0.031	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
IL1RN	-0.015	0.16	-9999	-0.86	17	17
TRAF6/TAK1/TAB1/TAB2	0	0	-9999	-10000	0	0
MAP2K6	0.044	0.028	-9999	-10000	0	0

×

Signaling mediated by p38-gamma and p38-delta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
EEF2K	0.036	0.055	-9999	-0.5	5	5
SNTA1	0.012	0.053	-9999	-0.81	2	2
response to hypoxia	0	0	-9999	-10000	0	0
STMN1	0.037	0.048	-9999	-0.48	4	4
MAPK12	0.03	0.083	-9999	-0.5	11	11
CCND1	0.013	0.07	-9999	-0.28	20	20
p38 gamma/SNTA1	0.034	0.088	-9999	-0.52	10	10
MAP2K3	0.016	0	-9999	-10000	0	0
PKN1	0.016	0	-9999	-10000	0	0
G2/M transition checkpoint	0.03	0.082	-9999	-0.5	11	11
MAP2K6	0.031	0.037	-9999	-0.48	2	2
MAPT	0.033	0.068	-9999	-0.46	6	6
MAPK13	0.026	0.055	-9999	-0.57	4	4
hyperosmotic response	0	0	-9999	-10000	0	0
ZAK	0.022	0.019	-9999	-0.39	1	1

×

Syndecan-3-mediated signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	0.016	0	-9999	-10000	0	0
Syndecan-3/Src/Cortactin	-0.014	0.07	-9999	-10000	0	0
Syndecan-3/Neurocan	-0.011	0.072	-9999	-0.48	11	11
POMC	0.014	0.035	-9999	-0.76	1	1
EGFR	-0.001	0.12	-9999	-0.85	9	9
Syndecan-3/EGFR	-0.01	0.068	-9999	-0.47	10	10
AGRP	0.006	0.05	-9999	-0.76	2	2
NCSTN	0.016	0	-9999	-10000	0	0
PSENEN	0.016	0	-9999	-10000	0	0
RP11-540L11.1	0	0	-9999	-10000	0	0
APH1B	0.016	0	-9999	-10000	0	0
APH1A	0.016	0	-9999	-10000	0	0
NCAN	-0.007	0.12	-9999	-0.86	10	10
long-term memory	-0.001	0.017	-9999	-10000	0	0
Syndecan-3/IL8	-0.032	0.12	-9999	-0.48	32	32
PSEN1	0.016	0	-9999	-10000	0	0
Src/Cortactin	0	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
limb bud formation	-0.001	0.019	-9999	-0.43	1	1
MC4R	-0.01	0.11	-9999	-0.86	8	8
SRC	0.016	0	-9999	-10000	0	0
PTN	-0.012	0.14	-9999	-0.76	17	17
FGFR/FGF/Syndecan-3	-0.001	0.02	-9999	-0.43	1	1
neuron projection morphogenesis	-0.022	0.089	-9999	-10000	0	0
Syndecan-3/AgRP	-0.003	0.032	-9999	-0.41	3	3
Syndecan-3/AgRP/MC4R	-0.01	0.067	-9999	-0.47	8	8
Fyn/Cortactin	0	0	-9999	-10000	0	0
SDC3	-0.001	0.02	-9999	-0.43	1	1
GO:0007205	0	0	-9999	-10000	0	0
positive regulation of leukocyte migration	-0.031	0.12	-9999	-0.47	32	32
IL8	-0.04	0.21	-9999	-0.85	31	31
Syndecan-3/Fyn/Cortactin	-0.001	0.017	-9999	-10000	0	0
Syndecan-3/CASK	-0.001	0.019	-9999	-0.41	1	1
alpha-MSH/MC4R	-0.012	0.089	-9999	-0.66	9	9
Gamma Secretase	0	0	-9999	-10000	0	0

×

Arf6 trafficking events

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
SLC2A4	-0.003	0.12	-9999	-0.82	11	11
CLTC	0.044	0	-9999	-10000	0	0
calcium ion-dependent exocytosis	0.037	0	-9999	-10000	0	0
Dynamin 2/GTP	0	0	-9999	-10000	0	0
EXOC4	0.016	0	-9999	-10000	0	0
CD59	0.04	0	-9999	-10000	0	0
CPE	0	0.12	-9999	-0.58	20	20
CTNNB1	0.016	0	-9999	-10000	0	0
membrane fusion	0	0	-9999	-10000	0	0
CTNND1	0.044	0	-9999	-10000	0	0
DNM2	0.016	0	-9999	-10000	0	0
mol:PI-4-5-P2	0.045	0	-9999	-10000	0	0
TSHR	-0.048	0.2	-9999	-0.59	57	57
INS	0.017	0.001	-9999	-10000	0	0
BIN1	0.016	0	-9999	-10000	0	0
mol:Choline	0	0	-9999	-10000	0	0
growth hormone secretagogue receptor activity	0	0	-9999	-10000	0	0
mol:GDP	0.025	0	-9999	-10000	0	0
membrane depolarization	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
JUP	0.038	0.022	-9999	-10000	0	0
ASAP2/amphiphysin II	0	0	-9999	-10000	0	0
ARF6/GTP	0	0	-9999	-10000	0	0
CDH1	0.028	0.055	-9999	-10000	0	0
clathrin-independent pinocytosis	0	0	-9999	-10000	0	0
MAPK8IP3	-0.05	0.23	-9999	-0.86	36	36
positive regulation of endocytosis	0	0	-9999	-10000	0	0
EXOC2	0.016	0	-9999	-10000	0	0
substrate adhesion-dependent cell spreading	0	0	-9999	-10000	0	0
insulin receptor binding	0	0	-9999	-10000	0	0
SPAG9	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.006	0.03	-9999	-10000	0	0
positive regulation of phagocytosis	0.025	0	-9999	-10000	0	0
ARF6/GTP/JIP3	-0.044	0.16	-9999	-0.59	36	36
ACAP1	-0.019	0.024	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CHRM2	0.033	0.012	-9999	-10000	0	0
clathrin heavy chain/ACAP1	0.043	0.011	-9999	-10000	0	0
JIP4/KLC1	0	0	-9999	-10000	0	0
EXOC1	0.016	0	-9999	-10000	0	0
exocyst	0	0	-9999	-10000	0	0
RALA/GTP	0	0	-9999	-10000	0	0
ARF6/GTP/ARF6/GTP/JIP4/Dynactin Complex	0	0	-9999	-10000	0	0
receptor recycling	0	0	-9999	-10000	0	0
CTNNA1	0.044	0	-9999	-10000	0	0
NME1	0.025	0	-9999	-10000	0	0
clathrin coat assembly	0.043	0	-9999	-10000	0	0
IL2RA	-0.015	0.11	-9999	-10000	0	0
VAMP3	0.025	0	-9999	-10000	0	0
GLUT4/clathrin heavy chain/ACAP1	-0.009	0.06	-9999	-0.43	6	6
EXOC6	0.016	0	-9999	-10000	0	0
PLD1	0	0	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
EXOC5	0.016	0	-9999	-10000	0	0
PIP5K1C	0.045	0	-9999	-10000	0	0
SDC1	0.037	0.029	-9999	-10000	0	0
ARF6/GDP	0	0	-9999	-10000	0	0
EXOC7	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin	-0.006	0.031	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
endocytosis	0	0	-9999	-10000	0	0
SCAMP2	0.016	0	-9999	-10000	0	0
ADRB2	0.05	0.028	-9999	-10000	0	0
EXOC3	0.016	0	-9999	-10000	0	0
ASAP2	0.016	0	-9999	-10000	0	0
Dynamin 2/GDP	0	0	-9999	-10000	0	0
KLC1	0.016	0	-9999	-10000	0	0
AVPR2	-0.13	0.21	-9999	-0.38	200	200
RALA	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.005	0.026	-9999	-10000	0	0

×

Class IB PI3K non-lipid kinase events

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
cAMP biosynthetic process	-0.007	0.081	0.78	5	-10000	0	5
PI3K Class IB/PDE3B	0.007	0.081	-10000	0	-0.78	5	5
PDE3B	0.007	0.081	-10000	0	-0.78	5	5

×

Arf6 downstream pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PLAUR	0.021	0.17	-10000	0	-0.72	24	24
regulation of axonogenesis	-0.034	0.032	-10000	0	-10000	0	0
myoblast fusion	0.016	0.069	0.32	24	-10000	0	24
mol:GTP	-0.01	0.043	-10000	0	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	0.009	0.041	0.46	1	-10000	0	1
ARF1/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GM1	0.007	0.035	-10000	0	-10000	0	0
mol:Choline	0.033	0.03	-10000	0	-10000	0	0
lamellipodium assembly	-0.016	0.072	-10000	0	-0.33	24	24
MAPK3	0.024	0.068	-10000	0	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.009	0.041	-10000	0	-0.46	1	1
ARF1	0.016	0	-10000	0	-10000	0	0
ARF6/GDP	-0.016	0.07	-10000	0	-0.32	24	24
ARF1/GDP	-0.014	0.062	-10000	0	-10000	0	0
ARF6	0.009	0.024	-10000	0	-10000	0	0
RAB11A	0.016	0	-10000	0	-10000	0	0
TIAM1	0.016	0.035	-10000	0	-0.76	1	1
fibronectin binding	0	0	-10000	0	-10000	0	0
MAPK1	0.024	0.068	-10000	0	-10000	0	0
actin filament bundle formation	0.014	0.062	-10000	0	-10000	0	0
KALRN	-0.012	0.055	-10000	0	-10000	0	0
RAB11FIP3/RAB11A	-0.001	0.026	-10000	0	-0.57	1	1
RhoA/GDP	-0.014	0.062	-10000	0	-10000	0	0
NME1	0.017	0.004	-10000	0	-10000	0	0
Rac1/GDP	-0.014	0.062	-10000	0	-10000	0	0
substrate adhesion-dependent cell spreading	-0.01	0.043	-10000	0	-10000	0	0
cortical actin cytoskeleton organization	-0.016	0.073	-10000	0	-0.33	24	24
RAC1	0.016	0	-10000	0	-10000	0	0
liver development	-0.01	0.043	-10000	0	-10000	0	0
ARF6/GTP	-0.01	0.043	-10000	0	-10000	0	0
RhoA/GTP	-0.007	0.029	-10000	0	-10000	0	0
mol:GDP	-0.016	0.07	-10000	0	-0.32	24	24
ARF6/GTP/RAB11FIP3/RAB11A	-0.006	0.03	-10000	0	-0.47	1	1
RHOA	0.016	0	-10000	0	-10000	0	0
PLD1	0.021	0.035	-10000	0	-10000	0	0
RAB11FIP3	0.014	0.035	-10000	0	-0.76	1	1
tube morphogenesis	-0.016	0.072	-10000	0	-0.33	24	24
ruffle organization	0.034	0.032	-10000	0	-10000	0	0
regulation of epithelial cell migration	-0.01	0.043	-10000	0	-10000	0	0
PLD2	0.021	0.035	-10000	0	-10000	0	0
PIP5K1A	0.034	0.032	-10000	0	-10000	0	0
mol:Phosphatidic acid	0.033	0.03	-10000	0	-10000	0	0
Rac1/GTP	-0.016	0.073	-10000	0	-0.33	24	24

×

Ephrin B reverse signaling

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
EFNB2	0.016	0	-10000	0	-10000	0	0
EPHB2	0.001	0.11	-10000	0	-0.78	9	9
EFNB1	0.018	0.095	-10000	0	-0.67	9	9
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.018	0.092	-10000	0	-0.76	2	2
Ephrin B2/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
neuron projection morphogenesis	-0.017	0.088	-10000	0	-0.72	2	2
Ephrin B1/EPHB1-2/Tiam1	-0.02	0.1	-10000	0	-0.83	2	2
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
cell-cell signaling	0.001	0.001	-10000	0	-10000	0	0
MAP2K4	0.025	0.086	-10000	0	-0.68	7	7
YES1	-0.013	0.11	-10000	0	-0.9	7	7
Ephrin B1/EPHB1-2/NCK2	-0.019	0.094	-10000	0	-0.83	1	1
PI3K	-0.009	0.083	-10000	0	-0.68	7	7
mol:GDP	-0.019	0.099	-10000	0	-0.81	2	2
ITGA2B	-0.012	0.15	-10000	0	-0.86	15	15
endothelial cell proliferation	0	0	-10000	0	-10000	0	0
FYN	-0.013	0.11	-10000	0	-0.9	7	7
MAP3K7	-0.01	0.087	-10000	0	-0.72	7	7
FGR	-0.013	0.11	-10000	0	-0.9	7	7
TIAM1	0.014	0.035	-10000	0	-0.76	1	1
PIK3R1	0.016	0	-10000	0	-10000	0	0
RGS3	0.016	0	-10000	0	-10000	0	0
cell adhesion	-0.019	0.12	-10000	0	-0.63	9	9
LYN	-0.013	0.11	-10000	0	-0.9	7	7
Ephrin B1/EPHB1-2/Src Family Kinases	-0.013	0.1	-10000	0	-0.85	7	7
Ephrin B1/EPHB1-2	-0.014	0.095	-10000	0	-0.79	7	7
SRC	-0.013	0.11	-10000	0	-0.9	7	7
ITGB3	0.014	0.035	-10000	0	-0.76	1	1
EPHB1	0.012	0.054	-10000	0	-0.81	2	2
EPHB4	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
alphaIIb/beta3 Integrin	-0.022	0.12	-10000	0	-0.66	16	16
BLK	-0.02	0.11	-10000	0	-0.89	7	7
HCK	-0.019	0.12	-10000	0	-0.94	7	7
regulation of stress fiber formation	0.019	0.093	0.81	1	-10000	0	1
MAPK8	0.034	0.082	-10000	0	-0.64	7	7
Ephrin B1/EPHB1-2/RGS3	-0.019	0.094	-10000	0	-0.83	1	1
endothelial cell migration	-0.007	0.075	-10000	0	-0.62	7	7
NCK2	0.016	0	-10000	0	-10000	0	0
PTPN13	-0.008	0.1	-10000	0	-0.86	7	7
regulation of focal adhesion formation	0.019	0.093	0.81	1	-10000	0	1
chemotaxis	0.019	0.093	0.81	1	-10000	0	1
PIK3CA	0.016	0	-10000	0	-10000	0	0
Rac1/GTP	-0.018	0.09	-10000	0	-0.75	2	2
angiogenesis	-0.014	0.094	-10000	0	-0.78	7	7
LCK	-0.018	0.11	-10000	0	-0.92	7	7

×

E-cadherin signaling in the nascent adherens junction

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CTTN	-0.02	0.1	-9999	-0.52	19	19
KLHL20	-0.013	0.045	-9999	-0.33	1	1
CYFIP2	0.003	0.099	-9999	-0.76	8	8
Rac1/GDP	0.068	0.076	-9999	-10000	0	0
ENAH	-0.02	0.1	-9999	-0.52	19	19
AP1M1	0.016	0	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.015	0.003	-9999	-10000	0	0
CDC42/GTP	-0.01	0.047	-9999	-10000	0	0
ABI1/Sra1/Nap1	-0.011	0.037	-9999	-0.22	7	7
E-cadherin/beta catenin/alpha catenin/beta7/alphaE Integrin	-0.017	0.085	-9999	-10000	0	0
RAPGEF1	0.055	0.099	-9999	-10000	0	0
CTNND1	0.016	0	-9999	-10000	0	0
regulation of calcium-dependent cell-cell adhesion	-0.021	0.11	-9999	-0.54	19	19
CRK	0.043	0.11	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin	-0.022	0.11	-9999	-0.51	21	21
alphaE/beta7 Integrin	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
NCKAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
DLG1	-0.02	0.1	-9999	-0.52	19	19
ChemicalAbstracts:7440-70-2	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.007	0.033	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
ARF6/GTP/NME1/Tiam1	-0.001	0.02	-9999	-0.45	1	1
PI3K	-0.009	0.043	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
E-cadherin/gamma catenin	-0.026	0.12	-9999	-0.59	21	21
TIAM1	0.014	0.035	-9999	-0.76	1	1
E-cadherin(dimer)/Ca2+	-0.016	0.08	-9999	-10000	0	0
AKT1	-0.005	0.024	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
RhoA/GDP	0.068	0.075	-9999	-10000	0	0
actin cytoskeleton organization	-0.01	0.033	-9999	-0.23	1	1
CDC42/GDP	0.068	0.075	-9999	-10000	0	0
E-cadherin/Ca2+/gamma catenin/alpha catenin/p120 catenin	-0.014	0.068	-9999	-0.33	21	21
ITGB7	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin/p120 catenin	-0.017	0.085	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin	-0.017	0.083	-9999	-0.42	19	19
mol:GDP	0.064	0.087	-9999	-10000	0	0
CDC42/GTP/IQGAP1	0	0	-9999	-10000	0	0
JUP	0.011	0.061	-9999	-0.76	3	3
p120 catenin/RhoA/GDP	-0.012	0.06	-9999	-10000	0	0
RAC1/GTP/IQGAP1	0	0	-9999	-10000	0	0
PIP5K1C/AP1M1	0	0	-9999	-10000	0	0
RHOA	0.016	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
positive regulation of S phase of mitotic cell cycle	0.035	0.066	-9999	-0.26	20	20
NME1	0.016	0	-9999	-10000	0	0
clathrin coat assembly	0	0	-9999	-10000	0	0
TJP1	-0.02	0.1	-9999	-0.52	19	19
regulation of cell-cell adhesion	-0.008	0.041	-9999	-10000	0	0
WASF2	-0.005	0.019	-9999	-10000	0	0
Rap1/GTP	-0.011	0.054	-9999	-10000	0	0
E-cadherin/gamma catenin/alpha catenin/beta7/alphaE Integrin	-0.018	0.088	-9999	-0.83	1	1
CCND1	-0.017	0.068	-9999	-0.33	20	20
VAV2	0.05	0.1	-9999	-0.51	1	1
RAP1/GDP	-0.011	0.056	-9999	-10000	0	0
adherens junction assembly	0.033	0.11	-9999	-0.5	19	19
homophilic cell adhesion	0	0	-9999	-10000	0	0
ABI1	0.016	0	-9999	-10000	0	0
PIP5K1C	0.016	0	-9999	-10000	0	0
regulation of heterotypic cell-cell adhesion	-0.017	0.083	-9999	-0.79	1	1
E-cadherin/beta catenin	-0.018	0.09	-9999	-0.46	19	19
mol:GTP	0	0	-9999	-10000	0	0
SRC	-0.02	0.1	-9999	-0.52	19	19
PIK3CA	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.021	0.073	-9999	-0.6	1	1
E-cadherin/beta catenin/alpha catenin	-0.019	0.095	-9999	-0.48	19	19
ITGAE	0.016	0	-9999	-10000	0	0
E-cadherin/Ca2+/beta catenin/alpha catenin/p120 catenin	-0.022	0.11	-9999	-0.56	19	19

×

p38 MAPK signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TRAF6/ASK1	0	0	-9999	-10000	0	0
TRAF2/ASK1	0	0	-9999	-10000	0	0
ATM	0.016	0	-9999	-10000	0	0
MAP2K3	0.038	0.042	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.051	0.041	-9999	-10000	0	0
hyperosmotic response	0	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
GADD45G	-0.004	0.13	-9999	-0.86	11	11
TXN	0.011	0	-9999	-10000	0	0
CALM1	0.016	0	-9999	-10000	0	0
GADD45A	0.016	0	-9999	-10000	0	0
GADD45B	0.016	0	-9999	-10000	0	0
MAP3K1	0.016	0	-9999	-10000	0	0
MAP3K6	0.014	0.035	-9999	-0.76	1	1
MAP3K7	0.016	0	-9999	-10000	0	0
MAP3K4	0.016	0	-9999	-10000	0	0
mol:Ca2+	0	0	-9999	-10000	0	0
ASK1/ASK2	-0.001	0.026	-9999	-0.57	1	1
TAK1/TAB family	0	0	-9999	-10000	0	0
RAC1/OSM/MEKK3	0	0	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	-0.003	0.011	-9999	-10000	0	0
TRAF6	0.011	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
CAMK2B	-0.11	0.28	-9999	-0.76	75	75
CCM2	0.016	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB	-0.079	0.18	-9999	-0.5	75	75
MAPK11	0.016	0	-9999	-10000	0	0
response to DNA damage stimulus	0	0	-9999	-10000	0	0
CaM/Ca2+/CAMKIIB/ASK1	-0.071	0.16	-9999	-0.53	5	5
OSM/MEKK3	0	0	-9999	-10000	0	0
TAOK1	0.02	0.035	-9999	-0.42	3	3
TAOK2	0.023	0	-9999	-10000	0	0
TAOK3	0.023	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
MAP3K7IP2	0	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAP3K10	0.014	0.035	-9999	-0.76	1	1
MAP3K3	0.016	0	-9999	-10000	0	0
TRX/ASK1	0	0	-9999	-10000	0	0
GADD45/MTK1/MTK1	-0.011	0.073	-9999	-0.5	10	10

×

Ras signaling in the CD4+ TCR pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
ERK1-2/ELK1	0.051	0.11	-9999	-0.65	4	4
MAP3K8	0.012	0.057	-9999	-0.86	2	2
FOS	0.043	0.1	-9999	-0.55	4	4
PRKCA	0.017	0.003	-9999	-10000	0	0
PTPN7	-0.037	0.21	-9999	-0.86	30	30
HRAS	0.016	0.002	-9999	-10000	0	0
PRKCB	0.008	0.086	-9999	-0.83	5	5
NRAS	0.016	0.002	-9999	-10000	0	0
RAS family/GTP	0	0	-9999	-10000	0	0
MAPK3	0.031	0.082	-9999	-0.52	2	2
MAP2K1	0.055	0.057	-9999	-0.48	5	5
ELK1	0.017	0.003	-9999	-10000	0	0
BRAF	-0.005	0.045	-9999	-0.46	4	4
mol:GTP	0	0.001	-9999	-0.006	9	9
MAPK1	0.031	0.082	-9999	-0.52	2	2
RAF1	-0.005	0.045	-9999	-0.46	4	4
KRAS	0.016	0.002	-9999	-10000	0	0

×

BARD1 signaling events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BARD1/CSTF1	-0.004	0.045	-10000	0	-0.57	3	3
ATM	0.016	0	-10000	0	-10000	0	0
UBE2D3	0.016	0	-10000	0	-10000	0	0
PRKDC	0.016	0	-10000	0	-10000	0	0
ATR	0.016	0	-10000	0	-10000	0	0
UBE2L3	0.016	0	-10000	0	-10000	0	0
FANCD2	0.035	0	-10000	0	-10000	0	0
protein ubiquitination	-0.008	0.062	-10000	0	-10000	0	0
XRCC5	0.016	0	-10000	0	-10000	0	0
XRCC6	0.016	0	-10000	0	-10000	0	0
M/R/N Complex	0	0	-10000	0	-10000	0	0
MRE11A	0.016	0	-10000	0	-10000	0	0
DNA-PK	0	0	-10000	0	-10000	0	0
FA complex/FANCD2/Ubiquitin	-0.035	0.069	-10000	0	-0.52	1	1
FANCF	0.016	0	-10000	0	-10000	0	0
BRCA1	0.016	0	-10000	0	-10000	0	0
CCNE1	0.005	0.098	-10000	0	-0.86	6	6
CDK2/Cyclin E1	-0.008	0.074	-10000	0	-0.67	6	6
FANCG	0.016	0	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1	-0.004	0.045	-10000	0	-0.57	3	3
FANCE	0.014	0.04	-10000	0	-0.86	1	1
FANCC	0.016	0	-10000	0	-10000	0	0
NBN	0.016	0	-10000	0	-10000	0	0
FANCA	-0.18	0.36	-10000	0	-0.86	105	105
DNA repair	0.044	0.13	-10000	0	-0.67	5	5
BRCA1/BARD1/ubiquitin	-0.004	0.045	-10000	0	-0.57	3	3
BARD1/DNA-PK	-0.003	0.034	-10000	0	-10000	0	0
FANCL	0.016	0	-10000	0	-10000	0	0
mRNA polyadenylation	0.004	0.045	0.57	3	-10000	0	3
BRCA1/BARD1/CTIP/M/R/N Complex	-0.002	0.022	-10000	0	-10000	0	0
BRCA1/BACH1/BARD1/TopBP1	-0.003	0.038	-10000	0	-0.48	3	3
BRCA1/BARD1/P53	-0.003	0.034	-10000	0	-10000	0	0
BARD1/CSTF1/BRCA1	-0.003	0.038	-10000	0	-0.48	3	3
BRCA1/BACH1	0.016	0	-10000	0	-10000	0	0
BARD1	0.011	0.061	-10000	0	-0.76	3	3
PCNA	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/UbcH5C	-0.003	0.038	-10000	0	-0.48	3	3
BRCA1/BARD1/UbcH7	-0.003	0.038	-10000	0	-0.48	3	3
BRCA1/BARD1/RAD51/PCNA	-0.016	0.088	-10000	0	-0.52	12	12
BARD1/DNA-PK/P53	-0.003	0.032	-10000	0	-10000	0	0
BRCA1/BARD1/Ubiquitin	-0.004	0.045	-10000	0	-0.57	3	3
BRCA1/BARD1/CTIP	-0.003	0.034	-10000	0	-10000	0	0
FA complex	-0.059	0.11	-10000	0	-0.57	1	1
BARD1/EWS	-0.004	0.045	-10000	0	-0.57	3	3
RBBP8	0.031	0	-10000	0	-10000	0	0
TP53	0.016	0	-10000	0	-10000	0	0
TOPBP1	0.016	0	-10000	0	-10000	0	0
G1/S transition of mitotic cell cycle	0.003	0.034	-10000	0	-10000	0	0
BRCA1/BARD1	-0.009	0.062	-10000	0	-10000	0	0
CSTF1	0.016	0	-10000	0	-10000	0	0
BARD1/EWS-Fli1	-0.004	0.046	-10000	0	-0.58	3	3
CDK2	0.016	0	-10000	0	-10000	0	0
UniProt:Q9BZD1	0	0	-10000	0	-10000	0	0
RAD51	-0.006	0.14	-10000	0	-0.86	12	12
RAD50	0.016	0	-10000	0	-10000	0	0
BRCA1/BARD1/DNA-directed RNA polymerase II holoenzyme	-0.004	0.045	-10000	0	-0.57	3	3
EWSR1	0.016	0	-10000	0	-10000	0	0

×

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

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MET/RANBP9	-0.007	0.068	-9999	-0.67	5	5
CRKL	0.041	0.065	-9999	-0.46	2	2
mol:PIP3	-0.03	0.003	-9999	-10000	0	0
AKT1	0.001	0.002	-9999	-10000	0	0
PTK2B	0.016	0	-9999	-10000	0	0
RAPGEF1	0.05	0.062	-9999	-10000	0	0
RANBP10	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
HGF/MET/SHIP2	-0.029	0.13	-9999	-0.58	24	24
MAP3K5	-0.024	0.12	-9999	-10000	0	0
HGF/MET/CIN85/CBL/ENDOPHILINS	-0.026	0.12	-9999	-0.6	14	14
AP1	-0.012	0.076	-9999	-0.52	10	10
mol:SU11274	0	0	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1
apoptosis	0.006	0.1	-9999	-0.7	10	10
STAT3 (dimer)	0.042	0.075	-9999	-0.51	2	2
GAB1/CRKL/SHP2/PI3K	-0.009	0.043	-9999	-10000	0	0
INPP5D	0.008	0.08	-9999	-0.86	4	4
CBL/CRK	0.048	0.062	-9999	-0.43	2	2
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0	0	-9999	-10000	0	0
PLCG1	0.016	0	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
ELK1	0	0.031	-9999	-0.29	5	5
mol:SU5416	0	0	-9999	-10000	0	0
SHP2/GRB2/SOS1GAB1	-0.008	0.039	-9999	-0.34	2	2
PAK1	0.011	0.002	-9999	-10000	0	0
HGF/MET/RANBP10	-0.029	0.13	-9999	-0.58	24	24
HRAS	0.032	0.095	-9999	-0.72	2	2
DOCK1	0.05	0.062	-9999	-10000	0	0
GAB1	0.031	0.068	-9999	-0.49	2	2
CRK	0.041	0.065	-9999	-0.46	2	2
mol:PHA665752	0	0	-9999	-10000	0	0
mol:GDP	-0.022	0.1	-9999	-0.55	12	12
JUN	0.016	0	-9999	-10000	0	0
EntrezGene:200958	0	0	-9999	-10000	0	0
HGF/MET	-0.013	0.061	-9999	-0.29	15	15
PIK3R1	0.016	0	-9999	-10000	0	0
cell morphogenesis	0.081	0.074	-9999	-10000	0	0
GRB2/SHC	-0.012	0.058	-9999	-0.54	3	3
FOS	0	0.11	-9999	-0.76	10	10
GLMN	0	0	-9999	-10000	0	0
cell motility	0	0.031	-9999	-0.29	5	5
HGF/MET/MUC20	-0.03	0.13	-9999	-0.59	24	24
cell migration	-0.012	0.057	-9999	-0.52	3	3
GRB2	0.016	0	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
MET/RANBP10	-0.007	0.068	-9999	-0.67	5	5
HGF/MET/Paxillin/FAK1/FAK12/RasGAP	-0.015	0.069	-9999	-0.57	2	2
MET/MUC20	-0.007	0.069	-9999	-0.68	5	5
RAP1B	0.058	0.059	-9999	-10000	0	0
RAP1A	0.058	0.059	-9999	-10000	0	0
HGF/MET/RANBP9	-0.029	0.13	-9999	-0.58	24	24
RAF1	0.042	0.09	-9999	-0.66	2	2
STAT3	-0.014	0.063	-9999	-0.52	2	2
cell proliferation	0.055	0.099	-9999	-0.64	3	3
RPS6KB1	-0.004	0.02	-9999	-10000	0	0
MAPK3	-0.006	0.028	-9999	-0.27	5	5
MAPK1	-0.006	0.028	-9999	-0.27	5	5
RANBP9	0.016	0	-9999	-10000	0	0
MAPK8	0.014	0.093	-9999	-10000	0	0
SRC	0.043	0.076	-9999	-0.54	2	2
PI3K	-0.011	0.05	-9999	-0.46	2	2
MET/Glomulin	0.009	0.064	-9999	-0.61	5	5
SOS1	0.016	0	-9999	-10000	0	0
MAP2K1	0.051	0.085	-9999	-0.6	2	2
MET	0.007	0.089	-9999	-0.86	5	5
MAP4K1	-0.037	0.12	-9999	-0.42	5	5
PTK2	0.016	0	-9999	-10000	0	0
MAP2K2	0.05	0.087	-9999	-0.6	2	2
BAD	0.01	0.02	-9999	-0.43	1	1
MAP2K4	-0.012	0.11	-9999	-10000	0	0
SHP2/GRB2/SOS1/GAB1	-0.011	0.057	-9999	-0.57	2	2
INPPL1	0.016	0	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
SH3KBP1	0.016	0	-9999	-10000	0	0
HGS	-0.012	0.055	-9999	-0.49	2	2
PLCgamma1/PKC	0	0	-9999	-10000	0	0
HGF	-0.021	0.17	-9999	-0.81	21	21
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0
NCK/PLCgamma1	-0.012	0.054	-9999	-0.48	2	2
PDPK1	-0.013	0.003	-9999	-10000	0	0
HGF/MET/SHIP	-0.034	0.14	-9999	-0.6	27	27

×

EPHB forward signaling

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
Ephrin A5/EPHB2	-0.057	0.16	-10000	0	-0.5	54	54
cell-cell adhesion	0.01	0.064	0.64	2	-10000	0	2
Ephrin B/EPHB2/RasGAP	-0.011	0.073	-10000	0	-0.83	1	1
ITSN1	0.016	0	-10000	0	-10000	0	0
PIK3CA	0.016	0	-10000	0	-10000	0	0
SHC1	0.014	0.04	-10000	0	-0.86	1	1
Ephrin B1/EPHB3	-0.014	0.082	-10000	0	-0.5	13	13
Ephrin B1/EPHB1	-0.002	0.035	-10000	0	-0.54	2	2
HRAS/GDP	-0.005	0.04	-10000	0	-10000	0	0
Ephrin B/EPHB1/GRB7	-0.011	0.066	-10000	0	-10000	0	0
Endophilin/SYNJ1	0.04	0.076	-10000	0	-0.56	3	3
KRAS	0.016	0	-10000	0	-10000	0	0
Ephrin B/EPHB1/Src	-0.005	0.046	-10000	0	-10000	0	0
endothelial cell migration	0	0	-10000	0	-10000	0	0
GRB2	0.016	0	-10000	0	-10000	0	0
GRB7	0.004	0.093	-10000	0	-0.76	7	7
PAK1	0.051	0.077	-10000	0	-0.78	1	1
HRAS	0.016	0	-10000	0	-10000	0	0
RRAS	0.04	0.077	-10000	0	-0.78	1	1
DNM1	-0.001	0.12	-10000	0	-0.86	9	9
cell-cell signaling	0	0	-10000	0	-10000	0	0
CRK	0.047	0.05	-10000	0	-10000	0	0
lamellipodium assembly	-0.01	0.064	-10000	0	-0.64	2	2
Ephrin B/EPHB1/Src/p52 SHC/GRB2	-0.004	0.03	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
EPHB2	0.001	0.11	-10000	0	-0.78	9	9
EPHB3	-0.005	0.13	-10000	0	-0.77	13	13
EPHB1	0.012	0.053	-10000	0	-0.81	2	2
EPHB4	0.016	0	-10000	0	-10000	0	0
mol:GDP	0	0.051	-10000	0	-10000	0	0
Ephrin B/EPHB2	-0.012	0.075	-10000	0	-0.61	3	3
Ephrin B/EPHB3	-0.015	0.082	-10000	0	-0.67	2	2
JNK cascade	0.043	0.075	-10000	0	-0.8	1	1
Ephrin B/EPHB1	-0.005	0.048	-10000	0	-0.5	1	1
RAP1/GDP	0	0.045	-10000	0	-10000	0	0
EFNB2	0.016	0	-10000	0	-10000	0	0
EFNB3	0.009	0.07	-10000	0	-0.76	4	4
EFNB1	0.016	0	-10000	0	-10000	0	0
Ephrin B2/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
RAP1B	0.016	0	-10000	0	-10000	0	0
RAP1A	0.016	0	-10000	0	-10000	0	0
CDC42/GTP	-0.011	0.071	-10000	0	-0.72	2	2
Rap1/GTP	-0.01	0.064	-10000	0	-0.66	2	2
axon guidance	-0.057	0.16	-10000	0	-0.5	54	54
MAPK3	0.068	0.033	-10000	0	-10000	0	0
MAPK1	0.068	0.033	-10000	0	-10000	0	0
Rac1/GDP	0	0.048	-10000	0	-10000	0	0
actin cytoskeleton reorganization	-0.008	0.048	-10000	0	-10000	0	0
CDC42/GDP	0	0.048	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
EFNA5	-0.057	0.23	-10000	0	-0.76	45	45
Ephrin B2/EPHB4	0	0	-10000	0	-10000	0	0
Ephrin B/EPHB2/Intersectin/N-WASP	-0.008	0.051	-10000	0	-0.61	1	1
CDC42	0.016	0	-10000	0	-10000	0	0
RAS family/GTP	-0.01	0.063	-10000	0	-0.63	2	2
PTK2	0.002	0.016	-10000	0	-10000	0	0
MAP4K4	0.043	0.076	-10000	0	-0.82	1	1
SRC	0.016	0	-10000	0	-10000	0	0
KALRN	0.016	0	-10000	0	-10000	0	0
Intersectin/N-WASP	0	0	-10000	0	-10000	0	0
neuron projection morphogenesis	-0.008	0.051	-10000	0	-0.51	1	1
MAP2K1	0.059	0.035	-10000	0	-10000	0	0
WASL	0.016	0	-10000	0	-10000	0	0
Ephrin B1/EPHB1-2/NCK1	-0.011	0.075	-10000	0	-0.61	4	4
cell migration	0.07	0.038	-10000	0	-10000	0	0
NRAS	0.016	0	-10000	0	-10000	0	0
SYNJ1	0.04	0.077	-10000	0	-0.57	3	3
PXN	0.016	0	-10000	0	-10000	0	0
TF	-0.073	0.23	-10000	0	-0.78	2	2
HRAS/GTP	-0.011	0.07	-10000	0	-0.7	2	2
Ephrin B1/EPHB1-2	-0.011	0.076	-10000	0	-0.52	10	10
cell adhesion mediated by integrin	0.008	0.055	0.49	4	-10000	0	4
RAC1	0.016	0	-10000	0	-10000	0	0
mol:GTP	-0.012	0.076	-10000	0	-0.77	2	2
RAC1-CDC42/GTP	-0.018	0.092	-10000	0	-0.87	3	3
RASA1	0.016	0	-10000	0	-10000	0	0
RAC1-CDC42/GDP	0	0.045	-10000	0	-10000	0	0
ruffle organization	0.075	0.078	-10000	0	-0.66	2	2
NCK1	0.016	0	-10000	0	-10000	0	0
receptor internalization	0.041	0.1	-10000	0	-0.73	1	1
Ephrin B/EPHB2/KALRN	-0.011	0.073	-10000	0	-0.83	1	1
ROCK1	0.021	0.079	-10000	0	-0.45	13	13
RAS family/GDP	-0.008	0.047	-10000	0	-10000	0	0
Rac1/GTP	-0.011	0.069	-10000	0	-0.7	2	2
Ephrin B/EPHB1/Src/Paxillin	-0.004	0.032	-10000	0	-10000	0	0

×

Osteopontin-mediated events

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.007	0.055	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.046	-9999	-10000	0	0
alphaV/beta3 Integrin/Osteopontin/Src	-0.004	0.044	-9999	-0.56	3	3
AP1	-0.013	0.074	-9999	-0.68	3	3
ILK	0.066	0.047	-9999	-10000	0	0
bone resorption	-0.022	0.096	-9999	-0.77	2	2
PTK2B	0.016	0	-9999	-10000	0	0
PYK2/p130Cas	-0.005	0.044	-9999	-10000	0	0
ITGAV	0.022	0.003	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CD44/Rho Family GTPase/ROCK2	-0.029	0.14	-9999	-0.66	21	21
alphaV/beta3 Integrin/Osteopontin	-0.004	0.043	-9999	-0.48	3	3
MAP3K1	0.066	0.047	-9999	-10000	0	0
JUN	0.016	0.002	-9999	-10000	0	0
MAPK3	0.078	0.07	-9999	-10000	0	0
MAPK1	0.078	0.07	-9999	-10000	0	0
Rac1/GDP	0	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAPK8	0.079	0.047	-9999	-10000	0	0
ITGB3	0.021	0.036	-9999	-0.76	1	1
NFKBIA	0.091	0.07	-9999	-10000	0	0
FOS	0	0.11	-9999	-0.76	10	10
CD44	-0.021	0.18	-9999	-0.86	20	20
CHUK	0.016	0	-9999	-10000	0	0
PLAU	0.092	0.16	-9999	-1.1	7	7
NF kappa B1 p50/RelA	-0.008	0.048	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
RELA	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.58	1	1
mol:GDP	0	0	-9999	-10000	0	0
SYK	0.062	0.055	-9999	-10000	0	0
VAV3	0.059	0.097	-9999	-0.8	1	1
MAP3K14	0.064	0.071	-9999	-0.5	4	4
ROCK2	0.014	0.035	-9999	-0.76	1	1
SPP1	0.018	0.061	-9999	-0.75	3	3
RAC1	0.016	0	-9999	-10000	0	0
Rac1/GTP	-0.014	0.073	-9999	-0.73	1	1
MMP2	0.1	0.11	-9999	-0.73	5	5

×

Cellular roles of Anthrax toxin

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
ANTXR1	0.016	0	-10000	0	-10000	0	0
ANTXR2	0.014	0.035	-10000	0	-0.76	1	1
negative regulation of myeloid dendritic cell antigen processing and presentation	0	0.004	-10000	0	-0.095	1	1
monocyte activation	0.005	0.087	-10000	0	-0.36	22	22
MAP2K2	-0.002	0.037	-10000	0	-0.8	1	1
MAP2K1	0	0.003	-10000	0	-10000	0	0
MAP2K7	0	0.003	-10000	0	-10000	0	0
MAP2K6	-0.002	0.029	-10000	0	-0.44	2	2
CYAA	0.021	0.021	-10000	0	-0.43	1	1
MAP2K4	0	0.003	-10000	0	-10000	0	0
IL1B	0.018	0.052	-10000	0	-0.33	9	9
Channel	-0.001	0.021	-10000	0	-0.46	1	1
NLRP1	-0.006	0.053	-10000	0	-0.53	5	5
CALM1	0.016	0	-10000	0	-10000	0	0
negative regulation of phagocytosis	0	0.005	-10000	0	-10000	0	0
mol:Ca2+	0	0	-10000	0	-10000	0	0
regulation of endothelial cell proliferation	0	0.004	0.095	1	-10000	0	1
MAPK3	0	0.003	-10000	0	-10000	0	0
MAPK1	0	0.003	-10000	0	-10000	0	0
PGR	-0.015	0.081	-10000	0	-0.45	16	16
PA/Cellular Receptors	-0.001	0.023	-10000	0	-0.5	1	1
apoptosis	0	0.004	-10000	0	-0.095	1	1
LOC728358	0	0	-10000	0	-10000	0	0
Lethal toxin (unfolded)	-0.001	0.019	-10000	0	-0.43	1	1
macrophage activation	0.028	0.004	-10000	0	-10000	0	0
TNF	0.002	0.11	-10000	0	-0.81	8	8
VCAM1	-0.016	0.084	-10000	0	-0.36	22	22
platelet activation	0	0.005	-10000	0	-10000	0	0
MAPKKK cascade	-0.023	0.009	-10000	0	-10000	0	0
IL18	0.016	0.063	-10000	0	-0.51	6	6
negative regulation of macrophage activation	0	0.004	-10000	0	-0.095	1	1
LEF	0	0.004	-10000	0	-0.095	1	1
CASP1	-0.003	0.024	-10000	0	-0.23	5	5
mol:cAMP	0	0.005	-10000	0	-10000	0	0
necrosis	0	0.004	-10000	0	-0.095	1	1
intracellular pH reduction	0	0	-10000	0	-10000	0	0
PAGA	0	0	-10000	0	-10000	0	0
Edema toxin (unfolded)	-0.001	0.02	-10000	0	-0.43	1	1
mol:Epigallocatechin-3-gallate (EGCG)	0	0	-10000	0	-10000	0	0

×

ceramide signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
MAP4K4	0.027	0.1	-9999	-10000	0	0
BAG4	0.016	0	-9999	-10000	0	0
BAD	0.031	0.041	-9999	-0.4	1	1
NFKBIA	0.016	0	-9999	-10000	0	0
BIRC3	-0.12	0.32	-9999	-0.86	74	74
BAX	0.032	0.037	-9999	-10000	0	0
EnzymeConsortium:3.1.4.12	0.011	0.028	-9999	-0.099	1	1
IKBKB	0.037	0.097	-9999	-10000	0	0
MAP2K2	0.046	0.055	-9999	-0.38	4	4
MAP2K1	0.047	0.052	-9999	-0.38	4	4
SMPD1	0.019	0.028	-9999	-10000	0	0
GO:0005551	0	0	-9999	-10000	0	0
FADD/Caspase 8	0.038	0.098	-9999	-10000	0	0
MAP2K4	0.041	0.035	-9999	-10000	0	0
protein ubiquitination	0.04	0.098	-9999	-10000	0	0
EnzymeConsortium:2.7.1.37	0.054	0.053	-9999	-0.38	4	4
response to UV	0.001	0	-9999	-0.003	4	4
RAF1	0.039	0.054	-9999	-0.42	4	4
CRADD	0.016	0.002	-9999	-10000	0	0
mol:ceramide	0.022	0.038	-9999	-10000	0	0
I-kappa-B-alpha/RELA/p50/ubiquitin	0	0	-9999	-10000	0	0
MADD	0.016	0.002	-9999	-10000	0	0
MAP3K1	0.032	0.037	-9999	-10000	0	0
TRADD	0.016	0.002	-9999	-10000	0	0
RELA/p50	0.016	0	-9999	-10000	0	0
MAPK3	0.05	0.052	-9999	-0.37	4	4
MAPK1	0.05	0.052	-9999	-0.37	4	4
p50/RELA/I-kappa-B-alpha	0	0	-9999	-10000	0	0
FADD	0.027	0.1	-9999	-10000	0	0
KSR1	0.029	0.057	-9999	-0.45	4	4
MAPK8	0.05	0.034	-9999	-10000	0	0
TRAF2	0.016	0.001	-9999	-10000	0	0
response to radiation	0	0	-9999	-10000	0	0
CHUK	0.037	0.097	-9999	-10000	0	0
TNF R/SODD	0	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
CYCS	0.033	0.037	-9999	-10000	0	0
IKBKG	0.037	0.097	-9999	-10000	0	0
TNF/TNF R/TRADD/MADD/cIAP/RIP/TRAF2/RAIDD	0.017	0.1	-9999	-0.44	1	1
RELA	0.016	0	-9999	-10000	0	0
RIPK1	0.016	0.001	-9999	-10000	0	0
AIFM1	0.033	0.037	-9999	-10000	0	0
TNF/TNF R/SODD	-0.009	0.068	-9999	-0.53	8	8
TNFRSF1A	0.016	0.001	-9999	-10000	0	0
response to heat	0	0	-9999	-10000	0	0
CASP8	0.028	0.03	-9999	-10000	0	0
NSMAF	0.028	0.099	-9999	-10000	0	0
response to hydrogen peroxide	0.001	0	-9999	-0.003	4	4
BCL2	0.016	0	-9999	-10000	0	0

×

RXR and RAR heterodimerization with other nuclear receptor

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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
TGFB1	-0.006	0.075	-9999	-0.73	5	5
VDR	0.011	0.061	-9999	-0.76	3	3
FAM120B	0.016	0	-9999	-10000	0	0
RXRs/LXRs/DNA/9cRA	0.076	0.052	-9999	-10000	0	0
RXRs/LXRs/DNA/Oxysterols	0.086	0.065	-9999	-10000	0	0
MED1	0.016	0	-9999	-10000	0	0
mol:9cRA	0.009	0.009	-9999	-10000	0	0
RARs/THRs/DNA/Src-1	-0.019	0.072	-9999	-10000	0	0
RXRs/NUR77	-0.018	0.091	-9999	-0.5	6	6
RXRs/PPAR	0.058	0.031	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.004	0.046	-9999	-0.58	3	3
RARs/VDR/DNA/Vit D3	-0.004	0.042	-9999	-10000	0	0
RARA	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.061	-9999	-0.76	3	3
RARs/RARs/DNA/9cRA	-0.001	0.027	-9999	-0.42	2	2
RARG	0.016	0	-9999	-10000	0	0
RPS6KB1	-0.001	0.036	-9999	-10000	0	0
RARs/THRs/DNA/SMRT	-0.019	0.072	-9999	-10000	0	0
THRA	0.014	0.035	-9999	-0.76	1	1
mol:Bile acids	0	0	-9999	-10000	0	0
VDR/Vit D3/DNA	-0.004	0.046	-9999	-0.58	3	3
RXRs/PPAR/9cRA/PGJ2/DNA	-0.003	0.055	-9999	-0.5	4	4
NR1H4	-0.01	0.14	-9999	-0.76	16	16
RXRs/LXRs/DNA	0.008	0.059	-9999	-10000	0	0
NR1H2	0.023	0.036	-9999	-0.75	1	1
NR1H3	0.025	0.006	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.005	0.055	-9999	-0.48	4	4
NR4A1	-0.01	0.14	-9999	-0.76	16	16
mol:ATRA	0	0	-9999	-10000	0	0
RXRs/FXR/9cRA/MED1	0.041	0.069	-9999	-0.42	2	2
RXRG	0.014	0.08	-9999	-0.85	4	4
RXR alpha/CCPG	0	0.004	-9999	-10000	0	0
RXRA	0.024	0.004	-9999	-10000	0	0
RXRB	0.025	0.006	-9999	-10000	0	0
THRB	-0.029	0.18	-9999	-0.76	28	28
PPARG	0.016	0	-9999	-10000	0	0
PPARD	0.016	0	-9999	-10000	0	0
TNF	0.083	0.13	-9999	-0.88	8	8
mol:Oxysterols	0.009	0.008	-9999	-10000	0	0
cholesterol transport	0.086	0.064	-9999	-10000	0	0
PPARA	0.016	0	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RARB	0.012	0.05	-9999	-0.76	2	2
RXRs/NUR77/BCL2	-0.012	0.06	-9999	-10000	0	0
SREBF1	0.092	0.068	-9999	-0.66	1	1
RXRs/RXRs/DNA/9cRA	0.005	0.059	-9999	-0.5	4	4
ABCA1	0.091	0.074	-9999	-0.66	2	2
RARs/THRs	-0.026	0.099	-9999	-10000	0	0
RXRs/FXR	-0.018	0.092	-9999	-0.51	7	7
BCL2	0.016	0	-9999	-10000	0	0

×

Paxillin-dependent events mediated by a4b1

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CRKL	0.016	0	-9999	-10000	0	0
Rac1/GDP	0.002	0.013	-9999	-10000	0	0
DOCK1	0.016	0	-9999	-10000	0	0
ITGA4	-0.014	0.16	-9999	-0.86	16	16
RAC1	0.016	0	-9999	-10000	0	0
alpha4/beta7 Integrin	-0.022	0.12	-9999	-0.67	16	16
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin	-0.019	0.1	-9999	-0.58	16	16
alpha4/beta7 Integrin/Paxillin	-0.017	0.094	-9999	-0.52	16	16
lamellipodium assembly	0.002	0.022	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
ARF6	0.016	0	-9999	-10000	0	0
TLN1	0.016	0	-9999	-10000	0	0
PXN	0.031	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
ARF6/GTP	-0.015	0.079	-9999	-10000	0	0
cell adhesion	-0.016	0.086	-9999	-10000	0	0
CRKL/CBL	0	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin	-0.017	0.094	-9999	-0.52	16	16
ITGB1	0.016	0	-9999	-10000	0	0
ITGB7	0.016	0	-9999	-10000	0	0
ARF6/GDP	0.002	0.013	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/VCAM1	-0.031	0.12	-9999	-0.98	1	1
p130Cas/Crk/Dock1	-0.001	0.022	-9999	-0.48	1	1
VCAM1	-0.011	0.15	-9999	-0.84	15	15
alpha4/beta1 Integrin/Paxillin/Talin	-0.016	0.087	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/GIT1	-0.016	0.087	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
mol:GDP	0.016	0.086	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GIT1	0.016	0	-9999	-10000	0	0
alpha4/beta1 Integrin/Paxillin/Talin/Actin Cytoskeleton	-0.016	0.087	-9999	-10000	0	0
Rac1/GTP	0.002	0.023	-9999	-10000	0	0

×

Regulation of p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
RIP1/MEKK3	0	0	-9999	-10000	0	0
response to insulin stimulus	0	0	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
MAP2K6	0.012	0.05	-9999	-0.76	2	2
mol:GTP	0	0	-9999	-10000	0	0
MAP2K4	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP/PAK family	-0.007	0.039	-9999	-10000	0	0
response to UV	0	0	-9999	-10000	0	0
YES1	0.016	0	-9999	-10000	0	0
interleukin-1 receptor activity	0	0	-9999	-10000	0	0
tumor necrosis factor receptor activity	0	0	-9999	-10000	0	0
MAP3K3	0.016	0	-9999	-10000	0	0
FYN	0.016	0	-9999	-10000	0	0
MAP3K12	0.016	0	-9999	-10000	0	0
FGR	0.01	0.069	-9999	-0.86	3	3
p38 alpha/TAB1	-0.012	0.039	-9999	-0.31	2	2
PRKG1	0	0.11	-9999	-0.76	10	10
DUSP8	0.014	0.035	-9999	-0.76	1	1
PGK/cGMP/p38 alpha	-0.018	0.059	-9999	-0.44	2	2
apoptosis	-0.012	0.037	-9999	-0.3	2	2
RAL/GTP	0	0	-9999	-10000	0	0
LYN	0.016	0	-9999	-10000	0	0
DUSP1	0.014	0.04	-9999	-0.86	1	1
PAK1	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
RAC1/OSM/MEKK3/MKK3	0	0	-9999	-10000	0	0
TRAF6	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
epidermal growth factor receptor activity	0	0	-9999	-10000	0	0
mol:LPS	0	0	-9999	-10000	0	0
mol:cGMP	0	0	-9999	-10000	0	0
CCM2	0.016	0	-9999	-10000	0	0
RAC1-CDC42/GTP	0	0	-9999	-10000	0	0
MAPK11	0.057	0.084	-9999	-0.42	2	2
BLK	-0.04	0.21	-9999	-0.86	30	30
HCK	-0.034	0.2	-9999	-0.86	27	27
MAP2K3	0.016	0	-9999	-10000	0	0
DUSP16	0.016	0	-9999	-10000	0	0
DUSP10	0.012	0.057	-9999	-0.86	2	2
TRAF6/MEKK3	0	0	-9999	-10000	0	0
MAP3K7IP1	0	0	-9999	-10000	0	0
MAPK14	0.057	0.067	-9999	-0.34	2	2
positive regulation of innate immune response	0.068	0.091	-9999	-0.44	2	2
LCK	-0.024	0.18	-9999	-0.85	22	22
p38alpha-beta/MKP7	0.074	0.088	-9999	-10000	0	0
p38alpha-beta/MKP5	0.072	0.092	-9999	-0.42	2	2
PGK/cGMP	-0.012	0.083	-9999	-0.58	10	10
PAK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/MKP1	0.073	0.09	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0
RALB	0.016	0	-9999	-10000	0	0
RALA	0.016	0	-9999	-10000	0	0
PAK3	-0.01	0.14	-9999	-0.83	14	14

×

Insulin Pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
CBL/APS/CAP	-0.007	0.055	-9999	-10000	0	0
TC10/GTP	-0.005	0.048	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/Shp2	-0.002	0.029	-9999	-10000	0	0
HRAS	0.016	0	-9999	-10000	0	0
APS homodimer	0.007	0.089	-9999	-0.86	5	5
GRB14	-0.029	0.18	-9999	-0.76	28	28
FOXO3	-0.003	0.012	-9999	-10000	0	0
AKT1	-0.02	0.082	-9999	-0.67	1	1
INSR	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insulin	0	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
SORBS1	0.014	0.035	-9999	-0.76	1	1
CRK	0.016	0	-9999	-10000	0	0
PTPN1	0.049	0.001	-9999	-10000	0	0
CAV1	-0.006	0.15	-9999	-0.51	36	36
CBL/APS/CAP/Crk-II/C3G	-0.006	0.053	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1/NCK2	-0.002	0.029	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	-0.002	0.025	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/PTP1B	-0.002	0.019	-9999	-10000	0	0
RPS6KB1	0.057	0.093	-9999	-0.6	1	1
PARD6A	0.011	0.061	-9999	-0.76	3	3
CBL	0.016	0	-9999	-10000	0	0
tumor necrosis factor-mediated signaling pathway	0	0	-9999	-10000	0	0
DOK1	0	0.002	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/Shc	-0.018	0.071	-9999	-0.62	1	1
HRAS/GTP	-0.006	0.051	-9999	-0.74	1	1
Insulin Receptor	0.018	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC	-0.003	0.035	-9999	-0.5	1	1
PRKCI	-0.005	0.019	-9999	-10000	0	0
Insulin Receptor/Insulin/GRB14/PDK1	-0.022	0.09	-9999	-0.74	1	1
SHC1	0.014	0.04	-9999	-0.86	1	1
negative regulation of MAPKKK cascade	0	0.003	-9999	-10000	0	0
PI3K	-0.002	0.026	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
RHOQ	0.016	0	-9999	-10000	0	0
mol:H2O2	0	0	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
AKT2	-0.02	0.082	-9999	-0.67	1	1
PRKCZ	-0.009	0.059	-9999	-0.7	3	3
SH2B2	0.007	0.089	-9999	-0.86	5	5
SHC/SHIP	-0.007	0.061	-9999	-0.87	1	1
F2RL2	-0.034	0.2	-9999	-0.86	27	27
TRIP10	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insulin/Shc	-0.001	0.025	-9999	-0.55	1	1
TC10/GTP/CIP4/Exocyst	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB2/Sos1	-0.001	0.023	-9999	-0.5	1	1
RAPGEF1	0.016	0	-9999	-10000	0	0
RASA1	0.016	0	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
CBL/APS/CAP/Crk-II	-0.006	0.057	-9999	-0.52	5	5
TC10/GDP	0	0	-9999	-10000	0	0
Insulin Receptor/Insulin/SHC/GRB10	-0.001	0.025	-9999	-0.54	1	1
INPP5D	0.031	0.065	-9999	-0.62	4	4
SOS1	0.016	0	-9999	-10000	0	0
SGK1	-0.001	0.005	-9999	-10000	0	0
mol:cAMP	0	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
IRS1	0.012	0.05	-9999	-0.76	2	2
p62DOK/RasGAP	0	0.003	-9999	-10000	0	0
INS	0.005	0.001	-9999	-10000	0	0
mol:PI-3-4-P2	0.031	0.064	-9999	-0.61	4	4
GRB2	0.016	0	-9999	-10000	0	0
EIF4EBP1	0.037	0.14	-9999	-0.69	4	4
PTPRA	0.018	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
TC10/GTP/CIP4	0	0	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
Insulin Receptor/Insuli/IRS1/GRB2/SHC/Sos	-0.002	0.023	-9999	-10000	0	0
Insulin Receptor/Insulin/IRS1	-0.002	0.03	-9999	-0.46	2	2
Insulin Receptor/Insulin/IRS3	0	0	-9999	-10000	0	0
Par3/Par6	-0.031	0.12	-9999	-0.5	27	27

×

Plasma membrane estrogen receptor signaling

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
GNB1/GNG2	-0.008	0.058	-10000	0	-0.5	4	4
ER alpha/Gai/GDP/Gbeta gamma	0.056	0.049	-10000	0	-10000	0	0
AKT1	0.05	0.053	-10000	0	-0.75	2	2
PIK3CA	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/PI3K	0.045	0.053	-10000	0	-0.76	2	2
mol:Ca2+	-0.01	0.18	-10000	0	-0.69	9	9
IGF1R	0.016	0	-10000	0	-10000	0	0
E2/ER alpha (dimer)/Striatin	-0.003	0.039	-10000	0	-0.5	3	3
SHC1	0.014	0.04	-10000	0	-0.86	1	1
apoptosis	-0.05	0.05	0.71	2	-10000	0	2
RhoA/GTP	-0.001	0.023	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p130 Cas	-0.006	0.039	-10000	0	-10000	0	0
regulation of stress fiber formation	-0.071	0.027	-10000	0	-10000	0	0
E2/ERA-ERB (dimer)	-0.009	0.07	-10000	0	-0.54	8	8
KRAS	0.016	0	-10000	0	-10000	0	0
G13/GTP	-0.002	0.029	-10000	0	-0.46	2	2
pseudopodium formation	0.071	0.027	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1	-0.002	0.032	-10000	0	-0.5	2	2
GRB2	0.016	0	-10000	0	-10000	0	0
GNG2	0.016	0	-10000	0	-10000	0	0
GNAO1	0.009	0.078	-10000	0	-0.84	4	4
HRAS	0.016	0	-10000	0	-10000	0	0
mol:GTP	0	0	-10000	0	-10000	0	0
mol:NO	0.066	0.051	-10000	0	-0.47	2	2
E2/ER beta (dimer)	-0.008	0.072	-10000	0	-0.65	6	6
mol:GDP	-0.007	0.052	-10000	0	-0.49	2	2
mol:NADP	0.066	0.051	-10000	0	-0.47	2	2
PIK3R1	0.016	0	-10000	0	-10000	0	0
mol:IP3	-0.013	0.19	-10000	0	-0.73	9	9
IGF-1R heterotetramer	0.016	0	-10000	0	-10000	0	0
PLCB1	-0.021	0.094	-10000	0	-0.56	9	9
PLCB2	-0.065	0.16	-10000	0	-0.48	60	60
IGF1	0.003	0.11	-10000	0	-0.86	7	7
mol:L-citrulline	0.066	0.051	-10000	0	-0.47	2	2
RHOA	0.016	0	-10000	0	-10000	0	0
Gai/GDP	-0.007	0.047	-10000	0	-0.63	1	1
JNK cascade	-0.008	0.072	-10000	0	-0.64	6	6
BCAR1	0.014	0.035	-10000	0	-0.76	1	1
ESR2	0.005	0.094	-10000	0	-0.83	6	6
GNAQ	0.016	0	-10000	0	-10000	0	0
ESR1	0.012	0.05	-10000	0	-0.76	2	2
Gq family/GDP/Gbeta gamma	-0.014	0.072	-10000	0	-0.55	3	3
E2/ER alpha (dimer)/PELP1/Src/p52 SHC/GRB2/SOS1	0.053	0.027	-10000	0	-10000	0	0
E2/ER alpha (dimer)/PELP1/Src/p52 SHC	-0.006	0.04	-10000	0	-10000	0	0
GNAZ	0.011	0.061	-10000	0	-0.76	3	3
E2/ER alpha (dimer)	-0.002	0.038	-10000	0	-0.58	2	2
STRN	0.014	0.035	-10000	0	-0.76	1	1
GNAL	0.016	0	-10000	0	-10000	0	0
PELP1	0.016	0	-10000	0	-10000	0	0
MAPK11	0.018	0.065	-10000	0	-0.56	6	6
GNAI2	0.016	0	-10000	0	-10000	0	0
GNAI3	0.016	0	-10000	0	-10000	0	0
GNAI1	0.011	0.061	-10000	0	-0.76	3	3
HBEGF	-0.037	0.14	-10000	0	-0.51	5	5
cAMP biosynthetic process	-0.007	0.056	-10000	0	-0.44	8	8
SRC	0.065	0.047	-10000	0	-10000	0	0
PI3K	0	0	-10000	0	-10000	0	0
GNB1	0.016	0	-10000	0	-10000	0	0
G13/GDP/Gbeta gamma	-0.006	0.045	-10000	0	-10000	0	0
SOS1	0.016	0	-10000	0	-10000	0	0
IGF-1R heterotetramer/IGF1	-0.009	0.05	-10000	0	-10000	0	0
Gs family/GTP	-0.007	0.057	-10000	0	-0.45	8	8
EntrezGene:2778	0	0	-10000	0	-10000	0	0
RAS family/GTP	0	0	-10000	0	-10000	0	0
vasodilation	0.065	0.049	-10000	0	-0.45	2	2
mol:DAG	-0.013	0.19	-10000	0	-0.73	9	9
Gs family/GDP/Gbeta gamma	-0.005	0.041	-10000	0	-10000	0	0
MSN	0.073	0.029	-10000	0	-10000	0	0
Gq family/GTP	-0.017	0.08	-10000	0	-0.5	9	9
mol:PI-3-4-5-P3	0.045	0.051	-10000	0	-0.73	2	2
NRAS	0.016	0	-10000	0	-10000	0	0
mol:E2	0	0	-10000	0	-10000	0	0
cell adhesion	-0.065	0.049	0.45	2	-10000	0	2
GRB2/SOS1	0	0	-10000	0	-10000	0	0
RhoA/GDP	-0.006	0.048	-10000	0	-0.46	2	2
NOS3	0.067	0.053	-10000	0	-0.49	2	2
GNA11	0.012	0.05	-10000	0	-0.76	2	2
MAPKKK cascade	0.076	0.052	-10000	0	-0.57	2	2
E2/ER alpha (dimer)/PELP1/Src	-0.005	0.039	-10000	0	-0.48	2	2
ruffle organization	0.071	0.027	-10000	0	-10000	0	0
ROCK2	-0.002	0.026	-10000	0	-10000	0	0
GNA14	0.004	0.093	-10000	0	-0.76	7	7
GNA15	-0.006	0.14	-10000	0	-0.86	12	12
GNA13	0.016	0	-10000	0	-10000	0	0
MMP9	-0.16	0.25	-10000	0	-0.66	7	7
MMP2	0.068	0.074	-10000	0	-0.64	2	2

×

PDGFR-beta signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
S1P1/Sphingosine-1-phosphate	-0.036	0.12	-9999	-0.46	16	16
PDGFB-D/PDGFRB/SLAP	-0.029	0.14	-9999	-0.67	21	21
PDGFB-D/PDGFRB/APS/CBL	-0.006	0.059	-9999	-0.58	5	5
AKT1	-0.001	0.013	-9999	-10000	0	0
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
mol:Sphingosine-1-phosphate	0.013	0.14	-9999	-0.48	16	16
PIK3CA	0.016	0	-9999	-10000	0	0
FGR	-0.004	0.03	-9999	-10000	0	0
mol:Ca2+	0.038	0.041	-9999	-10000	0	0
MYC	0.045	0.13	-9999	-0.57	16	16
SHC1	0.014	0.04	-9999	-0.86	1	1
HRAS/GDP	0	0.002	-9999	-10000	0	0
LRP1/PDGFRB/PDGFB	0	0	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.016	0	-9999	-10000	0	0
GO:0007205	0.038	0.042	-9999	-10000	0	0
PTEN	0.016	0	-9999	-10000	0	0
GRB2	0.016	0	-9999	-10000	0	0
GRB7	0.004	0.093	-9999	-0.76	7	7
PDGFB-D/PDGFRB/SHP2	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB10	0	0	-9999	-10000	0	0
cell cycle arrest	-0.029	0.14	-9999	-0.67	21	21
HRAS	0.016	0	-9999	-10000	0	0
HIF1A	0.09	0.017	-9999	-10000	0	0
GAB1	0.033	0.077	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
DNM2	0.036	0.083	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.004	0.012	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/LMW-PTP	0	0	-9999	-10000	0	0
S1P1/Sphingosine-1-phosphate/PDGFB-D/PDGFRB	-0.038	0.12	-9999	-0.51	9	9
positive regulation of MAPKKK cascade	0	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
mol:IP3	0.039	0.042	-9999	-10000	0	0
E5	0	0.001	-9999	-10000	0	0
CSK	0.004	0.007	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7	-0.008	0.069	-9999	-0.58	7	7
SHB	0.016	0	-9999	-10000	0	0
BLK	-0.023	0.087	-9999	-0.46	1	1
PTPN2	0.016	0.003	-9999	-10000	0	0
PDGFB-D/PDGFRB/SNX15	0	0	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
VAV2	0.036	0.088	-9999	-10000	0	0
CBL	0.016	0	-9999	-10000	0	0
PDGFB-D/PDGFRB/DEP1	0	0	-9999	-10000	0	0
LCK	-0.02	0.088	-9999	-0.62	3	3
PDGFRB	0.016	0.006	-9999	-10000	0	0
ACP1	0.016	0	-9999	-10000	0	0
HCK	-0.021	0.083	-9999	-10000	0	0
ABL1	0.033	0.061	-9999	-10000	0	0
PDGFB-D/PDGFRB/CBL	0.033	0.072	-9999	-10000	0	0
PTPN1	0.016	0.003	-9999	-10000	0	0
SNX15	0.016	0	-9999	-10000	0	0
STAT3	0.016	0	-9999	-10000	0	0
STAT1	0.014	0.04	-9999	-0.86	1	1
cell proliferation	0.045	0.12	-9999	-0.51	16	16
SLA	-0.023	0.18	-9999	-0.86	21	21
actin cytoskeleton reorganization	0.002	0.02	-9999	-10000	0	0
SRC	-0.001	0.013	-9999	-10000	0	0
PI3K	-0.001	0.015	-9999	-10000	0	0
PDGFB-D/PDGFRB/GRB7/SHC	-0.008	0.064	-9999	-0.5	8	8
SH2B2	0.007	0.089	-9999	-0.86	5	5
PLCgamma1/SPHK1	0.012	0.14	-9999	-0.5	16	16
LYN	-0.001	0.013	-9999	-10000	0	0
LRP1	0.016	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
STAT5B	0.016	0	-9999	-10000	0	0
STAT5A	0.016	0	-9999	-10000	0	0
NCK1-2/p130 Cas	-0.001	0.017	-9999	-10000	0	0
SPHK1	-0.057	0.24	-9999	-0.86	40	40
EDG1	0.001	0.003	-9999	-10000	0	0
mol:DAG	0.039	0.042	-9999	-10000	0	0
PLCG1	0.039	0.042	-9999	-10000	0	0
NHERF/PDGFRB	-0.001	0.022	-9999	-0.49	1	1
YES1	-0.001	0.013	-9999	-10000	0	0
cell migration	-0.001	0.022	-9999	-0.48	1	1
SHC/Grb2/SOS1	-0.001	0.021	-9999	-10000	0	0
SLC9A3R2	0.014	0.035	-9999	-0.76	1	1
SLC9A3R1	0.016	0	-9999	-10000	0	0
NHERF1-2/PDGFRB/PTEN	-0.001	0.02	-9999	-10000	0	0
FYN	-0.001	0.013	-9999	-10000	0	0
DOK1	0.044	0.009	-9999	-10000	0	0
HRAS/GTP	0	0	-9999	-10000	0	0
PDGFB	0.016	0	-9999	-10000	0	0
RAC1	0.046	0.1	-9999	-0.52	1	1
PRKCD	0.042	0.029	-9999	-0.53	1	1
FER	0.042	0.026	-9999	-10000	0	0
MAPKKK cascade	-0.001	0.021	-9999	-10000	0	0
RASA1	0.043	0.014	-9999	-10000	0	0
NCK1	0.016	0	-9999	-10000	0	0
NCK2	0.016	0	-9999	-10000	0	0
p62DOK/Csk	0.007	0.018	-9999	-10000	0	0
PDGFB-D/PDGFRB/SHB	0	0	-9999	-10000	0	0
chemotaxis	0.033	0.06	-9999	-10000	0	0
STAT1-3-5/STAT1-3-5	-0.001	0.021	-9999	-10000	0	0
Bovine Papilomavirus E5/PDGFRB	0	0	-9999	-10000	0	0
PTPRJ	0.016	0	-9999	-10000	0	0

×

E-cadherin signaling in keratinocytes

Figure 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
keratinocyte differentiation	0.06	0.046	-10000	0	-0.46	1	1
adherens junction organization	0.041	0.078	-10000	0	-0.68	1	1
mol:GTP	0	0	-10000	0	-10000	0	0
Rac1/GDP	-0.013	0.06	-10000	0	-10000	0	0
FMN1	0.025	0.12	-10000	0	-0.67	1	1
mol:IP3	-0.007	0.035	-10000	0	-0.48	1	1
E-cadherin/Ca2+/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.013	0.065	-10000	0	-0.72	1	1
CTNNB1	0.001	0.006	-10000	0	-10000	0	0
AKT1	0.056	0.052	-10000	0	-0.51	1	1
E-cadherin/beta catenin-gamma catenin/alpha catenin/p120 catenin	-0.016	0.11	-10000	0	-0.54	19	19
CTNND1	0.017	0.004	-10000	0	-10000	0	0
mol:PI-4-5-P2	0.046	0.071	-10000	0	-0.65	1	1
VASP	0.046	0.072	-10000	0	-0.67	1	1
ZYX	0.046	0.072	-10000	0	-0.67	1	1
JUB	0.044	0.077	-10000	0	-0.67	1	1
EGFR(dimer)	-0.021	0.084	-10000	0	-0.48	9	9
E-cadherin/beta catenin-gamma catenin	-0.021	0.1	-10000	0	-0.49	21	21
mol:PI-3-4-5-P3	-0.009	0.043	-10000	0	-0.55	1	1
PIK3CA	0.017	0.001	-10000	0	-10000	0	0
PI3K	-0.009	0.044	-10000	0	-0.56	1	1
FYN	-0.24	0.13	-10000	0	-10000	0	0
mol:Ca2+	-0.007	0.034	-10000	0	-0.47	1	1
JUP	-0.004	0.06	-10000	0	-0.76	3	3
PIK3R1	0.017	0.001	-10000	0	-10000	0	0
mol:DAG	-0.007	0.035	-10000	0	-0.48	1	1
CDH1	-0.03	0.15	-10000	0	-0.76	19	19
RhoA/GDP	-0.013	0.06	-10000	0	-10000	0	0
establishment of polarity of embryonic epithelium	0.046	0.071	-10000	0	-0.65	1	1
SRC	0.016	0	-10000	0	-10000	0	0
RAC1	0.016	0	-10000	0	-10000	0	0
RHOA	0.016	0	-10000	0	-10000	0	0
EGFR	-0.001	0.12	-10000	0	-0.85	9	9
CASR	-0.3	0.15	-10000	0	-0.53	14	14
RhoA/GTP	-0.006	0.03	-10000	0	-10000	0	0
AKT2	0.056	0.052	-10000	0	-0.51	1	1
actin cable formation	0.035	0.11	-10000	0	-0.64	1	1
apoptosis	0.008	0.038	0.5	1	-10000	0	1
CTNNA1	0.017	0.004	-10000	0	-10000	0	0
mol:GDP	-0.014	0.066	-10000	0	-0.49	1	1
PIP5K1A	0.046	0.072	-10000	0	-0.67	1	1
PLCG1	-0.007	0.036	-10000	0	-0.5	1	1
Rac1/GTP	-0.019	0.076	-10000	0	-0.43	9	9
homophilic cell adhesion	0.002	0.001	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class II

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
G beta1gamma2/HDAC5	-0.001	0.02	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC4	0	0	-9999	-10000	0	0
GATA1/HDAC4	-0.025	0.13	-9999	-0.67	18	18
GATA1/HDAC5	-0.026	0.13	-9999	-0.66	19	19
GATA2/HDAC5	-0.012	0.081	-9999	-0.57	10	10
HDAC5/BCL6/BCoR	-0.001	0.022	-9999	-0.48	1	1
HDAC9	0.016	0	-9999	-10000	0	0
Glucocorticoid receptor/Hsp90/HDAC6	-0.001	0.026	-9999	-0.58	1	1
HDAC4/ANKRA2	0	0	-9999	-10000	0	0
HDAC5/YWHAB	-0.001	0.026	-9999	-0.57	1	1
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
GATA2	0.001	0.1	-9999	-0.76	9	9
HDAC4/RFXANK	0	0	-9999	-10000	0	0
BCOR	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
HDAC10	0.014	0.035	-9999	-0.76	1	1
HDAC5	0.014	0.035	-9999	-0.76	1	1
GNB1/GNG2	0	0	-9999	-10000	0	0
Histones	-0.003	0.042	-9999	-0.85	1	1
ADRBK1	0.016	0	-9999	-10000	0	0
HDAC4	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
HDAC5/ANKRA2	-0.001	0.026	-9999	-0.57	1	1
HDAC4/Ubc9	0	0	-9999	-10000	0	0
HDAC7	0.016	0	-9999	-10000	0	0
HDAC5/14-3-3 E	-0.001	0.026	-9999	-0.57	1	1
TUBA1B	0.016	0	-9999	-10000	0	0
HDAC6	0.016	0	-9999	-10000	0	0
HDAC5/RFXANK	-0.001	0.026	-9999	-0.57	1	1
CAMK4	0.012	0.05	-9999	-0.76	2	2
Tubulin/HDAC6	-0.001	0.022	-9999	-0.48	1	1
SUMO1	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
GATA1	-0.02	0.17	-9999	-0.86	18	18
EntrezGene:8021	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
NR3C1	0.014	0.04	-9999	-0.86	1	1
SUMO1/HDAC4	0	0	-9999	-10000	0	0
SRF	0.016	0	-9999	-10000	0	0
HDAC4/YWHAB	0	0	-9999	-10000	0	0
Tubulin	-0.001	0.026	-9999	-0.57	1	1
HDAC4/14-3-3 E	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
BCL6/BCoR	0	0	-9999	-10000	0	0
HDAC4/HDAC3/SMRT (N-CoR2)	0	0	-9999	-10000	0	0
HDAC4/SRF	-0.002	0.031	-9999	-0.48	2	2
HDAC4/ER alpha	-0.002	0.037	-9999	-0.57	2	2
EntrezGene:23225	0	0	-9999	-10000	0	0
positive regulation of chromatin silencing	0.051	0.045	-9999	-0.84	1	1
cell motility	-0.001	0.022	-9999	-0.48	1	1
EntrezGene:23636	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
HDAC7/HDAC3	0	0	-9999	-10000	0	0
BCL6	0.016	0	-9999	-10000	0	0
HDAC4/CaMK II delta B	0.016	0	-9999	-10000	0	0
Hsp90/HDAC6	0	0	-9999	-10000	0	0
ESR1	0.012	0.05	-9999	-0.76	2	2
HDAC6/HDAC11	-0.002	0.037	-9999	-0.57	2	2
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
MEF2C	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
HDAC4/MEF2C	0	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
TUBB2A	0.014	0.035	-9999	-0.76	1	1
HDAC11	0.012	0.05	-9999	-0.76	2	2
HSP90AA1	0.016	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
ANKRA2	0.016	0	-9999	-10000	0	0
RFXANK	0.016	0	-9999	-10000	0	0
nuclear import	0.001	0.018	-9999	-10000	0	0

×

Hedgehog signaling events mediated by Gli proteins

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0.001	-9999	-10000	0	0
HDAC2	0.015	0.001	-9999	-10000	0	0
GNB1/GNG2	-0.001	0.022	-9999	-0.48	1	1
forebrain development	0.056	0.093	-9999	-0.5	2	2
GNAO1	0.009	0.078	-9999	-0.84	4	4
SMO/beta Arrestin2	-0.002	0.04	-9999	-0.62	2	2
SMO	0.015	0.036	-9999	-0.76	1	1
ARRB2	0.014	0.04	-9999	-0.86	1	1
GLI3/SPOP	0.062	0.021	-9999	-10000	0	0
mol:GTP	0.001	0.002	-9999	-10000	0	0
GSK3B	0.016	0	-9999	-10000	0	0
GNAI2	0.016	0.004	-9999	-10000	0	0
SIN3/HDAC complex	-0.017	0.094	-9999	-10000	0	0
GNAI1	0.011	0.061	-9999	-0.76	3	3
XPO1	0.019	0.005	-9999	-10000	0	0
GLI1/Su(fu)	-0.013	0.061	-9999	-10000	0	0
SAP30	-0.014	0.16	-9999	-0.86	16	16
mol:GDP	0.015	0.036	-9999	-0.76	1	1
MIM/GLI2A	0.023	0.008	-9999	-10000	0	0
IFT88	0.014	0.035	-9999	-0.76	1	1
GNAI3	0.016	0.004	-9999	-10000	0	0
GLI2	0.058	0.032	-9999	-10000	0	0
GLI3	0.056	0.023	-9999	-10000	0	0
CSNK1D	0.016	0	-9999	-10000	0	0
CSNK1E	0.016	0	-9999	-10000	0	0
SAP18	0.016	0.001	-9999	-10000	0	0
embryonic digit morphogenesis	0.014	0.035	-9999	-0.76	1	1
GNG2	0.016	0	-9999	-10000	0	0
Gi family/GTP	0.045	0.052	-9999	-0.56	1	1
SIN3B	0.015	0.001	-9999	-10000	0	0
SIN3A	0.016	0.001	-9999	-10000	0	0
GLI3/Su(fu)	0.058	0.043	-9999	-10000	0	0
GLI2/Su(fu)	0.075	0.038	-9999	-10000	0	0
FOXA2	-0.062	0.23	-9999	-0.85	35	35
neural tube patterning	0.056	0.093	-9999	-0.5	2	2
SPOP	0.016	0	-9999	-10000	0	0
Su(fu)/PIAS1	-0.001	0.014	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
CSNK1G2	0.014	0.035	-9999	-0.76	1	1
CSNK1G3	0.016	0	-9999	-10000	0	0
MTSS1	0.023	0.008	-9999	-10000	0	0
embryonic limb morphogenesis	0.056	0.093	-9999	-0.5	2	2
SUFU	0.038	0.022	-9999	-10000	0	0
LGALS3	-0.003	0.13	-9999	-0.86	10	10
catabolic process	0.093	0.029	-9999	-10000	0	0
GLI3A/CBP	0.018	0.052	-9999	-0.36	3	3
KIF3A	0.016	0	-9999	-10000	0	0
GLI1	0.056	0.094	-9999	-0.51	2	2
RAB23	0.016	0	-9999	-10000	0	0
CSNK1A1	0.016	0	-9999	-10000	0	0
IFT172	0.016	0	-9999	-10000	0	0
RBBP7	0.015	0.001	-9999	-10000	0	0
Su(fu)/Galectin3	-0.012	0.079	-9999	-0.55	10	10
GNAZ	0.011	0.061	-9999	-0.76	3	3
RBBP4	0.016	0.001	-9999	-10000	0	0
CSNK1G1	0.016	0	-9999	-10000	0	0
PIAS1	0.016	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GLI2/SPOP	0.061	0.03	-9999	-10000	0	0
STK36	0.019	0.005	-9999	-10000	0	0
Gi family/GNB1/GNG2/GDP	0.041	0.051	-9999	-0.49	1	1
PTCH1	0.063	0.1	-9999	-1.1	1	1
MIM/GLI1	0.053	0.15	-9999	-0.56	3	3
CREBBP	0.018	0.052	-9999	-0.36	3	3
Su(fu)/SIN3/HDAC complex	0.058	0.045	-9999	-10000	0	0

×

Class I PI3K signaling events mediated by Akt

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL2L1	0.031	0	-9999	-10000	0	0
BAD/BCL-XL/YWHAZ	-0.001	0.02	-9999	-10000	0	0
CDKN1B	0.051	0	-9999	-10000	0	0
CDKN1A	0.049	0.033	-9999	-0.47	2	2
FRAP1	0	0	-9999	-10000	0	0
PRKDC	0.016	0	-9999	-10000	0	0
FOXO3	0.051	0	-9999	-10000	0	0
AKT1	0	0	-9999	-10000	0	0
BAD	0.014	0.035	-9999	-0.76	1	1
AKT3	0.023	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
FOXO4	0.051	0	-9999	-10000	0	0
AKT1/ASK1	0	0	-9999	-10000	0	0
BAD/YWHAZ	-0.001	0.022	-9999	-0.48	1	1
RICTOR	0.016	0	-9999	-10000	0	0
RAF1	0.016	0	-9999	-10000	0	0
JNK cascade	0	0	-9999	-10000	0	0
TSC1	0.051	0	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
AKT1/RAF1	0	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
mol:PI-3-4-5-P3	0	0	-9999	-10000	0	0
TSC2	0.051	0	-9999	-10000	0	0
YWHAQ	0.016	0	-9999	-10000	0	0
TBC1D4	0.034	0	-9999	-10000	0	0
MAP3K5	0.016	0	-9999	-10000	0	0
MAPKAP1	0.016	0	-9999	-10000	0	0
negative regulation of cell cycle	-0.042	0.051	-9999	-10000	0	0
YWHAH	0.016	0	-9999	-10000	0	0
AKT1S1	0.051	0	-9999	-10000	0	0
CASP9	0.051	0	-9999	-10000	0	0
YWHAB	0.016	0	-9999	-10000	0	0
p27Kip1/KPNA1	0.058	0	-9999	-10000	0	0
GBL	0	0	-9999	-10000	0	0
PDK1/Src/Hsp90	0	0	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
AKT2/p21CIP1	-0.002	0.029	-9999	-0.45	2	2
KIAA1303	0	0	-9999	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.024	0	-9999	-10000	0	0
CHUK	0.051	0	-9999	-10000	0	0
BAD/BCL-XL	-0.001	0.016	-9999	-10000	0	0
mTORC2	0	0	-9999	-10000	0	0
AKT2	0.023	0	-9999	-10000	0	0
FOXO1-3a-4/14-3-3 family	0.061	0.057	-9999	-10000	0	0
PDPK1	0.016	0	-9999	-10000	0	0
MDM2	0.051	0	-9999	-10000	0	0
MAPKKK cascade	0	0	-9999	-10000	0	0
MDM2/Cbp/p300	0	0	-9999	-10000	0	0
TSC1/TSC2	0.06	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
glucose import	0.031	0.079	-9999	-0.48	11	11
mTOR/RHEB/GDP/Raptor/GBL/PRAS40	0.043	0	-9999	-10000	0	0
response to stress	0	0	-9999	-10000	0	0
SLC2A4	0.031	0.079	-9999	-0.48	11	11
GSK3A	0.051	0	-9999	-10000	0	0
FOXO1	0.051	0	-9999	-10000	0	0
GSK3B	0.051	0	-9999	-10000	0	0
SFN	-0.079	0.27	-9999	-0.84	53	53
G1/S transition of mitotic cell cycle	0.06	0	-9999	-10000	0	0
p27Kip1/14-3-3 family	0.038	0.077	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
KPNA1	0.016	0	-9999	-10000	0	0
HSP90AA1	0.016	0	-9999	-10000	0	0
YWHAG	0.016	0	-9999	-10000	0	0
RHEB	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0

×

Role of Calcineurin-dependent NFAT signaling in lymphocytes

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
BCL2L1	0.016	0	-10000	0	-10000	0	0
NFATC1	0.076	0.028	-10000	0	-10000	0	0
NFATC2	0.054	0.029	-10000	0	-10000	0	0
NFATC3	0.028	0.042	-10000	0	-0.49	3	3
YWHAE	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/CABIN1	0.034	0.067	-10000	0	-0.47	3	3
Exportin 1/Ran/NUP214	0	0	-10000	0	-10000	0	0
mol:DAG	0	0.001	-10000	0	-10000	0	0
CABIN1/MEF2D/CaM/Ca2+/CAMK IV	-0.011	0.053	-10000	0	-0.53	2	2
BCL2/BAX	0	0	-10000	0	-10000	0	0
CaM/Ca2+/Calcineurin A alpha-beta B1	0	0.001	-10000	0	-10000	0	0
CaM/Ca2+	0	0.001	-10000	0	-10000	0	0
BAX	0.016	0	-10000	0	-10000	0	0
MAPK14	0.016	0.003	-10000	0	-10000	0	0
BAD	0.014	0.035	-10000	0	-0.76	1	1
CABIN1/MEF2D	0.039	0.064	-10000	0	-0.44	3	3
Calcineurin A alpha-beta B1/BCL2	0.016	0	-10000	0	-10000	0	0
FKBP8	0.014	0.035	-10000	0	-0.76	1	1
activation-induced cell death of T cells	-0.039	0.063	0.43	3	-10000	0	3
KPNB1	0.016	0	-10000	0	-10000	0	0
KPNA2	0.016	0	-10000	0	-10000	0	0
XPO1	0.015	0.003	-10000	0	-10000	0	0
SFN	-0.079	0.27	-10000	0	-0.84	53	53
MAP3K8	0.012	0.057	-10000	0	-0.86	2	2
NFAT4/CK1 alpha	-0.002	0.025	-10000	0	-10000	0	0
MEF2D/NFAT1/Cbp/p300	-0.011	0.057	-10000	0	-10000	0	0
CABIN1	0.034	0.068	-10000	0	-0.47	3	3
CALM1	0.016	0.003	-10000	0	-10000	0	0
RAN	0.015	0.003	-10000	0	-10000	0	0
MAP3K1	0.016	0	-10000	0	-10000	0	0
CAMK4	0.012	0.05	-10000	0	-0.76	2	2
mol:Ca2+	0.001	0.004	-10000	0	-10000	0	0
MAPK3	0.016	0	-10000	0	-10000	0	0
YWHAH	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/AKAP79/PKA	-0.005	0.052	-10000	0	-0.57	4	4
YWHAB	0.016	0	-10000	0	-10000	0	0
MAPK8	0.016	0.003	-10000	0	-10000	0	0
MAPK9	0.016	0	-10000	0	-10000	0	0
YWHAG	0.016	0	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
NFAT1-c-4/YWHAQ	-0.002	0.029	-10000	0	-10000	0	0
PRKCH	0.016	0	-10000	0	-10000	0	0
CABIN1/Cbp/p300	0	0	-10000	0	-10000	0	0
CASP3	0.016	0.003	-10000	0	-10000	0	0
PIM1	0.016	0	-10000	0	-10000	0	0
Calcineurin A alpha-beta B1/FKBP12/FK506	0	0	-10000	0	-10000	0	0
apoptosis	0	0.01	-10000	0	-10000	0	0
14-3-3 family/BAD/CaM/Ca2+/Calcineurin A alpha-beta B1	0.032	0.073	-10000	0	-0.54	1	1
PRKCB	0.007	0.085	-10000	0	-0.82	5	5
PRKCE	0.016	0	-10000	0	-10000	0	0
JNK2/NFAT4	-0.003	0.035	-10000	0	-0.44	3	3
BAD/BCL-XL	-0.001	0.026	-10000	0	-0.57	1	1
PRKCD	0.014	0.04	-10000	0	-0.86	1	1
NUP214	0.015	0.003	-10000	0	-10000	0	0
PRKCZ	0.011	0.061	-10000	0	-0.76	3	3
PRKCA	0.016	0	-10000	0	-10000	0	0
PRKCG	-0.027	0.17	-10000	0	-0.86	19	19
PRKCQ	-0.004	0.12	-10000	0	-0.76	12	12
FKBP38/BCL2	-0.001	0.026	-10000	0	-0.57	1	1
EP300	0.016	0.003	-10000	0	-10000	0	0
PRKCB1	0	0	-10000	0	-10000	0	0
CSNK2A1	0.016	0	-10000	0	-10000	0	0
NFATc/JNK1	0.081	0.03	-10000	0	-10000	0	0
CaM/Ca2+/FKBP38	-0.001	0.023	-10000	0	-0.51	1	1
FKBP12/FK506	0	0	-10000	0	-10000	0	0
CSNK1A1	0.027	0.005	-10000	0	-10000	0	0
CaM/Ca2+/CAMK IV	-0.002	0.032	-10000	0	-0.5	2	2
NFATc/ERK1	0.081	0.027	-10000	0	-10000	0	0
CABIN1/YWHAQ/CaM/Ca2+/CAMK IV	-0.011	0.053	-10000	0	-0.53	2	2
NR4A1	0.071	0.14	-10000	0	-0.68	16	16
GSK3B	0.016	0.003	-10000	0	-10000	0	0
positive T cell selection	0.028	0.042	-10000	0	-0.49	3	3
NFAT1/CK1 alpha	-0.002	0.015	-10000	0	-10000	0	0
RCH1/ KPNB1	0	0	-10000	0	-10000	0	0
YWHAQ	0.016	0	-10000	0	-10000	0	0
PRKACA	0.016	0.003	-10000	0	-10000	0	0
AKAP5	0.009	0.07	-10000	0	-0.76	4	4
MEF2D	0.016	0.003	-10000	0	-10000	0	0
mol:FK506	0	0	-10000	0	-10000	0	0
YWHAZ	0.016	0	-10000	0	-10000	0	0
NFATc/p38 alpha	0.08	0.03	-10000	0	-10000	0	0
CREBBP	0.016	0.003	-10000	0	-10000	0	0
BCL2	0.016	0	-10000	0	-10000	0	0

×

Signaling events mediated by HDAC Class I

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NF kappa B/RelA	-0.007	0.056	-9999	-10000	0	0
Ran/GTP/Exportin 1/HDAC1	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha	-0.006	0.044	-9999	-10000	0	0
SUMO1	0.016	0	-9999	-10000	0	0
ZFPM1	0.011	0.061	-9999	-0.76	3	3
NPC/RanGAP1/SUMO1/Ubc9	0	0	-9999	-10000	0	0
FKBP3	0.016	0	-9999	-10000	0	0
Histones	-0.003	0.023	-9999	-10000	0	0
YY1/LSF	0	0	-9999	-10000	0	0
SMG5	0.016	0	-9999	-10000	0	0
RAN	0.016	0	-9999	-10000	0	0
I kappa B alpha/HDAC3	-0.005	0.042	-9999	-10000	0	0
I kappa B alpha/HDAC1	-0.004	0.028	-9999	-10000	0	0
SAP18	0.016	0	-9999	-10000	0	0
RELA	0.046	0.042	-9999	-10000	0	0
HDAC1/Smad7	0	0	-9999	-10000	0	0
RANGAP1	0.016	0	-9999	-10000	0	0
HDAC3/TR2	-0.004	0.028	-9999	-10000	0	0
NuRD/MBD3 Complex	0.064	0.011	-9999	-10000	0	0
NF kappa B1 p50/RelA	0.049	0.038	-9999	-10000	0	0
EntrezGene:23225	0	0	-9999	-10000	0	0
GATA2	0.001	0.1	-9999	-0.76	9	9
GATA1	-0.02	0.17	-9999	-0.86	18	18
Mad/Max	0	0	-9999	-10000	0	0
NuRD/MBD3 Complex/GATA1/Fog1	-0.008	0.037	-9999	-0.44	1	1
RBBP7	0.016	0	-9999	-10000	0	0
NPC	0	0	-9999	-10000	0	0
RBBP4	0.016	0	-9999	-10000	0	0
MAX	0.016	0	-9999	-10000	0	0
EntrezGene:9972	0	0	-9999	-10000	0	0
FBXW11	0.016	0	-9999	-10000	0	0
NFKBIA	-0.004	0.033	-9999	-10000	0	0
KAT2B	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
SIN3/HDAC complex	-0.007	0.036	-9999	-10000	0	0
SIN3 complex	-0.017	0.094	-9999	-10000	0	0
SMURF1	0.016	0	-9999	-10000	0	0
CHD3	0.016	0	-9999	-10000	0	0
SAP30	-0.014	0.16	-9999	-0.86	16	16
EntrezGene:23636	0	0	-9999	-10000	0	0
NCOR1	0.016	0	-9999	-10000	0	0
YY1/HDAC3	-0.003	0.024	-9999	-10000	0	0
YY1/HDAC2	0	0	-9999	-10000	0	0
YY1/HDAC1	0	0	-9999	-10000	0	0
NuRD/MBD2 Complex (MeCP1)	0.064	0	-9999	-10000	0	0
PPARG	-0.006	0.049	-9999	-10000	0	0
HDAC8/hEST1B	0	0	-9999	-10000	0	0
UBE2I	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
TNFRSF1A	0.016	0	-9999	-10000	0	0
HDAC3/SMRT (N-CoR2)	-0.004	0.028	-9999	-10000	0	0
MBD3L2	0	0	-9999	-10000	0	0
ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
NuRD/MBD3/MBD3L2 Complex	0	0.009	-9999	-10000	0	0
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	-0.004	0.033	-9999	-10000	0	0
HDAC2	0.016	0	-9999	-10000	0	0
YY1	0.041	0	-9999	-10000	0	0
HDAC8	0.016	0	-9999	-10000	0	0
SMAD7	0.016	0	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
MXD1	0.016	0	-9999	-10000	0	0
STAT3	0.035	0	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
EntrezGene:8021	0	0	-9999	-10000	0	0
RANBP2	0.016	0	-9999	-10000	0	0
YY1/LSF/HDAC1	0	0	-9999	-10000	0	0
YY1/SAP30/HDAC1	-0.017	0.091	-9999	-0.51	16	16
EP300	0.016	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)	0.035	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	-0.004	0.033	-9999	-10000	0	0
histone deacetylation	0.064	0	-9999	-10000	0	0
STAT3 (dimer non-phopshorylated)/HDAC3	-0.003	0.025	-9999	-10000	0	0
nuclear export	0	0	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
GATAD2B	0.016	0	-9999	-10000	0	0
GATAD2A	0.016	0	-9999	-10000	0	0
GATA2/HDAC3	-0.012	0.065	-9999	-0.43	9	9
GATA1/HDAC1	-0.025	0.13	-9999	-0.67	18	18
GATA1/HDAC3	-0.023	0.1	-9999	-0.52	18	18
CHD4	0.016	0	-9999	-10000	0	0
TNF-alpha/TNFR1A	-0.01	0.079	-9999	-0.62	8	8
SIN3/HDAC complex/Mad/Max	0.057	0.038	-9999	-10000	0	0
NuRD Complex	0	0.008	-9999	-10000	0	0
positive regulation of chromatin silencing	-0.003	0.023	-9999	-10000	0	0
SIN3B	0.016	0	-9999	-10000	0	0
MTA2	0.016	0	-9999	-10000	0	0
SIN3A	0.016	0	-9999	-10000	0	0
XPO1	0.016	0	-9999	-10000	0	0
SUMO1/HDAC1	0	0	-9999	-10000	0	0
HDAC complex	0	0	-9999	-10000	0	0
GATA1/Fog1	-0.029	0.13	-9999	-0.65	21	21
FKBP25/HDAC1/HDAC2	0	0	-9999	-10000	0	0
TNF	0.002	0.11	-9999	-0.81	8	8
negative regulation of cell growth	0.057	0.038	-9999	-10000	0	0
NuRD/MBD2/PRMT5 Complex	0.064	0	-9999	-10000	0	0
Ran/GTP/Exportin 1	0	0	-9999	-10000	0	0
NF kappa B/RelA/I kappa B alpha	-0.006	0.047	-9999	-10000	0	0
SIN3/HDAC complex/NCoR1	-0.005	0.027	-9999	-10000	0	0
TFCP2	0.016	0	-9999	-10000	0	0
NR2C1	0.016	0	-9999	-10000	0	0
MBD3	0.014	0.035	-9999	-0.76	1	1
MBD2	0.016	0	-9999	-10000	0	0

×

Retinoic acid receptors-mediated signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
HDAC1	0.016	0	-9999	-10000	0	0
HDAC3	0.016	0	-9999	-10000	0	0
VDR	0.011	0.061	-9999	-0.76	3	3
Cbp/p300/PCAF	0	0	-9999	-10000	0	0
EP300	0.016	0	-9999	-10000	0	0
RARs/AIB1/Cbp/p300/PCAF/9cRA	0.058	0.026	-9999	-10000	0	0
KAT2B	0.016	0	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
AKT1	0.031	0.037	-9999	-0.31	2	2
RAR alpha/9cRA/Cyclin H	-0.007	0.035	-9999	-10000	0	0
mol:9cRA	0	0	-9999	-10000	0	0
RARs/Src-1/Cbp/p300/PCAF/9cRA	0.054	0.028	-9999	-10000	0	0
CDC2	0.001	0.001	-9999	-10000	0	0
response to UV	0.002	0.001	-9999	-10000	0	0
RAR alpha/Jnk1	-0.008	0.038	-9999	-10000	0	0
NCOR2	0.016	0	-9999	-10000	0	0
VDR/VDR/Vit D3	-0.004	0.046	-9999	-0.58	3	3
RXRs/RARs/NRIP1/9cRA	0.065	0.079	-9999	-0.52	1	1
NCOA2	0.009	0.07	-9999	-0.76	4	4
NCOA3	0.016	0	-9999	-10000	0	0
NCOA1	0.016	0	-9999	-10000	0	0
VDR/VDR/DNA	0.011	0.061	-9999	-0.76	3	3
RARG	0.017	0.001	-9999	-10000	0	0
RAR gamma1/9cRA	0	0	-9999	-10000	0	0
MAPK3	0.017	0.001	-9999	-10000	0	0
MAPK1	0.016	0	-9999	-10000	0	0
MAPK8	0.017	0.001	-9999	-10000	0	0
mol:Vit D3	0	0	-9999	-10000	0	0
RXRs/VDR/DNA/Vit D3	-0.017	0.071	-9999	-10000	0	0
RARA	0.027	0.055	-9999	-10000	0	0
negative regulation of phosphoinositide 3-kinase cascade	0	0	-9999	-10000	0	0
RARs/TIF2/Cbp/p300/PCAF/9cRA	0.052	0.04	-9999	-0.32	2	2
PRKCA	0.021	0.001	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC1	0.057	0.08	-9999	-0.57	1	1
RXRG	0.014	0.088	-9999	-0.38	23	23
RXRA	0.038	0.052	-9999	-10000	0	0
RXRB	0.019	0.08	-9999	-0.37	19	19
VDR/Vit D3/DNA	-0.004	0.046	-9999	-0.58	3	3
RBP1	0.01	0.067	-9999	-0.83	3	3
CRBP1/9-cic-RA	-0.004	0.051	-9999	-0.65	3	3
RARB	0.016	0.05	-9999	-0.76	2	2
PRKCG	-0.022	0.17	-9999	-0.86	19	19
MNAT1	0.016	0	-9999	-10000	0	0
RAR alpha/RXRs	0.056	0.08	-9999	-10000	0	0
RXRs/RARs/SMRT(N-CoR2)/9cRA	0.063	0.071	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0.058	0.041	-9999	-10000	0	0
RXRs/RARs/NRIP1/9cRA/HDAC3	0.057	0.08	-9999	-0.57	1	1
positive regulation of DNA binding	-0.007	0.033	-9999	-10000	0	0
NRIP1	0.055	0.091	-9999	-1.2	1	1
RXRs/RARs	0.048	0.078	-9999	-10000	0	0
RXRs/RXRs/DNA/9cRA	-0.015	0.07	-9999	-10000	0	0
PRKACA	0.016	0	-9999	-10000	0	0
CDK7	0.016	0	-9999	-10000	0	0
TFIIH	0	0	-9999	-10000	0	0
RAR alpha/9cRA	-0.005	0.024	-9999	-10000	0	0
CCNH	0.016	0	-9999	-10000	0	0
CREBBP	0.016	0	-9999	-10000	0	0
RAR gamma2/9cRA	0	0	-9999	-10000	0	0

×

Atypical NF-kappaB 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	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
BCL3/RelA	-0.003	0.043	-9999	-0.67	2	2
FBXW11	0.016	0	-9999	-10000	0	0
NF kappa B1 p50/c-Rel	-0.002	0.031	-9999	-0.49	2	2
NF kappa B1 p50/RelA/I kappa B alpha	-0.008	0.037	-9999	-10000	0	0
NFKBIA	0.027	0.058	-9999	-10000	0	0
MAPK14	0.016	0	-9999	-10000	0	0
NF kappa B1 p105/p50	0	0	-9999	-10000	0	0
ARRB2	0.022	0.019	-9999	-0.39	1	1
REL	0.012	0.05	-9999	-0.76	2	2
response to oxidative stress	0	0	-9999	-10000	0	0
BCL3/NF kappa B1 p50	-0.002	0.037	-9999	-0.58	2	2
response to UV	0	0	-9999	-10000	0	0
NF kappa B1 p105/RelA	0	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
NF kappa B1 p50 dimer	0.027	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
NFKB1	0.031	0	-9999	-10000	0	0
RELA	0.016	0	-9999	-10000	0	0
positive regulation of anti-apoptosis	0.036	0.057	-9999	-10000	0	0
NF kappa B1 p50/RelA/I kappa B alpha/beta Arrestin2	-0.008	0.036	-9999	-10000	0	0
SRC	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
NF kappa B1 p50/RelA	-0.011	0.046	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
SYK	0.012	0.05	-9999	-0.76	2	2
I kappa B alpha/PIK3R1	0.034	0.054	-9999	-10000	0	0
cell death	-0.008	0.034	-9999	-10000	0	0
NF kappa B1 p105/c-Rel	-0.002	0.031	-9999	-0.49	2	2
LCK	-0.024	0.18	-9999	-0.85	22	22
BCL3	0.012	0.057	-9999	-0.86	2	2

×

IGF1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
NCK2	0.016	0	-9999	-10000	0	0
PTK2	0.016	0	-9999	-10000	0	0
CRKL	0.029	0.058	-9999	-10000	0	0
GRB2/SOS1/SHC	-0.001	0.026	-9999	-0.58	1	1
HRAS	0.016	0	-9999	-10000	0	0
IRS1/Crk	-0.007	0.053	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/PTP1B	-0.008	0.062	-9999	-0.52	7	7
AKT1	0.057	0.051	-9999	-10000	0	0
BAD	0.065	0.052	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.029	0.058	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/Shp2	-0.007	0.053	-9999	-10000	0	0
RAF1	0.07	0.046	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos	-0.007	0.05	-9999	-10000	0	0
YWHAZ	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1	-0.008	0.059	-9999	-0.45	7	7
PIK3CA	0.016	0	-9999	-10000	0	0
RPS6KB1	0.057	0.051	-9999	-10000	0	0
GNB2L1	0.014	0.04	-9999	-0.86	1	1
positive regulation of MAPKKK cascade	0.061	0.041	-9999	-10000	0	0
PXN	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
cell adhesion	0	0	-9999	-10000	0	0
GRB2/SOS1	0	0	-9999	-10000	0	0
HRAS/GTP	-0.007	0.047	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/GRB2/Sos/Shc	-0.007	0.054	-9999	-0.51	1	1
IGF-1R heterotetramer	0.015	0.012	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS/Nck	-0.007	0.053	-9999	-10000	0	0
Crk/p130 Cas/Paxillin	-0.007	0.049	-9999	-10000	0	0
IGF1R	0.015	0.012	-9999	-10000	0	0
IGF1	0.003	0.1	-9999	-0.85	7	7
IRS2/Crk	-0.015	0.079	-9999	-10000	0	0
PI3K	-0.007	0.049	-9999	-10000	0	0
apoptosis	-0.068	0.046	-9999	-10000	0	0
HRAS/GDP	0	0	-9999	-10000	0	0
PRKCD	0.049	0.061	-9999	-0.82	1	1
RAF1/14-3-3 E	0.073	0.041	-9999	-10000	0	0
BAD/14-3-3	0.071	0.049	-9999	-10000	0	0
PRKCZ	0.054	0.061	-9999	-10000	0	0
Crk/p130 Cas/Paxillin/FAK1	-0.005	0.036	-9999	-10000	0	0
PTPN1	0.016	0	-9999	-10000	0	0
IGF-1R heterotetramer/IGF1/IRS1/GRB2/Sos/Shc/RACK1	0.041	0.052	-9999	-10000	0	0
BCAR1	0.014	0.035	-9999	-0.76	1	1
IGF-1R heterotetramer/IGF1/SHC/GRB10	-0.008	0.06	-9999	-0.46	8	8
mol:GDP	0	0	-9999	-10000	0	0
SOS1	0.016	0	-9999	-10000	0	0
IRS1/NCK2	-0.007	0.053	-9999	-10000	0	0
GRB10	0.016	0	-9999	-10000	0	0
PTPN11	0.029	0.058	-9999	-10000	0	0
IRS1	0.018	0.062	-9999	-0.45	7	7
IRS2	0.019	0.091	-9999	-0.52	8	8
IGF-1R heterotetramer/IGF1	-0.01	0.079	-9999	-0.66	7	7
GRB2	0.016	0	-9999	-10000	0	0
PDPK1	0.047	0.053	-9999	-10000	0	0
YWHAE	0.016	0	-9999	-10000	0	0
PRKD1	0.05	0.049	-9999	-10000	0	0
SHC1	0.014	0.04	-9999	-0.86	1	1

×

Regulation of cytoplasmic and nuclear SMAD2/3 signaling

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	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations
SMAD4	0.016	-9999	-9999
SMAD2	0.019	-9999	-9999
SMAD3	0.057	-9999	-9999
SMAD3/SMAD4	0.063	-9999	-9999
SMAD4/Ubc9/PIASy	0	-9999	-9999
SMAD2/SMAD2/SMAD4	0	-9999	-9999
PPM1A	0.016	-9999	-9999
CALM1	0.016	-9999	-9999
SMAD2/SMAD4	0.027	-9999	-9999
MAP3K1	0.016	-9999	-9999
TRAP-1/SMAD4	0	-9999	-9999
MAPK3	0.016	-9999	-9999
MAPK1	0.016	-9999	-9999
NUP214	0.016	-9999	-9999
CTDSP1	0.016	-9999	-9999
CTDSP2	0.016	-9999	-9999
CTDSPL	0.016	-9999	-9999
KPNB1	0.016	-9999	-9999
TGFBRAP1	0.016	-9999	-9999
UBE2I	0.016	-9999	-9999
NUP153	0.016	-9999	-9999
KPNA2	0.016	-9999	-9999
PIAS4	0.016	-9999	-9999

×

Circadian rhythm pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
chromatin modification	-0.001	0.014	-10000	0	-10000	0	0
CLOCK	0.02	0.002	-10000	0	-10000	0	0
TIMELESS/CRY2	0.057	0.022	-10000	0	-10000	0	0
DEC1/BMAL1	-0.001	0.03	-10000	0	-0.66	1	1
ATR	0.016	0	-10000	0	-10000	0	0
NR1D1	0.055	0.064	-10000	0	-1.3	1	1
ARNTL	0.02	0.002	-10000	0	-10000	0	0
TIMELESS	0.057	0.025	-10000	0	-10000	0	0
NPAS2	0.006	0.1	-10000	0	-0.75	9	9
CRY2	0.016	0	-10000	0	-10000	0	0
mol:CO	-0.019	0.007	0.14	1	-10000	0	1
CHEK1	0.016	0	-10000	0	-10000	0	0
mol:HEME	0.019	0.007	-10000	0	-0.14	1	1
PER1	0.016	0	-10000	0	-10000	0	0
BMAL/CLOCK/NPAS2	0.045	0.072	-10000	0	-10000	0	0
BMAL1/CLOCK	0.066	0.048	-10000	0	-0.82	1	1
S phase of mitotic cell cycle	-0.001	0.014	-10000	0	-10000	0	0
TIMELESS/CHEK1/ATR	-0.001	0.014	-10000	0	-10000	0	0
mol:NADPH	0.019	0.007	-10000	0	-0.14	1	1
PER1/TIMELESS	0.057	0.022	-10000	0	-10000	0	0
PER1-2 / CRY1-2	0	0	-10000	0	-10000	0	0
DEC1	0.001	0.04	-10000	0	-0.86	1	1

×

mTOR signaling pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Number.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
GBL	0	0	-10000	0	-10000	0	0
MKNK1	0.016	0	-10000	0	-10000	0	0
mol:PIP3	-0.001	0.021	-10000	0	-10000	0	0
FRAP1	0.021	0.004	-10000	0	-10000	0	0
AKT1	-0.001	0.016	-10000	0	-10000	0	0
INSR	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/Insulin	0	0	-10000	0	-10000	0	0
mol:GTP	-0.001	0.012	-10000	0	-10000	0	0
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA/eIF3/40s Ribosomal subunit	0	0.003	-10000	0	-10000	0	0
TSC2	0.016	0	-10000	0	-10000	0	0
RHEB/GDP	-0.001	0.01	-10000	0	-10000	0	0
TSC1	0.016	0	-10000	0	-10000	0	0
Insulin Receptor/IRS1	0.019	0.027	-10000	0	-0.39	2	2
eIF4E/eIF4G1/eIF4A1/eIF4B/RNA	0	0.003	-10000	0	-10000	0	0
mol:GDP	0	0	-10000	0	-10000	0	0
EIF3A	0.016	0	-10000	0	-10000	0	0
RPS6KB1	0.038	0.01	-10000	0	-10000	0	0
MAP3K5	0.014	0	-10000	0	-10000	0	0
PIK3R1	0.016	0	-10000	0	-10000	0	0
apoptosis	0.014	0	-10000	0	-10000	0	0
mol:LY294002	0	0	-10000	0	-0.002	2	2
EIF4B	0.046	0.009	-10000	0	-10000	0	0
40S S6 ribosomal protein /40s Ribosomal subunit/eIF3	-0.001	0.018	-10000	0	-0.37	1	1
eIF4E/eIF4G1/eIF4A1	0	0	-10000	0	-10000	0	0
KIAA1303	0	0	-10000	0	-10000	0	0
PI3K	-0.001	0.022	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL	0.044	0.007	-10000	0	-10000	0	0
FKBP1A	0.016	0	-10000	0	-10000	0	0
RHEB/GTP	-0.001	0.009	-10000	0	-10000	0	0
mol:Amino Acids	0	0	-10000	0	-0.002	2	2
FKBP12/Rapamycin	0	0	-10000	0	-10000	0	0
PDPK1	-0.001	0.018	-10000	0	-10000	0	0
EIF4E	0.016	0	-10000	0	-10000	0	0
ASK1/PP5C	0.027	0.003	-10000	0	-10000	0	0
mTOR/RHEB/GTP/Raptor/GBL/eIF4E	0.023	0	-10000	0	-10000	0	0
TSC1/TSC2	-0.001	0.013	-10000	0	-10000	0	0
tumor necrosis factor receptor activity	0	0	0.002	2	-10000	0	2
RPS6	0.014	0.04	-10000	0	-0.86	1	1
PPP5C	0.016	0	-10000	0	-10000	0	0
EIF4G1	0.016	0	-10000	0	-10000	0	0
IRS1	0.01	0.028	-10000	0	-0.43	2	2
INS	0	0.001	-10000	0	-10000	0	0
PTEN	0	0.001	-10000	0	-10000	0	0
PDK2	-0.001	0.018	-10000	0	-10000	0	0
EIF4EBP1	-0.005	0.094	-10000	0	-0.46	20	20
PIK3CA	0.016	0	-10000	0	-10000	0	0
PPP2R5D	0.03	0.004	-10000	0	-10000	0	0
peptide biosynthetic process	0.023	0.001	-10000	0	-10000	0	0
RHEB	0.016	0	-10000	0	-10000	0	0
EIF4A1	0.016	0	-10000	0	-10000	0	0
mol:Rapamycin	0.001	0	-10000	0	-10000	0	0
EEF2	0.023	0.001	-10000	0	-10000	0	0
eIF4E/4E-BP1	0.005	0.084	-10000	0	-0.4	20	20

×

Nectin adhesion pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PDGFRB	0.016	0	-9999	-10000	0	0
alphaV beta3 Integrin	-0.001	0.026	-9999	-0.57	1	1
PTK2	0	0.008	-9999	-10000	0	0
positive regulation of JNK cascade	-0.001	0.014	-9999	-10000	0	0
CDC42/GDP	0.08	0.012	-9999	-10000	0	0
Rac1/GDP	0.082	0.011	-9999	-10000	0	0
RAP1B	0.016	0	-9999	-10000	0	0
RAP1A	0.016	0	-9999	-10000	0	0
CTNNB1	0.016	0	-9999	-10000	0	0
CDC42/GTP	-0.001	0.017	-9999	-10000	0	0
nectin-3/I-afadin	0	0	-9999	-10000	0	0
RAPGEF1	0.078	0.005	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
CRK	0.071	0.005	-9999	-10000	0	0
PDGFB-D/PDGFRB	0.016	0	-9999	-10000	0	0
TLN1	0.047	0	-9999	-10000	0	0
Rap1/GTP	0	0	-9999	-10000	0	0
IQGAP1	0.016	0	-9999	-10000	0	0
Rap1/GTP/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-3(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PVR	0.016	0	-9999	-10000	0	0
Necl-5(dimer)	0.016	0	-9999	-10000	0	0
mol:GDP	0.082	0.013	-9999	-10000	0	0
MLLT4	0.016	0	-9999	-10000	0	0
PIK3CA	0.016	0	-9999	-10000	0	0
PI3K	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
positive regulation of lamellipodium assembly	0	0.001	-9999	-10000	0	0
PVRL1	0.016	0	-9999	-10000	0	0
PVRL3	0.016	0	-9999	-10000	0	0
PVRL2	0.016	0	-9999	-10000	0	0
PIK3R1	0.016	0	-9999	-10000	0	0
CDH1	-0.015	0.15	-9999	-0.76	19	19
CLDN1	0.01	0.067	-9999	-0.83	3	3
JAM-A/CLDN1	-0.003	0.039	-9999	-0.52	2	2
SRC	0	0.003	-9999	-10000	0	0
ITGB3	0.014	0.035	-9999	-0.76	1	1
nectin-1(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
FARP2	0.072	0.029	-9999	-0.54	1	1
RAC1	0.016	0	-9999	-10000	0	0
CTNNA1	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/Necl-5(dimer)	0	0	-9999	-10000	0	0
nectin-1/I-afadin	0	0	-9999	-10000	0	0
nectin-2/I-afadin	0	0	-9999	-10000	0	0
RAC1/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
nectin-1(dimer)/I-afadin/I-afadin/nectin-3(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
CDC42/GTP/IQGAP1/filamentous actin	0	0	-9999	-10000	0	0
F11R	0.016	0	-9999	-10000	0	0
positive regulation of filopodium formation	-0.001	0.014	-9999	-10000	0	0
alphaV/beta3 Integrin/Talin	-0.001	0.017	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin/nectin-2(dimer/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
PIP5K1C	0	0	-9999	-10000	0	0
VAV2	0.072	0.006	-9999	-10000	0	0
RAP1/GDP	0	0.005	-9999	-10000	0	0
ITGAV	0.016	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin/nectin-2(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
nectin-3(dimer)/I-afadin/I-afadin	0	0	-9999	-10000	0	0
Rac1/GTP	0	0.001	-9999	-10000	0	0
PTPRM	0	0	-9999	-10000	0	0
E-cadherin/beta catenin/alpha catenin	-0.015	0.074	-9999	-10000	0	0
adherens junction assembly	0	0	-9999	-10000	0	0
CDC42	0.016	0	-9999	-10000	0	0

×

TRAIL signaling pathway

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
TNFSF10	0.014	0.035	-9999	-0.76	1	1
positive regulation of NF-kappaB transcription factor activity	-0.001	0.026	-9999	-0.57	1	1
MAP2K4	0.064	0.017	-9999	-10000	0	0
IKBKB	0.016	0	-9999	-10000	0	0
TNFRSF10B	0.016	0	-9999	-10000	0	0
TNFRSF10A	0.014	0.035	-9999	-0.76	1	1
SMPD1	-0.001	0.012	-9999	-0.27	1	1
IKBKG	0.016	0	-9999	-10000	0	0
mol:GTP	0	0	-9999	-10000	0	0
TNFRSF10D	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR2	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR3	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR1	-0.002	0.037	-9999	-0.57	2	2
TRAIL/TRAILR4	-0.001	0.026	-9999	-0.57	1	1
TRAIL/TRAILR1/DAP3/GTP	-0.002	0.029	-9999	-0.45	2	2
IKK complex	-0.001	0.008	-9999	-10000	0	0
RIPK1	0.016	0	-9999	-10000	0	0
response to oxidative stress	0	0	-9999	-10000	0	0
DAP3/GTP	0	0	-9999	-10000	0	0
MAPK3	0.03	0.027	-9999	-0.57	1	1
MAP3K1	-0.001	0.014	-9999	-10000	0	0
TRAILR4 (trimer)	0.016	0	-9999	-10000	0	0
TRADD	0.016	0	-9999	-10000	0	0
TRAILR1 (trimer)	0.014	0.035	-9999	-0.76	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP/TRAF2	-0.001	0.019	-9999	-10000	0	0
CFLAR	0.016	0	-9999	-10000	0	0
MAPK1	0.03	0.027	-9999	-0.57	1	1
TRAIL/TRAILR1/FADD/TRADD/RIP	-0.002	0.026	-9999	-10000	0	0
mol:ceramide	-0.001	0.012	-9999	-0.27	1	1
FADD	0.016	0	-9999	-10000	0	0
MAPK8	0.072	0.016	-9999	-10000	0	0
TRAF2	0.016	0	-9999	-10000	0	0
TRAILR3 (trimer)	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/FADD	-0.002	0.031	-9999	-0.48	2	2
DAP3	0.016	0	-9999	-10000	0	0
CASP10	-0.001	0.024	-9999	-0.46	1	1
JNK cascade	-0.001	0.026	-9999	-0.57	1	1
TRAIL (trimer)	0.014	0.035	-9999	-0.76	1	1
TNFRSF10C	0.016	0	-9999	-10000	0	0
TRAIL/TRAILR1/DAP3/GTP/FADD	-0.002	0.027	-9999	-10000	0	0
TRAIL/TRAILR2/FADD	-0.001	0.022	-9999	-0.48	1	1
cell death	-0.001	0.012	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP/TRAF2	-0.001	0.013	-9999	-10000	0	0
TRAILR2 (trimer)	0.016	0	-9999	-10000	0	0
CASP8	0	0.007	-9999	-10000	0	0
negative regulation of caspase activity	0	0	-9999	-10000	0	0
TRAIL/TRAILR2/FADD/TRADD/RIP	-0.001	0.018	-9999	-10000	0	0

×

Signaling mediated by p38-alpha and p38-beta

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
PTGS2	0.007	0.26	-9999	-1.1	25	25
MKNK1	0.016	0	-9999	-10000	0	0
MAPK14	0.023	0.073	-9999	-10000	0	0
ATF2/c-Jun	0.046	0.056	-9999	-10000	0	0
MAPK11	0.023	0.073	-9999	-10000	0	0
MITF	0.045	0.088	-9999	-10000	0	0
MAPKAPK5	0.045	0.088	-9999	-10000	0	0
KRT8	0.044	0.09	-9999	-10000	0	0
MAPKAPK3	0.016	0	-9999	-10000	0	0
MAPKAPK2	0.016	0	-9999	-10000	0	0
p38alpha-beta/CK2	0.033	0.11	-9999	-10000	0	0
CEBPB	0.034	0.11	-9999	-10000	0	0
SLC9A1	0.045	0.088	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ATF2	0.052	0.087	-9999	-10000	0	0
p38alpha-beta/MNK1	-0.018	0.07	-9999	-10000	0	0
JUN	0.047	0.056	-9999	-10000	0	0
PPARGC1A	-0.001	0.16	-9999	-0.75	2	2
USF1	0.045	0.088	-9999	-10000	0	0
RAB5/GDP/GDI1	-0.013	0.049	-9999	-10000	0	0
NOS2	0.041	0.12	-9999	-0.79	6	6
DDIT3	0.042	0.094	-9999	-10000	0	0
RAB5A	0.016	0	-9999	-10000	0	0
HSPB1	0.049	0.076	-9999	-0.48	1	1
p38alpha-beta/HBP1	-0.018	0.07	-9999	-10000	0	0
CREB1	0.05	0.092	-9999	-10000	0	0
RAB5/GDP	0	0	-9999	-10000	0	0
EIF4E	0.049	0.075	-9999	-10000	0	0
RPS6KA4	0.045	0.088	-9999	-10000	0	0
PLA2G4A	0.045	0.087	-9999	-10000	0	0
GDI1	0.045	0.088	-9999	-10000	0	0
TP53	0.047	0.11	-9999	-10000	0	0
RPS6KA5	0.045	0.088	-9999	-10000	0	0
ESR1	0.043	0.092	-9999	-10000	0	0
HBP1	0.016	0	-9999	-10000	0	0
MEF2C	0.045	0.088	-9999	-10000	0	0
MEF2A	0.045	0.088	-9999	-10000	0	0
EIF4EBP1	0.045	0.094	-9999	-10000	0	0
KRT19	-0.043	0.21	-9999	-0.91	8	8
ELK4	0.045	0.088	-9999	-10000	0	0
ATF6	0.045	0.088	-9999	-10000	0	0
ATF1	0.05	0.092	-9999	-10000	0	0
p38alpha-beta/MAPKAPK2	-0.018	0.07	-9999	-10000	0	0
p38alpha-beta/MAPKAPK3	-0.018	0.07	-9999	-10000	0	0

×

Sumoylation by RanBP2 regulates transcriptional repression

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

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

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

×

Rapid glucocorticoid signaling

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
Gs family/GDP/Gbeta gamma	0	0	-9999	-10000	0	0
MAPK9	0.011	0	-9999	-10000	0	0
adrenocorticotropin secretion	-0.003	0.07	-9999	-0.68	5	5
GNB1/GNG2	0	0	-9999	-10000	0	0
GNB1	0.016	0	-9999	-10000	0	0
regulation of calcium ion transport via voltage-gated calcium channel activity	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
MAPK14	0.011	0	-9999	-10000	0	0
Gs family/GTP	0	0	-9999	-10000	0	0
EntrezGene:2778	0	0	-9999	-10000	0	0
vasopressin secretion	0	0	-9999	-10000	0	0
G-protein coupled receptor activity	0	0	-9999	-10000	0	0
ChemicalAbstracts:86-01-1	0	0	-9999	-10000	0	0
glutamate secretion	0	0	-9999	-10000	0	0
GNAL	0.016	0	-9999	-10000	0	0
GNG2	0.016	0	-9999	-10000	0	0
CRH	-0.005	0.088	-9999	-0.86	5	5
mol:cortisol	0	0	-9999	-10000	0	0
MAPK8	0.011	0	-9999	-10000	0	0
MAPK11	0.011	0	-9999	-10000	0	0

×

Arf1 pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
coatomer protein complex	-0.001	0.024	-9999	-0.53	1	1
EntrezGene:79658	0	0	-9999	-10000	0	0
ARF1/GDP/Membrin/GBF1/p115/Brefeldin A	0.028	0	-9999	-10000	0	0
AP2	0	0	-9999	-10000	0	0
mol:DAG	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GTP	0	0	-9999	-10000	0	0
CLTB	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ER cargo protein	0	0	-9999	-10000	0	0
CD4	-0.001	0.12	-9999	-0.86	9	9
CLTA	0.016	0	-9999	-10000	0	0
mol:GTP	0.002	0	-9999	-10000	0	0
ARFGAP1	0.014	0.027	-9999	-0.58	1	1
mol:PI-4-5-P2	0	0	-9999	-10000	0	0
ARF1/GTP	0	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1/ER cargo protein	-0.001	0.022	-9999	-0.48	1	1
mol:Choline	0	0	-9999	-10000	0	0
mol:GDP	0	0	-9999	-10000	0	0
ARF1	0.016	0	-9999	-10000	0	0
DDEF1	0	0	-9999	-10000	0	0
ARF1/GDP	-0.001	0.022	-9999	-0.47	1	1
AP2M1	0.016	0	-9999	-10000	0	0
EntrezGene:1313	0	0	-9999	-10000	0	0
actin filament polymerization	0	0	-9999	-10000	0	0
Rac/GTP	0	0	-9999	-10000	0	0
ARF1/GTP/GGA3/ARF-GAP1	-0.001	0.02	-9999	-0.43	1	1
ARFIP2	0	0	-9999	-10000	0	0
COPA	0.016	0	-9999	-10000	0	0
RAC1	0.016	0	-9999	-10000	0	0
ARF1/GTP/coatomer protein complex	0.035	0	-9999	-10000	0	0
ARF1/GTP/ARHGAP10	0	0	-9999	-10000	0	0
GGA3	0.016	0	-9999	-10000	0	0
ARF1/GTP/Membrin	0	0	-9999	-10000	0	0
AP2A1	0.016	0	-9999	-10000	0	0
coatomer protein complex/ARF1/GTP/ARF-GAP1	-0.001	0.011	-9999	-10000	0	0
ARF1/GDP/Membrin	0	0	-9999	-10000	0	0
Arfaptin 2/Rac/GDP	0	0	-9999	-10000	0	0
CYTH2	0.016	0	-9999	-10000	0	0
ARF1/GTP/GGA3	0	0	-9999	-10000	0	0
mol:ATP	0	0	-9999	-10000	0	0
Rac/GDP	0	0	-9999	-10000	0	0
mol:Brefeldin A	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex/Coatomer protein complex/ARF1/GTP	-0.004	0.029	-9999	-10000	0	0
PLD2	0	0	-9999	-10000	0	0
ARF-GAP1/v-SNARE	0.014	0.027	-9999	-0.58	1	1
PIP5K1A	0	0	-9999	-10000	0	0
ARF1/GTP/Membrin/GBF1/p115	0	0	-9999	-10000	0	0
mol:Phosphatic acid	0	0	-9999	-10000	0	0
mol:Phosphatidic acid	0	0	-9999	-10000	0	0
KDEL Receptor/Ligand/ARF-GAP1	0.014	0.027	-9999	-0.58	1	1
GOSR2	0	0	-9999	-10000	0	0
USO1	0	0	-9999	-10000	0	0
GBF1	0	0	-9999	-10000	0	0
ARF1/GTP/Arfaptin 2	0	0	-9999	-10000	0	0
CD4/HIV Nef/AP2/vacuolar proton-transporting V-type ATPase complex	-0.011	0.078	-9999	-0.58	9	9

×

Alternative NF-kappaB pathway

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

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

Entity	Mean	Std.Dev	Mean.of.Up.Perturbations	Mean.of.Down.Perturbations	Number.of.Down.Perturbations	Number.of.Total.Perturbations
IKK alpha homodimer	-0.006	0.061	-9999	-0.67	4	4
FBXW11	0.016	0	-9999	-10000	0	0
proteasomal ubiquitin-dependent protein catabolic process	0	0	-9999	-10000	0	0
beta TrCP1/SCF ubiquitin ligase complex	0.016	0	-9999	-10000	0	0
CHUK	0.016	0	-9999	-10000	0	0
NF kappa B2 p100/RelB	-0.004	0.044	-9999	-10000	0	0
NFKB1	0.016	0	-9999	-10000	0	0
MAP3K14	0.008	0.08	-9999	-0.86	4	4
NF kappa B1 p50/RelB	0	0	-9999	-10000	0	0
RELB	0.016	0	-9999	-10000	0	0
NFKB2	0.016	0	-9999	-10000	0	0
NF kappa B2 p52/RelB	0	0	-9999	-10000	0	0
regulation of B cell activation	0	0	-9999	-10000	0	0

pid_entity	TCGA.EU.5906	TCGA.EU.5905	TCGA.EU.5904	TCGA.DV.5576
109_MAP3K5	0.074	0.074	0.074	0.074
47_PPARGC1A	0.016	0.016	0.016	0.016
105_BMP4	0.016	0.016	0.016	0.016
105_BMP6	0.016	0.016	0.016	0.016
105_BMP7	-0.76	0	-0.76	0.016
105_BMP2	0.016	0.016	0.016	0.016
131_RELN/VLDLR	0	-0.44	0	0
30_TGFB1/TGF beta receptor Type II	0.015	0.015	0.016	0.015
84_STAT5B	-0.032	-0.031	0.025	0.06
84_STAT5A	-0.032	-0.031	0.025	0.06